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Antivenin administration for Centruroides scorpion sting: risks and benefits.

STUDY OBJECTIVES: To assess the clinical severity of envenomation by the Centruroides scorpion in young children; the potential benefit of antivenin administration with regard to time to resolution of symptoms, prevention of hospitalization, and prevention of invasive intervention; and the risk of acute and delayed hypersensitivity reaction. DESIGN: Retrospective chart review with follow-up contact. SETTING: Referral toxicology management center. TYPE OF PARTICIPANTS: Children less than 10 years of age experiencing severe Centruroides scorpion envenomation. INTERVENTIONS: Administration of goat serum-derived anti-Centruroides antivenin. MEASUREMENTS AND MAIN RESULTS: Stings in young children may be life threatening, resulting in extreme neuromuscular activity, tachycardia, and respiratory distress. Administration of anti-Centruroides antivenin resulted in rapid resolution of all symptoms without acute reaction in all 12 patients so treated; 58% of patients treated with antivenin had a delayed onset of rash or symptoms of serum sickness. CONCLUSION: The benefit of rapid resolution of life-threatening symptoms and potential for outpatient management of severe envenomation in young children may justify the risk of acute and delayed reaction associated with antivenin use in this group. The use of antivenin for the less severe envenomation common in older children and adults may subject them to unjustified risk.

Animals↗

Delayed administration of Vipera xanthina palaestinae antivenin.

INTRODUCTION: Vipera xanthina palaestinae is the most widely distributed venomous snake in Israel, accounting for most envenomations. A specific equine antivenin is efficacious against both systemic and local manifestations if given within hours. This study sought to determine if delayed vipera xanthina palaestinae antivenin can be effective. METHODS: Patients who had been bitten by vipera xanthina palaestinae during 1991-1995 were evaluated. Those who continued to deteriorate beyond 24 h post envenomation, in spite of treatment or because of delayed diagnosis, were given vipera xanthina palaestinae antivenin. RESULTS: Ten patients were included in the study. Vipera xanthina palaestinae was identified in seven and diagnosis was considered probable in three patients. On admission, eight patients had local signs and seven patients had mild to severe systemic manifestations. The local signs were remarkable and progressive in all patients. In five, systemic signs and laboratory abnormalities were delayed as well. The time range for delayed antivenin administration was 1-6 days after envenomation. Following antivenin administration, progression of local signs ceased in all patients and swelling regressed within 24 h. In nine patients this occurred within 6 h. CONCLUSION: Vipera xanthina palaestinae antivenin administration should be considered in patients with envenomations complicated by marked and progressive local signs, delayed systemic signs and laboratory abnormalities more than 24 h after envenomation.

Adolescent↗

Studies of scorpion antivenins. 1. Paraspecificity.

This paper describes neutralization tests conducted to determine the effectiveness of five commercially available antivenins, each from a different geographical area, in neutralizing homologous and heterologous scorpion venoms. Venoms of eight scorpion species were used. The work was undertaken because of current interest in the development of polyvalent antivenins for the treatment of venomous bites and stings, and for determination of paraspecific action of existing antivenins as a first step in such a developmental programme. During the studies described, several instances of cross-protection were found, and in some tests heterologous antivenins were more effective than homologous antivenins in protecting white mice against the effects of venom injections. The results obtained should be of practical value in planning a systematic approach towards production of a polyvalent antivenin for use anywhere in the world.

Animals↗

[The detoxification of Naja naja atra venom and preparation of potent antivenin].

The 99.2% toxicity of Naja naja atra venom can be detoxified by treatment with 0.25% GA (glutaraldehyde) solution at pH 6.8 and still remains its antigenicity. Using the GA treated venom incorporated with Freund's complete adjuvant as immunogen, the titer of immune horse sera can be enhanced rapidly. The modified immunization method not only shortened the period of immunization (from 180 to 60 days), but also increased the potency of immune sera (from 75 to 170 units). The method also diminished the mortality rate of the horse during the immunization period (from 37 to 0%) and increased the antibody production rate (from 20 to 100%), as compared to Tanaka's method. With the present method, significant economic effects can be achieved. The neutralization antibody titer of Naja naja atra antivenin could be elevated 3.55 times through purification of the antivenin with the pepsin digestion method. The antivenin recovery rate using the pepsin digestion method was about 55.44%. The solubility of lyophilized antivenin was significantly improved by the addition of 2% glycine. In addition to an increase of antivenin potency and purity, the problem of an inadequate production rate has also been resolved. Now lyophilized antivenin can be supplied even to remote areas, thus providing excellent opportunities for clinical application. This Institute has already adopted this new immunization schedule in lieu of the old Tanaka method.

