Venomous snakes bite 6,000 to 8,000 people in the U.S. each year, accounting for approximately five to 15 deaths.¹ Though mortality is low, victims can suffer loss of function, disfigurement, or amputation. And most of these consequences are caused by inappropriate treatment, delay in seeking appropriate help, or inaccessible medical care. Because snakebite treatment is not part of a nurse’s general education, misconceptions about the proper treatment of these emergencies abound. Nurses need to monitor snakebite victims closely, even when they appear to be out of danger, and to use the expertise available from local poison control centers. They also need to understand the toxicity of the snakebite and be able to recognize a variety of symptoms in order to provide the proper treatment — antivenom.

Snakes and their victims

Poisonous snakes are found throughout the U.S., except in Maine, Alaska, and Hawaii.^1,2 Poisonous snakes are common in the Appalachian region, and western and southern states.¹ Victims of poisonous snakebites are most likely to be under the influence of drugs or alcohol, adolescent or young adult males, children, or participants in religious rituals involving snakes or snake handlers. In fact, those who have been previously bitten by a snake may be more likely to be bitten again than the general population. These individuals are also more susceptible to an anaphylactic reaction after being bitten a second time.¹

Two families of poisonous snakes are present in the U.S. — the Crotalidae or pit vipers, which include rattlesnakes, copperheads, and cottonmouths (water moccasins), and the Elapidae or coral snakes. An accurate identification of the snake is important because each family’s bite requires different antivenom, and the two treatments are not interchangeable. This article will focus on the treatment for the Crotalidae — therapy that is appropriate for rattlesnake bites or any other North American pit vipers.

Crotalidae identification

Snakes in the Crotalidae family are known as pit vipers because of a heat-sensing pit located halfway between the eye and the nose. This pit is an infrared heat-seeking organ that the reptiles use to locate prey. Their heads are large and triangular due to the lateral placement of large venom sacs. The eyes have a cat-like vertically slit pupil. Any snake indigenous to North America that possesses a large triangular head with a slit pupil is poisonous! Rattlesnakes have an interlocking series of rings on the tail that produce a hissing sound when vibrated. In contrast, cottonmouths and copperheads have a single row of scales on the underside of the tail that they shake silently. The rattlesnakes have the largest fangs, reaching approximately three to four centimeters long. The fangs retract posteriorly on a hinge-like mechanism into the roof of the mouth, which enables the snake’s mouth to close. Snakes can have one or more fangs. Rows of small teeth are also present. Fang replacement occurs throughout the snake’s life. So if a snake loses one or both fangs, they will grow back. And remember, even “baby” snakes are poisonous at birth — they are capable of envenomation.

Venom composition and effects

Crotalidae venom contains procoagulants (chemicals that will be metabolized into coagulants), anticoagulants, neurotoxins, hemotoxins, and cardiotoxins. These substances digest connective tissue, fats, proteins, and other biological material, explaining why such impressive tissue destruction and blood dyscrasias can accompany snakebites. These components cause changes in the capillary walls that lead to loss of fluid into the tissues, depletion of electrolytes and proteins, and the loss or destruction of red blood cells.² The interspecies variability of these components accounts for a wide variety of signs and symptoms.

Clinical manifestations following snakebite can be related to the size of the snake, potency and amount of injected venom, depth of envenomation (venom injection), location of the bite (for example, a vascular puncture or a bite to the face or neck can lead to immediate crisis), number of strikes, and the size and underlying health of the victim. Venom sacs are full when the snake is hungry and hasn’t eaten in a few weeks. Not all venom is discharged in the first bite. Approximately 25% to 75% of the venom is released initially, therefore subsequent strikes can produce further toxicity.¹ After a strike, the venom supply is replenished in 21 to 28 days.¹

Because venom is usually injected into subcutaneous tissue, intramuscular envenomation is rare. Vascular puncture is extremely rare, but leads to an immediate, life-threatening crisis. The patient may become anticoagulated, hypotensive, dyspneic, and hematuric within 30 minutes. However, an estimated 20% of all bites are dry, that is, no venom is injected despite puncture wounds.¹

Biting indications

The most conclusive diagnostic sign of a poisonous snakebite is rapid, progressive swelling at the site of the bite. Paresthesias of the face, specifically circumoral numbness, or the extremities, accompanied by unusual taste changes and muscle fasciculations, are common neurological symptoms. Patients may exhibit a change in mental status, ranging from excitation to confusion or coma. Common hematological signs are a reduction in platelet count (they are present in normal numbers, but clumped together), hemoglobin and hematocrit (due to hemolysis), and fibrinogen levels.

