Acute Severe Anaphylaxis in Nepali Patients with Neurotoxic Snakebite Envenoming Treated with the VINS Polyvalent Antivenom

Sanjib Kumar Sharma, Emilie Alirol, Anup Ghimire, Suman Shrestha, Rupesh Jha, Surya B Parajuli, Deekshya Shrestha, Surya Jyoti Shrestha, Amir Bista, David Warrell, Ulrich Kuch, Francois Chappuis, Walter Robert John Taylor, Sanjib Kumar Sharma, Emilie Alirol, Anup Ghimire, Suman Shrestha, Rupesh Jha, Surya B Parajuli, Deekshya Shrestha, Surya Jyoti Shrestha, Amir Bista, David Warrell, Ulrich Kuch, Francois Chappuis, Walter Robert John Taylor

Abstract

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 first 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 different healthy system levels needs more research. This trial is registered with NCT01284855.

Figures

Figure 1
Figure 1
Trial profile.
Figure 2
Figure 2
Time course of antivenom administrations, clinical events, and adrenaline treatment. Time 0 is the start of antivenom administration.
Box 1
Box 1
Signs of neurotoxicity. One point is given for each feature present to calculate the neurotoxicity score. ∗: defined as < 3 on the MRC scale, †: clinical indications for mechanical ventilation.

