Envenomated patients typically experience moderate-to-severe pain at the bite site within 5 to 10 minutes. The pain is often described as burning and may radiate along the bitten extremity. Swelling at the bite site soon follows and may progress along the entire extremity within hours. There is often local ecchymosis because of disruption of blood vessels. A persistent bloody effluent from the wound suggests the presence of snake venom anticoagulants. Rapid lymphatic absorption of venom may lead to impressive, early lymphangitis and regional adenopathy [3].

Within the first 24 to 36 hours, hemorrhagic bullae or serum-filled vesicles may develop at the bite site and along the bitten extremity. These are less common in bites treated early with adequate amounts of antivenom [4,7]. Petechiae or purpura may also be present.

Systemic manifestations of pit viper envenomation can involve virtually any organ system. Nausea and vomiting are common and may appear early with severe bites [7]. Weakness, diaphoresis, fever and chills, dizziness, and syncope may also occur [3,4]. Some patients experience a minty, rubbery, or metallic taste in their mouth and hypersalivation [4,7]. Muscle fasciculations or paresthesias of the scalp, face, tongue, or digits indicate a moderate-to-severe envenomation. Systemic coagulopathy can lead to bleeding at any anatomic site, including the gastrointestinal, respiratory, genitourinary, and central nervous systems, although clinically significant bleeding is uncommon following bites in North America [3,7].

Alterations in heart rate and blood pressure may occur. Early hypotension is usually due to pooling of blood in the pulmonary and splanchnic vascular beds, whereas delayed shock is due to blood loss, third spacing of intravascular volume, and hemolysis [3,4,8]. Pulmonary edema can occur in severe envenomations, and is secondary to disruption of pulmonary vasculature intimal linings and pooling of pulmonary blood [3,5].

Multifactorial renal failure may occur, but is uncommon. Contributing factors include hypotension; hemoglobin, myoglobin, and fibrin deposition in renal tubules; and direct venom nephrotoxicity [3,7].

Muscle weakness may be seen after bites by some rattlesnakes that possess phospholipase A₂ neurotoxins in their venoms, such as the eastern diamondback rattlesnake (Crotalus adamanteus) [9] or some specimens of the Mohave rattlesnake (Crotalus scutulatus) [10]. Neuromuscular respiratory failure is rare, but can occur in severe bites by the Mohave rattlesnake in certain geographic locations [7].

Snake venoms do not appear to cross the blood–brain barrier to any significant extent, and rare findings such as seizures and coma are secondary to hypotension, hypoxia, or intracranial bleeding [2].

Important aspects of the history include details of the incident (such as type and size of snake if known, time and number of bites, and methods of first aid applied) and the patient’s medical
history (including any prior snakebites, medications, allergies, and tetanus immunization status).

Pit viper envenomation is a true emergency with potential for multisystem involvement. The severity of the bite must be assessed, and the clinical severity grading scale in Table 132.1 may be useful in evaluating most pit viper bites [4]. Approximately 20% of bites by U.S. pit vipers result in no envenomation (“dry bites”) [4,7,11]. It must be understood, however, that severity can progress rapidly, and the patient must be frequently reevaluated for a worsening clinical condition. Good clinical judgment is more important than overreliance on grading scales. Consultation with an authority in the area of toxinology is prudent.

Puncture-wound patterns can be misleading in the diagnosis of snakebite. Occasionally, there is only a single puncture wound or many tiny punctures [12]. A dry bite may or may not have fang puncture marks, but there is no more pain than would be expected from simple puncture wounds. Envenomation is confirmed by the presence of local tissue effects (particularly progressive swelling), systemic effects, and/or laboratory abnormalities.

