Moderate-to-severe Vipera berus envenoming requiring ViperaTAb antivenom therapy in the UK.

BACKGROUND: Bites by the European adder (Vipera berus) in the UK are uncommon but potentially life threatening, and can be associated with marked limb swelling and disability. Following an interruption in Zagreb Imunoloski zavod antivenom supply around 2012, the UK changed its national choice of antivenom for Vipera berus to ViperaTAb, an ovine Fab monospecific antivenom. In the absence of randomised controlled trials, we established an audit to review its use in clinical practice. METHODS: A prospective audit of ViperaTAb use was conducted from March 2016 until November 2020 by the UK National Poison Information Service (NPIS). Users of the NPIS online toxicology database, TOXBASE, considering the use of antivenom for V. berus envenoming were invited to discuss the case with the on-call clinical toxicology consultant. Information was collected prospectively on indications, administration, adverse reactions and outcome of patients administered ViperaTAb antivenom. RESULTS: One hundred and seventy patients were administered ViperaTAb antivenom over five years. One hundred and thirty-two were adults and 38 children (median age and range: 38, 2-87 years). Bites occurred across the UK, but most commonly in coastal regions of Wales and of South-West and East England. Median time to presentation was 2.1 (IQR 1.5-4.0) h and to antivenom administration from presentation was 2.0 (IQR 0.9-3.6) h. A minority of patients presented to hospital more than 12 h after being bitten (n = 19, 11.2%) or received antivenom more than 12 h after presenting to hospital (n = 17, 10.0%). Features of systemic envenoming were present in 64/170 (37.6%) patients, including 23 (13.5%) with anaphylaxis and 26 (15.3%) with hypotension (nine with both). Clinician assessment considered the initial antivenom to have been effective in 122/169 (72.2%) patients. Repeated dosing was common, occurring in 55/169 (32.5%), predominantly due to persisting or worsening local effects (46/51, 90.2%). There were three cases of probable early adverse reaction. No deaths occurred during the study. Complications of envenoming were rare but included four patients that underwent surgery, three patients each with acute kidney injury, mild coagulopathy, or thrombocytopenia (one severe). The median duration of hospital stay was 43.7 (IQR 22.5-66.5) h, longer for children than adults (52.5 vs 41.3 h). CONCLUSION: ViperaTAb antivenom appears to be effective and safe and should be administered as soon as possible for patients meeting clinical criteria. Patients require close observation following antivenom to detect adverse reactions and progression or recurrence of envenoming. Close collaboration with expert NPIS consultant advice can help optimise antivenom timing, ensure repeated dosing is given appropriately, and avoid unnecessary surgical intervention. All hospitals, particularly those located in areas of relatively high incidence, should stock sufficient antivenom available at short notice, 24 h a day.

Failure of a Mexican antivenom on recovery from snakebite-related coagulopathy in French Guiana.

INTRODUCTION: In French Guiana, most snakebites are caused by crotalids, with the main signs being tissue damage and bleeding due to venom-induced coagulopathy. Since December 2014 the Western Guiana Hospital (WGH) has used Antivipmyn Tri TM, a Mexican polyvalent antivenom. The aim of the study was to assess its benefit on the correction of snakebite-related coagulopathy. METHODS: This retrospective study included patients hospitalized at the WGH with snakebite and a coagulopathy defined by: a prothrombin rate (PR) lower than 45%, an activated partial thromboplastin time ratio (aPTTr) greater than 2 or a fibrinogen lower than 100 mg.dL-1. The antivenom group included patients receiving Antivipmyn Tri TM from December 2014 to September 2017. The control group included patients admitted between January 2013 and November 2014 (when antivenom was unavailable) or admitted between December 2014 and September 2017 during times of antivenom shortage. We graphically compared the time courses of PR, aPTTr and fibrinogen between groups. Other endpoints were the length of hospital stay and the need for surgery or dialysis. RESULTS: 84 patients were included: 42 in the antivenom group, 42 in the control group. Both groups were similar for age, sex-ratio, proportion of bleedings, necrosis, and severity. Most patients in the antivenom group received 3 vials. There were no significant differences in recovery of PR, aPTTr and fibrinogen through the first 24 h. Fibrinogen declined again in the control group at 30 h and showed a slower rise to normal concentration. There were no significant differences in any secondary endpoint. CONCLUSION: Antivipmyn Tri TM as currently used did not show any benefit in recovery from coagulopathy.

