Printable List of All Gastroenterology and Hepatology SAQs

College Answer

The hepatorenal syndrome  is defmed as profound oliguria and avid sodium  retention in the setting of severe liver dysfunction.

{a) Causes: 
Can occur in the setting of both acute and acute-on-chronic liver disease of almost any cause 
eg. hepatitis, gestational liver failure, cirrl:tosis. 

(b) Mechanism: 
The  pathogenesis  appears  to be purely  functional  in  that  recovery:of :liver  function  or-· 
transplantation  of  the  failing  kidney  leads  to  recovery  of ·renal ·function.  Mechanisms··· implicated  include: hyperdynamic· circulation  with  lowering  of  renal  perfusion  pressure, activation   of   the  sympathetic   nervous   system   and   a  combination   of   precapillary vasoconstriction and past capillary dilatation  by vasoactive mediators leading to decreased glomerular  ultrafiltration  coefficient.  Hypovolaemia  and  raised  intra abdominal  pressure from ascites may also be factors. 

(c) Diagnosis: 
Is based on history (deteriorating renal function in the presence of severe liver disease) and the  combination   of  avid  sodiwn   retention  (UNa   <30mmolll),  oliguria,   unremarkable urinalysis and  sediment,  absence  of  obstruction and  exclusion  of  intravascular  volume depletion. 

(d) Treatment: 
Classic teaching is that. in the absence of liver function recovery or liver transplantation, 
there  is  no  treatment  other  than renal  replacement  therapy  for  established  hepatorenal 
syndrome. Other measures to be considered or experimental are: 
•  Volume expansion and albumin infusion 
•  Paracentesis 
•  Relief of portal hypertension (TIPS, shunt) 
•  Vasopressin analogs (omipressin), experimental 
•  Prostaglandin analogs -experimental

Discussion

Briefly, what is hepatorenal syndrome

Hepatorenal syndrome is kidney injury as the consequence of gradually reducing renal blood flow, in the context of gradually worsening liver failure.

Mechanism of hepatorenal syndrome

• Worsening hepatic function leads to worsening peripheral arterial vasodilation
• Vasodilation leads to increased cardiac output, renin-angiotensin-aldosterone overactivity, and sympathetic overactivity
• As a result, renal arterial vascular resistance increases in proportion to splanchnic and systemic arterial vasodilation
• This, there is progressive renal vasoconstriction and thus decreased glomerular filtration.
• In addition to this, worsening hepatic failure results in increasing ascites pressure (and thus decreasing renal perfusion pressure)

Causes of hepatorenal syndrome

• Sepsis of any origin
• Nephrotixic drugs in a patient with cirrhosis, particularly NSAIDs
• Rapid diuresis
• GI bleeding

Diagnosis

• This is a diagnosis of exclusion. The following criteria applied in the dawn age of Anno Domini 2000, when this paper was written:
  • presence of liver disease and portal hypertension
  • increase in creatinine to over 133micromol/L
  • no other obvious cause of renal failure
  • no microscopic hematuria
  • no reponse to fluid challenge (i.e. no pre-renal failure)
• These days, the criteria are:
  • Cirrhosis
  • Ascites
  • Acute kidney injury: 
    • Increase in serum creatinine ≥0.3 mg/dl (26.5 μmol/L) within 48hrs,
    • OR: ≥50% from baseline value within 7 days
    • AND/OR:  urine output ≤0.5 ml/kg for ≥6 h
  • Not improved with 24 hrs of fluid resuscitation
  • Absence of alternative explanation

Treatment of hepatorenal syndrome

• Albumin and fluid resuscitation
• Terlipressin
• Noradrenaline
• Octreotide

if all else fails, TIPS procedure may be appropriate.

UpToDate has an excellent synopsis of hepatorenal syndrome.

However, if you are cheap, you need free articles.

Salerno, Francesco, et al. "Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis." Postgraduate medical journal 84.998 (2008): 662-670.

Solà, Elsa, Mónica Guevara, and Pere Ginès. "Current treatment strategies for hepatorenal syndrome." Clinical Liver Disease 2.3 (2013): 136-139.

Angeli, Paolo, et al. "Diagnosis and management of acute kidney injury in patients with cirrhosis: Revised consensus recommendations of the International Club of Ascites." Journal of Hepatology 62.4 (2015): 968-974.

Angeli, Paolo, et al. "News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document." Journal of Hepatology 71.4 (2019): 811-822.

Nadim, Mitra K., et al. "Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting." Journal of Hepatology 81.1 (2024): 163-183.

College Answer

Principles of management include resuscitation (of someone who may well have lost >25% of blood volume), establishing a diagnosis, and definitive treatment while avoiding therapies that might worsen his underlying condition.

Resuscitation includes assessment of airway protection and breathing adequacy, which combined with neurological impairment indicates need for emergency intubation.

Circulatory support requires adequate intravenous access, but may not need to be too aggressive (as excessive resuscitation may worsen portal hypertension), and could be guided by factors including usual blood pressure (? accept MAP of 60 mmHg), urine output, and other signs of circulatory compromise.

Temporary use of a Sengstaken Blakemore tube (or equivalent eg Minnesota) may be considered if blood loss is uncontrollable. Invasive monitoring may be useful, but is not necessary in the early phase of resuscitation.

Establishing  a  diagnosis  for  the  cause  of  bleeding  includes  immediate  examination  (signs suggesting non-GI haemorrhage, chronic liver disease), history (from family/observers) of immediate event and possible precipitants (drugs, retching etc). Differential diagnosis of causes for jaundice should be considered (including hepatitic and toxins). More detailed history and examination will need to be completed later.

Immediate commencement of therapy (eg. intravenous vasoconstrictor such as somatostatin or vasopressin) should be considered while organising urgent endoscopy (which will usually result in banding or sclerotherapy for varices, and injection for some other pathologies). Initial investigations should include cross match, coagulation tests, full blood count, urea & electrolytes, liver function tests, blood glucose and paracetamol level. An ascitic tap should be undertaken early for microscopy and culture (as infection may well be present). Some rationale should have been given for the investigations listed.

Candidates should be aware of therapies that may be specifically required (correction of coagulopathy [FFP &/or platelets], prophylactic antibiotics, laxatives eg. lactulose; beta-blockers once stable, proton pump inhibitors) or contraindicated (sedatives worsening hepatic encephalopathy).

Discussion

I have attempted to force the coherent college answer into a familiar system.

(a)       Outline the principles of, and rationale for, the initial management of this patient.

• Attention to the ABCS, with management of life-threatening problems simultanous with a rapid focused examination and a brief history. History will focus on determining whether the source of the bleeding was indeed the gut (rather than a tracheal or bronchial source) and whether the vomiting preceded the hematemesis (which would be suspicious for a Mallory-Weiss tear or Boerhaave's syndrome)

• Airway:
  • This patient is likely to have hematemesis again; the airway needs to be protected
• Breathing/ventilation
  • Once he is intubated, ventilation settings will depend on the specifics of gas exchange and lung compliance
• Circulatory support
  • The inital stages of resuscitation will consist of replacement of blood and blood products
• Supportive management
  • Sedation should consist of anaesthetic agens with a short half-life and no long-lasting metabolites, such as propofol and remifentanyl
• Specific investigations
  • CXR to confirm ETT position and rule out GI perforation
  • FBC, G&H, coags, fibrinogen, EUC and CMP
  • Ultrasound of the abdomen to investigate the severity of portal hypertension
• Specific management
  • This patient requires urgent gastroscopy and banding or sclerotherapy of the varices
  • If a gastroscopy cannot be performed urgently, he will need to have a CT angiogram, with a view to proceed to angioembolisation of the bleeding vessels.
  • If blood loss is uncontrollable and gastroscopy/angioembolisation is delayed, a Sengstaken-Blakemore tube can be advanced and an attempt to tamponade the bleeding can be made.
  • Lactulose should be used to decrease the likelihood of hepatic encephalopathy

College Answer

Standard resuscitation goals and technique should be reiterated. Re-bleeding from varices requires repeat endoscopy for diagnosis and treatment. Additional treatments should be considered including vasoconstrictor infusions (eg. somatostatin or vasopressin with GTN), Trans-jugular Intra-hepatic Porto-systemic Shunt (TIPS), and surgical shunts (eg. spleno-renal). Balloon tamponade is being used less frequently because of a high incidence of complications (aspiration, oesophageal rupture, death).

Ongoing investigation and treatment of coagulopathy, and investigation of causes of jaundice should be undertaken. Treatment should include strategies to minimise hepatic encephalopathy.

Discussion

A systematic approach should be taken. I will not repeat the ABCs. Of course, one would ensure satisfactory maintenance of oxygenation and normotension. Certainly, one would replace the missing factors by transfusing blood products, as well as actual packed cells, and vitamin K.

Straight to the specific management:

• Hemostasis:
  • Re-bleeding from varices requires re-endoscopy. Sclerotherapy and/or banding would be the ideal way of managing this bleed, as it would have the fewest complications.
  • A Sengstaken-Blakemore tube is an option, but even when it was popular the experienced users noted that optimal pharmacological therapy is better than inexperienced use of balloon tamponade
• Reducing portal hypertension pharmacologically
  • Terlipressin is the drug of choice in decreasing portal venous congestion, and it has beenshown to decrease mortality in variceal bleeding
  • Octreotide is the next best choice
  • Non-selective beta blockade might be helpful to prevent further re-bleeding, but the jury is still out.
• Reducing portal hypertension invasively
  • TIPS decreases the chances of treatment failure in refractory variceal bleeding (in one study, the probability of remaining bleed-free was 97% in the TIPS group and 50% in the pharmacotherapy group)

Garcia-Tsao, Guadalupe, and Jaime Bosch. "Management of varices and variceal hemorrhage in cirrhosis." New England Journal of Medicine 362.9 (2010): 823-832.

García-Pagán, Juan Carlos, et al. "Early use of TIPS in patients with cirrhosis and variceal bleeding." New England Journal of Medicine 362.25 (2010): 2370-2379.

Vlavianos, P., et al. "Balloon tamponade in variceal bleeding: use and misuse."BMJ: British Medical Journal 298.6681 (1989): 1158.

Reverter, Enric, and Juan Carlos García‐Pagán. "Management of an acute variceal bleeding episode." Clinical Liver Disease 1.5 (2012): 151-154.

Ioannou, G. N., J. Doust, and D. C. Rockey. "Terlipressin in acute oesophageal variceal haemorrhage." Alimentary pharmacology & therapeutics 17.1 (2003): 53-64.

Corley, Douglas A., et al. "Octreotide for acute esophageal variceal bleeding: a meta-analysis." Gastroenterology 120.4 (2001): 946-954.

Reiberger, Thomas, et al. "Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol." Gut62.11 (2013): 1634-1641.

College Answer

Specific strategies to minimise hepatic encephalopathy should have been described if not already done so (including the use of lactulose). Precipitants must be minimised (treatment of infections, avoidance  of  sedatives,  correction  of  electrolyte  abnormalities/hypoxia, avoid  alkalosis,  limit dietary protein, consider unproven dietary supplements including BCAA etc.). Cautious volume expansion should be considered. Other reversible causes for renal dysfunction and coma should be sought and excluded. Management of ICP  may be necessary (and the CT does not exclude cerebral oedema). General supportive care should be considered (eg. physiotherapy, avoidance of line- related problems, family support etc.). Specific treatment may be required for ascites and its effects (drainage, colloid replacement etc).

Discussion

The college has given us a patient with a combination of several reasons to be encephalopathic; of these, the major one is liver failure -but we are also reminded that the creatinine has doubled.

Management of hepatic encephalopathy:

Specific management of hepatic encephalopathy

• Lactulose
• Rifaximin
• Avoidance of hyponatremia
• Nutritional management:
  • Branched-chain amino acids (BCAAs) and a reduced amount of aromatic amino acids
  • High fiber diet
  • Pro-biotics (though their benefit is unclear)

Management of the precipitating cause

• Stop GI bleeding (endoscopy, banding, etc)
• Antibiotics for SBP
• Correct dehydration
• Withdraw hepatotoxins

Supportive management of the encephalopathic patient

1. Support the airway.  If the patient is comatose or uncooperative, they may require intubation in order to correct disorders of gas exchange (as they may not be compliant with NIV and chest physiotherapy)
2. Wean ventilation to spontaneous mode as tolerated.​ Hypoxia and hpercapnea can be readily corrected if the patient is mechanically ventilated; otherwise, posture with chest physiotherapy and deep breathing exercises are crucial
   Avoid NIV; abdominal distension and a fluctuating level of consciousness will likely result in aspiration. HFNP is ok. 
3. Support haemodynamically;
   noradrenaline +/- terlipressin may be appropriate if hepatorenal syndrome is suspected
   Albumin (20%) is a reasonable resuscitation fluid
   Hepatic flow should be optimised by monitoring for abdominal compartment syndrome
4. Avoid sedation. As needed, use drugs which do not depend on hepatic metabolism (eg. remifentanyl).
   Cerebral oedema and the potential for intracranial catastrophe should be investigated with a CT brain
5. Correct electrolyte derangement
6. Monitor renal function (hepatorenal syndrome)
7. Ensure BSL is monitored and supplemental glucose is made available
   Ensure thiamine is co-administerd with glucose!
8. Correct clinically significant anaemia. 
   Address haematinic factor deficiencies.
9. Antibiotics as appropriate: ceftriaxone may be required if SBP is a real possibility.
   Blood cultures and inflammatory markers should be collected.

Pursuit of other explanations for decreased level of consciousness:

• Minimise sedation
• Optimise oxygenation and ventilation
• Screen for sepsis
• Observe for physical signs suggestive of raised intracranial pressure
• Manage uremia, and consider dialysis

Wendon, Julia, et al. "Critical care and cirrhosis: outcome and benefit." Current opinion in critical care 17.5 (2011): 533-537.

Riggio, Oliviero, et al. "Management of hepatic encephalopathy as an inpatient." Clinical Liver Disease 5.3 (2015): 79-82.

Bajaj, J. S. "Review article: the modern management of hepatic encephalopathy." Alimentary pharmacology & therapeutics 31.5 (2010): 537-547.

Amodio, Piero, et al. "The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus." Hepatology 58.1 (2013): 325-336.

Als-Nielsen, Bodil, Lise Lotte Gluud, and Christian Gluud. "Nonabsorbable disaccharides for hepatic encephalopathy." Cochrane Database Syst Rev 2 (2004).

Bass, Nathan M., et al. "Rifaximin treatment in hepatic encephalopathy." New England Journal of Medicine 362.12 (2010): 1071-1081.

College Answer

Prognosis of hepatic encephalopathy and associated organ dysfunction depends on whether the process is acute or chronic, and whether there are any reversible factors. The very high bilirubin level (350 mcgmol/L), and the fact that this man has rebled from his varices make his prognosis worse, but not unsalvageable. Shunting procedures may decrease his likelihood of further bleeding but are likely to worsen the encephalopathy.

Discussion

Severe hepatic encephalopathy in ICU seems to actually have a slightly better outcome than other sorts of organ system failures.

• The mortality at 1 year is about 54% according to one small study.
• Those patients who require nothing other than mechanical ventilation (i.e. ones who got intubated for low GCS and airway protection) tend to have better outcomes.
• The ones which have ascites, varices (which bleed) as well as sepsis - their 1-year mortalty tends to be as high as 60%.
• In spite of these grim numbers, the admission of cirrhosis patients to ICU is no longer viewed as a completely futile exercise, because there has been a gradual expansion of the treatment options available to them, and because their outcomes have improved with time.

Several things can be added, with regard to prognostication in chronic liver disease patients admitted to ICU:

• Childs-Pugh at admission is associated with survival at 12 months (Warren et al, 2015). Specifically:
  • Class A = 100% survival at 12 months
  • Class B = 50% survival at 12 months
  • Class C = 25% survival at 12 months
• The MELD score gives a 3- month  mortality prediction in patients awaiting a liver transplant:
  • 40 or more — 71.3% mortality
  • 30–39 — 52.6% mortality
  • 20–29 — 19.6% mortality
  • 10–19 — 6.0% mortality
  • <9 — 1.9% mortality
• In ICU, the liver scores have little influence because many other organ systems play are role in death or survival. Well-rounded models (SOFA, APACHE) are better at predicting ICU outcomes than liver-specific scoring systems (Levesque et al, 2012)

Fichet, Jérôme, et al. "Prognosis and 1-year mortality of intensive care unit patients with severe hepatic encephalopathy." Journal of critical care 24.3 (2009): 364-370.

García-Martínez, Rita, Macarena Simón-Talero, and Juan Córdoba. "Prognostic assessment in patients with hepatic encephalopathy." Disease markers 31.3 (2011): 171-179.

Wendon, Julia, et al. "Critical care and cirrhosis: outcome and benefit." Current opinion in critical care 17.5 (2011): 533-537.

Fichet, Jérôme, et al. "Prognosis and 1-year mortality of intensive care unit patients with severe hepatic encephalopathy." Journal of critical care 24.3 (2009): 364-370.

García-Martínez, Rita, Macarena Simón-Talero, and Juan Córdoba. "Prognostic assessment in patients with hepatic encephalopathy." Disease markers 31.3 (2011): 171-179.

Wendon, Julia, et al. "Critical care and cirrhosis: outcome and benefit." Current opinion in critical care 17.5 (2011): 533-537.

Pugh, R. N. H., et al. "Transection of the oesophagus for bleeding oesophageal varices." British Journal of Surgery 60.8 (1973): 646-649.

Forman, Lisa M., and Michael R. Lucey. "Predicting the prognosis of chronic liver disease: an evolution from Child to MELD." Hepatology 33.2 (2001): 473-475.

