What is the treatment for an adverse reaction to Anti-Snake Venom (ASV)?

Treatment of Adverse Reactions to Anti-Snake Venom (ASV)

Administer intramuscular epinephrine immediately for any acute adverse reaction to ASV, as this is the definitive treatment for anaphylaxis and allergic reactions to antivenom. 1

Immediate Management of ASV Reactions

First-Line Treatment: Epinephrine

• Give intramuscular epinephrine 0.3-0.5 mg (0.3-0.5 mL of 1:1000 solution) in the anterolateral thigh for adults and adolescents experiencing acute reactions to ASV. 1

• For children, administer 0.01 mg/kg (maximum 0.3 mg) of 1:1000 epinephrine intramuscularly. 1

• Repeat epinephrine every 5 minutes as clinically needed if symptoms persist or worsen—the interval can be shortened if the clinician deems more frequent dosing appropriate. 1

• Have epinephrine readily available before administering ASV, as reactions occur in up to 75% of patients and 89% of reactions occur within the first hour. 2, 3

Intravenous Epinephrine for Severe/Refractory Reactions

If multiple intramuscular doses fail or the patient has severe hypotension/shock:

• Prepare an epinephrine infusion by adding 1 mg (1 mL of 1:1000) to 250 mL D5W, yielding 4 mcg/mL concentration. 1

• Infuse at 1-4 mcg/min (15-60 drops/min with microdrop apparatus), increasing up to maximum 10 mcg/min for adults based on clinical response. 1

• For children, use 0.01 mg/kg (0.1 mL/kg of 1:10,000 solution) up to 10 mcg/min maximum. 1

• Continuous hemodynamic monitoring is essential when using intravenous epinephrine—this should only be done in emergency departments or intensive care settings. 1

Adjunctive Therapies

Corticosteroids:

• Administer hydrocortisone 200 mg IV or methylprednisolone 125 mg IV every 6 hours to potentially prevent protracted or biphasic reactions, though evidence is limited. 1

• Note: A 2011 randomized trial found that adding hydrocortisone actually negated the protective benefit of adrenaline pretreatment, so corticosteroids should NOT replace epinephrine as primary treatment. 3

H1-Antihistamines:

• Antihistamines like promethazine have NOT been shown to prevent or treat acute ASV reactions effectively in randomized trials. 3, 4

• If used, they should only be adjunctive to epinephrine, never as monotherapy. 1

Oxygen and Bronchodilators:

• Administer supplemental oxygen to patients with prolonged reactions, hypoxemia, or those requiring multiple epinephrine doses. 1

• Give inhaled albuterol (2.5 mg nebulized) for bronchospasm that persists despite epinephrine. 1

Fluid Resuscitation:

• Administer 1-2 L normal saline bolus for persistent hypotension despite epinephrine—some patients required up to 3 L total volume in clinical trials. 1

Critical Clinical Pitfalls

Common Errors to Avoid

• Do NOT delay epinephrine administration while giving antihistamines or corticosteroids first—epinephrine is the only proven life-saving intervention. 1

• Do NOT rely on skin testing to predict ASV reactions—studies show skin testing has zero positive predictive value for equine-derived products like ASV. 1

• Do NOT assume a negative skin test means the patient won't react—skin testing is ineffective and should not guide clinical decisions about ASV administration. 1

• Do NOT withhold necessary ASV due to fear of reactions—the risk of untreated envenomation far exceeds the risk of treatable allergic reactions when epinephrine is available. 2

Prevention Strategies for High-Risk Patients

Prophylactic Adrenaline (When ASV Known to Have High Reaction Rates)

• Consider prophylactic subcutaneous adrenaline 0.25 mL (1:1000) immediately before ASV infusion in regions where antivenom has documented high adverse reaction rates (>40%). 3, 5, 6

• Randomized trials from Sri Lanka showed prophylactic low-dose adrenaline reduced severe reactions by 43% at 1 hour and 38% at 48 hours. 3

• Meta-analysis confirms adrenaline-containing premedication reduces reaction risk (RR 0.32,95% CI 0.18-0.58), while non-adrenaline premedications show no significant benefit. 6

• This prophylactic approach is particularly important in resource-limited settings where antivenoms are less purified and reaction rates exceed 40-75%. 3, 6

Special Populations

Patients on Beta-Blockers:

• Patients taking beta-adrenergic blocking agents are at greater risk for severe anaphylaxis and may have blunted response to epinephrine. 1

• These patients may require higher or more frequent epinephrine doses and more aggressive fluid resuscitation. 1

Patients on ACE Inhibitors:

• ACE inhibitor use increases risk of more severe anaphylaxis (OR 2.27,95% CI 1.13-4.56). 1

• Exercise heightened vigilance and have epinephrine immediately available for these patients. 1

Monitoring and Disposition

• Observe all patients for minimum 48 hours after ASV administration, as delayed reactions can occur. 7

• Monitor continuously for signs of biphasic reactions—approximately 40% of patients required rescue medication during the first hour in clinical trials. 3

• Use pulse oximetry or arterial blood gas monitoring where hypoxemia is a concern, particularly with prolonged reactions. 1