Trimetazedine with hyperinsulinimea-euoglycemia, N-acetyl cysteine, and vitamin C: A new approach concept for management of aluminum phosphide poisoning.

Aluminum phosphide (AlP) is commonly used as a powerful suicidal tool. The exact mechanism of acute toxicity has not been well defined despite high mortality rates as well as its supportive treatment including rapid decontamination and institution of resuscitative measures. The current study aimed to investigate a new combination therapy using trimetazidine, N-acetyl cysteine, vitamin C, and hyperinsulinemia-euglycemia to manage acute AlP poisoning. Acute AlP-induced cardiotoxicity, hemodynamic changes, and hepatotoxicity were evaluated using electrocardiogram, creatinine kinase MB iso-enzyme, troponin-1, blood pressure, random blood glucose level, liver function tests, and histopathological changes in both the heart and liver in a rabbit model of AlP poisoning. The results showed that the new regimen therapy ameliorates the toxic effect of AlP with significant improvement in survival, cardiovascular and hemodynamic parameters in addition to histopathological changes. These results highlight the strong cardioprotective, antioxidant, hepatoprotective effects of the new combined therapy along with correction of hemodynamic changes and hyperglycemia as a potential target in the management of acute AlP poisoning.

Successful treatment of aluminium phosphide poisoning by dihydroxyacetone: A two-case report study.

WHAT IS KNOWN AND OBJECTIVE: Aluminium phosphide (AlP) is an agricultural fumigant which produces phosphine gas in the presence of moisture. Phosphine inhibits oxidative phosphorylation and causes cell death by inhibiting cytochrome C oxidase. Clinical manifestations of AlP poisoning are refractory hypotension, tachycardia, low oxygen saturation and severe metabolic acidosis. CASE SUMMARY: Two cases received dihydroxyacetone (DHA) in addition to routine management of AlP poisoning. Administration of DHA (7 gr in 50 mL sodium bicarbonate, gavage) 2 times at a 1-hour interval improved the clinical signs. WHAT IS NEW AND CONCLUSION: This is the first case report to highlight the safe and successful treatment of AlP poisoning with DHA. However, more clinical studies are recommended to determine the precise mechanism of DHA action.

Glucose-insulin-potassium infusion for the treatment of acute aluminum phosphide poisoning: an open-label pilot study.

Introduction: Acute aluminum phosphide poisoning is common in low- and middle-income countries, and is associated with very high case fatality. The addition of glucose-insulin-potassium (GIK) infusion to the standard supportive care has been proposed to improve outcomes. We aimed to assess the effectiveness of GIK infusion in acute aluminum phosphide toxicity.Methods: We performed a prospective open-label pilot study in a tertiary care hospital in north India in patients over 13 years of age with acute aluminum phosphide poisoning, to determine whether the treatment with GIK infusion improved outcomes. The primary outcome was in-hospital case fatality, and the secondary outcomes were the duration of hospital stay, the requirement of mechanical ventilation, and the change in hemodynamic and metabolic parameters.Results: A total of 60 patients were randomly assigned to groups that received either GIK infusion with supportive care or supportive care alone. Baseline parameters in both groups were comparable. Treatment with GIK infusion was associated with significantly lower in-hospital case fatality compared with supportive care alone (46.7% versus 73.3%; p-value 0.03). It was associated with a longer duration of hospital stay (p-value < 0.01) and reduced requirement of mechanical ventilation (p-value < 0.01). The treatment improved blood pressure (systolic, diastolic, and mean arterial pressure) and Glasgow coma scale score at various time intervals; however, pulse rate and metabolic acidosis (blood pH and bicarbonate levels) remained comparable in both the groups. Hyperglycemia was significantly higher in the GIK group but was easily managed.Conclusion: Treatment with GIK infusion may improve survival and hemodynamics in patients with acute aluminum phosphide poisoning.

[Progress in treatment of acute aluminum phosphide poisoning].

Aluminum phosphide (ALP) is frequently used for grain conservation despite its high toxicity. In some developing countries increased utilization of ALP has resulted in increment of ALP-attributed poisoning numbers. The mortality of ALP poisoning is extremely high and no effective antidote is available so far. However, the astute survey of potential misconceptions in the course of acute toxicity has led some scientists to introduce novel therapeutic approaches. Meanwhile, some new antioxidants were discovered and expected to be used in the management of ALP poisoning. In addition, the progress in intensive care has promoted technologies such as CRRT, IABP and ECMO for the treatment of ALP poisoning with reported success in alleviating severe toxicity. Recent studies on the therapy of ALP poisoning are reviewed in this article.

