Continuing Education Activity

Venomous snakebites pose a significant global health threat, leading to substantial morbidity and mortality, especially in regions with high venomous snakebite incidence. In the United States, an estimated 7000 to 8000 venomous snakebites occur annually, with approximately 5 to 10 deaths reported yearly. The clinical presentation of snakebites can vary depending on the species but often includes localized pain, swelling, coagulopathy, and systemic symptoms such as nausea, muscle cramping, and shock. Initial management focuses on immobilization and rapid transport to a healthcare facility, where antivenom therapy is the mainstay of treatment. Pre-hospital interventions like ice application and wound incisions are discouraged due to their potential to worsen outcomes.

This course teaches healthcare professionals to recognize, assess, and manage venomous snakebites effectively. Participants learn to identify the clinical features of snake envenomation, perform essential diagnostic evaluations, and administer appropriate antivenom therapy. The course emphasizes the importance of a coordinated interprofessional approach involving emergency medicine clinicians, toxicologists, nurses, and pharmacists to ensure timely and accurate treatment. Collaborative care enhances patient outcomes by facilitating rapid decision-making, improving antivenom administration, and preventing complications associated with improper management.

Objectives:

• Identify the clinical signs and symptoms of venomous snakebites, including localized swelling, pain, and systemic envenomation effects.
• Differentiate between various types of venomous snakebites based on geographic location, bite characteristics, and species involved.
• Screen for potential complications such as coagulopathy, neurotoxicity, and renal impairment through appropriate laboratory testing.
• Collaborate with the interprofessional healthcare team, including toxicologists, emergency clinicians, nurses, and pharmacists, to ensure timely and coordinated care.

Introduction

Venomous snakes inflict considerable morbidity and mortality worldwide, although specific data on the total number of venomous snakebites globally are lacking. In the United States, approximately 7000 to 8000 venomous snakebites occur each year, with about 5 to 10 deaths reported per year, although there is no mandated reporting for snakebites, so these data are likely incomplete. Notably, bees are responsible for significantly more deaths than snakes in the United States.[1][2]

Patients with venomous snakebites present with signs and symptoms that can include superficial puncture wounds, localized pain and swelling, nausea, vomiting, muscle cramping, dizziness, numbness, tingling around the mouth, dyspnea, life-threatening coagulopathy, and shock. Pre-hospital treatments, including the application of ice, alcohol consumption, wound incisions, and oral suction of venom, are not recommended. Evidence supports initial conservative management, such as immobilization. In North America, the use of lymphatic constriction bands is not advised, as these are reserved for venoms with significant neurotoxic effects only. Otherwise calming the patient and encouraging oral fluid intake prior to rapid evacuation to an emergency center where definitive care can be rendered. Initial assessment of the patient with a snakebite should include laboratory studies to evaluate for hematologic, neurologic, renal, and cardiovascular derangements. Antivenom is the definitive treatment, although the specific type of antivenom depends on the snake species. The previously used horse-serum-derived full immunoglobulin antivenom has now largely been replaced by sheep-derived Fab antivenom (FabAV or Fab) and a recently safer horse-derived F(ab)2.[1][2][3]

Etiology

Venomous snakebites generally occur when venomous snakes (most commonly pit vipers) are cornered or startled by humans. Increased interest in warm weather outdoor activities like hiking, backpacking, and fishing, as well as the increasing number of venomous snakes being kept as pets, has increased the number of venomous snakebites in recent decades. Many snakebites do not result in envenomation, although it is initially quite difficult to distinguish between an envenomated and non-envenomated bite.

Epidemiology

There are about 3000 species of snakes worldwide, 10% to 15% of which are venomous. These snakes primarily use their venom to obtain food.