References

    1. Antivenom Therapy and Reactions. The Lancet. vol. 315, no. 8176, pp. 1009-1010, 1980.
    1. Theakston R. D. G., Smith D. C. Antivenoms. BioDrugs. 1997;7(5):366–375. doi: 10.2165/00063030-199707050-00004.
    1. Stone S. F., Isbister G. K., Shahmy S., et al. Immune response to snake envenoming and treatment with antivenom; complement activation, cytokine production and mast cell degranulation. PLOS Neglected Tropical Diseases. 2013;7(7):p. e2326. doi: 10.1371/journal.pntd.0002326.
    1. De Nishioka S. A., Silveira P. V. P., Peixoto-Filho F. M., Jorge M. T., Sandoz A. Occupational injuries with captive lance-headed vipers (Bothrops moojeni): Experience from a snake farm in Brazil. Tropical Medicine & International Health. 2000;5(7):507–509. doi: 10.1046/j.1365-3156.2000.00585.x.
    1. Offerman S. R., Smith T. S., Derlet R. W. Does the aggressive use of polyvalent antivenin for rattlesnake bites result in serious acute side effects? Western Journal of Medicine. 2001;175(2):88–91. doi: 10.1136/ewjm.175.2.88.
    1. de Silva H. A., Pathmeswaran A., Ranasinha C. D., et al. Low-dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: a randomised, double-blind, placebo-controlled trial. PLoS Medicine. 2011;8(5):p. e1000435. doi: 10.1371/journal.pmed.1000435.
    1. Fan H. W., Marcopito L. F., Cardoso J. L. C., et al. Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for bothrops snake bites. British Medical Journal. 1999;318(7196):1451–1453. doi: 10.1136/bmj.318.7196.1451.
    1. Williams D. J., Jensen S. D., Nimorakiotakis B., Müller R., Winkel K. D. Antivenom use, premedication and early adverse reactions in the management of snake bites in rural Papua New Guinea. Toxicon. 2007;49(6):780–792. doi: 10.1016/j.toxicon.2006.11.026.
    1. Moran N. F., Newman W. J., Theakston R. G., Warrell D. A., Wilkinson D. High incidence of early anaphylactoid reaction to SAIMR polyvalent snake antivenom. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1998;92(1):69–70. doi: 10.1016/S0035-9203(98)90959-2.
    1. Isbister G. K., Shahmy S., Mohamed F., et al. A randomised controlled trial of two infusion rates to decrease reactions to antivenom. PLoS ONE. 2012;7(6):p. e38739. doi: 10.1371/journal.pone.0038739.
    1. Faiz M. A., Ahsan M. F., Ghose A., et al. Bites by the Monocled Cobra, Naja kaouthia, in Chittagong Division, Bangladesh: Epidemiology, Clinical Features of Envenoming and Management of 70 Identified Cases. The American Journal of Tropical Medicine and Hygiene. 2017;96(4):876–884. doi: 10.4269/ajtmh.16-0842.
    1. Cardoso J. L., Fan H. W., França F. O., et al. Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in São Paulo, Brazil. QJM: An International Journal of Medicine. 1993;86(5):315–325. doi: 10.1093/oxfordjournals.qjmed.a068818.
    1. Thiansookon A., Rojnuckarin P. Low incidence of early reactions to horse-derived F(ab′)2 antivenom for snakebites in Thailand. Acta Tropica. 2008;105(2):203–205. doi: 10.1016/j.actatropica.2007.09.007.
    1. Deshpande R. P., Motghare V. M., Padwal S. L., et al. Adverse drug reaction profile of anti-snake venom in a rural tertiary care teaching hospital. Journal of Young Pharmacists. 2013;5(2):41–45. doi: 10.1016/j.jyp.2013.02.003.
    1. Isbister G. K., Brown S. G., MacDonald E., White J., Currie B. J., Australian Snakebite Project Investigators Current use of Australian snake antivenoms and frequency of immediate-type hypersensitivity reactions and anaphylaxis. The Medical Journal of Australia. 2008;188(8):473–476.
    1. Brown S. G. A., Blackman K. E., Stenlake V., Heddle R. J. Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation. Emergency Medicine Journal. 2004;21(2):149–154. doi: 10.1136/emj.2003.009449.
    1. Smalligan R., Cole J., Brito N., et al. Crotaline snake bite in the Ecuadorian Amazon: Randomised double blind comparative trial of three South American polyspecific antivenoms. British Medical Journal. 2004;329(7475):1129–1133. doi: 10.1136/bmj.329.7475.1129.
    1. Raina S., Raina S., Kaul R., Chander V., Jaryal A. Snakebite profile from a medical college in rural setting in the hills of Himachal Pradesh, India. Indian Journal of Critical Care Medicine. 2014;18(3):134–138. doi: 10.4103/0972-5229.128702.
    1. Isbister G. K., Jayamanne S., Mohamed F., et al. A randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming. Journal of Thrombosis and Haemostasis. 2017;15(4):645–654. doi: 10.1111/jth.13628.
    1. Zafar J., Aziz S., Hamid B., Qayyum A., Alam M. T., Qazi R. A. Snake bite experience at Pakistan Institute of Medical Sciences. The Journal of the Pakistan Medical Association. 1998;48(10):308–310.
    1. Vongphoumy I., Chanthilat P., Vilayvong P., Blessmann J. Prospective, consecutive case series of 158 snakebite patients treated at Savannakhet provincial hospital, Lao People's Democratic Republic with high incidence of anaphylactic shock to horse derived F(ab')2 antivenom. Toxicon. 2016;117:13–21. doi: 10.1016/j.toxicon.2016.03.011.
    1. Brown S. G., Mullins R. J., Gold M. S. Anaphylaxis: diagnosis and management. The Medical Journal of Australia. 2006;185(5):283–289.
    1. Levis J. T., Ford J. B., Kuo A. M. Intracranial hemorrhage after prehospital administration of intramuscular epinephrine. The Journal of Emergency Medicine. 2011;40(6):e107–e110. doi: 10.1016/j.jemermed.2008.01.008.
    1. Sharma S. K., Kuch U., Höde P., et al. Use of molecular diagnostic tools for the identification of species responsible for snakebite in nepal: a pilot study. PLOS Neglected Tropical Diseases. 2016;10(4) doi: 10.1371/journal.pntd.0004620.e0004620
    1. Alirol E., Sharma S. K., Ghimire A., et al. Dose of antivenom for the treatment of snakebite with neurotoxic envenoming: Evidence from a randomised controlled trial in Nepal. PLOS Neglected Tropical Diseases. 2017;11(5):p. e0005612. doi: 10.1371/journal.pntd.0005612.
    1. Gawarammana I. B., Kularatne S. A. M., Kumarasiri R. P. V., Senanayake N., Dissanayake W. P., Ariyasena H. Parallel infusion of hydrocortisone +/- chlorpheniramine bolus injection to prevent acute adverse reactions to antivenom for snakebites. Medical Journal of Australia. 2004;180(1):20–23.
    1. Watt G., Meade B. D., Theakston R. D., et al. Comparison of Tensilon and antivenom for the treatment of cobra-bite paralysis. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1989;83(4):570–573. doi: 10.1016/0035-9203(89)90301-5.
    1. Edwards I. R., Aronson J. K. Adverse drug reactions: definitions, diagnosis, and management. The Lancet. 2000;356(9237):1255–1259. doi: 10.1016/s0140-6736(00)02799-9.
    1. Sampson H. A., Muñoz-Furlong A., Campbell R. L., et al. Second symposium on the definition and management of anaphylaxis: summary report—second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. Annals of Emergency Medicine. 2006;47(4):373–380. doi: 10.1016/j.annemergmed.2006.01.018.
    1. Warrell D. A., Arnett C. The importance of bites by the saw scaled or carpet viper (Echis carinatus): epidemiological studies in Nigeria and a review of the world. Acta Tropica. 1976;33(4):307–341.
    1. Soar J. Emergency treatment of anaphylaxis in adults: concise guidance. Clinical Medicine. 2009;9(2):181–185. doi: 10.7861/clinmedicine.9-2-181.
    1. Tse Y., Rylance G. Emergency management of anaphylaxis in children and young people: new guidance from the Resuscitation Council (UK) ADC - Education and Practice Edition. 2009;94(4):97–101. doi: 10.1136/adc.2007.120378.
    1. Gueugniaud P. Y., Peverelli E., Vaudelin T., Choux C., Petit P. Relative bradycardia in anaphylactoid shock. Presse medicale (Paris, France : 1983) 1989;18(14):p. 726.
    1. Brown S. G. A. Clinical features and severity grading of anaphylaxis. The Journal of Allergy and Clinical Immunology. 2004;114(2):371–376. doi: 10.1016/j.jaci.2004.04.029.
    1. Bawaskar H. S., Bawaskar P. H. Profile of snakebite envenoming in Western Maharashtra, India. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2002;96(1):79–84. doi: 10.1016/S0035-9203(02)90250-6.
    1. Isbister G. K., Brown S. G., Page C. B., McCoubrie D. L., Greene S. L., Buckley N. A. Snakebite in Australia: a practical approach to diagnosis and treatment. Medical Journal of Australia. 2013;199(11):763–768. doi: 10.5694/mja12.11172.
    1. Magar C. T., Devkota K., Gupta R., Shrestha R. K., Sharma S. K., Pandey D. P. A hospital based epidemiological study of snakebite in western development region, Nepal. Toxicon. 2013;69:98–102. doi: 10.1016/j.toxicon.2013.04.002.
    1. Sharma S. K., Khanal B., Pokhrel P., Khan A., Koirala S. Snakebite-reappraisal of the situation in Eastern Nepal. Toxicon. 2003;41(3):285–289. doi: 10.1016/S0041-0101(02)00289-1.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren