Venomous Bites

EXECUTIVE SUMMARY

• The order Hymenoptera comprises a large range of stinging insects that includes bees, wasps, and ants. In the United States alone, stings from these animals are responsible for an estimated 60 deaths annually. The most pressing concern after a Hymenoptera sting is the onset of anaphylaxis, since this can be fatal after only a single sting and is the number one cause of death by Hymenoptera.
• In the United States, deer flies (Chrysops), horse flies (Tabanidae), and blackflies (Simuliidae) are the primary examples of blood-sucking flies. These flies use large mouth parts to pierce the skin of large mammals (including humans) and lap the exposed blood, creating a painful bite in the process. Treatment is largely symptomatic, and bite prevention with the application of insect repellent is heavily encouraged.
• Arachnids are eight-legged invertebrates that include spiders, ticks, mites, scorpions, and other various predatory or parasitic species. In North America, spiders and scorpions contain the most medically relevant and dangerous species for the clinician.
• Classically, black widow spiders have a red hourglass marking on their abdomen. The female spiders are larger and poisonous, whereas the males are not. Local symptoms can give way to more severe systemic symptoms, specifically chest pain for an upper body bite or abdominal pain for a lower body bite. The general treatment for these symptoms includes benzodiazepines, along with tetanus vaccine administration, appropriate analgesia with nonsteroidal anti-inflammatory drugs, and, if pain is severe, opioids.
• Crotalids, or pit vipers, are found throughout tropical and temperate areas of the world. In North America, this group includes rattlesnakes, cottonmouths, and copperheads. They are identifiable from other snakes by several distinguishing characteristics. They have heat-sensing pits on the sides of their mouth (hence the name “pit viper”), slitlike vertical pupils that resemble cat pupils, and large hinged fangs that provide a very painful bite. In the United States, treatment often involves antibody fragment antivenom, known as CroFab. The antivenom should be administered if the patient is beginning to experience systemic effects, such as an elevated prothrombin time, life-threatening bleeding from the consumptive coagulopathy, and spread of the edema, particularly to sensitive areas, such as the neck.
• Jellyfish of the class Cubozoa, or “box jellyfish,” are the ones most often responsible for fatal reactions and have been associated with lethal envenomations in Australia, Indonesia, New Guinea, and surrounding waters. Immediate removal from the water is of primary importance. Fortunately, the immediate first aid treatment modalities are the same for all jellyfish stings, and deactivation of the nematocysts is of paramount importance, since they will continue to inject painful and potentially dangerous venom. Three effective treatment modalities exist: immersing the site in hot water around 40-45°C, soaking the area in acetic acid (vinegar), or applying a thick paste of water and baking soda.

Humans increasingly invade the environments of venomous creatures. The authors provide a review of venomous creatures and what acute care providers need to manage the patients affected by them.

— Ann M. Dietrich, MD, FAAP, FACEP, Editor

Throughout North America and the remainder of the world, there are a myriad of creatures people encounter in daily life that can be venomous. It is important to recognize that a creature is known as venomous if it possesses the ability to inject a detrimental chemical through a bite, a sting, or a specialized structure. Although most organisms that are capable of injecting venom leave no more than a painful bite or sting, a handful of them are dangerous to life or limb and are of medical importance. Venoms differ by species and can include four groups: cytotoxins, neurotoxins, myotoxins, and hemotoxins. Whether they fly, slither, or swim, many poisonous creatures can be found in environments to which humans expose themselves every day. From venomous spiders hiding within our homes, to dangerous jellyfish lurking in the water of our beaches, to snakes that inject a potent cocktail of toxins when provoked, acute care providers should have knowledge of medically important venomous creatures. This report will discuss the most important venomous organisms that can be found in North America, along with epidemiology, signs and symptoms of venomous bites, and treatments.

Insects

The order Hymenoptera comprises a large range of stinging insects that includes bees, wasps, and ants. In the United States alone, stings from these animals are responsible for an estimated 60 deaths annually.¹ Many of these deaths are the result of anaphylaxis from the venom inside of the sting. However, even without anaphylaxis, the stings often are quite painful and create significant morbidity and sometimes mortality given a sufficient number of stings.² This order shares a common bond where the ovapositor of the female worker (known as a drone) has a stinger that can be quite painful itself but also injects the painful and sometimes lethal venom. In North America, there are several different dangerous bees, large hornets, and aggressive ants that produce stings that range from annoying to immediately life-threatening when received in large numbers. In North America, Africanized honey bees represent a substantial risk to both humans and livestock in the southern United States, mostly because of their swarming and aggressive behavior. (See Figure 1.) Fire ants, which also are not native in the United States, are well established in areas of the southern United States and continue to encroach further north every year. (See Figure 2.) Personnel who are at especially high risk for Hymenoptera stings are farmers, ranchers, house painters, highway workers, construction machinery operators, and emergency personnel assisting others in flooded areas.³ These personnel usually are not equipped for the possibility of a Hymenoptera sting and often are not checking their equipment or environment for the presence of these insects.

