North American Snake Envenomation




Native US snakes that produce clinically significant envenomation can be divided into 2 groups, crotalids and elapids. The crotalids include rattlesnakes, cottonmouths, and copperheads. Crotalid envenomation can result in significant local tissue damage as well as thrombocytopenia and coagulopathy. Rarely are bites fatal. Native US elapids are all coral snakes that possess neurotoxic venom that can cause weakness, respiratory paralysis, and rarely death. Treatment of both types of envenomation revolves around general supportive care and antivenom administration when indicated. Previously advocated treatments, such as tourniquets, venom extraction, and bite site excision are not recommended.


Key points








  • Native North American venomous snakes fall into 3 categories: crotalids, elapids, and colubrids.



  • Crotalids include the rattlesnakes, copperheads, and cottonmouths, and their envenomations are characterized primarily by local tissue destruction and hematologic toxicity.



  • All native North American members of the elapid family are coral snakes and their envenomation can be characterized by neuromuscular blockade and subsequent muscular weakness.



  • Colubrids are generally considered medically inconsequential.



  • Treatment of envenomation of all types of snakes includes good supportive care with antivenom administration when indicated.






Introduction


It is important to have a general understanding of snake taxonomy to help organize venomous snake species and to some extent predict clinical effects. All life is categorized taxonomically under 7 increasingly specific categories. These categories include, in descending order; kingdom, phylum, class, order, family, genus, and species. In addition to these 7 main groups there are subdivisions and superdivisions between them. With regard to snakes and their medical significance, this further classification is most important as it relates to superfamilies and subfamilies. Snakes fall under the order Ophidia or Serpentes. Most modern snakes fall under the superfamily Colubridae, which includes all venomous snakes of medical significance. Within this superfamily, medically significant North American snakes can be classified into 2 main families and to a lesser clinically significant third family. The 2 main families are Viperidae and Elapidae. The third less significant family from a medical standpoint is the Colubridae family.


A majority of venomous North American snakes belong to the subfamily Crotalinae (often referred to as crotalids), which falls under the Viperidae family. These snakes include the rattlesnakes (genus Crotalus and Sistrurus ) as well as the cottonmouths and copperheads (genus Agkistrodon ). These snakes are also referred to as pit vipers due to heat-sensing pits behind their nostrils and can be differentiated from nonvenomous native US snakes by their triangular heads and elliptical pupils. An exception is the coral snake (discussed later). In addition, this rule does not necessarily hold true outside the United States. Rattlesnakes geographically cover much of the contiguous United States; however, a majority of the bites occur in Southwestern states, such as California, Arizona, New Mexico, and Texas, although there are a significant number reported in Florida as well. Copperheads and cottonmouths are found primarily in the Eastern and Southern United States, with a majority of envenomations occurring in the South. An average of 4735 native US venomous snakebites are reported every year and approximately half of these are from crotalids (the true fraction is likely higher given several unidentified snakes in this study). A majority of individuals bitten are male and older than 19 years of age but this is not specific for crotalid envenomations and is true across all US native venomous species. Deaths are rare, with an average of 5 to 6 reported a year, and usually occur in children, the elderly, or those with some delay in antivenom treatment. Deaths are almost always from crotalid envenomation and usually from a rattlesnake.


Elapidae snakes are frequently referred to as elapids. Two genera and 3 species of coral snakes make up the North American elapid population: the Arizona or Sonoran coral snake ( Micruroides euryxanthus ), the eastern coral snake ( Micrurus fulvius ), and the Texas coral snake ( Micrurus tener ). The eastern coral snake can be found in much of the South whereas the Texas coral snake resides west of the Mississippi river in Louisiana, Arkansas, and Texas. The Arizona coral snake can be found in Arizona and New Mexico. Despite this multistate distribution, 344 of 399 identified coral snake bites from 2001 to 2005 occurred in Florida and Texas. Coral snake bites comprise only approximately 2% of all US venomous snake bites annually, and up until 2006 no deaths had been reported to the American Association of Poison Control Centers since 1983. Coral snakes do not have elliptical pupils, triangular heads, or heat-sensing pits like the crotalids but are venomous. US coral snakes can be identified by their circumferential red, yellow, and black banding with red bands abutting yellow bands. This distinction is important to differentiate coral snakes from other similar appearing nonvenomous US snake species with noncircumferential banding (the shovel-nosed snake) or red bands abutting black bands (the king snake). These rules do not necessarily hold true outside the United States.


