1. Snakebite Traci Denton RN, CCRN Traci Denton RN, CCRN

2. Snakes in Tennessee Tennessee is home to 32 species of snakes; 4 of which are venomous. Tennessee is home to 32 species of snakes; 4 of which are venomous. Poisonous is not the correct terminology (poison is ingested and venom is injected.) Poisonous is not the correct terminology (poison is ingested and venom is injected.) All of Tennessee’s venomous snakes are from the Pit Viper family. They get that name from having a heat sensing pit just behind each nostril, which they use in sensing their prey. All of Tennessee’s venomous snakes are from the Pit Viper family. They get that name from having a heat sensing pit just behind each nostril, which they use in sensing their prey. The 4 venomous snakes in Tennessee are: The 4 venomous snakes in Tennessee are:

3. The Western Cottonmouth Of all the venomous snakes in Tennessee, the Cottonmouth has the meanest temperament. They will stand their ground when encountered, and they will give you a good dose of venom with each bite. It can bite underwater. All snakes in Tennessee have white mouths; so do not base your identification on that criterion alone.

4. The Timber Rattlesnake Timber rattlesnakes are a secretive, nonaggressive species. Their main defense is to lie motionless on the forest floor, relying on their color and pattern to camouflage them from predators.

5. The Northern and Southern Copperhead The Copperhead is a relatively shy snake, but they account for the most reported bites each year in Tennessee. They inject venom based on the amount required to render its prey inactive. They know that they cannot digest a human, so roughly 50% of their bites are dry bites (no venom injected)

6. The Western Pigmy Rattlesnake This is one of the smallest species of rattlesnakes in North America. The end of the tail has a small rattle on it that is seldom louder than a buzzing insect and is often not heard or even seen. The bite from this species is rarely fatal.

7. Worldwide, there are 50,000 deaths from venomous snakebites each year. Worldwide, there are 50,000 deaths from venomous snakebites each year. Only 12-15 are in the USA Only 12-15 are in the USA In Tennessee, only 4 snakebite related deaths have been reported since 1960. In Tennessee, only 4 snakebite related deaths have been reported since 1960. Most Tennessee snakes are nocturnal during summer months and only lay in midday sun to warm. Most Tennessee snakes are nocturnal during summer months and only lay in midday sun to warm. In early spring and late fall, they are more prevalent in daylight hours when temperatures are higher. In early spring and late fall, they are more prevalent in daylight hours when temperatures are higher. Tennessee snakes hibernate in winter and prefer temperatures > 50 F and 50 F and < 100 F.

8. Most bites occur when people are trying to kill or handle a snake. Snakes will always flee an area rather than strike, unless they are harassed or startled. More people die from bee stings and lightening strikes annually. Most bites occur when people are trying to kill or handle a snake. Snakes will always flee an area rather than strike, unless they are harassed or startled. More people die from bee stings and lightening strikes annually. Immediate medical help should be sought in case a bite occurs. Immediate medical help should be sought in case a bite occurs.

9. This is where we come in…..

11. Coagulation abnormalities are due directly to snake venom interference with the coagulation cascade

12. Pharmacotherapy Pearls Minimal envenomation: Swelling, pain, and bruising are limited to immediate bite site: no systemic signs and symptoms; normal coagulation parameters; no clinical evidence of bleeding. Minimal envenomation: Swelling, pain, and bruising are limited to immediate bite site: no systemic signs and symptoms; normal coagulation parameters; no clinical evidence of bleeding. Moderate envenomation: Swelling, pain, and bruising are limited to less than a full extremity (or<50 cm if bite was on head or trunk); systemic signs and symptoms are not life threatening (nausea, vomiting, oral paresthesia, unusual taste, mild hypotension, mild tachycardia, tachypnea); coagulation parameters may be abnormal; no bleeding other than minor hematuria, gum bleeding or nosebleeds, if not severe. Moderate envenomation: Swelling, pain, and bruising are limited to less than a full extremity (or<50 cm if bite was on head or trunk); systemic signs and symptoms are not life threatening (nausea, vomiting, oral paresthesia, unusual taste, mild hypotension, mild tachycardia, tachypnea); coagulation parameters may be abnormal; no bleeding other than minor hematuria, gum bleeding or nosebleeds, if not severe.

