Abstract
Background: the ingestion of wheat or rice pills poses a significant challenge in medical treatment due to their high mortality rate. In countries like pakistan, factors such as easy accessibility, inadequate safety regulations, low literacy rates, and a large population living below the poverty line contribute to both unintentional and intentional overdoses. The main toxic compounds found in rice pills, zinc or aluminium phosphide, are extremely harmful to the human body. The absence of an antidote or established treatment protocols further complicates the management of patients who present to emergency departments after ingestion.
Objective: the review aims to investigate existing literature on therapeutic interventions for individuals experiencing wheat pill poisoning. By synthesizing this information, it seeks to offer a summary that could serve as a basis for future research endeavours aimed at establishing standardized guidelines and management protocols for acute from wheat pill ingestion.
Methodology: a review was conducted across four databases (google scholar, pubmed, cochrane library and up-to-date) to identify various therapeutic modalities used for the treatment of patients presenting with wheat pill poisoning.
Results: we identified 57 publications, consisting of case reports, case series, clinical trials and literature reviews highlighting various aspects of management, complications, and outcomes.
Conclusion: while there is no specific antidote for wheat pill toxicity, supportive measures favour positive outcome. The authors have compiled and organised the findings from the limited evidence to serve as an initial guide for the development of a more comprehensive, evidence-based, and rigorously tested clinical guideline. The purpose is to facilitate the management of such patients presenting to the ed until more robust guidelines can be established through research and clinical testing.
Keywords: rice pills; therapeutic dilemma; wheat pill toxicity
Introduction
Wheat pill, also known as rice pill, is a cost-effective rodenticide frequently employed in developing nations to safeguard food crops like rice and wheat from infestation. In pakistan, an agricultural nation producing approximately 27 million metric tonnes of wheat and 8 million metric tonnes of rice annually, the use of wheat pill, containing aluminium phosphide (alp), is extensive1. To combat rodent damage, a considerable quantity of wheat pill is required, with an average recommendation ranging from 2 to 5 pills per ton of crop1.
The active ingredient in wheat pill is either zinc or aluminium phosphide (alp), typically constituting around 56% of the formulation. This primary component remains inert until it meets moisture, at which point it undergoes a chemical reaction, converting into phosphine gas2. Phosphine gas is colourless, highly inflammable, and has a garlicy odour. It is a potent enzyme inhibitor that generates free radicals in the human body. This results in high cellular toxicity and adverse effects manifest within hours of inhalation, with rapid deterioration and death within the first 24 to 72 hours3. The ingestion of the wheat pill produces phosphine intoxication when the solid phosphide reacts with the gastric contents causing necrosis of the gastrointestinal tract, kidney, and liver. The phosphine gas produced also causes pulmonary damage as it is inhaled. The multiorgan involvement can culminate in rapid death4.
The wheat pill is widely used in developing countries for deliberate self-harm (dsh) and suicide due to its easy availability, coupled with factors such as low literacy rates, lack of awareness, and socio-economic disparities. The incidence of poisoning resulting from the ingestion of wheat pills has been reported to be around 2.7%5. However, the lack of a centralised reporting and data collection system, combined with social stigmata may contribute to under-reporting, suggesting that the actual incidence of wheat pill poisoning is much higher than reported. This underscores the necessity for preventive vigilance at a national level, through a series of effective public awareness campaigns, enforcing stringent regulatory oversight and establishing governance mechanisms for the distribution, usage, and toxicity of wheat pills.
Despite ample literature on the epidemiology, aetiology, mechanism of action, and outcomes associated with wheat-pill poisoning, there remains a notable dearth of information concerning its management. Currently, there is no antidote available for wheat pill poisoning. Consequently, treatment primarily revolves around supportive measures aimed at addressing the systemic effects of phosphine gas and preventing associated complications3. There are several case reports of successful and unsuccessful treatment, no very little consolidated evidence that may be used as guidance for better outcomes. This view aims to consolidate various therapeutic options, albeit primarily supportive, to generate a comprehensive summary. The goal is to propose a skeletal management outline with potential for further research and development of evidence-based standardizes guidelines for the management of patients presenting to the emergency department (ed) with acute toxicity following wheat pill ingestion.
