What is the appropriate management of symptomatic hypoglycemia, including oral glucose, intravenous dextrose, intramuscular glucagon, and when should mannitol be administered for cerebral edema or refractory intracranial hypertension?

Management of Symptomatic Hypoglycemia

Immediate Treatment Based on Patient Consciousness

For conscious patients who can swallow, administer 15-20 grams of oral glucose immediately, preferably as pure glucose tablets, which provide the most rapid and predictable glycemic response. 1, 2 For unconscious patients or those unable to protect their airway, give intravenous dextrose if IV access is available, or glucagon 1 mg intramuscularly/subcutaneously/intranasally if IV access is unavailable. 3

Conscious Patient Protocol

• Give 15-20 grams of oral glucose as the first-line treatment for blood glucose ≤70 mg/dL (3.9 mmol/L). 1, 2
• Pure glucose tablets are superior to dietary sugars, producing faster symptom resolution at 15 minutes (glucose tablets show 88.8% resolution versus dietary alternatives). 4
• Instruct the patient to chew and swallow the tablets—do not use buccal or sublingual routes, as swallowed glucose yields higher plasma concentrations at 20 minutes. 2
• Recheck blood glucose at 15 minutes; if still <70 mg/dL, repeat the 15-20 gram dose. 1, 5
• Expect initial response within 10-20 minutes, with blood glucose rising approximately 40-60 mg/dL over 30-45 minutes depending on dose. 2
• Once blood glucose normalizes, provide a meal or snack to prevent recurrence by restoring liver glycogen. 3

Alternative Carbohydrate Sources (When Glucose Tablets Unavailable)

If glucose tablets are not accessible, use any of these containing 15-20 grams of simple carbohydrate: 1, 5

• 1 tablespoon table sugar or honey
• 6-8 oz orange juice or regular soda
• 15-25 jelly beans, gummy bears, or Skittles
• 6-8 Mentos or sugar cubes

Important caveat: Dietary sugars produce slower and less predictable responses than pure glucose, with lower symptom resolution rates at 15 minutes (risk ratio 0.89). 4 Avoid adding fat to carbohydrate treatment, as it retards the acute glycemic response. 2

Unconscious or Severely Impaired Patient Protocol

Activate emergency medical services immediately for any patient with severe hypoglycemia (blood glucose <54 mg/dL with altered consciousness, seizures, or inability to swallow). 3

Never attempt oral administration in unconscious patients—this risks fatal aspiration, even via buccal or sublingual routes. 3, 2

If IV Access Available:

• Administer intravenous dextrose as the preferred parenteral treatment. 3
• Consider D10 (10% dextrose) over D50 (50% dextrose) when possible—D10 achieves 99.2% resolution of hypoglycemia with fewer adverse events (0% versus 4.2% with D50) and lower post-treatment hyperglycemia (6.2 mmol/L versus 8.5 mmol/L). 6
• Recheck blood glucose after 15 minutes and administer additional doses if no response. 3

If No IV Access:

• Give glucagon 1 mg intramuscularly, subcutaneously, or intranasally immediately. 3
• For children, dose is 30 mcg/kg subcutaneously to a maximum of 1 mg. 3
• Once the patient awakens and can safely swallow, provide oral carbohydrates immediately to prevent recurrence. 3

Post-Treatment Management

• Any severe hypoglycemic episode mandates complete reevaluation of the diabetes management regimen. 1, 3
• Patients with hypoglycemia unawareness or clinically significant hypoglycemia (blood glucose <54 mg/dL) should raise glycemic targets for several weeks to partially reverse unawareness and reduce future episode risk. 1, 3
• Ongoing cognitive assessment is necessary with increased vigilance for hypoglycemia if declining cognition is detected. 1

Critical Pitfalls to Avoid

• Do not delay treatment in unconscious patients—untreated hypoglycemia can cause seizures, status epilepticus, permanent brain injury, and death. 3
• Do not use buccal or sublingual glucose in adults who can swallow—these routes produce inferior plasma glucose concentrations compared to swallowed glucose. 2
• Do not add protein to carbohydrate treatment—it does not prevent subsequent hypoglycemia and may increase insulin response in type 2 diabetes. 2
• Do not "overshoot" blood glucose goals by administering excessive sugar, as repeated hyperglycemic episodes may be as harmful as recurrent hypoglycemia. 1

When to Give Mannitol

Mannitol is NOT indicated for routine hypoglycemia management. The evidence provided does not support mannitol use for hypoglycemia-related complications. 7

Mannitol (or glycerol) is reserved for acute intracranial hypertension in severe encephalopathies such as Reye syndrome, administered at 0.5-1.0 gm/kg of 20% mannitol no faster than appropriate osmolar rates. 7 This is a separate clinical entity from hypoglycemia management and should only be considered if hypoglycemia has resulted in cerebral edema with documented elevated intracranial pressure—an exceedingly rare complication requiring neurocritical care consultation.