Zinc phosphide poisoning is recognised as a significant cause of morbidity and mortality among both socioeconomically low but economically active age demographics, especially in developing countries. A dosage of 4 to 5 g of zinc phosphide (55–70 mg/kg) had resulted in human deaths in acute toxicity . Our patient developed acute tubulointerstitial nephritis with subnephrotic range proteinuria, elevated hepatic enzymes with hyperbilirubinaemia, acute pancreatitis and dynamic ECG changes possibly due to an element of myocarditis following ingestion of 2.5 g (61 mg/kg) of zinc phosphide.
The common symptoms of zinc phosphide poisoning following inhalation are abdominal pain, cough, dizziness, headache, sorethroat and laboured breathing. The symptoms following ingestion are nausea, vomiting, abdominal pain, chest tightness, agitation, cyanosis, loss of consciousness and convulsions.
Lauterbach M et al., have concluded at the end of a study done in Germany analyzing a total number of 188 cases presenting with hydrogen phosphide poisoning, that most of the hydrogen phosphide poisoning was unintentional. They further commented that the severity of symptoms differs between intentional and unintentional phosphide poisoning and that careful monitoring is needed to those presenting with intentional phosphide poisoning . Congestive cardiac failure, adult respiratory distress syndrome, oliguric acute kidney injury (in about 50% patients), fulminant hepatic failure with elevated liver enzymes warranting liver transplant, thrombocytopaenia, metabolic acidosis, distal rental tubular acidosis, hypomagnesaemia, severe hypocalcaemia, hypokalaemia, intravascular haemolysis, disseminated intravascular coagulation and generalized tonic clonic seizures with delirium have all been recognized with phosphide poisoning . It also causes myocarditis and pericarditis with ECG changes such as sinus tachycardia, bradycardia, supraventricular ectopics, ventricular ectopics, atrial fibrillation, ventricular fibrillation, conduction defects namely wide QRS complex, A-V conduction defects, bundle branch block, complete heart block and ST-T changes such as ST depression, ST elevation, T wave changes [3, 4].
The mortality rate of zinc phosphide poisoning is around 37–100% . It causes both metabolic and non metabolic toxic effects. The mechanism of phosphide poisoning has been explained as follows by various studies.
Phosphine inhibits the oxygen uptake in the rat liver mitochondria .
It inhibits ADP uncoupled site and ion stimulated respiration thus affecting pyruvate malate, succinate, glycerophosphate and ascorbate cytochrome biomolecules in liver mitochondria . However the exact target site is a contentious issue.
It alters mitochondrial morphology, inhibits oxidative respiration by 70% and causes a large drop in mitochondrial membrane potential within 5 h of exposure .
Phosphine and hydrogen peroxide can interact to form the highly reactive hydroxyl radical that causes lipid peroxidation which is the main mechanism of oxidative damage to cell structures that lead to cell death .
Cytochrome C oxidase system is inhibited [2, 9].
There is decreased activity of cytochrome oxidase along with altered NADH and succinic dehydrogenase activities .
It increases the lipid peroxidation in the central nervous system while reducing the antioxidant defence system such as superoxide dismutase, catalase and glutathione reductase .
It inhibits protein synthesis and enzymatic activity
It has anti-choline esterase effects and also causes denaturation of oxy-haemoglobin molecules .
Phosphide poisoning is also known to cause glycaemic derangement. Severe hypoglycaemia is more commonly seen due to the reduced hepatic glycogenolysis and gluconeogenesis. However, interestingly a transient hyperglycaemia that could rarely occur is possibly due to pancreatic involvement. It is concluded in the literature that treatment of hyperglycaemia reduces the cellular oxygen consumption with re-entry of glucose into the intracellular compartment. Gunaratne et al., had suggested that the delayed presentation and having a hyperglycaemia that could rarely occur due to unexplained mechanisms, predict a poorer outcome . Jain et al., have also concluded that one should look for hyperglycaemia which warrants timely correction . Mehrpour et al., have added reinforcement to this fact at the end of an analytical study of aluminium phosphide poisoning in that the patients who had died had relatively significantly higher glucose values than those who had survived .
Surgit Singh et al., have concluded that the outcome of phosphide poisoning can be correlated with the number of induced vomiting the patient gets, severity of hypovolaemia and acidosis . Majority of the deaths had occurred in the first 12 to 24 h and the main causes identified are refractory hypotension and arrhythmias. The late deaths (beyond 24 h) had been commonly due to adult respiratory distress syndrome, liver failure and renal failure. Furthermore the outcome is poorer with delayed presentation, development of coagulopathy, hyperglycaemia and multiorgan failure .
