Objectives for Treatment of Patients with Envenomation
The specific treatment of a patient with a snakebite is controversial, and the literature contains confusing and contradictory recommendations. Folklore and home remedies abound. The benign natural history of many bites undoubtedly has accounted for many "miraculous cures" from such clearly unhelpful interventions as ethanol, electric shocks, carbolic acid, strychnine, cauterization, and cryotherapy. Many accepted treatment plans are based on anecdotal or biased information with conclusions drawn from animal studies or uncontrolled case reports. There are no universally accepted standards of care for many aspects of treatment.61 The initial objectives are to determine the presence or absence of envenomation, provide basic supportive therapy, treat the local and systemic effects of envenomation, and limit or repair tissue loss or functional disability (see Table 121-3).
A combination of medical therapy (mainly supportive care and possibly antivenom) and conservative surgical treatment (mainly debridement of devitalized tissue), individualized for each patient, will provide the best results. In general, the more rapidly treatment is instituted, the shorter the period of disability, but no specific standard of care exists for the institution of various interventions.
Observation of Asymptomatic Patients
All patients reporting a history of snakebite from North American crotalines should be observed for 8 to 12 hours after the bite if the skin is broken and the offending snake cannot be positively identified as nonpoisonous. The initial presentation of pit viper bites may be misleading, and significant worsening of a seemingly benign bite may occur as long as 24 hours after presentation,33 but such cases are unusual. Restlessness, anxiety, abdominal pain, nausea, and tachycardia are nonspecific symptoms but could signal systemic envenomation, and they should not be routinely dismissed as being a result of fear or anxiety. If the patient has been bitten by an exotic or nonnative snake, it would be prudent to extend the period of observation to 12 to 24 hours.
Eastern coral snake bites can initially be misleading with fang marks that are quite subtle and easily mistaken for scratches or teeth marks. Serious delayed neurologic and respiratory symptoms have been specifically noted, so patients bitten by these snakes should be observed for 24 hours regardless of their initial presenting symptoms. Sonoran coral snakes, indigenous to Arizona and California, have never been reported to cause significant toxicity, and bite victims can be discharged if the offending snake has been positively identified.
Field Treatment for Snakebite Victims
No first aid measures or specific field treatment has proven to positively affect the outcome from a crotaline envenomation, and undue importance has been placed on the immediate prehospital care of patients with snake bites. When the patient is not in extremis and medical attention is available within a few hours, the prudent approach is a conservative one. The excitement or hysteria generated by a possible poisonous snakebite compels some caregivers to intervene quickly with unproven or harmful procedures. In reality, both death and amputation are quite rare if proper medical attention is available within a few hours. Most morbidity stems from delayed treatment, either because of inaction on the patient's part (often related to alcohol intoxication) or because of inaccessible medical care. Prehospital care should generally be limited to immobilization of the patient's affected limb and rapid transport to a medical facility.42
In the past, various methods have been advocated to prevent systemic absorption of venom after snake bites. The traditional tourniquet that occludes venous and arterial flow is contraindicated and may compound the initial insult by increasing edema and aggravating ischemia. A constriction band is not a true tourniquet and is intended to collapse lymphatics and superficial veins; if it is applied properly, a finger may be easily placed between the band and the skin. The pressure immobilization technique with a constriction band has been used in the treatment of nonnecrotizing elapid snakebites in Australia, where systemic toxicity is the major concern and transit times can be prolonged.62 Utility of this technique for the more necrotizing bite of North American crotalines has not been demonstrated. A randomized, controlled study of pressure immobilization versus observation in a porcine model with intramuscular injection of Crotalus atrox venom showed a prolonged time to death in the pressure immobilization group but also markedly increased compartment pressures. With local tissue necrosis, the major morbidity associated with North American crotaline envenomations, not death, the authors concluded that pressure immobilization with a compression bandage cannot be suggested as a routine field procedure.9
Incision and suction, whether by mouth or with a commercially available device, cannot be recommended as standard first aid in the field. Incision may lead to damage of underlying structures such as nerves and tendons, and mouth suction is unproven and may introduce bacteria into the wound. Commercially available plunger-type suction devices in human models provide no benefit, and additional injury is possible from the device. Venom extractors are currently unproved therapy and are not recommended.1,10 Simple suction cups supplied in first aid kits are worthless.
