Hyperglycemic Hyperosmolar Syndrome – rudms.com

Hyperglycemic Hyperosmolar Syndrome


Hyperglycemic Hyperosmolar Syndrome

Hyperglycemic hyperosmolar syndrome (HHS) is a life-threatening complication of diabetes mellitus characterised by marked hyperglycemia, dehydration, electrolyte derangements, and hyperosmolality with or with out psychological obtundation, within the absence of great ketoacidosis.


  • Hyperosmolar hyperglycemic syndrome
  • Diabetic hyperosmolar syndrome
  • Hyperglycemic hyperosmolar nonketotic syndrome
  • Hyperglycemic hyperosmolar nonketotic coma
  • Hyperosmolar hyperglycemic state
  • Nonketotic hyperosmolar syndrome

Epidemiology & Demographics

Hyperglycemic Hyperosmolar Syndrome is a uncommon situation that mostly impacts sufferers with kind 2 diabetes mellitus.

Roughly 20% of sufferers don’t have any historical past of diabetes.

Aged people with new-onset diabetes or these with poorly managed kind 2 diabetes predisposed to extracellular fluid quantity depletion (so-called dehydration) are at elevated threat for Hyperglycemic Hyperosmolar Syndrome.

Mortality from Hyperglycemic Hyperosmolar Syndrome is estimated at 5% to twenty%, a higher mortality fee than for diabetic ketoacidosis.

Prognosis is decided by a number of components, together with age, diploma of dehydration, and presence of different comorbidities.

What are the Signs of Hyperglycemic Hyperosmolar Syndrome – Bodily Findings & Scientific Presentation

Listed here are the signs of Hyperglycemic Hyperosmolar Syndrome

  • •Polyuria, polydipsia, weight reduction, weak point
  • •Psychological standing adjustments that may vary from full alertness to coma
  • •Focal neurologic indicators (e.g., hemiplegia, hemianopsia) or seizures (focal or generalized), aphasia, visible hallucinations
  • •Signs of coexisting sicknesses or comorbidities that will have precipitated the occasion
  • •Indicators of extracellular fluid quantity depletion, together with dry mucous membranes, poor pores and skin turgor, sunken eyes, hypotension, and tachycardia
  • •Normothermia or hypothermia regardless of the presence of an infection, resulting from peripheral vasodilation

What causes this situation?

Hyperglycemic Hyperosmolar Syndrome will be precipitated by varied situations:

  • •An infection (commonest precipitant, particularly pneumonia and urinary tract infections)
  • •Insulin deficiency (undiagnosed diabetes, insufficient insulin, or remedy nonadherence)
  • •Inflammatory situations (e.g., acute pancreatitis, acute cholecystitis)
  • •Ischemia/infarction (e.g., myocardial infarction, stroke, bowel ischemia)
  • •Kidney failure
  • •Extreme dehydration (e.g., burns, heatstroke)
  • •Medicine (e.g., steroids, thiazides, beta blockers, atypical antipsychotics, sympathomimetics together with cocaine, alcohol, pentamidine)

A relative insulin deficiency supplies sufficient insulin to inhibit ketogenesis however is inadequate to inhibit hepatic gluconeogenesis, glycogenolysis, or promote peripheral glucose uptake, with consequent hyperglycemia.

With underlying sickness, counterregulatory hormone extra results in additional blood glucose elevation.

The resultant excessive hyperglycemia results in osmotic diuresis.

If satisfactory hydration is just not maintained, dehydration and worsening renal operate ensue. In these with insufficient fluid consumption resulting from altered thirst mechanisms or the lack to entry fluids, as could also be seen within the aged inhabitants, the danger of extreme dehydration additional will increase.

Diminished renal filtration additional impairs glucose excretion, thus exacerbating the hyperglycemia, dehydration, and hyperosmolality, and will increase the danger for cardiovascular collapse.

Differential Analysis

  • •Diabetic ketoacidosis
  • •Stroke (particularly within the aged with neurologic abnormalities)
  • •Hypovolemic or septic shock
  • •Encephalopathy

How is that this situation identified?

After the preliminary historical past is obtained, carry out a bodily examination that features quick analysis of airway, respiratory, circulation, psychological standing, quantity standing, and indicators suggestive of precipitating occasion together with an infection, myocardial infarction, or stroke.

Laboratory Assessments

  • •Hyperglycemia: Blood glucose >600 mg/dl

Diagnostic Testing Standards for Sufferers with Hyperglycemic Hyperosmolar State

From Adams JG et al (eds): Emergency medication: scientific necessities, ed 2, Philadelphia, 2013, Saunders.