The oft-ignored Colubridae family of snakes, often referred to as colubrids, are generally not considered poisonous. This is in contrast to being venomous because all snakes produce venom but snakes considered poisonous (such as the crotalids and elapids) are able to puncture human skin and deliver enough venom to produce a clinically significant envenomation. Colubrid snakes are rear-fanged and lack an efficient venom delivery system. If specialized venom glands are present, they do not have significant associated musculature to forcefully expel venom. Clinically significant envenomations from these snakes have been reported, but they are generally mild and of such little clinical significance that this family is not discussed further.




Introduction


It is important to have a general understanding of snake taxonomy to help organize venomous snake species and to some extent predict clinical effects. All life is categorized taxonomically under 7 increasingly specific categories. These categories include, in descending order; kingdom, phylum, class, order, family, genus, and species. In addition to these 7 main groups there are subdivisions and superdivisions between them. With regard to snakes and their medical significance, this further classification is most important as it relates to superfamilies and subfamilies. Snakes fall under the order Ophidia or Serpentes. Most modern snakes fall under the superfamily Colubridae, which includes all venomous snakes of medical significance. Within this superfamily, medically significant North American snakes can be classified into 2 main families and to a lesser clinically significant third family. The 2 main families are Viperidae and Elapidae. The third less significant family from a medical standpoint is the Colubridae family.


A majority of venomous North American snakes belong to the subfamily Crotalinae (often referred to as crotalids), which falls under the Viperidae family. These snakes include the rattlesnakes (genus Crotalus and Sistrurus ) as well as the cottonmouths and copperheads (genus Agkistrodon ). These snakes are also referred to as pit vipers due to heat-sensing pits behind their nostrils and can be differentiated from nonvenomous native US snakes by their triangular heads and elliptical pupils. An exception is the coral snake (discussed later). In addition, this rule does not necessarily hold true outside the United States. Rattlesnakes geographically cover much of the contiguous United States; however, a majority of the bites occur in Southwestern states, such as California, Arizona, New Mexico, and Texas, although there are a significant number reported in Florida as well. Copperheads and cottonmouths are found primarily in the Eastern and Southern United States, with a majority of envenomations occurring in the South. An average of 4735 native US venomous snakebites are reported every year and approximately half of these are from crotalids (the true fraction is likely higher given several unidentified snakes in this study). A majority of individuals bitten are male and older than 19 years of age but this is not specific for crotalid envenomations and is true across all US native venomous species. Deaths are rare, with an average of 5 to 6 reported a year, and usually occur in children, the elderly, or those with some delay in antivenom treatment. Deaths are almost always from crotalid envenomation and usually from a rattlesnake.


Elapidae snakes are frequently referred to as elapids. Two genera and 3 species of coral snakes make up the North American elapid population: the Arizona or Sonoran coral snake ( Micruroides euryxanthus ), the eastern coral snake ( Micrurus fulvius ), and the Texas coral snake ( Micrurus tener ). The eastern coral snake can be found in much of the South whereas the Texas coral snake resides west of the Mississippi river in Louisiana, Arkansas, and Texas. The Arizona coral snake can be found in Arizona and New Mexico. Despite this multistate distribution, 344 of 399 identified coral snake bites from 2001 to 2005 occurred in Florida and Texas. Coral snake bites comprise only approximately 2% of all US venomous snake bites annually, and up until 2006 no deaths had been reported to the American Association of Poison Control Centers since 1983. Coral snakes do not have elliptical pupils, triangular heads, or heat-sensing pits like the crotalids but are venomous. US coral snakes can be identified by their circumferential red, yellow, and black banding with red bands abutting yellow bands. This distinction is important to differentiate coral snakes from other similar appearing nonvenomous US snake species with noncircumferential banding (the shovel-nosed snake) or red bands abutting black bands (the king snake). These rules do not necessarily hold true outside the United States.


The oft-ignored Colubridae family of snakes, often referred to as colubrids, are generally not considered poisonous. This is in contrast to being venomous because all snakes produce venom but snakes considered poisonous (such as the crotalids and elapids) are able to puncture human skin and deliver enough venom to produce a clinically significant envenomation. Colubrid snakes are rear-fanged and lack an efficient venom delivery system. If specialized venom glands are present, they do not have significant associated musculature to forcefully expel venom. Clinically significant envenomations from these snakes have been reported, but they are generally mild and of such little clinical significance that this family is not discussed further.




