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Evaluation & Current Treatment Options for North American Poisonous Snake Envenomations

Evaluation & Current Treatment Options for North American Poisonous Snake Envenomations. Matthew T. Hamonko MD, MPH, FACEP, FAWM, FAAEM. Identification. Coral Snake. “Red on yellow, kill a fellow; red on black, venom lack.”. Auerbach , P.S. Wilderness Medicine. Mosby, 2007.

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Evaluation & Current Treatment Options for North American Poisonous Snake Envenomations

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  1. Evaluation & Current Treatment Options for North American Poisonous Snake Envenomations Matthew T. HamonkoMD, MPH, FACEP, FAWM, FAAEM

  2. Identification • Coral Snake “Red on yellow, kill a fellow; red on black, venom lack.” Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  3. Identification • Coral Snake “Red on yellow, kill a fellow; red on black, venom lack.” ONLY WORKS IN NORTH AMERICA, NORTH OF MEXICO CITY! Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  4. Identification: Pit Vipers • Pit Viper • Triangular head • Elliptical eyes • Fangs • Pit • Single row of subcaudal plates • Non-venomous snake • Rounded head • Round eyes • No fangs • No pits • Double row of subcaudal plates *Pits are the only 100% consistent finding *subcaudal plates only useful in North America Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, 2002.

  5. Identification • Corbett, S.W., et. al., “Most lay People can Correctly identify Indigenous Venomous Snakes.” Amer Journal Emerg Med.,2005;23:759-762. • N=265 (169 adults, 72 children) • 4 non-venomous snakes, 2 venomous snakes • Gopher snake, moutain king snake, common king snake, rosy boa, mojave rattlesnake, southern pacific rattlesnake • Southern California street fair • Random members of the public were able to differentiate venomous from non-venomous 81% of the time

  6. Present in all 48 contiguous states except Maine Distribution Rattlesnakes- all of North America Copperheads- central and southeastern U.S. Water moccasins- southeastern U.S. in to Texas Pit Vipers Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  7. Eastern Diamondback Rattlesnake can exceed 6.5 ft in length Maximum pit viper speed = 3 mph “Crotaline snakes do not chase people” Can voluntarily decide how much venom to inject Envenomation in 75%-80% of bites 35% mild, 25% moderate, 10-15% severe Most elaborate venom delivery system of all snakes Pit Vipers Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  8. Hollow fangs Individually foldable Up to 20mm in length Pit Vipers Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  9. Venom Roughly 100 chemical components Protein (90%-95%) and non-protein based (5%-10%) Phospholipase A2 neurotoxins Metalloproteinases Other Pit Vipers Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  10. Venom Phospholipase A2 neurotoxins Noncompetitively binds presynaptic calcium channels Inhibits acetylcholine release at NMJ Muscle inactivation Respiratory paralysis Damages muscle cell membranes Calcium influx CK release Myonecrosis, rhabdomyolysis Pit Vipers Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  11. Venom Metalloproteinase Primary cause of local tissue destruction Activation of TNF-α Activates endogenous metalloproteinases Causes RBC leakage from vasculature causing ecchymosis Pit Vipers Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  12. Venom Thrombin like enzymes Consumptive coagulopathy Disintegrins Inhibit platelet interaction with fibrinogen Bradykinins Hyaluronidase Decreased connective tissue viscosity Lysolecithin Damage mast cell membranes causing histamine release Pit Vipers Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  13. Table 38-3 -- Signs and Symptoms of Rattlesnake Bites Signs and symptoms after Rattlesnake envenomation Local: severe burning, swelling, bleeding, ecchymosis, fang marks, vesicles, bullae Systemic: nausea, vomit, generalized weakness, odd taste, tachypnea, tachycardia, pulmonary edema, hypo- or hypertension, shock, muscle fasciculations, parasthesias, numbness, focal muscle weakness, bleeding (Neuro, GI/GU, pulm, gingival) Estimated mortality for untreated bites: 2.6% Pit Vipers Auerbach, P.S. Wilderness Medicine. Mosby, 2007. Modified from Russell FE: Snake venom poisoning, New York, 1983, Scholium International.

