Hyperosmolar Hyperglycaemic State
Last updated 26th Feb 2020 - Tom Heaton
Hyperosmotic hyperglycaemic state HHS) is another complication of diabetes, usually type 2.
It was previously known as HONK (hyperosmolar nonketotic state).
It is a serious complication with a much higher mortality than DKA.
This is a good introductory video from Khan Academy: https://www.youtube.com/watch?v=iKKF5yuxvg8
It was previously known as HONK (hyperosmolar nonketotic state).
It is a serious complication with a much higher mortality than DKA.
This is a good introductory video from Khan Academy: https://www.youtube.com/watch?v=iKKF5yuxvg8
Pathophysiology
There is a similar pathophysiology to DKA, with the key difference being the lack of ketogenesis.
There is often a similar precipitant as in DKA, with a worsening of the relative insulin deficiency.
This leads to upregulation of the physiological response to counter hypoglycaemia (even though it is utilisation rather than true plasma), including increases in glucagon, growth hormone, glucocorticoids and catecholamines.
There is subsequent gluconeogenesis and glycogenolysis, although there is sufficient insulin to stop a switch to ketogenesis.
The result of this hyperglycaemia is that of osmotic diuresis.
This combines with the osmotic effects of the hyperglycaemia to produce a hyperosmolar state which contributes to much of the symptoms.
The time frame for the deterioration is less acute than with DKA.
Triggers include:
There is often a similar precipitant as in DKA, with a worsening of the relative insulin deficiency.
This leads to upregulation of the physiological response to counter hypoglycaemia (even though it is utilisation rather than true plasma), including increases in glucagon, growth hormone, glucocorticoids and catecholamines.
There is subsequent gluconeogenesis and glycogenolysis, although there is sufficient insulin to stop a switch to ketogenesis.
The result of this hyperglycaemia is that of osmotic diuresis.
This combines with the osmotic effects of the hyperglycaemia to produce a hyperosmolar state which contributes to much of the symptoms.
The time frame for the deterioration is less acute than with DKA.
Triggers include:
- Infection
- Cardiac event
- Trauma, including surgery
- Medication omission
Presentation
As noted, this is usually more gradual, over days or even weeks.
The features are related to dehydration and hyperosmotic state:
There may also be contributions from a precipitant illness e.g. MI.
The history should explore changes in medications.
The features are related to dehydration and hyperosmotic state:
- Polyuria
- Polydipsia
- Malaise
- Weight loss
- Altered mental status: coma, confusion,
- Visual disturbance
There may also be contributions from a precipitant illness e.g. MI.
The history should explore changes in medications.
Clinical Findings
- Resp
- Tachypnoea
- Tachypnoea
- CVS
- Tachycardia
- Hypotension - postural element
- Dry mucous membranes
- Increased skin turgor
- Tachycardia
- Neurological
- Reduced conscious level
- Confusion
- Seizures
- Reduced conscious level
Interestingly, the increased osmolality may preserve intravascular volume and CVS stability, despite profound dehydration.
Investigations
Bloods
Imaging
Osmolality can be calculated as:
Osmolality = 2[Na]+[K]+[Glucose]+[Urea].
The [K] is not always included which may not be important as long as the same method is used consistently.
- FBC
- U&E - AKI common, electrolyte derangement common
- Osmolality - often very high (>320mOsmol/l)
- Glucose
- Blood gas - usually pH.7.3
- CRP
Imaging
- CXR - infective trigger
- CT brain - may be indicated for altered conscious level
- Urine dip/cultures
- Blood cultures
Osmolality can be calculated as:
Osmolality = 2[Na]+[K]+[Glucose]+[Urea].
The [K] is not always included which may not be important as long as the same method is used consistently.
Diagnosis
The criteria for diagnosis are not rigid but and to help differentiate from DKA can be considered as:
Note that DKA and HHS can coexist.
Severe disease, indicating possible critical care admission include:
- Hypovolaemia
- Marked hyperglycemia (>30mmol/L)
- Minimal ketosis (ketones <3mmol/l)
- Minimal acidosis (pH >7.3)
- Minimal ketosis (ketones <3mmol/l)
- Hyperosmolality (>320mosmol/kg)
Note that DKA and HHS can coexist.
Severe disease, indicating possible critical care admission include:
- Osmolality >350mosmol/kg
- Sodium >160mmol/l
- pH<7.1
- Kyper/hypokalaemia
- CVS disturbance despite initial fluid resus
- GCS <12
- SpO2 <92%
- Hypothermia
Management
The principle of management are:
Patients can be severely unwell, so an A to E approach to life threatening problems is advised in such cases.
- Fluid replacement/osmolality correction
- Correction of electrolyte disturbances
- Normalisation of blood glucose
- Treatment of precipitant
- Avoidance of complications
Patients can be severely unwell, so an A to E approach to life threatening problems is advised in such cases.
