Poisoning with organophosphorus (OP)
insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of
pralidoxime, this
antidote's effectiveness remains unclear. We aimed to determine whether the addition of
pralidoxime chloride to
atropine and supportive care offers benefit.
METHODS AND FINDINGS: We performed a double-blind randomised placebo-controlled trial of
pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus
insecticide self-
poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive
pralidoxime (121) or saline placebo (114).
Pralidoxime produced substantial and moderate red cell
acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving
pralidoxime: 30/121 (24.8%) receiving
pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of
acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving
pralidoxime compared to placebo, further decreasing the likelihood that
pralidoxime is beneficial. The need for intubation was similar in both groups (
pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71-2.29]). To reduce confounding due to ingestion of different
insecticides, we further analysed patients with confirmed
chlorpyrifos or
dimethoate poisoning alone, finding no evidence of benefit.
CONCLUSIONS: Despite clear reactivation of red cell
acetylcholinesterase in diethyl organophosphorus
pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus
insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different
oximes are required.