CASE REPORT anaphylaxis; snakebite
Anaphylactic Shock Secondary to Rattlesnake Bite Anaphylactic reactions to Crotalidae envenomation are extremely rare. The presentation of anaphylaxis after envenomation can be a confusing variable in the timely diagnosis of both problems. The therapy of this dual disorder involves combining treatment of the obvious shock from the allergic reaction with a standard approach to Crotalidae envenomation. We present the case of a 22-year-old man who presented to the emergency department with urticaria, hypotension, and bronchospasm that developed immediately after his second envenomation from a rattlesnake. His symptoms resolved after administration of 0.8 mg SQ epinephrine, 100 mg IV diphenhydramine, 2,000 m L normal saline IV, and 250 mg IV methylprednisolone. Only one previous case report of anaphylactic shock from a rattlesnake bite could be found in the medical literature. [Hogan DE, Dire DJ: Anaphylactic shock secondary to rattlesnake bite. Ann Emerg Med July 1990;19:814-816.]
David E Hogan, DO* Daniel J Dire, MDt Fort Hood, Texas
INTRODUCTION An estimated 8,000 poisonous snakebites occur annually in the United States; 12 to 15 are fatal. 1 The treatment of snake envenomation is controversial. Death from snakebites may result from snake venom allergy, 2 but the prevalence of allergic reactions to snake venom is unknown. 3 When the clinical presentation of envenomation is complicated by the onset of a significant allergic reaction, the immediate diagnosis and appropriate therapy are even less clear. We present the case of a 22-year-old man with his second exposure to rattlesnake venom and discuss the pathophysiology and management of anaphylactic and anaphylaetoid reactions to envenomation.
The opinions or assertions contained herein are those of the authors and should not be construed as official or as representing the opinions of the Department of the Army or the Department of Defense.
From the Department of Emergency Medicine, Emergency Medicine Residency Program, Darnall Army Community Hospital, Fort Hood, Texas;* and Department of Internal Medicine, University of Texas A&M College of Medicine, Temple, Texas.t Received for publication October 12, 1989. Revision received February 1, 1990. Accepted for publication March 5, 1990.
Address for reprints: David E Hogan, DO, Department of Emergency Medicine, Darnall Army Community Hospital, Fort Hood, Texas 76544-5063.
CASE REPORT A 22-year-old man presented to the emergency department approx~ imately 30 minutes after he was bitten by a moderate-sized rattlesnake. He had not received any first aid before presentation. The snake had bitten him in the lower left leg and had seemed to remain attached despite vigorous shaking. After five or six seconds, the snake was removed manually and flung through the air. The patient noted an immediate severe burning pain at the site of the bite. Within two to three minutes, he noted dizzihess, general pruritus, and shortness of breath. He contacted a neighbor, who arrived within five minutes and drove him to the ED. No prehospital care was administered. The rattlesnake was not available for definitive identification. On arrival, the patient was responsive but combative with obvious respiratory difficulty, accessory muscle use, and a striking generalized urticarial rash. Chest examination demonstrated diffuse wheezes with prolonged expiratory phase and a rapid regular heart rate. Vital signs were blood pressure of 90/60 m m Hg; pulse, ll0; respirations, 36; and temperature, 37.2 C rectally. A lead II rhythm strip showed sinus tachycardia at a rate of 110 to 120. A nasopharyngeal airway was inserted, and supplemental oxygen was placed with a reservoir mask while preparations were made for possible nasotracheal intubation. The patient was given an initial SQ injection of 0.5 mg l:l,000 epinephrine, and two 18-gauge IV lines of normal saline were established. Diphenhydramine 100 mg IV was administered.