Child, CG_, and J. G. Turcotte. "Surgery and portal hypertension." Major problems in clinical surgery 1 (1964): 1.

Malinchoc, Michael, et al. "A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts." Hepatology 31.4 (2000): 864-871.

Zimmerman, Jack E., et al. "Intensive care unit admissions with cirrhosis: Risk‐stratifying patient groups and predicting individual survival." Hepatology 23.6 (1996): 1393-1401.

Cholongitas, E., et al. "Systematic review: the model for end‐stage liver disease–should it replace Child‐Pugh's classification for assessing prognosis in cirrhosis?." Alimentary pharmacology & therapeutics 22.11‐12 (2005): 1079-1089.

Ho, Yu-Pin, et al. "Outcome prediction for critically ill cirrhotic patients: a comparison of APACHE II and Child-Pugh scoring systems." Journal of intensive care medicine 19.2 (2004): 105-110.

Cholongitas, E., et al. "Risk factors, Sequential Organ Failure Assessment and Model for End‐stage Liver Disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit." Alimentary pharmacology & therapeutics 23.7 (2006): 883-893.

Levesque, Eric, et al. "Prospective evaluation of the prognostic scores for cirrhotic patients admitted to an intensive care unit." Journal of hepatology 56.1 (2012): 95-102.

Yeoh, Sern Wei, et al. "Cirrhotics Treated In Intensive Care Unit Have High Short Term Survival in the Absence of Extrahepatic Organ Dysfunction." Journal of Gastroenterology and Hepatology Research 5.2 (2016): 1984-1988.

Wiesner, Russell, et al. "Model for end-stage liver disease (MELD) and allocation of donor livers." Gastroenterology 124.1 (2003): 91-96.

Saliba, Faouzi, et al. "Cirrhotic patients in the ICU: prognostic markers and outcome." Current opinion in critical care 19.2 (2013): 154-160.

Peng, Ying, Xingshun Qi, and Xiaozhong Guo. "Child–Pugh Versus MELD Score for the Assessment of Prognosis in Liver Cirrhosis: A Systematic Review and Meta-Analysis of Observational Studies." Medicine 95.8 (2016).

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.

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.

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:

College Answer

Discussion on the effects of the ICS should include:

•    renal effects – capillary compression, decreased GFR/UO, ATN,

•    bowel – decreased SMA/coeliac flow, decreased pHi, bowel ischaemia

•    hepatic – decreased portal blood flow, lactate clearance

•    cardiac –decreased venous return/cardiac output, elevated PAOP/CVP/afterload

•    respiratory –increased PIP, shunt, Paw,

•    cerebral – increased ICP, decreased CPP

Description of a simple, sterile and practical technique for measurement of intra-vesical pressure was expected.

Pitfalls include:

•    using the wrong zero point

•    allowing a leak in the system to produce a falsely low reading

•    chronic cystitis, radiation cystitis producing a small contracted bladder with low compliance which gives a falsely high reading

•    pelvic haematoma producing a tight pelvic compartment with falsely elevated IAP.

Discussion

The majority of this question is answered by the discussion of Question 8 from the first paper of 2013. A slightly less formal discussion of abdominal compartment syndrome takes place in Question 21 from the second paper of 2006: "Outline the causes, consequences and the management of abdominal  compartment syndrome. "

The "pitfalls" section is not addressed anywhere else.

Briefly, the following are reasons as to why one's intrabdominal measurements may be wrong:

• Failure of technique
  • Improper setup of the measuring set
  • Improperly calibrated transducer
  • Inappropriate zero point
  • Leaking transducer system
• Confounding factors
  • Increased pelvic pressure
  • High detrusor tone
  • Detrusor fibrosis
  • Incompletely paralysed patient

College Answer

Ascitic fluid analysis provides – Fluid for General appearance

Albumin / protein content

Red cell count White cell count Culture and sensitivity Cytology

Biochemistry - amylase

Indications for performing a tap include: any patient with ascites and PUO, critical illness or suspected malignancy.

Discussion

I would expand the college list:

Information which can be derived from an ascitic fluid analysis:

• Appearance - turbidity would be very suspicious for SBP
• Albumin - to calculate serum/ascites albumin gradient
• Amylase/lipase - to consider pancreatitis as the cause of ascites
• LDH (low indicates hepatic cause, whereas >500 suggests malignancy)
• Gram stain - for bacteria
• India ink stain - for hyphae
• ZN stain for acid-fast bacilli (tuberculosis)
• Culture/sensitivities
• Flow cytometry and cell count - RBC/WCC ratio would raise suspicion of SBP
• Cytology - presence of malignant cells
• alpha-foetoprotein - to investigate for HCC

Indications for ascitic fluid drainage:

• Diagnostic
  • see above
• Therapeutic
  • patient discomfort
  • respiratory compromise due to adominal pressure
  • abdominal compartment syndrome
  • infected ascitic fluid (i.e. as source control)
  • for peritoneal dialysis (this can be viewed as a therapeutic paracentesis

Bar-Meir, Simon, Emanuel Lerner, and Harold O. Conn. "Analysis of ascitic fluid in cirrhosis." Digestive diseases and sciences 24.2 (1979): 136-144.

Boyer, Thomas D., Arthur M. Kahn, and Telfer B. Reynolds. "Diagnostic value of ascitic fluid lactic dehydrogenase, protein, and WBC levels." Archives of internal medicine 138.7 (1978): 1103-1105.

Runyon, Bruce A., John C. Hoefs, and Timothy R. Morgan. "Ascitic fluid analysis in malignancy‐related ascites." Hepatology 8.5 (1988): 1104-1109.

College Answer

Cisapride: selectively enhances physiologic release of acetylcholine at level of myenteric plexus. Part  of  effect  via  activation  of  serotonin  (5-HT4)  receptors.  Enhances  oesophageal  peristaltic activity, gastric emptying, intestinal propulsive activity and colonic transit. Extensively metabolised via cytochrome P450 3A4 enzymes. Highly protein bound. Only administered orally. Significant adverse effects and interactions, especially prolonged QT interval (and arrhythmias) in particular when administered in patients at risk of arrhythmias or when administered concurrently with drugs that  prolong  QT  or  drugs  that  inhibit  P450  3A4  enzymes  (e.g.  azole  antifungals,  macrolide antibiotics, and protease inhibitors). Problems with limited availability, restrictions on prescribing, large number of documented interactions.

Metoclopramide: mode of action unclear (? via selective dopamine-2 receptor antagonist effects); sensitises tissues to the action of acetylcholine (motility effects abolished by anticholinergic drugs and  narcotic  analgesics).  Increases  tone  and  amplitude  of  gastric  contractions,  relaxes  pyloric sphincter and increases peristalsis of duodenum and jejunum. Administered orally, IV or IM. Conjugated by liver and renally excreted (reduced clearance with renal failure). Minimal protein binding. Dopamine agonist activity responsible for adverse effects (e.g. sedation, dystonic/extrapyramidal reactions).

Erythromycin: macrolide antibiotic that seems to stimulate motilin receptors, and enhances motilin release from enterochromaffin  cells of duodenum. Enhanced contractile effects on gastric antrum and duodenum. Administered orally or intravenously  ( probably IV more effective). Highly protein bound. Substantial hepatic metabolism. Prolonged QT and arrhythmias reported, as have hepatic dysfunction, overgrowth of non-susceptible organisms and colitis (Cl. difficile). Elevated levels of many other drugs (as a result of inhibition of metabolism) can lead to toxicity (e.g. theophylline, HMG-CoA reductase inhibitors, anti-epileptics, digoxin, warfarin etc).

Discussion

One study ran all of these drugs against each other to evaluate their comparative efficacy. The only useful finding was that metoclopramide worked faster than cisapride. And then cisapride was withdrawn from the market, following concerns of toxicity. The current Canadian Critical Care Nutrition Guidelines only mention metoclopramide and erythromycin (as well as enteral naloxone).

MacLaren, Robert, et al. "Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: a randomized, placebo-controlled, crossover study." Critical care medicine 28.2 (2000): 438-444.

The best resource for all EBM in this topic is the Canadian Critical Care Nutrition Guidelineswebsite.

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

College Answer

Answers should address more than just prevention of gastric erosions/stress ulceration.

Consideration should be given to other causes including patients with known gastro-oesophageal varices (where sclerotherapy/banding, beta-blockers and techniques to lower venous pressure, and avoidance of local trauma should be considered).

With regard to stress ulceration many strategies have been employed, and should be considered in a broad answer.  General resuscitation of patients, correction of coagulopathy, early enteral feeding and avoidance of precipitants (eg. NSAIDs) in patients at risk are assumed to be beneficial (but not well studied).  Prospective randomised trials have generally compared drug regimens (antacids vs sucralfate vs H2-blockers vs proton pump inhibitors).  Other agents include prostaglandin analogs. Controversy surrounds the issues of widespread use of prophylactic agents, value of drugs vs placebo, nosocomial infection rates, and cost-benefit analyses.

Discussion

"Critically evaluate" demands a certain degree of structure. Contrary to the college answer, banding and sclerotherapy are not usually preventative techniques. If one were to dedicate any time during this ten minute answer to varices and leaking AVMs, one may wish to be very brief about it, as the meat is clearly in gastric ulceration.

Introduction

Gastrointestinal bleeding in the critically ill patient may be due to a variety of causes; these include bleeding from stress ulceration, oesophageal varices, and colonic polyps. Exacerbating causes include antiplatelet and anticoagulant medications, as well as poor perfusion of gastrointestinal mucosa in the context of shock. Given that in the ICU GI bleeding is combined with a series of other major organ dysfunction syndromes, it tends to have a castarophic mortality rate and it is important to be able to protect at-risk patients from this complication.

Rationale

Options:

• Proton pump inhibitors
• Histamine receptor antagonists
• non-pharmacological management - protective role of enteral feeding

Advantages

• Decreased risk of gastrointestinal bleeding
• Decreased exposure to blood products, and the attendent risks thereof

Disadvantages

• Decreased gastric acidity, thus increased risk of non-sterile aspiration
• Increased risk of gastrointestinal bacterial overgrowth and translocation
• Increased risk of Clostridium difficile infections
• Economic disadvantage (cost)

Evidence for the routine use of ulcer prophylaxis

• A recent meta-analysis suggests that the quality and quantity of the evidence is still poor, but on the weight of the available evidence there is neither a mortality improvement nor any increase in the risk of nosocomial pneumonia.
• There appears to be no benefit for stress ulcer prophylaxis in patients who are tolerating enteral feeding, and in these patients stress ulcer prophylaxis is not needed.
• There is insufficent evidence to recommend the mandatory use of stress ulcer prophylaxis in any specific patient group (again, 
• Obviously, correcting coagulopathy (and not triggering any new coagulopathy, nor disabling the platelets with NSAIDs) is a good way to prevent catsatropic bleeding in the ICU.

Evidence to support one drug class over another

• At the time of this paper having been written, there was insufficient evidence to recommend any specific medication (e.e H₂As vs PPIs); however the Danes recommended PPIs, because they are more effective at keeping the gastric pH at over 4.0.
• There is now lots of evidence, and it is still unclear whether PPIs or H₂As are more effective. Pro-PPI studies include a big 2016 meta-analysis by Alshamsi et al, which revealed them to be more effective at preventing clinically significant episodes of bleeding. However, it must be pointed out that many of the studies which met inclusion criteria didn't even specify what they meant by "bleeding". When other meta-analysis authors selected studies  limited to ones with a low risk of bias, the results they arrived at were not significant (Barletta et al, 2016).

Summary

PPIs are indicated in at-risk patient in ICU who are intolerant of eneteral feeding, and who are otherwise at risk of gastrointestinal bleeding. Further research is required to discriminated between different classes of drugs in terms of efficacy, and to identify the at-risk population.

Steinberg, Kenneth P. "Stress-related mucosal disease in the critically ill patient: risk factors and strategies to prevent stress-related bleeding in the intensive care unit." Critical care medicine 30.6 (2002): S362-S364.

Marik, Paul E., et al. "Stress ulcer prophylaxis in the new millennium: a systematic review and meta-analysis." Crit Care Med 38.11 (2010): 2222-2228.

Krag, Mette, et al. "Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients." Intensive care medicine 40.1 (2014): 11-22.

Madsen, Kristian Rørbæk, et al. "Guideline for Stress Ulcer Prophylaxis in the Intensive Care Unit." Danish medical journal 61.3 (2014): 1-4.

Alshamsi, Fayez, et al. "Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials." Critical Care 20.1 (2016): 120.

Barletta, Jeffrey F., et al. "Stress ulcer prophylaxis." Critical care medicine44.7 (2016): 1395-1405.

College Answer

Mental state could be severely depressed or patient may be agitated or confused.  

In general the potential aetiologies are the same, though some more likely in each type of state.   Consider: decreased oxygen delivery to braiin (hypoxaemia, low cardiac output, low blood pressure), effects of drugs (those administered or those withdrawing from), intracerebral pathology (thromboembolism, rarely bleed eg. into undetected secondaries), electrolyte disorders (especially glucose, Na and Calcium), infections (unlikely; eg. systemic/meningitis/encephalitis), postoperative confusional state (uncertain but probably multifactorial aetiology), post-ictal or psychiatric disorder.

Management involves exclusion of  reversible and  specific treatable causes considered likely/possible (eg. SpO2, vital signs, glucose, electrolytes, review drugs and history).  Appropriate treatment of any specific abnormalities detected. Protection of patient and staff with cautious use of restraint (chemical or physical) if absolutely necessary or specifically indicated.

Discussion

Potential aetiology for a severely altered mental status post hepatic resection:

• Hypoxia due to intrapulmonary portosystemic shunting, atelectasis or aspiration
• Hypercapnea due to right pleural effusion
• Hepatic encephalopathy due to high ammonia
• Cerebral oedema
• Diminished capacity to metabolise anaesthetic drugs and sedatives
• Intracranial haemorrhage in the context of coagulopathy
• Septic encephalopathy post-operatively

Management:

Specific management of hepatic encephalopathy

• Lactulose
• Rifaximin
• Avoidance of hyponatremia
• Nutritional management:
  • Branched-chain amino acids (BCAAs) and a reduced amount of aromatic amino acids
  • High fiber diet
  • Pro-biotics (though their benefit is unclear)

Management of the precipitating cause

• Stop GI bleeding (endoscopy, banding, etc)
• Antibiotics for SBP
• Correct dehydration
• Withdraw hepatotoxins

Supportive management of the encephalopathic patient

1. Support the airway.  If the patient is comatose or uncooperative, they may require intubation in order to correct disorders of gas exchange (as they may not be compliant with NIV and chest physiotherapy)
2. Wean ventilation to spontaneous mode as tolerated.​ Hypoxia and hpercapnea can be readily corrected if the patient is mechanically ventilated; otherwise, posture with chest physiotherapy and deep breathing exercises are crucial
   Avoid NIV; abdominal distension and a fluctuating level of consciousness will likely result in aspiration. HFNP is ok. 
3. Support haemodynamically;
   noradrenaline +/- terlipressin may be appropriate if hepatorenal syndrome is suspected
   Albumin (20%) is a reasonable resuscitation fluid
   Hepatic flow should be optimised by monitoring for abdominal compartment syndrome
4. Avoid sedation. As needed, use drugs which do not depend on hepatic metabolism (eg. remifentanyl).
   Cerebral oedema and the potential for intracranial catastrophe should be investigated with a CT brain
5. Correct electrolyte derangement
6. Monitor renal function (hepatorenal syndrome)
7. Ensure BSL is monitored and supplemental glucose is made available
   Ensure thiamine is co-administerd with glucose!
8. Correct clinically significant anaemia. 
   Address haematinic factor deficiencies.
9. Antibiotics as appropriate: ceftriaxone may be required if SBP is a real possibility.
   Blood cultures and inflammatory markers should be collected.

Wendon, Julia, et al. "Critical care and cirrhosis: outcome and benefit." Current opinion in critical care 17.5 (2011): 533-537.

Riggio, Oliviero, et al. "Management of hepatic encephalopathy as an inpatient." Clinical Liver Disease 5.3 (2015): 79-82.

Bajaj, J. S. "Review article: the modern management of hepatic encephalopathy." Alimentary pharmacology & therapeutics 31.5 (2010): 537-547.

Amodio, Piero, et al. "The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus." Hepatology 58.1 (2013): 325-336.

Als-Nielsen, Bodil, Lise Lotte Gluud, and Christian Gluud. "Nonabsorbable disaccharides for hepatic encephalopathy." Cochrane Database Syst Rev 2 (2004).

Bass, Nathan M., et al. "Rifaximin treatment in hepatic encephalopathy." New England Journal of Medicine 362.12 (2010): 1071-1081.

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.

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
  • In 2008, Marik et al conducted a meta-analysis of RCTs and found a slight benefit in infection risk among patients supplemented with fish oil.
  • In 2010, Marik et al also published a systematic review which supported the use of fish oil supplements in high-risk surgical patients.
  • A 2011 review of immunonutrition in gastrointestinal surgery patients found some improvement in hospital stay and infectious morbidity, but not in mortality.
  • A 2012 trial comparing immunonutrition to routine practice among preoperatively malnoursihed patients found no difference in major outcome measures.
  • The ASPEN guidelines make the following statements:
    • No evidence to recommend arginine
    • No evidence to recommend fish oil or antioxidants
    • No evidence to recommend ornithine ketoglutarate
    • No evidence to recommend zink supplements
    • Some evidence to support the use of glutamine (this recommendation has been downgraded since 2009)
    • Some evidence to support selenium
• 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.

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.

College Answer

The perioperative complications could be classified into (1) that of any major upper abdominal surgery and (2) specifically that of a hemi-hepatectomy for cholangiocarcinoma; or divided into various systems, ie.