It should be stressed that compression dressings and vacuum extraction should not be considered if the patient can rapidly reach a hospital. Minor pain or swelling is not an indication for zealous field treatment. Furthermore, these treatments are never a substitute for rapid transport, in-hospital evaluation, or antivenom therapy. The bitten area should not be placed in ice because cryotherapy is not effective in neutralizing venom and may compound the initial injury.41
Immediate in-Hospital Therapy
The initial in-hospital assessment of a patient with a snakebite should focus on airway, breathing, and circulation. Early airway management with endotracheal intubation should be considered in all patients with bites to the face or tongue.21 Intravenous (IV) lines should be placed and fluid boluses initiated. An epinephrine continuous infusion, starting at 0.1 μg/kg/minute and titrating as needed, is the vasopressor of choice for signs of shock. A complete medical history, including current tetanus immunization status and known allergies, should be obtained. A careful description of the bite and the extent of the local pathology should be documented, including measuring the diameter of the extremity and noting the extent of edema by marking the skin with a pen to help recognize progression of the envenomation. This evaluation should be repeated frequently as required by the clinical condition. A comprehensive physical examination should be done, with emphasis on vital signs, cardiorespiratory and neurologic status, neurovascular status of the extremity, and evaluation for evidence of bleeding. A baseline complete blood count, electrolytes, urinalysis, creatinine, glucose, prothrombin time (PT), fibrinogen level, and platelet count should be obtained initially, with platelets, fibrinogen, and PT repeated in 4 to 6 hours.
Pain and anxiety should be alleviated and tetanus prophylaxis addressed. The extremity should be immobilized in a well-padded splint in near-full extension and elevated to avoid dependent edema. This is especially important with hand bites because significant swelling of the hand and forearm mimicking compartment syndrome may be avoided. The patient should be reassessed frequently with repeat physical examinations, specifically noting any progression of swelling. This may be accomplished by taking measurements of the circumference of the involved extremity at multiple points proximal to the wound.
For Crotalinae envenomations, antivenom should be considered as first line therapy for those patients with moderate to severe envenomations (see Table 121–3). Although each case must be individualized, in the vast majority of patients who have a moderate or severe envenomation, the benefits of antivenom therapy outweigh the risks. Antivenom given in a timely manner can reverse coagulopathy and thrombocytopenia and halt progression of local swelling. There is no evidence, however, that antivenom can prevent the development of tissue necrosis, so patients should be informed of the risk of tissue loss. This is most commonly noted with rattlesnake bites to the fingers, which occasionally lead to amputation of the digit despite appropriate treatment with antivenom.
The only currently available antivenom for North American pit viper envenomations is Crotalidae polyvalent immune Fab (CroFab™, Protherics, Savage Laboratories). CroFab is an ovine-derived Fab fragment antivenom developed from commonly encountered North American pit vipers. It is less allergenic than the previously available equine-derived Antivenin Crotalidae Polyvalent (Wyeth-Ayerst). CroFab is administered IV in an initial dose of four to six vials reconstituted in normal saline. The infusion is initiated at a slow rate, and if no signs of an anaphylactoid reaction develop, increased to complete the infusion over one hour. The patient should be reassessed after completion of the infusion for evidence of continued swelling or coagulopathy, and, if present, an additional four to six vial dose is infused. This process is repeated until control of symptoms is achieved. Control is generally considered cessation of progression of swelling and systemic symptoms in addition to improvement in coagulopathy and thrombocytopenia. After control has been gained, maintenance doses are given as two vials every 6 hours times three, for six total additional vials. Antivenom therapy is discussed in detail in Antidotes in Depth A36: Antivenom (Crotaline and Elapid).
