Snakebites

Most snakebites are innocuous and are delivered by nonpoisonous species. North America is home to 25 species of poisonous snakes. Worldwide, only about 15% of the more than 3000 species of snakes are considered dangerous to humans. The family Viperidae is the largest family of venomous snakes, and members can be found in Africa, Europe, Asia, and the Americas. The family Elapidae is the next largest family of venomous snakes. In North America, the venomous species are members of the families Elapidae and Viperidae, subfamily Crotalidae.

A triangular-shaped head, nostril pits (heat-sensing organs), elliptical pupils, and subcaudal plates arranged in a single row are characteristic features of Crotalidae. They may be found in all regions of the country, and their habitat varies by species. Cottonmouths reside near swamps or rivers. Copperheads are found in aquatic and dry environments, and rattlesnakes prefer dry grasslands and rocky hillsides.

Coral snake pupils are round, and their subcaudal scales are arranged in double rows. The southern and southwestern states provide the dry, sandy conditions (and often a body of water) that coral snakes prefer.

Cobras, mambas, and kraits are also members of the family Elapidae but are not indigenous to the Americas. However, an increasing number of exotic species are kept by both zoos and private collectors making bites by nonindigenous species increasingly common.

Pathophysiology

Venom is produced and stored in paired glands below the eye. It is discharged from hollow fangs located in the upper jaw. Fangs can grow to 20 mm in large rattlesnakes. Venom dosage per bite depends on the elapsed time since the last bite, the degree of threat perceived by the snake, and size of the prey. Nostril pits respond to the heat emission of the prey, which may enable the snake to vary the amount of venom delivered.

Coral snakes have shorter fangs and a smaller mouth. This allows them less opportunity for envenomation than the crotalids, and their bites more closely resemble chewing rather than the strike for which the pit vipers are famous. Both methods inject venom into the victim to immobilize it quickly and begin digestion.

Venom is mostly water. Enzymatic proteins in venom impart its destructive properties. Proteases, collagenase, and arginine ester hydrolase have been identified in pit viper venom. Neurotoxins comprise the majority of coral snake venom. Specific details are known for several enzymes as follows: (1) hyaluronidase allows rapid spread of venom through subcutaneous tissues by disrupting mucopolysaccharides; (2) phospholipase A2 plays a major role in hemolysis secondary to the esterolytic effect on red cell membranes and promotes muscle necrosis; and (3) thrombogenic enzymes promote the formation of a weak fibrin clot, which, in turn, activates plasmin and results in a consumptive coagulopathy and its hemorrhagic consequences.

Enzyme concentrations vary among species, thereby causing dissimilar envenomations. Copperhead bites generally are limited to local tissue destruction. Rattlesnakes can leave impressive wounds and cause systemic toxicity. Coral snakes may leave a small wound that later results in respiratory failure from systemic neuromuscular blockade.

The local effects of venom serve as a reminder of the potential for systemic disruption of organ system function. One effect is local bleeding; coagulopathy is not uncommon with severe envenomation. Another effect, local edema, increases capillary leak and interstitial fluid in the lungs. Pulmonary mechanics may be altered significantly. The final effect, local cell death, increases lactic acid concentration secondary to changes in volume status and requires increased minute ventilation. The effects of neuromuscular blockade result in poor diaphragmatic excursion. Cardiac failure can result from hypotension and acidosis. Myonecrosis raises concerns about myoglobinuria and renal damage.

Frequency

Generally, only localized reporting of international data are available. Most snakebites and deaths due to snakebites are not reported, especially in the developing world.

Mortality/Morbidity

A 20-year review of data from the National Vital Statistics Systems identified 97 fatalities. The state of Texas had the most fatalities (17), followed by Florida (14), and Georgia (12).

• Deaths secondary to snakebites are rare.^{[1 ]}With the proper use of antivenin, they are becoming rarer still. The national average has been less than 4 deaths per year for the last several years.
• A review of morbidity associated with snakebites from Kentucky was published. Most bites were from copperheads and resulted in 8 days of pain, 11 days of extremity edema, and 14 days of missed work.^{[2 ]}A review specifically of copperhead bites in West Virginia described similar outcomes and noted that the peak effects of envenomation were not present until longer than 4 hours after the bite.^{[3 ]}
• Local tissue destruction rarely contributes to long-term morbidity. Occasionally, skin grafting is required to close a defect from fasciotomy, but wounds requiring fasciotomy to reduce compartment pressures from muscle edema are infrequent.
• Data gathered in a 5-year retrospective chart review from the University of Tennessee Medical Center at Knoxville (UTMCK), a level-I trauma center, focused on 25 bites. Of these, 4 required fasciotomy and 2 subsequently needed split-thickness skin grafting. The average length of stay was 3.2 days. No deaths occurred, and morbidity was limited to the local wounds.

