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Snake Bite: Coral Snakes
Snake Bite: Coral Snakes Michael E. Peterson, DVM, MS North American coral snakes are distinctively colored beginning with a black snout and an alternating pattern of black, yellow, and red. They have fixed front fangs and a poorly developed system for venom delivery, requiring a chewing action to inject the venom. The severity of a coral snake bite is related to the volume of venom injected and the size of the victim. The length of the snake correlates positively with the snakes venom yield. Coral snake venom is primarily neurotoxic with little local tissue reaction or pain at the bite site. The net effect of the neurotoxins is a curare like syndrome. In canine victims there have been reports of marked hemolysis with severe anemia and hemoglobinuria. The onset of clinical signs may be delayed for as much as 10 to 18 hours. The victim begins to have alterations in mental status and develops generalized weakness and muscle fasciculations. Progression to paralysis of the limbs and respiratory muscles then follows. The best flied response to coral snake envenomation is rapid transport to a veterinary medical facility capable of 24 hour critical care and assisted ventilation. First aid treatment advocated in Australia for Elapid bites is the immediate use of a compression bandage. The victim should be hospitalized for a minimum of 48 hours for continuous monitoring. The only definitive treatment for coral snake envenomation is the administration of antivenin (M. fulvius). Once clinical signs of coral snake envenomation become manifest they progress with alarming rapidity and are difficult to reverse. If antivenin is not available or if its administration is delayed, supportive care includes respiratory support. Assisted mechanical ventilation can be used but may have to be employed for up to 48 to 72 hours. Clin Tech Small Anim Pract 21:183-186 © 2006 Elsevier Inc. All rights reserved. KEYWORDS coral snake, snakebite, envenomation, neurotoxin, antivenin
F
ifty species of coral snakes are found in the New World. Two genera are indigenous to the United States. One genus is Micruroides euryxanthus, the Sonoran coral snake, which inhabits central and southeastern Arizona and southwestern New Mexico. The other genus is Micrurus, contains the primarily medically important three subspecies: M. fulvius fulvius (eastern coral snake), M. fulvius tenere (Texas coral snake), and M. fulvius barbouri (South Florida coral snake). North American coral snakes are distinctively colored beginning with a black snout and an alternating pattern of black, yellow (occasionally white), and red (Fig. 1). They can be differentiated from similar looking nonpoisonous snakes by the coral snake’s color bands, which completely encircle the snake’s body with the yellow band touching the red band. This color pattern can be best remembered by the warning that if caution (yellow) touches danger (red), the snake is a coral snake (note: this is not true in South America). Coral snakes are proteroglyphodonts, which have short fixed front fangs and a poorly developed system for venom delivery, thereby requiring a chewing action to inject the
Reid Veterinary Hospital, Albany, OR. Address reprint requests to Michael E. Peterson, DVM, MS, Reid Veterinary Hospital, 933 SW Queen Avenue, Albany, OR 97321. E-mail: [email protected]
1096-2867/06/$-see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.ctsap.2006.10.005
venom. Their pupils are always round, they have no facial “heat sensing” pits, and their heads are not triangular (Fig. 2). Coral snakes are relatively docile but will respond aggressively if disturbed, delivering a pugnacious bite. Veterinary patients occasionally are presented with the snake still attached. Bites by coral snakes are relatively rare. The Sonoran coral snake (Micruroides euryxanthus) is a small burrowing snake that is relatively innocuous.1 No human fatalities have been ascribed to this snake. There are no reported cases of dog or cat fatalities because of envenomation by this snake.
Toxic Dose The severity of a coral snake bite is related to the volume of venom injected and the size of the victim. Sixty percent of coral snake bites are nonenvenomating. It is suggested that this is because of a relatively primitive venom delivery apparatus.2 Approximately 4 to 5 mg of venom is a human lethal dose. A large coral snake can deliver a volume of up to 20 mg. The length of the snake correlates positively with the snake’s venom yield.3
Toxicokinetics Venom uptake can be delayed for many hours and can take 7 to 14 days to clear the body. One report involving enveno183
M.E. Peterson
184
sive salivation, quadriplegia with decreased spinal reflexes in all limbs, and respiratory paralysis. Dogs may exhibit intravascular hemolysis, anemia, hemoglobinuria, and morphologic alterations of red blood cells. Also reported in dogs are hypotension and ventricular tachycardia with pulse deficits. Hemolysis has been reported to occur within 72 hours after envenomation.5 Blood-tinged urine and diarrhea may be present.
