A pilot clinical study of the neuromuscular blocker rocuronium to reduce the duration of ventilation after organophosphorus insecticide poisoning

Abstract

Background: A common manifestation of organophosphorus insecticide self-poisoning is prolonged respiratory failure due to neuromuscular junction dysfunction and likely nicotinic receptor overstimulation. We aimed at collecting preliminary data on whether addition of the competitive nicotinic antagonist rocuronium to standard early therapy might be clinically feasible and associated with reduced duration of ventilation.

Methods: A pilot three-arm dose–response phase II trial was set up to compare bolus doses of rocuronium bromide titrated to produce initial >95% or 50% inhibition of neuromuscular function, measured using acceleromyography, plus standard treatment, versus standard treatment alone. After attaining inhibition, patients receiving bolus rocuronium then received rocuronium infusions for a maximum of 120 h. Primary outcome was duration of intubation; secondary outcome was case fatality. Plasma butyrylcholinesterase activity was measured throughout the inpatient stay. Blood was analysed to confirm the organophosphorus insecticide ingested.

Results: Forty-five patients were randomised to receive: rocuronium to initially attain 95% inhibition (Roc>95, n = 15), rocuronium to initially attain 50% inhibition (Roc50, n = 14), or no rocuronium (control, n = 16). The most commonly ingested pesticide was profenofos (29/45, 64.4%). Butyrylcholinesterase activity remained severely inhibited for the duration of the study for most patients. Case fatality was 9/45 (20%) and similar across study arms: control 3/16 (18.8%), Roc50 4/14 (28.6%) and Roc>95 2/15 (13.3%) (p = .5842). When excluding patients who died, median [IQR] duration of intubation was significantly longer in the Roc50 (259.5 [176–385] h) and Roc>95 (226.8 [186–355] h) groups compared to controls (88.5 [47–160] h, p = .0162 and p = .0016, respectively).

Conclusions: In this pilot dose–response study, we found no evidence that rocuronium in addition to standard therapy reduced the duration of intubation. It is possible that it worsened neuromuscular junction function. Further clinical research, including testing of shorter duration regimens, needs to be performed before nicotinic antagonists can be used in the clinical management of OP poisoning.

Keywords:

• Organophosphorus insecticide
• rocuronium
• duration of ventilation
• pilot clinical study
• neuromuscular blocker

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Acknowledgements

We thank the directors and the medical and nursing staff of the study hospital for their support, study doctors and staff of SACTRC for their immensely valuable work, and Professor Vajira Weerasinghe, Professor Vasanti Pinto, and Dr. Harini Ganegedara for their guidance in setting up the study. We also thank Dr. Thilini Wijerathna and Dr. Ayanthi Karunarathne for auditing the data and analysis, and Prof John Norrie for his help with the Jonckheere-Terpstra test.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Funded by the Association of Physicians of UK and Ireland’s Links with Developing Countries Scheme 2013-14, NHMRC neurotoxicity grant (1030069), and EU H2020 TOXI-triage grant (653409).