Sex

• National studies report a 9:1 male-to-female ratio.
• UTMCK studies report a 2.1:1 male-to-female ratio.

Age

• National studies report 50% of patients were aged 18-28 years. UTMCK studies report 25% were aged 18-28 years, with a mean of 29.5 years.
• National studies report 95% of bites were located on an extremity, especially the hand. UTMCK studies report 96% of bites were located on an extremity, 56% to the hand.
• National studies report a seasonal occurrence of 90% from April to October. UTMCK studies report 100% occurrence from April to October (May: 1 bite out of 25 cases; June to August: 19 bites out of 25 cases; and September to October: 5 bites out of 25 cases).
• In the pediatric population, most snakebites occurred in school-aged children and adolescents around the perimeter of the home during the afternoon in summer months. The most frequent wound sites were the lower limbs.^{[4 ]}

Clinical

History

History usually can be obtained from the patient. Most cases result from attempting to handle snakes, so the genus usually is known. Knowledge of indigenous fauna also is important.

The time elapsed since the bite is a necessary component of the history. This allows assessment of the temporal effects of the bite to determine if the process is confined locally or if systemic signs have developed.

• Obtain a description of the snake or capture it, if possible, to determine its color, pattern, or the existence of a rattle.
• Most snakes remain within 20 feet after biting.
• Assess the timing of events and onset of symptoms. Inquire about the time the bite occurred and details about the onset of pain. Early and intense pain implies significant envenomation.
• Local swelling, pain, and paresthesias may be present.
• Systemic symptoms include nausea, syncope, and difficulty swallowing or breathing.
• Determine history of prior exposure to antivenin or snakebite.
• Determine history of allergies to medicines because antibiotics may be required.
• Determine history of comorbid conditions (eg, cardiac, pulmonary, and renal disease) or medications (eg, aspirin, anticoagulants such as warfarin [Coumadin] or GPIIb/IIIa inhibitors, beta-blockers).

Physical

Follow the established routine for a complete comprehensive examination.

• Vital signs, airway, breathing, circulation
• Fang marks or scratches (determine coral snakebite pattern by expressing blood from the suspected wound)
• Local tissue destruction
  • Soft pitting edema that generally develops over 6-12 hours but may start within 5 minutes
  • Bullae
  • Streaking
  • Erythema or discoloration
  • Contusions
• Systemic toxicity
  • Hypotension
  • Petechiae, epistaxis, hemoptysis
  • Paresthesias and dysesthesias - Forewarn neuromuscular blockade and respiratory distress (more common with coral snakes)
• Effects from a copperhead bite are shown in the images below

Causes

• In the United States, more than 40% of victims put themselves in danger by either handling pets or attempting to capture reptiles in the wild. The popularity of keeping exotic species has increased the number of envenomations by nonnative species.
• UTMCK data support this by reporting that 15 of 25 patients were bitten handling snakes; 2 of these were involved in religious ceremonies.

Differential Diagnoses

• Anaphylaxis
  Serum Sickness
• Deep Venous Thrombosis
  Wasp Stings
• Extremity Vascular Trauma
  Wound Care
• Scorpion Envenomation
  Wound Infection
• Septic Shock

Other Problems to Be Considered

• Nonanimal wounds and injuries
  Nonvenomous bites

Workup

Laboratory Studies

• CBC with manual differential and peripheral blood smear
• Prothrombin time and activated partial thromboplastin time, international normalized ratio (INR).
• Fibrinogen and split products
• Type and cross
• Blood chemistries, including electrolytes, BUN, creatinine
• Urinalysis for myoglobinuria
• Arterial blood gas determinations and/or lactate level for patients with systemic symptoms

Imaging Studies

• Baseline chest radiograph in patients with pulmonary edema
• Plain radiograph to rule out retained fang(s)

Other Tests

Compartmental pressures may need to be measured. Commercially available devices exist that are sterile, simple to assemble and read, and reliable (eg, the Stryker pressure monitor). Measurement of compartmental pressures is indicated when significant swelling is present, pain is out of proportion to examination, and if paresthesias are present in the affected limb.

