When a patient with a snake envenomation presents for care, 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 tissue loss or functional disability (Table 122–3). A combination of medical therapy (mainly supportive care and, often, antivenom) and in some cases conservative surgical treatment (mainly débridement 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.
No first aid measure or specific field treatment has been proven to positively affect outcome following a crotaline envenomation. Prehospital care should generally be limited to immobilization of the affected limb, placement of an intravenous catheter, treatment of life-threatening clinical findings, and rapid transport to a medical facility. Patients who are volume depleted, vomiting, or experiencing systemic symptoms such as diarrhea should be given an intravenous fluid bolus. Hypotension that does not quickly respond to a fluid bolus should be treated with epinephrine.
In the past, various methods have been advocated to prevent systemic absorption of venom after snakebites. All of these methods are either ineffective and delay time to definitive care, or are potentially harmful. Such useless and potentially dangerous therapies include tourniquets, incision and suction, venom extractors, electrotherapy, and cryotherapy.
Pressure immobilization bandages (PIB), which are lymphatic-restricting bandages that are applied to the bitten extremity prior to immobilization with a splint, are not recommended for use in patients with North American Crotalinae bites. A randomized, controlled study of pressure immobilization versus observation in a porcine model with intramuscular injection of Crotalus atrox venom showed markedly increased compartment pressures in the pressure immobilization group. All animals died in this study, but the pressure immobilization group showed a prolonged time to death as compared to the control group. With local tissue necrosis being the major morbidity associated with pit viper envenomations in humans, not death, the authors concluded that PIB application cannot be suggested as a routine field procedure.9 The American College of Medical Toxicology, along with five other international organizations, released a position statement recommending against use of PIB for North American Crotalinae bites.1
When a patient presents to the hospital with history of crotaline snakebite, it is important to first determine whether an envenomation has occurred. While most patients do show early evidence of envenomation, absence of symptoms at presentation is not uncommon, and not all asymptomatic patients ultimately have “dry” bites. Patients who present with puncture wounds but without swelling or other evidence of envenomation must be observed for delayed onset of symptoms. Victims of a rattlesnake bite should be observed for 8 to 12 hours after the bite. If no swelling develops and laboratory studies remain normal, the bite is likely “dry,” and the patient may be discharged from medical care. A shorter, 6-hour observation period may be appropriate for copperhead bite victims prior to medical clearance.
The initial in-hospital assessment of North American crotaline envenomation should focus on airway, breathing, and circulation. Early airway management with endotracheal intubation should be considered in all patients with evidence of angioedema or with bites to the face or tongue. All patients, regardless of presenting symptoms, should have an intravenous catheter placed in an unaffected extremity and receive a bolus of IV fluids. Patients presenting with cardiovascular collapse should receive large volumes of fluid. An epinephrine continuous infusion, starting at 0.1 μg/kg/min and titrating as needed, is the vasopressor of choice for signs of shock.
The affected extremity should be immobilized in a padded splint in near-full extension and elevated above the level of the heart to avoid dependent edema. Although there are no studies to determine the effect of limb elevation on outcome, the authors believe this to be helpful since it may decrease dependent edema, which contributes to increased pain and physical examination findings concerning for compartment syndrome. The authors maximally elevate affected upper extremities by applying stocking net around the limb and attaching the distal end to a raised IV pole.
Marking the leading edge of swelling with a pen will help to identify progression of edema. A baseline complete blood count, PT, and fibrinogen concentration should be obtained initially and repeated in 4 to 6 hours. Patients who are systemically ill should also have electrolytes, creatinine phosphokinase, creatinine, glucose, and urinalysis checked. An electrocardiogram, chest radiograph, and blood gas may also be indicated in ill patients.
A comprehensive physical examination should be done, with emphasis on vital signs, cardiorespiratory and neurologic status, neurovascular status of the affected extremity, and evaluation for evidence of bleeding. Pain should be treated with opioid analgesics as needed, and tetanus prophylaxis should be addressed. The patient should be reassessed frequently with repeat physical examinations, specifically noting any progression of swelling. This may be accomplished by taking serial circumferential measurements of the involved extremity at multiple points proximal to the wound.