  14. Found in the Arizona, Texas and the Southeastern U.S. Bites uncommon Less aggressive, unable to strike like crotalines Simple venom delivery apparatus fixed fangs, about 2mm in length Must chew on the victim to inject sufficient venom Envenomation in 40% of bites Venom Minimum proteolytic activity Contains some hyaluronidase, myotoxins and phospholipases Primary component: Neurotoxin Elapids Auerbach, P.S. Wilderness Medicine. Mosby, 2007. Norris, R.L, et al, “Apparent Coral Snake Envenomation in a Patient Without Visible Fang Marks.” Amer Journ Emerg Med, 1989;7:402-405.

  15. Elapids • Venom • Neurotoxin • Low molecular weight protein • Non-depolarizing neuromuscular blocker • Postsynaptic competitive binding of acetylcholine receptors at NMJ Auerbach, P.S. Wilderness Medicine. Mosby, 2007. Norris, R.L, et al, “Apparent Coral Snake Envenomation in a Patient Without Visible Fang Marks.” Amer Journ Emerg Med, 1989;7:402-405.

  16. Elapids • Signs and Symptoms • Local: early, mild, transient pain, +/- fang marks (85%) • Systemic (4-10 hours later sometimes delayed up to 13 hours): nausea, vomit, headache, abdominal pain, diaphoresis, pallor, parasthesias, numbness, altered mental status, cranial nerve dysfunction, focal motor weakness, respiratory paralysis • Estimated mortality for untreated bite: 10% Auerbach, P.S. Wilderness Medicine. Mosby, 2007. Norris, R.L, et al, “Apparent Coral Snake Envenomation in a Patient Without Visible Fang Marks.” Amer Journ Emerg Med, 1989;7:402-405.

  17. Elapids • Norris, R.L, et al, “Apparent Coral Snake Envenomation in a Patient Without Visible Fang Marks.” Amer Journ Emerg Med, 1989;7:402-405. • 27 year old male • Bitten on finger by coral snake • Complains of finger parasthesias at bite site and blurred vision • No evidence of trauma on examination of the finger under magnification • Normal vital signs, normal exam • Given antivenin based on history and symptoms • Total resolution of symptoms after antivenin infusion completed (4 hours after bite)

  18. Evaluation • Rapid detailed history • Time of the bite • General description of the snake • First aid measures used • Coexisting medical conditions • Drug and food allergies • Allergies to horse or sheep products • History of previous snake bites and subsequent therapy • History of tetanus immunization (update if necessary) Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347-356.

  19. Evaluation • Physical exam • ABC’s • Special attention to cardiovascular, pulmonary and neurologic systems • Bite exam: • Fang or tooth marks (snakes have regular teeth too), scratches, edema, erythema, ecchymoses • Baseline circumferential measurement with repeat every 15-20 minutes • Evaluate for compartment syndrome • Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347-356. • Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, • 2002.

  20. Evaluation • Laboratory studies • CBC • PT, PTT, INR, fibrinogen, fibrin degradation products • Chem • UA • CK • Type and cross for 4 units • CXR • EKG • ABG (respiratory compromise) Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347-356. Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, 2002.

  21. Evaluation • Laboratory results • Coral Snakes • No likely laboratory abnormalities Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  22. Evaluation • Laboratory results • Pit Vipers • WBC elevation (neutrophil leukocytosis) • Thrombocytopenia • Hyperglycemia • Elevated CK • Elevated BUN and Crt • Elevated LFT’s • Elevated PT, PTT and INR • Low fibrinogen, elevated fibrin degradation products, (+)D-Dimer • UA:hematuria, proteinuria • EKG: ischemia • CXR: pulmonary vascular congestion, pulmonary edema Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  23. Treatment • General management • Refractory thrombocytopenia • Anaphylaxis • Antibiotic prophylaxis and empiric treatment • Antivenom administration • Pressure dressings • Surgical techniques • Suctioning

  24. Between 1000 and 600 BC Hindu physician: Sushruta Medical book: Ayurveda Treatment of snake bites: tourniquet, incision, suction, wound cautery Treatment Wingert, W.A., “Rattlesnake Bites in Southern California and Rationale for Recommended Treatment.” The Western Journal of Medicine, 1988;148:37-44.

