Can administering 300 units (u) of intravenous (IV) insulin as a direct IV push cause a severe insulin overdose and potentially life-threatening hypoglycemia if left untreated?

Insulin Overdose: IV Push of 300 Units

Yes, 300 units of IV insulin given as a direct IV push would cause severe hypoglycemia and death if left untreated. This dose represents a massive overdose that would rapidly deplete blood glucose and lead to life-threatening consequences without immediate intervention.

Pathophysiology of Insulin Overdose

Insulin is a potent hormone that facilitates glucose uptake into cells. When administered in excessive amounts:

• It causes rapid and severe hypoglycemia by dramatically increasing glucose uptake into cells
• The FDA label for insulin specifically warns that "severe hypoglycemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or death" 1
• IV administration has a particularly rapid onset of action compared to other routes, increasing the danger 1

Clinical Manifestations of Severe Insulin Overdose

The progression of symptoms would likely follow this pattern:

1. Initial symptoms (minutes after injection):

   • Tremors, sweating, light-headedness, irritability, confusion
   • Drowsiness progressing rapidly to altered mental status

2. Severe manifestations (if untreated):

   • Seizures
   • Loss of consciousness
   • Death from neurological damage and other complications

Evidence Supporting Lethality

The FDA label clearly states that "excess insulin may cause hypoglycemia and hypokalemia, particularly after intravenous administration" 1. This risk is substantially higher with direct IV push compared to subcutaneous administration because:

• IV insulin bypasses absorption barriers and enters circulation immediately
• A study examining insulin overdoses found a significant relationship between insulin dose and required treatment time, with larger doses requiring more aggressive and prolonged intervention 2
• The study concluded that "prolonged, aggressive IV glucose infusion and serial monitoring of serum glucose levels is required in insulin overdoses" 2

Quantifying the Risk

300 units represents an extreme overdose:

• Standard insulin boluses for hyperglycemia typically range from 5-15 units
• Even high-dose insulin therapy protocols for beta-blocker overdose use only 1 U/kg as a bolus (typically 70-100 units for an adult) 3
• The American Heart Association guidelines note that high-dose insulin therapy requires careful glucose monitoring and supplementation 3

Treatment Requirements for Survival

Without treatment, death would be virtually certain. Survival would require:

1. Immediate glucose administration:

   • IV dextrose (D50W or D10W) in large quantities
   • Continuous glucose infusion for extended periods

2. Close monitoring:

   • Blood glucose checks every 15-30 minutes initially
   • Continuous cardiac monitoring for arrhythmias related to hypokalemia

3. Extended observation:

   • One study found that the required treatment time in hours could be estimated by: 10.5 + (0.028 × insulin dose in units) 2
   • For 300 units, this suggests approximately 19 hours of IV glucose treatment

Complications Beyond Hypoglycemia

Even with treatment, additional life-threatening complications may occur:

• Hypokalemia: Insulin drives potassium into cells, potentially causing cardiac arrhythmias 1
• Cerebral edema: Rapid glucose fluctuations can cause brain swelling
• Hepatic steatosis: Excessive glucose administration during treatment can cause acute fatty liver 4

Conclusion

The evidence clearly demonstrates that 300 units of IV insulin given as a direct push represents a life-threatening overdose that would be fatal without prompt and aggressive treatment. The rapid onset of action with IV administration makes this particularly dangerous compared to other routes of insulin administration.