Management of Venomous Snake Bites in North America:
Separating the Evidence from Medical Folklore
by Linda Sanders MD
EM Resident Physician, Temple University Hospital
Edited by Alex Koyfman MD (@EMHighAK) and Stephen Alerhand MD (@SAlerhand)
In the United States, there are between 8,000 and 10,000 reported snakebites each year, approximately 30 percent of which are venomous, resulting in just 5 deaths annually.1,2,3,11 Due to underreporting, this is likely an underestimation of the actual incidence. Snakebites most often occur between April and September when people are exploring the outdoors. Men aged 17 to 27 years old are the most common victims, making up 80% of the cases. The circumstances surrounding the bite typically involve an attempt at handling the snake rather than an aggressive attack from the snake itself. As a result 98% of bites have been found to involve the extremities.4,5,11
Of the 120 species of snakes, there are only 20 venomous species native to North America, mostly present in the southwestern United States. Venomous snakes are native to every state except Alaska, Hawaii, and Maine.6 These include the crotalinae, the elapidae, and hydrophinae or sea snakes.7 This discussion will be limited to land snakes.
Crotaline include the cottonmouths, water moccasins, and rattlesnakes. They are deaf and have poor eyesight. Thus, they localize their prey and predators using a heat sensitive pit, located between each eye and nostril, for which they are named. Pit vipers are identified by their triangular head, elliptical pupils, and two curved fangs.6 Pit vipers make up 75-80% of bites resulting in envenomation.7
The Elapidae, on the other hand are coral snakes characterized by round pupils and colored black red and white or yellow bands. They are best known by the popular rhyme, “red on yellow will kill a fellow, red on black venom lack”. Importantly, this rhyme only applies to coral snakes in the United States. Elapidae account for only 20 to 25 bites per year in the US.6
The overall mortality associated with snake envenomation is extremely low, though higher rates are seen among children and the elderly and in those with a delay to definitive treatment and administration of antivenom.5,6
While much of the management between crotalinae and elapidae is similar there are distinct features of the two and they require individualized management strategies. Thus we will approach them separately.
Crotalinae (Pit vipers)
Mechanism of Crotaline Snake Venom
The crotaline snake venom contains several enzymes including transaminases, hyaluronidases, phospholipases, phosphodiesterases and endonucleases. Thus, the venom causes a tremendous amount of damage to the capillary endothelium and cell membranes resulting in a vascular breakdown and capillary leak. The end result is a large amount of local edema as well as systemic effects on almost every organ system. Unfortunately the proteins contained in pit viper venom are highly stable and resistant to temperature changes. Thus cryotherapy and heat application to the wound are ineffective and may potentially cause further tissue injury.6
Signs and Symptoms
The first sign of a crotaline bite is usually fang or puncture marks. Pain and a burning sensation at the site occur immediately followed by soft tissue swelling within an hour. Lymphangitis, ecchymosis, and hemorrhagic bullae may develop over the course of hours. Compartment syndrome is rare but can develop due to myonecrosis and the patient should be monitored for this complication.6,38 The location of the bite is of importance because bites to the face or neck may quickly result in airway compromise from local edema.8
The victim often experiences an overwhelming sense of fear, which often accounts for some of the autonomic response and may be difficult to distinguish from the systemic response to the venom. Systemic symptoms may develop and are variable. These include nausea, vomiting, diarrhea, generalized weakness, perioral paresthesias, a rubbery, minty, or metallic taste, muscle fasciculations, tachycardia, tachypnea, and respiratory distress. Respiratory distress may be a result of capillary leak resulting in pulmonary edema. Anaphylaxis and shock may also develop in severe cases. There are antigenic similarities between venom of different species, which has led to at least one case of anaphylaxis.12
There is also a phenomenon called myokymia which is described as repetitive muscle contractions resulting from Timber rattlesnake envenomation in particular, which responds to calcium administration as well as antivenom.9
There are several factors that affect the severity of the snakebite syndrome. These include the species, size of the snake, amount of venom, location of the bite, time to definitive treatment, and victim’s individual susceptibility.6
The mainstays of treatment for all venomous snake bites include early transport to definitive care, the administration of antivenom when indicated, and intensive care monitoring for progression of disease and adverse reactions.6
With regard to the management of snakebites, it is perhaps most important to remember the bioethical principal of non-maleficence. First, do no harm. Unfortunately there is a preponderance of misinformation regarding the management of snakebites, even on high quality websites. A review of 48 websites demonstrated that 54% of these sites had inappropriate recommendation regarding pre-hospital care of snakebites.14
The Do-Not’s of Pre-hospital Snakebite Care
- Do not attempt to capture the snake.