  25. Treatment • Early American method: Whiskey • 1908, Archives of Internal Medicine article reported a significant number of deaths more likely to be caused by forced alcohol intake than the bite itself, often in children • Dart, R.C., et al., “Efficacy, Safety, and Use of Snake Antivenoms in the United States.” Ann of Emerg Med, 2001;37:181-188. • Burch, J.M., et al, “The Treatment of CrotalidEnvenomation without Antivenin.” Journal of Trauma, 1988;28:35-43.

  26. General Management • Early intubation for pit viper bites to the face or neck • 2 large bore IV lines • Pulse ox and cardiac monitor • IV crystalloid • Albumin trial if refractory to 2 liters of crystalloid (or 40ml/kg in a child) • Vasopressors if hypotension refractory to fluid resuscitation and antivenom infusion has been started • Opioid analgesia (no NSAIDS, may exacerbate coagulopathy) • Tetanus prophylaxis if indicated • Wound cleaning • Splinting of involved extremity • Elevation of the extremity above the heart (if antivenom is indicated, start before elevating the limb) Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  27. Refractory Thrombocytopenia • Gold, B.S., et al., “Refractory Thrombocytopenia Despite Treatment for Rattlesnake Envenomation.” N Engl J Med, 2004;350:1912-1913. • 38 year old male bitten on left hand by timber rattlesnake • Swelling, ecchymosis, tenderness • Normal vital signs • Platelet count on admission: 157,000 • Platelet count five hours later: 28,300 • Received 46 vials of Crofab • Platelet count 10 days later prior to discharge: 26,300 • No incidence of spontaneous bleeding during his 10 day hospital stay • Platelet count 3 weeks after envenomation: 245,000

  28. Refractory Thrombocytopenia • Recommendation: • Administer antivenom prior to administration of blood products (FFP, platelets, PRBC’s, cryo) • Regardless of bleeding, platelet transfusion for levels below 20,000 • Consumptive coagulopathy refractory to replacement of coagulation factors or other blood components while un-neutralized venom components are present • Coagulopathy may resolve after antivenom alone Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347-356. Brooks, D.E., et. al. “Airway Compromise After First Rattlesnake Envenomation.” Wilderness and Environmental Medicine, 2004; 15:188-193. Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  29. Anaphylaxis • Brooks, D.E., et. al. “Airway Compromise After First Rattlesnake Envenomation.” Wilderness and Environmental Medicine, 2004; 15:188-193. • 26 year old male, bitten on the hand by a sidewinder rattlesnake (Crotalus cerastes) • History of handling and eating rattlesnakes but no previous envenomations • Initial BP 68/28, no rash or edema at wound site • Severe Airway edema developed within 45 minutes of ED presentation • Swelling of the entire right arm at 72 hours post envenomation • Subsequent hematuria, renal failure, large bowel enterocutaneous fistulas, sepsis and malnutrition

  30. Anaphylaxis • Ryan, K.C., et. al. “Life-threatening Anaphylaxis Following Envenomation by two Different Species of Crotalidae.” Journal of Wilderness Medicine, 1994;5:263-268. • 42 year old male bitten on the hand by a rattlesnake • Previous history of envenomation by another species of rattlesnake • 5 minutes post bite he present with dyspnea, nausea, vomiting, abdominal pain, intensely pruritic, erythematous rash covering his upper extremities, anterior chest and abdomen • 3 years later, bitten on the hand by another species of rattlesnake • Once again presents with vomiting, dyspnea, diffuse erythematous rash as well as expiratory wheezing • Symptoms responded well to SQ epinephrine and IV solumedrol • Discharged the following day with no antivenin administered on either occasion

  31. Anaphylaxis • Primarily case reports • Uncommon entity • Type I IgE mediated • Type III immune complex mediated • IgE and IgG shown to be produced after sensitization to venom • One type of venom may cause sensitization to another • Airborne, GI and cutaneous exposures may be involved • Treat like any other anaphylactic reaction • Brooks, D.E., et. al. “Airway Compromise After First Rattlesnake Envenomation.” Wilderness and Environmental Medicine, 2004; 15:188-193. • Ryan, K.C., et. al. “Life-threatening Anaphylaxis Following Envenomation by two Different Species of Crotalidae.” Journal of Wilderness Medicine, 1994;5:263-268.

