1. Adam Algren, MD Medical Toxicology Fellow Georgia Poison Center Clinical Instructor Emory University Dept. of Emergency Medicine Snakes, Spiders, and Creatures from the Sea

2. Objectives Review clinical manifestations of North American snake envenomations Review clinical manifestations of North American snake envenomations Review presentation and management of black widow and brown recluse spider bites Review presentation and management of black widow and brown recluse spider bites Discuss the indications for the use of antivenoms: CroFab and Lactrodectus Discuss the indications for the use of antivenoms: CroFab and Lactrodectus Discuss common marine envenomations Discuss common marine envenomations

3. Snake Envenomations Crotalids Crotalids Pit Vipers Pit Vipers Found in every state except Alaska, Hawaii, Maine Found in every state except Alaska, Hawaii, Maine 6000-8000 bites/yearly 6000-8000 bites/yearly 5-10 deaths/yearly 5-10 deaths/yearly Elapids Elapids Coral Snake Coral Snake 69 Bites reported in 2000 69 Bites reported in 2000 64% Florida 64% Florida

4. NEJM 2002;347:350

5. Crotalids

6. Crotalids

7. Crotalids Crotalus Crotalus C. adamanteusEastern Diamondback rattlesnake C. adamanteusEastern Diamondback rattlesnake C. atroxWestern Diamondback rattlesnake C. atroxWestern Diamondback rattlesnake C. horridus horridusTimber rattlesnake C. horridus horridusTimber rattlesnake C. horridus atricaudatusCanebrake rattlesnake C. horridus atricaudatusCanebrake rattlesnake C. scutulatusMojave rattlesnake C. scutulatusMojave rattlesnake C. viridis viridisPrairie rattlesnake C. viridis viridisPrairie rattlesnake C. cerastesSidewinder rattlesnake C. cerastesSidewinder rattlesnake Sistrurus Sistrurus S. milariusPigmy rattlesnake S. milariusPigmy rattlesnake S. catenatus spp.Massasauga rattlesnake S. catenatus spp.Massasauga rattlesnake Agkistrodon Agkistrodon A. contortixCopperheads A. contortixCopperheads A. piscivorusCottonmouths A. piscivorusCottonmouths

8. Eastern Diamondback Rattlesnake Crotalus adamanteus

10. Crotalids Majority of victims are male Majority of victims are male Majority of bites occur May-October Majority of bites occur May-October >50% victims of provoked bites are intoxicated >50% victims of provoked bites are intoxicated ¾ bites occur to upper extremities ¾ bites occur to upper extremities 0-75% of snake’s venom is discharged 0-75% of snake’s venom is discharged Venom replenished within 1 month Venom replenished within 1 month 5-20% of bites are “dry bites” 5-20% of bites are “dry bites”

11. Crotalids Venom Venom Components Components Metalloproteinases Metalloproteinases Collagenases Collagenases Hyaluronidases Hyaluronidases Proteases Proteases Composition/potency varies Composition/potency varies Snake Snake Species Species Age Age Season Season NEJM 2002;347:351

12. Western Diamondback rattlesnake Crotalus atrox

13. Crotalid Envenomations Pathophysiology Pathophysiology Local Effects Local Effects Most common Most common Metalloproteinases and other components damage vascular endothelium and basement membranes Metalloproteinases and other components damage vascular endothelium and basement membranes Edema, ecchymosis, blistering Edema, ecchymosis, blistering Systemic Effects Systemic Effects Coagulopathy Coagulopathy Hypotension Hypotension

14. Crotalid Envenomations Pre-hospital Management Pre-hospital Management Avoid exertion Avoid exertion Immobilize the extremity at or below level of heart Immobilize the extremity at or below level of heart Rapid transport to nearest emergency dept. Rapid transport to nearest emergency dept. Consider constriction band if there is going to be a prolonged transport time Consider constriction band if there is going to be a prolonged transport time Extractor devices probably not helpful Extractor devices probably not helpful Avoid tourniquet, cryotherapy, electric shock, excision, and incision Avoid tourniquet, cryotherapy, electric shock, excision, and incision McKinney. Ann Emerg Med. 2001;37:168-74. McKinney. Ann Emerg Med. 2001;37:168-74. Alberts. Ann Emerg Med. 2004;43:181-6. Alberts. Ann Emerg Med. 2004;43:181-6.

