The therapeutic effect of a novel parenteral formulation of dihydroxyacetone in aluminum phosphide-intoxicated patients

Hossein Niknahad; Reza Heidari; Ali Jangjou; Vahidreza Asghari; Fatemeh M Niknahad; Fazel Goudarzi; Nasim Tavakoli; Mitra Rahimi; Amir Mohammad Niknahad; Marziye Rashedinia

doi:10.1016/j.heliyon.2023.e22165

The therapeutic effect of a novel parenteral formulation of dihydroxyacetone in aluminum phosphide-intoxicated patients

Heliyon. 2023 Nov 10;9(11):e22165. doi: 10.1016/j.heliyon.2023.e22165. eCollection 2023 Nov.

Authors

Affiliations

¹ Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
² Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
³ Department of Emergency Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
⁴ Shiraz-Serum Pharmaceutical Industry, Shiraz, Iran.
⁵ School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
⁶ Toxicological Research Center, Excellence Center of Clinical Toxicology, Department of Clinical Toxicology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Background and objectives: Aluminum phosphide (AlP), known as "rice tablet," is widely used as an effective pesticide. However, AlP poisoning is a common cause of mortality in many countries, such as Iran. Unfortunately, there is no specific antidote for AlP toxicity to date. AlP releases phosphine gas when it is exposed to moisture or acid. Phosphine is a potent mitochondrial toxin that could significantly inhibit cellular energy metabolism. AlP poisoning is an emergency condition that needs instant and effective intervention. Dihydroxyacetone (DHA) is a simple saccharide used for several pharmacological as well as cosmetic purposes. Previously, we found that DHA could significantly prevent mitochondrial impairment induced by toxic agents such as cyanide and phosphine in various in vitro and in vivo experimental models.

Methods: Hospitalized patients (n = 111) were evaluated for eligibility criteria. Among these patients, n = 35 cases were excluded due to incomplete data (n = 11) and suspicion of poisoning with poisons other than AlP (n = 24). Meanwhile, n = 76 cases with confirmed AlP poisoning were included in the study. AlP-poisoned patients who did not receive DHA (n = 18) were used as the control group.Patients (n = 58) received at least one dose of DHA (500 ml of 5 % DHA solution w/v, i.v.) as an adjuvant therapy in addition to the routine treatment of AlP poisoning. Arterial blood gas (ABG), blood pH, bicarbonate levels, and other vital signs and biochemical measurements were monitored. Moreover, the mortality rate and hospitalization time were evaluated in DHA-treated and AlP-poisoned patients without DHA administration. Several biomarkers were assessed before (upon hospitalization) and after DHA treatment. The routine tests for AlP-poisoned patients in this study were the measurement of electrolytes (K⁺ and Na⁺), WBC, RBC, hemoglobin, INR, carbonate (HCO₃), blood pH, PaCO₂, and PaO₂ and SGPT, SGOT, BUN, Cr.

Results: Upon patients' admission, significant decreases in blood pH (acidosis), blood PaO₂, and HCO₃ levels were the hallmarks of AlP poisoning. It was found that DHA significantly alleviated biomarkers of AlP poisoning and tremendously enhanced patients' survival rate (65.52 % in DHA-treated vs 33.34 % in the control group) compared to patients treated based on hospital routine AlP poisoning protocols (no DHA). No significant adverse effects were evident in DHA-treated patients in the current study.

Interpretation and conclusions: These data suggest that parenteral DHA is a novel and effective antidote against AlP poisoning to be used as an adjuvant in addition to routine supportive treatment.

Trial registration: IR.SUMS.REC.1394.102.

Keywords: Aluminum phosphide; Clinical toxicology; Pharmacotherapy; Phosphine; Suicide.