A Review of Venomous Snakebites and Scorpion Stings
Executive Summary
- There are three main families of venomous snakes: colubrids, elapids, and viperids. Elapids and viperids account for the vast majority of severe envenomations.
- Elapid venoms generally are associated with neuromuscular paralysis and the development of bulbar and respiratory muscle compromise.
- Patient factors, such as age, volume of distribution, presence of comorbid illness, or medications/intoxicants also may contribute to the overall severity of a venomous snakebite.
- Dry bites can be painful and result in inflammation and secondary infection, but they have no evidence of venom effect. The frequency of dry bites depends on the species of venomous snake, but the overall frequency may be as high of 50% of all bites and as high as 80% for some species.
- In general, coral snake envenomation is uncommon because of the snake’s reticent nature, smaller fangs, and smaller venom delivery system.
- Most scorpion species globally produce only painful stings with mild, if any, systemic symptoms.
- The initial management of snake envenomation focuses on assessing and securing airway, breathing, and circulation. Patients should receive oxygen if they are found to be dyspneic or hypoxic. Intravenous (IV) access should be obtained in an uninvolved extremity, and a crystalloid bolus should be provided (20 mL/kg IV) if the patient is hypotensive or if there is evidence of shock.
- Snakebite patients should be calmed and prevented from walking, running, or making significant bodily movements unless safety demands it. Movement and agitation may promote venom circulation from the bite site.
- Snakebites may be at an increased risk for developing bacterial infection, but routine administration of antibiotics is not recommended. Gently irrigate and clean wounds without scrubbing or significantly manipulating the extremity. Tetanus prophylaxis should be administered, if appropriate.
- Compartment syndrome is uncommon in snakebites but may complicate cases where bites occur in restricted compartments, such as the digits or the anterior tibia, and clinicians should have a low threshold for measuring compartment pressures.
- Antivenom potentially is life- or limb-saving, and its administration should not be delayed. The indication for antivenom is relatively straightforward: progressive or severe local symptoms, or the development of any systemic symptoms of envenomation, including derangements in laboratory testing.
A Review of Venomous Snakebites and Scorpion Stings
Although not a common problem, fortunately, the knowledge and ability to manage venomous snakebites and scorpion stings is an essential component of the emergency medicine physician’s armamentarium.
— Ann M. Dietrich, MD, FAAP, FACEP, Editor
Introduction
Envenomation by snakes and scorpions presents a major public health challenge in many parts of the world, including North America. The World Health Organization (WHO) includes snakebites among its list of neglected tropical diseases and estimates that more than 5.4 million bites occur each year, resulting in 2.7 million envenomations and more than 100,000 deaths. An additional 300,000 people are left with severe disability or amputation as a result of snakebites each year.1 According to the American Association of Poison Control Centers, 4,318 cases of snakebite/envenomation were reported in the United States in 2019, with between 10% to 44% of venomous snakebite patients experiencing permanent disability.2,3 These figures almost certainly underestimate the true burden of snakebite envenomation. Improvements in the management of snakebites in North America have made fatalities rare. However, North America is home to some highly venomous snake species, and, similar to the global snakebite problem, most bites occur in rural areas where access to quality emergency care and critical treatment is limited. Furthermore, children, given their smaller size and volume of distribution, may have more severe venom effects, making this issue of particular importance for pediatricians and pediatric emergency physicians in regions where venomous snakes are common.
Scorpion envenomation also is a serious public health challenge in several regions, including Iran, sub-Saharan Africa, Mexico, and the Southwestern United States. Globally, more than 1.2 million scorpion stings occur annually, resulting in more than 3,000 deaths.4 Approximately 10,000 scorpion stings were reported to U.S. Poison Control Centers in 2019, with about one-third of cases occurring in children, and resulting in more than 1,000 hospitalizations, with higher severity among pediatric populations.2 In Mexico, home to 11 venomous scorpion species, it is estimated that scorpion bites may result in several hundred deaths annually, again with disproportionate severity in children.5
Southeast Asia, Africa, Oceania, and Central and South America are the regions with the most significant burden of medically significant snake and scorpion envenomations, but North America has its own significant species of concern, including rattlesnakes (such as the timber rattlesnake, Crotalus horridus; the prairie rattlesnake, Crotalus viridis; the Western rattlesnake, Crotalus oreganus; and species of diamondback rattlesnake, Crotalus atrox/adamanteus). There also are several non-rattlesnake North American venomous species, including the cottonmouth (also known as the water moccasin, Agkistrodon piscivorusas), the copperhead (Agkistrodon contortrix), and coral snakes (the Texas coral snake, Micrurus fulvius tenere; the Eastern coral snake, Micrurus fulvius; and the Sonoran coral snake, Micuroides euryxanthus). The copperhead is responsible for the vast majority of venomous snakebites in the United States.2
The Arizona bark scorpion (Centruroides sculpturatus) is the most dangerous scorpion species in the United States, responsible for the majority of scorpion sting-related hospitalizations and deaths. Furthermore, the market for exotic snake and reptile species continues to grow, and, in the United States, bites and stings from venomous exotic pet species are occurring with increasing frequency.6
The geographic areas most affected by snake and scorpion envenomation frequently are rural and generally have reduced access to quality emergency and critical care resources and treatments, such as antivenom.1,4,7 Decisions regarding using antivenom and other treatments, such as specific pharmacologic therapies (e.g., acetylcholinesterase inhibitors), blood product administration, and respiratory support, can be complex, and many clinicians lack significant background and experience in treating snake and scorpion envenomation. This review will focus on managing envenomations from North American snake and scorpion species, while providing discussion and background of the major snake and scorpion species that contribute to the wider global morbidity and mortality.
Ecology
There are three main families of venomous snakes: colubrids, elapids, and viperids, with elapids and viperids accounting for the vast majority of severe envenomations. The family Colubridae mostly is comprised of nonvenomous snakes (or snakes with venom that is minimally toxic to humans), with the exception of the boomslang (Dispholidus typus) and the twig snake (also known as the vine snake: Thelotornis capensis, Thelotornis kirtlandii, and Thelotornis mossambicanus), both of which are highly venomous and found throughout east and southern Africa. There are no species of colubrids with venom dangerous to humans found naturally in North America, although many specimens exist in zoos and as exotic pets, given the uniqueness, beauty, and coloration of these species.
