AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Most snakebites are innocuous and are delivered by nonpoisonous species. Twenty-five species of poisonous snakes make North America their home. 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 of this family 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). The Western diamondback, timber, and prairie rattlesnakes are pit vipers (see Image 1). 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; see Image 2). 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 warning is "red on yellow, kill a fellow; red on black, venom lack." 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 also 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 non-indigenous 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 the snake feels, and the size of the prey. The 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 smaller mouths. 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 small wounds that later result in respiratory failure from the typical systemic neuromuscular blockade.

The local effects of venom serve as a reminder of the potential systemic disruption of organ system function. One effect is local bleeding; coagulopathies are not uncommon with severe envenomations. 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

United States

Snakebites frequently go unreported. Approximately 4000-7000 bites are reported to national centers each year. North Carolina has the highest frequency, with 19 bites per 100,000 persons. The national average is approximately 4 bites per 100,000 persons.

International

There is in general only case or localized reporting of international data. Most snakebites and deaths due to snakebites are not reported, especially in the developing world. 

A new website (www.avru.org/index.html) 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 website is easily navigated and sectionally divided for the practitioner, interested epidemiologists, snake fanciers, and children of Australia and the Asia/Pacific region.

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 snake bites are rare. 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.¹ A review specifically of copperhead bites in West Virginia described similar outcomes and noted that the peak effects of envenomation were not present until over 4 hours from the bite.²
• 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.

Race

White males account for 76% of the victims.

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).

CLINICAL

Section 3 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• 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.
• 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 snake bite 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 dysthesias - Forewarn neuromuscular blockade and respiratory distress (more common with coral snakes)

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.

DIFFERENTIALS

Section 4 of 11  

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• Workup
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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Nonanimal wounds and injuries
Nonvenomous bites

WORKUP

Section 5 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab 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 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 (such as the Stryker pressure monitor). Measurement of compartmental pressures is indicated when significant swelling is present, pain is out of proportion to exam, and if paresthesias are present in the affected limb.

Staging

Please see the ensuing section for discussion of grading envenomation.

TREATMENT

Section 6 of 11  

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• Follow-up
• Miscellaneous
• Multimedia
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Medical Care

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

• Field care
• • As with all medical emergencies, the goal is to support patients until they arrive at the emergency department. The phrase "first, do no harm" has significant meaning here because many poorly substantiated treatment plans may do more harm than good, including making an incision over the bite, mouth suctioning, tourniquets, ice packs, or electric shock.
  • Appropriate field care should adhere to the basic tenants of emergency life support.
  • Reassure the patient to preclude hysteria during the implementation of ABCs.
  • Monitor vital signs and establish at least 1 large bore intravenous and 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.
• Hospital care
• • Physicians who have little experience treating snakebites frequently see patients.
  • Regional centers often have more experience in the care of snakebite victims. Surgical evaluation for envenomation 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 pit viper victims. Grades are defined as mild, moderate, or severe.
  • Mild envenomation is characterized by local pain, edema, no signs of systemic toxicity, and normal lab 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 lab values (eg, fallen hematocrit or platelet values).
  • 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 tests 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.
  • With the reduced side-effect profile of 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 fasciotomies after more liberal FabAV dosing.³ In a "randomized" study of scheduled versus PRN 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.⁴
  • 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.⁵
  • FabAV is generally considered safe for children, as many of the studies did not discriminate in age. A definitive study is warranted but improbable due to frequency.⁶
  • Give antivenin for coral snake bites 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.

Surgical Care

• Surgical assessment follows the injury site and assess for the development of compartment syndrome.
• • Fasciotomy is not indicated in every bite, only for those patients with objective evidence of elevated compartment pressures.
  • Liberal use of the Stryker pressure monitor is warranted. If this is not available, employ the physical hallmark of compartment hypertension (pain with passive range of motion) 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 envenomations, resuscitation, complications, and wound care. They can lead the inpatient treatment.

MEDICATION

Section 7 of 11  

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

Drug Category: Antivenins

A neutralizing antibody gives antivenin efficacy. Today, 2 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 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, Mojave rattlesnakes, and the cottonmouth/water moccasin. 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.

Drug Category: Antibiotics

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

Drug Category: Immunizations

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

FOLLOW-UP

Section 8 of 11  

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• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Admission to the hospital is routine for most envenomations.
• • For dry pit viper bites, observe in the emergency department for 8-10 hours; however, often this is not feasible. Patients with severe envenomations need specialized care in the ICU to administer blood products, provide invasive monitoring, and ensure airway protection.
  • Observe coral snake bites for a minimum of 24 hours.
• Make 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 counts, and fibrinogen levels.

