Aluminium phosphide poisoning

Acute aluminium phosphide poisoning (AAlPP) is a large, though under-reported, problem in the Indian subcontinent. Aluminium phosphide (AlP), which is readily available as a fumigant for stored cereal grains, is highly toxic when consumed from a freshly opened container.^[1][2] Death results from profound shock, myocarditis and multi-organ failure.^[3] Aluminium phosphide has a fatal dose of between 0.15 and 0.5 gram (0.0053 and 0.018 oz).^[4] It has been reported to be the most common cause of suicidal death in North India.^[5]

Mortality rates

The mortality rates from AAlPP published in the literature vary from 40–80%.^[1] However, the actual numbers of cases affected are thought to be much larger, as less than 5% of those with AAlPP eventually reach a tertiary care center.^[3] Since 1992, when aluminium phosphide became freely available in the market, it had, reportedly, overtaken all other forms of deliberate poisoning, such as organophosphorus and barbiturate poisoning in North India.^[6] In a 25 year study on 5,933 unnatural case fatalities in north-west India, AAlPP was concluded to be the major cause of death among all poisonings.^[7]

Despite these large numbers, there have been little progress in our understanding of the characteristics of the poison and limited Indian data is available on the predictors of mortality in these patients. One retrospective study^[3] looked at the profile of patients presenting themseleves with AAlPP to identify the factors at admission that might be useful in predicting mortality.

Mechanism of intoxication

Aluminium phosphide is an extremely toxic compound, resulting in a high mortality rate when consumed. The toxicity of aluminium phosphide is attributed to the liberation of phosphine gas, a cytotoxic compound that causes free radical mediated injury. The chemical formula for combination with water molecules is:

AlP + 3 H₂O → Al(OH)₃ + PH₃, and

AlP + 3 HCl → AlCl₃ + PH₃ (stomach)

Phosphine, a nucleophile, acts as a strong reducing agent capable of inhibiting cellular enzymes involved in several metabolic processes. Early studies on phosphine demonstrated specific inhibitory effects on mitochondrial cytochrome c oxidase.^[3] Experimental and observational studies have subsequently demonstrated that the inhibition of cytochrome c oxidase and other enzymes leads to the generation superoxide radicals and cellular peroxides. Cellular injury subsequently occurs through lipid peroxidation and other oxidant mechanisms.

The major lethal consequence of aluminium phosphide ingestion i.e., profound circulatory collapse, is reportedly secondary to these toxins generated, which lead to direct effects on cardiac myocytes,^[8] fluid loss, and adrenal gland damage. In addition, phosphine also has corrosive effects on tissues.^[3]

Signs and symptoms

The signs and symptoms are non-specific, instantaneous and depend on the dose, route of entry, and time lapse since exposure to the poison. After inhalation exposure, patients commonly exhibit airway irritation and breathlessness.^[5] The dominant clinical feature is severe hypotension refractory to dopamine.^[9] Other features may include dizziness, fatigue, tightness in the chest, headache, nausea, vomiting, diarrhoea, ataxia, numbness, paraesthesia, tremor, muscle weakness, diplopia and jaundice.^{[10][11][12][13]} If severe inhalation occurs, the patient may develop acute respiratory distress syndrome (ARDS), cardiac failure, cardiac arrhythmias, convulsion and coma, and late manifestation of hepatotoxicity and nephrotoxicity may also occur.^{[10][11][12][13]}

After ingestion, toxic features usually develop within a few minutes. Common clinical features in mild poisoning cases are nausea, repeated vomiting, diarrhoea, headache, abdominal discomfort or pain and tachycardia. These patients usually show recovery. On the other hand, in moderate to severe ingestional poisoning, the signs and symptoms of the gastrointestinal, cardiovascular, respiratory and nervous systems appear initially and, later on, features of hepatic and renal failure and disseminated intravascular coagulation may also occur.^[10]

The diagnosis of AlP usually depends on the clinical suspicion or history (self-report or by attendants). At some places, tablets of AlP are also referred to as “Rice Tablets” and, if there is a history of rice tablet ingestion, then it should be treated differently than other types of rice tablets that are made up of herbal products.^[14]

Tests

For a Silver nitrate test on gastric aspirate, diluted gastric content is heated in a flask up to 50 °C for 15–20 minutes, keeping silver nitrate paper on the mouth of the flask. If phosphine is present then the paper will turn black due to silver phosphate. As hydrogen sulfide also changes the colour, its presence could be differentiated using lead acetate paper, i.e. both papers will turn black in the presence of hydrogen sulfide. Further confirmation of phosphine can be done by putting a drop of ammonium molybdate solution on the black-turned filter paper, and the colour of the paper will change to blue.^[15]

Management and outcome

The management of AAlPP remains purely supportive because no specific antidote is known. Aluminium phosphide is an extremely toxic compound with a mortality rate close to 60%. The role of magnesium sulfate as a potential therapy in AlP poisoning may decrease the likelihood of a fatal outcome, and has been described in many studies.^[3][13]

After ingestion, effectiveness of gut decontamination to reduce the absorption of unabsorbed poison is primarily dependent on the duration of exposure to the poison, if administered within 1–2 hours it can be effective. Gut decontamination should not be performed if the patient has an unprotected airway without endotracheal intubation. Potassium permanganate (1:10,000) is used for gastric lavage through a nasogastric tube as it oxidises phosphine to non-toxic phosphate. This can be followed by approximately 100 g of activated charcoal to reduce absorption if the patient arrives within 1 hour after ingestion of a large amount of poison.

There is insufficient data to support the routine use of activated charcoal in AlP poisoning, as phosphine gas is rapidly absorbed through the gut. Also, a position paper on activated charcoal recommends that it should not be administered routinely in the management of poisoned patients.^[16]

Myocardial injury and hemodynamic instability is one of the most important features, and most of the deaths in ALP poisoning have been reported to be due to cardiovascular failure. All patients of severe AlP poisoning require continuous invasive hemodynamic monitoring and early resuscitation with fluid and vasoactive agents. Phosphine virtually affects all the organs in the body and, therefore, early identification of impending organ failure and appropriate supportive therapy is extremely important until the toxin is excreted from the body.

Requirement of endotracheal intubation and mechanical ventilation usually depends on the severity of the acute lung injury, sometimes, due to poor mental status. Hemodialysis is not very effective in removing phosphine but is helpful when renal failure, severe metabolic acidosis or if fluid overload is present.^[15]

References