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Timely Management of Snakebite
Every year, about 2000 people in the United States are bitten by an elapid or crotalid snake. The authors describe these two types of poisonous snake and explain how to diagnose and treat their bites.
By Justin Hopkin, MD, and Kennon Heard, MD
Managing snakebite victims promptly by implementing the proper treatment is a critical skill for emergency physicians. Poisonous snakes are native to all of the lower 48 states except Maine. During the past three years, the American Association of Poison Control Centers has reported an annual average of 6000 snakebites in the United States—2000 of them by venomous snakes—but only four deaths were reported in 2006. This low fatality rate is due to early recognition of envenomation and timely intervention by medical personnel. This article will review the presentation and management of the snakebite victim.
More than 100 species of snakes are found in the United States, but fewer than 30 species are considered venomous. The venomous snakes of medical significance come from two families, Elapidae and Viperidae (subfamily Crotalinae). Snakes from the subfamily Crotalinae (crotalids) are the offenders in the vast majority of venomous human snakebites in the United States.
MANAGING ELAPID BITES
Worldwide, elapids such as cobras and mambas account for much of the morbidity related to snakebites. Coral snakes are the only elapids found in the United States. These shy, unaggressive snakes bite only 20 to 30 people every year in this country. Most bites occur when people handle the snake intentionally, even though they often realize it is venomous. Three species of coral snake exist in the United States, and they are easily identified by their color pattern—red and yellow bands that are adjacent to each other. Nonpoisonous imitators have black bands between the bands of red and yellow. This can be remembered with the rhyme “red on yellow kills a fellow; red on black, venom lack.”
The likelihood of serious injury from a snakebite depends on the bite and the venom. Elapids have a primitive bite apparatus, so they have to repeatedly strike or chew on their victim to inject venom. Two historical features that suggest elapid envenomation are difficulty separating the snake from the skin (often reported as similar to pulling Velcro apart) and being repeatedly chewed on by the snake.
The clinician should consider three questions when taking a patient history for a possible elapid bite: Could the snake be an elapid? Could envenomation have occurred? Are there signs of envenomation? First, an attempt should be made to identify the snake based on the victim’s history. This can be difficult because people who keep poisonous snakes as pets may not want to admit it for fear of having them taken away. Elapids are native to the southern and eastern parts of the United States but can be kept as pets anywhere. If an elapid bite is suspected, monitor the patient for at least 12 hours in the emergency department because symptom development can be markedly delayed.
The next step is to determine if envenomation has occurred. If you are reasonably certain the snake was an elapid, and the patient gives a history of multiple bites, chewing, or having difficulty removing the snake from the bite site, the recommended treatment is antivenom before symptoms begin. Unfortunately, antivenom for elapid bites is no longer produced in the United States. Limited supplies are still available, but future availability may require importation. Clinicians treating a patient with a possible coral snake envenomation should contact their local poison center for help in locating a center where antivenom is available.
The last step is to check for signs and symptoms of envenomation. These include peripheral nerve findings of paresthesias (especially of the tongue and lips), tremors, marked salivation, ptosis, dysarthria, and dyspnea. These problems are caused by a protein that irreversibly blocks propagation at the neuromuscular junction by permanently binding to the receptor. Severe envenomations result in respiratory muscle and systemic paralysis until more receptors can be regenerated at the neuromuscular junction.
Untreated patients with severe envenomation may require mechanical ventilation until respiratory function returns (usually within several days). One study that reviewed 39 victims of coral snake bites showed no deaths and no permanent sequelae, although recovery from paralysis took several weeks in some patients. In this study, faster recovery occurred with early antivenom delivery (within 12 hours). However, a delay in administering the antivenom should not postpone or prevent treatment of a symptomatic patient.
MANAGING CROTALID BITES
Most venomous bites in the United States are from crotalids (also called pit vipers). Crotalids include rattlesnakes, copperheads, and cottonmouths (also known as water moccasins). These snakes (see image below) have large, triangular heads with heat-sensing pits located just above the nostrils. Copperheads and cottonmouths differ from rattlesnakes in that they lack a rattle. The copperhead is identified by its copper color, the inverted “Y” markings on its back, and pale-colored oral mucosa. It is an aggressive snake that often lives near water.
