Snakebite-related morbidity and mortality are reduced most effectively by rapid transport, intensive care support, and the administration of antivenin.
Pit viper envenomation may produce both painful local tissue injury and profound coagulopathy, leading to uncontrolled hemorrhage and shock. Coral snake envenomation may result in life-threatening descending paralysis due to its neurotoxic effects.
Antivenins can induce immediate anaphylactic or anaphylactoid reactions, which can be rapidly life-threatening. Treatment includes antihistamines, epinephrine, steroids, and ventilatory/circulatory support as needed.
All children with snake envenomation should be admitted to the hospital. Serious effects can be delayed and can recur even after treatment with antivenin.
Widow spider bites typically result in a “target” appearance at the site and envenomation can cause radiating pain that may mimic an acute abdomen.
Recluse spider envenomation is usually self-limiting and can be mistaken for cellulitis but can develop severe dermonecrosis or systemic loxoscelism characterized by hemolytic anemia, rhabdomyolysis, and renal failure.
Most scorpion stings cause intense, localized pain without significant tissue injury but can result in severe neuromuscular abnormalities, respiratory failure, and cardiogenic shock.
Bees, wasps, and ants can cause immediate and delayed toxic, even fatal, complications when they attack en masse.
The general principles of envenomation medicine are similar around the world, although the availability of therapeutic resources varies widely. A comprehensive discussion of all venomous snakes and available antivenins is beyond the scope of this text. In consideration of space constraints, the scope of this textbook, and its audience, this chapter focuses on US venomous snakes and antivenins. Readers are encouraged to become familiar with the prescribing information for the antivenin(s) available in their area(s) of practice for the envenomations they may encounter.
While this chapter focuses on envenomation in the United States, snakebite envenomation causes an immense burden of global morbidity and mortality. Annually, approximately 1.8 to 2.7 million envenomations and 94,000 to 125,000 deaths occur worldwide due to snakebites. Rural, agrarian communities in Asia and sub-Saharan Africa are disproportionately affected due to high snake exposure and inadequate access to high-quality, affordable, and region-appropriate antivenin. , In response to this growing crisis, the World Health Organization (WHO) added snakebite envenomation to the list of neglected tropical diseases in 2017. In 2018, the WHO adopted a resolution to decrease the death and disability associated with snakebite envenomation through coordinated global efforts. , Maps of global hotspots most vulnerable to snakebite envenomation are now available to better inform future research and public health interventions.
Up to 6500 snakebite envenomations and 7 to 15 deaths occur annually in the United States and Canada. Between 2000 and 2013, more than 1300 pediatric snakebites per year, half of which were venomous (most commonly copperheads and rattlesnakes), were reported to US Poison Control Centers. Snakebites were reported in all 50 states, but occurred most frequently in Texas and Florida (25%), and West Virginia, Oklahoma, and Louisiana. Although mortality was rare, 20% of snakebites resulted in intensive care unit (ICU) admission, making snakebite envenomation an important topic for critical care providers.
Venomous snakes in the united states
Of the 120 snake species indigenous to the United States, only 25 are venomous. The majority are pit vipers (family Viperidae , subfamily Crotalinae ) and include rattlesnakes, cottonmouths, and copperheads; the coral snake (family Elapidae ) represents the only other native venomous snake. However, exotic venomous snakes, such as those found in zoos and in amateur or professional collections, contribute to an increasing number of snakebites.
Pit vipers have elliptic pupils, a triangular head with temporal venom glands, a heat-sensing foramen (pit) between each eye and nostril that can sense warm-blooded prey or predators, and two curved fangs. Specifically, rattlesnakes (genera Crotalus and Sistrurus ) are native to most US states and have a group of interlocking keratin rings along their tails that vibrate against each other, creating the infamous rattle when the snake is aroused. Moccasins (genus Agkistrodon ) consist of two species, the cottonmouth and copperhead, which are native to the southeastern and southcentral United States. The cottonmouth is semiaquatic and has a dark olive to black color with a pale white oral mucosa. The copperhead has inverted-Y markings on the body and a reddish-brown/copper-colored head ( Fig. 112.1 ). Copperheads may reside within urban areas, and though their bites are not considered as toxic as rattlesnake or cottonmouth bites, severe, untreated envenomations can still lead to death.
