In the event of an actual or probable bite from a Bothrops, execute the following first aid measures without delay.

Snake:

1. Make sure that the responsible snake or snakes have been appropriately and safely contained, and are out of danger of inflicting any additional bites.

Transportation:

1. Immediately call for transportation.

   Telephone:

Victim:

1. Keep the victim calm and reassured. Allow him or her to lie flat and avoid as much movement as possible. If possible, allow the bitten limb to rest at a level lower than the victim's heart.

2. Identify the bite site, looking for fang marks, and apply the Sawyer Pump extractor with the largest cup possible over the bite site. If there are two or more fang marks noted on the limb, apply the pump extractor over at least one fang mark. If more than one pump extractor is available, they may be applied to the additional fang marks.

3. Immediately wrap a large constricting band snugly about the bitten limb at a level just above the bite site, ie. between the bite site and the heart. The constricting band should be as tight as one might bind a sprained ankle, but not so tight as to constrict blood flow.

4. DO NOT remove the constricting band until the victim has reached the hospital and is receiving antivenom.

5. Have the Wyeth Crotalidae Polyvalent Antivenom ready for the emergency crew to take with the victim to the hospital. Give them the following:
   1. the available antivenom (at least 20 vials)
   2. the accompanying instruction (Protocol) packet
   3. the victim's medical packet (if available)

The bite of Bothrops species can be fatal. In Central and South America it is responsible for the majority of snakebite fatalities. The snake is often aggressive and some species can be arboreal. Victims will usually complain of pain at the bite site and swelling may be evident. Tremendous local tissue destruction can ensue, along with a substantial coagulopathy. Prompt medical therapy avoids these problems. Please read the attached and respond appropriately.

1. First Aid:
   1. Apply constricting band if not already present, proximal to bite on arms, legs, hands, or feet. Apply suction with the Sawyer Pump extractor for 10-20 minutes. Rest the extremity below the patient's heart.

   2. Transport to a medical center emergency or trauma service.

2. Medical Management:
   1. Call your local Poison Control Center, or the San Diego Regional Poison Control Center (800 876-4766). They should locate a consultant to help you treat this patient.

   2. Observe for Signs and Symptoms of Envenomation.

   3. If signs or symptoms are present, perform the following:
      1. Apply intradermal skin test.

      2. Administer Lactated Ringers intravenously at a rate of 200 cc/hour. Obtain appropriate blood and urine laboratory data.

      3. Wait 20 minutes.

      4. Reconstitute 5 vials of Wyeth Crotalidae Polyvalent antivenom in 50 cc Lactated Ringers (10 ml/vial).

      5. If no reaction to intradermal skin test, administer antivenom by intravenous infusion 1 vial (10 cc) every 5-10 minutes. The constricting band can be removed after the first vial has been infused. One should anticipate using 5-10 vials for minor to moderate bites, and 10-40 vials for moderate to severe bites.

      6. Monitor signs, symptoms, and laboratory data and administer additional aliquots of 5 vials of antivenom as needed to neutralize signs and symptoms at a rate of 1 vial (10 cc) every 5-10 minutes.

      7. If patient is allergic to horse serum, administer gram Solu-Medrol IV push, wait 30-45 minutes, and then begin intravenous antivenom. Be prepared to administer Benadryl and epinephrine.

      8. In case of intravenous envenomation, administer antivenom IV push, 1 vial every 1 minute, until symptoms improve then continue by intravenous infusion until signs and symptoms are titrated.

This person has received a bite and probable envenomation from a Bothrops species. These snakes are very aggressive and one of the most venomous in Central and South America. They account for the majority of snakebite related fatalities on these continents. Envenomation presents predominately with edema, pain, and hematologic manifestations. Dizziness, headaches, and necrosis can also be present. In some less common species (such as B. jararacussu of Brazil), blindness may present early after a bite. In severe envenomations, peripheral circulatory collapse, acute renal failure, and cerebral hemorrhage may manifest.

Please read and execute the following procedures without delay.

1. A constricting band should be in place proximal to the bite site. If present, leave in place, if not apply a penrose drain as if for venipuncture. This retards venom absorption. DO NOT remove until the patient has arrived at the hospital and is receiving the antivenom.