Viperidae comprises an extremely diverse family of venomous snakes found throughout all continents of the world except Antarctica. North American members of the Viperidae family include the pit vipers (so named because of heat sensing pits just below the eyes), of which the multiple species of rattlesnakes are members, as well as the copperhead and the cottonmouth. These three species represent the vast majority of venomous snakebites in North America, with the copperhead being responsible for roughly 50% of venomous snakebites in this region.8,9 Globally, Viperidae includes a vast number of venomous snakes, including the puff adder (Bitis arietans) native to Southern and Eastern Africa; the saw scale vipers (also known as carpet vipers, genus Echis) native to sub-Saharan Africa, Arabia, and southern Asia; and the common European adder (Vipera berus).
The elapids are a diverse family of snakes, including the black and green mambas (Dendroaspis polylepis and Dendroaspis angusticeps), native to sub-Saharan Africa; the cobras (multiple species of the Naja and Ophiophagus genera, native to sub-Saharan Africa, Southern Asia, and Oceania); coral snakes; and the aquatic sea krait (genus Laticaudi). Oceania and Australia are notable for the presence of three highly venomous elapid species — the brown snake (Pseudonaja textilis), the inland taipan (Oxyuranus microlepidotus), and the tiger snake (Notechis scutatus). North America’s only naturally occurring members of family Elapidae are the three species of coral snake, found in Mexico and the Southern United States. Coral snake bites are rare and generally occur when coral snakes are handled or mistaken for nonvenomous snakes, since the banding pattern may be similar to harmless species, such as milk snakes or king snakes, which may have evolved similar coloration to mimic the more venomous coral snakes. Mnemonics, such as “red next to black, my friend Jack” or “red next to yellow, watch that fellow” may have some regional veracity, but, given variations in banding and color patterns across species and geography, they may be inaccurate and lead to misidentification.
Similar to venomous snakes, scorpions have a wide distribution across all of the continents of the world except Antarctica. The majority of severe envenomations occur in India, Iran, Africa, and the tropical and subtropical regions of the Western Hemisphere. Mexico is one of the countries most affected by scorpion envenomation, with an estimated 200,000 envenomations per year and resulting in several hundred deaths, although this number may be an underestimation.10 Scorpions do not bite, and envenomation occurs exclusively via sting. Scorpions avoid human contact, and most stings are either defensive or accidental.4,10 Less than 1% of all scorpion species are life threatening to humans, and most serious and fatal cases occur in the very young, the very old, or in patients with significant medical comorbidities.
Medically important scorpions include Hemiscorpius lepturus, native to the Middle East and Iran, and scorpions of the genera Tityus, Androctonus, Buthus, Parabuthus, Leiurus, and Hottentotta, which are widely distributed across the planet.
Scorpions of the genus Centruroides include multiple species and are found in the southern United States and Mexico. They include Centruroides exilicauda and Centruroides sculpturatus and are collectively known as the bark scorpion for their habit of living near or under tree bark. C. exilicauda and C. sculpturatus are found in Arizona, Texas, New Mexico, Southern California, and Mexico. Centruroides vittatus, also known as the common striped scorpion, is native to southwestern Texas, but its range extends north to Indiana and Illinois.11 Centruroides noxious is one of the most venomous scorpion species and is found in Mexico and Central America. Centruroides scorpions are responsible for nearly all severe cases of scorpion envenomation in the United States and Mexico.10,11
Venomology
Snakebite
Venom is a complex mix of proteins and enzymes, and venomous snakebites frequently produce a range of symptoms and effects. There also may be significant variation in venom composition, even among snakes of the same species, over different geographic ranges and at different stages in their development. However, general associations between snake family and expected venom toxidrome can be made. For instance, elapid venoms generally are associated with neuromuscular paralysis and the development of bulbar and respiratory muscle compromise. However, even in this case, significant diversity in venom effects exists, and elapid venom may produce complex and mixed toxidromes, with some species known for causing significant muscle and tissue destruction as well as dysregulation and consumption of coagulation factors, resulting in hemorrhage. Some elapids also can spit venom, which is thought to be more defensive than predatory. Venom streams generally are directed toward the face or eyes and with considerable accuracy, often at distances up to 3 meters. While no fatalities caused by elapid venom spitting have been recorded, corneal damage may occur, with resultant blindness.12-15
Neurotoxic snake venoms typically exert their effects at the neuromuscular junction, either at the presynaptic or postsynaptic membranes, or both. Venom-mediated presynaptic nerve toxicity may not be reversible; once the venom has been taken up by the presynaptic nerve, medical therapy or antivenom may have little impact. As a result, the rapid administration of antivenom is particularly important in regions known to have presynaptically acting snake venoms (Australia, South Asia, and Southeast Asia). Postsynaptic neurotoxins generally act by competitive inhibition of the postsynaptic acetylcholine receptor. This inhibition potentially can be overcome with antivenom and/or acetylcholinesterase inhibitor treatment (edrophonium or neostigmine). Acetylcholinesterase inhibitors serve to inhibit the enzyme-mediated clearance of acetylcholine from the neuromuscular junction, increasing the relative amount of acetylcholine available for receptor binding.3,8,15 (See Figure 1.)