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ANAPHYLACTIC SHOCK Hogan & Dire
Examination of the bite revealed a single puncture wound 3 em from an abrasion on the anterolateral left lower leg. The puncture was oozing a small a m o u n t of serosanguineous fluid. A light lymphatic constricting band was placed above the bite on the lower left leg. Additional therapy consisted of 2,000 mL normal saline, 250 mg methylprednisone IV push, and an additional SQ dose of 0.3 mg epinephrine 1:1,000. Repeat vital signs 15 minutes after presentation were blood pressure of 120/60 m m Hg; pulse, 160; and respirations, 20. Subsequent examination found the patient m u c h improved from his initial presentation; he was alert, oriented, cooperative, and in no respiratory difficulty. Head and neck e x a m i n a t i o n s were unremarkable. Cardiopulmonary evaluation demonstrated a rapid heart rate but clear lung fields. The abdomen was soft with normal bowel sounds, and the r e c t u m c o n t a i n e d guaiac-negative brown stool. Neurologic examination, including formal cranial nerve testing, was normal, and the patient exhibited no paresthesias. The patient's history revealed that he had been admitted to our facility approximately a year earlier for a rattlesnake bite to the hand. At that time, he had experienced only mild swelling and no sequelae. He had not been skin tested with horse serum or administered antivenin on that occasion. He had no history of any major m e d i c a l p r o b l e m s or s u r g e r y or known allergies. In preparation for antivenin therapy, skin testing was performed with 0.02 mL of the 1:10 horse serum included in the Antivenin (Crotalidae) Polyvalent ® kit (Wyeth Laboratories, Inc, Marietta, Pennsylvania) and was negative. Cefazolin 2 g IV and diphtheria-tetanus toxoid 0.5 mL IM were administered. He was admitted to the ICU by the orthopedic surgery service. Admission laboratory studies inc l u d e d WBC, 7 , 8 0 0 / m m 3 ; RBC, 5.7x106; hemoglobin, 17.3 g/dL; hematocrit, 50.9%; prothrombin time, 11 seconds; partial thromboplastin time, 24 seconds; fibrinogen, 230 mg/dL (normal range, 146 to 380 mg/ dL); fibrin split products, < 10 ~g/mL (normal, < 10 ixg/mL); blood alcohol, 149 mg/dL; glucose, 100 mg/dL; BUN, 10 mg/dL; creatinine, 1.2 mg/ 128/815
dL; calcium, 9.1 mg/dL; magnesium, 2.2 mg/dL; sodium, 142 mEq/L; potassium, 3.4 mEq/L; chloride, 107 mEq/L; and CO2, 22 mEq/L. An admission chest radiograph and ECG were normal. On admission to the ICU, the patient was placed on 250 mg methylprednisolone IV every six hours for 24 hours, 50 mg diphenhydramine IV every six hours, and 300 mg cimetadine IV every six hours. The patient experienced progressive swelling of his left lower leg and was started by the admitting service on five vials of antivenin in 100 mL of 5% dextrose in water IV drip app r o x i m a t e l y 3I/2 h o u r s after the snakebite. After administration of approximately 60 mL of the antivenin solution, he began to wheeze and complain of shortness of breath. Antivenin therapy was terminated, and 50 mg diphenhydramine IV was administered with resolution of his symptoms. Further laboratory studies revealed mildly elevated fibrin split products on the day of admission (> 10 ~g/mL but < 40 ~g/mL). This level quickly returned to normal. He did not develop clinical evidence of a compartment syndrome and was discharged from the hospital four days after the snakebite on analgesics with instructions to limit ambulation. A follow-up evaluation one week later found him to be fully recovered with no residual deficits. DISCUSSION Snake venoms are a complex mixture of metal ions, enzymes, biogenic amines, lipids, free amino acids, large and small proteins, and polypeptides. 1 T h i s v a r i e t y of p r o t e i n s , w h i c h m a k e s up 90% of its dry weight, behaves as heterologous proteins when introduced by the inhalation or injection route. 3 It is not surprising that sensitization occurs because snake venom is an excellent antigen. I m m e d i a t e systemic collapse or sudden death after snakebite envenomation may be due to allergy rather than toxicity.2, 3 A n a p h y l a x i s is an abrupt, systemic, frequently shocklike IgE-mediated reaction that occurs as certain chemicals are liberated when a sensitized host is exposed to an antigenic substance.4, s An indistinguishable clinical picture may occur without antibody mediation in previously unAnnals of Emergency Medicine
sensitized patients; this is referred to as an anaphylactoid reaction. 6 The hallmark of both reactions in human beings is urticaria, which is usually diffusely distributed but may be localized. 4 Bronchospasm is commonly seen in the anaphylactic patient and ranges from mild wheezes to respiratory failure. Hemodynamic changes are also seen; these range from mild hypotension to profound sudden vascular collapse, occasionally without antecedent urticaria. 