Stings are common to the head and neck area, followed by the limbs. Stings are noted on the trunk and abdomen usually only in more severe cases. Oral stings can occur when these animals become entrapped in a cup of sweet beverage and then are ingested. The venoms of these organisms vary by species, but almost all contain histamine and phospholipases, which are responsible for the localized reaction seen and most anaphylactoid reactions.⁴ A typical drone injects approximately 140-150 mcg of venom per sting, and with a median lethal dose (LD50) of 2.8 mg to 3.5 mg of venom per kg, approximately 1,500 stings are needed to provide a 50% fatal dose in an average human, although there are case reports of deaths from as few as 500 stings.⁴ Immediate treatment includes removal of the stinger, local wound care, and monitoring for anaphylaxis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and antihistamines can be used for symptom control.

Ants of the genus Solenopsis, or fire ants, have invaded many areas of the Southern United States. Originally from South America, these invasive ants have thrived in their introduced habitat, displacing other native ant species. They represent a great nuisance to gardeners, farmers, and ranchers. These small, reddish ants are named for the burning sensation their stings deliver. Their bite also has a particular appearance, with a red base with a white overlying pustule. Occurring in large mounds, these ants often are more aggressive than native ants. Although not considered acutely dangerous to humans, fire ants can trigger anaphylactic reactions. Individuals with previous anaphylactic reactions to other Hymenoptera venoms are at increased risk. Small children and older adults who fall into their large mounds are at particular risk. The LD50 of the venom in rats was demonstrated at 0.36 mg/kg, and with each ant carrying 0.5 mcg of venom, a toxic envenomation in a 1-kg rat is approximately 720 stings.⁵

The other assorted wasps, hornets, and flightless wasps that make up Hymenoptera all have similar venoms of varying potency. Found in Texas and the desert Southwest, the large tarantula hawks of the genus Pepsis are large, parasitoid wasps that possess extremely large, painful stingers that are described as producing some of the most painful of all Hymenoptera stings. These wasps are very large and strong, growing up to 6 cm in length. They are capable of dragging a much larger tarantula they have immobilized with their venom, within which the female wasp lays eggs that hatch parasitic larvae. (See Figure 3.) Although the stings of these wasps are extremely painful, the treatment is largely supportive. Opioid pain medications may be considered, since the pain can last for several hours if left untreated.

Wasps of the family Mutillidae, also known as “velvet ants,” also are worth a mention because of the common misconception that their venom is potent enough to kill bovines, hence their other common name of “cow-killers.” (See Figure 4.) Brightly colored, ranging from amber to bright red, they exhibit aposematic coloration to warn other organisms about their potent sting. Commonly encountered in wooded settings and mulch piles, these organisms are common throughout the Southeastern and Southwestern United States. The sting is described as extremely painful, often lasting several hours. As with the stings of the Pepsis wasps described earlier, the care of the sting is largely supportive and is not actually lethal despite widespread belief to the contrary. Ice packs, NSAIDs, intradermal local anesthetic, and, if required, systemic opioids all are reasonable treatment options.

The most pressing concern after a Hymenoptera sting is the onset of anaphylaxis, since this can be fatal after only a single sting and is the number one cause of death by Hymenoptera. The presence of a sting followed by a scratchy sensation in the mouth and rapid breathing with significant skin flushing, as well as syncope, tachycardia, pallor, or gastrointestinal upset, all are concerning signs that an anaphylactic reaction may be occurring. Epinephrine (1:1,000) 0.5 mL should be administered intramuscularly at the first indication of a serious hypersensitivity reaction.⁶ Epinephrine autoinjectors can be used in the prehospital and hospital setting. Oxygen should be administered if the patient is hypoxic, their blood pressure should be supported with the use of norepinephrine if required, and antihistamines, such as diphenhydramine at 25 to 50 mg intravenous (IV) and ranitidine 50 mg IV as well as steroids also are indicated.⁶ For nonanaphylactic reactions, ice packs, oral or topical antihistamines, and oral NSAIDs for pain control are indicated. It is important that the stinger be removed, generally with the use of forceps or by brushing it off. There should be no concern about squeezing the venom sac unless the residual venom sac from the organism that stung the patient is large in size.³ Young children are particularly susceptible to the toxins from the stings because of their smaller size and, depending on their age (especially if very young), their inability to remove themselves from a sting situation, which places them at greatest risk for a greater number of stings.⁷ Adults who have severe presentations or who have used multiple doses of epinephrine should be admitted for observation, whereas mild cases that received epinephrine and are symptom free four hours after epinephrine is given can be discharged with close follow-up. If the patient cannot be observed for four hours, overnight admission is encouraged.

Biting Flies

Although not nearly as dangerous as Hymenoptera, biting flies are worth mentioning, since they are a great nuisance to anyone exposed to them. In the United States, deer flies (Chrysops), horseflies (Tabanidae), and blackflies (Simuliidae) are the primary examples of blood-sucking flies. (See Figure 5.) These flies use large mouth parts to pierce the skin of large mammals (including humans) and lap the exposed blood, creating a painful bite in the process. Although rare, there are at least 30 case reports of these flies producing an anaphylactoid reaction, with some cross-reactivity with persons with previously documented anaphylaxis to Hymenoptera.³ Treatment is largely symptomatic, and bite prevention with the application of insect repellent is heavily encouraged. Of clinical significance in tropical Africa, the parasitic disease onchocerciasis, or “river blindness,” is spread by blackflies endemic to river bottoms.⁷ Care should be taken to prevent bites from flies in these endemic regions.

