Research Article: Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial

Date Published: May 10, 2011

Publisher: Public Library of Science

Author(s): H. Asita de Silva, Arunasalam Pathmeswaran, Channa D. Ranasinha, Shaluka Jayamanne, Senarath B. Samarakoon, Ariyasena Hittharage, Ranjith Kalupahana, G. Asoka Ratnatilaka, Wimalasiri Uluwatthage, Jeffrey K. Aronson, Jane M. Armitage, David G. Lalloo, H. Janaka de Silva, Ken Winkel

Abstract: In a factorial randomized trial conducted in Sri Lanka, de Silva and colleagues evaluate the safety and efficacy of pretreatments intended to reduce the risk of serious reactions to antivenom following snakebite.

Partial Text: Globally an estimated 421,000 envenomings and 20,000 deaths occur each year due to snakebite, although the incidence may be as high as 1,841,000 envenomings and 94,000 deaths [1]. Populations with the highest burden (in rural areas of South Asia, Southeast Asia, and sub-Saharan Africa) experience high morbidity and mortality because of poor access to often suboptimal health services; scarcity of antivenom, which is the only specific treatment for snakebite, may also be a problem [2]. The incidence of snakebite in Sri Lanka (based on hospital data) is about 200 per 100,000 individuals per year [1],[3], one of the highest in the world. In the North-Central and North-Western Provinces of the country, which have the highest incidence of bites by highly venomous snakes, three regional hospitals reported 1,851 snakebite admissions, with 11 deaths due to snakebite during 2000 [4].

From March 2005 to April 2008, 4,677 patients who presented after snakebite to trial hospitals were screened, and 1,007 eligible patients were randomized (53 at Anuradhapura, 16 at Embilipitiya, 152 at Hambantota, 353 at Kurunegala, and 433 at Polonnaruwa) (Text S2). The main reason for exclusion was lack of clinical indication for antivenom. Recruitment was stopped when the target sample size of 1,000 was reached in April 2008. All the randomized patients completed the study and were evaluated; there were no protocol deviations.

Reactions to antivenom present considerable challenges to clinicians treating snakebite. The frequency of early reactions varies markedly between individual antivenoms and between different batches of antivenom from the same manufacturer, occurring with a frequency that ranges from less than 0.5% up to 87%, although only a small proportion of reactions are life threatening [7]. The high reaction rates of 75% observed in this study are in line with the rates of between 43% and 81% that were observed in three previous Sri Lankan studies [10]–[12].

Source:

http://doi.org/10.1371/journal.pmed.1000435

 

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