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Question 15 - 2000, Paper 2

Comment briefly on the statement:  "lsotonic saline is an inappropriate fluid to use in the management of the patient with diabetic ketoacidosis".

College Answer

As with any drug/fluid there are problems associated with the use of normal saline as the sole fluid to  resuscitate the extracellular  fluid  deficit  of  DKA. Diabetic  ketoacidosis  is associated  with  a number of metabolic  disturbances, but most of the acute clinical  problems  are due to a lack of insulin (hyperglycaemia,  ketone  body  formation)  and  resultant  osmotic  diuresis  (severe  volume depletion [loss  of  water  and  sodium],  total  body electrolyte  depletion  [eg. K, Mg, PO.],  lactic acidosis. renal  insufficiency).  The  major  contributors  to  the  initial  metabolic  acidosis  are  the presence of ketone  bodies (increased anion gap), lactic acidosis (increased  anion gap), and hyperchloraemia  (normal   anion  gap).  The  first  two  of  these  will  be adequately   treated  by intravascular volume expansion and administration of exogenous insulin. Administration of isotonic saline (0.9% sodium  chloride)  may result in delayed correction of bicarbonate (ie. persistence of metabolic acidosis), now due predominantly to hyperchloraemia (normal anion gap).

Delayed correction of bicarbonate:
•   may  increase  the  time  that  the  patient  will  need  to  be  monitored  closely  (potentially confusing assessment patient response to treatment)
•  increases  the minute ventilation  (and work of breathing)  required to maintain steady state
(lower col for a given pH)
•  increases  the  temptation  to  administer  exogenous  bicarbonate  (with  associated  risks of hypokalaemia, hypophosphataemia, hypematraemia etc.)

Alternative crystalloid  solutions  are available  (eg. hartrnannslringers  lactate/plasmalyte/hypotonic saline) and should be considered  early  in the fluid resuscitation  of these patients. Choice of fluid should be based on the response of the patient to therapy (ie. ongoing, repeated assessment of Na [corrected for glucose], K, HC03 and Chloride).

Discussion

One cannot simply "comment briefly" on such a statement as this.

One must critically evaluate it.

Rationale for discussion

  • DKA patients have a significant fluid deficit due to glucose and ketone diuresis
  • Rehydration is a major part of therapy for DKA
  • Isotonic saline is a standard rehydration fluid
  • However, the large volumes which will be required may have undesirable consequences

Physiological basis for the statement

  • Isotonic saline contains 150mmol/L of chloride
  • The excess of chloride may contribute to the metabolic acidosis
  • This contribution may delay recovery from ketoacidosis

Advantages

  • Isotonic saline is a cheap widely available fluid
  • Its high sodium content can promote the retention of fluid in the intravascular space
  • It is safe to use in most settings
  • Volume replacement will result in a more rapid resolution of ketoacidosis and lactic acidosis in DKA
  • Normal anion gap acidosis due to the extra chloride may be mild and transient

Disadvantages

  • Normal anion gap metabolic acidosis may develop
  • Work of breathing may increase due to acidosis
  • Existing (already near-depleted) buffer systems may be further depleted by this NAGMA.

Evidence and opinion in the literature

In summary:

  • This matter is far from settled. The choice of resuscitation fluid in DKA must rely on careful electrolyte and acid-base monitoring, and may need to be tailored to individual scenarios.
  • Balanced fluid solutions may be beneficial in critically acidotic patients whose buffer systems are all but exhausted.
  • Normal saline is likely a safe and inexpensive alternative in patients with mild DKA.

References

Dhatariya, Ketan K. "Diabetic ketoacidosis." BMJ: British Medical Journal334.7607 (2007): 1284.

 

LeRoith D, Taylor SI, Olefsky JM. Diabetes mellitus. A fundamental and clinical text. Philadelphia: Lippincott Williams and Wilkins, 2000

 

Skellett, S., et al. "Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid resuscitation." Archives of disease in childhood 83.6 (2000): 514-516.

 

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes a consensus statement from the American Diabetes Association." Diabetes care 29.12 (2006): 2739-2748.

 

Chua, Horng-Ruey, et al. "Plasma-Lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis." Journal of critical care 27.2 (2012): 138-145.

 

Van Zyl, Danie G., Paul Rheeder, and E. Delport. "Fluid management in diabetic-acidosis—Ringer's lactate versus normal saline: a randomized controlled trial." Qjm 105.4 (2012): 337-343.

Question 10 - 2001, Paper 1

A 180cm, 200kg man presents to ICU following emergency cholecystectomy.  How does his obesity affect his physiology and how may it influence his ICU management?

College Answer

a)         Obesity affects the physiology of several systems:

Cardiovascular- there is increased left and right ventricular stroke work with a tendency to left ventricular hypertrophy.

Hypertension is significantly correlated with obesity

Respiratory- total respiratory compliance is reduced by decreased chest wall compliance with fat accumulation subcutaneously and intraabdominally. There is a reduction in FRC caused by

reduced ERC. If FRC is less than closing capacity, hypoxia may ensue.

b)         Obesity influences his ICU management via:

1)   interference with normal physiology (as above)

2)   coexisting  medical  problems  (hypertension,  ischaemic  heart  disease,  diabetes,  sleep apnoea, pulmonary hypertension)

3)   technical difficulties with

-intravenous access

-intubation

-     monitoring devices (eg NIBP cuffs)

-     bed size (nerve compression)

4) difficulty mobilising

-     DVT

-     Pressure areas

Discussion

Paul Marik has published an excellent review of this in 1998.

Since the late 1990s, obesity has remained obesity, and so I think this article is still very relevant.

The physiological effects of obesity (as relevant to critical illness)

Airway problems

  • Difficult intubation
  • Difficult tracheostomy
  • Difficult tracheostomy care

Respiratory effects

  • Expiratory reserve volume is decreased
  • FEV1 to FVC ratio is increased.
  • VC, TLC and FRC are decreased.
  • Work of breathing is increased
  • CO2 production is increased, thus ventilatory needs are greater
  • Increased risk of aspiration pneumonia
  • Increased risk of DVT and PE

Cardiovascular effects

  • Cardiac output is increased
  • Total blood volume is increased
  • LV contractility is impaired
  • LV size and wall thickness are increased
  • Hypertension is common
  • LV diastolic pressure is increased, and fluid loading is poorly tolerated

Pharmacokinetic effects

  • Volume of distribution is increased for many lipophilic drugs
  • Hepatic clearance may be reduced
  • Renal clearance may be impaired, but this may not be predicted by standard creatinine clearance formulae.

Nutritional effects

  • Increased requirement for dietary protein, given the tendency to mobilise protein instead of fat during a stress repsonse: currently, recommendation is for 1.5-2g/kg of IBW per day

Access problems

  • Vascular access is difficult
  • Cleaning CVC sites may be problematic

Monitoring issues

  • NIBP cuffs do not fit.

Radiology problems

  • Chest Xrays may be of poor quality
  • These patients cannot fit into CT or MRI scanners.

References

Akinnusi, Morohunfolu E., Lilibeth A. Pineda, and Ali A. El Solh. "Effect of obesity on intensive care morbidity and mortality: A meta-analysis*." Critical care medicine 36.1 (2008): 151-158.

 

Marik, Paul, and Joseph Varon. "The obese patient in the ICU." CHEST Journal113.2 (1998): 492-498.

 

Ling, Pei-Ra. "Obesity Paradoxes—Further Research Is Needed!*." Critical care medicine 41.1 (2013): 368-369.

Question 5 - 2001, Paper 2

A 45 year old man with severe pancreatitis is receiving Total Parenteral  Nutrition.  Discuss the role of intravenous lipids in his regimen.

College Answer

Enteral nutrition would be preferable. The question assumes that it is not feasible. Intravenous lipid infusion in TPN is important to prevent essential fatty acid deficiency and as an alternative calorie source. In an acute inflammatory disease or sepsis the standard approach would be to provide at least 50% of the non-protein calories of TPN as lipids, but acute pancreatitis may be associated with familial hyperlipidaemia and the hyperlipidaemia of alcoholism. Lipid infusion has been rarely associated with pancreatitis eg paediatric Crohn’s Disease. Lipid infusion in critically ill patients may cause deterioration in A-aDO2, haemagglutination and immune dysfunction via reticuloendothelial blockade.

It is therefore important to check the serum lipids of this patient and to understand the aetiology of the pancreatitis in this case. If there is no contraindication to lipid infusion, then infusion of 20 mls per hour of commercially available soybean emulsion, eg 20% Intralipid will provide 1000 kcal/day to balance the protein and carbohydrate. Clearing of the lipid can be checked by allowing 10mls of blood to settle and observing for a milky serum or by measuring serum lipid 1 hour after infusion is stopped.

Discussion

This is a frighteningly specific question. It requires the candidate to have a detailed knowledge of TPN constituents and metabolic pathways influenced by parenteral nutrition. Furthermore, it requires one to consider the use of intravenous lipids in a condition known to be exacerbated by hyperlipidaemia.

The specifics of daily macronutrient doses and details of TPN constituents are discussed elsewhere, in the chapter on nutrition in critical illness.

In general, one requires about 0.7-1.5g/kg/day of lipid emulsion via TPN. This talk of providing at least 50% of non-protein calories as lipid is surely madness. These days only about 30% of caloric needs is supplied as lipid.

Certainly, the evidence does not support the assertion that intravenous lipids contribute to mortality in pancreatitis. In a cohort of 18 patients, Van Gossum et al did not find any difference in infused lipid concentration between suvivors and non-survivors. The dead, however, did demonstrate elevated serum lipid profiles and increased insulin requirements, suggesting that pancreatitis patient at risk of death will be very inefficient at using nonprotein energy substrates.

Yes, perhaps IV lipids are bad, and can cause reticuloendothelial dysfunction, hypoxia, thrombophilia and hepatosteatosis. They are also essential nutrients. Without question, the pancreatitis patient should receive lipids as a part of their TPN.

References

Van Gossum, A., et al. "Lipid-associated total parenteral nutrition in patients with severe acute pancreatitis." Journal of Parenteral and Enteral Nutrition 12.3 (1988): 250-255.

 

Patel, Krutika S., Pawan Noel, and Vijay P. Singh. "Potential Influence of Intravenous Lipids on the Outcomes of Acute Pancreatitis." Nutrition in Clinical Practice 29.3 (2014): 291-294.

 

Question 9 - 2001, Paper 2

Following severe trauma a 35 year old woman is being enterally fed via a nasogastric tube. The dietitian  calculates  that  only 25% of  her  daily nutritional  requirements  are  being achieved. Outline your approach to this problem.

College Answer

Again, a sensible practical approach was expected. There may be a place for early jejunal feeding or, if laparotomy is performed, insertion of percutaneous enterostomy.

Otherwise a more conservative approach involves thorough assessment of history, recent events, combined  with  physical  examination  and  perhaps  some  simple  investigations  to  address  the problem.

Are the dietitians calculations appropriate?

Why are the feeds not meeting targets? Large aspirates, inappropriate orders, starving for procedures. If it is because the feeds are not being absorbed, is this due to GIT pathology, systemic illness or narcotic infusion?

Physical examination should be performed looking for distension, rebound tenderness and presence of bowel sounds.

AXR for position of NG tube, ileus.

Treatment will be aimed at reversible causes. If there is no sign of abdominal pathology, the NG tube is in good position, orders are being followed then prokinetics should be tried and if unsuccessful recourse to naso-enteral tube is next step.

Discussion

This nebulous question does not specify why the nutritonal goals are not being met.

The question may  be approached in the following fashion:

Causes for Failure of Nutritional Support
Problem Cause Solution
The calculated energy requirement was wrong The predictive equation was inaccurate -  for example, the patient belongs to a special population - severe burns, multi-trauma, hypothermia, etc.
Or, the dietitian assessing the intake is wrong because of some basic misunderstanding, eg. not being aware of the fact that the patient is hypothermic to 33º C.
Recalculate the goal rate using a more accurate method, eg. indrect calorimetry. Discuss basic mathematics with whoever miscalculated the energy requirement.
There are numerous interruptions to feeding,
but feeds are well tolerated
Frequent trips to the operating theatre or CT scanner Either rationalise the travel time, or continue feeding during the transfers.
Alternatively, increase the rate of feeds to contribute 100% of nutritional needs in a decreased timeframe
Frequent interruptions of NG feeds due to high gastric aspirates Ensure some of the aspirated gastric residual volume is returned.
Instruct staff not to stop feeds unless the residual volume is in excess of 500ml
There is genuine feed intolerance There could be numerous reasons; among them:
-  "chemical ileus " (eg. due to opiates)
- poor gut perfusion, eg. shock
- poor gastric emptying due to ANS dysfunction
- post-operative gut damage
-

- Adjust the patient's posture to semi-upright
- Advance the NGT into a post-pyloric position
- Administer prokinetics:
   - metoclopramide or domperidone
   - erythromycin
   - oral naloxone
   - neostigmine

- Consider a PEG or jejunostomy tube

If all else fails, contribute the additional calories via TPN (after trying for up to 7 days)

The feeds are well tolerated, in terms of gastric aspirates being low,  but the nutrients are poorly absorbed The gut is ischaemic, or the villi are denuded, or there is no enough gut (short gut), or the gut transit is too fast (eg. the diarrhoea is very severe). Antimotility agents (eg. loperamide) may be required for the fast transit; otherwise, one has little recourse other than to rely on TPN.

References

Question 7 - 2002, Paper 1

List the causes of hyperglycaemia in the intensive care patient population, and outline your management of hyperglycaemia.

College Answer

Causes:  consider  diabetes  mellitus  (previously  known  or not known,  type I or II, on diet, oral agents, insulin or combination), secondary causes of diabetes (e.g. pancreatitis, haemochromatosis, Cushing’s syndrome, acromegaly), insulin resistance (e.g. sepsis, systemic inflammatory response/stress response [including multiple trauma], beta-agonists [endogenous or exogenous], exogenous corticosteroids), carbohydrate load (e.g. feeding enteral/parenteral, peritoneal dialysis).

Management:  consider  control  of  factors  worsening  response  to  insulin  (sepsis,  drugs,  stress response), control glucose within acceptable range (minimise metabolic and immune effects), recommence oral agents or use insulin (dependent on severity).  Principle of glucose control in diabetics include always some insulin, administer some glucose, measure glucose frequently, expect sudden  changes,  and avoid  hypoglycaemia.    Recent  studies  suggest  tight glucose  control  using insulin  infusions  if necessary  may dramatically  reduce  mortality  after myocardial  infarction  (in diabetic patients: DIGAMI), and in the surgical intensive care (Van den Berghe et al).

Discussion

This question is identical to Question 24 from the first paper of 2006

References

Question 13 - 2002, Paper 1

Outline the pathophysiology, complications and treatment of hyper-osmolar non-ketotic coma.

College Answer

Pathophysiology:  insulin  deficiency  (and/or  resistance)  impairs  peripheral  glucose  utilisation  in skeletal  muscle,  increases  fat  and  muscle  breakdown  and  promotes  hepatic  gluconeogenesis; glucagon excess also promotes hepatic gluconeogenesis.   Other stressors may precipitate (e.g. infection, myocardial infarction, and surgery), partially by increasing cortisol and catecholamine release;  omission  of  normal  treatment  may  also  be  responsible.    Osmotic  diuresis  results  in significant fluid depletion (e.g. 8 to 10 litres), with associated deficits of potassium and phosphate (despite variable plasma levels).

Complications:  CNS  depression/coma,  hypovolaemia,  hyperosmolality,  metabolic  acidosis, potassium and phosphate depletion, and thromboembolism.  Cerebral oedema if glucose lowering or fluid shifts too rapid.

Treatment:  of  underlying  precipitants  (sepsis,  myocardial  infarction),  replace  fluid  deficit  (± invasive monitoring) without rapidly dropping osmolality, insulin therapy (eg. infusion), careful monitoring and replacement of electrolytes (esp. potassium, phosphate), prevention of pulmonary thromboembolism.

Discussion

HONK is discussed in greater detail in a chapter dedicated to the wonders of HONK. It is the natural partner to the chapter on diabetic ketoacidosis.

In brief, one would have to say that HONK results from uncontrolled hyperglycaemia in a patient with some residual insulin secretion. Like the DKA patient, these people usually have some sort of precipinant, be it myocardial infarction, stroke, sepsis, or what have you- anything that causes a stress response and decreases peripheral insulin sensitivity. However, unlike the type 1 diabetic who would switch to ketone production and become acidotic, the HONK patient suffers few symptoms initially. Their decreased insulin sensitivity ensures that the hyperosomolar hyperglycaemic state is maintained, and the residual insulin secretion ensures that hepatic metabolism resists conversion into ketone production.

The resulting hyperglycaemia results in an osmotic diuresis, gradually dehydrating the patient and producing a hyperosmolar state.

The complications of HONK are also asked about in Question 18.1 from the second paper of 2008. In brief summary, they are as follows:

  • HHS-specific physiological abnormalities
    • Hypotension and shock
    • Metabolic acidosis
    • Coma
  • Complications arising from the HHS disease state:
    • Cardiac arrest
    • Cardiovascular collapse
    • Myocardial infarction
    • Stroke
    • Cerebral oedema and brain injury
    • Venous thrombosis
    • Aspiration
  • Complications of therapy for HHS:
    • Dysnatraemia
    • Hyperchloremia from saline administration.
    • Phosphate depletion
    • Hypokalemia
    • Osmotic demyelination (Hegazi et al, 2013)

The stereotypical approach to management is listed below:

  1. Assess airway patency. Intubate to protect the airway if comatose.
  2. Ventilate with mandatory mode initially; aim for normocapnea if the metabolic acidosis is not particularly severe.
  3. Insert arterial line for frequent sampling and haemodynamic monitoring.
    Insert central line to manage electrolyte and fluid infusions.
    Expect a 200ml/kg total water deficit
    Commence fluid resuscitation:
    1. 15-20ml/kg in the first hour
    2. 4-14ml/kg in the second hour (of 0.45% NaCl)
    3. 4-14ml/kg again in the third hour (use 0.9% NaCl if the sodium is low)
    4. When glucose is under 15mmol/L, start 5% dextrose 100-250ml/hr
  4. May require benzodiazepines or anticonvulsants if the presentation history included seizures.
    May require a head CT venogram to rule out dural sinus thrombosis / venous infarction
  5. Watch for a precipitous drop in serum osmolality.
    A safe drop is 3–8 mOsm/kg/h
    Correct electrolyte deficit:
    1. Sodium deficit: 5-13mmol/kg
    2. Potassium deficit: 5-15mmol/kg
    3. Chloride deficit: 3-7mmol/kg
    4. Phosphate deficit: 1-2mmol/kg
    5. Magneisum deficit: 1-1.5mmol/Kg
    6. Calcium deficit: 1-2mmol/Kg 
  6. Monitor renal function and consider dialysis
  7. Insulin therapy may not be required, and may even be dangerous.
    BSL may decrease at a satisfactory rate with fluid resuscitation alone.
  8. May require anticoagulation for dural sinus thrombosis.
  9. May require antibiotics, given that infection is a common precipitant.
    A septic screen should be sent.

Key issues of "specific therapy:

  • Fluid resuscitation
  • Electrolyte replacement
  • Careful slow reduction of serum osmolality
  • Investigation for complications:
    • Myocardial infarction
    • Stroke
    • Cerebral oedema and brain injury
    • Venous thrombosis
  • Management of other possible precipitating causes:
    • Infection, systemic inflammatory response
    • Intracranial haemorrhage
    • Hepatic encephalopathy
    • Drugs, including illicit substances, steroids, phenytoin, diuretics, TPN, lithium

References

Hyperglycemic Comas by P. VERNON VAN HEERDEN from Vincent, Jean-Louis, et al. Textbook of Critical Care: Expert Consult Premium. Elsevier Health Sciences, 2011.

Oh's Intensive Care manual: Chapter 58  (pp. 629) Diabetic  emergencies  by Richard  Keays

Umpierrez, Guillermo E., Mary Beth Murphy, and Abbas E. Kitabchi. "Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome." Diabetes Spectrum15.1 (2002): 28-36.

ARIEFF, ALLEN I., and HUGH J. CARROLL. "Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of theraphy in 37 cases." Medicine 51.2 (1972): 73-94.

Gerich, John E., Malcolm M. Martin, and Lillian Recant. "Clinical and metabolic characteristics of hyperosmolar nonketotic coma." Diabetes 20.4 (1971): 228-238.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes." Diabetes care 32.7 (2009): 1335-1343.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes a consensus statement from the American Diabetes Association." Diabetes care 29.12 (2006): 2739-2748.

Ellis, E. N. "Concepts of fluid therapy in diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma." Pediatric clinics of North America 37.2 (1990): 313-321.

Pinies, J. A., et al. "Course and prognosis of 132 patients with diabetic non ketotic hyperosmolar state." Diabete & metabolisme 20.1 (1993): 43-48.

Hegazi, Mohamed Osama, and Anant Mashankar. "Central pontine myelinolysis in the hyperosmolar hyperglycaemic state." Medical Principles and Practice 22.1 (2013): 96-99.

Question 11 - 2002, Paper 2

Outline the clinical manifestations, appropriate investigations and treatment of hypothyroidism in Intensive Care.

College Answer

•    Hypothyroidism is very common in the ageing population, many unrecognised. Many clinical manifestations are specifically related to either generalised metabolic slowing (fatigue, delayed relation of deep tendon reflexes, bradycardia, depressed nervous system, and hypothermia) or accumulation of matrix glycosaminoglycans (coarse hair and skin, enlarged tongue, non-pitting oedema [myxoedema]). Other manifestations include pericardial effusion, hypertension, hypercholesterolaemia, respiratory muscle weakness, impaired gut motility, and normochromic normocytic anaemia. In some situations (usually
obvious), hypothyroidism occurs as a result of treatment for hyperthyroidism or after thyroid surgery.

•    Investigations should confirm diagnosis and detect complications (eg. hyponatraemia and lipid abnormalities). Confirmatory tests reveal high serum TSH and a low free T4. Uncommonly secondary or tertiary hypothyroidism (inappropriately low level of TSH for T4). Study of other pituitary or hypothalamic function may be required ± imaging.

•    Specific treatment involves replacement of thyroid hormone (usually as T4 50 – 200 mcg/day). Elderly, especially with heart disease require a more gradual introduction (eg. 25 mcg). Intravenous T3 (5-20mcg initially) may also be used in the treatment of myxoedema coma. Other treatment involves supportive care (ventilation, fluid and electrolyte management, temperature control) and corticosteroids (eg. hydrocortisone 100 mg tds) in severe cases until adrenal insufficiency excluded.

Discussion

Hypothyroidism in critical illness receives proper treatment in another chapter.

In order to render the process of revision simpler, I reproduce the table of clinical manifestations here:

The diagnosis of hypothyroidism rests on the measurement of TSH, T3 and T4 which can lead one to differentiate between the causes of hypothyroidism (eg. is it the pitutary, or is it the thyroid gland itself?). One may wish to test for rT3 - the "reverse" form of T3 - which is increased in "sick euthyroid" syndrome.

Lastly, the management is not clever, and consists of thyroxine replacement. The college insists we mentione corticosteroid replacement. One may wish to also mention the following features, unique to the intensive care setting:

  • need for intubation in the context of a decreased level of consciousness
  • delay in weaning from ventilation due to untreated hypothyroidism
  • increased sensitivity to sedating agents
  • decreased sensitivity to inotropes and vasopressors

References

Rosenstein, Nancy E., et al. "Meningococcal disease." New England Journal of Medicine 344.18 (2001): 1378-1388.

 

Mautner, L. S., and W. Prokopec. "Waterhouse-Friderichsen Syndrome."Canadian Medical Association journal 69.2 (1953): 156.

 

Kumar, Ajay, et al. "Plasma exchange and haemodiafiltration in fulminant meningococcal sepsis." Nephrology Dialysis Transplantation 13.2 (1998): 484-487.

 

 

Question 15 - 2003, Paper 1

Compare  and  contrast  the  advantages  and  disadvantages  of  enteral  feeding  via  a nasogastric tube, a PEG and a percutaneous feeding jejunostomy.

College Answer

Nasogastric tube: simple, commonly used, cheap, can assess and retrieve residual gastric contents (depends on tube size), advantages of gastric feeding (tolerant of bolus and continuous feeds, buffers gastric acids, bactericidal action of acid, gastric pepsin and lipase facilitate absorption of most feeds) BUT aesthetic appearance, potential trauma of insertion, potential misplacement during insertion (especially critically ill), requires radiological confirmation of placement, easily dislodged, sinusitis, increase aspiration risk (less competence gastro-oesophageal sphincter), potential for gastric distension, tolerance of feeding susceptible to gastroparesis (emesis, regurgitation).

PEG:  avoids nose/mouth issues, better tolerated than nasogastric, less likely to be displaced than nasaogastric, can assess and retrieve gastric contents (if large bore and in stomach), advantages of gastric  feeding  (see  above),  avoids  interfering  with  gastro-oesophageal  sphincter  BUT  more complex to insert, less commonly performed, more expensive tube, requires endoscopy (with associated complications), percutaneous wound, often larger bore tube with potential for trauma and displacement, potential for gastric distension, tolerance of feeding susceptible to gastroparesis (emesis, regurgitation).

Percutaneous feeding jejunostomy:  avoids nose/mouth issues, better tolerated than nasogastric, less  likely  to  be  displaced  than  others,  avoids  interfering  with  gastro-oesophageal sphincter, bypasses stomach and allows earlier feeding (avoids gastric distension and problems of gastroparesis), theoretically better for pancreatitis (less pancreatic exocrine secretion) BUT more complex  to  insert,  less  commonly performed, more  expensive tube,  requires  endoscopy &/or surgery (with associated complications), percutaneous wound, small bore tube with potential for displacement and blockage (eg. with enteral drugs), less tolerant of bolus or high volume infusions.

Discussion

This question is identical to Question 20 from the first paper of 2008.

References

Question 3 - 2003, Paper 2

Critically  evaluate  the  role  of “immunonutrition” in  the  management  of the  critically  ill patient.

College Answer

Critically evaluate implies evaluation (including risk/benefit assessment) is required rather than just providing a list of constituents. Immunonutrition usually refers to enteral feeding formulae that have been enriched with a variety of pharmaconutrients.  These include arginine, glutamine, omega-3 fatty acids, nucleotides, or a combination (eg. in commercial products such as Alitraq and Impact). Multiple randomised studies involving thousands of patients, and more recently meta-analyses have been performed.   Studies have been heterogeneous with regard to patient groups and nutritional limbs, and results have been variable with regard to specific outcomes (eg. infectious complications and mortality).   Some consistent benefits appear to be observed (eg. decreased infectious complications, or length of hospital stay) but are contradicted in other studies.  Given the increased cost, the lack of consistent benefit, and the potential for harm, the overall role in the critically ill is still to be established. Recent literature includes:
·           Montejo JC et al. Immunonutrition in the intensive care unit. A systematic review and consensus statement. Clin Nutr. 2003 Jun;22(3):221-33.
·           Bertolini G et al. Early enteral immunonutrition in patients with severe sepsis: results of an interim   analysis   of   a   randomized   multicentre   clinical   trial.   Intensive   Care   Med.   2003
May;29(5):834-40.
·           Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA. 2001 Aug 22-
29;286(8):944-53.

Discussion

The wacky topic of immunonutrition is discussed in greater detail elsewhere.

  • Introduction: why this technique is important/controversial
    • Immunonutrition is the use of pharmacologically active nutritional supplements to modify the stress response to critical illness, the immune response, and the inflammatory response.
  • Rationale: why this technique is proposed, the physiological basis for it
    • The theoretical benefits of immunonutrition include improved wound healing, improved resistance to infection, improved recovery from critical illness, diminished inflammatory and stress responses, decreased organ damage due to oxidative stress and decreased length of ICU stay.
    • Immunonutrition has been proposed both for the critical care population as a whole, and for select groups of ICU patients, such as burns patients, high risk surgical patients, patients recovering from gastrointestinal surgery and patients with acute lung injury.
  • Evidence: what the recent trials say
  • Advantages and disadvantages
    • Advantages of immunonutrition are thus far unproven, but there is community consensus that some immunonutrients (eg. glutamine) may have a beneficial effect.
    • Disadvantages of immunonutrients include cost and potential for harm (eg. with dangerous oversupplementation). Some immunonutrients may have a detrimental effect in certain patient populations (eg. glutamine supplementation appears to increase mortality among patients with multi-organ system failure)
  • In summary, the practice of immunonutrition remains controversial for lack of strng supportive evidence, and the routine use of immunonutrition cannot be supported. However, there may be a trend towards decreased mortality in carefully selected patients.

References

The three papers cited by the college answer are somewhat dated:

 

Montejo, Juan C., et al. "Immunonutrition in the intensive care unit. A systematic review and consensus statement." Clinical Nutrition 22.3 (2003): 221-233.

 

Bertolini, Guido, et al. "Early enteral immunonutrition in patients with severe sepsis." Intensive care medicine 29.5 (2003): 834-840.

 

Heyland, Daren K., et al. "Should immunonutrition become routine in critically ill patients?: A systematic review of the evidence." Jama 286.8 (2001): 944-953.

 

There is more recent data:

 

Marik, Paul E., and Gary P. Zaloga. "Immunonutrition in High-Risk surgical patients a systematic review and analysis of the literature." Journal of Parenteral and Enteral Nutrition 34.4 (2010): 378-386.

 

Hübner, Ma, et al. "Preoperative immunonutrition in patients at nutritional risk: results of a double-blinded randomized clinical trial." European journal of clinical nutrition 66.7 (2012): 850-855.

 

Cerantola, Y., et al. "Immunonutrition in gastrointestinal surgery." British Journal of Surgery 98.1 (2011): 37-48.

 

Marik, Paul E., and Gary P. Zaloga. "Immunonutrition in critically ill patients: a systematic review and analysis of the literature." Intensive care medicine 34.11 (2008): 1980-1990.

 

Heyland, Daren, et al. "A randomized trial of glutamine and antioxidants in critically ill patients.New England Journal of Medicine 368.16 (2013): 1489-1497.

Question 8 - 2004, Paper 2

Outline the causes, consequences and management of adrenal insufficiency in the critically ill.

College Answer

Causes of adrenal insufficiency in the critically ill can be categorised as primary (ie. diseases of the adrenal gland), secondary (interference with pituitary secretion of ACTH) and tertiary (interference with hypothalamic excretion of CRF).

Primary causes include autoimmune (may have vitiligo), haemorrhage (eg. with sepsis and/or anticoagulant therapy), emboli, sepsis and adrenal vein thrombosis.

Secondary causes include destruction of pituitary by tumour/cellular inflammation, infection, head trauma, and infarction.

Tertiary causes include abrupt cessation of high-dose corticosteroids, and any process that interferes with the hypothalamus (tumours, infiltration, irradiation). The stress of critical illness can unmask adrenal insufficiency in patients at risk


Consequences include shock (which may be refractory), abdominal tenderness, myalgias & arthralgias, nausea and vomiting, volume depletion, fever, and confusion. Electrolyte disturbances include hyperkalemia, and hyponatremia and hypoglycemia.

Management needs to commence before diagnosis is confirmed. Administration of corticosteroids (eg. hydrocortisone 100 mg or dexamethasone [4mg]; dexamethasone interferes least with cortisol assays associated with low or high dose short synacthen tests), fluid resuscitation (reversal of hypovolaemia and electrolyte abnormalities), and treatment for underlying causative and/or co-existing diseases (including sepsis) The diagnosis and treatment of stress induced impairment of the hypothalamic-pituitary–adrenal axis (functional adrenal insufficiency) remains controversial.

Discussion

Adrenal insufficiency in critical illness is discussed elsewhere.

