3,4-Diaminopyridine may improve neuromuscular block during botulism

In September 2011, two outbreaks of botulism toxemia (toxin A) incriminating the same artisanal product were responsible for nine cases of botulism in France. Among these cases, three women (Cases 1, 2, and 3) aged 27, 29, and 23 years, respectively, were hospitalized in our ICU for mechanical ventilation support. They rapidly received a trivalent botulism antitoxin serum. Two weeks later, Case 3 passed a spontaneous breathing trial but needed new ventilator support 24 hours after extubation. Association between respiratory failure and low compound muscle action potential (CMAP) amplitude measured at the forearm was reported in a study performed during a large outbreak in 2006 in Thailand [1]. CMAPs measured in the current Case 3 at the time of reintubation were <50% of theoretical values. Botulism could be considered a presynaptic myasthenia [2]. To reverse the effect of toxins, experimental models explored the effects of 3,4-diaminopyridine (3,4DAP) [3]. In Europe, 3,4-DAP is used to treat symptoms of Lambert–Eaton myasthenic syndrome [4,5]. We conducted a pilot study to evaluate the electrophysiological effects of 3,4-DAP (Clinical Trials Registration: NCT01441557). The clinical trial protocol was accepted by the local ethics committee and the French Agency for the Safety of Health Products (agence française de sécurité sanitaire des produits de santé). Patients signed an informed consent. Experiments were