Archives of Academic Emergency Medicine. 2019; 7 (1): e69 CA S E RE P O RT Inhalational Toxicity of Aluminum Phosphide as an Ongo- ing Concern; a Report of Two Cases Azam Shafahi1, Babak Mostafazadeh2,3, Bita Dadpour1∗ 1. Medical Toxicology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Toxicological Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Department of Forensic Medicine and Toxicology, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Received: August 2019; Accepted: October 2019; Published online: 17 November 2019 Abstract: Acute aluminium phosphide (ALP) poisoning is an extremely lethal poisoning. Ingestion is usually suicidal in intent, uncommonly accidental and rarely homicidal. Unfortunately, the absence of a specific antidote results in very high mortality and the key to successful treatment is in rapid decontamination and institution of resus- citative measures. Phosphine gas is highly toxic, and fatality is expected even several hours after continuous exposure. However, intensive supportive treatments may be lifesaving in some cases. Here, two cases of acci- dental inhalation intoxication with ALP are reported. One patient was discharged and another suffered cardiac arrest during treatment. Keywords: Aluminum phosphide; inhalation; inhalation exposure; gas poisoning Cite this article as: Shafahi A, Mostafazadeh B, Dadpour B. Inhalational Toxicity of Aluminum Phosphide as an Ongoing Concern; a Report of Two Cases. Arch Acad Emerg Med. 2019; 7 (1): e69. 1. Introduction Aluminium Phosphide (ALP) poisoning as a suicidal attempt or accidental poisoning has become notorious in Iran over the past decades. Phosphine gas is a colorless, flammable and highly toxic substance, which is released when Phos- phide comes in contact with water (moisture) or acid, with an odor of garlic or decaying fish (1-3). By inhibition of cytochrome oxidase c and inducing oxidative stress, phos- phine causes severe mitochondrial dysfunction, tissue hy- poxia, and finally multiple organ failure (2, 4). Common clinical manifestations include gastrointestinal symptoms, progressive metabolic acidosis, refractory hy- potension, and dysrhythmia (4). Most reports of ALP poison- ing are following ingestion of ALP. Unfortunately, phosphine gas inhalation also may lead to life threatening toxicity, even in large areas (4-6). To date, no specific antidote has been defined for this rapidly fatal poisoning and supportive measures are mainly recom- mended. Immediate diagnosis in addition to continued in- ∗Corresponding Author: Bita Dadpour; Department of Clinical Toxicology, Imam Reza Hospital, Mashhad, Iran. Tel: +98- 9155149842, E-mail: Dad- pourB@mums.ac.ir tensive monitoring and supportive measures may be lifesav- ing. We aimed at reporting this incident from a public health emergency viewpoint as this type of (ALP) poisoning may re- occur (although is relatively uncommon), at least in coun- tries where ALP is still used by general population. 2. Cases presentation: A 60-year-old woman (case one), with her 29-year-old daugh- ter (case two) were referred to a regional hospital and then transferred to clinical toxicology department of Imam Reza Hospital, Mashhad, Iran, with upper abdominal discomfort, nausea, and with primary suspicion to food poisoning. 2.1. Case one Case one suffered from shortness of breath, weakness, dizzi- ness, restlessness, and nausea on admission. Vital signs at ar- rival included: SBP / DBP = 100/40 mmHg, RR = 20 / minute, O2 Saturation= 93% on room air, and PR = 90 / minute. The patient had no fever and was alert and able to answer ques- tions. There was no history of any drug addiction. She had a history of hypertension and diabetes. QTC prolongation was the most important finding of her Electrocardiogram (ECG). Hydration, oxygen therapy, cardiac monitoring and other supportive measures were performed. Red Blood cells and This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem A. Shafahi et al. 2 Table 1: Laboratory findings of case one Laboratory parameters First day Second day Blood Sugar (mg/dl) 251 241 Creatinine (mg/dl) 1.1 1.2 Urea (mg/dl) 31 43 Sodium (mg/dl) 140 141 Potassium (mg/dl) 3.2 3.2 Calcium, Total (mg/dl) 8.9 Alanine Aminotransferase (ALT) (units/L) 46 37 Aspartate aminotransferase(AST) (units/L) 89 61 Alkaline Phosphatase(Alp) (units/L) 239 168 Creatine phosphokinase (units/L) 124 145 Cardiac troponin 89.30 - Magnesium (mg/dl) 2.4 - Serum Cholinesterase 7356 - RBC Cholinesterase 5.2 - Complete Blood Count Red Blood Cell ×106 4.56 4.20 Hemoglobin 15.1 14.1 Mean Corpuscular Volume(MCV ) 98.0 91.2 Mean Corpuscular Hemoglobin(MCH) 33.1 33.6 Mean corpuscular Hemoglobin Concentration (MCHC) 33.8 36.8 White blood cell ×3 7.4 6.0 Neutrophil (%) 87.4 60.6 Lymphocyte (%) 9.1 33.0 Platelets ×103 183 185 Table 2: Venous blood gas analysis of the first patient on admission and 2, 5, and 8 hours after presenting to emergency department Parameters On admission 2 hours 5 hours 8 hours pH 7.31 7.37 7.41 7.41 Pco2 18.2 23 25.6 36.9 Hco3 9.2 13.1 16 23.5 Base excess -14.4 - - -0.1 Serum cholinesterase levels were in normal range and serum test for the presence of acetaminophen, ethanol, methanol, and other toxic substance were negative. Mild Metabolic aci- dosis was evident in the first venous blood gas (VBG). Results of other laboratory tests are shown in Table 1. Cardiology consult and echocardiography were performed and left ven- tricle ejection fraction (LVEF) was 35%. With suspicion to ALP poisoning, based on clinical and para- clinical findings, magnesium sulfate, bicarbonate, N-acetyl cysteine (NAC) were initiated. NAC was discontinued be- cause of symptoms of hypersensitivity reactions. Insulin was prescribed based on the routine protocol because of high Blood Sugar. ECG was repeated and prothrombin time was also reported high, which became normal in recheck. VBG was repeated several times and improved with supportive acidosis treatment. 