North American coral snake antivenin for the neutralization of non-native elapid venoms in a murine model.
OBJECTIVE
North American coral snake antivenin (CSAV; Wyeth Antivenin [Micrurus fulvius], equine origin) is approved for the treatment of coral snake envenomations in the United States. The coral snake is the only elapid that is native to North America, but envenomations from non-native elapids are occurring more commonly in this country. This study was designed to evaluate the efficacy of CSAV in the neutralization of two exotic elapid envenomations: Naja naja (Indian cobra) and Dendroaspis polylepsis (black mamba).


METHODS
A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was employed. Venom potency was determined in preliminary dosing studies. Study animals then were divided into five groups: 1) N. naja venom + CSAV, 2) N. naja venom + 0.9% normal saline (NS), 3) D. polylepsis venom + CSAV, 4) D. polylepsis venom + NS, and 5) CSAV + NS. The venom dose was chosen to be twice the estimated LD50. The amount of CSAV injected was ten times the amount necessary for neutralization of a 2 x LD50 dose of M. f. fulvius venom in a murine model. Statistical analysis included Fisher's exact and log-rank testing to compare survival rates and times.


RESULTS
Preliminary studies estimated the venom LD50 to be 2.58 mg/kg and 0.45 mg/kg, respectively, for the N. naja and D. polylepsis. A significant difference was shown in comparison of survival times between CSAV-venom groups and normal saline-venom groups despite all animals in both treatment and control arms dying. Animals receiving CSAV and N. naja venom survived (mean +/- SD) 24.4 +/- 3.0 minutes, versus 17.8 +/- 1.3 minutes in the control group (p < 0.001), whereas those receiving CSAV and D. polylepsis venom survived 203.8 +/- 37.0 minutes versus 130.0 +/- 42.6 minutes in the control group (p < 0.001). All animals in the CSAV + NS group survived to the conclusion of the study.


CONCLUSIONS
When premixed with venom, CSAV increased survival time in a murine model of intraperitoneal N. naja and D. polylepsis venom injection. The clinical implications of this are unclear, given unchanged mortality rates.
Richardson
William H
WH
Palmetto Richland Memorial Hospital, Department of Emergency Medicine, Palmetto Poison Center, South Carolina College of Pharmacy, Columbia, SC, USA. whrichardson@sc.rr.com
Tanen
David A
DA
Tong
Tri C
TC
Betten
David P
DP
Carstairs
Shaun D
SD
Williams
Saralyn R
SR
Cantrell
Frank L
FL
Clark
Richard F
RF
D000818:Animals; D000997:Antivenins / Q000627:therapeutic use*; D003429:Cross Reactions; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000037:antagonists & inhibitors*; D017815:Elapidae; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D016019:Survival Analysis
D000997:Antivenins; D004546:Elapid Venoms