Is brain damage or death more likely with an insulin overdose?

Insulin Overdose: Brain Damage vs. Death Risk

Severe hypoglycemia from insulin overdose can lead to death within minutes to hours if untreated, with brain damage occurring rapidly due to the brain's inability to meet its energy needs, making both outcomes serious risks. 1

Pathophysiology and Progression

Insulin overdose causes severe hypoglycemia through several mechanisms:

• Excessive insulin drives glucose from bloodstream into cells
• Brain tissue cannot meet energy requirements during severe hypoglycemia
• Neuronal damage begins rapidly when blood glucose falls below critical levels

Timeline of Damage

1. Initial hypoglycemia (blood glucose <70 mg/dL) - cognitive impairment begins
2. Severe hypoglycemia (<54 mg/dL) - risk of seizures increases
3. Prolonged severe hypoglycemia - permanent brain damage occurs
4. Untreated severe hypoglycemia - death from respiratory paralysis, cardiac arrhythmia, or cerebral failure

Evidence on Outcomes

The evidence shows that both brain damage and death are significant risks with insulin overdose:

• Severe hypoglycemia can cause characteristic MRI changes including bilateral cortical involvement, hippocampus damage, basal ganglia lesions, white matter changes, and cerebral edema 1
• Hypoglycemia is independently associated with increased mortality risk (odds ratio 3.233,95% CI [2.251,4.644]) in critically ill patients 1
• Even mild-moderate hypoglycemia (blood glucose 54-63 mg/dL) increases mortality risk 2
• In a systematic review of 45 insulin overdose cases, one patient developed lasting hypoglycemic encephalopathy and one died 3

Risk Factors That Increase Mortality

Certain factors increase the risk of fatal outcomes from insulin overdose:

• Advanced age (≥75 years)
• Multiple comorbidities
• Cardiovascular disease
• Renal insufficiency
• Septic shock
• Mechanical ventilation
• Higher illness severity scores
• Recurrent hypoglycemia leading to hypoglycemia unawareness 1

Brain Damage Considerations

Brain damage from insulin overdose has several characteristics:

• Neuronal depletion or necrosis was found in 29.1% of autopsy cases following fatal insulin overdose 4
• Diabetes increases vulnerability to neuronal damage during severe hypoglycemia, particularly in the cortex 5
• Seizure activity during hypoglycemia strongly correlates with extent of neuronal damage 5
• Brain damage can be permanent and irreversible if hypoglycemia is prolonged 1

Treatment Approach

Immediate treatment is critical to prevent both death and brain damage:

1. For conscious patients: Administer 15-20g of fast-acting carbohydrate orally 1

2. For unconscious patients or severe cases:

   • Administer 25mL of 50% dextrose via slow IV push 1
   • Consider glucagon 3-10 mg IV/IM followed by infusion of 3-5 mg/h 2
   • High-dose insulin overdose may require prolonged glucose infusion (median 94 hours in severe cases) 3

3. Monitor for complications:

   • Electrolyte disturbances, particularly hypokalemia (49% of cases) 3
   • Cardiac toxicity including arrhythmias (9% of cases) 3
   • Hepatic disturbances (7% of cases) 3

Common Pitfalls and Caveats

• Delayed recognition: Symptoms may be nonspecific or attributed to other conditions
• Inadequate monitoring: Blood glucose should be checked every 15 minutes initially during treatment 2
• Premature discontinuation of treatment: IV glucose may be needed for up to a week in large overdoses 3
• Failure to recognize risk factors: Patients with renal or hepatic impairment are at higher risk 6
• Overaggressive potassium repletion: Can lead to asystole; target potassium levels of 2.5-2.8 mEq/L 2

Conclusion

While both brain damage and death are serious risks with insulin overdose, the evidence suggests that with prompt recognition and appropriate treatment, most patients can recover without permanent neurological sequelae. However, the window for effective intervention is narrow, and delayed treatment significantly increases the risk of both permanent brain damage and death.