Survival after aluminum phosphide poisoning with cardiotoxicity: a case report

Abstract

Introduction

Aluminum phosphide is a cheap and commonly used rodenticide that is also an effective solid fumigant and frequently used for grain preservation. The pill contains around 44% inert elements (ammonium carbonate) to avoid disintegration of the tablet, while the rest (about 56%) is aluminum phosphide. Because it is freely available on the market, it is one of the commonly used agents for self-poisoning in different parts of the developing world. Early signs of toxicity are manifested by shock and circulatory failure. Until now, no specific antidote is available. Aggressive supportive management is the key to survival in cases of aluminum phosphide poisoning.

Case presentation

We present a case of successful management of aluminum phosphide poisoning-induced cardiotoxicity with a favorable outcome in a 48-year-old Black African female patient who was taken to a private clinic 6 hours after intentional ingestion of two tablets of aluminum phosphide. She presented with repeated vomiting, restlessness, and confusion. Upon examination, the patient was drowsy, pale, cold, and clammy. She had nonrecordable blood pressure and radial pulsation. Glasgow Coma Scale was 14/15. Routine laboratory investigations and initial electrocardiogram were normal. Six hours after intensive care unit admission, the electrocardiogram showed atrial fibrillation with fast ventricular response, ST segment elevation, and inverted T-waves. Cardiac troponin level was elevated. With the diagnosis of acute aluminum phosphide poisoning with cardiotoxicity (acute myocardial infarction), hospital-based protocol was administered and medical treatment for myocardial infarction was given. She was discharged on the fourth day after full recovery. She came for regular follow-up visits and had normal clinical evaluation, electrocardiogram, and laboratory findings.

Conclusion

Exposure to phosphine gas released from aluminum phosphide fumigants increases the risk of major morbidity and mortality. The mortality due to aluminum phosphide poisoning is very high and variable. The use of magnesium sulfate to reduce cardiac arrhythmias and mortality is well documented, but there is no uniformity in dose or frequency of its administration worldwide.

Limitations

One of the limitations of this report is the nature of the case report, being a retrospective design, giving no chance to establish a cause–effect relationship. Arterial blood gas analysis, serum magnesium level, and cardiac computed tomography/magnetic resonance imaging modalities were not available in the town. The recommended gastric lavage with potassium permanganate solution was not used in this case, because potassium permanganate is not available in Ethiopia. The other limitation is that, as it is a case report from a single center, it may not be representative of the general population. These limitations might have a negative impact on the generalizability of the findings.

Introduction

The World Health Organization estimated that more than 7,000,000 people die every year because of suicide. Seventy-seven percent of all suicides occur in low‑ and middle‑income countries. Pesticide ingestion is a common means of suicide. The commonly available pesticides are organophosphates, organochlorine, and aluminum phosphide (ALP) [1]. ALP, which is a cheap and commonly used rodenticide, is also an effective solid fumigant that is frequently used for grain preservation. ALP is marketed as dark-gray 3-g tablets with common brand names of Celphos, Alphos, Synfume, Phostek, Phostoxin, Phosfume, and Quickphos. The pill contains around 44% inert elements (ammonium carbonate) to avoid disintegration of the tablet [2], while the rest (about 56%) is aluminum phosphide. The lethal dose of aluminum phosphide is between 0.15 and 0.5 g (0.0053–0.0176 oz). Aluminum phosphide is available in the form of 3-g pellets (releasing 1 g phosphine gas) or 0.6-g pellets (releasing 0.2 g phosphine gas). Because it is freely available on the market and accessibility is not controlled in developing countries, it is one of the commonly used agents for self-poisoning [3, 4]. During contact with atmospheric air and hydrochloric acid in the stomach, ALP liberates lethal phosphine (PH₃) gas, which is colorless and odorless. On exposure to air, it produces a garlicky odor. Phosphine gas is rapidly absorbed by the lungs or gut, which causes systemic toxic effects by free‑radical injury and inhibiting cytochrome c oxidase enzyme. Early signs of toxicity are manifested by shock and circulatory failure. Within minutes of ingestion, toxic features of poisoning may be seen, such as severe vomiting, resistant hypotension, metabolic acidosis, myocardial suppression, and acute respiratory distress syndrome (ARDS). Until now, no specific antidote is available. Aggressive supportive management is the key to survival in cases of ALP poisoning [1, 5, 6]. A retrospective study of 125 patients in Ethiopia showed high prevalence in females (57.6%). ALP poisoning is associated with a high mortality rate, ranging from 30% to 80%, mostly within the first 1–2 days after admission [7]. Acute cardiovascular collapse is the most common mode of presentation, seen in 60–100% of cases. Few patients present with anteroinferior wall ischemia, right bundle branch block, and T-wave flattening/inversion simulating myocardial ischemia. Autopsy results show heart congestion, separation and fragmentation of myocardial fibers, nonspecific vacuolation of myocytes, focal necrosis, as well as neutrophilic and eosinophilic infiltration. The focal myocardial necrosis and changes in membrane action potentials result in nonspecific ST-T wave changes in the electrocardiogram (EKG). EKG abnormalities and arrhythmias are signs of poor prognosis [8]. The mortality rate in hypotensive patients who were treated with magnesium sulfate (MgSO₄), intravenous (IV) calcium gluconate, IV hydrocortisone, and dopamine infusion was 55.6% [3]. A similar study in Iran suggested a mortality rate of ALP poisoning in Iranian population of 27%, with a good survival rate in younger age patients [9]. Contradictory results have been reported concerning the utilization of magnesium sulfate as a therapeutic agent in ALP-intoxicated patients and its dose adjustments [10]. We present herein the case of a patient who survived ALP-induced cardiotoxicity. The purpose of this case report is to share a single experience and not to advocate for a specific treatment approach.

