Insulin in aluminum phosphide poisoning: A systematic review of the current literature.

BACKGROUND: Aluminum phosphide (AlP) is a commonly used fumigant in agriculture and grain preservation because of its high potency and low cost. Due to the absence of a specific antidote and promising treatment modality, poisoning with this substance is deadly. Amid multiple studies in different parts of the world, each exploring options like lavage, inotropes, antioxidants, etc, we conducted a systematic review to find the possible role of exogenous insulin in treating symptomatic cases of AlP poisoning. METHODS: Experimental studies released before February 15, 2024, that reported the use of exogenous insulin were systematically reviewed following the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. The search was done on PubMed Central, Cochrane Library, and Google Scholar. RESULTS: After applying the inclusion and exclusion criteria, we finalized a few scientific papers for the review. Studying data from 4 scientific papers (3 quasi-experimental studies and 1 randomized controlled trial), we could postulate the significant improvement in survivability after the inclusion of exogenous insulin in the treatment of poisoned cases of AlP. Studies showed divergent results for the blood pressure, blood gases, and need for mechanical ventilation. Hypoglycemia, hyperglycemia, and hypokalemia were the reported adverse effects of this therapy. CONCLUSION: Our review found that the use of exogenous insulin in AlP poisoning reduced mortality rates, which was consistent across all studies. With available knowledge, its inclusion as a part of therapy might be beneficial in AlP poisoning, but to put it forward confidently, we still need high-quality randomized control trials. It is indeed a subject of interest for future research.

Assessment of the role of N-terminal pro-B-type natriuretic peptide as a predictive biomarker of mortality in acute aluminum phosphide poisoning.

BACKGROUND: In Egypt, aluminum phosphide (ALP) is a known lethal poison due to its cardiotoxicity. This study aimed to evaluate the predictive ability of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for mortality in ALP-poisoned patients. METHODS: This prospective study was conducted on patients with ALP poisoning admitted to the Poison Control Center Ain Shams University Hospitals between July and December 2022. Upon admission, all patients were followed up and had their levels of NT-proBNP, troponin I (cTnI), and creatine kinase myocardial band (CK-MB) analyzed. RESULTS: Thirty patients were enrolled in the study and were divided into survivors and non-survivors. The initial NT-proBNP levels were significantly higher among non-survivors in contrast to the initial cTnI and CK-MB levels. The study identified that the best cutoff point of NT-proBNP for predicting mortality was ≥72 pg/ml, with AUC (0.869). CONCLUSION: It can be concluded that NT-proBNP can serve as an early predictor of mortality in ALP poisoning.

Metal phosphide poisoning in a disaster-stricken area. Can early hemodialysis improve outcomes?

BACKGROUND: Phosphide metal poisoning results in tens of thousands of fatalities per year worldwide. The mortality in critically ill patients often exceeds 50%. The available treatment is supportive and there is no antidote. Dialysis is recommended to treat advanced complications but has not been prescribed early in the process. In this study we report our experience in using dialysis in the early hours of presentation of the patients and suggest it can favorably improve the prognosis. We also draw attention to the risk of suicide under conditions of chronic conflict such as those in northwestern Syria, and to the lack of necessary mental health support for patients after suicide attempts. METHODS: Retrospective review of records of patients poisoned with aluminum phosphide and admitted to critical care facilities in northwestern Syria between July 2022 and June 2023. RESULTS: During the observation period 16 cases were encountered. Suicide was the reason of the poisoning in 15 patients, the median patient age was 18 years and over two thirds of the patients were female. Early dialysis was used in 11 patients who were critically ill and their mortality rate was 18%. CONCLUSIONS: Phosphide metal poisoning is common in the disasters stricken area of northwestern Syria. Most cases are suicidal and impact young females. Early dialytic interventions may favorably impact the outcomes.

Poisoning cases and their management in Amhara National Regional State, Ethiopia: Hospital-based prospective study.

