1. Envenomations: Bees, Snakes and Spiders Jeff Hurley MD Emergency Medicine Department Martin Luther King

2. Objectives Epidemiology Pathophysiology Treatment …of bees, snakes and spiders.

3. Hymenoptera

4. More deaths than any other envenomation. Includes: bees, wasps, hornets, yellow jackets, and ants Incidence of approximately 1 million a year. Vast majority (17-56%) only minor reactions. Generalized reactions in 1-2%. Only about 5% seek medical care. Approximately 30-120 deaths annually. Social creatures…attack when disturbed.

5. Pathophysiology Allergic reaction mediated by IgE. Prior exposure to venom proteins Venom load (histamine, bradykinin, dopamine, serotonin, mast cell degranulating peptide)  30 vespid stings  200 honeybee stings Reaction:  Urticaria  Vasodilation  Bronchospasm  Laryngospasm  Angioedema

6. Hypersensitivity

7. Pathophysiology Rapid onset of symptoms.  50% of deaths in the first 30 minutes  75% in the first 4 hours Distinguish local versus generalized reactions. Local: pain, edema, pruritis, nausea and vomiting may also occur without generalization. Generalized: urticaria, confluent rash, shortness of breath, wheezing, weakness, edema, anxiety, chest pain.

8. Reactions

9. Prehospital Immediate treatment may be life-saving. Manage generalized reactions similar to anaphylaxis EVEN IN THE ABSENSE OF SHOCK.  Remove Stinger (pinching and traction is acceptable)  Airway prn  Breathing treatments: albuterol  Cardiovascular collapse: fluid bolus and epinephrine  Antihistamines  Apply Ice  Elevate Extremity Local reactions may be life threatening if swelling in proximal to airway.

10. Treatment Antihistamines –Diphenhydramine: Drug of choice. H1 and partial H2 blockade. Adult: 50-75 mg PO/IM Q4 Pediatric: 1-2 mg/kg PO/IM –Cimetidine: Indicated for systemic reactions that do not respond completely to diphenhydramine. Adult: 300-800 mg IV Q6 Pediatric: 5 mg/kg IV Q6 Epinephrine: Drug of Choice for systemic reactions. –Alpha agonist effects: reverse hypotension, vasodilation, vascular permeability –Beta agonist effects: causes bronchodilation, increased cardiac output Adult: 0.2 to 1 mg IV/SC Pediatric: 0.01 to 0.1 mg/kg IV/SC –Caution in older people with CAD, DM, HTN, CVA Hx, BPH. Rapid IV infusion may cause MI, hemorrhagic CVA, cardiac arrhythmias. Albuterol Steroids (solumedrol): Generalized reactions. Decrease PMN activity and capillary permeability. –Adults: 250 mg to 1 gm Q6 –Pediatric: 0.2 to 2 mg/kg IV Q6 Theophylline: Relieve bronchospasm in resistant cases.

11. Complications Infection: Especially in young children. Rebound Anaphylaxis Cross-over reactivity Serum-sickness reaction  6-14 days s/p sting  ASA, Benedryl, Prednisone  Complications: vasculitis, neuropathy, glomerulonephritis, shock and death.

12. Medical / Legal Failure to remove stinger Failure to observe Failure to educate and discharge with epi-pen. Failure to refer to allergist.

13. Snakes

14. Colubridae: 70% of snakes: nonvenomous except two species Hydrophidae: sea snake  Neurotoxic Elapidae: Coral snake and Cobra  Neurotoxic Crotalidae: Pit Viper: rattlesnakes, moccasins, copperheads  Hemotoxic >>> Neurotoxic  98% of envenomations in the US

15. Epidemiology Incidence greatest in Southern US. 97% on extremities: 2/3 on upper and 1/3 on lower. Males 9X than females. Young adults. Approx. 7000 bites reported annually. Rattlesnakes 2/3 of all bites. Dry bite (no venom): 30-50% 5.5 Deaths average annually.

16. Venomous vs. Non-Venomous “Red on Yellow, Kill a Fellow” “Red and Black, Venom Lack”

17. Pathophysiology Venom is composed of either neurotoxin or hemotoxin.  Proteins: Cause coagulation, anticoagulation, hemorrhage, hemolysis, myonecrosis.  Polypeptides: Target heart, lungs, kidney, synapses.  Variable delivery of toxin. Clinical: Local envenomation can lead to DIC, pulmonary edema, shock. Anaphylactic reactions secondary to VAPs. Can occur slowly from mild pain to multisystem organ failure.