Figure 1. Presynaptic and Postsynaptic Venom Effects |
 |
Pit viper venoms generally are associated with local, although occasionally systemic, cytotoxic and myotoxic effects. These venoms typically are comprised of a mixture of proteolytic and myotoxic enzymes, which may cause extensive and rapid local tissue damage, with possible systemic muscle and tissue destruction. Severe muscle breakdown can result in compartment syndrome and rhabdomyolysis, with resultant acute renal injury and hyperkalemia.3 Cytotoxic and myotoxic venom effects local to the bite may result in significant local tissue damage, may produce severe disability, and may require amputation of the affected body part.4,8,15,16
Viper venoms frequently produce derangements in coagulation, resulting in systemic hemorrhage. The mechanism of action of these venoms is variable, with multiple points of the coagulation cascade targeted in different ways by different components of a single species’ venom. Components of viper venom, including the family of venom enzymes known as the hemorrhagins, activate intravascular coagulation or fibrinolysis, leading to endothelial damage and the consumption of clotting proteins and platelets.15,16 Patients will demonstrate spontaneous hemorrhage at the bite site, injection site, or intravenous (IV) sites, as well as petechiae, epistaxis, and gingival hemorrhage. Death may occur from hypovolemia (secondary to internal and external hemorrhage) or central nervous system hemorrhage. The previously mentioned venomous colubrids produce venom that disrupts coagulation, producing an often-delayed coagulopathy that may be severe, resulting in death via central nervous system hemorrhage or hypovolemic shock.16,17
Hypotension and shock are common complications of snake envenomation. Shock that occurs rapidly after envenomation may be caused by anaphylaxis or vasovagal effects. Some snake venoms have been found to contain natriuretic peptides. The sum of these peptides may produce direct cardiotoxic effects and vasodilation, leading to cardiogenic and vasodilatory shock and inadequate response to the hypovolemia that may develop as a result of hemorrhage and third spacing.3,4,7,17
Snake venoms are diverse, and members of the same snake species may exhibit significant variations in their venom effects. Although pit vipers typically are thought of as producing cytotoxic and/or hemotoxic venoms, and elapids are associated with neurotoxic venoms, there is substantial variation. Bites from some vipers produce a mixed or even principally neurotoxic effect, while some elapids may cause significant local and systemic tissue and muscle breakdown, with or without derangements in coagulation, in addition to causing paralysis. The timber rattlesnake and the Mojave rattlesnake (Crotalus scutalatus), both pit vipers and members of Crotalidae, produce venom known to commonly cause flaccid paralysis and respiratory muscle weakness. Interestingly, juvenile rattlesnakes of several species seem to produce venoms with a higher content of neurotoxic venom components than do more mature rattlesnakes. This is thought to be because of the difference in target prey species between younger and older rattlesnakes, with younger snakes targeting small rodents or lizards, in which neurotoxic venom may be more helpful than hemotoxic or cytotoxic/myotoxic venoms.17-20
Scorpion Sting
Scorpion venoms exert their pathologic effect through a variety of mechanisms. H. lepturus venom causes tissue necrosis, cytolysis, and hemolysis and can result in rhabdomyolysis, disseminated intravascular coagulation (DIC), and hemolytic uremic syndrome (HUS). H. lepturus venom is similar in composition and molecular morphology to brown recluse spider venom and produces similar tissue destruction and necrosis. The complications of envenomation, as well as the renal failure that frequently develops, may lead to significant morbidity and mortality, particularly among very young patients.21,22
Venoms from scorpions of the genera Tityus, Androctonus, Buthus, Leiurus, and Hottentotta have alpha-toxins, which bind and activate sodium channels in the pre- and postsynaptic membranes of sympathetic and parasympathetic neurons, resulting in prolonged depolarization and sustained neuronal action potentials. This leads to an excessive, unregulated release of neurotransmitters, including acetylcholine, norepinephrine, and epinephrine, which can result in a clinical condition known as an autonomic storm. Autonomic storms can be marked by a dominance of either sympathetic or parasympathetic effects, depending on the venom.23,24 Scorpion venom from several species may stimulate the exocrine pancreas to release proteolytic enzymes, resulting in pancreatitis.25
The venoms of scorpions of the genera Centruroides and Parabuthus typically are associated with neuromuscular toxicity. Centruroides and Parabuthus scorpion venoms contain alpha-toxins similar to those found in Androctonus, Tityus, Buthus, Leiurus, and Hottentotta scorpions. However, Centruroides and Parabuthus venoms act principally at the neuromuscular junction, as opposed to the autonomic nervous system, causing a sustained and uncontrolled release of neurotransmitters and resulting in hyperactive and dysregulated activation of the muscular system. This can result in the agitated activation of multiple muscles, including the extraocular muscles, as well as the respiratory muscles, which can threaten respiration.26,27
Symptomology
Snakebite
The severity of snakebite envenomation depends on many factors. As discussed, some venomous snake species have been shown to modulate the enzymatic content of their venom as they develop, generating differences in the clinical effects produced by envenomation. Similarly, snake size has been shown to correlate with the amount of venom administered in several species.17-20 Furthermore, snakes of the same species may have differing venom content from one region to another. This diversity may reflect differing feeding and nutritional factors. Patient factors, such as age, volume of distribution, presence of comorbid illness, or medications/intoxicants also may contribute to the overall severity of a venomous snakebite. Additionally, it has been postulated that the rapid development of envenomation symptoms after snakebite might reflect incidental intravenous administration of venom. All this variability makes the severity of any given snakebite difficult to predict. Add to this the fact that a significant portion of snakebites from venomous snakes involve no envenomation at all. This phenomenon is termed “venomous snakebite without envenoming,” also known as “dry bite.”