Clinical manifestations and treatments of Protobothrops mucrosquamatus bite and associated factors for wound necrosis and subsequent debridement and finger or toe amputation surgery.

INTRODUCTION: Protobothrops mucrosquamatus bite induces wound necrosis, coagulopathy, thrombocytopenia, rhabdomyolysis, and acute renal failure. The severity of the hematological derangements and associated factors for wound necrosis and subsequent surgery and the appropriate management of these conditions have not been well characterized. Although severe renal failure requiring hemodialysis has been reported following P. mucrosquamatus bite, the culprit snake may be erroneously classified. MATERIALS AND METHODS: A total of 186 patients with P. mucrosquamatus bites were retrospectively evaluated. They were categorized into group 1 (patients receiving debridement or finger/toe amputation) and group 2 (all other patients) to identify the associated factors for surgery. Characteristic data were compared between groups 1 and 2 and between definite and suspected cases. RESULTS: No differences were observed between definite and suspected cases in terms of symptomatology and management. Of the 186 patients, 7 (3.8%) were asymptomatic, 179 (96.2%) experienced tissue swelling and pain, and 107 (57.5%) had local ecchymosis. Coagulopathy, thrombocytopenia, and renal impairment were found in 13 (7%), 19 (10.2%), and 7 (3.8%) patients, respectively. None of the patients required transfusion therapy or hemodialysis. Furthermore, no systemic bleeding or death occurred. Antivenom was administered to all 179 envenomed patients at a median of 1.5 h post-bite. The median total dose of the specific antivenom was 5.5 vials. In multivariate logistic regression analysis, finger as the bite site, bullae and blister formation, and wound infection were significantly associated with wound necrosis; whereas finger as the bite site and bullae and blister formation were related to debridement or finger/toe amputation. DISCUSSION AND CONCLUSIONS: Protobothrops mucrosquamatus envenomation mainly exerts effects on local tissue. Systemic effects are uncommon and generally nonsevere and transient after the treatment with the specific antivenom. We speculated that severe renal failure requiring hemodialysis is not a typical finding of P. mucrosquamatus envenomation. Patients with finger as the bite site and bullae or blister formation should be carefully examined for wound necrosis, secondary infection, and subsequent surgery. Further evaluations of the efficacy of antivenom against local tissue effects and the effect of selective antibiotics in the management of bite wound infection are urgently required. Although the antivenom manufacturer suggested a skin test prior to use, we believed that it could be omitted because it does not accurately predict the allergic responses.

Clinical studies of the effectiveness and safety of antivenoms.

In the 1890s, hyperimmune sera proved effective in animals against challenge by the snake venom against which they had been raised. They were first used, apparently successfully, in a human patient in about 1895. Since then, antivenoms have become accepted as the only reliable specific treatment for snake-bite envenoming. Despite decades of accumulated clinical experience and a number of published randomized comparative and observational studies, the clinical effectiveness and safety of some antivenoms remain open to question, due to a lack of robust randomized controlled trial data. Antivenoms in some poorly regulated markets may have high rates of potentially fatal adverse effects and their use must be balanced by demonstrable effectiveness. Even those manufactured to strict regulatory requirements may pose a rare risk of severe adverse reactions. Most antivenoms currently marketed around the world were registered without first being studied clinically. There is increasing pressure to subject antivenoms, even those that are long-established, to the same protocols of rigorous pre-clinical and clinical assessment that are standard regulatory requirements for other drugs. Conventional clinical testing progresses through Phases I, II, III to IV. Most authorities consider antivenoms too dangerous to be used in Phase I studies in healthy volunteers. An alternative method for preliminary estimation of safety, dose-finding and effectiveness, is proposed - the "3 + 3" dose escalation or de-escalation design, in volunteer patients, as used in oncology to test cytotoxic drugs. Antivenoms are so widely used and well trusted, that there are few ethical justifications for placebo controls. However, placebo might be ethically justified if there were no proven effective treatment and or if withholding or delaying treatment posed acceptably negligible risks to the participants. Antivenom trials are most urgently needed in low-to middle-income countries where there are many practical, logistical and funding challenges. Basic requirements for clinical trials include identification of the biting species of snake in every case; the use of objective, clinically-relevant endpoints, such as restoration of blood coagulability; definition of inclusion, exclusion and withdrawal criteria; assurance of antivenom safety; ethical considerations; inclusion of one or more control (comparator) groups; and analysis based on intention to treat. The highest quality evidence comes from Phase II and larger Phase III studies that have been designed as statistically powerful, randomized, controlled trials (RCTs), ideally with blinding of patients and investigators to avoid bias. Because of the challenges to carrying out clinical trials of antivenoms, Phase IV trials (post-marketing surveillance) are potentially more important and useful than for most other drugs.

