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Acute pulmonary edema as a complication of anti-snake venom therapy.

Polyvalent Anti-snake Venom (ASV) is a life-saving antivenin for severe envenomation due to snake bite in India. ASV infusion is occasionally associated with severe allergic reactions, i.e. anaphylaxis and death. We report a rare instance of non-cardiogenic pulmonary edema due to ASV infusion in an eleven years old boy.

Anaphylaxis↗

Snake envenomation. Incidence, clinical presentation and management.

Snake envenomation is a major cause of death and disability in the developing countries, particularly India and Southeast Asia. Species variation in venom components, yield, and lethality leads to quite different clinical presentations and mortality. Venomous snakes are divided into 5 families. Bites of the Viperidae, Crotalidae and Colubridae usually cause primarily local effects and bleeding; the Elapidae most commonly cause neurological symptoms, particularly paralysis; while the Hydrophidae cause paralysis and myolysis. Venoms are complex mixtures of enzymes, peptides and metalloproteins. 26 enzymes have been identified, and 10 of those are found in most venoms. Components have been identified that act as procoagulants, anticoagulants, hyaluronidases, RNases, DNases, postsynaptic toxins and presynaptic toxins. Other peptides induce capillary leak syndrome, haemolysis and shock. The clinical results of envenomation vary widely, and there may be no envenomation with a bite. Syndromes reported include oedema, haemolysis, shock, bleeding, pituitary failure, renal failure, myonecrosis, and combinations of the above. First aid measures that have been proposed include tourniquets, constricting bands, tight crepe bandages, incision and suction, cryotherapy, and high voltage electric shock. None of these has been shown to be effective except usage of a crepe bandage for Australian elapid bite. Tourniquets or cryotherapy, if used for extended periods may lead to gangrene. The most important first aid measure is rapid transport to comprehensive medical care. There is some controversy about medical treatment in the United States, but less in other countries. Supportive measures routinely required include intravenous fluids, tetanus prophylaxis and antibiotics. Anticholinergics may be useful in elapid bite. Intubation and ventilation may be necessary. Unproven surgical approaches include excision of envenomated tissues and fasciotomy. The former is disfiguring, the latter should be reserved for those patients with demonstrated increased intracompartmental pressure. More than 100 antivenins are produced by about 36 laboratories worldwide. The products are effective, but carry a high risk of serum sickness and a lesser risk of anaphylaxis. A more effective and less reactive product is under development.

Africa↗

Snakebites in the rainforests of Ecuador.

Epidemiologic information about snakebites in Ecuador is scarce. Snakebites are more common in the lowlands east of the Andes, in the Amazon basin. In the present study, a retrospective review of all ( n = 142) snakebite admissions to Hospital Pio XII, a regional health center/hospital in the canton of Sucúa, Morona Santiago, Ecuador was carried out between the years of 1996 and 2000. Bites occurred more frequently during the months of March to May. The largest group of patients were in the 15- to 49-year-old range (52.5%), and agricultural workers were the most affected of all patients by occupation (> 40%). In most cases of snakebite, patients could not identify the type of snake that had bitten them. A small number of patients ( n = 60, 42.3%) received some type of treatment prior to arrival at the hospital. Bites occurred most frequently on the left lower extremity (31.7%). Typical symptoms included pain and local edema at the snakebite site; generalized symptoms such as fever, nausea, and vomiting were less frequent. Most patients (almost 90%) received antivenin during hospitalization in addition to supportive care. The mean hospital stay was 4.3 days. More than 90% of all 142 patients recovered, about 8% with local abscesses. Mortality was 2.9% and occurred as a result of complications, including renal failure, respiratory failure, and disseminated intravascular coagulation.

Adolescent↗

Envenomation by the northern blacktail rattlesnake (Crotalus molossus molossus): report of two cases and the in vitro effects of the venom on fibrinolysis and platelet aggregation.

In two cases of human envenomation by the northern blacktail rattlesnake (Crotalus molossus molossus) there was marked swelling and ecchymosis of the bitten extremity and thrombocytopenia and, in one case, hypofibrinogenemia. Treatment consisted of i.v. antivenin, crystalloid solution, fresh frozen plasma and cryoprecipitates, with recovery in each case. In vitro studies showed that the venom had fibrinolytic and platelet aggregating properties; a coagulant effect, although present, was much less marked.