Dry bites can be painful and result in inflammation and secondary infection, but they have no evidence of venom effect. The frequency of dry bites depends on the species of venomous snake, but the overall frequency may be as high of 50% of all bites and as high as 80% for some species.28 Venom is thought to be metabolically expensive to produce, so venomous snakes may benefit from being able to deliver warning bites or to somehow “meter” the amount of venom they administer in a given bite.19,29 Furthermore, because nearly 100% of all venomous snakebites against humans are defensive in nature (rather than predatory), venomous snakes may benefit from being able to retain their venom for use against prey.28,29 Similarly, coral snakes have smaller fangs and an inefficient means of administering venom. Thus, only 40% of North American coral snake bites involve clinically significant envenomation. The incidence of pit viper dry bites is 25%, with 35% of bites resulting in mild envenomations, 25% resulting in moderate envenomations, and 15% resulting in severe envenomations.17
The clinical effects of envenomation generally may be divided into local and systemic. More than 90% of North American pit viper snakebite envenomations involve some degree of local tissue damage.30 This may manifest clinically as swelling, erythema, lymphadenopathy, and/or ecchymoses.17 The majority of bites by North American pit viper species are painful, with some being extremely painful. However, only mild pain is noted in some envenomations, which may mislead clinicians about their severity. Rhabdomyolysis is rare among pit viper envenomations, but local tissue injury may be severe, resulting in elevated compartment pressures and tissue necrosis, particularly in cases where emergency care is delayed. Envenomation in the digits or in constricted compartments, such as the forearm, may result in more severe necrosis and eventual disability.17
Systemic symptoms of pit viper envenomation vary depending on the multitude of variables previously described. Nausea and vomiting are common early symptoms and may indicate the development of neurotoxic symptoms. Abdominal pain also may be present, and some patients report vertigo. Patients may complain of a strange taste in their mouths, or paresthesias at the bite site or in the perioral area. The first signs of motor paralysis may be reported as generalized feelings of weakness or double vision. Myokymia, or repetitive, fine muscle fasciculations, may develop independent of muscle paralysis and may be severe, contributing to respiratory muscle failure.31 Derangement of coagulation may manifest as persistent or abnormal bleeding at the bite site (bleeding from the bite site over an hour after the bite occurred is considered pathological), gingival membranes, urinary tract, gastrointestinal tract, or at IV sites. Extending ecchymoses may be visible at the bite site or elsewhere.
Vital sign abnormalities may be present after pit viper envenomation. Early hypotension may reflect anaphylaxis to venom, a vasovagal response, or direct cardiotoxicity and inappropriate vasodilation affected by angiotensin-converting enzyme inhibitors, bradykinin potentiating proteins, and natriuretic peptides, as previously described. Hypotension developing several hours after envenomation may reflect hypovolemia, resulting from hemorrhage and/or third spacing of fluids. Respiratory distress may be present either because of respiratory muscle paralysis or from cardiogenic pulmonary edema.17,23,24
The severity of North American coral snake envenomation varies greatly. In general, coral snake envenomation is uncommon because of the snake’s reticent nature, smaller fangs, and smaller venom delivery system. Envenomation by the Sonoran coral snake typically is mild, with no fatalities having been documented. North American coral snake venom has a predominantly neurotoxic effect, but the onset of symptoms may be delayed 12 to 24 hours after envenomation. Some local tissue damage may occur, but bites generally are unimpressive, and fang marks and swelling may be absent. Early symptoms include nausea and vomiting, paresthesias, and/or numbness. Bulbar weakness may follow, with ptosis and/or difficulty swallowing preceding generalized paralysis. Respiratory insufficiency or aspiration may occur as oropharyngeal and respiratory muscles are compromised.
Scorpion Sting
Most scorpion species globally produce only painful stings with mild, if any, systemic symptoms. The sting site may have only unimpressive swelling and erythema and may not always be identifiable. Although adults are stung by scorpions more commonly, children have long been known to develop more severe illness. Scorpion stings in Arizona commonly were fatal in infants and small children when left untreated throughout much of the 20th century.32
Most dangerous scorpion species globally produce neurotoxicity with or without local symptoms. H. lepturus stings are unique in that they only rarely involve neurotoxic symptoms, but they may cause severe necrosis with rhabdomyolysis and HUS.33,34 Scorpions of the genera Tityus, Hottentotta, Androctonus, Buthus, and Leirus inhabit wide ranges, including the Caribbean, South America, South and West Asia, and the Mediterranean. Severity of envenomation varies, with a significant proportion of patients reporting only local pain or paresthesias.
However, the venom of these scorpions may produce uncontrolled release of neurotransmitters in parasympathetic and sympathetic nerves, resulting in an autonomic storm. Autonomic storms may produce either cholinergic or sympathetic predominant symptoms, or, as has been suggested recently, periods of both, commencing with initial parasympathetic excess and followed by sympathetic overload.10 Cholinergic excess manifests as diaphoresis, bronchorrhea, salivation, bronchospasm, diarrhea, vomiting, bradycardia, and priapism. Priapism may be a common clinical finding in some scorpion envenomations and may correlate with the severity of envenomation.10
Sympathetic excess may persist for hours to days after envenomation and is marked by hyperthermia, hypertension, tachycardia, agitation, and delirium. Pulmonary edema and cardiogenic shock may develop and are the principal causes of death. The mechanism of cardiotoxicity may be mediated by direct venom effect or via catecholamine overload, with an escalation of systemic vasoconstriction and afterload contributing.35 Early respiratory distress may occur because of cholinergic excess and resultant bronchorrhea and bronchoconstriction. Sympathetic overload may result in respiratory distress because of left heart failure and subsequent pulmonary edema.10 Severe headache and meningismus may suggest subarachnoid hemorrhage. Altered mental status and signs/symptoms of increased intracranial pressure should cause concern for hemorrhagic stroke that may occur because of uncontrolled hypertension. DIC is an uncommon occurrence, but it may make central nervous system hemorrhage more likely. A grading system to guide treatment decisions has been developed for scorpion stings producing autonomic storms.35 (See Table 1.)