Staging

Please see Treatment for discussion of grading envenomation.

Treatment

Medical Care

Treatment is based on the severity of envenomation; it is divided into field care and hospital management.

Prehospital Care

• As with all medical emergencies, the goal is to support the patient until arrival at the emergency department. The dictum " primum no nocere " (first, do no harm) has significant meaning here because many poorly substantiated treatments may cause more harm than good, including making an incision over the bite, mouth suctioning, tourniquet use, ice packs, or electric shock.
• Appropriate field care should adhere to the basic tenants of emergency life support.
• Reassure the patient during the implementation of ABCs.
• Monitor vital signs and establish at least one large-bore IV and initiate crystalloid infusion. Administer oxygen therapy. Keep a close watch on the airway at all times in case intubation becomes necessary.
• Restrict activity and immobilize the affected area (commonly an extremity); keep walking to a minimum.
• Negative-pressure suctioning devices offer some benefit if used within several minutes of envenomation. Again, do not make an incision in the field.
• Immediately transfer to definitive care.
• Do not give antivenin in the field.

Emergency Department Care

• Physicians who have little experience treating snakebites frequently care for such patients.
• Regional centers often have more experience in the care of snakebite victims. Surgical evaluation for an envenomation victim is paramount.
• Definitive treatment includes reviewing the ABCs and evaluating the patient for signs of shock (eg, tachypnea, tachycardia, dry pale skin, mental status changes, hypotension).
• Evenomation grading determines the need for antivenin in victims of pit viper envenomations. Grades are defined as mild, moderate, or severe.
  • Mild envenomation is characterized by local pain, edema, no signs of systemic toxicity, and normal laboratory values.
  • Moderate envenomation is characterized by severe local pain; edema larger than 12 inches surrounding the wound; and systemic toxicity including nausea, vomiting, and alterations in laboratory values (eg, decreased hematocrit or platelet count).Snakebite. Moderate rattlesnake envenomation in a toddler after treatment with antivenom. Photo by Sean Bush, MD.
  • Severe envenomation is characterized by generalized petechiae, ecchymosis, blood-tinged sputum, hypotension, hypoperfusion, renal dysfunction, changes in prothrombin time and activated partial thromboplastin time, and other abnormal test results defining consumptive coagulopathy.
• Grading envenomations is a dynamic process. Over several hours, an initially mild syndrome may progress to a moderate or even severe reaction.
• Horse-serum antivenin has been available since 1956; a purer antivenin with improved properties was released in 2000 (see Medication). With the reduced side-effect profile of antigen-binding fragment antivenom (FabAV) and the improvement in tissue injury with antivenin administration, the threshold for dosing is lower. One study from the southwest United States demonstrated a reduction in rate of fasciotomy after more liberal FabAV dosing.^{[5 ]}In a randomized study of scheduled versus as-needed FabAV dosing in patients whose symptoms were worsening, the Rocky Mountain Poison and Drug Center demonstrated a reduction in pain and other venom effects but noted a 20% acute and 23% delayed drug reaction.^{[6 ]}
• Although copperhead bites are generally self-limiting, morbidity was reduced in moderate envenomation 4 hours after 4 vials of FabAV in 88% of cases. The cases that failed to respond were not changed by further FabAV doses.^{[7 ]}
• FabAV is generally considered safe for children, as many of the studies did not discriminate in age. One large study from Mexico demonstrated no immediate or late allergic reactions to FabAV when administered according to grade of envenomation.^{[4 ]}
• Give antivenin for coral snakebites as a standard of care if the patient presents within 12 hours of the bite, regardless of local or systemic signs. Neurotoxicity may develop without warning and lead to respiratory failure.
• Although FabAV helps control local tissue effects and hemotoxicity, aggressive antivenom therapy does not usually ameliorate neurotoxic effects such as myokymia (spontaneous, fine fascicular contractions of muscle without muscular atrophy or weakness) and major muscle fasciculations. The physician must maintain continuous monitoring of those patients with myokymia especially of the shoulders, chest, and diaphragm for the development of respiratory failure and need for mechanical ventilation.^{[8,9 ]}

Surgical Care

• Surgical assessment focuses on the injury site and concern for the development of compartment syndrome.
  • Fasciotomy is indicated only for those patients with objective evidence of elevated compartment pressure.
  • Liberal monitoring of compartment pressure is warranted. If this is not available, utilize the physical hallmark of compartment hypertension (pain with passive range of motion), along with distal pallor, paresthesia, or pulselessness for the clinical assessment.
• Tissue injury after compartment syndrome is not reversible but is preventable.

