Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in Sao Paulo, Brazil

In São Paulo City, Brazil, 121 patients with moderatelysevere envenoming by Bothrops snakes (principally B. jararaca)were randomized for treatment with Brazilian polyspecific Bothropsantivenoms: Instituto Butantan (39 patients), Instituto VitalBrazil (41), Fundação Ezequiel Dias (FUNED) (41).The initial dose was four ampoules (40 ml) in 89 patients withless severe envenoming and eight ampoules (80 ml) in 32 patientswith more severe envenoming. A second dose of four ampouleswas required in 20 patients. Patients receiving the three antivenoms were comparable in allrespects before treatment There were no deaths. The majorityshowed rapid clinical improvement, resolution of local envenoming,cessation of bleeding and restoration of blood coagulability.No differences in the efficacy of the three antivenoms wererevealed by clinical or laboratory observations, including measuresof haematological, haemostatic and biochemical ab normalities.Twelve patients developed abscesses (Butantan 1, Vital Brazil6, FUNED 5) and seven developed local necrosis (3,1,3). Of 88patients followed up 20–30 days after the bite 33 (37.5%)still had symptoms or signs of local envenoming, especiallyswelling. Early (anaphylactic) reactions were unexpectedly frequent afterall three antivenoms but were significantly more frequent withButantan (87%) than with Vital Brazil (37%) or FUNED (56%) antivenoms(p < 0.001). A possible explanation was the higher totalprotein content and percentage immunoglobulin of Butantan antivenom. The doses of antivenom recommended in Brazil and used in thisstudy may be unnecessarily high, resulting in an unacceptablyhigh incidence of reactions. Results of the study should prompta critical re-evaluation of antivenom production techniquesand dosage recommendations in Brazil.