In the United States, greater than 95% of snakebites are caused by the Crotalidae ("pit viper") family of snakes, so named because of heat-sensitive "pits" between the eyes and the nostrils used to sense their prey. The Crotalidae family includes the following snakes:

• Rattlesnakes, genera Crotalus and Sistrurus 
• Copperheads, Agkistrodon contortrix
• Cottonmouths, or water moccasins, Agkistrodon piscivorous

The Elapidae or coral snakes (Micrurus species) account for a much smaller proportion of snakebites in the United States. Elapids are found along the southern edge of the United States, whereas pit vipers are dispersed throughout most of the continent. Rattlesnakes account for most snakebite-related deaths in people and domestic animals in the United States. Most coral snake bites in the United States occur in southern states, with Florida, Texas, North Carolina, and Georgia among the most common. Risk factors for snake bites include male sex, handling or disturbing a snake, and owning a venomous snake.[1][2][3]

Pathophysiology

Venomous snakes in the United States were previously classified as having either hemotoxic or neurotoxic venom, although more recent toxicology research suggests this binary classification is inadequate.[4] The venom contains proteins, phospholipases, enzymes that can cause necrosis, and hemolysis via mechanisms that are still under study.[5] A concomitant allergic response leading to the release of histamine and bradykinin may also contribute to the systemic effects seen in more severe envenomations. Hypotension after a snakebite is likely caused by a variety of mechanisms, including increased permeability of capillaries, leading to extravasation of plasma and direct effects of toxins on the cardiac muscle, smooth muscle, and other tissues.[4]

History and Physical

A focused history and physical should be performed, starting with a primary survey of the patient's airway, breathing, and circulation. Shock and respiratory failure are common sequelae of snakebites, so close observation is crucial. Establishing the time of the bite as well as any previous interventions and asking about existing medical problems (eg, cardiac, pulmonary, and renal disease), current symptoms, allergies, and last tetanus immunization are also important. Close examination and documentation of the patient's injuries are crucial, as worsening erythema, swelling, or blistering around the snakebite site could precede clinical deterioration. Although not advised, if the patient was able to take a sufficient quality photograph or physically capture the snake, identification of the species could be useful in guiding management. Time should not be wasted trying to find, photograph, or kill the snake. Bedside ultrasound of the bite location can be utilized to evaluate the depth and extent of associated skin and soft tissue involvement.[3]

Evaluation

Initial evaluation of suspected or confirmed venomous snakebite patients should include the following:

• Routine vital signs
• Electrocardiogram and continuous cardiac monitoring
• Complete blood count 
• Urinalysis 
• Prothrombin time
• Partial thromboplastin time
• Fibrinogen
• Complete metabolic panel (including blood urea nitrogen and creatinine) 
• Blood type and cross-matched for 2 to 4 units of packed red blood cells [3]

Treatment / Management

The initial management of suspected or confirmed venomous snakebites is divided into pre-hospital and emergency department care.

Prehospital Setting

• Ensuring the patient is in a safe, comfortable place (away from the snake)
• Calming and reassuring the patient
• Immobilization of the affected extremity with a sling, if possible
• Cleansing the wound
• Monitoring for swelling or skin changes surrounding the wound
• Oral hydration with clear fluids if the patient can tolerate them
• Identifying the snake only if it does not put the patient or others at risk of further injury
• Rapidly evacuating the patient to an emergency center

Do not incise the wound or attempt to suck the venom out by mouth or with commercial suction devices. Avoid applying ice to the wound or giving the patient alcoholic beverages. 

Emergency Department

• Placing 2 large-bore intravenous catheters
• Initiating of intravenous fluid (lactated Ringer solution or normal saline)
• Rapidly determining the severity of envenomation and whether to give antivenom
• Cleaning the snakebite wound
• Considering surgical consultation if compartment syndrome unresponsive to antivenom is suspected
• Monitoring minimal or moderate envenomation patients for at least 12 to 24 hours
• Immunizing (tetanus), as indicated

Envenomation severity is classified into 5 grades (0 to IV), with grade IV being very severe envenomation characterized by rapidly progressing swelling, bleb formation, and necrosis, as well as systemic symptoms including weakness, nausea, vomiting, muscle cramping, and convulsions. Minimal envenomation (grade 0) is characterized by fang wounds without other signs of envenomation and less than 1 inch of surrounding erythema, without systemic signs or symptoms of envenomation. Current treatment recommendations for crotalid (pit viper) envenomation include antivenom for progressive swelling, moderate envenomation, or laboratory findings or coagulopathy. Dosing is primarily based on the severity of symptoms at initial presentation and response to treatment; treating moderate envenomation should start with at least 4 vials.

