CHAPTER 3-6: ANTIVENOM, MICRURUS FULVIUS (CORAL SNAKE), AND EXOTIC ANTIVENOMS

Pharmacology

1. To produce the antivenom for North American coral snake bites, horses are hyperimmunized with venom from Micrurus fulvius, the eastern coral snake. The lyophilized protein preparation from pooled equine sera contains IgG antibodies to venom fractions as well as residual serum proteins. Administered intravenously, the antibodies distribute widely throughout the body, where they bind the target venom.

2. Exotic antivenoms. Companies outside the United States produce a variety of antivenoms for exotic snakebites. Most of these products are used to treat snakebites by elapids because this family of snakes causes the most severe envenomations worldwide. Many of these are still whole-antibody products derived from horses. A few are produced as Fab fragments, or the slightly larger F(ab)₂ molecule (cleaved with pepsin instead of papain). In both of these cases, the Fc is removed from the solution. Many foreign antivenom products are polyvalent, a mixture of antivenoms for several species.

Indications

1. Envenomation by the eastern coral snake (M. fulvius) or the Texas coral snake (M. fulvius tenere).

2. May not be effective for envenomation by the western, Arizona, or Sonora coral snake (Micrurus euryxanthus), but symptomatic bites by these small western US elapids are very rare.

Contraindications. Known hypersensitivity to Micrurus antivenom or to horse serum is a relative contraindication; if a patient with significant envenomation needs the antivenom, it should be given with caution. Antivenoms produced outside the United States may be made from horse or sheep serum.

Adverse effects

1. Immediate hypersensitivity, including life-threatening anaphylaxis, may occur even after a negative skin test for horse serum sensitivity.

2. Delayed hypersensitivity (serum sickness) may occur 1–3 weeks after whole-antibody antivenom administration, with the incidence and severity depending on the total quantity of antivenom administered.

3. Use in pregnancy. FDA Category C (indeterminate). There are no data on teratogenicity. Anaphylactic reactions resulting in shock or hypoxemia in expectant mothers could conceivably affect the fetus adversely. This should be weighed against the potential detrimental effect of the venom on both the placenta and the fetus (see Table III–1).

4. Exotic antivenoms. All whole-antibody preparations carry the same risk for immediate and delayed allergy.

Drug or laboratory interactions. There are no known interactions.

Dosage and method of administration. Generally, the recommended initial dose of Micrurus antivenom is three to five vials. The drug is most effective if given before the onset of signs or symptoms of envenomation. An additional three to five vials may be given, depending on the severity of neurologic manifestations but not on body weight (children may require doses as large as or even larger than those for adults).

The recommended dose of exotic snake antivenom will vary. With other elapids, such as cobras, the antivenom is also more effective if given early in the course of the envenomation.

1. Treat all patients in an intensive care unit setting.

2. Before a skin test or antivenom administration, insert at least one and preferably two secure intravenous lines.

3. Perform a skin test for horse serum sensitivity, using a 1:10 dilution of antivenom (some experts prefer this method) or the sample of horse serum provided in the antivenom kit (according to package instructions). If the skin test is positive, reconsider the need for antivenom as opposed to supportive care, but do not abandon antivenom therapy if it is needed. Even if the skin test is negative, anaphylaxis may occur unpredictably.

   Antivenoms to exotic species may not contain skin-testing solutions. A small amount (0.1 mL) of antivenom can be used as a skin test for these preparations, or this step may be omitted. Fab and F(ab)₂ antivenom preparations generally do not require skin testing before administration.

4. If antivenom is used in a patient with a positive skin test, pretreat with intravenous diphenhydramine and ranitidine or another H₂ blocker and have ready at the bedside a preloaded syringe containing epinephrine (1:10,000 for intravenous use) in case of anaphylaxis. Dilute the antivenom 1:10-1:1,000 and administer very slowly in these cases.

5. Reconstitute the lyophilized Micrurus antivenom with 10 mL of the diluent supplied, gently swirling for 10–30 minutes. Avoid shaking the preparation because this may destroy the immunoglobulins (as indicated by the formation of foam). Dilution with 50–200 mL of saline may aid solubilization.

6. Administer the antivenom intravenously over 15–30 minutes per vial.

7. Exotic elapids. Envenomation by exotic elapids, such as cobras, mambas, and all the poisonous snakes of Australia, would be expected to produce a degree of neurotoxicity the same as or worse than that seen in envenomation from coral snakes from the United States, and antivenom administration is required as soon as possible. It is conceivable that bites from snakes within the same family could respond to antivenom made from venom of another snake in that family. Therefore, if type-specific antivenom is not available for a severe snakebite, same-family antivenom may be substituted with some possible efficacy. Regional poison centers (1-800-222-1222) may be able to assist in obtaining exotic antivenoms from collectors or zoos.

Formulations

1. Antivenom (M. fulvius) vial of lyophilized powder with 0.25% phenol and 0.005% thimerosal as preservatives. Note: This product is also listed as antivenin (M. fulvius).

2. Suggested minimum stocking levels to treat a 100-kg adult for the first 8 hours and 24 hours: antivenom (M. fulvius), first 8 hours: five vials; first 24 hours: 10 vials. Note: The production of Micrurus antivenom has ceased in the United States. Stocks remain in some geographic locations where coral snakes are most common, but supplies will likely be scarce or run out in the future. No alternative foreign antivenom is currently available as a substitute, but clinical trials are underway that may result in new products. As a temporizing measure, the US Food and Drug Administration (FDA) has tested expiring lots of remaining vials of Micrurus antivenom and found that they are active beyond their expiration date. The FDA has therefore extended the expiration date on many remaining supplies of Micrurus antivenom.