BACKGROUND: Poisoning is a significant public health problem globally. Ethiopia is a low-income country undergoing technological and social change that may increase access to drugs and chemicals, potentially increasing the incidence of poisoning. This study describes the epidemiology of hospital admissions due to poisoning in a region of Ethiopia. METHODS: An institution based prospective observational study was employed, as a study design, in selected hospitals of the region from January to December 2018. RESULTS: Of 442 poisoning cases, 78 (17.6%) died. Almost all poisoning cases were intentional self-poisonings. The most frequent poisonings were organophosphate compounds, 145 (32.8%), and metal phosphides (majorly aluminum phosphide), 115 (26.0%). The ingested poison was most frequently accessed from the patients' homes, 243 (55.0%), followed by purchases from local shops, 159 (36%). The median duration of admission was 24 hours. Of all the cases, 23 (5.2%) were admitted to intensive care units (ICU) requiring mechanical ventilation. Most of the cases admitted to the ICU were aluminum phosphide-poisoned patients. The majority of deaths (43 of 78) were due to metal phosphides. From the multivariate logistic regression analysis, altered level of consciousness on hospital arrival, metal phosphide poisoning, and no laboratory result as a part of the diagnosis process or investigation of the extent of toxicity were found to be significantly associated with the likelihood of poor treatment outcome. CONCLUSION: The majority of the poisoning cases were females. The most common reasons for the intent of self-poisoning were dispute-related, mainly family disharmonies, followed by psychiatric conditions. The poisoning agents were mostly obtained from households. Organophosphate compounds and metal phosphides were the first and the second most frequently encountered poisoning agents, respectively, and it was noted that the later ones were responsible for most of the fatal cases. Of the pharmacologic interventions, atropine was the only agent regarded as an antidote. The most commonly employed agent for supportive treatment was cimetidine followed by maintenance fluids, while gastric lavage was the only GI decontamination method used among others. The fatality rate of poisoning in this study was found to be much higher than in other similar studies. Impaired consciousness upon hospital arrival, metal phosphide poisoning, and no involvement of laboratory investigation were found to significantly associate with the likelihood of death. Generally, the results dictate the need for the design and implementation of strategies to create awareness, prevent, and manage poisoning incidences in the community.

Gastrointestinal decontamination using oil-based solutions in patients with acute aluminum phosphide poisoning: a systematic review and meta-analysis.

Some studies suggested that gastrointestinal (GIT) decontamination with oil may improve the prognosis of patients who ingested aluminum phosphide (AlP). The aim of this study is to compare the efficacy and safety of gastric lavage with oil-based solutions to any method of gastric decontamination not using oils in patients presenting with acute AlP poisoning. The literature was searched for English-published randomized controlled trials (RCTs) from inception to 16 September 2023. The searched electronic databases included MEDLINE/PubMed, Cochrane Library, Web of Science, Egyptian Knowledge Bank, Scopus, and Google Scholar. Data were extracted and pooled by calculating the risk ratio (RR) for categorical outcomes and standardized mean difference (SMD) for numerical outcomes, with 95% confidence intervals (CI). Seven RCTs were included. Paraffin oil was significantly associated with a lower risk of mortality (RR = 0.59 [95% CI: 0.45, 0.76], p < .001), intubation (RR = 0.59 [95% CI: 0.46, 0.76], p < .001) and vasopressor need (RR = 0.71 [95% CI: 0.56, 0.91], p = .006). Survival time was significantly prolonged with paraffin oil (SMD = 0.72 [95% CI: 0.32, 1.13], p < .001). Coconut oil was significantly associated with prolonged survival time (SMD = 0.83 [95% CI: 0.06, 1.59], p = .03) as well as decreased risk of requiring intubation (RR = 0.78 [95% CI: 0.62, 0.99], p = .04). Oil-based GIT decontamination using paraffin oil showed benefits over conventional lavage regarding the incidence of in-hospital mortality and endotracheal intubation, and survival time. Coconut oil showed some benefits in terms of the intubation incidence and survival time. Decontamination using paraffin oil is recommended. Future clinical trials are warranted with larger sample sizes and focusing on cost-benefit and safety.

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.

Validation of Corrected and Dispersed QT as Predictors of Adverse Outcomes in Acute Cardiotoxicities.

Acute cardiovascular poisoning is a major cause of adverse outcomes in poisoning emergencies. The prognostic validity of corrected QT (QTc) and dispersed QT (QTd) in these outcomes is still limited. The present study aimed to determine the risk factors of mortality, adverse cardiovascular events (ACVE), and intensive care unit (ICU) admission in patients with acute cardiovascular toxicities and assess the validity of QTc and QTd intervals in predicting these outcomes. This study was conducted on adult patients admitted to Tanta University Poison Control Center with a history of acute cardiotoxic drugs or toxins exposure. The demographic and toxicological data of patients were recorded. Clinical examination, routine laboratory investigations, ECG grading, and measurement of QTc and QTd were performed. The patients were grouped according to their adverse outcomes. Among the included patients, 51 (31.48%) patients died, 61 (37.65%) patients had ACVE, and 68 (41.98%) patients required ICU admission. The most common cause of poisoning is aluminum phosphide, followed by cholinesterase inhibitors. QTd and QTdc showed no significant difference among outcome groups. The best cut-off values of QTc to predict mortality, ACVE, and ICU admission were > 491.1 ms, > 497.9 ms, and ≥ 491.9 ms, respectively. The derived cut-off QTc values were independent predictors for all adverse outcomes after adjusting for poison type, serum HCO3, and pulse. The highest odds ratios for all adverse outcomes were observed in aluminum phosphide poisoning and low HCO3 < 18 mmol/L. Thus, serum HCO3 and QTc interval should be monitored for acute cardiotoxicities, especially in aluminum phosphide and cholinesterase inhibitors poisoning.

