Atropine Alone vs. Atropine Plus Pralidoxime for Organophosphorus Poisoning: A Randomized Controlled Trial
Iranian Journal of Pharmaceutical Sciences,
Vol. 22 No. 1 (2026),
26 January 2026
,
Page 1-11
https://doi.org/10.22037/ijps.v22i1.48891
Abstract
Organophosphate (OP) poisoning accounts for approximately 300,000 annual global deaths. Despite WHO recommendations, pralidoxime's efficacy alongside atropine for OP poisoning treatment remains uncertain. This study aimed to evaluate whether the addition of pralidoxime to atropine and supportive care provides clinical benefits. A double-blind, randomized, placebo-controlled trial was conducted at Loghman Hakim Hospital in Tehran, Iran, between April 2022 and March 2023. Patients with OP poisoning were randomly allocated to either an intervention group (pralidoxime plus atropine) or a control group (atropine alone). The primary outcome was patient recovery. Secondary outcomes included duration of hospitalization and alteration in paraclinical parameters such as VBG, serum cholinesterase, sodium, potassium, blood glucose, etc., within the initial four hours post-treatment. Sixty participants were included, with 30 patients in each group. The odds of recovery were significantly higher in the control group compared to the intervention group (OR: 4 [95%CI: 1.3-12.6], p = 0.018). However, this difference became nonsignificant after adjusting for baseline discrepancies (adjusted OR: 6.5 [95% CI: 0.96-43.96], p = 0.054). Hospitalization duration was significantly shorter in the control group (6.23 vs 13.31; mean difference: 7.08 [95% CI: 2.17-11.98], p = 0.006). There was no significant between-group difference regarding alteration in paraclinical parameters during the first four hours post-treatment.
The addition of pralidoxime to atropine did not improve survival or reduce hospitalization in OP poisoning. The reasons for this lack of efficacy remain unclear. Further multi-center randomized controlled trials with larger sample sizes are needed to investigate alternative dosing regimens or other oximes.
- Organophosphates
- Pralidoxime compounds
- Atropine
- Poisoning
- Randomized controlled trial
How to Cite
References
1. De Silva HJ, Wijewickrema R, Senanayake N. Does pralidoxime affect outcome of management in acute organophosphorus poisoning? The Lancet. 1992;339(8802):1136-8.
2. Sontakke T, Kalantri S. Predictors of Mortality in Hospitalized Patients with Pesticide Poisoning. Cureus. 2023;15(7):e41284.
3. Mew EJ, Padmanathan P, Konradsen F, Eddleston M, Chang S-S, Phillips MR, et al. The global burden of fatal self-poisoning with pesticides 2006-15: Systematic review. Journal of Affective Disorders. 2017;219:93-104.
4. Ahrensberg H, Madsen LB, Pearson M, Weerasinghe M, Eddleston M, Jayamanne S, et al. Estimating the government health-care costs of treating pesticide poisoned and pesticide self-poisoned patients in Sri Lanka. Global Health Action. 2019;12(1):1692616.
5. Senanayake N, Karalliedde L. Neurotoxic Effects of Organohosphorus Insecticides. New England Journal of Medicine. 1987;316(13):761-3.
6. Karalliedde L, Henry JA. Effects of Organophosphates on Skeletal Muscle. Human & Experimental Toxicology. 1993;12(4):289-96.
7. Worek F, Diepold C, Eyer P. Dimethylphosphoryl-inhibited human cholinesterases: inhibition, reactivation, and aging kinetics. Archives of Toxicology. 1999;73(1):7-14.
8. Worek F, Reiter G, Eyer P, Szinicz L. Reactivation kinetics of acetylcholinesterase from different species inhibited by highly toxic organophosphates. Archives of Toxicology. 2002;76(9):523-9.
9. Sidell FR, Groff WA. The reactivatibility of cholinesterase inhibited by VX and sarin in man. Toxicology and applied pharmacology. 1974;27(2):241-52.
10. Eddleston M, Eyer P, Worek F, Juszczak E, Alder N, Mohamed F, et al. Pralidoxime in acute organophosphorus insecticide poisoning—a randomised controlled trial. PLoS medicine. 2009;6(6):e1000104.