Materials & methods
A broad-based literature review was conducted to include four electronic databases (google scholar, pubmed, cochrane library, up-to-date), grey literature, reference lists and bibliographies. Using the keywords [wheat pill + management + treatment], literature in the english language from the last decade (2014 - 2024) was examined for various therapeutic options, complications, and outcomes. Autopsy reports, opinions, comments, polypharmacy, mass exposure with multiple victims, letters to the editor, and studies on animals were excluded. Patients whose initial ed management was not mentioned or died within minutes of arrival, were also excluded as they would not have had sufficient time for management beyond cardiopulmonary resuscitation (cpr). Case reports, case series, clinical trials and studies, and literature reviews were all included to gather a broad spectrum of knowledge.
Results
The initial search showed 17,700 publications, titles of which were populated on microsoft excel (version 16.82) spreadsheet to identify and exclude duplicates. Following this, above-mentioned exclusion criteria were applied to the titles and screened for relevance, leaving 111 publications for thorough scrutiny. Two independent reviewers carefully examined the abstracts of these remaining articles and after applying exclusion criteria, 57 publications were deemed suitable for thorough exploration for this narrative review. These included eighteen case reports/series6-24, twenty-three clinical studies25-46 and sixteen literature reviews47-62.
Discussion
Clinical course
The clinical course of wheat pill poisoning resembles a roller coaster ride. In the initial 24 hours, the patients may experience a dramatic progression from mild symptoms like tachycardia to multiorgan involvement and potential cardiorespiratory arrest7,11,13. Subsequently, over several days, the condition fluctuates between periods of improvement and deterioration before gradually showing signs of improvement, typically by the end of the first week. Full recovery can take days to months7,13,15,20.
The severity of toxicity and the onset time of initial symptoms may or may not be directly related to the dose of the toxin, as insufficient evidence exists in the literature to establish a clear correlation. In general, the effects of toxicity can start manifesting from as early as 30 minutes6. The most common presenting complaints in acute phase are vague abdominal cramps, nausea, and vomiting6-20. The earliest clinical finding is tachycardia (110 -140 beats/min), followed by a sudden rapid fall in blood pressure (bp), increase in respiratory rate (rr) and a drop in the oxygen saturations (spo2), in this order6-24. The commonly noted biochemical abnormalities are metabolic acidosis within the first 6 -12 hours, deranged liver function tests (lfts) over 1-3 days and raised creatinine levels (acute kidney injury aki secondary to renal excretion of phosphine). Refractory shock and cardiac rhythm problems, ventricular tachycardia (vt) being most common, ischemic changes on ecg, global hypokinesia and transient reduction in left ventricular ejection fraction (lvef) are reported in most cases, requiring aggressive intervention6,10. Most of the cardiac complications occur within the first 24 hours and myocardial injury is usually reversible10. Severe metabolic acidosis and cardiotoxicity are the earliest and most common causes of early mortality within 24 hours of ingestion23,27.
Diagnosis is mostly clinical with relevant history and garlic odour-of breath. Several diagnostic tests are available. The most valuable diagnostic and prognostic tools in these patients are point-of-care blood gas analysis (metabolic acidosis), ecg (anterolateral ischemia and arrythmias), blood lactate levels, and bedside echocardiography (global hypokinesia and lvef measurement)6-23,34.
Therapeutic conundrum
This review highlights the challenges posed by the lack of a specific antidote for phosphine poisoning, coupled with its high cellular toxicity and rapid progression, which limit the window for effective treatment. Nonetheless, there are promising supportive treatment options that have demonstrated the potential to significantly reduce mortality17. For instance, in eighteen of the case reports, consisting of ninteen patients, varied supportive therapeutic measures in the acute phase showed a survival rate of nearly 80%6-24. The conventional supportive therapy commonly found in most literature typically includes a combination of some or all the following measures: gastric lavage (gl), oxygen (o2), sodium bicarbonate (nahco3), intubation and mechanical ventilation, intravenous (iv) fluids, inotropes, antiarrhythmic agents, n-acetylcysteine (nac) and magnesium sulphate (mgso4). Additional interventions such as haemodialysis, renal replacement therapy (rrt), extracorporeal membrane oxygenation (ecmo), intra-aortic balloon pump (iabp) and lipid emulsion therapy are showing promising results15,19-21.