Essential laboratory studies include a complete blood cell count, serum electrolytes, blood urea nitrogen, creatinine, prothrombin time or international normalized ratio, fibrinogen, fibrin degradation products, and urine analysis. Blood for type and screening should also be sent for evaluation as soon as possible as direct venom effects and antivenom effects may interfere with this process later [13]. Also helpful are creatine phosphokinase as a measure of muscle damage and intracompartmental pressure measurements in patients with suspected compartment syndrome. Obtain a chest radiograph, arterial blood gases, and an electrocardiogram as clinically indicated.

Occasionally, the history and diagnosis may be unclear, especially in children [14]. When patients present without having seen a snake and have no findings other than puncture wounds and mild pain, the differential diagnosis includes a dry bite, bite by other animal or arthropod (e.g., nonvenomous snake, centipede, or spider), and puncture wounds from inanimate objects (e.g., thorns).

First-aid efforts are best limited to reassuring the victim, immobilizing and splinting the extremity at heart level, and transporting the victim as quickly as possible to a hospital.

Previously recommended first-aid measures including incision, suction, constriction bands pressure immobilization, tourniquets, packing of the extremity in ice, or application of electric shocks should be avoided as they are ineffective and may result in further complications [15,16,17].

Two large-bore intravenous (IV) lines infusing normal saline should be established, preferably in sites other than the bitten extremity, and blood work sent to the laboratory. Continuous cardiac and pulse oximetry monitoring are indicated, and oxygen is administered if hemoglobin saturation is low or if the patient is experiencing any respiratory distress. Any devices applied in the field in an attempt to limit venom spread should be left in place until an IV line is established.

Management of significant pit viper envenomation centers on the judicious use of an appropriate antivenom. In North America, antivenom therapy is indicated for victims with progressive local tissue findings or systemic abnormalities (significant systemic symptoms or signs, or laboratory abnormalities [e.g., paresthesias, hypotension, prolongation of prothrombin time or international normalized ratio, hypofibrinogenemia, or thrombocytopenia]) (see Fig. 132.1). Controversy exists, however, on the use of antivenom for copperhead (A. contortrix) bites presenting with progressive soft-tissue swelling in the absence of systemic abnormalities. Given that most such bites do well with conservative therapy alone [7], the cost–benefit ratio of giving antivenom in these cases is currently unclear and requires further research [18,19].

If possible, informed consent should be obtained before antivenom administration. Antivenom should be administered in a closely monitored setting. Epinephrine and endotracheal intubation equipment should be immediately available at the bedside during antivenom administration, and a physician should be in attendance to observe and manage any acute adverse drug effects that may develop.

In the United States there is currently a single commercially available antivenom for pit viper bites—CroFab® Crotalidae Polyvalent Immune Fab, Ovine (BTG International Inc., West Conshohocken, PA). This antiserum contains purified Fab immunoglobulin fragments from sheep immunized with one of four different pit viper venoms. It comes in a lyophilized state and is effective against all North American pit vipers.

Antivenom should be started as soon as possible after indications for administration are met. Although there are no defined end points in terms of time or dosage for when to withhold antivenom, antivenom is beneficial for treating only findings directly related to continued presence of unbound venom in the circulation (e.g., ongoing coagulopathy). It is ineffective in reversing end-organ damage that has resulted from prior venom effects (e.g., renal failure). The efficacy of antivenom in preventing local wound necrosis is limited, as it cannot reverse local cellular damage once it has been initiated by rapidly acting venom enzymes and nonenzymatic polypeptides [14,20,21]. Any ability to reduce necrosis depends on early administration.

Dosing of CroFab® is based on severity of the bite (see Table 132.1), not on age or size of the patient. The initial dose is four to six vials for patients with signs or symptoms of systemic toxicity or evidence of progressive local venom effects. Each CroFab® vial should be reconstituted with 10 mL of warm sterile water or saline. The total dose to be administered is diluted in 250 mL of crystalloid and infused over 1 hour (starting slowly at the onset of infusion and gradually increasing the rate). During the hour after the initial dose is completed, the patient is monitored for further progression of local effects and systemic symptoms, and laboratory studies are repeated [13]. The starting dose of CroFab® is repeated if venom effects continue to progress. This pattern is continued until the patient stabilizes. Coagulation studies may not normalize after the initial dose, as time is required for repletion of coagulation factors after venom neutralization, but they should show evidence of improvement [22,23]. After stabilization, two vials of CroFab® are administered every 6 hours for three additional doses. Further doses may be needed at the physician’s discretion.

