Hyperosmolar Non Ketotic Hypergycaemic Coma (HONK)

Though a distinction is being made between diabetic ketoacidosis and HONK, the two really form a part of the same disease spectrum. Some ketoacidosis is present in HONK, and some hyperosmolarity is present in DKA. However, different mechanisms are at play. HONK is distinct form DKA, and the distinction is not entirely arbitrary, at least from the management point of view. For instance, even though the conditions co-exist 30% of the time, it is possible to treat pure HONK without any supplemental insulin (because there is a satisfactory amount of it in circulation already).DKA is 3 times more common, but HONK has 3 times greater mortality. The chapter on DKA presents a table of discriminating features to help distinguish HONK from DKA.

Past CICM SAQs involving HONk have included the following:

  • Question 24 from the first paper of 2017 (management strategy)
  • Question 1 from the second paper of 2016 (DKA vs HONK)
  • Question 17 from the first paper of 2014 (DKA vs HONK)
  • Question 18.1 from the second paper of 2008 (diagnosis and complications)
  • Question 13 from the first paper of 2002 (pathophysiology, complications and treatment)

Precipitants of HONK

Similarly to DKA, a stress response which mobilises metabolic substrates in a Type 2 diabetic will result in HONK.

Precipitating Factors for Hyperosmolar Hyperglycaemia

Mismanagement of diabetes

  • Poor treatment compliance
  • Dietary mismanagement

Drugs which trigger HONK

  • Corticosteroids
  • Diuretics
  • Phenytoin
  • Diazoxide
  • TPN
  • Lithium (by causing DI)

Physiological stress

  • Infection
  • Systemic inflammatory response
  • Myocardial infarction
  • Surgery
  • Substance abuse
  • Intracranial haemorrhage
  • Hepatic encephalopathy

Pathogenesis of HONK

The key distinction between DKA and HONK seems to be the fact that in HONk, there is still enough insulin to overcome the ketogenic effects of glucagon.

mechanisms of metabolic differences between DKA and HONK

Glucagon inhibits acetyl-CoA carboxylase, which normally converts acetyl-CoA into malonyl-CoA. Malonyl CoA inhibits acyl-carnitine synthesis; if this is uninhibited, it results in a stream of fatty acids being sucked up into the mitochondria to be converted into ketones.

Thus, we have a hyperglycaemic patient who remains reasonably asymptomatic because in them acidosis fails to develop (and thus, they are not short of breath). They remain hyperglycaemic for some time. As a result, they subject themselves to osmotic diuresis for a prolonged period, which allows them to become progressively more and more dehydrated.

The result is the hyperosmolar state which is usually associated with HONK.

This hyperosomolar hyperglycaemia is an intensely proinflammatory and prothrombotic state, which gives rise to the various complications of HONK.

Diagnostic features of HONK

In order to qualify as a HONK, you must strive towards the following diagnostic criteria:

  • Serum osmolality > 320mOsm/Kg
  • pH >7.30
  • urine/serum ketones dont matter, but may be present
  • BSL >30

One can summarise the presenting features of HONK in the form of a table:

Clinical Manifestations of Hyperosmolar Hyperglycaemia



Low PCO2



Hypotension due to hypovolemia


High anion gap metabolic acidosis (with lactate and uremia rather than ketones)


Hypokalemia (due to vomiting)




Obtundation and coma





Acute renal failure






Complications of HONK

Naturally, having your body fluid gradually concentrated up to a high osmolarity is not a consequence-free process. One must recall that there are various rheological changes which take place as the result of hyperosmolarity .The following list of complications of HHS is a combination of several sources, including local resources as well as he college answers to Question 18.1 from the second paper of 2008 and Question 13 from the first paper of 2002.

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

Management of HONK

Fluid replacement

The key issue is hyperosmolarity, and naturally the first instinct is to dilute the concentrated body fluids with some nice clean crystalloid. Indeed, Oh's Manual suggests that there is no specific difference between the fluid management in DKA and in HONK. On the basis of this consensus statement, they recommend the following fluid resuscitation schedule for both:

  • 15-20ml/kg in the first hour (and use colloid if they are shocked)
  • 4-14ml/kg in the second hour (of 0.45% NaCl)
  • 4-14ml/kg again in the third hour (use 0.9% NaCl if the sodium is low)
  • When glucose is under 15mmol/L, Oh's Manual recommends to start 5% dextrose 100-250ml/hr, as well as some other sort of sodium-containing fluid to prevent hyponatremia.