Gastric lavage (gl)
Gl is the mainstay of treatment in the acute phase as it helps decontamination of the gastrointestinal tract (git). It should be performed as soon as possible, as it is most effective during the first two hours of exposure. The choice of agent for gl has been a topic of interest with many clinical trials focusing on this aspect of management22. Oil-based gl is recommended as it creates a protective mechanical barrier over the git mucosa, reducing breakdown of alp to phosphine as well as slowing systemic absorption of phosphine gas. Both saturated (paraffin oil) and unsaturated (coconut, vegetable) oils may be used. The addition of 8.4% nahco3 to the lavage oil has the added benefit of further inhibiting the release of phosphine by neutralising the gastric acid. Another popular gl cocktail is a combination of potassium permanganate and activated charcoal. Here, the phosphine gas released from the breakdown of the wheat-pill is oxidised to potassium phosphate and aluminium permanganate, which adhere to the activated charcoal, reducing absorption into the git. Water-based and saline gl are strongly discouraged as phosphine is highly water- soluble resulting in adverse outcome26,30,48, 51.
1. Intravenous fluid therapy
Patients with wheat pill poisoning tend to develop a sudden dramatic drop in their bp resulting in rapid infusion of large volumes of iv fluids. While, early use of iv fluids should be initiated, aggressive fluid therapy can be counterproductive. After initial fluid replacement with one litre of crystalloids, further fluid therapy should be judicious, guided by clinical parameters such as urine output, cvp measurement, invasive bp monitoring (arterial line) and bedside assessment of the inferior vena cava (ivc) using point-of-care ultrasound (pocus). Overenthusiastic fluid resuscitation carries the risk of developing refractory shock10-15.
2. Oxygenation, intubation & mechanical ventilation
Respiratory features in case of ingestion are often a late sign and so low-dose prophylactic o2 (1 – 4 l/min) therapy should be started in all patients. It is crucial to monitor for hypotension and tachypnoea, as these are often rapidly followed by hypoxia necessitating intubation and mechanical ventilation.
3. Sodium bicarbonate (nahco3)
One of the main features of what pill toxicity is resistant metabolic acidosis. It is one of the first biochemical changes seen in these patients. Repeat doses of 8.4% nahco3 are usually required and may need to be continued for 24 hours or beyond.
Ionotropic support
In case of refractory shock and persistent metabolic acidosis, ionotropic support should be started early and may need to be continued for several days. While any combination of noradrenaline, dobutamine and vasopressin may be required, in the ed noradrenaline is preferred6,11.
Dopamine
Low-dose dopamine (4-6 mg/kg/min) should be considered for adequate hydration and renal perfusion in refractory shock.
Magnesium sulphate (mgso4)
Over the last decade, mgso4 has surfaced as an important therapeutic agent in various life-threatening conditions. In the case of phosphine intoxication, early administration of iv mgso4 plays a significant role in preventing fatal arrythmias. Its membrane stabilizing and antioxidant properties reduce the oxidative stress level of the myocardium, rendering it cardioprotective, subsequently reduce mortality by up to 50%15. The exact dose remains to be determined, however a stat dose followed by divided doses to a total of 12-20g in the first 24 hours is likely to be beneficial22,23,27.
1. N-acetylcysteine (nac)
Over the recent years, nac has emerged as an important adjunct to supportive management in wheat pill poisoning33,50,58. Nac prevents hepatic necrosis. High dose of nac (300mg/kg for 20 hrs) is associated with reduced myocardial oxidative stress, thereby reducing the risk of cardiac arrythmias. Lower doses (140mg/kg loading dose, followed by 70 mg/kg iv every four hours) has been shown to reduce duration of mechanical ventilation and hospital length of stay.
2. Haemodialysis, ecmo, iabp
Once multiorgan involvement sets in, persistent refractory shock, low lvef, severe metabolic acidosis, aki and other complications occur, placing the patient on a downhill path. Timely intervention with a combination of renal replacement therapy (rrt), haemodialysis, ecmo, and iabp has shown good outcomes. Recent studies have reported good outcomes with the use of ecmo7,13,20,23,24. Early institution of ecmo, before significant decline in levf is likely to give the best outcome. In a case report, daliri et al reports a patient with phosphine toxicity on whom ecmo was initiated after a prolonged cpr. The patient’s ef improved from less than 5% to 55% over the course of a few days13. Where advanced technology is not available, iabp should be considered as this has also shown good outcomes15,21,24.
