Rattlesnake Envenomation

Rattlesnakes are pit vipers and include the genera Crotalus and Sistrurus. Pit vipers may be identified by a heat-sensing pit anteroinferior to the eye. Rattlesnakes may be identified in all but one species by a rattle at the tip of the tail. Rattlesnakes are indigenous from North America to South America. See the image below.

Venom is usually injected into subcutaneous tissue via hollow movable fangs located in the anterior mouth. Occasionally, intramuscular or (probably rarely) intravenous injection occurs. Rattlesnake venom is generally composed of several digestive enzymes and spreading factors, which result in local and systemic injury.

Clinically, local effects most commonly predominate, progressing from pain and edema to ecchymosis and bullae. Hematologic abnormalities, including defibrination with or without thrombocytopenia, may result, but serious bleeding is uncommon.[1] Local or diffuse myotoxicity may result in complications such as compartment syndrome[2] or rhabdomyolysis. Other general effects include shock, myokymia/fasciculations, taste changes, and vomiting. Rarely, direct cardiotoxicity or allergy to venom may occur. Some rattlesnakes may exhibit neurotoxicity with minimal local tissue effects (see Mojave Rattlesnake Envenomation).

A large percentage of bites occur when a snake is handled, kept as a pet, or abused. These are considered intentionally interactive bites. Many bites are associated with ethanol use.

Frequency

United States

According to the American Association of Poison Control Centers (AAPCC) 2016 Annual Report, 804 rattlesnake envenomation case mentions were reported in 2016, with an additional 994 unknown crotalid envenomations.[3] In total, approximately 6,000 various snake envenomation case mentions were reported in 2016. However, this figure is probably conservative because of underreporting. Rattlesnakes cause the majority of all bites by identified venomous snakes in the United States.[4, 5] Dry bite (ie, no clinical evidence of envenomation) occurs in 10-50% of strikes. The American College of Medical Toxicology established the North American Snakebite Registry (NASBR) in 2013 to collect information about the epidemiology, clinical course, and management of snakebites. Between 2013 and 2015, 14 sites in 10 states entered 450 snakebites into the database.[6]

International

An estimated 300,000-400,000 venomous snakebites occur per year. Although rattlesnakes are not found naturally outside of North America, Central America, and South America, they are imported into zoos, museums, and private collections in other regions of the world.

Sex

Males are bitten more commonly than females.

Age

Young adults are bitten most commonly.[7] Elderly patients may have comorbidities and take medications that may increase the risk of hemotoxicity.[8]

Before antivenom, estimates of mortality rates ranged from 5-25%.

Since the development of antivenom, rapid EMS transport, and emergency/intensive care, mortality rates have improved to less than 0.28% when antivenom is administered and to 2.6% when antivenom is not administered.

Less specific figures are available for morbidity data, although most patients recover fully after rattlesnake envenomation. The best estimates suggest that rattlesnake envenomation results in tissue loss, deformity, or loss of function in approximately 10% of patients.

Mortality/morbidity

Fewer than half a dozen deaths occur per year as a result of snakebite in the United States; most are caused by rattlesnake bites. Estimates of deaths each year from snakebite range from 30,000-110,000 worldwide. Up to 5 times as many individuals experience permanent morbidity.[9, 10]

US mortality with administration of antivenin is approximately 0.28%. Without antivenin being administered, mortality is approximately 2.6%.

Call professionals, such as animal control, to move snakes (if it is necessary to move the snake).

Never attempt to handle, possess, or kill venomous reptiles.

For patient education resources, see the patient education article Snakebite.

All or none of the following may be present. Note that symptoms are subject to change, and this change can be very rapid or very insidious. In addition, severity is generally guided by the most severely affected parameter.[9, 11, 12, 13, 14] See the following:

• Pain around the bite site

• Swelling

• Taste changes (eg, a metallic taste)

• Difficulty breathing

• Chest pain

• Nausea, vomiting, or diarrhea

• Hematemesis, hematochezia

• Neurologic symptoms - Weakness, paresthesias

• Syncope, near syncope

Physical examination findings may include the following:

• Fang marks - May be 1, 2, or more, or may be unable to discern (See the image below.)