Attempts to capture an alive or dead snake have resulted in further injury to victims and bystanders. Decapitated rattlesnake heads maintain a bite reflex for up to 90 minutes after death and have caused further injury and even death.39 If possible, a photograph from a safe distance is often sufficient.32
- Do not tourniquet the extremity.
There is little evidence to support its effectiveness and pressure immobilization or constriction band techniques are preferred.15
- Do not attempt to suction the venom.
The marketed Sawyer Extractor vacuum pump has no documented benefit and is potentially harmful as is oral suction which risks exposing the wound to oral bacteria.15 Furthermore, there has been a case of a patient developing airway compromise after sucking venom from the bite site.19
- Do not incise the wound.
The theory behind excision of bites in humans was based on an uncontrolled study of snakebites in dogs. There is no evidence to support early incision of bites in humans.5,20
- Do not use cryotherapy.
Snake venom is temperature resistant. While ice application may be okay to relieve pain, it is generally not recommended. Cryotherapy is absolutely contraindicated. It has been known to cause worsened tissue injury and permanent disability.15
- Do not administer electric shocks to the victim.
It has been ineffective in animal studies and has resulted in significant burns, myocardial infarction and even seizures.15,39
The Do’s of Snake-bite Pre-hospital Care6
- Scene safety.
Ensure that the patient is at a safe distance from the snake and further harm. And keep the patient warm.
- Address the ABCs.
- Remove any tight fitting jewelry or clothing.
- Immobilize the affected extremity at a functional position slightly below the level of the heart.
This is thought to decrease the risk of systemic venom absorption. While this is the most commonly recommended position, there is no data to support it.
- Early transport.
Transport the patient regardless of symptoms because both local and systemic symptoms may be delayed up to 24 hours.
- Splint the affected extremity for pain relief and to reduce swelling and bleeding.
- Administer analgesics.
Opiates or Tylenol are recommended as compared to NSAIDs or Aspirin due to the adverse hematologic effects from crotaline bites.18
In-Hospital Management of Crotaline Snake Bites
A 2010 panel of experts reviewed the literature with regard to Crotaline snake bites and made recommendations regarding the management.13
Obtain the Important HPI
It’s important to obtain key information regarding the time of the bite, general description of the snake, and any of the patient’s comorbid medical conditions, any history of prior bites (due to the possibility of cross-reactivity among venoms) and allergies, especially those to horse or sheep products.6,7,12
As well as a thorough physical exam with initial attention to the ABCs, it is important to document circumferential measurements of the wound site every 15 to 30 minutes. This will guide your evaluation of the local progression of disease and need for additional antivenom.6
The Asymptomatic Snakebite Victim
If the patient is asymptomatic, this may have been a dry bite since pit vipers and coral snakes have the ability to selectively envenomate their victims. However, the patient should still be observed for 8 hours as a latent period is also possible. Labs should be obtained including a CBC, and coagulation studies (PT, PTT, and Fibrinogen) prior to discharge. In the case of minor local injury, the recommended observation period is extended to 12 to 24 hours.13
Cover wound with sterile dressing; blebs/necrotic tissue may need debridement.
Diagnostic labs are important for the detection of systemic effects of snake venom and help differentiate the severity of the syndrome. Labs to obtain include a complete blood count, coagulation factors including fibrinogen, type and screen, creatinine kinase, urinalysis, and comprehensive metabolic profile. An ECG is also recommended to evaluate for cardiovascular effects.6
Patients often demonstrate a leukocytosis and transaminitis, both of which resolve with antivenom treatment. Crotaline venom causes a consumptive coagulopathy that looks like DIC but is not associated with increased clotting because thrombin and factor XIII are not affected. Thrombocytopenia occurs from sequestration and direct venom effects as well as a prolonged prothrombin time (PT), activated partial-thromboplastin time (aPTT), low fibrinogen, and an elevated d-dimer.10
Myonecrosis from the local wound leads to an elevated creatinine kinase and resulting myoglobin deposition can cause renal dysfunction. Thus the patient should be monitored for renal failure from hypotension, rhabdomyolysis, intravascular hemolysis or the nephrotoxic effects of the venom itself.6
The poison control center should be contacted immediately.6 Tetanus should be administered to all snake bite patients. There is no indication for antibiotics if there is no sign of infection.6,7 Furthermore no controlled trials have demonstrated effective relief with H2 blockers or steroids.
