Hospital Medicine

Hyperosmolar coma

Jump to Section

Hyperosmolar coma

I. What every physician needs to know.

Hyperosmolar coma is also referred to as hyperosmolar hyperglycemic syndrome (HHS) or nonketotic hyperglycemic syndrome. It is characterized by severe hyperglycemia, hyperosmolality, and dehydration in the absence of significant ketoacidosis. Hyperosmolar coma and diabetic ketoacidosis (DKA) are hyperglycemic crises. They are the two most serious complications of diabetes and result from a combination of absolute or relative insulin deficiency in the setting of increased counter-regulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). Hyperglycemic crises are precipitated by patient stressors which either limit access to appropriate diabetic medications and/or fluid intake, or precipitate the disease by increasing fluid requirements and counter regulatory hormones with subsequent increase in gluconeogenesis and impaired utilization of glucose in the periphery. Although hyperosmolar coma is much less common than DKA, it carries a 10-fold higher risk of death. Patients with hyperosmolar coma are typically over the age of 65, with type 2 diabetes, and other comorbid conditions. They typically present with profound dehydration and increased osmolality as a result of persistent glycosuria that causes osmotic diuresis. Hyperosmolar coma is nearly always associated with some neurologic impairment. The exception to this is seen in patients with severe renal disease that lack of osmotic diuresis.

II. Diagnostic Confirmation: Are you sure your patient has hyperosmolar coma?

The American Diabetes Association (ADA) has defined hyperosmolar coma as:

  • Plasma glucose greater than 600 mg/dl

  • Arterial pH >7.3

  • Serum bicarbonate greater than 18 mEq/L

  • Serum osmolality greater than 320 mOsm/kg

  • Small or absent urine

  • Small or absent serum ketones

Despite being defined as separate entities, almost 1/3 of patients will have an overlap syndrome with diabetic ketoacidosis (DKA) with some laboratory evidence of acidosis.

A. History Part I: Pattern Recognition:

Hyperosmolar coma usually evolves over several days to weeks in comparison to the acute presentation typically seen with DKA. The classical clinical picture includes symptoms of hyperglycemia (polyuria, polydipsia, and weight loss), dehydration, weakness, and mental status changes. The neurologic manifestations may vary from lethargy to focal neurologic deficits, seizures, or coma. However, patients with underlying severe renal disease may present without mental status changes because osmolality increases are typically small in the absence of osmotic diuresis. While nausea, vomiting, and abdominal pain are present in most patients with DKA, they are uncommon in hyperosmolar coma. Although infection is the most common precipitating factor for hyperosmolar coma, patients tend to be normothermic or even hypothermic. This is primarily because of peripheral vasodilation. Severe and persistent hypothermia is a poor prognostic indicator.

The prototypical patient with hyperosmolar coma is an elderly diabetic who presents with mental status changes ranging from confusion to coma. Patients are typically over the age of 65 with type 2 diabetes and multiple other comorbidities. Most will present with another acute illness (such as infection, stroke, myocardial infarction, etc.) that has precipitated the hyperglycemic crisis. Severe hyperglycemia with admitting glucose levels in excess of 1000 mg/dL is typical. Most patients with hyperosmolar coma have an admission pH >7.30 and bicarbonate level >18. However, mild ketonemia may be present as more than one third of patients present with significant overlap between hyperosmolar coma and DKA.

B. History Part 2: Prevalence:

Hyperosmolar coma most commonly develops in individuals older than 65 years. Although hyperosmolar coma is much less common than DKA, its morbidity is 10-fold higher. The rate of hospital admissions for HHS accounts for less than 1% of all diabetic-related admissions. Hyperglycemic crises are normally precipitated by inadequate insulin therapy or medication non-compliance, acute infection, myocardial infarction, new renal insufficiency, stroke, burns, pulmonary embolism, or small bowel obstructions. Additionally, medications that affect glucose metabolism like beta blockers, steroids, antipsychotic, and diuretics can precipitate hyperglycemic crises. Pregnancy is an insulin-resistant state which means that gestational diabetes or pregnancy in established diabetics may also precipitate a hyperglycaemic crisis.

