When a snake bites •

CPT MARCO COPPOLA, DO, MC, USA DAVID E. HOGAN, DO

Primary care physicians may More than 3000 species of snakes exist through­ be required to treat snake-bitten patients out the world .. They are found anywhere from and must differentiate between venomous below sea level to above timberline. Worldwide, and nonvenomous snakes. The chief dis­ 300,000 snakebites occur with 30,000 to 40,000 tinguishing characteristics of venomous deaths per year. 1,2 In the United States, 45,000 snakes are fangs and a single row of sub­ snakebites occur with 12 to 15 deaths per year.2 caudal anal plates. The physiologic effects No clinician, whether practicing in a rural or a of snake venom are on the cardiovascular, large, inner city hospital, is exempt from treat­ hematologic, and neurovascular systems. ing snakebites. This article reviews the charac­ The snake-bitten patient first needs sup­ teristics of venomous snakes in the United States, portive treatment and stabilization. Then, the general management of snakebites, and com­ the physician must establish whether enven­ plications associated with envenomation. omation has occurred, grade it, and moni­ Two families of venomous snakes exist in the tor edema around the bite. Local treatment, United States: Elapidae and Viperidae (Table 1).3 broad-spectrum antibiotics, and tetanus The Elapidae family consists of two genera of prophylaxis should be used for all enveno­ coral snakes, Micrurus fulvius and Micruroides mation grades. The decision to administer euryxanthus. Crotalidae, a subfamily of Viperi­ antivenin therapy should be made on clin­ dae, consists of various species ofthe genera Agk­ ical grounds and the envenomation grade. istrodon (cottonmouths and copperheads), Sistru­ Its use, however, can lead to anaphylaxis rus (pigmy and massasauga rattlesnakes), and and anticomplement reactions. Crotalus. The genus Crotalus consists of rat­ (Key words: Snakebite, antivenin, enven­ tlesnakes including the eastern and western dia­ omation) mondbacks, mojave, sidewinder, timber, and prairie rattlesnakes. Venomous snakes exist in all states except Alaska, Hawaii, and Maine.3 Now the serpent was more subtle than any beast of (Figures 1 and 2 illustrate distributions of some the field which the Lord God had made. (Genesis 3:1) common snakes in the United States.4)

Dr Coppola is director, Emergency Medicine Residency Pro­ General characteristics gram, and director of research, Medical Department Activ­ ity, Darnall Army Community Hospital, Fort Hood, Tex, and Primary care physicians should have a basic assistant professor, Department of Emergency Medicine, understanding of the general characteristics of Texas A&M University Health Sciences Center, College of snakes. Differentiating venomous from nonven­ Medicine, Temple Campus, Temple, Tex. Dr Hogan is assis­ omous snakebites is a very important step in the tant professor of surgery, director of Disaster Emergency management of the snake-bitten patient. Non­ Medical Services, and undergraduate education coordinator, Section of Emergency Medicine and Trauma, University of venomous snakebites are benign and need only Oklahoma Health Sciences Center, Oklahoma City, Okla. local wound care. Opinions or assertions contained herein are the private In contrast, venomous snakebites are fre­ views of the authors and should not be construed as offi­ quently associated with complications. If patients cial or as reflecting the views of the Department of the Army or accompanying parties can describe the offend­ or the Department of Defense. ing snake, they will provide information important Correspondence to CPT Marco Coppola, DO, Depart­ ment of Emergency Medicine, Darnall Army Community in determining the course of treatment. Hospital, Fort Hood, TX 76544. The two most constant factors differentiating