Cats
Figure 1 Coral snake coloration black, yellow, red fully encircling bands. Courtesy of the Arizona Poison Drug Information Center, Tucson, AZ.
mated cats described clinical improvement by 36 hours, and by 48 hours after the bite, cats were moving their limbs.4
Mechanism of Toxicity Coral snake venom is primarily neurotoxic with little local tissue reaction or pain at the bite site. Several neurotoxins may be involved and in combination act as nondepolarizing postsynaptic neuromuscular blocking agents. The net effect of the neurotoxins is a curare like syndrome. The venom induces central nervous system depression, muscle paralysis, and vasomotor instability. In canine victims there have been reports of the venom causing hemolysis with severe anemia and marked hemoglobinuria.5 The cause of the red blood cell destruction is poorly understood. It is speculated that it is because of the effects of phospholipase A and its interaction with red blood cell membranes.5 Other Elapidae venom components, which can cause significant local tissue destruction, include hyaluronidase, proteinase, ribonuclease, desoxyribonuclease, and phosphodiesterase.6
Clinical signs of coral snake envenomation reported in cats are acute ascending flaccid quadriplegia, central nervous system depression, and reduced nociperception. Additionally, anisocoria, spinal reflexes absent in all four limbs, hypothermia, and loss of the cutaneous trunci reflex have been documented.4 Anal tone and micturition are typically normal. In one study examining anesthetized cats given 2 mg/kg body weight of eastern coral snake (M. fulvius) venom intravascularly the cats manifested the following signs: drop in blood pressure, respiratory depression 1 hour postinjection, no spontaneous respirations by 3 hours, and an increase in myoglobin release.8 Even at this high intravascular dose, hemoglobinuria was not observed in cats. Hemolysis and hemoglobinuria were not evident in three clinical cases of envenomated cats.4
Minimum Database Baseline laboratory data should include a complete blood count, measurement of electrolytes, and serum chemistries. Hyperfibrinogenemia and moderate leukocytosis are reported abnormalities. Creatine kinase can be significantly elevated. Early elevation of creatine kinase is an indicator that envenomation has occurred.4 In dogs red blood cell morphologic changes include burring and spherocytosis.5 Canine patients in which coral snake envenomation is suspected
Clinical Signs The onset of clinical signs may be delayed for as much as 10 to 18 hours.2,4,5,7 The mean time from bite to onset of clinical signs in one human report was 170 minutes.2 There are few if any local signs other than the puncture wounds themselves. Occasionally, local pain and regional paresthesia may occur. The victim then begins to have alterations in mental status and develops a generalized weakness and muscle fasciculations. Progression to paralysis of the limbs and respiratory muscles then follows. These signs are consistent with bulbar dysfunction. The patient is at risk of impending respiratory failure, with pharyngeal spasms, hypersalivation, cyanosis, and trismus (spasms of the masticatory muscles). Aspiration pneumonia is the major complication secondary to marked salivation because of dysphagia.
Dogs Clinical signs of coral snake envenomation reported in dogs are acute central nervous system depression, emesis, exces-
Figure 2 Small fixed front fangs. Courtesy of the Arizona Poison Drug Information Center, Tucson, AZ. (Color version of figure is available online.)
Snake bite: Coral snakes should be monitored for progressing anemia and hemoglobinuria. Radiographs of the thorax may be indicated because aspiration pneumonia is a major complication of coral snake envenomation secondary to pharyngeal paralysis.
