Annals of Emergency Medicine
Volume 45, Issue 6 , Pages 595-602, June 2005

Crotalidae Polyvalent Immune Fab (Ovine) Antivenom Is Effective in the Neutralization of South American Viperidae Venoms in a Murine Model

From the Department of Emergency Medicine, Palmetto Richland Memorial Hospital, Palmetto Poison Center, Columbia, SC (Richardson); Department of Emergency Medicine, Naval Medical Center–San Diego, San Diego, CA (Tanen, Carstairs); Department of Emergency Medicine, Division of Medical Toxicology, University of California San Diego Medical Center, San Diego, CA (Tong, Betten, Williams, Clark); and the California Poison Control System–San Diego Division, San Diego, CA (Cantrell)

Received 30 April 2004; received in revised form 30 June 2004 and 25 August 2004; accepted 30 August 2004. published online 07 March 2005.

Study objective

Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) is used in the treatment of symptomatic crotaline envenomations in North America. Unlike Antivenin (Crotalidae) Polyvalent, which is approved for treatment of crotaline envenomation in North and South America, FabAV is manufactured using only venoms from crotaline snakes native to the United States. This study was designed to evaluate the efficacy of FabAV in the neutralization of venom from 2 South American crotaline snakes: Crotalus durissus terrificus (tropical rattlesnake) and Bothrops atrox (fer-de-lance).

Methods

A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was used. Venom potency was determined in preliminary median lethal dose (LD50) dosing studies. Study animals were then divided into 7 groups: (1) C durissus terrificus venom (Sigma-Aldrich Co.)+FabAV, (2) C durissus terrificus venom (Sigma-Aldrich Co.)+0.9% normal saline solution, (3) C durissus terrificus venom (Biotoxins Inc.)+FabAV, (4) C durissus terrificus venom (Biotoxins Inc.)+normal saline solution, (5) B atrox venom+FabAV, (6) B atrox venom+normal saline solution, and (7) FabAV+normal saline solution. Twice the estimated LD50 was the chosen venom dose, and the amount of FabAV injected was 10 times the amount needed for venom neutralization. Statistical analysis included Fisher's exact test and log-rank testing to compare survival rates and times.

Results

The venom LD50 was found in preliminary studies to be 0.9 mg/kg and 1.35 mg/kg for the C durissus terrificus venom obtained from Sigma-Aldrich Co. and Biotoxins Inc., respectively. The LD50 for B atrox venom was 5.0 mg/kg. All animals receiving venom only and saline solution died. Animals receiving FabAV together with either venom survived to the end of the 24-hour observation period (P<.001). Comparison of survival times between groups demonstrated a significant difference in time to death between venom-only control groups and the FabAV+venom groups (P<.001). All animals in the FabAV+normal saline solution group survived to the conclusion of the study.

Conclusion

FabAV, when premixed with venom, decreases lethality in a murine model of intraperitoneal venom injection of the South American pit vipers, C durissus terrificus and B atrox.

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 Author contributions: WHR and RFC conceived the study, design, and research. WHR and RFC obtained funding for the project. WHR coordinated data collection, analysis, and drafted the manuscript. WHR and RFC supervised the study and data collection. WHR, DAT, TCT, DPB, SDC, SRW, and FLC assisted with dosing trials, data collection, and modification of the study. WHR, DAT, SRW, and RFC participated in revision of the manuscript. WHR takes responsibility for the paper as a whole.Funding and support: Supported in part by an unrestricted grant from Altana, Inc. (Melville, NY) and antivenom donation from Protherics, Inc. (Nashville, TN).Presented at the Society of Academic Emergency Medicine annual meeting, Orlando, FL, May 2004.Reprints not available from the authors.

PII: S0196-0644(04)01324-1

doi:10.1016/j.annemergmed.2004.08.038

Annals of Emergency Medicine
Volume 45, Issue 6 , Pages 595-602, June 2005

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