For the purposes of answering this question, I produce the following tables from the above-linked chapter:

Causes of Adrenal Insufficiency

Vascular aetiologies

Infarction due to arterial embolism

Infarction due to AAA

Postpartum pituitary necrosis

Infection

Sepsis

Tuberculosis

Histoplasmosis

Cytomegalovirus

Coccidiomycosis

Menigococcal sepsis, purpura fulminans

HIV

Neoplastic invasion

Renal cell carcinoma

Adrenal carcinoma

Breast carcinoma

Lung (NSCLC)

Malignant melanoma

Pituitary tumour

Drugs

Corticosteroid withdrawal

Etomidate (causes primary adrenal insufficiency)
Azole antifungals - Fluconazole, ketoconazole
Rifampicin (increases steroid metabolism)
Phenytoin (increases steroid metabolism)

Infiltrative systemic disease

Amyloid
Sarcoidosis
Haemochromatosis

 

Congential causes

Adrenal dysgenesis
Adrenoleucodystrophy
Impaired steroidogenesis

Autoimmune destruction

Addisons's disease

Traumatic destruction

Trauma is a major cause of adrenal insufficiency

Environmental factors

Hypothermia

Clinical Features of Adrenal Insufficiency

Specific features

Hypotension refractory to fluids

Eosinophilia

Hypoglycaemia

Hyponatremia

Hyperkalemia

Hyperpigmentation

Non-specific features

Decreased level of consciousness

Defects of other hormone systems (eg thyroid)

Normocytic anaemia

Hyperdynamic circulation

Metabolic acidosis

Diarhroea

Nausea

Vomiting

Management would have to be approached according tot he well-practiced answer algorithm:

  • Attention to the ABCs;
    • Airway assessment and control (in context of a decreased level of consciousness)
    • Ventilation support (in context of metabolic acidosis)
    • Circulatory support with vasopressors (in context of fluid-refractory shock)
  • Routine investigations, partiuclarly EUCs CMPs and BSL (looking for hypoglycaemia hyponatremia and hyperkalemia)
  • Specific investigations, such as a random cortisol level, and a short synacthen test
  • Specific management, featuring corticosteroid supplementation with hydrocortisone

References

Oh's Intensive Care manual: Chapter   61   (pp. 660) Adrenocortical  insufficiency  in  critical  illness by Balasubramanian  Venkatesh  and  Jeremy  Cohen

 

Oelkers, Wolfgang. "Adrenal insufficiency." New England Journal of Medicine335.16 (1996): 1206-1212.

 

Marik, Paul E. "Mechanisms and clinical consequences of critical illness associated adrenal insufficiency." Current opinion in critical care 13.4 (2007): 363-369.

 

Cooper, Mark Stuart, and Paul Michael Stewart. "Adrenal insufficiency in critical illness." Journal of intensive care medicine 22.6 (2007): 348-362.

 

Question 19 - 2005, Paper 1

When a patient is fed parenterally after a period of starvation certain metabolic problems can  occur.  Please  list these problems, and  outline  your principles  of management  for each.

College Answer

The refeeding syndrome is associated with a number of metabolic problems, which in general can be diminished by the gradual introduction of nutrients (eg. limit to 20 kcals/kg for first day), anticipation and pre-emptive replacement, and the careful monitoring of the patient.  These changes are more likely to occur in the severely malnoursished or those who have had a rapid weight loss. They can occur with both enteral and parenteral feeding.

Associated problems include:

•    Hypophosphatemia (which may be severe and associated with impaired myocardial function, weakness, rhabdomyolysis and even seizures), which is treated by replacement, but may be prevented to some degree by additional pre-emptive phosphate replacement

•    Hypokalaemia and hypomagnesemia (which can lead to weakness, and arrhythmias)

require monitoring and replacement

•    Thiamine deficiency (which may result in Wernicke’s encephalopathy) requiring thiamine replacement in anticipation or treatment

•    Fluid overload and cardiac failure (multifactorial), avoiding with careful monitoring and replacement

Discussion

Refeeding syndrome is discussed in greater detail elsewhere.

Examples of previous SAQs on this topic include the following:

  • Question 26.1 from the first paper of 2013 (characteristic features: name four)
  • Question 19 from the second paper of 2009 ( four characteristic features and five complications)
  • Question 28 from the second paper of 2007 (clinical and biochmical features of refeeding syndrome)
  • Question 19 from the first paper of 2005 (biochemical abnormalities and their management)

In the interest of click economy, I will include the table of refeeding syndrome complications here.

Organ System Complications of Refeeding Syndrome

Cardiovascular:

  • Heart failure (overload) due to atrophy
  • Hypotension and shock
  • Cardiac arrhythmia

Gastrointestinal

  • LFT derangement due to acute fatty liver
  • Diarrhoea due to intestinal atrophy
  • Delayed gastric emptying
  • Arrhythmias

Renal

  • Acute tubular necrosis

 

Respiratory

  • Respiratory muscle weakness
  • Prolonged ventilator weaning

Musculoskeletal

  • Muscle weakness
  • Tetany
  • Rhabdomyolysis due to low phosphate

Neurological

  • Seizures
  • Coma
  • Delirium

Immunological

  • Phagocyte dysfunction
  • Increased susceptibility to sepsis

References

Hearing, Stephen D. "Refeeding syndrome." BMJ 328.7445 (2004): 908-909.

 

Stanga, Z., et al. "Nutrition in clinical practice—the refeeding syndrome: illustrative cases and guidelines for prevention and treatment." European journal of clinical nutrition 62.6 (2008): 687-694.

 

Kraft, Michael D., Imad F. Btaiche, and Gordon S. Sacks. "Review of the refeeding syndrome." Nutrition in Clinical Practice 20.6 (2005): 625-633.

 

Khan, Laeeq UR, et al. "Refeeding syndrome: a literature review."Gastroenterology research and practice 2011 (2010).

 

Question 23 - 2005, Paper 1

Critically evaluate the role of glucose control in the critically ill.

College Answer

Routine ICU management includes the control of glucose to avoid the potential complications of hypoglycemia (arrhythmias, cardiac events, neurological deficits) and hyperglycemia (especially infections, eg.   documented using restrospective controls). Traditional goals have varied, but have in general been fairly broad (eg. glucose < 10-15 mmol/L).  Prospective randomised trails to guide therapy have been lacking until the last decade.

The potential role for tight glucose control in critically ill patients has been suggested in two main patient groups: acute myocardial infarction in diabetics, and the surgical ICU.

The DIGAMI study demonstrated that an insulin-glucose infusion followed by a multidose insulin regimen improved one year mortality in diabetic patients with acute myocardial infarction (Malmberg JACC 1995).

Much more interest, and significant debate, was generated by the study by Van den Berghe (NEJM 2001).   It demonstrated in a surgical intensive care population (enrolling 1548 patients) that tight glucose control using intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment (10 – 11.1 mmol/L) to 4.6 percent(4.5 - 6.5mmol/L)  (NNT = 29; P<0.04, with adjustment for sequential analyses) and “also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltration by 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care”.  This was apparently due to glucose control and not insulin dose, but the study could not properly blind the treating physicians, and there are problems in extrapolating this to the general Intensive care population, and further studies are underway.

Discussion

This question closely resembles Question 24 from the second paper of 2006. Essentially, it asks one to discuss the various studies which had (recently for 2006) been published to guide the management of sugars in the ICU. During this dark age, there was the belief that strict control over BSL had some sort of positive influence on the survival of ICU patients. The current strategies for BSL control in critical illness are discussed elsewhere.

References

Question 7 - 2006, Paper 1

A 65 year old obese lady with known alcoholic cirrhosis and long term thyroxine supplementation  was admitted to ICU with staphylococcal spinal  osteomyelitis 6 weeks ago.  Following discharge to the ward, she developed progressive abdominal distension, hypotension and  oliguria.   On examination  she was confused, with a flapping tremor. Her pulse rate was 42/min, in sinus rhythm and her blood pressure was 80/40 mm Hg. Her temperature  was 34.7˚C.   Bowel sounds were absent.   There was no abdominal tenderness

Investigations subsequent to her admission were as follows: Blood tests:

Normal

values

Hb

110

G/L

110 - 150

WCC

8.4

109/L

5 - 11

Platelets

173

109/L

150 - 300

Na

131

mmol/L

135 - 145

K

3.6

mmol/L

3.5 - 5.0

Urea

26

mmol/L

4 - 6

Creatinine

167

micromol/L

60 - 120

Glucose

2.2

mmol/L

4 - 6

Cholesterol

8.6

mmol/L

4 - 6

AST

40

U/L

35 - 45

ALT

51

U/L

35 - 45

Ammonia

41

micromol/L

50 - 80

Calcium

2.25

mmol/L

2.2 - 2.6

CT brain scan:        Normal

Echo:                     Moderate pericardial effusion

(a)        In light of this information, what is the most likely diagnosis? Justify your response.

(b)       List 2 precipitating factors.

College Answer

a) The most likely diagnosis is Myxoedema coma /severe hypothyroid coma. The normal CT brain excludes a significant organic brain pathology, and normal ammonia + normal hepatic enzymes make hepatic encephalopathy less likely. The clinical picture in concert with the features of a low Na, low glucose, high cholesterol, a pericardial effusion and the history of thyroxine supplementation is highly suggestive of hypothyroidism. Marks were also allocated if a reasonable alternative diagnosis was given, provided that this was accompanied by a rational justification.

b) Many precipitating factors could be present, but consider: sepsis, drugs (eg. betablockers, amiodarone), stroke, and a patient non-compliant with therapy.

Sixteen out of twenty-six candidates passed this question.

Discussion

The history is characteristic of myxoedema coma, which is discussed in greater detail elsewhere

In addition to the background of hypothyroidism, the patient has the trifecta of features:

  • cardiovascular collapse
  • hypothermia
  • decreased level of consciousness

The associated features of pericardial effusion and hyponatremia complete the classical picture.

The college have not given you the puffy face and non-pitting oedema, but they are hardly necessary.

Also, the history of cirrhosis is given, and the patient does have a "flap", but it is probably not a flap of hepatic encephalopathy, but of hypercapnea, which is associated with myxoedema coma. The ammonium level is 41, which (though not related to the severity of encephalopathy) is not sufficiently abnormal to cause concern.

As for the precipitating factors... Surely, the osteomyelitis itself might cause the myxoedematous decompensation, but the clever college examiners have probably thrown this in because they know that osteomyelitis of this sort tends to be treated with rifampicin, and rifampicin tends to increase the rate of hepatic clearance of thyroxine.

References

Summers, V. K. "Myxoedema coma." British medical journal 2.4832 (1953): 366.

 

Wartofsky, Leonard. "Myxedema coma." Endocrinology and metabolism clinics of North America 35.4 (2006): 687-698.

 

Mathew, Vivek, et al. "Myxedema coma: a new look into an old crisis." Journal of thyroid research 2011 (2011).

 

Lezama, Maybelline V., Nnenna E. Oluigbo, and Jason R. Ouellette. "Myxedema Coma and Thyroid Storm: Diagnosis and Management." Internal Medicine 14.Part 2 (2011): 1.

 

Chu, Michael, and Terry F. Seltzer. "Myxedema coma induced by ingestion of raw bok choy." New England Journal of Medicine 362.20 (2010): 1945-1946.

 

Wall, Cristen Rhodes. "Myxedema coma: diagnosis and treatment." American family physician 62.11 (2000).

 

Bondugulapati, Laxmi, Mohamed Adlan, and Lakdasa Premawardhana. "Thyroid Emergencies." Sri Lanka Journal of Critical Care 2.1 (2011): 1-12.

 

Question 24 - 2006, Paper 1

List the causes of hyperglycaemia in the intensive care patient  population, and outline your management of hyperglycaemia.

College Answer

A list of potential  causes should include: diabetes mellitus (previously known or not known, type I
or II, on diet, oral agents, insulin or combination), secondary causes of diabetes (e.g. pancreatitis, haemochromatosis, Cushing’s syndrome, acromegaly), insulin resistance (e.g. sepsis, systemic inflammatory response/stress response [including multiple trauma], beta-agonists [endogenous or exogenous], exogenous corticosteroids), carbohydrate load (e.g. feeding enteral/parenteral, peritoneal dialysis).

The outline  of management should include: control of factors worsening response to insulin (sepsis, drugs, stress response), control glucose within acceptable range (minimise metabolic and immune effects), recommence oral agents or use insulin (dependent on severity).   Principles of glucose control in diabetics include always administering some insulin, administer some glucose, measure glucose frequently, expect sudden  changes, and  avoid hypoglycaemia. Tight  glucose control is still controversial in the critically ill patients. Recent studies suggest tight glucose control using insulin infusions if necessary may dramatically reduce mortality after myocardial infarction (in diabetic patients: DIGAMI. BMJ. 1997 May 24;314(7093):1512-5), and in the surgical intensive care (N Engl J Med 2001;345:1359-67) but a more recent study by same group in medical ICU patients provides less striking results (N Engl J Med 2006;354:449-61), and the risk of hypoglycemia appears significant (Am J Respir Crit Care Med 2006;173:367-9).

Discussion

The below-linked table of causes can be found in the chapter on stress-induced hyperglycaemia

Causes of Hyperglycaemia in the ICU

Insulin resistance

  • NIDDM
  • Stress response
  • Corticosteroid therapy
  • Cushings disease

Inadequate insulin levels

  • Under-supplemented
  • Stress response
  • Pancreatitis
  • Haemochromatosis
  • Insulin antibodies

Excessive endogenous glucose release

  • Catecholamine infusion
  • Stress response
  • Glucagon administration

Excessive exogenous glucose supplements

  • TPN with 50% dextrose
  • Inappropriately sugary IV fluids
  • Overfeeding with enteric nutrition
  • Glucose-containing peritoneal dialysis fluid

As for the glucose control strategy: this is better discussed in the chapter on glucose control among the critically ill, but here is the basic breakdown of the current strategies, and the trials that spawned them. The college answer given here is written prior to 2009, and therefore shares the delusional attachment to tight glycaemic control which characterises the tumultuous first decade for the 21st century.

These days, with the benefit of the 2009 NICE-SUGAR trial and its 2012 post-hoc analysis, we know that keeping BSL under 10mmol/L is the ideal strategy, as it protects the patients from the evils of hyperglycaemia, while preventing the increase in mortality which is associated with unbearably tight glycaemic controls.

In summary,

  • Keep the BSL between 5 and 8mmol/L, and definitely keep it under 10mmol/L

References

Finfer, Simon, et al. "Hypoglycemia and risk of death in critically ill patients."The New England journal of medicine 367.12 (2012): 1108-1118.

 

Finfer, Simon, et al. "Intensive versus conventional glucose control in critically ill patients." N Engl J Med 360.13 (2009): 1283-1297.

 

Griesdale, Donald EG, et al. "Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data."Canadian Medical Association Journal 180.8 (2009): 821-827.

 

 

Question 28 - 2006, Paper 2

Outline how you would initiate a regime for Total Parenteral Nutrition in a critically ill septic malnourished 60kg man.

College Answer

Central venous access;

Mixture of Protein, Fat and Carbohydrate, low amounts and slowly building up as tolerated;

electrolytes supplementation (especially at the start to prevent refeeding syndrome);

supplemental vitamins, trace elements;

monitoring of clinical state, electrolytes, LFTs, BSL,

Discussion

Commencement of TPN, and the calculations of daily intake requrements relevant to this topic are discussed elsewhere. The specific chapters of greatest interest are:

This question closely resembles Question 7 from the first paper of 2015, where TPN prescription was re-explored. Like Question 7 , this question was not about the need or indication for TPN, nor was it asking the candidates to debate the relative merits of parenteral and enteral routes of nutrition. The decision was made for the candidates: TPN is required.

In short, the approach should resemble the following:

  • Assess daily metabolic requirements
    • Use predictive equations to make educated estimates
    • Measure energy expenditure with indirect calorimetry or reverse Fick equation
    • Apply coefficients to the findings to establish daily energy requirments in the context of a specific disease state, weg. whether one would need to contribute extra protein for a hypercatatbolic trauma patient, or extra lipid for a hypecapneic patient with COPD.
  • Establish the indications for TPN, and confirm that commencement of TPN is the ideal step to take (given that in many circumstances, it is actually better to wait for 7-10 days without nutrition)
  • Establish central access
  • Supply macronutrients by infusing a mixture of fat protein and carbohydrate, according to the proportions established by abovementioned methods.
    • Carbohydrate: fat ratio: 70:30.
    • Protein is also required: 1.5-2g/kg/day
      • Fat is supplied as 10% lipid emulsion, at  1.1 kcal/ml
      • Carbohydrate is supplied as 50% dextrose, at 1.7 kcal/ml
      • Protein is supplied as 10% amino acid solution, as 100g/L
  • Ensure regular contibution of trace elements, vitamins and micronutrients
  • Ensure regular monitoring of the following parameters:
    • BSL: to prevent hyperglycaemia
    • EUCs to watch for uraemia and hypokalemia
    • CMPs to watch for the hypophosphataemia of refeedig syndrome
    • LFTs to observe for steatohepatitis and acalculous cholecystitis
  • Ensure good thromboprophylaxis in view of prothrombotic effects of lipid emulsion
  • Ensure regular monitoring of the central venous access site, in view of the increased risk of CVC-associated infection associated with TPN.

References

Culebras, Jesus M., et al. "Practical aspects of peripheral parenteral nutrition."Current Opinion in Clinical Nutrition & Metabolic Care 7.3 (2004): 303-307.

 

Singer, Pierre, et al. "ESPEN guidelines on parenteral nutrition: intensive care."Clinical Nutrition 28.4 (2009): 387-400.

 

Question 28 - 2007, Paper 2

With regards to nutrition in the critically ill patient

a) list the methods available to estimate energy expenditure in the critically ill patient

b) list the metabolic and clinical problems associated with overfeeding

c) list the clinical and biochemical features of the  refeeding syndrome ?

College Answer

a) list the methods available to estimate energy expenditure in the critically ill patient

Indirect calorimetry
Fick principle ( in patients with a PAFC)

Predictive equations

b) list the metabolic and clinical problems associated with overfeeding

Hepatic steatosis

Hyperglycemia

Hyperlipidemia

Hypercarbia
Hyperosmolarity and hypertonic dehydration (in patients fed excess nitrogen who have impaired urine concentrating ability)
Azotemia (due to excess nitrogen intake)

c) list the clinical and biochemical features of the  refeeding syndrome ?

-seen when normal intake is resumed after a period of initial starvation
- Low PO4, Mg and K and thiamine deficiency
- Can presents with weakness, arrythmias and cardio-respiratory failure

Discussion

The article linked below compares all three methods mentioned in the college answer. Specifically, for each mentioned topic the following rambling digressions are available:

In brief:

A Comparison of Methods
to Estimate Metabolic Energy Requirements
in Critical Illness
Method Physiology Advantages Limitations
Predictive  Equations
  • Calculation of metabolic requirements made on the basis of empirical experimental data
  • Typically, input information is gender, height, age and weight
  • Specific metabolic abnormalities (eg. burns or sepsis) can be factored in as multipliers
  • Range from complex equations to simple (25cal×kg per day) formulae
  • Cheap
  • Quick
  • Requires no expertise
  • Accurate for many circumstances, particularly straightfrward ICU patients
  • Predict requirements, i.e. useful goals of management
  • Tend to be inaccurate
  • The sicker the patient, the less accurate the predictions
Reverse Fick method
  • Determines oxygen consumption from pulmonary artery catheter:
  • Oxygen utilisation in metabolic processes is correlated to the metabolic rate.
  • Knowing the cardiac output, one can calculate the oxygen consumption of the organism from the arteriovenous oxygen content difference.
  • Accurate - more so than predictive equations
  • Reproduceable
  • Cheaper than the metabolic cart, and more widely available
  • Invasive
  • Does not incorprate the metabolic requirements of the lungs
  • Inaccurate in severe pulmonary pathology, eg. ARDS
Indirect calorimetry
  • Oxygen uptake and CO2 production are monitored by a specialized module attached to the ventilator
  • From the consumption of oxygen, one can estimate the metabolic rate (assuming all oxygen is used to oxidise substrate)
  • The most accurate method of determining energy use
  • Module can integrate with the ventilator

Indications may include:

  • Extremes of obesity
  • Extremes of core body temperature (eg. in hypothermia)
  • Extremes of age
  • Very expensive
  • It makes the assumpation that all oxygen use is for oxidation of substrate
  • It is a complex procedure and it requires special equipment
  • It is a measure of metabolic fuel consumption, not demand.
  • It is not associated with any clinical benefit.
  • Inaccurate at high PEEP
  • Inaccurate with high FiO2
  • Invalid in the presence of circuit leak
  • Difficult to interpret if the ventilator settings keep changing rapidly

The complications of overfeeding the critically ill patient are discussed elsewhere.

In brief, they are as follows:

  • Hyperglycaemia
    • Thus, risk of hyperosmolar non-ketotic hyperglycaemia
  • Uraemia
    • Thus, risk of urea-induced hypertonic dehydration
  • Hyperlipidaemia
  • Fatty liver disease
  • Hypercapnea

Refeeding syndrome is also discussed elsewhere, but - in brief point form - its features are as follows:

  • Hypokalemia
  • Hypophosphatemia
  • Hyponatremia
  • Hypomagnesemia
  • Onset following the reintroduction of food after a prolonged starvation
  • Clinical features are most closely related to the magnitude of the electrolyte derangement

References

Flancbaum, Louis, et al. "Comparison of indirect calorimetry, the Fick method, and prediction equations in estimating the energy requirements of critically ill patients." The American journal of clinical nutrition 69.3 (1999): 461-466.

 

Klein, Catherine J., Gena S. Stanek, and CHARLES E. WILES III. "Overfeeding macronutrients to critically ill adults: metabolic complications." Journal of the American Dietetic Association 98.7 (1998): 795-806.

 

Hearing, Stephen D. "Refeeding syndrome." BMJ 328.7445 (2004): 908-909.

 

Stanga, Z., et al. "Nutrition in clinical practice—the refeeding syndrome: illustrative cases and guidelines for prevention and treatment." European journal of clinical nutrition 62.6 (2008): 687-694.

 

Kraft, Michael D., Imad F. Btaiche, and Gordon S. Sacks. "Review of the refeeding syndrome." Nutrition in Clinical Practice 20.6 (2005): 625-633.

 

Khan, Laeeq UR, et al. "Refeeding syndrome: a literature review."Gastroenterology research and practice 2011 (2010).

Question 9.2 - 2008, Paper 1

A 52 year old woman was admitted  the previous night with an altered level of consciousness which improved rapidly with administration of glucose. She is referred to ICU the next day with confusion, ataxia and a worsening level of consciousness. Her CT head was normal.

The blood sugar level in the morning is 8 mmol/l on a 5% Dextrose infusion at 80 ml/hr. Her full blood count from the previous night is available.

Test

Value

Normal Range

Hb

88

130-180 g/l

WCC

7.4 x 109 /l

4.5 – 11 x 109/l

Platelets

88 x 109 /l

150 – 400 x 109/l

MCV

110 fl

80 – 98 fl

MCH

30 pg

27 – 33 pg

MCHC

320 g/l

310 – 360 g/l

PT

12 sec

(12-18)

APTT

36

32-38

1.  What is the likely cause of her confusional state?

2.  What specific treatment would you institute for resolution of her mental status?

College Answer

1.  What is the likely cause of her confusional state?
Wernickes encephalopathy

2.  What specific treatment would you institute for resolution of her mental status?
Thiamine 100 mg IV

Discussion

This question closely resembles Question 13.3 from the second paper of 2013.

References

Question 15.1 - 2008, Paper 1

You are asked to review an 80 year old woman in the emergency department who has presented with a depressed conscious state. She has ischaemic heart disease and paroxysmal atrial fibrillation. Her medication  includes aspirin, metoprolol, and amiodarone. On examination  she has a temperature of 34.50 C she is drowsy with a GCS of 10, with a pulse of 50 bpm and a BP 90/40mmHg. CT brain scan shows age related atrophy.The blood results are shown.

Sodium

120

mmol/L

(137 -145)

Potassium

4

mmol/L

(3.5 – 5.0)

Urea

6

mmol/L

(2.5 – 7.5)

Creatinine

90

micromol/L

(50 - 100)

Measured Osmolality

255

mmol/kg

(280 - 300)

Glucose

3

mmol/L

3.5 – 6.0

CK

1000

U/L

(20 - 200)

Cholesterol

7.2

mmol/L

(3.0-5.5)

a. What is the likely diagnosis and cause to account for all these blood results?

b. List 4 measures essential for the specific management of this patient.

College Answer

a. What is the likely diagnosis and cause to account for all these blood results?
•    Hypothyroidism
•    Amiodarone

b. List 4 measures essential for the specific management of this patient.

•    Commence thyroxine, probably low dose (50-100ug/day and slowly increase) or administer T3 orally or intravenously
•    Commence on glucocorticoids (Hydrocortisone 50mg 6 hourly)
•    Correct the hypoglycaemia with intravenous glucose
•    Correct  the  hyponatraemia  very  slowly  with  hypertonic  saline  to  a  sodium 130mmol/L (no more than 2 mmol/L per hour)

Discussion

This is no mere hypothyroidism, college - its myxoedema coma. The condition is characterised by shock, hypothermia and obtundation; and its triggered by amiodarone therapy, among other things.The chapter on myxoedema coma treats these complications with a deserving degree of detail.

Management of this condition consists of the following steps:

  • Replace thyroid hormone - preferably IV
    • loading dose is 300-400μcg
    • a rising body temperature and normalising cardiovascular parameters alert you to the success of your management strategy
  • Replace corticosteroids - there is usually a concomitant adrenal insufficiency. One would use a "stress dose".
  • Good solid supportive management:
    • Establish an airway if this is needed
    • Maintain normoxia and normocapnea with the ventilator
    • Maintain normotension to support organ system perfusion, with a catecholamine infusion
    • Correct the Na+ deficit slowly- I am not sure why the college have specified such a vigorous replacement rate; most people would replace at a rate of rise of no more than 0.5mmol/L/hr, and one might even consider using water restriction alone.
    • Correct hypoglycaemia
    • Correct hypothermia with warming blanket

References

Summers, V. K. "Myxoedema coma." British medical journal 2.4832 (1953): 366.

Mathew, Vivek, et al. "Myxedema coma: a new look into an old crisis." Journal of thyroid research 2011 (2011).

Question 15.2 - 2008, Paper 1

A 50 year old lady is admitted to the coronary care unit for investigation of resistant hypertension and chest pain. A cardiac arrest call is put out because she drops her blood pressure to 60/30mmHg, upon your arrival she is pale, diaphoretic, tremulous with a pulse of 130 bpm and a BP 300/120mmHg. No medications have been administered to account for the hypertension. A similar episode had occurred the previous day.

a. What diagnosis is likely?

b. List 5 treatment measures for the management of the haemodynamic instability associated with this condition.

College Answer

a. What diagnosis is likely?
•    Phaeochromocytoma

b. List 5 treatment measures for the management of the haemodynamic instability associated with this condition.
•    Admit to the intensive care unit for invasive monitoring
•    SNP/GTN for HT crisis
•    Alpha Blockade followed by beta blockade,
•    Intravenous magnesium has been shown to have an effective role in this situation
•    Hypotension with fluids / Adrenaline/noradrenaline

Discussion

This question on phaeochromocytoma closely resembles Question 22 from the second paper of 2010. The details of management are discussed there, as well as in the brief summary on phaeochromocytoma in the section on endocrine disorders in the ICU.

References

Question 15.3 - 2008, Paper 1

You are asked to see a 24 year old man in the emergency department for hypotension (80/40 mmHg) and hypoglycaemia (2.2mmol/L) with associated drowsiness.  He has a long-standing history of insulin dependant diabetes mellitus (IDDM) which has been well controlled until recently, when he was admitted for a short stay in hospital with diabetic keto acidosis (DKA).

a. List 4 likely causes of hypoglycaemia in this patient.

College Answer

a. List 4 likely causes of hypoglycaemia in this patient.
•    Accidental or non accidental overdose of long acting insulin
•    Sepsis
•    Glucocorticoid deficiency
•    Hypothyroidism
•    Insulin secreting tumour
•    Less likely: severe liver disease

Discussion

The causes of hypoglycaemia are protean. Here are just a few:

Causes of Hypoglycaemia

Drugs

  • Insulin (duh)
  • Glucagon
  • Indomethacin
  • Lithium
  • ACE-inhibitors
  • β-blockers
  • Alcohol
  • Sulfonylurea drugs
  • Perhexiline
  • THAM

Illness

  • Starvation
  • Hepatic failure
  • Cardiac failure
  • Renal failure
  • Sepsis
  • Adrenal insufficiency
  • Insulinoma
  • Antibodies to insulin receptor
  • Hypothyroidism
  • Massive burden of bulky maligancy
  • Islet cell hyperplasia

Pragmatically speaking, it is very rarely anything quite as exciting as an insulinoma.

Pragmatically speaking, it is very rarely anything quite as exciting as an insulinoma. A study of patients admitted with hypoglycaemia has identified several common causes, listed below and ordered from most to least common:

  • Inadequate intake of carbohydrate (28%)
  • Ingestion of alcohol (19%)
  • Deliberate overdose of insulin (13%)
  • Accidental overdose of insulin (6%)
  • Strenuous exercise (7%)

References

UpToDate has a nice article on this for the paying customer.

Cryer, Philip E., Stephen N. Davis, and Harry Shamoon. "Hypoglycemia in diabetes." Diabetes care 26.6 (2003): 1902-1912.

Hart, S. P., and B. M. Frier. "Causes, management and morbidity of acute hypoglycaemia in adults requiring hospital admission." Qjm 91.7 (1998): 505-510.

Question 20 - 2008, Paper 1

Compare and contrast the advantages  and disadvantages of enteral feeding via a nasogastric tube, a PEG and a percutaneous feeding jejunostomy.

College Answer

 

Nasogastric tube: simple, commonly used, cheap, can assess and retrieve residual gastric contents (depends on tube size), advantages of gastric feeding (tolerant of bolus and continuous feeds, buffers gastric acids, bactericidal action of acid, gastric pepsin and lipase facilitate absorption of most feeds)

BUT aesthetic appearance, potential trauma of insertion, potential misplacement during insertion (especially critically ill), requires radiological confirmation of placement, easily dislodged, sinusitis, increase aspiration risk (less competence gastro-oesophageal sphincter), potential for gastric distension, tolerance of feeding susceptible to gastroparesis (emesis, regurgitation).

 

PEG: avoids nose/mouth issues, better tolerated than nasogastric, less likely to be displaced than nasaogastric, can assess and retrieve gastric contents (if large bore and in stomach), advantages of gastric feeding (see above), avoids interfering with gastro- oesophageal sphincter

BUT more complex to insert, less commonly performed, moreexpensive  tube,  requires  endoscopy  (with  associated  complications),  percutaneous wound, often larger bore tube with potential for trauma and displacement, potential for gastric  distension,  tolerance  of  feeding  susceptible  to  gastroparesis  (emesis, regurgitation).

 

Percutaneous feeding jejunostomy:  avoids nose/mouth issues, better tolerated than nasogastric, less likely to be displaced than others, avoids interfering with gastro- oesophageal sphincter, bypasses stomach and allows earlier feeding (avoids gastric distension and problems of gastroparesis), theoretically better for pancreatitis (less pancreatic exocrine secretion)

BUT more complex to insert, less commonly performed, more expensive tube, requires endoscopy &/or surgery (with associated complications), percutaneous wound, small bore tube with potential for displacement and blockage (eg. with enteral drugs), less tolerant of bolus or high volume infusions.

 

Discussion

Elsewhere, there is a brief summary of the routes of enteral nutrition, and it contains this table, which is essentially a tabulated form of the stream-of-consciousness answer offered by the college.

 

~Enteral Feeding Routes~
A Comparison of the Nasogastric Tube, Percutaneous Endogastic Tube and Feeding Jejunostomy
Tube type Advantages Disadvantages
Nasogastric
  • Easy to insert
  • The tubes are cheap
  • Gastric aspiration is possible
  • Gastric food delivery buffers gastric acids and protects the gastric mucosa
  • The gastric acid has a bactericidal action which helps prevent gastroenteritis
  • Gastric secretions (gastric pepsin and lipase) facilitate absorption of feeds, which means one is not limited to any specialised feed mixtures
  • Uncomfortable in the awake patient
  • It is easily dislodged by a delirious patient
  • It may increase aspiration risk because the gastro-oesophageal sphincter is less competent when there is something constantly in it.
Nasojejunal tube
  • Decreased risk of aspiration.
  • Decreased stimulus to pancreatic secretion.
  • Uncomfortable in the awake patient
  • Difficult to place.
  • Not exactly cheap
  • One must wait for the tip to migrate into the jejunum
  • Impossuble to administer large boluses.
  • Gastric mucosa is unprotected from acid, and loses trophic stimulus
  • The feeds do not benefir from the bactericidal eactivity of stomach acid
  • Absorption may be impaired due to the loss of gastric pepsin and lipase; specialised mixtures may be required
PEG tube
  • Improved tolerance in the awake patient
  • None of the facial pressure are complications
  • No sinusitis or mucositis
  • No risk of oesophageal stricture
  • Better tolerance in the extremely long term (one can have a percutaneous tube for their entire life)
  • Nice, large bore tube - less likely to block
  • All the advantages of gastric feeding (eg. tolerance of bolus feeds, sterilising effects of stomach acid and usefulness of gastric digestive enzymes)
  • All the advantages of NG sumps - can aspirate and sample gastric contents
  • Less likely to result in aspiration, as it does not interfere with the gastrooesophageal sphincter.
  • Alows earlier feeding, as poor gastric emptying is not an issue
  • Needs to be surgically placed
  • Requires endoscopy to position
  • Risk of early dislodgement and loss of the imamture fistula tract
  • Tube can block unless it is wide-bore
  • Skin erosion and ulceration may take place.