Envenomation may mimic a compartment syndrome by producing distal paresthesias, tense soft tissue swelling, pain on passive stretch of muscles within a compartment, and muscular weakness. However, because subfascial envenomation is uncommon, much of the impressive edema produced by envenomation does not occur in compartmentalized areas. Using noninvasive vascular arterial studies and skin temperature determinations in patients with rattlesnake envenomation, one report demonstrated that pulsatile arterial blood flow to an envenomated extremity actually increased after envenomation, even distal to the site of envenomation.15 Compartment syndrome cannot be reliably diagnosed in envenomated extremities without directly measuring compartment pressures. Although there is little doubt that some crotaline bites may eventually require some surgical debridement or even skin grafting, the initial routine use of tissue excision or "exploration and debridement" is not recommended.30,57 Fasciotomy is rarely needed and should be done only based on objective data of measured compartment pressures. Successful treatment of documented elevated compartment pressure after rattlesnake evenomation with antivenom and mannitol alone has been reported.26 Debridement of hemorrhagic blebs and blisters may be performed to evaluate underlying tissue and relieve discomfort. Some patients may require surgical debridement of necrotic tissue or even amputation of a digit 1 to 2 weeks after the bite. Referral to a hand surgeon is most appropriate for patients with evidence of extensive tissue necrosis. Physical therapy should be instituted early to ameliorate joint stiffness and decrease swelling.
Immeasurably low fibrinogen levels, prothrombin times greater than 100 seconds, and platelet counts lower than 20,000 are routinely encountered after rattlesnake envenomation, and such abnormal laboratory results alone should not prompt the clinician to treat with blood products in the absence of clinically significant bleeding. The circulating crotaline venom responsible for the initial bleeding diathesis is still present and will likely inactivate any component transfusions. For this reason, the mainstay of treatment for crotaline envenomation—induced coagulopathy is antivenom, not blood products. Correction of laboratory coagulation abnormalities and bleeding can frequently be achieved with antivenom alone. Monitoring trends in the coagulation profile is one objective way of assessing the seriousness of envenomation and the response to antivenom therapy.
Rarely, a patient will have active bleeding, and antivenom alone will not correct the coagulopathy. In such cases, fresh frozen plasma, cryoprecipitate, packed red blood cells, or platelet transfusions may be required. The criteria for the use of blood products appears to be quite arbitrary in clinical practice, but in general, blood products should be administered along with antivenom if the patient is actively bleeding.
Venom-induced thrombocytopenia that occurs after bites by many rattlesnake species is responsive to treatment with antivenom. The Timber rattlesnake, however, is known for producing thrombocytopenia resistant to antivenom. In some cases, thrombocytopenia may be difficult, or impossible, to totally correct with even large amounts of antivenom. The initial correction of platelet counts that occurs after treatment may be transient (lasting only 12–24 hours), with thrombocytopenia sometimes persisting for days to weeks after normalization of other coagulation parameters. In the absence of bleeding, thrombocytopenia is a benign, self-limiting disorder, resolving within 2 to 3 weeks of envenomations. It may be best to closely follow patients with resistant thrombocytopenia who are not bleeding clinically rather than attempt further platelet transfusions or antivenom administration.13
Victims of proven copperhead bites should be observed for 4 to 6 hours and evaluated for signs of systemic involvement, the development of coagulation abnormalities, and progression of the local pathology. In the absence of progression of local symptoms and the lack of any systemic symptoms, this shorter observation period may be sufficient. In many instances, the entire care of a patient with a minimal copperhead envenomation can be accomplished in the emergency department, but a conservative approach is advised. Hospital admission for further observation is warranted for unreliable patients or if there are questions as to the identification of the snake or progression of symptoms.50
Prophylactic antibiotics are not needed because studies show extremely low (0%–3%) rates of wound infections.39 There is no rationale for the use of corticosteroids or antihistamines in the routine treatment of patients with snakebites, except for the rare case of anaphylaxis. Tetanus prophylaxis should be administered as clinically indicated.