  Moderate rattlesnake envenomation in a toddler after treatment with antivenom. Photo by Sean Bush, MD.

• Tenderness surrounding the bite site

• Local edema: Use a pen to mark and time the border of advancing edema every 15-20 minutes initially. Once stabilization with antivenom has occurred, repeat measurements every 1-2 hours. Rapidly progressive swelling is usually indicative of a severe envenomation.

• Erythema

• Ecchymosis

• Bullae

• Bleeding

• Hypotension/hypertension

• Tachycardia

• Myokymia (muscle fasciculations)

• Neurologic effects

• Lethargy

Complications of snake envenomation may include the following:

• Bleeding, such as gastrointestinal or intracranial

• Compartment syndrome

• Necrosis with resulting tissue loss or loss of function

• Rhabdomyolysis, myoglobinuric renal failure

• Infection

• Respiratory difficulty

• Death (rare in the United States)

• Antivenom-associated anaphylaxis  - Type I (immediate) hypersensitivity reaction, which may be life threatening; characterized by urticaria, airway swelling, wheezing, and shock

• Antivenom-associated serum sickness - Type III (delayed) hypersensitivity reaction; characterized by fever, urticaria, lymphadenopathy, and arthritis and may occur 3 days to 3 weeks after antivenom

Coagulopathy commonly occurs with rattlesnake envenomation, although clinical bleeding is uncommon.[15, 16, 17, 18, 19] Defibrination and/or thrombocytopenia most often characterize snakebite coagulopathy. Defibrination is manifested by low serum fibrinogen, elevated prothrombin time, and elevated fibrin split products (FSP). Venom-induced thrombocytopenia may exist in association with or independently of defibrination. Abnormal coagulation parameters may last for a week or more. Recurrence of coagulopathy after resolution with antivenom has been reported.

• Complete blood cell (CBC) count with differential

• Platelets

• Prothrombin time

• Activated partial thromboplastin time

• Fibrinogen

• Type and screen

• Urinalysis

• Thromboelastography

Rhabdomyolysis may occur from severe envenomation but is best described after canebrake (Crotalus horridus atricaudatus)[20] and Mojave (Crotalus scutulatus)[21] rattlesnake envenomations. Rhabdomyolysis may lead to myoglobinuric renal failure and subsequent electrolyte abnormalities, such as hyperkalemia, hypokalemia, or hypocalcemia.

• Creatine kinase (CK)

• Electrolytes

• Blood urea nitrogen (BUN), creatinine

• Calcium

• Phosphorus

• Urinalysis

For respiratory difficulty, consider arterial blood gases (ABGs), although arterial puncture should be avoided if a severe venom-induced coagulopathy develops.

Obtain laboratory and other diagnostic data on a case-by-case basis. Factors to consider may include severity of envenomation, physician preference, and cost.

Plain radiographs may depict teeth or fangs retained in the wound.

Consider a head CT scan if the patient has a headache or altered level of consciousness (ALOC) with a severe coagulopathy.

Obtain an electrocardiogram (ECG), if indicated.

Skin testing is not necessary before administering either Crotalidae polyvalent immune Fab, ovine (CroFab) or Crotalidae immune Fab, equine (Anavip) antivenins.

Central venous or interosseous access may need to be obtained. However, avoid placing a central line in a noncompressible site (eg, internal jugular) because of the risk of bleeding from venom-induced coagulopathy.

Fasciotomy may be indicated if measured compartment pressures remain persistently and severely elevated despite adequate antivenom. CroFab has been shown to limit the decrease in perfusion pressure associated with compartment syndrome. Compartment syndrome may manifest subjectively, with complaints of increasing pain, and objectively, with tenderness on passive muscle stretch, a rock hard feel to the compartment or a diminished capillary refill. True compartment syndrome is rare following snakebite, even in patients with severe edema, because most envenomations are believed to be subcutaneous. Myonecrosis has been shown to occur from direct myotoxicity, even after fasciotomy of the affected compartment.