Fluid Replacement
As noted, fluid losses in these patients are often profound; potentially between 10-20L (100-220 ml/kg).
The goal is to correct 50% of the deficit (or around 3-6L) in the first 12 hours.
Subsequent rehydration of the deficit is ideally over the next 12 hours, but will be guided by the rate of parameter changes, and tolerance of fluid resuscitation e.g. cardiac function.
The resuscitation fluid of choice is usually 0.9%NaCl, as there are usually notable deficist of both sodium and chloride as well.
A goal is a drop in osmolality by 3-8mOsmol/kg/hr.
The goal is to correct 50% of the deficit (or around 3-6L) in the first 12 hours.
Subsequent rehydration of the deficit is ideally over the next 12 hours, but will be guided by the rate of parameter changes, and tolerance of fluid resuscitation e.g. cardiac function.
The resuscitation fluid of choice is usually 0.9%NaCl, as there are usually notable deficist of both sodium and chloride as well.
A goal is a drop in osmolality by 3-8mOsmol/kg/hr.
Correction of Electrolyte Disturbances
Measured sodium can change with rehydration, but it is important to note the impact of the osmolality on true sodium levels.
The corrected sodium= measured [Na+] + glucose/3
The true sodium change should not be more than 10mmol/l over 24 hour, and will change with fluid repletion.
It may initially rise, as water moves intracellularly with a BG drop, but this is not necessarily an indication for hypotonic solutions.
As with DKA, potassium replacement should be provided when the K+ is in the normal range (i.e. whenever it is not elevated), because of the total body depletion and effect of treatment to drop it.
Phosphate and magnesium levels are often also low, but replacement is not essential unless causing significant effects.
The corrected sodium= measured [Na+] + glucose/3
The true sodium change should not be more than 10mmol/l over 24 hour, and will change with fluid repletion.
It may initially rise, as water moves intracellularly with a BG drop, but this is not necessarily an indication for hypotonic solutions.
As with DKA, potassium replacement should be provided when the K+ is in the normal range (i.e. whenever it is not elevated), because of the total body depletion and effect of treatment to drop it.
Phosphate and magnesium levels are often also low, but replacement is not essential unless causing significant effects.
Normalisation of Blood Glucose
Some drop in BG will occur with rehydration, simply as a dilutional effect.
This is adequate initially, and indeed desired, as too rapid correction can lead to major osmotic changes and CVS instability (these patients can be insulin sensitive).
After appropriate fluid resuscitation, once the BG level is no longer falling, insulin can be commenced at 0.05unit/kg/hr.
It may be commenced earlier if there is significant ketonaemia (>1mmol/l), as this indicates a more absolute insulin deficit.
A goal for glucose drop of <5mmol/l/hr is described.
This is adequate initially, and indeed desired, as too rapid correction can lead to major osmotic changes and CVS instability (these patients can be insulin sensitive).
After appropriate fluid resuscitation, once the BG level is no longer falling, insulin can be commenced at 0.05unit/kg/hr.
It may be commenced earlier if there is significant ketonaemia (>1mmol/l), as this indicates a more absolute insulin deficit.
A goal for glucose drop of <5mmol/l/hr is described.
Treatment of Precipitant
This should be investigated for and appropriately treated.
This will clearly be dependent on the specific precipitant.
This will clearly be dependent on the specific precipitant.
Avoidance of Complications
There are a number of complications that can arise from HHS.
Active management to mitigate these risks is essential.
Thromboprophylaxis is the key part of this.
The rate of correction of osmolality and Na+ is also an important factor for avoiding complications.
Careful management for foot ulceration is also essential.
Active management to mitigate these risks is essential.
Thromboprophylaxis is the key part of this.
The rate of correction of osmolality and Na+ is also an important factor for avoiding complications.
Careful management for foot ulceration is also essential.
Complications
- Vascular/thrombotic
- MI
- VTE
- CVA
- MI
- Cerebral oedema
- Seizures
- Central pontine myelinolysis
- Pressure sores
- Renal failure
- Rhabdomyolysis
- Fluid overload
Links & References
- KhanAcademy. Acute complications of diabetes - Hyperosmolar hyperglycemic nonketotic state. Youtube. 2015. https://www.youtube.com/watch?v=iKKF5yuxvg8
- Nickson, C. Hyperosmolar hyperglycaemic state. 2019. LITFL. https://litfl.com/hyperosmolar-hyperglycemic-state/
- Kerr, D. Wenham, T. Endocrine problems in the critically ill 1: diabetes and glycaemic control. BJA Education. 2017. 17(11):370-376. https://academic.oup.com/bjaed/article/17/11/370/3870459
- Joint British Diabetes Societies Inpatient Care Group. The management of hyperosmolar hyperglycaemic state (HHS) in adults with diabetes. 2012. https://diabetes-resources-production.s3-eu-west-1.amazonaws.com/diabetes-storage/migration/pdf/JBDS-IP-HHS-Adults.pdf