Minimal envenomation does not require treatment with antivenom, but these patients in this category should be monitored for a minimum of 12 hours.[3][6][7] A patient with minimal signs of envenomation should have a repeat coagulation panel performed to evaluate for delayed coagulopathy before discharge, and patients with progressive swelling, moderate envenomation, or coagulopathy should be given antivenom. In North America, there are 2 Crotalidae antivenoms approved for use.

Crotalidae Polyvalent Immune Fab Dosing

Crotalidae polyvalent immune Fab is derived from 4 snake species (Western diamondback, Eastern diamondback, Mojave rattlesnake, and cottonmouth) and immunized into sheep (ovine-derived). The whole immunoglobin is extracted, affinity purified, and cleaved by papain into the terminal Fab fragment of the immunoglobin. This reduces its size by about one-third and allows tissue penetration. However, it is cleared renally, and repeat dosing is usually necessary.

The initial controlling dose consists of 4 to 6 vials mixed in 250 mL of normal saline administered over 1 hour; the same number of vials is used for children. Initiate treatment at 10 mL/hr, observing for adverse events. If none are noted, increase every few minutes to complete administration in 1 hour. Observe patients for local swelling and systemic symptoms. Repeat with 4 to 6 vials over 1 hour if there are signs of progression. Do not administer to try to normalize abnormal coagulation markers completely. Repeat until initial control is achieved (eg, local swelling improves or stops, systemic signs are resolved, and clinically relevant bleeding is resolved). After achieving control, maintenance doses of 2 vials every 6 hours for 18 hours are recommended for rattlesnakes, patients with coagulopathy, and those with severe clinical envenomations. This is not usually required for moderate copperhead envenomations. However, if only a controlling dose is used, close and repeated monitoring for progression is important to decide if additional doses are required. Repeat the initial bolus protocol if recurrent swelling or coagulopathy occurs during maintenance doses.

Repeat coagulation panel (prothrombin time [PT]/partial thromboplastin time [PTT]/international normalized ratio [INR]), fibrinogen, platelets, and hemoglobin on days 2 to 3 and days 5 to 7. Recurrent coagulopathy without clinically significant bleeding has been known to occur. Some repeat and follow parameters to normalization. Indications for repeat dosing if coagulopathy occurs between 3 and 7 days after the last dose of Crofab are:

• INR >3.0
• PTT >50 seconds
• Platelet count <25,000
• Fibrinogen <50 ug/ml
• Multicomponent coagulopathy

Crotalidae Immune F(ab)2 Dosing

Crotalidae Immune F(ab)2 is derived from 2 snake species (Bothris asper and Crotalus duressis) and immunized in horses (equine-derived). The whole immunoglobin is extracted, purified, and cleaved by pepsin digestion into a fragment with 2 binding sites for venom components, F(ab)2. Despite being derived from horses, it is less immunogenic than the original rattlesnake antivenom produced; it is larger than Crotalidae polyvalent immune Fab and persists in the serum longer with a more sustained duration of the activity, therefore usually not requiring repeat maintenance dosing.

The initial controlling dose consists of 10 vials mixed in 250 mL normal saline (NS) administered over 1 hour (same number of vials for children). The initial infusion rate for the first 10 minutes should start at 25 to 50 ml/hr, then if no adverse reaction occurs the remained of the 250 ml solution can be given over 1 hour.[8]

Evaluate the number of each antivenom available and not mix loading and maintenance doses between the 2 products. In rare severe envenomations, a repeat dose of 10 vials of Anavip may be needed. Crotalidae polyvalent immune Fab is contraindicated in a patient with a known allergy to sheep protein, in which case Crotalidae immune F(ab)2 can be administered. Crotalidae immune F(ab)2 is contraindicated with a known allergy to horse protein, in which case Crotalidae polyvalent immune Fab should be used.