Distinguishing compartment syndrome from the effects of envenomation may be difficult. Similar to compartment syndrome, rattlesnake envenomation may cause a bluish discoloration of the skin or pallor (because of subcutaneous bruising), severe swelling, paresthesias, and pain. If effects are only caused by envenomation and the patient does not have compartment syndrome, capillary refill is normal and compartmental pressure is not elevated.

Do nothing to injure the patient or impede travel to the ED.

Give general support of airway, breathing and circulation per advanced cardiac life support (ACLS) protocol with oxygen, monitors, 2 large bore intravenous lines, and fluid challenge. Minimize activity (if possible), remove jewelry or tight-fitting clothes in anticipation of swelling, and transport the patient to the ED as quickly and as safely as possible. Use a pen to mark and time the border of advancing edema often enough to gauge progression.

In some studies, no benefit was demonstrated when a negative pressure venom extraction device (eg, The Extractor from Sawyer Products) was evaluated; additional injury can result.[22, 23] Incision across fang marks is not recommended. Mouth suction is contraindicated. See the image below.

Lymphatic constriction bands and pressure immobilization techniques may inhibit the spread of venom, but whether they improve outcome is not clear.[24, 25] Limiting venom spread actually may be deleterious for pit viper envenomation if it increases local necrosis or compartment pressure. Tourniquets are not recommended.

Maintain the extremity in a neutral position.

First aid techniques that lack therapeutic value or are potentially more harmful than the snakebite include electric shock, alcohol, stimulants, aspirin, placing ice on the wound, and various folk and herbal remedies. Cost and risk of acute adverse reactions generally preclude field use of antivenom.

Attempts to capture or kill the snake cannot be recommended because of the risk of additional injury. If uncertainty exists about whether a particular snake is venomous, consider taking photographs of the snake from a safe distance of at least 6 feet away using a digital camera.

Adequate hydration with intravenous fluids is indicated. Patients with hypotension should be resuscitated first with two isotonic sodium chloride solution challenges (eg, 20 mL/kg). Treat persistent shock with colloids, followed by pressors as indicated.

Administer antivenom for signs of envenomation progression or imminent risk of an acute complication of envenomation (see Complications). Crotalidae polyvalent immune FAB ovine (CroFab) is a safe option[26, 27] and it is indicated even if the envenomation is minimal or mild.[28, 29] An equine Crotalidae immune FAB antivenin was approved in the United States in 2015. An antivenin should be given as a preventative measure if any signs of envenomation exist. Do not wait for the envenomation to get worse—permanent injury could result.

It is emphasized that grading envenomations is a dynamic process and additional antivenom should be given as indicated by a worsening clinical course.[30] When considering the use of antivenom, the risk of adverse reaction to antivenom must be weighed against the benefits of reducing venom toxicity.[31] Alternatives (eg, a different type of antivenom, if available) should be considered as well.

It should be noted that a retrospective review of 21 cases of male patients with C horridus (timber rattlesnake) envenomation, patient age 19-71, found severe thrombocytopenia despite antivenom administration. While there were no deaths and no red blood cell transfusions required among this patient group, the mean time to platelet count recovery was 10 days after envenomation.[32]  

Nonenvenomation, ie, dry bite (probably occurs in < 10% of rattlesnake bites, although estimates as high as 50% exist), is characterized by the following:

• Local effects - Puncture wounds only

• Systemic effects - None

• Coagulation abnormalities - No laboratory evidence of coagulation abnormalities and no clinical evidence of abnormal bleeding or clotting

Minimal or mild envenomation is characterized by the following:

• Local effects - Swelling, pain, tenderness, and/or ecchymosis confined to the immediate bite area

• Systemic effects - None

• Coagulation abnormalities - No laboratory evidence of coagulation abnormalities and no clinical evidence of abnormal bleeding or clotting

Moderate envenomation is characterized by the following:

• Local effects - Swelling, pain, tenderness, and/or ecchymosis extending beyond the immediate bite area but involving less than the entire part

