Snakebites

The complex venom of most North American pit vipers has local effects as well as systemic effects such as coagulopathy. Effects may include

• Local tissue damage, causing edema and ecchymosis

• Vascular endothelial damage

• Hemolysis

• A disseminated intravascular coagulation (DIC)–like (defibrination) syndrome

• Pulmonary, cardiac, renal, and neurologic defects

Venom alters capillary membrane permeability, causing extravasation of electrolytes, albumin, and red blood cells through vessel walls into the envenomated site. This process may occur in the lungs, myocardium, kidneys, peritoneum, and, rarely, the central nervous system. Common clinical syndromes secondary to severe pit viper envenomation include the following:

• Edema: Initially, edema, hypoalbuminemia, and hemoconcentration occur.

• Hypovolemia: Later, blood and fluids pool in the microcirculation, causing hypotension, lactic acidemia, shock, and, in severe cases, multisystem organ failure. Effective circulating blood volume falls and may contribute to cardiac and renal failure.

• Bleeding: Clinically significant thrombocytopenia (platelet count < 20 × 10⁹ cells/L [20,000 cells/mcL]) is common in severe rattlesnake bites and may occur alone or with other coagulopathies. Venom-induced intravascular clotting may trigger a DIC-like syndrome, resulting in bleeding.

• Renal failure: Renal failure may result from severe hypotension, hemolysis, rhabdomyolysis, nephrotoxic venom effects, or a DIC-like syndrome. Proteinuria, hemoglobinuria, and myoglobinuria may occur in reaction to severe rattlesnake bites.

Snakebite Wound

Image

Photo courtesy of Thomas Arnold, MD.

The venom of most North American pit vipers causes very minor changes in neuromuscular conduction, except for Mojave and eastern diamondback rattlesnake venom, which may cause serious neurologic deficits (eg, muscle weakness, respiratory depression).

Coral Snake

Image

Photo courtesy of Mike Cardwell (Victorville, CA).

Coral snakes are the most common elapids found in the United States. Other elapids include cobras and mambas. Venom of these snakes contains primarily neurotoxic components, which cause a presynaptic neuromuscular blockade, potentially causing respiratory paralysis. The lack of significant proteolytic enzyme activity accounts for the paucity of symptoms and signs at the bite site.

Approximately 25% of pit viper bites are dry (venom is not deposited), and no systemic symptoms or signs develop.

Local signs include ≥ 1 fang marks and scratches. Oozing from the wound suggests envenomation. If envenomation has occurred, edema and erythema at the bite site and in adjacent tissues occur, usually within 30 to 60 minutes. Edema can progress rapidly and may involve the entire extremity within hours. Lymphangitis and enlarged, tender regional lymph nodes may develop; temperature increases over the bite area. In moderate or severe envenomations, ecchymosis is common and may appear at and around the bite site within 3 to 6 hours. Ecchymosis is most severe after bites by

• Eastern and western diamondbacks

• Cottonmouths

• Prairie, Pacific, and timber rattlesnakes

The skin around the bite may appear tense and discolored. Bullae—serous, hemorrhagic, or both—usually appear at the bite site within 8 hours. Edema resulting from North American rattlesnake envenomations may be severe but is usually limited to dermal and subcutaneous tissues, although severe envenomation rarely causes edema in subfascial tissue, causing compartment syndrome (defined as compartment pressures ≥ 30 mm Hg for > 1 hour, or as < 30 mm Hg below the diastolic pressure). Necrosis around the bite site is common after rattlesnake envenomations. Most venom effects on soft tissues peak within 2 to 4 days.

Ecchymosis is less common after copperhead and Mojave rattlesnake bites.

Systemic manifestations of envenomation can include nausea, vomiting, diarrhea, diaphoresis, anxiety, confusion, spontaneous bleeding, fever, chest pain, difficulty breathing, paresthesias, hypotension, and shock. Some patients with rattlesnake bites experience a rubbery, minty, or metallic taste in their mouth. The venom of most North American pit vipers causes minor neuromuscular conduction changes, including generalized weakness and paresthesias and muscle fasciculations. Some patients have alterations in mental status. Venom of Mojave and eastern diamondback rattlesnakes may cause serious neurologic deficits, including respiratory depression.