3. Novel therapies
Several novel therapies have come to light in recent literature with promising results, but a significant amount of research work needs to be done before they may be considered safe and efficient. One of these novel therapies is lipid emulsion. The potential role of lipid emulsion is being explored to see its utility in wheat pill / phosphine gas poisoning. Taalab y et al 2022, and elabdeen s et al 202, have conducted clinical trials with promising results in increasing survival time32,35. The administration of 20% lipid emulsion infused at the rate of 10ml/hr is considered safe. Further studies are required to establish the full benefits of lipid emulsion therapy. Insulin is another drug under the spotlight22,36 to assess its role in management of wheat pill toxicity. Two studies conducted by sedaghattalab m et al 2022, adel b et al 2023 have shown that insulin-euglycemic therapy is safe and effective in the first six hours after ingestion. Overall mortality and need for mechanical ventilation are also lower in these patients.
4. Miscellaneous
Several other supportive modalities have been used such as exchange transfusions, diuretics to prevent fluid overload, l-carnitine, and other anti-oxidants such as melatonin and vitamins e &c. Further studies are required to determine the extent of benefit these additional therapies might provide.
Proposed management approach
Although the evidence is weak and inadequate to formulate a guideline, the authors propose the following holistic management plan for consideration when dealing with patients suffering from acute wheat pill poisoning. This proposed approach needs to be validated through robust clinical trials. The authors recommend that all patients who have ingested wheat pills should be promptly managed in the critical area of the emergency department (ed). This recommendation is made because of the aggressive nature of wheat pill toxicity, necessitating immediate initiation of treatment to mitigate its adverse effects. (table 1) summaries the proposed management approach to patients presenting to the ed with acute wheat pill poisoning.
Table 1. Proposed approach to wheat pill toxicity in the ed
Acute wheat pill poisoning (ed) | |
Preferably within 2 hours Of ingestion | Triage to high acuity area such as the resuscitation room |
Focused history, establish time of ingestion | |
Continuous monitoring Maintain observation chart (eg. News) | |
Oxygen therapy | |
iv access (2 large bore cannula) | |
Point-of-care tests: (blood gas analysis, ecg, random blood glucose) | |
Oil-based gastric lavage (paraffin / coconut / vegetable) with 8.4% nahco3 Repeat gl every few minutes until lavage fluid is clear | |
Iv fluids (isotonic saline or ringer’s lactate) | |
Laboratory investigations: complete blood picture, renal profile, liver profile, s electrolytes, blood lactate levels | |
Metabolic acidosis | Intravenous nahco3 (8.4%) |
Tachycardia (unresponsive to iv fluids therapy | Iv mgso4 (loading dose 4g) |
Iv nac (loading dose: 140 mg/kg) | |
Adjuvant antioxidants (if available): vitamin c & vitamin e | |
Process for icu admission | |
Hypotension / refractory shock | Noradrenaline / norepinephrine infusion Dopamine infusion Consider lipid emulsion therapy (20% @ 10ml/hr |
Hypoxia |
Intubate and ventilate (sedation: midazolam; paralysis: rocuronium) |
Monitoring | 1. Non-invasive bp (arterial line) 2. Volume assessment: a. Pocus to assess ivc b. Cvp monitoring 3. Intake/output monitoring: foley’s catheter, i/o chart |
Prepare for icu admission as soon as possible | |
Consider further management of complications (in ed or icu) (with expert multidisciplinary input) | |
Cardiopulmonary arrest | Cardiopulmonary resuscitation as per acls/als guidelines |
Cardiogenic shock with severe lvf dysfunction | Iabp Ecmo Euglycemic-insulin therapy |
Broad-complex tachycardia | Cardioversion +/- antiarrhythmics depending on hemodynamic status of the patient |
Heart block | Pacemaker |
Deranged liver function tests | No intervention required, will resolve spontaneously as the patient starts to recover |
Acute kidney injury | Haemodialysis, rrt |
Ttp | Consider: prednisolone, therapeutic plasma exchange, prbcs |
Conclusion
Wheat pill poisoning represents a grim reality, characterized by a high mortality rate ranging from 40% to 91%. Despite the absence of a specific antidote, various supportive therapeutic interventions are available. Timely initiation of these treatments holds the potential to reduce mortality rates17. However, to devise a comprehensive and effective treatment strategy, there is a pressing need for multicentre, large-scale studies. Such studies are essential for synthesizing evidence-based, time-specific, and aggressive treatment protocols aimed at enhancing patient care and outcomes.
Limitations
The literature on wheat pill poisoning is diverse and often lacks crucial information, particularly regarding medication doses and treatment timelines. This dearth of comprehensive data poses challenges in reaching solid, evidence-based conclusions.