Table 1. Grading System of Scorpion Stings Producing Autonomic Storms35 | |
Grade |
Symptoms |
Grade 1 |
Local symptoms only |
Grade 2 |
Systemic autonomic symptoms |
Grade 3 |
Evidence of cardiotoxicity |
Grade 4 |
Progressive cardiogenic shock or other symptoms of multisystem organ failure |
C. sculpturatus, the Arizona bark scorpion, and related species (including scorpions of the genus Parabuthus from Southern Africa) produce venom that also causes uncontrolled release of neurotransmitters. However, instead of an autonomic storm producing circulatory and cardiopulmonary instability, C. sculpturatus venom produces predominantly neuromuscular symptoms. Patients of C. sculpturatus envenomation generally report minimal pain at the envenomation site, with only mild swelling and/or erythema. Infants may show only irritability or inability to be consoled. Approximately 10% to 30% of patients develop neurotoxicity, with children developing more severe symptoms and experiencing them more rapidly.36 Table 2 describes a severity grading system for scorpions producing neuromuscular toxicity.37
Table 2. Grading System for Scorpion Stings Producing Neuromuscular Toxicity7 | |
Grade |
Symptoms |
Grade 1 |
Local pain and paresthesias |
Grade 2 |
Local symptoms and remote symptoms (usually pain or paresthesias) |
Grade 3 |
Cranial nerve dysfunction or skeletal muscle dysfunction |
Grade 4 |
Cranial nerve and skeletal muscle involvement |
Grade 1, or minor envenomation, involves only pain and paresthesias at the sting site. The “tap test,” in which the patient is distracted before the possible sting site is tapped, causing worsening of pain, may assist in making the diagnosis, since this finding is not thought to occur with other stings. However, its diagnostic utility has not been rigorously evaluated. Given that the sting may not have been noticed initially and a puncture wound may not be visible, consider other differential diagnoses, including widow spider envenomation or toxic ingestion.
Grade 2 envenomation produces local pain and paresthesias as well as remote symptoms. Remote symptoms may include systemic symptoms or symptoms in the contralateral limbs.
Grade 3 envenomation produces either cranial nerve or skeletal muscle dysfunction. Autonomic dysfunction is not common but does occur and typically involves parasympathetic symptoms, including bronchoconstriction, bronchorrhea, vomiting, and salivation. Cranial nerve dysfunction often manifests as dysphagia or abnormal eye movements. Cranial nerve symptoms may first manifest as blurry or double vision, and patients frequently prefer to keep their eyes closed. Eye movements often are disorganized and can resemble a rotatory nystagmus. Inability to swallow or control secretions may contribute to respiratory distress. Skeletal muscle involvement resembles restlessness, with fasciculations, jerking of the extremity muscles, and opisthotonos. In infants, the skeletal symptoms may be difficult to diagnose.
Lastly, grade 4 envenomation involves both skeletal muscle involvement and cranial nerve involvement. Hyperthermia and rhabdomyolysis, thought to be secondary to skeletal muscle activation, may occur. Respiratory failure may develop secondary to autonomic abnormalities, including bronchoconstriction and bronchorrhea or failure of respiratory muscles.
Snakebite Treatment
Initial Management
The initial management of snake envenomation focuses on assessing and securing airway, breathing, and circulation (ABCs). Patients should receive oxygen if they are found to be dyspneic or hypoxic. Peripheral venous access should be obtained in an uninvolved extremity, and a crystalloid bolus should be provided (20 mL/kg IV) if the patient is hypotensive or if there is evidence of shock. Airway compromise, such as obstruction or inability to manage secretions or maintain patency, is an indication for endotracheal intubation. Snakebite patients should be calmed and prevented from walking, running, or making significant bodily movements unless safety demands it. Movement and agitation may promote venom circulation from the bite site. Some snake venoms have a very rapid onset of action, and patients may report ominous symptoms, such as weakness, dizziness, double vision, or severe pain within minutes of the bite. Emergency medical care should be sought if immediately available.
In the United States, identifying the culprit snake species is not as crucial as in other regions, given that most venomous U.S. snakebites are caused by pit vipers, and coral snakes are unique enough in appearance that they usually can be differentiated from pit viper species. Serious snake envenomation is a complex and relatively uncommon occurrence in much of the United States, and care decisions are best made with the consultation of a clinician with experience treating snakebites. The system of Poison Control Centers in the United States (1-800-222-1222) serves as a valuable resource to physicians and may assist in identifying a particular species, clinically managing patients, and helping identify nearby antivenom stores.
Pressure Immobilization
Pressure immobilization has been suggested as a technique to limit the spread of venom from the bite site. To perform pressure immobilization, the limb should be immobilized with a splint. An elastic gauze bandage or wrap should then be applied below the envenomation site, wrapping cephalad. The extremity should be immobilized, and the patient should be prevented from significantly moving. Pressure immobilization is distinguished from tourniquets, which interrupt arterial blood flow to an extremity. Patients with a pressure bandage in place should still have palpable distal pulses. Pressure bandages should not be removed until the patient reaches emergency medical care, since this may result in bolus release of venom from the bite site.
Pressure immobilization may be helpful in regions where snake venoms are known to have significant systemic effects while not exhibiting severe local tissue damage. In areas where snake venoms may cause substantial local necrosis, pressure immobilization may increase compartment pressures and local tissue destruction and risk compartment syndrome. In North America, where viper bites predominantly cause local tissue destruction and death is uncommon, pressure immobilization may be deleterious.16 Furthermore, studies also have demonstrated that pressure immobilization frequently is improperly performed, potentially leading to worse outcomes.37 In locations such as Australia, where several species exist whose predominant venom effect is via life-threatening, systemic neurotoxicity and where local tissue effects are more modest, pressure immobilization may have a role in reducing systemic venom spread until definitive care can be reached.
A similar discussion surrounds the issue of elevating or lowering an envenomed limb. Lowering an envenomed limb below the level of the heart will retard systemic venom elaboration, prolonging survival until definitive care can be provided. However, keeping an envenomed limb below the level of the heart may decrease venous drainage, particularly in a limb that is swelling, which may contribute to increased compartment pressures. Similar to pressure immobilization, further study is required to be able to definitively provide recommendations. However, in areas such as Australia, where snake species’ venoms are known to have life-threatening systemic neurotoxins and provoke less-active local tissue toxicity, lowering the envenomed limb below the level of the heart may impede venom spread. In most circumstances, maintaining the extremity at the level of the heart is a reasonable approach.