4 Sporadic case reports appear in the medical literature describing local and systemic urticaria and local mucous membrane reactions in snake handlers while w o r k i n g with dry venom.2,7, 8 These local reactions include coryza, rhinorrhea, sneezing paroxysms, ocular pruritus, lacrimation, c o n j u n c t i v i t i s , and eyelid edema. The first allergic reaction to snake venom was reported in 1930 in a patient who had a previous copperhead bite; the patient received experimental intradermal injections of Crotalus, Agkistrodon, Bothrops, and Naja venom.9 Subsequent to this, he developed coryza and violent sneezing whenever handling dried snake venoms. Confirmation of this allergy was demonstrated by a positive skin test to Crotalus venom. In 1959, Parrish and Pollard ~ described 14 patients who had been bitten two or more times by N o r t h American pit vipers. Four of these patients had positive skin tests to Crotalus or Agkistrodon v e n o m , whereas none of 20 control patients (no history of snakebites) exhibited hypersensitivity. It is n o t e w o r t h y that two of their patients reacted to Crotalus venom but were previously b i t t e n o n l y by s n a k e s of t h e Agkistrodon genus. This is not surprising because of the presence of similar a n t i g e n i c p r o t e i n s in the venoms of these two genera. Serious systemic allergic reactions to snake v e n o m are m u c h m o r e rarely reported. One case report of an a p p a r e n t episode of a n a p h y l a c t i c shock occurred in a male professional snake handler who had a prior d o c u m e n t e d s e n s i t i v i t y to snake venom (determined by skin testing). 3 This patient was bitten by a small rattlesnake on the hand; within 90 seconds, he collapsed, appeared unresponsive, and developed cyanosis, wheezing, a sensation of his throat 19:7 July 1990
" c l o s i n g , " a s e n s e of " i m p e n d i n g d o o m , " and peripheral vascular collapse. T h e p a t i e n t had no urticaria. He was resuscitated by "heroic measures," w h i c h were n o t described. O n e s n a k e handler, who had n o t experienced a previous venomous snakebite, developed acute dyspnea, rhinorrhea, conjunctivitis, and thickness of the tongue and palate after a n o n b i t e exposure to r i n k a l s ( H a e m achates haemachatus) venom. 8 This patient had specific IgE antibodies to rinkals, black mamba, green mamba, cape cobra, Egyptian cobra, and spitting cobra v e n o m as demonstrated by ELISA. His sensitization was thought to have occurred from repeated inhalations or contact of the v e n o m w i t h skin or m u c o u s membranes. S c h m u t z a n d StahelZ d e s c r i b e d seven cases of serious allergic react i o n s f r o m b i t e s of t h e V i p e r a , A g k i s t r o d o n , C r o t a l u s , and S i s t r u r u s genera i n p a t i e n t s b i t t e n a second, third, or fourth time. The reactions i n c l u d e d u r t i c a r i a , dyspnea, angioneurotic edema, and hypotension. T h e r a p y for a s n a k e b i t e v i c t i m who presents with anaphylaxis should i n c l u d e t r e a t m e n t aimed at reversing the effects of the chemical m e d i a t o r s of a n a p h y l a x i s . H u m i d i fied oxygen, active airway control (if needed), IV line, and cardiac monitoring should be initiated on presentation. Initially, volume expansion w i t h crystalloids m a y be used to correct hypotension. Epinephrine is the preferred therapy for anaphylaxis and should be administered at a dose of 0.3 to 0.5 mL of a 1:1,000 s o l u t i o n s u b c u t a n e o u s l y or 3 to 5 mL of a 1:10,000 s o l u t i o n IV or by an endotracheal tube (0.01 mg/kg i n children) every five to 20 m i n u t e s for a total of three doses.lO, 11 If the patient is hyp o t e n s i v e , the s u b c u t a n e o u s r o u t e s h o u l d be a v o i d e d b e c a u s e of u n predictable absorption. The standard t r e a t m e n t of anaphylaxis also i n c l u d e s the use of H lblockers. D i p h e n h y d r a m i n e s h o u l d be given i n a dose of 50 m g orally or IM i n m i l d cases and IV i n severe cases (1.25 m g / k g i n children) a n d m a y be repeated every four to six h o u r s . 1° H 2 - B l o c k a d e w i t h c i m e t i d i n e has been used alone i n the t r e a t m e n t of anaphylaxis and acute skin reactions with some suc-
19:7 July 1990
tess. ]2,13 We u s e 300 m g IV c i m etidine (which can be repeated every six hours) in c o n j u n c t i o n w i t h H Iblocking agents in severe allergic reactions. I n h a l e d O-agonists are u s u a l l y eff e c t i v e for t h e relief of b r o n c h o spasm. A m i n o p h y l l i n e may be used in some settings where the bronchospastic c o m p o n e n t is resistant to epinephrine or inhaled [~-agonists. Vasopressors should be used i n hyp o t e n s i v e p a t i e n t s w h o do n o t respond to fluids or e p i n e p h r i n e . T h e vasopressor agent of choice is somew h a t controversial; n o r e p i n e p h r i n e or d o p a m i n e can be used i n t h e i r standard doses. 4 Military antishock trousers (MAST) m a y be indicated in the ED m a n a g e m e n t of patients w i t h persist e n t h y p o t e n s i o n secondary to anaphylaxis. ]4 M A S T h a v e b e e n u s e d specifically i n the t r e a t m e n t of anaphylactic shock recalcitrant to standard therapy3S MAST should be used c a u t i o u s l y for l o w e r - e x t r e m i t y snakebites because they m a y significantly contribute to increasing comp a r t m e n t pressures. Steroids should be considered for patients with persistent bronchospasm or h y p o t e n s i o n (125 to 250 m g m e t h y l p r e d n i s o l o n e IV e v e r y s i x hours). 16 Patients who experience moderateto-severe anaphylactic reactions should be a d m i t t e d to the hospital for 24 to 48 hours because sudden rec u r r e n c e of s y m p t o m s m a y be u n predictable. 1o, 16,17 A n t i v e n i n therapy is n o t indicated for p a t i e n t s w h o p r e s e n t w i t h anap h y l a x i s from s n a k e b i t e s . F u r t h e r more, a n t i v e n i n therapy is not necessary i n all patients w i t h e n v e n o m a tion. 18 A n t i v e n i n m a y be w i t h h e l d w h e n there are n e i t h e r signs of syst e m i c toxicity nor local signs other t h a n m i l d swelling about the bite.