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| Complex injection system. With the long fangs characteristic of crotalid snakes, this Western Diamondback rattler needs only one strike to administer an effective dose of its special cocktail of destructive enzymes and toxins. |
Crotalids have a complex venom-injection apparatus that enables them to inject venom through their fangs in a single strike. The number, depth, and location of the strikes all affect the clinical severity of the bite. Venom from deep bites is usually absorbed more quickly and causes more rapid onset of symptoms. Bites that are not on the extremities (torso, neck, and head bites) usually cause more severe systemic symptoms. Bites on the face and tongue may compromise the airway of the victim secondary to local edema.
Venom composition varies greatly in different species of snake and can even vary throughout the year in a given species. Crotalid venom contains enzymes, including phospholipases, collagenases, and metalloproteases, as well as serotonin, histamines, kinins, and leukotrienes, which produce both local and systemic effects. Enzymes immobilize prey and facilitate digestion. Metalloproteases cause endothelial damage, leading to ecchymosis and edema. Various other enzymes cause effects ranging from red blood cell destruction to activation of the clotting cascade with resultant consumptive coagulopathy. Kinins, histamines, leukotrienes, and serotonin cause vomiting and pain.
PATIENT PRESENTATION
Up to 20% of crotalid bites are dry bites, meaning that venom is not injected. One goal of clinicians is to identify this 20% of patients who do not need antivenom therapy. Recognizing dry bites can be very difficult because patients may present with anxiety, which mimics systemic symptoms. Patients may also be asymptomatic or have subtle symptoms that are easily overlooked.
After a crotalid bite, the victim commonly experiences a sense of impending doom. It is unclear if this sympathetic response of tachycardia, tachypnea, and nausea is mediated by the venom or the instinctual fight-or-flight response. True envenomation is established by identifying local changes around the wound, hematologic abnormalities, and systemic changes in various organ systems.
Local changes. Puncture marks should be noted on examination. Although the absence of marks does not rule out snakebite, identifying one or more marks is helpful in establishing the diagnosis. Pain usually starts within minutes of the bite. Edema (see image below, top) and ecchymosis can be seen hours later. Paresthesias and bullae formation (see image below, bottom) are also common local findings after envenomation.
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| Local swelling. Swelling at the envenomation site is another common finding. This patient was bitten by a copperhead. |
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| Hemorrhagic bullae. Bullae are common local findings after envenomation. This patient was bitten by a rattlesnake. |
Hematologic abnormalities. Envenomation can cause dramatic hematologic abnormalities. Fibrinogen and platelet counts drop precipitously. Defects in the coagulation cascade result in prolonged prothrombin and partial thromboplastin times and an unmeasurable whole blood clotting time. Despite these findings, bleeding is rare following a snakebite.
Systemic changes. The systemic changes caused by crotalid envenomation—nausea, vomiting, tachycardia, and tachypnea—are difficult to differentiate from signs of anxiety following the bite. Other systemic signs more indicative of envenomation are perioral paresthesias, a minty or metallic taste in the mouth, hypotension, and respiratory distress. Altered sensorium is probably not a direct result of envenomation, so alternative diagnoses, such as intoxication or hypotension, should be investigated.
Some patients present with anaphylactic-type symptoms after envenomation. People previously exposed to venomous snakes (such as snake handlers and previous bite victims) seem to be at higher risk of developing anaphylaxis, but these reactions may also occur in patients with no prior exposure. This presentation may be caused by venom activation of the protein signals that mediate anaphylaxis. Patients should be treated immediately for anaphylaxis with epinephrine, steroids, and antihistamines in conjunction with antivenom therapy.
The table above summarizes the local, hematologic, and systemic changes that are diagnostically supportive of envenomation.