Animals↗

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.

Adolescent↗

Rattlesnake venom-induced thrombocytopenia response to Antivenin (Crotalidae) Polyvalent: a case series.

OBJECTIVE: To test the hypothesis that rattlesnake venom-induced thrombocytopenia would improve following Antivenin (Crotalidae) Polyvalent administration, and that the degree of platelet increase would correlate with the dosage of antivenom. METHODS: The authors conducted a retrospective review of all patients admitted for rattlesnake envenomation at two southern California hospitals between 1980 and 1998. Patients were included if platelet count was less than 150 x 10(9)/L following a rattlesnake bite. Patients were excluded if they received platelet transfusion. The relationship between Antivenin (Crotalidae) Polyvalent administration and venom-induced thrombocytopenia was evaluated by linear regression and paired t-test. RESULTS: The authors identified 103 cases of rattlesnake envenomation. Seventeen cases met inclusion criteria for thrombocytopenia. Two patients were excluded because they received platelet transfusions. One additional patient was excluded from paired t-test only because no antivenom was given. Thrombocytopenia usually improved between presentation and discharge (mean difference, 44 x 10(9)/L), although complete resolution was often not achieved. A statistically significant partial improvement in platelet counts immediately after antivenom administration was observed in a subset of patients with severe thrombocytopenia (platelet count <100 x 10(9)/L) (mean difference, 64 x 10(9)/L). Using regression analysis, the authors did not detect a linear relationship between the amount of Antivenin (Crotalidae) Polyvalent administered and the degree of improvement. CONCLUSIONS: Although rattlesnake venom-induced thrombocytopenia usually improves immediately after Antivenin (Crotalidae) Polyvalent administration and by the time of discharge, the degree of improvement is frequently incomplete and of uncertain clinical significance in the absence of life-threatening bleeding. The authors found no correlation between the degree of improvement and the dosage of Antivenin (Crotalidae) Polyvalent.

Animals↗

Venoms of coral snakes (Micrurus spp.): report on a multivalent antivenin for the Americas.

A multivalent coral snake antivenin was prepared in horses immunized with a mixture of venoms from the species Micrurus nigrocinctus, M. mipartitus, and M. frontalis, following immunization procedures previously reported (2). Plasma from the horses was fractionated with ammonium sulfate. The antivenin produced was then tested against venoms from ten species. The neutralization titers obtained indicate it would be useful in treating bites received from most of the important coral snake species in North and South America, namely: M. fulvius, M. alleni, M. carinicaudus dumerilii, M. corallinus, M. frontalis, M. lemniscatus, M. mipartitus, M. nigrocinctus, and M. spixii. The authors note that appropriate cooperation by scientists in various countries would make production of this antivenin an easy matter, and that the product could conveniently be distributed via PAHO or other international agencies. They also note that the antivenin showed no significant neutralizing effect against M. surinamensis venom. This situation would appear to justify preparing a monovalent antivenin against M. surinamensis, or else including M. surinamensis venom in an immunization formula for a multivalent antidote.

Animals↗

Use of CroFab antivenin in the management of a very young pediatric copperhead envenomation.

The use of crotalid Fab antivenin (CroFab) in the treatment of snake envenomations in the pediatric population is still an underexplored area. There are very limited data to confirm the efficacy and safety of dosing children the same as adults and even less information available to evaluate this antivenin use in copperhead snake bites in children. We report the first use of crotalid Fab antivenin in an adult dose for a copperhead snake envenomation in a 2-year-old child. She had rapid resolution of symptoms with no adverse effects. The report serves to increase the literature supporting the current dosing recommendations of crotalid Fab antivenin in very young pediatric patients evidenced by its effectiveness in this patient.

Agkistrodon↗

Complications of Crotalidae antivenin therapy.

Polyvalent antivenin is the mainstay of treatment of serious snake envenomation. Its use, however, has been challenged as being unnecessary in minor envenomations and potentially hazardous due to allergic complications. Our institution routinely uses antivenin, and this report focuses on the allergic complications of this therapy. Forty patients with Crotalidae snake bites were evaluated and treated over a 7-year period. Twenty-six patients received a total of 507 vials of antivenin, the dose correlating with the clinical severity of envenomation. All patients were skin tested. Immediate hypersensitivity reactions occurred in six patients (23%). Cutaneous manifestations alone occurred in three of these patients, while systemic anaphylaxis occurred in three. Twenty patients were available for followup, and ten (50%) developed serum sickness. Skin testing was not reliable in predicting the development of immediate (anaphylaxis) or delayed (serum sickness) hypersensitivity reactions. Treatment of antivenin allergic reactions was uniformly effective, with no mortality, minimal morbidity, and no chronic sequelae.

