Antivenin Crotalidae Polyvalent Research Articles

Venomous Snakebites

More than 5 million people are bitten by venomous snakes annually and more than 100 000 of them die. In Europe, one person dies due to envenomation every 3 years. There is only one venomous snake species in Lithuania – the common adder (Vipera berus) – which belongs to the Viperidae family; however, there are some exotic poisonous snakes in the zoos and private collections, such as those belonging to the Elapidae family (cobras, mambas, coral snakes, etc.) and the Crotalidae subfamily of the Viperidae family (pit vipers, such as rattlesnakes). Snake venom can be classified into hemotoxic, neurotoxic, necrotoxic, cardiotoxic, and nephrotoxic according to the different predominant effects depending on the family (i.e., venom of Crotalidae and Viperidae snakes is more hemotoxic and necrotoxic, whereas venom of Elapidae family is mainly neurotoxic). The intoxication degree is estimated according to the appearance of these symptoms: 1) no intoxication (“dry” bite); 2) mild intoxication (local edema and pain); 3) moderate intoxication (pain, edema spreading out of the bite zone, and systemic signs); 4) severe intoxication (shock, severe coagulopathy, and massive edemas). This topic is relevant because people tend to make major mistakes providing first aid (e.g., mouth suction, wound incision, and application of ice or heat). Therefore, this article presents the essential tips on how first aid should be performed properly according to the “Guidelines for the Management of Snake-Bites” by the World Health Organization (2010). Firstly, the victim should be reassured. Rings or other things must be removed preventing constriction of the swelling limb. Airway/breathing must be maintained. The bitten limb should be immobilized and kept below heart level to prevent venom absorption and systemic spread. Usage of pressure bandage is controversial since people usually apply it improperly. Incision, mouth suction, or excision should not be performed; neither a tourniquet nor ice or heat should be applied. A doctor must monitor respiratory rate, blood pressure, heart rate, renal function, fluid balance, and coagulation status. The only specific treatment method is antivenin – serum with antibodies against antigens of snake venom. Antivenins against pit vipers used in the United States are Antivenin Crotalidae Polyvalent (ACP) and a more purified and hence causing less adverse reactions – Crotalidae Polyvalent Immune Fab (CroFab). In Europe, a polyvalent antiserum against Viperidae family snakes (including the common adder) can be used. Antivenins often may cause severe hypersensitivity reactions because of their protein nature. The bite of the common adder (the only poisonous snake in such countries as Lithuania and Great Britain) relatively rarely results in death; thus, considering the risk of dangerous reactions the antivenin causes itself, the usage of it is recommended to be limited only to life-threatening conditions.

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.

Treatment of US Crotalidae Bites

In the US, two antivenins are marketed for the treatment of snake envenomation. The horse-derived serum-globulin-based Antivenin (Crotalidae) Polyvalent (ACP) has been available since 1954. There are few data on the efficacy and incidence of adverse events that occur following the administration of ACP. Most of the data are retrospective, anecdotal, or case reports. In 2000, ovine-derived serum-globulin-based ACP (Crofab) became available. Crofab is said to cause fewer reactions than ACP, but there are few comparative data to substantiate this claim. Although both antivenins ameliorate the systemic symptoms following snake envenomation, the efficacy of either antivenin in decreasing oedema and swelling is unknown for a number of reasons. Clinical trials are small and have not included control arms. The degree of oedema, as well as the efficacy of the antivenin in decreasing oedema, may depend on the genera of the snake (usually unknown) that envenomated the patient. This article compares available data on clinical aspects of the two antivenins. More prospective data are needed to determine the comparative efficacy of the two antivenins, or the efficacy of Crofab in preventing tissue oedema. There are still unanswered questions regarding the optimal dosing regimen of Crofab.