With this regimen, for a 70kg DKA/HONK patient, one ends up giving about 1.5-3L in the first 3 hours. The total deficit in HONK may be around 200ml/kg of free water (that might be 20 litres for a big person).

Avoidance of cerebral oedema

The college touched on this issue in Question 24 from the first paper of 2017. Specifically, the candidates were asked for "risk factors for all patients that predispose to the development of cerebral oedema" in HONK/HHS. Turns out, in adults this is a fairly uncommon complication (Matz, 1999).

The college give the following risk factors in their model answer:

  • 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

The precise origin of these risk factors is unclear.

Looking through the literature, one finds such authoritative sources as the American Diebates Association (Kitabchi et al, 2009) making a commend regarding bicarbonate being one of the causes of cerebral oedema. In the same article one may find the statistic that the majority of deaths from HHS in children are due to cerebral oedema, and a reference to an article by EC Quintana (2004) where severity of dehydration is mentioned as one of the predictors of mortality. Lawrence et al (2005) offer a population-based study of Canadian children (n=13!) where risk of cerebral oedema was associated with a lower bicarbonate, higher urea and higher glucose on presentation. Bialo et al (2015) scraped together a few other risk factors, including new onset Type 1 diabetes and a low PaCO2. Oh'Manual (p. 635 of the 7th edition) also mentions the failure of serum sodium to rise with treatment. Following a trail of references from Oh's one comes across the 2011 paper from Glaser et al, who also had low CO2 and high BUN. Then there is Rosenbloom (1990), where age under 3 years and Down syndrome were mentioned. Where the college got the rest of these risk factors, that is anybody's guess. If one had to put them all together into a list, it would look like this:

Risk Factors for Cerebral Oedema in HONK
  • 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)

How does one avoid cerebral oedema in HHS? Though there is a real risk of cerebral oedema with vigorous fluid resuscitation, there is only some vague mention of the need to be careful. Gouveia et al (2013) and Dhatariya (2014) both authored review articles which warn of cerebral oedema and central myelinolysis. A recent Diabetes UK Position Statement (Scott et al, 2015) recommends we reduce osmolality by 3–8 mOsm/kg/h, as a safe rate. 

Choice of resuscitation fluid in HONK

There is little evidence to demonstrate the advantage of one form of crystalloid fluid over another. In HONK, there is no acidosis to defeat, which robs Hartmanns and Plasmalyte of their advantage.

However, don't let this fool you into thinking that the choice of fluid does not matter. One will be infusing an awful lot of crystalloid into this patient, and in context of that perhaps a little bit of intellectual processing is in order. I suppose one might make a comment about the chloride content of 20 litres of normal saline, and whether the patient requires this much chloride. In short, when in doubt one cannot go wrong with a "physiologically balanced solution".

Electrolyte replacement in HONK

Table 58.1 on page 631 of the new Ohs Manual presents a list of electrolyte deficits which develop in DKA and HONK. A 2003 article contains a similar table. I will summarise the relevant features:

  • Water deficit: 200ml/kg
  • Sodium deficit: 5-13mmol/kg
  • Potassium deficit: 5-15mmol/kg
  • Chloride deficit: 3-7mmol/kg
  • Phosphate deficit: 1-2mmol/kg
  • Magneisum deficit: 1-1.5mmol/Kg
  • Calcium deficit: 1-2mmol/Kg

Thus, the 70kg HONK patient stands to be infused with up to 14 litres of water, 910mmol of sodium, 1050mmol of potassium, 490mmol of chloride, and 140mmol each of phosphate, magnesium and calcium. In reality, the total infusion requirement may be greater due to diuresis.

A stereotypical approach to a HONK question in the CICM SAQs

"Describe your specific treatment", the examiner cackles malignantly.

The stereotypical approach 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

The chances of a poor outcome in HONK

Mortality is higher for HONK than for DKA, and the patients tend to be older. One study sheds some light on poor prognostic indicators:

  • cardiovascular disease
  • old age
  • hypotension
  • hyponatremia
  • acidosis
  • high urea (the most important risk factor for death).



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.