Adolescent↗

Intraarterial vs intravenous administration of antivenin for the treatment of Crotalidae atrox envenomation: a pilot study.

OBJECTIVE: Standard therapy for significant snake envenomation includes antivenin. i.v. administration is currently the only recommended route. Intraarterial (i.a.) administration has potential advantages over i.v. that could improve outcome. To study this, the authors compared i.v. and i.a. antivenin administrations for the treatment of experimental snake envenomations. METHODS: 14 adult female swine were anesthetized and prepared with femoral artery and ear vein catheters, and baseline hoof, forearm, and thigh circumference and volume displacement measurements were taken. Crotalidae atrox venom was injected into the subcutaneous tissue of the hoof. The doses of venom were 4.75, 9.50, 19.00, 37.90, 47.30, 56.90, and 66.40 mg. Immediately following injection of venom, polyvalent antivenin (Crotalidae) (0.285 mg/10 mL saline) was infused over 30 minutes into the femoral artery (i.a. group) or ear vein (i.v. group). As a control, 10 mL of saline was infused into the ear vein (i.a. group) or femoral artery (i.v. group). Measurements were recorded up to 48 hours. Linear mixed-effect regression models were used for each measurement and to compare the i.a. and i.v. groups. RESULTS: Venom dose and time after administrations were associated with increased circumferences and increased volumes (p < 0.05). i.v. administration was associated with larger hoof (1.26 cm) and forearm (0.42 cm) sizes and volume displacement (21.71 mL) when compared with i.a. administration ( p < 0.05). CONCLUSION: i.a. antivenin results in a modest but significant decrease in tissue edema when compared with i.v..

Animals↗

Serological analysis of venoms and antivenins.

The immunological relationship between the venoms of six species of the snake genus Bothrops (alternata, atrox, cotiara, jararaca, jararacussu, neuwiedii) was investigated by assay against the corresponding species-specific antivenins in more than 11,000 intravenous and subcutaneous mouse tests. The observations were statistically analysed after the probit method.Both ways of antivenin assay gave numerically identical results, within the limits of error, in the majority of the tests. The width of the neutralization spectra of the monovalent sera anti-atrox, anti-jararaca, and anti-neuwiedii against the heterologous venoms is similar to that of a polyvalent antivenin obtained by immunization with all the six species of venom. The titre of a polyvalent antibothropic serum may vary with the venom species used in the assay.THE FOLLOWING ARE DISCUSSED: reasons for occasional difficulties in reproducing results, variations in the toxicity of different samples of the same venom species, divergences in the susceptibility of various species of laboratory animals to venom, and inter-relations between venoms and antivenins.

Animals↗

Interaction of Bothrops venoms and antivenin on the release of creatine kinase from skeletal muscle.

A polyvalent antivenin (5 microliter/ml) inhibited the increase in creatine kinase (CK) release from rat extensor digitorum longus muscles exposed to the venoms of B. jararacussu (20 micrograms/ml) or B. jararaca (150 micrograms/ml). The increase in plasma CK activity induced by intramuscular injection of B. jararacussu venom (2.5 micrograms/g) into mice was reduced by pretreatment with antivenin and was abolished by preincubation of the venom with the antivenin. Changes in CK release from isolated muscles or in plasma CK activity provide simple, quantitative methods for evaluating the effectiveness of antivenin against the myotoxicity of Bothrops venoms.

Animals↗

Inhibitory effects on phospholipase A2 and antivenin activity of melanin extracted from Thea sinensis Linn.

Antivenin activity of melanin extracted from black tea (MEBT) was reported for the first time. The antagonistic effect of MEBT was evaluated for Agkistrodon contortrix laticinctus (broadbanded copperhead), Agkistrodon halys blomhoffii (Japanese mamushi), and Crotalus atrox (western diamondback rattlesnake) snake venoms administered i.p. to ICR mice. MEBT was injected i.p. immediately after the venom administration in dose of 3 mg per mouse in the same place of venom injection. MEBT demonstrated neutralization effect against all venoms tested. The greatest antivenin effect of MEBT was found against Japanese mamushi snake venom. In this case, half the mice died within 2.5 +/- 0.7 h after injection of 0.9 mg/kg of venom. An immediate injection of MEBT substantially reduced the toxic effect of venom and extended time at the 50% level of survival up to 52.3 +/- 2.3 h. The antivenin activity of MEBT is due to chelating of Ca++ and non-specific binding of phospholipase A2. The inhibitory effect of MEBT on phospholipase A2 assessed for different venoms was similar to that obtained with pure enzyme. Low toxicity of MEBT in combination with its antagonistic activity against different venoms may allow effective life-saving treatment against snakebites. Such application of MEBT is important when identification of the snake is impossible or if specific treatment is unavailable.