Anaphylaxis can cause systemic symptoms immediately.

Rattlesnake envenomations may induce various coagulation abnormalities, including thrombocytopenia, prolongation of prothrombin time (PT, measured by the INR [international normalized ratio]) or activated partial thromboplastin time (PTT), hypofibrinogenemia, elevated fibrin degradation products, or a combination of these findings, causing a disseminated intravascular coagulation (DIC)-like syndrome. Thrombocytopenia is usually the first manifestation and may be asymptomatic or, in the presence of a multicomponent coagulopathy, cause spontaneous bleeding. Patients with coagulopathy typically hemorrhage from the bite site or from venipuncture sites or mucous membranes, with epistaxis, gingival bleeding, hematemesis, hematochezia, hematuria, or a combination. A rise in hematocrit (Hct) is an early finding secondary to edema and hemoconcentration. Later, Hct may fall as a result of fluid replacement and blood loss due to DIC-like syndrome. In severe cases, hemolysis may cause a rapid fall in Hct.

Pain and swelling may be minimal or absent and are often transitory. The absence of local symptoms and signs may erroneously suggest a dry bite, producing a false sense of security for both patient and clinician.

Weakness of the bitten extremity may become evident within several hours. Systemic neuromuscular manifestations may be delayed for 12 hours and include weakness and lethargy; altered sensorium (eg, euphoria, drowsiness); cranial nerve palsies causing ptosis, diplopia, blurred vision, dysarthria, and dysphagia; increased salivation; muscle flaccidity; and respiratory distress or failure. Once the neurotoxic venom effects manifest, they are difficult to reverse and may last 3 to 6 days. Untreated, respiratory muscle paralysis may be fatal.

Patients often cannot recall details of the snake’s appearance. Pit vipers and nonvenomous snakes can be distinguished by some physical features (see figure Identifying Pit Vipers). Consultation with a zoo, an aquarium, or a poison center (eg, in the Unites States 1-800-222-1222) can help in the identification of snake species.

Identifying Pit Vipers

Pit vipers have the following features, which help differentiate them from nonvenomous snakes: Arrowhead-shaped (triangular) heads Elliptical pupils Heat-sensing pits between the eyes and nose Retractable fangs A single row of subcaudal plates extending from the anal plate on the underside of the tail

Timber Rattlesnake

Image

Image courtesy of Edward J. Wozniak, DVM, PhD via the Public Health Image Library of the Centers for Disease Control and Prevention.

Southern Copperhead

Image

Image courtesy of CDC/James Gathany via the Public Health Image Library of the Centers for Disease Control and Prevention.

Eastern Cottonmouth

Image

Image courtesy of CDC/James Gathany via the Public Health Image Library of the Centers for Disease Control and Prevention.

Coral snakes in the United States have round pupils and black snouts but lack facial pits. They have blunt or cigar-shaped heads and alternating bands of red, yellow (cream), and black, often causing them to be mistaken for the common nonvenomous scarlet king snake, which has alternating bands of red, black, and yellow. The distinguishing feature in the coral snake is that the red bands are adjacent to only yellow bands, not black bands (“red on yellow, kill a fellow; red on black, venom lack”). Coral snakes have short, fixed fangs and inject venom through successive chewing movements.

Fang marks are suggestive but not conclusive; rattlesnakes may leave single or double fang marks or other teeth marks, whereas bites by nonvenomous snakes usually leave multiple superficial teeth marks. However, the number of teeth marks and bite sites may vary because snakes may strike and bite multiple times.

A dry pit viper bite is diagnosed when no symptoms or signs of envenomation appear within 8 hours after the bite.

Severity of envenomation depends on the following:

• Size and species of the snake (rattlesnakes > cottonmouths > copperheads)

• Amount of venom injected per bite (cannot be determined by history)

• Number of bites

• Location and depth of the bite (eg, envenomation in bites to the head and trunk tends to be more severe than in bites to the extremities)

• Age, size, and health of the patient

• Time elapsed before treatment

• Patient’s susceptibility (response) to the venom

Severity of envenomation can be graded as minimal, moderate, or severe based on local findings, systemic symptoms and signs, coagulation parameters, and laboratory results (see table Severity of Pit Viper Envenomation). Grading should be determined by the most severe symptom, sign, or laboratory finding within 8 hours from the time of the bite.

