ADVERSE REACTIONS TO ANTIVENOM

PRETREATMENT WITH EPINEPHRINE TO PREVENT EARLY REACTIONS

Epinephrine is the only prophylactic treatment (pretreatment) that has been shown to effectively reduce the incidence of early adverse reactions (EARs) such as anaphylaxis.60,98,133–136 See Antivenom Reactions Algorithm.

1. DO NOT pretreat with steroids or antihistamines, as they not only have no benefit prior to a reaction but may reduce the efficacy of epinephrine as a pretreatment for EARs.134,273

2. DO NOT administer test doses of antivenom to check for hypersensitivity.60–63

Relative contraindications to epinephrine pretreatment include age > 70, hypertension, ischemic heart disease, history of stroke, suspected or confirmed intracranial hemorrhage. No absolute contraindications.

1. Pretreatment with epinephrine prior to antivenom administration is not indicated by default for all antivenoms, and is recommended only under the following circumstances:

a. Unstable snakebite patients with signs of shock.

b. Known history of atopy (asthma, eczema, etc.), equine hypersensitivity, or severe reactions to antivenom in the past.

c. Use of certain second or third line antivenom due to the high rate of serious EARs associated with these products.

2. Standard epinephrine pretreatment protocol:

a. Adult dose is 0.25 mg of 1:1000 epinephrine given by IM injection several minutes prior to antivenom administration.

b. Pediatric doses should be weight based at a dose of 0.01 mg/kg, up to 0.25 mg.60,134,135,137,138

c. Alternatively, consider establishing two intravenous catheters (one for the antivenom and one for epinephrine) and preparing an epinephrine infusion that can be immediately initiated in the event an allergic reaction to the antivenom occurs.

ALPHA-GAL SYNDROME AND INCREASED RISK OF EARLY ADVERSE REACTIONS

Practice implication: Alpha-gal Syndrome is not a contraindication to antivenom when envenomation is life or limb threatening but warrants pre-treatment with epinephrine and up-tiering of risk management (infusion strategy, ICU capable monitoring, product selection). There are NO absolute contraindications to antivenom for a patient with a significant symptomatic envenomation).

Early but compelling clinical evidence suggests that patients with Alpha-Gal syndrome (a mammalian meat allergy) may experience higher rates of reaction in response to antivenoms due to conservation of the alpha-gal epitope in mammalian antibody proteins. Some early studies from the United States indicated higher rates of reactions with with the F(ab’)2 Anavip versus CroFab which is a F(ab), but other studies have shown that patients who reacted to CroFab tolerated Anavip.274–276 Regardless, pretreatment should be considered for patients with elevated risk factors (patient from high prevalence area, medical Hx suspicious for alpha-gal, etc) and in patients with known or suspected alpha-gal syndrome. If both CroFab and Anavip are available for a CONUS bite with a known history or high risk of alpha-gal, it may be worth discussing CroFab as first line if available due to possible lower risk of reaction with a medical toxicologist. If a patient had a reaction to CroFab or Anavip CONUS, it may be worth discussing switching to the alternative product with a medical toxicologist.

While additional research is needed, the key points are as follows:

1. In US servicemembers and other patients with a known or suspected history of alpha-gal syndrome, pretreatment with 1:1000 epinephrine prior to antivenom may be advisable due to early evidence indicating higher incidence of EARs including anaphylaxis. Pretreatment with epinephrine has not been proven to reduce the incidence of these reactions, but has strong evidence base to support its use in typical EARs and the MAST cell stabilization resulting from epinephrine may also benefit these patients.
2. If a patient with known or suspected alpha-gal syndrome has a reaction to one antivenom and a second line alternative exists, it may be appropriate to try a different product if additional doses are needed.
3. In all cases, it is advisable to contact DoD advisor line and consult a toxicologist (or contact poison control if CONUS) in cases where an alpha-gal sensitivity is known or suspected.
4. In all cases, antivenom should not be delayed for patients suffering from instability or other possible threats to life or limb due to envenomation. Be prepared to treat the reaction if it occurs but do not delay antivenom for sick patients.