Crotalidae Polyvalent Immune Fab and Cost-Effective Management of Hospital Admissions for Snakebites.

BACKGROUND: Venomous snakebites are a common clinical scenario in the Southeastern United States. CroFab® (Crotalidae Polyvalent Immune Fab (Ovine), BTG, Wales, UK) antivenom is indicated in cases involving pit vipers and is known to be expensive. The treatment protocol for snakebites is based on clinically subjective measures triggering the application, or escalation of, antivenom administration. The purpose of this study is to characterize the use of CroFab at our institution and to evaluate the impact of its use regarding cost and overall outcomes. We suspect that it is often used but potentially less often needed. We hypothesized that CroFab use was associated with increased length of stay (LOS) without an observed difference in patient outcomes. MATERIALS AND METHODS: A retrospective chart review of snakebite patients at our level-1 trauma center from 2000 to 2016 was performed. Snakebite location, snake species, number of vials of CroFab administered, hospital LOS, intensive care unit (ICU) LOS, and complications were identified for each patient. Patients were divided into CroFab (C) and no CroFab (NC) groups. RESULTS: One hundred ninety patients with venomous snakebites were included. 53.7% of patients received CroFab. There was no difference in the complication rate of C versus NC groups, (P = .1118). CroFab use was associated with longer hospital LOS (P < .0001) and ICU LOS (P < .0001). DISCUSSION: CroFab use was associated with increased LOS in our patient population. There was no difference in observed outcomes between the C and NC groups. These findings imply that CroFab is potentially over-used in our patient population.

Health and economic burden estimates of snakebite management upon health facilities in three regions of southern Burkina Faso.

BACKGROUND: Snakebite has become better recognized as a significant cause of death and disability in Sub-Saharan Africa, but the health economic consequences to victims and health infrastructures serving them remain poorly understood. This information gap is important as it provides an evidence-base guiding national and international health policy decision making on the most cost-effective interventions to better manage snakebite. Here, we assessed hospital-based data to estimate the health economic burden of snakebite in three regions of Burkina Faso (Centre-Ouest, Hauts Bassins and Sud-Ouest). METHODOLOGY: Primary data of snakebite victims admitted to regional and district health facilities (eg, number of admissions, mortality, hospital bed days occupied) was collected in three regions over 17 months in 2013/14. The health burden of snakebite was assessed using Disability-Adjusted Life Years (DALYs) calculations based upon hospitalisation, mortality and disability data from admitted patients amongst other inputs from secondary sources (eg, populations, life-expectancy and age-weighting constants). An activity-based costing approach to determine the direct cost of snake envenoming included unit costs of clinical staff wages, antivenom, supportive care and equipment extracted from context-relevant literature. FINDINGS: The 10,165 snakebite victims admitted to hospital occupied 28,164 hospital bed days over 17 months. The annual rate of hospitalisation and mortality of admitted snakebite victims was 173 and 1.39/100,000 population, respectively. The estimated annual (i) DALYs lost was 2,153 (0.52/1,000) and (ii) cost to hospitals was USD 506,413 (USD 49/hospitalisation) in these three regions of Burkina Faso. These costs appeared to be influenced by the number of patients receiving antivenom (10.90% in total) in each area (highest in Sud-Ouest) and the type of health facility. CONCLUSION: The economic burden of snake envenoming is primarily shouldered by the rural health centres closest to snakebite victims-facilities that are typically least well equipped or resourced to manage this burden. Our study highlights the need for more research in other regions/countries to demonstrate the burden of snakebite and the socioeconomic benefits of its management. This evidence can guide the most cost-effective intervention from government and development partners to meet the snakebite-management needs of rural communities and their health centres.

Snakebite Envenomation in Rwanda: Patient Demographics, Medical Care, and Antivenom Availability in the Formal Healthcare Sector.