A study of the predictive factors of mortality in acute poisoning with aluminum phosphide with special reference to echocardiography and SOFA score.

Aluminum phosphide (AlP) is considered now one of the most common causes of poisoning among agricultural pesticides. Poisoning with AlP is extremely toxic to humans with high mortality rate. The aim of this work was to evaluate the prognostic factors and outcome of acute aluminum phosphide poisoning in Alexandria Main University Hospital during a period of 6 months from 1 November 2017 until the end of April 2018, highlighting the role of SOFA score and echocardiography in predicting the mortality. The prospective study was conducted on all patients admitted with acute AlP poisoning to Alexandria Main University Hospital for those 6 months. Patients' data were collected in a special sheet and included biosocial data, medical history, poisoning history, complete medical examination, investigations, duration of hospital stay, and the outcome. All patients were assessed according to SOFA score on admission. Thirty patients were admitted during the period of the current study. Females outnumbered males in all age groups with a sex ratio of 2.75:1. The mean age of patients was 22.77 ± 12.79 years. 96.6% of patients came from rural areas. 93.3% of the cases were exposed to poisoning at home, where suicidal poisoning accounted for (86.7%) of cases. 43.3% of patients died (n = 13), and the median value of SOFA score among non-survivors was 10, versus 1 among survivors. The median value of ejection fraction among non-survivors (25%) was half its value in survivors (50%). Although there were many predictors of severity of AlP poisoning, SOFA score was the most predictive factor of mortality detected by multivariate analysis.

Cardiogenic Shock Due to Aluminum Phosphide Poisoning Treated with Intra-aortic Balloon Pump: A Report of Two Cases.

The mortality rate from aluminum phosphide (AlP) poisoning is as high as 70-100%, with refractory hypotension and severe metabolic acidosis being the two most common presentations in this poisoning. As this poisoning has no specific antidote, treatments revolve around supportive care. Cardiogenic shock created by toxic myocarditis is considered the main cause of mortality in these patients. Meanwhile, the intra-aortic balloon pump (IABP) has been suggested for the treatment of cardiogenic shock. This article reports the successful treatment of cardiogenic shock caused by AlP poisoning in a 17-year-old man and a 21-year-old woman using the IABP procedure.

Extracorporeal membrane oxygenation in aluminum phosphide poisoning in Nepal: a case report.

BACKGROUND: Aluminum phosphide is a very common suicide agent in developing countries like Nepal. Due to the unavailability of a specific antidote, mortality is very high because the phosphine molecule that is formed leads to inhibition of the cytochrome oxidase enzyme system in mitochondria. Extracorporeal membrane oxygenation provides life-saving support to the cardiovascular and respiratory systems until the deadly poison is eliminated from the body. CASE PRESENTATION: We encountered one case of 67-year-old Asian woman, a known case of major depressive disorder, who presented to our center with suicidal ingestion of aluminum phosphide with cardiovascular and respiratory dysfunction. On presentation in our emergency room, she had an ejection fraction of 20% and had to be immediately intubated for respiratory failure. Based on the evidence of almost 100% mortality with aluminum phosphide poisoning, extracorporeal membrane oxygenation was initiated in our intensive care unit. Her general condition and hemodynamics gradually improved over the course of 2 days and she was weaned from extracorporeal membrane oxygenation and ventilator by post-extracorporeal membrane oxygenation days 3 and 4, respectively. After psychiatric evaluation and establishment of normal vital parameters, she was moved out of intensive care unit on post-extracorporeal membrane oxygenation day 6 and discharged to home on post-extracorporeal membrane oxygenation day 10. CONCLUSIONS: Although this seems to be a small step in terms of global perspective, it is a giant stride for a developing country. The management of reversible but severe cardiac and respiratory failure certainly opens up newer scopes where we can ensure a quality health care service being made accessible even to the most underprivileged people.

Incidental Aluminum Phosphide Poisoning: Case Report and Current Management.