Antivenom therapy: efficacy of premedication for the prevention of adverse reactions

Antivenoms or antitoxins have been effectively used for more than a century. During this time, these products have always proven to be highly effective in the treatment of infections and envenomations. However, antivenoms did not exhibit good safety results in their initial applications. After many improvements, antivenoms have substantially better safety profiles but still have some side effects. Due to the occurrence of adverse reactions, the practice of using premedication with the intent to decrease side effects has become accepted or mandatory in many countries. The drugs used for premedication belong to the histamine H1 antagonist, glucocorticoid and catecholamine groups. Currently, this practice is being questioned due to low or controversial efficacies in clinical assays. In this article, we discuss the causes of adverse reactions, the mechanisms of drugs that block the undesired effects and the results obtained in clinical trials. Although these three families of drugs could have positive effects on reducing adverse reactions, only adrenaline has demonstrated positive results in clinical assays.(AU)

Medically significant late bleeding after treated crotaline envenomation: a systematic review.

STUDY OBJECTIVE: We estimate the proportion of patients with crotaline snake envenomation who are treated with Crotalidae polyvalent immune Fab (ovine) antivenom and who develop medically significant late bleeding. METHODS: We performed a systematic review of all published cohort studies of North American crotaline snake envenomation patients treated with Fab antivenom. We searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to April 30, 2012. Data were extracted by 2 trained researchers. Late bleeding was defined as bleeding that began or recurred after initial control of the envenomation syndrome. Medically significant late bleeding was defined a priori as late bleeding treated with RBC transfusion, vasoactive drug infusion, surgery, or rehospitalization or associated with a hemoglobin decrease of greater than or equal to 3 g/dL, hematocrit decrease of greater than or equal to 8%, disability, or death. Summary incidence and 95% confidence intervals (CIs) were calculated with a random-effects Poisson regression model. RESULTS: Nineteen unique cohort studies were identified. Four studies collected data prospectively, and in 9 studies, patients were followed actively after hospital discharge. A total of 1,017 subjects were enrolled in these cohort studies. Late bleeding was reported in 9 subjects (0.9%; 95% CI 0.4% to 2.2%), of whom 5 subjects (0.5%; 95% CI 0.1% to 1.7%) had medically significant late bleeding. Three patients received RBC transfusion; no deaths or permanent sequelae were reported. Estimates of risk may be affected by underreporting. CONCLUSION: Medically significant late bleeding appears to be uncommon in snakebite victims treated with Fab antivenom.

Immune response to snake envenoming and treatment with antivenom; complement activation, cytokine production and mast cell degranulation.