2. Make sure that at least 20 vials of Crotalidae Polyvalent Antivenom (Wyeth) are present with the patient. This antivenom contains the necessary fractions to neutralize the venoms of all Central and South American species of Bothrops.

3. If the patient has been envenomated, the initial treatment is 5 to 40 vials of intravenous antivenom. Envenomation is diagnosed by the presence of characteristic signs and symptoms. Necessary information follows and is organized in sections:
   Signs and Symptoms of Envenomation
   Medical Management
   General Considerations
   Special Considerations
   Consultants
   References

Signs and Symptoms of Envenomation:

1. These signs and symptoms will usually manifest earliest, though their development will vary considerably from case to case. Not all of these will necessarily occur, even with severe envenomation.

   Edema & Pain

   100%
   Hemorrhage (gingival, nasal, wound, rectal)	40%
   Headaches	29%
   Microscopic hematuria	25%
   Dizziness	23%
   Necrosis	17%
   Tingling of extremities	17%
   Vomiting	15%
   Macroscopic hematuria	2%
   Ecchymosis	2%
   Hematemesis	1%
   Blindness

2. General: The above symptoms can manifest within 5 hours after envenomation. Edema usually begins within the first few minutes after the bite.

3. Local Symptoms: Though pain and edema are the major local manifestations, hemorrhage around the bite site is common. Tissue necrosis is seen less frequently. Extensive necrosis can occur. Other local signs include:
   Local blister formation
   Local and scattered skin discoloration
   Ecchymosis
   Blindness

4. Hematology: Bothrops venom has been shown to consume prothrombin, fibrinogen, and clotting factors II, V, VIII, IX, X, and XI. This results in a DIC type coagulopathy with an increase in PTT and bleeding times. Fibrinogen levels and sedimentation rates are generally decreased. However, platelets are within normal limits. Microembolism to the lung and other organs is seen along with a greater than 50% occurrence of leucocytosis (10,000-50,000).

5. Urinary Symptoms:

   Albuminuria, >200mg	26%
   Microscopic hematuria	8% - 25%
   RBC casts	10%
   Macroscopic hematuria	2%
   Hyaline and granular casts	2%
   Hemoglobinuria	2%

6. Fang Marks: Fang marks may be present as one or more well defined punctures, as a series of small lacerations, or scratches, or there may not be any noticeable or obvious markings where the bite occurred. The absence of fang marks does not preclude the possibility of a bite (especially if a juvenile snake is involved). The presence of fang marks does not always imply that envenomation occurred. Multiple bites inflicted by a single snake are also possible, and should be noted if present. WATCH THE PATIENT CLOSELY.

7. Severe Envenomation: One or more of the following clinical pictures can occur:
   1. Hypotension and increased heart rate secondary to peripheral circulatory collapse.

   2. Acute Renal Failure secondary to diffuse glomerulonephritis.

   3. Cerebral hemorrhage and edema secondary to DIC.

Medical Management:

1. Admit patient to an emergency or trauma service and call the consultant identified by the Poison Control Center.

2. Begin a peripheral intravenous infusion (18 gauge catheter) of Lactated Ringers Solution at the rate of 250 cc/hr.

3. Draw blood from the contralateral arm, and collect urine for the following laboratory tests. Mark STAT.
   1. Type and Cross Match TWO units of whole blood.

   2. CBC with differential and platelets.

   3. Coagulation Parameters:
      1. Prothrombin Time (PT)
      2. Partial Thromboplastin Time (PTT)
      3. Fibrinogen levels
      4. Fibrin Degradation Products

   4. Serum Electrolytes, BUN/Creatinine, Calcium, Phosphorus.

   5. Lactate Dehydrogenase (with Isoenzyme analysis). Isoenzyme analysis may indicate multiple targets of venom components which may dictate further management.

   6. Urinalysis (Macroscopic and Microscopic Analysis). Must include analysis for:
      1. Free Protein
      2. Hemoglobin
      3. Myoglobin
      4. Casts

   7. Electrocardiogram. Place patient on continuous cardiac monitoring.

   8. A brisk urine output measurement should be obtained. Intermittent or indwelling Foley Catheter to monitor urine output may be necessary in the conscious impaired patient.

   9. Additional tests as needed or indicated by the patient's hospital course.

   10. It may be necessary or practical to repeat some of the above serum and urine tests periodically over the hospital course to monitor the effects of antivenom therapy or to detect late changes in laboratory values.

4. OBSERVE PATIENT CLOSELY for signs and symptoms of envenomation which usually manifest between 15 minutes and two hours after the bite occurred.
   1. If NONE of the signs or symptoms have been noted after two hours, there is a possibility that the patient received a dry bite (no venom injected).
      1. Remove the constricting band, watching carefully for any changes in the patient's status. If any changes occur, assume the patient has been envenomed, and prepare to give antivenom immediately (as directed below).

   2. If signs and symptoms still fail to manifest, continue CLOSE observation of the patient for an additional 12 to 24 hours.

5. IF ANY SIGN OR SYMPTOM becomes apparent or has been noted during the course of treatment, begin antivenom therapy as follows:
   1. Patients manifesting severe symptoms or those suspected of having an intravenous injection of venom should be treated immediately with antivenom and should not undergo skin testing. Corticosteroid adjuncts may facilitate the delivery of rapid infusion. One should use the dilutions below, but infuse at a rate of 1 vial (10 cc) per minute.

   2. If the patient is exhibiting minor or moderate signs of envenomation, or has a prior history of anaphylactic or anaphylactoid response to antivenom, inject intracutaneously the skin test sample included in the antivenom package, sufficient to raise a small weal.

   3. The skin test should be read after 15 minutes, but it is wise to check the test area and observe the patient constantly during the period following the injection. If there is no evidence of erythema or vesicular response, the test should be considered negative.

   4. A positive test IS NOT a contraindication to giving antivenom, but should alert the clinician that the rate at which the antivenom is delivered and/or the use of corticosteroids may need to be adjusted to control potential untoward responses.

   5. Assuming that the above skin testing precautions have been done, reconstitute the contents of 5 vials of Wyeth Crotalidae Polyvalent Antivenom in Lactated Ringers Solution. Gently shake the vials to assure that the contents are thoroughly mixed, and that there is a minimum of undissolved particles. Transfer the dissolved solution via a syringe to an IV piggyback setup with a volumetric regulator. Make sure that there are no undissolved particles in the solution transfer.

   6. Administer the diluted antivenom intravenously over a period of 10 minutes for the first vial (1 cc/minute).

   7. Should any signs of ALLERGY/ANAPHYLAXIS (e.g. coughing, dyspnea, urticaria, itching, increased oral secretions, etc.) develop, immediately discontinue the administration of antivenom and treat symptoms with Corticosteroids, Epinephrine, Benadryl, Atarax, and/or other Antihistamines as necessary. As soon as the patient is stabilized, continue the antivenom infusion at a slower rate.

   8. After 10 minutes of antivenom administration, the constricting band may be removed.

   9. Assuming that the patient is tolerating the infusion well, additional antivenom may be given at a rate of one vial/5-10 minutes. The first 5 vials should be given over the first hour of treatment.

6. Antivenom Therapy is the mainstay of treatment for rattlesnake envenomation. Many of the symptoms are ameliorated or entirely eliminated by the antivenom alone. Other symptoms will require additional modalities of therapy to correct.
   1. Cardiovascular symptoms are usually seen only in severe envenomations. They usually present as hypotension and increased heart rate. Patients should be treated for peripheral circulatory collapse by continuing peripheral I.V. infusion of Lactated Ringers about 250 cc/hr and administering vasopressors and volume expanders.

   2. Acute Renal Failure is seen in severe envenomations. It may necessitate Peritoneal Dialysis.

   3. If significant limb swelling occurs, orthopaedic evaluation with intracompartment and subcutaneous tissue pressure measurements can be obtained. Surgical debridement or fasciotomy is very rarely if ever indicated.

   4. Hematologic symptoms may present as a Disseminated Intravascular Coagulopathy, and are treated as other DICs.

7. It is important to keep venom neutralization current and continuous. The best method to accomplish this is to keep a close watch on the patient's status. If the present condition does not improve, or should it worsen for any reason, additional antivenom should be administered. Give all additional antivenom in 5 vial increments. Again, dilute the antivenom 1 to 10 in Lactated Ringers, transfer the solution to an IV piggyback setup, and deliver over a period of 7-10 minutes per vial. One should anticipate using 5-10 vials for minor to moderate bites, and up to 40 vials for severe bites.

8. It is advisable to check periodic serum and urine analyses during therapy as outlined above.

9. It is always best to keep the patient in an Intensive Care setting until free of major symptoms for 24 hours. The patient should be observed in the hospital for at least 24 hours after the major symptoms abate.

General Considerations:

1. It is important that the patient be placed at rest, kept warm, and avoid unnecessary movement.

2. Symptom variablility: As noted above, the variability of symptoms in rattlesnake envenomation can be great. It is important to note the continual progression of symptoms throughout the course of therapy, and give additional antivenom as necessary to titrate these symptoms.

3. Fluid management is very important in snakebite cases. The patient should be well hydrated and a brisk urine output maintained.

4. Morphine is CONTRAINDICATED because of its tendency to suppress respiration. Alcohol should also be avoided.

5. In cases which Circulatory Shock remains uncorrected by antivenom therapy, plasma volume expanders and/or vasopressor agents may be given with appropriate considerations.

6. If the patient remains oligoanuric, dialysis should be considered early.

7. Tetanus prophylaxis should be current

8. Antibiotics are NOT recommended prophylactically.

Special Considerations:

1. Local Necrosis: Prompt delivery of antivenom following the bite may lessen the extent of local tissue damage, although some evidence suggests that certain antivenoms have less efficacy in ameliorating or protecting against the local action of Bothrops venom. This latter statement should not be held as a contraindication to the use of antivenom in those Bothrops bites in which local symptoms predominate.

2. Multiple Bites: It is possible for Bothrops to deliver more than one bite in a single attack and thus may inject a large volume of venom. If there is evidence that such an attack occurred (i.e. history or multiple bite sites), twice the initial dose of antivenom should be given (i.e. 10 vials over 70-100 minutes at the rate of one vial per 7-10 minutes). Always watch closely for signs of allergic response; if they occur, treat appropriately and with slow infusion rate. Give all subsequent doses in 5 vial increments at a rate of 1 vial per 7-10 minutes as necessitated by the presence of continued signs and symptoms.

3. Severe Envenomations: If the patient shows severe signs of envenomation, particularly if early after the bite, treat as a multiple bite, administering 10 vials of antivenom over the first 70-100 minutes. Give all subsequent doses in 5 vial increments at a rate of 1 vial/7-10 minutes as necessitated by the presence of continued signs and symptoms.

4. If the patient is otherwise stable, but has elevated blood levels of urea and serum creatinine and/or has persistent oliguria or anuria, long term follow-up on kidney function should be instituted to rule out renal cortical necrosis.

References:

The following references are recommended for further indepth reading. This material includes case histories, guidelines, and recent findings in South American literature. These should be read only after treatment has begun and the patient is in stable status.

1. Wyeth Crotalidae Polyvalent Antivenom: Wyeth Laboratories. Lyophilized polyvalent Anti-snake venom: Directions of Use (Package insert with Antivenom). January 1984.

2. Silva, J.: Accidentes Humanos por Las Serpientes de los Generos Bothrops y Lachesis. Mem. Inst. Butantan. 44/45:403-423, 1980/81.

3. Ayerbe, S., Paredos, A., Galves, D.A.: Estudio Retrospectivo Sobre Ofidiotoxicosis en el Departamento del Cauca. Caud Med. Pop. (Columbia) 40-2: 33-45, 1979.

4. Ayerbe, S., Otero, L.M., Galves, D., Paredes, A., Vasquez, A.: Estudio Retrospectivo Sobre Ofidiotoxicosis en el Departamento del Cauca. Cuadernos de Medicina Popayan (Columbia) 2(3), November 1977.

5. Barrantes, A., Solis, V., Bolanos, R.: Alteracion de los Mechanisimos de la Coagulacion en el Envenenamiento por Bothrops asper (Terciopelo). Toxicon 23. No. 3, 399-407, 1985.

6. Marinkelle, C.J.: Accidents by Venemous Animals in Columbia. Industrial Medicine and Surgery. 35:11, 988-992, 1966.

7. Morre, G.M., Dewling, H., Minton, S.A., Russell, F.E.: Poisonous Snakes of the World. U.S. Government Printing Office, Washington, D.C., 1968.

8. Russell, F.E.: Snake Venom Poisoning. Scholium International, Inc. Great Neck, New York, 1983.