Adverse effects of antivenoms, as heterologous serum products, are divided into three major groups: acute allergic and nonallergic anaphylaxis, and delayed serum sickness. Acute reactions most commonly manifest with hives and/or bronchospasm [24], though hypotension and angioedema can also occur. Serum sickness is characterized by pruritus, fever, arthralgias, lymphadenopathy, and malaise, which can occur 1 to 2 weeks after antivenom therapy [3]. The incidence of acute reactions to CroFab® is approximately 15% and serum sickness occurs in approximately 3% of patients [25]. Management of acute reactions centers on rapid diagnosis, temporarily halting the infusion and treating with epinephrine, antihistamines, and steroids (see Chapter 194). Generally, once the reaction is controlled, the antivenom infusion can be restarted, possibly in a more dilute state and at a slower rate. Serum sickness is relatively benign and easily treated with steroids, antihistamines, and nonsteroidal anti-inflammatory drugs until symptoms resolve [26]. Most cases do well with oral prednisone (1 to 2 mg per kg per day) until symptoms resolve, followed by a taper over another week.

Venom-induced hypotension should be treated with antivenom and volume expansion. If organ perfusion fails to respond promptly with crystalloid infusion (1 to 2 L in an adult and 20 to 40 mL per kg in a child), administration of albumin is advisable as this agent is likely to stay in the leaky vascular system for longer periods of time [4,8]. Pressors should be used as a last resort [4].

Although pit viper envenomation can result in significant coagulopathies, the incidence of clinically significant bleeding in the United States is low [13,27]. Management of coagulopathy in patients with evidence of clinically significant bleeding, other than microscopic hematuria or minor gingival bleeding, may require administration of packed red blood cells, platelets, fresh-frozen plasma, and/or cryoprecipitate [4,28]. There is limited experience using recombinant factor VIIa for severe coagulopathy following rattlesnake bite [29]. It is important to begin antivenom therapy before the infusion of such products to avoid adding fuel to an unabated consumptive coagulopathy.

Therapy to prevent acute renal failure includes ensuring adequate hydration and monitoring urinary output. Hemoglobinuria and myoglobinuria are treated in standard fashion. If renal failure occurs, dialysis may be required, although it does not remove circulating venom components [4,7].

Although steroids are useful in the management of adverse reactions to antivenom (see previous discussion), there is no role for them in the primary management of snake envenomation.

Wound care begins with cleaning the bite site with a suitable germicidal solution and covering it with a dry, sterile dressing. As soon as antivenom has been started, if indicated, the extremity should be elevated in a well-padded splint in a position of function with cotton between the digits [3,4]. Antibiotics are unnecessary unless field management involved incisions into the bite site [30] or the wound becomes clinically infected. Tetanus immunization status should be updated as necessary.

Intact hemorrhagic blebs and bullae should be protected. If ruptured, they should be unroofed after any attendant coagulopathy has been reversed [7,31]. Further debridement may be necessary if there is significant tissue necrosis. The use of hyperbaric oxygen therapy to treat these wounds has yet to be fully studied [4,32]. Physical therapy is important in returning the extremity to functional capacity.

The role of surgery in the primary management of pit viper envenomation is very limited. The speed with which snake venom is absorbed makes routine excision of the bite site fruitless [33], and routine exploration of the site does nothing to mitigate systemic effects of venom, may worsen the overall outcome by adding surgical trauma, and prolongs hospitalization [4].