SUMMARY A case of a n a p h y l a c t i c shock occ u r r i n g after a r a t t l e s n a k e b i t e is reported and the existing medical literature on this e n t i t y reviewed. Recognition of potentially life-threatening allergic reactions to snake enveno m a t i o n is i m p o r t a n t i n therapeutic d e c i s i o n s m a d e by t h e e m e r g e n c y physician. Aggressive therapy against
Annals of Emergency Medicine
a n a p h y l a x i s s h o u l d be c o m b i n e d w i t h the standard approach to envenomation. Anaphylaxis to snake v e n o m without other clinical indicators of significant v e n o m toxicity is n o t an indication for a n t i v e n i n therapy.
REFERENCES 1. Ellenhorn MJ, Barceloux DG: Medical Toxicology: Diagnosis and Treatmel~t of Human Poisoning. New York, ElsevierSciencePublishing, 1988, p 1112-1132. 2. Parrish HM, Pollard CB: Effects of repeated poisonous snakebite in man. A m J Med Sci 1959;237:277-286. 3. Ellis EF, Smith RT: Systemicanaphylaxisaf~ ter rattlesnake bite. JAMA 1965;193:151-152. 4. Lucke WC, Thomas H: Anaphylaxis:Pathophysiology, clinical presentationand treatment. J Emerg Med 1983;1:83-95. 5. Valentine MD, Lichtenstein LM: Anaphylaxis and stinginginsect hypersensitivity.JAMA 1987;258:2881-2885. 6. Sheffer AL: Anaphylaxis. J Allergy Clin Immnnol 1985;75:227-233. 7. Schmutz J, Stahel E: Anaphylactoidreactions to snakebite. Lancet 1985;2:1306. 8. WadeeAA, RabsonAR: Developmentof specific IgE antibodies after repeated exposure to snake venom. J Allergy Clin Immunol 1987;80: 695-698. 9. Zozaya J, Stadelman RE: Hypersensitiveness to snake venom proteins: A case report. Bull Antivenin Inst A m 1930;3:93. 10. EMERGINDEX®system, HonigmanB, Barkin R, Rumack BH (eds): EMERGINDEX ® information System. Denver, Micromedex, Inc, (ed expires August 31, 1989). 11. Baraeh EM, Nowak RM, Lee TG, et al: Epinephrine for treatment of anaphylactic shock. JAMA 1984;251:2118-2122. 12. MayumiH, KimuraS, AsanoM, et al: Intravenous cimetidine as an effective treatment for systemic anaphylaxisand acute allergicskin re~ actions. Ann Allergy 1987;58:447-450. 13. Moscati RM, Moore GP: Comparison of cimetidine and diphenhydramine in the treatment of acute urticaria. A n n Emerg Med 1990;19:12q5. 14. Oertel T, Loehr MM: Bee-stinganaphylaxis: The use of medical antishock trousers. Ann Emerg Med 1984;13:459-461. 15. Bickell WH, Dice WH: Military antishock trousers in a patient with adrenergic-resistant anaphylaxis.Ann Emerg Med 1984;13:189-190. 16. Lindzon RD, Silvers WS: Anaphylaxis, in Rosen P, Baker FJ, BarkinRM, et al (eds): Emergency Medicine: Concepts and Clinical Practice, ed 2. St Louis, CV Mosby, 1988, vol 1, p
203-231. 17. Lasater v Clare Osteopathic HospiLal (ED Mich 1985J. 18. Nelson BK: Snake envcnomation: Incidence, clinical presentation and management. Med Toxicol 1989;4:17-31.