Treatment The best field response to coral snake envenomation is rapid transport to a veterinary medical facility capable of 24-hour critical care and assisted ventilation. The wound site should be cleaned with a germicidal soap. The following first-aid measures should be avoided: incisions, ice, hot packs, and/or electroshock treatment. First-aid treatment advocated in Australia for Elapid bites is the immediate use of a compression bandage. The compression bandage, such as an elastic or crepe bandage material, is rapidly applied to the bitten extremity, starting at the bite site and progressing to encompass the entire limb. The bandage should be wrapped as tightly as one would wrap a sprained ankle. This bandage should not be removed until primary therapy, specifically antivenin, is administered. The victim should be hospitalized for a minimum of 48 hours for continuous monitoring. Pretreatment blood and urine samples should be collected to establish a clinical laboratory baseline. Of utmost importance is good supportive medical care along with an appreciation and anticipation of events that might develop. This includes care of a paralyzed patient and prevention of aspiration pneumonia. Any evidence of respiratory distress should be aggressively addressed with endotracheal intubation to prevent aspiration. Cardiac and pulse oximetry monitoring should be started. Fluid administration through an intravenous catheter should be given at a maintenance rate. Because the onset of clinical signs can be delayed for hours, extreme vigilance should be maintained in monitoring the patient. The only definitive treatment for coral snake envenomation is administration of antivenin (M. fulvius) that was made by Wyeth Laboratories (Marietta, PA). This antivenin is effective against the venom of all North American coral snakes except the Sonoran coral snake.9 However, Wyeth-Ayerst has discontinued production of antivenin (M. fulvius). Currently, there is no other approved coral snake antivenin available in the United States. Studies have shown protective cross reactivity with either the Australian Tiger snake (Notechis scutatus)10 or the Mexican coral snake (Micrurus)10,11 antivenins in the mouse model. Other South and Central American coral snake antivenins do not protectively cross react with North American Micrurus species of coral snakes venom. The earlier antivenin is administered the more effective it is. Once clinical signs of coral snake envenomation become manifest they progress with alarming rapidity and are difficult to reverse. Antivenin treatment is recommended in animals with clinical findings of one or more fang marks from which blood can be expressed or those with a history of the snake hanging by its mouth from the victim regardless of the absence of neurologic abnormalities. The antivenin is produced by inoculating horses with the venom of the eastern coral snake (M. f. fulvius). Once the horse develops a certain titer, serum is harvested and processed to concentrate the antivenom immunoglobulins. The processes used to extract these proteins result in a final prod-
185 uct that, though rich in antibodies, has extraneous equine protein components. It is these proteins that are responsible for the allergic reactions that can be associated with antivenin usage. Antivenin should be reconstituted with the provided dilulent. It should not be shaken but can be swirled to facilitate reconstitution. This usually takes between 10 and 15 minutes. Warming the vial to body temperature aids in dissolution into the liquid state. Shaking or overheating can destroy the proteins and (with shaking) can cause excessive foaming, which makes it difficult to collect the antivenin into a syringe. Skin testing to predict allergic reactions to the antivenin is difficult to evaluate in the veterinary patient. Human victims of snake bites are often subjected to cutaneous hypersensitivity testing before equine-origin antivenin is administered.12 A 1:10 dilution of antivenin at 0.02 mL is injected intracutaneously. A positive reaction, manifested by a wheal surrounded by erythema, occurs within 30 minutes. Drawbacks to skin testing are that it does not guarantee prevention of a severe reaction and the time it takes to perform delays prompt administration of antivenin. Generally, a slow infusion of the antivenin initially with close monitoring will identify those patients who may experience a reaction with responses such as nausea, hyperemia of the inner pinna, and pruritus. Antivenin should be diluted at a ratio of 1 vial