What is Hyperosmolar Hyperglycemic Non-Ketotic (HHNK) syndrome?

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From the Guidelines

Hyperosmolar non-ketotic syndrome, now referred to as Hyperosmolar Hyperglycemic State (HHS), is a serious diabetic emergency that requires immediate hospitalization for aggressive fluid replacement and insulin therapy, with the goal of restoring circulatory volume, resolving hyperglycemia, and correcting electrolyte imbalances, as outlined in the most recent guidelines 1.

Key Characteristics of HHS

  • Extremely high blood glucose levels (typically >600 mg/dL)
  • Severe dehydration
  • Altered mental status without significant ketoacidosis

Treatment Approach

  • Immediate hospitalization for aggressive fluid replacement, starting with 1-2 liters of normal saline in the first hour, followed by continued IV fluids based on sodium levels and hydration status
  • Insulin therapy should be initiated with an IV insulin infusion at 0.1 units/kg/hour after fluid resuscitation has begun, as recommended in the latest standards of care 1
  • Potassium replacement is often necessary once levels fall below 5.5 mEq/L and urine output is confirmed
  • The underlying cause of HHS must be identified and treated, which commonly includes infections, stroke, medication non-compliance, or undiagnosed diabetes

Monitoring and Outcomes

  • Close monitoring of vital signs, mental status, electrolytes, and glucose levels is essential, with glucose reduction targets of 50-75 mg/dL per hour to prevent cerebral edema
  • HHS carries a mortality rate of 10-20%, significantly higher than diabetic ketoacidosis, primarily due to the advanced age and comorbidities of affected patients, as well as the profound dehydration that occurs with this condition, highlighting the importance of prompt and effective treatment, as emphasized in recent reviews 1

From the Research

Definition and Characteristics

  • Hyperosmolar non-ketotic coma is a life-threatening condition characterized by marked hyperglycemia, hyperosmolarity, and little or no ketosis 2.
  • It is a metabolic emergency usually seen in elderly non-insulin dependent diabetics, with symptoms including severe hyperglycemia, volume depletion, altered consciousness, confusion, and less frequently neurological deficit 3.
  • The condition is associated with a high mortality rate, which has changed little over the past twenty years 4.

Diagnosis and Delayed Diagnosis

  • The diagnosis of hyperosmolar non-ketotic coma can sometimes be delayed or missed, as patients often present with neurological abnormalities resembling a cerebrovascular accident 4.
  • It is essential to consider hyperosmolar diabetic non-ketotic coma in any patient with altered consciousness or neurologic deficit in conjunction with hyperglycemia 3.
  • Routine early measurement of blood glucose can help avoid delays in diagnosis and management of glycaemic emergencies presenting as a constellation of neurological abnormalities 3.

Treatment and Management

  • The treatment of hyperosmolar non-ketotic coma involves aggressive rehydration, insulin therapy, correction of electrolyte abnormalities, and treatment of any underlying illnesses 3.
  • Vigorous correction of dehydration with normal saline is critical, requiring an average of 9 L in 48 hours 2.
  • Insulin should be given as an initial bolus of 0.15 U per kg intravenously, followed by a drip of 0.1 U per kg per hour until the blood glucose level falls to between 250 and 300 mg per dL 2.
  • Identification and treatment of the underlying and precipitating causes are necessary, and physicians should focus on preventing future episodes using patient education and instruction in self-monitoring 2.

Complications and Precipitating Causes

  • The precipitating causes of hyperosmolar non-ketotic coma are numerous, including underlying infections, certain medications, non-compliance, undiagnosed diabetes, substance abuse, and coexisting disease 2.
  • Complications of therapy can include congestive heart failure secondary to excessive fluid administration, hypoglycemia if too much insulin is given, and hypokalemia if potassium is inadequately replaced 5.
  • Vascular occlusions, such as mesenteric artery occlusion, myocardial infarction, low-flow syndrome, and disseminated intravascular coagulopathy, are potential complications of hyperosmolar hyperglycemic state 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hyperosmolar hyperglycemic state.

American family physician, 2005

Research

Hyperosmolar diabetic non-ketotic coma, hyperkalaemia and an unusual near death experience.

European journal of emergency medicine : official journal of the European Society for Emergency Medicine, 2001

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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