BACKGROUND: Snake bite is one of the most neglected public health issues in poor rural communities worldwide. In addition to the clinical effects of envenoming, treatment with antivenom frequently causes serious adverse reactions, including hypersensitivity reactions (including anaphylaxis) and pyrogenic reactions. We aimed to investigate the immune responses to Sri Lankan snake envenoming (predominantly by Russell's viper) and antivenom treatment. METHODOLOGY/PRINCIPAL FINDINGS: Plasma concentrations of Interleukin (IL)-6, IL-10, tumor necrosis factor α (TNFα), soluble TNF receptor I (sTNFRI), anaphylatoxins (C3a, C4a, C5a; markers of complement activation), mast cell tryptase (MCT), and histamine were measured in 120 Sri Lankan snakebite victims, both before and after treatment with antivenom. Immune mediator concentrations were correlated with envenoming features and the severity of antivenom-induced reactions including anaphylaxis. Envenoming was associated with complement activation and increased cytokine concentrations prior to antivenom administration, which correlated with non-specific systemic symptoms of envenoming but not with coagulopathy or neurotoxicity. Typical hypersensitivity reactions to antivenom occurred in 77/120 patients (64%), satisfying criteria for a diagnosis of anaphylaxis in 57/120 (48%). Pyrogenic reactions were observed in 32/120 patients (27%). All patients had further elevations in cytokine concentrations, but not complement activation, after the administration of antivenom, whether a reaction was noted to occur or not. Patients with anaphylaxis had significantly elevated concentrations of MCT and histamine. CONCLUSIONS/SIGNIFICANCE: We have demonstrated that Sri Lankan snake envenoming is characterized by significant complement activation and release of inflammatory mediators. Antivenom treatment further enhances the release of inflammatory mediators in all patients, with anaphylactic reactions characterised by high levels of mast cell degranulation but not further complement activation. Anaphylaxis is probably triggered by non allergen-specific activation of mast cells and may be related to the quality of available antivenom preparations, as well as a priming effect from the immune response to the venom itself.

Use of antivenoms for the treatment of envenomation by Elapidae snakes in Guinea, Sub-Saharan Africa

Background In Guinea Elapids are responsible for 20% of envenomations. The associated case fatality rate (CFR) ranged 15-27%, irrespective of treatment. Results We studied 77 neurotoxic envenomations divided in 3 groups: a set of patients that received only traditional or symptomatic treatments, and two other groups that received either 2 or 4 initial vials of Antivipmyn® Africa renewed as necessary. CFR was 27.3%, 15.4% and 17.6%, respectively. Although antivenom treatment was likely to reduce CFR, it didn’t seem to have an obvious clinical benefit for the patients, suggesting a low treatment efficacy. Mean delay to treatment or clinical stages were not significantly different between the patients who recovered and the patients who died, or between groups. Interpretation of these results is complicated by the lack of systematic studies under comparable conditions. Of particular importance is the absence of assisted ventilation, available to patients in all the other clinical studies of neurotoxic envenomation. Conclusion The apparent lack of clinical benefit may have several causes. The hypothesis of a limited therapeutic window, i.e. an insufficient formation of antigen-antibody complexes once toxins are bound to their targets and/or distributed beyond the reach of antivenom, should be explored. .

Management of envenomations during pregnancy.

CONTEXT: Envenomations during pregnancy pose all the problems of envenomation in the nonpregnant state with additional complexity related to maternal physiologic changes, medication use during pregnancy, and the well-being of the fetus. OBJECTIVE: We review the obstetric literature and management options available to prevent maternal morbidity and mortality while limiting adverse obstetric outcomes after envenomation in pregnancy. METHODS: In January 2012, we searched the U.S. National Library of Medicine Medline/PubMed, Toxline, Reprotox, Google Scholar and Micromedex databases, core surgery and internal medicine textbooks, and references of retrieved articles for the years 1966 through 2011. Search terms included "envenomation in pregnancy," "stings in pregnancy," "antivenom use in pregnancy," "anaphylaxis in pregnancy," and variants of these with known venomous animals. Reference lists generated further case reports and articles. We included English language articles and abstracts. Levels of Evidence (LOE) for the reports cited and Grades of Recommendations (GOR) based on LOE for our recommendations use the National Guidelines Clearinghouse metric of the US DHHS. RESULTS: Recommendations for the management of envenomation in pregnancy are guided primarily by studies on nonpregnant persons and case reports of pregnancy. Clinically significant envenomations in pregnancy are reported for snakes, spiders, scorpions, jellyfish, and hymenoptera (bees, wasps, hornets, and ants). Adverse obstetric outcomes including miscarriage, preterm birth, placental abruption, and stillbirth are associated with envenomation in pregnancy. The limited available literature suggests that adverse outcomes are primarily related to venom effects on the mother. Optimization of maternal health such as management of anaphylaxis and antivenom administration is likely the best approach to improve fetal outcomes despite potential risks to the fetus of medication administration during pregnancy. Obstetric evaluation and fetal monitoring are imperative in cases of severe envenomation. CONCLUSION: The medical literature regarding envenomation in pregnancy includes primarily retrospective reviews and case series. The limited available evidence suggests that optimal management includes a venom-specific approach, including supportive care, antivenom administration in appropriate cases, treatment of anaphylaxis if present, and fetal assessment. The current available evidence suggests that antivenom use is safe in pregnancy and that what is good for the mother is good for the fetus. Further research is needed to clarify the optimal management schema for envenomation in pregnancy.