2.2. Case two Vital signs of daughter on arrival included: Systolic Blood Pressure (SBP)/ Diastolic Blood Pressure (DBP) = 120/80 mmHg, Respiratory Rate (R.R) = 12 / minute, Pulse Rate (P.R) = 65 / minute. The patient had a seizure attack on admission and after a short time had a cardiac arrest. She was imme- diately intubated and cardiopulmonary resuscitation (CPR) was performed. Unfortunately, resuscitation efforts were un- successful and she died after an hour. The course of events was so rapid that there was no time for any laboratory test. 2.3. Cause of poisoning After taking a more accurate history it was revealed that the patient’s neighbor had sprayed a pesticide in his home two days earlier and had left the house. Following investiga- tions, it was determined that the mentioned poison was rice tablet (aluminum phosphide) which was obtained from an il- legal center and was placed in the neighboring house in large numbers. The mother and daughter had been inhaling the poison odor for the past two days and had been at home all the time until they had progressive symptoms leading them to refer to hospital. History, clinical signs, and results of lab- oratory tests were in concordance with inhalation poisoning This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 3 Archives of Academic Emergency Medicine. 2019; 7 (1): e69 with aluminum phosphide. On the fourth day of hospital- ization after partial recovery, case one was discharged with personal consent against medical advice. 3. Discussion Cardiac arrest due to cardiac toxicity of ALP inhalation led to death of case two in this report. Phosphine gas toxicity fol- lowing unintentional inhalation is not a common report in medical literature, although suicidal ingestion of aluminum phosphide tablets has been reported frequently in our coun- try (2, 7, 8). The National Institute for Occupational Safety and Health (NIOSH) has established a limit for occupational exposure to phosphine gas at 0.3 ppm and has deemed it "immediately dangerous to life or health" at 50 ppm or more."(9). A study on different animals regarding degree of lethal exposure it has been reported that 200 ppm-hours leads to roughly 50% mortality (10). However, another study on male rats reported 11 ppm for 4 hours resulting in 50% lethality (9). Phosphine gas concentration in this family’s home was cer- tainly sufficient for major toxicity following several hours of exposure. An accurate estimation of fatality rates of phos- phine gas inhalation is not possible. However, it is docu- mented that phosphine is placed in the highest category of toxicity based on the Environmental Protection Agency (EPA) (9, 11, 12). In the current report, after 48 hours of inhalational exposure, death occurred. Unfortunately, since there is no accepted definitive treatment for this lethal poisoning, supportive measures are the only treatment option at present. Sev- eral maneuvers are suggested for possibly improving the out- come, including administration of N-acetylcysteine, magne- sium sulfate, pralidoxime, and hyperinsulinemia uglycemia (13). Although none of them are sufficiently evidence advo- cated at the present time (6). However, intensive supportive treatments may be lifesaving in some cases, like in the cur- rent report. 4. Conclusion: Phosphine gas is highly toxic, and fatality is expected even several hours after continuous exposure. A high level of vigi- lance and a more restrictive policy is needed for keeping the general population from having access to these pesticides and consequently preventing the high rate of mortality fol- lowing this preventable poisoning in our community. 5. Appendix 5.1. Acknowledgements The authors express their appreciation to department of Clinical Toxicology, Imam Reza Hospital, Mashhad Univer- sity of Medical Sciences, Mashhad, Iran. 5.2. Authors contribution All authors devised the work, the main conceptual ideas, proof outline and interpretation of the data. Also, all authors discussed the cases and commented on the manuscript. Authors ORCIDs Azam Shafahi: 0000-0002-1253-6262 Babak Mostafazadeh: 0000-0003-4872-9610 Bita Dadpour: 0000-0001-6004-0344 5.3. Conflict of interest Hereby, the authors declare that there is no conflict of interest regarding the present work. 5.4. Funding All the expenses of this research were paid by the researchers. 5.5. Ethical consideration All the authors met the criteria of authorship based on the recommendations of the international committee of medical journal editors. References 1. Singh I, Gupta K, Agarwal S, Bansal MK, Samad A, Kalra P. 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