Arachnids

Arachnids are eight-legged invertebrates that include spiders, ticks, mites, scorpions, and other various predatory or parasitic species. Many of these possess venom, but not all are medically relevant, since they often leave only a painful but harmless bite or sting. In North America, spiders and scorpions contain the most medically relevant and dangerous species for the clinician. Knowledge of these can help the clinician determine next steps to take to care for the patient.

Spiders

One of the most famous of the venomous spiders belong to the genus Latrodectus, more commonly known as black widow spiders. They have been found in all parts of the United States with the exception of Alaska.⁸ These spiders can be found in dark, damp places, such as woodpiles, old buildings, and closets, where they most often encounter humans. Their distinctive look gives rise to their name: Black widows have a jet-black coloration, with a small cephalothorax and a larger abdomen, giving them a rotund shape.⁹ Classically, black widow spiders have a red hourglass marking on their abdomen, but it should be noted that this is only present for one of the species of Latrodectus, specifically Lactrodectus mactans.¹⁰ (See Figure 6.) The female spiders are larger and poisonous, whereas the males are not.¹¹ It is thought that they are responsible for approximately 2,500 human bites per year, with varying degrees of envenomations.¹² Black widow spiders usually bite only when their web or home is disturbed, and their bite often can go unnoticed initially or may be just felt as a pin prick. The bites initially can cause local irritation, followed by erythema. The majority of bites occur in older homes and sheds where the spiders hide among the detritus. Old shoes and boots are another common source of bites when unsuspecting victims place their feet into these previously undisturbed articles.

The black widow venom contains a unique compound, alpha-latrotoxin, which can act on synaptic vesicles and motor end plates to cause neural depolarization leading to uncontrolled acetylcholine release. This causes calcium to flow into muscles cells, causing muscle spasms, sweating, and muscle rigidity.^8,9 In murine models, the LD50 of the toxin is 40 mcg/kg, and, although rare, an adult spider is capable of delivering a fatal bite, especially in children.¹⁰ Local symptoms can give way to more severe systemic symptoms, specifically chest pain for an upper body bite or abdominal pain for a lower body bite. Due to muscle spasms, trismus can be present, or the patient’s abdomen can be so tender and rigid that it resembles an acute abdomen.^8,9 Additional systemic symptoms can include high blood pressure, salivation, sweating, seizures, and psychosis.⁹

The first-line treatment for these symptoms includes IV benzodiazepines, such as lorazepam 1 mg IV for spasms. Appropriate analgesia includes NSAIDs, and, if pain is severe, systemic opioids.^8,9 Previous literature has suggested the use of calcium gluconate to stabilize the cell membrane, but this has been shown to be ineffective.⁸ If spasms are severe, examining for and treating rhabdomyolysis is prudent to prevent systemic kidney injury. If the symptoms are more severe, antivenom (Antivenin Lactrodectus mactans) at a dose of one to two vials diluted in 100 mL of 0.9% sodium chloride is indicated for systemic illness, although use is controversial because of relatively low overall mortality and the potential for anaphylaxis or serum sickness reaction to the antivenom itself. Contact the poison control center for antivenom recommendations. Overall, the prognosis for these patients is good, with only a few documented cases of death worldwide reported.⁸

The Steatoda genus is another group of spiders that exist throughout the world and belongs in the same classification family as Latrodectus. Their similarity to Latrodectus in appearance even earned them the nickname “false black widow spiders,” and they can be mistaken by the patient for black widows on report of the bite. Their bites create local symptoms similar to black widow bites, although their bites are considered to be less severe. Although this generally is true, more severe cases have been reported, with significant symptoms overlapping with the earlier description of Latrodectus severe reactions. For this reason, it has been postulated that the same antivenom used for black widow spiders could be used for this species, but there is no sufficient evidence to support this in the literature. Therefore, treatment focuses primarily on supportive care and local wound dressing, with considerations for follow-up for the patient in a wound clinic. Benzodiazepines could be considered if spasms occur and are severe enough to warrant treatment. Tetanus should be updated in patients experiencing false black widow spider bites as well.

Other spiders known to inhabit North America include the recluse spiders. The term recluse spider actually includes six separate species of spider, of which Loxosceles reclusa is the most common.⁹ These spiders are most active during the spring to fall, and they usually only bite humans during accidental encounters.⁸ Entomology studies have demonstrated significant numbers of these spiders living in homes throughout the South and Midwest United States, with as many as 2,000 spiders being found in a single Kansas home over a period of several months.¹³ Like the black widow, L. reclusa likes to hide in refuse around old homes and sheds, where the spider can occupy small nooks and crannies. Humans come into contact with them when these items are disturbed during cleaning or reorganization. Concerningly, the sheets of bedding are another place this spider can be commonly found.

