After a venomous snakebite, the time to symptom onset and clinical presentation can be quite variable and depend on the species involved, the anatomic location of the bite, and the amount of venom injected. Envenomations by most viperids and some elapids with necrotizing venoms cause progressive local pain, swelling, ecchymosis (Fig. 136-1), and (over a period of hours to days) hemorrhagic or serum-filled vesicles and bullae. In serious bites, tissue loss can be significant (Figs. 136-2 and 136-3). Systemic findings are extremely variable and can include tachycardia or bradycardia, hypotension, generalized weakness, changes in taste, mouth numbness, muscle fasciculations, pulmonary edema, renal dysfunction, and spontaneous hemorrhage (from essentially any anatomic site). Envenomations by neurotoxic elapids such as kraits (Bungarus species), many Australian elapids (e.g., death adders [Acanthophis species] and tiger snakes [Notechis species]), some cobras (Naja species), and some viperids (e.g., the South American rattlesnake [Crotalus durissus] and some Indian Russell’s vipers [Daboia russelii]) cause neurologic dysfunction. Early findings may consist of nausea and vomiting, headache, paresthesias or numbness, and altered mental status. Victims may develop cranial nerve abnormalities (e.g., ptosis, difficulty swallowing) followed by peripheral motor weakness. Severe envenomation may result in muscle paralysis, including the muscles of respiration, and lead to death from respiratory failure and aspiration. Sea snake envenomation results in local pain (variable), generalized myalgias, trismus, rhabdomyolysis, and progressive flaccid paralysis; these manifestations can be delayed for several hours.
TREATMENT Venomous Snakebite FIELD MANAGEMENT
The most important aspect of prehospital care of a person bitten by a venomous snake is rapid transport to a medical facility equipped to provide supportive care (airway, breathing, and circulation) and antivenom therapy. Most of the first-aid measures recommended in the past are of little benefit, and some actually worsen outcome. It is reasonable to apply a splint to the bitten extremity to lessen bleeding and discomfort and, if possible, to keep the extremity at approximately heart level. In developing countries, indigenous people should be encouraged to seek immediate care at a health care facility equipped with antivenom instead of consulting traditional healers and thus incurring significant delays in reaching appropriate care. Attempting to capture and transport the offending snake, alive or dead, is not advised; instead, digital photographs of the snake taken from a safe distance may assist with snake identification and treatment decisions.
Incising and/or applying suction to the bite site should be avoided, as these measures are ineffective and exacerbate local tissue damage. Similarly ineffective and potentially harmful are the application of poultices, ice, and electric shock. Techniques or devices used in an effort to limit venom spread (e.g., lymphoocclusive bandages or tourniquets) are ineffective and may result in greater local tissue damage by restricting the spread of potentially necrotizing venom. Tourniquet use can result in loss of function and amputation even in the absence of envenomation.
Elapid venoms that are primarily neurotoxic and have no significant effects on local tissue may be localized by pressure-immobilization, a technique in which the entire limb is wrapped immediately with a bandage (e.g., crepe or elastic) and then immobilized. For this technique to be effective, the wrap pressure must be precise (40–70 mmHg in upper-extremity application and 55–70 mmHg in lower-extremity application) and the victim must be carried out of the field because walking generates muscle-pumping activity that—regardless of the anatomic site of the bite—will disperse venom into the systemic circulation. Pressure-immobilization should be used only in cases in which the offending snake is reliably identified and known to be primarily neurotoxic, the rescuer is skilled in pressure-wrap application, the necessary supplies are readily available, and the victim can be fully immobilized and carried to medical care—an uncommon combination of conditions, particularly in the regions of the world where such bites are most common. HOSPITAL MANAGEMENT
In the hospital, the victim should be closely monitored (vital signs, cardiac rhythm, oxygen saturation, urine output) while a history is quickly obtained and a rapid, thorough physical examination is performed. To objectively evaluate the progression of local envenomation, the level of swelling in the bitten extremity should be marked and limb circumference should be measured every 15 min until the swelling has stabilized. During this period of observation, the extremity should be positioned at approximately heart level. Measures applied in the field (such as bandages or wraps) should be removed once IV access has been obtained, with cognizance that the release of such ligatures may result in hypotension or dysrhythmias when stagnant acidotic blood containing venom is released into the systemic circulation. Two large-bore IV lines should be established in unaffected extremities. Because of the potential for coagulopathy, venipuncture attempts should be minimized, and noncompressible sites (e.g., a subclavian vein) should be avoided. Early hypotension is due to pooling of blood in the pulmonary and splanchnic vascular beds. Later, systemic bleeding, hemolysis, and loss of intravascular volume into the soft tissues may play important roles. Fluid resuscitation with isotonic saline (20–40 mL/kg IV) should be initiated if there is any evidence of hemodynamic instability, and a trial of 5% albumin (10–20 mL/kg IV) may be given if the response to saline infusion is inadequate. Only after aggressive volume resuscitation and antivenom administration (see below) are accomplished should vasopressors (e.g., dopamine) be added. Invasive hemodynamic monitoring (central venous and/or continuous arterial pressures) can be helpful in such cases, although obtaining central vascular access is risky if coagulopathy has developed. Victims of neurotoxic envenomation should be watched carefully for evidence of cranial nerve dysfunction (e.g., ptosis) that may precede the onset of difficulty swallowing or respiratory insufficiency that necessitates definitive airway protection by endotracheal intubation.