15. Crotalid Envenomations History History Circumstance of bite Circumstance of bite Type of snake Type of snake Number of bites Number of bites Time since envenomation Time since envenomation First aid provided First aid provided Previous history of snake envenomation/antivenom treatment Previous history of snake envenomation/antivenom treatment Sensitivity to horse/sheep sera Sensitivity to horse/sheep sera Be cautious with any snakes brought to the ED Be cautious with any snakes brought to the ED

16. Copperhead Akistrodon contortix

17. Crotalid Envenomations Clinical Manifestations Clinical Manifestations Local Local Fang marks Fang marks Number of fang marks helpful, but not definitive Number of fang marks helpful, but not definitive Edema Edema Ecchymosis Ecchymosis Bullae Bullae

18. Crotalid Envenomations

20. Clinical Manifestations Clinical Manifestations Systemic Systemic Anaphylaxis Anaphylaxis Nausea, vomiting, diaphoresis, metallic taste Nausea, vomiting, diaphoresis, metallic taste Hypotension Hypotension Coagulopathy Coagulopathy Thrombocytopenia Thrombocytopenia Rhabdomyolysis Rhabdomyolysis Neurologic Effects Neurologic Effects Mojave rattlesnake Mojave rattlesnake

21. NEJM 2002;347:351

22. Timber rattlesnake Crotalus horridus horridus

23. Canebrake rattlesnake Crotalus horridus atricaudatus

24. Mojave rattlesnake Crotalus scutulatus

25. Crotalid Envenomations Treatment Treatment Remove any constriction band slowly Remove any constriction band slowly Tetanus Tetanus Prophylactic antibiotics unnecessary Prophylactic antibiotics unnecessary Consult poison center Consult poison center Determine antivenom supplies Determine antivenom supplies Document neurovascular exam for extremity bites Document neurovascular exam for extremity bites Measure limb circumference every 15 minutes Measure limb circumference every 15 minutes Labs- CBC, chemistries, PT, PTT, Fibrinogen, CK Labs- CBC, chemistries, PT, PTT, Fibrinogen, CK

28. Cottonmouths Agkistrodon piscivorus

29. Crotalid Envenomations Treatment Treatment Surgical treatment Surgical treatment Routine surgical treatment not recommended Routine surgical treatment not recommended Measure compartment pressures if there is concern Measure compartment pressures if there is concern Digit dermotomy Digit dermotomy Hall E. Ann Emerg Med. 2001;37:175-180. Hall E. Ann Emerg Med. 2001;37:175-180.

30. Crotalid Envenomations Antivenom Antivenom Wyeth polyvalent antivenom Wyeth polyvalent antivenom CroFab CroFab Indications: Indications: Rapid progression of local effects Rapid progression of local effects Compartment syndrome Compartment syndrome Coagulopathy, Thrombocytopenia Coagulopathy, Thrombocytopenia Neurologic Symptoms Neurologic Symptoms Shock Shock

32. Crotalid Envenomations CroFab CroFab FDA approved in 2000 FDA approved in 2000 Sheep derived Fab IgG Sheep derived Fab IgG Less immunogenic Less immunogenic Eastern/Western Diamondback rattlesnake, Mojave rattlesnake, Cottonmouth Eastern/Western Diamondback rattlesnake, Mojave rattlesnake, Cottonmouth Skin testing not required Skin testing not required 0-14% incidence of immediate hypersensitivity 0-14% incidence of immediate hypersensitivity <5% incidence of serum sickness <5% incidence of serum sickness