Coral snakes (genera Micruroides and Micrurus ) have round pupils, no facial pit, black snouts, short fangs, and characteristic broad red and black bands separated by yellow bands ( Fig. 112.2 ). Because several harmless snakes have similar colors, the rhyme “red on yellow will kill a fellow; red on black venom lack” has been used to differentiate coral snakes in the United States. Native to the southern United States, from the southeastern coast across to the southwest, coral snakes are nocturnal and account for few bites annually.
Last, snakebites from exotic species in the United States are most commonly from cobras (family Elapidae , genus Naja ) because of their popularity in zoos and with amateur snake keepers ( Fig. 112.3 ). Similar to coral snakes, cobras have two short fangs in the front of their mouth that allow them to bite, hold a victim, and inject venom with chewing maneuvers.
Pathophysiology and clinical presentation
Snake venoms are highly complex. The venom of a single species may contain more than 100 different toxic and nontoxic proteins and peptides, in addition to other smaller molecules. Moreover, venom composition can vary from snake to snake, even within species, making it difficult to predict which snakebites may lead to severe injury or death. Depending on fang size, snake venom is injected subcutaneously or intramuscularly into the victim and may be absorbed into blood vessels and the lymphatic system.
Envenomation syndromes may present quickly or insidiously, and severity may vary. Though most cases of envenomation result in clinical symptoms or abnormal laboratory values within 6 hours of a bite, victims seeking medical attention soon after attack may initially present only with fang bites. Even in asymptomatic patients, prompt evaluation is crucial to prevent irreversible injury.
Pit viper envenomations typically produce local and systemic symptoms. Local enzymatic destruction of both muscle fiber and capillary membranes causes myonecrosis that may progress to rhabdomyolysis. Within minutes, a victim may have acute-onset, radiating pain at the site. Within several hours, the victim may develop rapid progression of painful edema and erythema, bullae formation ( Fig. 112.4 ), ecchymosis, lymphangitis, and prolonged bleeding from the puncture site. , Secondary infection, including cellulitis, abscess, or osteomyelitis, may also develop.
Systemic effects include weakened capillary basement membranes that lead to extravasation and profound systemic hemorrhage. Venom may also contain enzymes that disrupt normal coagulation, resulting in a consumptive coagulopathy. , , Uncontrolled hemorrhage and systemic inflammation that leads to capillary leak can quickly progress to profound shock. Venom proteins that inhibit angiotensin-converting enzyme or act as natriuretics may exacerbate shock. Acute renal injury may develop from a variety of mechanisms, including rhabdomyolysis, direct nephrotoxic effects of venom proteins, thrombotic microangiopathy of the renal vasculature, and ischemia in the setting of hemodynamic compromise. ,
Envenomation from coral snakes (and other elapids, such as cobras, kraits, mambas, and sea snakes worldwide) typically causes milder local symptoms compared with pit viper envenomation and classically presents as a neurotoxic syndrome characterized by rapid-onset, descending flaccid paralysis. , Often, the first sign is bilateral ptosis with external ophthalmoplegia ( Fig. 112.5 ); paralysis then progresses caudally to other cranial nerves and onto bulbar, respiratory, trunk, and limb muscles within minutes to hours. , Bulbar and respiratory muscle involvement can lead to life-threatening respiratory failure. , Victims may exhibit tremors, marked salivation, drowsiness, or euphoria. Notably, several rattlesnake species in the United States are also capable of similar neurotoxicity syndromes.
Emergency and critical care
Emergency medical services (EMS) should be called following all snakebites. In the United States, rapid transport, intensive care, and administration of antivenin have been most associated with reduction in snakebite-related injury and death.