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 snakebites.
• Local wound complications may include infection and skin loss.
• Cardiovascular complications, hematologic complications, and pulmonary collapse may occur.
• Death is rare.
• Prolonged neuromuscular blockade may occur from coral snake envenomations.
• 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.

Prognosis

Full recovery is the rule. 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.

MISCELLANEOUS

Section 9 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Overnight observation in the hospital allows the staff to quickly diagnose delayed signs and symptoms.
• Envenomation determination is time-independent.
• Determining the genus of the snake often is 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.

MULTIMEDIA

Section 10 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Western diamondback rattlesnake.
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Media file 2:  Western coral snake.
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Media file 3:  Southern Copperhead Snake, from snakesandfrogs.com
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Media file 4:  Copperhead bite day 3; initial wounds to finger.
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Media file 5:  Copperhead bite day 3; initial wounds to finger.
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Media file 6:  Copperhead bite day 3; initial wounds to finger.
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
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• Follow-up
• Miscellaneous
• Multimedia
• References

1. Spiller HA, Bosse GM. Prospective study of morbidity associated with snakebite envenomation. J Toxicol Clin Toxicol. 2003;41(2):125-30. [Medline].
2. Scharman EJ, Noffsinger VD. Copperhead snakebites: clinical severity of local effects. Ann Emerg Med. Jul 2001;38(1):55-61. [Medline].
3. Corneille MG, Larson S, Stewart RM, Dent D, Myers JG, Lopez PP. A large single-center experience with treatment of patients with crotalid envenomations: outcomes with and evolution of antivenin therapy. Am J Surg. Dec 2006;192(6):848-52. [Medline].
4. Dart RC, Seifert SA, Boyer LV, Clark RF, Hall E, McKinney P. A randomized multicenter trial of crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States. Arch Intern Med. Sep 10 2001;161(16):2030-6. [Medline].
5. Lavonas EJ, Gerardo CJ, O'Malley G, Arnold TC, Bush SP, Banner W Jr. Initial experience with Crotalidae polyvalent immune Fab (ovine) antivenom in the treatment of copperhead snakebite. Ann Emerg Med. Feb 2004;43(2):200-6. [Medline].
6. Schmidt JM. Antivenom therapy for snakebites in children: is there evidence?. Curr Opin Pediatr. Apr 2005;17(2):234-8. [Medline].
7. Cowles RA, Colletti LM. Presentation and treatment of venomous snakebites at a northern academic medical center. Am Surg. May 2003;69(5):445-9. [Medline].
8. Holstege CP, Singletary EM. Images in emergency medicine. Skin damage following application of suction device for snakebite. Ann Emerg Med. Jul 2006;48(1):105, 113. [Medline].
9. Hunsaker DM, Hunsaker JC 3rd, Clayton T, Spiller HA. Lethal envenomation: medicolegal aspects of snakebites and religious snake handlers in Kentucky: a report of three cases with comment on medical, legal, and public policy ramifications. J Ky Med Assoc. Nov 2005;103(11):542-56. [Medline].
10. Jordan GH, Deitch EA, Britt LD. Management of Poisonous Snakebites. American College of Surgeons: Consensus statement. 1997.
11. Kravitz J, Gerardo CJ. Copperhead snakebite treated with crotalidae polyvalent immune fab (ovine) antivenom in third trimester pregnancy. Clin Toxicol (Phila). 2006;44(3):353-4. [Medline].
12. Kularatne SA, Kumarasiri PV, Pushpakumara SK, Dissanayaka WP, Ariyasena H, Gawarammana IB. Routine antibiotic therapy in the management of the local inflammatory swelling in venomous snakebites: results of a placebo-controlled study. Ceylon Med J. Dec 2005;50(4):151-5. [Medline].
13. Lavonas EJ, Gerardo CJ, O'Malley G, Arnold TC, Bush SP, Banner W Jr. Initial experience with Crotalidae polyvalent immune Fab (ovine) antivenom in the treatment of copperhead snakebite. Ann Emerg Med. Feb 2004;43(2):200-6. [Medline].
14. Shires TG, Thal ER, Jones RC. Trauma. Principles of Surgery. 1994;6:183-5.
15. Stewart RM, Page CP. Wounds, Bites, and Stings. Trauma. 1996;3:929-34.
16. Sullivan JB, Wingert WA, Norris Jr RL. North American Venomous Reptile Bites. Wilderness Medicine: Management of Wilderness and Environmental Emergencies. 1995;3:680-709.
17. Whitley RE. Conservative treatment of copperhead snakebites without antivenin. J Trauma. Aug 1996;41(2):219-21. [Medline].

Article Last Updated: Jun 17, 2008