Famously, the venom of L. reclusa produces an ugly necrotic lesion that can take some time to heal and can be of significant psychological trauma to patients. (See Figure 7.) However, because of the common occurrence of bacterially mediated necrotic skin lesions, the spider is unfairly accused of as many as 2,500 bites reported to U.S. poison control centers each year, many of these in areas without endemic recluse spiders.¹³

Like other protease-heavy venoms described herein, the venom of the brown recluse spider acts directly on cell walls. It causes immediate injury and cell death. This leads to local tissue destruction, and this cell wall damage can be followed by a cascade of clotting abnormalities and a resulting necrotic ulcer that develops over days. This ulcer is characteristic of the brown recluse spider bite, which is referred to as necrotic arachnidism.⁸ There also is a documented immune reaction to the phospholipase-D in this chemical venom mixture, which also is responsible for the necrotic tissue ulcer.¹² The immune component of this reaction is partially responsible for the wide range of reactions seen to L. reclusa bites.¹²

For a patient experiencing such a bite, the clinical response can vary from just local irritation to a full systemic reaction that can be life-threatening. More severely affected patients can experience coagulopathies, hypotension, seizures, and renal failure. Although quite rare, disseminated intravascular coagulation (DIC) is the feared lethal complication of these bites. The treatment of DIC should be done with guidance from expert hematology and/or critical care consultation. Supportive care is the mainstay of treatment, while antibiotics could be considered if there are signs of secondary infection, although this type of secondary infection is uncommon.^8,9 Should signs of secondary infection develop, dapsone generally is recommended at 50 mg per day, based on case series and expert opinion, with wound cultures guiding the remainder of the therapy.¹² Hyperbaric therapy also may be indicated as part of the rehabilitation process of the wound that has poor secondary wound healing.¹²

Found in the Pacific Northwest of the United States and Canada, the hobo spider (Tegenaria agrestis) is another well-known North American spider. Although believed to have some behaviors similar to the recluse spider, the hobo spider generally is considered to be more aggressive.¹³ Their bites can cause local inflammation. Rarely, systemic reactions have occurred. If a patient presents after one of these bites, a tetanus shot should be administered. Antibiotics generally are contraindicated unless there is a concern that the patient is experiencing a secondary infection. Bites from the hobo spider can rarely cause a necrotic reaction, and there is no consensus opinion on any treatments that minimize this reaction.¹³ Dapsone has been suggested in the past as a means to decrease scarring, but there is no study to date that shows any efficacy with this treatment. In almost all cases, these patients should be able to be sent home from the emergency department after a period of observation.¹³

Spiders of the Phoneutria genus exist primarily in South America, with a large percentage from Brazil. One of the most common of these to cause bites is the Phoneutria nigriventer, also known as the armed or banana spider. These spiders have a mixture of proteins and other molecules that act on ion channels affecting neurotransmitter release.¹³ A unique aspect of these spiders is that they catch their food by active hunting and do not construct webs. Bites from these spiders can cause variable pain, but they usually do not leave fang marks. Local effects, such as erythema, tenderness, and local diaphoresis, can occur. Systemic symptoms from these spider bites have been noted to include nausea, vomiting, autonomic effects, and, in some cases, priapism. Death has been reported in rare cases. However, most cases represent mild envenomation where the ideal treatment includes supportive care, warm compresses, and systemic analgesia. Antivenom can be considered for the more severe envenomations, and it is recommended that the patient receive the antivenom within three hours of the initial bite.¹³

A discussion of venomous spiders would not be complete without mentioning funnel web spiders from the Atrax and Hadronyche species. These spiders are considered the deadliest spiders in the world.¹³ By the same token, their impact from a lethality standpoint is mitigated by the fact that they are primarily confined to the eastern Australia region, a less populous area. They do not interact with humans often, and even when a funnel web spider does bite a human, envenomation rarely occurs with their bite, called a dry bite.

Funnel web spiders can be found on the ground and in trees, and most bites are believed to occur during mating season when males are searching for females.¹³ Their venom has small peptide neurotoxins that act on sodium channels, leading to the clinical effects seen in patients. Patients can experience systemic neuromuscular and autonomic excitation, as well as pulmonary and cerebral edema in some cases. Nonspecific vomiting, headache, and fatigue can occur as well. Late effects for the most severe cases can include hypotension, which can lead to multi-organ failure. Even when the patient does not sustain a bite that introduces venom, local discomfort and pain can occur as a result of the size of the fangs.

For immediate treatment of a suspected envenomation, a pressure bandage/immobilization should be placed if it has not already been placed in the field. Antivenom (known as FWSAV) is crucially important, and it should be given as soon as possible after envenomation.¹³ Case reports support its use, and it appears to be effective for all species of funnel web spiders. One important consideration is that there are other spiders in this region that resemble the funnel web spider in appearance. This can lead to confusion for patients and practitioners alike. Therefore, a standardized approach would be to monitor a patient for four hours for systemic symptoms. If none occur, a patient can be safely discharged.¹³

Tarantulas

Large, hairy Theraphosidae spiders, commonly known as tarantulas, may look dangerous because of their impressive size but are generally harmless. Their large chelicerae, which resemble fangs, can cause a painful bite when the spiders are provoked. Tarantulas are covered in spines that resemble hair, which can be shed as a defense mechanism and create localized irritation in the form of urticaria on the skin and keratitis in the eye.⁸ Given their popularity in the exotic pet trade, tarantulas from all over the world can be found in the United States.

