In the event of an actual or probable bite from a Puff Adder, 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. Immediately wrap a large crepe bandage snugly around the bitten limb starting at the site of the bite and working proximally up the limb (the full length if possible). The bandage should be as tight as one might bind a sprained ankle.

3. Secure the splint to the bandaged limb to keep the limb as rigid and unmoving as possible. Avoid bending or moving the limb excessively while applying the splint.

4. DO NOT remove the splint or bandages until the victim has reached the hospital and is receiving Antivenom.

5. Have the SAIMR (South African Institute for Medical Research) polyvalent antivenom ready for the Lifeflight 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

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

The bite of the Puff Adder with subsequent envenomation is a medical emergency and can be fatal if the patient is not treated appropriately. Please read the attached Medical Management Protocol and respond appropriately.

1. First Aid:
   1. Bandage and immobilize the bitten limb with crepe bandages and splint as described in the Immediate First Aid section. Rest this extremity below the level of the patient's heart (if practical).

   2. Transport to U.C.S.D. Medical Center 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 significant systemic signs or symptoms are present, perform the following:
      1. Administer Lactated Ringers Solution at 200 to 250 mls per hour.

      2. Draw samples and collect initial laboratory data.

      3. Dilute the contents of 5 vials of SAIMR Polyvalent Antivenom in Lactated Ringers Solution to a total volume of 300ml. Administer the antivenom I.V. piggyback over 75 minutes at a rate of 240ml/hour (i.e. one vial per 15 minutes). The combined rate of diluted antivenom and Lactated Ringers Solution is now approximately 500ml/hour. The rate of Lactated Ringers Solution may be adjusted accordingly to avoid fluid overload, however a brisk urine output should be a treatment goal.

      4. When one complete vial has been infused (i.e. 15 minutes, 60 cc), remove the splints and crepe bandage slowly over a period 10 minutes. If symptoms progress rapidly, reapply the bandage, wait 10 minutes, and then again release the bandage slowly over 10 minutes while antivenom administration is continuing.

      5. Allergic or untoward reactions to the antivenom should be treated with Benadryl, Epinephrine, and/or Corticosteroids. A patient with known sensitivity to horse serum may be pretreated with 1 gm of Solumedrol, administered I.V. push.

      6. Monitor Signs, Symptoms, and Laboratory data, and administer additional antivenom in 1 vial increments at a rate of one vial every 15 minutes as necessary to control the progression of symptoms.

      7. The required amount of antivenom will vary with the severity of envenomation. One should anticipate using (including the initial dose):

         5 vials for a minor bite with envenomation

         10 vials may be necessary for moderate or severe bites.

         The use of less than five vials of antivenom in the treatment of a bite with systemic envenomation increases the risk for complications and may even result in death.

This person has received a bite and probable envenomation from a Puff Adder (Bitis arietans). This is a very venomous and dangerous snake native to much of Africa and portions of Saudi Arabia. Studies have shown that more than 50% of severe envenomations left untreated result in death. Envenomation may cause severe hypotension/shock as well as hemolytic, coagulopathic, hemorrhagic, and local reactions. Death may ensue rapidly but more commonly occurs in 12-24 hours.

Please read and execute the following procedures without delay.

1. A crepe bandage and splint have been applied as immediate first aid adjuncts to retard the absorption of the venom. DO NOT remove until the patient has arrived at the hospital and is receiving the antivenom.

2. Make sure 10 vials of SAIMR Polyvalent Antivenom are present with the patient. This antivenom is specific and is only available directly from the San Diego Zoo Reptile Department. Refrigerate the antivenom upon arrival to the hospital.

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

Signs and Symptoms of Envenomation:

1. Local Affects:
   Pain and swelling: onset almost immediately after bite
   
   Blistering, bleb formation
   
   Ecchymosis
   
   Tissue necrosis: onset usually days after bite

2. Cardiovascular:
   
   Hypotension: onset immediately
   
   Bradycardia
   
   Tachycardia

3. Hematological:

   Coagulation defects
   

   Thrombocytopenia: onset within four hours after bite
   

   Spontaneous bleeding:
   

   Mucosal bleeding: within 4 hours after bite
   

   Epistaxsis
   

   Ecchymosis
   

   Gastrointestinal bleeding
   

   Internal hemorrhage
   

   Hematuria
   

   Anemia: secondary to bleeding into bitten limb,
   spontaneous bleeding, microangiopathic hemolysis etc.
   