Patient evaluation overview


Crotalid Envenomation


Crotalid venom is a complex mixture of multiple proteins, other macromolecules, and metals with diverse activity ( Box 1 ). More than 50 components have been identified. Many of these components have enzymatic activity and the specific components can vary between species and even among the same species depending on geography, diet, and time of year. The venom is primarily cytotoxic and hemotoxic, although all organ systems can be affected. Local tissue destruction and hematologic toxicity are the 2 classic manifestations of crotalid envenomation, although systemic and neurotoxicity are also important.



Box 1





  • Arginine ester hydrolase



  • Thrombin-like enzyme



  • Collagenase



  • Hyaluronidase



  • Phospholipase A2



  • Phospholipase B



  • Phosphomonoesterase



  • Phosphodiesterase



  • Acetylcholinesterase



  • RNase



  • DNase



  • 5′-Nucleotidase



  • NAD nucleotidase



  • l -Amino acid oxidase



Various components of crotalid venom

Data from Gold BS, Dart RC, Barish RA. Bites of venomous snakes. N Engl J Med 2002;347(5):347–56.


Tissue toxicity


Crotalid venom injection locally causes vascular endothelial and basement membrane damage, destruction of the extracellular matrix, and an inflammatory cascade leading to swelling, erythema, and pain. Myotoxic components have also been reported and rhabdomyolysis from local and systemic myotoxic venom effects are rare but occur. Only approximately 10% of envenomations (not including dry bites) lack local tissue manifestations. Local effects tend to occur within 30 minutes to 60 minutes; however, they can be delayed for several hours. Ecchymosis, bullae, and necrosis may develop over time ( Figs. 1 and 2 ). The severity is variable, from mild local pain and swelling to severe pain with rapidly advancing swelling and necrosis with autoamputation, particularly with bites to the fingers. Tissue toxicity from rattlesnake envenomations tends to be more severe than that from cottonmouths or copperheads although there can be considerable overlap.




Fig. 1


Dorsal hand envenomation from a rattlesnake with ecchymosis extending into the proximal arm, axilla, and lateral thorax.



Fig. 2


Significant bullae and tissue damage following dorsal hand bite from C viridis helleri .


Hematologic toxicity


Coagulopathy manifesting as hypofibrinogenemia with an elevated prothrombin time (PT) and thrombocytopenia are the major hematologic manifestations of crotalid envenomation. The incidence of such abnormalities has been reported to be 33%, 49%, and 60% (PT >14 seconds), respectively. Although severe bleeding is rare, it can occur. Thrombocytopenia and hypofibrinogenemia may be protracted, recur, or develop late after the envenomation. There is some question as to whether late developing hemotoxicity could be due to early antivenom administration, masking initial effects, with subsequent antivenom clearance allowing free venom concentrations to rise and late hemotoxicity to manifest. Delayed hemotoxicity has not been well documented in the absence of antivenom administration. The mechanism of snakebite-induced thrombocytopenia is unclear but is thought to be from platelet membrane damage secondary to venom phospholipases, which results in platelet destruction. This theory may conflict with the fact that platelet values often improve significantly after the administration of antivenom. Other evidence points to platelet aggregation as a cause of thrombocytopenia. Rattlesnake venom contains thrombin-like enzymes, which inefficiently cleave fibrinogen, resulting in poorly cross-linked fibers, forming unstable clots while consuming fibrinogen. In addition, venom also contains fibrinolysins, which degrade fibrinogen and fibrin. Both mechanisms contribute to coagulopathy and hypofibrinogenemia.


Neurotoxicity


Neurotoxicity is not a major factor in most crotalid envenomations. The Mojave rattlesnake ( Crotalus scutulatus ) is the major exception. It is known to possess a neurotoxic venom component named Mojave toxin that prevents the presynaptic release of acetylcholine. Envenomation can produce cranial nerve dysfunction, weakness, and paralysis. Local tissue effects may be nonexistent or mild in such cases. The Southern Pacific rattlesnake ( C helleri ) has also been shown to possess at least 1 isoform of the Mojave toxin and a neurotoxic presentation has been reported in some cases. Timber rattlesnake ( C horridus ) envenomations are known to cause myokymia, a rippling movement of muscles often noted in the face. Other species of rattlesnakes may also cause myokymia and rarely more significant weakness.