(1) Respiratory:                     Inadequate  or  excessive  analgesia,  pulmonary oedema  from  fluid overload, R. haemothorax, R. pneumothorax, R diaphragmatic dysfunction, V/Q mismatch from hepatic failure, aspiration and possibly early pulmonary infection or thromboembolism. Very rarely, intraoperative air embolism ®ARDS.
(2) Cardiovascular:                Hypotension from bleeding, epidural block, perioperative myocardial ischaemia / infarction, Arrhythmias associated with electrolyte abnormalities.
(3) Gastro-intestinal failure:   Prolonged ileus, pseudo-obstruction, ascites, G I haemorrhage. (4) Renal:                                                Hepatorenal syndrome, acute tubular necrosis, oliguria.
(5) Hepatic:                             Cholangitis, hepatic failure, encephalopathy, coagulopathy, (6) CNS:                                                Encephalopathy.
(7) Metabolic:                        hyperlactataemia, iNa+, lK+, hypoglycaemia.
(8) Premorbid condition:        Possible ulcerative colitis/primary sclerosing cholangitis: Therefore, medication issues ie steroids, immune state, nutritional status etc.

Treatment is basically meticulous perioperative care with special regard to fluid and electrolyte balance, analgesia, coagulation control, and specific and supportive therapy for any individual complications that develop ie encephalopathy, hepatorenal syndrome etc.

Discussion

This question closely resembles Question 1 from the second paper of 2006. In the interest of simplified revision, the answer to that question is reproduced below:

Jarnagin, William R., et al. "Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade." Annals of surgery 236.4 (2002): 397-407.

Page, Andrew J., and David A. Kooby. "Perioperative management of hepatic resection." Journal of gastrointestinal oncology 3.1 (2012): 19-27.

Wrighton, Lindsay J., et al. "Postoperative management after hepatic resection." Journal of gastrointestinal oncology 3.1 (2012): 41-47.

Thorat, Ashok, and Wei-Chen Lee. Critical Care Issues After Major Hepatic Surgery. INTECH Open Access Publisher, 2013.

Pagano, Duilio, et al. "The unreliability of continuous postoperative lactate monitoring after extended hepatectomies: single center experience." Updates in surgery 67.1 (2015): 33-37.

Ciuni, Roberto, et al. "Nutritional aspects in patient undergoing liver resection." Updates in surgery 63.4 (2011): 249-252.

Hotta, Tsukasa, et al. "Evaluation of postoperative nutritional state after hepatectomy for hepatocellular carcinoma." Hepato-gastroenterology 50.53 (2002): 1511-1516.

Richter, B., et al. "Nutritional support after open liver resection: a systematic review." Digestive surgery 23.3 (2006): 139-145.

Marchesini, Giulio, et al. "Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial." Gastroenterology 124.7 (2003): 1792-1801.

Kim, Say-June, Dong-Goo Kim, and Myung Duk Lee. "Effects of branched-chain amino acid infusions on liver regeneration and plasma amino acid patterns in partially hepatectomized rats." Hepato-gastroenterology 58.109 (2010): 1280-1285.

Neelakanta, Gundappa, et al. "Early tracheal extubation after liver transplantation." Journal of cardiothoracic and vascular anesthesia 11.2 (1997): 165-167.

Narita, Masato, et al. "Noninvasive ventilation improves the outcome of pulmonary complications after liver resection." Internal Medicine 49.15 (2010): 1501-1507.

College Answer

This is a complex field with a large amount of literature to collate. Pancreatitis is usually presents with persistent upper abdominal pain, associated with nausea and vomiting, which can be associated with signs of local tenderness through to peritonism, and/or signs of a systemic inflammatory response  (e.g.  fever,  tachycardia) or  signs  of  associated  disorders  (e.g.  jaundice  with  biliary obstruction) or rarely signs of complications (e.g. ecchymotic discoloration in flank [Grey-Turner’s sign] or peri-umbilical [Cullen’s sign] regions). These signs may be difficult to elicit or masked in critically ill patients. Investigations that assist in the diagnosis include: serum amylase (usually > 3 times normal) (serum lipase does not improve diagnostic accuracy); liver function tests (looking for evidence of obstructive pattern with gall stone induced pancreatitis); plain abdominal radiograph (excludes other aetiologies, and may show localised ileus [“sentinel loop”]; abdominal ultrasound (enlarged hypo-echoic pancreas, and looking for gall stones); and abdominal CT scan with contrast (confirm diagnois and looking for areas of necrosis or pseudocysts). Ranson’s criteria (or more recently Glasgow criteria or Imrie score) are used to assess severity and predict outcome, and they include white cell count (>16,000/mm3), glucose (>11 mmol/L), AST > 250 IU/L, Ca < 2mmol/L, hypoxaemia (<8kPa), and a decrease in haematocrit (>10%) and an increase in urea (>1.8 mmol/L).

Complications include: those associated with a systemic inflammatory response (e.g. myocardial depression/shock,  ARDS,  renal  failure,  death);  respiratory  (including  pleural  effucsion  and atelectasis);  metabolic  (including  hypocalcaemia,  glucose  disturbances);  and   intrabdominal problems (including ileus, necrosis, pseudo-cysts, abscess formation, etc).

Treatment should include: aggressive fluid resuscitation to stabilise the haemodynamic state, treatment of underlying cause (e.g. ERCP if gall stones present, withdrawal of offending drug), treatment of pain (morphine controversial), surgical treatment of complications (e.g. aspiration/drainage of infected collections) and general support of the critically ill patient. More contentious issues that should be considered include: early prophylactic broad spectrum antibiotics (evidence that decrease complications), prophylactic anti-fungal therapy, jejunal feeding (safe, feasible, cheaper than TPN, possibly of benefit), the use of somatostatin, octreotide or protease inhibitors (none have sufficient evidence base to use routinely), and the timing and nature of surgical interventions.

Discussion

This question dates back to a time when there was a whole massive period during which one had plenty of thinking room, planning, and then the process of written communication could take place at a civilised pace, without rush. Now, of course, a question like this has the candidate trying to fit the last 30 years of pancreatitis literature into a ten minute answer.

One patently cannot do this.

The suggested answer below is one which could easily be produced over the course of ten minutes.

Diagnostic features

• Presentation with severe abdominal pain, nausea and vomiting on presentation
• Metabolic acidosis and shock; hypocalcemia
• Elevated pancreatic enzyme levels, of which lipase is the more pancreas-specific
• An abdominal CT may reveal that a widened common bile duct is present, potentially with an impacted stone in the bile duct.

Complications

• SIRS and hemodynamic compromise
• renal failure
• infection of pancreatic necrosis
• hepatic failure
• abdominal comaprtment syndrome
• ARDS
• hypocalcemia
• metabolic acidosis
• myocardial contractility depression
• ileus

Treatment

• Airway:
  • intubation may be required; aspiration may be a major risk
• Breathing:
  • mechanical ventilation with PEEP titrated to permit recruitment of collapsed lung bases
  • As ARDS develops, tidal volumes may nee to be reduced and lung-protective ventilation may need to be adopted, with permissive hypercapnea
• Circulation:
  • Initial stages of resuscitation will likely consist of fluids only
  • The SIRS response may lead to cardiovascular collapse; given that metabolic acidosis and SIRS-associated cardiomyopathy may also be present, inotropes as well as vasopressors will likely be required
• Pain control:
  • this will be vitally important in the non-intubated patient, in order to maintain VQ matching by continuing deep breathing
• Electrolytes- particularly calcium - must be carefully monitored
• Fluid balance management neesd to be careful, and dialysis may be required
• Feeds via the NG tube may be commenced; there does not appear to be any evidence that "pancreatic rest" is in any way beneficial. The necrotic pancreas is not going to be responsive to the normal secretory stimuli, and the
• Coagulation factors need to be corrected, and careful surveillance of the abdominal vessels must occur, as the splenic artery has a tendency to form aneurysms and bleed everywhere
• Antibiotics are probably not indicated
• ERCP to manage the cause of CBD obstruction should take place at the earliest opportunity, as indicated. if there is no ERCP-amenable cause, surgical drainage of the necrotic pseudocyst may take place as soonas the pseudocyst has formed a sufficiently distinct "wall".
• An alternative to surgical cyst drainage is endoscopic ultrasound-guided drainage, which may be a better option for the frail patient.

Wilmer, Alexander. "ICU management of severe acute pancreatitis." European journal of internal medicine 15.5 (2004): 274-280.

College Answer

(c)       Over the next 48 hours he develops increasing jaundice, with severe derangement of his Liver Function  Tests. What are the likely causes, and how are you going to manage this problem?

The potential causes of jaundice and abnormal LFTs within the first 72 hours are many. The pattern of elevation may help the diagnosis (eg. hepatocellular pattern [elevated transaminases, but minor elevation of Alkaline Phosphatase], cholestatic [minor elevation of transaminases]), and a systematic approach is helpful. Most likely causes include infection (systemic sepsis, mild hepatitic/intravascular cholestasis, liver abscess, acalculous cholecystitis), drug induced (cholestatic/hepatitic), haemodynamic/shock (ischaemic hepatitis) or haemolysis (sepsis, early destruction of transfused blood). Pre-existing intercurrent diseases (hepatitis, gall stones) could also be present.

Management depends on the specific/likely aetiology. A careful history (including drug history [eg. high dose of paracetamol before presentation]) and clinical examination (eg. signs of right heart failure, chronic liver disease, abdominal pain) followed by specific liver function tests to delineate the pattern of abnormality (including alkaline phosphatase [AP], gamma glutamyl transpeptidase [GGT] and/or conjugated/unconjugated bilirubin). More specific blood tests may be indicated (eg. haemolysis screen or viral serology). Imaging of right upper quadrant with ultrasound (to assess obstruction &/or stones) would usually be indicated (± other imaging eg. nuclear medicine or CT scan). After addressing the specific aetiology, further treatment would be largely supportive (with awareness of effects on drug metabolism).

Discussion

 The college has cheated the candidate by not presenting them with a list of LFTs to analyse. With no information, the differentials (and thus the manaement options) are distrubingly broad.

One can work though this systematically.

The following tests will need to be ordered, in order of escalating expense, invasiveness and esotericims:

• Albumin is a test of synthetic liver function, but is very nonspecific in critical illness.
• Coags: APTT, PT, fibrinogen and mixing studies. These test the synthetic liver function. PT will be raised if the liver has stopped storing fat-soluble vitamins, and APTT will be raised if the synthetic function is so poor that clotting factor synthesis is impaired. Mixing studies help to demonstrate that the addition of healthy plasma corrects the factor deficiency.
• Bilirubin differential (conjgated vs. unconjugated) helps discriminate biliary from nonbiliary causes of jaundice
• Amylase and lipase (to exclude pancreatitis)
• Ultrasound of the liver and biliary tree to rule out bile duct obstruction and any interruption of the hepatic vascular supply; and to look at the hepatic parenchymal texture (eg. fatty, cirrhotic, etc)
• Hepatitis virus tests  to rule out acute hepatitis
• Iron studies (to look for haemochromatosis)
• Ceruloplasmin (if Wilson's disease is a realistic possibility)
• Anti-smooth muscle antibodies (primary sclerosing cholangitis)
• Anti-liver microsomal antibodies (autoimmune hepatitis)
• Serum α-1 antitrypsin level (for deficiency)
• Liver biopsy (gold standard)

Differentials and their management

• Poor hepatic blood flow
  • decrease the PEEP to improve viscera
• Right heart failure
  • maintain cardiac output with inotropes and fluids
• Generalised shock state
  • maintain normotension with fluids and vasopressors
• Idiopathic drug reaction
  • change the offending drug to an analogue
• Hepatic vein thrombosis
  • anticoagulation
• Hepatic infarction
  • anticoagulation
• Infectious cause
  • viral serology
  • blood cultures

In addition, one would need to adjust drug doses and dosing intervals to allow for changes in hepatic clearance.

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.

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).

College Answer

Most likely cause is hepatic encephalopathy, but many other conditions would be excluded as part of her work up.  She has obvious liver dysfunction (GGT, ALT, bilirubin), supported by a low albumin and a very high ammonia level. Other results (eg. Na, Cr/urea, glucose) are not as extreme and less likely to contribute to her reduced conscious state.

An additional assessment of the synthetic function of the liver would support the diagnosis(eg. prothrombin time, which is a marker of severity and should be prolonged).

The high plasma creatinine probably reflects significant renal impairment (not rhabdomyolysis as CK only mildly elevated).   The urea value is probably a reflection of decreased production and a nutritional deficiency.  A normal value makes gastrointestinal bleeding and severe hypovolaemia unlikely as precipitants for the encephalopathy.

Discussion

This question closely resembles (but is not identical to) Question 29.2 from the second paper of 2011. The key difference is that in 2011, it was a 48 yr old male who escaped from the alcohol rehab camp. However, the bloods were identical.

In contrast to the 2011 question, this time the examiners are asking us for ONE diagnosis.

So, if the candidate were to put all their money on one pony, it would be hepatic encephalopathy. The ammonia, bilirubin, LFTs and background history all point to this. The one test which the college has not provided us with is the coags- coagulopathy would be informative as a part of the staging process for this condition, particularly the prothrombin time.

The significance of the creatitine and urea disparity is probably an issue of dehydration. The patient, haveing collapsed some time ago, has spent some hours/days slowly dehydrating. However, owing to the greatly diminished oral intake and muscle mass, the patient probably has a very slow rate of urea production. The absence of CK demonstrates the fact that rhabdomyolysis has no role to play in this process.

College Answer

Diagnostic features include: Watery Diarrhoea, Bloody diarrhoea, Pseudomembranes (may be passed with stool or may be visible on bowel mucosa on colonoscopy), Recent or current course of antibiotics, Abdominal tenderness, fever, increased WCC. Clostridium difficile infection can be asymptomatic.

Diagnosis confirmed by detection of clostridium difficile toxins (A &/or B) in stool (toxin present in 95% of patients with pseudomembranous colitis).

Other features on investigations: Plain AXR - mucosal thickening, "thumbprinting", or colonic distension; CT abdo – wall thickening, irregular bowel wall margin, pericolonic stranding, ascites. Features of complications include: electrolyte disturbances (low K, normal anion gap acidosis due to bicarbonate loss), hypoalbuminaemia, dehydration, toxic megacolon, perforation, pneumoperitoneum, possibly progressing to shock MOF.

Likely causes in patients in Intensive Care: Clostridium difficile infection; Overgrowth of clostridium due to eradication of other organisms; Antibiotics – particularly reported following clindamycin, cephalosporins (particularly 3rd generation), ampicillin/amoxycillin but can occur after any (less likely with ticarcillin/clavulanate, aminoglycosides, quinolones). More likely following shock and decreased gut perfusion, renal failure and in the old and debilitated or in patients with immunocompromise such as haematological malignancy or HIV infections.

Discussion

C.difficile infection is a favourite of the college, and appears frequently in the papers.

For instance, Question 3 from the first paper of 2013 asks even more detailed questions.

To bring together all the previously exmained aspects of pseudomembranous colitis, a summary ofC.difficile infection is available in the Required Reading section.

Diagnostic features:

• Abdominal pain
• Loose stools
• History of broad spectrum antibiotics, particularly Clindamycin
• Characteristic "thumbprinting" of bowel on plan Xrays
• Inflamed appearance of bowel on CT
• Direct confirmation of pseudomembranes on colonoscopy
• C.difficile toxin A or B on stool PCR
• Toxic megacolon
• Perforation and pneumoperitoneum
• Fever > 38°
• Renal failure

Causes of pseudomembranous colitis in ICU:

Surely, the college - being composed of people with a certain respect for specificity- would be asking for the specific causes of pseudomembranous colitis. Of which there really is only one: C.difficile. The rest of the "likely causes" mentioned in the model answer are associated factors. The use of clindamycin does not "cause" this disease.

That said, not all pseudomembranous colitis is due to C.difficile infection.

Alternative pathogens include:

• Strongyloides stercoralis
• Staphylococcus aureus
• Clostridium perfringens
• Yersinia
• CMV
• Entamoeba
• Listeria
• All the enterohaemorrhagic diarrhoea organisms:
  • Salmonella
  • Shigella
  • Campylobacter
  • E.coli

Factors associated with C.difficile enterocolitis are as follows:

• Broad spectrum antibiotics in particular clindamycin, quinolones, amoxycillin, cephalosporins

• Immunosuppressive therapy /Cytotoxic chemotherapy

• Gastric acid suppression

• Age > 65

• Prolonged hospitalisation

• Renal impairment

Loo, Vivian G., et al. "Host and pathogen factors for Clostridium difficile infection and colonization." New England Journal of Medicine 365.18 (2011): 1693-1703.

Thomas, Claudia, Mark Stevenson, and Thomas V. Riley. "Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review." Journal of antimicrobial chemotherapy 51.6 (2003): 1339-1350.

Anand, Ajay, and Aaron E. Glatt. "Clostridium difficile infection associated with antineoplastic chemotherapy: a review." Clinical Infectious Diseases 17.1 (1993): 109-113.

Cunningham, R., et al. "Proton pump inhibitors as a risk factor for Clostridium difficilediarrhoea." Journal of Hospital Infection 54.3 (2003): 243-245.

Pépin, Jacques, Louis Valiquette, and Benoit Cossette. "Mortality attributable to nosocomial Clostridium difficile–associated disease during an epidemic caused by a hypervirulent strain in Quebec." Canadian Medical Association Journal 173.9 (2005): 1037-1042.

Cunney, Robert J., et al. "Clostridium difficile colitis associated with chronic renal failure." Nephrology Dialysis Transplantation 13.11 (1998): 2842-2846.