• Systemic effects - Present but not life threatening; may include nausea, vomiting, oral paresthesias or unusual tastes, fasciculations (myokymia), mild hypotension (systolic blood pressure < 90 mm Hg), mild tachycardia (heart rate < 150 bpm), and tachypnea

• Coagulation abnormalities - Laboratory evidence of coagulation abnormalities may be present, but no clinical evidence of abnormal bleeding or clotting exists; rattlesnake venom-induced coagulopathies commonly include thrombocytopenia, decreased fibrinogen, and/or elevated PT

Severe envenomation is characterized by the following:

• Local effects - Swelling, pain, tenderness, and/or ecchymosis extending beyond the entire extremity or threatening the airway

• Systemic effects - May include severe hypotension or shock, severe tachycardia or tachypnea, respiratory insufficiency, and/or severe altered mental status

• Coagulation abnormalities - Markedly abnormal with serious bleeding or severe threat of bleeding

Discharge instructions

Return immediately if swelling worsens or pain becomes severe.

Return immediately if any abnormal bleeding or bruising, petechiae, dark tarry stools, or severe headache occur.

Return for signs of wound infection, such as swelling, excessive tenderness, redness or streaks, heat, or drainage (pus).[33]

Return or follow up if a fever, itchy rash, joint pain, or swollen lymph nodes occur any time during the next few weeks.

Do not take nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen (Motrin, Advil), or naproxen (Naprosyn, Aleve) for 2 weeks after the snakebite. Acetaminophen (Tylenol) or a prescribed pain medication can be taken.

Do not participate in contact sports, undergo elective surgery, or have dental work for 2 weeks after the snakebite.

Drink plenty of liquids. Return if urine decreases in amount or becomes cola colored.

Referral to a physical therapist or surgeon may be indicated. If bitten on the foot or leg, crutches and crutch training should be provided. Elevate and mobilize affected extremity as tolerated.

Next day wound check should be performed at the physician's discretion on a case-by-case basis. The patient should return to the ED or follow up every 3 days for 2 weeks with repeat CBC, PT/INR, and fibrinogen. Laboratory results may need to be rechecked more or less frequently or for a longer or shorter duration on a case-by-case basis.

Further inpatient care

All patients with rattlesnake envenomation should be admitted to the hospital and remain there while undergoing treatment with antivenom. Close observation and frequent measurements of swelling (every 1-2 h) for approximately 24 hours after initial control is recommended.

Patients who are believed to have a dry bite in which no venom effects develop should be observed for at least 8 hours. A close follow-up and/or recheck examination is recommended.

Several reports in the literature have documented instances in which patients who were initially discharged with a mild envenomation returned in several hours with significant injury and required antivenom and admission.[34]

Transfer

All hospitals should have enough antivenom to treat at least one patient. However, antidote stocking varies and shortages do occur. Therefore, if antivenom is not available at the presenting hospital, the patient should be transferred to a facility where antivenom may be administered. However, if it is available, antivenom may be necessary to optimize stabilization of a patient prior to transfer.

The American Association of Poison Control Centers may assist in the management of envenomations.

For assistance regarding use of CroFab for a patient bitten by a snake, contact the CroFab hotline at 1-87-SERPDRUG (1-877-377-3784).

Consider consulting a surgeon (eg, general, orthopedic, hand) if compartment syndrome is suspected.

Never handle a rattlesnake, even if it is believed to be dead. Serious, even fatal, envenomations have been documented to occur after handling the decapitated head of a rattlesnake up to 90 minutes after it was severed.

Do not reach or step into places outdoors that are not visible.

At home, remove debris in which snakes might hide (eg, log piles). Remove items, such as bird feeders, that might attract snakes—seeds that fall from bird feeders attract rodents, which attract snakes.

Heavy clothing (such as hiking boots) may retard some strikes.

Young children should be closely supervised, and older children should be educated to avoid snakes in indigenous areas.

Keep the garage door closed to prevent rattlesnakes from seeking shelter in the garage.

Many cases of envenomation involve alcohol. Do not use alcohol and place oneself in an environment that may be shared with rattlesnakes or play with snakes while intoxicated.