There are case reports of muscle spasms from tarantula envenomation that can last a couple of days or weeks.¹⁰ Their venoms are not as well understood as that of other spiders, but an isolated compound unique to tarantulas, heteroscodratoxin, causes inhibition of voltage-dependent potassium channels.¹⁰ Injections of the poison into mice demonstrate severe muscle spasms, which then cause respiratory arrest.¹⁰

Supplemental magnesium for symptom relief has been demonstrated, but the effect is temporary.¹⁰ Overall, care should be supportive, with NSAIDs for pain control, since the venom from a single tarantula bite is unlikely to have lasting sequelae.⁸ Tetanus should be updated, and local wound care should be used. Tape is a good way to remove irritating hairs from skin. If the eye is involved, tetracaine and an eye shield should be given, and the patient requires ophthalmology consultation. Patients exhibiting more severe spasms should be kept overnight for observation and supportive care until they improve.

Scorpions

Scorpions are armored, impressive-appearing arachnids with two claws and a mobile tail equipped with a large, venom-injecting stinger. Inhabiting dark spaces, forests, and fields, scorpions often come into contact with humans, with an estimated 1.2 million stings per year worldwide, resulting in approximately 3,000 deaths.^3,8,14 Their venoms are a complex mixture of collagen digestants, protease inhibitors, histamine activators, and neurotoxins, all with concentrations that vary by species.¹⁴ Although the stings are universally painful, most scorpion venoms are not life-threatening to adults, but children are more sensitive because of their smaller body mass.

In North America, scorpions that inhabit Mexico and the Southwestern United States are a cause of tremendous morbidity, with an estimated 250,000 stings annually.³ The petite, often yellow scorpions of the genus Centruroides, colloquially known in the United States as bark scorpions, are the most clinically significant ones in North America. (See Figure 8.) These scorpions produce a wide range of signs and symptoms in their human victims, including, but not limited to, nausea, emesis, dyspnea, tachycardia, bradycardia, diarrhea, and hyperthermia.^3,14 If stung, the patient should be treated symptomatically. If the envenomation is found to be severe, with unstable vital signs or altered mental status, treatment with an equine antibody antivenom, known as Anascorp, recently approved by the Food and Drug Administration, is indicated. Treatment should be initiated as soon as possible if systemic symptoms exist. The initial dose should be three vials, with additional vials given every 60 minutes if symptoms persist.

Scorpion stings outside of North America, particularly in Northern Africa and the Indian subcontinent, often are more dangerous, since there are species containing both cardiotoxic or neurotoxic venoms.^3,14 Famously, some of these scorpions, particularly in the Middle East and the Caribbean, have venoms that act as potent secretagogues, causing pancreatic hypersecretion resulting in pancreatitis.¹⁷ Of note, the Trinidad thick-tailed scorpion, Tityus trinitatis, is the scorpion responsible for many of the cases of scorpion-mediated pancreatitis in the Caribbean area. Related Tityus scorpions also are found in South America and are equally dangerous, with victims often developing pancreatitis and requiring intensive care unit (ICU) care. ICU admission for scorpion stings because of pancreatitis, takotsubo cardiomyopathy, and other severe systemic symptoms also is common in areas with dangerous scorpions, such as North Africa and India.¹⁸

Of special note is the Indian red scorpion, Hottentotta tamulus, considered to be the world’s most dangerous scorpion.¹⁹ The sting of this scorpion causes significant pulmonary edema in addition to the other effects of scorpion venom described earlier and has a fatality rate as high as 22%.¹⁹ Treatment for stings from these scorpions is accomplished through a combination of anti-venom and supportive care.^20,21 As with the Centruroides scorpions, children are at particular risk from these scorpions because of their lower body mass.

As with other envenoming creatures, education on the species found locally and their dangerous venoms should be obtained prior to venturing into the habitats of these organisms. If on expedition or practicing remotely, evacuation should be considered before the onset of dangerous symptoms, especially if the offending scorpion can be identified. Occasionally, a dangerous scorpion sting may result from a person handling one via the exotic pet trade or as a zoo keeper maintaining an exhibit of these animals. If this is the case, a careful history should be obtained and treatment should be supportive. A consultation to your local poison control center would be prudent when treating one of these rare envenomations.

Snakes

Many venomous snakes are found throughout North America and the world. Primarily, these are the crotalids and the elapids, with the crotalids being far more common in North America and representing a much more substantial portion of the disease burden. The two groups are described in the following sections.

