Question 13

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

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College Answer

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

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

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


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

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

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

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

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

The stereotypical approach to management is listed below:

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

Key issues of "specific therapy:

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


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

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

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

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

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

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

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

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

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

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