The use and tolerability of Crotalidae Polyvalent Immune FAB (Ovine) in pediatric envenomations.

There are limited data on the use of Crotalidae Polyvalent Immune FAB-Ovine (CroFab) in the management of crotalid envenomations in children. Thus, the primary objective of this retrospective chart review was to evaluate the safety and tolerability of CroFab in a pediatric population. Over an 8-year time period at this institution, there were 204 admissions for snakebite of which 82 received CroFab. Children who received CroFab were more often associated with bites to the hands and fingers and tended to have more significant envenomations as indicated by longer hospital stays, greater tissue injury, and a tendency to require surgery more often. Six (7.3%) of the 82 patients who received CroFab experienced an adverse drug reaction. Reactions consisted of allergic symptoms that were mild, responded to minimal interventions, and did not limit the subsequent use of CroFab. It is concluded that CroFab use is typically well tolerated in pediatric patients.

Severe snakebites in northern KwaZulu-Natal: treatment modalities and outcomes.

OBJECTIVE: We aimed to study the outcomes of severe snakebites in patients admitted to Ngwelezana Hospital in north-eastern KwaZulu-Natal, the seasonal variations, and the effectiveness and complications of antivenom. DESIGN: A prospective observational outcomes study was conducted over one year (1 June 2007 to 31 May 2008). The study group was from the north-eastern KwaZulu-Natal region of South Africa, with a population of approximately 3 million people, and included all patients bitten by snakes and admitted to the Ngwelezana Hospital Emergency Medicine Unit (EMU). Departmental practice guidelines were documented and followed. OUTCOME MEASURES: End-points for patient outcomes included transfer from the EMU to the ward, discharge home from the EMU, and follow-up of patients who required surgery or ICU care. RESULTS: A total of 243 snakebite patients were recorded. The highest incidence was in the summer months; 46 (18.93%) patients experienced one or more severe complications; 29 (11.93%) patients received some form of definitive management in hospital; and 22 (9.05%) of the latter patients received antivenom. Antivenom was administered to more children than adults. Adverse reactions to antivenom were common: an allergic response occurred in 4 (15.4%) patients, and anaphylaxis in 6 (23.1%); the highest incidence occurred in the <10-year-old age group. No deaths were recorded. CONCLUSIONS: Snakebites are common in the summer months in north eastern KwaZulu-Natal. Children are particularly vulnerable to snakebites and the effects of antivenom. Adverse reactions to antivenom are common. Severe snakebites that require antivenom should be managed in a hospital setting with advanced airway support. The syndromic approach to treatment is simple and effective.