to 100 to 250 mL of crystalloid fluids. In smaller patients the clinician should adjust the volume of fluid infusion to prevent fluid overload of the patient. In one study in which antivenin labeled with radioactive iodine-131 was given intravenously, 85% of the antivenin accumulated at the site of envenomation within 2 hours. In contrast, there was a 1.4% local concentration when the antivenin was given intramuscularly and a 5.6% local concentration when it was given subcutaneously.13 Antivenin should not be injected into the bite site, and its uptake can be delayed up to 12 hours when it is given intramuscularly. Administration should begin slowly as an intravenous infusion. If there is no evidence of an allergic reaction (eg, nausea, hyperemia of the inner pinna, pilo erection of tail hair, pruritus), the rate of infusion can be increased. The entire initial dosage should be given within a half hour. The patient must then be reevaluated for further progression of the envenomation syndrome using the appropriate clinical and laboratory parameters. The dosage of antivenin needed is calculated relative to the amount of venom injected and the body mass of the victim. Smaller patients require higher doses of antivenin because the dose of venom per kilogram body weight of the victim is higher. A single vial of antivenin neutralizes 2 mg of coral snake venom. The recommended initial dose is one to two vials of antivenin. Repeated doses are administered as indicated by the progression of the syndrome.5 Multiple vials may be necessary to adequately treat severe envenomations. The clinician must keep in mind that the dose of antivenin is based on the amount of venom injected in relation to body mass. Patients with allergic reactions to the antivenin can still receive the antivenin if needed. It can be given as a slow intravenous drip and piggybacked with diphenhydramine
M.E. Peterson
186 and possibly epinephrine. Data in both human and veterinary envenomation databases have not identified a significantly higher reaction rate in patients having received antivenin previously (M. Peterson, unpublished data).14 Some veterinary patients have received antivenin yearly for several consecutive years (M. Peterson, unpublished data). Allergic reactions, though rare, are possible when administering antivenin. These may become manifest in one of three ways: true anaphylaxis, an anaphylactoid reaction, and delayed serum sickness. The most common reaction to antivenin is an anaphylactoid reaction. This is a complement-mediated reaction to rapid administration of a foreign protein, such as a blood transfusion. Anaphylactoid reactions can usually be treated by stopping the antivenin infusion, administering diphenhydramine IV or SC (small dogs and cats, 10 mg; large dogs, 25-50 mg), waiting 5 minutes, and then restarting the infusion of antivenin at a slower rate. Stopping the infusion of antivenin and administering epinephrine, corticosteroids, and a crystalloid fluid infusion effectively controls anaphylaxis. Patients taking beta-blockers must be monitored very closely. Beta-blockers may mask the early onset of anaphylaxis, which becomes more difficult to reverse as the reaction progresses. Delayed serum sickness is rare in dogs and cats. This may be because of the smaller volumes of antivenin administered compared with human patients. Delayed serum sickness usually occurs 7 to 14 days after antivenin administration. If it does occur, treatment consists of antihistamines, often type 1 and type 2 inhibitors, and/or corticosteroids. If antivenin is not available or if its administration is delayed, supportive care includes respiratory support. Assisted mechanical ventilation can be used but may have to be employed for up to 48 to 72 hours.15 Broad-spectrum antibiotics are recommended in the veterinary patient after envenomation owing to the number of pathogenic bacteria found in snakes’ mouths. This is an area of controversy in the therapy of human snake bite victims.16,17 The use of corticosteroids in the treatment of coral snake envenomation is not recommended, the justification for their use being tenuous at best. Treatment of Sonoran coral snake envenomation at this time is largely empirical because no specific antivenin is available for this venom.18 General supportive care and response to clinical manifestations are the mainstays of therapy.
Differential Diagnoses Differential diagnoses include tick paralysis, botulism, acute polyneuritis, iatrogenic drug administration, polyradiculoneuritis, and myasthenia gravis.
