What is the mortality rate and mechanism of action of aluminum (Al) phosphide poisoning?

Aluminum Phosphide Poisoning: Mortality and Mechanism of Action

Mortality Rate

Aluminum phosphide poisoning carries an extremely high mortality rate of 38.5% to 70%, with some reports documenting mortality as high as 91% in severe cases. 1, 2, 3 Ingestion of as little as 150-500 mg (approximately one tablet containing 3 grams of aluminum phosphide) can be fatal, and all exposures require ICU-level care. 4, 1

Key Mortality Predictors

• Hemodynamic instability with severe hypotension and shock unresponsive to conventional treatment is the most common cause of death 1, 3
• Elevated blood lactate levels during 8-16 hours post-ingestion significantly correlate with mortality 2
• Metabolic acidosis with low pH and bicarbonate levels distinguishes non-survivors from survivors 1, 2
• Multi-organ failure including hepatic injury (markedly elevated AST/ALT), rhabdomyolysis (elevated CPK), and acute renal failure predict poor outcomes 1

Mechanism of Action

Aluminum phosphide releases phosphine gas (PH₃) upon contact with stomach acid and moisture, which causes cellular toxicity primarily through mitochondrial dysfunction and oxidative stress. 5, 3

Cellular-Level Toxicity

• Mitochondrial damage is the primary site of toxicity, with phosphine inhibiting cytochrome c oxidase in the electron transport chain 5
• ATP depletion results from impaired oxidative phosphorylation, leading to metabolic shutdown and multi-organ dysfunction 5
• Free radical generation occurs due to impaired electron flow in mitochondria, causing reactive oxygen species-induced damage 5
• Rather than targeting a single organ, aluminum phosphide works at the cellular level causing widespread damage to all organ systems simultaneously 5

Clinical Manifestations by System

Cardiovascular toxicity:

• Circulatory failure with severe refractory hypotension is the hallmark feature 1, 3
• Highly variable ECG abnormalities including ST-segment elevation, T-wave inversions, and atrial fibrillation with fast ventricular response 1, 6
• Direct cardiotoxicity with elevated cardiac troponin mimicking acute myocardial infarction 6

Metabolic derangements:

• Severe metabolic acidosis develops rapidly and requires continuous monitoring 4, 1, 3
• Electrolyte disturbances including hyperkalemia requiring cardiac membrane stabilization 4

Multi-organ failure:

• Hepatic injury with markedly elevated transaminases (AST >2000 U/L, ALT >2000 U/L) 1
• Rhabdomyolysis with elevated CPK requiring hydration and urine alkalinization 4, 1
• Acute renal failure with elevated creatinine and blood urea nitrogen 1
• Respiratory failure requiring mechanical ventilation 1

Gastrointestinal symptoms:

• Vomiting and abdominal pain are the earliest manifestations 1, 6, 3

Neurological effects:

• Restlessness, confusion, and altered sensorium progressing to coma 1, 6, 3

Critical Management Principles

There is no specific antidote for aluminum phosphide poisoning—aggressive supportive care initiated immediately is the only effective treatment. 4, 1, 5, 3

Essential Supportive Measures

• Fluid resuscitation and vasopressor support for refractory shock 4, 7
• Sodium bicarbonate (1-2 mEq/kg IV push) for severe metabolic acidosis 4
• Calcium gluconate (100-200 mg/kg/dose) via slow infusion with ECG monitoring for life-threatening arrhythmias 4
• Magnesium sulfate to reduce cardiac arrhythmias, though no uniformity exists in dosing worldwide 6
• Continuous cardiac monitoring with immediate access to resuscitation equipment 4

Important Caveats

• Do not administer sodium bicarbonate and calcium through the same IV line to avoid precipitation 4
• Avoid physical restraints without adequate sedation as this worsens outcomes 4
• Phosphine gas is highly toxic to healthcare providers—ensure proper ventilation of treatment areas 4
• Survivors recover completely without residual organ damage if they survive the acute phase 3