C. History Part 3: Competing diagnoses that can mimic hyperosmolar coma.

Hyperosmolar hyperglycemic state (HHS) and diabetic ketoacisosis (DKA) represent two extremes in the spectrum of hyperglycemic crisis. Both HHS and DKA are characterized by relative or absolute insulin deficiency and clinically differ only by severity of dehydration and ketoacidosis. As noted earlier, the two disease states overlap in over 1/3 of the patients. The main differences between these two conditions are that DKA is associated with a significant ketoacidosis due to lipolysis from lack of insulin. Although there is enough insulin present in hyperosmolar coma to prevent lipolysis and ketogenesis, it is not enough to cause adequate glucose utilization. The end result is severe hyperglycemia with serum glucose values frequently exceeding 1000 mg/dL. Additionally, patients with hyperosmolar coma tend to have higher free water deficits than patients with DKA but both sets of patients are typically profoundly dehydrated. Whenever a diagnosis of hyperosmolar coma is being considered, competing diagnoses of infection, stroke, myocardial infarction, and intoxication should be considered.

D. Physical Examination Findings.

Physical exam findings of dehydration including dry mucous membranes, poor skin turgor, sunken eye balls, decreased axillary sweat, tachycardia, hypotension, and shock in severe cases may be present. The physical exam findings related to the mentation are noteworthy. They may include lethargy, stupor or confusion. Additionally, focal neurological deficits or seizures can also be present.

E. What diagnostic tests should be performed?

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Initial diagnostic testing in hyperosmolar coma should include plasma glucose, blood urea nitrogen, serum creatinine, serum osmolality, serum and urine ketones, arterial pH, bicarbonate level, urinalysis, and complete blood count with differential. Electrolytes (in particular sodium, potassium, calcium, magnesium, and phosphate) are also necessary. Identifying the precipitating illness is crucial and patients should therefore have EKG, blood, urine or sputum cultures and chest X-ray performed.

In general, consideration should be made for testing drug and alcohol levels (especially in a patient who appears malnourished or exhibit signs of drug intoxication. Also salicylate levels, TCA levels, cardiac biomarkers, lactate, and serum lipase should be checked. The presence of lateralizing neurologic signs or lack of improvement in level of consciousness should mandate urgent brain imaging such as computed tomographic (CT) scanning. Any other testing should be targeted based on symptoms or findings of the initial work up.

  • Plasma glucose is greater than 600 mg/dL, and typically greater than 1000 mg/dL.

  • Patients with antecedent severe renal disease will not have large elevations in their plasma osmolality since there is no excessive free water loss in the urine.

  • Plasma osmolality is greater than 320 mosm/kg.

  • Serum and urine ketones are typically absent but can be seen in small amounts. The presence of small amounts of serum or urinary ketones does not preclude the diagnosis of hyperosmolar coma.

  • Arterial pH is typically greater than 7.3.

  • Bicarbonate level is typically greater than 18.

  • The sodium can be low, normal, or high. An increased or even normal serum sodium in the presence of hyperglycemia indicates profound degree of free water loss. The serum sodium may be corrected by adding 1.6 mg/dL to the measured serum sodium for each 100 mg/dL of glucose above 100 mg/dL to assess severity of sodium and water deficit.

  • Serum potassium levels are typically normal and may be slightly elevated due to extracellular shift of potassium caused by insulin deficiency and hypertonicity. However, the patient’s total body potassium is usually low and requires careful cardiac monitoring and adequate potassium replacement once treatment is started.

  • Serum phosphate levels, like potassium, are elevated but do not reflect actual body deficits due to extracellular shift.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

No imaging studies are necessary to establish the diagnosis of hyperosmolar coma.

As noted above, patients should have urgent brain imaging such as computed tomographic (CT) scanning in the presence of lateralizing neurologic signs or lack of improvement in level of consciousness despite correction of metabolic derangements. There are multiple reports of patients with hyperglycaemic crises and focal neurologic damage, most commonly due to cerebrovascular accidents (CVA). CVA may be the precipitating factor for development of hyperosmolar coma and the hyperosmolar state may also predispose to thrombotic CVA.