Surawicz, Christina M., et al. "Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections." The American journal of gastroenterology 108.4 (2013): 478-498.

Henrich, Timothy J., et al. "Clinical risk factors for severe Clostridium difficile–associated disease." Emerging infectious diseases 15.3 (2009): 415.

FujitaniMD, Shigeki, W. Lance GeorgeMD, and A. Rekha MurthyMD. "Comparison of clinical severity score indices for Clostridium difficile infection."Infection Control and Hospital Epidemiology 32.3 (2011): 220-228.

Janvier, Jack, Susan Kuhn, and Deirdre Church. "Not all pseudomembranous colitis is caused by Clostridium difficile." The Canadian Journal of Infectious Diseases & Medical Microbiology 19.3 (2008): 256.

College Answer

The perioperative complications could be classified into (1) that of any major upper abdominal surgery and (2) specifically that of a hemi-hepatectomy for cholangiocarcinoma; or divided into various systems, i.e.

(1) Respiratory:                     Inadequate or excessive analgesia, pulmonary oedema from fluid overload, R. haemothorax, R. pneumothorax, R diaphragmatic dysfunction, V/Q mismatch from hepatic failure, aspiration and possibly early pulmonary infection or thromboembolism. Very rarely, intraoperative air embolism ®ARDS.

(2) Cardiovascular:                Hypotension   from   bleeding,   epidural   block,   perioperative myocardial ischaemia / infarction, Arrhythmias associated with electrolyte abnormalities.

(3) GI failure:                          Prolonged ileus, pseudo-obstruction, ascites, G I haemorrhage

(4) Renal:                                                Hepatorenal syndrome, acute tubular necrosis, oliguria.

(5) Hepatic:                             Cholangitis, hepatic failure, encephalopathy, coagulopathy,

(6) CNS:                                                Encephalopathy.

(7) Metabolic:                        hyperlactataemia, low Na+, high K+, hypoglycaemia.

(8) Premorbid condition possible ulcerative colitis/primary sclerosing cholangitis: Therefore, medication issues i.e. steroids, immune state, nutritional status etc.

Discussion

This is a question which benefits from a systematic approach. The college answer has already made this attempt.

Thus: a table of Problems and Solutions:

Jarnagin, William R., et al. "Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade." Annals of surgery 236.4 (2002): 397-407.

Page, Andrew J., and David A. Kooby. "Perioperative management of hepatic resection." Journal of gastrointestinal oncology 3.1 (2012): 19-27.

Wrighton, Lindsay J., et al. "Postoperative management after hepatic resection." Journal of gastrointestinal oncology 3.1 (2012): 41-47.

Thorat, Ashok, and Wei-Chen Lee. Critical Care Issues After Major Hepatic Surgery. INTECH Open Access Publisher, 2013.

Pagano, Duilio, et al. "The unreliability of continuous postoperative lactate monitoring after extended hepatectomies: single center experience." Updates in surgery 67.1 (2015): 33-37.

Ciuni, Roberto, et al. "Nutritional aspects in patient undergoing liver resection." Updates in surgery 63.4 (2011): 249-252.

Hotta, Tsukasa, et al. "Evaluation of postoperative nutritional state after hepatectomy for hepatocellular carcinoma." Hepato-gastroenterology 50.53 (2002): 1511-1516.

Richter, B., et al. "Nutritional support after open liver resection: a systematic review." Digestive surgery 23.3 (2006): 139-145.

Marchesini, Giulio, et al. "Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial." Gastroenterology 124.7 (2003): 1792-1801.

Kim, Say-June, Dong-Goo Kim, and Myung Duk Lee. "Effects of branched-chain amino acid infusions on liver regeneration and plasma amino acid patterns in partially hepatectomized rats." Hepato-gastroenterology 58.109 (2010): 1280-1285.

Neelakanta, Gundappa, et al. "Early tracheal extubation after liver transplantation." Journal of cardiothoracic and vascular anesthesia 11.2 (1997): 165-167.

Narita, Masato, et al. "Noninvasive ventilation improves the outcome of pulmonary complications after liver resection." Internal Medicine 49.15 (2010): 1501-1507.

College Answer

Causes:

Abdominal trauma
Massive retroperitoneal hematomas

Major burns following fluid resuscitation

Massive intra-abdominal hemorhage

Major Consequences:
a)  Decrease in Qt because of a decrease in venous return

b)  Decreased renal perfusion

c)  Impaired thoracic compliance

d)  Bowel ischemia

Management
a)  Monitoring intra-abdominal pressure

b)  Abdominal decompression

c)  Adequate decompression of GI tract

d)  Avoiding excess fluid resuscitation

Discussion

A slightly more formal-looking exploration of abdominal compartment syndrome can be found in Question 8 from the first paper of 2013. Brief notes on the pathophysiology of abdominal compartment pressure and its measurement are available, with references for the time-rich exam candidate.

Causes of abdominal compartment syndrome:

Primary ACS: increased compartment pressure due to abdominal pathology

• Massive ascites, eg. portal vein thrombosis
• Retroperitoneal hematoma
• Abdominal trauma with crush injury

Secondary ACS: increased compartment pressure due to fluid resuscitation

• Abdominal infection eg peritonitis
• Pancreatitis
• Major trunk burns with massive fluid resusicitation (thus, restriction of abdominal expansion)

Consequences of abdominal compartment syndrome:

• Hypotension due to decreased preload
• Renal failure due to decreased renal blood flow (venous and arterial)
• Lactic acidosis due to impared hepatic blood flow
• Gastric erosions and ulceration due to impaired gastric blood flow
• Intestinal ischaemia due to impaired intestinal blood flow
• Poor gut transit, ileus, and decreased tolerance of NG feeds
• Decreased FRC and therfore increased atelectasis, worsening gas exchange, decreased compliance of the respiratory system, leading to hypoxia and hypercapnea
• Raised intracranial pressure

Management of abdominal compartment syndrome:

• Prevention:
  • Avoid overvigorous fluid resusictation
  • Patients at risk of ACS should perhaps remain open-abdomen after largescale abdominal surgery
  • monitor the compartment pressure
• Management
  • Staged closure of abdominal defect
  • Vasopressors to maintain MAP within a certain range (some aim for an abdominal perfsion pressure of >60mmHg)
  • Titrate PEEP to optimise V-Q matching, to maintain normoxia and normocapnea
  • If compartment pressure remains elevated, neuromuscular blockade can be considered
  • If pressure remains high in spire of NMJ blockade, may consider opening the abdomen (if it is closed)

Cheatham, Michael Lee. "Abdominal compartment syndrome." Current opinion in critical care 15.2 (2009): 154-162.

Maerz, Linda, and Lewis J. Kaplan. "Abdominal compartment syndrome."Critical care medicine 36.4 (2008): S212-S215.

Saggi, Bob H., et al. "Abdominal compartment syndrome." Journal of Trauma-Injury, Infection, and Critical Care 45.3 (1998): 597-609.

Cheatham, Michael L., et al. "Abdominal perfusion pressure: a superior parameter in the assessment of intra-abdominal hypertension." Journal of Trauma-Injury, Infection, and Critical Care 49.4 (2000): 621-627.

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:

• Daily nutritional requirements of the critically ill patient
• Enteral nutrition vs parenteral nutrition in the critically ill
• When and how to start parenteral nutrition
• Contents and properties of the parenteral nutrition mixture

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.

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.

College Answer

a)  What is the most likely cause of the renal deterioration? Give reasons.

Hepatorenal syndrome .
Reasons: Fulfils criteria for Type 1 HRS -(Acute deterioration, absent renal parenchymal disease, absent proteinuria, no shock and no history of nephrotoxic drugs)

List 4 important management measures specifically for the treatment of this patient's renal dysfunction.
Management of complications of renal dysfunction- hyperbilirubinaemia
Albumin administration
Terlipressin I Midodrine/ Octreotide
TIPS 
Consideration for liver transplantation

Discussion

Hepatorenal syndrome is discussed in greater detail in the answer to Question 13 from the first paper of 2001, and in a chapter or rambling digressions.

This case fits the old criteria for diagnosis, which in 2007 were as follows:

These days, we define it slightly differently (the main change is the incorporation of the current AKI definition, instead of using some kind of weird rogue definition and upsetting a million nephrologists):

• Cirrhosis
• Ascites
• Acute kidney injury: 
  • Increase in serum creatinine ≥0.3 mg/dl (26.5 μmol/L) within 48hrs,
  • OR: ≥50% from baseline value within 7 days
  • AND/OR:  urine output ≤0.5 ml/kg for ≥6 h
• Not improved with 24 hrs of fluid resuscitation
• Absence of alternative explanation

In either case, it is renal failure in a patient with coexisting liver failure and no other good reason to have renal failure. "Absence of proteinuria" promotes a view that this is a purely pre-renal disease, with no glomerular damage.

Type 1 hepatorenal syndrome was previously  the definition for an acute episode, whereas Type 2 was gradual in onset. These days we call it:

• HRS-AKI : 2-7 days
• HRS-AKD: duration up to 90 days (which starts from day 0 of HRS-AKI)
• HRS-CKD: longer than 90 days 

As for "4 important management measures"...

• Albumin and fluid resuscitation:
  • On its own, the effect from this is minimal; mortality is ~ 70%
• Terlipressin
  • Improves mortality to from 70% to 50%
  • Thought to improve renal perfusion by decreasing the tension within the ascites compartment.
• Noradrenaline
  • The idea is to increase renal perfusion by increasing the MAP by about 10mmHg
• Octreotide
  • potent agent of splanchnic vasoconstriction
  • Mortality perhaps 60% 

If all else fails, TIPS procedure may be appropriate. As this disorder has an abysmal survival rate, those who qualify for transplant should be worked up for one.

The college examiners prescriptively asked for "management measures specifically for the treatment of this patient's renal dysfunction", but in their answer gave a generic support strategy ("Management of complications of renal dysfunction- hyperbilirubinaemia"). This answer is puzzling on several levels, and probably had no value in terms of marks for the actual trainees, revealing more information about the CICM quality control process than about hepatorenal syndrome.

UpToDate has an excellent synopsis of hepatorenal syndrome.

Salerno, Francesco, et al. "Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis." Postgraduate medical journal 84.998 (2008): 662-670.

Solà, Elsa, Mónica Guevara, and Pere Ginès. "Current treatment strategies for hepatorenal syndrome." Clinical Liver Disease 2.3 (2013): 136-139.

Arroyo, Vicente, et al. "Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis." Hepatology 23.1 (1996): 164-176.

Velez, Juan Carlos Q., and Paul J. Nietert. "Therapeutic response to vasoconstrictors in hepatorenal syndrome parallels increase in mean arterial pressure: a pooled analysis of clinical trials." American Journal of Kidney Diseases 58.6 (2011): 928-938.

Gluud, L. L., M. S. Kjaer, and E. Christensen. "Terlipressin for hepatorenal syndrome." Cochrane Database Syst Rev 4 (2006).

Kalambokis, Georgios, et al. "The effects of chronic treatment with octreotide versus octreotide plus midodrine on systemic hemodynamics and renal hemodynamics and function in nonazotemic cirrhotic patients with ascites."The American journal of gastroenterology 100.4 (2005): 879-885.

Rössle, Martin, and Alexander L. Gerbes. "TIPS for the treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update." Gut59.7 (2010): 988-1000.

Malinchoc, Michael, et al. "A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts." Hepatology 31.4 (2000): 864-871.

Nadim, Mitra K., et al. "Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting." Journal of Hepatology 81.1 (2024): 163-183.

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:

• Predictive equations
• Reverse Fick method
• Indirect calorimetry

In brief:

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

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).

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.

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 .

College Answer

.

Candidates listing 3 correct differentials for a fluid thrill (see a-c below) or providing 3 conditions which may result in massive ascites (see d-f below) were awarded  full marks.

a)  Massive ascites
b)  Massive ovarian cyst
c)  Pregnancy with hydramnios

d)  Severe liver disease
e)  Budd-Chiari syndrome
f)   Severe right heart failure or pericardial constriction

g)  Abdominal malignancy.

Discussion

This question asks for a fairly random detail from Talley and O'Connor.

The "fluid thrill" is one of the tests for ascites; however it will be positive in any condition where a major part of the abdomen is taken up by a big lake of sloshing fluid. Essentially, it consists of somebody (possibly the patient) pressing down on the middle of their abdomen, and the physician percussing one side while feeling for the percussion wave in the other side. A big sloshy lake of fluid will allow the percussion wave to transmit across, whereas bowel gas or stool will transmit nothing.

This generally held to be pretty unreliable sign of ascites, as it requires the ascites to be massive, and under tension.

In either case, the college was fairly non-specific in their expected answer. They would have been happy to hear several different explanations for abdominal fluid (cysts of all sorts, ascites or massive hydramnios are all valid causes). They were equally happy about three different reasons for massive ascites (which leaves the answer pretty well open to any suggestion.. Budd-Chiari? Liver cirrhosis? Severe right heart failure?).

A good description of the fluid thrill test can be found at the website of the University of California, San Diego.

College Answer

Hepatic failure
Inherited disorders of urea cycle
Drugs: Valproate, glycine, carbamezapine
Porta-systemic shunts
Increased protein load: GI bleed, TPN,
Infection with urease splitting organisms – proteus Gastric bypass, urinary diversion procedures Cancers – myeloma
Chemotherapy.

Discussion

This question closely resembles, though is not identical to, Question 14 from the second paper of 2012. There, one may find a discussion of the usefulness of the serum ammonia levels in critical illness.

Here, one is merely expected to regurgitate a series of differentials.

Using a familiar template, an easily remembered list would look like this:

• Hepatic vascular insufficiency, eg. hepatic necrosis due to ischaemia
• Hepatic failure
• Portosystemic shunts
• Infection with urea splitting organisms eg. Proteus mirabilis, H.pylori
• Multiple myeloma
• Drugs - eg. valproate, carbamazepine
• Congential disorders of urea cycle
• Increased protein catabolism, eg. chemotherapy, starvation, GI bleeding, or TPN

More detail, you beg? Impossibly large tables, useless for the purpose of rapid revision?

Another method of arranging the differentials, according to the physiological mechanism:

College Answer

23.1) What are the differential diagnoses of this patient’s  presentation?

1)  Pancreatitis
2)  Perf DU
3)  Intestinal obstruction
4)  Acute cholecystitis with sepsis
5)  Aspiration and sepsis
6)  Gut ischaemia

23.2) What are the causes of hypotension in acute pancreatitis?

a) sequestration (3rd spacing) of protein rich fluids in and around the pancreas and abbdominal cavity, retroperitoneum
b) compounded by pre existing fluid depletion.

c) direct myocardial depression
d) SIRS / sepsis
e) Intra-abd hypertension

f) Bleeding

23.3) List 3 causes of a raised A-a gradient in acute pancreatitis?

Pulmonary dysfunction - Aspiration, pleural effusions, ARDS, atelectasis.

23.4) What do you understand is the role for prophylactic antimicrobial therapy in sterile pancreatic necrosis?

a) Antibiotic use in SAP without overt infection controversial and trial data are conflicting.

b) Antibiotics have been given either IV or IV plus orally/rectally via SDD.
c) Early trials - underpowered, mostly non blinded and included patients with differing disease severity suggested a reduction in both infections and improved outcome with early use of prophylactic antibiotics (Cefuroxime and imipenem) in necrotising SAP when compared with placebo. Subsequent meta analyses including a Cochrane review also suggested that antibiotics reduced infections and mortality and need for surgery in necrotic pancreatitis.
d) 2 recent RCTs (Isenmann 2004 and Dellinger 2007) have however demonstrated no effect on outcome or infection rate when prophylactic antibiotics were used in necrotic pancreatitis. The SCCM (2004) consensus conference on severe pancreatitis recommends against the use of routine prophylactic antibiotics.

Discussion

23.1) What are the differential diagnoses of this patient’s  presentation?

An obese hypoxic woman presents in a state of shock, febrile, and with this story of vomiting and abdominal pain. A systematic approach is called for, even though the lipase is high and the obvious single diagnosis is pancreatitis.

Vascular causes:

• acute mesenteric vasculitis
• mesenteric ischaemia, embolic or otherwise

Infectious causes: sepsis from any origin, but more likely the gut,

• biliary sepsis
• colitis

Neoplastic causes

• perforated colorectal mass
• SIRS due to a systemic cytokine release, due to lymphoma or leukaemia

Drug-induced causes

• Drug-induced pancreatitis or hepatitis

Autoimmune causes eg. inflammatory bowel disease with perforation

Traumatic causes eg. Boerhaave's syndrome due to excessive vomiting

Endocrinological cause of abdo pain and SIRS, eg. pacreatitis due to any number of causes

23.2) What are the causes of hypotension in acute pancreatitis?

Again, there are several mechanisms:

• "Third space losses" due to capillary leak, particularly sequestration in the abdomen
• Systemic inflammatory response due to cytokine release
• Gastrointestinal losses due to vomiting, diarrhoea, decreased oral intake, and gastric bleeding
• Retroperitoeal hematoma (maybe from a ruptured splenic artery aneurysm)
• Decreased preload due to abdominal compartment syndrome
• Cardiac ouput decrease due to acidosis and SIRS-associated cardiomyopathy

23.3) List 3 causes of a raised A-a gradient in acute pancreatitis?

• ARDS due to systemic cytokine release
• Pleural effusions due to third space fluid mobilisation and aggressive fluid resuscitation
• Pulmonary oedema due to decreased cardiac contractility and depressed systolic function
• Aspiration pneumonia given that the patient has a decreased level of consciousness and presents with a history of vomiting

23.4) What do you understand is the role for prophylactic antimicrobial therapy in sterile pancreatic necrosis?