 

 

Feeding jejunostomy
  • Improved tolerance in the awake patient
  • None of the facial pressure are complications
  • No sinusitis or mucositis
  • No risk of oesophageal stricture
  • Least likely to be dislodged
  • Alows earlier feeding, as poor gastric emptying is not an issue
  • Decreased stimulus to pancreatic secretion.
  • Needs to be surgically placed
  • Requires endoscopy, or more usually laparoscopy, to position
  • It is a small bore tube which is blocked more easily
  • One can neither aspirate it, nor bolus-feed through it

 

 

 

References

M Keymling Technical aspects of enteral nutrition Gut 1994; supplement 1: S77-S80

 

Hayden White1*, Kellie Sosnowski1, Khoa Tran1, Annelli Reeves2 and Mark Jones A randomised controlled comparison of early post-pyloric versus early gastric feeding to meet nutritional targets in ventilated intensive care patients. Critical Care 2009, 13:R187 doi:10.1186/cc8181

 

Eatock FC, Chong P, Menezes N, Murray L, McKay CJ, Carter CR, Imrie CW. A randomized study of early nasogastric versus nasojejunal feeding in severe acute pancreatitis. Am J Gastroenterol. 2005 Feb;100(2):432-9.

 

O. Odocha, R. C. Lowery, Jr, H. M. Mezghebe, S. M. Siram, and O. G. WarnerTracheopleuropulmonary injuries following enteral tube insertion J Natl Med Assoc. 1989 March; 81(3): 275–281. PMCID: PMC2571629 .

Question 18.1 - 2008, Paper 2

An 81 year old woman is admitted to the ICU with a 24 hour history of altered mental  state and confusion. She has a history of type II diabetes  managed with metformin. The following blood results were taken  on admission.

Arterial blood

Value

Reference values

pH

7.30

7.36-7.44

PCO2

31 mmHg (4.0 kPa)

40 mmHg       (5.3-5.7 kPa)

PO2

90 mmHg (12.0 kPa)

80-100 mmHg (10.5-13.0 kPa)

HCO3 -

20

22-33 mmol/L

Na+

140

135 -145 mmol/L

K+

3.9

3.2-4.5 mmol/L

Cl -

105

100-110 mmol/L

Urea

21.8

3.0-8.0 mmol/L

Creatinine

220

50-100 micromol/L

Glucose

40

3.0-7.8 mmol/L

Lactate

4.8

< 2 mmol/L

a. Which clinical condition  is most consistent  with the above data? - Justify your answer from the results provided.

b. List 3 complications of this condition.

College Answer

a. Which clinical condition  is most consistent  with the above data? - Justify your answer from the results provided.

Answer: Non ketotic hyper osmolar state

•    Marked hyperglycaemia (higher than usually observed DKA) plasma glucose may be >55mmol/L.
•    Hyperosmolarity (by definition osmolarity should be >320)
•    Relatively normal pH/HCO3 suggesting non ketotic state. A small anion gap acidosis may be present secondary to lactate.

b. List 3 complications of this condition.

•    Cerebral oedema:
•    Vascular thrombosis:
•    Electrolyte derangements in particular hypokalemia, dysnatraemia.
Hyperchloremia from saline administration.
•    Intercurrent events such as sepsis, aspiration,  myocardial infarction, iatrogenic (
eg vascular access related complication)
•    Hypotension and shock due to intravascular volume depletion or inadequate resuscitation.

Discussion

To analyase this gas, let us turn to the well-rehearsed bedside rules for blood gas compensation.

So, this appears to be a metabolic acidosis.

The respiratory compensation for a HCO3- of 20 should be (1.5 x 20)+8, or 38 mmHg; thus, there is also a mild respiratory alkalosis.

The anion gap is raised (18.9); the delta ratio is 1.7 suggesting that the metabolic alkalosis is almost entirely due to the unmeasured anions.

The lactate is raised (4.8) and this accounts for much of the rise in the anion gap. The rest can be blamed on the non-volatile acids retained in renal failure. There is probably little ketosis, as the pH is essentially normal (whereas in ketoacidosis one would expect a profound acidosis).

In summary, after reading the question again, one might come to the conclusion that this woman has the following combination of problems:

  • Hyperosmolar hyperglycaemic state
  • Metformin-induced lactic acidosis, due to decreased renal clearance of metformin, and probably also due to hypovolemic shock

The college did not give us a serum osmolarity, but we are expected to infer from the BSL that it is high.

Complications of HONK are discussed in greater detail elsewhere.

In brief summary, they are as follows:

  • Cardiac arrest
  • Cardiovascular collapse and shock
  • Myocardial infarction
  • Stroke
  • Cerebral oedema and brain injury
  • Venous thrombosis (particularly hideous is the possibility of dural sinus thrombosis)

References

Hyperglycemic Comas by P. VERNON VAN HEERDEN from Vincent, Jean-Louis, et al. Textbook of Critical Care: Expert Consult Premium. Elsevier Health Sciences, 2011.

Oh's Intensive Care manual: Chapter 58  (pp. 629) Diabetic  emergencies  by Richard  Keays

Umpierrez, Guillermo E., Mary Beth Murphy, and Abbas E. Kitabchi. "Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome." Diabetes Spectrum15.1 (2002): 28-36.

ARIEFF, ALLEN I., and HUGH J. CARROLL. "Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of theraphy in 37 cases." Medicine 51.2 (1972): 73-94.

Question 14.1 - 2009, paper 1

A 24 year old  male is admitted to the ICU following a spontaneous intracranial haemorrhage. He is noted to have labile blood pressure that is difficult to control, and a persistent tachycardia in spite of high dose sedatives. Further investigation reveals raised plasma and urinary catecholamines.  List 4 potential  causes of the above biochemical finding in this patient.

College Answer

  • Causes
    • Phaeochromocytoma
    • Physical stress - critical illness, hypoxia, hypercapnia, hypoglycemia
    • Use of catecholamines, amphetamine use
    • Prior h/o tricyclic use

Discussion

Proudly, I can report that there is an article out there (free full text) which responds to the question, "what non-phaeochromocytoma aetiology could be causing raised plasma catecholamine levels?" Thank you for answering, David S. Goldstein.

Causes of Raised Plasma Catecholamine Levels

Malignancy

  • Phaeochromocytoma (adrenaline)
  • Neuroblastoma (DOPA)
  • Malignant melanoma (DOPA)
  • Menke's disease (dopamine)

Decreased clearance

  • MAO A/B inhibition
  • Altered COMT activity
  • Tricyclic antidepresant use
  • Hepatic insufficiency

 

Autonomic nervous system

  • Normal stress response
  • Asphyxiation
  • Morbid obesity
  • Hypoglycaemia
  • Intracranial haemorrhage (eg. SAH)
  • Acute clonidine withdrawal

Spurious results

  • Anti-parkinsonian medications
  • Amphetamine use
  • Methyldopa

 

References

Goldstein, David S., Graeme Eisenhofer, and Irwin J. Kopin. "Sources and significance of plasma levels of catechols and their metabolites in humans."Journal of Pharmacology and Experimental Therapeutics 305.3 (2003): 800-811.

Question 2 - 2009, Paper 2

You are asked to review a 27 year old girl, a known diabetic, admitted following a 48- hour illness characterised by nausea, vomiting and shortness of breath. She has been unable to eat or drink and has not taken her regular insulin. On examination she has a heart rate 137 /min, respiratory rate 36 breaths /min, O2 saturation is 99% on room air, blood pressure 92/34 mm Hg. She weighs 80kg and her blood sugar level is 32 mmol/l. Outline your plan of management for the first 24 hours.

College Answer

This young lady most probably has diabetic ketoacidosis and is critically unwell. She requires:-

1. Resuscitation:
May need supplemental oxygen
Peripheral iv access
Commence iv fluids (hartmanns, plasmalyte, n/saline or colloid)

500ml to 1 litre stat then reassess BP/HR/RR/
blood test and ABG should be available to adjust fluid therapy
 Maintenance IV fluids with N.Saline, 0.45% saline
 Start 5% dextrose when BSL <15mmol/L

Monitoring:

ECG, pulse oximetry, NIBP
Early Art line and CVC
Bloods for    EUC (Na+, Creat, Urea),Mg++, Phos-, Ca++, FBC, LFTs, BSL 
Urine dipstick
IDC
 
Confirmation of diagnosis: Blood gases, a raised AG metabolic acidosis, ketones in urine/blood

2. Insulin therapy:

Insulin infusion - short acting insulin (actrapid)
Infusion Dose (candidate should provide a dosing regimen and rationale)
- 0.01 to 0.1units/kg/hr (max)
- Daily dose /24 as units per hour

Titrate to decrease in BSL 1-2 mmol/L/hr
Continue until metabolic disturbance is corrected (acidaemia and ketosis) rather than correction of BSL. May need dextrose infusion if BSL drops below normal range

3. Electrolyte replacement:

Potassium:- Start replacement when plasma K+ <5mmol/L as insulin therapy and correction of acidaemia may lead to precipitous fall and arrhythmias
Sodium:- May need to correct Na+ for BSL. Need to take care to avoid large shifts in Na as it may predispose to cerebral oedema
Bicarbonate:- almost no indication for bicarbonate therapy. Phosphate and Mg++ likely to need replacement
**Need very regular (Q2-4h) ABG and EUC for 1st 24 hours to avoid large electrolyte and BSL changes. Need regular urine dipstick q4-6h for ketones.

4. Identify and treat precipitant:

Common precipitants to consider include;
Non compliance and psycho-social issues
Infection:- gastroenteritis, UTI, respiratory tract, cholecystitis, meningitis, cellulitis

Ischaemia:- AMI, stroke, peripheral vascular disease, mesenteric `  ischaemia

Pregnancy

5. Prevention of expected complications:

Hypoglycaemia (q1h BSL, decrease insulin infusion, dextrose infusion) Hyponatraemia (regular electrolyte monitoring)
Hypokalaemia (regular electrolyte monitoring)
Hypomagnasaemia and hypophosphataemia (regular electrolyte monitoring) Venous thromboembolism (sci heparin/LMWH)
Hyperchloraemic acidosis (avoid N/saline when able)

Complications of critical illness (upper GIT bleeding, ARDS..)

Discussion

Like all the management questions, this one can be dissected into manageable pieces:

  • Attention to the ABCS, with management of life-threatening problems simultanous with a rapid focused examination and a brief history.
  • Airway
    • Assess the need for intubation - will rarely be required, unless cardiorespiratory arrest occurs
  • Breathing/ventilation
    • Assess the need for supplemental oxygen- this will rarely be required, as oxygenation is rarely an issue
    • If intubated, maintain a high MV to prevent an exacerbation of acidosis
  • Circulatory support
    • IV fluids and vasopressors may be required if the initial presentation is in a shocked state
  • Supportive management
    • Ensure adequate thiamine supplementation
    • Protect gut mucosa with PPIs
    • DVT prophylaxis (s/c heparin)
  • Monitoring
    • Frequent (hourly) ABGs
    • Frequent (4-6hourly) electrolyte levels
      • watch for hypokalemia and hypophosphataemia
  • Specific management
    • Initial resuscitation with choride-poor fluids (eg. Plasmalyte)
    • Insulin infusion - 0.01 to 0.1units/kg/hr (to reduce the rate of ketogenesis)
    • Add 5% glucose when BSL is under 15mmol/L
    • Correct electrolytes aggressively
    • Search for and address the precipitating cause.

Out there, every man and his dog has a protocol for the management of diabetic ketoacidosis. One Google Scholar search for "management of diabetic ketoacidosis" has yielded several pages of articles, monotonously titled "Management of diabetic ketoacidosis".

As my primary reference, I have chosen a representative statement - the "Joint British Diabetes Societies guideline. Among the various issues raised by the guideline, a few stand out as mildly interesting:

  • You may safely use VBGs instead of ABGs
  • You should use crystalloid IVF (though there was never any controversy)
  • You should use your judgement and give fluids at a careful rate, because there is no evidence regarding any befit from rapid fluid resuscitation
  • The Brits recommend you use saline as your crystalloid of choice, which is heretical. The reasons given were "unfamiliar and not routinely kept on medical wards". My response would be "train your staff and stock better fluids".

References

Savage, M. W., et al. "Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis." Diabetic Medicine 28.5 (2011): 508-515.

Question 19 - 2009, Paper 2

A 73 year old man, body mass index 17.5 kg/m2, is commenced on total parenteral nutrition (TPN) following surgery for a gastric malignancy.  Four days later he develops increasing breathlessness and hypotension. Blood results are as follows:

Test

Value

Normal Range

Haemoglobin*

109 G/L

135 – 180

White Cell Count*

13.6 x 109/L

4.0 – 11.0

Platelets

178 x 109/L

150 – 400

Urea*

10.3 mmol/L

3.0 – 8.0

Creatinine

84 µ mol/L

45 – 90

Sodium

145 mmol/L

134 – 146

Potassium*

1.8 mmol/L

3.4 – 5.0

Chloride*

115 mmol/l

98 – 108

Bicarbonate*

14 mmol/L

22 – 32

Calcium (albumin adjusted)*

1.82 mmol/L

2.15 – 2.6

Albumin*

26 G/L

35 – 50

Magnesium*

0.41 mmol/L

0.7 – 1.1

Phosphate inorganic*

0.26 mmol/L

0.8 – 1.5

Glucose*

18.6 mmol/L

3.0 – 5.4

a)          What is the likely diagnosis? Provide 4 reasons which support your answer.

b)         Give 5 associated complications.

College Answer

a)          What is the likely diagnosis? Provide 4 reasons which support your answer.

Refeeding syndrome (Nutritional recovery syndrome) Clinical history, Low Po4, K 1.8 and Mg

b)         Give 5 associated complications.

Respiratory

Respiratory failure

Respiratory muscle weakness

Cardiac 
Cardiac failure / Cardiomyopathy
Hypotension
Arrhythmias

Neurologic 
Altered mental state

Paraesthesiae

Seizures

Renal 
Acute tubular necrosis

Skeletal

Rhabdomyolysis

Weakness

Endocrine 
Insulin resistance
Osteomalacia

Haematologic 
White cell dysfunction
Thrombocytopenia / decreased platelet function
Haemolytic anaemia

Immune function 
Sepsis

Discussion

It is difficult to mistake refeeding syndrome. One if forced into this conclusion by the constellation of low potassium, low phosphate and low magnesium, in the context of recently recommenced nutrition.

Refeeding syndrome is discussed in greater detail elsewhere.
The complications are detailed in a large table, which I reproduce below.

Organ System Complications of Refeeding Syndrome

Cardiovascular:

  • Heart failure (overload) due to atrophy
  • Hypotension and shock
  • Cardiac arrhythmia

Gastrointestinal

  • LFT derangement due to acute fatty liver
  • Diarrhoea due to intestinal atrophy
  • Delayed gastric emptying
  • Arrhythmias

Renal

  • Acute tubular necrosis

 

Respiratory

  • Respiratory muscle weakness
  • Prolonged ventilator weaning

Musculoskeletal

  • Muscle weakness
  • Tetany
  • Rhabdomyolysis due to low phosphate

Neurological

  • Seizures
  • Coma
  • Delirium

Immunological

  • Phagocyte dysfunction
  • Increased susceptibility to sepsis
  •  
 

References

Hearing, Stephen D. "Refeeding syndrome." BMJ 328.7445 (2004): 908-909.

Stanga, Z., et al. "Nutrition in clinical practice—the refeeding syndrome: illustrative cases and guidelines for prevention and treatment." European journal of clinical nutrition 62.6 (2008): 687-694.

Kraft, Michael D., Imad F. Btaiche, and Gordon S. Sacks. "Review of the refeeding syndrome." Nutrition in Clinical Practice 20.6 (2005): 625-633.

Khan, Laeeq UR, et al. "Refeeding syndrome: a literature review."Gastroenterology research and practice 2011 (2010).

Question 4 - 2010, Paper 1

Stress induced hyperglycaemia (S.I.H) is common in critically ill patients.

a) Define S.I.H

b) Outline the mechanisms thought important in the pathogenesis of S.I.H.

c) Outline clinical implications and treatment of S.I.H.

College Answer

a) Define S.I.H
Transient hyperglycaemia during acute illness –usually restricted to patients without prior evidence of diabetes with reversion to normal after discharge.

b) Outline the mechanisms thought important in the pathogenesis of S.I.H.

•    S.I.H is thought to develop due to complex interplay between counter regulatory hormones such as catecholamines, GH, cortisol and cytokines.
•    The   underlying   illness   and   treatments   (TPN,   enteral   feed,   steroids,   and vasopressors) might affect the scale of these derangements.
•    The   key   contributor   would   appear   to   be   high   hepatic   glucose   output   via gluconeogenesis  driven by glucagon,  adrenaline  and cortisol.  Cytokines  such as TNFα interact to enhance this response.
•    Insulin resistance plays a role.
•    Underlying abnormalities in glucose regulation may be present.

c) Outline clinical implications and treatment of S.I.H.

•    Recent  data  suggests  that  S.I.H  and  diabetic  hyperglycaemia  are  two  different phenomena with differing clinical outcomes.
•    Patients with S.I.H have been shown in several studies to have increased risk of mortality, adverse events, and greater organ failure scores compared to those with diabetes.
•    Whether S.I.H per se causes harm or instead is a marker of severity of counter regulatory response and degree of illness is unknown.
•    Management  of S.I.H cannot be distinguished  from hyperglycaemia  due to other causes.  In  most  cases  it  is  not  generally  predictable  or  preventable.   Early recognition and interception might prevent persistence and exacerbation. Recommendations include insulin therapy with more conservative glucose targets.
•    Candidates mentioning recent data from RCTs were given credit.

Discussion

Stress-induced hyperglycaemia is discussed elsewhere. In brief, one would define it as hyperglycaemis which occurs in the presence of severe illness and in the absence of pre-existing diabetes. Marik & Bellomo have a nice review of this from 2013.

One could summarise the mechanisms as follows:

  • Increased glucose synthesis is due to the following mechanisms:
    • Increased lipolysis due to catecholamine activity
    • Increased gluconeogenesis due to catecholamine activity
    • Increased glycogenolysis due to catecholamine activity
  • Increased insulin resistance is due to the decreased sensitivity of skeletal muscle to insulin, via the effects of the following hormones:
    • Catecholamines
    • Growth hormone
    • Cortisol
    • TNF-α
  • Additional effects are the direct inhibition of insulin release by adrenaline, and the activation of hepatic glycolysis by glucagon.

Clinical implications of stress-induced hyperglycaemia and its treatment are detailed in the chapter on glycaemic conrol in critical illness.

The key points can be summarised as a list:

  • Increased mortality
  • Pro-inflammatory effects
  • Increased susceptibility to infection

The college points out that association with mortality is not evidence of causation. Glucose may just be another acute phase reactant.

And as for management? In short, keep the BSL between 5 and 8. Finfer et al have demonstrated (NICE-SUGAR) that tight glycaemic control hurts more people than it helps.

References

McCowen, Karen C., Atul Malhotra, and Bruce R. Bistrian. "Stress-induced hyperglycemia." Critical care clinics 17.1 (2001): 107-124.

Falciglia, Mercedes, et al. "Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis." Critical care medicine 37.12 (2009): 3001.

Finfer, Simon, et al. "Intensive versus conventional glucose control in critically ill patients." N Engl J Med 360.13 (2009): 1283-1297.

Marik, Paul E., and Rinaldo Bellomo. "Stress hyperglycemia: an essential survival response!." Critical Care 17.2 (2013): 305.

Question 20 - 2010, Paper 2

Outline your approach to the assessment of nutritional status in a critically ill patient, including the use of appropriate laboratory tests.

College Answer

History and physical examination:

Indicators of malnutrition – recent involuntary weight loss, changes in appetite or bowel habit, presence of persistent GI symptoms, muscle wasting, signs of specific micro-nutrient deficiency e.g. glossitis, angular stomatitis, anaemia, bleeding gums, skin/hair/nail condition.

Ancillary blood tests: serum hepatic protein levels are linked to nutritional status and severity of illness.

•    Serum albumin and pre-albumin levels. ( Albumin will be a better indicator of chronic nutritional status and pre-albumin serves more as a marker of changes in current nutritional status).

•    Transferrin and coagulation factors: Useful but may more reflect the poor synthetic function of the liver in this case than nutritional deficiency per se.

•    Fat-soluble vitamin deficiency levels of vitamins A, D and E should be checked.
Water-soluble vitamin deficiency, (thiamine), is common in alcoholic liver disease and therefore levels of thiamine and other treatable vitamins e.g. zinc, selenium, Vit B12 and folate should also be checked.

•     Other  

(1)  delayed   hypersensitivity   skin  testing

 (2)  total  lymphocyte   count  

(3) anthropometric measurements e.g. mid-arm muscle circumference and skin-fold thickness

 (4) indirect calorimetry  to measure  energy expenditure  – metabolic  cart, VO2,  VCO2,

 (6) nitrogen  balance  – but calculations  inaccurate  in liver and  renal failure.

Discussion

An extensive examination of the methods of nutritional assessment is available elsewhere:

In brief, these are the key features one should mention in such an answer:

History:

  • Premorbid weight and the pattern of its change
  • Premorbid nutritional routine
  • Diseases affecting gastrointestinal function (eg. coeliac disease)
  • Disease affecting satiety control (eg. Prader-Willi syndrome)
  • Factors influencing metabolic substrate utilisation (eg. thyroid dysfunction, hypoadrenalism, Cushings disease or corticosteroid therapy)

Examination:

  • Observed quality of nails and hair (an indicator of chronic protein intake)
  • Subcutaneous fat measurements (triceps)
  • Muscle bulk and muscle tone of quadriceps and deltoids
  • Presence of oedema and ascites
  • Evidence of any specific micronutrient deficiency

Anthropometry

  • BMI
  • Ideal body weight
  • Lean body mass

Biochemistry and physiology:

  • Cholesterol and triglycerides
  • Random BSL
  • HbA1C
  • Serum cortisol
  • TFTs
  • FBC for lymphocyte count
  • Delayed hypersensitivity skin-testing
  • Albumin and prealbumin
  • Transferrin
  • Calculation of nitrogen balance
  • Micronutrient levels:
    • Fat-soluble vitamins A, D and E
    • Thiamine
    • Zinc
    • Selenium
    • Vitamin B12
    • Folate
  • Indirect calorimetry

References

http://www.criticalcarenutrition.com/ is an excellent resource for all things nutrition-related.

Berger, Mette M., and Claude Pichard. "Best timing for energy provision during critical illness." Crit Care 16.2 (2012): 215.

Dhaliwal, Rupinder, et al. "The Canadian Critical Care Nutrition Guidelines in 2013 An Update on Current Recommendations and Implementation Strategies."Nutrition in Clinical Practice 29.1 (2014): 29-43.

de Souza Menezes, Fernanda, Heitor Pons Leite, and Paulo Cesar Koch Nogueira. "Malnutrition as an independent predictor of clinical outcome in critically ill children." Nutrition 28.3 (2012): 267-270.

Norman, Kristina, et al. "Prognostic impact of disease-related malnutrition."Clinical nutrition 27.1 (2008): 5-15.

Detsky, Allan S., et al. "What is subjective global assessment of nutritional status." JPEN J Parenter Enteral Nutr 11.1 (1987): 8-13.

Sauberlich, Howerde E. Laboratory tests for the assessment of nutritional statusVol. 21. CrC Press, 1999.

Gorstein, Jonathan, et al. "Issues in the assessment of nutritional status using anthropometry." Bulletin of the World Health Organization 72.2 (1994): 273.

Shenkin, Alan. "Serum prealbumin: Is it a marker of nutritional status or of risk of malnutrition?." Clinical chemistry 52.12 (2006): 2177-2179.

Ritchie, Robert F., et al. "Reference distributions for the negative acute‐phase serum proteins, albumin, transferrin and transthyretin: a practical, simple and clinically relevant approach in a large cohort." Journal of clinical laboratory analysis 13.6 (1999): 273-279.

Desborough, J. P. "The stress response to trauma and surgery." British journal of anaesthesia 85.1 (2000): 109-117.

Klein, S. "The myth of serum albumin as a measure of nutritional status."Gastroenterology 99.6 (1990): 1845.

Don, Burl R., and George Kaysen. "Poor nutritional status and inflammation: serum albumin: relationship to inflammation and nutrition." Seminars in dialysis. Vol. 17. No. 6. Blackwell Science Inc, 2004.

Schoenfeld, Patricia Y. "Albumin is an unreliable marker of nutritional status."Seminars in Dialysis. Vol. 5. No. 3. Blackwell Publishing Ltd, 1992.

Shenkin, A., et al. "Laboratory assessment of protein-energy status." Clinica chimica acta 253.1 (1996): S5-S59.

Clark, Matthew A., et al. "Sequential changes in insulin-like growth factor 1, plasma proteins, and total body protein in severe sepsis and multiple injury."Journal of Parenteral and Enteral Nutrition 20.5 (1996): 363-370.

Casati, A., et al. "Rapid turnover proteins in critically ill ICU patients. Negative acute phase proteins or nutritional indicators?." Minerva anestesiologica 64.7-8 (1997): 345-350.

Rand, William M., Peter L. Pellett, and Vernon R. Young. "Meta-analysis of nitrogen balance studies for estimating protein requirements in healthy adults."The American journal of clinical nutrition 77.1 (2003): 109-127.

 

Hoffer, L. John, and Bruce R. Bistrian. "Appropriate protein provision in critical illness: a systematic and narrative review." The American journal of clinical nutrition 96.3 (2012): 591-600.

Kopple, Joel D. "Uses and limitations of the balance technique." Journal of Parenteral and Enteral Nutrition 11.5 suppl (1987): 79S-85S.

Question 22 - 2010, Paper 2

A 43 year old female presents with a severe episode of palpitations, sweating, vomiting and breathlessness  after taking a dose of propranolol prescribed by her  General  Practitioner  for  panic  attacks.  She  gives  a  history  of  similar symptoms  occurring  episodically  over  the  preceding  three  months  and  her past medical history includes medullary thyroid cancer.

Vital signs:

  • SaO2  88% on oxygen 15 L/min via mask 
  • Heart rate: 150, Atrial Fibrillation 
  • BP 175/100 mm Hg 

Chest X-Ray: Consistent with acute pulmonary oedema.

a.   What is the likely diagnosis?

b.  What investigations will help you confirm the diagnosis?

c. Outline your immediate management of this patient.

d. List four complications of this condition.

College Answer

a.   What is the likely diagnosis?

Phaeochromocytoma

b.  What investigations will help you confirm the diagnosis?

Investigations

•          Plasma free metanephrine
•          24 hour urine collection for creatinine, total catecholamines, vanillylmandelic acid and metanephrines
•           Imaging

-       MRI – most sensitive 
-       CT scan – less accurate for lesions <1cm 
-       MIBG  scan  – biochemical  confirmation  but  no tumour  seen  on CT scan or MRI 
-       PET scan

c. Outline your immediate management of this patient.

•    Admission to ICU or HDU for close monitoring
•    Increase inspired oxygen concentration
•    Start alpha blockade with IV phentolamine to control BP acutely and start phenoxybenzamine  orally.  Rate control of AF with calcium channel blocker
•    Once alpha blockade established, beta blockade can be added
•    IV fluid replacement as vasodilation occurs to normalise blood volume
•    Some authorities recommend magnesium sulphate infusion
•    Screen for myocardial damage with serial troponins, ECG and echo. Echo may show takutsubo type abnormality

d. List four complications of this condition.

•Malignancy 
•Death 
•Myocardial infarction 
•Arrhythmias 
•Seizures 
•Stroke

Discussion

The red herring of medulary thyroid cancer is thrown in, but the question is about a catecholamine-secreting adenoma. Of course, the examiners are taking advantage of the well-known associationbetween thyroid cardinoma and phaeochromocytoma - investigators in 1961 concluded that "the incidence of carcinoma of the thyroid gland is increased far beyond expectation based on chance concurrence". The features of the history which make one think of phaeochromocytoma in this instance is the onset of symptoms after the administration of a non-selective beta blocker. Propanolol, one ought to remember, is a potent agent used to control thyrotoxic crises- so it should not have been associated with the sudden onset of worsening symptoms.

The physiology here is likely to involve the selective blockade of beta-receptors, which has resulted in an unopposed alpha-agonist effect. The massive afterload increase resulting from this has caused the left ventricle to decompensate; LV falure in turn caused the LA dilatation (and AF), as well as the pulmonary oedema.

Investigations for phaeochromocytoma should include the following:

  • Tests for catecholamines and their metabolites
    • Urinary catecholamines
    • Plasma catecholamines
    • Urinary fractionated metanephrines
    • Plasma free metanephrines (these appear to be the best single investigation)
    • Urinary vanillylmandelic acid
  • Clonidine suppression test
    • In patients with phaeochromocytoma, serum catecholamine levels will not decrease in responswe to clonidine.
  • Imaging: MRI and/or PET scan

The management of phaeochromocytoma is discussed in an excellent article from the Royal Adelaide hospital. The key is to block the alpha receptors first. Phenoxybenzamine is an exciting exotic substance used exclusively for this purpose, as it is a non-competitive alpha-antagonist. It binds irreversibly to alpha receptors, inactivating them, and no concentration of catecholamines will ever displace it. This is good, because competitive inhibition of alpha-receptors in this context will face strong opposition from the thousand-times-increased concentration of serum catecholamines.

The Adelaide paper does meantion that their practice has been to use atenolol before giving phenoxybenzamine, so as to ablate the reflexive tachycardia which will result from its use. This is probably because the population reported on in the paper were stable pre-operative outpatients. In the context of an acute crisis, one is obliged to control the vasoconstriction first, using something like phentolamine or sodium nitroprusside. In any case, the patient in this scenario has already taken a beta-blocker.

Thus, in brief, the list of management options should resemble this:

  • Attention to the airway, oxygenation and ventilation
  • Control of hypertension
    • Rapidly acting alpha-1 antagonist: phentolamine
    • Slowly acting non-competitive alpha-1 antagonist: phenoxybenzamine
    • Beta-antagonist
  • Maintenance of circulating volume in the face of vasodilation:
    • IV fluid replacement
  • Control of AF
    • Verapimil, diltiazem, or amiodarone
  • Assessment of myocardial damage
    • ECG
    • TTE
    • CK and troponin

The college answer mentions a TTE. The typical findings are actually catecholamine-induced cardiomyopathy, but a Takotsubo pattern can also emerge. Such things are generally known from case reports, so it is difficult to broadly generalise.

References

Sardesai, Suhrud H., et al. "Phaeochromocytoma and catecholamine induced cardiomyopathy presenting as heart failure." British heart journal 63.4 (1990): 234-237.

Lenders, Jacques WM, et al. "Biochemical diagnosis of pheochromocytoma: which test is best?." Jama 287.11 (2002): 1427-1434.

Russell, Walter John, et al. "The preoperative management of phaeochromocytoma." Anaesthesia and intensive care 26.2 (1998): 196-200.

Eschen, Ole, et al. "Pheochromocytoma, a rare cause of acute cardiogenic shock." Clinical research in cardiology 96.4 (2007): 232-235.

Li, Ling, et al. "Transthoracic Echocardiographic Features of Cardiac Pheochromocytoma: A Single‐Institution Experience." Echocardiography 29.2 (2012): 153-157.

Leissner, Kay B., et al. "Catecholamine-induced cardiomyopathy and Pheochromocytoma." Anesthesia & Analgesia 107.2 (2008): 410-412.

Sanchez-Recalde, Angel, et al. "Pheochromocytoma-related cardiomyopathy inverted Takotsubo contractile pattern." Circulation 113.17 (2006): e738-e739.

Sipple, John H. "The association of pheochromocytoma with carcinoma of the thyroid gland." The American Journal of Medicine 31.1 (1961): 163-166.

Question 25.4 - 2010, Paper 2

The following haemodynamic  and metabolic data were obtained from a patient admitted to the ICU with sepsis.

Pulmonary artery catheter data:

CI                                         4.2L/min/m2 
DO2                                     900 ml/min 
VO2                                     190 ml/min

Indirect calorimetry data:

VO2                                     220 ml/min 
VCO2                                  290 ml/min

a)  Why   is   the   VO2     different   between   the   two   methods?   (Assume   no measurement errors).

b)  What  changes  in  patient  management  will  you  consider  based  on  the indirect calorimetry data?

College Answer

a)  Why   is   the   VO2     different   between   the   two   methods?   (Assume   no measurement errors).

Indirect calorimetry also measures lung oxygen consumption.

b)  What  changes  in  patient  management  will  you  consider  based  on  the indirect calorimetry data?

A high RQ suggests excess carbohydrate load. Reduce caloric intake and consider changing to a higher fat intake.

Discussion

Indirect calorimetry and the reverse Fick method are discussed in detail elsewhere.

