title: Efficacy of intravenous hydrocortisone administered 2-4 h prior to antivenom as prophylaxis against adverse drug reactions to snake antivenom in Sri Lanka: An open labelled randomized controlled trial.
abstract: The prevention of adverse drug reactions to antivenom serum poses a formidable challenge in the management of snakebite. Hydrocortisone is being used concurrently with antivenom in order to prevent these adverse drug reactions without a proven benefit. However, all previous studies seemed to ignore the testing of effectiveness of hydrocortisone therapy during its pharmacological effects, which come hours later. On this principle, we aimed to test the effectiveness of intravenous hydrocortisone given 2 h or more prior to the commencement of antivenom therapy to reduce adverse drug reactions to antivenom. In an open-labelled randomized controlled trial, patients with a history of snakebite were randomly assigned to receive either 500 mg intravenous hydrocortisone bolus given 2 h or more prior to antivenom therapy (Group A) or at the time of antivenom therapy (Group B). The primary endpoint was the reduction of adverse drug reactions to antivenom of any grade of severity within the first 48 h. This trial has been registered with the "Sri Lanka Clinical Trials Registry", number SLCTR/2010/005. A total of 236 patients were randomized to group A or Group B. In the group A, 38 participants received hydrocortisone 2 h before administration of antivenom whilst 33 received hydrocortisone less than 2 h before administration of antivenom. In the Group B, 84 participants received hydrocortisone at the time of antivenom therapy. In Group A (n, 38), and Group B (n, 84), 15 patients (39%) and 29 patients (35%) developed reactions respectively and the difference is not significant (p = 0.598). Moreover, hydrocortisone therapy did not significantly reduce the occurrence of antievnom reactions of any grade of severity. Further, it didn't delay the occurrence of antivenom reactions in patients who received hydrocortisone either more than 2 h or less than 2 h before the antivenom as opposed to the control group (group B). Intravenous hydrocortisone shows no difference in the timing, rate or severity of adverse drug reactions to antivenom when administered simultaneously and up to 4 h prior to antivenom.
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Peradeniya, Sri Lanka.
authors.forename: Senanayake A M
authors.initials: SA
authors.lastname: Kularatne
authors.affiliation: Department of Parasitology, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Sri Lanka.
authors.forename: Kosala
authors.initials: K
authors.lastname: Weerakoon
authors.affiliation: Department of Parasitology, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Sri Lanka; Department of Pharmacology, Faculty of Medicine, Nursing and Health Sciences, Building 15E, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Anjana
authors.initials: A
authors.lastname: Silva
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Peradeniya, Sri Lanka. Electronic address: kalanapm@gmail.com.
authors.forename: Kalana
authors.initials: K
authors.lastname: Maduwage
authors.affiliation: Teaching Hospital, Anuradhapura, Sri Lanka.
authors.forename: Chamara
authors.initials: C
authors.lastname: Walathara
authors.affiliation: Teaching Hospital, Anuradhapura, Sri Lanka.
authors.forename: Ishani
authors.initials: I
authors.lastname: Rathnayake
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Peradeniya, Sri Lanka.
authors.forename: Senal
authors.initials: S
authors.lastname: Medagedara
authors.affiliation: Teaching Hospital, Anuradhapura, Sri Lanka.
authors.forename: Ranjith
authors.initials: R
authors.lastname: Paranagama
authors.affiliation: Teaching Hospital, Anuradhapura, Sri Lanka.
authors.forename: Suresh
authors.initials: S
authors.lastname: Mendis
authors.affiliation: Department of Community Medicine, Faculty of Medicine, University of Peradeniya, Sri Lanka.
authors.forename: P V R
authors.initials: PV
authors.lastname: Kumarasiri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000997:Antivenins / Q000009:adverse effects*; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012909:Snake Bites / Q000188:drug therapy*; D013188:Sri Lanka
chemical_list: D000997:Antivenins; D006854:Hydrocortisone
keywords: Adverse drug reactions; Antivenom; Hydrocortisone; Snakebite