Treatments to Avoid
Many snakebite first aid interventions never have been shown to demonstrate any benefit to patients, and some may cause significant harm. Techniques such as burning, electrifying, or cauterizing the bite site have no proven benefit. There are no known herbal remedies or plant-based preparations that have any role in the management of serious envenomations. Techniques such as applying ice, cutting, or attempting to suck out venom (orally, or with an extractor device) from the bite site have no role in the management of snakebite. Lastly, tourniquets may contribute significantly to local tissue damage and ischemia, potentially worsening eventual disability and elevating the chance of amputation.3,5,8,9,17
Workup
Many snakebite patients can provide little information to suggest the culprit snake species or if the bite was dry. Some regions (Australia) employ the use of antibody-based venom tests to determine if a snakebite was venomous. However, negative tests may occur even in the setting of envenomation, and care should be directed by the patient’s clinical condition. In patients where severe toxicity is feared or suspected, such as in geographic regions with highly venomous snakes, observation for at least 24 to 36 hours usually is indicated.10
In addition to observation, diagnostic studies may be useful in evaluating for the presence of venom effects. Generally, laboratory studies are targeted at detecting evidence of significant muscle or tissue damage and/or coagulopathy. The following laboratory tests should be considered:
- complete blood count;
- electrolytes (including potassium and calcium);
- renal function (blood urea nitrogen and creatinine);
- creatine kinase;
- lactate;
- prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio (INR);
- D-dimer/fibrinogen;
- urinalysis;
- troponin I or other cardiac biomarkers.
Laboratory studies in patients of pit viper envenomation may demonstrate various abnormalities. The complete blood count typically will reveal an elevated leukocyte count. The hematocrit may be elevated initially because of hemoconcentration caused by third spacing of fluids and increased vascular permeability. However, progressive coagulopathy eventually may lead to hemorrhage and a declining hematocrit. Intravascular consumptive processes may lead to thrombocytopenia and anemia caused by hemolysis.
Peripheral blood smears may demonstrate evidence of schistocytes or spherocytes if microangiopathic hemolytic anemia or DIC is present. The presence of myotoxic and cytotoxic venom components may lead to derangements in blood chemistry testing, including hyperkalemia and elevations of creatine kinase. Renal failure may result as a direct effect of venom, shock, or myoglobin and/or hemoglobin deposition in the glomeruli. Transaminases also may be elevated, reflecting direct hepatic toxicity, shock liver, or nonhepatic necrosis of muscle tissue.
Coagulation studies, including PT, INR, and aPTT, may be elevated. Elevations in fibrin degradation products, D-dimer, and a concomitant decline in fibrinogen level demonstrates evidence of consumptive coagulopathy and DIC. In resource-limited settings, the whole blood clotting test can be used to provide a qualitative measure of coagulopathy. In that test, 2 mL of venous blood is drawn from the patient and placed in an empty glass test tube. The test tube should be free of any contaminants or preservatives. After 20 minutes, the tube is tipped a single time to 45 degrees to see if a clot is present. The absence of visible clot suggests coagulopathy.17
Close monitoring of urine output and urinalysis is critical. Declining urine output may be evidence of inadequate perfusion, shock, or renal injury secondary to rhabdomyolysis, hemolysis, or direct venom effect. Urinalysis may reveal evidence of rhabdomyolysis (positive for blood but negative for hemoglobin). Laboratory testing should be repeated at one- or two-hour intervals to assess for worsening or treatment effectiveness.
The electrocardiogram has an important role in assessing the cardiac effects of envenomation. Venom-mediated cardiotoxicity may manifest as bradycardia, atrioventricular conduction delay, or ST and/or T wave changes. Arterial blood gas can be very helpful in detecting evidence of declining ventilatory drive, with subtle increases in blood carbon dioxide preceding hypoxia as a sign of respiratory inadequacy (arterial punctures should be minimized if coagulopathy is suspected). Elevations in lactic acid and progressive anion gap acidosis may be evidence of tissue necrosis, shock, compartment syndrome, or renal failure. Multiple techniques are available for monitoring ventilatory force. Venous or arterial blood gas may reveal uptrending carbon dioxide levels portending mental status decline and eventual respiratory failure. Other tools, such as peak inspiratory flow meters, and measurements of forced expiration or negative inspiratory flow may be helpful in measuring the trend of ventilatory strength.
Direct venom testing has been a research tool for some time, with enzyme-linked immunoassays being used to generate qualitative and quantitative (dilutional) confirmation of venom presence, species of origin, and the potency of an antivenom’s effect. The only country to use venom detection kits routinely and clinically is Australia. These kits may be helpful in early differentiation between dry bites and envenomations as well as assisting in antivenom selection. While venom kits generally may be helpful in detecting envenomation, they may not be sensitive enough to allow for species differentiation between snakes of genetically similar genera.17
Wound Care
Snakebites may be at an increased risk for developing bacterial infection, but routine administration of antibiotics is not recommended. Gently irrigate and clean wounds without scrubbing or significantly manipulating the extremity. Tetanus prophylaxis should be administered, if appropriate.
Wounds should be monitored for evidence of infection, although inflammation associated with venom- or histamine-mediated reactions may mimic cellulitis and lymphangitic inflammation. Compartment syndrome is uncommon in snakebites but may complicate cases where bites occur in restricted compartments, such as the digits or the anterior tibia, and clinicians should have a low threshold for measuring compartment pressures. Recall that a loss of sensation and distal perfusion are late signs of compartment syndrome and, by the time these findings are noted, a disabling injury may have already occurred. If compartment pressures are measured and found to be elevated, the relevant specialist with experience in fasciotomy should be involved.
Osmotic diuretics, such as IV mannitol (1 g/kg), may be considered if patients are hemodynamically stable, and antivenom administration should be prioritized.17 Analgesia may be provided with acetaminophen or opiate pain medications as necessary. Nonsteroidal anti-inflammatory medications should be avoided, given their effects on the coagulation and renal systems.
Supportive Care
Patients of potentially venomous snakebites should receive standard medical supportive therapy. Close monitoring, laboratory draws at least every two hours, and assessments of neurologic function, wound appearance, and ventilatory ability should be performed. Shock should be treated with crystalloid boluses (20-40 mg/kg isotonic saline or Ringer’s lactate) until the patient is assessed to be euvolemic, then followed with IV pressor support medications as needed to maintain adequate mean arterial pressure. Antivenom therapy (discussed later) is critical to reversing venom-mediated cardiogenic and circulatory shock.