The VO2, or the oxygen consumption, is different between the caloric cart and the PA catheter because the PA catheter measurement (of systemic oxygen extraction) neglects the lungs as a oxygen user. But the lung does use oxygen- in this particular patient, 30ml/min are used.

The RQ is calculated using the VO2 and the VCO2 (RQ = VCO2/VO2).

In this case, it comes to 1.31 - which is well in excess of what one would expect (0.8). The college suggests that a high carbohydrate foodsource may be responsible, and that the patient should go on a fat and protein enriched diet.

References

LITFL has an excellent summary dedicated to indirect calorimetry. I stole a couple of their references.

Holdy, Kalman E. "Monitoring energy metabolism with indirect calorimetry: instruments, interpretation, and clinical application." Nutrition in Clinical Practice 19.5 (2004): 447-454.

Flancbaum, Louis, et al. "Comparison of indirect calorimetry, the Fick method, and prediction equations in estimating the energy requirements of critically ill patients." The American journal of clinical nutrition 69.3 (1999): 461-466.

Weir, JB de V. "New methods for calculating metabolic rate with special reference to protein metabolism." The Journal of physiology 109.1-2 (1949): 1.

McClave, Stephen A., Robert G. Martindale, and Laszlo Kiraly. "The use of indirect calorimetry in the intensive care unit." Current Opinion in Clinical Nutrition & Metabolic Care 16.2 (2013): 202-208.

Lev, Shaul, Jonathan Cohen, and Pierre Singer. "Indirect calorimetry measurements in the ventilated critically ill patient: facts and controversies—the heat is on." Critical care clinics 26.4 (2010): e1-e9.

Fraipont, Vincent, and Jean-Charles Preiser. "Energy Estimation and Measurement in Critically Ill Patients." Journal of Parenteral and Enteral Nutrition 37.6 (2013): 705-713.

Question 12 - 2011, Paper 2

An 86-year-old gentleman is admitted to intensive care with acute lung injury causing respiratory failure, secondary to gallstone-induced acute pancreatitis. Evidence in the literature suggests enteral nutrition is appropriate.


a. How would you approach his enteral nutrition after a successful ERCP?

b. List the complications that need to be considered with utilising enteral nutrition?

c. When might you consider parenteral nutrition?

College Answer

a. How would you approach his enteral nutrition after a successful ERCP?


Access: Nasojejunal tube although nasogastric appears safe and well tolerated.
Any reasonable approach OK

  1. Determine target rate for enteral nutrition, commencing 30ml/hour and increasing as tolerated and delivered as a continuous infusion to maximise chances of achieving nutritional target rates.
  2. Prokinetics could be considered if large aspirates are experienced. A feeding protocol should be utilised to maximise the chances of achieving nutritional target rates.
  3. Nutritional targets in the critically ill can be determined by either indirect calorimetry, predictive equations (eg: Harris-Benedict equation) or simplistic formulae (25-30kcal/kg/day) with at least 1.2-2g/kg/day of protein.
  4. Avoid probiotics (the only multi-centre RCT showed increased mortality and incidence of MOF in treatment group)

b. List the complications that need to be considered with utilising enteral nutrition?

  1. Tube complications
    Misplacement: Pneumothorax, inadvertent pulmonary infusion
    Sinusitis
    Pressure areas on nose/lip
    Trauma to nasopharynx, oesophagus, stomach and haemorrhage
  2. Feed complications
    Inadequate caloric intake from gastric stasis
    Diarrhoea
    Ventilator associated pneumonia
    Electrolyte abnormalities
    Hyperglycaemia

c. When might you consider parenteral nutrition?

Despite following a rigorous enteral feeding protocol, there is inadequate caloric intake after five days. Combined enteral and parenteral nutrition to meet targets may be beneficial. Recent NEJM article June 2011 comparing early (day 2) with late (day 8) TPN in ICU patients not meeting nutritional targets with EN showed better outcomes in late TPN group

Discussion

The college preambles the answer with "any reasonable approack OK". This to me suggests that there may not be a scholarly consensus of experts regarding this.The college answer consists of answers picked from the most recent Guidelines

Furthermore, here we have the red herring of "successful ERCP". Judging by the college answer, it was thrown in to confuse and bewilder the candidate. One might take this to mean that the patient now has normal exocrine pancreatic fnction, and no loger requires "pancreatic rest", even if that was a real issue.

The real question should read "Briefly discuss the management of enteral nutrition in severe pancreatitis and acute lung injury".

The role of enteral nutrition in the management of pancreatitis is discussed elsewhere, as are the complications of enteral nutrition and the complex problem of determining nutritional requirements in the critically ill patients.

In short, nutrition for the pancreatitis patient who has had a successful ERCP should be approached thus:

  • Mild-moderate pancreatitis:
    • Safe to not feed at all for ~ 7 days
    • Consider enteral therapy if they fail to preogress to oral diet at the end of one week
  • Severe pancreatitis:
    • Enteral nutrition should start early
    • If enteral nutrition is poorly tolerated,
      • Change to a fat-free feed formulation
      • Change from whole protein to peptide fragments
      • Move the NG tube tip beyond the ligament of Treitz
      • If the feeds are still not tolerated, one may start TPN... but it is better to wait until day 5 or later.

Complications of enteral nutrition are as follows:

  • Aspiration
  • Diarrhoea
  • Constipation
  • Dehydration
  • Malnutrition (owing to intolerance)
  • Complications relating to the feeding tube:
    • Poor placement, eg. into the lung
    • Oesophageal or gastric perforation
    • Increased tendency towards gastro-oesophageal reflux
    • Pressure areas due to prolonged tube dwell time (eg. pressure on the nares)
    • Sinusitis (for nasal tubes)
    • Poor oral hygiene( for oral tubes)
    • Oesophageal stricture
    • Discomfort in the awake patient

References

Society Of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient. Crit Care Med 2009 Vol. 37, No. 5 , 2009

Eatock FC, Chong P, Menezes N, Murray L, McKay CJ, Carter CR, Imrie CW. A randomized study of early nasogastric versus nasojejunal feeding in severe acute pancreatitis. Am J Gastroenterol. 2005 Feb;100(2):432-9.

Windsor AC, Kanwar S, Li AG, et al. Compared with parenteral  nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Gut. 1998;42: 431-435.

Ragins H, Levenson SM, Signer R, Stamford W, Seifter E Intrajejunal administration of an elemental diet at neutral pH avoids pancreatic stimulation. Studies in dog and man. .Am J Surg. 1973 Nov;126(5):606-14.

B. W. M. Spanier,1, M. J. Bruno, E. M. H. Mathus-Vliegen Enteral Nutrition and Acute Pancreatitis: A Review Gastroenterol Res Pract. 2011; 2011: 857949. Published online 2010 August 3.

Kudsk KA, Croce MA, Fabian TC, et al. Enteral versus parenteral feeding: effects on septic morbidity after blunt and penetrating abdominal trauma. Ann Surg. 1992;215:503-513.

Lewis SJ, Egger M, Sylvester PA, Thomas S SO Early enteral feeding versus "nil by mouth" after gastrointestinal surgery: systematic review and meta-analysis of controlled trials. BMJ. 2001;323(7316):773.

Society Of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient. Crit Care Med 2009 Vol. 37, No. 5 , 2009

Luft VC, Beghetto MG, de Mello ED, Polanczyk CA. Role of enteral nutrition in the incidence of diarrhea among hospitalized adult patients. Nutrition. 2008 Jun;24(6):528-35. Epub 2008 Apr 15.

Montejo JC Enteral nutrition-related gastrointestinal complications in critically ill patients: a multicenter study. The Nutritional and Metabolic Working Group of the Spanish Society of Intensive Care Medicine and Coronary Units. .Crit Care Med. 1999 Aug;27(8):1447-53.

Rushdi TA, Pichard C, Khater YH Control of diarrhea by fiber-enriched diet in ICU patients on enteral nutrition: a prospective randomized controlled trial. Clin Nutr. 2004;23(6):1344.

M.D. Bastow; Complications of enteral nutrition. Gut, 1986, 27, SI, 51-55

S. M. Mostafa, S. Bhandari, G. Ritchie, N. Gratton, R. Wenstone. Constipation and its implications in the critically ill patient. Br. J. Anaesth. (2003) 91 (6): 815-819.

 

Question 2 - 2011, Paper 2

Define cachexia.

List the factors that may predispose to cachexia AND the consequences of cachexia in a ventilated patient with sepsis and multi-organ dysfunction syndrome.

College Answer

College answer

Define Cachexia 
Weight loss and skeletal muscle wasting due to illness where the body does not reduce catabolism 
(unlike the adaptive reduction in protein metabolism that occurs in starvation)

Predisposing factors 
Mechanisms not clearly understood 
Pre-existing malnutrition / malabsorption. 
Cytokine-induced up-regulation of muscle protein degradation 
Neuro-endocrine – stimulation of hypothalamic-pituitary-adrenal axis 
Reduced circulating anabolic hormones
Immobility and prolonged length of stay 
Corticosteroid therapy 
Malignancy

Consequences
Increased risk of death
Prolonged time on ventilator
Increased ICU and hospital length of stay 
Increased risk of nosocomial infections
Poor wound healing 
Malnutrition and nutritional deficiency syndromes

 

Discussion

This question asks one to produce a handful of causes for cachexia.

A more recent definition of cachexia is "A syndrome characterised by a loss of body weight and muscle tissue, which occurs in absence of starvation and is not associated with an adaptive decrease in catabolism." This syndrome is briefly discussed in the chapter on cachexia. Moreover, the consequences of malnutrition in the critically ill patient are discussed in detail in yet another chapter.

Oh’s Manual mentions cachexia only once, in the causes of ionized hypocalcemia (pp. 658).

This was disappointing.

There is no widely agreed-upon definition of cachexia (this article told me so). There was a Cachexia Consensus Conference in 2008 during which a new definition was proposed. This definition included only “cachexia proper”, excluding causes such as malnutrition (starvation), malabsorption, and hyperthyroidism. The experts were keen to make the distinction between this weird metabolic syndrome which occurs often in the presence of optimal nutrition, and all other forms of weight loss.

I would go further to separate the college answer into causes and exacerbating factors:

Exacerbating factors:

  • Catecholamine excess
  • Corticosteroid use
  • Immobility
  • Hyperthyroidism
  • Malabsorption
  • Malnutrition

Causes and mechanisms:

  • Unclear mechanism; possible combination of the following:
    • Decreased  circulating anabolic hormones (eg. androgens)
    • Increased circulating catabolic cytokines and hormones (eg. cortisol and catecholamines)
    • Pathologically increased nutrient demand by tissues:
      • Aggressively multiplying malignant tissue
      • Increased workload in pathological states, eg. respiratory effort in COPD
    • Pathologically decreased nutrient supply to tissues:
      • Chronically decreased cardiac output in cardiac cachexia
      • Chronic hypoxia in respiratory failure

Consequences of cachexia in ICU patients

These are very similar to the consequences of malnutrition in the critically ill patient, which are discussed in greater detail in a dedicated chapter.

  • Poor wound healing
  • Impaired immune function and increased risk of sepsis
  • Muscle wasting due to protein catabolism:
    • Decreased ventilatory drive
    • Weakness complicating separation from the ventilator
    • Weakness complicating physiotherapy and mobilisation
      • Exposure to the complications of immobility, eg. DVT
  • Cardiomyopathy as a consequence of atrophy
  • Mucosal atropthy and diminished barrier function of the gut
  • Apathy and depression
  • Increased duration of ICU stay
  • Increased in-hospital mortality

References

Anker SD, Coats AJ. Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation. Chest. 1999 Mar;115(3):836-47.

Steinborn W, Anker S.D., Cardiac Cachexia: Pathophysiology and Clinical Implications. Basic Appl Myol 13 (4): 191-201, 2003

The experts report that at least in cardiac failure cachexia is a strong independent risk factor for mortality.

 

Question 11.1 - 2012, Paper 1

a) A 62-year-old woman has been admitted to hospital for investigation, giving a history of episodic facial flushing and diarrhoea, and fatigue. You are called to review her on the ward because she is hypotensive. Your examination shows features of right heart failure, with a tricuspid regurgitant murmur.
 
 ECHO REPORT:

  • Normal LV size and systolic function.
  • The right ventricle is dilated, with normal systolic function.
  • Triscuspid valve leaflets are thickened, retracted, and relatively immobile.
  • There is severe tricuspid regurgitation.
  • Pulmonary valve leaflets are thickened.
  • Mild pulmonary regurgitation.
  • Other valves are normal.

 
i. What is the most likely diagnosis?
 
ii. What is the most useful investigation to confirm this diagnosis?

College Answer

a)

i. Diagnosis: Carcinoid syndrome with cardiac involvement

ii. Investigation: 24 hour urinary HIAA (5-hydroxyindoleacetic acid) OR Serum chromogranin-A

Discussion

This sadistic question separates the wheat from the chaff.

Is there any wonder the pass rate was only 10%?

Carcinoid syndrome is freakishly rare. One ought to feel no remorse at knowing little about it, because in the course of one's medical practice one might never bump into one of these.

However, the facial flushing is a dead giveaway.

First described as a "unique syndrome" of facial flushing and elevated serotonin, carcinoid syndrome has become grouped together with all the other sorts of syndromes of malignant origin, particularly of neuroendocrine tumours. Carcinoid tumours are slowly growing neuroendocrine tumours of upper GI origin; indeed the term "carcinoid" refers to the fact that they are only carcinoma-like.

Additionally, the presence of facial flushing AND right heart valve damage is pathognomonic.

Its just a pattern one learns to recognise.

The damage is typically to the valve structures, and is typically a sclerosis, resulting in right heart failure. The mechanism is thought to be an effect of the vasoactive substances secreted by the tumour on the myocardium, resulting in fibrotic changes.

As for the diagnosis...

Twenty-four-hour measurement of urinary 5-hydroxyindole-3-acetic acid (5-HIAA), which is the degradation product of serotonin, is apparently 88% specific for serotonin-producing carcinoid tumours.

The MJA article cautions that tryptophan/serotonin-rich foods (bananas, avocados, plums, eggplants, tomatoes, plantains, pineapples and walnuts) can produce a falsely elevated 5-HIAA level.

Serum chromogranin-A is a much better test, because it is more reliable, does not require 24 hours of urine collection, and can be later used to monitor treatment.

References

Oates, John A., and Albert Sjoerdsma. "A unique syndrome associated with secretion of 5-hydroxytryptophan by metastatic gastric carcinoids." The American journal of medicine 32.3 (1962): 333-342.1 

 

Lundin, L., et al. "Carcinoid heart disease: relationship of circulating vasoactive substances to ultrasound-detectable cardiac abnormalities." Circulation 77.2 (1988): 264-269.

 

Modlin, Irvin M., et al. "Gastrointestinal neuroendocrine (carcinoid) tumours: current diagnosis and management." Med J Aust 193.1 (2010): 46-52.

 

Stridsberg, Mats, et al. "Measurements of chromogranin A, chromogranin B (secretogranin I), chromogranin C (secretogranin II) and pancreastatin in plasma and urine from patients with carcinoid tumours and endocrine pancreatic tumours." Journal of Endocrinology 144.1 (1995): 49-59.

Question 24 - 2012, Paper 1

A 46-year-old female patient with class 3 (BMI > 40kg/m2) obesity has been admitted to your ICU with community-acquired pneumonia. She is sedated and ventilated with no other organ dysfunction. You are considering starting nutritional therapy.

  • Outline the metabolic derangements likely to be present in this patient.
  • How would you make an assessment of this patient’s current nutritional status?
  • Outline your nutritional regimen in particular your optimal target protein and energy delivery.

College Answer

A) A number of metabolic derangements affect fuel utilization:

  • Insulin resistance
  • Impaired glucose tolerance,
  • Increased fatty acid mobilization
  • Hyperlipidemia
  • Obese patients, compared to lean counterparts, may have accelerated protein degradation and depletion of lean body mass.
  • “Metabolic X syndrome” may exist: insulin resistance, hyperinsulinemia, hyperglycaemia, coronary artery disease, hypertension, and hyperlipidemia.
  • Obese patients are more likely to have a pre-existing pro inflammatory state.
  • Obese patients have increased resting energy expenditure secondary to increased BMI, with central adipose tissue being more metabolically active than peripheral adipose tissue.

b) Assessment

  • Assess patterns of weight change and nutrition intake prior to the admission
  • Anthropometrics –actual body weight, ideal body weight, usual body weight, height, BMI, and waist circumference should be determined
  • (Biomarkers of the metabolic syndrome; triglycerides, cholesterol, glucose serum albumin and pre-albumin)

c) Nutritional Regimen

• High protein (anabolic) hypocaloric feeding (reduced complications from overfeeding) should be provided to the obese critically ill patient regardless of whether the route of nutrition therapy is enteral or parenteral

  • Most studies using this method give 11-14 kcal/kg/actual BW per day or 22-25 kcal/kg IBW per day- equates to about 60-70% of calorie requirement determined by indirect calorimetry or predictive equation.
  • Protein requirements should be met to maximise protein synthesis and preserve lean body mass (> 2.0g/kg IBW/d for class 1 and 2 obesity and > 2.5g/kg IBW/d for class 3).

Discussion

The spectrum of metabolic derangements present in the obese ICU patient is detailed elsewhere.  In short, these are the major metabolic abnormalities one can expect from an obese patient in the ICU:

  • Insulin resistance and impaired glucose tolerance
  • Increased fatty acid mobilization and hyperlipidemia
  • Accelerated protein degradation
  • The proinflammatory state of obesity
  • The endocrine derangements due to an excess of fatty tissue
  • The increased resting metabolic rate of obesity

Assessment of nutritional status is also detailed elsewhere; in brief the assessment takes the shaped of a structured approach, from history to investigatons:

History:

  • Premorbid weight and the pattern of its change
  • Premorbid nutritional routine
  • Diseases affecting gastrointestinal function (eg. coeliac disease)
  • Disease affecting satiety control (eg. Prader-Willi syndrome)
  • Factors influencing metabolic substrate utilisation (eg. thyroid dysfunction, hypoadrenalism, Cushings disease or corticosteroid therapy)

Examination:

  • Observed quality of nails and hair
  • Subcutaneous fat measurements (triceps)
  • Muscle bulk and muscle tone of quadriceps and deltoids
  • Presence of oedema and ascites

Anthropometry

  • BMI
  • Ideal body weight
  • Lean body mass

Biochemistry:

  • Cholesterol and triglycerides
  • Random BSL
  • HbA1C
  • Serum cortisol
  • TFTs
  • Albumin and prealbumin

Nutrition for the obese ICU patient is presently a topic of hot debate. The most recent suggestions are summarised elsewhere. In short, the published consensus statements suggest we follow a certain pattern:

References

http://www.criticalcarenutrition.com/ is an excellent resource for all things nutrition-related.

Berger, Mette M., and Claude Pichard. "Best timing for energy provision during critical illness." Crit Care 16.2 (2012): 215.

 

Dhaliwal, Rupinder, et al. "The Canadian Critical Care Nutrition Guidelines in 2013 An Update on Current Recommendations and Implementation Strategies."Nutrition in Clinical Practice 29.1 (2014): 29-43.

 

de Souza Menezes, Fernanda, Heitor Pons Leite, and Paulo Cesar Koch Nogueira. "Malnutrition as an independent predictor of clinical outcome in critically ill children." Nutrition 28.3 (2012): 267-270.

 

Norman, Kristina, et al. "Prognostic impact of disease-related malnutrition."Clinical nutrition 27.1 (2008): 5-15.

 

Detsky, Allan S., et al. "What is subjective global assessment of nutritional status." JPEN J Parenter Enteral Nutr 11.1 (1987): 8-13.

 

Sauberlich, Howerde E. Laboratory tests for the assessment of nutritional status. Vol. 21. CrC Press, 1999.

 

Gorstein, Jonathan, et al. "Issues in the assessment of nutritional status using anthropometry." Bulletin of the World Health Organization 72.2 (1994): 273.

 

Shenkin, Alan. "Serum prealbumin: Is it a marker of nutritional status or of risk of malnutrition?." Clinical chemistry 52.12 (2006): 2177-2179.

 

Port, Ava M., and Caroline Apovian. "Metabolic support of the obese intensive care unit patient: a current perspective." Current opinion in clinical nutrition and metabolic care 13.2 (2010): 184.

 

McClave, Stephen A., et al. "Nutrition Therapy of the Severely Obese, Critically Ill Patient Summation of Conclusions and Recommendations." Journal of Parenteral and Enteral Nutrition 35.5 suppl (2011): 88S-96S.

 

Wichansawakun, Sanit, et al. "Metabolic Support of the Obese Intensive Care Unit Patient." Integrative Weight Management. Springer New York, 2014. 215-224.

Question 26.1 - 2013, Paper 1

A 69-year-old male, body mass index 17.5 kg/m2, is commenced on total parenteral nutrition (TPN) following surgery for a gastric malignancy. Four days later he develops increasing breathlessness and hypotension. Blood results are as follows:

 

Test

Value

Normal Adult Range

Haemoglobin*

109 G/L

115 – 155

White Cell Count*

13.6 x 109 /L

4.0– 11.0

Platelets

178 x 109 /L

150 – 400

Urea*

10.3 mmol/L

3.0– 8.0

Creatinine

84 µmol/L

45– 90

Sodium

145 mmol/L

134 – 146

Potassium*

1.8 mmol/L

3.4– 5.0

Chloride*

115 mmol/L

98– 108

Bicarbonate*

14 mmol/L

22– 32

Calcium (albumin

adjusted)*

1.82 mmol/L

2.15 – 2.6

Albumin*

26 G/L

35– 50

Magnesium*

0.41 mmol/L

0.7– 1.1

Phosphate inorganic*

0.26 mmol/L

0.8– 1.5

Glucose*

18.6 mmol/L

3.0– 5.4

  • What is the likely diagnosis?
  • Give four reasons that support your answer.

College Answer

Refeeding syndrome (Nutritional recovery syndrome).

  • Clinical history
  • Low PO4
  • Profound hypokalaemia
  • Hypomagnesaemia

Discussion

An underweight elderly gentleman gets TPN after a prolonged period of malnutrition. It does not take a massive cognitive effort to recognise refeeding syndrome, given the hypokalemia and hypophosphataemia.

Refeeding syndrome is discussed in greater detail elsewhere.

Its typical biochemical features are:

  • Hypophosphatemia
  • Hypomagnesemia
  • Hypokalemia

Lesser known abnormalities include:

  • Thiamine depletion
  • Depletion of micronutrients (eg. selenium, copper and zinc)
  • Hypernatremia (with protein-dominant nutritional replacement)
  • Hyponatremia (with carbohydrate-dominant nutritional replacement)

The shortness of breath and hypotension in this case are likely to a combination of low phosphate and fluid overload in the context of myocardial atrophy. Arrhythmia and respiratory muscle weakness cannot be ruled out.

References

Hearing, Stephen D. "Refeeding syndrome." BMJ 328.7445 (2004): 908-909.

Stanga, Z., et al. "Nutrition in clinical practice—the refeeding syndrome: illustrative cases and guidelines for prevention and treatment." European journal of clinical nutrition 62.6 (2008): 687-694.

Kraft, Michael D., Imad F. Btaiche, and Gordon S. Sacks. "Review of the refeeding syndrome." Nutrition in Clinical Practice 20.6 (2005): 625-633.

Khan, Laeeq UR, et al. "Refeeding syndrome: a literature review."Gastroenterology research and practice 2011 (2010).

Question 13.3 - 2013, paper 2

A 52-year-old female was admitted the previous night with an altered level of consciousness that improved rapidly with administration of glucose.

She is referred to ICU the next day with confusion, ataxia and a worsening level of consciousness.

Her CT head is normal. The blood sugar level in the morning is 8 mmol/L on a 5% Dextrose infusion at 80 mL/hr.

Her full blood count from the previous night is available as follows:

Parameter

Patient Value

Normal Adult Range

Haemoglobin

88 G/L*

130-180

White Cell Count

7.4 x 109 /L

4.5 – 11

Platelets

88 x 109 /L*

150 – 400

Mean Cell Volume

110 fL*

80 – 98

Mean Cell Haemoglobin

30 Pg

27 – 33

Mean Cell Haemoglobin Concentration

320 G/L

310 – 360

Prothrombin Time

12 seconds

12 – 18

Activated Partial Thromboplastin Time

36 seconds

32 – 38

a) What is the likely cause of her confusional state?
 
b) What specific treatment would you prescribe for this?

College Answer

a) Wernicke’s encephalopathy.

b) Thiamine 100 mg IV daily.

Discussion

So, here is a case of confusion and ataxia following the administration of glucose for hypoglycaemia. Not only that, but in the bloods you see this absurdly elevated MCV - 110fL.

Thus, this woman is an experienced drinker, and likely has thiamine deficiency.

Now, confusion and ataxia are suspicious of Wernicke's encephalopathy, a reversible response to the administration of glucose in somebody who is thiamine-deficient. The only other thing the college did not give you as a feature of Wernicke's is the oculomotor disturbances (be it nystagmus, ophthalmoplegia or other sort of gaze palsy).

The diagnostic criteria of Wernicke's are as follows:

  • (1) dietary deficiencies
  • (2) oculomotor abnormalities,
  • (3) cerebellar dysfunction, and
  • (4) either an altered mental state or mild memory impairment.

Thus, the treatment consists of some IV thiamine. The college suggests 100mg IV daily is a big enough dose.

References

Caine, D., et al. "Operational criteria for the classification of chronic alcoholics: identification of Wernicke's encephalopathy." Journal of Neurology, Neurosurgery & Psychiatry 62.1 (1997): 51-60.

Harper, Clive G., et al. "Prevalence of Wernicke-Korsakoff syndrome in Australia: has thiamine fortification made a difference?." Medical Journal of Australia 168.11 (1998): 542-544.

Thomson, Allan D., et al. "The Royal College of Physicians report on alcohol: guidelines for managing Wernicke’s encephalopathy in the accident and emergency department." Alcohol and Alcoholism 37.6 (2002): 513-521.

Question 25 - 2013, paper 2

With reference to thyroid function:

a) Briefly outline the thyroid function/hormone profile expected in the sick euthyroid syndrome or non-thyroidal illness syndrome (NTIS).

b) For each of the following drugs, list its effect(s) on thyroid function.

  • Amiodarone
  • Propranolol
  • Glucocorticoids
  • Opiates

c) Briefly outline your pharmacological approach to the treatment of thyrotoxic crises. Include in your answer the rationale for each drug used.

College Answer

a)

  • Low serum total T3 is most commonly observed-mean values are 40% of normal.
  • Free T3 is also reduced but less so.
  • Reverse T3 (rT3) is increased. Low T3 is caused by a reduced peripheral conversion of T4 to T3 secondary to inhibition of type 1 5’-deiodinase.
  • Serum T4 and TSH may transiently rise then return to normal.
  • On recovery T3 and rT3 return to normal.

b)

i. Amiodarone 
Inhibition of peripheral conversion T4 to T3

ii. Propranolol 
Inhibition of peripheral conversion T4 to T3

iii. Glucocorticoids

Inhibition of peripheral conversion T4 to T3

Suppression of TSH secretion

iv. Opiates 
Suppression of TSH secretion

c)

A sequential, multidrug approach is vital and the order of therapy is important. Three pathways need consideration-halting synthesis, preventing release of stored hormone and blockade of peripheral effects including blocking conversion of T4 toT3 as well as control of adrenergic symptoms.

Halting synthesis:

First line therapy with Thionamides- thiouracils (Propylthiouracil or PTU) and or imidazoles (methimazole and carbimazole) may be used. Both block thyroperoxidase coupling of idotyrosine residues in formation of T4 and T3.PTU (not imidazoles) will also block peripheral conversion of T4 to T3. 
Both given gastrically/PO/retention enema.

Halting release:

Thionamides block synthesis only but not secretion of preformed glandular stores of hormone. Separate treatment is needed to inhibit proteolysis of colloid and continuing release of T3 and 4. Inorganic iodine therapy either with orally administered Lugol solution or potassium iodide should be used. Iodine should only be used 30 -60 minutes

AFTER administration of Thionamides since hormone synthesis may be stimulated. 
Alternatives include Li Carbonate and some of the older radiographic contrast agents.

Blocking peripheral action: 
B blockade is essential to control peripheral actions of thyroid hormone.

Propranolol is commonly used either gastrically or IV. A drop in T3 levels may be seen with its use (decreases T3-T4 conversion). Glucocorticoids have a role in that they also block conversion of T4 to T3 and may treat any relative adrenal or vasomotor insufficiency that occurs.

Discussion

The sick euthyroid syndrome is discussed in greater detail elsewhere.

In brief, the TFT abnormalities are:

  • T3: low
  • rT3: high
  • T3/rT3 ratio: low
  • T4: high ...or normal
  • TSH: high ...or normal

The drugs which affect thyroid metabolism are also discussed in another chapter("The influence of drugs on thyroid function")

In short:

  • Amiodarone decreases the peripheral conversion of T4 to T3. It can either inhibit thyroid gland synthetic function, or it can stimulate them (particularly when it causes a thyroiditis). It can also decrease the clearance of T4.
  • Propanolol merely inhibits the peripheral conversion of T4 to T3
  • Corticosteroids decrease the secretion of TSH, and inhibit the peripheral conversion of T4 to T3
  • Opiates merely inhibit the secretion of TSH.

In not so short:

Drugs Which Affect Thyroid Function
~Organised by Their Effect on Thyroid Hormones~
TSH Inhibition of release

Dopamine

Dobutamine

Corticosteroids

Octreotide

Opiates

Stimulation of release

Metaclopromide

Antipsychotics, especially amisulpiride

T3 and T4 synthesis Inhibition of thyroid synthetic function

Thiouracils (eg. propylthiouracil)

Imidazoles (eg. carbimazole)

Lithium carbonate

Amiodarone

Thalidomide

Stimulation of thyroid synthetic function

Inorganic iodine (eg. potassium iodide) - if you have a normal thyroid gland

Iodinated contrast agents (high iodine content)

Amiodarone

T3 and T4 release from the thyroid gland Inhibition of release

Inorganic Iodine (eg. potassium iodide)

Iodinated contrast agents (high iodine content)

Stimulation of release

Amiodarone (by thyroiditis)

Conversion of T4 into T3 Inhibition of conversion

Amiodarone

Propanolol

Corticosteroids

Thiouracils (eg. propylthiouracil)

Stimulation of conversion

Sorafenib

Selenium (a cofactor in T4-T3 conversion; selenium supplementation will not result in a supranormal T3 level - merely a return to normal)

Transport of thyroid hormones by binding to thyroid-binding globulin (TBG)

Increased TBG levels

(thus decreased free T3)

Oestrogens

Tamoxifen

5-fluorouracil (5-FU)

Heroin

Methadone

Decreased TBG levels

(thus increased free T3)

Androgen hormones

Corticosteroids

Niacin (nicotinic acid)

Increased binding of T4 to TBG

Estrogens, particularly in the setting of pregnancy

Decreased binding of T4 to TBG (by displacement)

Aspirin and salicylates in general

Frusemide (and ethacrynic acid)

Heparin

Clearance of T4 Increased clearance

Phenytoin

Carbamazepine

Rifampicin

Phenobarbital

Decreased clearance

Amiodarone

Glycosylflavones in millet-rich diets of the poor in the developing world, or in the weird hippies who think it is healthy to emulate them.

The management of thyrotoxic crisis is well summarised by the college answer, but could be whittled down to point-form to improve the cerebral dwell-time among time-poor exam candidates:

  • Prevent synthesis of T3 and T4:
    • Thiouracils: propylthiouracil - blocks synthesis of T3 and T4 as well as peripheral T4-T3 conversion
    • Imidazoles: carbimazole - block synthesis of T3 and T4
  • Prevent T3 and T4 release:
    • Inorganic iodine therapy, eg. potassium iodide (given after synthesis is blocked)
  • Block peripheral T3 and T4 activity:
    • β-blockade: propanolol (which also decreases T4-T3 conversion)
    • Corticosteroids: also decrease T4-T3 conversion

For those uncomfortable with the austere minimalism of point-form, an extensive rambling digression is also available.

 

References

UpToDate has an excellent entry on this topic, for the paying customer.

Alternatively, one can attempt to piece things together from free-full-text articles, and from this Life In The Fast Lane summary.

Zargar, A. H., et al. "Prevalence and pattern of sick euthyroid syndrome in acute and chronic non-thyroidal illness-its relationship with severity and outcome of the disorder." JOURNAL-ASSOCIATION OF PHYSICIANS OF INDIA 52 (2004): 27-32.

Peeters, Robin P., et al. "Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients." Journal of Clinical Endocrinology & Metabolism 88.7 (2003): 3202-3211.