In addition, other imaging may be indicated to diagnose a precipitating illness such as chest X-ray to evaluate for pneumonia, abdominal X-ray to evaluate for bowel obstruction, or CT to evaluate for other possible pathologies.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Patients are typically critically ill and often have concurrent medical issues, so most medical testing that is done is clinically warranted.

III. Default Management.

The goals of treatment include uncovering and managing underlying condition, fluid resuscitation, improving mental status, re-establishing euglycemia, repleting electrolytes and minerals, and avoiding complications. The initial evaluation of patients should focus on airway, breathing, and circulation (ABC) status. Additionally, mental status and volume status should be assessed. The patient should be in a monitored in acute care setting with measurement of serum glucose every hour. Electrolytes should be sent frequently (initially every few hours) and close attention should be paid to cardiopulmonary status during volume resuscitation.

Fluid therapy:

Adequate intravenous access should be established for fluid resuscitation as it is the most important treatment in hyperosmolar coma. Fluid resuscitation should begin immediately with 0.9% NaCl infused intravenously at a rate of 15-20 mL/kg/hr or 1-1.5 L during the first hour. Fluid status should be reassessed hourly with hemodynamic monitoring (blood pressure), urine output, and laboratory values (electrolytes and kidney function). The initial fluid choice in the absence of cardiac compromise is isotonic saline (which is still hypo-osmotic for these patients) to expand intravascular, interstitial, and intracellular volume; and restore renal perfusion.

Subsequent choice for fluid replacement after improvement in hydration status should be guided by corrected serum sodium (add 1.6 mEq to serum sodium for each 100 mg/dL of glucose above 100 mg/dL). Most patients with hyperosmolar coma will have hypernatremia when sodium level is corrected. ADA guidelines recommend that patients with corrected sodium that is normal or elevated be switched to 0.45% NaCl at an infusion rate of 250-500 mL/hr. If the patient has low corrected serum sodium, consider continuing isotonic saline (0.9% NaCl) instead of switching to 0.45% NaCl. Fluid resuscitation should correct estimated volume deficits within the first 24 hours. Elderly patients with cardiac or renal disease may require more tailored fluid management, because routine management can lead to acute pulmonary edema. In addition, lactated ringers fluid and pH balanced solutions (Plasmalyte, Isolyte, Normosol, etc.) should be considered in patients who develop hyperchloremia and continue to require fluid resuscitation.

Insulin therapy:

Blood glucose checks should be obtained hourly and patients with subcutaneous insulin pumps should have them inactivated prior to initiation of treatment. Insulin infusion should be started immediately after initial saline bolus. Continuous intravenous infusion with regular insulin should begin at 0.14 units/kg/hr. The expected rate of decrease in glucose concentration is 50-75 mg/dL/hr. If serum glucose does not decreased by at least 10% after the first hour a bolus of 0.14 units/kg of regular IV insulin should be administered. When serum glucose falls to 300 mg/dL or less the rate of insulin infusion should be decreased to 0.02-0.05 units/kg/hr and 5% dextrose containing fluids should be infused to maintain blood glucose between 250-300 mg/dL until hyperglycemic coma has resolved. This is done because rapid correction of hyperglycemia and hyperosmolality is associated with the development of cerebral edema. When the patient is ready to transition from intravenous to subcutaneous insulin; the intravenous infusion should be continued for 1-2 hours after subcutaneous insulin is administered to ensure adequate plasma insulin levels and avoid relapse into hyperglycemic crisis.

Electrolyte management:

1. Potassium:

Serum potassium can be elevated on initial labs, but most patients are total body potassium depleted. Serum potassium should be monitored every 2 hours during hyperglycemic crisis and EKG should be considered if laboratory assessment is delayed to assess for hyper or hypokalemia. Once potassium levels fall into the normal range, potassium repletion should be started to maintain serum potassium in normal range of 4.0-5.0 mEq/L. This is often accomplished by switching to 0.45% NaCl and adding 20-40 mEq of potassium to each liter. This should only be done when urine output is adequate. Insulin should be held when serum potassium is below 3.3 meq/L as it will drive potassium into the cells and can precipitate hypokalemic symptoms including dangerous arrhythmias and respiratory weakness.