Differential Diagnosis

Although venomous snakebites are usually fairly straightforward to diagnose, the differential diagnosis includes:

• Snakebites from nonvenomous snakes
• Spider bites
• Tick bites
• Scorpion bites
• Hymenoptera stings
• Soft-tissue infections (folliculitis or furuncle)

Prognosis

If treated promptly, the prognosis of most venomous snakebites in the United States is quite good. There is an estimation that 25% of snakebites from venomous snakes do not result in envenomation.[3] Even though several thousand venomous snakebites occur each year in the United States, there are usually less than 10 reported deaths; deaths that occur are generally in those who delay or avoid treatment.

Complications

Complications of venomous snakebite include: 

• Coagulopathy
• Shock
• Respiratory failure
• Acute renal failure
• Local skin infection
• Compartment syndrome
• Serum sickness

Consultations

A regional poison center will have knowledge of snakes in their service area and the availability of antivenom at nearby hospitals and can provide a medical toxicologist for consultation by phone.

Deterrence and Patient Education

Prevention of venomous snakebites mostly centers on taking precautions to avoid snakes in the wild and not owning or handling venomous snakes at home. The United States Centers for Disease Control and Prevention (CDC) recommends wearing long pants and boots when working or walking outdoors in known snake habitats and wearing leather gloves when handling brush or reaching into areas where snakes may be. Leather chaps or snake gaiters are also popular options for protecting against snakebites. The CDC also recommends that no venomous snake be handled. Patients who own venomous snakes should take extra precautions when handling them and use secure enclosures to ensure they do not escape.

Enhancing Healthcare Team Outcomes

Preventing snakebites and improving snakebite management requires collaboration among various healthcare professionals, including emergency medical service personnel, rural hospitals and emergency departments, medical toxicologists, research institutions, and antivenom researchers and manufacturers. A recent article highlighted these challenges in South Asia.[9]

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References

1.

Warrell DA. Venomous Bites, Stings, and Poisoning: An Update. Infect Dis Clin North Am. 2019 Mar;33(1):17-38. [PubMed: 30712761]

2.

Bawaskar HS, Bawaskar PH. Snakebite envenoming. Lancet. 2019 Jan 12;393(10167):131. [PubMed: 30638580]

3.

Juckett G, Hancox JG. Venomous snakebites in the United States: management review and update. Am Fam Physician. 2002 Apr 01;65(7):1367-74. [PubMed: 11996419]

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Warrell DA. Snake bite. Lancet. 2010 Jan 02;375(9708):77-88. [PubMed: 20109866]

5.

Williams HF, Mellows BA, Mitchell R, Sfyri P, Layfield HJ, Salamah M, Vaiyapuri R, Collins-Hooper H, Bicknell AB, Matsakas A, Patel K, Vaiyapuri S. Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. PLoS Negl Trop Dis. 2019 Jan;13(1):e0007041. [PMC free article: PMC6368331] [PubMed: 30695027]

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Harding SA. Calculated decisions: Antivenom dosing algorithm. Emerg Med Pract. 2018 Sep 01;20(9):CD1-CD2. [PubMed: 30179411]

7.

Lavonas EJ, Ruha AM, Banner W, Bebarta V, Bernstein JN, Bush SP, Kerns WP, Richardson WH, Seifert SA, Tanen DA, Curry SC, Dart RC., Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority. Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emerg Med. 2011 Feb 03;11:2. [PMC free article: PMC3042971] [PubMed: 21291549]

8.

Mascarenas DN, Fullerton L, Smolinske SC, Warrick BJ, Seifert SA. Comparison of F(ab')₂ and Fab antivenoms in rattlesnake envenomation: First year's post-marketing experience with F(ab')₂ in New Mexico. Toxicon. 2020 Oct 30;186:42-45. [PubMed: 32763251]

9.

Ralph R, Sharma SK, Faiz MA, Ribeiro I, Rijal S, Chappuis F, Kuch U. The timing is right to end snakebite deaths in South Asia. BMJ. 2019 Jan 22;364:k5317. [PMC free article: PMC6340368] [PubMed: 30670457]

Disclosure: Stephen Meyers declares no relevant financial relationships with ineligible companies.

Disclosure: Prasanna Tadi declares no relevant financial relationships with ineligible companies.