Envenomation may progress rapidly from minimal to severe and must be reassessed continually.

If systemic symptoms begin immediately, anaphylaxis should be assumed.

Treatment of snakebites begins immediately, before patients are moved to a medical facility.

In the field, patients should move or be moved beyond the snake’s striking distance. They should avoid exertion and be reassured, kept warm, and transported rapidly to the nearest medical facility. A bitten extremity should be wrapped loosely and immobilized in a functional position at about heart level, and all rings, watches, and constrictive clothing should be removed. Pressure immobilization to delay systemic absorption of venom (eg, by wrapping tourniquets or other fabric bandages around the limb) may be appropriate for coral snake bites but is not recommended in the United States, where most bites are from pit vipers; pressure immobilization may cause arterial insufficiency and necrosis.

First responders should support airway and breathing, administer oxygen, and establish IV access in an unaffected extremity while transporting patients. All other out-of-hospital interventions (eg, tourniquets, topical preparations, any form of wound suction with or without incision, cryotherapy, electrical shock) are of no proven benefit, may be harmful, and may delay appropriate treatment. However, tourniquets that are already placed, unless causing limb-threatening ischemia, should remain in place until patients are transported to the hospital and envenomation is excluded or definitive treatment is initiated.

Serial assessment and testing begin in the emergency department. Outlining the leading margin of local edema with an indelible marker every 15 to 30 minutes can help clinicians assess progression of local envenomation. Extremity circumference should be measured on arrival and at regular intervals until local progression subsides. All but trivial pit viper bites require

• A baseline complete blood count (including platelets)

• Coagulation profile (eg, prothrombin time, partial thromboplastin time, fibrinogen)

• Measurement of fibrin degradation products

• Urinalysis

• Measurement of serum electrolytes, blood urea nitrogen (BUN), and creatinine (1)

For moderate and severe envenomations, patients require blood typing and cross-matching, ECG, chest radiograph, and creatine kinase tests, as governed by the patient’s status, often as frequently as every 4 hours for the first 12 hours and then daily. In the management of patients with coral snake bites, neurotoxic venom effects necessitate monitoring of oxygen saturation and baseline and serial pulmonary function tests (ie, peak flow, vital capacity).

Duration of close observation for all patients with pit viper bites should be at least 8 hours. Patients without evidence of envenomation after 8 hours may be sent home after adequate wound care. Patients with coral snake bites should be monitored closely for at least 12 hours in case respiratory paralysis develops. Envenomation initially assessed as mild may progress to severe within several hours.

Supportive care may include respiratory support, benzodiazepines for anxiety relief and sedation, opioids for pain, and fluid replacement and vasopressor support for shock. Transfusions (eg, packed red blood cells, fresh frozen plasma, cryoprecipitate, platelets) may be required but should not be given before patients have received adequate quantities of neutralizing antivenom because most coagulopathies respond to sufficient quantities of neutralizing antivenom. Suspected anaphylaxis (eg, with immediate onset of systemic symptoms) is treated with standard measures, including epinephrine.Tracheostomy may be needed if trismus, laryngeal spasm, or excessive salivation is present.

Along with aggressive supportive care, antivenom is the mainstay of treatment for patients with anything more than the mildest envenomation grade.

For pit viper envenomation, the mainstay of treatment in the United States is an ovine-derived Crotalidae polyvalent immune FAb antivenom (purified FAb fragments of IgG harvested from pit viper venom–immunized sheep) (1). The effectiveness of this antivenom is time and dose related; it is most effective in preventing venom-induced tissue damage when given as soon as possible. It is less effective if delayed but can reverse coagulopathies and be effective even when started 24 hours after envenomation. Crotalidae polyvalent immune FAb is very safe, although it can still cause acute (cutaneous or anaphylactic) reactions and delayed hypersensitivity reactions (serum sickness). Serum sickness develops in up to 16% of patients 1 to 3 weeks after administration of the FAb product.