Case presentation

We present a case of successful management of aluminum phosphide poisoning-induced cardiotoxicity with a favorable outcome. A 48-year-old Black African female patient was taken to a private clinic 6 hours after intentional ingestion of two tablets of ALP, locally known as rat poison. The reason for ingestion was marital disharmony. During her presentation, her husband stated that she had restlessness of 3 hours duration with associated confusion. She was given half a liter of milk, and following that, she had six episodes of vomiting of ingested matter. On physical examination, she had nonrecordable blood pressure and radial pulsation. Apical pulse rate was 112 beats per minute. Gastric lavage was not done. She was resuscitated with 1 L of normal saline and referred to our hospital.

Upon her arrival at our emergency department, the family members gave additional history. She swallowed the tablets with water, directly unpacking them from the sealed container. She was found lying on the floor covered with her vomitus. She had fecal incontinence and was agitated. Her family members reported that she had no history of psychiatric illness, addiction, use of medications, or any recreational drugs. She had no history of chronic medical illnesses such as diabetes, hypertension, or retroviral infection, nor did she have history of cardiac or renal diseases. She had no history of previous poisoning. Upon physical examination, the patient was drowsy, pale, cold, and clammy. Her blood pressure was 85/55 mmHg, radial pulse rate 114 beats per minute, which was feeble and low in volume, respiratory rate of 38 breaths per minute, oxygen saturation (SPO₂) was 97% at room air, and she had a temperature of 35.2 °C. There were clear and resonant lungs with good air entry bilaterally. On cardiovascular examination, she had normal heart sounds with regular rhythm. Jugular venous pressure was not raised. There was no edema on the lower or upper limbs. On central nervous system (CNS) examination, Glasgow Coma Scale (GCS) was 14/15 (4,4,6; best eye response = 4/4, best verbal response = 4/5, best motor response = 6/6). She was not oriented to time, place, and person. Her pupils were normal sized and reactive to light. Examinations on other systems were unremarkable.

Routine investigations (complete blood count, C-reactive protein, random blood glucose, troponin, liver functions, and kidney functions) were done and were within normal limits (Table 1). Chest X-ray was normal. Electrocardiogram (ECG) was done and showed normal sinus rhythm (Fig. 1). After 3 hours, she was admitted to the intensive care unit (ICU) for close monitoring and for administration of local protocol for hypotensive patients with aluminum phosphide poisoning.

Table 1 Laboratory values from admission time to discharge with reference ranges

Fig. 1

Electrocardiogram of the patient at the emergency department showing sinus rhythm with heart rate of 94 beats per minute and left ventricular hypertrophy

During admission to the ICU (day 1), her vital signs were as follows: nonrecordable blood pressure, pulse rate was 118 beats per minute, which was feeble and irregular in rhythm, respiratory rate was 28 breaths per minute, and oxygen saturation was 96% on room air.

Six hours after ICU admission, the ECG was repeated, and it showed atrial fibrillation with fast ventricular response (heart rate of 120 beats per minute), ST segment elevation on the anteroseptal leads with inverted T-waves on inferior and lateral leads (Fig. 2), and cardiac troponin level was elevated (Table 1). Bedside echocardiography showed septal-wall hypokinesis with ejection fraction of 50%.