Snakebite envenomation (SBE) is a neglected One Health issue that overwhelmingly affects people living in rural and impoverished regions of Africa and Asia. Information on SBE is scarce in Rwanda; thus, our objectives were to 1) describe the demographics of SBE patients seeking hospital care, 2) evaluate physician adherence to national treatment guidelines, and 3) assess availability of snake antivenom at hospitals in Rwanda. To achieve these goals, we obtained national data on animal bites/stings and visited every district and provincial hospital in Rwanda to obtain physical records of SBE patients treated in 2017 and 2018. Hospital pharmacies were assessed for antivenom availability. We identified snakes as the second leading cause of animal bites, after dogs, among patients who sought hospital care in 2017 and 2018. Of 363 SBE patients, the highest number of cases occurred among children (< 18 years; 32%) and young adults (18-30 years; 33%), females (61%), farmers (82%), and those living in Eastern Province (37%). Overall, physician adherence to treatment guidelines was 63%. Prescriptions of vitamin K and antivenom were low (4% and 13%, respectively), and only 8% of hospital pharmacies had antivenom in stock throughout the study period. The antivenom stocked was an Indian generic suited for Asian snakes. This minimum estimate of hospitalization cases does not include individuals who died in communities or sought care outside the formal sector. Our study highlights the need to map incidence, risk factors, and patient experiences to mitigate human-snake conflicts and improve patient outcomes.

Review of North American pit viper antivenoms.

PURPOSE: For the first time in nearly 20 years, 2 antigen-binding fragment (Fab) antivenoms are available to treat patients who incur North American pit viper snakebites: Crotalidae polyvalent immune Fab (ovine), or simply FabAV; and Crotalidae immune F(ab')2 (equine), or simply F(ab')2. Pharmacists are in a key position for the selection, dosing, reconstitution, administration, and monitoring of antivenom therapy; however, they encounter inconsistent exposure and experience with these drugs. Thus, an updated review of the literature is necessary. METHODS: The search strategy and selection incorporated both controlled vocabulary terms and keywords to describe concepts relevant to the search. Retrieval was limited to literature published from 1997 to the present in English, Portuguese, or Spanish. RESULTS: Given the paucity of available prospective literature, the authors elected to include all prospective evidence to best describe the role of antivenom. For the primary literature review, manuscripts were excluded if they were observational studies, conference abstracts, narrative or opinion articles, letters to the editor, or in-progress studies. CONCLUSION: While there is limited evidence-based guidance on the superiority of F(ab')2 to FabAV, or vice versa, individual and regional considerations should contribute to formulary decisions. Pharmacists must play a role in the development of clinical pathways to ensure appropriate evaluation, supportive care, and antivenom procurement, administration, and monitoring.

Venomous Snakebites in Canada: A National Review of Patient Epidemiology and Antivenom Usage.

INTRODUCTION: There are 3 pit viper species in Canada. Limited Canadian literature exists on the epidemiology of venomous snakebites and the treatment patterns with antivenom. This study described the epidemiology, the utilization of antivenom, and estimated expenditures due to forfeited antivenom for pit viper envenomations in Canada. METHODS: A retrospective review of the Health Canada Special Access Program records to generate descriptive statistics. Data are presented as mean±SD (range), as appropriate. RESULTS: The geographic distribution of Canadian pit viper species is presented. There were 99 envenomations reported in Canada from January 2009 to December 2015. The number of envenomations per year was 14±6 (6-21). CroFab and Antivipmyn are used in Canada to treat envenomations. The number of vials for patient treatment was 17±12 (3-66) and 16±9 (6-42) for CroFab and Antivipmyn, respectively. Antivenom stock usage for patient treatment varied across the country with provincial means reported for British Columbia (33%), Alberta (37%), Saskatchewan (27%), and Ontario (71%). The costs incurred secondary to forfeited stock where estimated as: $1,280,000 USD in British Columbia, $255,000 in Alberta, $60,000 in Saskatchewan, and $0 in Ontario. CONCLUSIONS: The absolute number of annual envenomations is small and the 3 Crotalinae species are limited to relatively narrow geographic areas in British Columbia, Alberta, Saskatchewan, and Ontario. The utilization of antivenom in the treatment of patients revealed that regions where the western and prairie rattlesnake reside forfeited a substantial amount of antivenom from 2009 to 2015. Organizations responsible for maintaining antivenom supplies on a provincial or regional level could use these data to guide antidote stocking and reduce costs.

