In the event of an actual or probable bite from a Vipera russelli, 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.

   (See the attached copy from "First Aid for Snakebite", by Dr. S.K. Sutherland.)

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 Haffkine Bio-Pharmaceutical Corporation 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 10 vials)
      
   2. the accompanying instruction (Protocol) packet
      
   3. the victim's medical packet (if available)

DO NOT cut or incise the bite site.
DO NOT apply ice to the bite site.

The bite of Vipera russelli can be fatal. In Sri Lanka, Burma and India it is responsible for the majority of snakebite incidents. It is a very dangerous snake. Large members of some species can easily deliver a lethal dose in humans. Victims will usually complain of pain at the bite site, and swelling may be evident. Substantial coagulopathy and acute renal failure may ensue. Unique to certain subspecies, there has been reported symptoms indicative of a neurotoxic and myotoxic venom including ptosis, dysarthrias, and generalized weakness. Prompt medical therapy avoids these problems. Please read the attached and respond appropriately.

1. First Aid:
   1. Apply a constricting band if not already present, proximal to the bite site 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 the contents of 2 vials of Haffkine Bio-Pharmaceutical Corp. Polyvalent Antivenom with Lactated Ringers solution (10 cc/vial).

      5. If there is no reaction to the intradermal skin test, administer antivenom by intravenous infusion over 20 minutes at a rate of 1 vial (10 cc) per 10 minutes. The constricting band can be removed after the first two vials have been infused. One should anticipate using 2-8 vials or more for minor to severe bites.

      6. Monitor signs, symptoms, and laboratory data and administer additional antivenom in 1 vial (10 cc) increments at a rate of 1 vial per 10 minutes (1 cc/min) as necessary to control the progression of symptoms. Ideally one should wait 2 hours or less from the first two vials before giving the third vial.

      7. If the patient is allergic to horse serum, administer 1 gram Solu-Medrol IV push, wait 30-45 minutes, and then begin intravenous antivenom. Be prepared to administer Benadryl and epinephrine.

This person has received a bite and probable envenomation from a Vipera russelli. This is a dangerous snake, as it can strike with great force and speed, and deliver greater than the lethal dose in humans. This snake accounts for the majority of snakebites in southeast Asia. Envenomation presents predominately with edema, pain, and hematologic manifestations. Unique to a certain subspecies (Vipera russelli pulchella), there has been reported symptoms indicative of neurotoxic and myotoxic venom including ptosis, dysarthrias, and generalized weakness. Vomiting, drowsiness, and epigastric pain can also be present. In severe envenomations, peripheral circulatory collapse and acute renal failure 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 absorbtion. DO NOT remove until the patient has arrived at the hospital and is receiving the antivenom.

2. Make sure that at least 10 vials of Haffkine Bio-Pharmaceutical Corp. Polyvalent Antivenom are present with the patient. This antivenom contains the necessary fractions to neutralize the venoms of all southeast Asian subspecies of Vipera russelli.

3. If the patient has been envenomated, the initial treatment is 2 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.

   Symptoms:

   Local pain at bite site	80%
   Pain in regional lymph nodes	55%
   Vomiting	26%
   Bleeding from distant sites	24%
   Drowsiness	14%
   Epigastric pain	8%
   Lower back pain	7%
   Dizziness/impaired consciousness	2%

   Signs:

   Local

   Local swelling	68%
   Tender, enlarged lymph nodes	54%
   Bleeding at bite site	31%
   Local blistering and necrosis	2%

   Systemic envenomation

   Spontaneous systemic bleeding	46%
   Hypotension	35%
   Conjunctival edema	24%
   Bleeding from gums	20%
   Bleeding from venipuncture sites	15%
   Hematemesis	11%
   Melena	7%
   Bleeding from incisions	6%
   Subconjunctival hemorrhage	6%
   Epistaxis	2%

2. General: The above symptoms can manifest within 5 hours after envenomation. Pain and local bleeding (if present) usually begins within the first few minutes after the bite. Pain may persist for two weeks or longer. Swelling is usually greatest 1-4 days after the bite. Unlike the rattlesnakes and other New World pit vipers, tissue necrosis and local blister formation is rarely seen.

   Neurological muscle signs:

   Bilateral ptosis Generalized muscle pain & tenderness

   External ophthalmoplegia	(up to 86%)
   (up to 86%)
   (up to 77%)
   Dysphagia
   Dysarthria

   Neurological signs generally occur during the first 24-48 hours. Neurological manifestations gradually improve and disappear by 5-7 days. Myalgias disappear usually within a few days.

3. Hematology: Generally Vipera russelli venom shows both procoagulant (Factor V, IX, & X activation) enzyme activity and direct fibrinolytic activity. This presents as a DIC-type coagulopathy, and results in non coagulating blood and hemorrhage.

   Fibrinogen, platelet counts, and hemoglobin levels are generally decreased. Fibrin microthrombi to renal glomeruli is seen, along with a greater than 50% occurrence of leucocytosis (11,000-29,000) with 70-90% PMNs. A fall in albumin may also be expected secondary to a generalized increase in capillary permeability.

4. Urinary Symptoms and Renal Failure:

   Hematuria	72%
   BUN range	14 - 68%
   Proteinuria (>1 gm/liter)	55%
   RBC casts	55%
   Oliguria	44%
   Renal-angle tenderness	39%

   Oliguria develops rapidly; usually after 1-3 days in systemic envenomations. Renal-angle tenderness precedes the onset of oliguria in greater than 85% of the patients, and can be used as a valuable clinical sign of impending renal failure. Renal failure is usually secondary to acute tubular necrosis (from fibrin microthrombi), and is often the main cause of death in Russell's Viper snake bites in Burma.

5. 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.

6. 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 acute tubular necrosis.

   3. Internal bleeding secondary to DIC.

   4. Neurological symptoms including ptosis, external ophthalmoplegia, and dysphagia.

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. 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 are 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.

   2. If the patient is exhibiting minor to 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 2 vials of Haffkine Institute Polyvalent Antivenom. Each vial is packaged as a lyophilized dry preparation in a glass vial with an accompanying vial of sterile water (to reconstitute the antivenom). It is preferable to reconstitute the antivenom in Lactated Ringers solution. The contents of TWO vials of antivenom are to be used as the initial dose. CAREFULLY score both vials and break open. Withdraw 20ml of room temperature Lactated Ringers solution into a sterile syringe, and then transfer 10ml to each antivenom vial.

   6. Carefully mix and reconstitute the antivenom in each vial by covering the open ends with several thicknesses of sterile gauze sponges, and then shaking each vial vigorously for one minute or longer. Allow the vials to stand still for one minute to clear. Withdraw the CLEAR solution into a clean sterile syringe (leaving froth and undissolved particles behind), and prepare to transfer to an intravenous piggyback set-up.

   7. Administer the reconstituted antivenom intravenously over a period of 20 minutes at a rate of 1 vial per 10 minutes (1cc/minute).

   8. Should any signs of ALLERGY/ANAPHYLAXIS develop (e.g. coughing, dyspnea, urticaria, itching, increased oral secretions, etc.), 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.

   9. After 20 minutes of antivenom administration, the constricting band may be slowly removed.

   10. 1. If the patient's condition worsens, reapply the constricting band and immediately infuse a third vial at 1.0cc/minute for 10 minutes. Additional vials can be administered as above until symptoms/signs are stabilized.

       2. If the patient's condition persists but is not worsening, a third dose at 1.0cc/minute can be administered 1-2 hours after the initial two vial dose. Additional vials can be administered as above until the patient's condition is stabilized. The dose range for mild to severe bites is 2-8 vials.

6. Antivenom Therapy is the mainstay of treatment for Vipera envenomation. Many of the symptoms are ameliorated or entirely eliminated by the antivenom alone. Other symptoms will require additional specific therapy to correct.
   1. Acute Renal Failure is seen in systemic envenomation. It may necessitate Peritoneal Dialysis.

   2. Cardiovascular symptoms are usually seen only in systemic envenomation. 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 at 250 cc/hr and administering vasopressors and volume expanders.