Complicated central catheterization in atypical celphos poisoning simulating throttling homicide: Review of neck resuscitation artefacts.

Therapeutic artefacts are a challenge for forensic pathologists for correct interpretation at autopsy. A 23-year-old female was found unconscious at home and immediately admitted to an emergency of a tertiary care hospital where resuscitative measures were taken. However, she died after 4 h of hospitalization. The injuries (abrasions, subcutaneous bruising and haemorrhage in the deep structures of the neck) discovered at autopsy simulated the findings of throttling and aroused the suspicion of homicide. Later, enquiry revealed that it happened due to mal-positioned central line in the carotid artery during internal jugular vein access to provide fluid as the patient was in shock due to aluminium phosphide (Celphos)poisoning. The bleeding diatheses in Celphos poisoning might have precipitated the extensive neck haemorrhage in this case.

Three Years Analysis Of Poisoning Cases Of Forensic Medicine Toxicological Laboratory, Khyber Medical College, Peshawar.

BACKGROUND: Poison is defined as any substance which harms, endangers or even kills a person irrespective of the quality or quantity. Pakistan is a developing country and farming is the major occupation of the majority of the population. Due to the easy availability and increased use of pesticides, the accidental and suicidal poisoning is very common. The objective of the study is to find out the most common poison used by the people in the general population and its frequency in our setup. METHODS: The present cross-sectional study with retrospective data collection was undertaken in the Department of Forensic Medicine, Khyber Medical College (KMC) Peshawar to determine the frequency of different poisons detected in various samples brought to the toxicological laboratory. A three-year data (1stJanuary 2014 to 31 December 2016) was retrieved from Forensic Laboratory of KMC, Peshawar. Different methods were used for the detection of poisons. All the cases coming from Khyber Pakhtunkhwa province were included whereas; cases from other provinces were excluded. RESULTS: The study revealed that poisoning was more common among females and the most common age group affected was 21-25 years. The incidence of positive cases was more in Peshawar district followed by Swat district. The common poison detected was phosphine (wheat pill). CONCLUSIONS: Female and young people from Peshawar and Swat are more prone to Aluminum Phosphide (wheat pill) poison. It is a dangerous and lethal poison, so healthcare workers at emergency department ought to be prepared for such cases. Furthermore, its routine use as a domestic pesticide has to be strictly prohibited by creating awareness among the public.

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.

Epidemio-toxicological profile of poisoning cases - A five years retrospective study.

Poisoning is recognized as a major factor for deaths in majority of low-income and middle-income countries. Although it is considered as a global burden, the nature of poisoning may vary in different areas across the world. The Charutar region in the state of Gujarat in western India has a unique topography and cultivation practises which sets it apart from the rest of the state. Due to the dearth of studies pertaining to the access of the population at this area to different types of poisons and pattern of poisoning, we planned this study to find magnitude, morbidity and mortality of poisoning with a specific consideration of gender, age and poison in contrast to the usual adopted cumulative approach. In a retrospective study, 1092 cases were identified as poisoning cases. The study revealed a higher vulnerability to poisoning in males, married individuals, during the third decade of life, from rural areas, due to accidental causes, during day time events and during the monsoon seasons. The gender specific approach clarified additional comparative data. More deaths were reported from suicidal poisoning than accidental ones. 49 specific poisons were found in the study, among which accidental snake bite poisoning, insecticidal substances and aluminium phosphide were prevalent. Aluminium phosphide and quinalphos were responsible for the highest fatalities (in terms of number of persons died). Gender predominance was observed for specific poisons. Age wise distribution of specific poisons was derived. Treatment duration and survival period for specific poisons were calculated.

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.

The effects of amiodarone prophylaxis on cardiac dysrhythmia in acute aluminium phosphide poisoning.