History and perspectives on how to ensure antivenom accessibility in the most remote areas in Brazil.

A plan to achieve self-sufficiency in manufacturing biologicals for public health has been structured for the last 40 years in Brazil, in the context of a reform in the health system. Industrial plants of the national public laboratories have been modernized, and a program for reducing morbidity and mortality of venomous snakebite has been created, as part of the National Epidemiological Surveillance System. The epidemiological data are essential to plan for the antivenom production of 400,000 vials of snake antivenoms per year, and the acquisition by the Ministry of Health, which is the exclusive purchaser in the country. Distribution is decentralized to reach hospitals in almost 3000 municipalities, and to provide free of charge antivenom treatment. The National Sanitary Surveillance Agency organized the regulatory environment to implement rules and supervise compliance of GMP procedures, elevating the quality of the biologicals that are produced, as well as reducing the costs in production. Despite all the advances in the health system, antivenom availability and accessibility is not uniform in regards to the most vulnerable parts of the populations, which inhabit remote areas in the Brazilian Amazon region. Better logistics and transportation of liquid form antivenoms is an issue to be addressed and realistic and comprehensive health programs for indigenous groups should be effectively structured, in order to reduce the high morbidity and mortality rates associated with snakebite envenoming.

Bites by the Monocled Cobra, Naja kaouthia, in Chittagong Division, Bangladesh: Epidemiology, Clinical Features of Envenoming and Management of 70 Identified Cases.

AbstractWe describe 70 cases of monocled cobra (Naja kaouthia) bite admitted to Chittagong Medical College Hospital, Bangladesh. The biting snakes were identified by examining the dead snake and/or detecting N. kaouthia venom antigens in patients' serum. Bites were most common in the early morning and evening during the monsoon (May-July). Ligatures were routinely applied to the bitten limb before admission. Thirty-seven patients consulted traditional healers, most of whom made incisions around the bite site. Fifty-eight patients experienced severe neurotoxicity and most suffered swelling and pain of the bitten limb. The use of an Indian polyvalent antivenom in patients exhibiting severe neurotoxicity resulted in clinical improvement but most patients experienced moderate-to-severe adverse reactions. Antivenom did not influence local blistering and necrosis appearing in 19 patients; 12 required debridement. Edrophonium significantly improved the ability of patients to open the eyes, endurance of upward gaze, and peak expiratory flow rate suggesting that a longer-acting anticholinesterase drug (neostigmine) could be recommended for first aid. The study suggested that regionally appropriate antivenom should be raised against the venoms of the major envenoming species of Bangladesh and highlighted the need to improve the training of staff of local medical centers and to invest in the basic health infrastructure in rural communities.

Cost Minimization Analysis of Different Strategies of Management of Clinically Significant Scorpion Envenomation Among Pediatric Patients.

OBJECTIVE: Scorpion antivenom was recently approved for use in patients with clinically significant scorpion envenomation in the United States; no formal economic analysis on its impact on cost of management has been performed. METHODS: Three different strategies of management of scorpion envenomation with systemic neurotoxic symptoms in children were compared for cost minimization from a societal perspective. In strategy I, patients were managed with supportive care only without antivenom. In strategy II, an aggressive strategy of full-dose antivenom (initial dose of 3 vials with the use of additional vials administered 1 vial at a time) was considered. In strategy III, a single-vial serial antivenom dosing strategy titrated to clinical response was considered. Clinical probabilities for the different strategies were obtained from retrospective review of medical records of patients with scorpion envenomation over a 10-year period at our institution. Baseline cost values were obtained from patient reimbursement data from our institution. RESULTS: In baseline analysis, strategy I of supportive care only with no antivenom was least costly at US $3466.50/patient. Strategy III of single-vial serial dosing was intermediate but less expensive than strategy II of full-dose antivenom, with an incremental cost of US $3171.08 per patient. In a 1-way sensitivity analysis, at a threshold antivenom cost of US $1577.87, strategy III of single-vial serial dosing became the least costly strategy. CONCLUSIONS: For children with scorpion envenomation, use of a management strategy based on serial dosing of antivenom titrated to clinical response is less costly than a strategy of initial use of full-dose antivenom.