2. Phosphate:

Serum phosphate (like potassium) can be elevated on initial labs despite total body depletion. However, phosphate replacement is not recommended with the exception of patient with severe skeletal muscle weakness or rhabdomyolysis associated with hypophosphatemia. Randomized studies have failed to show any benefit of phosphate replacement and hyperphosphatemia may cause severe hypocalcemia.

A. Immediate management.

The first steps in management are to assess the airway and the hemodynamic status of the patient. Patients that present with altered mentation may require intubation if they are unable to protect their airway. If the patient requires intubation, avoid succinylcholine until hyperkalemia has been ruled out by laboratory tests. Once adequate airway protection has been ensured or airway established the primary concern is to return perfusion with volume resuscitation. As noted above, fluid resuscitation should begin immediately with 0.9% NaCl infused intravenously at a rate of 15-20 mL/kg/hr or 1-1.5 L during the first hour. Next, appropriate diagnostic investigation should be performed to uncover underlying and/or precipitating causes of hyperglycemic crisis. Intravenous insulin infusion should be started at a rate up to 0.14 units/kg/hr. Glucose may fall more than what is predicted from insulin alone because of concomitant fluid repletion. This fall in glucose can be profound in patients with hyperosmolar coma and serum glucose should therefore be monitored hourly once insulin infusion is initiated. Dextrose should be added to the intravenous fluids when the serum glucose reaches 300 mg/dL and the insulin infusion rate decreased to prevent cerebral edema. Mental status should be assessed and urgent brain imaging obtained if there are any lateralizing neurologic signs or lack of improvement in level of consciousness despite correction of metabolic derangements. Thiamine should be considered if the patient has signs of malnutrition and naloxone if there is a suspicion for opiate ingestion. All patients should have continuous monitoring of their oxygenation, blood pressure and telemetry, looking for arrhythmia and signs of either hyper or hypokalemia. If precipitating causes such as infection or myocardial infarction are identified, they should be addressed and treated promptly.

B. Physical Examination Tips to Guide Management.

Initial assessment should include a complete neurologic assessment to look for focal neurologic deficits that would prompt urgent brain imaging. Additionally, gag reflex should be assessed to ensure airway protection if there is any alteration in mental status. Examination should also focus on potential sources of infection that could be precipitating the hyperglycemic crisis. Evaluation of skin for decubitus ulcer or rashes should be included.

Follow up examination should focus on cardiopulmonary status as large volume of fluid is given during volume resuscitation. In addition, close monitoring of the urine output is recommended, as most of these patients will receive potassium repletion.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Monitor the serum glucose hourly. If serum glucose does not decreased by at least 10% after the first hour with insulin infusion a bolus of 0.14 units/kg of regular IV insulin should be administered. When serum glucose falls to 300 mg/dL or less the rate of insulin infusion should be decreased to 0.02-0.05 units/kg/hr and 5% dextrose should be infused to maintain blood glucose between 250-300 mg/dL until hyperglycemic coma has resolved to avoid cerebral edema.

Monitor sodium every 4 hours. Patients with corrected sodium that is normal or elevated should be switched to 0.45% NaCl.

Monitor the potassium at least every 2 hours until it is established in a safe range. If the potassium is less than 3.3 mEq/L, insulin should be held until potassium can be replaced. If the potassium is less than 5.2 mEq/L, add 20-40 mEq of potassium chloride into intravenous fluids to maintain a goal of serum potassium of 4.0-5.0 mEq/L. If the potassium is greater than 5.2 mEq/L, all supplemental potassium should be discontinued. Hyperkalemia with EKG changes should prompt treatment of the hyperkalemia with typical protocols (including calcium carbonate, insulin and bicarbonate which is otherwise generally held in patients with hyperosmolar coma).