Baruah, M. P., and R. J. Singh. "Effects of drugs on thyroid function." Thyroid Research and Practice 9.1 (2012): 3.

Question 27 - 2013, paper 2

a) Outline the metabolic changes seen in:

  • Starvation
  • Stressed state

b) List the consequences of underfeeding in the critically ill.

College Answer

a)

Starvation:

Overall an adaptive hypometabolism whereby fat is used as the primary energy fuel and protein is relatively spared. (Essential point)

Increase in lipolysis and ketosis with marginal increase in catabolism, glycogenolysis or gluconeogensis.

Mobilization of protein, glucose and lipids is passive as a result of decrease in insulin levels.

After 24-48hrs gluconeogenesis does increase from peripherally released amino acids and glycerol (from lipolysis) -supplies glucose dependant tissues e.g. brain, immune system and renal medulla.

Beyond 48hrs ketosis occurs and FFAs are used for energy, which minimizes the need for amino acids and so preserves muscle.

Decrease energy expenditure with stable albumin initially. Urine urea low if adequate protein and energy stores.

Stress:

Endogenous ‘stress’ mediators such as cortisol, catecholamines, GH, glucagon and cytokines are increased and contribute to the pattern of metabolism and mobilisation of the fuel required

Catabolism, glycogenolysis, and gluconeogenesis increased. Lipolysis with no increase in ketosis.

Mobilisation of protein is an active process. Energy expenditure is active.

Albumin levels drop precipitously.( negative acute phase reactant)

Gluconeogenesis decoupled from hormone control so can increase blood glucose levels Urine urea increases (>10g/day)

b)

  • Impaired immune function
  • Increased incidence of infection
  • Weakness and fatigue
  • Decreased ventilatory drive
  • Prolonged mechanical ventilation
  • Poor wound healing
  • Muscle breakdown
  • Depression and apathy
  • Prolonged ICU and hospital stay

Discussion

The physiological responses to starvation and the stress of critical illness  are discussed elsewhere in gratuitous detail:

In point form, the answer would resemble this:

Starvation response:

  • Characterised by a switch from carbohydrate metabolism to fat metabolism, in the context of a hypometabolic state, with minimised catabolism.
  • Initially, stores of carbohydrate precursors (eg. glycogen) are depleted
  • Then, initially (in the first 24-48hrs) there is increased gluconeogenesis from amino acids and glycerol
  • Subsequently, ketogenesis takes over, and much of the body metabolic needs are met by ketone bodies and free fatty acids. This is the consequence of decreasing insulin levels, and relatively increased influence from catecholamines and cortisol.
  • Over prolonged starvation, protein catabolism begins, resulting in degradation of structurally important proteins, and organ system dysfunction

Stress response:

  • Characterised by a mobilisation of available body fuels, and a hypermetabolic hypercatabolic state.
  • Under the influence of cortisol, cytokines and catecholamines the rates of protein catabolism, lipolysis glycogenolysis and gluconeogenesis are increased.
  • There is typically no ketosis, as there is a reasonably normal insulin response to the increase in circulating metabolic substrate. However, the insulin response is not completely coupled to the BSL, and hyperglycaemia results.
  • Hyperglycaemia, uraemia and hypoalbuminaemia may result.

LITF as part of their Critical Care Compendium have excellent entries on both the starvation and stress repsonses, as a response to the stress of the 2013 CICM fellowship paper.

The consequences of malnutrition in critical illness are also discussed elsewhere.

The brief point-form list provided by the college will perhaps suffice.

In short, the consequences of malnutrition in critical illness are as follows:

  • Poor wound healing
  • Impaired immune function and increased risk of sepsis
  • Muscle wasting due to protein catabolism:
    • Decreased ventilatory drive
    • Weakness complicating separation from the ventilator
    • Weakness complicating physiotherapy and mobilisation
      • Exposure to the complications of immobility, eg. DVT
  • Cardiomyopathy as a consequence of atrophy
  • Mucosal atropthy and diminished barrier function of the gut
  • Apathy and depression
  • Increased duration of ICU stay
  • Increased in-hospital mortality

References

Cahill GF; Parris, Edith E.; Cahill, George F. (1970). "Starvation in man". N Engl J Med 282 (12): 668–675.

Benedict, FG: A study of prolonged fasting. Washington DC Carnegie Institute, 1915 (Publication No. 203)

Klein S, Peters EJ, Shangraw RE, Wolfe RR. Lipolytic response to metabolic stress in critically ill patients. Crit Care Med. 1991 Jun;19(6):776-9.

Epstein, Jay, and Michael J. Breslow. "The stress response of critical illness."Critical care clinics 15.1 (1999): 17-33.

Charmandari, Evangelia, Constantine Tsigos, and George Chrousos. "Endocrinology of the stress response 1." Annu. Rev. Physiol. 67 (2005): 259-284.

Question 7.4 - 2014, Paper 1

The following haemodynamic and metabolic data were obtained from a patient admitted to the ICU with sepsis.

Pulmonary artery catheter data:

  • CI 4.2 L/min/m2
  • DO2 900 ml/min
  • VO2 190 ml/min

Indirect calorimetry data:

  • VO2 220 ml/min
  • VCO2 290 ml/min

a) Why is the VO2 different between the two methods? (Assume no measurement errors.)

b) What changes in patient management will you consider based on the indirect calorimetry data?

College Answer

a) Indirect calorimetry also measures lung oxygen consumption.


b) A high RQ suggests excess carbohydrate load. Reduce caloric intake and consider changing to a higher fat intake.

Discussion

This question is identical to Question 25.4 from the second paper of 2010.

Indirect calorimetry and the reverse Fick method are discussed in detail elsewhere.

References

Question 17 - 2014, Paper 1

a) List the features which distinguish diabetic ketoacidosis (DKA) from the hyperosmolar hyperglycaemic state (HHS).

b) Describe your specific treatment for a 62-year-old female presenting with a decreased conscious state secondary to HHS.

College Answer

a)
1. History
i. Known type 1 DM; discontinuation of insulin therapy
ii. Presentation: DKA evolves rapidly (24 hours); HHS typically days-weeks with polydipsia, polyuria and weight loss.
2. Clinical features
i. Neurological symptoms more common in HHS.
ii. Abdominal pain and hyperventilation more common in DKA.
3. Laboratory features
i. Degree of hyperglycaemia (HHS typical higher, exceeding 56 mmol/l; DKA usually < 44 mmol/L)
ii. Degree of acidosis: severe in DKA, mild in HHS
iii. Anion gap acidosis present in DKA; absent (or mild in case of concomitant lactic acidosis) in HHS
iv. Ketones: HHS small ketonuria, absent to low ketonaemia [there is sufficient basal insulin secretion to prevent ketogenesis]; both high in DKA
v. Hyperosmolality more severe in HHS, typically > 320 mosm/L
4. NOTE: Significant overlap can occur in 30% of patients – represent part of a spectrum
b)
1. Fluid replacement
i. Expect fluid replacement of up to 10 litres, but GO SLOW (replace over 48 hours)
ii. Start with isotonic crystalloids (boluses if in shock, infusion rate up to 1L/hour). Need justification for choice of fluid, while recognising there is substantial controversy in this area.
iii. Continue isotonic if serum Na+ low; change to 0.45% NaCl if serum Na+ is normal or elevated.
iv. Change to 5% dextrose with 0.45% NaCl when serum glucose reaches 15 mmol/L or below
v. Individual tailoring based on heart rate, blood pressure, peripheral perfusion, urine output
2. Insulin infusion 0.05 U/kg/hr. initially following adequate fluid resuscitation aiming for steady but slow reduction in blood sugar levels (e.g. 5 mmol/hr)
3. Electrolyte replacement
i. Expect potassium deficit even if level appears normal
ii. Give 20 - 30 mmol K+ in each Litre of fluid or use separate infusion; aim for serum K+ 4 – 5 mmol/L
iii. Phosphate depletion only requires treatment if levels are very low (e.g. < 0.3 mmol/L) or symptomatic (Ref: BMJ best practice)
4. Treat possible precipitating cause (infection? need for broad spectrum antibiotics? Think about underlying precipitant in this case – there is a long list of possible causes (e.g. pancreatitis). What about drugs [both β blockers and HMGCo-A reductase inhibitors have been associated with HHS. Other common precipitating drugs e.g. antipsychotics, steroids…] Does she even have diabetes? [Check HbA1C].
5. Thromboprophylaxis mandatory – consider risks and benefits of heparin infusion.

6. Monitor
i. Haemodynamic situation
ii. Mental state
iii. Urine output
iv. Levels of glucose and electrolytes every 1 – 4 hours
v. Levels of ketones in DKA
7. Consider CT brain scan (possibility of ischaemic stroke).

Discussion

a)

In summary:

  • DKA presents with acidosis as the major feature
  • HONK presents with hyperglycaemia as the major feature
Discriminating Between HONK and DKA
Domain

Features suggestive of DKA

Features suggestive of HONK

History
  • Known Type 1 diabetic
  • Rapid clinical course
  • Abdominal pain
  • Known Type 2 diabetic
  • Prolonged course
  • Polydipsia, polyuria, weight loss
Examination
  • Tachypnoea
  • Normal level of consciousness, or only slightly decreased
  • Coma
  • Seizures
Biochemistry
  • Severe acidosis
  • Severe ketosis
  • Mild hyperglycaemia
  • Renal function normalises rapidly
  • Mild acidosis
  • Little ketosis; mainly lactate is raised
  • Severe hyperglycaemia
  • Established renal failure

b)

A stereotypical approach to management is offered below:

  1. Assess airway patency. Intubate to protect the airway if comatose.
  2. Ventilate with mandatory mode initially; aim for normocapnea if the metabolic acidosis is not particularly severe.
  3. Insert arterial line for frequent sampling and haemodynamic monitoring.
    Insert central line to manage electrolyte and fluid infusions.
    Check ECG/serial enzymes  for MI (common complication)
    Expect a 200ml/kg total water deficit
    Commence fluid resuscitation:
    1. 15-20ml/kg in the first hour
    2. 4-14ml/kg in the second hour (of 0.45% NaCl)
    3. 4-14ml/kg again in the third hour (use 0.9% NaCl if the sodium is low)
    4. When glucose is under 15mmol/L, start 5% dextrose 100-250ml/hr
  4. May require benzodiazepines or anticonvulsants if the presentation history included seizures.
    May require a head CT venogram to rule out dural sinus thrombosis / venous infarction
  5. Watch for a precipitous drop in serum osmolality.
    A safe drop is 3–8 mOsm/kg/h
    Correct electrolyte deficit:
    1. Sodium deficit: 5-13mmol/kg
    2. Potassium deficit: 5-15mmol/kg
    3. Chloride deficit: 3-7mmol/kg
    4. Phosphate deficit: 1-2mmol/kg
    5. Magneisum deficit: 1-1.5mmol/Kg
    6. Calcium deficit: 1-2mmol/Kg 
  6. Monitor renal function and consider dialysis
  7. Insulin therapy may not be required, and may even be dangerous.
    BSL may decrease at a satisfactory rate with fluid resuscitation alone.
  8. May require anticoagulation for dural sinus thrombosis.
  9. May require antibiotics, given that infection is a common precipitant.
    A septic screen should be sent.

Key issues of "specific therapy:

  • Fluid resuscitation
  • Electrolyte replacement
  • Careful slow reduction of serum osmolality
  • Investigation for complications:
    • Myocardial infarction
    • Stroke
    • Cerebral oedema and brain injury
    • Venous thrombosis
  • Management of other possible precipitating causes:
    • Infection, systemic inflammatory response
    • Intracranial haemorrhage
    • Hepatic encephalopathy
    • Drugs, including illicit substances, steroids, phenytoin, diuretics, TPN, lithium

References

UpToDate has a nice summary of this topic for the paying customer.

Oh's Intensive Care manual: Chapter 58  (pp. 629) Diabetic  emergencies  by Richard  Keays

Umpierrez, Guillermo E., Mary Beth Murphy, and Abbas E. Kitabchi. "Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome." Diabetes Spectrum15.1 (2002): 28-36.

ARIEFF, ALLEN I., and HUGH J. CARROLL. "Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of theraphy in 37 cases." Medicine 51.2 (1972): 73-94.

Alberti, K. G. M. M., et al. "Role of glucagon and other hormones in development of diabetic ketoacidosis." The Lancet 305.7920 (1975): 1307-1311.

Kitabchi, Abbas E., et al. "Management of hyperglycemic crises in patients with diabetes." Diabetes care 24.1 (2001): 131-153.

Foster, Jennifer Ruth, Gavin Morrison, and Douglas D. Fraser. "Diabetic ketoacidosis-associated stroke in children and youth." Stroke research and treatment 2011 (2011).

Edge, J. A., et al. "The risk and outcome of cerebral oedema developing during diabetic ketoacidosis." Archives of disease in childhood 85.1 (2001): 16-22.

Woodrow, G., A. M. Brownjohn, and J. H. Turney. "Acute renal failure in patients with type 1 diabetes mellitus." Postgraduate medical journal 70.821 (1994): 192-194.

Bonfanti, R., et al. "Disseminated intravascular coagulation and severe peripheral neuropathy complicating ketoacidosis in a newly diagnosed diabetic child." Acta diabetologica 31.3 (1994): 173-174.

Chua, Horng-Ruey, et al. "Plasma-Lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis." Journal of critical care 27.2 (2012): 138-145.

Stowe, Michele L. "Plasma-Lyte vs. Normal Saline: Preventing Hyperchloremic Acidosis in Fluid Resuscitation for Diabetic Ketoacidosis." (2012).

Jivan, Daksha. "A comparison of the use of normal saline versus Ringers lactate in the fluid resuscitation of diabetic ketoacidosis." (2013).

Basnet, Sangita, et al. "Effect of Normal Saline and Half Normal Saline on Serum Electrolytes During Recovery Phase of Diabetic Ketoacidosis." Journal of intensive care medicine 29.1 (2014): 38-42.

Hillman, K. "Fluid resuscitation in diabetic emergencies—a reappraisal."Intensive care medicine 13.1 (1987): 4-8.

Wagner, Arnd, et al. "Therapy of severe diabetic ketoacidosis. Zero-mortality under very-low-dose insulin application." Diabetes care 22.5 (1999): 674-677.

Chiasson, Jean-Louis, et al. "Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state." Canadian Medical Association Journal 168.7 (2003): 859-866.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes a consensus statement from the American Diabetes Association." Diabetes care 29.12 (2006): 2739-2748.

Question 30.1 - 2014, Paper 1

You are asked to review an 80-year-old female in the Emergency Department who has 
presented with a depressed conscious state. She has ischaemic heart disease and 
paroxysmal atrial fibrillation. Her medication includes aspirin, metoprolol, and 
amiodarone.
On examination she has a temperature of 34.5°C, she is drowsy with a GCS of 10, a 
pulse of 50 beats/min and a blood pressure 90/40 mmHg. CT brain scan shows age 
related atrophy. The blood results are as follows:

 

Parameter

Patient Value

Normal Adult Range

Sodium

120 mmol/L*

137 – 145

Potassium

4.0 mmol/L

3.5 – 5.0

Urea

6.0 mmol/L

2.5 – 7.5

Creatinine

90 micromol/L

50 – 100

Measured Osmolality

255 mmol/kg*

280 – 300

Glucose

3.0 mmol/L*

3.5 – 6.0

CK

1000 U/L*

20 – 200

Cholesterol

7.2 mmol/L

3.0 – 5.5

a) Give the likely diagnosis and the underlying cause to account for all these blood results.
 
b) List four measures essential for the specific management of this patient.

College Answer

a)
Hypothyroidism secondary to amiodarone toxicity.

b)
 Commence thyroxine, probably low dose (50 – 100ug/day and slowly increase) or consider T3 orally or intravenously (give cautiously).
 Commence on glucocorticoids (Hydrocortisone 50 mg 6 hourly).
 Correct the hypoglycaemia with intravenous glucose.
 Correct the hyponatraemia very slowly with hypertonic saline to sodium 130 mmol/L (no more than 2 mmol/L per hour).

Discussion

The generic approach to myxoedema coma is offered here.  Clearly, that is what is happening here: the patient is bradycardic, hypotensive and hypothermic, with hyponatremia, a raised CK and high cholesterol.

Management of this condition consists of the following steps:

  • Replace thyroid hormone - preferably IV
    • loading dose is 300-400μcg
    • a rising body temperature and normalising cardiovascular parameters alert you to the success of your management strategy
  • Replace corticosteroids - there is usually a concomitant adrenal insufficiency. One would use a "stress dose".
  • Correct the sodium: this is usually a hypervolemic hyponatremia which resembles that of CCF (in fact, it is because of exactly the same mechanism: poor cardiovascular performance leads to ADH and aldosterone driven retention of water and sodium, with a resulting hypervolemic hyponatremia. Because the patient is usually obtunded, one is obliged to correct a particularly low sodium with hypertonic saline, being careful not to demyelinate the CNS.
  • Good solid supportive management:
    • Establish an airway if this is needed
    • Maintain normoxia and normocapnea with the ventilator
    • Maintain normotension to support organ system perfusion, with a catecholamine infusion
    • Correct the Na+ deficit - consider using water restriction alone.
    • Correct hypoglycaemia
    • Correct hypothermia with warming blanket

For interest and reference, the generic manifestations of myxoedema coma are tabulated below:

Clinical Manifestations of Myxoedema Coma

Cardinal features

Cardiovascular collapse, shock

Hypothermia

Decreased level of consciousness

Associated examination findings

A "puffy" face

Macroglossia

Periorbital oedema

Coarse, sparse hair

Non-pitting oedema

Goitre

Biochemistry

  • Hypothyroidism
  • Hypercapnea
  • Hypoxia
  • Hyponatremia
  • Hyposmolarity
  • Elevated protein levels on LP
  • High serum cholesterol

Other findings

Decreased QRS voltages

Prolonged QT

Bradycardia

Pericardial effusion

References

Question 25 - 2014, paper 2

A 76-year-old male is admitted to the ICU with acute lung injury causing respiratory failure, secondary to acute pancreatitis.

a) Outline how you would establish enteral nutrition in this patient, including in the answer your nutritional targets.

b) List the complications that need to be considered with the use of enteral nutrition.

c) When might you consider parenteral nutrition?

College Answer

a)
Access: Nasojejunal tube although nasogastric (appears safe and well tolerated)
Any reasonable approach OK

1) Determine target rate for enteral nutrition, commencing 30ml/hour and increasing as tolerated and
delivered as a continuous infusion to maximise chances of achieving nutritional target rates.

2) Prokinetics could be considered if large aspirates are experienced. A feeding protocol should be
utilised to maximise the chances of achieving nutritional target rates.

3) Nutritional targets in the critically ill can be determined by either indirect calorimetry, predictive
equations (e.g.: Harris-Benedict equation) or simplistic formulae (25-30kcal/kg/day) with at least 1.2-
2g/kg/day of protein.

b)

1) Tube complications

  • Misplacement: Pneumothorax, inadvertent pulmonary infusion
  • Sinusitis
  • Pressure areas on nose/lip
  • Trauma to nasopharynx, oesophagus, stomach and haemorrhage

2) Feed complications

  • Inadequate caloric intake from gastric stasis
  • Diarrhoea
  • Ventilator associated pneumonia
  • Aspiration
  • Electrolyte abnormalities
  • Hyperglycaemia

c)
Despite following a rigorous enteral feeding protocol, there is inadequate caloric intake after five
days. Combined enteral and parenteral nutrition to meet targets may be beneficial.
NEJM article June 2011 comparing early (day 2) with late (day 8) TPN in ICU patients not meeting
nutritional targets with EN showed better outcomes in late TPN group

Discussion

a) Outline how you would establish enteral nutrition in this patient, including in the answer your nutritional targets.

For this, the candidate could fall back on either the ASPEN guidelines (2009) or the ESPEN guidelines (2002).

A comparison of these guidelines is offered below.

A Comparison of Nutrition Guidelines for Severe Acute Pancreatitis

ASPEN guidelines

  • For mild or moderate pancreatitis:
    • It is safe to fast these people for up to 7 days! They "... do not require nutrition support therapy (unless ... there is failure to advance to oral diet within 7 days)" - pp. 207
  • For severe pancreatitis:
    • Enteral (nasogastric) feeding should commence as soon as initial resuscitation is complete.
    • Feed tolerance may be enhanced by the following measures:
      • Early enteral nutrition (to minimise ileus)
      • Pushing the NGT distally (into the jejunum) -  it doesn't seem to matter in terms of pain or pancreatitis severity, but feed tolerance may improve
      • Changing to elemental feeds (small peptides, medium-chain triglycerides)
      • Using continuous infusion rather than bolus feeding
    • TPN should not be initiated until after you have made a solid attempt with enteral nutrition for at least 5 days, i.e. when it is obvious that there is profound enteral feed intolerance in spite of various "tolerance-enhancing " measures.

ESPEN guidelines :

  • For mild or moderate pancreatitis:
    • "There is no evidence that either enteral or parenteral nutrition has a beneficial effect on clinical outcome"
  • For severe pancreatitis:
    • Enteral feeding should be attempted in all patients
    • Nutritional requirements should be:
      • 25-35 kcal/kg of total body weight per day
      • 1.2 to 1.5g/kg of protein
      • 3-6g/kg of carbohydrate
      • go easy on the lipiuds (up to 2g/kg)
    • Start feeding via a jejunal tube (remember, this is a 2002 statement)
    • If enteral nutrition is poorly tolerated and caloric goals are not being achieved, add some TPN but keep going with small-volume or elemental enteral feeding

The college seems to be using generic guidelines for nutrition in the critically ill in their answer, rather than any specific pancreatitis guidelines. "Any reasonable approach OK".

As far as specific guidelines go, apart from the elderly 2002 ESPEN position and the somewhat less elederly 2009 ASPEN statement, we can turn to the  2012 "International consensus guidelines for nutrition therapy in pancreatitis."

In summary, these guidelines make the following recommendations:

  • For mild or moderate pancreatitis:
    • Fast for the first 3-4 days
    • Advance to normal diet after this
    • Only progress to enteral nutrition of the patient has been fasted for 5-7 days
  • For severe pancreatitis:
    • EN is preferable to PN
    • Tube position does not matter (gastric vs jejunal)
    • Elemental feeds are preferred
    • Nutritional requirements are 25-35kcal/kg/day, and 1.2-1.5g/kg/day of protein
    • When to use parentral nutrition? These guidelines are much less prescriptive than previous statements. "when EN is contraindicated or not well tolerated", they say.

b) List the complications that need to be considered with the use of enteral nutrition.

Complications of enteral nutrition are well describe in a chapter from the "Required reading" section.
In brief, the complications are:

  • Aspiration
  • Diarrhoea
  • Constipation
  • Dehydration
  • Malnutrition (owing to intolerance)
  • Complications relating to the feeding tube:
    • Poor placement, eg. into the lung
    • Oesophageal or gastric perforation
    • Increased tendency towards gastro-oesophageal reflux
    • Pressure areas due to prolonged tube dwell time (eg. pressure on the nares)
    • Sinusitis (for nasal tubes)
    • Poor oral hygiene( for oral tubes)
    • Oesophageal stricture
    • Discomfort in the awake patient

c) When might you consider parenteral nutrition?

The college refer to a certain 2011 NEJM study, which I assume is the "early vs late PN" trial by Casaer et al. "Late initiation of parenteral nutrition was associated with faster recovery and fewer complications", they said. Of course, that is not a study which regarded pancreatitis specifically.

The ASPEN guidelines recommend you wait for 5 days of good-quality EN trials before you resort to TPN. Both ASPEN and ESPEN recommend the addition of TPN if it is clear that nutritional goals are not being met. The 2012 international guidelines recommend PN "when EN is contraindicated or not well tolerated".

References

Casaer, Michael P., et al. "Early versus late parenteral nutrition in critically ill adults." N Engl J Med 365.6 (2011): 506-517.

ASPEN guidelines

Specifically, section K of the 2009 statement

ESPEN guidelines :
specifically,
MACFIE, J., and ESPEN CONSENSUS GROUP. "ESPEN guidelines on nutrition in acute pancreatitis." Clinical Nutrition 21.2 (2002): 173-183.

Mirtallo, Jay M., et al. "International consensus guidelines for nutrition therapy in pancreatitis." Journal of Parenteral and Enteral Nutrition (2012): 0148607112440823.

Question 7 - 2015, Paper 1

A 26-year-old female is admitted to the ICU post operatively with faecal peritonitis as a result of multiple bowel perforations secondary to Crohn’s disease. She has had the majority of her small bowel resected and is to be prescribed total parenteral nutrition (TPN).

a) Describe the available methods to estimate total energy expenditure in critically ill patients and outline their advantages and limitations. (70% marks)

The basal energy expenditure of this patient is determined to be 2000 kcal (8400 kJ) / day and she weighs 50 kg.

b) Describe how you would prescribe her TPN. (30% marks)

College Answer

a)

Empiric:

  • This may be based just upon weight or surface area – Most critically ill patients will have requirements of approx. 25 kCal/kg/day.
  • Advantages – quick, simple and cheap. Universally available
  • Disadvantages – may be inaccurate

Predictive equations:

  • Many versions such as Harris-Benedict, PennState, Faisy etc., based upon various direct measurements.
  • Advantages – quick, simple and cheap. Universally available
  • Disadvantages – Inaccuracy, usually underestimate requirements. Need for multiple correction factors.

Indirect Calorimetry:

  • Measures oxygen uptake and carbon dioxide production using the assumption that all of the oxygen uptake is used for oxidation of substrates.
  • Advantages: Most accurate method. Bedside monitor than can be integrated with ventilator.
  • Disadvantages: Expensive; requires technical expertise, limited availability. Inaccurate in the setting of high FiO2 or PEEP, leaks in circuit, recent ventilator changes, changes in oxygen concentration, hemodynamic instability, temperature changes or haemodialysis.

Fick method

  • Determines oxygen consumption from indwelling pulmonary artery catheter, then uses caloric value for oxygen to calculate energy expenditure.
  • Advantages: More accurate than predictive equations, cheaper and more available than indirect calorimtery.
  • Disadvantages: Highly invasive. Does not account for pulmonary oxygen consumption.

b)

Standard TPN delivery 2 litre bags

If the total non-protein kCal required is 2000/day, ratio for CHO to fat is 70:30

Dextrose:

  • 1400Kcal
  • 824mls (412g dextrose at 50% solution at 3.4Kcal/gram and requiring 1400KCal)

Lipid:

  • 600Kcal
  • Using 10% lipid (1.1kcal/ml), will need 545mls 10% lipid
  • Adjust if using propofol as sedation (approx. 1kcal/ml as fat)

Protein 1.5-2g/kg/day

  • 2 x 50 = 100 grams/day of amino acids
  • Using 10% solution amino acid solution (100g/L) 1 Litre of 10% amino acid solution

Electrolyte, vitamins and trace elements are added to the solution in a standard fashion, but may be individually tailored to the patient’s requirements.

Additional comments:
Other  valid  methods  for  measurement  of  energy  expenditure  were  given  credit.  Detail  on
nutritional requirements was lacking in some answers

Discussion

a) Methods to estimate energy expenditure:

A Comparison of Methods
to Estimate Metabolic Energy Requirements
in Critical Illness
Method Physiology Advantages Limitations
Predictive  Equations
  • Calculation of metabolic requirements made on the basis of empirical experimental data
  • Typically, input information is gender, height, age and weight
  • Specific metabolic abnormalities (eg. burns or sepsis) can be factored in as multipliers
  • Range from complex equations to simple (25cal×kg per day) formulae
  • Cheap
  • Quick
  • Requires no expertise
  • Accurate for many circumstances, particularly straightfrward ICU patients
  • Predict requirements, i.e. useful goals of management
  • Tend to be inaccurate
  • The sicker the patient, the less accurate the predictions
Reverse Fick method
  • Determines oxygen consumption from pulmonary artery catheter:
  • Oxygen utilisation in metabolic processes is correlated to the metabolic rate.
  • Knowing the cardiac output, one can calculate the oxygen consumption of the organism from the arteriovenous oxygen content difference.
  • Accurate - more so than predictive equations
  • Reproduceable
  • Cheaper than the metabolic cart, and more widely available
  • Invasive
  • Does not incorprate the metabolic requirements of the lungs
  • Inaccurate in severe pulmonary pathology, eg. ARDS
Indirect calorimetry
  • Oxygen uptake and CO2 production are monitored by a specialized module attached to the ventilator
  • From the consumption of oxygen, one can estimate the metabolic rate (assuming all oxygen is used to oxidise substrate)
  • The most accurate method of determining energy use
  • Module can integrate with the ventilator

Indications may include:

  • Extremes of obesity
  • Extremes of core body temperature (eg. in hypothermia)
  • Extremes of age
  • Very expensive
  • It makes the assumpation that all oxygen use is for oxidation of substrate
  • It is a complex procedure and it requires special equipment
  • It is a measure of metabolic fuel consumption, not demand.
  • It is not associated with any clinical benefit.
  • Inaccurate at high PEEP
  • Inaccurate with high FiO2
  • Invalid in the presence of circuit leak
  • Difficult to interpret if the ventilator settings keep changing rapidly

b) 

How do you prescribe TPN?

  • Usually the bag is about 2L
  • Carbohydrate: fat ratio: 70:30.
  • Protein is also required: 1.5-2g/kg/day
    • Fat is supplied as 10% lipid emulsion, at  1.1 kcal/ml
    • Carbohydrate is supplied as 50% dextrose, at 3.4 kcal/gram, or 1.7 kcal/ml
    • Protein is supplied as 10% amino acid solution, as 100g/L
  • Normal requirements are 25 kcal/kg/day
  • Thus, 17.5 kcal/kg/day is supplied by carbohydrate, and 7.5 kcal/kg/day is supplied by fat
  • Thus, a normal ICU patient getting 2000 kcal/day requires the following dose of TPN:
    • 1400 kcal/day of 50% dextrose (which makes about 824 ml)
    • 600 kcal/day of 10% lipid emulsion (which makes about 545ml)
    • 100 g/day of protein, which makes about 1000ml of 10% amino acid solution

This discussion of TPN is prescription is brief and offers little in addition to the college answer, but this is perhaps for the beast, as the authors' tendency to hold forth extensively on TPN is clearly demonstrated eslewhere. The 2014 ASPEN Clinical Guidelines on "Parenteral Nutrition Ordering, Order Review, Compounding, Labeling, and Dispensing" are probably the most important official resource for this answer.

References

Fink's Textbook of Critical Care: Chapter 94: Critical Care Nutrition by JUAN B. OCHOA, DAREN K. HEYLAND, STEPHEN A. McCLAVE.

Boullata, Joseph I., et al. "ASPEN Clinical Guidelines Parenteral Nutrition Ordering, Order Review, Compounding, Labeling, and Dispensing." Journal of Parenteral and Enteral Nutrition (2014): 0148607114521833

Singer, Pierre, et al. "ESPEN guidelines on parenteral nutrition: intensive care."Clinical Nutrition 28.4 (2009): 387-400.

Martindale, Robert G., et al. "Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition: Executive Summary*." Critical care medicine 37.5 (2009): 1757-1761.

Casaer, Michael P., et al. "Early versus late parenteral nutrition in critically ill adults." N Engl J Med 365.6 (2011): 506-517.

Marik, Paul E., and Michael Hooper. "Parenteral versus enteral nutrition in the critically ill patient: a re-analysis of a flawed meta-analysis." Intensive care medicine 39.5 (2013): 979-980.

Doig, Gordon Stuart. "Parenteral versus enteral nutrition in the critically ill patient: additional sensitivity analysis supports benefit of early parenteral compared to delayed enteral nutrition." Intensive care medicine 39.5 (2013): 981-982.

Doig, Gordon S., et al. "Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial." JAmA 309.20 (2013): 2130-2138.

Fremont, Richard D., and Todd W. Rice. "How soon should we start interventional feeding in the ICU?." Current opinion in gastroenterology 30.2 (2014): 178.

Stawny, M., et al. "Pharmaceutical point of view on parenteral nutrition." The Scientific World Journal 2013 (2013).

Waitzberg, Dan L., Raquel Susana Torrinhas, and Thiago Manzoni Jacintho. "New parenteral lipid emulsions for clinical use." Journal of Parenteral and Enteral Nutrition 30.4 (2006): 351-367.

Question 13 - 2015, Paper 2

Outline the key issues in the post-operative management of a super-obese (BMI 59) patient with type 2 diabetes following sleeve gastrectomy.