FIELD MANAGEMENT
Poison control centers have a saying: “The best treatment for snakebite is a cell phone.” Because very little can be done in the field to effectively treat crotalid snakebites, the emphasis should be on quickly transferring the victim to a medical facility for evaluation and treatment. If possible, someone should stay with the patient and someone else should go ahead and arrange for transport to a medical facility. The victim should be kept as calm as possible; exertion will only increase heart rate, blood pressure, and muscle contractility, leading to increased systemic absorption of the venom. The affected limb should be immobilized and kept below the heart. Any jewelry or tight-fitting clothes should be removed from affected extremities because they can become tourniquets with subsequent swelling.
Over the past several years, many field management therapies have been proven ineffective or even harmful. Local incision with the goal of removing venom is ineffective and may increase the chance of local infection or injury to neurovascular structures. Electrical shocks and cryotherapy are ineffective in neutralizing venom. Ice can be applied locally to reduce pain, but it does not decrease the toxicity of the venom.
Tourniquets are generally discouraged because the major source of morbidity from snakebites is local tissue damage. Although a tourniquet prevents systemic absorption of the venom, it keeps a higher concentration of venom at the site of the wound, which will likely worsen local tissue destruction. A tourniquet-like wrap known as the Sutherland wrap is widely used for field management of snakebites in Australia, but most of the venomous snakes there are elapids, and their venom causes very little local tissue damage.
HOSPITAL MANAGEMENT
Some snakebite victims will need immediate resuscitation and stabilization. Initial assessment for evidence of hemodynamic or airway compromise should be performed and addressed as needed. If the bite occurs on the face or lips, tissue edema could rapidly compromise the airway and intubation may be necessary. Victims suffering from anaphylaxis should be treated with epinephrine, steroids, and antihistamines. Intravenous access should be obtained in an unaffected limb. As in the field, tight-fitting clothes or jewelry on affected limbs should be removed promptly because edema can develop rapidly. If a tourniquet has been placed, do not remove it until antivenom therapy is delivered.
Note the amount of edema and record it by outlining the margins on the skin every 15 to 30 minutes until the antivenom stops its progression. This is important in evaluating the effectiveness of antivenom therapy. Once antivenom therapy is delivered, clean the wound and loosely immobilize the limb. Finally, take a detailed history and administer a tetanus vaccine if the patient needs one.
A crotalid bite can cause severe pain that often requires analgesia. Narcotics are the preferred agent for pain because nonsteroidal anti-inflammatory drugs (NSAIDs) may worsen platelet dysfunction. An ice bag may be applied to the site for comfort only.
After taking the history, determine if clinically significant envenomation has occurred. Look for fang marks, which can be subtle. Identifying fang marks helps verify that a bite has occurred but is not diagnostic of envenomation because 20% of crotalid bites do not result in envenomation. While no strict guidelines exist on who should receive antivenom, it is generally agreed that anyone who has symptoms of envenomation should receive antivenom. Patients without evidence of envenomation should be monitored for 8 to 12 hours before discharge because clinical signs can be delayed.
The sections below describe three key areas of crotalid bite management: antivenom therapy, treatment of recurrent signs and symptoms, and blood product administration.
Antivenom therapy. Before administering antivenom therapy, contact the local poison control center for guidance on dosing. People there are experienced in administering antivenom and treating snakebites. The emergency department staff should prepare to admit the patient to the ICU for the necessary monitoring associated with giving antivenom.
Over the past 15 years, treatment of crotalid envenomation has changed. Antivenin (Crotalidae) polyvalent (ACP), a whole immunoglobulin G (IgG) antibody, was the standard for more than 50 years, but its use was complicated by high rates of acute reaction and serum sickness. (Note: Antivenin and antivenom are synonymous terms; Crotalidae is another name for the Crotalinae subfamily of snakes.) Crotalidae polyvalent immune Fab (ovine) is a bovine anti-IgG antibody fragment. Animal data suggest this drug’s potency is superior to ACP. Two observational studies involving 42 patients established the efficacy and safety profiles of Crotalidae polyvalent immune Fab (ovine). This drug is highly purified, and this processing is probably why the rates of acute reaction and serum sickness are lower. Pretreatment with antihistamines, steroids, or epinephrine is not necessary with this drug, and previous exposure to it does not preclude its future use.