Monitor the phosphorus. Treat only if the patient has phosphorus of 1.0 mg/dL or if there are any symptoms of phosphate deficiency (hemolytic anemia, severe skeletal muscle weakness, rhabdomyolysis, or new cardiac dysfunction).

D. Long-term management.

Once the patient has had serum glucose of 250-300 mg/dl for 24 hours and mental status has improved, the patient should be converted to subcutaneous insulin and started on a carbohydrate consistent diet. To prevent recurrence of hyperglycemia during the transition period to subcutaneous insulin, there should be a 2 hour overlap between administration of subcutaneous insulin and discontinuation of intravenous insulin.

The search for a precipitating cause should continue unless one has been identified.

The patient should have extensive education around their disease process and ways to avoid similar situations in the future. The ADA guidelines recommend that education regarding sick day management as described in detail in section VI below.

E. Common Pitfalls and Side-Effects of Management

Identify and treat precipitating causes of hyperglycaemic crises by obtaining thorough history, review of systems, and physical examination. Most are caused by infection or inadequate insulin administration.

Avoid hypokalemia which lead to iatrogenic cardiac arrhythmias. Check potassium before administration of insulin which will cause hypokalemia and hypoglycemia.

Avoid hypoglycemia which can lead to iatrogenic seizures and cerebral edema. Prevention of cerebral edema includes avoidance of excessive hydration and rapid reduction in plasma osmolarity, a gradual decrease in serum glucose, and maintenance of serum glucose between 250-300 mg/dL until the patient’s serum osmolality is normalized and mental status improved. Signs and symptoms of cerebral edema are variable but may include headache, gradual deterioration in level of consciousness, seizures, sphincter incontinence, pupillary changes, papilledema, bradycardia, elevation in blood pressure, and respiratory arrest. Cerebral edema is associated with 20-40% mortality and should be treated aggressively.

Avoid phosphate over-repletion as hyperphosphatemia can lead to hypocalcemia. Replete only in patients with skeletal muscle weakness or rhabdomyolysis.

Overlap intravenous and subcutaneous insulin by 1-2 hours to avoid relapse of hyperglycaemic crises.

IV. Management with Co-Morbidities

A. Renal Insufficiency.

Patients with renal insufficiency and hyperosmolar coma may need to be managed in conjunction with a nephrologist. They typically present with greater sodium disturbances but lesser increase in osmolarity. Fluid resuscitation will be more conservative in this patient population for obvious reasons. Treatment should consist of close monitoring of electrolytes and judicious insulin use.

B. Liver Insufficiency.

No change in standard management.

C. Systolic and Diastolic Heart Failure

Patients with heart failure and hyperosmolar coma are challenging to manage because the heart failure often precludes proper fluid resuscitation. Conservative approach to fluid resuscitation is recommended when hemodynamically stable. Nevertheless, intubation is often unavoidable and patients can be difficult to wean from the ventilator. They require very close monitoring of urine output and cardiopulmonary status.

D. Coronary Artery Disease or Peripheral Vascular Disease

Care must be taken with coronary disease and fluid resuscitation.

E. Diabetes or other Endocrine issues

No change in standard management.

F. Malignancy

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc.).

Opportunistic infections should be included in the differential for precipitating causes of hyperglycaemic crisis in this patient population.

H. Primary Lung Disease (COPD, Asthma, ILD)

Patients with primary lung disease are more susceptible to the effects of electrolyte disturbances on their respiratory drive. Frequent monitoring of phosphorus and magnesium is necessary. Patients with underlying lung disease need close monitoring and often need intubation. Acute respiratory distress syndrome (ARDS) is a known complication of hyperosmolar coma. The etiology is not entirely clear. Low-tidal volume (6 mL/kg) lung protective ventilator strategy should be used to minimize the barotrauma and potential complications of ARDS.

I. Gastrointestinal or Nutrition Issues

Patients often present with hyperosmolar coma after a gastrointestinal illness or a limitation in access to water. Special attention should be given to electrolytes that could have been lost with vomiting or diarrhea.