The only proven therapy for snakebites is treatment with antivenins.[35] The physician also must be prepared to support the victim's cardiovascular and respiratory systems.[36]  Administer antihistamines if serum sickness develops. Steroids may be indicated for more severe cases of serum sickness.

 

Class Summary

These agents neutralize toxins from snakebites caused by North American pit vipers.

Crotalidae polyvalent immune FAB (ovine) (CroFab)

It is indicated for envenomation by North American pit vipers (eg, cottonmouths/water moccasins, copperheads, rattlesnakes) in adults and children.

Crotalidae immune FAB (equine) (Anavip)

Crotalidae immune FAB (equine) contains venom-specific F(ab’)2; fragments of immunoglobulin G (IgG) that bind and neutralize venom toxins, thereby facilitating redistribution away from target tissues and elimination from the body. It is indicated for management of adults and children with  envenomation caused by North American pit vipers, including rattlesnakes, copperheads, and cottonmouths (water moccasins).

Class Summary

These agents are used for treatment of acute allergic reactions to antivenom or venom (not for treatment of envenomation).

Diphenhydramine (Benadryl)

Diphenhydramine is used for the symptomatic relief of allergic symptoms caused by histamine released in response to allergens

Class Summary

Patients should be immunized against tetanus.

Diphtheria-tetanus toxoid (dT)

Diphtheria-tetanus toxoid is used to induce active immunity against tetanus in selected patients. Tetanus and diphtheria toxoids are the immunizing agents of choice for most adults and children older than 7 years. Booster doses are necessary to maintain tetanus immunity throughout life because tetanus spores are ubiquitous.

Pregnant patients should receive only tetanus toxoid, not the diphtheria antigen–containing product. In children and adults, one may administer into deltoid or midlateral thigh muscles. In infants, the preferred site of administration is the mid thigh laterally.

Class Summary

Prophylactic antibiotics are not routinely indicated. However, wound infections should be treated with antibiotics. Common etiologic bacteria in wound infections include Pseudomonas aeruginosa, Staphylococcus epidermidis, Enterobacteriaceae species, and Clostridium species. For infected wounds, empiric therapy may include ciprofloxacin (contraindicated in pediatric patients and pregnant women) as a single agent or a combination of ceftriaxone plus amoxicillin-clavulanate, pending wound culture and sensitivity results. Retained foreign bodies (eg, a fang, other tooth) are a common cause of wound infection.

Ceftriaxone (Rocephin)

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.

Class Summary

Pain control is essential to quality patient care. It ensures patient comfort and promotes pulmonary toilet. Most analgesics have sedating properties, which are beneficial for patients who have sustained painful snakebites. Opioid analgesics are recommended for pain control as needed. NSAIDs may contribute to coagulopathies.

Morphine sulfate (Astramorph, Duramorph, and MS Contin)

Morphine sulfate is the drug of choice for narcotic analgesia because of its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Morphine sulfate administered intravenously may be dosed in a number of ways and commonly is titrated until the desired effect is obtained.

Class Summary

Consider transfusion if antivenom does not correct coagulopathy or if imminent risk of serious bleeding. Transfusion is generally recommended for life-threatening bleeding (rare), platelets <20,000 mm3, or hemoglobin <7 g/dL. Transfusion should be utilized after antivenom as a temporizing or adjuvant measure because antivenom may correct coagulopathies more definitively (although this is an area with particularly contradictory literature). Coagulopathy often recurs and may persist for 2 weeks or more after envenomation.

Red blood cells (RBCs)

Red blood cells are used preferentially to whole blood because they limit volume, immune, and storage complications. Packed RBCs (PRBCs) have 80% less plasma, are less immunogenic, and can be stored about 40 days (versus 35 d for whole blood). PRBCs are obtained after centrifugation of whole blood. Leukocyte-poor PRBCs are used in patients who are transplant candidates/recipients or in those with prior febrile transfusion reactions. Washed or frozen PRBCs are used in individuals with hypersensitivity transfusion reactions. Blood can be administered over 3-4 hours, premedicating with acetaminophen and diphenhydramine to prevent febrile transfusion reactions.