Ethical approval
This research does not contain any human subjects.
Disclaimer
The views expressed in this narrative review are those of the authors and do not reflect the official policy of affiliated institutes.
References
1. Raza a. Pakistan: grain and feed annual. Usda foreign agricultural service 2024.
2. Ghazi ma. Wheat pill (aluminium phosphide) poisoning”; commonly ignored dilemma. A comprehensive clinical review. Professional med j 2013;20(6):855-863.
3. Phosphine: lung damaging agent. Cdc.gov 2024.
4. Tintinalli je, john o, yealy d, et al. Tintinalli’s emergency medicine: a comprehensive study guide, 9th edition. 9th ed 2019
5. Dabholkar s, pirani s, davis m, khan m, eddleston m. Suicides by pesticide ingestion in pakistan and the impact of pesticide regulation. Bmc public health 2023;23(1):676.
6. Ben ghezala h, ben jazia a, saad s, brahmi n. Fatal aluminium phosphide poisoning associated with brugada electrocardiographic pattern: an exceptionalcase report. Ann toxicolanal 2024;36(1):70-74.
7. Shi l, jian t, tao y, et al. Case report: acute intoxication from phosphine inhalation. Int j environ res public health 2023;20(6):5021.
8. Alpaslan m. Rapid death from aluminium phosphide poisoning. Eur j toxicol 2023;5(1):11-13.
9. Alizadeh n, borran m, behnoosh b, dianatkhah m. A rare case of aluminium phosphide induced thrombotic thrombocytopenic purpura. J pharm care 2021;9(3)
10. Akkaoui m, achour s, abidi k, et al. Reversible myocardial injury associated with aluminium phosphide poisoning. Clin toxicol (phila) 2007;45(6):728-731.
11. Katwal s, malbul k, mandal sk, et al. Successfully managed aluminium phosphide poisoning: a case report. Ann med surg (lond) 2021;70(102868):102868.
12. Hallaj s, student research committee, tabriz university of medical sciences, tabriz, iran. Successful management of an aluminium phosphide poisoned patient following ventricular tachycardia. Int j med toxicol forensic med 2020;10(4):30473
13. Daliri m, hosseini s, amin a, et al. Possible role of ecmo in multiorgan failure and prolonged cpr: aluminium phosphide poisoning. Asia pacific j med toxicol 2020;9(4):154-158.
14. Anjum z, habib mn, tariq z, ali s. Inhalational wheat-pill poisoning: a household chemical warfare agent. Cureus 2019;11(9):e5597.
15. Mehrpour o, asadi s, yaghoubi ma, azdaki n, mahmoodabadi n, javadmoosavi s. Cardiogenic shock due to aluminium phosphide poisoning treated
withintra-aortic balloon pump:a report of two cases. Cardiovasc toxicol 2019;19(5):474-481.
16. Çakın o, tazegul g, gümüş a, cengiz m, ramazanoğlu a. Incidental aluminium phosphide poisoning: case report and current management. Folia med (plovdiv) 2018;60(3):464-467.
17. Bansal p, giri s, bansal r, tomar l. Survival in a case of aluminium phosphide poisoning with severe myocardial toxicity. Indian j health sci biomed res 2017;10(3):343.
18. Issa s, hafez e, al-mazroua m, saad m. Fatal suicidal ingestion of aluminium phosphide in an adult syrian female-a clinical case study. J of pharmacol clinical toxicology 2015;3(5).
19. Bhatnagar s, pal v. Rare survival after severe aluminium phosphide poisoning after myocarditis with l-carnitine and steroid. Int j pharm pahrma sci 2015 (9):522-523.
20. Hakimoğlu s, dikey i, sarı a, kekeç l, tuzcu k, karcıoğlu m. Successful management of aluminium phosphide poisoning resulting in cardiac arrest. Turk j anaesthesiol reanim 2015;43(4):288-290.
21.Mehrpour o, amouzeshi a, dadpour b, et al. Successful treatment of cardiogenic shock with an intraaortic balloon pump following aluminium phosphide poisoning. Arh hig rada toksikol 2014;65(1):121-126.
22. Sedaghattalab m. Treatment of critical aluminium phosphide (rice tablet) poisoning with high-dose insulin: a case report. J med case rep 2022;16(1):192.