Rhabdomyolysis may manifest as elevated blood creatine kinase or liver enzymes (aspartate transaminase or alanine transaminase, in this case likely reflective of skeletal muscle injury along with or instead of hepatic injury, although direct hepatic venom toxicity has been described). Urinalysis may reveal a characteristic opaque brown color, positive for hemoglobin (the heme component of myoglobin) but negative for blood or red blood cells. Urine output may diminish, and markers of renal function, such as glomerular filtration rate, may decline. Patients with rhabdomyolysis should receive aggressive fluid resuscitation to support renal function, and urine output should be monitored closely with the aid of an indwelling catheter. Patients should be examined and periodically reassessed for the development of bulbar and respiratory muscle weakness. Serial cranial nerve examinations and measurements of ventilatory strength, such as end tidal carbon dioxide monitoring, blood gas sampling, and/or measurements of ventilatory strength, such as peak inspiratory flow, forced exhalation, and negative inspiratory force, should be performed to surveil for worsening ventilatory and respiratory strength.
Anticholinesterase agents may be considered in the treatment of snake envenomation that produces severe neurotoxic symptoms. Anticholinesterase medications may at least partially reverse postsynaptically active venoms by increasing the relative amount of acetylcholine in the synapse and overcoming postsynaptic venom-mediated receptor blockade. Patients may be given a test dose of edrophonium or neostigmine to determine if the venom’s effect may be at least partially reversed. Atropine (50 mcg/kg) should be administered just prior to neostigmine (0.04 mg/kg in children). Meanwhile, edrophonium dosing is 0.25 mg/kg in children.17
Derangements of the coagulation system are a frequent complication of viper envenomation. Laboratory parameters, including platelet count and PT/aPTT/INR, and fibrinogen/fibrin degradation products, are helpful in detecting worsening coagulation function. Patients should be clinically monitored, and signs of spontaneous hemorrhage, such as gingival hemorrhage, or persistent hemorrhage from the bite or IV insertion site should be noted. Patients with DIC or evidence of inadequate coagulation should not have arterial punctures or punctures in noncompressible locations performed. Patients may receive blood product support in the form of plasma and/or plasma concentrates to arrest hemorrhage, but the key to arresting venom-mediated coagulation derangement is the timely administration of the appropriate antivenom, which should precede the administration of blood products. Some patients even experience recurring coagulopathy days to weeks after pit viper envenomation, requiring repeat administration of antivenom.38
Antivenom
Antivenoms are solutions of antibodies (mainly immune globulin G [IgG]) developed and harvested from animals (typically sheep, horses, or cows) that have been inoculated with a given venom or venoms. Antivenoms essentially impart passive immunity against a single (monovalent) or multiple (polyvalent) venoms. Additionally, some antivenoms exist as a mixture of monovalent antivenoms. Polyvalent antivenoms may be useful in that they may impart immunity against a wide variety of venomous species in a region, making identification of the culprit snake species less critical. Antivenom potency may be limited by the divergence of a given species of snake and the diversity of venom proteins among members of the same venomous snake species. For instance, antivenoms developed against carpet viper species in Asia may be less potent against the venom of carpet vipers from other regions.39 Most antivenoms are administered intravenously, although some may be given intramuscularly (IM), although the IM route likely leads to slower systemic absorption.
Many antivenoms are preparations of the entire IgG protein, including two Fab proteins (where the venom binding occurs) and a single linking Fc protein. However, the principal side effect of antivenom administration is the potential for allergic reaction, which seems to be frequently mediated by the Fc portion of the molecule. Thus, some newer antivenom preparations include the active Fab proteins, while excluding the allergenic Fc component. While these preparations do have fewer associated allergic complications, they have shorter half-lives, often requiring repeat administrations.
Antivenom may cause life-threatening, immediate hypersensitivity reactions, such as anaphylaxis, and antivenom administration should be performed under close medical monitoring in emergency or critical care settings. Symptoms of immediate hypersensitivity reactions include urticaria, bronchospasm, vasodilatory shock, and airway obstruction. First-line therapy is IM epinephrine. Some studies have assessed the value of pretreatment with epinephrine, antihistamines, or glucocorticoids prior to antivenom administration, but this is not standard practice.17 Delayed type hypersensitivity reactions, including serum sickness, may occur days or weeks after antivenom administration. Serum sickness generally is not dangerous, and symptoms are temporary and may be treated with corticosteroids.
The most commonly available pit viper antivenom in North America is CroFab. CroFab is effective in treating envenomations from a wide range of North American pit vipers, but it has not been tested against all species, and some variation in potency may exist. Furthermore, as a Fab antivenom (no Fc fragment), CroFab has a half-life of only 12 hours, and repeat dosing often is necessary. Several cases have been published of rebound coagulopathy and thrombocytopenia, resulting in hemorrhage after initial antivenom treatment.40,41 Anavip, another polyvalent Fab fragment North American pit viper antivenom, has a longer half-life than CroFab and may reduce the incidence of recurrent coagulopathy.38
Antivenom potentially is life- or limb-saving, and its administration should not be delayed. The indication for antivenom is relatively straightforward: progressive or severe local symptoms, or the development of any systemic symptoms of envenomation, including derangements in laboratory testing. Antivenom is not dosed by weight or age, and because children receive the same amount of venom as an adult in any given venomous snakebite, they should receive the same amount of antivenom. Dosing of CroFab is as follows: Administer four to six vials (CroFab is produced in lyophilized vials that require reconstitution with 18 mL of sterile water) and monitor for progression. If, at one hour after initial administration, there is no improvement, administer another four to six vials. Once control is achieved, two vials should be administered every six hours for up to 18 hours.42 While antivenom may control and reduce many venom effects, including reducing compartment pressures and reversing coagulopathy, local tissue necrosis may not be reversible. There are no absolute contraindications to antivenom administration because all potentially negative effects should be balanced against the possibility of unchecked, progressive envenomation.
Table 3 (online at https://bit.ly/3GO7YWZ) summarizes the treatment of snakebites for patients in North America.