Upon arrival, EMS personnel should prioritize attention to airway, breathing, circulation, establishment of intravenous (IV) access contralateral to the bite, and swift transport to a medical facility. The limb should be immobilized and patient secured at rest to minimize venom absorption. Marking extent of local swelling and tenderness with ink can help to track progression during transport. Given lack of evidence of benefit and risk of further injury, the following first-aid measures are not recommended: incision and suction, cryotherapy, tourniquets, electric shock therapy, and application of traditional medicines or snakestones to the wound. , Tourniquets or constriction bands placed prior to EMS arrival that are not producing limb ischemia should be left in place until hospital evaluation given risk of acute toxicity and/or immediate hypersensitivity from potential bolus effect after removal. , Extractor devices used for suctioning should be removed immediately to prevent secondary injury. Although it may be helpful to identify the species of snake, , transporting it (alive or dead) is discouraged because of inherent dangers with capturing it.
Assessment, stabilization, and disposition
Upon arrival to a medical facility, goals of treatment include aggressive supportive care and antivenin administration. A rapid, thorough history should be obtained if possible, to include a general description of the snake, first aid measures taken, medical history, allergies, and history of snakebites as well as response to prior therapy. Physical examination should focus on cardiovascular, respiratory, and neurologic systems as well as the bite site. Circumferential measurements of the limb above and below the bite and serial marking of the leading edge of tenderness and swelling every 15 to 30 minutes provides evidence of local progression. Pediatric advanced life support principles should be followed, including fluid boluses for shock and airway support with oxygen or endotracheal intubation in the setting of respiratory failure or airway compromise. Importantly, resuscitation resources and IV access should be obtained prior to removal of constrictive bandages given risk of sudden deterioration. , Risk of coagulopathy after pit viper envenomation may warrant avoidance of central-line placement in a noncompressible site (e.g., subclavian vein).
Because snakebites in the United States are most commonly caused by pit vipers, diagnostic workup should focus on the risk of coagulopathy and rhabdomyolysis. Initial laboratory studies should include a complete blood count, coagulation profile, type and screen, electrolytes, blood urea nitrogen, serum creatinine, and creatine kinase. Normal initial values do not reliably predict disease severity, as envenomation syndromes may have an insidious onset. Thus, it is crucial to repeat laboratory studies based on the clinical picture; abnormal coagulation studies should be repeated after infusion of antivenin to monitor treatment efficacy. Other diagnostic studies, such as electrocardiogram and chest radiography, may be indicated on the basis of a patient’s comorbidities or clinical presentation.
While prompt treatment is essential for symptomatic patients, asymptomatic pediatric snakebite victims should also be admitted to the hospital for at least 24 hours to monitor closely for delayed onset of symptoms. , , Confirmed coral snakebite should prompt ICU admission and immediate treatment regardless of symptoms because neurotoxic effects are difficult to reverse once manifested and can last several days despite treatment. Suspected but unconfirmed coral snakebite victims should be admitted to the ICU for 24 to 48 hours to monitor for delayed neurotoxicity requiring ventilatory support. Monitoring should focus on trending of vital signs, level of consciousness, swelling progression, and urine output as well as evaluation for cranial nerve abnormalities (particularly ptosis) and spontaneous bleeding. Patients should not eat or drink until it has been determined that they will not need airway support.
In the United States, the decision to administer antivenin is based on clinical presentation and potential for progression. The benefits of treatment must be weighed with the risks of adverse effects, including anaphylaxis and serum sickness. Relative contraindications include individuals with hypersensitivity to papaya or papain.
After pit viper bites, indications for antivenin include progressive local tissue injury, coagulopathy, or systemic effects, such as hypotension or altered mental status. Early treatment allows the antivenin to bind venom components, which can reverse coagulopathy and hypotension and prevent progression of local tissue necrosis. , , In contrast, immediate treatment with coral snake antivenin is recommended in any proven or strongly suspected coral snakebite, even in asymptomatic victims, to prevent or limit potential neurotoxicity. ,
All hospitals should stock at least enough antivenin to treat one patient. Currently, the bovine-derived Crotalidae Polyvalent Immune Fab (trade name: CroFab) is the only commercially available treatment for pit viper envenomation. This treatment is effective and associated with lower rates of adverse effects compared with its predecessor. , Importantly, CroFab does not include coral snake venom antigens; thus, it is not effective in coral snake envenomation. Instead, the equine-derived Antivenin Micrurus fulvius (North American Coral Snake Antivenin) is the specific antidote for coral snakebites. Though it is no longer produced, the US Food and Drug Administration has annually extended the expiration date for the remaining supply of Micrurus fulvius after assessing product stability; the most recent expiration was extended to January 2020.
