• Aluminium Phosphide
• Magnesium Phosphide
• Zinc Phosphide
• Calcium Phosphide
• Phosphine gas

Ingestion of aluminium phosphide pellets is a common and highly lethal means of suicide in South Asia. The phosphine gas produced by the pellets is rapidly absorbed and it causes shock, marked electrolyte abnormalities and multi-organ failure by a complex mechanism involving oxidative stress and inhibition of multiple critical enzymes. Treatment is primarily supportive but correction of hypomagnasaemia and antioxidants may be beneficial.

Metal phosphides (e.g. Al, Mg, Zn) react readily with water (and/or hydrochloric acid in the stomach) to form hydrogen phosphide gas (PH3 - phosphine). Phosphine is a very strong reducing agent and is highly reactive. It causes marked oxidative stress leading to a range of non-specific cytotoxic effects. It also binds to and inhibits a range of enzymes including those involved in cellular respiration (i.e. it inhibits oxidative phosphorylation). There is also significant inhibition of catalase, leading to accumulation of hydrogen peroxide, induction of superoxide dismutase, and further creation of oxygen free radicals, lipid peroxidation and protein denaturation of cell membrane components. Many other critical enzymes may be inhibited, and it is not known which of the multiple toxic mechanisms are most critical. Many texts refer to inhibition of cellular respiration as being the most important effect, however cytochrome oxidase is rarely more than 50% inhibited and the clinical syndrome does not closely resemble that of cyanide or hydrogen sulphide. Moreover in animal models, increased respired oxygen increases the toxicity of phosphine and some antioxidants are protective, supporting the hypothesis that overwhelming oxidant stress is the most important toxicological mechanism.

There are often marked changes in plasma electrolyte concentrations – it is possible that these relate to forming complexes with phosphine or to altered cell membrane permeability. Therefore, electrocardiographic changes and arrhythmias may be secondary to altered K, Mg, Ca concentrations or indeed to altered intracellular cardiac ion concentrations. Methemoglobinemia may also arise from the increased generation of oxygen free radicals.

The multi-organ failure and shock are likely to be due to direct cytotoxic oxidative damage. Damage to the heart, lungs and the vasculature will then have secondary contributing effects due to resultant hypoxia and hypoperfusion. Similarly damage to the gut and lungs may lead to secondary opportunistic infections.

Phosphine is rapidly absorbed via inhalation or in the gut after hydrolysis of ingested phosphide salts. Dermal absorption is low and generally insignificant.

Phosphine is soluble and yet is a highly reactive and very simple substance. Consequently, very little is known about it’s distribution or metabolic fate. It reacts with oxygen to form phosphite and hypophosphite and the phosphorus also may bind to many other proteins.

About 40% of absorbed phosphine is excreted in the urine as phosphite and hypophosphite. The metabolic fate of the rest of the phosphorus is unknown. It is unlikely that any procedure will enhance elimination.

The clinical effects differ in acute and chronic exposures.

The onset of symptoms is usually within a few hours but the effects may get progressively worse over the first 24 hours. Local gastrointestinal effects include retrosternal pain, vomiting, diarrhoea and abdominal pain. Multiple organ failure with acute cardiac failure, shock, ARDS, acute renal and hepatic failure may lead rapidly to death. CNS effects (seizures, coma) usually only occur in severe poisoning and may be secondary to the multi-organ failure. Direct cardiac toxicity combined with acidosis and marked electrolyte abnormalities (particularly of K Ca and Mg) mean that arrhythmias are a common and frequently lethal complication. Bradyarrhythmias and atrial or ventricular tachyarrhythmias may occur.

Phosphine gas
The above symptoms may be seen but upper and lower respiratory effects are more prominent and gastrointestinal symptoms are less so. Mild exposures to phosphine can cause nasal and eye irritation, cough, headache, fatigue, nausea, vomiting, and abdominal pain. More serious exposures typically cause severe dyspnoea, pulmonary edema, cardiac arrhythmias, and hypotension.

Repeated exposures most commonly lead to multiple repeated episodes of mild symptomatic poisoning. Chronic exposure to low doses of phosphines resembles the effects of chronic phosphorus poisoning.

This is based on a clinical judgment based largely on the blood pressure and presence of organ failure. The extent of hypomagnesaemia also appears to correlate with poor outcome. Note that toxicity may worsen over at least 24 hours and clinical observation for this time is necessary.

The following investigations may be useful:

• Phosphites - Blood or urine phosphate and hypophosphite concentrations are not generally useful to determine the need for specific treatment but do confirm poisoning. They are most useful for forensic purposes in industrial, suicidal or homicidal poisonings.
• Full blood count and coagulation studies - The full blood count will detect haemolysis and DIC is a common complication.
• Electrolytes & Liver Function tests - hepatic and renal toxicity is common as is a lactic acidosis. Hypomagnesaemia, hypermagnesaemia (much less common), hyperkalaemia, hypocalcaemia and hyponatraemia are all common and should be corrected where possible.

Arrhythmias are common in severe poisoning and QRS & QT prolongation may be seen as may findings associated with electrolyte abnormalities.

Chest X-ray should be performed in any patient with abnormal gas exchange or clinical signs of pulmonary involvement.

Treatment is primarily supportive and may include intensive cardiovascular and respiratory support, and correction of electrolyte abnormalities.

Note that supplemental oxygen appears to substantially increase the toxicity of phosphine and should only be given when patients are significantly hypoxaemic (e.g. <85-90% saturation), when the prognosis is extremely poor and treatment is palliative.

Magnesium Sulphate
While experience and clinical trials supporting its use are limited, one study suggested correction of magnesium and reduced mortality with an IV regimen of 1 g STAT followed by 1 g/h for 3 hours and then 1g q6 hourly. However, others have not found benefit and the treatment is not routinely used in many places where aluminium phosphide poisoning is common.

Antioxidants
Acetylcysteine has been shown to reduce toxicity in animal models, presumably due to antioxidant effects. The optimal dose is not known but it seems reasonable to use the dose used in paracetamol poisoning, with a slower infusion of the loading dose given the potential of acetylcysteine to worsen hypotension.

It is not known if phosphide salts or phosphine are significantly adsorbed to charcoal. However given the high dose–related lethality of aluminium phosphide ingestions, it seems warranted to try some form of gastrointestinal decontamination. Patients with confirmed ingestion of a potentially toxic dose of a phosphide salt should have gastric lavage and polyethylene glycol whole bowel irrigation.

Haemodialysis may be needed to correct electrolyte abnormalities but is unlikely to significantly enhance elimination.

Long term sequelae after non-lethal exposure have not been systematically studied.p

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Singh S, Singh D, Wig N, et al. Aluminum phosphide ingestion: a clinico-pathologic study. J Toxicol Clin Toxicol 1996; 34: 703-6.
Chugh SN, Kumar P, Aggarwal HK, et al. Efficacy of magnesium sulphate in aluminium phosphide poisoning: comparison of two different dose schedules. J Assoc Physicians India 1994; 42: 373-5.
Siwach SB, Yadav DR, Arora B, et al. Acute aluminum phosphide poisoning - an epidemiological, clinical and histopathological study. J Assoc Physicians India 1988; 36: 594-6.
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