• Short answer: there is no role for antibiotics in acute pancreatitis.
• In the 1990s, authors were fond of using prophylactic antibiotics because small-scale trials demonstrated a benefit.
• These days the evidence does not support the use of antibiotics
• Cochrane has an even more recent review which agrees that there does not appear to be any benefit, even on the basis of studies which were not adequately powered to detect a subtle benefit
• For some reason, imipenem seems to stand out as an antibiotic which on its own prevents pancreatic necrosis infections. This, again, was the result of an inadequately powered trial.

Again, thank you to Rajkumar (you know who you are) for pointing out the error in this answer. There was a duplication of content from Question 22 of the same paper. Well spotted!

Pederzoli, Paolo, et al. "A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem." Surgery, gynecology & obstetrics 176.5 (1993): 480-483.

Wilmer, Alexander. "ICU management of severe acute pancreatitis." European journal of internal medicine 15.5 (2004): 274-280.

Villatoro, Eduardo, Mubashir Mulla, and Mike Larvin. "Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis."Cochrane Database Syst Rev 5.5 (2010).

College Answer

1. Splenomegaly
2. Ascites
3. Caput medusae
4. Haemorrhoids

Discussion

This question is identical to Question 5.1 from the second paper of 2010.

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.

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).

College Answer

List 4 clinical signs of portal hypertension.

•     Splenomegaly
•    Caput medusae
•     Ascites
•    Haemorrhoids on rectal examination
•    Haematemesis? Melaena

Discussion

This is fairly straightforward.

• Ascites
• Caput medusae
• Hepatomegaly and splenomegaly
• Haemorrhoids
• Oesophageal varices (and thus haematemesis)

Escorsell, Angels, Joan Carles García-Pagán, and Jaume Bosch. "Assessment of portal hypertension in humans." Clinics in liver disease 5.3 (2001): 575-589.

de Franchis, Roberto. "Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension." Journal of hepatology 53.4 (2010): 762-768.

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:

• Assessment of nutritional status
• Predictive equations to estimate nutritional requirements
• Estimation of energy expenditure by indirect calorimetry
• Estimation of energy expenditure by the reverse Fick method
• Daily nutritional requirements of the critically ill patient

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

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.

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.

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.

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.

College Answer

a)  Based on the above information, what do you think this woman is suffering from?

Acute liver failure (without more detail it is hard to say, hyperacute, acute, subacute or chronic)

b)  List 5 important aetiologies which could result in this presentation.

•     Sepsis
•    Viral hepatitis – Hep B/C/D, CMV/EBV
•    Drug induced
•     Poisoning
•    Miscellaneous  (wilson’s disease, acute fatty liver of pregnancy, ischaemic necrosis, Budd-Chiari, complications of hepatic surgery)
•     Idiopathic
•    Pregnancy related

c)  List 4 important complications (apart from respiratory failure) she is at risk of developing.

•    Cerebral oedema and herniation
•     Coagulopathy
•    GI bleed
•     Sepsis
•    Renal failure

d)  List 4 reasons why this woman might progress  to developing  respiratory failure.

•    Impaired ventilation because of coma
•    Pleural effusions
•    ARDS
•    Intra-pulmonary shunts
•    Aspiration pneumonia
•    Sepsis- pulmonary or extrapulmonary

Discussion

a)  Based on the above information, what do you think this woman is suffering from?

With the transaminases in their thousands, a raised bilirubin, coagulopathy and fever, one might assume that this lady has some sort of acute hepatitis. As the college rightly points out, "acute hepatic failure" is the only description one can make without any further history.

b)  List 5 important aetiologies which could result in this presentation.

• Vascular causes, eg. acute hepatic artery thrombosis or ischaemic hepatic injury
• Infectious causes, eg. acute viral hepatitis or liver abscess
• Neoplastic causes, eg. decompensation due to hepatocellular carcinoma
• Drug-induced hepatitis eg. paracetamol overdose
• Exacerbation of congenital disorder, eg. Wilson's disease
• Autummune hepatitis, eg. cryptogenic cirrhosis or idiopathic autoimmune hepatitis (IAIH)
• Traumatic hepatic injury

c)  List 4 important complications (apart from respiratory failure) she is at risk of developing.

There is a brilliant article on this subject which outlines all the possible and impossible complications of acute hepatic failure. I will summarise their Panel 1:

d)  List 4 reasons why this woman might progress  to developing  respiratory failure.

This answer calls for differentials of respiratory failure in a semiconscious shocked woman with fever.

• ARDS due to SIRS
• Aspiration pneumonia
• Decreased respiratory drive due to decreased level of consciousness
• Pleural effusions due to hypoalbuminaemia / ascites
• Intrapulmonary shunts - the so-called "hepatopulmonary syndrome" (very interesting to read about)

Bernal, William, et al. "Acute liver failure." The Lancet 376.9736 (2010): 190-201.

Fallon, Michael B., and Gary A. Abrams. "Pulmonary dysfunction in chronic liver disease." Hepatology 32.4 (2000): 859-865.

College Answer

a) What is a TIPS procedure and why is it used in patients with portal hypertension?

The hepatic vein is accessed via the internal jugular vein and IVC. A needle is then passed to connect the hepatic vein with the large portal vein near the centre of the liver, the needle tract  dilated  and  a stent  inserted  to maintain  the tract and form  the shunt  between  the higher pressure portal vein and the lower pressure hepatic vein.   This reduces portal hypertension.

b) What are 2 recognised indications for this procedure?

a)     Variceal bleeding that has failed endoscopic and pharmacological treatment. b)  Refractory ascites

c) Excluding mortality list 5 COMMON complications of TIPS procedure

•   thrombosis
•   occlusion of the stent
•   capsular puncture
•   bleeding
•   encephalopathy
•   stent migration

d) Describe  one  classification  system  used  in assessing  severity  of chronic  liver disease and outline its utility.

Either: Childs-Pugh score
Classified A,B or C by a composite of Total bilirubin, albumin, INR, ascites and hepatic encephalopathy.  Originally  used for prognostication  for surgery  – also used for prognostication  in  chronic  liver  disease  and  prediction  of  likelihood  of  complications  of cirrhosis

Or: MELD score severity scoring system for assessing severity of chronic liver that uses the serum  bilirubin,  creatinine  and INR. Initially developed  to predict  three month survival  in patients post TIPS. Now used for prognosis of liver disease and prioritizing liver transplant recipients

Discussion

The first 3 parts of this question are reasonably straightforward.

• TIPS is the transjugular intrahepatic portosystemic shunt, a conduit for portal venous blood to bypass the ineffective liver and thereby relieve portal hypertension.

Indications for TIPS:

• Refractory ascites
• Refractory rebleeding in variceal disease
• Hepatorenal syndrome
• Hepatopulmonary syndrome
• Hepatic vein thrombosis
• Hepatic veno-occlusive disease
• Portal vein thrombosis

Technical complications of TIPS:

• Vascular access complications
• Hepatic damage (through-and-through puncture): risk of intraperitoneal haemorrhage is 1-2%
• Haemobilia (damage to the biliary tree)
• Shunt stenosis or thrombosis (it happens in up to 70%)
• Shunt migration
• Hepatic vein stenosis (this can sabotage a future transplant)

Complications from portal venous shunting:

• Worsening hepatic encephalopathy
• Bilirubin rise: the diseased liver doesn't even get a chance to metabolise it
• Ischaemic hepatitis: the liver gets much of its oxygen from the portal vein, and even in spite of the hepatic arterial buffer response there is a risk of ischaemic hepatitis.
• Tricuspid endocarditis (organisms may now travel directly from the leaky gut into the systemic circulation)
• Haemolysis (due to the direct shearing effect of being in contact with the shunt)
• "Unmasked" cardiomyopathy: the TIPS returns splanchnic blood to the heart and acts as a volume challenge, and if there was pre-existing cardiomyopathy, it may be dramatically revealed in this manner.

The last part of the question is far from straightforward. How does one "briefly outline the utility" of something like the Childs-Pugh scoring system?

The system itself has existed since the 1970s, and it includes in its assessment the albumin level, the prothrombin time, the bilirubin, the presence of encephalopathy and the presence of ascites.

It seems the main point is prognosis. The utility of the scoring systems in general has been to estimate the expected lifespan of a cirrhosis patient, which has implications for liver transplantation. However, in the ICU, the overall mortality for cirrhosis patients is about 43%, irrespective of Childs-Pugh score. In general, SOFA and APACHE are better systems for predicting in-ICU mortality than the liver-specific scoring systems.

Thus, the answer to the "briefly outline utility" question should look like this:

Classification system:

• Childs-Pugh scoring system for cirrhosis
• Uses bilirubin, albumin, ascites, encephalopathy and INR to stratify the severity of cirrhosis according to risk of mortality and morbidity, particularly in the context of preoperative assessment

Its utility, briefly:

• Pre-transplant risk stratification
• Pre-TIPS risk stratification
• Helps estimate prognosis in untreated liver disease
• Does not discriminate survivors and non-survivors among cirrhosis patients admitted to ICU.

Ochs, Andreas, et al.New England Journal of Medicine 332.18 (1995): 1192-1197."The transjugular intrahepatic portosystemic stent–shunt procedure for refractory ascites." 

Guevara, Mónica, et al. "Transjugular intrahepatic portosystemic shunt in hepatorenal syndrome: effects on renal function and vasoactive systems."Hepatology 28.2 (1998): 416-422.

Papatheodoridis, George V., et al. "Transjugular intrahepatic portosystemic shunt compared with endoscopic treatment for prevention of variceal rebleeding: A meta‐analysis." Hepatology 30.3 (1999): 612-622.

Azoulay, D., et al. "Transjugular intrahepatic portosystemic shunt (TIPS) for severe veno-occlusive disease of the liver following bone marrow transplantation." Bone marrow transplantation 25.9 (2000).

Ganger, Daniel R., et al. "Transjugular intrahepatic portosystemic shunt (TIPS) for Budd-Chiari syndrome or portal vein thrombosis." The American journal of gastroenterology 94.3 (1999): 603-608.

Freedman, A. M., et al. "Complications of transjugular intrahepatic portosystemic shunt: a comprehensive review." Radiographics 13.6 (1993): 1185-1210.

Angermayr, B., et al. "Child-Pugh versus MELD score in predicting survival in patients undergoing transjugular intrahepatic portosystemic shunt." Gut 52.6 (2003): 879-885.

Bazarah, Salem M., et al. "Utility of MELD and Child-Turcotte-Pugh scores and the Canadian waitlisting algorithm in predicting short-term survival after liver transplant." Clinical and investigative medicine 27 (2004): 162-167.

Singh, Nina, et al. "Outcome of patients with cirrhosis requiring intensive care unit support: prospective assessment of predictors of mortality." Journal of gastroenterology 33.1 (1998): 73-79.

Levesque, Eric, et al. "Prospective evaluation of the prognostic scores for cirrhotic patients admitted to an intensive care unit." Journal of hepatology 56.1 (2012): 95-102.

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
    • Increased duration of ventilation, with associated complications (eg. increased risk of VAP)
  • 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

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.

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

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.

College Answer

a)  Given this presentation, list 3 possible causes of his altered conscious state?

Alcohol intoxication

Hepatic encephalopathy 
Drug ingestion 
GI bleed

Sepsis 
Intracranial bleed

b)  Interpret the biochemical abnormalities

Liver dysfunction as demonstrated by elevated enzymes, reduced albumin, hypoglycaemia with decompensation indicated by marked elevation of ammonia. Hyponatraemia in keeping with cirrhosis. Raised lactate as a result of liver dysfunction / alcoholic ketoacidosis / sepsis / thiamine deficiency Raised creatinine indicates renal dysfunction and urea may be apparently “normal” because of decreased hepatic dysfunction and possible nutritional deficiencies. Urea:creatine ratio suggests that GI bleed and/or dehydration are unlikely

Discussion

a)

Ok, the college has given us an alcoholic and put 342 µmol/l of ammonia into him.

Thus one of the differentials would have to be hepatic encephalopathy.

Given the extent of the other liver function abnormalities, and of course the borderline BSL, one could surmise that hypoglycaemia is another valid differential.

Being a drunk, alcohol intoxication is not out of the question.

One might wish to use the VINDICATE acronym to come up with some differentials.

• V- Stroke
• I- Sepsis
• N- Seizures; hepatic encephalopathy
• D- Drug intoxication (including alcohol)
• I -
• C-
• A-
• T- Intracerebral bleed, GI bleed
• E- hyponatremia, hypoglycaemia

Fortunately, the college only asks for three answers. Hepatic encephalopathy, alcohol intoxication and sepsis seem the most likely, given the bloods.

b)  Interpret the biochemical abnormalities

• Sodium is low due to the hypervolemic hyponatremia of cirrhosis
• Creatinine is high potentially due to dehydration or hepatorenal syndrome.
• Urea is normal likely due to nutritional deficiency or failure of the urea cycle. (so its probably not a GI bleed)
• The LFTs are deranged in keeeping with a history of chronic liver disease, featuring a degree of synthetic failure (albumin of only 20) and hypoglycaemia.
• The CK is only slightly elevated, suggesting seziures were probably not taking place before the police arrived
• The lactate is raised, and there could be numerous reasons for this - but its likely either increased production due to sepsis or thiamine deficiency, combined with a decreased hepatic clearance.

There is some good material out there on the biochemical abnormalities of chronic liver disease, and their interpretation.

Chung, Raymond T., David L. Jaffe, and Lawrence S. Friedman. "Complications of chronic liver disease." Critical care clinics 11.2 (1995): 431-463.

Heidelbaugh, Joel J., and Michael Bruderly. "Cirrhosis and chronic liver failure: part II. Complications and treatment." American family physician 74.5 (2006).

College Answer

a) Patient-related risk factors

• Broad spectrum antibiotics in particular clindamycin, quinolones, amoxycillin, cephalosporins

• Immunosuppressive therapy /Cytotoxic chemotherapy

• Gastric acid suppression

• Age > 65

• Prolonged hospitalisation

• Renal impairment

• Prior GI surgery

b) Diagnostic tests

• Faecal culture determination of the toxigenic status of the infecting C. difficile isolate

• Screening EIA to detect C. difficile glutamate dehydrogenase (GDH)

• EIAs to detect toxins A and/or B

• Cell culture cytotoxicity assays that directly detect stool cytotoxic activity

• PCR-based assays to detect conserved gene targets within the pathogenicity locus of C. difficile

c) Markers of severity

• Clinical
  • Fever (> 38.5°C), rigors
  • Haemodynamic instability
  • Peritonitis or evidence of bowel perforation
  • Ileus or toxic megacolon
• Laboratory
  • White blood cell count >15 × 109/L and < 20% neutrophils
  • Elevated lactate level
  • Rise in creatinine level (> 50% above baseline)
  • Albumin level < 25 mg/L
• Other investigations
  • Large intestine distension, colonic wall thickening, fat stranding, unexplained ascites (imaging)
  • Pseudomembranous colitis (colonoscopy)

d) Other infective causes of diarrhoea

• Viruses –Norovirus, adenovirus, CMV (rotavirus in children)
• Bacterial pathogens – Campylobacter, E.Coli, cholera, salmonella Protozoa – Cryptosporidium, Giardia
• Parasitic -Strongyloides

Discussion

This question favours the candidate who has a very detailed understanding of C. difficile infection. A long rant about C.difficile is available in the Required Reading section.

The risk factors for C.difficile infection are discussed here, in a NEJM article.

Where did the college answer get its evidence from, you ask?

• Broad spectrum antibiotics in particular clindamycin, quinolones, amoxycillin, cephalosporins

• Immunosuppressive therapy /Cytotoxic chemotherapy

• Gastric acid suppression

• Age > 65

• Prolonged hospitalisation

• Renal impairment

As for diagnosis of C.difficile, the current recommendations are:

• PCR is better than toxin A or B identification
• You should only test loose stools
• You should not re-test

Markers of "severe" enterocolitis, which means the sort that ends up either killing you or results in a colectomy, are deliniated in this retrospective study. They are as follows:

• age >70 years
• maximum leukocyte count >20,000 cells/mL
• minimum albumin level <25 g/L
• maximum creatinine level >200 mcg/L
• small bowel obstruction or ileus
• CT evidence of colorectal inflammation

To this list, another study adds more markers of severity:

• Fever (>38.0°)
• Abdominal distension

Loo, Vivian G., et al. "Host and pathogen factors for Clostridium difficile infection and colonization." New England Journal of Medicine 365.18 (2011): 1693-1703.

Thomas, Claudia, Mark Stevenson, and Thomas V. Riley. "Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review." Journal of antimicrobial chemotherapy 51.6 (2003): 1339-1350.

Anand, Ajay, and Aaron E. Glatt. "Clostridium difficile infection associated with antineoplastic chemotherapy: a review." Clinical Infectious Diseases 17.1 (1993): 109-113.

Cunningham, R., et al. "Proton pump inhibitors as a risk factor for Clostridium difficilediarrhoea." Journal of Hospital Infection 54.3 (2003): 243-245.

Pépin, Jacques, Louis Valiquette, and Benoit Cossette. "Mortality attributable to nosocomial Clostridium difficile–associated disease during an epidemic caused by a hypervirulent strain in Quebec." Canadian Medical Association Journal 173.9 (2005): 1037-1042.

Cunney, Robert J., et al. "Clostridium difficile colitis associated with chronic renal failure." Nephrology Dialysis Transplantation 13.11 (1998): 2842-2846.

Surawicz, Christina M., et al. "Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections." The American journal of gastroenterology 108.4 (2013): 478-498.

Henrich, Timothy J., et al. "Clinical risk factors for severe Clostridium difficile–associated disease." Emerging infectious diseases 15.3 (2009): 415.