Dogan et al., had reported a 21-year-old female who had presented with toxic level of zinc phosphide poisoning and deteriorated into severe hypovolaemic shock and acidosis making her unfit for haemodialysis and expired while awaiting bedside haemofiltration. Mostly the victims succumbed despite of fluid resuscitation, inotropic support, renal replacement or bicarbonate therapy . Ozgur et al., had reported another 22 year old patient who expired following severe refractory acute pulmonary oedema with renal as well as liver impairment, myopericarditis leading to refractory acidosis and respiratory arrest. The autopsy had revealed congested liver, lungs and spleen . Churgh and Aggarwal., had reported twenty cases of zinc phosphide poisoning who had presented between years 1992 to 1996 in India. All the victims had vomiting and abdominal pain; the majority had autonomic symptoms (80%), dyspnoea (75%) and metabolic acidosis (60%). Forty Percent of patients had suffered hypotension with shock out of which 25% patients had died .
Gunaratne et al., have recently reported a case of zinc phosphide poisoning in the Ceylon Medical Journal. This patient also has had liver and renal derangement similar to our patient. However the degree of severity had been to a relatively lesser extent. The liver enzymes had risen to ALT 157 U/L and AST 93U/L; serum creatinine 145 μmol/L. This patient had deteriorated into haemorrhagic acute pulmonary oedema and developed asystolic cardiac arrest while being ventilated. She had been haemodynamically unstable to undergo haemodialysis unlike our patient .
Saleki et al., had analysed the histologic changes that manifest in the liver of 38 cases of fatal phosphine poisonings. The following were listed out as the main histologic alterations: sinusoidal congestion; 12 cases (31.6%), severe sinusoidal congestion; 25 cases (45.8%), central vein congestion; 23 cases (60.5%), centrilobular necrosis; 3 cases (7.9%), hepatocytes nuclear fragmentation; 6 cases (15.8%), sinusoidal clusters of polymorphonuclear leukocytes; 12 cases (31.6%), and mild macrovesicular steatosis; 5 cases (13.2%) . Resistant hypotension and resistant metabolic acidosis have been the two main well recognized causes of death in most of the cases reported . However Gokdemir et al., have concluded that the mortality rate is twice as higher in the patients who develop elevated hepatic enzymes following zinc phosphide poisoning . The metabolic acidosis could occur due to hypoxia induced lactic acid production, renal and liver impairment leading to fatal outcomes.
There have been very rare instances where renal biopsy had been performed in the survivors of zinc phosphide poisoning. However there are few cases reports including autopsy findings of the renal tissue. Most of the patients had developed acute tubular necrosis especially proximal convoluted tubules in a patchy distribution probably due to prerenal hypoxic insult . Our patient had mainly tubular inflammation, granular casts associated with interstitial infiltration by neutrophils, eosinophils and lymphocytes. There was evidence of acute tubular necrosis as well, mainly in the regenerative phase as the biopsy was performed at the end of 2 weeks from the initial presentation.
On analysis of the predictive factors of prognosis as discussed above our patient did not have a delay in presenting to seek treatment, was hydrated adequately and did not have hyperglycaemia despite of the pancreatic involvement. Furthermore, the renal impairment was amenable to renal replacement therapy as she was haemodynamically stable unlike in most of the cases reported in the literature.
Management is merely symptomatic and supportive as there is no definite antidote against phosphides. Adequate fluid resuscitation via oral and intravenous routes is essential. Inotropic support with Dobutamine and further hydrocortisone or dexamethasone is recommended if the response is poor despite fluid resusucitation. Vitamin K (phytomenadione) can be given if the Prothrombin time is prolonged . A definite selection criterion for liver transplantation for patients who deteriorate into acute fulminant hepatic failure is yet to be studied. However a study held in Kerala has suggested that the presence of a MELD score of 31 on the sixth day or the presence of encephalopathy at any time after ingestion is a strong predictor of mortality without a liver transplant .
The problems encountered in Asian countries are that such rodenticides are abundantly available although its usage is illegal. The tropical countries and the rural population engaged in agriculture have easier access to the compound, as it is available at a lower cost. Furthermore, the lack of an antidote and advanced resuscitative measures such as inotropic supportive therapy and renal replacement facilities in most of the peripheral hospitals make the management of victims presenting with a lethal dose a major challenge.