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

   4. Neurological symptoms are usually mild and transient. Often these are improved by the antivenom. If breathing becomes impaired, provide respiratory assistance. Secretions may become copious, necessitating suctioning.

   5. If severe muscle paralysis develops and persists, administer 0.6 mg of Atropine IV. Follow by giving 0.5 mg of Neostigmine IV.

   6. 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.

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 1 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 10 minutes per vial. One should anticipate using 2-8 vials for minor to 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 variability: As noted above, the variability of symptoms in viper 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 where 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, peritoneal 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 Vipera venom. This latter statement should not be held as a contraindication to the use of antivenom in those Vipera bites in which local symptoms predominate.

2. Multiple Bites: It is possible for Vipera 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. 4 vials over 40 minutes at the rate of one vial per 10 minutes). Always watch closely for signs of allergic response; if they occur, treat appropriately and with a slower infusion rate. Give all subsequent doses in one vial increments at a rate of 1 vial per 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 4 vials of antivenom over the first 40 minutes. Give all subsequent doses in one vial increments at a rate of 1 vial/10 minutes as necessitated by the presence of continued signs and symptoms.

4. Neurological Manifestations: The onset of neurotoxic symptoms can be rapid and subtle, but usually mild and transient. It may be necessary to wake the patient and perform a brief neurological check every hour or so to assure that breathing and other neurological functions are not impaired. Carefully note the progress of any paralysis which may be present.

   If the patient should develop difficulties in breathing or airway management, respiratory support will be required. If the tongue, jaw, or pharynx become paralyzed, insert an oral airway; intubation may be required. Make sure adequate suction equipment is available and operative.

   If any signs of Oropharyngeal paralysis or impaired swallowing exist, give NOTHING BY MOUTH, and keep patient on his side with head down. Watch for airway compromise and aspiration.

References:

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

1. Buckley, E.E. and Porges, N.: Venoms, 1956. The American Association for the Advancement of Science, Washington, D.C.

2. Chugh, K.S., Pal, Y., et al.: Acute Renal Failure Following Poisonous Snakebite. American Journal of Kidney Diseases, IV(1): 30-38, July 1984.

3. Date, A. and Shastry, J.C.M.: Renal Ultrastructure in Acute Tubular Necrosis Following Russell's Viper Envenomation. J. Pathology, 137:225-241, 1982.

4. Haffkine Bio-Pharmaceutical Corporation Ltd.: Lyophilized Polyvalent Anti-Snake-Venom serum (package insert). Parel, Bombay, 400012, India.

5. Indraprusit, S. and Boonpucknavig, V.: Acute Interstitial Nephritis after a Russell's Viper Snake Bite (letter). Clin. Nephrol., 25(2):111, February 1980.

6. Jeyerajah, R.: Russell's Viper Bite in Sri Lanka: A Study of 22 Cases. Am. J. Trop. Med. Hyg. 33(3):506-510, 1984.

7. Minton, S.: Snake Venoms and Envenomation. Marcel Dekker, Inc. New York, 1971.

8. Myint, L., Warrell, D., et al.: Bites by Russell's Viper (Vipera russelli siamensis) in Burma: Hemostatic, Vascular and Renal Disturbances and Response to Treatment. Lancet, 2(8467):1250-64, Dec. 7, 1985.

9. Moore, G., Dewling, H., Minton, S., and Russell, F.: Poisonous Snakes of the World. U.S. Government Printing Office, Washington, D.C., 1968.

10. Pe, T., and Cho, K.A.: Amount of Venom Injected by Russell's Viper (Vipera russelli) Toxicon, 24(7):730-733, 1986.

11. Russell, F.: Snake Venom Poisoning, 2nd. Edition, 1983. Scholium International, Great Neck, New York.

12. Sitprija, V, Suvanpha, R., et al.: Acute Nephritis in Snake Bite. Am. J. Trop. Med. Hyg. 31(2):408-410, 1982.
13. Tu, A.: Chemistry and Molecular Biology, 1st. Edition, 1977. John Wiley and Sons, New York.