23. Sharma r, mukherjee s, chaturvedi k, sharma n, khoj l, bansal r. Venoarterial extracorporeal membrane oxygenation in aluminium phosphide poisoning: a
case report. J pediatrcrit care 2023;10(2):80.
24. Dukhin o, bala d, felker e, et al. Case report: combination of veno-arterial extracorporeal membrane oxygenation and intra-aortic balloon pump in a young male patient with refractory cardiogenic shock due to aluminium phosphide poisoning. Front cardiovasc med 2023;10:1226827.
25. Elsharkawy re, ghonem mm, el-sarnagawy gn, nagy aa, heshmat mm. Cardioprotective role of the coenzyme q10 and coconut oil in acute aluminium phosphide poisoning: a randomized controlled clinical trial. Toxicol res (camb) 2023;12(3):507-519.
26. Elbastawesy s, elmansy a. Comparison between gastric lavage with paraffin oil versus coconut oil in acute aluminium phosphide poisoning: a randomized controlled clinical trial. Ain shams j forensic medicine and clinical toxicology 2023;40(1):1-14.
27. Khalaf m, amin f, hishmat a. Outcomes of acute aluminium phosphide poisoning and role of magnesium sulfate as an antidote in minia poisoning control center. The egyptian jforensic sci appl toxicol 2023;23(4):135-148.
28. Abdelkader m, elsayed r, shokry m. Pattern and outcome of acute aluminium phosphide intoxicated cases at sohag university hospitals: special consideration to paraffin oil as a supportive treatment. Zagazig j forensic med 2023;21(1):133-156.
29. Sobh zk, ghanem m, kholief m. Physicians’ perspectives on different therapeutic approaches for aluminium phosphide poisoning and their relevant outcomes. Toxicol res (camb) 2023;12(4):615-625.
30. Helal ne, lashin hi, nagy aa, shama ma, mostafa t, wahdan aa. Potential role of paraffin oil gastric lavage in acute aluminium phosphide poisoning: a randomized controlled trial. Environ sci pollut res int 2022;29(22):33844-33855.
31. Malve h, more d, wankhede m. Management of aluminium phosphide poisoning with a holistic approach at nhl municipal medical college and hospital,
ahmedabad. J forens sci med 2022;8(1):6.
32. Taalab y, helmy m, el -hassan a. Evaluation of the role of intravenous lipid emulsion as a putative treatment for acute aluminium phosphide poisoning. Mansoura j forensic medicine and clinical toxicology 2022;30(1):71-84.
33. Ashraf s, nazar t, aziz b, farooq h, nazar n. Effect of n-acetylcysteine therapy on mortality rate in patients of acute aluminium phosphide poisoning. Esculapio 2022;18(3):324-328.
34. Bogale de, ejigu bd, muche ta. Clinical profile and treatment outcome of aluminium phosphide poisoning in felege hiwot referral hospital, northwest ethiopia: a retrospectivestudy. Open access emerg med 2021;13:239-248.
35. Elabdeen s, saad k, oreby m, elgazzar f. Assessment of intravenous lipid emulsion as an adjuvant therapy in acute aluminium phosphide poisoning: a randomized controlled trial. Ain shams j forensic medicine and clinical toxicology 2020;34(1):51-68.
36. Adel b, elgharbawy nm, shahin mm, abo-elfadl aa, saad km. Insulin-euglycemia therapy in acute aluminium phosphide poisoning: a randomized clinical trial. Clin toxicol (phila). Published online 2023:1-9.
37. Elhosary n, hodeib ِ. Blood lactate and lactate pyruvate ratio as prognostic biomarkers of outcome in acute aluminium phosphide poisoning. Theegyptian jforensic sci appl toxicol 2020;20(2):15-30.
38. Elgazzar f, keshk w, khalifa h. Early l-carnitine therapy in severe acute aluminium phosphide poisoning: a randomized controlled clinical trial. Theegyptian j forensic sci appl toxicol 2019;19(4):147-164.
39. Hegazy m, elagamy s, salem e. Pattern and predictors of death from aluminium and zinc phosphide poisoning: a two years prospective study. Theegyptian j forensic sci appl toxicol 2019;19(2):77-91.
40. Abdel-hady h, mohamed a, mohammed k, rahman aa. Supportive measures in the treatment of aluminium phosphide poisoning as a trial to reduce mortality at assiut university hospital, egypt. Egypt arab j forensic sci forensic med 2019;1(9):1210-1222.
