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DESCRIPTION
The antivenoms described here are for use against bites by crotalid (pit viper) snakes (rattlesnakes, cottonmouths, and copperheads) and elapid snakes (coral snakes).
FORMS AND USES
Pit Viper (Crotalid Snakes) Antivenoms
- Antivenin (Crotalidae) Polyvalent, commonly referred to as Wyeth antivenom. Each antidote package contains one vial of lyophilized antivenom, one vial of horse serum for skin testing, and one vial of bacteriostatic water for injection.
- Affinity-purified, mixed monospecific crotalid antivenom ovine Fab is an investigational drug. It is currently under consideration by the U.S. Food and Drug Administration and should be approved by December 1999.
- Antivenin (Crotalidae) Polyvalent (Wyeth) and affinity-purified, and mixed monospecific crotalid antivenom ovine Fab are used for envenomation by North or South American rattlesnakes, cottonmouth, or copperhead snakes.
Coral Snake Antivenom (Micrurus fulvius) Merck
- Each antidote package contains one vial of lyophilized antivenom and one vial of bacteriostatic water for injection.
- It is used in the treatment of envenomation by the eastern or Texas coral snakes.
MECHANISM OF ACTION
- Wyeth antivenom and coral snake antivenom contain immunoglobulin G (IgG) isolated from horses immunized to snake venom; they act by conferring passive immunity to the components of snake venom.
- The Wyeth antivenom is produced by immunization with venom of eastern and western diamondback rattlesnakes, the tropical rattlesnake, and the fer-de-lance.
- Coral snake antivenom is produced by immunization with eastern coral snake venom.
- Affinity-purified, mixed monospecific crotalid antivenom ovine Fab is sheep derived and is composed of IgG fragments termed Fab. It is expected to produce fewer adverse reactions.
PREGNANCY AND LACTATION
Use of antivenom in pregnancy for crotalid snakebite is recommended and appears to decrease the likelihood of spontaneous abortion and bleeding complications.
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CONTRAINDICATIONS
Known hypersensitivity to horse serum or to antivenom are relative contraindications. If history of true acute allergic reaction is obtained, consultation with a medical toxicologist, poison control center, or other physician experienced in the use of antivenom is recommended.
ADVERSE EFFECTS
Mild Acute Allergic Reactions (Rash, Bronchospasm)
- These occur in 20% to 25% of patients treated with Wyeth antivenom; incidence for other products is unknown.
- Administration of H1 and H2 antihistamine is recommended. Diphenhydramine: adult dose is 25 to 50 mg (child, 1 mg/kg up to 50 mg) intravenously. Cimetidine: adult dose is 300 mg intravenously. Pediatric dose is 10 mg/kg up to 300 mg.
- Bronchospasm is treated with albuterol 0.15 mg/kg (maximum of 10 mg) in saline with humidified oxygen via nebulizer every 20 to 30 minutes.
Anaphylaxis or Shock
- This occurs rarely, but its true frequency is unknown; overwhelming anaphylaxis and death are possible within minutes of administration of Wyeth antivenom.
- First, the patient is administered 100% oxygen and the airway is secured.
- Epinephrine should be administered immediately. In severe cases an intravenous bolus of epinephrine 3 to 5 ml of 1:10,000 diluted 10:1 should be administered by slow intravenous push over several minutes. A continuous infusion may be started for persistent effects as described below.
Antihistamine
Both diphenhydramine and cimetidine (or other H2 blocker) should be administered. The adult dose of diphenhydramine is 25 to 50 mg (child 1 mg/kg up to 50 mg) administered intravenously every 6 to 8 hours. The adult dose of cimetidine is 300 mg intravenously every 6 hours; pediatric dose is 10 mg/kg up to 300 mg every 6 hours.
Bronchospasm
- Albuterol 0.15 mg/kg (maximum of 10 mg) is administered in saline with humidified oxygen via nebulizer every 20 to 30 minutes.
- Epinephrine 1:1,000 is administered subcutaneously; adult dose is 0.3 to 0.5 ml (pediatric, 0.01 ml/kg up to 0.5 ml) subcutaneously.
Hypotension (Type I Hypersensitivity)
Crystalloid and epinephrine are administered.
- An initial bolus of 0.9% sodium chloride 10 to 20 ml/kg should be infused rapidly.
- If necessary, the initial epinephrine bolus is followed with an infusion; 1 mg of 1:1,000 epinephrine is diluted in 250 ml D5W; infusion starts at 1 µg/min and is titrated to desired blood pressure.
- Methylprednisolone is administered intravenously; adult dose is 60 to 125 mg (1.0-1.5 mg/kg); pediatric dose is 1 to 2 mg/kg up to 125 mg every 6 to 8 hours
Type IV Hypersensitivity (Serum Sickness)
- Serum sickness typically begins 3 to 14 days after the antivenom infusion as malaise and fever, and progresses to diffuse rash, arthralgia, pruritus, and (rarely) pericarditis and glomerulonephritis.
- It occurs in 70% to 75% of patients treated with Wyeth antivenom and 5% to 10% for Fab antivenom; the incidence is unknown for coral snake antivenom.
- Treatment consists primarily of antihistamines and steroids. Both should be administered except in the mildest of cases. The adult dose of diphenhydramine is 25 to 50 mg (child 1 mg/kg up to 50 mg) orally every 6 to 8 hours.
- The adult dose of prednisone is 40 to 60 mg/day (child 1 mg/kg per day up to 60 mg) orally for 7 to 10 days.