Crotalids, or pit vipers, are found throughout tropical and temperate areas of the world. In North America, this group includes rattlesnakes, cottonmouths, and copperheads, which, combined, are responsible for approximately 2,500 envenomations in the United States each year. Snakebites result in significant morbidity to patients and cause five to six deaths per year.²² These snakes generally are of a modest size, usually less than 4 feet, but specimens of Eastern diamondback rattlesnakes have exceeded 2 m. (See Figure 9.) Their size is important because the striking distance for these animals is approximately 50% of their body length.³ Pit vipers are identifiable from other snakes by several distinguishing characteristics. They have heat sensing pits on the sides of their mouth (hence the name “pit viper”), slit-like vertical pupils that resemble cat pupils, and large hinged fangs that provide a very painful bite, even if it does not result in envenomation.

Crotalid venom consists of a cocktail of tissue-destroying metalloproteinases, thrombin-like procoagulants, and phospholipase-A₂ neurotoxins, with the concentrations of the two varying by the species and the age of the snake.^3,22 Crotalids possess a degree of control in the amount of venom they inject and have been shown to inject more venom with defensive bites, with approximately 80% of defensive bites injecting some venom, and 10% of these resulting in severe envenomation.³ As with other envenomations, children are at greater risk of severe symptoms, given their smaller body mass.²³

Bites often are painful because of the size of the snake’s fangs, but injection of a large amount of venom produces a rapid reaction, resulting in a discoloration of the area and significant pain and swelling. The metalloproteinases create localized tissue destruction within a very short period of time, resulting in rapidly progressing edema that can travel some distance from the site of envenomation, sometimes as soon as 60 minutes post-bite.¹⁸ Thrombin-like complexes activate clotting without the clotting cascade, creating a paradoxical prothrombotic state through consumptive coagulopathy, often with systemic effects, an elevated prothrombin time (PT), and thrombocytopenia.²⁴ With all envenomations, especially in repeat victims, anaphylactic reactions can occur.¹⁸

As with any wilderness injury, ensuring that the patient’s airway is secure, their breathing is intact, and their circulation is attended to are the paramount first steps. Bites to the face and neck are of significant concern for rapid airway compromise. In limb bites, take care to ensure that the patient has adequate limb perfusion during transportation and definitive care because of the edema these bites can cause. Because of the coagulopathic nature of the toxin, PT/partial thromboplastin time (PTT)/international normalized ratio (INR) and fibrinogen should be ordered, along with a basic metabolic panel and a complete blood count.

In the United States, treatment often involves antibody fragment antivenom, known as CroFab. An older antivenom made by Wyeth still may be available in some hospitals, and a new Fab2 antivenom known as Anavip is now available. All of these antivenoms are very costly, which is a barrier to stocking them widely. The antivenom is indicated if the patient has systemic effects such as an elevated PT, has any life-threatening bleeding from the consumptive coagulopathy, and/or rapid spread of the edema, particularly to sensitive areas such as the neck.²² The accepted treatment is four to six vials of antivenom dissolved into 100 mL of normal saline infused over a one-hour period, with additional doses given as symptoms dictate over the next 24-48 hours.^3,22

Nonpharmacological treatments include tourniquets and fasciotomies, but their use has been largely discredited and even shown to cause the patient harm in the form of limb loss and worse functional outcomes.^15,23 The edema caused by a limb bite from one of these animals often resembles compartment syndrome, but a true compartment syndrome is quite rare in crotalid bites. Compartment pressures must be documented if there are clinical concerns.^3,24 Analgesia must be provided to ensure patient comfort, and both opioids and regional anesthetic blocks have been demonstrated to have good results.²⁵

Discharge planning can be considered once the patient’s laboratory values have stabilized, their pain is controlled, and their mobility concerns have been addressed. Admission for all envenomations is indicated for monitoring of the patient’s coagulopathy and pain control. Close follow-up within a couple of days after discharge is highly advised to ensure the swelling continues to diminish and the patient does not have any recurrence of the coagulopathy.³

Elapids comprise the other group of venomous North American snakes, a group that includes coral snakes, mambas, and kraits. In the United States, only the coral snakes (Micrurus) are found in the wild. Envenomation from the exotic species found in zoos and the exotic animal trade do occur.²⁰ Brightly colored with red, black, and yellow bands, other snakes have evolved with Mullerian mimicry to resemble these snakes. A common mnemonic to differentiate coral snakes from these mimics is “Red on yellow, kill a fellow; red on black, venom lack,” since the coral snakes of North America all have red bands touching their yellow bands, whereas the mimics have red bands touching black bands. Of the total snake bites reported in North America, elapids are responsible for 20-50 cases of snake envenomations each year.

Although they have a neurotoxic venom with potentially lethal systemic side effects, coral snakes are not as aggressive and possess smaller fangs and, therefore, a less effective venom delivery system. (See Figure 10.) Elapid venom is primarily composed of phospholipase-A₂, which blocks acetylcholine release, and three-finger toxins (TFTs), which block the activation of the nicotinic acetylcholine receptors on muscle tissue.²¹ Unlike pit viper venom, the venom of coral snakes is effectively delivered only approximately 40% of the time. Patients present primarily with neurotoxic symptoms, typically paresthesias, numbness, or weakness.³ The systemic signs of nausea, vomiting, headache, and abdominal pain can be delayed about 13 hours.³ Severe cases may involve cranial nerve dysfunctions, peripheral motor nerve dysfunction, and respiratory insufficiency requiring ventilation. Since envenomations of this severity are rare, other causes of altered mental status and ascending paralysis should not be overlooked.