The primary treatment for crotaline envenomation is antivenom with Crofab if indicated.
Indications for Antivenom
The snakebite syndrome is traditionally categorized according to severity, which helps guide the administration of antivenom.6
- Minimal: local confined to bite site, no systemic/no coagulopathy
- Moderate: progression of swelling beyond bite site, non-life threatening symptoms
- Severe: shock, severe local envenomation, coagulopathies
Antivenom should be administered to all patients with moderate to severe snake bite envenomation. In the past, preliminary skin testing and pretreat was recommended, however this is controversial.10 Earlier administration is theoretically superior because it binds the venom and may decrease the insult from the inflammatory cascade.10 Those administered antivenom should be monitored during and after the administration of antivenom and admitted to the ICU.6,13
Complications of Crotaline envenomation should also be treated primarily with antivenom. Coagulopathies and thrombocytopenia are not responsive to FFP, replacement of clotting factors, platelet transfusion or heparin and have been found to improve with antivenom alone. Thus, significant thrombocytopenia (<50,000 platelets) should be treated conservatively.4 Similarly, local wounds should be monitored for compartment syndrome which can typically be treated with additional antivenom with the understanding that compartment pressures need to be monitored in case fasciotomy is needed.21,30 An exception to this is in the case of a digital compartment syndrome in which it is difficult to accurately monitor compartment pressures. In such cases a digital dermotomy is recommended which involves a longitudinal incision through the skin only with extension as needed.31
Crofab: Efficacy and Adverse Reactions
Crotalidae Polyvalent Immune Fab (Crofab) is a mixed, monospecific polyvalent antivenom produced by immunizing sheep with the venom of 4 crotaline snakes. The immune serum is then cleaved to remove the immunogenic antibody fragment Fc, while the Fab fragment is retained. Thus, reducing the adverse reactions from acute hypersensitivity and serum sickness.22 Crofab was developed in 2000 and since has replaced its predecessor Antivenin Polyvalent (ACP), which was developed in 1954 and is no longer in production. The last batch of ACP expired in 2007.13
Crofab is both safe and efficacious. In two prospective studies it was shown to decrease the snake bite severity score, in particular with regard to systemic effects.23,24 Crofab was initially only studied for moderate envenomations but since then Lavonas et al. have demonstrated its efficacy in treating severe envenomations as well.35
Because Crofab is thought to have a shorter half-life of only 6 hours compared to crotaline venom, redosing is necessary prevent a recurrence phenomenon. 24 The current recommended dosing is an initial control dose of 3-12 vials followed by scheduled re-dosing of 2 vials at 6, 12, and 18 hours.25,26 It is important to appreciate that the reconstitution of the serum takes up to 40 minutes and should be factored in to the care plan if symptoms are severe.25
Crofab has been found to be five times as potent as ACP and adverse reactions have been fairly rare (14.3%) compared to ACP (23-56%) which had retained the immunogenic Fc fragment.22,23,25,33,34 A more recent multicenter observational case series found an incidence of acute hypersensitivities of 6% and serum sickness of only 5%.35
If an acute hypersensitivity reaction does occur, it is recommended to stop the infusion, administer an H2 blocker and potentially epinephrine to stabilize the patient. Then, dilute the antivenom and re-deliver at a slower rate. Serum sickness on the other hand is a type III hypersensitivity reaction occurring 7-21 days after the exposure and can be treated with a prednisone taper.10
A literature search also found that Crofab is likely safe in pregnancy and should be given if clinically indicated. While no maternal deaths have occurred from native venomous snakes in the United States, venom is known to have adverse effects on the fetus resulting in a fetal death rate of approximately 40%. The adverse effects of crotaline venom include inducing uterine contractions, hemorrhage (abruption), and it has been associated with congenital abnormalities.27
Elapidae (Coral snakes)
Coral snakes account for a smaller percentage of venomous snake bites. There are three species of elapidae in the United States: the Eastern coral, Texas coral, and Arizona coral. The Eastern Coral snake is the most deadly of the three. They are characterized by colorful rings of black, yellow, and red that encircle their entire body.32 The rule follows that when the yellow band is adjacent to red the snake is venomous, but this only applies to coral snakes in the US and the yellow can be replaced by white in the rule.37 The elapidae have a less efficient venom delivery system, thus only 40% of elapidae bites result in envenomation.