Low Health System Performance, Indigenous Status and Antivenom Underdosage Correlate with Spider Envenoming Severity in the Remote Brazilian Amazon.

BACKGROUND: A better knowledge of the burden and risk factors associated with severity due to spider bites would lead to improved management with a reduction of sequelae usually seen for this neglected health problem, and would ensure proper use of antivenoms in remote localities in the Brazilian Amazon. The aim of this study was to analyze the profile of spider bites reported in the state of Amazonas in the Western Brazilian Amazon, and to investigate potential risk factors associated with severity of envenomation. METHODOLOGY/PRINCIPAL FINDINGS: We used a case-control study in order to identify factors associated with spider bite severity in the Western Brazilian Amazon from 2007 to 2014. Patients evolving to any severity criteria were considered cases and those with non-severe bites were included in the control group. All variables were retrieved from the official Brazilian reporting systems. Socioeconomical and environmental components were also included in a multivariable analysis in order to identify ecological determinants of incidence and severity. A total of 1,181 spider bites were recorded, resulting in an incidence of 4 cases per 100,000 person/year. Most of the spider bites occurred in males (65.8%). Bites mostly occurred in rural areas (59.5%). The most affected age group was between 16 and 45 years old (50.9%). A proportion of 39.7% of the bites were related to work activities. Antivenom was prescribed to 39% of the patients. Envenomings recorded from urban areas [Odds ratio (OR) = 0.40 (95%CI = 0.30-0.71; p<0.001)] and living in a municipality with a mean health system performance index (MHSPI >median [OR = 0.64 (95%CI = 0.39-0.75; p<0.001)] were independently associated with decreased risk of severity. Work related accidents [OR = 2.09 (95%CI = 1.49-2.94; p<0.001)], Indigenous status [OR = 2.15 (95%CI = 1.19-3.86; p = 0.011)] and living in a municipality located >300 km away from the state capital Manaus [OR = 1.90 (95%CI = 1.28-2.40; p<0.001)] were independently associated with a risk of severity. Living in a municipality located >300 km away from the state capital Manaus [OR = 1.53 (95%CI = 1.15-2.02; p = 0.003)] and living in a municipality with a MHSPI 300 km away from the state capital Manaus could be contributing factors to higher severity of spider envenomings in this area, as well as to antivenom underdosage.

High or low- a trial of low dose anti snake venom in the treatment of poisonous snakebites.

OBJECTIVE: To demonstrate that use of lower doses of anti-snake venom is as effective as high doses and is associated with less complications and lower mortality especially in the wake of rising cost of medical treatment, the people most affected by snakebites being the poor farmers. METHODOLOGY: A prospective descriptive study consisting of 54 snakebite patients fulfilling the inclusion criteria who were admitted to Bangalore Baptist Hospital, Bengaluru, between November 2006 and November 2008 and were treated with a low dose ASV regime. The patients were initially given 2 vials of ASV followed later with 1 vial at a time according to clotting time. Any other supportive measures were undertaken as necessary. RESULTS: In this study the average dose of ASV required was only 6.70 +/- 3.24 vials. The complications--12.9% patients had ARF, and another 12.9% patients had neuropraralysis severe enough to require ventilatory support. There were 2 deaths (mortality of 3.7%) in the study. CONCLUSION: Low dose ASV regime in poisonous snakebites along with supportive treatment as necessary is as good as high dose regime, and has lesser adverse effects while reducing the cost of treatment too. Hence low dose regime can be used with beneficial results in poisonous snakebites.

Consequences of neglect: analysis of the sub-Saharan African snake antivenom market and the global context.