494 • JAOA • Vol 94 • No 6 • June 1994 Clinical practice • Coppola and Hogan ogous to the human parotid gland. Table 1 Venom is discharged via the Common Venomous Snakes in the United States actions of the external jaw mus­ cle. The amount of venom dis­ Family: Elapidae charged depends on the weight and size of the victim as deter­ Micruroides euryxanthus Arizona coral snake mined by the thermoreceptors.5 Micrurus fulvius American coral snake Because the comparatively large size of a human being overwhelms Family: Viperidae the snake's thermoreceptors, Subfamily: Crotalidae injection of a larger amount of Agkistrodon contortrix American copperhead venom may result. Most aver­ Agkistrodon piscivorus Cottonmouth age-sized snakes discharge between 25% and 75% of their Crotalus adamanteus Eastern diamondback rattlesnake stored venom per strike.6 The Crotalus atrox Western diamondback rattlesnake larger and older snake injects Crotalus cerastes Sidewinder more, but less-concentrated, Crotalus horridus Timber rattlesnake venom, whereas the younger and Crotalus scutulatus Mojave rattlesnake smaller snake injects less, but Crotalus viridis Prairie rattlesnake more-concentrated, venom. Sistrurus catenatus Massasauga rattlesnake Venom is delivered to the vic­ Sistrurus miliarius Pigmy rattlesnake tim via fangs (Figure 4). All but the coral snakes have hinged fangs venomous from nonvenomous snakes are fangs that fold posteriorly against the upper jaw. Coral and the presence of a single row of subcaudal anal snakes have a fixed pair of fangs that are short­ plates (Figures 3 and 4). Nonvenomous snakes er and fatter than those of Viperidae. Snakes shed lack fangs and have a double row of subcaudal their fangs as they do their skin. Reserve fangs may anal plates. With some exceptions, for example, the be in place at times resulting in one to four fang rat snake, venomous snakes generally have a tri­ marks. angular shaped head. Nonvenomous and the Rattlesnakes are named for their "rattle" American and Arizona coral snakes (M fulvius located on the tail. The rattle is a group of inter­ and M euryxanthus) have a round head that is locking segments formed on the tail each time indistinct from the neck (Figure 3). Venomous the snake sheds. It is erroneous to determine the snakes generally have elliptical pupils. Nonven­ age of the snake by counting the number of rat­ omous and coral snakes have round pupils. Coral tles.4 Snakes shed one to four times a year, the num­ snakes may be easily identified by their red-on-yel­ ber depending on the temperature, climate, mois­ low-on-black circumferential markings. Snakes ture, and the amount of food available. that display red-on-black-on-yellow markings, such as the king snake, are nonvenomous. One Venom need only to remember the following: Snake venom is a complex substance evolved for Red-on-black; venom-lack. immobilizing, killing, and digesting the snake's Red-on-yellow; kill-a-fellow. prey. It is 90% water, 10% protein, and various Characteristic of Crotalidae is a thermore­ trace elements. Table 2 lists some components of ceptor "pit" located between the eyes and nose; venom.5 The proteolytic enzymes in snake venom hence, the term "pit viper." This pit allows the are capable of tissue necrosis; whereas hyalu­ snake to sense gradations in temperature and ronidase, "the tissue spreading enzyme," cleaves locate prey. The thermoreceptor functions well mucopolysaccharide bonds, allowing venom to trav­ with small prey but is overwhelmed by larger ani­ el through tissue. Thrombinlike esterases form mals such as human beings. This feature may in unstable fibrin clots that are easily lysed by part account for the defensive strike of the snake other enzymes in venom.5 resulting in snakebite. The physiologic actions of snake venom are gen­ Venomous snakes have an elaborate enven­ erally directed toward the hematologic, cardio­ omation apparatus, which consists of venom vascular, and neuromuscular systems (Figure 5). glands, ducts, and fangs. The venom gland is anal- The proteolytic action of snake venom wreaks

Clinical practice • Coppola and Hogan JAOA • Vol 94 • No 6 • June 1994 • 495 Crotalus atrox

------Crotalus adamanteus

...... Crotalus horridus

Figure 1. Distribution of Crotalus atrox, Crotalus adamanteus, and Crotalus horridus .

...... - "

,,

Micruroides euryxanthus

------Micrurus fulvius , --- ...... Crotalus viridis ------

Figure 2. Distribution ofMicruroides euryxanthus, Micrurus fulvius, and Crotalus viridis.