Blood should be drawn for typing and cross-matching and for laboratory evaluation as soon as possible. Important studies include a complete blood count to determine the degree of hemorrhage or hemolysis and to identify thrombocytopenia; studies of renal and hepatic function; coagulation studies to diagnose consumptive coagulopathy; creatine kinase for suspected rhabdomyolysis; and testing of urine for blood or myoglobin. In developing regions, the 20-min whole-blood clotting test can be used to reliably diagnose coagulopathy. A few milliliters of fresh blood are placed in a new, clean, plain glass receptacle (e.g., a test tube) and left undisturbed for 20 min. The tube is then tipped once to 45° to determine whether a clot has formed. If it has not, coagulopathy is diagnosed. Arterial blood gas studies, electrocardiography, and chest radiography may be helpful in severe envenomations or when there is significant comorbidity. Any arterial puncture in the setting of coagulopathy requires great caution and must be performed at an anatomic site amenable to direct-pressure tamponade. After antivenom therapy (see below), laboratory values should be rechecked every 6 h until clinical stability is achieved. If initial laboratory values are normal, the complete blood count and coagulation studies should be repeated every hour until it is clear that no systemic envenomation has occurred.
The mainstay of treatment of a venomous snakebite resulting in significant envenomation is prompt administration of specific antivenom. Antivenoms are produced by injecting animals (generally horses or sheep) with venoms from medically important snakes. Once the stock animals develop antibodies to the venoms, their serum is harvested and the antibodies are isolated for antivenom preparation, which may involve varying degrees of digestion and purification of the IgG molecules. The goal of antivenom administration is to allow antibodies (or antibody fragments) to bind and deactivate circulating venom components before they can attach to target tissues and cause deleterious effects. Antivenoms may be monospecific (directed against a particular snake species) or polyspecific (covering several medically important species in the region) but rarely offer cross-protection against snake species other than those used in their production unless the species are known to have homologous venoms. Thus, antivenom selection must be specific for the offending snake; if the antivenom chosen does not contain antibodies to that snake’s venom components, it will provide no benefit and may lead to unnecessary complications (see below). In the United States, assistance in finding appropriate antivenom can be obtained from regional poison control centers.
For victims of bites by viperids or cytotoxic elapids, indications for antivenom administration include significant progressive local findings (e.g., soft tissue swelling crossing a joint or involving more than half the bitten limb) and any evidence of systemic envenomation (systemic symptoms or signs, laboratory abnormalities). Caution must be used in determining the significance of isolated soft tissue swelling after the bite of an unidentified snake because the saliva of some relatively harmless species can cause mild edema at the bite site; in such bites, antivenoms are useless and potentially harmful. Antivenoms have limited efficacy in preventing tissue damage caused by necrotizing venoms, as venom components bind to local tissues very quickly, before antivenom administration can be initiated. Nevertheless, antivenom should be administered as soon as the need for it is identified to limit further tissue damage and systemic effects. Antivenom administration after bites by neurotoxic elapids is indicated at the first sign of any evidence of neurotoxicity (e.g., cranial nerve dysfunction, peripheral neuropathy). In general, antivenom is effective only in reversing active venom toxicity; it is of no benefit in reversing effects that already have been established (e.g., renal failure, established paralysis) and that will improve only with time and other supportive therapies.