BACKGROUND: The worldwide neglect of immunotherapeutic products for the treatment of snakebite has resulted in a critical paucity of effective, safe and affordable therapy in many Third World countries, particularly in Africa. Snakebite ranks high among the most neglected global health problems, with thousands of untreated victims dying or becoming permanently maimed in developing countries each year because of a lack of antivenom-a treatment that is widely available in most developed countries. This paper analyses the current status of antivenom production for sub-Saharan African countries and provides a snapshot of the global situation. METHODS: A global survey of snake antivenom products was undertaken in 2007, involving 46 current and former antivenom manufacturers. Companies producing antivenom for use in sub-Saharan Africa were re-surveyed in 2010 and 2011. RESULTS: The amount of antivenom manufactured for sub-Saharan Africa increased between 2007 and 2010/11, however output and procurement remained far below that required to treat the estimated 300,000-500,000 snakebite victims each year. Variable potency and inappropriate marketing of some antivenoms mean that the number of effective treatments available may be as low as 2.5% of projected needs. Five companies currently market antivenom for sale in Africa; three others have products in the final stages of development; and since 2007 one has ceased production indefinitely. Most current antivenom producers possess a willingness and capacity to raise output. However inconsistent market demand, unpredictable financial investment and inadequate quality control discourage further production and threaten the viability of the antivenom industry. CONCLUSION: Financial stimulus is urgently needed to identify and develop dependable sources of high-grade antivenoms, support current and emerging manufacturers, and capitalise on existing unutilised production capacity. Investing to ensure a consistent and sustainable marketplace for efficacious antivenom products will drive improvements in quality, output and availability, and save thousands of lives each year.

Safety and cost-effectiveness of a clinical protocol implemented to standardize the use of Crotalidae polyvalent immune Fab antivenom at an academic medical center.

STUDY OBJECTIVE: To evaluate the safety and cost-effectiveness of a clinical protocol adopted in June 2006 that included a comprehensive, objective assessment of snake bite envenomations and standardized the use of Crotalidae polyvalent immune Fab antivenom (FabAV). DESIGN: Retrospective medical record review. SETTING: Academic medical center that serves as the regional level I trauma center. PATIENTS: Seventy-five adults treated with FabAV for snake envenomations in the emergency department between June 1, 2003, and June 1, 2009; 30 patients received treatment according to the protocol (treatment group), and 45 patients received treatment that did not adhere to the protocol (control group). MEASUREMENTS AND MAIN RESULTS: Demographic and envenomation characteristics, as well as treatment details, were collected for all patients. In addition, information on quantity of FabAV vials required, length of hospital stay, and length of intensive care unit stay were compared between the treatment and control groups. In the treatment group, significantly fewer vials of FabAV were used (2.5 vs 4.727 vials, p=0.007). This decreased in usage correlated to a cost savings of approximately $2000/patient. Despite no significant difference in the severity of the envenomations between the two groups (p=0.379), the treatment group experienced a significantly shorter hospital length of stay (1.933 vs 2.791 days, p=0.030). No significant difference in the progression to fasciotomy or the development of allergic reactions was noted between the two groups. CONCLUSION: Use of a clinical protocol related to snake envenomations resulted in approximately two fewer vials of FabAV required for each patient. In addition, the treatment group experienced a shorter hospital length of stay without a corresponding increase in adverse events or envenomation progression. Data show that use of the protocol was cost-effective. The development of institution-specific multidisciplinary protocols regarding snake bite envenomations is recommended. Clinical pharmacists can play a vital role in the protocol development to ensure that optimal care is provided for this distinct patient population.

The impact of snake bite on household economy in Bangladesh.