Adult↗

An indirect haemolytic assay for assessing antivenoms.

Dilutions of antivenom, venom, human erythrocytes and a phosphatidylcholine suspension, were incubated for 30 min at 37 degrees C. After centrifugation, the liberated haemoglobin was measured spectrophotometrically. The assay was used to assess an ovine antivenom against the venom from the South American rattlesnake, Crotalus durissus terrificus, and an equine Wyeth antivenin (Crotalidae, polyvalent). The ovine antivenom was more than five times as effective as the equine product. It also neutralized venoms from the Western diamondback rattlesnake, Crotalus atrox, and the fer-de-lance, Bothrops atrox. However, antivenoms raised against venoms from other Crotalus and Bothrops species provided little protection against the haemolytic activity of C. d. terrificus venom.

Antivenins↗

Local heat and cold application after eastern cottonmouth moccasin (Agkistrodon piscivorus) envenomation in the rat: effect on tissue injury.

We studied the effect of local application of heat or cold on the development of tissue necrosis in envenomated rats. Anesthetized animals had 6 mg/kg venom from Agkistrodon piscivorus injected subcutaneously into the lateral aspect of a hind limb. Heat or cold was applied to the site of envenomation in the experimental groups for 4-6 hr, and the injected area was examined histologically after 24 hr. Neither local treatment, with or without the presence of systemic antivenin, significantly affected the severity of tissue necrosis induced by the venom in comparison to a control group left at ambient temperature.

Animals↗

Analgesic effect evoked by low molecular weight substances extracted from Crotalus durissus terrificus venom.

Crude venom obtained from Crotalus durissus terrificus (Cdt) was tested for its possible analgesic effect in mice. Subcutaneous (s.c.), intraperitoneal (i.p.) or oral (p.o.) administration of the venom caused an antinociceptive effect in mice as measured by the acetic acid-induced writhing method and the hot plate test. The antinociceptive activity was dose and time dependent and persisted after neutralization of the venom with a specific antivenin. It was demonstrated that the factor(s) has an apparent mol. wt of less than 3000 and that its antinociceptive effect is abolished by trypsin treatment. The demonstration that morphine enhances the analgesic effect of Cdt venom and naloxone antagonizes this effect suggests an endorphin-like activity for the factor(s) herein described.

Analgesics↗

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

STUDY OBJECTIVE: Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) is used in the treatment of symptomatic crotaline envenomations in North America. Unlike Antivenin (Crotalidae) Polyvalent, which is approved for treatment of crotaline envenomation in North and South America, FabAV is manufactured using only venoms from crotaline snakes native to the United States. This study was designed to evaluate the efficacy of FabAV in the neutralization of venom from 2 South American crotaline snakes: Crotalus durissus terrificus (tropical rattlesnake) and Bothrops atrox (fer-de-lance). METHODS: A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was used. Venom potency was determined in preliminary median lethal dose (LD 50) dosing studies. Study animals were then divided into 7 groups: (1) C durissus terrificus venom (Sigma-Aldrich Co.)+FabAV, (2) C durissus terrificus venom (Sigma-Aldrich Co.)+0.9% normal saline solution, (3) C durissus terrificus venom (Biotoxins Inc.)+FabAV, (4) C durissus terrificus venom (Biotoxins Inc.)+normal saline solution, (5) B atrox venom+FabAV, (6) B atrox venom+normal saline solution, and (7) FabAV+normal saline solution. Twice the estimated LD 50 was the chosen venom dose, and the amount of FabAV injected was 10 times the amount needed for venom neutralization. Statistical analysis included Fisher's exact test and log-rank testing to compare survival rates and times. RESULTS: The venom LD 50 was found in preliminary studies to be 0.9 mg/kg and 1.35 mg/kg for the C durissus terrificus venom obtained from Sigma-Aldrich Co. and Biotoxins Inc., respectively. The LD 50 for B atrox venom was 5.0 mg/kg. All animals receiving venom only and saline solution died. Animals receiving FabAV together with either venom survived to the end of the 24-hour observation period ( P <.001). Comparison of survival times between groups demonstrated a significant difference in time to death between venom-only control groups and the FabAV+venom groups (P <.001). All animals in the FabAV+normal saline solution group survived to the conclusion of the study. CONCLUSION: FabAV, when premixed with venom, decreases lethality in a murine model of intraperitoneal venom injection of the South American pit vipers, C durissus terrificus and B atrox .