496 • JAOA • Vol 94 • No 6 • J une 1994 Clinical practice • Coppola and Hogan consider the possibility of a Crotalidae Nonvenomous "dry bite": a bite without the injection of venom. 2 Also impor- tant is the species and size of the snake involved. Larger snakes inject more venom. The roundhead venom of the coral snakes is predominantly neurotoxic, n whereas the venom of the rat­ tlesnake generally causes hem­ orrhage and tissue necrosis. Pathogens that are normal elliptical eyes round eyes flora of the snake mouth, such ~ ~ as Clostridium, Pseudomonas, or Staphylococcus species, may complicate the wound site with infection. Although extremely rare, anaphylactic and ana- phylactoid shock have also been single plates double plates reported to be a complication of snake envenomation.7 Common signs and symp­ toms of snake envenomation Figure 3. General characteristics of Crotalidae uerslLS nonuenoTrWlLS snakes. (Aoopted from Dowl­ appear in Table 3. One or two ing and coauthors,4 and Podgorny.5) fang marks approximately 0.5 cm to 4.0 cm apart is pathog­ havoc on cell membranes throughout the body. nomonic of a venomous snakebite.3-6 After sig­ Cells undergo lysis or become dysfunctional, vas­ nificant envenomation, victims notice pain, burn­ cular structures begin to leak, and microvascu­ ing, and progressive swelling within 5 minutes lar thrombosis develops because of platelet aggre­ which can be followed by edema and hemorrhage. gation. Disseminated intravascular coagulation may occur. Many of these effects are mediated by phospholipase ~. Increased vascular permeabil­ ity leads to hypotension, lactic acidemia, hemo­ Venomous concentration, and hypoproteinemia. Venom may act at the site of the neuromuscular junction caus­ ing neuromuscular blockade, weakness, paraly­ sis, and myonecrosis.

Clinical presentation The clinical presentation of snake envenomation is dependent on several factors. Infants, children, and elderly or low-weight adults are more preg­ nable to snake envenomation and suffer more harm. Also important is the nature, location, Nonvenomous depth, and number of bites. As a rule, the more superior the location of the bite on the body, the more serious the effects can be. The condition of the fangs and venom glands, the amount of venom injected, the amount and kind of clothing through which the fangs pass, and the length of time the snake holds on are also important factors. Greater complications occur with more venom injected. Figure 4. Fangs and no fangs. (Aoopted from Dowling and coau­ In the absence of symptoms, the physician should thors/ and Podgorny.5)

Clinical practice • Coppola and Hogan JAOA • Vol 94 • No 6 • June 1994 • 497 The limb should be immobilized and be kept Table 2 in a position below the level of the heart.2,5 A Components of Venom 5 light constriction band should be applied proxi­ mal to the bite site. In a recent study using a porcine model of snake envenomation, constric­ Proteolytic enzymes Phosphomonoesterase tion bands were associated with decreased systemic Arginine ester hydrolase Phosphodiesterase absorption of venom; their removal did not result Thrombinlike enzyme Acetylcholinesterase in a sudden surge in venom absorption.8 Collagenase RNase Use of a suction device, such as the Extrac­ Hyaluronidase A, (A) DNase tor, in animal studies has been shown to remove Phospholipase B 5' -nucleotidase up to 30% of venom proteins from the enveno­ Phospholipase C NAD-nucleotidase mation site.9 The clinical effect of suction in Lactate dehydrogenase L-amino-acid oxidase human subjects is yet to be established. Popular with the lay public is electrical treat­ If they are severe, hypotension, shock, and coma ment of snake envenomation.6 One method involves may result. Swelling may occur to such a degree the use of a car battery and jumper cables hooked that compartment syndrome of the affected limb proximal and distal to the envenomation site. may develop. Paresthesia of the face, scalp, and This practice stems from a letter published in lips along with periorbital muscle fasciculations The Lancet regarding 34 cases in which Equado­ suggest significant envenomation.2,5,6 Some patients rian tribesmen so treated reportedly had favor­ may complain of a metallic taste in the mouth, able outcomes.10 Controlled studies on the use weakness, sweating, nausea, and light-headedness. of electric shock therapy for snakebite do not Neuromuscular blockade may be heralded by exist. A recently published case report illustrates hoarseness, dysphagia, and ptosis. Paralysis may the failure and the complications of electrother­ progress to the diaphragm and cause respirato­ apy.ll It is unclear at this time if electrotherapy ry arrest. Hemorrhage can occur within 6 hours has any role in the therapy of snakebite, and it of envenomation; its manifestations include epis­ cannot be recommended. taxis, hematemesis, petechiae, or hematochezia. Cryotherapy at one time was recommended. However, it has been found ineffective and pos­ Management sibly deleterious. The patient and prehospital personnel must leave Initial hospital management of the snake­ the immediate area of the snake. Snakes are ter­ envenomated patient is directed toward stabiliz- ritorial and will not strike again if the victim is out of range. Snakes are capable of striking within a range I Damaged ce ll membrane I roughly equal to their body length. 5 Children are at higher risk for mul- tiple bites because they commonly are / / 1M,;t "II hl;t,mloe ce'N",1 so fearlul they fail to leave the snake's vicinity. Prehospital healthcare providers ~~ ~ lecithin \ ~ lysolecithin .. IMuscle fiber necrosis I should keep the patient calm. Anx­ iety and fear result in increased heart rate, which in turn increases fatty acids ~ Increased RBC ~ membrane distribution of venom throughout permeabil ity the body. These emotional states also cause hyperventilation, light- headedness, and nausea, and may water obscure the effects of a nonvenomous influx bite from those of a venomous bite. Patients should be transported rapid- ly to the nearest emergency depart- I Hemolysis I ment. Intravenous fluids and car- diac monitoring should be instituted. Figure 5. The effects ofphospholipase A2.