Prothrombin (PT) and partial prothrombin time (PTT) levels rise along with fibrin split products as venom breaks down the number of fibrin split products into many smaller, nonfunctioning units. The patient may develop huge hemorrhagic bullae at the envenomation site and petechiae in remote areas. Other general symptoms are nausea, vomiting, muscle weakness, and lethargy^.3 Hypotension and shock may develop secondary to severe volume depletion as the venom enhances vascular permeability and fluid shifts from intra- to extravascular spaces.

Pain at the bite area is out of proportion to the apparent injury. Practitioners may only observe a swollen puncture wound, but victims feel tissue being eaten away as though an acid had been poured on their skin. The pain has been compared to slamming a car door on your hand. This is a significant warning sign — nonpoisonous snakes do not elicit this response, and in the presence of this extreme pain, practitioners should assume that the snake was poisonous, even in the absence of any other symptoms. Pain is most severe after a bite from an Eastern or Western diamondback rattlesnake, but may be minimal with the highly neurotoxic Mojave rattler found in the southwest. The Mojave rattlesnake does not produce coagulopathies like other rattlers.¹

How not to treat a snakebite

In the prehospital setting, the two most important tools for a snakebite victim are car keys or a cell phone. If you cannot drive the victim to a hospital, you should call 911 or an ambulance or rescue squad. Transport the patient with the affected area maintained at or below the heart level, not elevated.^1,2

Toxicologists are not in complete agreement about how to treat snakebites, but most concur about what not to do.

Do not use —

• Ice, which can cause further tissue damage.
• Tourniquets, which can lead to limb ischemia.
• Electric shock, which is not supported by research.
• Incisions into the wound, including cutting or mouth sucking, which can worsen tissue injury and may cause infection.

In situations when transport to a hospital will be significantly delayed, such as in the wilderness, the Sawyer Extractor, a commercially available, plunger-like suction device, is marketed as a tool to extract venom from the bite site if applied within three minutes of envenomation, but its use is not supported by current research.^1,2 Likewise, the simple suction cup devices found in first-aid kits are useless.¹

Hospital treatment

Upon receiving a patient with a snakebite in the hospital setting, cleanse the area with soap and water or antimicrobials. Update the patient’s tetanus immunization. Antibiotic prophylaxis is not routinely recommended unless severe tissue destruction has occurred or the wound has been incised.¹ Remove all jewelry and constricting clothing. Keep the affected area at or below the level of the heart because elevating the area can shift the venom from the bite site into the central vascular compartment.^1,2 A patient with the affected area at heart level may remain asymptomatic for hours in the emergency department; and then when the patient resumes daily activities following hospital discharge, the venom may move into the central circulation triggering signs and symptoms. Explain this situation to the patient including instructions to return to the emergency department if it occurs. With that said, all patients suspected of having a poisonous snake bite who initially appear asymptomatic should be observed for at least 8 to12 hours in the emergency department prior to discharge.¹

Clinicians need to mark and then measure the bite site every 15 to 30 minutes to assess the progression of swelling, along with vital signs and neuro checks. Measure the circumference of the area and observe for swelling, both distal and proximal to the site. Snakebites are treated for progression of swelling, which doesn’t have to be severe in nature to warrant treatment, especially when systemic signs are apparent. Prophylactic fasciotomy is not recommended,^1,2 because most bites are subcutaneous and not intramuscular, and acute compartment syndrome is rare even with severe swelling. However, compartment pressure should be measured if compartment syndrome is suspected. The extremity should be elevated above heart level only when compartment pressure exceeds 30 mmHg to 40 mmHg, and IV Mannitol (1g/kg-2 g/kg) is administered if the patient is hemodynamically stable.2 Compartment syndrome is caused by myonecrosis; administration of antivenin will neutralize venom components and may reduce compartment pressure, preventing the need for fasciotomy.² Fasciotomy should only be considered if the compartment pressure is not reduced within 60 minutes.2 Some wounds may require surgical debridement and skin grafting three to six days after the bite.