Consultations

• Contacting the poison control center is important.
• Consultation with a surgeon often is warranted in bite management. General and trauma surgeons often have experience with envenomation, resuscitation, complications, and wound care. They can lead the inpatient treatment.

Medication

The goals of pharmacotherapy are to neutralize the toxin, to reduce morbidity, and to prevent complications.

Antivenins

A neutralizing antibody gives antivenin efficacy. Two kinds of antivenin are available. One has been manufactured since 1956. It is derived from horse serum after the horse is injected with sublethal doses of snake venom (Wyeth). The antivenin is purified but still contains other serum proteins that can be immunogenic. The latest version, approved by the US Food and Drug Administration (FDA) in 2000 (CroFab, Savage), is a monovalent immunoglobulin fragment derived from sheep but purified to avoid other antigenic proteins.

The old antivenin may still be available, but it is generally recommended to use the more specific and purified drug. Even with the newer agent, one must remember while the antivenin may be life saving, it also may lead to immediate hypersensitivity (anaphylaxis) and delayed hypersensitivity (serum sickness) reactions and must be used with caution. To achieve maximum efficacy, administer within 4-6 hours of bite.

CroFab is made specifically from venom of the eastern and western diamondback snakes, Mohave rattlesnakes, and the cottonmouth/water moccasin snakes. The purpose of any antivenin is to bind the toxins in the venom and prevent both local and systemic results.

CroFab has been used in Crotalid bites with good effect (reduced fasciotomy) and reductions in antivenin toxicity. With this information, more liberal dosing may follow, certainly with Crotalids, possibly with copperheads.

Ovine Crotalidae polyvalent immune fab-purified (Crofab) FabAV

Affinity-purified, mixed monospecific Crotalidae antivenom. Used to neutralize toxins from snakebite.
Grading is dynamic, and requirements for antivenin may increase over time.
Reduced tissue injury and need for fasciotomy with no allergic consequences documented in one study.^{[5 ]}Study from the southwest United States and indigenous snakes include Crotalus species.
Most authors withhold antivenin for copperhead envenomations unless wound is particularly painful (early clue for significant envenomation).

Dosing

Adult

Dosage for pit viper envenomation based on degree of envenomation
Mild envenomation: None
Moderate envenomation: Initially 6-10 vials IV
Severe envenomation: May require >25 vials IV
Coral snakes: Initially 4-6 vials IV, may require as many as 10 vials, use specific antivenin for coral snakes

Pediatric

Pit viper envenomation: May require twice adult dose
Coral snake envenomation: Most favor equal dosing

Interactions

None reported

Contraindications

Documented hypersensitivity; may administer in severe envenomation despite hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

If older (1956, horse) antivenin is being used, consider skin testing; agents for emergency treatment of anaphylaxis should be available

Antibiotics

Antibiotics are often given upon arrival to hospital but most likely benefit only severe cases. However, broad-spectrum antibiotic prophylaxis is still recommended.

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.

Dosing

Adult

1-2 g IV q12-24h

Pediatric

75 mg/kg/d IV divided q12h

Interactions

Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Adjust dose in renal impairment; caution in breastfeeding women and in those with allergy to penicillin; approximately 15-20% of patients allergic to penicillin may react

Immunizations

Snakes do not harbor Clostridium tetani in their mouths, but bites may carry other bacteria, especially gram-negative species. Tetanus prophylaxis is recommended if the patient is not immunized.

Diphtheria-tetanus toxoid (Decavac)

Used to induce active immunity against tetanus in selected patients. Immunizing agent of choice for most adults and children >7 y are tetanus and diphtheria toxoids. Necessary to administer booster doses to maintain tetanus immunity throughout life.
Pregnant patients should receive only tetanus toxoid not a product containing diphtheria antigen.
In children and adults, may administer into deltoid or midlateral thigh muscles. In infants, preferred site of administration is the mid thigh laterally.