498 • JAOA • Vol 94 • No 6· June 1994 Clinical practice • Coppola and Hogan ing and supporting the patient. A "safety net" Table 4 that generally includes supplemental oxygen, car­ Grades of Envenomation diac monitoring, and an intravenous line of nor­ mal saline or lactated Ringer's solution should be established for all patients. Grade Signs and symptoms Routine laboratory tests include complete blood cell count, urinalysis, prothrombin timeJpar­ 1 (minimal) Moderate pain, 22.5- to 15-cm tial thromboplastin time, and electrolyte, crea­ edema, erythema, no systemic symptoms tinine, and blood urea nitrogen determination. - Creatine phosphokinase levels may help to deter­ 2 (moderate) Severe pain , tenderness, mine the degree of muscle necrosis. If the use of erythema, vomiting, antivenin is anticipated, the patient's blood should petechiae, fever,w eakness, be typed and crossmatched prior to administra­ 20- to 40-cm edema tion. Antivenin may cause an antigen cross-reac­ tion and interfere with the crossmatch proce­ 3 (severe) Widespread pain, tenderness, ecchymosis, systemic signs, dure. vertigo, 40- to 50-cm edema After completing primary and secondary sur­ veys, the physician must establish whether enven­ 4 (very severe) Rapid swelling, ecchymosis, omation has occUrred. Up to 85% of snakebites eNS symptoms, visual result in insignificant or no envenomation.12 Pain, disturbance, shock, and erythema, edema, and ecchymosis in the bite convulsions region indicate deposition of venom. Systemic symptoms such as tingling, visual disturbances, course ofthe patient. The exact clinical findings altered sensorium, seizures, or shock indicate should still be documented. Assigning only a severe envenomation. number to the patient's envenomation is not If envenomation is confirmed, it may be grad­ helpful in following the clinical progress of the ed5 (Table 4). Gradation schemes are useful in bite. predicting the use of antivenin and the clinical Local wound treatment, broad-spectrum antibi­ otics, and tetanus prophylaxis should be adrn.i.n­ istered to the patient with any grade of enveno­ Table 3 mation. Some Common Signs and Symptoms Monitoring the amount of edema around the of Snake Envenomation* bite is useful to follow the progression of local venom activity. The extremity circumference Sign or symptom Frequency (%) should be documented and reevaluated hourly. Increasing edema could result in compartment Fang marks 100 syndrome of the involved extremity. Relying on the Swelling and edema 74 classic signs and symptoms of compartment syn­ Weakness 72 drome as an indic~tion of its development in Pain 65 snake envenomation will underestimate the sever­ Diaphoresis or chills 64 ity of compartment pressures. If compartment Numbness or tingling not at syndrome is suspected, compartment pressures affected part 63 should be monitored and kept below 30 mm Hg. Orthostatic symptoms 57 Prompt surgical consultation is warranted if com­ Ecchymosis 51 partment syndrome develops. Nausea and vomiting 48 Allergic reactions to snake venom is an uncom­ Numbness or tingling at mon but difficult situation.13,14 Therapy involves affected part 42 a combined approach to envenomation and ana­ Fasciculations 41 phylaxis.7,15 Vesicula tions 40 The technique of incision and suction first Regional lymphadenopathy 40 described by the Hindu is controversial.6 Its effec­ tiveness has never been proved in human beings. Also reported in the literature are excision and *Adapted from Russell .2 debridement. These procedures are no longer rec-