Crotalidae polyvalent immune Fab (ovine) is a lyophilized powder packaged in vials. Each vial should be reconstituted with 10 ml of sterile water for injection and mixed by continuous gentle swirling. All reconstituted vials should be further diluted in 250 ml of 0.9% sodium chloride and delivered as a slow infusion (25 to 50 ml per hour) over the first 10 minutes. If this is well tolerated, the rest of the infusion can be completed over the course of an hour. The current recommendation is to give four to six vials initially and evaluate for symptom control.
Control of symptoms entails a decrease in pain, cessation of the progression of swelling, improvement in coagulation abnormalities, and resolution of systemic symptoms like nausea, hypotension, and paresthesias. Antivenom usually stops the progression of edema but does not reverse it. Tissue destruction and cell death are irreversible, so ecchymosis, bullae, and skin necrosis do not usually improve with antivenom therapy. If the initial treatment does not control symptoms, an additional four to six vials of Crotalidae polyvalent immune Fab (ovine) should be administered using the same dosing described previously. This cycle should be repeated until symptoms are controlled. In a trial involving 31 patients with minimal to moderate envenomation, none required more than 12 vials of the drug to control symptoms. However, there are reports of patients requiring more than 50 vials to treat local effects and coagulopathies.
Recurrence of signs and symptoms. Recurrence of signs and symptoms has been described with many antibody-based therapies like digoxin antibody fragments. The etiology of recurrence is not entirely understood. Theories include unbinding of the venom/antivenom complex or continued absorption of the venom beyond the half-life of the antivenom. Regardless of the mechanism, recurrence occurs in up to half of all patients with crotalid envenomations after the initial symptoms are controlled. Recurrence of the coagulopathy is common and has been reported several days after antivenom therapy. Because of this, a maintenance dose of crotalidae polyvalent immune Fab (ovine) should be given every six hours for a total of six additional vials after initial control of symptoms is achieved.
Blood product administration. Administration of blood products is very rarely necessary even in the setting of a coagulopathy. If a transfusion is necessary, antivenom should be administered first to prevent an exacerbation of the consumptive coagulopathy.
COMPLICATIONS OF CROTALID SNAKEBITE
Complications of a crotalid snakebite include antivenom reaction, infection, compartment syndrome, and serum sickness.
Antivenom reaction. As stated previously, Crotalidae polyvalent immune Fab (ovine) has a lower incidence of acute reaction than ACP. The most common reactions to this drug are flushing, rash, and pruritus. Stop the infusion immediately if a patient develops these symptoms. Antihistamines are the first-line therapy for mild reactions. More severe reactions, such as wheezing or shortness of breath, should be treated with inhaled beta agonists, intravenous steroids, or subcutaneous epinephrine (or all three). Patients who develop severe reactions, such as hypotension, airway swelling, or refractory respiratory symptoms, should be treated as if they had an anaphylactic reaction.
Before resuming antivenom treatment, consider the patient’s clinical picture and the severity of the reaction. Because few guidelines exist on resuming treatment, clinicians should contact a poison control center or another expert in snakebite treatment for advice. If the decision is made to restart the antivenom, it should be done at a slow rate with careful monitoring.
Infection. Infection secondary to a snakebite is extremely rare. If a bite does get infected, it is often because of contamination from incising the skin or sucking the wound with the goal of removing venom. These methods are not effective and should not be attempted. Empiric antibiotic therapy is not necessary unless there is clear evidence of infection. Most infections involve gram-negative bacteria. If antibiotics are necessary, ciprofloxacin is a reasonable first-line therapy. Amoxicillin/clavulanate may also be used in patients who cannot take quinolones.