Specific comments related to the management of venomous snakebites in the United States and Canada appear in Table 136-1. The package insert for the selected antivenom can be consulted regarding species covered, method of administration, starting dose, and need (if any) for re-dosing. The information in antivenom package inserts, however, is not always accurate and reliable. Whenever possible, it is advisable for treating physicians to seek advice from experts in snakebite management regarding indications for and dosing of antivenom.
Antivenom should be administered only by the IV route, and the infusion should be started slowly, with the physician at the bedside ready to intervene immediately at the first signs of an acute adverse reaction. In the absence of an adverse reaction, the rate of infusion can be increased gradually until the full starting dose has been administered (over a total period of ~1 h). Further antivenom may be necessary if the patient’s acute clinical condition worsens or fails to stabilize or if venom effects that were initially controlled recur. The decision to administer further antivenom to a stabilized patient should be based on clinical evidence of persistent circulation of unbound venom components. For viperid bites, antivenom administration generally should be continued until the victim shows definite improvement (e.g., stabilized vital signs, reduced pain, restored coagulation). Neurotoxicity from elapid bites may be more difficult to reverse with antivenom. Once neurotoxicity is established and endotracheal intubation is required, further doses of antivenom are unlikely to be beneficial. In such cases, the victim must be maintained on mechanical ventilation until recovery, which may take days or weeks.
Adverse reactions to antivenom administration include immediate (nonallergic and, less commonly, allergic anaphylaxis) and delayed-type hypersensitivity reactions (serum sickness). Clinical manifestations of immediate hypersensitivity include urticaria, laryngeal edema, bronchospasm, and hypotension. Skin testing for potential hypersensitivity, although recommended by some antivenom manufacturers, is insensitive and nonspecific and should be omitted. Worldwide, the quality of antivenoms is highly variable. Rates of acute nonallergic anaphylactic reactions to some of these products exceed 50%. For this reason, some authorities have recommended pretreatment with IV antihistamines (e.g., diphenhydramine, 1 mg/kg to a maximum of 100 mg; and cimetidine, 5–10 mg/kg to a maximum of 300 mg) or even a prophylactic SC or IM dose of epinephrine (0.01 mg/kg, up to 0.3 mg). Further research is necessary, however, to determine whether any pretreatment measures are truly beneficial. Modest expansion of the patient’s intravascular volume with crystalloids may blunt acute adverse blood pressure decline. Epinephrine and airway equipment should always be immediately available during antivenom infusion. An acute anaphylactic reaction may be heralded by a single hive or mild itching or may present as bronchospasm or acute cardiovascular collapse. If the patient develops an acute reaction to antivenom, the infusion should be temporarily stopped and the reaction immediately treated with IM epinephrine and IV antihistamines and glucocorticoids. Once the reaction has been controlled, if the severity of the envenomation warrants additional antivenom, the dose should be diluted further in isotonic saline and restarted as soon as possible. Rarely, in cases of recalcitrant hypotension, a concomitant IV infusion of epinephrine may be initiated and titrated to clinical effect while antivenom is administered. The patient must be monitored very closely during such therapy, preferably in an intensive care setting. Serum sickness typically develops 1–2 weeks after antivenom administration and may present as fever, chills, urticaria, myalgias, arthralgias, lymphadenopathy, and renal or neurologic dysfunction. Treatment of serum sickness consists of systemic glucocorticoids (e.g., oral prednisone, 1–2 mg/kg daily) until all symptoms have resolved, followed by a taper over 1–2 weeks. Oral antihistamines and analgesics may provide additional relief of symptoms.
Blood products are rarely necessary in the management of an envenomed patient. The venoms of many snake species can deplete coagulation factors and cause a decrease in platelet count or hematocrit. Nevertheless, these components usually rebound within hours after administration of adequate antivenom. If the need for blood products is thought to be great (e.g., a dangerously low platelet count in a hemorrhaging patient), these products should be given only after adequate antivenom administration to avoid fueling ongoing consumptive coagulopathy.
Rhabdomyolysis and hemolysis should be managed in standard fashion. Victims who develop acute renal failure should be evaluated by a nephrologist and referred for hemodialysis or peritoneal dialysis as needed. Such renal failure, which usually is due to acute tubular necrosis, is frequently reversible. If bilateral cortical necrosis occurs, however, the prognosis for renal recovery is less favorable, and long-term dialysis with possible renal transplantation may be necessary.