Mechanism of Elapidae Venom
As compared to crotaline venom, elapidae venom has no proteolytic activity and thus causes fewer local symptoms but does have a potent neurotoxic component.
Signs and Symptoms
The initial elapidae bite causes a variable degree of pain and local swelling is uncommon. Early signs of envenomation include nausea and vomiting, but systemic signs may be delayed up to 13 hours. The elapidae venom is a neurotoxin and can cause altered mental status, paresthesias, ptosis may be the first sign, dysarthria, dysphagia, and eventually respiratory failure which is the most common cause of death. It can cause paralysis lasting three to five days if no antivenom is administered.10,37 Elapidae venom is not toxic to the renal or hematologic systems.
The same “Dos” and Do-Nots” of prehospital care also apply to Elapidae bites. However, for coral snake bites there is a recommendation to use a form of compression to the affected expression. The two commonly recommended options for extremity compression of the venous system: constriction bands and pressure immobilization. Constriction bands is a broad, flat band that exerts enough pressure to compress the superficial veins and lymphatics but is loose enough to admit 1 to 2 fingers underneath to maintain arterial flow.15,16 However, most recommendations now advise pressure immobilization instead which involves the application of an ace wrap and splint at pressures similar to that one would apply to a sprained ankle.17 Case studies have reported a possible bolus effect after release of the compression device. Thus these should be left these in place until the patient has reached definitive care. There have been no definitive benefit established fore either technique. But regardless of whether a compression method is apply the limb should be splinted to reduce pain, swelling and bleeding.
There are no quality studies to guide the management of North American coral snake bites.37 All coral snake bite victims should be admitted for 24 to 48 hours because of the potential delay in presentation. Sedating analgesics should be avoided as they have the potential to exacerbating respiratory depression and depressed mental status. 6
Lab evaluation is generally less helpful in cases of Elapidae envenomation. However, it is generally recommended to obtain a complete blood count, metabolic panel, and urinalysis.
Unfortunately the North American Coral snake antivenom has been discontinued since 2008. This is the only approved treatment for elapidae envenomation in the United States. The FDA however has extended its expiration date to April 30, 2016. There is an alternative antivenom being tested in clinical trials. If a coral snake envenomation is suspected, it is suggested to give 5 vials immediately, though the patient may require up to 15 vials.6
- Avoid commonly used prehospital therapies which cause more harm.
- The goals of prehospital snake bite care include removal of potential tourniquets, immobilization, and early transport.
- Observe suspected dry bite victims for 8 hours.
- Crofab is safe and efficacious and should be administered in a timely manner for crotaline bites.
- Admit all patients given Crofab.
- Observe elapidae bite victims for 24 to 48 hours.
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- Langley RL, Morrow WE. Deaths resulting from animal attacks in the United States. Wilderness Environ Med 1997;8:8-16.
- Langley R. L. Animal-related fatalities in the United States – an update. Wilderness Environ Med. 2005;16:67-74.
- Spano S., Macias F., Snowden B., and Vohra R. Snakebite Survivors Club: Retrospective review of rattlesnake bites in Central California. Toxicon 2013; 61:38-41.
- Wingert WA, Chan L. Rattlesnake bites in southern California and rationale for recommended treatment. West J Med 1988;148:37-44.
- Gold B.S., Barish R.A., and Dart R.C. North American snake envenomation: diagnosis, treatment, and management. Emerg Med Clin N Am 2004;22:423-443.
- Gold B.S., Dart R.C., and Barish, R.A. Bites of venomous snakes. N Engl J Med 2002; 347(5):347-356.