Worldwide, several manufacturers produce other antivenins targeted for treatment of endemic venomous species though, unfortunately, several major manufacturers have stopped production, creating severe shortages. , Each antivenin has varying specificity, efficacy, and safety. Practitioners should be familiar with the antivenins available for envenomations that they may encounter.
Antivenin dosage is the same for adults and children and is dependent on snake species and the patient’s symptoms. The technique for administering CroFab relies on the concepts of initial control and maintenance therapy and is outlined as an example based on available prescribing information and evidence-based treatment guidelines. , Four to six vials of CroFab should be given as the initial dose for moderate to severe or progressing local tissue injury; coagulopathy; or any systemic effects, such as vital sign abnormalities, bleeding, vomiting, diarrhea, or neurotoxicity. Those with immediate, life-threatening venom effects, such as shock or serious active bleeding, should receive 8 to 12 vials as the initial dose. Each vial should be reconstituted into solution with 18 mL of normal saline, then all vials (4–12) should be combined and diluted into normal saline to a total volume of 250 mL. The infusion should be started at a rate of 25 to 50 mL/h for the first 10 minutes. If tolerated without evidence of an adverse reaction, the rate should be increased to 250 mL/h to complete the total volume. The goal is to achieve initial control, defined as arrest or significant slowing of swelling progression, improved hypotension, and improving coagulopathy. If initial control is not attained by 1 hour after administration, the dose (4–12 vials) should be repeated. Following initial control, maintenance dosing of two vials every 6 hours for three more doses is recommended, except in minor envenomations. Importantly, maintenance dosing has not been shown to reduce recurrence phenomena in all cases.
Other supportive care
In addition to fluid resuscitation and antivenin administration, vasoactive agents should be given as needed for shock. Transfusion of blood products is indicated for bleeding or coagulopathy that is severe or not corrected by antivenin. Consider head computed tomography if the patient has a severe headache or an altered level of consciousness with a severe coagulopathy. Ocular exposure to venom necessitates copious irrigation and an ophthalmology evaluation. Acute kidney injury that persists may require renal replacement therapy. Acetylcholinesterase inhibitors may temporarily improve neuromuscular transmission after coral snake envenomation, but antivenin is still required in all cases.
Pain control with aspirin or nonsteroidal antiinflammatory agents should be avoided for 2 weeks after pit viper envenomation given the risk of bleeding. Opioid analgesia may be considered for pain control but should be avoided in cases of suspected coral snake, eastern diamondback rattlesnake, and Mojave rattlesnake envenomation given the risk that opioids may exacerbate venom-associated respiratory compromise.
Tetanus prophylaxis should be considered in all victims. , Antibiotics should be initiated only if infection develops and after wound cultures have been obtained. Abscesses should be drained in standard fashion. Infected wounds should prompt further examination to evaluate for retained teeth or fangs.
Pit viper envenomations can produce remarkable swelling, discoloration (ecchymosis), paresthesias, and pain concerning for compartment syndrome, but true elevated compartmental pressures are rare. With adequate antivenin treatment, fasciotomy or digit dermotomy is rarely indicated. Unnecessary fasciotomy, particularly in the setting of coagulopathy, can prolong hospital stay and contribute to long-term morbidity. , In the case of true compartment syndrome, antivenin has been shown to limit the associated decrease in perfusion pressure. Noninvasive measures such as limb elevation, IV mannitol, hyperbaric oxygen, and additional antivenin may be employed, but consultation with a surgeon should be initiated concurrently.
Recurrence and therapeutic complications
Recurrence of envenomation syndrome presents as new progressive swelling or coagulopathy after initial control. Many antivenins are associated with recurrence, which are attributed to differences in pharmacokinetics and pharmacodynamics between the antivenin and venom components. , In the case of CroFab, unbound antivenin is cleared significantly faster than venom components, allowing symptoms to recur as absorption of venom continues at the site. Recurrent local swelling should prompt administration of additional CroFab. Though medically significant late bleeding after CroFab treatment is rare, coagulopathic recurrence may be delayed by several days to weeks. Thus, follow-up within 5 days of discharge for repeat blood work is recommended. Indications for additional CroFab are the following: serious abnormal bleeding, fibrinogen less than 50 µg/mL, platelet count less than 25,000 mm , international normalized ratio greater than 3, multicomponent coagulopathy, worsening trend in a patient with prior severe coagulopathy, high-risk behavior for trauma, or comorbid conditions that increase bleeding risk.
