Cerebral edema in DKA

Background

• 1% of patients with DKA
• Almost all affected patients are <20yr
• Associated with initial bicarb level; not rate of glucose drop
  • Children presenting with higher blood urea nitrogen levels and more severe acidosis are at higher risk

Pathophysiology

Thought to be due to cerebral hypoperfusion and less likely osmotic shifts with rapid infusion of IVF's

Risk Factors

• Age <5yo
• Severe hyperosmolality
• Failure of Na to rise with therapy
• Severe acidosis
• Previous episodes of DKA
• Late presentation for medical evaluation
• Overaggressive fluid resuscitation is NOT a risk factor

Clinical Features

• Begins 6-12hr after onset of therapy or may begin before initiation of treatment or up to 48h afterward
  • Many appear to be improving from their DKA before deteriorating from cerebral edema
• Premonitory symptoms:
  • Headache
  • Incontinence
  • Seizure
  • Acute Mental Status Change
  • Signs of herniation

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

• Stat head CT (non-contrast)
• Capillary glucose measurement to rule out hypoglycaemia as the cause of altered mental status

Management

• Head of bed at 30 degrees
• Mannitol 0.5-1gm/kg IV bolus over 20 minutes
  • Give a repeat does if there is an inadequate response
  • If 2 doses of mannitol are ineffective, consider 3% saline 10mL/kg over 30min
• Fluid restriction - decrease the IVF infusion rate by 30%
  • Treat noncardiogenic pulmonary edema, if present
• Consult PICU and neurosurgery

Disposition

Admit PICU/ICU

See Also

• Diabetes mellitus (main)
• DKA
• DKA (Peds)