A Controlled Clinical Trial of A Novel Antivenom in Patients Envenomed by Bungarus multicinctus

Abstract

In northern Vietnam, a majority of severely envenomed patients are bitten by Bungarus multicinctus. Hitherto, these victims have received supportive care only. The aims of this study were to assess the possible efficacy and side effects of a new antivenom. This trial (ClinicalTrials.gov Identifier: NCT00811239) was performed during [2004][2005][2006] at an ICU in Hanoi. For ethical reasons, the study was not randomized. All patients who fulfilled the inclusion criteria during 2004-2005 were prospectively enrolled, carefully recorded, and treated with optimal supportive therapy (control group). The patients who entered the study 2006 were treated with antivenom in addition to supportive care (antivenom group). The inclusion criteria were: envenomation by B. multicinctus, presence of systemic envenomation, and (during 2006) provision of written informed consent. Predefined endpoints were number of patients requiring mechanical ventilation, duration of mechanical ventilation, length of ICU stay, duration of muscle paralysis, and number of patients with ventilatorassociated pneumonia. Eighty-one patients were included, 54 during 2004-2005 and 27 during 2006. Baseline characteristics were similar in the groups. The antivenomgroup patients had a shorter duration of muscle paralysis of the limbs (p<0.001), of the diaphragm (p<0.001), and of ptosis (p<0.001). The duration of mechanical ventilation and length of ICU stay were shorter in the antivenom group (p<0.001). The rate of ventilator-associated pneumonia was lower in the antivenom group (p<0.02). However, the relative number of patients requiring mechanical ventilation was not reduced in the antivenom group. The rate of adverse reactions to the antivenom was 7.4%. A favorable efficacy and acceptable safety of this antivenom were demonstrated.

Production and Characterization of Neutralizing Antibodies against Bungarus multicinctus Snake Venom

“…The Bungarus multicinctus snake of the Elapidae family, which is also called the banded krait, is one of the major causes of snake envenomation in Taiwan. Neurotoxic venom proteins from B. multicinctus contain different toxins, enzymes, and components that damage the central nervous system and cause neuromuscular blockage, which results in different symptoms, such as ptosis and especially paralysis of the respiratory muscles leading to death (2,3). Among these components, bungarotoxins, which belong to a three-finger toxin family, are considered the major lethal components in B. multicinctus proteins.…”

Antivenom for Neuromuscular Paralysis Resulting From Snake Envenoming

“…The search also yielded numerous cohort studies that discussed the effects of antivenom on neuromuscular paralysis, including studies on envenoming by elapids such as Indian krait ( Bungarus caeruleus ) [4,18,87,88], multi-banded krait ( B. multicinctus ) [48,89], Malayan krait ( B. candidus ) [48,90], common cobra ( Naja naja ) [8,21], monocellate cobra ( N. kaouthia ) [91,92,93,94], Philippine cobra ( N. philippinensis ) [7], eastern coral snake ( Micrurus fulvius fulvius ) [95], coastal taipan ( Oxyuranus scutellatus ) [96], Papuan taipan ( O. canni ) [10,97,98], tiger snake ( Notechis scutatus ) [11,99], rough-scaled snake ( Tropidechis carinatus ) [100], Papuan death adder ( Acanthophis laevis ) [101], Australian death adders ( Acanthophis sp.) [12], Papuan black snake ( Pseudechis papuanus ) [102], and viperids such as Sri Lankan Russell’s viper ( Daboia russelii ) [5,103,104,105], Balken adder ( Viper berus bosniensis ) [17], southern tropical rattlesnake ( Crotalus durissus terrificus ) [106,107] and Mojave rattlesnake ( C. scutulatus scutulatus ) [108] and North American crotalids [109].…”

Neurotoxicity in Snakebite—The Limits of Our Knowledge

“…Some toxins (e.g., alpha-cobratoxin) have been shown to produce a competitive, non-depolarising type of post-synaptic blockade similar to dTC [138], [139]. In this type of toxicity, antivenom may facilitate dissociation of toxin from the ACh receptor and accelerate recovery [11], [110], and a clinical response to AChEIs, similar to myasthenia, is more likely [140]. Most of the alpha-neurotoxins, however, bind almost irreversibly to the post-synaptic nAChRs, even though they produce a non-depolarising type of block [106], [134], [136].…”

“…Ptosis is reported in between 70–93% of patients in most series, and extraocular muscle weakness in 68–82% [9]–[11], [42], [73], [75], [156]. Respiratory muscle weakness is reported in 27–87% [9]–[11], [25], [42], [45], [156].…”