Clinical practice • Coppola and Hogan JAOA • Vol 94 • No 6' June 1994' 499 ommended because they increase morbidity.16,17 decision has been made to use antivenin, it should The use of antivenin is a controversial treat­ be used regardless of the results of skin testing. ment modality for snake envenomation. Inter­ The presence of a positive skin test allows the estingly, the controversy exists almost exclusively physician to prepare for potentially serious aller­ in the United States; antivenin has long been gic reactions during antivenin administration. the accepted treatment of snake envenomation else­ The patient should be pretreated with diphen­ where in the world. Antivenin, prepared from hydramine hydrochloride, 50 mg to 100 mg (2 horse serum, contains antibodies directed against mg/kg in pediatric patients) administered intra­ a particular snake's venom. Antivenin therapy venously followed by a slow intravenous infusion is frequently associated with side effects, some of one antivenin vial (10 mL) in a 1:20 dilution with of which are severe. The treating physician should 0.45 normal saline solution over 60 minutes. If the obtain informed consent before its use. patient does not react to skin testing, antivenin In the United States, antivenins for Crotal­ is administered intravenously at a rate of 10 vials idae and M fulvius are produced and marketed over 60 to 90 minutes. If anaphylaxis occurs dur­ by Wyeth-Ayerst Laboratories. (Antivenin for M ing administration of antivenin, 0.3 mL to 0.5 euryxanthus does not exist.) The antivenin kit mL of a 1:1000 solution of epinephrine adminis­ contains one vial with 1.5 lyophilized horse serum, tered subcutaneously may be all that is needed one 10-mL vial of bacteriostatic water, one vial of to treat the patient. One may also administer 1:10 dilution of horse serum used for skin testing, methylprednisolone, ciinetidine, and an intra­ and the package insert. Antivenin is prepared venous fluid bolus.1,2,5.7,14 by gently mixing lyophilized horse serum in 10 mL Antivenin administration has been recom­ of bacteriostatic water (Package insert. Crotal­ mended during pregnancy. One case of abrup­ idae antivenin, Wyeth Laboratories). tio placentae has been reported after snake enven­ The decision to use antivenin must be made omation.19 Epinephrine should be avoided in on a clinical basis, on the grade of the patient's pregnancy because it decreases uterine blood envenomation, and after consultation with a local flow. 20 The intravenous use of 25 mg to 50 mg poison control center. It is best given within 12 of ephedrine has proved to be an effective alter­ hours, but its use after 72 hours has been suc­ native if serious allergic reactions develop.6 cessful.6 The use of antivenin is associated with Pediatric envenomation should be treated a high incidence of anaphylaxis and anticomple­ with the same antivenin dose used for the adult ment reactions. Anaphylaxis, an IgE-mediated patient. Antivenin works on the snake venom on type I hypersensitivity reaction, may be precip­ a molecule-per-molecule basis, so children should itated by skin testing or antivenin administra­ receive the same volume of antivenin as an adult. tion. Common early manifestations are nausea, Serum sickness is a common complication dyspnea, rash, and a hot, flushed feeling. Anti­ after the use of antivenin. It occurs 1 to 4 weeks complement reactions can also occur because of after administration of antivenin, and is a type immunoglobulin and protein aggregates in IV hypersensitivity reaction. Patients complain antivenin.18 This reaction often occurs when con­ of urticaria, arthralgia, fever, myalgia, malaise, centrated antivenin is administered rapidly. 6 headache, wheezing, nausea, vomiting, and light­ If antivenin is to be use,d, the patient must be headedness. A regimen of diphenhydramine scrutinized for history of horse serum sensitivi­ hydrochloride, 50 mg every 4 hours; hydroxyzine, ty, asthma, and general allergic reactions, and 10 mg every 4 hours; oxycodone/acetaminophen, should undergo skin testing. The latter is accom­ one to two tablets every 4 hours as needed; cime­ plished by intradermally injecting the patient tidine, 400 mg every 12 hours; and prednisone with 0.01 mL to 0.3 mL of the 1:10 dilution of 80 mg every morning for 14 days without a taper­ the horse serum provided in the antivenin kit. ing dose may be beneficial. A positive reaction consists of erythema or pseudopodia (or both) at the site of injection. Comment Skin testing with horse serum should never be All physicians involved in primary care may be done unless one fully intends to use antivenin, called on to treat snake-bitten patients. Evalua­ because it may sensitize the patient to additional tion for the presence and degree of envenoma­ equine-derived products. tion is important in the decision to use antivenin. Not all persons sensitive to horse serum will Medical management usually results in a suc­ react to skin testing. It is our belief that if the cessful outcome. The primary care physician