There are many snakes that mimic the color pattern of the coral snake, such as the king and milk snakes. When possible, an initial step after a possible envenomation should be safe identification of the offending snake, including photographs if possible. Since the toxin spreads lymphatically, application of a pressure dressing over the bite wound has been shown to be experimentally effective.^2,27

For both minor and severe exposures, supportive care is the mainstay, with particular vigilance for respiratory muscle paralysis. There was an approved antivenom, but the last lot in the United States expired in January 2019.²⁸ However, case reports have demonstrated good cross reactivity between the antivenoms of Central American coral snakes for the venoms of their northern cousins.²⁹ This antivenom can sometimes be located for emergency use at local zoos.^26,29 Regardless of which antivenom is available, it is recommended to give patients the antivenom, known as Coralmyn, even if they are not presenting with symptoms, since the antivenom lowers the severity of the reaction. Anyone with a high suspicion of envenomation by a coral snake should be admitted for observation for at least 24 hours because of the sometimes insidious nature of the weakness.²³

Cnidarians

Cnidarians are invertebrate marine animals that include jellyfish, hydras, corals, and Portuguese man-of-war. Ubiquitous throughout the world’s oceans, scyphozoans, or jellyfish, are a common sight in many waters. These primitive but efficient organisms ensnare prey using long, thin tentacles equipped with tiny nematocysts, which act like small poison darts, immobilizing prey. Some species have nematocysts large enough to puncture human skin, creating reactions that range from mild dermatitis to severe pain and systemic toxicity, and, in the most dangerous examples, cardiac arrest. However, the vast majority of jellyfish stings are painful but not harmful. Common species, such as members of the genuses Chrysaora and Cassiopea, are irritating or more painful depending on the species encountered, but usually are not dangerous. As with all stinging organisms, anaphylaxis is of significant concern in individuals with repeat exposures and a history of anaphylactoid reactions to other toxins.

Jellyfish of the class Cubozoa or “box jellyfish” are the ones most often responsible for fatal reactions and have been associated with lethal envenomations in Australia, Indonesia, New Guinea, and surrounding waters.³⁰ (See Figure 11.) There are documented cases of fatal box jellyfish stings in the Gulf of Mexico from the species Chiropsalmus quadrumanus. Smaller box jellyfish (Carukia barnesi) also can produce a type of sympathomimetic toxicity known as Irukandji syndrome. It is characterized by nausea, tremors, tachycardia, hypertension, pulmonary edema, and even T-wave inversions with elevated troponin levels.³¹ Although quite rare for North American providers, Irukandji syndrome has been documented in the Gulf of Mexico and Florida.³² Although more common in tropical waters, the possibility of a box jellyfish sting cannot be excluded anywhere patients are swimming in warm salt water.

For any patient who has been stung by a jellyfish, immediate removal from the water is of paramount importance. Regardless of the severity of the initial reaction, the possibility of anaphylaxis or severe envenomation cannot be excluded, and if these patients develop a severe reaction while still in the water, they may drown. Care should be taken to remove these individuals if in open water to ensure that the rescuers are not injured in the process of placing them into a boat or another vehicle.

It is important to remember that stings can occur both in and outside the water; all that is required is contact with the intact nematocysts, as is the case when individuals handle dried jellyfish washed ashore. Professionals who spend large periods of time in contact with the ocean, such as commercial fishermen, lifeguards, diving instructors, pearl divers/farmers, and aquaculturists, should be aware of the signs and symptoms of a jellyfish sting and have the recommended first aid on hand to treat these envenomations.

Fortunately, the immediate first aid treatment modalities are the same for all jellyfish stings, and deactivation of the nematocysts is of paramount importance, since they will continue to inject painful and potentially dangerous venom. Three effective treatment modalities exist: immersing the site in hot water around 40-45°C, soaking the area in acetic acid (vinegar), or applying a thick paste of water and baking soda.³⁰ Shaving cream also has been shown to be effective. If these techniques do not work, the treatment is largely supportive to include NSAIDs and symptomatic management. For severe box jellyfish envenomations, an antivenom is available in Australia only.³¹

Commensal aquatic organisms of the order Siphonophorae are another type of cnidarian that are very similar in appearance to most jellyfish, but actually are a colony of smaller individuals with different specialized morphologies to assist the colony as a whole. Like the hydrozoans, they have dart-like nematocysts that are able to puncture human skin, resulting in severe reactions and, occasionally, death. The most encountered siphonophore of medical significance is the Portuguese man-of-war (Physalia physalis, also called blue bottle), a large creature that can grow to impressive sizes. Nearly 10,000 people are stung annually, and those who are stung by these describe a severe burning sensation that can last hours. (See Figure 12.) Because these animals are large, swimmers who get caught up in their long tentacles are at significant risk for very painful, debilitating stings that can result in drowning due to the severity of the pain or systemic inflammatory responses. Of clinical significance is the fact that these organisms tend to have cyclical population booms, with thousands of specimens appearing suddenly during certain times of the year only to die off as suddenly as they appeared.