13. Severe envenomation: Swelling, pain, and bruising involve more than the entire extremity or threaten the airway; systemic signs and symptoms are markedly abnormal (severe alteration of mental status, severe hypotension, severe tachycardia, tachypnea, respiratory insufficiency); coagulation parameters are abnormal; serious bleeding or severe threat of bleeding. Severe envenomation: Swelling, pain, and bruising involve more than the entire extremity or threaten the airway; systemic signs and symptoms are markedly abnormal (severe alteration of mental status, severe hypotension, severe tachycardia, tachypnea, respiratory insufficiency); coagulation parameters are abnormal; serious bleeding or severe threat of bleeding.

14. Treatment…….. CroFab is a venom-specific fragment of IgG, which binds and neutralizes Venom toxin, helping to remove the toxin from the target tissue and Eliminate it from the body.

15. Dosing: Adult Crotalid envenomation Initial dose : 4-6 vials, dependent upon patient response. Treatment should begin within 6 hours of snakebite; monitor for 1 hour following infusion. Repeat with an additional 4-6 vials if control is not achieved with initial dose. Continue to treat with 4- 6 vial doses until complete arrest of local manifestations, coagulation tests and systemic signs are normal. Monitor closely. Initial dose : 4-6 vials, dependent upon patient response. Treatment should begin within 6 hours of snakebite; monitor for 1 hour following infusion. Repeat with an additional 4-6 vials if control is not achieved with initial dose. Continue to treat with 4- 6 vial doses until complete arrest of local manifestations, coagulation tests and systemic signs are normal. Monitor closely.

16. Maintenance dose : Once control is achieved, administer 2 vials every 6 hours for up to 18 hours. Optimal dosing past 18 hours has not been established; however, treatment may be continued if deemed necessary based on the patient’s condition. Maintenance dose : Once control is achieved, administer 2 vials every 6 hours for up to 18 hours. Optimal dosing past 18 hours has not been established; however, treatment may be continued if deemed necessary based on the patient’s condition. Dosing: Geriatric Refer to adult dosing Dosing: Geriatric Refer to adult dosing Dosing: Pediatric Refer to adult dosing Dosing: Pediatric Refer to adult dosing Note: Clinical trials included patients as young as 11 years of age. Specific pediatric studies have not been conducted. Because the absolute venom dose is expected to be the same in adults and children, adult dosing should be used. Note: Clinical trials included patients as young as 11 years of age. Specific pediatric studies have not been conducted. Because the absolute venom dose is expected to be the same in adults and children, adult dosing should be used. Products contain thimerosal with 0.11 mg of mercury per vial, which in high doses has been associated with neurological and renal toxicity. Fetuses and very young children are most susceptible for mercury related toxicities. Products contain thimerosal with 0.11 mg of mercury per vial, which in high doses has been associated with neurological and renal toxicity. Fetuses and very young children are most susceptible for mercury related toxicities.

17. Reconstitution: Reconstitute each vial with 10 mL sterile water for injection and mix by gentle swirling. Further dilute total dose in 250 ml NS: use within 4 hours of reconstitution. Reconstitute each vial with 10 mL sterile water for injection and mix by gentle swirling. Further dilute total dose in 250 ml NS: use within 4 hours of reconstitution. Note : Reconstitution with 25 mL sterile water for infusion and hand rolling/inverting may result in shorter dissolution times and allow for more rapid administration. Note : Reconstitution with 25 mL sterile water for infusion and hand rolling/inverting may result in shorter dissolution times and allow for more rapid administration.

18. Administration: I.V. Administer I.V. over 60 minutes at a rate of 25-50 mL/hour for the first 10 minutes. If no allergic reaction is observed, increase rate to 250 mL/hour. Monitor closely. Epinephrine and diphenhydramine should be available during the infusion. Administer I.V. over 60 minutes at a rate of 25-50 mL/hour for the first 10 minutes. If no allergic reaction is observed, increase rate to 250 mL/hour. Monitor closely. Epinephrine and diphenhydramine should be available during the infusion. Decreasing the rate of infusion may help control some adverse effects. Decreasing the rate of infusion may help control some adverse effects.

19. Contraindications: Hypersensitivity to any component of the formulation (including papaya or papain), unless benefits outweigh the risks and appropriate management for anaphylaxis is readily available. Hypersensitivity to any component of the formulation (including papaya or papain), unless benefits outweigh the risks and appropriate management for anaphylaxis is readily available. Processed with papain and my cause hypersensitivity reactions in patients allergic to papaya, other papaya extracts, papain, chymopapain, or the pineapple-enzyme bromelain. There may also be cross allergencity with dust mite and latex allergens. Processed with papain and my cause hypersensitivity reactions in patients allergic to papaya, other papaya extracts, papain, chymopapain, or the pineapple-enzyme bromelain. There may also be cross allergencity with dust mite and latex allergens.

20. Adverse effects: Hypersensitivity reactions: Derived from sheep plasma; anaphylaxis and anaphylactoid reactions are possible, especially in patients with known allergies to sheep protein. Immediate treatment (including epinephrine 1:1000) for anaphylactoid and/or hypersensitivity reactions should be available. Incidence of acute hypersensitivity reactions may be lower than previously thought. This product lacks the immunogenic Fc fragments and proteins found in the older equine-derived product. Sensitization may occur with repeated doses. Hypersensitivity reactions: Derived from sheep plasma; anaphylaxis and anaphylactoid reactions are possible, especially in patients with known allergies to sheep protein. Immediate treatment (including epinephrine 1:1000) for anaphylactoid and/or hypersensitivity reactions should be available. Incidence of acute hypersensitivity reactions may be lower than previously thought. This product lacks the immunogenic Fc fragments and proteins found in the older equine-derived product. Sensitization may occur with repeated doses.

21. Adverse Reactions: Cardiovascular: Hypotension Cardiovascular: Hypotension Central nervous system: Chills Central nervous system: Chills Dermatologic: Pruritus, rash, urticaria Dermatologic: Pruritus, rash, urticaria Respiratory: Asthma, cough, dyspnea, wheezing Respiratory: Asthma, cough, dyspnea, wheezing Miscellaneous: Anaphylaxis, anaphylactoid reaction, hypersensitivity reactions (5% to 19%), serum sickness (5%) Miscellaneous: Anaphylaxis, anaphylactoid reaction, hypersensitivity reactions (5% to 19%), serum sickness (5%)

22. Drug Interactions: There are no known significant interactions. There are no known significant interactions. Lactation: Excretion in breast milk unknown/use caution Lactation: Excretion in breast milk unknown/use caution

23. Disease-related concerns: CroFab should be used within 4-6 hours of snakebite to prevent clinical deterioration and development of coagulation abnormalities. These are due directly to snake venom interference with the coagulation cascade. Recurrent coagulopathy occurs in approximately 50% of patients and may persist for 1-2 weeks or more. Repeat dosing may be indicated. Patients should be monitored for at least 1 week and evaluated for other pre-existing conditions associated with bleeding disorders. In severe envenomations, a decrease in platelets may occur, lasting hours to several days. Blood products are generally ineffective as they are rapidly consumed by circulating venom. CroFab should be used within 4-6 hours of snakebite to prevent clinical deterioration and development of coagulation abnormalities. These are due directly to snake venom interference with the coagulation cascade. Recurrent coagulopathy occurs in approximately 50% of patients and may persist for 1-2 weeks or more. Repeat dosing may be indicated. Patients should be monitored for at least 1 week and evaluated for other pre-existing conditions associated with bleeding disorders. In severe envenomations, a decrease in platelets may occur, lasting hours to several days. Blood products are generally ineffective as they are rapidly consumed by circulating venom.

24. Monitoring: Parameters: Vital signs, CBC, platelet count, prothrombin time, aPTT, fibrinogen levels, fibrin split products, clot retraction, bleeding and coagulation times, BUN, electrolytes, bilirubin, size of bite area (repeat every 15-30 minutes); intake and output, signs and symptoms of anaphylaxis/allergy. Parameters: Vital signs, CBC, platelet count, prothrombin time, aPTT, fibrinogen levels, fibrin split products, clot retraction, bleeding and coagulation times, BUN, electrolytes, bilirubin, size of bite area (repeat every 15-30 minutes); intake and output, signs and symptoms of anaphylaxis/allergy. CBC, platelet counts, and clotting studies are evaluated at 6-hour intervals until patient is stable. CBC, platelet counts, and clotting studies are evaluated at 6-hour intervals until patient is stable.

25. Size of bite area marked every 15 minutes

26. Cost Generic not available in the U.S. Generic not available in the U.S. Pricing (www.drugstore.com) is $4687.76 (2vials) Pricing (www.drugstore.com) is $4687.76 (2vials)www.drugstore.com

27. References Buchanan JA, Varney SM, Mlynarchek SL, et al, “Immediate Adverse Events (AEs) After Administration of Crotalidae Polyvalent Immune Fab,” Clin Toxicol, 2009, 47(7):703. Buchanan JA, Varney SM, Mlynarchek SL, et al, “Immediate Adverse Events (AEs) After Administration of Crotalidae Polyvalent Immune Fab,” Clin Toxicol, 2009, 47(7):703. Cannon R, Ruha AM, and Kashani J, “Acute Hypersensitivity Reactions Assocoated With Administration of Crotalidae Polyvalent Immune Fab Antivenom”, Ann Emergency Medicine, 2008, 51(4):407-11. Cannon R, Ruha AM, and Kashani J, “Acute Hypersensitivity Reactions Assocoated With Administration of Crotalidae Polyvalent Immune Fab Antivenom”, Ann Emergency Medicine, 2008, 51(4):407-11. Crotalidae Polyvalent Immune Crotalidae Polyvalent Immune Duke, J, “The Venomous Snakes in Tennessee”, About.com Guide. Duke, J, “The Venomous Snakes in Tennessee”, About.com Guide. Levonas EJ, Kokko J, Schaeffer TH, et al “Short-Term outcomes After Fab Antivenom Therapy for Severe Crotaline Snakebite,” Ann Emerg Med, 2011, 579(2): 128-37[PubMed20952098]. Levonas EJ, Kokko J, Schaeffer TH, et al “Short-Term outcomes After Fab Antivenom Therapy for Severe Crotaline Snakebite,” Ann Emerg Med, 2011, 579(2): 128-37[PubMed20952098]. Ohio Valley Poisonous Snakes: Kentucky, Ohio, Tennessee, West Virginia, and Indiana, OhioValleyFishing.com, 2011. Ohio Valley Poisonous Snakes: Kentucky, Ohio, Tennessee, West Virginia, and Indiana, OhioValleyFishing.com, 2011. Quan, AN, Quan D, and Curry SC, “Improving Crotalidae Polyvalent Immune Fab Reconstitution Times, “ Am J Emerg Med,2010, 28(5):593-3 {PubMed 20579555] Quan, AN, Quan D, and Curry SC, “Improving Crotalidae Polyvalent Immune Fab Reconstitution Times, “ Am J Emerg Med,2010, 28(5):593-3 {PubMed 20579555]