- Auerbach P.S. Bites by Venomous Reptiles in Canada, the United States and Mexico. Auerbach PS, ed. Wilderness Medicine. 6th Ed. Philadelphia, PA: Mosby; 2012.
- Brick JF, Gutmann L, Brick J, Apelgren KN, Riggs JE. Timber rattlesnake venom-induced myokymia: evidence for peripheral nerve origin. Neurology 1987;37:1545–1546.
- Quan, D. North American poisonous bites and stings. Crit Care Clin 2012;28:633-659.
- O’Neil M.E., Mack K.A., Gilchrist J. and Wozniak E.J. Snakebite injuries treated in United States emergency departments, 2001-2004. Wilderness Environ Med 2007; 18:281-287.
- Ryan K.C. and Caravati E.M. Life-threatening anaphylaxis following envenomation by two different species of Crotalidae. Journal of Wilderness Medicine 1994;5:263-268.
- Lavonas E.J., Ruha A., Banner W., et al. Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emergency Medicine 2011;11: 2.
- Barker S., Charlton N.P., and Holstege, C.P. Accuracy of internet recommendations for prehospital care of venomous snake bites. Wilderness Environ Med. 2010;21:298-302.
- McKinney P.E. Out-of-hospital and interhospital management of crotaline snakebite. Ann Emerg Med 2001;32:168.
- Burgess JL, Dart RC, Egen NB, et al. Effects of constriction bands on rattlesnake venom absorption: a pharmacokinetic study. Ann Emerg Med. 1992;21:1086-1093.
- Sutherland SK, Coulter AR, Harris RD. Rationalisation of first-aid measures for elapid snakebite. Lancet. 1979;1:183-186.
- Boyd, J.J., Agazzi G., Svajda D. , Morgan A.J., Ferrandis S., and Norris, R.L. Venomous snakebite in mountainous terrain: prevention and management. Wilderness Environ Med 2007;18:190-202.
- Brooks, D.E. and Graeme, K.A. Airway compromise after first rattlesnake envenomation. Wild & Environ Med 2004;15:1880193.
- Stewart ME, Greenland S, Hoffman JR, et al. First-aid treatment of poisonous snakebite: are currently recommended procedures justified? Ann Emerg Med. 1981;10:331-335.
- Garfin SR, Castilonia RR, Mubarak SJ, et al. The effect of antivenin on intramuscular pressure elevations induced by rattlesnake venom. Toxicon. 1985;23:677-680.
- Cannon R., Ruha A., and Kashani J. Acute hypersensitivity reactions associated with administration of Crotalidae Polyvalent Immune Fab Antivenom. Ann Emerg Med 2008;51:407-411.
- Dart RC, Seifert SA, Carroll L, et al. Affinity-purified, mixed monospecific crotalid antivenom ovine Fab for the treatment of crotalid venom poisoning. Ann Emerg Med 1997;30:33-9.
- Dart RC, Seifert SA, Boyer LV, et al. A randomized multicenter trial of Crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for Crotalinae snakebite in the United States. Arch Intern Med. 2001;161:2030-2036.
- Dart R.C. and McNally J. Efficacy, safety and use of snake antivenoms in the United States. Ann Emerg Med 2001;37:181-188.
- Bogdan GM, McKinney P, Porter RS, et al. Clinical efficacy of two dosing regimens of affinity purified mixed monospecific crotalid antivenom ovine Fab (Crofab). Acad Emerg Med. 1997;4:518Langley R.L. Snakebite during pregnancy: a literature review. Wilderness Environ Med. 2010;21:54-60.
- Lavonas E.J., Schaeffer T.H., Kokko J. et al. Crotaline Fab antivenom appears to be effective in cases of severe North American pit viper envenomation: an integrative review. BMC Emergency Medicine 2009;9:13.
- Hall E.L. Role of surgical intervention in the management of crotaline snake envenomation. Ann Emerg Med 2001; 37(2): 175-180.
- Stewart RM, Page CP, Schwesinger WH, et al. Antivenin and fasciotomy/debridement in the treatment of the severe rattlesnake bite. Am J Surg. 1989;158:543-547.
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- Lavonas, E.J., Kokko J., Schaeffer T.H. et al. Short-term outcomes after Fab antivenom therapy for severe crotaline snakebite. Ann Emerg Med. 2011; 128-137.
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