Assessment of a therapeutic protocol for the management of snakebite envenomations in Benin

Abstract

Snakebite envenomation is a major public health issue in Sub-Saharan Africa (SSA). Antivenoms are the only etiological treatment. However, the dose recommended by the manufacturer (2 vials renewed every 2 hours in case of persistent bleeding) is usually not applied due to the high cost which is borne only by the patient. Based on clinical presentation, we evaluated the administration of a single vial on admission (instead of 2 vials), which corresponds to the therapeutic protocol used in current practice in most health centers in Benin and beyond in SSA. Renewal of antivenom followed manufacturer's recommendation. The study took place in a first referral hospital in Tanguiéta, North Benin. All envenomed patients received a slow intravenous vial of Inoserp® Pan-Africa (IPA) upon arrival. A clinical assessment identical to that of inclusion was carried out 2, 4, 6, 12 and 24 hours later to assess the tolerance and efficacy of the IPA, as well as the need to readminister the antivenom. The occurrence, persistence or worsening of clinical hemorrhages or neurological disorders, the latter reflecting envenomation by elapids, systematically led to the injection of 2 or 4 vials of IPA, respectively. Signs of intolerance were sought before and after each administration of antivenom, then 2 weeks to 1 month after treatment, in order to estimate the incidence of adverse effects attributable to the antivenom. Efficacy of IPA was assessed by cessation of bleeding and/or normalization of whole blood coagulation test (WBCT) within 24 hours of initial administration. The study took place from July 31 to October 31, 2019. We received 53 cases of snakebites of which 43 were included. The median age was 21 [IQR: 18-31] years and the sex ratio (M/F) was 1.5. Farmers were the majority (48%). The median time to admission was 1 [IQR: 0-2] day. On admission, 32 patients (74%) presented hemostasis disorders marked by bleeding and/or abnormal WBCT. None of the patients showed neurological symptoms. The median time to normalization of WBCT was 24 [IQR: 4-72] hours. The median time to stop bleeding was 6 [IQR: 4-12] hours. In 3 of the 11 patients whose bleeding had stopped at H2, a recurrence occurred within the following 24 hours. In addition, 3 patients presented with late bleeding 24 hours after admission. Two patients (5%) died as a result of envenomation. The simplified protocol represents a significant saving in the number of vials used, i.e. 1.8±0.4 vials per patient instead of the 2.4±0.2 which would have been necessary in these same patients treated according to the standard protocol (p = 2.6·10-4). However, in comparison with the results obtained during the previous clinical study, the cessation of bleeding is delayed, as is the normalization of the WBCT at the different follow-up times. In addition, the number of re-administrations of antivenom after H2 is higher in the light protocol than in the standard one, respectively 13 patients out of 43 treated versus 4 patients out of 59 (p = 0.006). There was no significant difference between the incidence of signs of early antivenom intolerance in this study compared to the previous one (16% and 11%, respectively; p = 0.79). This delay can put up to a third of patients at risk of complications. Despite its effectiveness and the antivenom savings made, it does not seem reasonable to recommend it.