Impact of N-acetylcysteine Infusion and Intralipid Infusion on Myocardial Injury in Aluminum Phosphide Toxicity

Impact of N-acetylcysteine Infusion and Intralipid Infusion on Myocardial Injury in Aluminum Phosphide Toxicity

Impact of Combining N-acetylcysteine Intravenous Infusion and Intralipid Emulsion Infusion Versus Intralipid Infusion Alone on Myocardial Injury in Aluminum Phosphide Toxicity

Assess impact of ILE and NAC in morbidity and mortality when used as adjuvant therapy to routine management of acute ALP poisoning.

Aluminum phosphide (ALP) is one of the solid fumigant pesticides. In Egypt, ALP is extensively used to protect grains against insects and rodents. It is available in the form of tablets known as "grain tablet". Suicidal ingestion of ALP tablets is obviously increasing in developing countries. This is attributed to its wide use, free availability in the market, and its low cost. Aluminum phosphide toxicity is extremely fatal. The conveyed mortality rate differs from 37-100%. More than 90% of patients die within the first 24 hours, mainly due to cardiac dysrhythmia. Despite continuous research, no effective antidote has been reported for this lethal poisoning so far. PH3 is phosphorus trihydride and solubility of phosphorus can affect PH3. Solubilities of phosphorus are as follows: In water: 1 part/300,000 parts water; in absolute alcohol: 1 g/400 mL. One gram phosphorus dissolves in 80 ml olive oil, 60 ml oil of turpentine, and about 100 mL of almond oil. So, PH3 might also have lipid soluble property and used IV lipid emulsion may counter its effects. Intravenous lipid emulsion (ILE) is a sterile fat emulsion prepared for intravenous administration as a source of calories and essential fatty acids. Its main components include up to 20% soybean oil, 1.2% egg yolk phospholipids, 2.25% glycerin, and water for injection. In addition, sodium hydroxide has been added to adjust the pH, so that the final pH is 8. Based on animal models and clinical studies, ILE is an established antidote for local-anesthetic drugs systemic toxicity. Besides, ILE has been well used for resuscitation of severe toxicities caused by various lipophilic non-local anesthetic drugs. N-acetylcysteine (NAC) is a well-studied compound which is commonly used in the treatment of paracetamol poisoning. It has shown to replenish cellular glutathione stores in addition to the strong antioxidant properties. NAC has shown to reduce mortality, hospitalization time, and need for mechanical ventilation in ALP poisoning. A cohort study by Agarwal reported survival benefit in patients who received treatment with NAC compared to the control group. Brain natriuretic peptide (BNP) is an excellent biomarker because it can be detected in the early stages of ischemia and decreases shortly after ischemia allowing better detection of re-injury. A metabolite of BNP, Nterminal pro-BNP, NT-proBNP, is relatively easy to measure and predicts short and long term outcomes. BNP is a 32-amino-acid peptide synthesized predominantly from the ventricular myocardium and is released in proportion to the degree of wall stress. Although it has gained recent prominence in the diagnosis and treatment of heart failure, BNP has recently shown promise in predicting the extent of myocardial ischemia in acute coronary syndromes. For instance, the magnitude of BNP released between 1 and 7 days after a myocardial infarction is predictive of left ventricular dysfunction, heart failure, and mortality.

Aluminum phosphide poisonings, Intralipid emulsion, N-acetylcystiene, Myocardial injury, Echocardiography

Conservative management + ILE infusion 10 ml/hr + N-acetyl cysteine (NAC) infusion 150 mg/kg body weight in 200 ml of 5% dextrose over 1 h, followed by 50 mg/kg body weight in 500 ml of 5% dextrose over 4 h, and then 100 mg/kg body weight in 1000 ml of 5% dextrose over 16 h.

Intravenous infusion of NAC 150 mg/kg body weight in 200 ml of 5% dextrose over 1 h, followed by 50 mg/kg body weight in 500 ml of 5% dextrose over 4 h, and then 100 mg/kg body weight in 1000 ml of 5% dextrose over 16 h.

Inclusion Criteria: Presentation with symptomatic acute ALP poisoning. History of exposure including reliable identification of the compound based on the container brought by patient's relatives. The suggestive clinical manifestations following shortly after a single exposure to ALP. Exclusion Criteria: Co-ingestion or exposure to other substances in addition to ALP. Patients had major medical conditions (e.g., cardiovascular disease, renal or hepatic failure). Patients received treatment in any hospital or medical center before admission - other than emergency department of Assiut University Hospital.

Baruah U, Sahni A, Sachdeva HC. Successful management of aluminium phosphide poisoning using intravenous lipid emulsion: Report of two cases. Indian J Crit Care Med. 2015 Dec;19(12):735-8. doi: 10.4103/0972-5229.171412.

Tehrani H, Halvaie Z, Shadnia S, Soltaninejad K, Abdollahi M. Protective effects of N-acetylcysteine on aluminum phosphide-induced oxidative stress in acute human poisoning. Clin Toxicol (Phila). 2013 Jan;51(1):23-8. doi: 10.3109/15563650.2012.743029. Epub 2012 Nov 14.

Agarwal A, Robo R, Jain N, Gutch M, Consil S, Kumar S. Oxidative stress determined through the levels of antioxidant enzymes and the effect of N-acetylcysteine in aluminum phosphide poisoning. Indian J Crit Care Med. 2014 Oct;18(10):666-71. doi: 10.4103/0972-5229.142176.

Tsutamoto T, Wada A, Maeda K, Hisanaga T, Maeda Y, Fukai D, Ohnishi M, Sugimoto Y, Kinoshita M. Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction. Circulation. 1997 Jul 15;96(2):509-16. doi: 10.1161/01.cir.96.2.509.