Compartment syndrome. Compartment syndrome is rare following a snakebite. Diagnosing this problem is difficult because the symptoms of envenomation can mimic compartment syndrome. If compartment syndrome is suspected, obtain a surgical consultation and measure intracompartmental pressures to confirm the diagnosis. A pressure of more than 30 mm Hg is diagnostic. If the diagnosis is confirmed, administer antivenom and mannitol and elevate the affected limb immediately if this is not already being done. If compartment pressures remain elevated after a brief observation period, fasciotomy should be performed.
Serum sickness. Serum sickness is a type III hypersensitivity reaction to the antivenom that manifests with arthralgias, rash, fever, and lymphadenopathy. It occurs one to three weeks after antivenom therapy. Mild symptoms can be managed with antihistamines and NSAIDs, but most patients should be treated with about 60 mg of prednisone daily.
SPECIAL CIRCUMSTANCES
Bites by cottonmouths and copperheads are generally not as severe as bites by rattlesnakes. Some clinicians manage these bites without antivenom. However, each patient should be monitored closely for evidence of severe envenomation (swelling, pain, and ecchymosis), which requires antivenom therapy. Poison control centers can help determine whether treatment with antivenom is necessary.
There is little data on how to treat crotalid bites in children. Crotalidae polyvalent immune Fab (ovine) is not a weight-based product, so don’t try to adjust the dosage for age or weight. The current recommended starting dose of this antivenom is four to six vials. Pregnant patients may be at increased risk for preterm labor and placental abruption from the effects of the venom. Therefore, treatment with standard doses of antivenom is recommended if evidence of coagulopathy exists.
Patients with hematologic abnormalities should have repeat laboratory studies within a day of discharge to evaluate for recurrence. If findings persist, the patient should be monitored closely. Antivenom has been used effectively several days after the initial bite for recurrence of local symptoms or severe coagulopathy. Advise patients to avoid NSAIDs, which could magnify platelet dysfunction, for a few weeks after discharge. Physical therapy is often necessary to regain strength and range of motion in affected limbs.
COMMON PROBLEM, RARE MORTALITY
Venomous snakebites are common in the United States, but mortality is rare. The low mortality rate is due to prompt transfer to a medical facility, early stabilization by the clinician, and treatment with antivenom. The clinician’s goal is to stabilize the patient and determine who needs antivenom therapy. Crotalidae polyvalent immune Fab (ovine) has replaced ACP as the antivenom of choice for crotalid envenomations because it has a superior safety profile and efficacy. For help in diagnosing or treating a venomous snakebite, contact a poison control center.
Suggested Reading
Dart RC, McNally J: Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med 37(2):181, 2001.
Dart RC, et al.: A randomized multicenter trial of crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States. Arch Intern Med 161(16):2030, 2001.
Dart RC and Daly FFS: Reptile bites. In Tintinalli J, et al.: Emergency Medicine: A Comprehensive Study Guide, 6th ed, McGraw-Hill Companies, 2004, chapter 195.
Gold BS, et al.: North American snake envenomation: diagnosis, treatment, and management. Emerg Med Clin North Am 22(2):423, 2004.
Gold BS, et al.: Bites of venomous snakes. N Engl J Med 347(5):347, 2002.
Hall EL: Role of surgical intervention in the management of crotaline snake envenomation. Ann Emerg Med 37(2):175, 2001.
Heard K, et al.: Antivenom therapy in the Americas. Drugs 58(1):5, 1999.
Kitchens CS and Van Mierop LH: Envenomation by the eastern coral snake (Micrurus fulvius): a study of 39 victims. JAMA 258(12):1615, 1987.
Moss ST, et al.: Association of rattlesnake bite location with severity of clinical manifestations. Ann Emerg Med 30(1):58, 1997.
Norris RL and Bush SP: Bites by venomous reptiles in the Americas. In Auerbach PS: Wilderness Medicine, 5th ed, Elsevier Health Sciences, 2007, chapter 48.
Riley BD, et al.: Snakes and other reptiles. In Flomenbaum N, et al.: Goldfrank’s Toxicologic Emergencies, 8th ed, McGraw-Hill Companies, 2006, pp. 1171. |
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