Snake antivenoms: adverse reactions and production technology: [review]

Antivenoms have been widely used for more than a century for treating snakebites and other accidents with poisonous animais. Despite their efficacy, the use of heterologous antivenoms involves the possibility of adverse reactions due to activation of the immune system. In this paper, alternatives for antivenom production already in use were evaluated in light of their ability to minimize the occurrence of adverse reactions. These effects were classified according to their molecular mechanism as: anaphylactic reactions mediated by IgE, anaphylactoid reactions: aused by complement system activation, and pyrogenic reactions produced mainly by the presence of endotoxins in the final product. ln the future, antivenoms may be replaced by humanized antibodies, specific neutralizing compounds or vaccination. Meanwhile, improvements in antivenom quality will be focused on the obtainment of more purified and specific product in compliance with good manufacturing practices and at an affordable cost

A large single-center experience with treatment of patients with crotalid envenomations: outcomes with and evolution of antivenin therapy.

BACKGROUND: Antivenin (crotalid) polyvalent (ACP; Antivenin Crotalidae Polyvalent; Wyeth, Melville, NY) is associated with frequent allergic reactions. Allergic reactions are fewer with ovine Fab antivenin (FabAV). This study describes the management of crotalid envenomations in patients treated with FabAV or ACP, and without antivenin. METHODS: We performed a retrospective chart review of crotalid envenomations over 10 years. Demographic data, hematologic profiles, details of antivenin administration, and in-hospital morbidity and mortality were collected. RESULTS: There were no mortalities and a single amputation. Fewer fasciotomies were performed in the FabAV (9%) group versus the ACP group (24%). Mean hospital stay was 3.4 days. No allergic reactions were associated with FabAV. Fourteen of 211 reactions were associated with ACP (P < .001). Coagulopathy was frequent. CONCLUSIONS: FabAV represents an improvement in management of crotalid envenomations because of reduced allergic reactions. Serious morbidity and mortality is rare. Coagulopathy is frequent but bleeding is not. Limb salvage is high. Surgical debridement and ACP are contraindicated when FabAV is available.

Clinical applications of commonly used contemporary antidotes. A US perspective.

Poisonings are a common problem. In 1995, over 2 million exposures were reported to American poison information centres alone. The majority of poisoning exposures can be treated without major therapeutic intervention. If therapy is indicated, it is usually in the form of gastrointestinal decontamination with activated charcoal, to prevent absorption of the toxin and the subsequent toxicity that may occur. In a limited number of cases, more aggressive life-support measures may be necessary to treat the adverse effects of poisons. Occasionally, that intervention may include the use of pharmacological antagonists, more commonly referred to as antidotes. According to the American Association of Poison Control Centers, the most commonly used antidotes are acetylcysteine, naloxone, atropine, deferoxamine (desferrioxamine) and antivenins. Overall, 17 antidotes account for 99% of all antidote use and those agents are reviewed in this article. With the exception of naloxone, most antidotes have pharmacological effects that are independent of their inherent antidotal properties. Therefore, antidotes should be used judiciously because their pharmacological properties may exacerbate pre-existing toxicity and only in rare circumstances are they used prophylactically. Some antidotes, such as digoxin-specific antigen binding fragments (digoxin immune Fab), are very expensive, and both the risk: benefit ratio and the associated cost should be considered before the antidote is administered. The principle aims are to "treat the patient, not the poison' and to do no harm to the patient. Antidotes should be used only when they are indicated and may help a patient.

Snakebite treatment at a southeastern regional referral center.

Our objective was to determine the prevalence of poisonous snakebite victims admitted to a regional trauma center in Southeastern Georgia over a 10-year period, as well as the type of snake, grade of envenomation, treatment administered, morbidity and mortality, and outcome. Records of patients admitted to the center for snakebite from a 24-county catchment area during the 10-year period (January 1984 to January 1994) were retroactively reviewed. Sixty-three (63) bites in 62 victims of venomous snakebites were treated. The snake distribution was rattlesnake: 19 (30%), copperhead: 18 (29%), cottonmouth moccasin: 8 (12%), unknown: 18 (29%). Envenomation grades were Grade I: 20 (32%), Grade II: 24 (38%), Grade III: 10 (16%), and Grade IV: 9 (14%). Fourteen of 19 (74%) Grades III and IV envenomations were from rattlesnakes. Antivenin was used in all Grade IV and half of the Grade III envenomations. Antivenin was administered within 3 hours of injury in all but one case. Five patients had surgery. Two patients (both Grade I) developed anaphylaxes from antivenin given before hospitalization. All patients recovered. An average of 6 snakebites were treated each year. Expeditious transport, attention to the type of snake inflicting the bite, and judicious use of antivenin will result in a favorable outcome for the snakebite victim.