- Antipyretics and analgesics are used as guided by the patient's symptoms
- Acetaminophen. Adult, 1 g every 4 to 6 hours, not to exceed 4 g/day; pediatric, 10 mg/kg every 4 to 6 hours
- Ibuprofen. Adult, 200 to 600 mg every 8 hours; pediatric, 5 to 10 mg/kg every 6 to 8 hours
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- Antivenom should be administered in an emergency department or intensive care unit.
- Clinician should be prepared to treat abrupt onset of airway obstruction and hypotension due to anaphylaxis; epinephrine and equipment for endotracheal intubation should be immediately available.
ANTIVENIN (CROTALIDAE) POLYVALENT, WYETH
- No antivenom is needed for patients without clinical effects.
- Initial dose of 20 vials should be administered to adult or pediatric patients with rapidly progressive swelling, severe coagulation abnormalities, presence of frank bleeding, or severe hypotension.
- All other patients should receive 10 vials initially.
- Additional rounds of antivenom (10 vials) are administered if venom effects persist or worsen after initial dose; common examples are continued swelling, any persistent coagulation abnormality despite antivenom, or recurrence of any toxic venom effect after antivenom therapy.
- For copperhead bite with progressive swelling, some physicians recommend an initial dose of five vials.
- Bite site should not be infiltrated locally with antivenom.
- Method of administration is as follows:
- Intravenous access should be established.
- Skin test should be performed with 0.02 ml of horse serum intradermally, and patient observed 20 to 30 minutes for wheal and flare reaction; the test should be read using same parameters as tuberculosis skin test (wheal and erythema larger than 10 mm).
- Ten vials of lyophilized antivenom powder should be prepared [each vial is reconstituted with 10 ml of sterile water (included) for injection]; dissolution may take 15 to 60 minutes (rolling vials between hands speeds dissolution; vials should not be shaken).
- Ten vials (100 ml) should be injected into 250- or 500-ml bag of D5W or 0.9% sodium chloride (an equivalent amount of fluid should be removed from the bag first).
- The infusion should begin slowly (10 to 25 ml/h) using infusion controller; rate can be increased slowly, while patient is observed for evidence of acute allergic reaction, until rate is reached that will infuse initial dose over a 1-hour period.
- Allergic reaction during infusion occurs in 25% of patients.
- The infusion should be halted, and the severity of reaction assessed; the reaction should be treated as described above under "Adverse Effects."
- The decision of whether to restart antivenom infusion requires a difficult risk-benefit analysis; severe or rapidly progressive effects generally warrant an attempt to restart the infusion.
- If the infusion is restarted, antivenom should be mixed in a more dilute solution (e.g., five vials in 1,000 cc diluent) and the patient should be pretreated with diphenhydramine and cimetidine (some clinicians would also administer an epinephrine or steroid dose).
- The infusion should be started very slowly and the rate titrated upward very slowly.
- Concurrent infusion of epinephrine has been used in difficult cases.
- The patient should be monitored continuously during antivenom infusion.
AFFINITY-PURIFIED, MIXED MONOSPECIFIC CROTALID ANTIVENOM OVINE FAB (INVESTIGATIONAL DRUG)
- Until greater experience is available, this antivenom should also be administered in an emergency department or ICU. However, no skin test is needed.
- The patient should be infused with four vials initially and assessed to determine whether initial control of venom effects has been achieved (four-vial dose may be repeated up to two times to achieve initial control).
- Thereafter, two vials should be administered every 6 hours for three additional doses; subsequent doses are administered at the physician's discretion.
- Each dose should be diluted in 250 cc of crystalloid and infused intravenously over 1 hour.
- Acute adverse effects occur during infusion in 15% to 20% of patients.
MICRURUS FULVIUS ANTIVENIN, MERCK
- An initial dose of three to five vials should be administered to adult or pediatric patient with evidence of coral snake bite.
- Coral snake venom binds irreversibly to presynaptic nerve terminals; therefore, antivenom should be administered before clinical effects develop.
- A skin test should be performed with 0.02 ml of horse serum intradermally, and the patient should be observed for 20 to 30 minutes for wheal and flare reaction; the test should be read with the same parameters as the tuberculosis skin test (wheal and erythema larger than 10 mm).
- If the skin test result is negative, three to five vials of lyophilized powder should be prepared [each vial is reconstituted with 10 ml of sterile water (included) for injection] and injected into 100- or 250-ml bag of dextrose 5% in water or 0.9% sodium chloride (an equivalent amount of fluid should be removed from the bag first).
- The infusion should begin slowly (10-25 ml/h) with an infusion controller; the rate should be increased slowly while the patient is observed for evidence of an acute allergic reaction.
- The initial dose (three to five vials) should be infused over a 1-hour period.
- The patient should be monitored continuously during administration; the clinician should be prepared to manage airway and treat anaphylaxis.
Section Outline:
ICD-9-CM 989.5Toxic effect of other substances, chiefly nonmedicinal as to source: venom.
See Also: SECTION IV, Snakebite—North American Crotalids and Snakebite—North American Coral Snakes chapters.
RECOMMENDED READING
Horowitz R, Dart RC. Antivenins and immunobiologicals: immunotherapeutics of envenomation. In: Auerbach P, ed. Management of wilderness emergencies. Chicago: Mosby Year Book, 1995:731-741.
Kitchens CS, Van Mierop LHS. Envenomation by the eastern coral snake (Micrurus fulvius fulvius): a study of 39 victims. JAMA 1987;258:1615-1618.
Russell FE. Snake venom poisoning. New York: Scholium, 1983.
Author: Katherine M. Hurlbut
Reviewer: Luke Yip