  • Glucose larger than 600 mg/dl
  • Regular pH (classically, nonetheless, sufferers are sometimes mildly acidotic)
  • No vital ketosis ∗Serum acetoacetate is commonly current, usually an absent or low β-hydroxybutyrate degree.
  • Serum osmolarity
    • •>320 mOsm/L with any psychological standing adjustments, or
    • •>350 mOsm/L
  • Serum osmolality: Often >320 mOsm/kg
  • •Full metabolic panel: Serum creatinine, blood urea nitrogen (BUN), electrolytes, glucose
  • •Serum sodium: Could also be low, regular, or excessive. Hyperglycemia will increase plasma osmolality that translocates intracellular water to the extracellular compartment, reducing serum sodium. Serum sodium will be corrected by including 1.6 mmol/L to the measured serum sodium for every 100 mg/dl rise in serum glucose above 100 mg/dl. Marked osmotic diuresis induced by hyperglycemia could trigger the serum sodium degree to be regular or excessive
  • •Serum potassium and phosphate: Whole physique potassium and phosphate deficits usually happen resulting from urinary losses from osmotic diuresis. Nonetheless, these ranges could also be acutely regular or excessive resulting from extracellular shift secondary to insulin deficiency and hyperosmolality
  • •Anion hole and serum lactate: Anion hole could also be regular or elevated within the setting of lactic acidosis
  • •Arterial blood gasoline: pH >7.30
  • •Serum and urine ketones: Damaging or small
  • •Serum bicarbonate: >15 mmol/L
  • •Hemoglobin A1c (if not carried out in previous 3 mo)
  • •Full blood depend with differential (could point out presence of underlying an infection [leukocytosis >25,000 mm3], inflammatory situation, hemoconcentration. A leukocytosisof 10,000 to fifteen,000 mm3 is predicted from the stress of sickness alone)
  • •Urinalysis, urine/sputum/blood cultures as indicated based mostly on bodily examination findings to judge the precipitating sickness and different comorbidities

Imaging Research

ECG, chest radiograph, and different imaging research as indicated to judge the precipitating causes of Hyperglycemic Hyperosmolar Syndrome

How is Hyperglycemic Hyperosmolar Syndrome handled?

Acute Common Therapy

Aggressive fluid resuscitation, intravenous insulin, and electrolyte correction are the mainstays of remedy.

The preliminary objective of Hyperglycemic Hyperosmolar Syndrome remedy consists of restoring the water deficit with intravenous fluids.

It will assist to normalize the plasma hyperosmolality, enhance renal perfusion and insulin resistance, scale back the counterregulatory hormone launch, and finally appropriate hyperglycemia.

Deciding on the suitable kind of fluid is vital to forestall problems associated to dysnatremia.

Improper administration of plasma sodium focus and plasma osmolality throughout remedy of Hyperglycemic Hyperosmolar Syndrome has been related to the life-threatening complication of cerebral edema.

Aggressive Intravenous Fluid Substitute

As a consequence of trivial ketonemia and the insulin sensitivity of most Hyperglycemic Hyperosmolar Syndrome sufferers, preliminary remedy is intravenous fluid alone with out insulin.

Insulin used previous to intravenous hydration or early in resuscitation dangers a precipitous drop in serum osmolality.

Within the absence of cardiac compromise or end-stage renal illness, infuse 0.9% regular saline (NS) at an preliminary fee of 1 L/hr for the primary hour.

That is then adopted by changes within the fee of infusion based mostly on electrolyte values and hemodynamics.

A decrease fee of 250 to 500 ml/hr could also be satisfactory within the absence of extreme dehydration. If the corrected serum sodium is elevated, 0.45% NS could also be infused as a substitute.

Reassess corrected sodium wants by frequent checks and calculation. Advisable sodium decline is 0.5 mmol/L/hr and mustn’t surpass 10 to 12 mmol/L per day. Use measured or calculated osmolality to information the speed of fluid resuscitation for gradual normalization of osmolality.

Advisable serum osmolality decline is 3 mOsm/kg per hour. As soon as serum glucose decreases to 300 mg/dl, change the intravenous fluid to five% dextrose with 0.45% NS at 150 to 250 ml/hr.


As soon as glucose is now not considerably bettering with fluids alone, reassess affected person’s fluid standing and provoke intravenous insulin.

Administer preliminary bolus of intravenous common insulin 0.1 items/kg adopted by 0.1 items/kg per hour infusion or a steady infusion of 0.14 items/kg per hour with out preliminary bolus.

If serum glucose declines by lower than 50 to 75 mg/dl within the first hour, enhance the insulin infusion fee each hour till a decline is famous.