18. Elapidae Coral and Cobra snakes. Venom blocks neuromuscular transmission, and has direct effects on the heart and muscles. Signs and Symptoms include:  Minor pain at area of bite.  Local painful paresthsias  Mild STS  AMS  Cranial Nerve dysfunction Ptosis is common and may be the first sign of envenomation.  Respiratory distress and cyanosis Onset may be delayed 10-12 hours but may progress rapidly thereafter. Respiratory failure is the usual cause of death.

19. Crotalidae Rattlesnakes, moccasins, copperheads Pain immediately after bite. Severity related to dose to venom. Progressive subcutaneous edema. Possibility for a compartment syndrome, but it has not been described. Possible need for fasciotomy. Recommended to monitor cap refill as it may be difficult to distinguish between compartment syndrome and the effects of the envenomation. Petechiae, eccyhmosis, bullae (serous and hemorrhagic). Death related to failure of coagulation and increased capillary membrane permeability. Pulmonary edema, shock and death follow. Allergic reactions may occur as well. Labs: CBC/Platelets, PT/PTT, fibrinogen, FSP, type and cross, UA Rhabdomyolysis: total CK, electrolytes, (EKG)

20. Grading Envenomation - Crotalidae Grade 0: no evidence of envenomation (< 1 inch) Grade I: 1-5 inches of edema and erythema Grade II: moderate envenomation, severe widely distributed pain, petechiae, eccyhmosis Grade III: spread within 12 hours to entire extremity and trunk, systemic manifestations, tachycardia, hypotension, temperature abnormalities Grade IV: very severe, swelling of extremity and trunk within a few hours, systemic within 15 minutes, convulsions, coma, death may occur

21. Reactions

22. Prehospital All snakebites should be considered emergencies especially in the first 6-8 hours. ABCs Remove clothing. Spread of venom should be slowed.  Immobilize bitten area.  NPO  Constricting band that impedes venous flow but not arterial flow If patient is seen in 15 minutes, suction can be performed to remove venom.  Sawyer Extractor (mouth suction is contraindicated)  No benefit has been demonstrated, and additional damage may be inflicted. Ice is not helpful in slowing the spread of venom, but does help with pain control. If capable, identify the snake, or transport the dead snake. (avoid touching the head, as envenomizations may occur) Cardiac Monitor, IV fluids (2), pain control. Arizona Poison Control (520-626-6016)

23. Treatment Supportive: IVF, pain control, antihistamines Antibiotics, tetanus Elapidae: Intubation prn, do not use gradation scale Crotalidae: DIC may require FFP Antivenin

24. Elapidae Epinephrine if hypotensive despite fluid administration Consider dopamine and levophed Micrurus fulvius Antivenin  Give 3-6 vials IV over 1-2 h, if signs or symptoms continue to progress, add 3-5 vials over 1-2 h Read package insert Slow IV infusion that increases rate Similar to IVIG protocols  rarely, more than 10 vials are required  Before administration, the patient's IV volume should be expanded using crystalloid solutions  Pretreat with antihistamines, diphenhydramine +/- cimetidine  Skin testing prior to giving antivenin  Horse-based antivenin. Possibility of anaphylactic shock.

25. Crotalidae Can use severity table to aid in decision to use. Old horse based polyvalent Crotalidae antivenin.  Moderate envenomation: 5-10 vials  Severe envenomation: 15-20 vials  Premedication with diphenhydramine.  Pretreatment with epinephrine 0.25 mg SC  Monitor for anaphylactic reaction. New Fab antigen binding fragments from ovine (sheep). Fewer allergic reactions. Similar to Digibind Fab.  Pretesting is not required

26. Spiders

27. Only spiders to be feared are the Black Widow and the Brown Recluse. Other spiders simply cause pain. Incidence is unknown. Bites rarely cause death…less than 1%. Children more vulnerable. Older patients with CAD also at risk. 13,000 reported bites with 1,300 described as severe.

28. Black Widow – Lactrodectus Bites only when disturbed. Neurotoxin released that causes localized pain that may be followed by muscle cramps, abdominal pain, weakness, tremor, headache, anxiety, and insomnia.  Reactions may take 15 minutes to 6 hours to develop. Severe bites can cause nausea, vomiting, dizziness, chest pain, and respiratory difficulties. Abdominal pain mimic acute abdomen, colic, or food poisoning. Little local damage to tissues. Fang marks. Patients experience immediate pain. Possible metallic taste in mouth. Side effect of hypertension and tachycardia.

