Hyperosmolar hyperglycemic state

Background

• Prototypical patient is elderly with uncontrolled type II DM without adequate access to H2O
• Occurs due to 3 factors:
  • Insulin resistance or deficiency
  • Increased hepatic gluconeogenesis and glycogenolysis
  • Osmotic diuresis and dehydration followed by impaired renal excretion of glucose
    • May result in TBW losses of 8-12L
• Ketosis usually absent (may be mild)
• Cerebral edema is uncommon complication (case reports)
• Estimated mortality 10-20%, usually due to underlying precipitant
  • In contrast to DKA, in which mortality is 1-5%
  • Incidence of HHS < 1% of hospital admissions of patients with diabetes

Precipitants

• Pneumonia (Main)
• Urinary tract infection
• Medication non-adherence
• Cocaine intoxication
• Meds: Beta-blockers, diuretics
• GI bleed
• Pancreatitis
• Heat related emergencies
• Acute coronary syndrome
• Stroke

Clinical Features

• Dehydration
  • Hypotension
• Seizure (15% of patients)
• Altered mental status
• Lethargy/coma

Differential Diagnosis

Hyperglycemia

Diabetic Emergencies

• Diabetic ketoacidosis (DKA)
• Diabetic ketoacidosis (peds)
• Hyperosmolar hyperglycemic state (HHS)
• Nonketotic hyperglycemia
• Euglycemic DKA (SGLT-2 inhibitors, pregnancy, fasting)

Diabetes Mellitus (New or Known)

• Type 1 diabetes mellitus (new-onset or uncontrolled)
• Type 2 diabetes mellitus (new-onset or uncontrolled)
• Medication noncompliance or insulin pump malfunction
• Gestational diabetes
• Latent autoimmune diabetes of adults (LADA)

Medication/Drug-Induced

• Corticosteroids (most common drug-induced cause)
• Thiazide diuretics
• Atypical antipsychotics (olanzapine, clozapine, quetiapine)
• Beta-blockers (especially non-selective)
• Phenytoin
• Tacrolimus, cyclosporine (transplant patients)
• Protease inhibitors (HIV antiretrovirals)
• Catecholamines (epinephrine, norepinephrine infusions)
• SGLT-2 inhibitors (paradoxical DKA with euglycemia)
• Total parenteral nutrition (TPN)
• Dextrose-containing IV fluids (iatrogenic)
• Niacin
• Pentamidine (initially hyperglycemia, then hypoglycemia from beta-cell destruction)

Physiologic Stress Response

• Sepsis / critical illness (stress hyperglycemia — very common in the ED)
• Trauma / major surgery / burns
• Acute coronary syndrome / myocardial infarction
• Stroke (especially hemorrhagic)
• Pancreatitis (both a cause and consequence)
• Shock (any etiology)
• Pain (catecholamine surge)
• Seizure (postictal)
• Physiologic stress alone rarely causes glucose >200 mg/dL in non-diabetics; glucose >200 in a "stress response" should prompt evaluation for undiagnosed diabetes or prediabetes

Endocrine

• Cushing syndrome / Cushing disease (cortisol excess)
• Pheochromocytoma (catecholamine excess)
• Hyperthyroidism / thyroid storm
• Acromegaly (growth hormone excess)
• Glucagonoma (rare)
• Somatostatinoma (rare)

Pancreatic

• Pancreatitis (acute or chronic — destruction of islet cells)
• Pancreatic malignancy (adenocarcinoma, neuroendocrine tumors)
• Post-pancreatectomy
• Cystic fibrosis-related diabetes
• Hemochromatosis (iron deposition in pancreas — "bronze diabetes")

Toxic/Overdose

• Iron toxicity (hepatic injury → impaired glucose regulation)
• Salicylate toxicity (can cause both hyper- and hypoglycemia)
• Sympathomimetic toxicity (cocaine, methamphetamine)
• Calcium channel blocker toxicity (impairs insulin secretion)
• Carbon monoxide toxicity (stress response)

Other

• Renal failure (chronic kidney disease, acute kidney injury — impaired insulin clearance AND insulin resistance)
• Cirrhosis / hepatic failure (impaired glycogenolysis regulation)
• Pregnancy (gestational diabetes, steroid administration for fetal lung maturity)
• Parenteral nutrition (TPN, dextrose-containing fluids)
• Post-transplant diabetes (immunosuppressants)

Complications of Diabetes (Not Causes of Hyperglycemia)

These are associated conditions that may be present alongside hyperglycemia but do not themselves cause elevated glucose:

• Diabetic foot infection
• Diabetic peripheral neuropathy
• Cerebral edema in DKA
• Diabetic retinopathy
• Diabetic nephropathy

Evaluation

Work Up

• Chemistry
• Serum osm
• Lactate
• Serum ketones
• CBC
• Also consider:
  • Blood cultures
  • Urinalysis/Urine culture
  • LFTs
  • Lipase
  • Troponin
  • CXR
  • ECG
  • Head CT

Diagnosis

• Glucose >600
• Osm >320
• Bicarb >15
• pH >7.3
• Serum ketones negative or mildly positive
• Neurologic abnormalities frequently present (coma in 25-50% of cases)

Management

1. Fluid replacement
   • Average fluid deficit is 8-12L
     • 50% should be replaced over the initial 12hr
     • May have to replace slower if patient has cardiac/renal impairment
     • Aggressiveness of fluid replacement must be weighed against the risk of cerebral edema, which increases with younger age
2. Hypokalemia
   • Must treat aggressively
   • Once adequate urinary output has been established K+ replacement should begin
3. Hyperglycemia
   • Do not start insulin until K > 3.3 and adequate urinary output has been established
4. Hypomagnesemia
   • Repletion will help correct hypokalemia
5. Hypophosphatemia
   • Routine correction unnecessary unless phos <1.0

Disposition

• Most patients require ICU admission

See Also

• Diabetes mellitus (main)
• Diabetic ketoacidosis
• Hypoglycemia