As soon as the serum glucose reaches 300 mg/dl, lower the insulin infusion fee to 0.02 to 0.05 items/kg per hour to take care of serum glucose between 200 to 300 mg/dl till decision of Hyperglycemic Hyperosmolar Syndrome.

Potassium Substitute

Insulin remedy shifts potassium intracellularly, regularly inflicting hypokalemia. If serum potassium at presentation is between 3.3 and 5.2 mmol/L, infuse 20 to 30 mmol of potassium chloride (KCl) with every liter of intravenous fluid to take care of serum potassium between 4 and 5 mmol/L.

If the serum potassium focus at presentation is <3.3 mmol/L, exchange potassium by administering KCl infusion at 20 to 30 mmol/h, and withhold insulin till the serum potassium focus is >3.3 mmol/L.

If the serum potassium at presentation is >5.2 mmol/L, monitor serum potassium degree each 2 hours with out intravenous potassium supplementation.

Phosphorus and Magnesium Substitute

  • •Phosphorus and magnesium substitute usually are not routinely advisable. There are not any research of the utility of phosphate administration throughout remedy of HHS. Very low phosphorus ranges could restrict adenosine triphosphate (ATP) technology, thus limiting satisfactory diaphragm operate. In sufferers with cardiac dysfunction, respiratory despair, or anemia and serum phosphate <1 mg/dl, add 20 to 30 mmol/L potassium phosphate to intravenous fluids.
  • •Monitor serum glucose hourly and serum electrolytes, BUN, and creatinine each 2 to 4 hours till decision of HHS.

Transition to Subcutaneous Insulin

Normalization of serum osmolality and psychological standing signifies decision of HHS.

At this level, a transition to subcutaneous insulin needs to be carried out. Overlap the initiation of subcutaneous intermediate- or long-acting insulin and discontinuation of intravenous insulin by 2 to 4 hours to make sure satisfactory insulin ranges and stop rebound hyperglycemia.

In sufferers with a recognized historical past of diabetes, their residence insulin routine could also be initiated if satisfactory previous to presentation.

In sufferers with poorly managed diabetes, the subcutaneous insulin dose will be decided based mostly on their steady insulin drip requirement.

Insulin-naive sufferers could also be began on basal-bolus insulin remedy both by calculation of complete each day dose of 0.5 to 0.8 items/kg (break up as half-basal and half-bolus; administer one-third complete bolus for every meal) or by their particular person steady insulin drip necessities.

Additional subcutaneous insulin dose titration is predicated on subsequent blood glucoses. Decision of glucotoxicity and inciting situation(s) will lower insulin necessities. The underlying an infection/inflammatory situation or precipitating occasion should be adequately handled.

Continual Remedy

Most sufferers will want insulin at discharge, at the least brief time period.

Sufferers whose diabetes was beforehand nicely managed on oral brokers could resume oral remedy after blood glucose stabilization by insulin.


Most sufferers require administration in an emergency care setting, such because the intensive care unit or in a step-up facility.

Pearls & Issues

  • •When sufferers with ESRD expertise growth of HHS, particular administration concerns are wanted. Aggressive fluid resuscitation is pointless in anuric ESRD sufferers, as a result of most sufferers can not produce the osmotic diuresis related to regular kidney operate. Be aware that urinary potassium and phosphorus losses is not going to happen, thereby limiting the necessity for supplementation. Decrease steady insulin infusion charges are required in ESRD sufferers due to decreased insulin clearance. Hemodialysis is often delayed till serum glucoses are corrected. Precipitous decreases in serum glucose from insulin administration and hemodialysis could end in speedy shifts in tonicity, predisposing cerebral edema.
  • •Schooling of the affected person, household, and caregivers at continual care services relating to optimum glycemic management, limiting modifiable threat components for HHS, and prevention of dehydration is paramount.

Advised Readings

  • French E.Ok., et al.: Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: overview of acute decompensated diabetes in grownup sufferers. BMJ 2019; 365: pp. I1114.
  • Kitabchi A.E., et al.: Hyperglycemic crises in grownup sufferers with diabetes. Diabetes Care 2009; 32: pp. 1335-1343.
  • Muneer M., Akbar I.: Acute metabolic emergencies in diabetes: DKA, HHS and EDKA. In Crusio W.E., et al. (eds): editors: advances in experimental medication and biology. 2020. Springer, New York pp. 1-30.
  • Schaapveld-Davis C.M., et al.: Finish-stage renal illness will increase charges of opposed glucose occasions when treating diabetes ketoacidosis or hyperosmolar state. Clin Diabetes 2017; 35 (4): pp. 202-208.