Scorpion Sting Treatment
Initial Management
Most scorpion stings will produce only local pain and swelling that requires simple analgesia and wound care. Even for these mild stings, observation (12 to 24 hours) may be indicated for the young, the old, and those with medical comorbidities. Analgesia may be accomplished with acetaminophen or opiates, although local nerve blocks with lidocaine or bupivacaine have been used.17 Wound care involves gentle cleansing, tetanus prophylaxis, and observation for signs of cellulitis. Empiric antibiotics are not indicated, and secondary infection is rare.
Supportive Care
The symptoms of scorpion envenomation may progress rapidly, and prehospital personnel or emergency department physicians should closely monitor vital signs and ABCs. Airway compromise secondary to dysregulation of neck or bulbar muscle function as well as excessive secretions may develop rapidly, requiring endotracheal intubation. Autonomic storm, resulting in bronchorrhea and bradycardia, may be treated with IV atropine. However, many patients presenting with an autonomic storm demonstrate signs and symptoms of both parasympathetic and sympathetic stimulation, and atropine should be avoided when patients begin developing adrenergic effects, such as hypertension and tachycardia.
The management of scorpion stings producing autonomic or neuromuscular toxicity depends largely on the severity of symptoms. For grade 1 and 2 stings, pain control with anti-inflammatory medicines and tetanus prophylaxis is all that is required. In envenomations of grade 3 or higher severity, intensive care unit (ICU) monitoring should be considered, and consultation with a medical toxicologist with experience in treating scorpion envenomation should be sought. In cases of grade 2 or higher envenomation with symptoms of systemic autonomic toxicity, prazosin should be considered. Prazosin is an alpha-1 adrenergic receptor blocker that has been shown to reduce the effects of sympathetic overload in patients with scorpion venom-induced autonomic storm (dosing in scorpion envenomation has not been evaluated, but prazosin is dosed 0.05-0.5 mg/kg/day orally divided every eight hours; start 0.05-0.1 mg/kg/day orally divided every eight hours — max 20 mg/day). Sodium nitroprusside (3-4 mcg/kg/min IV titrate to effect; max 10 mcg/kg/min × 10 mins) may be considered in severe afterload-mediated, cardiogenic pulmonary edema. Vasodilators such as nifedipine or hydralazine also have been used to lower blood pressure.
Patients with significant skeletal muscle involvement may benefit from the use of benzodiazepines. However, care should be taken to avoid oversedation, particularly if antivenom use is contemplated, since antivenom-mediated neutralization of circulating venom may lead to an exaggerated benzodiazepine effect. Acetaminophen or active cooling may be considered for patients with hyperthermia.
Evidence regarding the use of scorpion antivenom is limited, controversial, and varies depending on the region and culprit species. The reasons for this may lie in the fact that scorpion venom has a very rapid distribution and onset of action. Thus, agents that block the downstream effects of venom may be more efficacious than antivenom if even a short delay in treatment has occurred.17 Limited beneficial effect is suspected in cases of envenomation by Leiurus, Tityus, and Hottentotta species, and antivenom should be considered in the geographic regions where these scorpions predominate.17,19,20 In the United States, antivenom administration has been shown to have beneficial effects in cases of severe Centruroides envenomation.35 A previously used goat-derived (caprine) Centruroides antivenom was associated with high rates of both immediate and delayed hypersensitivity reactions and has been replaced by a Centruroides-specific F(ab')2 equine antivenom (Anascorp), which has been shown to improve the clinical course in children and has far lower rates of hypersensitivity reactions.42,43 In Mexico, an equine-derived scorpion Fab fragment antivenom with activity against several Centruroides species has been used for more than 10 years with low rates of hypersensitivity reactions and has seen limited use in the United States.43
Workup
The diagnostic workup in suspected scorpion envenomation should assess for systemic toxicity and rule out other diagnostic considerations, since a scorpion sting may not always be reported (particularly in infants) or in cases where the sting was not felt and a stinger wound is not obvious. Diagnostic studies are not necessarily indicated in simple scorpion stings without severe or systemic symptoms. The following studies should be considered:
- serum electrolytes, including potassium and calcium;
- complete blood count with peripheral blood smear;
- coagulation studies, including fibrinogen and D-dimer;
- creatine kinase;
- blood glucose;
- serum lactate;
- hepatic and pancreatic enzymes;
- blood urea nitrogen and creatinine/glomerular filtration rate;
- urinalysis.
Table 4 (online at https://bit.ly/3MgZDfI) summarizes the treatment of scorpion stings for patients in North America.
Conclusion
Although fatalities from snake and scorpion envenomation remain rare in North America, they are a significant public health challenge in many parts of the world. Ultimately, as long as humans live or travel within the habitats of these venomous species, potentially serious envenomations will continue to present to emergency departments. Numerous venomous species exist in North America, including multiple species of pit viper, three species of coral snake, and the bark scorpion.
Potentially serious envenomations frequently occur in some regions. Children are disproportionately affected by snake and scorpion envenomation and frequently manifest severe consequences of envenomation. Poison Control Centers provide an invaluable resource for managing these challenging and complex cases. Antivenom is a critical treatment and, in cases with evidence of significant toxicity, may be life or limb saving. However, preparation for allergic side effects, including anaphylaxis, is crucial. Further research is needed to establish strong evidence-based guidelines and better delineate the role of treatments, such as pressure dressings, in the clinical care of patients with snake or scorpion envenomation. Despite this, multiple resources and consensus guidelines exist to help guide care.
Information and Society Guidelines
- The World Health Organization’s snakebite envenoming page: https://www.who.int/news-room/fact-sheets/detail/snakebite-envenoming and https://www.who.int/health-topics/snakebite
- Toxinology.com’s online clinical toxicology resources and references: www.toxinology.com
- American Association of Poison Control Centers: 1-800-222-1222 or https://aapcc.org
- Wilderness Medical Society: https://www.wms.org/
References
To view the references, visit https://bit.ly/3anhxjn.
Although not a common problem, the knowledge and ability to manage venomous snakebites and scorpion stings is an essential component of the emergency medicine physician’s armamentarium.
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