Cardiovascular toxicity is the most common cause of fatality in the first 24 hours of poisoning with aluminium phosphide (AlP). Most often manifesting itself in cardiac dysrhythmias. The aim of this study was to evaluate the benefits of amiodarone prophylaxis against cardiac dysrhythmia in 46 patients with acute AlP poisoning. They were divided in two groups of 23: one receiving amiodarone and the other not (control). The treatment group received amiodarone prophylaxis in the initial intravenous bolus dose of 150 mg, followed by a drip of 1 mg/min for six hours and then of 0.5 mg/min for eighteen hours. Both groups were Holter-monitored for 24 hours since admission. Save for amiodarone, both groups received the same standard treatment. Amiodarone had a significant beneficial effect in reducing the frequency of ST-segment elevation and ventricular fibrillation plus atrial fibrillation (P=0.02 and P=0.01, respectively), but the groups did not differ significantly in mortality (9 vs 11 patients, respectively). The mean time between ICU admission and death (survival time) was significantly longer in the treatment group (22 vs 10 h, respectively; P=0.03). Regardless its obvious limitations, our study suggests that even though amiodarone alone did not reduce mortality, it may provide enough time for antioxidant therapy to tip the balance in favour of survival and we therefore advocate its prophylactic use within the first 24 h of AlP poisoning.

Impact of extra-corporeal membrane oxygenation on outcome of aluminium phosphide poisoning complicated with myocardial dysfunction.

Background: Aluminium phosphide (AlP) poisoning is associated with a high mortality rate when patients are complicated with myocardial dysfunction and refractory shock or severe metabolic acidosis. We studied the role of veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) in patients of AlP poisoning induced myocardial dysfunction. Methods and results: This is a tertiary care, single-centre, retrospective study. Between January 2011 and June 2016, total of 107 patients with AlP poisoning were identified and of those 67 were categorised in high-risk category as per the criteria. The in-hospital mortality of patients who received ECMO (n = 35) was compared to those who received conventional treatment (n = 32) only. The use of ECMO in addition to conventional treatment has reduced the in-hospital mortality from 84.4% to 40% (odds ratio: 0.47; 95% confidence interval 0.31-0.73). Among survivors, the ECMO group had a significantly lower baseline left ventricular ejection fraction (LVEF; median: 24%; IQR: 22-29 vs. median: 32%; IQR: 32-33.5; p < .003) but a non-significantly higher LVEF at the time of discharge (median: 52%; IQR: 48-60 vs. median: 48%; IQR: 47-49; p: .064) than did the conventional group. On logistic regression analysis the higher sequential organ failure assessment (SOFA) score, lower pH and the non-usage of ECMO were found to be the independent predictors of mortality. Conclusion: The use of ECMO in high-risk patient of AlP poisoning has resulted in a significant reduction in the mortality. A high baseline SOFA score has been found to be the independent predictor of mortality.

Adjuvant potential of selegiline in treating acute toxicity of aluminium phosphide in rats.

Aluminium phosphide (AlP) is a highly toxic substance with a high mortality rate and no effective antidote. Once exposed to the moisture and acidic conditions of the stomach, AlP releases toxic phosphine (PH3 ) gas, which results in severe toxicity in poisoned subjects. Selegiline is a monoamine oxidase inhibitor with antioxidant and anti-apoptotic properties, which is mostly prescribed for the treatment of mood disorders and Parkinson's disease. Since AlP has detrimental effects on cardiac physiology and mitochondrial function, we tested the protective effects of acute selegiline treatment on cardiac mitochondrial function, redox status and electrocardiographic parameters in rats after AlP poisoning. To do this, AlP was given to rats by gavage to induce toxicity. Selegiline was injected intraperitoneally in the treatment groups 1 hour after AlP poisoning. Selegiline treatment after AlP intoxication was not associated with a significant difference in the mortality rate of animals. However, selegiline reduced oxidative stress (decreased the reactive oxygen species and malondialdehyde) and increased glutathione in the cardiac tissue of rats exposed to AlP. Further, the mitochondrial membrane potential (ΔΨm) collapse reversed after treatment with selegiline. Selegiline also improved the electrocardiographic (ECG) parameters and enhanced heart rate. The histopathological evaluation revealed that selegiline eliminated the inflammation and injuries induced by AlP in the stomach and duodenum, as well as cardiac tissue. In conclusion, selegiline treatment can ameliorate the AlP-induced cardiac and gastrointestinal injuries in rats via boosting redox status and mitochondrial function with no significant effect on survival. We suggest that using selegiline, apart from other clinical treatments, may improve the quality of treatment process for AlP toxicity.