FujitaniMD, Shigeki, W. Lance GeorgeMD, and A. Rekha MurthyMD. "Comparison of clinical severity score indices for Clostridium difficile infection."Infection Control and Hospital Epidemiology 32.3 (2011): 220-228.

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:

• Feed enterally wherever possible
• Hypocaloric high-protein feeding is recommended:
  • Supply 60-70% of energy requirements;
    • some authors recommend 21kcal/d of actual body weight
  • Oversupply protein:
    • 2.0-2.5g/kg of ideal body weight, or
    • 1.3-1.5g/kg of actual body weight

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.

College Answer

a) CT Scan:

• • Extensive hypodense areas in liver consistent with hepatic infarction
  • Splenomegaly
  • Hypodense areas in spleen consistent with splenic infarcts
  • Free fluid in abdomen

b) Cause:

•  Portal venous thrombosis

c) Causes of anti-thrombin III deficiency:

•   Hereditary

•   Acquired

o Post-operative state

o Liver disease

o Disseminated intravascular coagulation

o Nephrotic syndrome

o Vasculitis

• Further investigations:
  • Ultrasound of hepatic/abdominal vasculature.
  • ATIII activity on blood sample … Prothombotic screen also acceptable

e) Treatment:

• • Heparinisation
  • If there is heparin resistance or low ATIII activity, either antithrombin III concentrate or fresh frozen plasma.
  • Referral for advice regarding surgical (endovascular Vs open) options

Discussion

The CT scan I used was mined shamelessly from Google Images. It is not the one which appeared in the paper.

The first two parts of this question are straightforward.

The CT features of portal vein thrombosis are as follows:

• Direct visualisation of the clot:
  • Usually seen as a hypodense filling defect in the portal vein lumen
  • The decreased density inside the portal vessels is best seen in the contrast phase
  • Non-contract CT will not pick this up: you need portal venous phase contrast enhanced studies.
  • You can also sometimes see enhancement of the walls of the portal vein, which is either dilated vasa vasorum or a thin film of contrast flowing around the obstruction
  • The thrombus itself should not enhance with contrast. If there is enhancement, particularly in the arterial phase, the thrombus is probably malignant in origin (i.e a HCC has eroded into the lumen).
• Sequelae of portal vein obstruction:
  • Venous infarcts of the liver and spleen
  • Cavernous transformation of the portal vein (looks like a varicocele!)
  • Posrtosystemic collateral vessels and arterioportal shunts
  • Gut ischaemia
  • Ascites

The second half of the question requires detailed knowledge of AT-III deficiency. One can arrive at at least half of a sensible answer by logically asking why AT-III might not be present in sufficient quantities. Either you hereditarily fail to synthesise enough of it, or your liver is so damaged that it cannot produce enough. Or, it has been used up somehow, eg. in the context of DIC, MAHA, or in a bypass circuit. Lastly, it is possible that you are losing it along with other proteins via your leaky nephrotic kidneys.

The chapter which discusses thrombophilia screening tests contains within it this table, which lists the causes of AT-III deficiency with greater granularity.

The management of AT-III deficiency is, predictably, supplementation with AT-III. If the expensive purified factor is not available, FFP will suffice. Heparinisation for thrombosis actually will not work unless there is some antithrombin for the heparin to act upon.

Management options for PVT include the following:

• Do nothing:  If the patient is asymptomatic, or if significant risks are associated with anticoagulation (eg. bleeding varices), one may also rely on portal cavernous transformation to divert venous flow around the thrombus. However, rate of spontaneous resolution is low (~ 17%).
• Anticoagulate with heparin, LMWH or warfarin: Ideally, anticoagulation should be started in the first week (according to Basit et al, "Rate of recanalization is 69% if anticoagulation is started in the first week, but 25% if anticoagulation is started in second week").
• Control portal venous hypertension: 
  • ​β-blockers, eg. propanolol
  • Diuretics, eg. spironolactone
  • TIPS procedure
  • Intraportal thrombolysis
  • Surgical thrombectomy

UpToDate offers a good article about Antithrombin III deficiency, for a price.

Beresford, C. H. "Antithrombin III deficiency." Blood reviews 2.4 (1988): 239-250.

Mathieu, Didier, Norbert Vasile, and P. Grenier. "Portal thrombosis: dynamic CT features and course." Radiology 154.3 (1985): 737-741.

Lee, Hae-Kyung, et al. "Portal vein thrombosis: CT features." Abdominal imaging 33.1 (2008): 72-79.

Denninger, Marie‐Hélène, et al. "Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors." Hepatology31.3 (2000): 587-591.\

Valla, Dominique-Charles, and Bertrand Condat. "Portal vein thrombosis in adults: pathophysiology, pathogenesis and management." Journal of hepatology 32.5 (2000): 865-871.

Boyer, Thomas D. "Management of portal vein thrombosis."Gastroenterology & hepatology 4.10 (2008): 699.

Basit, Syed Abdul, Christian D. Stone, and Robert Gish. "Portal vein thrombosis." Clinics in liver disease 19.1 (2015): 199-221.

College Answer

a)

Haemodynamic stabilization – optimize cardiac output and tissue perfusion and avoid fluid overload as ventricular function may be impaired. Close haemodynamic monitoring. Vaso-active agents as indicated.

Correction of anaemia and coagulopathy – maintain haemocrit 0.25 – 0.3 to keep blood viscosity low. INR £2, APTT £50 secs, Fibrinogen above 0.5 g/L and Platelets above 30 x 109/L.

Fluid and electrolyte management – appropriate negative fluid balance day 1 decreases risk of pulmonary complications. Fluid overload may aggravate graft congestion and oedema caused by ischaemic-reperfusion. Electrolyte imbalances are common and need to be corrected.

Correction of metabolic abnormalities – hypoglycaemia is an ominous sign of compromised liver recovery, hyperglycaemia also may occur, acid-base abnormalities also occur

Early weaning from mechanical ventilation – associated with better outcome but not feasible in patients with respiratory failure, haemodynamic instability, pulmonary oedema, primary graft dysfunction, encephalopathy etc. Unsucessful early extubation may result in impaired oxygen delivery to transplanted liver

Monitoring of graft function LFTs, lactate, BSL, coagulation, hepatic artery doppler

Early detection of surgical complications - bleeding

Immunosuppressants

Infection prophylaxis

Housekeeping including analgesia (PCA) and appropriate nutrition plan

Other – ICP monitoring if decompensated CLD pre-op

b)

Delayed metabolism of sedative / anaesthetic drugs

Metabolic derangements – hypoglycaemia, hyponatraemia, hyperosmolar syndrome

Hepatic encephalopathy

Hypoxic-ischaemic cerebral injury

Seizures

Intracerebral haemorrhage

Discussion

This is a delicate topic for anybody who has not had the privilege of working in one of the sandstone centres of excellence, where liver transplants for the rich and famous serve as a constant source of private funding and media attention.

Thus, let there be a brief digression into the specifics of managing a post-op orthotopic liver transplant patient in the ICU.

(Incidentally, for those like me who were unsure precisely what the long words mean, "orthotopic" transplantation is the total removal of the old diseased liver, and the implantation of the donated organ into the same anatomical position).

The above link points to a scanned document from the Atlas of Organ Transplantation, which deals extensively with the pre-operative and peri-operative management of liver transplantation, detailing such interesting time intervals as "the Anhepatic stage". It however, is more aimed at the surgeons. Because the quality of the scanner leaves much to be desired, the gory pictures of open livers are just black-and-white blurs.

However, there is plenty of literature regarding the critical care management of liver transplant recipients.

Let us approach this answer systematically.

• Airway:
  • Historically these patients tend to remain intubated for the first 12-24 hours, although there is good evidence that early extubation (eg. in theatre) has no adverse effects.
• Breathing:
  • In order for the graft to survive normoxia must be established
  • The general "word of mouth" advice in these situations is to minimise the PEEP. In order for the anastomoses to remain intact, PEEP should be minimised, as it will increase the CVP and thus compromise the venous vascular anastomotic sites. However, some studies have reported no significant change to the hepatic venous flow even with PEEP as high as 15cm H2O.
  • Positive pressure ventilation in general is a bad idea, as organ perfusion is decreased by positive pressure, and perfusion of the donated liver is very important in the early stages.
  • Thus, early weaning from invasive ventilation is one of the major goals
• Circulation
  • There is likely to be a degree of shock. Given that fluid management must remain relatively conservative, vasopressors and inotropes must be deployed liberally. After all, the graft needs to remain perfused.
  • Hepatic oedema due to over-resuscitation should be avoided.
  • Arbitrarily, the CVP should remain within the range of 6-10.
  • Observe for reactive vasoconstriction
    • These patients, with heir dead livers, have been in a vasodilated state, associated with nitric oxide synthase hyperactivity.
    • Now, with their new livers, normal vascular tone will return.
    • This might mean a sudden massive increase in the afterload.
    • Thus, their left ventricles, which are chronically deconditioned, might decompensate when faced with such demands.
    • Thus, GTN or nitroprusside infusions should be used liberally in these people.
  • The need for RF and LV functional assessment as well as pulmonary arterial pressure measurements and
• Neurology and sedation
  • No specific recommendations can be made, rather than to say that both hepatic and renal dysfunction in the post-operative period is to be anticipated, and thus drugs which do not rely on organ metabolism should be used. Remifentanyl and propofol spring to mind.
• Fluids and electrolytes
  • There is some "magical" preload at which the CVP is reasonable, preload adequate, and cardiac output satisfactory. Finding this magic preload is something of an art.
  • Initially, fluid resuscitation should take place, but the fluid of choice should not be Hartmanns because the new liver will probably not be able to metabolise the lactate.
  • After the initial post-operative resuscitation phase is over, a negative fluid balance should be pursued; generating a lower pressure in the right side of the thoracic circulation will serve to draw blood from the graft, and thus theoretically should improve graft perfusion.
  • Renal function needs to be watched closely - renal failure is associated with poor graft survival.
• Graft function
  • There is a phase of "preservation injury" with very high LFTs but this tends to disappear over the first 3-4 days. Thereafter, synthetic function should be restored.
  • Monitoring of the graft consist of several sequential assessments:
    • Hepatic arterial Doppler
    • BSL
    • Lactate
    • Bilirubin
  • Typically, 1-9% of liver transplants fail within hours of surgery.
• Surveillance for abdominal compartment syndrome
  • Due to the extensive nature of the procedure and due to the preexisting portal venous pathology, this issue (with pressure over 25mmHg) is fairly common.
  • Abdominal girth values are required as sequential measurements.
• Nutritional support
  • There is no string reason to recommend TPN here. Like in most other situation, nasogastric enteral feeding is probably best. A degree of ileus is to be expected, and usually resolves
• Hematological support
  • This consists of the replacement of missing blood products and blood cells.
  • Essentially, there is no specific hemoglobin goal, and what you are trying to do is prevent bleeding from the anastomotic sites.
  • Its probably OK to be slightly coagulopathic, because you don't want to develop a hepatic arterial thrombus.
• Immune suppression
  • I will not litter this summary with discussion of the relative merits of each class of antirejection drug. Suffice to say, cyclosporin tacrolimus and mycophenolate are gradually giving way to monoclonal antibodies and other immunomodulator drugs which have slightly less devastating organ system effects.
• Antibiotics and sepsis surveillance
  • Many of these patients die from postoperative infectious complications
  • 48 hrs of IV antibiotics are typically administered
  • The Sanford Guide recommends linezolid, ciprofloxacin and fluconazole.
  • The belowlinked article from 2011 also suggests 14 days of aciclovir, given the propensity for embarrassing HSV reactivation.

The second part of this question is far less interesting, and refers mainly to the candidate's ability to generate differentials for a decreased level of consciousness.

Using a usual template, one can arrive at a series of differential easily:

• Vascular causes, eg. stroke or hypoxic brain injury
• Infectious causes, eg. reactivated HSV or CMV encephalitis
• Drug-related causes, eg. slow metabolism of anaesthetic drugs reliant on hepatic clearance
• Hepatic encephalopathy
• Haematological, eg. intracranial bleeding due to coagulopathy
• Electrolyte disturbances, for instance cerebral oedema due to hyponatremia
• Endocrine disturbance eg. hypoglycaemia

The best, most comprehensive source is this article:

Feltracco, Paolo, et al. "Intensive care management of liver transplanted patients." World journal of hepatology 3.3 (2011): 61.

The rest are also helpful.

Stieber, Andrei C., R. D. Gordon, and J. R. Galloway. "Orthotopic liver transplantation." Hepatology. A text book of liver disease. WB Saunders, Philadelphia (1996): 1759-1780.

Mazariegos, George V., Ernesto P. Molmenti, and David J. Kramer. "Early complications after orthotopic liver transplantation." Surgical Clinics of North America 79.1 (1999): 109-129.

Razonable, Raymund R., et al. "Critical care issues in patients after liver transplantation." Liver Transplantation 17.5 (2011): 511.

Mandell, M. Susan, et al. "Reduced use of intensive care after liver transplantation: influence of early extubation." Liver Transplantation 8.8 (2002): 676-681.

College Answer

• Serum Ammonia
  • Used as an indicator of hepatic encephalopathy
  • Normal values do not rule out encephalopathy – therefore of limited utility in patients with known chronic liver disease
  • Not useful as a monitor during therapy
  • Very high levels may indicate cerebral herniation
  • May be useful to indicate undiagnosed cirrhosis in patients presenting with altered mental status
  • May also be elevated in: TPN, GI Bleed and steroid use, portosytemic shunts and inborn errors of metabolism.
• B-type natriuretic peptide (BNP)
  • Released from cardiac cells in response to ventricular wall distension
  • Elevated in heart failure
  • Can be used as a diagnostic marker in patients presenting with dyspnoea to emergency department, and can be useful prognostically and to guide therapy in heart failure
  • May be elevated in many other conditions in critical care, including sepsis, acute lung injury, PE and intracranial bleed
  • Interpretation of BNP in ICU patients is therefore complex and while it may have a role in prognosis and response to therapy in future its current place is unclear.

Discussion

This question was quite arbitrarily placed into the gastroenterology section, on no grounds other than the interesting association of ammonia with various metabolic disturbances, versus the rather boring association of BNP with heart failure.

The question asks us to "critically evaluate", which means a certain systematic approach. I note that this approach was not used in the college answer.

The use of ammonia levels in critical care:

• Introduction:
  • Ammonia is a metabolic byproduct of amino acid catabolism; there has been interest in measuring ammonia levels and making attempts to associate them with various forms of pathology.
• Rationale:
  • The most prolific site of production of ammonia ions is in the gut, where amino acids are converted into ammonia by gut microflora. The ammonia is then absorbed into the portal circulation and converted into urea in the hepatic urea cycle.
  • Hepatic damage and the failure of the urea cycle is therefore usually associated with a rise in the serum ammonia levels
  • The normal compensatory responses to raised serum ammonia (eg. conversion into glutamine) can give rise to cerebral oedema and thus is thought to play some role in the pathogenesis of hepatic encephalopathy
  • Other causes of raised ammonia levels include
    • Increased rates of protein catabolism, eg. extreme starvation or hematological malignancy
    • TPN
    • Inherited errors of metabolism
• Evidence:
  • Ammonia levels in the brain and in the venous circulation do not usually correlate in stable liver disease; however there is some degree of correlation in severe hepatic encephalopathy.
  • The severity of encephalopathy does not correlate with the magnitude of ammonia elevation. Severely encephalopathic patients may have normal levels of ammonia, and patients with mild and moderate hyperammonaemia may have reasonably intact sensorium.
  •  
• Summary:
  • The use of ammonia to assess the severity of hepatic encephalopathy is still controversial
  • a raised ammonia level may point to an undiagnosed error of metabolism in a patient with an otherwise unexplainable loss of consciousness

The use of BNP levels in critical care:

• Introduction:
  • BNP is a peptide released by stressed atria which has been a tempting target of laboratory analysis in determining the aetiology of breathlessness in the acutely distressed patient
• Rationale
  • BNP (brain natriuretic peptide) is a 32-amino acid peptide released by the human atria and ventricles in response to distending pressure. In spite of its name, its presence in the human brain is rather minimal- it was first identified in porcine brain tissue, where for some reason it is concentrated. BNP is a peptide which has natriuretic and diuretic actions in the renal tubule, and is though to be a part of the natural homeostatic mechanisms which work in defence of normal intravascular volume.
  • Thus, a raised BNP, suggesting increased atrial stretch, may be a serum marker which may differentiate cardiac failure and pulmonary oedema from respiratory infection in situations when both are equally likely on the basis of history and examination.
  • The classical patient for such serology would be the elderly lady or gentleman with severe COPD and CCF, who presents to the ED with shortness of breath, wheeze, fever, and clinical features of fluid overload.
  • It may also be a useful serum marker to guide the management of heart failure
• Evidence:
  • BNP is promoted by the college answer as if it helps emergency physicians identify heart failure, but actual emergency physicians and clinical trial evidence disagree with this statement.
  • BNP is not a very good indicator of head injury
  • There is no strong evidence supporting the use of BNP in discriminating between cardiac and non-cardiac causes of respiratory failure in the critically ill patients.
  • Though a 2007 study promoted BNP as a useful way to discriminate between cardiogenic pulmonary oedema and ARDS (its elevated in ARDS, but even more elevated in APO), a later 2008 study (Yardan et al) detrmined that its sensitivity is poor
  • BNP is also elevated in sepsis, acute lung injury of any cause,  and after cardiac surgery.
  • For pulmonary embolism, BNP may be useful to identify submassive PE (which would reveal right hear tstrain though a BNP leak)- something which has both management and prognostic implications
• Summary:
  • BNP is a non-specific marker of atrial and ventricular strain, and has limited diagnostic utility. Its role in treatment monitoring and risk stratification remains to be established.

