Mechanism of Liver Dysfunction in Aluminum Phosphide Poisoning
Aluminum phosphide causes liver dysfunction through direct mitochondrial damage, oxidative stress from hydroxyl radical formation, and hepatocellular necrosis, leading to acute liver failure that requires intensive supportive care as no specific antidote exists.
Pathophysiological Mechanisms
Direct Cellular Toxicity
Mitochondrial disruption is the primary mechanism: phosphine gas (released when aluminum phosphide contacts moisture) rapidly perturbs mitochondrial morphology, inhibits oxidative respiration by 70%, and causes severe drops in mitochondrial membrane potential 1
Oxidative stress occurs through dual mechanisms: phosphine interacts with hydrogen peroxide to form highly reactive hydroxyl radicals, and simultaneously inhibits catalase and peroxidase, resulting in lipid peroxidation and cellular membrane damage 1
Hepatocellular necrosis develops as a direct consequence of failed cellular respiration and oxidative damage, manifesting as hepatic dysfunction in the clinical presentation 2, 1
Clinical Manifestations of Hepatotoxicity
Hepato-biliary impairment appears alongside multi-organ failure, typically presenting with elevated transaminases and hepatic dysfunction within hours of exposure 3, 2
The liver damage is part of a systemic toxicity syndrome that includes refractory shock, metabolic acidosis, cardiac arrhythmias, and acute renal failure 3, 4
Management Approach for Liver Dysfunction
Immediate Supportive Care
Intensive monitoring and aggressive supportive management are the only available treatments, as there is no specific antidote for aluminum phosphide poisoning 4, 1
Early ICU admission is mandatory for all patients with aluminum phosphide exposure, given the rapid progression to multi-organ failure 4
Hemodynamic support with crystalloid resuscitation and vasopressors (norepinephrine) should be initiated immediately for circulatory collapse 4
Adjunctive Therapies
N-acetylcysteine should be administered as a membrane stabilizer and antioxidant, though evidence is limited to case reports showing potential benefit 3, 4
Magnesium sulfate may provide membrane stabilization effects and should be considered in the treatment protocol 3
Cardioprotective agents including trimetazidine, thiamine, vitamin C, and hydrocortisone have been suggested in case reports to potentially decrease fatal outcomes 3
Gastric Decontamination
Gastric lavage should be performed immediately if the patient presents within hours of ingestion, using specialized protocols that may improve survival 5
Standard activated charcoal is not specifically mentioned for aluminum phosphide, but early gastrointestinal decontamination is critical 5
Monitoring and Complications
Metabolic acidosis requires aggressive correction with close monitoring of arterial blood gases 3, 4, 2
Hepatic function tests should be monitored serially, though the liver dysfunction is typically part of multi-organ failure rather than isolated hepatotoxicity 2, 1
Acute renal failure frequently accompanies hepatic dysfunction and may require renal replacement therapy 1
Critical Prognostic Factors
Early intubation requirement, presence of thirst, sore throat, and absence of nausea on presentation indicate worse prognosis 5
Mortality remains 70-100% even with small ingestions (150-500 mg), though survival is possible with aggressive early supportive care 3
The short interval between exposure and systemic toxicity (minutes to hours) necessitates immediate recognition and treatment 1
Key Clinical Pitfalls
Do not delay supportive care waiting for specific antidotes—none exist, and early aggressive management is the only factor that may improve survival 4, 1
Inhalational exposure can cause severe toxicity even without ingestion, particularly in enclosed spaces with aluminum phosphide tablets 4, 2
The corrosive nature of phosphides adds direct tissue damage to the systemic toxicity, complicating management 1