References 1. Lowe C Jr., Limbacher H: Micruroides euryxanthus, the Sonoran coral snake. AZ Med 8:128, 1961 2. Kitchens C, Van Mierop L: Envenomation by the eastern coral snake (Micrurus fulvius fulvius): A study of 39 victims. JAMA 258:1615-1618, 1987 3. Fix J: Venom yield of the North American coral snake and its clinical significance. South Med J 73:737-738, 1980. 4. Chrisman C, Hopkins A, Ford S, et al: Acute, flaccid quadriplegia in three cats with suspected coral snake envenomation. J Am Anim Hosp Assoc 32:343-349, 1996 5. Marks S, Mannella C, Schaer M: Coral snake envenomation in the dog: Report of four cases and review of the literature. J Am Anim Hosp Assoc 26:629-634, 1990 6. Ellis M: Venomous and Non-Venomous Snakes. Dangerous Plants, Snakes, Arthropods and Marine Life: Toxicity and Treatment. Hamilton, IL, Drug Intelligence Publications Inc., 1978, pp 125–142 7. Parrish H, Klan M: Bites by coral snakes: Report of 11 representative cases. Am J Med Sci 253:561-568, 1967 8. Russell F: Bites by the Sonoran coral snake Micruroides euryxanthus. Toxicon 5:39-42, 1967 9. Antivenin (Micrurus fulvius) (equine origin) (drug circular). Marietta, PA, Wyeth Laboratories, 1983 10. Wisniewski M, Hill R, Havey J, et al: Australian tiger snake (Notechis scutatus) and Mexican coral snake (Micruris species) antivenoms prevent death from United States coral snake (Micrurus fulvius fulvius) venom in a mouse model. J Toxicol Clin Toxicol 41:7-10, 2003 11. de Roodt A, Paniagua-Solis J, Dolab J, et al. Effectiveness of two common antivenoms for North, Central, and South American Micrurus envenomations. J Toxicol Clin Toxicol 42:171-178, 2004 12. Malasit P, Warrell D, Chanthavanich P: Prediction, prevention, and mechanism of early (anaphylactic) antivenom reactions in victims of snakebites. BMJ 292:17-20, 1986. 13. Christopher D, Rodning C: Crotalidae envenomation. South Med J 79:159-162, 1986. 14. McNalley J, Dart R, O’Brien P: Southwestern rattlesnake envenomation database (abstract). Vet Hum Toxicol 29:486, 1987 15. Kerrigan K, Mertz B, Nelson S, et al: Antibiotic prophylaxis for pit viper envenomation: Prospective, controlled trial. World J Surg 21:369-372, 1997 16. Moseley T: Coral snake bite: Recovery following symptoms of respiratory paralysis. Ann Surg 163:943-948, 1966 17. Clark R, Selden B, Furbee B: The incidence of wound infection following crotalid envenomation. J Emerg Med 11:583-586, 1993 18. Russell F, Lauritizen L: Antivenins. Trans R Soc Troop Med Hyg 60: 797, 1966
F
ifty species of coral snakes are found in the New World. Two genera are indigenous to the United States. One genus is Micruroides euryxanthus, the Sonoran coral snake, which inhabits central and southeastern Arizona and southwestern New Mexico. The other genus is Micrurus, contains the primarily medically important three subspecies: M. fulvius fulvius (eastern coral snake), M. fulvius tenere (Texas coral snake), and M. fulvius barbouri (South Florida coral snake). North American coral snakes are distinctively colored beginning with a black snout and an alternating pattern of black, yellow (occasionally white), and red (Fig. 1). They can be differentiated from similar looking nonpoisonous snakes by the coral snake’s color bands, which completely encircle the snake’s body with the yellow band touching the red band. This color pattern can be best remembered by the warning that if caution (yellow) touches danger (red), the snake is a coral snake (note: this is not true in South America). Coral snakes are proteroglyphodonts, which have short fixed front fangs and a poorly developed system for venom delivery, thereby requiring a chewing action to inject the
Reid Veterinary Hospital, Albany, OR. Address reprint requests to Michael E. Peterson, DVM, MS, Reid Veterinary Hospital, 933 SW Queen Avenue, Albany, OR 97321. E-mail: [email protected]
1096-2867/06/$-see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.ctsap.2006.10.005
venom. Their pupils are always round, they have no facial “heat sensing” pits, and their heads are not triangular (Fig. 2). Coral snakes are relatively docile but will respond aggressively if disturbed, delivering a pugnacious bite. Veterinary patients occasionally are presented with the snake still attached. Bites by coral snakes are relatively rare. The Sonoran coral snake (Micruroides euryxanthus) is a small burrowing snake that is relatively innocuous.1 No human fatalities have been ascribed to this snake. There are no reported cases of dog or cat fatalities because of envenomation by this snake.
