What dose of short-acting insulin (e.g. Humalog (insulin lispro)) is lethal in a person with normal blood glucose levels?

Lethal Dose of Short-Acting Insulin with Normal Blood Sugar

There is no established specific lethal dose of short-acting insulin for a person with normal blood glucose, but doses exceeding 1 unit/kg can be potentially fatal due to severe hypoglycemia when administered without glucose supplementation.

Understanding Insulin Lethality

Short-acting insulins like Humalog (insulin lispro) can cause severe, life-threatening hypoglycemia when administered in excessive doses to individuals with normal blood glucose levels. The mechanism of death is primarily through:

1. Severe hypoglycemia leading to neurological deterioration
2. Cardiac arrhythmias secondary to electrolyte disturbances
3. Brain damage from prolonged hypoglycemia

Risk Factors and Considerations

Several factors influence the lethality of insulin:

• Initial blood glucose level: Starting with normal blood glucose (70-140 mg/dL) provides less buffer before critical hypoglycemia occurs
• Body weight: Insulin sensitivity varies by weight
• Insulin resistance status: People with insulin resistance may tolerate higher doses
• Presence of counter-regulatory hormones: May be impaired in long-standing diabetes
• Timing of intervention: Rapid intervention can prevent mortality

Evidence from Clinical Guidelines

According to Critical Care Medicine guidelines, severe hypoglycemia (<40 mg/dL) is associated with significant mortality risk 1. The guidelines highlight that even mild hypoglycemia (54-70 mg/dL) can be dangerous, with studies showing mortality rates of 52% in some critically ill populations experiencing severe hypoglycemia 1.

The American Diabetes Association recommends immediate administration of 10-20g of dextrose when blood glucose falls below 70 mg/dL in patients receiving insulin therapy 2. This underscores how quickly intervention is needed to prevent fatal outcomes.

Potentially Lethal Dosing

While there is no single defined lethal dose, clinical evidence suggests:

1. High-dose insulin therapy protocols used in beta-blocker and calcium channel blocker poisoning utilize doses of 1-10 units/kg/hour with continuous glucose supplementation 3. Without glucose supplementation, these doses would be rapidly fatal.

2. Typical therapeutic dosing for type 2 diabetes is significantly lower, with most patients requiring <1 unit/kg/day total insulin 1.

3. Risk of mortality increases significantly with any dose causing blood glucose to drop below 40 mg/dL 1.

Critical Thresholds and Monitoring

• Blood glucose <40 mg/dL: Severe hypoglycemia with high mortality risk
• Blood glucose <20 mg/dL: Likely to cause irreversible neurological damage
• Blood glucose <10 mg/dL: Typically incompatible with life

Treatment of Insulin Overdose

If insulin overdose is suspected:

1. Immediately administer 10-20g IV dextrose (D10W or D50W)
2. Monitor blood glucose every 15 minutes until stabilized
3. Establish continuous glucose infusion
4. Consider glucagon 1mg IM if IV access is unavailable

Important Caveats

• Individual responses to insulin vary significantly
• Rapid-acting analogs like insulin lispro have faster onset but shorter duration than regular insulin, potentially allowing faster intervention but causing more rapid hypoglycemia 4
• Concurrent medications (especially beta-blockers) may mask hypoglycemic symptoms and impair counter-regulatory responses
• The presence of exogenous glucose (recent meals) may temporarily offset insulin effects

In summary, while there is no single defined lethal dose, any dose of short-acting insulin exceeding typical therapeutic ranges (>1 unit/kg) administered to a person with normal blood glucose without glucose supplementation has the potential to be fatal through severe hypoglycemia.