Patients who present with numerous linear red, “whip-like” welts and a history of swimming at a beach should be asked about the possibility of Physalia physalis exposure. Treatment of these stings is identical to the treatment for other jellyfish stings, with hot water (40-45°C), acetic acid, shaving cream, hydrocortisone, and sodium bicarbonate paste all demonstrating efficacy. Otherwise, symptomatic management with NSAIDs and other pain relievers is appropriate if these first-line remedies prove ineffective.

Venomous Lizards

The Gila monster (Heloderma suspectum, see Figure 13) and the Mexican beaded lizard (Heloderma horridum) both are found in the desert regions of the Southwestern United States. They also are kept as pets. These venomous lizards have a unique bite, with teeth that cause local crush and compression injury. During the bite, the venom then drips down grooves in the teeth and enters the wound.

The venom is composed of various enzymatic and nonenzymatic proteins that cause pain, edema, and inflammation. Unlike previously described reptile venoms, there are no neurotoxins or procoagulation factors. In addition to the local crush injury that can occur, a patient can experience systemic symptoms, including dizziness, low blood pressure, sweating, rigors, nausea, and vomiting. The treatment is largely supportive, and the most critical intervention is fluid resuscitation if there is hypotension related to vasoactive kinins.³³ Systemic analgesia might be needed for these extremely painful bites. Coagulopathy, electrocardiographic changes, myocardial infarction, and acute kidney injury have been reported in the literature. There have been no reported fatalities since 1930.³³

Venomous Fish

In the waters surrounding North America, there are a number of aquatic vertebrates that can cause envenomation. Stingrays and the Scorpaenidae family, including the invasive lionfish, the stonefish, and the catfish of the order Nematognathi, all possess poisonous barbs through which humans can become envenomated. Humans often are envenomated when they have provoked the fish and come into contact with the spines, either through fishing and then handling the fish, or, in the case of stingrays, accidentally stepping on the animal. Once the barb has pierced the flesh, the initial pain is from the physical damage caused by the stinger. Stingers often inflict punctures or lacerations.

The injured area should be submerged in hot water at or near 45°C to inactivate the heat-labile toxin. Supportive care should be given, which includes removing the spine and stinger if visible. X-ray and or computed tomography imaging can be used to identify retained foreign bodies more reliably, but ultrasound also can be used with good success. As with any large, dirty wound, the patient should receive tetanus prophylaxis. Antibiotic prophylaxis should be considered in any severe marine injury, with five days of doxycycline as the antibiotic of choice to cover Vibrio species and their potential for aggressive infection.³ Care should be taken to monitor the injury continually on either an inpatient or outpatient basis to ensure healing is occurring.

The Scorpaenidae family, which includes the invasive lionfish as well as other stonefish, have spines with associated venom glands. (See Figure 14.) The venom is extremely dangerous and even fatal to humans, especially in children and given a sufficient dosage.^3,34 Like the crotalid venoms, this venom is a cocktail of proteases and other destructive enzymatic proteins that can cause significant pain and swelling.³⁵ Once stung, the victim experiences erythema, ecchymoses, and swelling accompanied by extreme pain. Should a sufficient enough dose be experienced, a systemic toxicity will develop. The most dangerous symptoms are hypotension, arrhythmogenic tachycardias, and pulmonary edema. If a patient develops these severe symptoms, there is an equine-based stonefish antivenom available from Seqirus, but it is not available in all areas.³⁴ The dose is one vial IV over 15 minutes, which usually results in good resolution of symptoms. Local poison centers often are helpful in locating antivenoms.

Catfish, common food fish of the order Siluriformes, dwell in muddy and dark waters of American rivers and lakes. Named for the large whiskers they have around their mouth, these fish possess spines both near their mouths and, in many cases, their fins as well. The spines act as a defense mechanism. As mentioned earlier, stings occur when the fish is handled, resulting in both an envenomation and a mechanical injury from the spines themselves.³⁵ Envenomation causes local skin damage and pain.

As with other aquatic envenomations, immersion in 45°C or 113°F water for 30-90 minutes is recommended to inactivate the heat labile toxins. Ultimately, the best policy when educating individuals coming into contact with areas where poisonous fish are present focuses on prevention. Education should be focused on the choice of footwear when wading in concerning areas, which can be a mitigating prevention technique for individuals.

Conclusion

Human cohabitation with venomous creatures is as old as our species itself and despite advances in pest control and wildlife management, shows no signs of abating. Interestingly, many of these organisms seem to thrive with human influence — poisonous spiders enjoy our homes as much as we do. Venomous snake populations have grown as a result of agricultural practices that increase rodent populations. Furthermore, as outdoor recreational activities such as hiking and diving continue to remain popular, humans will encounter these animals and may become envenomated by them. As with many items in medicine, the severity of envenomations exists on a spectrum, and good clinical judgement is required when evaluating each of these bites or stings. The mainstays of treatment include aggressive supportive management, a knowledge of antidote options, and recognition and management of anaphylaxis. Consultation with local poison control resources and medical toxicologists, when available, is essential to providing the best care possible to envenomations throughout the spectrum of their presentations.

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