Of about 3000 snake species throughout the world, only about 15% worldwide and 20% in the US are dangerous to humans because of venom or toxic salivary secretions (see table Significant Venomous Snakes by Region Significant Venomous Snakes by Region Of about 3000 snake species throughout the world, only about 15% worldwide and 20% in the US are dangerous to humans because of venom or toxic salivary secretions (see table Significant Venomous... read more ). At least one species of venomous snake is native to every state in the US except Alaska, Maine, and Hawaii. Almost all are crotalines (also called pit vipers because of pitlike depressions on either side of the head, which are heat-sensing organs):
Cottonmouths (water moccasins)
More than 60,000 bites and stings are reported to poison centers and result in about 100 deaths each year in the US. About 45,000 are snakebites (of which 7000 to 8000 are venomous and cause about 5 deaths). Rattlesnakes account for the majority of snakebites and almost all deaths. Copperheads and, to a lesser extent, cottonmouths account for most other venomous bites. Coral snakes (elapids) and imported species (in zoos, schools, snake farms, and amateur and professional collections) account for 1% of all bites.
Most patients are males between 17 and 27 years; 50% of them are intoxicated and deliberately handled or molested the snake. Most bites occur on the upper extremities. Five or 6 deaths occur annually in the US. Risk factors for death include age extremes, handling of captive snakes (rather than wild encounters), delay in treatment, and undertreatment.
Outside the US, fatal snakebites are much more common, accounting for > 100,000 deaths yearly.
Pathophysiology of Snakebites
Snake venoms are complex substances, chiefly proteins, with enzymatic activity. Although enzymes play an important role, the lethal properties of venom are caused by certain smaller polypeptides. Most venom components appear to bind to multiple physiologic receptors, and attempts to classify venom as toxic to a specific system (eg, neurotoxin, hemotoxin, cardiotoxin, myotoxin) are misleading and can lead to errors in clinical judgment.
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
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 20,000/mcL) is common in severe rattlesnake bites and may occur alone or with other coagulopathies. Venom-induced intravascular clotting may trigger 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.
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.
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.
Symptoms and Signs of Snakebites
A snakebite, whether from a venomous or nonvenomous snake, usually causes terror, often with autonomic manifestations (eg, nausea, vomiting, tachycardia, diarrhea, diaphoresis), which may be difficult to distinguish from systemic manifestations of envenomation.
Nonvenomous snakebites cause only local injury, usually pain and 2 to 4 rows of scratches from the snake’s upper jaw at the bite site.
Symptoms and signs of envenomation may be local, systemic, or a combination, depending on degree of envenomation and species of snake. Anaphylaxis Treatment Anaphylaxis is an acute, potentially life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized people when they are reexposed to the sensitizing antigen. Symptoms... read more can occur, particularly in snake handlers who have been previously sensitized.
About 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. If envenomation has occurred, edema and erythema at the bite site and in adjacent tissues occur, usually within 30 to 60 minutes. Oozing from the wound suggests envenomation. 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 Severity of envenomation Of about 3000 snake species throughout the world, only about 15% worldwide and 20% in the US are dangerous to humans because of venom or toxic salivary secretions (see table Significant Venomous... read more , 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
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 Compartment Syndrome Compartment syndrome is increased tissue pressure within a closed fascial space, resulting in tissue ischemia. The earliest symptom is pain out of proportion to the severity of injury. Diagnosis... read more (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) or activated partial thromboplastin time (PTT), hypofibrinogenemia, elevated fibrin degradation products, or a combination of these disorders, resembling 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.
Pearls & Pitfalls
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.
Diagnosis of Snakebites
Identification of the snake
Grading severity of envenomation
Definitive diagnosis is aided by positive identification of the snake and clinical manifestations of envenomation. History should include the time of bite, description of the snake, type of field therapy, underlying medical conditions, allergy to horse or sheep products, and history of previous venomous snakebites and therapy. A complete physical examination should be done. A marker should be used to indicate the leading edge of edema on the affected limb or area, and the time the mark was made should be recorded.
Snakebites should be assumed to be venomous until proved otherwise by clear identification of the species or by a period of observation.
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 Identifying pit vipers Of about 3000 snake species throughout the world, only about 15% worldwide and 20% in the US are dangerous to humans because of venom or toxic salivary secretions (see table Significant Venomous... read more ). Consultation with a zoo, an aquarium, or a poison center (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:
Coral snakes in the US 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
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 Severity of Pit Viper Envenomation Of about 3000 snake species throughout the world, only about 15% worldwide and 20% in the US are dangerous to humans because of venom or toxic salivary secretions (see table Significant Venomous... read more ). Grading should be determined by the most severe symptom, sign, or laboratory finding.
Envenomation may progress rapidly from minimal to severe and must be reassessed continually.
If systemic symptoms begin immediately, anaphylaxis Anaphylaxis Anaphylaxis is an acute, potentially life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized people when they are reexposed to the sensitizing antigen. Symptoms... read more should be assumed.