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Anaphylactic Shock Secondary to Rattlesnake Bite Anaphylactic reactions to Crotalidae envenomation are extremely rare. The presentation of anaphylaxis after envenomation can be a confusing variable in the timely diagnosis of both problems. The therapy of this dual disorder involves combining treatment of the obvious shock from the allergic reaction with a standard approach to Crotalidae envenomation. We present the case of a 22-year-old man who presented to the emergency department with urticaria, hypotension, and bronchospasm that developed immediately after his second envenomation from a rattlesnake. His symptoms resolved after administration of 0.8 mg SQ epinephrine, 100 mg IV diphenhydramine, 2,000 m L normal saline IV, and 250 mg IV methylprednisolone. Only one previous case report of anaphylactic shock from a rattlesnake bite could be found in the medical literature. [Hogan DE, Dire DJ: Anaphylactic shock secondary to rattlesnake bite. Ann Emerg Med July 1990;19:814-816.]
David E Hogan, DO* Daniel J Dire, MDt Fort Hood, Texas
INTRODUCTION An estimated 8,000 poisonous snakebites occur annually in the United States; 12 to 15 are fatal. 1 The treatment of snake envenomation is controversial. Death from snakebites may result from snake venom allergy, 2 but the prevalence of allergic reactions to snake venom is unknown. 3 When the clinical presentation of envenomation is complicated by the onset of a significant allergic reaction, the immediate diagnosis and appropriate therapy are even less clear. We present the case of a 22-year-old man with his second exposure to rattlesnake venom and discuss the pathophysiology and management of anaphylactic and anaphylaetoid reactions to envenomation.
The opinions or assertions contained herein are those of the authors and should not be construed as official or as representing the opinions of the Department of the Army or the Department of Defense.
From the Department of Emergency Medicine, Emergency Medicine Residency Program, Darnall Army Community Hospital, Fort Hood, Texas;* and Department of Internal Medicine, University of Texas A&M College of Medicine, Temple, Texas.t Received for publication October 12, 1989. Revision received February 1, 1990. Accepted for publication March 5, 1990.
Address for reprints: David E Hogan, DO, Department of Emergency Medicine, Darnall Army Community Hospital, Fort Hood, Texas 76544-5063.
CASE REPORT A 22-year-old man presented to the emergency department approx~ imately 30 minutes after he was bitten by a moderate-sized rattlesnake. He had not received any first aid before presentation. The snake had bitten him in the lower left leg and had seemed to remain attached despite vigorous shaking. After five or six seconds, the snake was removed manually and flung through the air. The patient noted an immediate severe burning pain at the site of the bite. Within two to three minutes, he noted dizzihess, general pruritus, and shortness of breath. He contacted a neighbor, who arrived within five minutes and drove him to the ED. No prehospital care was administered. The rattlesnake was not available for definitive identification. On arrival, the patient was responsive but combative with obvious respiratory difficulty, accessory muscle use, and a striking generalized urticarial rash. Chest examination demonstrated diffuse wheezes with prolonged expiratory phase and a rapid regular heart rate. Vital signs were blood pressure of 90/60 m m Hg; pulse, ll0; respirations, 36; and temperature, 37.2 C rectally. A lead II rhythm strip showed sinus tachycardia at a rate of 110 to 120. A nasopharyngeal airway was inserted, and supplemental oxygen was placed with a reservoir mask while preparations were made for possible nasotracheal intubation. The patient was given an initial SQ injection of 0.5 mg l:l,000 epinephrine, and two 18-gauge IV lines of normal saline were established. Diphenhydramine 100 mg IV was administered.
