Subcutaneous Crotaline Fab antivenom for the treatment of rattlesnake envenomation in a porcine model.

INTRODUCTION: This study was designed to investigate whether the local, subcutaneous injection of Crotaline Fab antivenom (CroFab) at the rattlesnake envenomation site would result in less extremity edema when compared to intravenous (i.v.) antivenom infusion alone. METHODS: This is a randomized, three-arm laboratory experiment using a porcine model. Each animal was anesthetized, intubated, and maintained on mechanical ventilation. About 6 mg/kg of Crotalus atrox venom was injected subcutaneously at the hock of the right hind leg. Animals were then randomized to immediately receive subcutaneous and i.v. antivenom (SC/IV), i.v. antivenom only, or saline control. SC/IV animals received two vials of CroFab subcutaneously at the envenomation site and two vials intravenously. IV animals received four vials of CroFab intravenously. Limb edema was tracked by serial circumference and volumetric measurements over an 8-h period. Limb circumference was measured at four pre-determined locations hourly. Limb volume was measured by a water displacement method at baseline, 4, and 8 h. RESULTS: Twenty-six animals were randomized to the three treatment groups. The SC/IV and IV arms included nine animals each. Two animals in the SC/IV group died suddenly during the study, leaving seven animals for data analysis. There were eight controls. Increasing limb edema was observed in all groups. No differences were detected in limb circumferences or limb volumes between control and either treatment arms. CONCLUSION: In this porcine model of crotaline envenomation, no differences in limb edema were found between animals treated with SC/IV or IV CroFab when compared to saline controls.

Comparative treatment of alpha-amanitin poisoning with N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin in a murine model.

STUDY OBJECTIVE: The foraging of wild mushrooms can be complicated by toxicity from several mushroom types. Amatoxin, a peptide contained in several mushroom species, accounts for the majority of severe mushroom poisonings by binding to RNA polymerase II irreversibly, leading to severe hepatonecrosis. There is no effective antidote for severe amatoxin poisoning. We compare the effectiveness of 5 potential antidotal therapies in limiting the degree of hepatonecrosis in a randomized, controlled, murine model of amatoxin-induced hepatotoxicity. METHODS: One hundred eighty male Institute of Cancer Research mice were randomized into 6 equal groups. Within each group, 21 mice were intraperitoneally injected with 0.6 mg/kg of alpha-amanitin (amatoxin); the remaining 9 were injected with 0.9% normal saline solution. Four hours postinjection, each group of 30 mice was randomized to 1 of 5 intraperitoneal treatments (N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, or silybin) or normal saline solution. Repeated dosing was administered intraperitoneally every 4 to 6 hours for 48 hours. After 48 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurements (alanine transaminase and aspartate transaminase), and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was determined by a pathologist blinded to the treatment group and divided into 5 categories according to percentage of hepatonecrosis. RESULTS: Amanitin significantly increased aspartate transaminase in treated mice compared with normal saline solution-treated controls (mean [SD] 2,441 [2,818] IU/L versus 310 [252]; P=.03). None of the antidotal therapies were found to significantly decrease the increase in aminotransferases compared with controls. Further, none of the antidotal therapies demonstrated an important decrease in hepatonecrosis compared with controls when a histologic grading scale was used. CONCLUSION: In this murine model, N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin were not effective in limiting hepatic injury after alpha-amanitin poisoning. Increases of aminotransferases and degrees of histologic hepatonecrosis were not attenuated by these antidotal therapies.

Massive honey bee envenomation-induced rhabdomyolysis in an adolescent.

Massive envenomations by honey bees are capable of causing multiorgan dysfunction as a result of the direct toxic effects of the large venom load received. Although all varieties of honey bee have the potential for these attacks, the Africanized honey bee (Apis mellifera scutellata) is the most commonly implicated subspecies. In the United States, the Africanized strain is found primarily in the southwestern states and is known for its highly defensive behavior if disturbed. Mechanisms behind the multiorgan dysfunction produced by these mass envenomations are not clearly understood. We present a case of a 13-year-old male who was stung by approximately 700 honey bees and developed progressive upper-body swelling and systemic manifestations of mass envenomation including rhabdomyolysis, renal insufficiency, and a transient transaminase elevation.

North American coral snake antivenin for the neutralization of non-native elapid venoms in a murine model.

OBJECTIVES: 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.

Kikuchi's disease: a rare cause of cervical lymphadenitis and fever.

Cervical lymphadenitis and fever are common in patients presenting to the Emergency Department (ED). Kikuchi's disease is a rare, self-limited cause of fever and cervical lymphadenitis often misdiagnosed as lymphoma or lupus and inappropriately treated, potentially causing numerous ED visits for unrelieved symptoms. The case described is that of a 29-year-old with persistent fever and cervical lymphadenitis who presented to the ED with a suspected allergic reaction to an antibiotic. The diagnosis of Kikuchi's disease was made in association with nasopharyngeal carcinoma and partial hydatidiform mole. The case highlights the clinical features, diagnosis, and treatment of Kikuchi's disease.

Crotalidae polyvalent immune Fab (ovine) antivenom is effective in the neutralization of South American viperidae venoms in a murine model.

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 (LD 50) 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 LD 50 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 LD 50 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 LD 50 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 .

Rattlesnake envenomation to the face of an infant.

BACKGROUND: Mortality from rattlesnake envenomation in the United States is rare. Despite approximately 8000 crotaline (pit vipers) bites annually, it is estimated that only 10 to 15 deaths occur. Besides direct intravascular envenomation and anaphylaxis, bites to the head and neck may account for some of these rare fatalities. We report a pediatric case of severe facial envenomation requiring emergent intubation and antivenom administration. CASE REPORT: A 14-month-old female toddler was envenomated by a Southern Pacific rattlesnake (Crotalus viridis helleri) above the right upper lip while playing in her backyard. Rapid swelling and ecchymosis developed, and the patient was airlifted to a pediatric tertiary care hospital. Within 3 hours, stridorous respirations complicated by significant facial and oropharyngeal edema necessitated emergent orotracheal intubation. A total of 16 vials of FabAV [Crotalidae Polyvalent Immune Fab (ovine) antivenom] were administered over the next 24 hours. The child gradually improved and was successfully extubated 5 days later. A 3-month follow-up demonstrated no significant cosmetic facial abnormalities. CONCLUSION: Crotaline bites to the head and neck have the potential for significant swelling and airway compromise. Facial bites, anaphylaxis, and rare intravascular envenomation may account for many of the fatalities from rattlesnake envenomation. Early intubation may be required to maintain airway patency.

Vasopressin treatment of verapamil toxicity in the porcine model.

INTRODUCTION: Vasopressin is a novel vasopressor agent used for intractable hypotension. There is little published data available on its use in the poisoned patient. We performed a randomized, controlled, blinded trial in a porcine model to study the effects of vasopressin infusion on mean arterial pressure after verapamil poisoning. METHODS: Eighteen anesthetized monitored swine received a verapamil infusion of 1 mg/kg/hr until the mean arterial pressure (MAP) had decreased to 70% of baseline. At this time, a continuous infusion of either vasopressin (0.01 U/kg/min) or an equal volume of normal saline was initiated. The swine were monitored for 60 minutes after initiation of the study infusion. The primary outcome was MAP. RESULTS: There was no statistically significant difference between the two groups in MAP, cardiac output or systemic vascular resistance. One half (four of eight) of the animals in the vasopressin group died, compared with 20% (two of ten) of those in the saline group. CONCLUSIONS: Vasopressin infusion decreased the survival of verapamil-poisoned swine when compared to those treated with saline alone in this experimental model.