Clay, Alison S., and Bryan E. Hainline. "Hyperammonemia in the ICU." CHEST Journal 132.4 (2007): 1368-1378.

Ong, Janus P., et al. "Correlation between ammonia levels and the severity of hepatic encephalopathy." The American journal of medicine 114.3 (2003): 188-193.

McKinney, A. M., et al. "Acute hepatic (or hyperammonemic) encephalopathy: diffuse cortical injury and the significance of ammonia." American Journal of Neuroradiology 32.7 (2011): E142-E142.

Richter, Derek, and Rex MC Dawson. "The ammonia and glutamine content of the brain." Journal of Biological Chemistry 176.3 (1948): 1199-1210.

Summar, Marshall L., et al. "Unmasked adult-onset urea cycle disorders in the critical care setting." Critical care clinics 21.4 (2005): S1-S8.

Troughton, Richard W., et al. "Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations." The Lancet355.9210 (2000): 1126-1130.

McCullough, Peter A., et al. "B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure analysis from Breathing Not Properly (BNP) multinational study."  Circulation 106.4 (2002): 416-422.

Hall, Christian. "Essential biochemistry and physiology of (NT-pro) BNP."European Journal of Heart Failure 6.3 (2004): 257-260.

Silver, Marc A., et al. "BNP Consensus Panel 2004: A clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases." Congestive Heart Failure 10.s5 (2004): 1-30.

Jefic, Dane, et al. "Utility of B-type natriuretic peptide and N-terminal pro B-type natriuretic peptide in evaluation of respiratory failure in critically ill patients."CHEST Journal 128.1 (2005): 288-295.

Karmpaliotis, Dimitri, et al. "Diagnostic and prognostic utility of brain natriuretic Peptide in subjects admitted to the ICU with hypoxic respiratory failure due to noncardiogenic and cardiogenic pulmonary edema." CHEST Journal 131.4 (2007): 964-971.

Demir, Ali, et al. "The value of Serum BNP for diagnosis of intracranial injury in minor head trauma." World journal of emergency surgery 9.1 (2014): 16.

Li, Nan, et al. "BNP and NT-proBNP levels in patients with sepsis." Ront Biosei18 (2013): 1237-1243.

Mitaka, Chieko, et al. "Increased plasma concentrations of brain natriuretic peptide in patients with acute lung injury." Journal of critical care 12.2 (1997): 66-71.

Kucher, Nils, Gert Printzen, and Samuel Z. Goldhaber. "Prognostic role of brain natriuretic peptide in acute pulmonary embolism." Circulation 107.20 (2003): 2545-2547.

Meyer, Brigitte, et al. "511: Nt-Pro-Bnp Is A Strong Predictor of Outcome in Critically Ill Patients Admitted to the Icu After Cardiac Surgery." Critical Care Medicine 39.12 (2011): 141.

Yardan, T., et al. "B-type natriuretic peptide as an indicator of right ventricular dysfunction in acute pulmonary embolism." International journal of clinical practice 62.8 (2008): 1177-1182.

College Answer

1. Definitions
   • IAH is defined as a sustained IAP ≥12 mmHg
   • ACS is defined as a sustained IAP >20 mmHg (with or without APP <60 mmHg) that is associated with new organ dysfunction OR as IAH-induced new organ dysfunction without a strict IAP threshold.

(iii) IPP = MAP – IAP

1. Measuring IAP
   • Patient is supine and no active abdominal muscle contractions
   • Clamp the urinary catheter, after ensuring it is freely flowing and not obstructed.
   • 25 ml of sterile saline is instilled into the bladder via a port in the urinary catheter catheter and the catheter filled with fluid
   • A pressure transducer is connected to the urinary catheter, between the clamp and the bladder
   • Allow 30-60 seconds after instillation of the saline so as to allow for bladder detrusor muscle relaxation
   • Zero transducer at the mid-axillary line and at the level of the iliac crest
   • Measure pressure at end-expiration
2. Physiological mechanisms

Cardiac 
Decreased cardiac output –

• Reduced venous return - due to intrabdominal venous compression and raised intrathoracic pressure.
• Increased systemic afterload – due to increased compression of intrabdominal arterial vessels, and PVR due to raised intrathoracic pressure.
• Decreased Right Ventricular output from raised intrathoracic pressure, raised PVR Increased CVP and LVEDP - Reduced compliance - due to elevation of diaphragm displacing the heart and increased afterload (see above).

Hypotension – decreased cardiac output.

Respiratory

• Deteriorating O2 A-a gradients due to increased – raised diaphragm and atelectasis, increased intrapulmonary shunt / V/Q mismatch
• Hypercapnia – decreased chest wall and lung compliance.
• Increased airway pressure – altered respiratory compliance.

Discussion

A slightly less formal discussion of abdominal compartment syndrome takes place in Question 21from the second paper of 2006: "Outline the causes, consequences and the management of abdominal  compartment syndrome. "Brief notes on the pathophysiology of abdominal compartment pressure and its measurement are available, with references for the time-rich exam candidate.

First, the definitions. These are derived from a 2011 consensus statement, from which much of the below information is derived.

Specifically, the definitions were copied verbatim from Table 1, "Consensus definitions list"; one might notice that they are identical to the college answer.

Intra-abdominal Hypertension (IAH)

A sustained or repeated pathological elevation in IAP ≥ 12 mmHg

Abdominal Compartment Syndrome (ACS)

A sustained IAP> 20 mmHg (with or without an APP < 60 mmHg) that is associated with new organ dysfunction/failure

Abdominal Perfusion Pressure (APP)

APP = MAP − IAP.

Measurement of intra-abdominal pressure

• Empty the bladder
• Clamp IDC
• Attach noncompressible tubing and transducer
• Inject 20ml of fluid into the bladder
• Wait for the detrusor to relax (60 seconds)
• Zero the transducer to atmosphere, at mid-axillary line and at the level of the iliac crest
• Measure the pressure at end-expiration
• The measurement is valid under the following conditions:
  • Patient is supine
  • Muscle contraction is eliminated (eg. NMJ blockers)

List the adverse cardiorespiratory effects of an increase in IAP in a mechanically ventilated patient and outline the physiological mechanisms that account for these effects.

The college demands we focus on the cardiorespiratory consequences.

Thus:

• Decreased respiratory compliance, increased peak airway pressures- due to the pressure of the abdominal contents on the diaphragm
  • Atelectasis
  • Risk of pneumonia
  • Increased intrathoracic pressure due to the compensatory reliance on higher PEEP
• Decreased preload, thus hypotension
• Increased afterload, thus increased LV workload

Oh's Intensive Care manual: Chapter   45   (pp. 520) Abdominal  surgical  catastrophes by Stephen  J  Streat

Malbrain, Manu LNG, et al. "Results from the international conference of experts on intra-abdominal hypertension and abdominal compartment syndrome. I. Definitions." Intensive care medicine 32.11 (2006): 1722-1732.

Cheatham, Michael L., et al. "Abdominal perfusion pressure: a superior parameter in the assessment of intra-abdominal hypertension." Journal of Trauma-Injury, Infection, and Critical Care 49.4 (2000): 621-627.

Bailey, Jeffrey, and Marc J. Shapiro. "Abdominal compartment syndrome."Critical Care 4.1 (2000): 23.

Cheatham, Michael Lee. "Abdominal compartment syndrome." Current opinion in critical care 15.2 (2009): 154-162.

Maerz, Linda, and Lewis J. Kaplan. "Abdominal compartment syndrome."Critical care medicine 36.4 (2008): S212-S215.

Saggi, Bob H., et al. "Abdominal compartment syndrome." Journal of Trauma-Injury, Infection, and Critical Care 45.3 (1998): 597-609.

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.

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).

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.

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.

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:

• The "Stress Response" to critical illness
• Physiological adaptation to prolonged starvation

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
    • Increased duration of ventilation, with associated complications (eg. increased risk of VAP)
  • 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

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.

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.

College Answer

a) Risk factors:
 Exposure to antibiotics
 Clindamycin
 Cephalosproins
 Fluoroquinolones
 Extended spectrum penicillins
 Extremes of age
 Immunosuppression
 Proton pump inhibitors and H2 antagonists
 Nursing home or group care home

b) Complications:
 Related to the diarrhoea
o Hypovolaemia
o Electrolyte disturbance; hypokalaemia, hypomagnesaemia
 Related to the intestinal infection
o Sepsis and septic shock
o Perforation
o Toxic megacolon
o Bleeding

c) Diagnosis:
Clinical and investigation:
 Clinical findings
o Diarrhoea, but may have severe disease without diarrhoea
o Abdominal pain, colic in nature
o Fever
o Shock
 Microbiology
o Stool; C. difficile toxin (false negatives problematic)
o PCR for C. difficile (false positives problematic)
o ELISA for C difficile glutamate dehydrogenase
 Sigmoidoscopy, colonoscopy
o Pseudomembranes
 CT scan
o Abdominal and pelvis
o Oral and ivi contrast
o Helps to diagnose complications such as toxic megacolon, perforation and exclude differential diagnosis

d)
Prevention and treatment:
Prevention
 Antibiotics stewardship, limitation of broad spectrum antibiotics
 Isolation of C diff positive cases with notices advising contact precautions
 Limit spread with hand washing with soap and water, alcohol hand rub is ineffective
Treatment
 Supportive care and resuscitation
 Specific
o Medical
 Antibiotics;

Oral vancomycin (250 – 500 mg enteral q6h)
o Metronidazole oral or ivi
o Tigecycline

o Surgical
 For perforation or toxic megacolon
 Subtotal colectomy
o Monoclonal antibodies and vaccine under development
o Faecal transplant
 More for recurrent infection than for acute severe illness

Examiners' comments: Overall, candidates' knowledge of this topic was limited.

Discussion

This question resembles several other C.difficile questions:

• Question 3 from the first paper of 2012
• Question 27 from the second paper of 2005

They usually ask about the same things.

Oh well, here we go again.

Risk factors for C.difficile infection

The risk factors for C.difficile infection are discussed here, in a NEJM article.

• Broad spectrum antibiotics in particular clindamycin, quinolones, amoxycillin, cephalosporins

• Immunosuppressive therapy /Cytotoxic chemotherapy

• Gastric acid suppression

• Age > 65

• Prolonged hospitalisation

• Renal impairment

College Answer

a) Comment, with explanation, on each of the biochemical abnormalities.

Liver dysfunction as demonstrated by elevated enzymes, reduced albumin. Hypoglycaemia with decompensation indicated by marked elevation of ammonia. Hyponatraemia in keeping with cirrhosis.

Raised lactate as a result of liver dysfunction / alcoholic ketoacidosis / sepsis / thiamine deficiency
Raised creatinine indicates renal dysfunction and urea may be apparently “normal” because of
decreased hepatic dysfunction and possible nutritional deficiencies. Urea:creatinine ratio suggests
that GI bleed and/or dehydration are unlikely

b) List three possible causes of his altered conscious state.

• Alcohol intoxication
• Hepatic encephalopathy
• Drug ingestion
• Sepsis
• Intracranial bleed
• Wernickes encephalopathy

Discussion

This question is nearly identical to Question 29.2 from the second paper of 2011. The answer to that question is also duplicated here, to simplify revision

The following is a list of biochemical abnormalities and plausible explanations for them:

• Sodium is low due to the hypervolemic hyponatremia of cirrhosis
• Creatinine is high potentially due to dehydration or hepatorenal syndrome.
• Urea is normal likely due to nutritional deficiency or failure of the urea cycle. (so its probably not a GI bleed)
• The LFTs are deranged in keeeping with a history of chronic liver disease, featuring a degree of synthetic failure (albumin of only 20) and hypoglycaemia.
• Features of synthetic liver failure are present:
  • Ammonia is elevated.
  • Albumin is low.
  • Total protein is low.
  • Bilirubin is high
• The CK is only slightly elevated, suggesting seziures were probably not taking place before the police arrived
• The lactate is raised, and there could be numerous reasons for this - but its likely either increased production due to sepsis or thiamine deficiency, combined with a decreased hepatic clearance.

The college asks for three possible causes of unconsciousness in this comatose drunk. Three only. The most relevant ones would have to be

• Hepatic encephalopathy
• Alcohol intoxication
• Sepsis

A possible list of differentials would have to also include the following:

• V- Stroke
• I- Septic encephalopathy
• N- Seizures
• D- Drug intoxication
• I -
• C-
• A-
• T- Intracerebral bleed, GI bleed
• E- hyponatremia, hypoglycaemia

Johnston, David E. "Special considerations in interpreting liver function tests." American family physician 59 (1999): 2223-2232.

Limdi, J. K., and G. M. Hyde. "Evaluation of abnormal liver function tests." Postgraduate medical journal 79.932 (2003): 307-312.

Hoekstra, Lisette T., et al. "Physiological and biochemical basis of clinical liver function tests: a review." Annals of surgery 257.1 (2013): 27-36.

Giannini, Edoardo G., Roberto Testa, and Vincenzo Savarino. "Liver enzyme alteration: a guide for clinicians." Canadian medical association journal 172.3 (2005): 367-379.

Kim, W., et al. "Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease." Hepatology 47.4 (2008): 1363-1370.

Pratt, Daniel S., and Marshall M. Kaplan. "Evaluation of abnormal liver-enzyme results in asymptomatic patients." New England Journal of Medicine 342.17 (2000): 1266-1271.

Whitfield, J. B. "Gamma glutamyl transferase." Critical reviews in clinical laboratory sciences 38.4 (2001): 263-355.

Balistreri, William F., et al. "Intrahepatic cholestasis: Summary of an American Association for the Study of Liver Diseases single‐topic conference." Hepatology 42.1 (2005): 222-235.

Assy, N., et al. "Diagnostic approach to patients with cholestatic jaundice." World journal of gastroenterology 5.3 (1999): 252-262.

Stellpflug, Samuel J. "Transaminitis: The Lab Test That Has Inflammation…." Journal of Medical Toxicology 7.3 (2011): 252-253.

College Answer

a) What is the underlying diagnosis?

Hyperacute (fulminant) hepatic failure

b) List the possible causes in this patient.

Paracetamol
Idiosyncratic drug reaction
Other toxin e.g. Amanita phalloides
Viral (hepatitis A and E as hyperacute consider B, CMV, Epstein Barr)
Ischaemic hepatitis
Budd-Chiari

c) Outline your immediate management.

Concurrent resuscitation and institution of supportive care and monitoring with focussed assessment
to identify underlying cause and definitive management as indicated.

Airway management and oxygen – likely to need intubation and mechanical ventilation with
ARDSNet targets and PCO2 32-38 mmHg

Haemodynamic support for adequate MAP and CPP >60 and appropriate monitoring (A-line,
PAC/PiCCO, bedside echo etc.). Avoid fluid overload

Strategies to offset cerebral oedema (head-up, neutral position, sedation, PCO2 targets, Na 145-155
etc.) 

ICP monitoring controversial

Consider renal replacement therapy
Extracorporeal albumin dialysis therapies (SPAD, MARS and Prometheus) have limited evidence to
support use

Monitoring of coagulopathy using TEG/ROTEM to guide correction. Correction to cover invasive
procedures or if bleeding otherwise not.

Monitor blood glucose

Screening for infection and antibiotics as indicated +/- empiric broad spectrum cover including antifungal

Stress ulcer prophylaxis

Nutrition

Specific 
NAC
Lactulose / Neomycin / Rifaximin controversial and use varies from unit to unit

Investigations including liver USS, viral screen

Discussion with liver transplant team / transfer to ICU with liver unit (does not currently meet
transplantation criteria)

Discussion

The diagnosis is clearly liver failure. The college further qualify their description as "fulminant". That term is very 1990s. What makes a liver failure fulminate? Well, apparently that just means it is acute (see Sass et al, 2005). The term was originally applied to patients in whom encephalopathy developed within two weeks of the development of jaundice. These days, the terminology we use is hyparcute (0-7 days), acute (8-28 days) and subacute  (29 days to 8 weeks). The disorders were redefined by Williams et al in 1993, on the basis of the fact that they correlate better with survival statistics (paradoxically, the hyperacute ones do much better).

Possible categories of the causes:

Of these, the following short list is relevant. However, it must be added that the college did not specify how many differentials they wanted. You could have brought up your various azathiprine-induced hepatitis and Amanita phalloides mushrooms.

Thus:

• Hepatic ischaemia
• Acute viral hepatitis or liver abscess
• Acute right heart failure due to PE
• Drug-induced hepatitis eg. paracetamol overdose (or Amanita)
• Autummune hepatitis, eg. cryptogenic cirrhosis or idiopathic autoimmune hepatitis (IAIH)
• Traumatic hepatic injury due to fall

Management

As with most things, management falls into the category of specific management and supportive management. Specific management may be viewed as a series of antidotes or proven solutions tailored to specific causes of the liver failure.

A discussion of supportive management might take the following shape:

1.  Intubate the patient for airway protection, as they will be obtunded (and to control the CO₂)
2. Hyperventilation to low-normal PaCO2 (35 mmHg)
3. Maintain haemodynamic stability using noradrenaline preferentially.
4. Use propofol instead of benzodiazepines, and avoid long-acting opiates.
   Consider an ICP monitor
5. Hypothermia to a temperature of 32-33°
   Hypernatremia (to control ICP, with hypertonic saline) to achieve a sodium of 145-155 mmol/L
6. Haemodiafiltration - continuously - to remove ammonia
7. Anticipate hypoglycaemia.
8. Anticipate coagulopathy.
   Administer Vitamin K empirically.
   Consider blood products, but view complete correction as unobtainable.
9. Vigilant surveillance for sepsis: they are prone to it, and it makes the encephalopathy worse

​Sass, David A., and A. Obaid Shakil. "Fulminant hepatic failure." Liver Transplantation 11.6 (2005): 594-605.