Cardiovascular collapse is a life-threatening consequence of severe systemic crotaline envenomation and should be treated aggressively. It may be prudent to use initial doses of eight to 10 vials of antivenom as opposed to the four to six vial doses indicated for mild to moderate envenomations, although this has not been studied. Blood pressure support with epinephrine may be required, and respiratory compromise should be anticipated in severe cases. Because of sudden and unpredictable respiratory paralysis associated with coral snake envenomation, tracheal intubation should be considered at the first sign of bulbar paralysis.
Recurrence Phenomena of Crotaline Envenomation
In a significant proportion of patients treated with Crotalidae polyvalent immune Fab antivenom, a return of swelling, coagulopathy, or thrombocytopenia may be noted after initial successful resolution of the effect after antivenom initial treatment. This has been termed recurrence of venom effect and is attributed to the interrelated kinetics and dynamics of venom and antivenom.4,54 Simply stated, Fab antivenom has a clinical half-life shorter than that of venom. Administration of "maintenance" doses of antivenom are used in an attempt to prevent development of recurrent effects. Anecdotally, this appears to be effective in preventing recurrence of local swelling in most cases, but many patients develop hematologic recurrence within 3 to 4 days of antivenom treatment despite administration of maintenance doses. Additionally, patients who never manifested thrombocytopenia or coagulopathy on their hospital presentation may later develop the effect, presumably because of initial "masking" of the effect by early antivenom. The exact clinical significance of these observations and the need for clinical intervention are uncertain. Currently, the most reasonable way to address possible recurrent hematologic effects of crotaline envenomation is careful outpatient follow-up after hospital discharge. The safest approach is to measure platelets and coagulation studies in all patients with rattlesnake envenomation 3 to 5 days after the last antivenom treatment. If values are abnormal or trending in the wrong direction, the studies should be repeated every few days until normalized. Patients should be advised to avoid surgical procedures and activities that place them at risk for injury. Opinions on when to retreat patients exhibiting recurrence with antivenom vary. Our general approach is to treat any patient with evidence of bleeding and recurrence, as well as patients with severe isolated thrombocytopenia (platelets <30,000/mm3) or moderate thrombocytopenia (platelets 30,000–50,000 /mm3) in combination with severe coagulopathy (fibrinogen <80 mg/dL). Many clinicians choose to cautiously observe patients with isolated coagulopathy as outpatients rather than to retreat them with antivenom.
Special Considerations for the Management of Pregnant Patients with Snakebites
There is scant information available on the effects of poisonous snakebites during pregnancy. Case series show that although maternal death is rare, fetal demise may be as high as 43%.18 Proposed mechanisms of injury to the fetus from envenomation include uterine artery hypotension with subsequent hypoxia, hemorrhagic complications such as abruptio placentae, and uterine contractions initiated by venom. As in each case of snakebite, it is prudent to evaluate the need for antivenom carefully during pregnancy. A single case report exists of a woman treated with CroFab in the third trimester of pregnancy without complications.36 Given the relative safety of this antivenom and the high rate of fetal demise after envenomation, a low threshold for treatment should be considered. Fetal and maternal monitoring should be carried out throughout the patient's care.19
Repeated Exposure to Snake Venom
Snake handlers and collectors are at risk for multiple bites over their careers, and questions have been raised about possible immunity. No evidence was established that immunity develops as a result of repeated envenomation in one report of 14 patients with two or more bites.46 Victims of repeat bites may actually be at greater risk for anaphylaxis because of prior sensitization and the development of IgE antibodies to venom.