Aluminum phosphide (AlP) is a commonly used cheap rodenticide, insecticide, and fumigant. Most intoxications in the literature are suicidal ingestions, however, AlP may cause incidental inhalational toxicities as well. After ingestion or inhalation, nausea, vomiting, dyspnea and abdominal pain develops within minutes. Hallmark of toxicity is refractory hypotension, cardiac failure and severe metabolic acidosis developing within a matter of hours are the major cause of mortality. In Turkey, AlP tablets are widely accessible and are sold without any restrictions. However, there are few local case reports in the literature. Additionally, incidental AlP intoxications are rarely reported. Herein, we present a 25-year-old male patient incidentally poisoned with AlP. He was found unconscious in a grain storage unit protected by aluminum phosphide tablets. He had hypotension and tachycardia. Arterial blood gas analysis did not reveal metabolic acidosis. He was quickly intubated and admitted to Intensive Care Unit (ICU). Supportive care crystalloid solution, n-acetyl cysteine and norepinephrine infusion was administered. After 36 hours, he was extubated and discharged without any complications. There is no specific antidote or treatment for AlP toxicity. Literature is controversial regarding treatment approach. Inhalational toxicity may occur under extreme conditions, as presented in this case report. Preventive strategies should be considered to reduce incidents. Clinicians should also be aware that AlP is a widely available and highly toxic compound that has no specific antidote and toxicity needs to be urgently treated with best supportive care.

Aluminum phosphide poisoning in Saudi Arabia over a nine-year period.

BACKGROUND: Aluminum phosphide (AlP) is an insecticide and rodenticide used to protect stored grains from rodents and other household pests. This substance is highly toxic to humans and has been the cause of many accidental and intentional deaths due in part to poor regulation of sales and distribution in many countries. OBJECTIVES: Describe poisonings reported to the Ministry of Health in Saudi Arabia in terms of demographic variables and by time and geographic distribution. DESIGN: Retrospective medical record review. SETTING: Ministry of Health hospitals nationwide. PATIENTS AND METHODS: Using a semi-structured checklist, data was collected from patient records that contained sociodemographic variables and the outcome (died or discharged). MAIN OUTCOME MEASURES: Aggregated data, summary statistics and statistical comparisons. SAMPLE SIZE: 68 patients. RESULTS: Thirty-eight (56%) were female and the mean (SD) age of patients was 18.6 (1.86) years. Eighteen of 22 (82%) patients who died were younger than 20 years old. Mortality in patients younger than 20 years of age was greater than in adults (P=.043). Mortality was highest in patients younger than 7 years of age (P=.006). The cases were reported by the Islamic years 1427-1435, corresponding approximately to Gregorian years 2006 to 2017. Fifty-six cases (83%) were reported from Jeddah. Most cases were due to accidental exposure to phosphine gas during fumigation. CONCLUSION: Mortality due to AlP poisoning was highest in children and most commonly occurred during fumigation of households. Delays in medical attention and diagnosis may have contributed to mortality. LIMITATIONS: Retrospective data collection and relatively small sample size. Data on exact amount and route of phosphide ingestion or exposure not available. CONFLICT OF INTEREST: None.

Mortality from aluminum phosphide poisoning in Kermanshah Province, Iran: characteristics and predictive factors.

OBJECTIVES: Aluminum phosphide (ALP), also known in Iran as rice tablets, is one of the most effective rodenticides used to protect stored grain. However, ALP poisoning regularly causes mortality in humans. The aim of this study was to evaluate the characteristics and predictive factors of mortality from ALP poisoning. METHODS: This study evaluated all patients with ALP poisoning referred to Imam Khomeini Hospital in Kermanshah Province, Iran from 2014 to 2015. For each patient, the following information was recorded: age, sex, the number of tablets consumed, the number of suicide attempts, the time elapsed from consumption to treatment, blood pressure, blood pH, HCO3 levels, and PCO2 . Differences between the survivors and non-survivors of ALP poisoning were analyzed using univariate logistic regression and multivariate analysis. RESULTS: In this study, 48 patients were male and 29 patients were female (total: 77 patients). The average age of the survivors and non-survivors was 28.7 and 31.3 years, respectively. All cases (100%) of ALP poisoning were intentional, with the goal of committing suicide. The main predictive variables of mortality from ALP poisoning were blood pressure, blood pH, and time elapsed from consumption to treatment. CONCLUSIONS: The likelihood of mortality in patients with ALP poisoning can be predicted using blood pressure, blood pH, and time elapsed from consumption to treatment. These findings may help healthcare providers take more effective measures to treat patients with ALP poisoning.

Therapeutic effects of oral liothyronine on aluminum phosphide poisoning as an adjuvant therapy: A clinical trial.

