Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in people bitten by snakes: randomised, placebo controlled trial. Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for bothrops snake bites.
To assess the efficacy and safety of low dose adrenaline injected subcutaneously to prevent acute adverse reactions to polyspecific antivenom serum in patients admitted to hospital after snake bite.
                Prospective, double blind, randomised, placebo controlled trial.
                District general hospital in Sri Lanka.
                105 patients with signs of envenomation after snake bite, randomised to receive either adrenaline (cases) or placebo (controls) immediately before infusion of antivenom serum.
                Adrenaline 0.25 ml (1:1000).
                Development of acute adverse reactions to serum and side effects attributable to adrenaline.
                56 patients (cases) received adrenaline and 49 (controls) received placebo as pretreatment. Six (11%) adrenaline patients and 21 (43%) control patients developed acute adverse reactions to antivenom serum (P=0.0002). Significant reductions in acute adverse reactions to serum were also seen in the adrenaline patients for each category of mild, moderate, and severe reactions. There were no significant adverse effects attributable to adrenaline.
                Use of 0.25 ml of 1:1000 adrenaline given subcutaneously immediately before administration of antivenom serum to patients with envenomation after snake bite reduces the incidence of acute adverse reactions to serum. To investigate the efficacy of the H1 antihistamine promethazine against early anaphylactic reactions to antivenom.
                Sequential randomised, double blind, placebo controlled trial.
                Public hospital in a venom research institute, São Paulo, Brazil.
                101 patients requiring antivenom treatment after being bitten by bothrops snakes.
                Intramuscular injection of promethazine (25 mg for adults and 0.5/kg for children) or placebo given 15-20 min before starting intravenous infusion of antivenom.
                Incidence and severity of anaphylactic reactions occurring within 24 hours after antivenom.
                Reactions occurred in 12 of 49 patients treated with promethazine (24%) and in 13 of 52 given placebo (25%); most were mild or moderate. Continuous sequential analysis indicated that the study could be interrupted at the 22nd untied pair, without preference for promethazine or placebo.
                Prophylaxis with promethazine does not prevent early reactions. Patients should be observed carefully during antivenom infusion and the subsequent few hours.
Routine prophylactic adrenaline for polyvalent antivenom known to have high adverse event rates seems sensible, based on this one trial. If clinicians believe local factors do not justify routine adrenaline, then they should test their belief in a randomized trial. Antihistamine appears to be of no obvious benefit in preventing acute reactions from antivenoms.