Serum Sickness Following Administration of Antivenin (Crotalidae) Polyvalent in 181 Cases of Presumed Rattlesnake Envenomation

To describe the incidence and characteristics of serum sickness (SS) following administration of Wyeth Antivenin (Crotalidae) Polyvalent (ACP). A retrospective chart review was conducted involving presumed rattlesnake bite victims referred to our poison center. Serum sickness was defined as unexplained rash developing 3 to 21 days following the administration of ACP. Patients were monitored until complete resolution of all symptoms. Data collected included total number of ACP vials administered, associated signs and symptoms, duration of signs and symptoms, and medications used to treat SS. Of the 181 cases included in our study, SS occurred in 102 (56%) patients. The frequency of SS in patients receiving fewer than 20, 20 to 29, 30 to 39, or 40 or more vials was 34%, 36%, 88%, and 100%, respectively. Duration of SS averaged 6.1 days (range, 1-21 days). Associated symptoms included subjective fever (49%), arthralgia (20%), and pruritus (40%). Reported medications used included prednisone (98%), antihistamines (92%), and histamine-2 blockers (3%). Serum sickness following administration of Wyeth ACP is common, with a strong correlation between ACP dosage and SS frequency.

Regional vs Systemic Antivenom Administration in the Treatment of Snake Venom Poisoning in a Rabbit Model: A Pilot Study

To develop a model that compares 2 different routes of antivenom administration (standard intravenous [IV] administration vs regional administration below a tourniquet) to assess their ability to limit muscle necrosis in a rabbit model of rattlesnake venom poisoning. New Zealand white rabbits were randomly assigned to 4 groups. All animals underwent general anesthesia and were then injected intramuscularly (IM) with a sublethal dose of western diamond-back rattlesnake (Crotalus atrox) venom in the right thigh and a similar volume of normal saline (NS) control in the left thigh. Thirty minutes later, standard treatment group animals (n = 4) received 1 vial of reconstituted Antivenin (Crotalidae) Polyvalent (ACP) and 10 mL of NS through an ear vein. Experimental treatment group animals (n = 4) had their lower extremities exsanguinated and isolated by arterial tourniquets. One vial of ACP was then given through a distal IV in the envenomed extremity, and 10 mL of NS was given through an IV in the sham extremity. Tourniquets were removed 30 minutes later. Positive control group animals (n = 2) similarly had their lower extremities exsanguinated and isolated by tourniquets. They then received 10 mL of NS through distal IVs in each lower extremity. Tourniquets were again removed after 30 minutes. Negative control group animals (n = 2) received 2 doses of NS only (10 mL each) through an ear vein. Serum creatinine phosphokinase (CPK) levels were drawn at baseline and 48 hours following venom injection. At 48 hours, the animals were injected with technetium pyrophosphate. Two hours later, they were euthanized, and the lower extremities were scanned to determine levels of radionucleotide uptake in envenomed muscles compared to contralateral sham-injected muscles. The anterior thigh muscle groups were then removed, fixed, stained, sectioned, and analyzed in a blinded fashion by a veterinary pathologist for muscle necrosis grading. There was no evidence of statistically significant differences in changes in serum CPK levels (from baseline to 48 hours), technetium pyrophosphate uptake ratios (right leg/left leg), or muscle necrosis indices in any 2-group analysis. Results of this pilot study do not suggest any beneficial effect of ACP, in the dose and routes used, in limiting local muscle necrosis following IM rattlesnake venom poisoning in the rabbit model.

Snakebite envenomation in children: a 10-year retrospective review

To describe the epidemiology, short-term outcomes, and clinical characteristics of rattlesnake bites (RSB) in children. This was a 10-year retrospective chart review of all patients who were <13 years old admitted to a medical toxicology referral service in a major metropolitan area of the southwestern United States with a diagnosis of RSB. Sixty-six children (mean age, 6.33 years) presented to or were transferred to our center with a diagnosis of RSB. Sixty-three percent were male, and the majority of bites (71.93%) occurred on the lower extremities. Forty-nine children (85.96%) developed coagulopathies, and 50 children (87.72%) received Antivenin (Crotalidae) Polyvalent (ACP) administration. Of the 50 children receiving ACP, 19 developed an immediate hypersensitivity reaction. Five cases of morbidity resulted, but no deaths were recorded. Serious morbidity is infrequent in children following RSB.