BACKGROUND: In aluminum phosphide (AlP) poisoning, death is mainly due to cardiovascular failure and refractory acute heart failure. There is a lot of evidence showing thyroid hormones have cardioprotective effects. OBJECTIVE: The purpose of this study was to evaluate the effect of oral liothyronine in the treatment of AlP poisoning. METHODS: Twenty-four patients from intensive care unit of Baharloo Hospital, Tehran, Iran, were included based on the inclusion and exclusion criteria. They were randomly divided into two parallel groups of 12 cases and 12 controls. Intervention in the case group was administration of 50 µg liothyronine via nasogastric tube after gastric lavage, in the first 6 h of poisoning. In both groups, the routine treatment of AlP poisoning was performed. Blood samples were prepared at the beginning of the study and after 12 h. Patients were followed up till discharge from the hospital or death. RESULTS: The findings demonstrated that oral liothyronine was able to significantly improve systolic blood pressure, arterial blood pH, and total thiol molecules and also could decrease lipid peroxidation, increase catalase activity, and prevent further decline in total antioxidant capacity. CONCLUSION: Liothyronine administration is effective in controlling AlP poisoning and can improve patients' outcome.

Aluminum Phosphide Poisoning Presenting like Acute Myocardial Infarction in a Young Girl.

Aluminium phosphide poisoning is very common in India. It is one of the most fatal poisons. The clinical spectrum of poisoning varies depending upon the dosage and duration of consumption. The main effect of the poison is due to the release of phosphine which inhibits cytochrome oxidase and thereby hampers cellular oxygen utilization. Almost any organ can be affected by aluminium phosphide poisoning. We report a case where the heart was the predominantly affected organ. Cardiac involvement usually manifests with nonspecific ST-T changes in ECG. Here we report a case presented with ECG finding mimicking acute anteroseptal myocardial infarction which is extremely rare.

Vitamin E as a novel therapy in the treatment of acute aluminum phosphide poisoning.

BACKGROUND/AIM: Aluminum phosphide (AlP) is commonly used as a fumigant in developing countries. Induction of oxidative stress is one of the most important mechanisms of its toxicity. In this regard, and considering that there is no specific antidote for its treatment, the aim of this study was to evaluate the effect of vitamin E in the treatment of acute AlP poisoning. MATERIALS AND METHODS: This was a clinical trial on acute AlP poisoned patients. All patients received supportive treatment. In addition, the treatment group received vitamin E (400 mg/BD/IM). Level of malondialdehyde (MDA) and total antioxidant capacity of plasma were measured. RESULTS: There was no significant difference between the treatment and control groups with regard to demographic, clinical, or paraclinical data or Simplified Acute Physiology Score II (SAPSII) on admission. Systolic blood pressure significantly increased during the first 24 h in the treatment group (P < 0.05). The plasma MDA level significantly decreased in the treatment group (P < 0.05). Vitamin E administration decreased the necessity (30% vs. 62%, P < 0.05) and duration of intubation and mechanical ventilation (P < 0.05). It significantly reduced the mortality rate in the treatment group compared to the control group (15% vs. 50%, respectively, P < 0.05). CONCLUSION: Vitamin E along with supportive treatment could have a therapeutic effect in acute AlP poisoning.

Successful Treatment of Severe Metabolic Acidosis Due to Acute Aluminum Phosphide Poisoning With Peritoneal Dialysis: a Report of 2 Cases.

Aluminum phosphide poisoning is common in our region. It can cause severe metabolic acidosis and persistent hypotension, which lead to cardiogenic shock and subsequently mortality. Oliguric or anuric acute kidney injury is seen in almost all patients with aluminum phosphide poisoning. Renal replacement therapies are recommended in these patients to improve metabolic acidosis and increase the rate of survival. We report 2 cases of severe acute aluminum phosphide poisoning treated successfully with peritoneal dialysis.

Diagnosis of aluminum phosphide poisoning using a new analytical approach: forensic application to a lethal intoxication.

Aluminum phosphide (AlP) is an effective and cheap pesticide that is commonly used worldwide, but it is also a common cause of human poisoning and carries a high mortality rate. AlP reacts with moisture in air, water, and hydrochloric acid in the stomach to produce phosphine (PH3) gas. Two routes of exposure are ingestion of AlP and inhalation of phosphine generated by the action of moisture on AlP. Absorbed phosphine is rapidly metabolized into phosphite and hypophosphite. A method is described for the analysis of the phosphine metabolites in various biological matrices. The method involves reacting the sample with zinc and aqueous H2SO4 in a volatile organic analysis vial. The metabolites were transformed into phosphine gas and then analyzed by headspace gas chromatography coupled with mass spectrometry (HS-GC-MS). This method is capable of detecting quantities of PH3 as low as 0.2 µg/mL in a sample. After validation, the method was applied to animal experiments and a real case of human AlP intoxication. This approach has the advantage of detecting metabolites of PH3, in case the PH3 was converted, and can be considered a useful additional tool for the diagnosis of AlP poisoning in forensic science.