Prophylactic antibiotics are not indicated as studies show extremely low (0%–3%) rates of wound infections.35 There is no indication for corticosteroids or antihistamines in the routine treatment of patients with snakebites, except for treatment of anaphylaxis.
Patients with dry bites or with mild envenomations, such as those who present only with localized swelling that does not progress, do not meet criteria for antivenom34 (Table 122–3). Patients who present with progressive swelling, thrombocytopenia, coagulopathy, neurotoxicity, or significant systemic toxicity are candidates for antivenom therapy. 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 or reverse 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 FDA approved antivenom for North American pit viper envenomation is Crotalidae polyvalent immune Fab (CroFab, BTG). CroFab is an ovine-derived Fab fragment antivenom developed from commonly encountered North American pit vipers (C. atrox, C. adamanteus, C. scutulatus, A. piscivorus). CroFab is administered IV in an initial dose of four to six vials reconstituted in 0.9% sodium chloride solution. Patients who present with cardiovascular collapse or other life-threatening toxicity should be treated aggressively with a starting dose of 8 to 12 vials of CroFab.34 The infusion is initiated at a slow rate for several minutes, 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 worsening thrombocytopenia, and, if present, an additional four- to six-vial dose is infused. This process is repeated until control of symptoms is achieved. Fibrinogen and PT may be slower to recover in response to antivenom. If these are the only findings that continue to be abnormal after antivenom, it is reasonable to repeat these studies in 4 hours to determine if redosing of antivenom is necessary. Control is generally considered cessation of progression of swelling and systemic symptoms in addition to improvement in coagulopathy and thrombocytopenia. After control has been achieved, maintenance doses of antivenom are given as two vials every 2 hours for three doses (six total additional vials after control). Although recommended in the package insert for CroFab, maintenance therapy is not routinely administered by all practitioners.5 For example, maintenance doses may be unnecessary in the management of copperhead envenomations. Practitioners can learn local practices and recommendations through consultation with regional poison centers. An algorithm for treatment of North American crotaline snakebite is also available online.34 Antivenom therapy is discussed in detail in Antidotes in Depth: A37.
Antivenom administration in children follows the same guidelines as adults, with doses based on clinical presentation and laboratory findings rather than weight. Attention should be paid to total amount of fluid received, and if necessary, antivenom can be reconstituted in a smaller total volume of fluid. Generally, patients with severe snake envenomation have large fluid requirements, and fluid overload is not a problem.
Pregnant patients who meet criteria for treatment should also receive antivenom. Crotalidae polyvalent Fab (ovine) is currently listed as pregnancy category C, but it has been used safely during pregnancy.32 Given the relative safety of this antivenom and the potential for 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.33
Surgery is not routinely indicated following snakebites. An extensive review of the literature failed to identify any evidence to support the use of fasciotomy in the treatment of snakebites.14 A single case of elevated compartment pressure (55 mm Hg) after rattlesnake envenomation was managed without fasciotomy. The authors treated this patient with antivenom, as well as mannitol and hyperbaric oxygen.23 When compartment syndrome is suspected, intracompartmental pressures should be measured. It is reasonable to attempt to treat moderately elevated compartment pressures with antivenom initially, but clinical examination and compartment pressures should be followed closely. Just as there is no strong evidence to support the use of fasciotomy, similarly there is a lack of evidence demonstrating that surgery is unnecessary when intracompartmental pressures are high. If the patient develops evidence of limb ischemia or increasing compartment pressures, fasciotomy may be indicated.
Patients with bites to the digit may present with evidence of ischemia. The finger may appear cyanotic or pale, tense, and lack sensation. The small diameter of the digit and limited ability of the skin to expand essentially creates a small compartment. In such cases it may be reasonable to perform a digital dermotomy, where a longitudinal incision is made through the skin on the medial or lateral aspect of the digit in order to decompress the neurovascular structures. Although there are no studies evaluating the efficacy of dermotomy in preventing tissue loss, the authors have seen patients with cyanotic and insensate digits regain color and sensation immediately following this procedure. Dermotomy should not be performed prophylactically in cases of digital envenomation, as most patients have good outcome without any surgical intervention.25
Debridement of hemorrhagic blebs and blisters is often 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 appropriate for patients with evidence of extensive tissue necrosis.