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ANAPHYLACTIC SHOCK Hogan & Dire
Examination of the bite revealed a single puncture wound 3 em from an abrasion on the anterolateral left lower leg. The puncture was oozing a small a m o u n t of serosanguineous fluid. A light lymphatic constricting band was placed above the bite on the lower left leg. Additional therapy consisted of 2,000 mL normal saline, 250 mg methylprednisone IV push, and an additional SQ dose of 0.3 mg epinephrine 1:1,000. Repeat vital signs 15 minutes after presentation were blood pressure of 120/60 m m Hg; pulse, 160; and respirations, 20. Subsequent examination found the patient m u c h improved from his initial presentation; he was alert, oriented, cooperative, and in no respiratory difficulty. Head and neck e x a m i n a t i o n s were unremarkable. Cardiopulmonary evaluation demonstrated a rapid heart rate but clear lung fields. The abdomen was soft with normal bowel sounds, and the r e c t u m c o n t a i n e d guaiac-negative brown stool. Neurologic examination, including formal cranial nerve testing, was normal, and the patient exhibited no paresthesias. The patient's history revealed that he had been admitted to our facility approximately a year earlier for a rattlesnake bite to the hand. At that time, he had experienced only mild swelling and no sequelae. He had not been skin tested with horse serum or administered antivenin on that occasion. He had no history of any major m e d i c a l p r o b l e m s or s u r g e r y or known allergies. In preparation for antivenin therapy, skin testing was performed with 0.02 mL of the 1:10 horse serum included in the Antivenin (Crotalidae) Polyvalent ® kit (Wyeth Laboratories, Inc, Marietta, Pennsylvania) and was negative. Cefazolin 2 g IV and diphtheria-tetanus toxoid 0.5 mL IM were administered. He was admitted to the ICU by the orthopedic surgery service. Admission laboratory studies inc l u d e d WBC, 7 , 8 0 0 / m m 3 ; RBC, 5.7x106; hemoglobin, 17.3 g/dL; hematocrit, 50.9%; prothrombin time, 11 seconds; partial thromboplastin time, 24 seconds; fibrinogen, 230 mg/dL (normal range, 146 to 380 mg/ dL); fibrin split products, < 10 ~g/mL (normal, < 10 ixg/mL); blood alcohol, 149 mg/dL; glucose, 100 mg/dL; BUN, 10 mg/dL; creatinine, 1.2 mg/ 128/815
dL; calcium, 9.1 mg/dL; magnesium, 2.2 mg/dL; sodium, 142 mEq/L; potassium, 3.4 mEq/L; chloride, 107 mEq/L; and CO2, 22 mEq/L. An admission chest radiograph and ECG were normal. On admission to the ICU, the patient was placed on 250 mg methylprednisolone IV every six hours for 24 hours, 50 mg diphenhydramine IV every six hours, and 300 mg cimetadine IV every six hours. The patient experienced progressive swelling of his left lower leg and was started by the admitting service on five vials of antivenin in 100 mL of 5% dextrose in water IV drip app r o x i m a t e l y 3I/2 h o u r s after the snakebite. After administration of approximately 60 mL of the antivenin solution, he began to wheeze and complain of shortness of breath. Antivenin therapy was terminated, and 50 mg diphenhydramine IV was administered with resolution of his symptoms. Further laboratory studies revealed mildly elevated fibrin split products on the day of admission (> 10 ~g/mL but < 40 ~g/mL). This level quickly returned to normal. He did not develop clinical evidence of a compartment syndrome and was discharged from the hospital four days after the snakebite on analgesics with instructions to limit ambulation. A follow-up evaluation one week later found him to be fully recovered with no residual deficits. DISCUSSION Snake venoms are a complex mixture of metal ions, enzymes, biogenic amines, lipids, free amino acids, large and small proteins, and polypeptides. 1 T h i s v a r i e t y of p r o t e i n s , w h i c h m a k e s up 90% of its dry weight, behaves as heterologous proteins when introduced by the inhalation or injection route. 3 It is not surprising that sensitization occurs because snake venom is an excellent antigen. I m m e d i a t e systemic collapse or sudden death after snakebite envenomation may be due to allergy rather than toxicity.2, 3 A n a p h y l a x i s is an abrupt, systemic, frequently shocklike IgE-mediated reaction that occurs as certain chemicals are liberated when a sensitized host is exposed to an antigenic substance.4, s An indistinguishable clinical picture may occur without antibody mediation in previously unAnnals of Emergency Medicine
sensitized patients; this is referred to as an anaphylactoid reaction. 6 The hallmark of both reactions in human beings is urticaria, which is usually diffusely distributed but may be localized. 4 Bronchospasm is commonly seen in the anaphylactic patient and ranges from mild wheezes to respiratory failure. Hemodynamic changes are also seen; these range from mild hypotension to profound sudden vascular collapse, occasionally without antecedent urticaria. 