Salbutamol in acute organophosphorus insecticide poisoning – a pilotdose-response phase II study

Abstract

Background: Treatment of acute organophosphorus (OP) insecticide poisoning is difficult, with many patients dying despite best care. Pre-clinical studies have shown benefit from salbutamol, possibly due speeding alveolar fluid clearance or reducing bronchoconstriction. In this small pilot dose-response study, we aimed to explore whether addition of nebulized salbutamol to standard care might improve resuscitation.

Methods: We performed a single-blind phase II study comparing the effect of two different doses of nebulized salbutamol versus saline placebo, in addition to standard treatment. Primary outcome was oxygen saturations over the first 60 min of resuscitation; secondary outcomes included heart rate, incidence of dysrhythmias, time to ‘atropinization’, atropine dose required, and mortality.

Result: Seventy-five patients were randomized to receive 5 mg (Salb5, n = 25) or 2.5mg (Salb2.5, n = 25) of salbutamol, or saline placebo (NoSalb, n = 25), by nebulizer. Oxygen saturations did not differ between groups over the first 60 min of resuscitation (median AUC NoSalb: 1376 [95% CI 1282 to 1470], Salb2.5: 1395 [1305 to 1486], Salb5: 1233 [1100 to 1367]; p = .9898). Heart rate was also similar across the three arms. Median time to full atropinization, and atropine dose required, were the same for all three arms (NoSalb 15.0 [10–16] min and 12.6 [8.0–13.4] mg, Salb2.5 15.0 [10–16] min and 12.6 [9.3–16.8] mg, and Salb5 15.0 [10–20] min and 12.6 [10.7–20.6] mg; p = .4805 and p = .1871, respectively). Three (12%) patients died in the Salb2.5 and Salb5 groups and two (8%) in the NoSalb group.

Conclusion: This pilot study, within the limitations of its small size and variation between patients, found no apparent evidence that administration of nebulized salbutamol improved resuscitation of patients with acute OP insecticide self-poisoning. The data obtained provides a basis to design further studies to ultimately test the role of salbutamol in OP insecticide poisoning.

Keywords:

• Salbutamol
• nebulization
• organophosphorus
• insecticide
• poisoning

Acknowledgements

We especially thank Dr. Shamim Ara Keya and Dr. Nazia Hassan for database management. We also thank the doctors and staff of the Medicine Department, Sylhet M.A.G. Osmani Medical College Hospital, especially Dr. Ratan Bhomik, Dr. Kaiser Khokon, Dr. Nobendu Chowdhury, and Dr. Mohammed Mirazur Rahman for patient care, and to the hospital administration authority for their full support and cooperation.

Disclosure statement

We declare that we have no conflict of interest.

Additional information

Funding

This research was funded by Lister Research Prize Fellowship which was awarded to ME.