Acetylcholinesterase inhibitors (e.g., edrophonium and neostigmine) may promote neurologic improvement in patients bitten by snakes with postsynaptic neurotoxins. Snakebite victims with objective evidence of neurologic dysfunction should receive a test dose of acetylcholinesterase inhibitors, as outlined in Table 136-2. If they exhibit improvement, additional doses of long-acting neostigmine can be administered as needed. Close monitoring is required to prevent aspiration if repetitive dosing of neostigmine is used in an attempt to obviate endotracheal intubation. Acetylcholinesterase inhibitors are not a substitute for administration of an appropriate antivenom when available.
Care of the bite wound includes simple cleansing with soap and water; application of a dry, sterile dressing; and splinting of the affected extremity with padding between the digits. Once antivenom therapy has been initiated, the extremity should be elevated above heart level to reduce swelling. Tetanus immunization should be updated as appropriate. Prophylactic antibiotics are generally unnecessary after bites by North American snakes, as the incidence of secondary infection is low. In some regions, secondary bacterial infection is more common and the consequences are dire; in these regions, prophylactic antibiotics (e.g., cephalosporins) are used commonly. Antibiotics may also be considered if misguided first aid efforts have included incision or mouth suction of the bite site. Pain control should be achieved with acetaminophen or narcotic analgesics. Salicylates and nonsteroidal anti-inflammatory agents should be avoided because of their effects on blood clotting.
Most snake envenomations involve SC deposition of venom. On occasion, however, venom can be injected more deeply into muscle compartments, particularly if the offending snake was large and the bite occurred on the lower leg, forearm, or hand. Intramuscular swelling of the affected extremity may be accompanied by severe pain, decreased strength, altered sensation, cyanosis, and apparent pulselessness—signs suggesting a muscle compartment syndrome. If there is clinical concern that subfascial muscle edema may be impeding tissue perfusion, intracompartmental pressures should be measured by a minimally invasive technique (e.g., wick catheter or digital readout device). If the intracompartmental pressure is high (>30–40 mmHg), the extremity should be kept elevated while antivenom is administered. A dose of IV mannitol (1 g/kg) can be given in an effort to reduce muscle edema if the patient is hemodynamically stable. If the intracompartmental pressure remains elevated after 1 h of such therapy, a surgical consultation should be obtained for possible fasciotomy. Although evidence from animal studies suggests that fasciotomy may actually worsen myonecrosis, compartmental decompression is still necessary to preserve nerve function. Fortunately, the incidence of compartment syndrome is very low after a snakebite, with fasciotomies required in <1% of cases. Nevertheless, vigilance is essential. If a fasciotomy is deemed necessary, it should be undertaken with the patient’s informed consent whenever possible.
Wound care in the days after the bite should include careful aseptic debridement of clearly necrotic tissue once coagulation has been restored. Intact serum-filled vesicles or hemorrhagic blebs should be left undisturbed. If ruptured, they should be debrided with sterile technique. Any debridement of damaged muscle should be conservative because there is evidence that such muscle may recover to a significant degree after antivenom therapy.
Physical therapy should be started as soon as possible so that the victim can return to a functional state. The incidence of long-term loss of function (e.g., reduced range of motion, impaired sensory function) is unclear but is probably quite high (>30%), particularly after viperid bites.
Any patient with signs of envenomation should be observed in the hospital for at least 24 h. In North America, a patient with an apparently “dry” viperid bite should be watched for at least 8 h before discharge, as significant toxicity occasionally develops after a delay of several hours. The onset of systemic symptoms commonly is delayed for a number of hours after bites by several of the elapids (including coral snakes, Micrurus species), some non–North American viperids (e.g., the hump-nosed pit viper [Hypnale hypnale]), and sea snakes. Patients bitten by these snakes should be observed in the hospital for at least 24 h. Patients whose condition is not stable should be admitted to an intensive care setting.
At hospital discharge, victims of venomous snakebites should be warned about symptoms and signs of wound infection, antivenom-related serum sickness, and potential long-term sequelae, such as pituitary insufficiency from Russell’s viper (D. russelii) bites. If coagulopathy developed in the acute stages of envenomation, it can recur during the first 2–3 weeks after the bite. In such cases, victims should be warned to avoid elective surgery or activities posing a high risk of trauma during this period. Outpatient analgesic treatment, wound management, and physical therapy should be provided.