4 Sporadic case reports appear in the medical literature describing local and systemic urticaria and local mucous membrane reactions in snake handlers while w o r k i n g with dry venom.2,7, 8 These local reactions include coryza, rhinorrhea, sneezing paroxysms, ocular pruritus, lacrimation, c o n j u n c t i v i t i s , and eyelid edema. The first allergic reaction to snake venom was reported in 1930 in a patient who had a previous copperhead bite; the patient received experimental intradermal injections of Crotalus, Agkistrodon, Bothrops, and Naja venom.9 Subsequent to this, he developed coryza and violent sneezing whenever handling dried snake venoms. Confirmation of this allergy was demonstrated by a positive skin test to Crotalus venom. In 1959, Parrish and Pollard ~ described 14 patients who had been bitten two or more times by N o r t h American pit vipers. Four of these patients had positive skin tests to Crotalus or Agkistrodon v e n o m , whereas none of 20 control patients (no history of snakebites) exhibited hypersensitivity. It is n o t e w o r t h y that two of their patients reacted to Crotalus venom but were previously b i t t e n o n l y by s n a k e s of t h e Agkistrodon genus. This is not surprising because of the presence of similar a n t i g e n i c p r o t e i n s in the venoms of these two genera. Serious systemic allergic reactions to snake v e n o m are m u c h m o r e rarely reported. One case report of an a p p a r e n t episode of a n a p h y l a c t i c shock occurred in a male professional snake handler who had a prior d o c u m e n t e d s e n s i t i v i t y to snake venom (determined by skin testing). 3 This patient was bitten by a small rattlesnake on the hand; within 90 seconds, he collapsed, appeared unresponsive, and developed cyanosis, wheezing, a sensation of his throat 19:7 July 1990
" c l o s i n g , " a s e n s e of " i m p e n d i n g d o o m , " and peripheral vascular collapse. T h e p a t i e n t had no urticaria. He was resuscitated by "heroic measures," w h i c h were n o t described. O n e s n a k e handler, who had n o t experienced a previous venomous snakebite, developed acute dyspnea, rhinorrhea, conjunctivitis, and thickness of the tongue and palate after a n o n b i t e exposure to r i n k a l s ( H a e m achates haemachatus) venom. 8 This patient had specific IgE antibodies to rinkals, black mamba, green mamba, cape cobra, Egyptian cobra, and spitting cobra v e n o m as demonstrated by ELISA. His sensitization was thought to have occurred from repeated inhalations or contact of the v e n o m w i t h skin or m u c o u s membranes. S c h m u t z a n d StahelZ d e s c r i b e d seven cases of serious allergic react i o n s f r o m b i t e s of t h e V i p e r a , A g k i s t r o d o n , C r o t a l u s , and S i s t r u r u s genera i n p a t i e n t s b i t t e n a second, third, or fourth time. The reactions i n c l u d e d u r t i c a r i a , dyspnea, angioneurotic edema, and hypotension. T h e r a p y for a s n a k e b i t e v i c t i m who presents with anaphylaxis should i n c l u d e t r e a t m e n t aimed at reversing the effects of the chemical m e d i a t o r s of a n a p h y l a x i s . H u m i d i fied oxygen, active airway control (if needed), IV line, and cardiac monitoring should be initiated on presentation. Initially, volume expansion w i t h crystalloids m a y be used to correct hypotension. Epinephrine is the preferred therapy for anaphylaxis and should be administered at a dose of 0.3 to 0.5 mL of a 1:1,000 s o l u t i o n s u b c u t a n e o u s l y or 3 to 5 mL of a 1:10,000 s o l u t i o n IV or by an endotracheal tube (0.01 mg/kg i n children) every five to 20 m i n u t e s for a total of three doses.lO, 11 If the patient is hyp o t e n s i v e , the s u b c u t a n e o u s r o u t e s h o u l d be a v o i d e d b e c a u s e of u n predictable absorption. The standard t r e a t m e n t of anaphylaxis also i n c l u d e s the use of H lblockers. D i p h e n h y d r a m i n e s h o u l d be given i n a dose of 50 m g orally or IM i n m i l d cases and IV i n severe cases (1.25 m g / k g i n children) a n d m a y be repeated every four to six h o u r s . 1° H 2 - B l o c k a d e w i t h c i m e t i d i n e has been used alone i n the t r e a t m e n t of anaphylaxis and acute skin reactions with some suc-
19:7 July 1990
tess. ]2,13 We u s e 300 m g IV c i m etidine (which can be repeated every six hours) in c o n j u n c t i o n w i t h H Iblocking agents in severe allergic reactions. I n h a l e d O-agonists are u s u a l l y eff e c t i v e for t h e relief of b r o n c h o spasm. A m i n o p h y l l i n e may be used in some settings where the bronchospastic c o m p o n e n t is resistant to epinephrine or inhaled [~-agonists. Vasopressors should be used i n hyp o t e n s i v e p a t i e n t s w h o do n o t respond to fluids or e p i n e p h r i n e . T h e vasopressor agent of choice is somew h a t controversial; n o r e p i n e p h r i n e or d o p a m i n e can be used i n t h e i r standard doses. 4 Military antishock trousers (MAST) m a y be indicated in the ED m a n a g e m e n t of patients w i t h persist e n t h y p o t e n s i o n secondary to anaphylaxis. ]4 M A S T h a v e b e e n u s e d specifically i n the t r e a t m e n t of anaphylactic shock recalcitrant to standard therapy3S MAST should be used c a u t i o u s l y for l o w e r - e x t r e m i t y snakebites because they m a y significantly contribute to increasing comp a r t m e n t pressures. Steroids should be considered for patients with persistent bronchospasm or h y p o t e n s i o n (125 to 250 m g m e t h y l p r e d n i s o l o n e IV e v e r y s i x hours). 16 Patients who experience moderateto-severe anaphylactic reactions should be a d m i t t e d to the hospital for 24 to 48 hours because sudden rec u r r e n c e of s y m p t o m s m a y be u n predictable. 1o, 16,17 A n t i v e n i n therapy is n o t indicated for p a t i e n t s w h o p r e s e n t w i t h anap h y l a x i s from s n a k e b i t e s . F u r t h e r more, a n t i v e n i n therapy is not necessary i n all patients w i t h e n v e n o m a tion. 18 A n t i v e n i n m a y be w i t h h e l d w h e n there are n e i t h e r signs of syst e m i c toxicity nor local signs other t h a n m i l d swelling about the bite.