Immeasurably low fibrinogen concentrations, prothrombin times greater than 100 seconds, and platelet counts lower than 20,000 K/mm3 are routinely encountered after rattlesnake envenomation. 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 thrombocytopenia and coagulopathy is still present and will likely inactivate any transfused components. For this reason, the mainstay of treatment for crotaline envenomation–induced coagulopathy and thrombocytopenia is antivenom, not blood products. Correction of coagulopathy, thrombocytopenia, and bleeding can frequently be achieved with antivenom alone. Rarely, a patient will have active bleeding, and antivenom alone will not correct the platelets and fibrinogen. In such cases, fresh frozen plasma, cryoprecipitate, packed red blood cells, or platelet transfusions may be required.
In some cases, thrombocytopenia may be difficult, or impossible, to correct with even large amounts of antivenom. The Timber rattlesnake, for example, is known for producing thrombocytopenia resistant to antivenom. The initial correction of platelet counts 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 envenomation. It may be best to closely follow patients with resistant thrombocytopenia who are not bleeding, rather than attempt further platelet transfusions or antivenom administration.37
Hospital stays for patients with uncomplicated pit viper envenomations are typically short, lasting approximately 1 to 2 days.39 Upon discharge from the hospital, patients often have residual swelling and functional disability. They may have continued progression of hemorrhagic bullae with underlying necrosis. Patients should have an out-patient follow-up evaluation to ensure wounds are healing appropriately and extremity function is returning. If joint mobility does not return to baseline as swelling resolves, the patient should be referred for physical and occupational therapy.
In a significant proportion of rattlesnake bite patients treated with Crotalidae polyvalent immune Fab antivenom, a return of swelling, coagulopathy, or thrombocytopenia may be noted after initial resolution of the effect after initial treatment with antivenom. This has been termed “recurrence” of venom effect and is attributed to the interrelated kinetics and dynamics of venom and antivenom.39,42 Simply stated, Fab antivenom has a clinical half-life shorter than that of venom. Administration of maintenance doses of antivenom is used in an attempt to prevent development of recurrent effects. Maintenance doses appear to be effective in preventing recurrence of local swelling in most cases, but many patients develop hematologic recurrence within 3 to 7 days of antivenom treatment despite administration of maintenance doses. Additionally, patients who never manifested thrombocytopenia or coagulopathy during their hospital presentation may later develop the effect, presumably because of initial “masking” of the effect by early antivenom administration. These recurrent or late hematologic effects have been associated with life-threatening bleeding.30 No risk factors have been identified to predict which patients will develop late thrombocytopenia or coagulopathy.
The most reasonable way to address possible late hematologic effects of crotaline envenomation is careful outpatient follow-up after hospital discharge. Patients with copperhead bites may be followed as needed.34,39 The safest approach is to provide careful discharge instructions and consider all patients who have been treated with Crotalidae polyvalent immune Fab antivenom to be at risk for late hematologic toxicity. Patients who use antiplatelet or anticoagulant medications should be continued on these medications only after a careful risk-benefit analysis. Whenever possible the medications should be discontinued until the risk of recurrent or late hematologic toxicity passes. Patients must be warned not to undergo dental or surgical procedures for up to 3 weeks unless platelet and coagulation studies are documented to be normal immediately prior to the procedure. High-risk activities, such as contact sports, should be avoided. All patients should have platelets and coagulation studies measured 2 to 3 days, and again 5 to 7 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 late hematologic toxicity with antivenom vary. The general approach of the authors is to retreat any patient with evidence of bleeding, as well as patients with severe isolated thrombocytopenia (platelets <25,000/mm3) or moderate thrombocytopenia (platelets 25,000–50,000/mm3) in combination with severe coagulopathy (fibrinogen <80 mg/dL).39 Many clinicians choose to observe patients with isolated coagulopathy cautiously as outpatients rather than to retreat them with antivenom. However, if patients with isolated severe coagulopathy have other risk factors for bleeding, such as use of antiplatelet medications, retreatment with antivenom should be considered.