  32. Antibiotics? • LoVecchio, F., et. al., “Antibiotics After Rattlesnake Envenomation.” Journ of Emerg Med, 2002;23:327-328. • Prospective observational study • N=56 • Inclusion criteria: presentation to hospital within 24 hours, completion of follow up at 7-10 day • Exclusion criteria: antibiotics initiated before evaluation at research institution • (+) infection defined as: report of infection by a physician, use of antibiotics within 10 days, report of purulent discharge by patient, positive wound culture • 61% bites to upper extremity, 39% bites to lower extremity • 70% had tender proximal lymph nodes • No cases of documented infection • Antibiotics given to 3 patients by their primary doctor • Reasoning: prophylaxis, presumed standard of care, ecchymosis

  33. Antibiotics? • Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347-356. • Recommendation: • “Wound infections are rare after pit viper bites; therefore, the prophylactic use of antibiotics is not recommended. Antibiotics should be administered if there is clinical and microbiologic evidence of wound infection.”

  34. Antibiotics? • Secondary infection pending cultures • Ciprofloxacin 500 mg PO BID • +/- metronidazole or clindamycin (anaerobic) • Pregnant woman and children • Ceftriaxone 50mg/kg up to1 gram IV or IM then amoxicillin/clavulanate 40mg/kg PO divided TID Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  35. Antivenom • To give or not to give? • Coral snakes: • If a coral snake is identified: give it • If There is evidence by history or exam that the snake delivered an effective bite: give it • If there are systemic findings: give it • If there are no systemic findings after a confirmed coral snake envenomation: give it • If there are no local findings after a confirmed coral snake envenomation: give it Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  36. Antivenom • To give or not to give? • Pit vipers • Grading systems • Decision rules

  37. Antivenom Gold, B.S., et. al., “Bites of Venomous Snakes.” NEJM, 2002;347:347-356.

  38. Antivenom • Crofab • Mild 4-6 vials • Moderate 4-6 vials • Severe 6 vials • ACP • Mild 0 or 5 vials • Moderate 10 vials • Severe 15-20 vials Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  39. Antivenom • Wyeth’s (manufacturer) scale • 0- no evidence of envenomation, fang wound may be present, minimal pain, <1 inch surrounding edema/erythema, no systemic manifestations during the 1st 12 hours, no lab changes • I- minimal envenomation, fang wound usually present, moderate pain at wound site, 1-5 inch of surrounding erythema, no systemic involvement after 12 hours of observation, no lab changes Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, 2002.

  40. Antivenom • Wyeth’s (manufacturers) scale • II- moderate envenomation, more severe and widely distributed pain, edema spreading toward trunk, petechiae and ecchymosis limited to area of edema. Nausea, vomit, giddiness and mild temp elevation usually present • III- severe envenomation, rapidly progressive, within 12 hours edema spreads up extremity and may involve trunk, petechiae and ecchymoses may be generalized. Systemic manifestations may include tachycardia, hypotension, subnormal temp Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, 2002.

  41. Antivenom • Wyeth’s (manufacturers) scale • IV- very severe envenomation, sudden pain, rapidly progressing swelling that may reach the trunk within a few hours, ecchymoses, bleb formation, necrosis. Systemic manifestations (often within 15 minutes) of weakness, nausea, vomiting, vertigo, numbness and tingling of the lips and face, muscle fasciculations, muscle cramps, pallor, sweating, cold/clammy skin, rapid/weak pulse, incontinence, convulsions, coma, death Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, 2002.

  42. Antivenom Marx, et. al. Rosen’s Emergency Medicine: Concepts and Clinical Practice 5th ed. Mosby, 2002.

  43. Antivenom • Copperhead snakes • Rosen’s: “Bites by copperheads usually cause a moderate amount of edema but do not usually require antivenin” • Gold, et. al, “Bites of Venomous Snakes” NEJM : “Envenomations by copperheads are not considered to be as toxic as rattlesnake or cottonmouth bites and rarely require treatment; however, severe envenomations left untreated in children or elderly persons may result in death”

  44. Antivenom • Preparation • Informed consent ( all U.S. antivenoms are class C in pregnancy) • No skin test (ineffective, may cause allergic reaction) • Expand intravascular volume with crystalloid • Pretreat with H1 and H2 antihistamines • Consider prophylactic dose of SQ epinephrine in high risk patients Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  45. Antivenom • Auerbach, P.S. Wilderness Medicine. Mosby, 2007. • Brubacher, J.R., et al, “Efficacy of Wyeth Polyvalent Antivenin use in the Pretreatment of Copperhead Envenomation in mice.” Wilderness and Environ Med, 1999;10:142-145.