Fig. 2

Electrocardiogram of the patient in the intensive care unit, showing atrial fibrillation with fast ventricular response (heart rate of 120 beats per minute) and ST segment elevation on the anteroseptal leads with inverted T-waves on inferior and lateral leads

Routine hospital-based protocol for hypotensive patients with aluminum phosphide poisoning was administered, which includes dopamine 5 µg/kg/minute infusion, hydrocortisone 200 mg intravenously four times a day (QID) for 48 hours, calcium gluconate 1 vial (10 mL of 10% solution) with 10 mL of normal saline (NS) to run over 10 min slowly, QID for 48 h; MgSO₄ 1 g (2 mL of 50% solution) with 5 mL of NS intravenous push over 2 min, and MgSO₄ 0.5 mg (1 mL) with 1 mL of lidocaine intramuscularly in each buttock, then MgSO₄ 1 g in 100 mL of NS after 1 hour, 2 hours, and 3 hours, then MgSO₄ 1 g in 100 mL of NS intravenous three times a day for 48 hours.

With the diagnosis of acute aluminum phosphide poisoning with cardiotoxicity (acute myocardial infarction), aspirin 300 mg loading then 81 mg oral daily, clopidogrel 300 mg loading then 75 mg oral daily, atorvastatin 80 mg oral daily, unfractionated heparin 60 international unit (IU)/kg intravenous (IV) loading followed by 12 IU/kg/h via infuser, and cimetidine 200 mg IV twice per day for stress ulcer prophylaxis were added.

On day 2 in the ICU, her blood pressure returned to normal, 100/60 mmHg, pulse rate was 86 beats per minute, and hence the dopamine was tapered off. Her CNS examination improved, with GCS returning to normal 15/15, and she became oriented to time, place, and person. The repeated ECG in the ICU showed complete resolution of the atrial fibrillation and significant improvement of the ST segment elevation (Fig. 3). She stayed another 24 hours in the ICU for close monitoring of her vital signs. After staying for 3 days in the ICU, she was transferred to medical ward and discharged on the next day, after proper psychiatric evaluation and counseling.

Fig. 3

Electrocardiogram of the patient on the second day in the intensive care unit, showing sinus rhythm with heart rate of 100 beats per minute and significant improvement of the ST segment elevation and T-wave inversions

After 2 weeks, she came to follow-up clinic. She gave a history of improvement of the dispute in the family. She had intermittent–mild global headache, but otherwise no cough, shortness of breath, or dyspnea. She did not have chest pain or palpitation. There were no hallucinations, abnormal body movements, or change in mentation. During investigation, she had normal ECG and echocardiography. Liver and renal function tests were all within the normal range. She was comfortable in the counseling sessions by the psychiatry department.

One month after her previous follow-up, she came for a second follow-up visit. She reported that she was doing well with her health condition and reported no major complaints. The ECG and other routine laboratory results were within the normal range.

Discussion

ALP poisoning is the second most common cause of death due to pesticide poisoning after organophosphate. ALP is a solid fumigant and ideal pesticide since 1940 as it is cheap, most efficacious, easy to use, and freely available over the counter in India, Morocco [2], Nepal [5], Iran [11], and Ethiopia [3]. ALP has a relatively high vapor pressure, which allows it to penetrate porous material effectively. Phosphine, like cyanide, inhibits mitochondrial cytochrome oxidase and cellular oxygen utilization. The direct toxic effects of phosphine on cardiac myocytes, fluid loss, and adrenal gland can induce profound circulatory collapse [2].

In most patients, like ours, vomiting, abdominal pain, and restlessness are frequent presenting complaints. Cardiovascular involvement results in weak pulse, tachycardia, tachypnea, acidosis, marked hypotension, palpitation, and, ultimately, unresponsive shock [11]. Patients remain mentally lucid until cerebral anoxia because of shock. Several ECG changes, including ST segment elevation/depression, PR and QRS interval prolongation, complete heart block to ectopic pace making, and also atrial fibrillation, have been reported [12]. One study showed that 10% developed cardiac arrhythmia, and the most frequent arrhythmia was atrial fibrillation (31% of patients), followed by ventricular fibrillation (20%), ventricular tachycardia (17%), and AV block (12%). These changes are because of toxic injury to myocardium [11, 13]. Our patient’s ECG showed atrial fibrillation with fast ventricular response, ST elevation on the anteroseptal leads, and T wave inversions on inferolateral leads.

Laboratory investigation may show leukopenia, increased alanine aminotransferase (ALT) or aspartate aminotransferase (AST), and metabolic acidosis, which indicates severe toxicity. Electrolyte analysis may show decreased magnesium, whereas potassium may be increased or decreased [2, 11]. Our patient had normal complete blood count, AST, ALT, creatinine, and urea levels.

