Snakebite

Background

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.

The subfamily Crotalidae (pit vipers) includes rattlesnakes (Crotalus and Sistrurus), cottonmouths (Agkistrodon), and copperheads (Agkistrodon). A Southern copperhead is shown in the image below.

View Image

Snakebite. Southern Copperhead snake, from snakesandfrogs.com

The Western diamondback (shown in the image below), timber, and prairie rattlesnakes are pit vipers.

View Image

Snakebite. Western diamondback rattlesnake.

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.

Elapidae includes the coral snakes (Micrurus fulvius fulvius and Micrurus fulvius tenere; this is shown in the image below).

View Image

Snakebite. Western coral snake.

The eastern and western species that inhabit the United States are smaller and brightly colored with red, yellow, and black rings. The nonvenomous king snakes share the same colors but not in the same order. A common mnemonic to recall the order of bands is "red on yellow, kill a fellow; red on black, venom lack." These snakes are shown in the image below.

View Image

Snakebite. Comparison of the harmless Lampropeltis triangulum annulata (Mexican milksnake) (top) with Micrurus tener (Texas coral snake) (bottom). Pho....

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.

• References

Pathophysiology

Crotalid 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.

Evidence suggests that the differences between the venom components of different snake species resulted from a diet/prey directed evolution occurring over time.^[1] 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.

• References

Etiology

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.

• References

Epidemiology

Frequency

United States

Snakebites frequently go unreported. Approximately 8,000 bites are reported in the United States annually, with approximately 2,000 delivered by venomous snakes. North Carolina has the highest frequency, with 19 bites per 100,000 persons. The national average is approximately 4 bites per 100,000 persons. Mortality from snakebites is rare, with no more than 12 cases of death due to venomous snake bites per year reported between the years of 1960 and 1990.^[2]

International

Generally, only localized reporting of international data is available. Most snakebites and deaths due to snakebites are not reported, especially in the developing world. An estimated 1.8-2.5 million venomous snakebites occur worldwide each year, resulting in an estimated 100,000 to 125,000 annual deaths, but this may be underreported.^[3] Worldwide, snakebites disproportionately affect low socioeconomic populations in more rural locations. They are often seen as bites to the lower extremities by farmers or workers who step on or disturb a snake in the field or rice paddies, or they can present as a bite to the head or trunk in individuals sleeping outside on the ground.^{[4, 5]}

Race

White males account for 76% of the victims.

Sex

National studies report a 9:1 male-to-female ratio. University of Tennessee Medical Center at Knoxville (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, of which 56% were 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.^[6]

• References

Prognosis

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

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.^[7] 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.^[8] 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.^[9]

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.

• References

Patient Education

For patient education resources, see the 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.

• References

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 a human.

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).

• References

Physical Examination

Follow the established routine for a complete comprehensive examination. Keep in mind that acute patients still need to be stabilized (ie, treat airway compromise or shock). See Table 1 in Medical Care for the Snakebite Severity Scale.

Note the following important tips:

• Vital signs: Initial stabilization is same as in any acute patient and includes airway, breathing, and circulation.
• Fang marks or scratches: Determine the coral snakebite pattern by expressing blood from the suspected wound.
• Local tissue destruction: Soft pitting edema generally develops over 6-12 hours but may start within 5 minutes; not bullae, streaking, erythema or discoloration, and contusions.
• Systemic toxicity: Note hypotension; petechiae, epistaxis, and hemoptysis; and paresthesias and dysesthesias, which forewarn neuromuscular blockade and respiratory distress (more common with coral snakes).

Effects from a copperhead bite are shown in the images below.

View Image

Snakebite. Copperhead bite day 3; initial wounds to finger.

View Image

Snakebite. Copperhead bite day 3; initial wounds to finger.

View Image

Snakebite. Copperhead bite day 3; initial wounds to finger.

• References

Laboratory Studies

See the list below:

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

• References

Imaging Studies

See the list below:

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

• References

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.

• References

Severity of Envenomation

Treatment is based on the severity of envenomation; it is divided into field care and hospital management. See Tables 1 and 2 below.

Table 1. Snakebite Severity Scale

View Table

See Table

Patients are eligible for therapy with CroFab if they have moderate or severe envenomation as described or any degree of envenomation with progression of the envenomation syndrome. Note: As the antivenom dose reflects venom size, not patient size, the US Food and Drug Administration recommends the same initial and subsequent doses for pediatric patients. Data show efficacy and safety for patients as young as 14 months.

Table 2. Severity of Envenomation

View Table

See Table

• References

General Management Principles

Important considerations when encountering patients with snakebites are described.

Patients with acute presentations require a rapid assessment of the patient's airway. Obstruction or respiratory failure requires the acquisition of a definitive airway, which might require rapid sequence intubation (RSI). Breathing and circulation should also be assessed in the initial state once an airway has been established.

Remove the patient from the snake's territory as soon as stabilization has occurred in order to avoid further harm.

Remove any jewelry or constricting clothing from the patient's affected area. If clothing is not causing any compression or constriction, it can be left alone until the patient is transferred to a hospital for further care.

In the immediate/acute setting, withhold all alcohol and any drugs that may confound clinical assessment or interfere with treatment.

Do not incise the bite site or perform suction.^[10]

The most urgent priority, following the initial assessment, is to promptly evacuate the patient to a hospital where antivenin can be given if needed.