The present study aims to assess the different types of costs for treatment of snake bite patients, to quantify household economic impact and to understand the coping mechanisms required to cover the costs for snake bite patients in Bangladesh. The patients admitted to four tertiary level hospitals in Bangladesh were interviewed using structured questionnaires including health-care-related expenditures and the way in which the expenditures were covered. Of the snakes which bit the patients, 54.2% were non-venomous, 45.8% were venomous and 42.2% of the patients were given polyvalent antivenom. The total expenditure related to snake bite varies from US$4 (US$1 = Taka 72) to US$2294 with a mean of US$124 and the mean income loss was US$93. Expenditure for venomous snake bite was US$231, which is about seven times higher than non-venomous snake bite (US$34). The treatment imposes a major economic burden on affected families, especially in venomous snake bite cases.

Evidence-based, multidisciplinary approach to the development of a crotalidae polyvalent antivenin (CroFab) protocol at a university hospital.

BACKGROUND: Several thousand people are bitten annually by venomous snakes in the US. While the development of ovine Crotalidae polyvalent immune Fab antivenin (FabAV) for Crotalinae snakebite envenomations has greatly changed the way this clinical presentation is treated, multiple issues complicate its use. From patient assessment and evaluation, to medication preparation and administration, to the management of adverse drug reactions, the use of this antidote carries with it multiple points of possible medication variances. The inappropriate use of this agent can result in adverse patient consequences and a significant financial burden for both the hospital and the patient. OBJECTIVE: To describe an evidence-based, multidisciplinary approach that was taken to ensure optimal, safe, and cost-effective treatment of patients with FabAV. METHODS: Following an analysis of the available literature, a multidisciplinary committee was formed to construct a protocol for use of FabAV. This group included clinical pharmacists, pharmacy administrators, emergency medicine physicians who specialized in wilderness medicine and pharmacy residents. RESULTS: A multidisciplinary FabAV usage protocol was constructed and implemented to ensure appropriate patient evaluation, FabAV use and preparation, monitoring, and follow-up. This protocol was based on the available literature and the expert opinion of the committee. Through the use of a 24-hour in-house pharmacy resident on-call system, clinical pharmacy services were provided to ensure a multidisciplinary approach to the care of these patients emergently. Although limited, initial data show that this approach is effective and may result in substantial cost savings. CONCLUSIONS: Initial results from implementation of a protocol for use of FabAV have limited inappropriate use, reduced medication wastage, and decreased costs.

Effect of antivenin dose on outcome from crotalid envenomation: 218 dogs (1988-2006).

OBJECTIVE: To determine whether the dose of antivenin administered is associated with a difference in survival of crotalid-envenomated dogs. A secondary objective was to determine whether other covariables affect survival. DESIGN: Retrospective study (1988-2006). SETTING: Private referral center and university small animal teaching hospital. ANIMALS: Two hundred and eighteen dogs with evidence of crotalid envenomation and treatment with equine-derived antivenin. INTERVENTIONS: Administration of antivenin. MEASUREMENTS AND MAIN RESULTS: Patient signalment, physical and clinicopathologic data at time of presentation, treatments, complications of antivenin therapy, length and cost of hospitalization, and outcome were recorded. Confidence intervals were determined for the difference in median number of vials administered and for median dosage for patients that lived versus died. Penalized logistic regression was performed to evaluate the effect of other covariables on survival. The median age of affected dogs was 3 years (range 6 w-12 y) with a median weight of 25.7 kg (range 1.95-86.4 kg). The median number of antivenin vials administered was 1.0 (range 1.0-10.0). Acute and chronic reactions were reported in 7% (16/218) and 0.9% (2/218) of dogs, respectively. Nine of 218 dogs (4.1%) died. The median number of vials administered to the nonsurvivors and survivors were 2.0 (range 1-5 vials) and 1.0 (range 1-10 vials), respectively. The median number of vials received was significantly different in dogs that died versus those that lived (P<0.05). Increased heart rate (P=0.02) and petechiation (P=0.04) were associated with decreased likelihood of survival, while diphenhydramine (P=0.02) and fluoroquinolone (P=0.046) administration was associated with increased likelihood of survival. The median duration of hospitalization was 1.0 day (range 2 h-22 d). The median cost of hospitalization was US$1592.00 (range US$267.20-US$6738.00). CONCLUSION: The administration of more vials of antivenin is potentially associated with negative outcome; however, a causal relationship has not been established. Controlled, prospective studies are needed to optimize antivenin administration.