A loading dose of 4 to 12 vials of reconstituted Crotalidae polyvalent immune FAb diluted in 250 mL of normal saline should be infused slowly at 20 to 50 mL/hour for the first 10 minutes; then, if no adverse reactions occur, the remainder is infused over the next hour. The same dose can be repeated 2 times as needed to achieve initial control of symptoms, reverse coagulopathies, and correct physiologic parameters. In children, the dose is not decreased (eg, based on weight or size). Measuring the circumference of the involved extremity at 3 points proximal to the bite and measuring the advancing border of edema every 15 to 30 minutes can guide decisions about the need for additional doses. Once control is achieved, a 2-vial dose in 250 mL saline is given at 6, 12, and 18 hours to prevent recurrence of limb swelling and other venom effects.

Crotalidae immune F(ab')2 (equine) is a horse-derived antivenom consisting of reconstituted Crotalidae immune Fab2 fragments. It is used to treat North American rattlesnake bites in adults and children.

Pit viper species may affect dose. Cottonmouth, copperhead, and pygmy rattlesnake envenomations may require smaller doses of antivenom. However, antivenom should not be withheld based on the species of snake and should be given based on envenomation grading regardless of the species.

For coral snake envenomation, equine-derived polyvalent coral snake antivenom (coral snake antivenin) is given for adults and children.

Antivenom pretreatment precautions should be considered for patients with known hypersensitivity to the specific antivenom being considered or to horse or sheep serum and those with a history of asthma or multiple allergies. In such patients, if the envenomation is considered life or limb threatening, H1 and H2 blockers should be given before antivenom in a critical care setting equipped to treat anaphylaxis. Early anaphylactoid reactions to antivenom have been noted and usually result from too-rapid infusion; treatment is to temporarily stop the infusion and give epinephrine, H1 and H2 blockers, and IV fluid, depending on severity. Usually, antivenom can be resumed after diluting the antivenom further and infusing it at a slower rate.

Serum sickness may develop, manifesting 7 to 21 days after treatment as fever, rash, malaise, urticaria, arthralgia, and lymphadenopathy. Treatment is H1 blockers and a tapering course of oral corticosteroids.

Patients should receive tetanus prophylaxis (toxoid and sometimes Ig) as indicated by their history (see table Tetanus Prophylaxis in Routine Wound Management). Snakebites rarely become infected, and antibiotics are indicated only for patients with clinical evidence of infection. If necessary, options include a first-generation cephalosporin (eg, oral cephalexin, IV cefazolin) or a broad-spectrum penicillin (eg, oral amoxicillin/clavulanic acid, IV ampicillin/sulbactam). Subsequent antibiotic choices should be based on culture and sensitivity results from wound cultures.

Wound care for bites is similar to that for other puncture wounds. The area is cleaned and dressed. For limb bites, the extremity is splinted in a functional position and elevated. Wounds should be examined and cleaned daily and covered with a sterile dressing. Blebs, bloody vesicles, or superficial necrosis should be surgically debrided between days 3 and 10, in stages if needed. Sterile whirlpool sessions may be indicated for wound debridement and physical therapy. Fasciotomy (ie, for compartment syndrome) is rarely indicated and should be considered only when compartment pressure is ≥30 mm Hg for > 1 hour or mannitol 1 to 2 g/kg IV, and appropriate doses of antivenom have failed. Massive edema alone isnot an indication for fasciotomy. Joint motion, muscle strength, sensation, and limb girth should be evaluated within 2 days after the bite. Contractures can be prevented by interrupting immobilization with frequent periods of gentle exercise, progressing from passive to active.

Regional poison centers and zoos are excellent resources when dealing with snakebites, including those by nonnative snakes. These facilities maintain a list of physicians trained in snake identification and snakebite care as well as the Antivenom Index, published and periodically updated by the American Zoo and Aquarium Association and the American Association of Poison Control Centers. This index catalogs the location and number of vials of antivenom available for all native venomous snakes and most exotic species. In the United States a national help line is available at 1-800-222-1222.

1. 1. Lavonas EJ, Ruha AM, Banner W, et al. Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emerg Med. 2011;11:2. Published 2011 Feb 3. doi:10.1186/1471-227X-11-2