Bioscavenger therapy for organophosphate poisoning – an open-labeled pilot randomized trial comparing fresh frozen plasma or albumin with saline in acute organophosphate poisoning in humans

Abstract

Introduction. Traditional treatment of organophosphate poisoning (OP) with oximes has had limited success. Fresh frozen plasma (FFP) or albumin, acting as bioscavengers to mop up free organophosphate, has been recently proposed as a treatment modality. In this pilot open-label, three-arm, randomized controlled study exploring proof of concept, we evaluated if bioscavenger therapy had a role in OP. Patients and methods. Sixty patients with significant poisoning presenting within 12 hours, with suppression of pseudocholinesterase activity to < 1,000 U/L, were randomized to receive FFP (8 bags, 250 mL each over 3 days), 20% human albumin (4 × 100 mL over 3 days), or saline (2,000 mL over 3 days) in addition to atropine and supportive care. Pseudocholinesterase and organophosphate levels were measured pretreatment, post-infusion (Day 2, Day 3), and predischarge and expressed as mean ± standard error. The incidence of intermediate syndrome, need for mechanical ventilation, atropine requirement, and mortality were assessed. Results. Twenty patients received albumin and 19 patients each FFP or saline. FFP increased pseudocholinesterase levels (250 ± 44–1,241 ± 364 U/L) significantly (p = 0.007). Small, nonsignificant increases were observed with saline (160 ± 30–259 ± 78) and albumin (146 ± 18–220 ± 61). Organophosphate levels reduced in all 3 arms; no clear-cut trends were observed. We observed more cases of intermediate syndrome with FFP [10/19 (53%) vs. 5/20 (25%) vs. 5/19 (26%), FFP, albumin, and saline arms (p = 0.15)]. The interventions did not affect ventilatory requirements (14/19 vs. 15/20 vs. 14/19) or prevent delayed intubation. There were no differences in mean (±standard error) atropine requirement (in milligrams) in the first 3 days (536 ± 132 vs. 361 ± 125 vs. 789 ± 334) and duration (in days) of ventilation (10.0 ± 2.1 vs. 7.1 ± 1.5 vs. 7.5 ± 1.5) or hospital stay (12.4 ± 2.2 vs. 9.8 ± 1.4 vs. 9.8 ± 1.6). Two patients developed adverse effects with FFP. Mortality was similar (4/19 vs. 5/20 vs. 2/19, p = 0.6). Conclusions. Despite significant increase in pseudocholinesterase levels with FFP, this pilot study did not demonstrate favorable trends in clinical outcomes with FFP or albumin.

• Bioscavenger
• Intermediate syndrome
• Organophosphate
• Outcome
• Poisoning
• Ventilation

Acknowledgments

We gratefully acknowledge the contributions of Professor Andrew Dawson and Professor Nick Buckley who have throughout the course of this study given valuable suggestions and constructive criticism to improve the quality of this study as well as of the manuscript.

Declaration of interest

This study was conceived by George John (GJ); Kishore Pichamuthu (KP) and John Victor Peter (JVP) planned and designed this study; initial patient assessment and recruitment were done by Jayakumar Jerobin (JJ), Anupama Nair (AN), and Joseph Kamalesh (JK); follow-up clinical assessments, data collection, and data entry were done by AN, JJ, KP, and JVP; statistical analysis by JVP; biochemical aspects of this study, estimation of organophosphate levels, and pseudocholinesterase assays by Arun Jose Nell (AJN) and Jude Joseph Fleming (JJF); literature search, write up, and overall coordination of this study by GJ, Kurien Thomas (KT), Anand Zachariah (AZ), Suresh S. David (SSD), KP, and JVP; transfusion-related aspects by Dolly Daniel (DD). All authors read the final version of the manuscript and approved for publication. This project was supported by the South Asian Clinical Toxicology Research Collaboration, which is funded by the Wellcome Trust International Collaborative Research Grant (GR071669MA).