Our patient presented with repeated vomiting, restlessness, and hypotension, which are also common presenting symptoms in patients with ALP poisoning [7, 14]. Since there are no effective antidotes, there has been different treatment practices worldwide associated with different ranges of mortality rate. For instance, trimetazidine for reversal of cardiovascular manifestations of phosphine poisoning, coconut oil for prevention of absorption of ALP, digoxin for the management of cardiogenic shock, hydroxyethyl starch, venoarterial extracorporeal membrane oxygenation, magnesium sulfate, infusion of glucose–insulin–potassium (GIK), and different inotropes have been used in different centers [7, 15, 16]. Our patient was managed in the ICU with dopamine infusion, magnesium sulfate, hydrocortisone IV injection, and calcium gluconate infusion. This approach was practiced for more than 10 years in Felege Hiwot Referral Hospital, in Northwest Ethiopia. In a retrospective study of 2.5 years, done in Felege Hiwot Referral Hospital, the overall mortality of ALP poisoning patients was 31.2%, while mortality in hypotensive patients who were treated with the above regimen was 55.6%, which used to be nearly 100% prior to the practice of this approach [3]. The use of intravenous magnesium sulfate has been shown to reduce mortality up to 50% in many studies [5]. In a study of 50 patients, individuals receiving repeated doses of intravenous magnesium showed significant improvement in indicators of oxidative stress and lower incidence of mortality in comparison with control participants [2]. Magnesium sulfate acts by stabilizing the cell membrane and hence reducing the incidence of fatal arrhythmias. Another role of magnesium sulfate is to decrease free radical injury owing to its anti-peroxidant effect. Different studies recommended different doses of intravenous magnesium sulfate. Calcium gluconate is used to treat ECG changes related to ALP poisoning for its membrane stabilizing effect. As both hypomagnesemia and arrhythmias are found in hypotensive patients, and because there is a direct relationship between hypomagnesemia and ECG changes in ALP poisoning, treatment of patients with hypotension with MgSO₄ and calcium gluconate is rational. The additional treatments in the protocol, dopamine and hydrocortisone, directly address the hypotension. Hydrocortisone combats shock, reduces the dose of dopamine, and additionally, checks capillary leakage in the lungs to prevent ARDS [3].

Our patient had serious myocardial toxicity, as demonstrated by ECG and raised cardiac biomarker, which are predictors of poor survival and high mortality [17]. A study from Iran showed that the combination of low blood pressure (systolic blood pressure below 90 mmHg), lower blood pH, and time elapsed from consumption to treatment (greater than 1 hour) predicted almost 77.3% of mortality in cases of ALP poisoning. Additionally, patients with low blood pressure are highly likely to die, having a mortality rate of 91.7% [18]. Similarly, another study showed that the survival of patients had a significant relationship with the number of tablets consumed, the time elapsed to reach the first treatment center, hypotension, blood pH, and bicarbonate (HCO₃) levels. They showed that the mortality rate of ALP poisoning was higher in patients with systolic blood pressure below 90 mmHg, blood pH < 7.2, or HCO₃ level < 15.0, who took over half of a rice tablet, or for whom more than half an hour elapsed from consumption to treatment [18]. Our patient had most of the predictors of high mortality rate; she presented to her first treatment center 6 hours after ingestion, had low blood pressure, and took two tablets. Fortunately, with the help of her favorable baseline health condition, her relatively early presentation, aggressive supportive treatment, and our treatment protocol, she survived and was discharged with complete improvement.

Conclusion

Exposure to phosphine gas released from ALP fumigants increases the risk of major morbidity and mortality. The mortality due to ALP poisoning is very high and variable, depending on a number of factors, including the lack of a specific antidote or standardized treatment guidelines and presenting with poor prognostic signs. This case suggests a potential role for magnesium sulfate in the management of ALP poisoning. The use of magnesium sulfate to reduce cardiac arrhythmias and mortality is well documented, but there is no uniformity in the dose and frequency of its administration worldwide. We present herein a patient who survived ALP poisoning with cardiotoxicity who had a good baseline general health condition, presented relatively early, and received aggressive supportive care. Additionally, she was treated by a local treatment protocol that incorporates MgSo₄, dopamine, calcium gluconate, and hydrocortisone.

Challenges and limitations

Aluminum phosphide poisoning is a life-threatening condition, still without an effective antidote. Affecting every system in the body, it is a very challenging condition to treat effectively in patients in the lack of a uniform management guideline worldwide.

One of the limitations of this report is the nature of the case report, being a retrospective design and thus giving no chance to establish a cause–effect relationship. As it is a retrospective study, certain clinical parameters and laboratory values were not complete owing to documentation problems and limitations of the setup. Arterial blood gas analysis, serum magnesium level, and cardiac CT/MRI imaging modalities were not available in the town. The recommended gastric lavage with potassium permanganate (KMnO₄) solution was not used in this case, because KMnO₄ is not available in Ethiopia. The other limitation is caused by the fact that this is a case report from a single center; it may not be representative of the general population. These limitations might have a negative impact on the generalizability of the findings.