Is high dose insulin (HDI) euglycemia therapy effective for treating aluminium phosphide poisoning?

High-Dose Insulin Euglycemia Therapy for Aluminium Phosphide Poisoning

High-dose insulin euglycemia therapy appears to be highly effective and should be strongly considered as a primary treatment for aluminum phosphide poisoning, based on recent randomized controlled trial evidence showing dramatic mortality reduction from 96% to 65%. 1

Evidence for Insulin-Euglycemia Therapy in Aluminum Phosphide Poisoning

Mortality Benefit

• A 2023 randomized clinical trial demonstrated that insulin-euglycemia therapy reduced mortality from 96.3% in the control group (receiving only norepinephrine and supportive care) to 64.8% in the intervention group (P <0.001). 1

• This represents a substantial survival benefit in a poisoning with notoriously high mortality rates and no established antidote. 1

Hemodynamic Improvements

• Insulin-euglycemia therapy significantly improved blood pressure parameters at 6 hours post-admission: median systolic BP was 80 mmHg versus 20 mmHg in controls, diastolic BP was 55 mmHg versus 10 mmHg, and mean arterial pressure was 65 mmHg versus 13 mmHg (P <0.001). 1

• Patients receiving insulin-euglycemia required significantly lower doses of vasopressors (median 7 mg versus 26 mg norepinephrine; P = 0.006). 1

• Fewer patients required intubation (61.1% versus 81.5% in controls; P = 0.019). 1

Metabolic Improvements

• The therapy significantly improved bicarbonate and lactate concentrations, suggesting correction of metabolic acidosis. 1

• An earlier 2020 pilot study using glucose-insulin-potassium (GIK) infusion similarly showed reduced mortality (46.7% versus 73.3%; P = 0.03) and improved hemodynamic parameters. 2

Recommended Dosing Protocol

Standard High-Dose Insulin Regimen

• Initial bolus of 1 U/kg regular insulin followed by continuous infusion at 1 U/kg/hr. 3

• Concurrent dextrose infusion (typically D10 at 60 mL/hour providing 6 grams carbohydrates/hour) to maintain euglycemia. 3

• Close monitoring of serum glucose and potassium levels is mandatory. 3

Monitoring Requirements

• Frequent blood glucose monitoring (every 30-60 minutes initially) to prevent hypoglycemia. 3

• Serial potassium measurements with supplementation as needed to prevent hypokalemia. 3

• Continuous hemodynamic monitoring including blood pressure and cardiac function assessment. 1

Clinical Algorithm for Aluminum Phosphide Poisoning

Initial Assessment and Stabilization

• Evaluate for signs of severe toxicity: hypotension, bradycardia, metabolic acidosis, and cardiac dysfunction. 1

• Initiate standard resuscitative measures including airway management and IV access. 1

Primary Treatment Strategy

• Start high-dose insulin euglycemia therapy early as primary intervention rather than relying solely on vasopressor support. 1

• The 2023 trial demonstrated that vasopressor-only therapy was associated with very poor outcomes (96% mortality). 1

• Add vasopressors (norepinephrine) as needed for blood pressure support, but insulin therapy should be the cornerstone. 1

Adjunctive Therapies to Consider

• N-acetylcysteine (NAC) may provide additional mortality benefit: a 2023 meta-analysis showed reduced mortality with IV NAC (pooled risk ratio 0.5; 95% CI 0.32-0.77). 4

• Combined therapy with trimetazidine, N-acetylcysteine, vitamin C, and hyperinsulinemia-euglycemia showed cardioprotective and hepatoprotective effects in animal models. 5

• Continuous renal replacement therapy (CRRT) has been reported as a novel therapy in severe cases with successful outcomes. 6

Critical Pitfalls to Avoid

Relying Solely on Vasopressors

• The most important pitfall is treating aluminum phosphide poisoning with vasopressors alone without insulin therapy. The 2023 RCT showed this approach resulted in 96% mortality. 1

• Vasopressors should be used as adjunctive therapy to insulin-euglycemia, not as monotherapy. 1

Delayed Initiation of Insulin Therapy

• Early initiation of insulin-euglycemia therapy appears critical for optimal outcomes. 1

• Do not wait for refractory shock to develop before starting insulin therapy. 1

Inadequate Glucose and Electrolyte Monitoring

• Hyperglycemia can occur but is manageable with appropriate monitoring. 2

• Hypoglycemia and hypokalemia are serious complications that require vigilant monitoring and correction. 3

Mechanistic Rationale

• While the exact mechanism of aluminum phosphide toxicity remains incompletely defined, the dramatic hemodynamic improvement with insulin therapy suggests it addresses the core pathophysiology of cardiovascular collapse. 1, 5

• Insulin improves cardiac contractility and facilitates myocardial carbohydrate utilization, similar to its mechanism in calcium channel blocker and beta-blocker poisoning. 3

• The therapy appears to correct both the cardiogenic and vasodilatory components of shock in aluminum phosphide poisoning. 1

Important Distinction from Other Poisonings

• The evidence base for insulin-euglycemia therapy in aluminum phosphide poisoning comes from direct randomized controlled trials in this specific poisoning, not extrapolation from calcium channel blocker or beta-blocker guidelines. 1, 2

• This represents Level 1 evidence specifically for aluminum phosphide, making the recommendation particularly strong. 1