Treatment of Coral Snake Envenomation
The benign local effects of coral snake envenomation can be misleading and mistakenly equated with a dry bite.44 Because it is difficult to judge initially which patients are envenomated, any patient with a confirmed coral snake exposure with fang marks or other evidence of skin penetration is recommended to receive antivenom therapy even in the absence of symptoms. This currently presents a problem because North American Coral Snake Antivenin, produced by Wyeth Pharmaceuticals, has been discontinued. Limited remaining supplies expired in October 2009. Until another antivenom becomes available, patients must be treated supportively with close observation and mechanical ventilation when indicated. Acetylcholinesterase inhibitors, neostigmine 0.5 mg, and edrophonium 10 mg have been successfully used to treat patients with South American coral snake bites, but their use should be considered experimental.7
A conservative approach is taken even for patients with less suspicion for envenomation. Any patient in whom coral snake bite cannot be excluded requires 24 hours of observation in a monitored unit where resuscitative measures, including endotracheal intubation, can be performed. Clinical deterioration may be totally unexpected and progress rapidly. In one series, 15% of patients required intubation and ventilation, but none died or suffered tissue loss or permanent neurologic sequelae.37 Surgery is not a concern because no local tissue destruction is seen. Coral snake venom does not alter coagulation, so no bleeding diathesis is to be expected. Eastern coral snake envenomation can be fatal, but with supportive care and antivenom therapy, if available, patients usually recover completely.
About 3% of poisonous snakebites reported in the United States are from nonnative species.2,27 Many such snakes are owned by collectors, illegally imported, or stolen from zoos or pet stores. However, private individuals may easily purchase a plethora of vipers, cobras, and adders by mail or at reptile shows. Out of fear of legal retribution, some owners of exotic snakes can be quite vague about the circumstances of their envenomation. If they do not provide accurate identification, the local zoo, regional poison center, or herpetology society may be helpful in identification.
Bites from many nonnative Elapidae snakes, such as mambas, kraits, cobras, and several Australian species, are associated with high morbidity and mortality rates. Approximately one-third of bites from the king cobra are fatal.27 Bites from these snakes may not display early local or systemic signs; therefore, the grading system developed for North American pit vipers is not helpful. Although local tissue destruction and edema may develop, classically, it is the neurologic signs, such as ptosis, dysphagia, muscular weakness, paresis, ophthalmoplegia, and respiratory failure that are noted. Cobra envenomation usually produces significant local toxicity, and these snakes are the only elapids whose venom possesses hemorrhagic activity.
Compression immobilization of an entire extremity with an elastic bandage (the Sutherland wrap) for the bite of some elapids (eg, sea snakes, kraits, cobras, and brown snakes) experimentally decreases the movement of elapid snake venom from the bite site to the systemic circulation and may be useful when antivenom is not available. This intervention, when it does not delay transport to medical care, has been recommended for bites from exotic elapids.62 Local incision and suction should be avoided.
After the snake has been identified, attempts should be made to obtain appropriate antivenom. A good place to start is by contacting a regional poison center (800-222-1222) that has access to the Online Antivenom Index, a listing of available antivenoms for exotic snakes. Zoos may also stock exotic antivenoms and may be useful resources. Guidelines for the administration of antivenom for exotic snakes are vague and empiric. In addition, there is little standardization of the antivenoms for the same snake by different manufacturer. Because exotic snakes are generally quite poisonous, if fang marks are present, envenomation is strongly suspected, the snake has been identified, and the specific antivenom has been obtained, many physicians believe that it is logical to proceed with antivenom administration empirically. Antivenom is administered according to the package insert under the same monitoring guidelines as for crotaline antivenom. If the antivenom cannot be obtained then supportive care and close in-hospital observation, with prolonged mechanical ventilation in severe cases, may be all that is possible. Crotalidae polyvalent immune Fab (CroFab) may be effective in South American pit viper envenomations.49
One report documents rather dramatic reversal of the neurotoxic effects of a monocellate cobra (Naja kaouthia) bite after IV administration of the anticholinesterase neostigmine methyl sulfate (0.5 mg every 20 minutes for four doses).24 The major neurotoxin from this snake is believed to resemble curare, causing a postsynaptic blockade of nicotinic neuromuscular receptor sites. The neurotoxicity from sea snakes and other elapids has been experimentally reversed with neostigmine.53 Edrophonium chloride (10 mg administered IV with 0.5 mg of atropine) has also been suggested.