41. Oswatch f, magwenya rh. Aluminium phosphide poisoning: a case series at two hospitals in the manzini region, eswatini. Pyramid j med 2020;2(2).
42. Ali z, afridi mar, muhammad r, et al. Outcome and predictors of in-hospital mortality in patients presenting with acute poisoning to a teaching hospital. J postgrad med inst 2018;32(2).
43. Ali z, afridi mar, muhammad r, et al. Outcome and predictors of in-hospital mortality in patients presenting with acute poisoning to a teaching hospital. J postgrad med inst 2018;32(2).
44. El-sarnagawy g. Predictive factors of mortality in acute aluminium phosphide poisoning: 5 years retrospective study in tanta poison control unit. Ain shams journal of forensic medicine and clinical toxicology 2017;29(2):70-79.
45. Kumar r, choudhray r, bhushan m, barnawa r, nigam p. Aluminium phosphide poisoning - a prospective clinic therapeutic study in tertiary care hospital of eastern u.p. (gorakhpur). World j of pharmaceutical research 2015;(7):2243-2253.
46. Narendra ss, karthik rch. Aluminium phosphide poisoning: a case series in south india. Int j of sci and research 2013;6
47. Koreti s, verma s, prasad y, patel s, rajput s. Aluminium phosphide poisoning in children-challenges in diagnosis and management 2014.
48. Santi d, orellana o, niro d, lashin ca, greco hi. The adjuvant effect of oil-based gastric lavage on the outcome of acute aluminium phosphide poisoning: a
systematic review and meta-analysis. Toxicol res (camb) 2024;13(2).
49. Sobh zk, kholief m, sobh ek, balah m. Exploring research gaps and trends in the management of acute phosphide poisoning: a systematic review. Crit rev
toxicol 2023;53(3):181206.
50. Hussien s, teftazany a, hagras e, elhelaly a, abdelhamed h. N-acetylcysteine use in treatment of acute aluminium phosphide poisoning: systematic review
and meta-analysis. Ainshams journal of forensic medicine and clinical toxicology 2023;41(2):50-62.
51. Santi od. Oil-based gastric lavage in acute aluminium phosphide (alp) poisoning: a systematic review and meta-analysis.
52. Naddafi m, mehrizi aa, eghbal ma, et al. Reducing the risk of death induced by aluminium phosphide poisoning: the new therapies. Chemosphere 2022;294(133800):133800.
53. Manouchehri a, ghareghani s, shamaei s, nilechi m. A review on aluminium phosphide (rice tablets) poisoning; from exposure to the applicable and new strategies of clinicalmanagement. Intl quarterly j of life sci 2021;8:326-332.
54. Anbalgan lc, arora n, pannu a. Management of acute aluminium phosphide poisoning: has anything changed? Drug metabolism letters: bentham science publishers 2021;14.
55. Nourbakhsh f, barangi s, dadpour b, tajoddini s. Aluminium phosphide poisoning, mechanism of action and treatment: a literature review. Journal of kerman university of medicalsciences 2019;26(5):406-419.
56. Kumar rs, ponnusankar s. Aluminium phosphide (slow) poisoning: a narrative case review. Int j of sci & tech research 2019;8(12).
57. Karimani a, mohammadpour ah, zirak mr, et al. Antidotes for aluminium phosphide poisoning – an update. Toxicol rep 2018;5:1053-1059.
58. Shaker ho, rageh o, alnajar m, alshamaly nf, abdelmaged wa. Abd-elgawad m. Efficacy of intravenous n acetylcysteine as an adjuvant therapy in the
treatment of acute aluminium phosphide poisoning: a systematic review and meta-analysis. Bmc pharmacol toxicol 2023;24(1).
59. Toussi a. Successful treatment of aluminium phosphide: is it possible? Asia pac j of med toxicol 2017;6:92-98
60. Farahani mv, soroosh d, marashi sm. Thoughts on the current management of acute aluminium phosphide toxicity and proposals for therapy: an evidence-based review. Indian jcrit care med 2016;20(12):724-730.
61. Berry a, singh g, kaur sj, bala k. Aluminium phosphide: toxicity mechanism and credible treatments. World j of pharmacy and pharmaceutical sci 2015;4(10):2276-2293.
62. Sobh zk, abd-elhameed a. The therapeutic benefit of antioxidants on the outcome of acute aluminium phosphide poisoning: a systemic review and metaanalysis. Toxicol res (camb) 2023;12(3):345-354