33. Crotalid Envenomations Dart et al. Arch Intern Med. 2001;161:2030-6. Dart et al. Arch Intern Med. 2001;161:2030-6. 31 patients 31 patients 6 or 12 vials CroFab initially 6 or 12 vials CroFab initially 16 patients PRN, 15 scheduled 16 patients PRN, 15 scheduled 8 patients in PRN group required additional CroFab 8 patients in PRN group required additional CroFab 0 patients in scheduled group 0 patients in scheduled group All patients had significant improvement in snakebite severity scores All patients had significant improvement in snakebite severity scores 6 allergic reactions 6 allergic reactions 4 urticaria, 1 urticaria/cough, 1 urticaria/dyspnea/wheezing 4 urticaria, 1 urticaria/cough, 1 urticaria/dyspnea/wheezing

35. Crotalid Envenomations CroFab for Copperhead envenomations CroFab for Copperhead envenomations 32 cases 32 cases 25 (78%) were moderate severity 25 (78%) were moderate severity 7 had mild laboratory abnormalities 7 had mild laboratory abnormalities 23 (72%) achieved control with 4 vials 23 (72%) achieved control with 4 vials 4 cases progressed following CroFab 4 cases progressed following CroFab No allergic reactions No allergic reactions 1 mild case serum sickness 1 mild case serum sickness Lavonas et al. Ann Emerg Med. 2004;43:200-6. Lavonas et al. Ann Emerg Med. 2004;43:200-6.

36. Crotalid Envenomations Safety and Efficacy of CroFab for Pediatric Envenomations Safety and Efficacy of CroFab for Pediatric Envenomations 24 patients 24 patients Mean age 7.3 (range 1.9-13) Mean age 7.3 (range 1.9-13) All had local swelling All had local swelling 14 (58%) PT >13sec 14 (58%) PT >13sec 3 (12.5%) platelets <150,000 3 (12.5%) platelets <150,000 2 (8.3%) fibrinogen <150 mg/dl 2 (8.3%) fibrinogen <150 mg/dl Mean number of CroFab vials used 12.3 (4-24) Mean number of CroFab vials used 12.3 (4-24) 5 patients progressive thrombocytopenia 5 patients progressive thrombocytopenia ? 1 allergic reaction ? 1 allergic reaction Pizon et al. Acad. Emerg Med. 2007;14:373-6. Pizon et al. Acad. Emerg Med. 2007;14:373-6.

37. Crotalid Envenomations Recurrence- Local or systemic Recurrence- Local or systemic Possible explanations Possible explanations Pharmacokinetic/pharmacodynamic mismatch of venom/antivenom Pharmacokinetic/pharmacodynamic mismatch of venom/antivenom CroFab elimination ½ life 15-20 hours CroFab elimination ½ life 15-20 hours Late onset of venom effects Late onset of venom effects Prolonged absorption of venom from wound Prolonged absorption of venom from wound Dissociation of venom/antivenom complex Dissociation of venom/antivenom complex Development of host anti-antivenom response Development of host anti-antivenom response

38. Crotalid Envenomations Post-marketing study of CroFab for rattlesnakes Post-marketing study of CroFab for rattlesnakes 28 patients (3 children) 28 patients (3 children) 16/28 achieved local control with 4-6 vials 16/28 achieved local control with 4-6 vials 20/28 elevated PT, 6/28 thrombocytopenia, 12/28 hypofibrinogenemia 20/28 elevated PT, 6/28 thrombocytopenia, 12/28 hypofibrinogenemia Control achieved in all, 67-80% required >10 vials Control achieved in all, 67-80% required >10 vials 6/21 had systemic recurrence 6/21 had systemic recurrence No significant bleeding No significant bleeding No anaphylactic reactions No anaphylactic reactions Ruha et al. Ann Emerg Med. 2002;39:609-615 Ruha et al. Ann Emerg Med. 2002;39:609-615

39. Ann Emerg Med 2001;37:2

41. Crotalid Envenomation Disposition Disposition Observe for 6-8 hours if asymptomatic Observe for 6-8 hours if asymptomatic May discharge if asymptomatic with normal labs May discharge if asymptomatic with normal labs Admit all suspected Mojave rattlesnake envenomations for 24 hours Admit all suspected Mojave rattlesnake envenomations for 24 hours Admit for significant local effects or if labs abnormal Admit for significant local effects or if labs abnormal