Dosing

Adult

0.5 mL IM

Pediatric

<6 weeks: Not established
6 weeks to 6 years: Three 0.5-mL IM doses of DT at least 4 wk apart and a boost dose 6-12 mo after third injection

Interactions

Patients receiving immunosuppressants, including corticosteroids or radiation therapy, may remain susceptible despite immunization due to poor immune response; cimetidine may enhance or augment delayed hypersensitivity responses to skin-test antigens; avoid concurrent use of medication with systemic chloramphenicol because it may impair amnestic response to tetanus toxoid; concurrent use of tetanus immune globulin may delay development of active immunity by several days (interaction is nevertheless clinically insignificant and does not preclude its concurrent use)

Contraindications

Documented hypersensitivity; history of any neurological symptoms or signs following administration; FDA recommends elective tetanus immunization be deferred during any outbreak of poliomyelitis because tetanus toxoid injections are an important cause of provocative poliomyelitis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use to treat actual tetanus infections or for immediate prophylaxis of unimmunized individuals (instead use tetanus antitoxin, preferably human tetanus immune globulin); diminished antibody response to active immunization may be observed in patients receiving immunosuppressive therapy, deferring primary diphtheria immunization until immunosuppressive therapy is discontinued is better; routine immunization of symptomatic and asymptomatic patients infected with HIV is recommended

Follow-up

Further Inpatient Care

• Admission to the hospital is routine for most envenomation cases. A "dry bite" without envenomation can occur in a significant percentage of cases (50% in coral snake, 25% from pit viper).
  • For dry pit viper bites, observe in the emergency department for 8-10 hours; however, often this is not feasible. Patients with severe envenomation need specialized care in the ICU to administer blood products, provide invasive monitoring, and ensure airway protection.
  • Observe coral snakebites for a minimum of 24 hours.
• Perform serial evaluations for further grading and to rule out compartment syndrome. Depending on clinical scenarios, measure compartment pressures every 30-120 minutes. Fasciotomy is indicated for pressures greater than 30-40 mm Hg.
• Depending on the clinical severity of the bite, further blood work may be needed, especially clotting studies, platelet count, and fibrinogen level.

Further Outpatient Care

Limit outpatient care to local wound care.

Deterrence/Prevention

Wear protective clothing and never handle snakes.

Complications

• Compartment syndrome is the most frequent complication of pit viper snakebite.
• Local wound complications may include infection and skin loss.
• Cardiovascular complications, hematologic complications, and pulmonary collapse may occur.
• Neurotoxicity with myokymia of the respiratory muscles may lead to respiratory failure and mechanical ventilation.
• Death is rare.
• Prolonged neuromuscular blockade may occur from coral snake envenomation.
• Antivenin-associated complications include immediate (anaphylaxis, type I) and delayed (serum sickness, type III) hypersensitivity reactions.
  • Anaphylaxis is an event mediated by immunoglobulin E (IgE), involving degranulation of mast cells that can result in laryngospasm, vasodilatation, and leaky capillaries. Death is common without pharmacological intervention.
  • Serum sickness occurs 1-2 weeks after administering antivenin. Precipitation of antigen-immunoglobulin G (IgG) complexes in the skin, joints, and kidneys is responsible for the arthralgias, urticaria, and glomerulonephritis (rarely). Usually more than 8 vials of antivenin must be given to produce this syndrome. Supportive care consists of antihistamines and steroids.
  • Newer studies now report a lower incidence (5.4%) of acute hypersensitivity reactions with FabAV.^{[10 ]}

Prognosis

Full recovery is the rule, though local complications from envenomation may occur. Death occurs in less than 1 bite in 5000.

Patient Education

• For excellent patient education resources, visit eMedicine's Bites and Stings Center. Also, see eMedicine's patient education article Snakebite.
• A new web site (Australian Venom Research Unit) based at the University of Melbourne in Australia comprehensively outlines the species, first aid, and treatment of all venomous creatures indigenous to the region. The web site is easily navigated and sectionally divided for the practitioner, interested epidemiologists, snake fanciers, and children of Australia and the Asia/Pacific region.

Miscellaneous

Medicolegal Pitfalls

• Overnight observation in the hospital allows staff to quickly diagnose delayed signs and symptoms.
• Envenomation determination is time-independent.
• Determining the genus of the snake may be difficult.
  • Because most snakebites happen with known or visualized snakes, at least their physical characteristics can be determined.
  • Knowledge of indigenous snakes, from either local experts or zoological experts, can be helpful.