Though snake antivenom (SAV) is the mainstay of therapy for poisonous snake bites, there is no universally accepted standard regimen regarding the optimum dose (low vs. high). We therefore, undertook this systematic review to address this important research question. We searched all the published literature through the major electronic databases till August 2014. Randomized clinical trials (RCTs) were included. Eligible trials compared low versus high dose SAV in poisonous snake bite. The review has been registered at PROSPERO (Registration number: CRD42014009700). Of 36 citations retrieved, a total of 5 RCTs (n = 473) were included in the final analyses. Three trials were open-label, 4 conducted in Indian sub-continent and 1 in Brazil. The doses of SAV varied in the high dose group from 40 ml to 550 ml, and in the low dose group from 20 ml to 220 ml. There was no significant difference between the two groups for any of the outcomes except duration of hospital stay, which was lower in the low dose group. The GRADE evidence generated was of \"very low quality.\" Low-dose SAV is equivalent or may be superior to high-dose SAV in management of poisonous snake bite. Low dose is also highly cost-effective as compared to the high dose. But the GRADE evidence generated was of \"very low quality\" as most were open label trials. Further trials are needed to make definitive recommendations regarding the dose and these should also include children <9 years of age.
Kasturiratne A, Wickremasinghe AR, de Silva N, Gunawardena NK, Pathmeswaran A, Premaratna R, et al. The global burden of snakebite: A literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med 2008;5:e218.
Warrell DA. WHO/SEARO. Guidelines for the Clinical Management of Snake Bites in the Southeast Asian Region. Available from: http://www.searo.who.int/linkfiles/bct_snake_bite_guidelines.pdf. [Last accessed on 2014 Aug 21].
Rivière G, Choumet V, Audebert F, Sabouraud A, Debray M, Scherrmann JM, et al. Effect of antivenom on venom pharmacokinetics in experimentally envenomed rabbits: Toward an optimization of antivenom therapy. J Pharmacol Exp Ther 1997;281:1-8.
Bawaskar HS. Snake venoms and antivenoms: Critical supply issues. J Assoc Physicians India 2004;52:11-3.
Agarwal R, Aggarwal AN, Gupta D, Behera D, Jindal SK. Low dose of snake antivenom is as effective as high dose in patients with severe neurotoxic snake envenoming. Emerg Med J 2005;22:397-9.
Tariang DD, Philip PJ, Alexander G, Macaden S, Jeyaseelan L, Peter JV, et al. Randomized controlled trial on the effective dose of anti-snake venom in cases of snake bite with systemic envenomation. J Assoc Physicians India 1999;47:369-71.
Vijeth SR, Dutta TK, Shahapurkar J, Sahai A. Dose and frequency of anti-snake venom injection in treatment of Echis carinatus (saw-scaled viper) bite. J Assoc Physicians India 2000;48:187-91.
Gadwalkar SR, Kumar NS, Kushal DP, Shyamala G, Mohammad MZ, Vishwanatha H. Judicious use of antisnake venom in the present period of scarcity. Indian J Crit Care Med 2014;18:722-7.
Yap CH, Ihle BU. Coagulopathy after snake envenomation. Neurology 2003;61:1788.
Vijeth SR, Dutta TK, Shahapurkar J. Correlation of renal status with hematologic profile in viperine bite. Am J Trop Med Hyg 1997;56:168-70.
Reid HA, Chan KE, Thean PC. Prolonged coagulation defect (defibrination syndrome) in Malayan viper bite. Lancet 1963;1:621-6.
The Nordic Cochrane Centre The Cochrane Collaboration. Review Manager (RevMan). 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration; 2012.
Srimannarayana J, Dutta TK, Sahai A, Badrinath S. Rational use of anti-snake venom (ASV): Trial of various regimens in hemotoxic snake envenomation. J Assoc Physicians India 2004;52:788-93.
Paul V, Pratibha S, Prahlad KA, Earali J, Francis S, Lewis F. High-dose anti-snake venom versus low-dose anti-snake venom in the treatment of poisonous snake bites - A critical study. J Assoc Physicians India 2004;52:14-7.
Thomas PP, Jacob J. Randomised trial of antivenom in snake envenomation with prolonged clotting time. Br Med J (Clin Res Ed) 1985;291:177-8.
Jorge MT, Cardoso JL, Castro SC, Ribeiro L, França FO, de Almeida ME, et al. A randomized ′blinded′ comparison of two doses of antivenom in the treatment of Bothrops envenoming in São Paulo, Brazil. Trans R Soc Trop Med Hyg 1995;89:111-4.
Isbister GK, Shahmy S, Mohamed F, Abeysinghe C, Karunathilake H, Ariaratnam A. A randomised controlled trial of two infusion rates to decrease reactions to antivenom. PLoS One 2012;7:e38739.
Abubakar IS, Abubakar SB, Habib AG, Nasidi A, Durfa N, Yusuf PO, et al. Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus) envenoming in Nigeria. PLoS Negl Trop Dis 2010;4:e767.
Pardal PP, Souza SM, Monteiro MR, Fan HW, Cardoso JL, França FO, et al. Clinical trial of two antivenoms for the treatment of Bothrops and Lachesis bites in the north eastern Amazon region of Brazil. Trans R Soc Trop Med Hyg 2004;98:28-42.
Whitaker R, Whitaker S. Venom, antivenom production and the medically important snakes of India. Curr Sci 2012;103:635-43.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.
Schünemann H, Brozek J, Oxman A, editors. GRADE Handbook for Grading Quality of Evidence and Strength of Recommendation. Version 3.2. Jan Brozek, Andrew Oxman, Holger Schünemann; 2008.