College Answer

Maintain ABCs

  • Monitoring of vital signs
  • SpO2 and ABGs for PCO2
  • Use of CPAP post op if required. May use patient’s own CPAP device but issues with leak, need for oxygen supplementation, etc. may require ICU machine usage
  • Monitor electrolytes especially K+, urine output

Maintain hydration

  • Appropriate fluids can be Hartmanns, 5% glucose, dextrose saline all of which will provide an energy substrate and avoid starvation ketosis

Maintain euglycaemia (BSL 4-10)

  • Insulin either as an intravenous infusion or intermittent sub-cut bolus to maintain BSL 4-10. No evidence even in this group to support tight BSL control

Avoid starvation ketosis

  • Post-operative oral fluids or diet should be discussed with surgical team and appropriate diet commenced as soon as practical

Housekeeping

  • Adequate analgesia avoiding opioids
  • DVT prophylaxis- mechanical prophylaxis for all with low molecular weight heparin if no contraindications.

Positioning

  • Ensure appropriate posture/positioning in bed to optimize respiratory function and minimize gastro-oesophageal reflux and for pressure care
  • Early mobilization is essential. Goals should be set in conjunction with physiotherapy staff including, for example, sitting out of bed within 18 hours, walking within the next 24 hours.
  • Special bariatric beds required and may also need large chairs so patients can be sat out of bed. Hoists etc. / manual handling training for staff

Surgical

  • Test for leak as per surgical protocol e.g. ice water test, gastrograffin swallow.

Additional Examiners’ Comments:

Candidates who scored well mentioned specific challenges and considerations (rather than just generic “ABCs”) and suggested strategies to address these.

Discussion

The best resource for this was actually the UpToDate article on bariatric surgery. The college answer had some fairly generic suggestions (eg. "Monitoring of vital signs""appropriate diet commenced as soon as practical"as if without such recommendations the trainees would leave their bariatric patients unfed and unmonitored.

In trying to separate these generic issues from the real unique problems of post-operative care for the super-obese patient, the following summary was formed:

Avoidance of opiate excess

  • Already the medulla is less sensitive to hypoxia and hypercapnea, from years of sleep apnoea.
  • The addition of opiates is likely to upset this further
  • The use of remifentanil may be appropriate while the patient is intubated, to avoid a residual opiate respioratory drive depression when it comes time to extubate them.

Mechanical ventilation for the morbidly obese patient

  • The weight of the chest wall contributes to a decreased respiratory compliance
  • A higher PEEP and Paw is the expected norm.
  • Still, one should try to keep the Pplat under 35 cmH2O
  • Oesophageal manometry may help to calculate the actual transpulmonary pressure
  • You need a higher PEEP than you think. A recent study (Pirrone et al, 2016) found poorer lung compliance with clinician-set PEEPs (10-14 cmH2O) among  patients who were all of horrendous size (BMI >50). The best PEEP settings were actually around 20cmH2O.

Staged extubation

  • If the elective airway was genuinely difficult, emergent re-intubation may be impossible.
  • A hollow exchange catheter may be used to make re-intubation possible
  • After the endotracheal tube is removed, the exchange catheter guidewire may remain in situ for some hours
  • If the patient is breathing comfortably and a satisfactory period has passed, the guidewire may be removed.

Extubation on to NIV

  • CPAP after extubation improves lung function by preventing post-extubation atelectasis (Neligan et al, 2009)
  • The patient may already be on CPAP nocturnally, or at least have a CPAP machine with which they are noncompliant
  • It would be helpful to extubate the patient on to their own CPAP machine
  • Alternatively, post-extubation NIV could be titrated to a "normal" PaO2 / PaCO2  for the patient.

Logistics of mobilisation postural positioning and pressure area care

  • They will need a special bed and a special chair to sit in
  • The nurses who turn them will need a special air mattress to change the position of the patient
  • The pressure area care requires more staff
  • Manual handling techniques need to be reinforced by educators
  • Lifting and cleaning may require specialised hoists
  • Mobilising them will require extra physiotherapy staff and additional equipment

References

Akinnusi, Morohunfolu E., Lilibeth A. Pineda, and Ali A. El Solh. "Effect of obesity on intensive care morbidity and mortality: A meta-analysis*." Critical care medicine 36.1 (2008): 151-158.

Marik, Paul, and Joseph Varon. "The obese patient in the ICU." CHEST Journal113.2 (1998): 492-498.

Ling, Pei-Ra. "Obesity Paradoxes—Further Research Is Needed!*." Critical care medicine 41.1 (2013): 368-369.

Gross, Neil D., et al. "‘Defatting’tracheotomy in morbidly obese patients." The Laryngoscope 112.11 (2002): 1940-1944.

Brodsky, Jay B., et al. "Morbid obesity and tracheal intubation." Anesthesia & Analgesia94.3 (2002): 732-736.

Neligan, Patrick J., et al. "Continuous positive airway pressure via the Boussignac system immediately after extubation improves lung function in morbidly obese patients with obstructive sleep apnea undergoing laparoscopic bariatric surgery." The Journal of the American Society of Anesthesiologists 110.4 (2009): 878-884.

Pirrone, Massimiliano, et al. "Recruitment Maneuvers and Positive End-Expiratory Pressure Titration in Morbidly Obese ICU Patients." Critical Care Medicine 44.2 (2016): 300-307.

Robinson, Malcolm K., et al. "The Relationship Among Obesity, Nutritional Status, and Mortality in the Critically Ill*." Critical care medicine 43.1 (2015): 87-100.

Amundson, Dennis E., Svetolik Djurkovic, and Gregory N. Matwiyoff. "The obesity paradox." Critical care clinics 26.4 (2010): 583-596.

Hutagalung, Robert, et al. "The obesity paradox in surgical intensive care unit patients."Intensive care medicine 37.11 (2011): 1793-1799.

Curtis, Jeptha P., et al. "The obesity paradox: body mass index and outcomes in patients with heart failure." Archives of internal medicine 165.1 (2005): 55-61.

Gruberg, Luis, et al. "The impact of obesity on the short-term andlong-term outcomes after percutaneous coronary intervention: the obesity paradox?." Journal of the American College of Cardiology 39.4 (2002): 578-584.

Fonarow, Gregg C., et al. "An obesity paradox in acute heart failure: Analysis of body mass index and inhospital mortality for 108927 patients in the Acute Decompensated Heart Failure National Registry.American heart journal 153.1 (2007): 74-81.

Sasabuchi, Yusuke, et al. "The dose-response relationship between body mass index and mortality in subjects admitted to the ICU with and without mechanical ventilation."Respiratory care 60.7 (2015): 983-991.

Marik, Paul Ellis. "Obesity in the ICU." Evidence-Based Critical Care. Springer International Publishing, 2015. 787-795.

Question 1 - 2016, Paper 2

a) Outline the distinguishing features that differentiate between diabetic ketoacidosis (OKA) and
hyperosmolar hyperglycaemic state (HHS). (70% marks)

b) List six possible complications seen during treatment of HHS. (30% marks)

College answer

a) 

  1. History
    1. Known type 1 DM; discontinuation of or inadequate insulin therapy in DKA
    2. HHS – history of type 2 DM +/- non-compliance
    3. Age – DKA usually younger, HHS usually older
    4. Presentation: DKA evolves rapidly (24 hours); HHS typically days-weeks with polydipsia, polyuria and weight loss.
    5. Abdominal pain may be a presenting symptom in DKA
  2. Clinical features
    1. Neurological symptoms more common in HHS. ii. Abdominal pain more common in DKA.
    2. Kussmaul respiration / hyperventilation in DKA
    3. Ketotic breath
  3. Laboratory features
    1. Degree of hyperglycemia (HHS typical higher, exceeding 56 mmol/l; DHA usually< 44 mmol/l)
    2. i. Degree of acidosis: severe in DKA, mild in HHS
    3. Anion gap acidosis present in DKA; absent (or mild in case of concomitant lactic acidosis) in HHS
    4. Ketones: HHS small ketonuria, absent to low ketonaemia [there is sufficient basal insulin secretion to prevent ketogenesis]; both high in DKA
    5. Hyperosmolality more severe in HHS, typically > 320 mosm/l
  4. NOTE: Significant overlap can occur in 30% of patients

 b) 

  1. Hypoglycaemia
  2. Hypokalaemia
  3. Hypophosphataemia
  4. Hypo or Hypernatremia
  5. Cerebral oedema (more common in DKA, has been reported in HHS), may result in decreased LOC, seizures, bradycardia and respiratory arrest
  6. Pulmonary oedema
  7. Deep venous thrombosis and pulmonary embolism
  8. Hyperchloraemic acidosis (usually not clinically significant)

Additional Examiners‟ Comments:

There was a lack of reference to clinical features. Surprisingly few candidates mentioned the presence of ketones and ketoacidosis as a distinguishing feature.

Discussion

Most intelligent people would view the presence of ketones and acidosis in ketoacidosis to be so obvious that it does not merit a mention in a serious discussion. However, it appears to have been one of the tickboxes for the marking examiners. Let that be a lesson to all us candidates. Next time in an exam answer regarding lactic acidosis, be sure to strongly stress the fact that lactate and acidaemia are cardinal features.

a)

This question closely resembles the first part of Question 17 from the first paper of 2014.

In summary:

  • DKA presents with acidosis as the major feature
  • HONK presents with hyperglycaemia as the major feature
Discriminating Between HONK and DKA
Domain

Features suggestive of DKA

Features suggestive of HONK

Demographic
  • Young
  • Known Type 1 diabetic
  • Elderly
  • Known Type 2 diabetic
History
  • Rapid clinical course
  • History of noncompliance with insulin
  • Abdominal pain
  • Shortness of breath
  • Prolonged course
  • History of noncompliance with oral antihyperglycaemic agents and insulin
  • Polydipsia, polyuria, weight loss
  • Neurological symptoms
Examination
  • Tachypnoea
  • Normal level of consciousness, or only slightly decreased
  • Coma
  • Seizures
Biochemistry
  • Severe acidosis
  • Severe ketosis
  • Mild hyperglycaemia
  • Renal function normalises rapidly
  • Mild acidosis
  • Little ketosis; mainly lactate is raised
  • Severe hyperglycaemia
  • Established renal failure

b)

The following list of complications of HHS is a combination of several sources, including local resources as well as the college answers to Question 18.1 from the second paper of 2008 and Question 13 from the first paper of 2002.

  • HHS-specific physiological abnormalities
    • Hypotension and shock
    • Metabolic acidosis
    • Coma
  • Complications arising from the HHS disease state:
    • Cardiac arrest
    • Cardiovascular collapse
    • Myocardial infarction
    • Pulmonray oedema
    • Stroke
    • Cerebral oedema and brain injury
    • Venous thrombosis (DVT, PE)
    • Aspiration
  • Complications of therapy for HHS:
    • Dysnatraemia
    • Hyperchloremia from saline administration
    • Phosphate depletion
    • Hypokalemia
    • Hypoglycaemia
    • Osmotic demyelination (Hegazi et al, 2013)

References

Hyperglycemic Comas by P. VERNON VAN HEERDEN from Vincent, Jean-Louis, et al. Textbook of Critical Care: Expert Consult Premium. Elsevier Health Sciences, 2011.

Oh's Intensive Care manual: Chapter 58  (pp. 629) Diabetic  emergencies  by Richard  Keays

Gerich, John E., Malcolm M. Martin, and Lillian Recant. "Clinical and metabolic characteristics of yperosmolar nonketotic coma." Diabetes 20.4 (1971): 228-238.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes." Diabetes care 32.7 (2009): 1335-1343.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes a consensus statement from the American Diabetes Association." Diabetes care 29.12 (2006): 2739-2748.

Hegazi, Mohamed Osama, and Anant Mashankar. "Central pontine myelinolysis in the hyperosmolar hyperglycaemic state." Medical Principles and Practice 22.1 (2013): 96-99.

Question 3.3 - 2016, Paper 2

A 52-year-old female was admitted the previous night with an altered level of consciousness that improved rapidly with administration of glucose. She is referred to ICU the following admission with confusion, ataxia and a worsening level of consciousness. Her CT head scan was normal.

The blood sugar level in the morning is 8 mmol/L on a 5% dextrose infusion at 80 ml/hr. Her full blood count from the previous night is available below:

Parameter

Patient Value

Normal Adult Range

Haemoqlobin

88 g/L*

130 - 175

White Cell Count

7.4 x 10!:1/L

4.0 - 11.0

Platelets

88 x 10!:1/L*

150 - 450

Mean Cell Volume

110 fl*

80 - 98

Mean Cell Haemoqlobin

30 pq/cell

27 - 34

Mean Cell Haemoglobin Concentration

320 g/L

310 - 360

Prothrombin time

12 sec

12 - 18

Activated partial thromboplastin time

36 sec

32 - 38

a)    What is the likely cause of her confused state?    (20% marks)

b)    What specific treatment would you institute for resolution of her mental status?    (10% marks)

c)    What blood test would support the diagnosis?    (10% marks)

College answer

  1. Wernickes encephalopathy                                                                                                
  2. Thiamine IV
  3. Red blood cell transketolase activity (reduced)                                                                                                  

Discussion

This question closely resembles Question 13.3 from the second paper of 2013 and Question 9.2  from the first paper of 2008. Each time, the college accepts "Wernicke's encephalopathy" and "100mg thiamine" as sufficient two-word responses.

The college also asks for a laboratory test. Of course, Wernicke's encephalopathy is a clinical diagnosis.  However, thiamine deficiency is readily diagnosed by the levels of red cell transketolase.   One may test the levels before and after thiamine supplementation. A low transketolase level along with a >25% rise in level following thiamine supplementation is diagnostic of thiamine deficiency.

Of note is the dose of thiamine. Historuically, the college has accepted 100mg IV daily. However, locally we give 300mg IV tds, UpToDate recommends 500mg IV tds, and Cook et al (1998) recommended 1g daily. Obviously there is disagreement about the ideal dose. A Cochrane review (Day et al, 2013) was not able to reac hany sensible conclusions about the dosage, siting methodological problems in the one and only trial which met the inclusion criteria (Ambrose et al, 2001).

References

Flynn, Alexandra, et al. "Wernicke’s Encephalopathy: Increasing Clinician Awareness of This Serious, Enigmatic, Yet Treatable Disease." The primary care companion for CNS disorders 17.3 (2015).

Thomson, Allan D., and E. Jane Marshall. "The natural history and pathophysiology of Wernicke's encephalopathy and Korsakoff's psychosis." Alcohol and Alcoholism 41.2 (2006): 151-158.

Gussow, Leon. "Myths of toxicology: thiamine before dextrose." Emergency Medicine News 29.4 (2007): 3-11.

Isenberg-Grzeda, Elie, Haley E. Kutner, and Stephen E. Nicolson. "Wernicke-Korsakoff-syndrome: under-recognized and under-treated." Psychosomatics 53.6 (2012): 507-516.\

Watson, A. J. S., et al. "Acute Wernickes encephalopathy precipitated by glucose loading." Irish journal of medical science 150.1 (1981): 301-303.

Kissoon, Niranjan. "Thiamine before glucose to prevent Wernicke encephalopathy: examining the conventional wisdom." JAMA 279.8 (1998): 583.

Day, Ed, et al. "Thiamine for prevention and treatment of Wernicke‐Korsakoff Syndrome in people who abuse alcohol." The Cochrane Library (2013).

Ambrose, Margaret L., Stephen C. Bowden, and Greg Whelan. "Thiamin Treatment and Working Memory Function of Alcohol‐Dependent People: Preliminary Findings." Alcoholism: Clinical and Experimental Research 25.1 (2001): 112-116.

Cook, Christopher CH, Phillip M. Hallwood, and Allan D. Thomson. "B Vitamin deficiency and neuropsychiatric syndromes in alcohol misuse." Alcohol and Alcoholism 33.4 (1998): 317-336.

Question 14 - 2016, Paper 2

With respect to nutritional support in the critically ill:

a) Outline how you would assess the nutritional status of a patient with suspected malnutrition. (70% marks)

b) Outline the pathophysiology of severe re-feeding syndrome. (30% marks)

College answer

a) Assessments of nutritional status: 
 
This is notoriously unreliable as there are many conditions that can alter the non-specific markers of nutritional status.  
 
A good history should include the circumstances of poor intake (duration, cause, etc.), a background of previous eating behaviours, and GIT symptoms (nausea, vomiting diarrhoea, weight loss)  
 
a.    Specifics in the examination, beyond the general examination and vital signs are: Anthropometric 
              Weight, height and BMI calculation 
              Arm circumference 
              Triceps skin fold thickness 
 
b.    Clinical: 
          Hair: Hair loss or abnormal distribution (lanugo), 
          Skin: Conjunctival pallor and skin pallor, xerosis (dry skin, A), spooning of nails (Iron),            ecchymoses or petechiae (C or K), pressure ulcers, poor wound healing 
          Mouth: Glossitis (Niacin, Folate, B12, B2, B6), bleeding or sores on the gums and oral mucosa (C), angular cheilosis or stomatitis (B2, B6), leucoplakia, poor dentition 
              Neck: Thyromegaly 
          Extremities: loss of muscle mass (arm circumference, bitemporal wasting), loss of subcutaneous fat (triceps skin thickness), bone tenderness (Vit D) 

Investigations to assess protein status for protein calorie malnutrition, must all be taken in context of other evidence of acute and chronic illness and will alter as part of acute phase response. 

Serum albumin (longest half-life at 18 – 20d) 

Serum transferrin (half-life of 8 – 9d), but also reflects iron status, and low transferrin should be considered an indicator of protein status only in the setting of normal serum iron. 

Serum pre albumin (half-life at 2 – 3d) - responds quickly to the onset of malnutrition and rises rapidly with adequate protein intake, but altered in the acute phase response due to acute or chronic inflammation. 
 
Other investigations: 
o    Anaemia with Fe levels, or B12 / Folate if macrocytic.

o Vitamin and trace elements 

o    Ca, PO4, Mg, Glucose, UEC are all non-specific

o Retinol binding protein 

b) Pathophysiology of Re-feeding Syndrome 

Reintroduction of glucose into diet after a considerable period of fasting with a low BMI 
     Insulin in response to glucose load moves the glucose into cells (with K and Mg) 
     The first step of glycolysis is the phosphorylation of glucose.  This holds the glucose in cells.        This leads to sudden and precipitous fall in phosphate that is the hallmark of refeeding      syndrome 
     Severely reduced phosphate is available for ATP, cAMP 
     Failure of tissues with high energy requirement - heart, kidney, muscle (rhabdomyolysis),      brain, respiratory (diaphragm) 
     Untreated leads to death 
 
Additional Examiners' Comments: 
Poorly answered, with no specific details about the relative importance of measures of nutritional status. Candidates were expected to comment that nutritional assessment in the critically ill is difficult with many of the objective measures confounded by the consequences of the acute illness. A simple list of anthropometry, clinical signs and investigations was not sufficient as it missed the point that a careful history is crucial. 

 

Discussion

a)

An approach to the assessment of nutritional status:

History:

  • Premorbid weight and the pattern of its change
  • Premorbid nutritional routine
  • Diseases affecting gastrointestinal function (eg. coeliac disease)
  • Disease affecting satiety control (eg. Prader-Willi syndrome)
  • Factors influencing metabolic substrate utilisation (eg. thyroid dysfunction, hypoadrenalism, Cushings disease or corticosteroid therapy)

Examination:

  • Observed quality of nails and hair (an indicator of chronic protein intake)
  • Subcutaneous fat measurements (triceps)
  • Muscle bulk and muscle tone of quadriceps and deltoids
  • Presence of oedema and ascites
  • Evidence of any specific micronutrient deficiency

Anthropometry

  • BMI
  • Ideal body weight
  • Lean body mass

Biochemistry and physiology:

  • Cholesterol and triglycerides
  • Random BSL
  • HbA1C
  • Serum cortisol
  • TFTs
  • FBC for lymphocyte count
  • Albumin and prealbumin
  • Transferrin
  • Calculation of nitrogen balance
  • Micronutrient levels:
    • Fat-soluble vitamins A, D and E
    • Thiamine
    • Zinc
    • Selenium
    • Vitamin B12
    • Folate
  • Delayed hypersensitivity skin-testing

b)

Though the pathophysiology of refeeding syndrome can expressed as a stupidly complex flowchart,  the non-insane candidate may wish to make use of a logical point-form description:

  • With starvation, less carbohydrate becomes available
  • As the result of this, there is a switch to fatty acid and ketone based metabolism
  • This switch is in part mediated by a decrease in the insulin levels
  • Low oral intake also means decreased phosphate intake
  • However, there is a daily requirement for phosphate (for ATP synthesis)
  • This phosphate is not replenished by the poor oral intake
  • As a result, intracellular phosphate is depleted
  • Homeostatic mechanisms maintain a normal serum phosphate in spite of this
  • As carbohydrate is reintroduced, the secretion of insulin results in a large-scale uptake of phosphate into the tissues
  • As the intracellular phosphate is depeleted, there is nowhere to mobilise more phosphate from, and hypophosphataemia results.

Or, the diagram.

mechanism of refeeding syndrome

References

Hearing, Stephen D. "Refeeding syndrome." BMJ 328.7445 (2004): 908-909.

Kraft, Michael D., Imad F. Btaiche, and Gordon S. Sacks. "Review of the refeeding syndrome." Nutrition in Clinical Practice 20.6 (2005): 625-633.

Stanga, Z., et al. "Nutrition in clinical practice—the refeeding syndrome: illustrative cases and guidelines for prevention and treatment." European journal of clinical nutrition 62.6 (2008): 687-694.

Keys, Ancel, et al. "The biology of human starvation.(2 vols)." (1950).

Khan, Laeeq UR, et al. "Refeeding syndrome: a literature review."Gastroenterology research and practice 2011 (2010).

Crook, Martin A. "Refeeding syndrome: problems with definition and management." Nutrition 30.11 (2014): 1448-1455.

Rio, Alan, et al. "Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study." BMJ open 3.1 (2013): e002173.

Whitelaw, Melissa, et al. "Does aggressive refeeding in hospitalized adolescents with anorexia nervosa result in increased hypophosphatemia?." Journal of Adolescent Health 46.6 (2010): 577-582.

Agostino, Holly, Julius Erdstein, and Giuseppina Di Meglio. "Shifting paradigms: continuous nasogastric feeding with high caloric intakes in anorexia nervosa." Journal of Adolescent Health 53.5 (2013): 590-594.

Suzuki, Satoshi, et al. "Hypophosphatemia in critically ill patients." Journal of critical care 28.4 (2013): 536-e9.

Doig, Gordon S., et al. "Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial." The Lancet Respiratory Medicine 3.12 (2015): 943-952.

Alfaro Martínez, José Joaquín, et al. "Etiology and Complications of Refeeding Syndrome in the ICU." Diet and Nutrition in Critical Care (2015): 1065-1078.

Korbonits, Márta, et al. "Metabolic and hormonal changes during the refeeding period of prolonged fasting." European Journal of Endocrinology 157.2 (2007): 157-166.

GAULT, M. HENRY, et al. "Hypernatremia, azotemia, and dehydration due to high-protein tube feeding." Annals of internal medicine 68.4 (1968): 778-791.

National Collaborating Centre for Acute Care (UK. Nutrition support for adults: oral nutrition support, enteral tube feeding and parenteral nutrition. National Collaborating Centre for Acute Care (UK), 2006.

Crook, M. A., V. Hally, and J. V. Panteli. "The importance of the refeeding syndrome." Nutrition 17.7 (2001): 632-637.

Question 30.1 - 2016, Paper 2

The following results are from a 29-year-old post-partum female, day 6 following elective Caesarean section at 37 weeks gestation for placenta accreta, complicated by massive intra-operative haemorrhage.

She made a good recovery but has had a persisting dull headache, dizziness, lethargy, polyuria and failure of lactation.

Parameter

Patient Value

Normal Adult Range

Sodium

114 mmol/L*

135 - 145

Potassium

4.6 mmol/L

3.5 - 5.0

Bicarbonate

26 mmol/L

22 - 32

Urea

2.2 mmol/L*

3.0 - 8.0

Creatinine

46 mmol/L

45 - 90

Serum osmolalitv

232 mOsm/L*

275 - 295

Urine osmolality

493 mOsm/L

a) Give the diagnosis for this clinical picture. (20% marks)

b) How will you confirm the diagnosis? (20% marks)

c) Outline the underlying pathophysiology of this condition. (20% marks)

d) What is your immediate treatment? (10% marks)

College answer

a)    Sheehan's syndrome.                                         
 
b)    MRI brain showing empty pituitary fossa                      
Hormone profile – cortisol, TFTs, prolactin 
 
c)    Ischaemic pituitary necrosis due to severe post-partum haemorrhage. Vasospasm, thrombosis and vascular compression of hypophyseal arteries with an enlarged pituitary gland and DIC are possible factors. 
 
d)    Hydrocortisone.  
 

Discussion

a) This is a hypoosmolar hyponatremia with history of polyuria, failure of lactation, and lethargy. All sounds very endocrine. Given the history of pospartum haemorrhage, one must consider post-partum hypopituitarism, or Sheehan' syndrome.

b) Endocrine-sounding tests are in order.

  • Prolactin level
  • TFTs
  • Random cortisol (or short synacthen test)
  • MRI of the sella turcica

c) The pituitary gland in pregnancy is enlarged, and in context of haemorrhagic shock it can become infarcted. As a result of this:

  • Vasopression stores are depleted, resulting in initial polyuria
  • ACTH secretion decreases, resulting in hypoadrenalism, with lethargy and hyponatremia
  • TSH secretion decreases, also resulting in lethargy and hyponatremia
  • Prolactin secretion cannot increase, resulting in failed lactation

d) Supplement the following:

  • Cortisol (as hydrocortisone)
  • Thyroid hormone (as oral thyroxine)

References

Cukierman, Ronit L., et al. "Post-Partum Hyponatraemia in the Setting of Massive Haemorrhage: An Unusual Presentation of Sheehan? s Syndrome." Critical Care Obstetrics and Gynecology (2016).

Question 15.1 - 2017, Paper 1

You are called to review a 48-year-old male in the post-operative recovery unit (PACU) who has just undergone resection of a TSH-secreting pituitary adenoma via a trans-sphenoidal approach. He is febrile (38.5°C) and is hypertensive (160/50 mmHg) with tachycardia (130 beats/min) and hyper-dynamic circulation, and is hyper-reflexic.

Give the likely diagnosis.        (10% marks)

List your immediate pharmacological management.            (30% marks)

College answer

a) Thyroid storm

b) Propranolol 60-80mg 4-6 hourly (or other beta blocker) to control BP and HR Propylthiouracil (200mg 4hrly) or Carbimazole 20-30 mg every 4-6 hours Hydrocortisone 100mg 6hrly

Discussion

The patient clearly demonstrates many classic features of hyperthyroidism:

  • Tachycardia
  • Hypertension
  • Hyperthermia
  • Hypereflexia

The intuitive candidate will leap immediately to the conclusion that this is a TSH release mediated thyroid storm, as seen in one case report every ten years or so. How being able to identify this zebra diagnosis discriminates good intensivists from bad, one can only guess. 

Pharmacological management of thyroid storm consists of the following steps:

  • Prevent synthesis of T3 and T4:
    • Thiouracils: propylthiouracil - blocks synthesis of T3 and T4 as well as peripheral T4-T3 conversion
    • Imidazoles: carbimazole - block synthesis of T3 and T4
  • Prevent T3 and T4 release:
    • Inorganic iodine therapy, eg. potassium iodide (given after synthesis is blocked)
  • Block peripheral T3 and T4 activity:
    • β-blockade: propanolol (which also decreases T4-T3 conversion)
    • Corticosteroids: also decrease T4-T3 conversion
  • Other potentially useful agents include lithium and cholestyramine.
  • Severe refractory disease may call for extracorporal clearance of thyroid hormone by plasma exchange or charcoal haemoperfusion.

References

Question 23 - 2017, Paper 1

With respect to hypocaloric enteral nutrition in the critically ill:

a) Explain the following terms:

i.  Trophic feeding

ii.  Permissive underfeeding       

(40% marks)

b) 
Outline the potential advantages of hypocaloric enteral nutrition and the available evidence for its use.            (60% marks)

College answer

Trophic feeding refers to enteral feeding below the minimum required caloric intake, with the aim of maintaining gut integrity rather than meeting patient’s nutritional requirements. Definition of volume feed/energy required varies. Between 10-30ml/hr or 15-25% of calculated caloric intake. Can’t be used as sole nutritional strategy long term. 

Permissive underfeeding is the provision of a reduced non-protein caloric target (around 40-60% of calculated total) hypothesing that lower non-protein calorie intake may be beneficial. May be used as sole nutritional strategy.

Trophic feeding
Advantages of trophic feeding
Include potential beneficial effects on the gut such as preserving intestinal epithelium, stimulating secretion of brush border enzymes, enhancing immune function, preserving epithelial tight cell junctions, and preventing bacterial translocation. Could be considered in patients unable to tolerate full enteral nutrition. May minimise complications associated with full enteral feeding such as feed intolerance, aspiration, high gastric volumes, and diarrhoea.

Available evidence for trophic feeding
2 RCT’s of patients with respiratory failure/ARDS (largest = EDEN trial JAMA 2012)

  • Trophic feeding for up to 6 days does not improve ventilator free days, 60 day mortality or infectious complications.
  • Less feed intolerance with trophic feeding (e.g. less prokinetic agents, vomiting, gastric residual volumes, lower GI symptoms), 
  • lower blood glucose, less insulin requirement

Permissive underfeeding
Advantages of permissive underfeeding

  • Based on the premise that ideal caloric targets for critically ill patients are unknown, calorie restriction is associated with increased longevity in animal models, and may have beneficial effects on critically ill patients via hormonal or metabolic pathways
  • May be established with either enteral or parenteral routes
  • Avoids delivery of large volumes that may predispose to fluid overload
  • If tolerated may avoid other strategies such as placement of NJ tube, prokinetics

Available evidence for permissive underfeeding:

  • Arabi et al, (PermiT trial) NEJM 2015
  • Randomised >800 patients to permissive underfeeding vs. standard care. No difference in mortality, feeding intolerance or diarrhoea

Specific trials not needed for pass.
Additional Examiners Comments:
This question was answered poorly. The majority of candidates were unable to accurately describe or define the two feeding strategies. There was limited appreciation of the available evidence

Discussion

a) 

Trophic feeding: Sondheimer et al (2004); "The generally accepted definition of trophic feeding is a small volume of balanced enteral nutrition insufficient for the patient's nutritional needs but producing some positive gastrointestinal or systemic benefit." 

Permissive underfeeding: The systematic review by Owais et al (2010) reveals a massive variation of historical definitions, ranging though 13-14 kcal/kg/day, <20 kcal/kg/day, 1000 kcal/day,  or <33% of estimated requirement, or 5,000-10,000 kcal/week. The college used the 40-60% goal from Arabi et al (2015). The distinction is that this a nutritional strategy, rather than one focused on intestinal mucosal health.

b)

Advantages of permissive underfeeding:

  • Avoids the disadvantages of full-volume enteral nutrition:
    • Gastric distension
    • Aspiration
    • Diarrhoea/constipation
    • Hyperglycaemia
    • Excess insulin use
    • Exposure to toxic prokinetics
    • Need for NJ tubes, etc
  • Cheaper 
  • Does not suppress the (possibly) constructive autophagy which may be required to recover from critical illness

Evidence for permissive underfeeding:

  • Arabi et al.
  • n=894 patients (mostly intubated)
  • Randomised to either receive 70-100% of their calculated requirements, or 40-60%; for 14 days
  • The groups ended up well separated (average 835 kcal vs. 1299)
  • No difference in any of the primary outcome measures was found.
  • A post-hoc analysis (Arabi et al, 2017) did not find any difference even among patients defined as being at a high nutritional risk.
  • This has been viewed as evidence of safety.

Advantages of trophic feeding:

  • Improved feed tolerance (reduced gastric residual volumes)
  • Maintenance of gastric and intestinal mucosal integrity
  • Prevention of bacterial overgrowth and bacterial translocation
  • Prevention of excessive protein catabolism (prevention of starvation)

Evidence for trophic feeding:

  • EDEN trial (Rice et al, 2012)
  • 5 days of <25% of their estimated requirements
  • No difference in any primary outcomes
  • Again, can be viewed as a demonstration of safety
  • Limitation: many patients were underfed with protein (0.6g/kg/day)

References

Sondheimer, J. M. "A critical perspective on trophic feeding." Journal of pediatric gastroenterology and nutrition 38.3 (2004): 237.

McClave, Stephen A., et al. "Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN).Journal of Parenteral and Enteral Nutrition 40.2 (2016): 159-211.

Rice TW,  et al. "Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial." JAMA: the journal of the American Medical Association 307.8 (2012): 795.

Rice, Todd W., et al. "A randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure." Critical care medicine 39.5 (2011): 967.

Zaloga, G. P., and P. Roberts. "Permissive underfeeding." New horizons (Baltimore, Md.) 2.2 (1994): 257-263.

Jeejeebhoy, Khursheed N. "Permissive underfeeding of the critically ill patient." Nutrition in clinical practice 19.5 (2004): 477-480.

Arabi, Yaseen M., et al. "Permissive underfeeding or standard enteral feeding in critically ill adults." New England Journal of Medicine 372.25 (2015): 2398-2408.

Owais, Anwar E., Rachael Frances Bumby, and John Macfie. "permissive underfeeding in short‐term nutritional support." Alimentary pharmacology & therapeutics 32.5 (2010): 628-636.

Van Zanten, Arthur RH. "Full or hypocaloric nutritional support for the critically ill patient: is less really more?." Journal of thoracic disease 7.7 (2015): 1086.

Dudrick, Stanley J. "The genesis of intravenous hyperalimentation.Journal of Parenteral and Enteral Nutrition 1.1 (1977): 23-29.

Spanier, A. H., and H. M. Shizgal. "Caloric requirements of the critically ill patient receiving intravenous hyperalimentation.The American Journal of Surgery 133.1 (1977): 99-104.

Weindruch, Richard, et al. "The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake." J Nutr116.4 (1986): 641-54.

Arabi, Yaseen M., et al. "Permissive Underfeeding or Standard Enteral Feeding in High–and Low–Nutritional-Risk Critically Ill Adults. Post Hoc Analysis of the PermiT Trial." American journal of respiratory and critical care medicine 195.5 (2017): 652-662.

Schetz, Miet, Michael Paul Casaer, and Greet Van den Berghe. "Does artificial nutrition improve outcome of critical illness?." Critical care 17.1 (2013): 302.

Choi, Augustine MK, Stefan W. Ryter, and Beth Levine. "Autophagy in human health and disease." New England Journal of Medicine 368.7 (2013): 651-662.

Streat, Stephen J., Alun H. Beddoe, and Graham L. Hill. "Aggressive nutritional support does not prevent protein loss despite fat gain in septic intensive care patients." Journal of Trauma and Acute Care Surgery 27.3 (1987): 262-266.

Van den Berghe, Greet. "Intensive insulin therapy in the ICU—reconciling the evidence." Nature Reviews Endocrinology 8.6 (2012): 374-378.

Question 24 - 2017, Paper 1

A 53-year-old known type 1 diabetic male is brought to the Emergency Department (ED) by ambulance after being found collapsed at home.His arterial blood gas result on admission is shown below:

Parameter

Patient Value

Adult Normal Ranae

FiO2

0.21

pH

6.84'

7.35 - 7.45

pCO2

8.7 mmHg

35.0 -45.0 

pO2

80 mmHg

Bicarbonate

1.4 mmol/L"

22.0 - 26.0

Sodium

126 mmol/L*    

135 - 145

Potassium

5.5 mmaVL*

3.5 - 5.2

Chloride

98 mmolfl

95 - 105

Glucose

54.0 mmol/L*

3.5 - 6.0

Lactate

4.1 mmol/L'

< 2.0

Haemoglobin

96 a/L'

115 - 160

Creatinine

150 umol/L*

45 - 90

He has a Glasgow Coma Scale (GCS) of 12 (E4 V3 MS) and is uncooperative, agitated and combative.

The ED Registrar suggests intubating the patient.

Outline your immediate management of this patient.     (80% marks)

List the risk factors for all patients that predispose to the development of cerebral oedema in this condition.      (20% marks)

College answer

a)

  • The first priority is to prevent intubation. Induction will reduce minute ventilation and  worsen acidosis with a probably fatal result. Many ED ventilators would struggle to provide 40 Lpm ventilation and the PPV in a severely hypovolaemic patient may cause  haemodynamic collapse. Avoid sedation. Acidosis should resolve rapidly with fluid resuscitation and insulin.
  • IV line and fluids – preferably HCO3- containing to minimise hyperchloraemic acidosis (note CVC is optional) e.g. CSL. Water deficit around 4L for 70 kg man
  • IV insulin infusion (suggest 2-5 U/hr) with hourly glucose monitoring. Institute IV glucose once BGL < 12, and continue insulin until ketones cleared and beyond
  • Hourly K+ and early replacement – watch for massive drop as pH rises
  • Replace other electrolytes as needed (Mg, PO4)
  • Check for precipitants esp. intoxication and infection
  • Investigate cause of anaemia
  • Disposition to appropriate high-care area (HDU/ICU/other)

b)

  • Younger age (especially under 5’s)
  • Newly diagnosed diabetes
  • Severity of acidosis & hyperglycaemia
  • Severity of dehydration
  • Change in corrected [Na]
  • Speed of rehydration & correction of hyperglycaemia
  • Administration of bicarbonate

Additional Examiner Comments:
Many candidates stated they would intubate the patient; this would likely have precipitated a cardiac arrest due to acute rise in CO2 and worsening acidosis.

Discussion

a)

The ED registrar is unimpressed with the agitated patient's behaviour, and would prefer to intubate them to improve their manners. The college wisely cautions against this, as it might precipitate cardiac arrest from acidosis. This is likely correct. A CO2 of 9 likely represents the physiological limits of hyperventilation. An important early goal would be to correct this acidosis, bringing the patient closer to the possibility of safe airway control. The story of "found collapsed" is going to score a head CT, and judging by the way the situation is evolving this guy will not hold still for it, so an intubation is still on the cards at some stage.

The college suggested insulin. This is rarely required in pure HHS; fluid resuscitation alone is often enough because the hyperosmolar state is frequently associated with an abnormally elevated insulin level in a Type 2 diabetic. However, in this scenario the patient is a Type 1 diabetic, and is probably more DKA than HHS (he clearly has high ketones; the anion gap is around 26.6, and only 4.0 mmol/L of this is explaied by lactate). So some insulin would be required (but probably not the 0.1u/kg/hr recommended by the usual DKA protocols, as you do not want to drop the BSL too quickly)

Thus, a standard approach to DKA is described below.

  1. Assess airway patency. Intubate to protect the airway if comatose.
  2. Ventilate with mandatory mode initially; aim for normocapnea if the metabolic acidosis is not particularly severe. 
  3. Insert arterial line for frequent sampling and haemodynamic monitoring.
    Insert central line to manage electrolyte and fluid infusions.
    Expect a 200ml/kg total water deficit
    Commence fluid resuscitation:
    1. 15-20ml/kg in the first hour (and use colloid if they are shocked)
    2. 4-14ml/kg in the second hour (of 0.45% NaCl)
    3. 4-14ml/kg again in the third hour (use 0.9% NaCl if the sodium is low)
    4. When glucose is under 15mmol/L, Oh's Manual recommends to start 5% dextrose 100-250ml/hr, as well as some other sort of sodium-containing fluid to prevent hyponatremia 
  4. May require benzodiazepines or anticonvulsants if the presentation history included seizures.
    May require a head CT venogram to rule out dural sinus thrombosis / venous infarction
  5. Watch for a precipitous drop in serum osmolality.
    A safe drop is 3–8 mOsm/kg/h
    Correct electrolyte deficit:
    1. Sodium deficit: 5-13mmol/kg
    2. Potassium deficit: 5-15mmol/kg
    3. Chloride deficit: 3-7mmol/kg
    4. Phosphate deficit: 1-2mmol/kg
    5. Magneisum deficit: 1-1.5mmol/Kg
    6. Calcium deficit: 1-2mmol/Kg
  6. Monitor renal function and consider dialysis
  7. May require anticoagulation for dural sinus thrombosis.
  8. May require antibiotics, given that infection is a common precipitant.
    A septic screen should be sent.

Key issues of "specific therapy:

  • Fluid resuscitation
  • Electrolyte replacement
  • Careful slow reduction of serum osmolality
  • Careful introduction of insulin
  • Investigation for complications:
    • Myocardial infarction
    • Stroke
    • Cerebral oedema and brain injury
    • Venous thrombosis
  • Management of other possible precipitating causes:
    • Infection, systemic inflammatory response
    • Intracranial haemorrhage
    • Hepatic encephalopathy
    • Drugs, including illicit substances, steroids, phenytoin, diuretics, TPN, lithium

b) This list of risk factors from the college seems to come from multiple references (see the list from the HHS chapter) and may be mainly paediatric in origin, as it appears this complication is much less common among adult patients  (Matz, 1999).

A complete list of risk factors from around the literature would look like this:

  • Children (esp. under 3s)
  • New diagnosis of diabetes
  • Down syndrome
  • Use of bicarbonate
  • Rapid change in serum sodium concentration
  • Severe acidosis
  • Severe hypoglycaemia
  • Severe dehydration
  • Low presenting PaCO2
  • High urea
  • Rate of rehydration (rapid)

References

Hyperglycemic Comas by P. VERNON VAN HEERDEN from Vincent, Jean-Louis, et al. Textbook of Critical Care: Expert Consult Premium. Elsevier Health Sciences, 2011.

Oh's Intensive Care manual: Chapter 58  (pp. 629) Diabetic  emergencies  by Richard  Keays

Umpierrez, Guillermo E., Mary Beth Murphy, and Abbas E. Kitabchi. "Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome." Diabetes Spectrum15.1 (2002): 28-36.

ARIEFF, ALLEN I., and HUGH J. CARROLL. "Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of theraphy in 37 cases." Medicine 51.2 (1972): 73-94.

Gerich, John E., Malcolm M. Martin, and Lillian Recant. "Clinical and metabolic characteristics of hyperosmolar nonketotic coma." Diabetes 20.4 (1971): 228-238.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes." Diabetes care 32.7 (2009): 1335-1343.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes a consensus statement from the American Diabetes Association." Diabetes care 29.12 (2006): 2739-2748.

Ellis, E. N. "Concepts of fluid therapy in diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma." Pediatric clinics of North America 37.2 (1990): 313-321.

Pinies, J. A., et al. "Course and prognosis of 132 patients with diabetic non ketotic hyperosmolar state." Diabete & metabolisme 20.1 (1993): 43-48.

Gouveia, Catherine F., and Tahseen A. Chowdhury. "Managing hyperglycaemic emergencies: an illustrative case and review of recent British guidelines." Clinical Medicine 13.2 (2013): 160-162.

Dhatariya, Ketan. "Diabetic ketoacidosis and hyperosmolar crisis in adults." Medicine 42.12 (2014): 723-726.

Scott, A. R. "Management of hyperosmolar hyperglycaemic state in adults with diabetes." Diabetic Medicine 32.6 (2015): 714-724.

Matz, R. O. B. E. R. T. "Management of the hyperosmolar hyperglycemic syndrome." American family physician 60.5 (1999): 1468-1476.

Matz, R. "How big is the risk of cerebral edema in adults with DKA." J Crit Illn 11 (1996): 768-772.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes." Diabetes care 32.7 (2009): 1335-1343.

Quintana, E. C. "Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema." Annals of Emergency Medicine 43.6 (2004): 793-794.

Bialo, Shara R., et al. "Rare complications of pediatric diabetic ketoacidosis."World journal of diabetes 6.1 (2015): 167.

Lawrence, Sarah E., et al. "Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis." The Journal of pediatrics 146.5 (2005): 688-692.

Marcin, James P., et al. "Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema." The Journal of pediatrics 141.6 (2002): 793-797.

Glaser, Nicole, et al. "Risk factors for cerebral edema in children with diabetic ketoacidosis." New England Journal of Medicine 344.4 (2001): 264-269.

Rosenbloom, Arlan L. "Intracerebral crises during treatment of diabetic ketoacidosis." Diabetes care 13.1 (1990): 22-33.

Question 8 - 2017, Paper 2

Outline how the pathophysiological changes associated with morbid obesity may impact on the management of critically ill obese patients.

College answer

Anatomical problems:

  • Weight
    • Too heavy for certain investigations e.g. CT
    • Difficulty in establishing non-invasive monitoring such as ECG and NIBP o Too large for many ICU beds leading to discomfort o Difficult to mobilise and move around between beds-chair
    • Difficult to deliver cares due to inability to access areas required, and requiring multiple staff to do so 
  • Excess adipose tissue o Difficult venous and arterial access: establishing, securing, and suitable equipment

Increased risk of complications of vascular access o Difficult epidural access o Difficult to clinically examine o Invasive procedures e.g. chest drains more difficult.

  • Metabolic and endocrine o Altered body composition leading to different catabolism in the critically ill, and different nutritional requirements
    • Altered response to endogenous hormones in the critically ill 
    • Altered inflammatory response “Chronic inflammatory state” making interpretation of biomarkers of infection difficult
    • Increased incidence of crystal arthropathy which is often difficult to diagnose because of size
    • Insulin resistance, hyperglycaemia

Respiratory:

  • Prone to atelectasis due to abdominal mass
  • More difficult to ventilate due to higher airway pressures with obesity acting like a restrictive lung deficit
  • Increased incidence of central and peripheral sleep apnea increasing the difficulty of ventilator weaning and extubation

Cardiovascular

  • Hypertension making BP responses more variable to sedation and catacholamines, and increasing risk of CVA’s
  • Coronary artery disease leading to potential episodes of myocardial ischaemia and arrhythmias
  • Peripheral vascular disease leading to skins changes and ulceration, with greater propensity for pressure sores and difficulties with skin integrity
  • VTE

Airway 

  • Difficult bag-mask ventilation due to excess facial tissue
  • Difficult laryngoscopy 

Musculoskeletal

  • Greater incidence of arthritis and bony pain
  • PRESSSURE AREAS
  • Increased incidence of soft tissue infections

Pharmacological 

  • Pharmaceutics o Actual weight different from ideal body weight making drug dose calculation more

difficult

  • Pharmacokinetics o Altered absorption of drugs through the sc / topical route due to altered blood flow o Altered distribution of drugs due to altered plasma proteins and fat solubility / distribution

o Altered metabolism of drugs due to impaired hepatic function o Altered excretion of drugs due to impaired renal function

  • Pharmacodynamics o Larger doses of medications often needed increasing potential for exaggerated sideeffects and toxicity 

Emotional and environment

  • Increase incidence of depression and mood disorders affecting interaction in the

critically ill

  • Prejudice and stigma of staff towards the difficulty of looking after morbidly obese patients

Discussion

This question closely resembles Question 10 from the first paper of 2001. The answer to that question is reproduced here to simplify revision.

The physiological effects of obesity (as relevant to critical illness)

Airway problems

  • Difficult intubation
  • Difficult tracheostomy
  • Difficult tracheostomy care

Respiratory effects

  • Expiratory reserve volume is decreased
  • FEV1 to FVC ratio is increased.
  • VC, TLC and FRC are decreased.
  • Work of breathing is increased
  • CO2 production is increased, thus ventilatory needs are greater
  • Increased risk of aspiration pneumonia
  • Increased risk of DVT and PE

Cardiovascular effects

  • Cardiac output is increased
  • Total blood volume is increased
  • LV contractility is impaired
  • LV size and wall thickness are increased
  • Hypertension is common
  • LV diastolic pressure is increased, and fluid loading is poorly tolerated

Pharmacokinetic effects

  • Volume of distribution is increased for many lipophilic drugs
  • Hepatic clearance may be reduced
  • Renal clearance may be impaired, but this may not be predicted by standard creatinine clearance formulae.

Nutritional effects

  • Increased requirement for dietary protein, given the tendency to mobilise protein instead of fat during a stress repsonse: currently, recommendation is for 1.5-2g/kg of IBW per day

Access problems

  • Vascular access is difficult
  • Cleaning CVC sites may be problematic

Monitoring issues

  • NIBP cuffs do not fit.

Radiology problems

  • Chest Xrays may be of poor quality
  • These patients cannot fit into CT or MRI scanners.

References

Akinnusi, Morohunfolu E., Lilibeth A. Pineda, and Ali A. El Solh. "Effect of obesity on intensive care morbidity and mortality: A meta-analysis*." Critical care medicine 36.1 (2008): 151-158.

Marik, Paul, and Joseph Varon. "The obese patient in the ICU." CHEST Journal113.2 (1998): 492-498.

Ling, Pei-Ra. "Obesity Paradoxes—Further Research Is Needed!*." Critical care medicine 41.1 (2013): 368-369.

Question 12.2 - 2018, Paper 1

You are asked to see a 73-year-old female on the ward. She was admitted to the Emergency Department in a dishevelled state.

She has the following vital signs and investigation results:

            Temperature:                         34.5°C

           Blood pressure:                     80/40 mmHg

           Glasgow Coma Score:          11

Parameter

Patient Value

Adult Normal Range

Fi02

0.28

pH

7.26*

7.35 - 7.45

P02

62 mmHg (8.3 kPa)

PC02

37.0 mmHg (4.7 kPa)

35.0 -45.0 (4.6 - 6.0)

sp02

92%

Bicarbonate

16.0 mmol/L*

22.0 - 26.0

Base Excess

-10.0 mmol/L*

_2.0 _ +2.0

Lactate

3.1 mmol/L*

0.5 - 1.6

Sodium

128 mmol/L*

135 - 145

Potassium

3.1 mmol/L*

3.5 -5.0

Chloride

90 mmol/L*

95- 105

Glucose

3.2 mmol/L*

3.5 -6.0

Urea

13.0 mmol/L*

3.0 - 8.0

Creatinine

132 umol/L*

45 — 90

Creatinine Kinase

1500 U/L*

55 - 170

Haemoglobin

80 g/L*

120 - 160

White Cell Count

15.0 x 109/L*

4.0 - 1 1.0

Platelet count

250 x 109/1-

150 - 350

a) Comment on the acid base status and ECG abnormalities 

(ECG show below)

ECG from LITFL

(30% marks) b) List the two most likely differential diagnosis. (20% marks)

College answer

a) 
Primary metabolic acidosis  
Associated respiratory acidosis, or inadequate compensation 
Increased anion gap. (22) 
Delta ratio 1.2 –pure high anion gap acidosis 
 
ECG: low voltage  
Relative bradycardia 
Prolonged QT 
 
b) 
Myxoedema coma. 
Sepsis 
 

Discussion

Acid base status, in detail:

  1. There is acidaemia
  2. The CO2 is within normal range, which is inappropriate (it should be low)
  3. There is metabolic acidosis, as the SBE is -10
  4. There is also a respiratory acidosis: the expected CO2 is 30 (or 32 by the Boston rules)
  5. The anion gap is 25.1, or 22 sans potassium. Either way, the lactate of 3.1 does not fully explain it. 
  6. The delta ratio is either 1.6 or 1.25, but either way it points to a pure HAGMA.

ECG abnormalities 

  • Bradycardia
  • Long PR interval
  • Long QT interval
  • Borderline widened QRS
  • Low voltage QRS in the limb leads

Overall, the ECG is consistent with hypothermia. Which the patient has. And with ... one other thing.

So... those two most likely differentials? 

Well. One of them HAS to be myxoedema coma. 

How can one be so confident? It's easy, when the college lifted their ECG directly from the LITFL page on ECG changes in hypothyroidism. Which is excellent: as that work is covered by the Creative Commons license, this offers the author a rare opportunity to reproduce the original college image without fear of the CICM intellectual property stormtroopers. 

The other differential could easily be sepsis, MI, acute kidney injury due to prolonged lie and rhabodomyolysis, and so on. 

References

Question 13 - 2018, Paper 2

a)    List important clinical features of thyroid storm.                                (30% marks) 
 
b)    Outline the principles of management of myxoedema coma.                     (70% marks) 

 

College answer

  1. List important clinical features of thyroid storm.                                            3 marks
    1. Hyperpyrexia – temperature 40 - 41º C
    2. CVS – sinus tachycardia usually exceeding 140, atrial fibrillation, decompensated CCF, hypotension/shock and in extreme cases cardiac arrest.
    3. CNS – agitation, anxiety, delirium, stupor and coma.         
    4. GI symptoms – diarrhoea, abdominal pain, jaundice
    5. Physical exam may reveal Goiter, opthalmopathy, lid lag, tremors, warm moist skin.
  1. Outline the principles of management of myxoedema coma.                            7 marks
    1. Establish IV access including CVC and collect blood for Investigations including thyroid function tests, BSL, electrolytes etc.
    2. Establish monitoring – arterial BP, ECG, temp, pulse oximetry etc.
    3. Airway – Intubation to protect airway and Mechanical ventilation to normal gas exchange
    4. Fluid + vasopressors as appropriate to a MAP 65-70 mmHg.
    5. Passive rewarming while close monitoring of haemodynamics and temperature.
    6. slow replacement is key. IV T3 and T4 – T3 has greater biologic activity and quicker onset of action. Daily monitoring of T3 and T4 levels to avoid toxicity.
    7. IV hydrocortisone to treat possible coexisting adrenal insufficiency. viii.     IV dextrose to maintain BSL, NG feeding if possible.
    1. Consider IV antibiotic if clinical evidence of infection after collecting appropriate cultures.
    2. Monitor and treat cardiac arrhythmias, coronary ischaemia

Discussion

Clinical features of thyroid storm:

  1. Goitre: possible airway compromise)
  2. Tachypnoea due to increased CO2 production;
    Increased O2ER (increased metabolic fuel use)
  3. Tachycardia,
    Atrial fibrillation and ventricular arrhythmias
    Heart failure
    Hypertension (early), hypotension (late)
  4. Tremor;
    Agitation, progressing to encephalopathy, coma and seizures.
    There is the phenomenon of "apathetic thyrotoxicosis" which presents with weakness
  5. Low potassium and magnesium (particularly in "apathetic thyrotoxicosis")
    Serum cortisol should be elevated. If it is not, one might consider a relative adrenal insufficiency, and supplement some hydrocortisone.
  6. Rhabdomyolysis may be present; CK may be elevated. This is "thyrotoxic myopathy"
  7. Diarrhoea, nausea and vomiting
    Increased metabolic rate; increased demand for metabolic substrate.
    Nutritional requirements are increased
    Hyperglycaemia may be apparent in the non-diabetic patient
    Jaundice may develop
  8. Leukocytosis; a left shift
  9. Fever: in fact, may go up to 41°C. This is apparently the most characteristic feature.

Management of myxoedema coma

The model answer offered for this section is somewhat surprising, as some of its components - on first assessment - could not possibly score any marks in a question which asks for the principles of management of myxoedema coma. Statements such as "mechanical ventilation to normal gas exchange" and "consider IV antibiotic if clinical evidence of infection after collecting appropriate cultures" not only violate the rules of grammar but do nothing to support one's impression that the writer was an expert on extreme hypothyroidism. But, as these generic supportive strategies are offered by the college in their model answer template, one must assume that they expected them to also appear in the candidate's written responses, and so they are offered as a post-script in the management strategy here.

Thus:

  • Replace thyroid hormone - preferably IV
    • loading dose is 300-400μcg
    • a rising body temperature and normalising cardiovascular parameters alert you to the success of your management strategy
  • Replace corticosteroids - there is usually a concomitant adrenal insufficiency. One would use a "stress dose".
  • Correct the sodium: this is usually a hypervolemic hyponatremia which resembles that of CCF (in fact, it is because of exactly the same mechanism: poor cardiovascular performance leads to ADH and aldosterone driven retention of water and sodium, with a resulting hypervolemic hyponatremia. Because the patient is usually obtunded, one is obliged to correct a particularly low sodium with hypertonic saline, being careful not to demyelinate the CNS.
  • Good solid supportive management:
    • Establish an airway if this is needed
    • Maintain normoxia and normocapnea with the ventilator
    • Maintain normotension to support organ system perfusion, with a catecholamine infusion
    • Correct the Na+ deficit - consider using water restriction alone.
    • Correct hypoglycaemia
    • Correct hypothermia with warming blanket

References

Summers, V. K. "Myxoedema coma." British medical journal 2.4832 (1953): 366.

Wartofsky, Leonard. "Myxedema coma." Endocrinology and metabolism clinics of North America 35.4 (2006): 687-698.

Mathew, Vivek, et al. "Myxedema coma: a new look into an old crisis." Journal of thyroid research 2011 (2011).

Lezama, Maybelline V., Nnenna E. Oluigbo, and Jason R. Ouellette. "Myxedema Coma and Thyroid Storm: Diagnosis and Management." Internal Medicine 14.Part 2 (2011): 1.

Chu, Michael, and Terry F. Seltzer. "Myxedema coma induced by ingestion of raw bok choy." New England Journal of Medicine 362.20 (2010): 1945-1946.

Wall, Cristen Rhodes. "Myxedema coma: diagnosis and treatment." American family physician 62.11 (2000).

Bondugulapati, Laxmi, Mohamed Adlan, and Lakdasa Premawardhana. "Thyroid Emergencies." Sri Lanka Journal of Critical Care 2.1 (2011): 1-12.

Question 9.1 - 2019, Paper 1

A 24-year-old male is admitted to the ICU following a spontaneous intracranial haemorrhage. He is noted to have labile blood pressure that is difficult to control, and a persistent tachycardia in spite of high dose sedatives. Further investigation reveals raised plasma and urinary catecholamine levels.

a)    List four potential causes of the above findings in this patient.    (25% marks)
 

College answer

•    Phaeochromocytoma
•    Physical stress - critical illness, hypoxia, hypercapnia, hypoglycaemia
•    Use of catecholamines, amphetamine use
•    Prior h/o tricyclic/MAOI use

Discussion

This question appears to be an endocrinology question, in spite of the neurosurgical garnish. "What are the causes of raised catecholamine testing levels" is probably the real question. There are multiple possible answers:

Causes of Raised Plasma Catecholamine Levels

Malignancy

  • Phaeochromocytoma (adrenaline)
  • Neuroblastoma (DOPA)
  • Malignant melanoma (DOPA)
  • Menke's disease (dopamine)

Decreased clearance

  • MAO A/B inhibition
  • Altered COMT activity
  • Tricyclic antidepresant use
  • Hepatic insufficiency

 

Autonomic nervous system

  • Normal stress response
  • Asphyxiation
  • Morbid obesity
  • Hypoglycaemia
  • Intracranial haemorrhage (eg. SAH)
  • Acute clonidine withdrawal

Spurious results

  • Anti-parkinsonian medications
  • Amphetamine use
  • Methyldopa
  • Labetalol

In terms of pharmacological causes of raised catecholamine levels, multiple drugs exist for the use of which there might be a "prior h/o". Monoamine oxidase inhibitors, antiparkinsonian medications (eg. L-dopa), amphetamines and methyldopa are the biggest culprits. 

References

Goldstein, David S., Graeme Eisenhofer, and Irwin J. Kopin. "Sources and significance of plasma levels of catechols and their metabolites in humans."Journal of Pharmacology and Experimental Therapeutics 305.3 (2003): 800-811.

Sardesai, Suhrud H., et al. "Phaeochromocytoma and catecholamine induced cardiomyopathy presenting as heart failure." British heart journal 63.4 (1990): 234-237.

Lenders, Jacques WM, et al. "Biochemical diagnosis of pheochromocytoma: which test is best?." Jama 287.11 (2002): 1427-1434.

Question 25 - 2019, Paper 1

A 46-year-old female patient with class 3 (BMI > 40 kg/m2) obesity has been admitted to your ICU with community-acquired pneumonia. She is sedated and ventilated with no other organ dysfunction. You are considering starting nutritional therapy.

a)    Outline the metabolic derangements likely to be present in this patient. (20% marks)

b)    How would you make an assessment of this patient’s current nutritional status?
(40% marks)

c)    Outline your nutritional regimen in particular your optimal target protein and energy delivery.
(40% marks)
 

College answer

  1. A number of metabolic derangements affect fuel utilization:

    • Insulin resistance

    • Impaired glucose tolerance,

    • Increased fatty acid mobilization

    • Hyperlipidemia

    • Obese patients, compared to lean counterparts, may have accelerated protein degradation and depletion of lean body mass.

    • “Metabolic X syndrome” may exist: insulin resistance, hyperinsulinemia, hyperglycaemia, coronary artery disease, hypertension, and hyperlipidemia.

    • Obese patients are more likely to have a pre-existing pro inflammatory state.

    • Obese patients have increased resting energy expenditure secondary to increased BMI, with central adipose tissue being more metabolically active than peripheral adipose tissue.

  1. Assessment

    • Assess patterns of weight change and nutrition intake prior to the admission

    • Anthropometrics –actual body weight, ideal body weight, usual body weight, height, BMI, and waist circumference should be determined

    • (Biomarkers of the metabolic syndrome; triglycerides, cholesterol, glucose serum albumin and pre-albumin)

  1. Nutritional Regimen

  • High protein (anabolic) hypocaloric feeding (reduced complications from overfeeding) should be provided to the obese critically ill patient regardless of whether the route of nutrition therapy is enteral or parenteral

  • Most studies using this method give11-14kcal/kg/actualBWperday or 22-25kcal/kgIBW per day- equates to about 60-70% of calorie requirement determined by indirect calorimetry or predictive equation.

  • Protein requirements should be met to maximise protein synthesis and preserve lean body mass (> 2.0g/kg IBW/d for class 1 and 2 obesity and > 2.5g/kg IBW/d for class 3). Note: TARGET trial suggested hypocaloric and eucaloric feeding have same effects on mortality when protein level constant

Discussion

This SAQ is identical to Question 24 from the first paper of 2012. The only difference is that the college added "Note: TARGET trial..." at the end. The spectrum of metabolic derangements present in the obese ICU patient is detailed elsewhere.  In short, these are the major metabolic abnormalities one can expect from an obese patient in the ICU:

  • Insulin resistance and impaired glucose tolerance
  • Increased fatty acid mobilization and hyperlipidemia
  • Accelerated protein degradation
  • The proinflammatory state of obesity
  • The endocrine derangements due to an excess of fatty tissue
  • The increased resting metabolic rate of obesity

Assessment of nutritional status is also detailed elsewhere; in brief the assessment takes the shaped of a structured approach, from history to investigatons:

History:

  • Premorbid weight and the pattern of its change
  • Premorbid nutritional routine
  • Diseases affecting gastrointestinal function (eg. coeliac disease)
  • Disease affecting satiety control (eg. Prader-Willi syndrome)
  • Factors influencing metabolic substrate utilisation (eg. thyroid dysfunction, hypoadrenalism, Cushings disease or corticosteroid therapy)

Examination:

  • Observed quality of nails and hair
  • Subcutaneous fat measurements (triceps)
  • Muscle bulk and muscle tone of quadriceps and deltoids
  • Presence of oedema and ascites

Anthropometry

  • BMI
  • Ideal body weight
  • Lean body mass

Biochemistry:

  • Cholesterol and triglycerides
  • Random BSL
  • HbA1C
  • Serum cortisol
  • TFTs
  • Albumin and prealbumin

Nutrition for the obese ICU patient is presently a topic of hot debate. The most recent suggestions are summarised elsewhere. In short, the published consensus statements suggest we follow a certain pattern:

References

Marik, Paul, and Joseph Varon. "The obese patient in the ICU." CHEST Journal113.2 (1998): 492-498.

El-Solh, Ali, et al. "Morbid obesity in the medical ICU." CHEST Journal 120.6 (2001): 1989-1997.

Jeevanandam, Malayappa, David H. Young, and William R. Schiller. "Obesity and the metabolic response to severe multiple trauma in man." Journal of Clinical Investigation 87.1 (1991): 262.

YALE, JEAN-FRANÇOIS, LAWRENCE A. LEITER, and ERROL B. MARLISS. "Metabolic Responses to Intense Exercise in Lean and Obese Subjects*." The Journal of Clinical Endocrinology & Metabolism 68.2 (1989): 438-445.

Port, Ava M., and Caroline Apovian. "Metabolic support of the obese intensive care unit patient: a current perspective." Current opinion in clinical nutrition and metabolic care 13.2 (2010): 184.

McClave, Stephen A., et al. "Nutrition Therapy of the Severely Obese, Critically Ill Patient Summation of Conclusions and Recommendations." Journal of Parenteral and Enteral Nutrition 35.5 suppl (2011): 88S-96S.

Wichansawakun, Sanit, et al. "Metabolic Support of the Obese Intensive Care Unit Patient." Integrative Weight Management. Springer New York, 2014. 215-224.

Mogensen, Kris M., et al. "Validation of the Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition Recommendations for Caloric Provision to Critically Ill Obese Patients A Pilot Study." Journal of Parenteral and Enteral Nutrition (2015): 0148607115584001.

Frankenfield, David C., Christine M. Ashcraft, and Dan A. Galvan. "Prediction of resting metabolic rate in critically ill patients at the extremes of body mass index." Journal of Parenteral and Enteral Nutrition 37.3 (2013): 361-367.

Ireton-Jones, Carol S., and Coni Francis. "Obesity: nutrition support practice and application to critical care." Nutrition in clinical Practice 10.4 (1995): 144-149.

Ireton-Jones, C. S., and W. W. Turner Jr. "Actual or ideal body weight: which should be used to predict energy expenditure?." Journal of the American Dietetic Association 91.2 (1991): 193-195.

Ravussin, Eric, et al. "Twenty-four-hour energy expenditure and resting metabolic rate in obese, moderately obese, and control subjects." The American Journal of Clinical Nutrition 35.3 (1982): 566-573.

