TREATMENT OF ADVERSE REACTIONS PRINCIPLES OF EARLY ADVERSE REACTION (EAR) MANAGEMENT

Most EARs to antivenom are mild and limited to either skin and mucosal signs, gastrointestinal signs, or both. In some cases, patients may experience a severe reaction (anaphylaxis), this can be life-threatening and should be treated aggressively. Refer to the Antivenom Reactions Algorithm for a stepwise approach to management of mild, moderate, and severe reactions.

When a reaction has occurred but is mild, simply increasing the antivenom’s dilution (for example, moving the remaining dose from a 50 mL bag of NS into 100 mL of NS), increase the duration of infusion (for example, from 15 mins to 30 mins) and treating the skin/mucosal or GI signs with antihistamines or antiemetics may resolve the problem. With mild reactions, start by either increasing the dilution of the antivenom (add more fluid to the antivenom infusion), decreasing the rate of infusion, or both. When a severe reaction such as anaphylaxis occurs, pause the antivenom infusion, treat the reaction, then resume it using twice the volume of dilution and half the rate of administration. In most cases, epinephrine given to treat a severe reaction will also reduce the risk of subsequent reactions for up to 48 hours. Always contact DoD ADVISOR if you have questions about reaction management.

NOTE: Refer to the detailed Antivenom Reactions Algorithm for guidance on the approach to reactions.

MILD OR MODERATE REACTION DURING INFUSION

1. Manage mild or moderate reactions (e.g. nausea, vomiting, urticaria, pruritus, chills, fever, etc.) symptomatically as needed with antiemetics, antihistamines, steroids, etc. as shown in the Antivenom Reactions Algorithm.
2. Consider increasing the volume of dilution of the antivenom and/or slowing the rate of infusion. You may be able to treat symptomatically with antiemetics, antihistamines, etc. without the need to stop the infusion. If the patient fails to improve to first line medications or appears to be worsening, consider giving a dose of IM epinephrine and then resuming at a slower rate once the symptoms are improving.
3. If the infusion was paused, reassess the patient once the reaction has been controlled; if the antivenom treatment criteria for cytotoxic, hemotoxic, or neurotoxic syndromes have not resolved completely then resume the infusion at a slower rate over 30 minutes.
4. If giving via push, dilute the remaining dose of antivenom in a 100 - 500 mL bag of normal saline and give as 30-minute infusion.

SEVERE REACTION (ANAPHYLAXIS) DURING INFUSION

1. Pause the infusion and treat according to the anaphylaxis treatment protocol and the Antivenom Reactions Algorithm.
2. Reassess the patient once the reaction has been controlled; if the antivenom treatment criteria for cytotoxic, hemotoxic, or neurotoxic syndromes have not resolved completely then resume the infusion at a slower rate or larger volume of fluid (e.g., if 250 bag, dilute in 500 cc) over 30 minutes.
3. If giving via push, dilute the remaining dose of antivenom in a 100-250 mL bag of normal saline and give as 30-minute infusion.
4. If the reaction occurs, stop the infusion, and consult a physician expert via telemedicine to discuss next steps for management.

ANAPHYLAXIS TREATMENT PROTOCOL

NOTE: Intubate for airway edema not rapidly responsive to epinephrine.

If anaphylaxis occurs after antivenom administration, treat according to the following protocol (also refer to the Antivenom Reactions Algorithm):

1. First line treatment of anaphylaxis is rapid administration of 1:1000 epinephrine (initial adult dose = 0.5 mg IM (0.01 mg/kg IM in pediatric patients) in the lateral thigh for rapid absorption). Epinephrine can be repeated as needed until the patient has stabilized and/or an intravenous or intraosseous infusion administered as per standard protocols if the patient fails to respond to IM doses.

Epinephrine should always be given prior to antihistamines or steroids to counter the immediate life-threats of bronchospasm and vasodilation.

2. After epinephrine has been given:

a. Give methylprednisolone 125 mg IV (2 mg/kg IV in pediatric patients).

b. Give diphenhydramine 50 mg IV (1-2 mg/kg IV in pediatric patients).

c. Consider adding an H2 antihistamine such as famotidine.

If anaphylaxis occurs during administration of antivenom, stop the antivenom administration to treat the reaction, then resume the antivenom administration as described below. ^{15,61,95,99,128,129,140–146}

LATE REACTIONS TO ANTIVENOM (SERUM SICKNESS)

1. Serum sickness is characterized by flu-like symptoms ± rash that typically develops between 1-3 weeks after antivenom administration. Serum sickness may be uncomfortable, but it is not dangerous.
2. Management is either symptomatic with antihistamines, acetaminophen, or with a course of oral steroids for patients who are in significant discomfort.^{94,95,97–99}