When the decision has been made to retreat a patient with late hematotoxicity with antivenom, an initial starting dose of two vials is recommended. Late thrombocytopenia appears to be more resistant to antivenom than early venom-induced thrombocytopenia, and it is unclear whether a different mechanism may be responsible for the late effect. It is unknown how much antivenom is needed to reverse late thrombocytopenia or at what dose a patient may be considered “resistant” to antivenom. Patients who have evidence of bleeding with severe thrombocytopenia may require platelet transfusion. Some clinicians have also given steroids to patients who have not responded to antivenom and platelet transfusions, but there is no evidence to support the efficacy of steroids in this setting.
As with North American pit viper bites, patients who are bitten by North American coral snakes should be taken to a hospital for definitive medical care as soon as possible. There are no field treatments that have been shown to affect outcome in these patients. Pressure immobilization bandages (PIB) have been shown to delay the systemic absorption of venom from Australian elapid snakes. A swine model of coral snake envenomation suggests that pressure immobilization bandaging may be effective in delaying systemic absorption of venom following coral snakebite.21 Patients who present for care after a PIB has been placed should have the dressing left in place until resuscitative equipment and personnel are present and, ideally, antivenom is available. The PIB should be checked to ensure it is not functioning as a tourniquet.
Patients with a history concerning for possible Eastern or Texas coral snakebite should be observed for 24 hours in a monitored unit where resuscitative measures, including endotracheal intubation, can be performed. Since neuromuscular weakness and respiratory paralysis can develop quickly, endotracheal intubation should be considered at the first sign of bulbar paralysis. Traditionally, treatment with Wyeth Antivenin (Micrurus fulvius) (equine origin) North American Coral Snake Antivenin (NACSA) has been recommended for all patients in whom there is strong suspicion of coral snakebite, even in the absence of signs of envenomation. This is mainly because paralysis can develop quickly and symptoms may not reverse following antivenom treatment. Approximately 10 years ago Wyeth ceased production of NACSA, creating a shortage of antivenom and prompting many clinicians to take a more conservative approach to treating patients with coral snakebites. A recent study comparing patients who received empiric treatment with antivenom to patients who were treated when symptoms developed suggests that a conservative approach (waiting for symptoms to develop before administering antivenom) does not result in worse outcomes for patients.58 The expiration date of current supplies of NACSA was extended to April 2014.51 Pfizer is expected to take over production of this antivenom in the near future.
If a patient is symptomatic following a coral snake envenomation, antivenom, if available, is indicated. If antivenom is unavailable, patients may be managed with supportive care alone. Mechanical ventilation may be necessary for many weeks. Acetylcholinesterase inhibitors, neostigmine and edrophonium, have been successfully used to treat patients with South American coral snakebites, but their use should be considered experimental.6
Sonoran coral snakes, indigenous to Arizona and California, have never been reported to cause significant toxicity, and bite victims do not require observation in the hospital or antivenom administration.
Management of helodermatid envenomation consists of supportive care. There is no antivenom available against lizard venom. Routine wound care should be performed, and the clinician should look for the presence of teeth in the wound. There is no evidence to guide clinicians when deciding whether to administer antibiotics to patients with erythema surrounding and extending from the bite site. Most case reports describing patients with erythema also report empiric use of antibiotics. There are no reports of confirmed infections following these bites.
Patients who are symptomatic following a bite should be attached to a cardiac monitor and have an intravenous catheter placed. Although serious morbidity from lizard bites is unusual, envenomation may be life threatening. Angioedema, other evidence of respiratory compromise, or airway obstruction should prompt endotracheal intubation. Hypotension may require treatment with intravenous fluid boluses as well as vasopressors such as epinephrine. Epinephrine, corticosteroids, and antihistamines may be indicated for the treatment of anaphylactoid reactions.