Experimental evaluation of ovine antisera to Thai cobra (Naja kaouthia) venom and its alpha-neurotoxin.

Conventional treatment of Naja kaouthia (Thai cobra) envenoming requires large volumes (up to 600 ml) of equine antivenom, which results in a high incidence of serum reactions. The inefficiency of the antivenom is assumed to be related to the high percentage (approx. 20%) of alpha-neurotoxin, a relatively weak and highly toxic immunogen, present in the native venom. First, antibodies to N. kaouthia venom were raised in sheep, which protected mice against challenge with whole venom. Second, ovine antibodies to the purified neurotoxin and to three different neurotoxin conjugates were developed and their neutralising abilities against either whole venom or neurotoxin were compared using murine ED50 tests. High titre antibodies, assessed by enzyme immunoassay and Western blot, were obtained from all four neurotoxin immunisation regimens. Neurotoxin conjugated to rabbit anti-sheep IgG produced the highest titres against both neurotoxin and whole venom. This antiserum provided protection against neurotoxin challenge but failed to protect against whole venom. Furthermore, the addition of neurotoxin antibodies to whole venom antiserum did not enhance the neutralisation efficacy of the latter. These findings raise the possibility that in mice other toxins apart from the neurotoxin may significantly contribute to the lethal effect of N. kaouthia venom.

Crotalidae envenomation in children.

Poisonous snakebites cause a severe envenomation syndrome in children, yet treatment remains controversial. Sixty-seven patients were treated for poisonous snakebites at our institution between 1975 and 1990; 18 were children < or = 12 years old. There were 13 rattlesnake bites, 4 copperhead bites, and 1 unidentified bite. Initial management included intravenous fluids and antibiotic administration, laboratory studies, tetanus prophylaxis, affected limb elevation, and a limited excision of the bite site in the emergency room. Antivenin was administered only if signs of systemic involvement such as shock, coagulopathy, gastrointestinal cramping, or neurological involvement were present. Children developed systemic involvement 72% of the time, 9 children (50%) developed coagulopathy. Consequently, 11 (61%) children received antivenin. The dose of antivenin they received was 3.2 ml/kg and the children tolerated it well with only 36% of them demonstrating adverse reactions to the antivenin. Clinically, the pediatric patients demonstrated signs and symptoms of a fulminant envenomation syndrome (8 days, average hospital stay), yet, they had a good eventual outcome. Only 11% of children reported long-term morbidity. No deaths occurred and 100% of patients were able to return to full preinjury activities. We conclude that Crotalidae envenomation in children is a serious disease and warrants hospitalization, early surgical involvement, and frequent use of antivenin.

Poisonous snakebite in central Texas. Possible indicators for antivenin treatment.

Sixty-seven patients hospitalized for poisonous snakebite between 1975 and 1990 were managed by elevation, tetanus prophylaxis, intravenous fluids and antibiotics, and often by a limited excision of the bite site in the Emergency Department, with sequential laboratory studies as needed. Antivenin was used for systemic envenomation, and 23 of the 67 patients (34%) received 133 vials. Thirteen of the twenty-three patients (56%) had adverse reactions to the antivenin. Two significant observations arose. First age was an indicator. Eleven of eighteen patients 12 years or younger (61%) received antivenin, whereas 12 of 49 patients older than 12 years (24%) received antivenin (p = 0.0085, Fisher's exact test). Second species of snake was an indicator. Sixty-two snakes were identified (93%). Of 39 rattlesnake (Crotalus and Sistrurus) bites, 20 patients received antivenin (53%), but of 23 copperhead and water moccasin (Agkistrodon) bites, only three patients (12.5%) received antivenin (p = 0.0025). Antivenin may be indicated for use in systemic rattlesnake envenomation, especially in younger patients.