Laboratory monitoring includes a complete blood count (CBC), PT, PTT, fibrinogen, fibrin split products, electrolytes, and a urinalysis to detect blood and protein. Patients over 40 years of age should have an ECG to assess for cardiac ischemia. A type and crossmatch should be done on the initial blood draw. If the patient becomes systemically envenomed, the foreign proteins of the snake will interfere with crossmatching blood that is drawn later. Coagulation studies need to be repeated in four to six hours. It is not uncommon to find initial lab values within normal ranges, only to discover dyscrasias with the next blood draw. As venom leaves the affected extremity and travels to the central circulation, digestion of the blood components may begin — a process that can take four to eight hours to appear. However, victims who have no dyscrasias after eight hours are unlikely to be systemically envenomed. On the other hand, those affected by the neurotoxic Mojave rattlesnake may not exhibit dyscrasias, but experience neurological symptoms after many hours. Mojave bite victims need to be admitted and observed for 24 hours.

Crystalloid IV solutions, such as lactated ringers or normal saline, are used to replace vascular fluid volume. Once IV access is established, consider narcotics for pain control only if the patient is hemodynamically stable. Narcotics may encourage a hypotensive event, especially in the presence of severe swelling and volume depletion.

Antivenin therapy

Antivenin therapy is indicated for coagulopathy, demonstrated by lab changes or evidence of internal or external bleeding; progressive swelling; or the presence of systemic effects, including vomiting, numbness, hypotension, or central nervous system changes. The importance of early administration cannot be overemphasized.

Although several symptom-based grading scales are available to guide therapy, they cannot replace a consultation with the local poison center. After initial contact, follow-up calls to update the patient’s condition can allow the center to assess the need for repeat antivenin and other treatments. Two types of antivenin are available to treat North American Crotalid envenomation and the administration guidelines are discussed below.

Antivenin (Crotalidae) Polyvalent, Wyeth (Equine Origin): preparation and administration

Before conventional (equine) antivenin administration, the manufactuer recommends performing a skin test to assess patients for a possible allergic reaction. The antivenin kit includes a test dose for injection into the intradermal skin on the volar forearm. Reaction to the horse-serum skin test, consisting of a wheal and flare within five to 30 minutes, does not preclude the use of antivenom; it alerts the practitioner that anaphylaxis may occur and appropriate supportive equipment must be ready. In addition, a negative skin test does not preclude the possibility of a reaction. Because the results of skin testing are highly unreliable and taking the time to perform the test delays therapy, experts now advise that the skin test should be completely omitted.²

Antivenin (Crotalidae) Polyvalent, Wyeth, is most effective if given within the first four hours, but in severe envenomation, it may be given after 24 hours to reverse coagulation defects. Each vial of powder comes with a bottle of diluent. When reconstituting the powder, the solution must be rolled until dissolved, which may take 10 minutes per vial. The vial should not be shaken to mix the solution because this will destroy the proteins and render the antivenin ineffective.

For a moderate envenomation, five to 10 vials of conventional antivenin (Wyeth) are added to 250 mL of Normal Saline Solution, and the infusion is started very slowly, 1 mL to 5 mL per hour. As long as the patient is not showing any allergic signs, the rate can be doubled every minute until the solution is infusing over 10 to 20 minutes per vial, or between one to two hours total infusion time. Children are treated with the same dose or higher doses. Some practitioners give children 50% more antivenin than adults,¹ because children may have more venom circulating per volume of blood and may need more antivenin to bind it.

Always have a second IV access site available for resuscitation. Do not leave the patient unattended. An allergic reaction may manifest as anxiety, chills, weakness, wheezing, stridor, vomiting, dyspnea, diaphoresis, throat constriction, sneezing, or red streaking from the injection site. Should this occur, stop the infusion, administer epinephrine if needed, and treat with IV diphenhydramine (Benadryl) and cimetidine (Tagamet). Both H1 and H2 antagonists are needed. Simultaneous infusion of epinephrine and antivenin has been successful in patients with severe allergic reactions. The antivenin can be diluted or restarted at a slower rate and increased until reaching a rate that is 25 mL per hour below the rate at which the infusion was stopped. For example, if the infusion was previously set to deliver 100mL/hour and it’s restarted at a slower rate, it can be gradually increased to a maximum dose of 75ml/hour.