Toxic Dose The severity of a coral snake bite is related to the volume of venom injected and the size of the victim. Sixty percent of coral snake bites are nonenvenomating. It is suggested that this is because of a relatively primitive venom delivery apparatus.2 Approximately 4 to 5 mg of venom is a human lethal dose. A large coral snake can deliver a volume of up to 20 mg. The length of the snake correlates positively with the snake’s venom yield.3
Toxicokinetics Venom uptake can be delayed for many hours and can take 7 to 14 days to clear the body. One report involving enveno183
M.E. Peterson
184
sive salivation, quadriplegia with decreased spinal reflexes in all limbs, and respiratory paralysis. Dogs may exhibit intravascular hemolysis, anemia, hemoglobinuria, and morphologic alterations of red blood cells. Also reported in dogs are hypotension and ventricular tachycardia with pulse deficits. Hemolysis has been reported to occur within 72 hours after envenomation.5 Blood-tinged urine and diarrhea may be present.
Cats
Figure 1 Coral snake coloration black, yellow, red fully encircling bands. Courtesy of the Arizona Poison Drug Information Center, Tucson, AZ.
mated cats described clinical improvement by 36 hours, and by 48 hours after the bite, cats were moving their limbs.4
Mechanism of Toxicity Coral snake venom is primarily neurotoxic with little local tissue reaction or pain at the bite site. Several neurotoxins may be involved and in combination act as nondepolarizing postsynaptic neuromuscular blocking agents. The net effect of the neurotoxins is a curare like syndrome. The venom induces central nervous system depression, muscle paralysis, and vasomotor instability. In canine victims there have been reports of the venom causing hemolysis with severe anemia and marked hemoglobinuria.5 The cause of the red blood cell destruction is poorly understood. It is speculated that it is because of the effects of phospholipase A and its interaction with red blood cell membranes.5 Other Elapidae venom components, which can cause significant local tissue destruction, include hyaluronidase, proteinase, ribonuclease, desoxyribonuclease, and phosphodiesterase.6
Clinical signs of coral snake envenomation reported in cats are acute ascending flaccid quadriplegia, central nervous system depression, and reduced nociperception. Additionally, anisocoria, spinal reflexes absent in all four limbs, hypothermia, and loss of the cutaneous trunci reflex have been documented.4 Anal tone and micturition are typically normal. In one study examining anesthetized cats given 2 mg/kg body weight of eastern coral snake (M. fulvius) venom intravascularly the cats manifested the following signs: drop in blood pressure, respiratory depression 1 hour postinjection, no spontaneous respirations by 3 hours, and an increase in myoglobin release.8 Even at this high intravascular dose, hemoglobinuria was not observed in cats. Hemolysis and hemoglobinuria were not evident in three clinical cases of envenomated cats.4
Minimum Database Baseline laboratory data should include a complete blood count, measurement of electrolytes, and serum chemistries. Hyperfibrinogenemia and moderate leukocytosis are reported abnormalities. Creatine kinase can be significantly elevated. Early elevation of creatine kinase is an indicator that envenomation has occurred.4 In dogs red blood cell morphologic changes include burring and spherocytosis.5 Canine patients in which coral snake envenomation is suspected
Clinical Signs The onset of clinical signs may be delayed for as much as 10 to 18 hours.2,4,5,7 The mean time from bite to onset of clinical signs in one human report was 170 minutes.2 There are few if any local signs other than the puncture wounds themselves. Occasionally, local pain and regional paresthesia may occur. The victim then begins to have alterations in mental status and develops a generalized weakness and muscle fasciculations. Progression to paralysis of the limbs and respiratory muscles then follows. These signs are consistent with bulbar dysfunction. The patient is at risk of impending respiratory failure, with pharyngeal spasms, hypersalivation, cyanosis, and trismus (spasms of the masticatory muscles). Aspiration pneumonia is the major complication secondary to marked salivation because of dysphagia.