High-dose anti-snake venom versus low-dose anti-snake venom in the treatment of poisonous snake bites--a critical study.

OBJECTIVES: To asses the optimum dose of anti-snake venom to treat snake bites cases effectively. This is particulary relevant in the present scenario when the cost of anti-snake venom ( Serum Institute of India) has gone up to nearly Rs. 400 per vial and the cross-section of people usually affected belong to the poor socioeconomic class. METHODOLOGY: One hundred snake bite cases with envenomation, irrespective of whether they were bitten by viper, cobra or krait, brought within 24 hours of the bite to Jubilee Mission Hospital, Trichur, Kerala State during the 15 months from August 2001 to October 2002 were randomized into two groups of 50 cases each, irrespective of the severity of the cases. One group received a fixed dose regime of six vials of anti-snake venom and the other 12 vials of the same. RESULTS: In the low-dose group there were five deaths giving a mortality rate of 10%, nine (18%) required dialysis and three (6%) required ventilatory support. In the high-dose group there were seven deaths giving a mortality rate of 14%, 13 (26%) required dialysis and three (6%) required ventilatory support. The average hospital stay for the low-dose group was 8.42 days while that of the high-dose group was 9.02 days. CONCLUSION: While there was no additional advantage in following a high-dose regime for snake bite cases, there was considerable financial gain by following the low-dose regime, Most of the parameters showed a beneficial trend for the low-dose group though the differences were not statistically significant.

Preclinical assessment of the ability of polyvalent (Crotalinae) and anticoral (Elapidae) antivenoms produced in Costa Rica to neutralize the venoms of North American snakes.

Polyvalent (Crotalinae) and anticoral (Elapidae) antivenoms produced by Instituto Clodomiro Picado, Costa Rica, were assessed for their ability to neutralize various toxic activities of the venoms of North American snakes of the genera Crotalus, Agkistrodon and Micrurus, in assays involving preincubation of venom and antivenom. When the intraperitoneal route of injection was utilized, polyvalent (Crotalinae) antivenom was effective in the neutralization of the venoms of Crotalus atrox, Crotalus adamanteus, Crotalus viridis viridis, Crotalus horridus atricaudatus, Agkistrodon contortrix contortrix and Agkistrodon piscivorus piscivorus, whereas the venom of Crotalus scutulatus was not neutralized. When the intravenous route was used, results differed depending on the "challenge dose" of venom employed. Polyvalent antivenom neutralized all venoms when mice were challenged with 2 LD(50)s of venom. When 5 LD(50)s were used, antivenom neutralized the venoms of C. atrox, C. adamanteus, C. v. viridis and C. h. atricaudatus, being ineffective in the neutralization of C. scutulatus, A. c. contortrix and A. p. piscivorus. Polyvalent antivenom was effective in the neutralization of hemorrhagic and myotoxic activities of all venoms studied. It also neutralized coagulant activity of C. adamanteus venom, whereas most of the venoms were devoid of clotting activity on plasma in vitro. Moreover, it neutralized defibrinating activity of the only three venoms that induced this effect (i.e. C. adamanteus, A. c. contortrix and A. p. piscivorus). Anticoral (Elapidae) antivenom neutralized lethality induced by the venom of Micrurus fulvius, using either the intravenous or the intraperitoneal routes of injection. Moreover, it neutralized myotoxic effect of this venom as well. It is concluded that polyvalent antivenom neutralizes lethality and other activities of most of the crotaline venoms tested. However, since it is ineffective in neutralizing the lethal effect of C. scutulatus venom, it is suggested that a venom containing presynaptically-active neurotoxic phospholipases A(2) related to "mojave toxin" needs to be introduced in the immunizing mixture in order to increase the neutralizing scope of this product in North America. Anticoral antivenom is highly effective in the neutralization of the venom of M. fulvius.