Treatment of Snakebites
Treatment 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 wide crepe or other fabric bandages around the limb) may be appropriate for coral snake bites but is not recommended in the US, 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.
Pearls & Pitfalls
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 also 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
Measurement of serum electrolytes, blood urea nitrogen, and creatinine
For moderate and severe envenomations, patients require blood typing and cross-matching, ECG, chest x-ray, 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 Pulse Oximetry Gas exchange is measured through several means, including Diffusing capacity for carbon monoxide Pulse oximetry Arterial blood gas sampling The diffusing capacity for carbon monoxide (DLCO)... read more 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 Adjunctive measures Of about 3000 snake species throughout the world, only about 15% worldwide and 20% in the US are dangerous to humans because of venom or toxic salivary secretions (see table Significant Venomous... read more . 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 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 Tracheostomy If the upper airway is obstructed because of a foreign body or massive trauma or if ventilation cannot be accomplished by other means, surgical entry into the trachea is required. Historically... read more 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 US is an ovine-derived Crotalidae polyvalent immune FAb antivenom (purified FAb fragments of IgG harvested from pit viper venom–immunized sheep). The effectiveness of this antivenom is time and dose related; it is most effective in preventing venom-induced tissue damage when given early. 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 newly available horse-derived antivenom consisting of reconstituted Crotalidae immune Fab2 fragments and is used to treat North American rattlesnake bites in adults and children. The recommended initial dose is 10 vials diluted in 250 mL of normal saline and infused at 25 to 50 mL/hour for the first 10 minutes, while watching for any evidence of allergic reactions. If no reactions occur, the infusion may proceed at the full rate of 250 mL/hour until completed. This initial dose may be repeated every hour if needed to arrest the progression of symptoms. Late or reemerging symptoms may be treated with additional 4 vial doses.
Pearls & Pitfalls
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. Special attention is warranted for children, older patients, and patients with medical conditions (eg, diabetes mellitus, coronary artery disease) who may be more susceptible to venom effects.
For coral snake envenomation, equine-derived polyvalent coral snake antivenom is given at a dose of 5 vials for suspected envenomation and an additional 10 to 15 vials if symptoms develop. Dose is similar for adults and children. This dosing recommendation may be reduced during national shortages of coral snake antivenom.
Antivenom pretreatment precautions should be considered for patients with known hypersensitivity to the specific antivenom being considered, 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 Anaphylaxis Anaphylaxis is an acute, potentially life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized people when they are reexposed to the sensitizing antigen. Symptoms... read more . 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 Symptoms and Signs Drug hypersensitivity is an immune-mediated reaction to a drug. Symptoms range from mild to severe and include rash, anaphylaxis, and serum sickness. Diagnosis is clinical; skin testing is occasionally... read more 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 Tetanus Prophylaxis in Routine Wound Management Tetanus is acute poisoning from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for the name lockjaw... read more ). Snakebites rarely become infected, and antibiotics are indicated only for patients with clinical evidence of infection. If necessary, options include a 1st-generation cephalosporin (eg, oral cephalexin, IV cefazolin) or a broad-spectrum penicillin (eg, oral amoxicillin/clavulanate, 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 Compartment Syndrome Compartment syndrome is increased tissue pressure within a closed fascial space, resulting in tissue ischemia. The earliest symptom is pain out of proportion to the severity of injury. Diagnosis... read more ) is rarely indicated and should be considered only when compartment pressure is ≥ 30 mm Hg for > 1 hour or < 30 mm Hg below the diastolic pressure, causes severe vascular compromise, is unresponsive to limb elevation and mannitol 1 to 2 g/kg IV, and appropriate doses of antivenom have failed. Massive edema alone is not 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. A national help line is available at 1-800-222-1222.
In the US, common venomous snakes include rattlesnakes, copperheads, and cottonmouths (all pit vipers), but rattlesnakes account for most bites and almost all deaths.
Pit viper envenomation can cause local effects (eg, pain, progressive swelling, ecchymosis) and systemic effects (eg, vomiting, diaphoresis, confusion, bleeding, fever, chest pain, dyspnea, paresthesias, hypotension).
Features that can help differentiate pit vipers from nonvenomous snakes include an elliptical pupil, a triangular head, retractable fangs, heat-sensing pits between the eyes and nose, and a single row of subcaudal plates extending from the anal plate on the underside of the tail.
In the field, remove the patient out of striking distance from the snake, arrange rapid transport, wrap a bitten limb loosely, immobilize it in a position at about heart level, and remove constricting devices such as rings and watches; do not incise bite wounds or apply tourniquets.
Monitor patients with pit viper bites serially for at least 8 hours, longer if any findings suggest envenomation.
Treat wounds and symptoms, and consult a poison center.
Give antivenom early and at adequate doses, including full adult doses for children.