Although less common with Fab-based antivenins compared with previous whole immunoglobulin formulations, antivenins can induce variable hypersensitivity reactions, including anaphylaxis (type I) and serum sickness (delayed, type III). Anaphylaxis or anaphylactoid reactions are characterized by airway edema, wheezing, urticaria, and shock and can be life-threatening. For this reason, all patients treated with antivenin should be monitored in the ICU. Treatment of anaphylactoid reactions involves antihistamines, epinephrine, steroids, and ventilatory/circulatory support as needed. Notably, pretreatment with subcutaneous low-dose epinephrine has been shown to be safe and reduce the risk of acute severe reactions to snake antivenin. ,
Serum sickness is characterized by fever, urticaria, lymphadenopathy, and polyarthralgias days to weeks after treatment. Although an uncomfortable experience, serum sickness is usually benign and self-limited, and patients are treated on an outpatient basis with antihistamines and steroids.
Finally, antivenins available in the United States use mercury, in the form of thimerosal, as a preservative. Although controversy exists regarding the potential for nerve and kidney toxicities in small children at high dose of thimerosal, current evidence suggests that the benefits of treating a significant envenomation far outweigh the potential risks.
Upon discharge, patients should be counselled to return immediately for recurrence of local pain or swelling, signs of wound infection, abnormal bleeding or bruising, severe headache, or signs of serum sickness after antivenin treatment. Patients should avoid contact sports, elective surgery, dental work, aspirin, and nonsteroidal antiinflammatory drugs for 2 weeks following a pit viper bite. Acetaminophen with or without a combined opiate analgesic may be prescribed. Patients should also maintain hydration and seek care if they experience decreased urination or cola-colored urine.
All patients should return for follow-up within a few days, with repeat laboratory studies as indicated by snake species and symptoms. Wound checks or a surgical referral for debridement or (less commonly) skin grafting may be appropriate for significant tissue injury. Blisters, blebs, and bullae should be left in place until evaluated by a wound specialist or surgeon. Patients with foot or leg wounds should be provided crutches and crutch training, though weight bearing and mobilization as tolerated should be encouraged.
Preventive measures should be explained to parents and children, stressing the importance of leaving snakes alone when encountered. If a child finds a snake, the child should tell an adult. Individuals should wear boots and long pants; avoid reaching or stepping into places one cannot see; and never touch, handle, or try to kill venomous snakes. Even after a snake is believed to be dead, fangs can still inject venom and cause serious envenomations.
In the United States, mortality after snakebite is rare. , Most patients recover fully after snakebite if medical care is sought promptly. However, pit viper envenomation can result in significant limb injury , with the potential for later development of osteomyelitis or malignant transformation.
Minimal or absent presenting symptoms, difficulty obtaining a reliable history, or wounds that mimic punctures from other causes (e.g., a plant thorn) may all lead to low suspicion for an envenomation syndrome. However, snakebite symptoms usually progress if significant envenomation has occurred. A high index of suspicion in areas with venomous snakes is warranted. Observation and diagnostic studies may help clarify the diagnosis in uncertain cases.
The American Association of Poison Control Centers (AAPCC) can assist in the management of envenomations. The AAPCC or the Antivenom Index ( www.aza.org/antivenom-index ) may help locate an antivenin for exotic snakes in the United States, as many zoos stock antivenins for the exotic species they keep. Poison Control may be contacted at 800-222-1222.
There are two medically important groups of spiders in North America: widow spiders and recluse spiders. In the United States, there are five species of widow spiders (genus Latrodectus ) that together cover every state except Alaska: black widow, western black widow ( Fig. 112.6 ), northern black widow, red widow, and brown widow. Important species of recluse spiders (genus Loxosceles ) include the brown recluse in the Midwest and five other species widely distributed across the southwest.