There are approximately 50,000 snakebites annually in the United States, and most (90%–95%) are from nonvenomous snakes.25 Most snakes in the United States are nonvenomous, and the majority are of the Colubrid family, which are generally considered harmless to humans. However, several authors have reported toxic secretions from Duvernoy glands in many common species, including the hognose snake, garter snake, parrot snake, banded water snake, and ringneck snake.28,43 Although no deaths have been reported, some victims developed coagulopathies and local edema and hemorrhage that could be confused with early crotaline envenomation.41 There is no antivenom available to treat bites from these snakes, and serious complications from nonvenomous snakebites are extremely rare.
When there is no sign of envenomation after an appropriate period of observation after a suspected nonpoisonous snakebite, attention should be focused on the basic principles of wound care. Incision and suction, excision, and wide debridement are unnecessary in such bites. The wound should be treated as a contaminated puncture wound because it may contain foreign material, especially broken teeth. Any foreign material should be removed and an appropriate dressing applied. Certain large snakes of the Biodae family (not seen in the United States, except as pets or in zoologic gardens), including boas, pythons, and anacondas, may present a special problem because the force of contraction of their jaws may be great enough to cause severe tissue contusion or fractures and retained teeth. These reptiles also have numerous large, brittle teeth that commonly are broken off and lodged in the wound when the bitten part is forcibly extricated from the snake's mouth. Radiographs of the bitten area are needed to exclude fracture or foreign body.
Antibiotics are not recommended for routine use after nonvenomous snakebites. In one report, no infections occurred after snakebites in 72 patients bitten by a variety of nonpoisonous snakes indigenous to New England and imported boa constrictors and pythons.59 Although Clostridium tetani has not been isolated from the mouths of snakes, the ubiquitous nature of this organism requires prophylaxis after the recommended approach for a contaminated wound. A cogent argument can be made for administering prophylactic antibiotics in nonvenomous snakebites if tooth fragments are retained or if there is significant soft tissue contusion. Outpatient therapy is appropriate; the patient should be instructed with regard to wound care and to seek medical care if signs of infection occur. Minor abrasions from nonvenomous snakes require only local wound care and tetanus prophylaxis. Delayed infection should prompt an investigation for a retained foreign body, especially a tooth fragment.32
Other Poisonous Reptiles in the United States
In North America, there are two indigenous species of venomous lizards that belong to the order Squamata, the same order as venomous snakes: the Gila monster (Heloderma suspectum) and the beaded lizard (Heloderma horridum). These lizards are found primarily in the desert areas of Arizona, southwestern Utah, southern Nevada, New Mexico, California, and Mexico. They are large, slow-moving, nocturnal, thick-bodied lizards that are prized by collectors and hobbyists. Adults are 30 to 40 cm long and are generally shy creatures, so bites are relatively rare and usually secondary to handling. Gila monsters are known for their forceful bites and propensity to hang on tenaciously during a bite, and they may be difficult to disengage. Some rather innovative anecdotal techniques have been developed to remove a Gila monster from an extremity, including the use of chisels, screwdrivers, and crowbars; pouring gasoline or ammonia into the lizard's mouth; or holding a flame to the animal's jaw. Teeth may break off in the wound.
Gila monster venom is complex, containing components similar to those of snake venoms, including numerous enzymes, hyaluronidase, phospholipase A, kallikrein, and serotonin.31,52 Helothermine is the suspected toxin. Their venom delivery systems are not as efficient as those of poisonous snakes and consist of venom glands and grooved teeth rather than fangs. Dry bites often occur because of the ineffective mechanism of delivery. After skin puncture and venom release, the victim experiences local tenderness and soft tissue swelling, pain, and edema. There are occasional reports of anaphylactoid reactions; hypotension; angioedema of lip, tongue, and throat; respiratory depression; coagulopathy; and myocardial infarction.47,48 Significant tissue destruction is unusual, but maceration may occur, and a cyanosis or blue discoloration is noted about the wound. There is no antivenom available against lizard venom. Treatment consists of avoiding over aggressive local treatment and providing supportive care and wound care. Epinephrine, corticosteroids, and antihistamines may be indicated for the treatment of anaphylactoid reactions. Serious morbidity from lizard bites is unusual. The characteristics of the beaded lizard are similar, but their bites are less commonly confronted clinically.