Dogs Clinical signs of coral snake envenomation reported in dogs are acute central nervous system depression, emesis, exces-
Figure 2 Small fixed front fangs. Courtesy of the Arizona Poison Drug Information Center, Tucson, AZ. (Color version of figure is available online.)
Snake bite: Coral snakes should be monitored for progressing anemia and hemoglobinuria. Radiographs of the thorax may be indicated because aspiration pneumonia is a major complication of coral snake envenomation secondary to pharyngeal paralysis.
Treatment The best field response to coral snake envenomation is rapid transport to a veterinary medical facility capable of 24-hour critical care and assisted ventilation. The wound site should be cleaned with a germicidal soap. The following first-aid measures should be avoided: incisions, ice, hot packs, and/or electroshock treatment. First-aid treatment advocated in Australia for Elapid bites is the immediate use of a compression bandage. The compression bandage, such as an elastic or crepe bandage material, is rapidly applied to the bitten extremity, starting at the bite site and progressing to encompass the entire limb. The bandage should be wrapped as tightly as one would wrap a sprained ankle. This bandage should not be removed until primary therapy, specifically antivenin, is administered. The victim should be hospitalized for a minimum of 48 hours for continuous monitoring. Pretreatment blood and urine samples should be collected to establish a clinical laboratory baseline. Of utmost importance is good supportive medical care along with an appreciation and anticipation of events that might develop. This includes care of a paralyzed patient and prevention of aspiration pneumonia. Any evidence of respiratory distress should be aggressively addressed with endotracheal intubation to prevent aspiration. Cardiac and pulse oximetry monitoring should be started. Fluid administration through an intravenous catheter should be given at a maintenance rate. Because the onset of clinical signs can be delayed for hours, extreme vigilance should be maintained in monitoring the patient. The only definitive treatment for coral snake envenomation is administration of antivenin (M. fulvius) that was made by Wyeth Laboratories (Marietta, PA). This antivenin is effective against the venom of all North American coral snakes except the Sonoran coral snake.9 However, Wyeth-Ayerst has discontinued production of antivenin (M. fulvius). Currently, there is no other approved coral snake antivenin available in the United States. Studies have shown protective cross reactivity with either the Australian Tiger snake (Notechis scutatus)10 or the Mexican coral snake (Micrurus)10,11 antivenins in the mouse model. Other South and Central American coral snake antivenins do not protectively cross react with North American Micrurus species of coral snakes venom. The earlier antivenin is administered the more effective it is. Once clinical signs of coral snake envenomation become manifest they progress with alarming rapidity and are difficult to reverse. Antivenin treatment is recommended in animals with clinical findings of one or more fang marks from which blood can be expressed or those with a history of the snake hanging by its mouth from the victim regardless of the absence of neurologic abnormalities. The antivenin is produced by inoculating horses with the venom of the eastern coral snake (M. f. fulvius). Once the horse develops a certain titer, serum is harvested and processed to concentrate the antivenom immunoglobulins. The processes used to extract these proteins result in a final prod-
185 uct that, though rich in antibodies, has extraneous equine protein components. It is these proteins that are responsible for the allergic reactions that can be associated with antivenin usage. Antivenin should be reconstituted with the provided dilulent. It should not be shaken but can be swirled to facilitate reconstitution. This usually takes between 10 and 15 minutes. Warming the vial to body temperature aids in dissolution into the liquid state. Shaking or overheating can destroy the proteins and (with shaking) can cause excessive foaming, which makes it difficult to collect the antivenin into a syringe. Skin testing to predict allergic reactions to the antivenin is difficult to evaluate in the veterinary patient. Human victims of snake bites are often subjected to cutaneous hypersensitivity testing before equine-origin antivenin is administered.12 A 1:10 dilution of antivenin at 0.02 mL is injected intracutaneously. A positive reaction, manifested by a wheal surrounded by erythema, occurs within 30 minutes. Drawbacks to skin testing are that it does not guarantee prevention of a severe reaction and the time it takes to perform delays prompt administration of antivenin. Generally, a slow infusion