42. Which snake is poisonous? King snake Lampropeltis getulus Coral Snake Micrurus fulvius “Red on yellow, kill a fellow” “Red on black, venom lack”

43. Coral Snake Envenomations Uncommon Uncommon Florida, Georgia Florida, Georgia Eastern, Texas, Sonoran Eastern, Texas, Sonoran Small, ~40 inches full grown, small teeth Small, ~40 inches full grown, small teeth 25% of bites are “dry bites” 25% of bites are “dry bites” Venom Venom Components not well understood Components not well understood Zinc dependent acetylcholinesterase Zinc dependent acetylcholinesterase

45. Coral Snake Envenomations Clinical Presentation Clinical Presentation 1/3 have mild local swelling 1/3 have mild local swelling Mild systemic symptoms Mild systemic symptoms May develop localized pain or fasciculations May develop localized pain or fasciculations Neurologic symptoms Neurologic symptoms Normal mental status Normal mental status CN palsies, weakness/paralysis, respiratory failure CN palsies, weakness/paralysis, respiratory failure Avg. delay to symptom onset is ~ 2 hours Avg. delay to symptom onset is ~ 2 hours May be delayed up to 13 hours May be delayed up to 13 hours Kitchens et al. JAMA. 1987;258:1615-8. Kitchens et al. JAMA. 1987;258:1615-8.

46. Coral Snake Envenomations Treatment Treatment Supportive Care Supportive Care Aggressive airway management, monitor NIF Aggressive airway management, monitor NIF Consult poison center, determine antivenom supplies Consult poison center, determine antivenom supplies Consider Neostigmine Consider Neostigmine Early antivenom administration even if asymptomatic Early antivenom administration even if asymptomatic Equine derived Equine derived 3-5 vials initially, redose additional 5 vials in symptomatic pts 3-5 vials initially, redose additional 5 vials in symptomatic pts Reconstitution 15-30 minutes Reconstitution 15-30 minutes Immediate hypersenitivity- 6/17 urticaria, 1/39 anaphylaxis Immediate hypersenitivity- 6/17 urticaria, 1/39 anaphylaxis Serum sickness- 4/39 patients Serum sickness- 4/39 patients

47. Coral Snake Envenomations Disposition Disposition Admit all suspected Coral snake bites for at least 24 hours Admit all suspected Coral snake bites for at least 24 hours

48. Black Widow Envenomations

49. Latrodectus mactans Latrodectus mactans ~2500 bites/year ~2500 bites/year 300-400 severe 300-400 severe Prefer dry, dark environments Prefer dry, dark environments Only females envenomate Only females envenomate No deaths in US in past 20 years No deaths in US in past 20 years α-lactrotoxin α-lactrotoxin Stimulates release of acetylcholine and catecholamines Stimulates release of acetylcholine and catecholamines

50. Black Widow Envenomations Non-specific symptoms can make diagnosis difficult Non-specific symptoms can make diagnosis difficult Bite is not always felt Bite is not always felt Pain within 10-60 min, but may be delayed Pain within 10-60 min, but may be delayed 75% will only have local symptoms 75% will only have local symptoms Pain, diaphoresis, piloerection Pain, diaphoresis, piloerection Systemic symptoms may develop over several hours Systemic symptoms may develop over several hours Generalized pain, abdominal pain, priapism, diaphoresis, tachycardia, hypertension, headache, vomiting, tremor Generalized pain, abdominal pain, priapism, diaphoresis, tachycardia, hypertension, headache, vomiting, tremor Symptoms peak within 12-24 hours Symptoms peak within 12-24 hours Typically resolves over 24-72 hours Typically resolves over 24-72 hours

51. Black Widow Envenomations Treatment Treatment Opiates, benzodiazepines Opiates, benzodiazepines 115/163 patients had resolution of pain 115/163 patients had resolution of pain No evidence to support calcium No evidence to support calcium 23/24 no improvement 23/24 no improvement Antivenom Antivenom Severe/refractory pain, severe hypertension, threatened abortion Severe/refractory pain, severe hypertension, threatened abortion Equine IgG Equine IgG 58 patients received 1 vial; all had pain resolution <2 hrs 58 patients received 1 vial; all had pain resolution <2 hrs 4 urticaria, 1 analphylaxis death 4 urticaria, 1 analphylaxis death Clark et al. Ann Emerg Med. 1992;21:782-7. Clark et al. Ann Emerg Med. 1992;21:782-7.

52. Black Widow Envenomations Disposition Disposition Discharge if symptoms improve Discharge if symptoms improve May discharge if antivenom given May discharge if antivenom given Observe for 2 hours after completion of infusion Observe for 2 hours after completion of infusion

53. Brown Recluse Envenomations Loxosceles reclusa Loxosceles reclusa April-October ? more bites at night Prefers warm, dry environment Venom Sphingomyelinase D, Sphingomyelinase D, hyaluronidase, phosphohydrolases

55. Brown Recluse Envenomations Most bites have a benign course Most bites have a benign course May progress over several hours May progress over several hours Pain, induration, ecchymosis Pain, induration, ecchymosis May develop serous/bloody blisters May develop serous/bloody blisters Gravitational Gravitational Necrosis at 2-4 days, heals over 6-8 weeks Necrosis at 2-4 days, heals over 6-8 weeks

56. Brown Recluse Envenomations

58. Bacterial Infections Bacterial Infections Orf, Anthrax, Leishmaniosis Orf, Anthrax, Leishmaniosis Bee Sting Bee Sting Skin cancer Skin cancer Drug reactions Drug reactions Coumadin, TEN, SJS Coumadin, TEN, SJS Ecthyma gangrenosum Ecthyma gangrenosum Erythema migrans Erythema migrans Erythema nodosum Erythema nodosum Erythema multiforme Erythema multiforme Emboli, septic Emboli, septic Fire ants Fire ants Frostbite Frostbite Mites Mites Necrotizing fascitis Necrotizing fascitis Polyarteritis nodosa Polyarteritis nodosa Purpura fulminans Purpura fulminans Pyoderma gangrenosum Pyoderma gangrenosum Scrofula Scrofula Sporotrichosis Sporotrichosis Systemic gonorrhea Systemic gonorrhea Scleroderma Scleroderma Tick bites Tick bites Ulcers Ulcers Viral infections Viral infections Vasculitis Vasculitis

59. Brown Recluse Envenomations Systemic loxoscelism Systemic loxoscelism Not proportional to dermal findings Not proportional to dermal findings 4/111 patients 4/111 patients 6/546 pediatric series 6/546 pediatric series ? More common in children ? More common in children Develops within 72-96 hours Develops within 72-96 hours Fever, nausea, myalgias, arthralgias, headache Fever, nausea, myalgias, arthralgias, headache Jaundice, coagulopathy, hemolysis, renal failure Jaundice, coagulopathy, hemolysis, renal failure Mortality from hemolysis, DIC Mortality from hemolysis, DIC Wright et al. Ann Emerg Med. 1997;30:28-32. Wright et al. Ann Emerg Med. 1997;30:28-32. Elbahlwan et al. Pediatr Emerg Care. 2005;21:177-180. Elbahlwan et al. Pediatr Emerg Care. 2005;21:177-180.

60. Brown Recluse Envenomations Treatment Treatment Wound care Wound care Prophylactic antibiotics unnecessary Prophylactic antibiotics unnecessary Labs Labs CBC, chemistries, LDH, retic count, PT, PTT, fibrinogen, UA, plasma free hemoglobin, type & screen CBC, chemistries, LDH, retic count, PT, PTT, fibrinogen, UA, plasma free hemoglobin, type & screen Avoid dapsone/early surgical treatment Avoid dapsone/early surgical treatment ? Early HBO ? Early HBO Steroids for hemolysis Steroids for hemolysis

61. Brown Recluse Envenomations Disposition Disposition Admit for systemic complications Admit for systemic complications Children Children Consider daily out-patient labs for 96 hours Consider daily out-patient labs for 96 hours

62. Marine Envenomations Jellyfish Jellyfish Box Jellyfish Box Jellyfish Portuguese man-of-war Portuguese man-of-war Stingrays Stingrays Scorpaenidae Scorpaenidae Lionfish Lionfish

63. Box Jellyfish Chironex fleckeri Chironex fleckeri 15 tentacles up to 7 meters in length Found along northern coast of Australia Responsible for >60 deaths in past century

64. Box Jellyfish Millions of nematocysts/jellyfish tentacle Millions of nematocysts/jellyfish tentacle Venom Venom Cardiotoxic/myotoxic Cardiotoxic/myotoxic Increases intracellular Na/Ca Increases intracellular Na/Ca Most stings are minor Most stings are minor Death possible within minutes Death possible within minutes with severe envenomations

65. Box jellyfish Clinical Manifestations Clinical Manifestations Immediate pain Immediate pain Skin wheals/vesicles Skin wheals/vesicles Delayed hypersensitivity reaction common Delayed hypersensitivity reaction common Hypotension/cardiac arrest Hypotension/cardiac arrest O’Reilly. Med J Aust. 2001;175:652-5. O’Reilly. Med J Aust. 2001;175:652-5.

66. Box jellyfish

67. Portuguese man-of-war

68. Physalia sp. Physalia sp. Responsible for thousands of stings in US Responsible for thousands of stings in US Found along Atlantic/Gulf coasts Found along Atlantic/Gulf coasts Tentacles may be up to 30 meters Tentacles may be up to 30 meters Most envenomations minor, deaths rare Most envenomations minor, deaths rare Immediate pain/skin reaction Immediate pain/skin reaction

69. Jellyfish Treatment Supportive care Supportive care Irrigate with 5% acetic acid Irrigate with 5% acetic acid Remove tentacles Remove tentacles Wound care Wound care Pain meds Pain meds Consider prophylactic antibiotics Consider prophylactic antibiotics Monitor for delayed reactions Monitor for delayed reactions

70. Stingrays

71. Stingrays Tropical/temperate environments Tropical/temperate environments Shallow waters Shallow waters Non-aggressive Non-aggressive 1-4 spines 1-4 spines 17 deaths reported worldwide 17 deaths reported worldwide Venom Venom Phosphodiesterases, serotonin, Phosphodiesterases, serotonin,5’-nucleotidase Immediate pain lasting 6-48 hr Immediate pain lasting 6-48 hr Vomiting, dizziness, weakness, Vomiting, dizziness, weakness, syncope, cramps, arrhythmias, hypotension

72. Stingrays Immediate cold water irrigation Immediate cold water irrigation Then warm water (40-42°) immersion Then warm water (40-42°) immersion Pain meds Pain meds Wound management Wound management Consider prophylactic antibiotics Consider prophylactic antibiotics Cook et al. J Emerg Med. 2006;30:345-7. Cook et al. J Emerg Med. 2006;30:345-7.

73. Lionfish

74. Lionfish Pterois sp. Pterois sp. Atlantic, Pacific, Caribbean Atlantic, Pacific, Caribbean Popular aquarium fish Popular aquarium fish 12 or 13 dorsal spines with 12 or 13 dorsal spines with venom glands Venom poorly characterized Venom poorly characterized Severe pain lasting 6-12 hours Severe pain lasting 6-12 hours Systemic effects rare Systemic effects rare

75. Lionfish Warm water (45°) immersion for 30-90 min Warm water (45°) immersion for 30-90 min Pain meds Pain meds Wound care Wound care Consider prophylactic antibiotics Consider prophylactic antibiotics Vetrano et al. J Emerg Med. 2002;23:379-382. Vetrano et al. J Emerg Med. 2002;23:379-382.

76. Questions?