500 • JAOA • Vol 94 • No 6 • June 1994 Clinical practice • Coppola and Hogan should be aware of the indications for surgical consultation.

Acknowledgment The authors gratefully acknowledge the assistance of Mr Frank Norton, Medical Library, Darnall Commu­ nity Hospital, Fort Hood, Tex, and the Poison Control Center, University of Arizona, Tucson.

References 1. Otten EJ: Antivenin therapy in the emergency department. Am J Emerg Med 1983;1:83-93. 2. Russell FE: When a snake strikes. Emerg Med 1990;6:21-43. 3. Weidensaul S: Snakes of the World. Secaucus, NJ, Chartwell Books, 1991. 4. Dowling HG, Minton SA, Russel FE: Poisonous Snakes of the World. us Government Printing Office, 1968. 5. Podgorny G: Reptile bites and scorpion stings, in Tintinalli JE, Krone RL, Ruiz E (eds): Emergency Medicine: A Comprehensive Study Guide, ed 3. New York, NY, McGraw Hill Book Co, 1~92. 6. Sullivan JB, Wingert WA: Reptile bites, in Auerbach PS, Geehr EC (eds): Management of Wilderness and Environmental Emer· gencies, ed 2. St Louis, Mo, CV Mosby Co, 1989. 7. Hogan DE, Dire DJ: Anaphylactic shock secondary to rattlesnake bite. Ann Emerg Med 1990;19:814-816. B. Burgess JL, Dart RC, Egen NB, Mayersohn M: Effects of con­ striction bands on rattlesnake venom absorption: A pharmacoki­ netic study. Ann Emerg Med 1992;21:1086-1093. 9. Bronstein AC, Russell FE, Sullivan JB: Negative pressure suc­ tion in field treatment of rattlesnake bite. Vet Human Toxicol 1985;28:297. 10. Guderian RH, MacKenzie CD, Wil4ams JF: High voltage shock treatment for snakebite. Lancet 1986;2:229. 11. Dart RC, Gustafson RA: Failure of electric shock treatment for rattlesnake envenomation. Ann Emerg Med 1991;20:659-661. 12. Arnold RF: Controversies and hazards in the treatment of pit viper bites. South Med J 1979;72:902-906. 13. Wadee AA, Rabson AR: Development of specific IgE antibod­ ies after repeated exposure to snake venom. J Allergy Clin ImmU/wl 1987;80:695-698. 14. Otten EJ, McKimm D: Venomous snakebite in a patient aller­ gic to horse serum. Ann Emerg Med 1983;12:624-627. 15. Moscati RM, Moore GP: Comparison of cimetidine and diphen­ hydramine in the treatment of acute urticaria. Ann Emerg Med 1990;19:12-15. 16. Huang TI: Surgical management of poisonous snakebites. J Miss State Med Assoc 1987;3:65-71. 17. Glass ill: Early debridement in pit viper bite. Surg Gynecol Obstet 1973;136:774-777. lB. Sutherland SK: Serum reactions-an analysis of commercial antivenoms and the possible role of anti-complementary activity in de novo reactions to anti-venins and anti-toxins. Med J Aust 1977;1:613-615. 19. Zugaib M, de-Barrios AC , Bithar RE, et al: Abruptio placentae following snakebite. Am J Obstet GynecoI1985;151:754-755. 20. Entman SS, Moise KJ: Anaphylaxis in pregnancy. South Med J 1984;77:402.

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