11. Willems J, De Bisschop H, Verstraete A, Declerck C, Christiaens Y, Vanscheeuwyck P, et al. Cholinesterase reactivation in organophosphorus poisoned patients depends on the plasma concentrations of the oxime pralidoxime methylsulphate and of the organophosphate. Archives of toxicology. 1993;67:79-84.
12. Kharel H, Pokhrel NB, Ghimire R, Kharel Z. The Efficacy of Pralidoxime in the Treatment of Organophosphate Poisoning in Humans: A Systematic Review and Meta-analysis of Randomized Trials. Cureus. 2020;12(3):e7174.
13. Blumenberg A, Benabbas R, deSouza IS, Conigliaro A, Paladino L, Warman E, et al. Utility of 2-pyridine aldoxime methyl chloride (2-PAM) for acute organophosphate poisoning: a systematic review and meta-analysis. Journal of Medical Toxicology. 2018;14:91-8.
14. Eddleston M, Dawson A, Karalliedde L, Dissanayake W, Hittarage A, Azher S, et al. Early management after self-poisoning with an organophosphorus or carbamate pesticide - a treatment protocol for junior doctors. Crit Care. 2004;8(6):R391-7.
15. Petroianu G, Arafat K, Kuča K, Kassa J. Five oximes (K‐27, K‐33, K‐48, BI‐6 and methoxime) in comparison with pralidoxime: in vitro reactivation of red blood cell acetylcholinesterase inhibitied by paraoxon. Journal of applied toxicology. 2006;26(1):64-71.
16. Rios J, Repetto G, Galleguillos I, Jos A, Del Peso A, Repetto M. High concentrations of pralidoxime are needed for the adequate reactivation of human erythrocyte acetylcholinesterase inhibited by dimethoate in vitro. Toxicology in vitro. 2005;19(7):893-7.
17. Thiermann H, Worek F. Pro: Oximes should be used routinely in organophosphate poisoning. British Journal of Clinical Pharmacology. 2022;88(12):5064-9.
18. Johnson MK, Jacobsen D, Meredith TJ, Eyer P, Heath AJ, Ligtenstein DA, et al. Evaluation of antidotes for poisoning by organophosphorus pesticides. Emergency Medicine. 2000;12(1):22-37.
19. Pawar KS, Bhoite RR, Pillay CP, Chavan SC, Malshikare DS, Garad SG. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. The Lancet. 2006;368(9553):2136-41.
20. Worek F, Bäcker M, Thiermann H, Szinicz L, Mast U, Klimmek R, et al. Reappraisal of indications and limitations of oxime therapy in organophosphate poisoning. Human & experimental toxicology. 1997;16(8):466-72.
21. Zhao D, Guan L, Wang H. The domestic application of oxime in the treatment of organophosphorus insecticide poisoning. Chin J Emerg Med. 2003;12:382-3.
22. Hilmas E, Hilmas CJ. Medical management of chemical toxicity in pediatrics. Handbook of toxicology of chemical warfare agents: Elsevier; 2015. p. 1003-34.
23. Cherian M, Roshini C, Visalakshi J, Jeyaseelan L, Cherian A. Biochemical and clinical profile after organophosphorus poisoning--a placebo-controlled trial using pralidoxime. The Journal of the Association of Physicians of India. 2005;53:427-31.
24. Syed S, Gurcoo SA, Farooqui AK, Nisa W, Sofi K, Wani TM. Is the World Health Organization-recommended dose of pralidoxime effective in the treatment of organophosphorus poisoning? A randomized, double-blinded and placebo-controlled trial. Saudi journal of anaesthesia. 2015;9(1):49-54.
25. Corby G. Pralidoxime Is no Longer Fit for Purpose as an Antidote to Organophosphate Poisoning in the United Kingdom. Disaster Medicine and Public Health Preparedness. 2024;18:e32.
26. Kharel H, Pokhrel NB, Ghimire R, Kharel Z, Pokhrel NB. The efficacy of pralidoxime in the treatment of organophosphate poisoning in humans: a systematic review and meta-analysis of randomized trials. Cureus. 2020;12(3).
- Abstract Viewed: 215 times
- IJPS_Volume22_Issue1_Pages1-11 Downloaded: 143 times