29. Treatment Pain control: Demerol as it may produce less smooth muscle spasm. Calcium Gluconate: Mechanism unknown. Controversial.  Normalizes nerve and cardiac function.  1-2 ml/kg of 10% solution as slow IV, not to exceed 10 ml  Contraindications: dig toxicity, renal or cardiac disease Latrodectus Antivenin: Neurtalizes the toxin.  Produces rapid relief of pain.  Some recommend usage only in children, elderly or those with underlying medical problems.  2.5 ml IM in anterolateral thigh  Or diluted in 10-50 cc NS and infused IV over 15 minutes in severe cases, children less than 12, or in cases of shock.  Same dose in children as adults.  Horse serum: potential for anaphylaxis (uncommon…much more likely with snake antivenins)

30. Brown Recluse Spider

31. Loxosceles

32. Brown Recluse Distribution in Southern US. Fiddle-back appearance. Severity mild, local, urticarial, to full- thickness necrosis. Less than 10% of bites result in severe necrosis or systemic manifestations. Death uncommon. Documented cases affecting children with hemotological problems.

33. Distribution

34. History and Physical BITE IS PAINLESS. Symptoms: Fever, headache, malaise, nausea, vomiting, arthralgia Cutaneous manifestations: macular, papular, petechial eruption. May not be seen for 6-12 hours after bite. May progress to a necrotic lesion. (less than 10% of the time) Wounds that do become necrotic, show sgins in 2-3 days. Discoloring occurs with the center purple discolored, an area of blanched skin do to skin edema, and then erythema surrounding.  Characteristic “red, white, and blue” pattern.  Significant pain at this stage. Wounds may take months to heal. Patient with severe reactions show bullae formation, cyanosis, and pain within 6-12 hours. Hemolysis my occur.  Labs to monitor hemolysis: CBC, unconjugated bilirubin, decreased haptoglobin, LDH  UA to monitor for hemoglobinuria

35. Lesions

36. Treatment Virtually all bites heal without treatment in 2-3 months. Clean wound. Ice, elevate, and provide pain medications (anti-inflammatory) and anti-ich medications (diphenhydramine or atarax). If tissue breakdown occurs, antibiotics are indicated as well as tetanus prophylaxis. Dapsone may limit tissue damage, but it must be started early. Delay in starting dapsone may negate its benefits.  Believed to supress a halide-myeloperoxidase in PMNs.  Adults: 100 mg PO BID x 2 wks  Pediatrics: 1-2 mg/kg/day  Contraindicated in patients with G6PD deficiency as it may cause hemolysis. Hyperbaric Oxygen: may speed recovery. Necrotic skin lesions occur in 10% of pts. Surgical care may be instituted but only after 6-8 wks. Early intervention is not advised. Steroids possibly cause more damage than good. Follow up daily to monitor necrosis. Possible referral to a plastic surgeon.

37. References Rosen’s Emergency Medicine, Concepts and Clinical Practice. 2002 eMedicine. www.emedicine.comwww.emedicine.com Merck Manual. www.merck.comwww.merck.com Vegas Review

38. Poisonous?

39. Pt. complains of rash, joint pain, itching, and muscle aches 10 days after being bitten by a bunch of wasps. What is the cause of her problem? A) sensitized lymphocytes causing delayed type hypersensitivity B) IgE-mediated release of histamine C) inflammatory reaction to antigen-antibody complexes D) antibody mediated cell lysis E) G6PD deficiency

40. Five year old girl (20 kg) bitten by a honeybee five minutes ago complains of wheezing and body rash. Estimated 30 minute transport time. Best treatment choice? A) cont. albuterol nebs, antihistamine, IVF B) epinephrine 0.2 mg of 1:10,000 SC C) epinephrine 2 mg 1:1000 IV D) epinephrine 0.2 mg of 1:1,000 SC E) epinephrine 0.2 mg 1:10,000 IV F) epinephrine 2 mg 1:10,000 SC

41. No antivenin exists for which envenomation? A) Black Widow B) Brown Recluse C) Coral Snake D) King Snake E) Rattlesnake

42. Serum sickness may not be seen in which of the following? A) Crotalidae polyvalent antivenin B) Horse serum antivenin C) Etalidae antivenin D) Hymenoptera envonomation E) CroFab antivenin