Clinical Study Acute Severe Anaphylaxis in Nepali Patients with Neurotoxic Snakebite Envenoming Treated with the VINS Polyvalent Antivenom Sanjib Kumar Sharma, 1 Emilie Alirol, 2 Anup Ghimire, 1 Suman Shrestha, 3 Rupesh Jha, 4 Surya B. Parajuli , 5 Deekshya Shrestha, 4 Surya Jyoti Shrestha, 4 Amir Bista, 3 David Warrell, 6 Ulrich Kuch, 7 Francois Chappuis, 2 and Walter Robert John Taylor 2,8 1 B.P. Koirala Institute of Health Sciences, Dharan, Nepal 2 Division of Tropical and Humanitarian Medicine, University Hospitals of Geneva, Geneva, Switzerland 3 Snake Bite Treatment Centre Nepal Red Cross Society, Chapter Damak, Jhapa, Nepal 4 Bharatpur Hospital, Bharatpur, Chitwan 44200, Nepal 5 Snake Bite Management Centre Charali, Charali, Jhapa, Nepal 6 Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK 7 Institute of Occupational Medicine, Social Medicine and Environmental Medicine, Goethe University, Frankfurt am Main, Germany 8 Mahidol Oxford Tropical Medicine Research Unit, Bangkok, ailand Correspondence should be addressed to Walter Robert John Taylor; bob@tropmedres.ac Received 28 November 2018; Revised 7 March 2019; Accepted 25 March 2019; Published 2 May 2019 Academic Editor: Marcel Tanner Copyright © 2019 Sanjib Kumar Sharma et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Diagnosing and treating acute severe and recurrent antivenom-related anaphylaxis (ARA) is challenging and reported experience is limited. Herein, we describe our experience of severe ARA in patients with neurotoxic snakebite envenoming in Nepal. Patients were enrolled in a randomised, double-blind trial of high vs. low dose antivenom, given by intravenous (IV) push, followed by infusion. Training in ARA management emphasised stopping antivenom and giving intramuscular (IM) adrenaline, IV hydrocortisone, and IV chlorphenamine at the frst sign/s of ARA. Later, IV adrenaline infusion (IVAI) was introduced for patients with antecedent ARA requiring additional antivenom infusions. Preantivenom subcutaneous adrenaline (SCAd) was introduced in the second study year (2012). Of 155 envenomed patients who received ≥ 1 antivenom dose, 13 (8.4%), three children (aged 5−11 years) and 10 adults (18−52 years), developed clinical features consistent with severe ARA, including six with overlapping signs of severe envenoming. Four and nine patients received low and high dose antivenom, respectively, and six had received SCAd. Principal signs of severe ARA were dyspnoea alone (n=5 patients), dyspnoea with wheezing (n=3), hypotension (n=3), shock (n=3), restlessness (n=3), respiratory/cardiorespiratory arrest (n=7), and early (n=1) and late laryngeal oedema (n=1); rash was associated with severe ARA in 10 patients. Four patients were given IVAI. Of the 8 (5.1%) deaths, three occurred in transit to hospital. Severe ARA was common and recurrent and had overlapping signs with severe neurotoxic envenoming. Optimising the management of ARA at diferent healthy system levels needs more research. Tis trial is registered with NCT01284855. 1. Introduction Snake antivenoms are the only specifc treatments for snakebite envenoming; they save lives but are associated with acute pyrogenic reactions, due to endotoxin contamination whilst in production, and acute anaphylaxis [1]. Te mechanisms underlying antivenom-related anaphy- laxis (ARA) are uncertain and are probably a combination of complement activation, a type I hypersensitivity reaction, non-allergen-specifc activation of mast cells triggered by the antivenom impurities and immune priming due to the venom itself [2, 3]; indeed, anaphylaxis has been reported in snake Hindawi Journal of Tropical Medicine Volume 2019, Article ID 2689171, 12 pages https://doi.org/10.1155/2019/2689171