CroFab — Crotalidae Polyvalent Immune Fab, Ovine: preparation and administration

CroFab, a safe and effective newer intravenous product, is now commonly used to treat Crotalidae envenomation.^4,5 It is made from the blood of healthy sheep immunized with North American snake venom. CroFab is composed of specific antibody fragments that bind to toxic substances in crotalid venom. Toxins are then neutralized, redistributed away from target tissues, and removed from the body.

CroFab has an enhanced safety profile when compared with conventional antivenin therapy.^1,2,5 Mild to moderate allergic reactions can occur, such as pruritus, urticaria, and rash, but anaphylactic reactions are rare. Skin testing is not required with this product.⁵

CroFab is administered as soon as possible, optimally within six hours of poisonous snakebite with evidence of progressive envenomation.⁵ The vial’s powder is reconstituted with 10 mL Sterile Water for Injection USP and mixed by gently swirling it continually until dissolved.⁵. The recommended initial adult and pediatric dose is 4 to 6 reconstituted vials added to 250 mL Normal Saline Solution and infused IV over one hour. The infusion rate is set at 25 mL to 50 mL per hour for the first 10 minutes in order to evaluate for signs and symptoms of an allergic reaction. An additional 4 to 6 vials should be administered if the first dose fails to control signs and symptoms, or they reoccur. Following symptom control, 2 vials of CroFab should be given every six hours for up to 18 hours.^4,5 A follow-up dose of 2 additional vials may be given as deemed necessary by the treating practitioner based upon the patient’s clinical course.

CroFab is contraindicated if the patient has a known history of hypersensitivity to ovine (sheep) products, or to papain or papaya, which are used to prepare antivenom.5 Precautions include a known allergic response to conventional antivenin therapy, hypersensitivity to bromelain, renal/ hepatic impairment, pregnancy, and sensitivity to mercury-containing products.⁵

Facts to keep in mind about antivenom

A slowing or stopping of the swelling, a reduction in systemic symptoms, and the correction of hematological abnormalities are indicators of antivenin effectiveness. Lab values may return to normal after the infusion but become abnormal again in four to six hours if the antivenin dose administered was not adequately bound to the toxins. Another treatment is indicated if this occurs. Treatment efficacy is determined by two sets of lab values that are within normal limits and usually obtained four hours apart.

Attempting to reverse dyscrasias with platelets, fresh frozen plasma, and transfusions, instead of giving the antivenom, is not recommended. Normal lab values may occur one to two hours after the administration of blood products, but then dyscrasias reoccur because the venom digests the infused blood products. Delaying appropriate treatment may cause crippling, disfiguring, or life-threatening situations to occur. Occasionally patients may need replacement products, for example, when a patient is unstable from blood dyscrasias, but this treatment is palliative; it is the antivenin that reverses the coagulopathies.

Do not expect an immediate reduction in swelling. This usually resolves after two to three days, and the extremity will return to normal function soon afterward.

Reports indicate that approximately 50% to 60% of all patients will develop serum sickness one to three weeks after treatment with conventional antivenin therapy.⁶ There appears to be a much lower incidence of serum sickness when CroFab is used.² Symptoms of serum sickness include fever, chills, joint pain, lymphadenopathy, itchy rash, and general malaise and can usually be treated on an outpatient basis with oral steroids and diphenhydramine. Occasionally, myocarditis and glomerulonephritis require hospital admission for these patients.

Antivenin is the antidote for snakebites. Of course, supportive care such as intubation and fluid replacement may be warranted. Treating snakebites is a specialized area in which most practitioners receive limited instruction. If you are an emergency or critical care nurse, you need to ensure that patients receive optimum care by calling your regional poison center for treatment recommendations. The certified specialists are eager to teach you about your patient’s needs, and experienced toxicologists are available to offer free treatment advice. Your increased knowledge and confidence will lead to a more positive outcome for these patients.