J. Hematologic or Coagulation Issues

Patients should be monitored for thrombosis and disseminated intravascular coagulation (DIC).

K. Dementia or Psychiatric Illness/Treatment

Patients with mental illness and dementia are challenging to manage, as improvement in mental status with therapy will be less obvious in this population. Additionally, mental status changes may take longer to clear and paradoxically, keeping these patients in the ICU can contribute to the worsened mental state.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

In the first 24 hours of treatment, goal glucose is 250-300 mg/dL, not euglycemia. If the sugar level is under 300 mg/dL, dextrose should be added to the fluids and insulin should be dropped. Additionally, electrolytes should be monitored closely and potassium should be placed replaced as needed to avoid hypokalemia and potentially life threatening arrhythmias.

B. Anticipated Length of Stay.

Length of stay is more variable than seen with DKA because it tends to occur in older patients and tends to be associated with comorbid conditions. Most patients can be transitioned out of the ICU at 24-48 hours, but usually require a few more days to establish normal glycemic goals and to treat the precipitating condition.

C. When is the Patient Ready for Discharge.

The patient is ready for discharge when they are euglycemic on an outpatient diabetic regimen, have regained normal mental functioning, and tolerate diet. In addition, the precipitating illness is controlled.

D. Arranging for Clinic Follow-up.

Patients who have been admitted for hyperosmolar coma should be seen by the physician who will manages their diabetes within a week of discharge. ADA recommends education about sick day management. Also, through medication reconciliation should be performed with the assessment of patients’ ability to take their diabetic medications. Many of these patients will have their anti-hypertensive medications held during their hypovolemic episode in the hospital and will need monitoring of their blood pressure and assessment of their glucose management when back on their home diet.

1. When should clinic follow up be arranged and with whom.

Patients should be seen by their primary care doctor within a week of discharge. Diabetic teaching should be scheduled if it was not provided before discharge.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

A hemoglobin A1c is not typically helpful in the management of hyperosmolar coma but can give some indication of how poorly the patient was doing prior to admission. This information can be useful for the managing physician.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

Patient should be advised to keep a log of their home blood glucose values and their ability to properly use their meter should be checked against a blood glucose value at the office.

E. Placement Considerations.

None.

F. Prognosis and Patient Counseling.

Hyperosmolar coma has an approximately 10% mortality rate.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

None currently.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

The ADA guidelines recommend education regarding sick day management to prevent recurrence of hyperglycemic crises. Education for sick day management should include the following:

  • Early contact with the health care provider.

  • Emphasizing the importance of insulin during an illness and reasons never to discontinue without contacting the health care team.

  • Review of blood glucose goals and to use of supplemental short- or rapid-acting insulin.

  • Having medications available to manage fever and treat an infection.

  • Initiation of an easily digestible liquid diet containing carbohydrates and salt when nauseated.

  • Education of family members on sick day management and record keeping including assessing and documenting temperature, blood glucose, and urine/blood ketone testing; insulin administration; oral intake; and weight.

VII. What’s the Evidence?

Van Ness-Otunnu, R, Hack, JB. "Hyperglycemic crisis". J Emerg Med.. vol. 45. 2013. pp. 797-805.

Pasquel, FJ, Umpierrez, GE. "Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment". Diabetes Care.. vol. 37. 2014. pp. 3124-3131.

Kitabchi, AE, Umpierrez, GE, Miles, JM, Fisher, JN. "Hyperglycemic crises in adult patients with diabetes". Diabetes Care.. vol. 32. 2009. pp. 1335-1343.

Gosmanov, AR, Gosmanova, EO, Kitabchi, AE, De Groot, LJ, Beck-Peccoz, P, Chrousos, G. "Hyperglycemic crises: diabetic ketoacisosis (DKA), and hyperglycemic hyperosmolar state (HHS)". Endotext [Internet]. MDText.com, Inc.. 2000–2015 May 19.

You must be a registered member of Renal and Urology News to post a comment.

Sign Up for Free e-newsletters