Systemic toxicity


Mild systemic symptoms, including nausea, vomiting, and diaphoresis, are most common. More severe manifestations, including hypotension, tachycardia, respiratory distress, angioedema, cardiovascular collapse and confusion, are less frequent. Third spacing of fluid secondary to capillary endothelial damage likely contributes to hypotension as does the presence of a protein that depresses myocardial function found in some rattlesnake venoms. This fluid shift does not explain the totality of systemic manifestations (described previously), and severe acute hypersensitivity reactions (anaphylactic and anaphylactoid) are thought to contribute to cases of hypotension, cardiovascular collapse, and angioedema. There are many reports of anaphylactic reactions in individuals with previous exposure to rattlesnakes, from prior envenomations, ingestion of rattlesnake meat, or simply handling of the snakes. Alternatively, there is at least 1 case report of a similar presentation in an individual with no prior rattlesnake envenomations or exposures, raising the question of an anaphylactoid reaction. Regardless, treatment should include assessment of airway, breathing, and circulation as well as administration of antihistamines, corticosteroids, and epinephrine in addition to antivenom, discussed later. Fortunately, these severe presentations are rare, representing only approximately 1% of envenomations.


Coral Snake Envenomation


Bites by the eastern coral snake are generally more severe than those of the Texas coral snake. Bites by the Arizona coral snake are essentially not medically significant. Envenomation results in little to no local tissue damage. The major manifestation is neuromuscular blockade that can present with ptosis, cranial nerve palsies, dysarthria, and dysphagia and can progress to complete respiratory paralysis and death. The mechanism is postsynaptic acetylcholine blockade at the neuromuscular junction. Symptom onset may be delayed for up to 12 hours, but generally patients with significant envenomations develop symptoms within 6 hours. No deaths were reported to the American Association of Poison Control Centers from 1983 to 2007 and only 4% of bites were coded as major effects from 2001 to 2005. There was not a documented coral snake fatality from 1967 until 2009 (although the envenomation occurred in 2006 in Florida). Interpretation of this data is complicated because incidence of treatment with coral snake antivenom among severity groups is not provided and this could alter the severity of a patient’s course. In addition, severity of coral snake bites may be mitigated by more intensive care as represented by a higher rate of admissions to ICUs.




General treatment considerations


Crotalid Envenomations


General emergency department care of snakebites begins as usual with attention to airway, breathing, and circulation. Intravenous access should be obtained so that intravenous fluids and parenteral pain control can be administered. Tetanus vaccination should be updated if indicated (this is true of coral snake envenomations as well). Antibiotics are not routinely indicated because the incidence of infections is low, approximately 3%. Elevation of the affected extremity can help mitigate some of the edema. Particular attention to the airway and consideration of early intubation is important in bites to the head, face, or tongue because obstruction from swelling can occur.


Initial evaluation should focus on the bite site. One, two, or even multiple puncture marks corresponding to a snake’s fangs are often identifiable. Frequent examination of the affected extremity or area of envenomation is important to assess for worsening swelling. Distal pulses and capillary refill should be assessed in extremity envenomations. Many sources advocate circumferential markings on extremities or marking the leading edge of swelling to ensure consistent measurements in the same location. Initial laboratory evaluation should include a complete blood count, international normalized ratio (INR), PT, fibrinogen, and fibrinogen degradation products. A creatinine kinase (CK) level can be considered if there is concern for rhabomyolysis. Elevated fibrinogen degradation products can be an early sign of coagulopathy but are not as useful as fibrinogen levels in subsequently assessing coagulopathy or after antivenom response.


Any patients with signs, symptoms, or laboratory evidence of envenomation should be admitted at least for observation even if antivenom is not indicated (discussed later). Although infrequent, local tissue manifestations can be delayed or worsen over time and hematologic toxicity can manifest late.


Coral Snake Envenomations


Given the potentially serious and deadly effects of coral snake envenomation, all patients suffering a bite are recommended to seek medical care immediately. General care in an emergency department includes assessment of airway, breathing, and circulation with preparation to control the patient’s airway in cases of respiratory insufficiency. CK levels should be checked in addition to basic laboratory tests because Micrurus fulvius venom contains a myotoxic component and CK elevations have been reported in the tens of thousands. Other prehospital interventions are discussed later, as is antivenom treatment.

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Dec 2, 2017 | Posted by in Uncategorized | Comments Off on North American Snake Envenomation
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