A secondary priority is to mark the extent of the redness and swelling with ink, indicating the date and time, so that further progression can be measured.

Further inpatient care

Admission to the hospital is appropriate 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). Observation in the emergency department for 8-10 hours may be needed for dry bites to ensure lack of progression of symptoms. Patients with severe envenomation need specialized care in the ICU, including provision of blood products, invasive monitoring, and airway protection. Coral snakebites should be observed 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 can be considered for pressures greater than 30-40 mm Hg. However, fasciotomy has not been shown to improve outcomes, even when compartment pressures are elevated, and is not routinely indicated for crotalid snake envenomation.^{[11, 12]} Antivenin alone has successfully treated documented elevated compartment pressures.^[13]

Depending on the clinical severity of the bite, further blood work may be needed, especially clotting studies, platelet count, and fibrinogen level. Late coagulopathy has been reported after using FABAV. F(ab’)2 immunoglobulin derivatives under development have a longer half life than CroFab and have been shown to decrease late coagulopathy after antivenin treatment.^[14]

• References

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 tenets of emergency life support.

Reassure the patient during the implementation of ABCs.

Monitor vital signs and establish at least one large-bore intravenous line 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, unless it is necessary to expedite evacuation.

Immediately transfer to definitive care.

Do not give antivenin in the field.

• References

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).

For victims of pit viper (crotaline snake) bites, evenomation grading determines the need for antivenin. 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). 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. See Tables 1 and 2 above.

Grading envenomations is a dynamic process. Over several hours, an initially mild syndrome may progress to a moderate or even severe reaction.

For pit viper envenomations, horse-serum antivenin was made available in 1956. The older equine antivenin has been replaced in 2000 by an improved polyvalent antivenin with fewer adverse effects (see Medication). The antigen-binding fragment antivenom (CroFab) is the only FDA-approved snakebite antivenin on the market in the United States. With the reduced adverse-effect profile and demonstrated 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 CroFab dosing.^[15] In a randomized study of scheduled versus as-needed CroFab 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.^[16]

Although copperhead bites are generally self-limiting, morbidity was reduced in moderate envenomation 4 hours after 4 vials of CroFab in 88% of cases. The cases that failed to respond were not changed by further CroFab doses.^[17]

CroFab 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 CroFab when administered according to grade of envenomation.^[6]

Although CroFab 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.^{[18, 19]}

Coral snakes are not pit vipers and their bites should not be treated with CroFab. A previously available Wyeth antivenin for Micruris fulvius is no longer manufactured in the United States. Victims of bites by M fulvius (eastern coral snake) and M tener (Texas coral snake) should receive general wound care and supportive care, including respiratory support in the event of respiratory failure. Poison control and toxicologist consultation should be contacted for suspected coral snake envenomations to obtain the latest location-specific treatment recommendations. See also Coral Snake Envenomation.

• References

Surgical Care

Surgical assessment focuses on the injury site and concern for the development of compartment syndrome. Fasciotomy is controversial in snakebites and should be considered only for those patients with objective evidence of elevated compartment pressure. If compartment pressures cannot be measured directly, use 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.

• References

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.

• References

Complications

Coagulopathy, including delayed coagulopathy, is a 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. True compartment syndrome is a rare complication. 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 CroFab.^[20]

• References

Prevention

Wear protective clothing and never handle snakes.

• References

Medication Summary

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

• References

Crotalidae polyvalent immune FAB (ovine) (Copperhead Antivenom (Immune FAB), Cottonmouth Antivenom (Immune FAB), CroFab)

• Dosing, Interactions, etc.

Clinical Context:  Crotalidae polyvalent immune FAB is an affinity-purified, mixed monospecific Crotalidae antivenom. It is used to neutralize toxins from a snakebite. Grading is dynamic, and requirements for antivenin may increase over time.

It can reduce tissue injury and need for fasciotomy with fewer allergic consequences, as has been documented in one study. Most authors withhold antivenin for copperhead envenomations unless the wound is particularly painful (early clue for significant envenomation).

• References

Class Summary

A neutralizing antibody gives antivenin efficacy. One kind of antivenin is available. [JA1] It was approved by the US Food and Drug Administration (FDA) in 2000 (CroFab, Savage). It 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 for agricultural/veterinary use.[JA2]  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.

• References

Ceftriaxone (Rocephin)

• Dosing, Interactions, etc.

Clinical Context:  Ceftriaxone is a third-generation cephalosporin with broad-spectrum gram-negative activity; it has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Ceftriaxone arrests bacterial growth by binding to one or more penicillin-binding proteins.

• References

Class Summary

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

• References

Diphtheria-tetanus toxoid (Decavac)

• Dosing, Interactions, etc.

Clinical Context:  Diphtheria-tetanus toxoid is used to induce active immunity against tetanus in selected patients. The immunizing agents of choice for most adults and children older than 7 years are tetanus and diphtheria toxoids. It is necessary to administer booster doses to maintain tetanus immunity throughout life.

Pregnant patients should receive only tetanus toxoid, not a product containing the diphtheria antigen.

In children and adults, one may administer into the deltoid or midlateral thigh muscles. In infants, the preferred site of administration is the mid thigh laterally.

• References

Class Summary

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.

• References