Animals↗

Sympathetic nervous system activation, antivenin administration and cardiovascular manifestations of scorpion envenomation.

We performed two-dimensional echocardiograms and determined plasma norepinephrine levels on admission and at 24h after hospitalization, in 16 children with scorpion envenomation. All patients came from areas where scorpions have been identified as Tityus zulianus and received antivenin at the site of the accident or upon admission. Based on the presence or absence of cardiovascular manifestations, patients were divided into two groups. GROUP A: 10 patients had cardiovascular manifestations of pulmonary edema. Four patients had mild pulmonary edema (Left ventricular ejection fraction: 0.43+/-0.19) and six had moderate to severe pulmonary edema (Ejection fraction: 0.31+/-0.09. p=NS, M+/-SD). Plasma norepinephrine was elevated on admission (1279+/-824) and decreased at 24h in seven of eight patients (474+/-140 pg/ml, p<0.03). GROUP B: Six patients had no cardiovascular manifestations. These patients had normal chest X-rays and normal echocardiograms. Plasma norepinephrine was not elevated (188+/-180 pg/ml). Time interval from the accident to antivenin administration was significantly longer in Group A compared to Group B (4.5+/-3.3 vs 1.2+/-0.4h, p<0.03) and correlated directly with the absolute change in plasma norepinephrine (r=0.76, p<001). Consequently, we strongly recommend very early administration of antivenin in the medical management of scorpion envenomation by T. zulianus.

Animals↗

Significant envenomation from a preserved rattlesnake head (in a patient with a history of immediate hypersensitivity to antivenin).

We present a case of significant envenomation from a severed, preserved rattlesnake head in a 22-year-old man. The patient was treated successfully with 15 vials of Crotalidae polyvalent antivenin despite a history of severe immediate hypersensitivity reaction to antivenin. The patient developed a mild case of serum sickness five days after antivenin infusion that was treated successfully with a course of steroids. The patient experienced complete recovery. This case demonstrates the hazard of even preserved snake heads and fangs.

Administration, Oral↗

Successful venomous snakebite neutralization with massive antivenin infusion in a child.

Intravenous antivenin requirements to neutralize venomous snake bites can be appropriately calculated based on accurate estimations of injury severity, and/or safely titrated if systemic symptoms are present. This report describes a case in a child given 13 10-ml vials of crotalidae antivenin before and during transfer, and tetanus prophylaxis, cephalosporin (200 mg IV q 6 h), and the titration of 62 additional 10-ml vials of antivenin within 14 hours, based on the child's response to therapy. By the tenth day all symptoms had resolved.

Antivenins↗

Levels of therapeutic antivenin and venom in a human snakebite victim.

An enzyme-linked immunosorbent assay was used to measure the levels of therapeutic antivenin (Antivenin [Crotalidae] Polyvalent, Wyeth-Ayerst) in serum and the levels of venom in the urine of a patient bitten by a western diamondback rattlesnake (Crotalus atrox). Serum and urine samples were taken on admission, during hospitalization, and during follow-up until 5 months after the bite. Photographs were taken of the bite site on admission to the hospital and during follow-up. Serum levels of therapeutic antivenin were highest between 1 and 3 days after the bite but were still detectable 46 days as well as 4 months after the bite. Crotalus atrox venom was detectable in the urine 4 days after the bite and was still measurable 6 days after the bite.

Animals↗

Release of creatine kinase from skeletal muscles by Bothrops venoms: heparin potentiation of inhibition by antivenin.

The glycosaminoglycan, heparin (50 micrograms/ml) inhibited the increase in creatine kinase (CK) released from rat extensor digitorum longus (EDL) muscles exposed to Bothrops jararaca venom (150 micrograms/ml). Heparin (2 micrograms/ml) and polyvalent antivenin (0.5 microliter/ml) did not affect the increase in CK release induced by exposure of the muscles to 50 micrograms/ml B. jararacussu venom. Simultaneous exposure of the muscles to venom plus heparin (2 micrograms/ml) plus antivenin (0.5 or 1 microliter/ml) reduced CK release after 160 min by 50% and 80% compared to that induced by venom alone. These changes in CK release from rat EDL muscle show that heparin inhibits the myotoxic effects of Bothrops venoms and increases the potency of their antivenin.

Animals↗