of the antivenin initially with close monitoring will identify those patients who may experience a reaction with responses such as nausea, hyperemia of the inner pinna, and pruritus. Antivenin should be diluted at a ratio of 1 vial to 100 to 250 mL of crystalloid fluids. In smaller patients the clinician should adjust the volume of fluid infusion to prevent fluid overload of the patient. In one study in which antivenin labeled with radioactive iodine-131 was given intravenously, 85% of the antivenin accumulated at the site of envenomation within 2 hours. In contrast, there was a 1.4% local concentration when the antivenin was given intramuscularly and a 5.6% local concentration when it was given subcutaneously.13 Antivenin should not be injected into the bite site, and its uptake can be delayed up to 12 hours when it is given intramuscularly. Administration should begin slowly as an intravenous infusion. If there is no evidence of an allergic reaction (eg, nausea, hyperemia of the inner pinna, pilo erection of tail hair, pruritus), the rate of infusion can be increased. The entire initial dosage should be given within a half hour. The patient must then be reevaluated for further progression of the envenomation syndrome using the appropriate clinical and laboratory parameters. The dosage of antivenin needed is calculated relative to the amount of venom injected and the body mass of the victim. Smaller patients require higher doses of antivenin because the dose of venom per kilogram body weight of the victim is higher. A single vial of antivenin neutralizes 2 mg of coral snake venom. The recommended initial dose is one to two vials of antivenin. Repeated doses are administered as indicated by the progression of the syndrome.5 Multiple vials may be necessary to adequately treat severe envenomations. The clinician must keep in mind that the dose of antivenin is based on the amount of venom injected in relation to body mass. Patients with allergic reactions to the antivenin can still receive the antivenin if needed. It can be given as a slow intravenous drip and piggybacked with diphenhydramine
M.E. Peterson
186 and possibly epinephrine. Data in both human and veterinary envenomation databases have not identified a significantly higher reaction rate in patients having received antivenin previously (M. Peterson, unpublished data).14 Some veterinary patients have received antivenin yearly for several consecutive years (M. Peterson, unpublished data). Allergic reactions, though rare, are possible when administering antivenin. These may become manifest in one of three ways: true anaphylaxis, an anaphylactoid reaction, and delayed serum sickness. The most common reaction to antivenin is an anaphylactoid reaction. This is a complement-mediated reaction to rapid administration of a foreign protein, such as a blood transfusion. Anaphylactoid reactions can usually be treated by stopping the antivenin infusion, administering diphenhydramine IV or SC (small dogs and cats, 10 mg; large dogs, 25-50 mg), waiting 5 minutes, and then restarting the infusion of antivenin at a slower rate. Stopping the infusion of antivenin and administering epinephrine, corticosteroids, and a crystalloid fluid infusion effectively controls anaphylaxis. Patients taking beta-blockers must be monitored very closely. Beta-blockers may mask the early onset of anaphylaxis, which becomes more difficult to reverse as the reaction progresses. Delayed serum sickness is rare in dogs and cats. This may be because of the smaller volumes of antivenin administered compared with human patients. Delayed serum sickness usually occurs 7 to 14 days after antivenin administration. If it does occur, treatment consists of antihistamines, often type 1 and type 2 inhibitors, and/or corticosteroids. If antivenin is not available or if its administration is delayed, supportive care includes respiratory support. Assisted mechanical ventilation can be used but may have to be employed for up to 48 to 72 hours.15 Broad-spectrum antibiotics are recommended in the veterinary patient after envenomation owing to the number of pathogenic bacteria found in snakes’ mouths. This is an area of controversy in the therapy of human snake bite victims.16,17 The use of corticosteroids in the treatment of coral snake envenomation is not recommended, the justification for their use being tenuous at best. Treatment of Sonoran coral snake envenomation at this time is largely empirical because no specific antivenin is available for this venom.18 General supportive care and response to clinical manifestations are the mainstays of therapy.
Differential Diagnoses Differential diagnoses include tick paralysis, botulism, acute polyneuritis, iatrogenic drug administration, polyradiculoneuritis, and myasthenia gravis.
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