SUMMARY A case of a n a p h y l a c t i c shock occ u r r i n g after a r a t t l e s n a k e b i t e is reported and the existing medical literature on this e n t i t y reviewed. Recognition of potentially life-threatening allergic reactions to snake enveno m a t i o n is i m p o r t a n t i n therapeutic d e c i s i o n s m a d e by t h e e m e r g e n c y physician. Aggressive therapy against
Annals of Emergency Medicine
a n a p h y l a x i s s h o u l d be c o m b i n e d w i t h the standard approach to envenomation. Anaphylaxis to snake v e n o m without other clinical indicators of significant v e n o m toxicity is n o t an indication for a n t i v e n i n therapy.
REFERENCES 1. Ellenhorn MJ, Barceloux DG: Medical Toxicology: Diagnosis and Treatmel~t of Human Poisoning. New York, ElsevierSciencePublishing, 1988, p 1112-1132. 2. Parrish HM, Pollard CB: Effects of repeated poisonous snakebite in man. A m J Med Sci 1959;237:277-286. 3. Ellis EF, Smith RT: Systemicanaphylaxisaf~ ter rattlesnake bite. JAMA 1965;193:151-152. 4. Lucke WC, Thomas H: Anaphylaxis:Pathophysiology, clinical presentationand treatment. J Emerg Med 1983;1:83-95. 5. Valentine MD, Lichtenstein LM: Anaphylaxis and stinginginsect hypersensitivity.JAMA 1987;258:2881-2885. 6. Sheffer AL: Anaphylaxis. J Allergy Clin Immnnol 1985;75:227-233. 7. Schmutz J, Stahel E: Anaphylactoidreactions to snakebite. Lancet 1985;2:1306. 8. WadeeAA, RabsonAR: Developmentof specific IgE antibodies after repeated exposure to snake venom. J Allergy Clin Immunol 1987;80: 695-698. 9. Zozaya J, Stadelman RE: Hypersensitiveness to snake venom proteins: A case report. Bull Antivenin Inst A m 1930;3:93. 10. EMERGINDEX®system, HonigmanB, Barkin R, Rumack BH (eds): EMERGINDEX ® information System. Denver, Micromedex, Inc, (ed expires August 31, 1989). 11. Baraeh EM, Nowak RM, Lee TG, et al: Epinephrine for treatment of anaphylactic shock. JAMA 1984;251:2118-2122. 12. MayumiH, KimuraS, AsanoM, et al: Intravenous cimetidine as an effective treatment for systemic anaphylaxisand acute allergicskin re~ actions. Ann Allergy 1987;58:447-450. 13. Moscati RM, Moore GP: Comparison of cimetidine and diphenhydramine in the treatment of acute urticaria. A n n Emerg Med 1990;19:12q5. 14. Oertel T, Loehr MM: Bee-stinganaphylaxis: The use of medical antishock trousers. Ann Emerg Med 1984;13:459-461. 15. Bickell WH, Dice WH: Military antishock trousers in a patient with adrenergic-resistant anaphylaxis.Ann Emerg Med 1984;13:189-190. 16. Lindzon RD, Silvers WS: Anaphylaxis, in Rosen P, Baker FJ, BarkinRM, et al (eds): Emergency Medicine: Concepts and Clinical Practice, ed 2. St Louis, CV Mosby, 1988, vol 1, p
203-231. 17. Lasater v Clare Osteopathic HospiLal (ED Mich 1985J. 18. Nelson BK: Snake envcnomation: Incidence, clinical presentation and management. Med Toxicol 1989;4:17-31.
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