Therapeutic role of hyperinsulinemia/euglycemia in aluminum phosphide poisoning.

BACKGROUND: Different protocols have been suggested to treat aluminum phosphide (ALP) poisoning. We aimed to evaluate the possible therapeutic effect of hyperinsulinemia/euglycemia (HIE) in treatment of ALP poisoning. METHODS: In a prospective interventional study, a total of 88 ALP-poisoned patients were included and assigned into HIE group undergoing glucose/insulin/potassium (GIK) protocol and a control group that was managed by routine conventional treatments. The 2 groups were then compared regarding the signs and symptoms of toxicity and their progression, development of complications, and final outcome to detect the possible effect of GIK protocol on the patients' course of toxicity and outcome. RESULTS: The 2 groups were similar in terms of demographic characteristics and on-arrival vital signs and lab tests. Using GIK protocol resulted in significantly longer hospital stays (24 vs 60 hours; P < 0.001) and better outcomes (72.7% vs 50% mortality; P = 0.03). Regression analysis showed that GIK duration was an independent variable that could prognosticate mortality (odds ratio [95% confidence interval] = 1.045 [1.004,1.087]). The risk of mortality decreased by 4.5% each hour after initiation of GIK. CONCLUSION: GIK protocol improves the outcome of ALP poisoning and increases the length of hospital stay.

Hydroxyethyl Starch Could Save a Patient With Acute Aluminum Phosphide Poisoning.

A 40-year-old male patient with suicidal ingestion of one tablet of aluminium phosphide was referred to the department of toxicology emergency of Baharloo Hospital, Tehran, Iran. The garlic odor was smelled from the patient and abdominal pain and continuous vomiting as well as agitation and heartburn were the first signs and symptoms. Systolic and diastolic blood pressures at the arrival time were 95 and 67 mmHg, respectively. Gastric lavage with potassium permanganate (1:10,000), and 2 vials of sodium bicarbonate through a nasogastric tube was started for the patient and the management was continued with free intravenous infusion of 1 liter of NaCl 0.9% serum plus NaHCO3, hydrocortisone acetate (200 mg), calcium gluconate (1 g) and magnesium sulfate (1 g). Regarding the large intravenous fluid therapy and vasoconstrictor administering (norepinephrine started by 5 µg/min and continued till 15 µg/min), there were no signs of response and the systolic blood pressure was 49 mmHg. At this time, hydroxyethyl starch (HES) (6% hetastarch 600/0.75 in 0.9% sodium chloride) with a dose of 600 cc in 6 hours was started for the patient. At the end of therapy with HES, the patient was stable with systolic and diastolic blood pressure of 110 and 77 mmHg, respectively. He was discharged on the 6th day after the psychological consultation, with normal clinical and paraclinical examinations. This is the first report of using HES in the management of AlP poisoning and its benefit to survive the patient.

Outcome of patients supported by extracorporeal membrane oxygenation for aluminum phosphide poisoning: An observational study.

INTRODUCTION: Aluminum phosphide (AlP) poisoning has a high mortality rate despite intensive care management, primarily because it causes severe myocardial depression and severe acute respiratory distress syndrome. The purpose of this study was to evaluate the impact of the novel use of extracorporeal membrane oxygenation (ECMO), a modified "heart-lung" machine, in a specific subset of AlP poisoning patients who had profound myocardial dysfunction along with either severe metabolic acidosis and/or refractory cardiogenic shock. METHODS: Between January 2011 and September 2014, 83 patients with AlP poisoning were enrolled in this study; 45 patients were classified as high risk. The outcome of the patients who received ECMO (n=15) was compared with that of patients who received conventional treatment (n=30). RESULTS: In the high-risk group (n=45), the mortality rate was significantly (p<0.001) lower in patients who received ECMO (33.3%) compared to those who received conventional treatment (86.7%). Compared with the conventional group, the average hospital stay was longer in the ECMO group (p<0.0001). In the ECMO group, non-survivors had a significantly (p=0.01) lower baseline LV ejection fraction (EF) and a significantly longer delay in presentation (p=0.01). CONCLUSION: Veno-arterial ECMO has been shown to improve the short-term survival of patients with AlP poisoning having severe LV myocardial dysfunction. A low baseline LVEF and longer delay in hospital presentation were found to be predictors of mortality even after ECMO usage. Large, adequately controlled and standardized trials with long-term follow-up must be performed to confirm these findings.