Choban, Patricia S., et al. "Hypoenergetic nutrition support in hospitalized obese patients: a simplified method for clinical application." The American journal of clinical nutrition 66.3 (1997): 546-550.

Dickerson, Roland N. "Management of the Obese Patient." Nutrition Support for the Critically Ill. Springer International Publishing, 2016. 173-193.

Jeevanandam, Malayappa, David H. Young, and William R. Schiller. "Obesity and the metabolic response to severe multiple trauma in man." The Journal of clinical investigation87.1 (1991): 262-269.

Coeffier, Moise, and Fabienne Tamion. "The Stress Response of Critical Illness: Metabolic and Hormonal Aspects, Hormonal Regulation, Particular Clinical Situations “Morbid Obesity”." The Stress Response of Critical Illness: Metabolic and Hormonal Aspects. Springer, Cham, 2016. 217-225.

Question 28 - 2019, Paper 1

With respect to phaeochromocytoma:

a)    What is the usual mode of clinical presentation?    (30% marks)

b)    What biochemical tests and imaging can be performed to make the diagnosis?
(20% marks)

c)    Outline the key features of preoperative preparation and postoperative management.
(50% marks)
 

College answer

a)    What is the usual mode of clinical presentation
Symptomatic patient. Classic triad of symptoms consists of episodic headache, sweating, and tachycardia. Sustained or paroxysmal hypertension and less commonly visual blurring, papilledema, weight loss, polyuria, polydipsia and cardiomyopathy.
Incidental adrenal mass
Family history in patients with familial disease.

b)    What biochemical tests and imaging can be performed to make the diagnosis
24-hour urinary excretion of catecholamines and total metanephrines.
Plasma fractionated catecholamines (dopamine, norepinephrine, and epinephrine) and fractionated metanephrines (metanephrine and normetanephrine)
CT or MRI of abdomen and pelvis Scintigraphy and PET scanning

c)    Outline the key features of preoperative preparation and postoperative management

Combined alpha and beta-adrenergic blockade

Calcium channel blockers

Metyrosine which inhibits catecholamine synthesis

Post-operative management in ICU

Hypertensive crises or arrhythmias common complications

Patients who have bilateral adrenalectomies will require steroid cover
 

Discussion

"What is the usual mode of clinical presentation", they ask. Depending on what one means by mode, the answer may be "private car, ambulance, or fixed wing aircraft". Judging by the college answer, what they wanted was something about the clinical manifestations of a symptomatic patient, as well as the various ways in which an incidental phaechromocytoma may be discovered. About 10% of them are found on random CTs and MRIs which are done for other reasons (Kudva et al, 1999).

The typical features of symptomatic phaeochromocytoma are predominantly cardiovascular:

  • Paroxysmal or sustained hypertension
  • Palpitations and tachycardia
  • Headaches
  • Tremor
  • Sweating
  • Anxiety
  • Chest pain and myocardial infarction
  • Symptoms and signs of heart failure
  • Acute pulmonary oedema

There is also a possibility that one has their phaemochromocytoma diagnosed in the course of intentional phaeochromocytoma screening, because of some some sot of familial predisposition. There is also a well-known association between thyroid carcinoma and phaeochromocytoma - investigators in 1961 concluded that "the incidence of carcinoma of the thyroid gland is increased far beyond expectation based on chance concurrence".

What biochemical tests and imaging can be performed to make the diagnosis?

Investigations for phaeochromocytoma should include the following:

  • Tests for catecholamines and their metabolites
    • Urinary catecholamines
    • Plasma catecholamines
    • Urinary fractionated metanephrines
    • Plasma free metanephrines (these appear to be the best single investigation)
    • Urinary vanillylmandelic acid
  • Clonidine suppression test
    • In patients with phaeochromocytoma, serum catecholamine levels will not decrease in response to clonidine.

Overall, one's management should be guided by some sort of interational consensus guidelines, which take the following shape:

Outline the key features of preoperative preparation and postoperative management

  • Control of hypertension
    • Rapidly acting α-1 antagonist: phentolamine
    • Slowly acting non-competitive α-1 antagonist: phenoxybenzamine
    • β-antagonist (after α-antagonist)
  • Maintenance of circulating volume in the face of vasodilation:
    • IV fluid replacement
  • Control of AF
    • Verapimil, diltiazem, or amiodarone
  • Assessment of myocardial damage

References

Kudva, Yogish C., et al. "Adrenal incidentaloma: an important component of the clinical presentation spectrum of benign sporadic adrenal pheochromocytoma." The endocrinologist9.2 (1999): 77-80.

Goldstein, David S., Graeme Eisenhofer, and Irwin J. Kopin. "Sources and significance of plasma levels of catechols and their metabolites in humans."Journal of Pharmacology and Experimental Therapeutics 305.3 (2003): 800-811.

Sardesai, Suhrud H., et al. "Phaeochromocytoma and catecholamine induced cardiomyopathy presenting as heart failure." British heart journal 63.4 (1990): 234-237.

Lenders, Jacques WM, et al. "Biochemical diagnosis of pheochromocytoma: which test is best?." Jama 287.11 (2002): 1427-1434.

Russell, Walter John, et al. "The preoperative management of phaeochromocytoma." Anaesthesia and intensive care 26.2 (1998): 196-200.

Eschen, Ole, et al. "Pheochromocytoma, a rare cause of acute cardiogenic shock." Clinical research in cardiology 96.4 (2007): 232-235.

Li, Ling, et al. "Transthoracic Echocardiographic Features of Cardiac Pheochromocytoma: A Single‐Institution Experience." Echocardiography 29.2 (2012): 153-157.

Leissner, Kay B., et al. "Catecholamine-induced cardiomyopathy and Pheochromocytoma." Anesthesia & Analgesia 107.2 (2008): 410-412.

Sanchez-Recalde, Angel, et al. "Pheochromocytoma-related cardiomyopathy inverted Takotsubo contractile pattern." Circulation 113.17 (2006): e738-e739.

Sipple, John H. "The association of pheochromocytoma with carcinoma of the thyroid gland." The American Journal of Medicine 31.1 (1961): 163-166.

Pacak, Karel, et al. "Pheochromocytoma: recommendations for clinical practice from the First International Symposium." Nature clinical practice Endocrinology & metabolism 3.2 (2007): 92-102.

Reisch, Nicole, et al. "Pheochromocytoma: presentation, diagnosis and treatment." Journal of hypertension 24.12 (2006): 2331-2339.

Cohen, C. D., and D. M. Dent. "Phaeochromocytoma and acute cardiovascular death (with special reference to myocardial infarction).Postgraduate medical journal 60.700 (1984): 111-115.

Liao, Wei-Ber, et al. "Cardiovascular manifestations of pheochromocytoma."The American journal of emergency medicine 18.5 (2000): 622-625.

Jiang, Lei, et al. "123I-labeled metaiodobenzylguanidine for diagnosis of neuroendocrine tumors." Reports in Medical Imaging 2 (2009): 79-89.

Question 9 - 2019, Paper 2

Critically evaluate the provision of early (within seven days) nutrition in the critically ill patient.

College answer

Rationale

  • Critical illness associated with a catabolic state. Patients likely to have an energy deficit which may lead to muscle weakness and wasting
  • Some patients may have pre-existing malnutrition
  • Common for establishment of feeding regime to be delayed, or interrupted.
  • May be a role for micronutrients both to treat deficits and to prevent refeeding complications

Advantages

  • May reduce energy deficit, leading to overall improved outcome
  • Small volume “trophic feeding” may improve gut integrity and outcomes

Disadvantages

  • May lead to hyperglycaemia
  • May be poorly tolerated leading to gastric distension, reflux and aspiration risk
  • Disadvantages e.g. access etc. associated with TPN

Evidence

  • No clear evidence that early commencement of enteral nutrition within the first week improves outcomes
    • Notable trials:
      • EDEN (JAMA 2012, ARDSNET Investigators) Full enteral feeds vs “trophic” showed equivalent “hard” outcomes and “trophic” did better in terms of reflux, BSL control and had negative fluid balance
      • PERMiT (NEJM 2015, Saudi Arabia) 50% vs 100% caloric intake showed very similar results
      • No evidence for early supplementation with TPN (EPaNIC trial)
      • More recently TARGET (ANZICS 2017) showed no outcome difference between 1.5 and 1.0 kcal/mL feeds in an unselected ICU population (burns excluded), but more hyperglycaemia and upper GI effects in the 1.5 kcal/mL group (4,000 patients)

Note: TARGET was not examining timing of feeds but may be mentioned in the context of reduced caloric intake showing similar outcomes.

  • Trophic feeding for gut integrity and health (25% calories) delivered enterally improves outcomes in many groups, most notably pancreatitis

Summary Statement

Allow hypocaloric feeding for up to 7 days in previously well-nourished patients Early provision of vitamin and trace element supplementation

Examiners Comments:

Generally, well answered question. Most candidates were able to give reasonable responses to the questions addressing the important issues. Those that failed were unable to state why early feeding may be important and describe advantages/disadvantages or unable to discuss evidence around the topic.

Discussion

Rationale and definition:

  • Early nutrition is defined as nutrition provided within the first 48 hours of ICU stay
  • This window is characterised by:
    • Hypercatabolic state and increased requirement for macro/micronutrients
    • Decreased gut health and increased need for trophic stimulus
    • A greater susceptibility of the patient to the added insults of gut bacterial translocation and malnutrition
  • The rationale for providing early nutrition during this period is:
    • A critically ill patient has increased energy requirements
    • Their gut health is compromised because of shock and the stress response state
    • Mucosal integrity is compromised and bacterial translocation may occur
    • Delaying nutrition produces the risk of refeeding syndrome once nutrition is eventually reintroduced
    • Early nutrition addresses these specific concerns

Advantages:

  • Maintained delivery of macro and micronutrients
  • Defence of gut flora and intestinal mucosal integrity
  • Prevent refeeding syndrome
  • Treatment for any sort of underlying malnutrition
  • Enteral is safer than parenteral nutrition

Disadvantages

  • May be poorly tolerated (in terms of high residual gastric volumes); risk of aspiration
  • May not be absorbed (oedematous or poorly perfused intestine)
  • Diarrhoea and abdominal distension may develop
  • Total body utilisation of these nutrients may not be normal; we don't know what nutrient dose these patients need
  • There is no evidence that early 100%-of-goal nutrition actually prevents muscle catabolism
  • The hypercatabolic stress response is adaptive, and working against it may be counterproductive
  • Together with the stress response, hyperglycaemia may result, which has many disadvantages in the critically ill
  • Trials tend to focus on high risk critically ill patients with high illness severity, excluding the routine low-risk patients (i.e. these probably will not benefit)
  • Parenteral route has a host of unique complications (LFT derangement, infection risk, etc)

Evidence in support of early nutrition

  • There does not appear to be any harm from early nutrition (Heighes et al, 2016).
  • Meta-analysis suggests a decreased risk (RR 0.76) for infectious complications, but only when non-ICU patients were included (ESPEN)
  • The evidence seems to support early enteral nutrition rather than parenteral, particularly with respect to infectious complications
  • There is good evidence that "trophic feeding" is beneficial, i.e. early nutrition need not be targeting a full goal rate

Evidence against early nutrition

  • None of the RCT studies have ever demonstrated a mortality benefit from early nutrition
  • Many studies have demonstrated that hyperglycaemia has a significant association with increased mortality and morbidity in the ICU
  • When used in shocked patients, early enteral nutrition may increase the risk of gut ischaemia (Reignier et al, 2018)

These "notable trials" which the trainees should probably know:

References

Rice, Todd W., et al. "A randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure." Critical care medicine 39.5 (2011): 967.

Heighes, Philippa T., Gordon S. Doig, and Fiona Simpson. "Timing and Indications for Enteral Nutrition in the Critically Ill." Nutrition Support for the Critically Ill. Springer International Publishing, 2016. 55-62.

McClave, Stephen A., et al. "Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN)." Journal of Parenteral and Enteral Nutrition 40.2 (2016): 159-211.

Mentec, Hervé, et al. "Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications." Critical care medicine 29.10 (2001): 1955-1961.

Heyland, Daren K., et al. "Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients." Journal of Parenteral and Enteral nutrition 27.5 (2003): 355-373.

Montejo, J. C., et al. "Gastric residual volume during enteral nutrition in ICU patients: the REGANE study." Intensive care medicine 36.8 (2010): 1386-1393.

Poulard, Fanny, et al. "Impact of Not Measuring Residual Gastric Volume in Mechanically Ventilated Patients Receiving Early Enteral Feeding A Prospective Before–After Study." Journal of Parenteral and Enteral Nutrition 34.2 (2010): 125-130.

Desachy, Arnaud, et al. "Initial efficacy and tolerability of early enteral nutrition with immediate or gradual introduction in intubated patients." Intensive care medicine 34.6 (2008): 1054-1059.

Juvé-Udina, Maria-Eulàlia, et al. "To return or to discard? Randomised trial on gastric residual volume management." Intensive and Critical Care Nursing 25.5 (2009): 258-267.

Bing, Guo. "Gastric residual volume management in critically ill mechanically ventilated patients: A literature review." Proceedings of Singapore Healthcare (2015): 2010105815598451.

Nguyen, Nam Q. "Pharmacological therapy of feed intolerance in the critically ills." World journal of gastrointestinal pharmacology and therapeutics 5.3 (2014): 148.

Marino, L. V., et al. "To determine the effect of metoclopramide on gastric emptying in severe head injuries: a prospective, randomized, controlled clinical trial." British journal of neurosurgery 17.1 (2003): 24-28.

Nguyen, Nam Q., et al. "Erythromycin is more effective than metoclopramide in the treatment of feed intolerance in critical illness*." Critical care medicine 35.2 (2007): 483-489.

Fraser, R. J., A. M. Deane, and Marianne J. Chapman. "Prokinetic drugs for feed intolerance in critical illness: current and potential therapies." Critical Care and Resuscitation 11.2 (2009): 132.

Singer, Pierre, et al. "ESPEN guidelines on parenteral nutrition: intensive care." Clinical nutrition 28.4 (2009): 387-400.

van Zanten, Arthur RH, et al. "Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis." Critical Care 19.1 (2015): 1-16.

Oldani, Massimo, et al. "Glutamine Supplementation in Intensive Care Patients: A Meta-Analysis of Randomized Clinical Trials." Medicine 94.31 (2015).

Wernerman, Jan. "How to understand the results of studies of glutamine supplementation." Critical Care 19.1 (2015): 1-3.

van Zanten, Arthur RH, Zandrie Hofman, and Daren K. Heyland. "Consequences of the REDOXS and METAPLUS Trials The End of an Era of Glutamine and Antioxidant Supplementation for Critically Ill Patients?." Journal of Parenteral and Enteral Nutrition (2015): 0148607114567201.

Heyland, Daren, et al. "A randomized trial of glutamine and antioxidants in critically ill patients." New England Journal of Medicine 368.16 (2013): 1489-1497.

Van Zanten, Arthur RH, et al. "High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial." Jama 312.5 (2014): 514-524.

Ridley, Emma, Dashiell Gantner, and Vincent Pellegrino. "Nutrition therapy in critically ill patients-a review of current evidence for clinicians." Clinical Nutrition 34.4 (2015): 565-571.

Singer, Pierre, et al. "The tight calorie control study (TICACOS): a prospective, randomized, controlled pilot study of nutritional support in critically ill patients." Intensive care medicine 37.4 (2011): 601-609.

Casaer, Michael P., et al. "Early versus late parenteral nutrition in critically ill adults." N Engl J Med 365.6 (2011): 506-517.

Heidegger, Claudia Paula, et al. "Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial." The Lancet 381.9864 (2013): 385-393.

Doig, Gordon S., et al. "Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial." Jama 309.20 (2013): 2130-2138.

Davies, Andrew R., et al. "A multicenter, randomized controlled trial comparing early nasojejunal with nasogastric nutrition in critical illness*." Critical care medicine 40.8 (2012): 2342-2348.

Harvey, Sheila E., et al. "Trial of the route of early nutritional support in critically ill adults." New England Journal of Medicine 371.18 (2014): 1673-1684.

Andrews, Peter JD, et al. "Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients." Bmj 342 (2011): d1542.

Vassilyadi, Frank, Alkistis-Kira Panteliadou, and Christos Panteliadis. "Hallmarks in the History of Enteral and Parenteral Nutrition From Antiquity to the 20th Century." Nutrition in Clinical Practice 28.2 (2013): 209-217.

Tian, Feng, et al. "Effect of initial calorie intake via enteral nutrition in critical illness: a meta-analysis of randomised controlled trials." Crit Care 19 (2015): 180.

Jeejeebhoy, Khursheed N. "Nutrition Needs Should Be Modified to Consider Nutrition Status and Acuity of Illness Lessons From the INTACT Trial." Journal of Parenteral and Enteral Nutrition 40.1 (2016): 10-11.

Marik, Paul E., and Michael H. Hooper. "Normocaloric versus hypocaloric feeding on the outcomes of ICU patients: a systematic review and meta-analysis." Intensive care medicine (2015): 1-8.

Rice, Todd W., et al. "A randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure." Critical care medicine 39.5 (2011): 967.

Arabi, Yaseen M., et al. "Permissive Underfeeding or Standard Enteral Feeding in High–and Low–Nutritional-Risk Critically Ill Adults. Post Hoc Analysis of the PermiT Trial." American journal of respiratory and critical care medicine 195.5 (2017): 652-662.

Casaer, Michael P., et al. "Early versus late parenteral nutrition in critically ill adults." New England Journal of Medicine 365.6 (2011): 506-517.

TARGET Investigators, for the ANZICS Clinical Trials Group. "Energy-Dense versus Routine Enteral Nutrition in the Critically Ill." New England Journal of Medicine 379.19 (2018): 1823-1834.

Reignier, Jean, et al. "Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2)." The Lancet 391.10116 (2018): 133-143.

Question 23 - 2020, Paper 1

With respect to nutritional support in the critically ill:

a)    Outline how you would assess the nutritional status of a patient with suspected malnutrition.
(70% marks)

b)    Outline the pathophysiology of severe re-feeding syndrome.    (30% marks
 


 

College answer

  1. Assessments of nutritional status:

This is notoriously unreliable as there are many conditions that can alter the non-specific markers of nutritional status.

A good history should include the circumstances of poor intake (duration, cause, etc.), a background of previous eating behaviours, and GIT symptoms (nausea, vomiting diarrhoea, weight loss)

  1. Specifics in the examination, beyond the general examination and vital signs are:
  • Anthropometric
  • Weight, height and BMI calculation
  • Arm circumference
  • Triceps skin fold thickness
  1. Clinical:
  • Hair: Hair loss or abnormal distribution (lanugo),
  • Skin: Conjunctival pallor and skin pallor, xerosis (dry skin, A), spooning of nails (Iron), ecchymoses or petechiae (C or K), pressure ulcers, poor wound healing
  • Mouth: Glossitis (Niacin, Folate, B12, B2, B6), bleeding or sores on the gums and oral mucosa (C), angular cheilosis or stomatitis (B2, B6), leucoplakia, poor dentition
  • Neck: Thyromegaly
  • Extremities: loss of muscle mass (arm circumference, bitemporal wasting), loss subcutaneous fat (triceps skin thickness), bone tenderness (Vit D)
  • Neurologic: Peripheral neuropathy, reflexes, tetany, mental status, handgrip strength Investigations to assess protein status for protein calorie malnutrition, must all be taken in context of other evidence of acute and chronic illness and will alter as part of acute phase response.

Serum albumin (longest half-life at 18 – 20d)

Serum transferrin (half-life of 8 – 9d), but also reflects iron status, and low transferrin should be considered an indicator of protein status only in the setting of normal serum iron.

Serum pre albumin (half-life at 2 – 3d) - responds quickly to the onset of malnutrition and rises rapidly with adequate protein intake, but altered in the acute phase response due to acute or chronic inflammation.

Other investigations:

    • Anaemia with Fe levels, or B12 / Folate if macrocytic.
    • Vitamin and trace elements
    • Ca, PO4, Mg, Glucose, UEC are all non-specific
    • Retinol binding protein
  1. Pathophysiology of Re-feeding Syndrome

Reintroduction of glucose into diet after a considerable period of fasting 

Insulin  in   response   to   glucose   load   moves   the   glucose   into   cells   (with   K   and   Mg) The first step of glycolysis is the phosphorylation of glucose. This holds the glucose in cells. This leads to sudden and precipitous fall  in  phosphate  that  is  the  hallmark  of  refeeding  syndrome  Severely reduced phosphate is available for ATP, cAMP

Failure of tissues with high energy requirement - heart, kidney, muscle (rhabdomyolysis), brain, respiratory (diaphragm)

Discussion

Nutritional assessment:

History:

  • Premorbid weight and the pattern of its change
  • Premorbid nutritional routine
  • Diseases affecting gastrointestinal function (eg. coeliac disease)
  • Disease affecting satiety control (eg. Prader-Willi syndrome)
  • Factors influencing metabolic substrate utilisation (eg. thyroid dysfunction, hypoadrenalism, Cushings disease or corticosteroid therapy)

Examination:

  • Observed quality of nails and hair (an indicator of chronic protein intake)
  • Subcutaneous fat measurements (triceps)
  • Muscle bulk and muscle tone of quadriceps and deltoids
  • Presence of oedema and ascites
  • Evidence of any specific micronutrient deficiency
    • eg. neuropathy for Vitamin B12 deficiency

Anthropometry

  • BMI
  • Ideal body weight
  • Lean body mass

Biochemistry and physiology:

  • Cholesterol and triglycerides
  • Random BSL
  • HbA1C
  • Serum cortisol
  • TFTs
  • FBC for lymphocyte count
  • Albumin and prealbumin
  • Transferrin
  • Calculation of nitrogen balance
  • Micronutrient levels:
    • Fat-soluble vitamins A, D and E
    • Thiamine
    • Zinc
    • Selenium
    • Vitamin B12
    • Folate
  • Delayed hypersensitivity skin-testing

  Refeeding syndrome pathophysiology:

  • Total body phosphate depletion occurs during starvation:
    • Exogenous sources of phosphate are inadequate to supplement the daily phosphate requirements
    • Intracellular phosphate stores are used to synthesise ATP (using protein and fat as fuel)
    • Homeostatic mechanisms maintain serum concentrations of these ions at the expense of intracellular stores
  • With recommencement of nutrition:
  • An abrupt conversion of body fuel use from a catabolic starvation state to a normal anabolic state occurs.
  • Whereas during starvation fat catabolism was the chief source of energy (requiring no transmembrane electrolyte shifts), carbohydrate metabolism requires an intracellular migration of electrolytes (predominantly phosphate, which is required to trap glucose inside the cells).
  • Thus, the insulin surge associated with the reintroduction of carbohydrate metabolism results in a sudden and massive intracellular movement of electrolytes.
  • All the clinical features of refeeding syndrome are the result of extracellular electrolyte depletion, and the failure of normal concentration gradients.
  • Clinically, this will result in heart failure due to hypophosphataemia, and arrhythmias due to hypokalemia.

References

Detsky, Allan S., et al. "What is subjective global assessment of nutritional status." JPEN J Parenter Enteral Nutr 11.1 (1987): 8-13.

Sauberlich, Howerde E. Laboratory tests for the assessment of nutritional status. Vol. 21. CrC Press, 1999.

Gorstein, Jonathan, et al. "Issues in the assessment of nutritional status using anthropometry." Bulletin of the World Health Organization 72.2 (1994): 273.

Shenkin, Alan. "Serum prealbumin: Is it a marker of nutritional status or of risk of malnutrition?." Clinical chemistry 52.12 (2006): 2177-2179.

Klein, S. "The myth of serum albumin as a measure of nutritional status."Gastroenterology 99.6 (1990): 1845.

Hearing, Stephen D. "Refeeding syndrome." BMJ 328.7445 (2004): 908-909.

Kraft, Michael D., Imad F. Btaiche, and Gordon S. Sacks. "Review of the refeeding syndrome." Nutrition in Clinical Practice 20.6 (2005): 625-633.

Stanga, Z., et al. "Nutrition in clinical practice—the refeeding syndrome: illustrative cases and guidelines for prevention and treatment." European journal of clinical nutrition 62.6 (2008): 687-694.

Keys, Ancel, et al. "The biology of human starvation.(2 vols)." (1950).

Khan, Laeeq UR, et al. "Refeeding syndrome: a literature review."Gastroenterology research and practice 2011 (2010).

Crook, Martin A. "Refeeding syndrome: problems with definition and management." Nutrition 30.11 (2014): 1448-1455.

Rio, Alan, et al. "Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study." BMJ open 3.1 (2013): e002173.

Whitelaw, Melissa, et al. "Does aggressive refeeding in hospitalized adolescents with anorexia nervosa result in increased hypophosphatemia?." Journal of Adolescent Health 46.6 (2010): 577-582.

Agostino, Holly, Julius Erdstein, and Giuseppina Di Meglio. "Shifting paradigms: continuous nasogastric feeding with high caloric intakes in anorexia nervosa." Journal of Adolescent Health 53.5 (2013): 590-594.

Suzuki, Satoshi, et al. "Hypophosphatemia in critically ill patients." Journal of critical care 28.4 (2013): 536-e9.

Doig, Gordon S., et al. "Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial." The Lancet Respiratory Medicine 3.12 (2015): 943-952.

Alfaro Martínez, José Joaquín, et al. "Etiology and Complications of Refeeding Syndrome in the ICU." Diet and Nutrition in Critical Care (2015): 1065-1078.

Korbonits, Márta, et al. "Metabolic and hormonal changes during the refeeding period of prolonged fasting." European Journal of Endocrinology 157.2 (2007): 157-166.

GAULT, M. HENRY, et al. "Hypernatremia, azotemia, and dehydration due to high-protein tube feeding." Annals of internal medicine 68.4 (1968): 778-791.

National Collaborating Centre for Acute Care (UK. Nutrition support for adults: oral nutrition support, enteral tube feeding and parenteral nutrition. National Collaborating Centre for Acute Care (UK), 2006.

Crook, M. A., V. Hally, and J. V. Panteli. "The importance of the refeeding syndrome." Nutrition 17.7 (2001): 632-637.

Question 10.1 - 2020, Paper 2

The following results were obtained from a 62-year-old female one week following a subarachnoid haemorrhage with increasing confusion:

Parameter

Patient Value

Adult Normal Range

Sodium

130 mmol/L*

135 – 145

Potassium

4.0 mmol/L

3.5 – 5.0

Chloride

96 mmol/L

95 – 105

Bicarbonate

26.5 mmol/L*

22.0 – 26.0

Glucose

5.5 mmol/L

3.5 – 6.0

Urea

2.5 mmol/L*

3.0 – 8.0

Creatinine

37 μmol/L*

45 – 90

Magnesium

0.87 mmol/L

0.75 – 0.95

Albumin

33 g/L*

35 – 50

Protein

74 g/L

60 – 80

Total bilirubin

10 μmol/L

< 26

Alanine transferase          

26 U/L

< 35

Serum Osmolality

274 mosm/kg*        

285 – 295

Ionised calcium

1.19 mmol/L

1.10 – 1.35

Calcium corrected

2.34 mmol/L

2.12 – 2.62

Phosphate

0.97 mmol/L

0.80 – 1.50

a) What are the two most likely causes for this biochemical profile? (10% marks)

b) How would you distinguish between the two biochemically and clinically? (30% marks)

College answer

Not available.

Discussion

What we are seeing here is a patient with recent CNS pathology who has now developed

  • Hypoosmolar hyponatremia
  • Mild metabolic alkalosis
  • A low urea (suggestive of low protein metabolism or protein intake)
  • New confusion

The two most likely causes of this bicohemical profile would surely have to be endocrine, and related to the SAH.

  • SIADH
  • Hypoadrenalism (due to pituitary dysfunction)

One could also make the argument that any pituitary injury from SAH that is bad enough to cause hypoadrenalism would probably also cause hypothyroidism.

References

Question 14 - 2021, Paper 2

Regarding thyroid dysfunction in critically ill patients:

a)    List the likely clinical and laboratory findings that are seen in a patient with severe hypothyroidism, that requires ICU management.    (25% marks)

b)    Outline your approach to managing this patient in a).
(40% marks)

c)    List the laboratory findings in ‘euthyroid sick’ syndrome (ESS) in a critically ill patient.
(20% marks)

d)    Outline your approach to managing a patient with ESS in the ICU.
(15% marks)
 

College answer

Not available.

Discussion

It's difficult not to introduce false subtext into the exam stems, as this is a high-stakes piece of text, and people will surely scrutinise each letter as carefully as Biblical scholars, inflating the meaning of seemingly random choices of wording and grammar. For example, "list the likely clinical and laboratory findings" leaves the reader to wonder how many findings such a list ought to contain.  These should be findings "that are seen in a patient with severe hypothyroidism, that requires ICU management", presumably implying that one should not list findings seen in relatively healthy community-based outpatients with hypothyroidism (and the comma in the middle is suspicious). And then, we are invited to "outline your approach to managing this patient in a)", but..... there is no specific patient case mentioned in a), only "a patient with severe hypothyroidism, that requires ICU management". What mysterious grade items lurk in the difference between this wording, and simply asking the candidates to "otline your approach to managing a patient with severe hypothyroidism in the ICU"?

Pushing down the paralysing fear that one completely misinterpreted the question, the following potential answer can be offered:

a) Clinical and laboratory findings in severe hypothyroidism: left without instructions regarding how many of these were required, the author has listed all of them; though one might make the argument that postural dizziness  amenorrhoea and decreased libido are unlikely to be important in a patient that requires ICU management, and could have been omitted.

  • Symptoms
    • Lethargy
    • Depression
    • Psychosis
    • Decreased level of consciousness
    • Cold intolerance
    • Dry skin
    • Hoarse voice
    • Neck swelling (goitre)
    • Postural dizzyness
    • Gastro-oesophageal reflux
    • Constipation
    • Myalgia
    • Amenorrhoea
    • Decreased libido
  • Signs

    • Hair loss
    • Loss of the lateral eyebrows (Queen Anne sign)
    • Dry thickened skin
    • Oedema (usually, non-pitting)
    • Proximal muscle weakness
    • Periorbital oedema
    • Enlarged tongue
    • Bradycardia
    • Pericardial effusion
    • Hypothermia
    • Delayed reflexes
  • Laboratory features

    • Decreased T4 and T3
    • Increased TSH
    • Hyperlipidaemia
    • Hyponatremia
    • Normochromic normocytic anaemia

b) An approach to the management of the severely hypothyroid patient: for 40% of the total mark, this should have been a relatively thick paragraph or point-form list. What follows is a management plan for a patient with a very severe ICU-level hypothyroidism, bordering on myxoedema coma:

  • Specific management:
    • Replace thyroxine.   
      • Initially, IV triiodothyronine 10mcg 8-hourly
      • Also large loading dose (300-500 mcg per day) of enteral thyroxine
      • Decrease to 200mcg/day as the symptoms improve
      • Monitor TSH and clinical response
    • Add corticosteroids (stress dose of hydrocortisone, 50mg 8-hourly)
  • Supportive management:
    • Intubate and ventilate if unconscious 
    • Vasopressors and inotropes (expecting catecholamine resistance)
    • Gentle sedation (expecting increased sensitivity to anaesthetics)
    • Correct hyponatremia
    • Correct hypoglycaemia
    • Watch for bleeding (increased rate of fibrinolysis)

c) Features of sick euthyroid: 

  • T3: low
  • rT3: high
  • T3/rT3 ratio: low
  • T4: high ...or normal
  • TSH: high ...or normal

The sick euthyroid syndrome is a biochemical pattern of decreased circulating T3 levels, without a strong compensatory TSH response. The raised levels of rT3 result in a disproportionate degree of thyroid dysfunction, as rT3 is an inactive form, and therefore a competitive antagonist of "real" T3.

d) Management of sick euthyroid syndrome, in 90 seconds, 

  • There is no benefit in routinely supplementing T3 or T4
  • Focus on the management of the underlying critical illness
  • Correct malnutrition (euthyroid sick syndrome is strongly associated with malnutrition and hypercatabolic states)
  • Use IV triiodothyronine to support patients who have euthyroid sick syndrome and some degree of heart failure or cardiogenic shock

References

Farwell, Alan P. "Nonthyroidal illness syndrome." Current Opinion in Endocrinology, Diabetes and Obesity 20.5 (2013): 478-484.

De Groot, Leslie J. "Dangerous dogmas in medicine: the nonthyroidal illness syndrome." The Journal of Clinical Endocrinology & Metabolism 84.1 (1999): 151-164.

Ringel, Matthew D. "Management of hypothyroidism and hyperthyroidism in the intensive care unit." Critical care clinics 17.1 (2001): 59-74.

Almandoz, Jaime P., and Hossein Gharib. "Hypothyroidism: etiology, diagnosis, and management." Medical Clinics of North America 96.2 (2012): 203-221.