Efficacy, safety, and use of snake antivenoms in the United States

The mainstay of hospital treatment for venomous snakebite is antivenom. There is currently only one antivenom available in the United States for the treatment of pit viper envenomation, Antivenin (Crotalidae) Polyvalent (ACP). The general indication for the administration of antivenom is presence of progressive venom injury. Progressive injury is defined as worsening local injury (eg, swelling, ecchymosis), a clinically important coagulation abnormality, or systemic effects (eg, hypotension, altered mental status). Unfortunately, there are no prospective data available regarding the efficacy of ACP. The efficacy of a new antivenom (CroFab; FabAV) composed of purified Fab specific to indigenous snake species has been demonstrated in prospective trials. FabAV appears as effective as IgG antivenoms. However, Fab molecules have a shorter half-life than IgG molecules and may allow recurrence of venom effects, if additional doses are not administered. It has also been found that other antivenoms, including ACP, also allow recurrence of venom effects. The Fab preparation has produced fewer acute or delayed (serum sickness) allergic reactions; however, further experience is needed to confirm this observation. Evaluation of this new antivenom has led to advances in our understanding of antivenoms in terms of solubility and durability. Fab fragments enter solution quickly, thereby shortening the time to antivenom administration and are remarkably stable under extreme conditions of heat and handling. [Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med. February 2001;37:181-188.]

Trimeresurus elegans (Gray, 1849), the Sakishima habu, a venomous pit viper from the Ryukyu Islands.

Summary The Sakishima habu, Trimeresurus elegans (Gray, 1849) has been reported only on islands of Yaeyama-retto, Sakishima-gunto, about 240 miles south of Okinawa. Color and scutellation serve to distinguish this species from other pit-vipers of the Ryukyu islands and Taiwan. Reddish-brown snakes, differing from typical elegans only in coloration, are rarely taken. T. elegans is smaller than the Okinawan habu, and adult specimens are usually between 3 and 4 feet in length. On the islands where it occurs, T. elegans is found in several types of terrain, and is active mainly at night. Venom of T. elegans was not neutralized in therapeutically significant amounts by an antivenin produced at Tokyo University, or by a polyvalent antivenin produced by Wyeth Laboratories. The latter product, Antivenin Crotalidae Polyvalent (North and South American Antisnakebite Serum), was highly effective in neutralizing venoms of some Asian species of the genera Trimeresurus and Agkistrodon, but almost without effect against venoms of other snakes of these genera. Clinical observations reported were based on a series of 24 cases of snake bite due to T. elegans, which occurred between December, 1950, and December, 1955, on islands of Yaeyama-retto. Most of these bites had been inflicted at night, and were seen during summer and autumn months. Most of the bites were located on the legs and hands. Symptoms included hemorrhagic spots at fang punctures, pain, swelling and cyanosis. Localized necrosis was severe in some patients. Only two patients of the 24 in the series developed general symptoms. Treatment included incision and cleaning of the bitten area; administration of antivenin produced in Tokyo; and supportive treatment, including use of vita-camphor, cardiac stimulants, Ringer's solution, and dextrose injections. Tissue damage occurred in some patients who had applied tourniquets and had allowed them to remain in place for long periods of time. There was also some local tissue damage in patients who had burned the bitten areas as a first-aid measure. Dressings with 5% solution of KMnO4 were applied in five cases, but were discontinued when they proved to be without therapeutic effect. Only one fatal case was seen. This patient, an adult male, developed the usual symptoms, and several hours after the bite was inflicted experienced difficulty in breathing. Chest pains were felt; the pulse became fast and weak; the nails became cyanotic, and the patient expired 24 hours after being bitten.