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

Parameter

Patient Value

Adult Normal Ranae

FiO2

0.21

pH

6.84'

7.35 - 7.45

pCO2

8.7 mmHg

35.0 -45.0 

pO2

80 mmHg

Bicarbonate

1.4 mmol/L"

22.0 - 26.0

Sodium

126 mmol/L*    

135 - 145

Potassium

5.5 mmaVL*

3.5 - 5.2

Chloride

98 mmolfl

95 - 105

Glucose

54.0 mmol/L*

3.5 - 6.0

Lactate

4.1 mmol/L'

< 2.0

Haemoglobin

96 a/L'

115 - 160

Creatinine

150 umol/L*

45 - 90

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

The ED Registrar suggests intubating the patient.

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

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

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College answer

a)

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

b)

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

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

Discussion

a)

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

The college suggested insulin. This is rarely required in pure HHS; fluid resuscitation alone is often enough because the hyperosmolar state is frequently associated with an abnormally elevated insulin level in a Type 2 diabetic. However, in this scenario the patient is a Type 1 diabetic, and so some insulin would be required (but probably not the 0.1u/kg/hr recommended by the usual DKA protocols)

Otherwise, a standard approach to HHS is described below.

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

Key issues of "specific therapy:

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

b) This list of risk factors from the college seems to come from multiple references (see the list from the HHS chapter) and may be mainly paediatric in origin, as it appears this complication is much less common among adult patients  (Matz, 1999).

A complete list of risk factors from around the literature would look like this:

  • Children (esp. under 3s)
  • New diagnosis of diabetes
  • Down syndrome
  • Use of bicarbonate
  • Rapid change in serum sodium concentration
  • Severe acidosis
  • Severe hypoglycaemia
  • Severe dehydration
  • Low presenting PaCO2
  • High urea
  • Rate of rehydration (rapid)

References

References

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

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

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

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

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

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

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

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

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

Gouveia, Catherine F., and Tahseen A. Chowdhury. "Managing hyperglycaemic emergencies: an illustrative case and review of recent British guidelines." Clinical Medicine 13.2 (2013): 160-162.

Dhatariya, Ketan. "Diabetic ketoacidosis and hyperosmolar crisis in adults." Medicine 42.12 (2014): 723-726.

Scott, A. R. "Management of hyperosmolar hyperglycaemic state in adults with diabetes." Diabetic Medicine 32.6 (2015): 714-724.

Matz, R. O. B. E. R. T. "Management of the hyperosmolar hyperglycemic syndrome." American family physician 60.5 (1999): 1468-1476.

Matz, R. "How big is the risk of cerebral edema in adults with DKA." J Crit Illn 11 (1996): 768-772.

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

Quintana, E. C. "Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema." Annals of Emergency Medicine 43.6 (2004): 793-794.

Bialo, Shara R., et al. "Rare complications of pediatric diabetic ketoacidosis."World journal of diabetes 6.1 (2015): 167.

Lawrence, Sarah E., et al. "Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis." The Journal of pediatrics 146.5 (2005): 688-692.

Marcin, James P., et al. "Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema." The Journal of pediatrics 141.6 (2002): 793-797.

Glaser, Nicole, et al. "Risk factors for cerebral edema in children with diabetic ketoacidosis." New England Journal of Medicine 344.4 (2001): 264-269.

Rosenbloom, Arlan L. "Intracerebral crises during treatment of diabetic ketoacidosis." Diabetes care 13.1 (1990): 22-33.