Animals↗

Treating the snakebitten child in North America: a study of pit viper bites.

BACKGROUND/PURPOSE: Snakebite envenomation is a potentially life-threatening form of trauma, the dangers of which are amplified in children because their smaller size increases the relative dose of venom received. The authors reviewed a large series of snakebitten children to address the medical and fiscal issues of treating these patients. METHODS: The records of 37 snakebitten children (1987 through 1997) were analyzed for demographic data, signs of envenomation, use of specific therapies (antivenin, blood products, or surgery), length of hospitalization, complications, and cost of care. RESULTS: Fifty-four percent of the children had a major envenomation demonstrated by systemic symptomatology, laboratory analysis, or need for surgery. All children made full recoveries with most receiving only supportive care (92%). The average time to emergency department presentation was 8 hours, where all children with major envenomations and those requiring specific therapies (surgery, clotting factors) were identified. Cost analysis showed an average of $2,450 dollars per child with the majority of expenses attributable to length of hospitalization. CONCLUSIONS: Most snakebitten children completely recover with minimal supportive care, and they can be cared for safely and cost effectively as outpatients if no signs of major envenomation are noted within 8 hours of the bite.

Adolescent↗

Time to reconstitution: purified Fab antivenom vs. unpurified IgG antivenom.

We conducted prospective, randomized analytical and observational trials to assess reconstitution times of two lyophilized crotaline snake antivenoms, Antivenin (Crotalidae) Polyvalent [Wyeth-Ayerst] (ACP) and affinity-purified, mixed monospecific crotalid antivenom ovine Fab (CroTAb) (Fab antivenom). The analytical experiment indicated Fab antivenom and ACP reached their maximum protein concentration at 25 and 45min, respectively. In the observational experiment, Fab antivenom (median 40min) had a shorter reconstitution time than ACP (>90min, p<0.008).

Antivenins↗

Cobra envenomation: an uncommon emergency.

An unusual case involving a cobra snake envenomation is presented. The patient developed transient neurological sequelae during air evacuation to a regional trauma center and required endotracheal intubation. He developed a hypersensitivity reaction to cobra antivenin which responded to diphenhydramine. The bite wound became edematous and necrotic, but responded to conservative therapy. He was discharged on the fifth hospital day and did well.

Adult↗

Life-threatening airway obstruction from rattlesnake bite to the tongue.

We describe the case of a 41-year-old man who suffered a bite to the tongue from the Western Diamondback rattlesnake (C atrox). Life-threatening obstruction of his upper airway secondary to massive edema of the tongue and other soft tissue structures quickly followed envenomation. Nasotracheal intubation, IV antivenin, and supportive care resulted in complete recovery with no permanent deficits. Rattlesnake bites to the tongue are rare and pose an unusual cause of airway obstruction.

Adult↗

Thrombocytopenia following timber rattlesnake envenomation.

STUDY OBJECTIVE: To better characterize timer rattlesnake venom--induced thrombocytopenia and coagulopathy and the response to therapy with Antivenin (Crotalidae) Polyvalent. METHODS: We conducted a retrospective multicenter review of timber rattlesnake envenomation. RESULTS: We reviewed 18 cases at two institutions. Restoration of normal prothrombin time and partial thromboplastin time was achieved in all cases with antivenom therapy. In contrast, complete reversal of thrombocytopenia was not achieved, despite antivenom therapy. CONCLUSION: Antivenom (Crotalidae) Polyvalent was less effective in reversing thrombocytopenia than coagulopathy after timber rattlesnake envenomation, suggesting that a component of timber rattlesnake venom persists in the blood despite antivenom therapy. Persistent thrombocytopenia may be due to a venom factor that the antivenom does not neutralize or to inadequate dosing of antivenom. Prompt reversal of thrombocytopenia following treatment of timber rattlesnake envenomation with this antivenom appears unlikely.

Animals↗

Airway obstruction following canebrake rattlesnake envenomation.

We report an unusual case of canebrake rattlesnake (Crotalus horridus atricaudatus) envenomation whose major manifestation was orolingual edema and airway compromise. The likely source of swelling was mucosal absorption of venom following the first aid technique of cutting and sucking the bite site. Except for airway compromise, the patient had mild local bite site effects (swelling) and mild systemic findings (depressed fibrinogen and elevated creatinine phosphokinase). He was managed with fiberoptic nasotracheal intubation and Crotalid antivenin with good outcome.

Administration, Oral↗

Antibiotics after rattlesnake envenomation.

To record the outcome, with regard to infection rate, of patients with rattlesnake bites (RSBs) who do not receive prophylactic antibiotics, a prospective observational study was performed of patients with RSBs treated at our institution during a consecutive 18-month period. The inclusion criteria were RSBs <24 h old and completion of follow-up (telephone call, mail reply, medical toxicologist, or private physician examination) 7-10 days following envenomation. Fifty-six consecutive patients (Median age: 32.8 years [range 4-67 years]) were enrolled. One patient was excluded because of presentation 38 h after envenomation and two patients failed to complete the required follow-up. One patient received a dose of antibiotics before transfer. Antibiotics were discontinued upon arrival. Of the total 56 RSB patients, 34 (61%) RSBs involved the upper extremity and 22 (39%) involved the lower extremity. Six patients (11%) applied ice and two (4%) used a tourniquet before evaluation. The mean arrival time was 2.7 h (Range <1-24 h). Forty-three patients (81%) received antivenin. Fifty-three patients (100%) had extremity swelling and 38 patients (72%) had tender proximal lymph nodes. Of the 53 patients who completed the study, 3 (6%) received antibiotics from their primary care physicians at 7-10 day follow-up, with no cases (0%) of documented infection. Prophylactic antibiotics are not indicated in patients with rattlesnake bites.

Adolescent↗

Biphasic rattlesnake venom-induced thrombocytopenia.

Thrombocytopenia is a common occurrence in moderate to severe crotaline envenomation. The exact mechanism by which rattlesnake venom leads to thrombocytopenia is unclear, but aggressive treatment with crotaline-specific antivenom often leads to resolution of this disorder. Crotalinae Polyvalent Immune Fab (CroFab(TM), Protherics Inc., Nashville, TN) (crotaline Fab) is now available for the treatment of symptomatic rattlesnake envenomation. Although recurrence of thrombocytopenia has been reported in patients after envenomation treated with crotaline Fab, cases refractory to this therapy have not been described. We report a case of severe crotaline envenomation that appears to have exhibited two separate episodes of thrombocytopenia, only one of which responded to antivenom. The second, later phase was refractory to both crotaline Fab as well as traditional Antivenin (Crotalinae) Polyvalent (Wyeth-Ayerst Pharmaceuticals, Philadelphia, PA) (ACP). By reviewing the literature regarding venom-induced thrombocytopenia, we attempt to explain this "biphasic" phenomenon and the inability of crotaline Fab to reverse this toxic effect.

Adult↗

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.

Animals↗

Immediate and delayed allergic reactions to Crotalidae polyvalent immune Fab (ovine) antivenom.

Allergic reactions are the most commonly reported adverse events after administration of antivenoms. Conventional horse serum-based crotalid antivenom used in the United States (Antivenin [Crotalidae] polyvalent) can lead to both immediate and delayed hypersensitivity reactions. Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) has recently been approved for use in the United States. Experience from premarketing trials of this product and in the administration of other types of Fab, such as in digoxin poisoning, has demonstrated these fragments to be safe and effective, with a low incidence of sequella; however, allergic reactions can occur when any animal-protein derivatives are administered to human subjects. We report in detail the nature and course of allergic reactions that occurred in 4 patients treated with FabAV. Cases of anaphylaxis, acute urticaria, angioedema, and delayed serum sickness are described. All reactions were easily treated with some combination of antihistamines, epinephrine, and steroids, with prompt resolution of signs and symptoms enabling further dosing of antivenom as required. Several of these cases may have resulted from batches of antivenom contaminated with Fc fragments. The overall incidence of immediate and delayed allergic reactions to this product appears so far to be lower than that reported with conventional whole-immunoglobulin G (IgG) antivenom, but postmarketing surveillance is warranted.

Adult↗