The incidence of compartment syndrome after snake envenomation appears low despite the frequently impressive local findings of bitten extremities [34,35]. Myonecrosis that occurs is usually due to direct venom effects and rarely vascular compromise from elevated intracompartmental pressures [21,34,35]. In combined series of nearly 2,000 victims of pit viper envenomation, only 4 patients required fasciotomy; each of these patients received inappropriate ice treatment or inadequate antivenom [34,35]. If there is concern about an impending compartment syndrome, intracompartmental pressures should be checked using any standard technique. If pressures exceed 30 to 40 mm Hg and remain elevated for more than 1 hour despite appropriate antivenom administration, limb elevation and possibly mannitol infusion (1 to 2 g per kg in a normotensive patient), fasciotomy may be required [35,36]. While some evidence suggests that fasciotomy may actually worsen local myonecrosis [37], unabated elevation of intracompartmental pressures can have disastrous effects, such as debilitating neuropathy [38], and fasciotomy may still be required. Whenever possible, informed consent should be obtained prior to proceeding with fasciotomy.

Patients with apparent dry bites can be discharged from the emergency department if they remain asymptomatic with normal laboratory values (repeated prior to discharge) after 8 hours of observation [39]. The envenomated patient can be discharged from the hospital when all venom effects have begun to resolve and when antivenom therapy is complete, which is usually within 48 hours after admission. At the time of discharge, every patient should have appropriate follow-up arranged for continued wound care and physical therapy, and should be warned about the symptoms of serum sickness. If such symptoms occur, the patient should seek medical care promptly.

Venom-induced coagulopathy and thrombocytopenia may recur anytime up to 14 days after the last dose of antivenom [40]. Therefore, patients should be followed closely for this phenomenon after discharge from the hospital. If there is evidence of clinically significant bleeding on follow-up or if the laboratory coagulopathy is severe, additional antivenom can be considered, although its efficacy at reversing delayed recurrence of coagulopathy appears to be reduced and the need to treat asymptomatic coagulopathy during recovery is controversial [22,23,40]. Nevertheless, patients who developed coagulopathy during the acute phase of envenomation should be warned to avoid elective procedures and risky activities (such as contact sports) for at least 2 weeks.

The historical mortality rate for patients treated with antivenom in the United States was 0.28%, compared to 2.61% for patients not receiving antivenom [41]. The impact of CroFab® on mortality rates remains to be determined. Death after pit viper poisoning is most likely to occur 6 to 48 hours after envenomation [41,42]. Fewer than 17% of deaths occur within 6 hours and fewer than 4% within 1 hour [41,42]. The major reasons for poor outcome in pit viper envenomation are delay in presentation, inadequate fluid resuscitation, inappropriate use of vasopressors, and delay in administration or inadequate dosing of antivenom [2,43]. The incidence of upper-extremity functional disability after pit viper envenomation is at least 32% [44], and may be higher when careful, objective functional measurements are obtained [45].

Coral snake venoms are primarily neurotoxic; low-molecular-weight polypeptides in the venom are capable of inducing nondepolarizing, postsynaptic blockade at neuromuscular junctions [3,53]. There are few local findings at the bite site, and the onset of systemic symptoms may be delayed for many hours [3,49,54]. Fang marks may be small and difficult to detect [55], with variable pain and little swelling at the site [54]. The patient may experience local paresthesias that may radiate proximally and be associated with muscle fasciculations [54,56]. The earliest systemic findings may include alteration of mental status [3,57]. Nausea and vomiting may occur, along with increased salivation [3,49]. Bulbar-type paralysis can occur as early as 90 minutes after the bite and progress to peripheral paralysis [4]. Findings may include extraocular muscle paresis, ptosis, pinpoint pupils, dysphagia, dysphonia, slurred speech, and laryngeal spasm [49,54,56]. Death from coral snake envenomation has been reported because of respiratory failure or cardiovascular collapse [4].