  46. Antivenom *Atleast 3 anaphylaxis related deaths reported after ACP administration • Auerbach, P.S. Wilderness Medicine. Mosby, 2007. • Dart, R.C., et al., “Efficacy, Safety, and Use of Snake Antivenoms in the United States.” Ann of Emerg Med, 2001;37:181-188.

  47. Antivenom • Crofab vs. ACP • Crofab less likely to cause acute reaction or serum sickness • Recent data suggests Crofab may be more effective especially against mojave rattlesnake venom • Crofab has a shorter half life and faster clearance rate leading to recurrence phenomena • *less long term data on Crofab (Crofab introduced in 2000, ACP introduced in 1954) • ACP IgG may maintain binding ability better than Crofab fragments • Time for reconstitution: Crofab 40 minutes, ACP 90 minutes • Auerbach, P.S. Wilderness Medicine. Mosby, 2007. • Dart, R.C., et al., “Efficacy, Safety, and Use of Snake Antivenoms in the United States.” Ann of Emerg Med, 2001;37:181-188. • Seifert, S.A., et. al., “Recurrence Phenomena After Immunoglobulin Therapy for Snake Envenomations: Part 1. Pharmacokinetics and Pharmacodynamics of Immunoglobulin Antivenoms and Related Antibodies.” Ann Emerg Med., 2001;37:189-195. • Boyer, L.V., et al, “Recurrence Phenomena After Immunoglobulin Therapy for Snake Envenomation: Part 2. Guidelines for Clinical Management with CrotalineFabAntivenom.” Ann of Emerg Med,2001;37:196-201.

  48. Antivenom • Administration • Coral snake antivenom • Initial dose: 3-6 vials diluted in 500-1000 ml crystalloid in adults and or 20-40 ml/kg in peds (same dose) • IV infusion at slow rate (1 ml/min) to be completed over 2 hours with gradual increase in rate if no signs of allergic reaction occur • Redosing: 3-5 more vials as needed (rarely more than 10 needed) • *Questionable role for anticholinesterase administration (i.e. neostigmine) • No reported deaths since antivenom went in to use Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

  49. Antivenom • Administration • Crofab (recommended within first 6 hours but case reports have documented efficacy after 9 hours) • Initial dose: 4-6 reconstituted vials diluted in 250 ml of normal saline for adults or 20-40 ml/kg for peds up to 250 ml (same dose) • IV infusion at slow rate (1ml/min) to be completed over 1 hour with gradual increase in rate if no signs of allergic reaction occur • Redosing: repeat initial dose if signs, symptoms or laboratory abnormalities do not improve or worsen • Post stabilization: 2 vials Q6H times 3 (shown to prevent recurrence phenomena) • Auerbach, P.S. Wilderness Medicine. Mosby, 2007. • Bebarta, V., et al, “Effectiveness of Delayed Use of Crotalidae Polyvalent Immune Fab (ovine) Antivenom.” Journ of Toxicology, 2004;42:321-324. • Boyer, L.V., et al, “Recurrence Phenomena After Immunoglobulin Therapy for Snake Envenomation: Part 2. Guidelines for Clinical Management with CrotalineFabAntivenom.” Ann of Emerg Med,2001;37:196-201.

  50. Antivenom • Administration • ACP • Intial dose: 5-20 vials based on severity diluted in 1 liter of crystalloid for adults and 20-40 ml/kg in peds (same dose) • IV infusion at slow rate (1ml/min) to be completed over 1-2 hours with gradual increase in rate if no signs of allergic reaction occur • Redosing: 5-10 vials every 30 minutes to 2 hours if signs, symptoms or laboratory abnormalities do not improve or worsen (typical total dose 20-40 vials) • Mortality rate reduced from 5-25% to 0.28% after antivenom went in to use Auerbach, P.S. Wilderness Medicine. Mosby, 2007.

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