4. Renal/Urinary:
   
   Hematuria
   
   Hemoglobinuria
   
   Myoglobinuria
   
   Renal failure

5. General:
   Nausea/Emesis
   
   Fever
   
   Regional Lymphadenopathy

6. Fang Marks: The presence of fang marks does not always imply envenomation as the Puff Adder is known to bite without injecting venom into the victim. However, the absence of fang marks does not necessarily preclude the possibility of a bite, nor does it give any indication of the severity of the bite. 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. Finally, multiple bites inflicted by a single snake are possible and should be noted if present.

   Those signs and symtoms which give strong evidence for systemic envenomation include spontaneous bleeding, thrombocytopenia, hypotension, bradycardia, and local swelling of more than half the affected limb. Antivenom should be administered without delay in such cases.

Medical Management:

1. Admit patient to the Trauma Service and call consultants listed on the last page. Terence M. Davidson, M.D. is the local consultant for snake bites, and should be notified immediately.

2. Begin a peripheral intravenous infusion (16 gauge catheter) of Lactated Ringers Solution at a rate of 250 cc/hour.

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. Obtain fresh, frozen plasma.

   2. CBC with differential and quantitive platelet count.

   3. Coagulation Parameters:

      a. Prothrombin Time (PT)
      b. Partial Thromboplastin Time (PTT)
      c. Fibrinogen Levels
      d. Fibrin Degradation Products

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

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

   6. Urinalysis (Macroscopic and Microscopic Analysis).

      Must include analysis for:

      1. Free Protein
         
      2. Hemoglobin
         
      3. Myoglobin

   7. Electrocardiogram (Sinus Tachycardia would be expected).

   8. Continuous Urine Output Monitoring (In dwelling Foley Catheter if unconscious). Watch for possible oliguria or anuria.

   9. Additional tests as needed or indicated by the patient's hospital course.
      1. The patient's vital signs should be monitored frequently the first 48 hours after the bite for evidence of hypotension, bradycardia, or circulatory shock.

      2. Coagulation parameters should be repeated at four hour intervals until coagulation factors begin to recover.

      3. CBC with platelet counts should be repeated periodically. Plateletes and hematocrit levels may continue to decline up to 48 hours after the bite especially in the undertreated patient.

      4. It may be necessary or practical to repeat some of the above serum and urine tests 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 the possibility that the patient received a dry bite (no venom injected).
      1. VERY SLOWLY begin to remove the bandages and splint watching carefully for any changes in the patient's status. If any changes occur, assume the patient has been envenomated 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 SIGNIFICANT SYSTEMIC SIGNS OR SYMPTOMS become apparent, begin antivenom therapy as follows:
   1. Dilute the contents of 5 vials of SAIMR Polyvalent Antivenom in Lactated Ringers Solution to a total volume of 300ml. Administer the antivenom I.V. piggyback over 75 minutes at a rate of 240ml/hour (i.e. one vial per 15 minutes). The combined rate of diluted antivenom and Lactated Ringers Solution is now approximately 500ml/hour. The rate of Lactated Ringers Solution may be adjusted accordingly to avoid fluid overload, however a brisk urine output should be a treatment goal.

   2. 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 Antihistamines. As soon as the patient is stabilized, continue the antivenom infusion at a slower rate. (i.e. 120ml/hour).

   3. After 15 minutes of antivenom administration, the splint and the bandages may be removed. This should be done VERY SLOWLY over a period of 10 minutes to prevent a bolus release of venom. If the patient's condition worsens, reapply the crepe bandage, wait 10 minutes and release the bandage again slowly over 10 minutes while antivenom administration is continuing.

6. Antivenom Therapy is the mainstay of treatment for Puff Adder snake envenomation. Many of the symptoms are ameliorated or entirely eliminated by the antivenom alone. Other symptoms will require additional therapeutic modalities in order to be corrected.
   1. Cardiovascular status: The administration of antivenom alone will help correct hypotension, bradycardia, and signs of circulatory shock provided the patient is not hypovolemic. Intravenous administration of Lactated Ringers Solution is warranted in all cases. Cardiovascular stability and a brisk diuresis are desired.

   2. Hematological signs and symptoms: Puff Adder venom has both procoagulant and anticoagulant activity, and thus bite victims may show a variety of responses. In addition the venom is toxic to vascular endothelial tissue and has hemorrhagic activity as well. Bite victims frequently develop thrombocytopenia, decreased fibrinogen levels, and spontaneous bleeding. Disseminated intravascular coagulopathy and anemia may likewise occur. Case reports reveal no consistent change in the PT or PTT; these parameters may be normal or prolonged. Death from severe envenomation is usually the result of internal hemorrhage and circulatory shock. The patient should be monitored closely and blood products including whole blood, packed RBC's platelets, cryoprecipitate, and fresh frozen plasma should be given when indicated.