Williams, R., S. W. Schalm, and J. G. O'Grady. "Acute liver failure: redefining the syndromes." The Lancet 342.8866 (1993): 273-275.

Chapter 44   (pp. 501) Liver  failure by Christopher  Willars  and  Julia  Wendon

Daly, Frank FS, et al. "Guidelines for the management of paracetamol poisoning in Australia and New Zealand-explanation and elaboration." Medical journal of Australia 188.5 (2008): 296.

Bailey, Benoit, René Blais, and Anne Letarte. "Status epilepticus after a massive intravenous N-acetylcysteine overdose leading to intracranial hypertension and death." Annals of emergency medicine 44.4 (2004): 401-406.

Parsons-Smith, B. G., et al. "The electroencephalograph in liver disease." The Lancet 270.7001 (1957): 867-871.

Ramos, Juan Francisco Rivera, and Celina Rodríguez Leal. "Review of the final report of the 1998 Working Party on definition, nomenclature and diagnosis of hepatic encephalopathy." Ann Hepatol 10 (2011): S36-S39.

Walsh, Timothy S., et al. "Energy expenditure in acetaminophen-induced fulminant hepatic failure." Critical care medicine 28.3 (2000): 649-654.

Ichai, Philippe, et al. "Usefulness of corticosteroids for the treatment of severe and fulminant forms of autoimmune hepatitis." Liver transplantation 13.7 (2007): 996-1003.

O’Grady, John G., et al. "Early indicators of prognosis in fulminant hepatic failure." Gastroenterology 97.2 (1989): 439-445.

Dhiman, Radha K., et al. "Early indicators of prognosis in fulminant hepatic failure: An assessment of the Model for End‐Stage Liver Disease (MELD) and King's College Hospital Criteria." Liver transplantation 13.6 (2007): 814-821.

Yantorno, Silvina E., et al. "MELD is superior to King's college and Clichy's criteria to assess prognosis in fulminant hepatic failure." Liver transplantation13.6 (2007): 822-828.

Wiesner, Russell, et al. "Model for end-stage liver disease (MELD) and allocation of donor livers." Gastroenterology 124.1 (2003): 91-96.

Gleisner, Ana L., et al. "Survival benefit of liver transplantation and the effect of underlying liver disease." Surgery 147.3 (2010): 392-404.

Ding, G. K. A., and N. A. Buckley. "Evidence and consequences of spectrum bias in studies of criteria for liver transplant in paracetamol hepatotoxicity." QJM101.9 (2008): 723-729.

Lee, William M., R. Todd Stravitz, and Anne M. Larson. "Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011." Hepatology 55.3 (2012): 965-967.

McPhail, Mark JW, Julia A. Wendon, and William Bernal. "Meta-analysis of performance of Kings’s College Hospital Criteria in prediction of outcome in non-paracetamol-induced acute liver failure." Journal of hepatology 53.3 (2010): 492-499.

Stravitz, R. Todd, et al. "Intensive care of patients with acute liver failure: recommendations of the US Acute Liver Failure Study Group." Critical care medicine 35.11 (2007): 2498-2508.

Warrillow, S. J., and R. Bellomo. "Preventing cerebral oedema in acute liver failure: the case for quadruple-H therapy." Anaesthesia and intensive care 42.1 (2014): 78.

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.

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
  • Swallowing dysfunction / oropharyngeal dysphagia

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".

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.

College Answer

b)

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:

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.

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.

College Answer

a)    

• Acute liver failure

b)

• Toxins – paracetamol, alcohol, mushrooms. Viral hepatitis – hep A,B,C,D,E, EBV,CMV
• Idiosyncratic drug reaction
• Ischaemic hepatitis due to shock – cardiogenic, septic. Acute fatty liver of pregnancy.
• Congenital/genetic - Wilson’s disease. Hyperthermia - Heat stroke.
• Autoimmune hepatitis. Budd-chiari syndrome.
• Malignant hepatic infiltrations – breast cancer, lung cancer, melanoma, lymphoma, myeloma.

Discussion

Well, you can't call it "acute liver failure" or "hyper-acute" or subacute" because these have specific time intervals as definitions. All you can really say is that there is liver failure. The college gives malingant infiltration as a differential, which gives one the impression that they would be willing to consider the more insidious causes of liver damage.

Possible categories of the causes:

College Answer

a)

Haemodynamic stabilization – optimize cardiac output and tissue perfusion and avoid fluid overload as ventricular function may be impaired. Close haemodynamic monitoring. Vaso-active agents as indicated.

Correction of anaemia and coagulopathy – maintain haemocrit 0.25 – 0.3 to keep blood viscosity low. INR 2, APTT 50 secs, Fibrinogen above 0.5 g/L and Platelets above 30 x 10⁹/L.

Fluid and electrolyte management – appropriate negative fluid balance day 1 decreases risk of pulmonary complications. Fluid overload may aggravate graft congestion and oedema caused by ischaemic-reperfusion. Electrolyte imbalances are common and need to be corrected.

Correction of metabolic abnormalities – hypoglycaemia is an ominous sign of compromised liver recovery, hyperglycaemia also may occur, acid-base abnormalities also occur

Early weaning from mechanical ventilation – associated with better outcome but not feasible in patients with respiratory failure, haemodynamic instability, pulmonary oedema, primary graft dysfunction, encephalopathy etc. Unsuccessful early extubation may result in impaired oxygen delivery to transplanted liver

Monitoring of graft function LFTs, lactate, BSL, coagulation, hepatic artery doppler

Early detection of surgical complications - bleeding

Immunosuppressants

Infection prophylaxis

Housekeeping including analgesia (PCA) and appropriate nutrition plan

Other – ICP monitoring if decompensated CLD pre-op

b)

Delayed metabolism of sedative / anaesthetic drugs

Metabolic derangements – hypoglycaemia, hyponatraemia, hyperosmolar syndrome Hepatic encephalopathy

Hypoxic-ischaemic cerebral injury

Seizures

Intracerebral haemorrhage

Discussion

This question is essentially identical to Question 11 from the second paper of 2012. The answer has been reproduced below, in the face of goof SEO but in the interest of siplified revision.

There is also plenty of literature regarding the critical care management of liver transplant recipients.

Let us approach this answer systematically.
The following management steps may be followed in the first 24 hour period:

• Airway:
  • Historically these patients tend to remain intubated for the first 12-24 hours, although there is good evidence that early extubation (eg. in theatre) has no adverse effects.
• Breathing:
  • In order for the graft to survive normoxia must be established
  • The general "word of mouth" advice in these situations is to minimise the PEEP. In order for the anastomoses to remain intact, PEEP should be minimised, as it will increase the CVP and thus compromise the venous vascular anastomotic sites. However, some studies have reported no significant change to the hepatic venous flow even with PEEP as high as 15cm H2O.
  • Positive pressure ventilation in general is a bad idea, as organ perfusion is decreased by positive pressure, and perfusion of the donated liver is very important in the early stages.
  • Thus, early weaning from invasive ventilation is one of the major goals
• Circulation
  • There is likely to be a degree of shock. Given that fluid management must remain relatively conservative, vasopressors and inotropes must be deployed liberally. After all, the graft needs to remain perfused.
  • Hepatic oedema due to over-resuscitation should be avoided.
  • Arbitrarily, the CVP should remain within the range of 6-10.
  • Observe for reactive vasoconstriction
    • These patients, with heir dead livers, have been in a vasodilated state, associated with nitric oxide synthase hyperactivity.
    • Now, with their new livers, normal vascular tone will return.
    • This might mean a sudden massive increase in the afterload.
    • Thus, their left ventricles, which are chronically deconditioned, might decompensate when faced with such demands.
    • Thus, GTN or nitroprusside infusions should be used liberally in these people.
  • The need for RF and LV functional assessment as well as pulmonary arterial pressure measurements and
• Neurology and sedation
  • No specific recommendations can be made, rather than to say that both hepatic and renal dysfunction in the post-operative period is to be anticipated, and thus drugs which do not rely on organ metabolism should be used. Remifentanyl and propofol spring to mind.
• Fluids and electrolytes
  • There is some "magical" preload at which the CVP is reasonable, preload adequate, and cardiac output satisfactory. Finding this magic preload is something of an art.
  • Initially, fluid resuscitation should take place, but the fluid of choice should not be Hartmanns because the new liver will probably not be able to metabolise the lactate.
  • After the initial post-operative resuscitation phase is over, a negative fluid balance should be pursued; generating a lower pressure in the right side of the thoracic circulation will serve to draw blood from the graft, and thus theoretically should improve graft perfusion.
  • Renal function needs to be watched closely - renal failure is associated with poor graft survival.
• Graft function
  • There is a phase of "preservation injury" with very high LFTs but this tends to disappear over the first 3-4 days. Thereafter, synthetic function should be restored.
  • Monitoring of the graft consist of several sequential assessments:
    • Hepatic arterial Doppler
    • BSL
    • Lactate
    • Bilirubin
  • Typically, 1-9% of liver transplants fail within hours of surgery.
• Surveillance for abdominal compartment syndrome
  • Due to the extensive nature of the procedure and due to the preexisting portal venous pathology, this issue (with pressure over 25mmHg) is fairly common.
  • Abdominal girth values are required as sequential measurements.
• Nutritional support
  • There is no string reason to recommend TPN here. Like in most other situation, nasogastric enteral feeding is probably best. A degree of ileus is to be expected, and usually resolves
• Hematological support
  • This consists of the replacement of missing blood products and blood cells.
  • Essentially, there is no specific hemoglobin goal, and what you are trying to do is prevent bleeding from the anastomotic sites.
  • Its probably OK to be slightly coagulopathic, because you don't want to develop a hepatic arterial thrombus.
• Immune suppression
  • I will not litter this summary with discussion of the relative merits of each class of antirejection drug. Suffice to say, cyclosporin tacrolimus and mycophenolate are gradually giving way to monoclonal antibodies and other immunomodulator drugs which have slightly less devastating organ system effects.
• Antibiotics and sepsis surveillance
  • Many of these patients die from postoperative infectious complications
  • 48 hrs of IV antibiotics are typically administered
  • The Sanford Guide recommends linezolid, ciprofloxacin and fluconazole.
  • The belowlinked article from 2011 also suggests 14 days of aciclovir, given the propensity for embarrassing HSV reactivation.

The second part of this question is far less interesting, and refers mainly to the candidate's ability to generate differentials for a decreased level of consciousness.

Using a usual template, one can arrive at a series of differential easily:

• Vascular causes, eg. stroke or hypoxic brain injury
• Infectious causes, eg. reactivated HSV or CMV encephalitis
• Drug-related causes, eg. slow metabolism of anaesthetic drugs reliant on hepatic clearance
• Hepatic encephalopathy
• Haematological, eg. intracranial bleeding due to coagulopathy
• Electrolyte disturbances, for instance cerebral oedema due to hyponatremia
• Endocrine disturbance eg. hypoglycaemia

The best, most comprehensive source is this article:

Feltracco, Paolo, et al. "Intensive care management of liver transplanted patients." World journal of hepatology 3.3 (2011): 61.

The rest are also helpful.

Stieber, Andrei C., R. D. Gordon, and J. R. Galloway. "Orthotopic liver transplantation." Hepatology. A text book of liver disease. WB Saunders, Philadelphia (1996): 1759-1780.

Mazariegos, George V., Ernesto P. Molmenti, and David J. Kramer. "Early complications after orthotopic liver transplantation." Surgical Clinics of North America 79.1 (1999): 109-129.

Razonable, Raymund R., et al. "Critical care issues in patients after liver transplantation." Liver Transplantation 17.5 (2011): 511.

Mandell, M. Susan, et al. "Reduced use of intensive care after liver transplantation: influence of early extubation." Liver Transplantation 8.8 (2002): 676-681.

College Answer

Increasing anion gap due to worsening renal impairment and possibly increasing lactate.

LFTs deranged with predominant finding of transaminitis. (This is likely to be associated with an increase in lactate).

Aetiologies

• Liver ischaemia due to hypoperfusion
• cardiac failure (poor output +/- liver congestion) severe sepsis with profound hypotension
• other shock states e.g. obstructive thrombo-embolic disease
• Drug related e.g. paracetamol (inadvertent or deliberate)
• (NB Acute alcoholic hepatitis is unlikely with such a high AST)

Discussion

The following biochemical abnormalities are present in the second set of results:

• High anion gap metabolic acidosis
• Renal impairment (raised urea and creatinine)
• Hypoalbuminaemia
• Borderline raised bilirubin
• Trivially elevated cholestatic liver enzymes
• Massively elevated hepatic transaminases
• A high AST to ALT ratio
• Trivially elevated inflammatory markers

The raised transaminases are described as a "transaminitis" by the college, a term which has been in use since 1977, in spite of some authors referring to it as "made up and improper" (Stellpflug, 2011). The previous set of results from Question 23.1 demonstrated a raised lactate and severe acidaemia wioth a normal glucose and normal haemoglobin. From the list of causes of elevated transaminases, the following are relevant diferentials, and parenthesised comments as to why they are relevant:

• Congestive heart failure (he has COPD: maybe the right heart?)
• Portal vein thrombosis (past history of cancer)
• Malignant infiltration (past history of cancer)
• Drug overdose (this is always an option)
• Viral hepatitis (this is always an option)
• Fatty liver or NASH
• Liver abscess (right lower lobe "infiltrate" may be sympathetic effusion)
• α1-antitrypsin deficiency (the college has given a history of COPD, implying emphysema, but no history of any actual smoking)
• Poor liver perfusion and ischaemia ("shock liver") - however, no history of profound hypotension

And then those things which this is not:

• Alcoholic hepatitis (unlikely: no history of drinking and GGT is not elevated)
• Pancreatitis (not a cholestatic picture)
• Traumatic causes (no history of trauma)
• Congenital issues, haemochromatosis, Wilson's disease (he's 70)

Stellpflug, Samuel J. "Transaminitis: The Lab Test That Has Inflammation…." Journal of Medical Toxicology 7.3 (2011): 252-253.

Johnston, David E. "Special considerations in interpreting liver function tests." American family physician 59 (1999): 2223-2232.

Limdi, J. K., and G. M. Hyde. "Evaluation of abnormal liver function tests." Postgraduate medical journal 79.932 (2003): 307-312.

Hoekstra, Lisette T., et al. "Physiological and biochemical basis of clinical liver function tests: a review." Annals of surgery 257.1 (2013): 27-36.

College Answer

Treatment:

• Immediate goal is to alleviate the active symptoms of diarrhoea and colitis.
• Ultimate goal is restoration of normal gut flora.
• Discontinue all unnecessary antibiotics.
• Fluid and electrolyte replacement as indicated to compensate for GI losses
• Antibiotic therapy
  • First line agent is PO metronidazole especially in milder disease.
  • Second Line is PO vancomycin for patients with more severe disease, or who are intolerant or do not respond to metronidazole. There has been recent debate that vancomycin should possibly be first line therapy, due to increasing treatment failure rates with metronidazole not seen with vancomycin. Cost and increasing nosocomial vancomycin resistance are other issues within this debate.
• Assess for complications of colitis – severe sepsis or toxic megacolon
• Faecal transplant should be considered to restore normal gut flora

Infection Control and Prevention Strategies:

• The ultimate goal in combating disease is prevention/eradication.
• Specific infection control measures, and thus a Unit Policy, are very important MUST be instituted, championed and audited.
  • Isolation of CDI patients in single rooms or cohorted together o Hand Hygiene – The “5 Moments of Hand Hygiene”.
    • Soap and water
    • Not alcohol-based hand rubs (don’t kill the spores) 
  • Contact Precautions.
    • Gown and glove.
  • Environmental cleaning and disinfection.
    • Ammonium-based disinfectants are not sporicidal
    • Solutions must include unbuffered hypochlorite (bleach), which is sporicidal. In other words, chlorine-based solutions.
  • Restriction of antimicrobial use.
• Education, via a widespread campaign, and audit, of staff and compliance will be important.
• Consider the introduction of a formal CDI Team which would help educate, raise awareness, implement and audit your policy
• Consider the introduction of CDI Bundles similar to other hospitals 
  • Education Bundle
  • Prevention Bundle
  • Treatment Bundle
• Introduction of an Antibiotic Stewardship Program would help monitor appropriate antibiotic use and cessation etc.
• Consider restricting the use of gastric acid suppressive agents. Multiple large trials now support the association between CDI and PPI use. One would have to weigh up the riskbenefit on a patient-to-patient basis though.
• Finally there are ongoing trials looking at the use of probiotics for the prevention of CDI. Their role is unclear at present.

Discussion

Approach to specific patient treatment:

Mild-moderate C.difficile infection:

• Treat empirically in the absence of positive results, if the pre-test suspicion is strong.
• Stop the inciting antibiotics
• Give oral metronidazole for 10 days
  • Change metronidazole to vancomycin if there is no response in 5-7 days
• For severe infection, just give oral vancomycin straight away(125mg qid for 10 days)
• Vancomycin enemas are an option
• Avoid anti-diarrhoea medications

Severe and complicated C.difficile infection:

• CT of the abdomen is indicated
• Oral vacomycin PLUS intravenous metronidazole are indicated
• If there is significant abdominal distension, the vancomycin should be given as an enema

Recurrent C.difficile infection:

• First recurrence: treat in the same way as the first episode
• Second recurrence: change to vancomycin
• Third recurrence: consider a faecal microbiota transplant

When to consider surgery: