1. The Creepy and Crawling: Bites and Stings in North America Dr. Rebecca C. Bowers FACEP Assistant Professor Department of Emergency Medicine University of Kentucky

2. Learning Objectives Discuss scope of problem in the US and worldwide Discuss scope of problem in the US and worldwide Recognize the major groups of animals that pose an envenomation threat Recognize the major groups of animals that pose an envenomation threat Gain an understanding of the prehospital and hospital management of North American snake envenomations Gain an understanding of the prehospital and hospital management of North American snake envenomations Gain an understanding of the prehospital and hospital management of North American arachnid envenomation Gain an understanding of the prehospital and hospital management of North American arachnid envenomation Gain an understanding of prehospital and hospital management of Hymenoptera envenomation Gain an understanding of prehospital and hospital management of Hymenoptera envenomation Discuss the disposition of envenomation victims Discuss the disposition of envenomation victims

3. Hymenoptera Envenomation

4. North American Offenders Bees and Wasps Bees and Wasps Bees: Honeybees, bumblebees, and africanized honeybees Bees: Honeybees, bumblebees, and africanized honeybees Wasps: true wasps, yellow jackets, hornets Wasps: true wasps, yellow jackets, hornets Found throughout USA. AHBs found in Southwest Found throughout USA. AHBs found in Southwest Ants Ants Imported red fire ant Imported red fire ant Imported from South America. Found from Virginia to Texas Imported from South America. Found from Virginia to Texas Native ant species Native ant species

8. Epidemiology Scope of the Problem In 2005 AAPCC reported 10,792 bee and wasp exposures In 2005 AAPCC reported 10,792 bee and wasp exposures 1200 required a hospital visit with only 1 death 1200 required a hospital visit with only 1 death Very underreported Very underreported 2100 fire ant exposures with 250 requiring a hospital visit and no deaths 2100 fire ant exposures with 250 requiring a hospital visit and no deaths AAAI survey 20,750 fire ant exposures annually AAAI survey 20,750 fire ant exposures annually

9. Venom Pathophysiology Bees and Wasps Bees and Wasps Bees: Melittin, hyaluronidase, mast-cell degranulation protein Bees: Melittin, hyaluronidase, mast-cell degranulation protein Wasps: very similar with addition of Ach and serotonin Wasps: very similar with addition of Ach and serotonin Red fire ants Red fire ants Piperidine alkaloid causing histamine release and skin necrosis Piperidine alkaloid causing histamine release and skin necrosis Cytotoxic and hemotoxic properties Cytotoxic and hemotoxic properties

10. Taken from WebMD.com Taken from WebMD.com

13. Clinical Syndromes Bees and Wasps Bees and Wasps Small, local pruritic skin lesion. Larger local reactions >5cm do occur and may last longer. Small, local pruritic skin lesion. Larger local reactions >5cm do occur and may last longer. Occasionally a mild systemic reaction occurs with n/v, diarrhea, diffuse urticarial skin lesions. Occasionally a mild systemic reaction occurs with n/v, diarrhea, diffuse urticarial skin lesions. Very rarely, a victim will present with full blown anaphylaxis Very rarely, a victim will present with full blown anaphylaxis Massive envenomation >50 stings CV collapse Massive envenomation >50 stings CV collapse Delayed systemic toxicity: This includes hemolysis, thrombocytopenia, liver dysfunction, and rhabdomyolysis with subsequent renal failure Delayed systemic toxicity: This includes hemolysis, thrombocytopenia, liver dysfunction, and rhabdomyolysis with subsequent renal failure

14. Red fire ants Multiple stings rule rather than exception Multiple stings rule rather than exception Hundreds of pustules at bite sites Hundreds of pustules at bite sites Burning pain at each lesion Burning pain at each lesion 25% of population in endemic areas has hypersensitivity 25% of population in endemic areas has hypersensitivity Resultant anaphylactic reaction possible Resultant anaphylactic reaction possible Systemic venom toxicity after mass envenomation Systemic venom toxicity after mass envenomation

15. Treatment Prehospital: Prehospital: Airway management, nebulizers, epinephrine, fluids Airway management, nebulizers, epinephrine, fluids Note number and location of stings, progression Note number and location of stings, progression Hospital: Hospital: Same with addition of steroids and H1 and H2 blockers, pressors as needed for CV support, tetanus Same with addition of steroids and H1 and H2 blockers, pressors as needed for CV support, tetanus Massive envenomation requires monitoring for rhabdo, hemolysis, ARF, and liver failure Massive envenomation requires monitoring for rhabdo, hemolysis, ARF, and liver failure

16. Disposition Local: discharge after symptomatic care Local: discharge after symptomatic care Mild allergic reaction: discharge after 6 hours with 3 days of oral antihistamines and oral steroids Mild allergic reaction: discharge after 6 hours with 3 days of oral antihistamines and oral steroids Moderate to anaphylaxis: admission, Epi-pen, allergist referral, medic-alert bracelet Moderate to anaphylaxis: admission, Epi-pen, allergist referral, medic-alert bracelet Mass envenomation: admission even if asymptomatic due to delayed systemic toxicity Mass envenomation: admission even if asymptomatic due to delayed systemic toxicity

17. Reptilian Envenomation

18. North American Offenders Crotalidae or Pit Vipers Crotalidae or Pit Vipers Rattlesnake Rattlesnake Cottonmouth Cottonmouth Copperhead Copperhead Elapidae Elapidae Coral Snake Coral Snake Multiple species of each located all over the USA except Maine, Alaska and Hawaii Multiple species of each located all over the USA except Maine, Alaska and Hawaii

19. Epidemiology Scope of the Problem In 2005 AAPCC reported 2900 pit viper bites with 1875 being evaluated at a hospital and 6 deaths. 171 considered life-threatening. Not all reported. 25% of bites are “dry bites” In 2005 AAPCC reported 2900 pit viper bites with 1875 being evaluated at a hospital and 6 deaths. 171 considered life-threatening. Not all reported. 25% of bites are “dry bites” Reported 58 coral snake bites with 6 life- threatening and no deaths Reported 58 coral snake bites with 6 life- threatening and no deaths Morbidity fairly high with lost productivity due to pain and reduced function Morbidity fairly high with lost productivity due to pain and reduced function

20. Worldwide a much bigger problem Worldwide a much bigger problem Best estimates are as high as 1.8 million bites per year with 94,000 deaths Best estimates are as high as 1.8 million bites per year with 94,000 deaths Biggest problem in southern Asia and Sub- Saharan Africa due to lack of antivenin, rural locales, and much higher incidence of lethal species Biggest problem in southern Asia and Sub- Saharan Africa due to lack of antivenin, rural locales, and much higher incidence of lethal species

25. Venom Pathophysiology Hemotoxic venom (Pit Vipers) Hemotoxic venom (Pit Vipers) One of most complex venoms One of most complex venoms Thrombin-like enzymes: coagulopathy Thrombin-like enzymes: coagulopathy Phospholipases: platelet dysfunction Phospholipases: platelet dysfunction Metalloproteinases:leaky vasculature with edema and ecchymosis Metalloproteinases:leaky vasculature with edema and ecchymosis Bradykinin: hypotension, N/V/D, pain Bradykinin: hypotension, N/V/D, pain

26. Neurotoxic venom (Coral Snake and Mojave Rattlesnake) Neurotoxic venom (Coral Snake and Mojave Rattlesnake) Disrupts neuromuscular transmission by blocking Ach receptors with resultant weakness, paresthesias, and respiratory paralysis Disrupts neuromuscular transmission by blocking Ach receptors with resultant weakness, paresthesias, and respiratory paralysis

27. Taken from emedicine article published by University of Tennessee

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32. Pit Viper Treatment Prehospital Prehospital ABCs ABCs Assess for systemic symptoms Assess for systemic symptoms Note bite site, bite time and snake type Note bite site, bite time and snake type Mark initial area with time and follow progression Mark initial area with time and follow progression Elevate to level of heart Elevate to level of heart Compression dressing or pressure-immobilization Compression dressing or pressure-immobilization Transport immediately to facility with antivenin Transport immediately to facility with antivenin

33. Do Not….. Perform Perform Cryotherapy (the old ice bucket) Cryotherapy (the old ice bucket) Electrotherapy (jumper cables…I’m not kidding) Electrotherapy (jumper cables…I’m not kidding) Cut and suck method Cut and suck method Sawyer extractor Sawyer extractor Tourniquets Tourniquets

35. Treatment Hospital Hospital ABCs ABCs Note progression Note progression Labs Labs Grade envenomation Grade envenomation Determine need for CroFab (see next slide) Determine need for CroFab (see next slide) Tetanus update Tetanus update

36. Weant KA, Johnson PN, Bowers RC, Armitstead JA; Evidence-Based, Multidisciplinary Approach to the Development of a Crotalidae Polyvalent Antivenin (CroFab) Protocol at a University Hospital. The Annals of Pharmacotherapy 2010; 44:xxxx.

38. To cut or not to cut…. Fasciotomy very rarely indicated Fasciotomy very rarely indicated Mimics compartment syndrome Mimics compartment syndrome Usually subcutaneous edema Usually subcutaneous edema Antivenin will almost always reverse true compartment syndrome Antivenin will almost always reverse true compartment syndrome Only proceed to fasciotomy if elevated pressure sustained and confirmed with measurement Only proceed to fasciotomy if elevated pressure sustained and confirmed with measurement

39. A word on CroFab…. Only FDA approved Pit Viper antivenin currently Only FDA approved Pit Viper antivenin currently Other good antivenins used in Central and South America for pit vipers Other good antivenins used in Central and South America for pit vipers Much less expensive Much less expensive Do work on North American species Do work on North American species Used by local venom expert Used by local venom expert

40. Treatment Coral Snakes (Elapids) Coral Snakes (Elapids) Respiratory support as needed Respiratory support as needed Return of muscular function can take weeks requiring prolonged intubation Return of muscular function can take weeks requiring prolonged intubation Antivenin is available in USA but whole IgG so no longer produced Antivenin is available in USA but whole IgG so no longer produced Other possibilities include mexican product and Tiger snake antivenin from Australia Other possibilities include mexican product and Tiger snake antivenin from Australia

41. Disposition Pit Viper (Crotalid) Pit Viper (Crotalid) Observe 8 hours. If no symptoms then may discharge Observe 8 hours. If no symptoms then may discharge No CroFab warranted but envenomated: Discharge with lab and MD follow up 24-48 hours No CroFab warranted but envenomated: Discharge with lab and MD follow up 24-48 hours CroFab given: admission to floor versus ICU depending on clinical scenario CroFab given: admission to floor versus ICU depending on clinical scenario

42. Coral Snake (Elapid) Coral Snake (Elapid) Admission warranted even if asymptomatic Admission warranted even if asymptomatic Some argue to give antivenin empirically given severity of envenomation Some argue to give antivenin empirically given severity of envenomation

43. Arachnid Envenomation

44. North American Offender Centruroides exilicauda or the Bark Scorpion Centruroides exilicauda or the Bark Scorpion Found in Southwestern USA mainly in Arizona Found in Southwestern USA mainly in Arizona Few in Texas, Northern Mexico, and areas of California Few in Texas, Northern Mexico, and areas of California

45. Epidemiology Scope of the Problem In 2005 AAPCC reported 14,521 reports of scorpion envenomation In 2005 AAPCC reported 14,521 reports of scorpion envenomation 20 victims felt to have life threatening outcomes 20 victims felt to have life threatening outcomes No deaths reported that year No deaths reported that year Almost all lethal envenomations are children or occur outside the US Almost all lethal envenomations are children or occur outside the US

47. Venom Pathophysiology No cytotoxins No cytotoxins 2 potent neurotoxins enhance membrane depolarization and prolong action potential 2 potent neurotoxins enhance membrane depolarization and prolong action potential Over stimulation of parasympathetic and sympathetic nervous system with Ach and catecholamine release Over stimulation of parasympathetic and sympathetic nervous system with Ach and catecholamine release

48. Clinical Syndrome + tap test over sting site + tap test over sting site Autonomic dysfunction Autonomic dysfunction Fasciculations and roving eye movements Fasciculations and roving eye movements Uncontrolled limb movements Uncontrolled limb movements Increased secretions including bronchorrhea Increased secretions including bronchorrhea Mild envenomation: adrenergic syndrome Mild envenomation: adrenergic syndrome Severe envenomation: cholinergic syndrome Severe envenomation: cholinergic syndrome

50. Additional treatments Sympatholytic antihypertensive agents for hypertension Sympatholytic antihypertensive agents for hypertension Atropine may be used to control secretions Atropine may be used to control secretions

51. Antivenin Antivenin: Antivenin: Previous goat serum derived has expired Previous goat serum derived has expired New drug Anascorp manufactured in Mexico is being trialed in Arizona New drug Anascorp manufactured in Mexico is being trialed in Arizona Using since 2004 and over 1500 patients treated Using since 2004 and over 1500 patients treated Still pending FDA approval Still pending FDA approval

52. Disposition Most adults require supportive treatment only Most adults require supportive treatment only Children more likely to suffer with neuromuscular dysfunction and require ICU admission and antivenin Children more likely to suffer with neuromuscular dysfunction and require ICU admission and antivenin

53. North American Offenders Only 2 medically significant spiders in the USA Only 2 medically significant spiders in the USA Loxosceles reclusa or the Brown Recluse Loxosceles reclusa or the Brown Recluse Found mainly in central and southern US decreasing towards the coast Found mainly in central and southern US decreasing towards the coast Latrodectus or the Black Widow Spider Latrodectus or the Black Widow Spider Found throughout the US Found throughout the US

54. Epidemiology Scope of the Problem In 2005 the AAPCC reported 2236 recluse bites with 14 being life-threatening. High morbidity In 2005 the AAPCC reported 2236 recluse bites with 14 being life-threatening. High morbidity Over last 20 years 40,000 Black Widow envenomations have been reported to AAPCC. Mortality highest in children Over last 20 years 40,000 Black Widow envenomations have been reported to AAPCC. Mortality highest in children

57. Venom Pathophysiology Black Widow (Latrodectus) Black Widow (Latrodectus) No cytotoxins No cytotoxins Alpha-latrotoxin most important Alpha-latrotoxin most important Decreases reuptake of acetylcholine at NMJ Decreases reuptake of acetylcholine at NMJ Also epinephrine Also epinephrine Brown Recluse (Loxosceles) Brown Recluse (Loxosceles) Many cytotoxic components and inflammatory mediators Many cytotoxic components and inflammatory mediators Sphingomyelinase D as well prostaglandins, leukotrienes, and thromboxanes Sphingomyelinase D as well prostaglandins, leukotrienes, and thromboxanes

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59. Brown Recluse Brown Recluse Local tissue destruction Local tissue destruction Systemic loxoscelism Systemic loxoscelism 24-72 hours flu-like illness 24-72 hours flu-like illness Hemolysis, DIC, ARF, shock, pulmonary edema Hemolysis, DIC, ARF, shock, pulmonary edema

60. Verified Brown Recluse Bite Bites of Brown Recluse Spiders and Suspected Necrotic Arachnidism David L. Swanson, M.D., and Richard S. Vetter, M.S. N Engl J Med 2005; 352:700-707February 17, 2005 February 17, 2005February 17, 2005

62. Treatment of Brown Recluse Delayed surgical excision Delayed surgical excision No to Dapsone No to Dapsone No to Steroids No to Steroids No to nitroglycerine No to nitroglycerine No to HBO No to HBO Systemic Loxoscelism requires supportive treatment Systemic Loxoscelism requires supportive treatment Antivenin Antivenin Rabbit-derived Fab fragments Rabbit-derived Fab fragments Must be administered within 4 hours Must be administered within 4 hours Typical delay makes this impractical Typical delay makes this impractical

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65. Black Widow antivenin Whole IgG with high incidence of serum sickness and hypersensitivity Whole IgG with high incidence of serum sickness and hypersensitivity Reserved for severe autonomic dysfunction and pain Reserved for severe autonomic dysfunction and pain A Fab antivenin is being tested A Fab antivenin is being tested

66. Disposition Black Widow Black Widow May discharge after 6 hours if asymptomatic May discharge after 6 hours if asymptomatic Admission otherwise for IV opiates and benzos Admission otherwise for IV opiates and benzos Brown Recluse Brown Recluse Most can be discharged with follow-up for long- term wound care Most can be discharged with follow-up for long- term wound care ICU admission for systemic syndrome ICU admission for systemic syndrome

67. Be careful out there!!!

68. ?????? Questions

69. 1. Bites and Stings-Snakes, spiders, and scorpions in the United States. Pediatric Emergency Medicine Practice May 2007 Vol. 4 No. 5 2. Hymenoptera envenomation: Bees, Wasps, and Ants. Pediatric Emergency Medicine Practice June 2008 VOl. 5 No.6 3. Antivenom for Critically Ill Children with Neurotoxicity from Scorpion Stings. NEJM 2009; 3360:2090-8. 4. Bites of Brown Recluse Spiders and Suspected Necrotic Arachnidism. NEJM 2005; 352:700-7 5. The global burden of snakebite: a literature analysis and modeling based on regional estimates of envenoming and deaths. PLoSMed. 2008 Nov 4;5(11):e218 The global burden of snakebite: a literature analysis and modeling based on regional estimates of envenoming and deaths The global burden of snakebite: a literature analysis and modeling based on regional estimates of envenoming and deaths 6. Evidence-Based, Multidisciplinary Approach to the Development of a Crotalidae Polyvalent Antivenin (CroFab) Protocol at a University Hospital. The Annals of Pharmacotherapy March 2010 Vol. 44