   3. Renal: Puff Adder venom binds to renal tissue resulting in hematuria. Hemoglobinuria and myoglobinuria may likewise affect renal function, and if severe, acute renal failure may necessitate peritoneal dialysis.

   4. Neurological symptoms are uncommon with Puff Adder bites.

7. It is important to keep venom neutralization current and continuous. The best method to accomplish this is to monitor 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 one vial increments. Dilute the antivenom in Lactated Ringers as before and administer the antivenom I.V. piggyback over approximately 15 minutes. Bites with envenomation require at least 5 vials but severe envenomations may require up to 10 vials of antivenom.

8. It is advisable to perform 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 all symptoms abate.

General Considerations:

1. It is important that the patient remain resting and warm. Avoid unnecessary movement.

2. Symptom variability: There is a marked variability of symptoms in response to a Puff Adder bite. It is important to note the continual progression of signs and symptoms throughout the course of therapy and to give additional antivenom as necessary.

3. Circulatory Shock: Hypotension and bradycardia are frequent complications of Puff Adder bites. Plasma expanders and/or vasopressor agents may be given when appropriate, but will be most effective if adequate antivenom has been appropriately administered.

4. Fluid Management: The patient should be well hydrated, and a brisk urine output should be maintained. Blood products should not be given until circulating venom has been neutralized with antivenom.

5. Compartment Syndrome: It should be noted that fascial compartment syndromes in Puff Adder bites are uncommon. Limbs may swell significantly, but rarely involve specific fascially bound compartments. If however the logistics of the bite raise a high index of suspicion for compartment syndrome, monitoring with a Wick Catheter or appropriate pressure device may be necessary. Fasciotomy is rarely, if ever, recommended.

6. Tetanus Prophylaxis should be current.

7. Antibiotics are not recommended prophylactically.

8. Antivenom is the best treatment for all signs and symptoms of Puff Adder bites and should be utilized prior to other treatment modalities.

Special Considerations:

1. Multiple Bites:
   1. It is possible for a Puff Adder to deliver more than one bite in a single attack. If there is evidence that such an attack occurred (i.e., history or multiple bite sites), give the initial dose of 5 vials but be prepared to give a total of 10 vials to adequately treat the bite. Titrate antivenom administration to signs and symptoms as discussed previously.

2. Testing for Equine Protein Sensitivity:
   1. It is NOT ADVISABLE to utilize subcutaneous or intradermal testing for sensitivity to equine products in that such testing may be unreliable, and may unnecessarily delay antivenom therapy which must be used if any signs of Puff Adder envenomation are present.

   2. If there is reason to believe that the patient may be sensitive to equine protein products:
      1. Premedicate the patient with 1 gm Solumedrol, administered I.V. push. Assuming the patient's condition is stable, wait 15-30 minutes before administering the antivenom.

      2. Administer the diluted antivenom at a rate as tolerated by the patient beginning at a rate of 120ml/hour (as opposed to the normal 240ml/hour rate). If the patient tolerates this, increase the rate up to 240ml/hour.

      3. Monitor Pulse and Blood Pressure carefully. Be prepared to treat for Anaphylaxis.

3. Clinical Experience with the Puff Adder:
   1. The Puff Adder (Bitis arietans) probably accounts for more deaths than any other snake in Africa. An adult Puff Adder may have enough venom to kill 4-5 men and studies show severe envenomations have a 52% mortality rate. The utilization of antivenom dramatically reduces the mortality rate but deaths have occurred when inadequate amounts of antivenom (i.e. four vials or less) have been administered.

   2. Prompt recognition of clinical envenomation, and adequate amounts of antivenom delivered early in the treatment course will facilitate a good recovery. The use of at least 5 vials of antivenom reduces the incidence of serious complications.

References:

The following references are recommended for further reading. This material includes case histories, guidelines and recent findings in treatment of Puff Adder bites. These should be read only after treatment has begun, and the patient is stable.

1. Warrell, D.A., Ormerod, L.D., Davidson, N. NcD., Bites by

   Puff-Adder (Bites arietans) in Nigeria, and value of antivenom, British Medical Journal, 1975, 4:697.

2. Mebs, D., Pohlman, S., Von Tenspolde, W., Snake venom hemorrhagins: neutralization by commerical antivenoms, Toxicon, 1988, 26:453.

3. Brink, S., Steytler, J.G., Effects of Puff-Adder venom on coagulation, fibrinolysis and Platelet aggregation in the baboon, South African Medical Journal, 1974, 48:1205.

4. Homma, H., Tu, A.T., Morphology of local tissue damage in experimental snake envenomation, British Journal of Experimental Pathology, 1971, 52:538.