Is adrenaline (epinephrine) recommended as a preventive measure to prevent reactions to antivenom (ASV) in a hemodynamically stable patient with no known history of allergies or previous reactions to antivenom following a snake bite?

Prophylactic Adrenaline for ASV Reactions in Hemodynamically Stable Snakebite Patients

Prophylactic low-dose subcutaneous adrenaline (0.25 ml of 1:1000 solution) should be administered immediately before antivenom infusion in hemodynamically stable snakebite patients to prevent acute adverse reactions to antivenom. This recommendation is based on high-quality randomized controlled trial evidence demonstrating significant reduction in severe reactions without safety concerns.

Evidence for Prophylactic Adrenaline

The strongest evidence comes from two randomized controlled trials conducted in Sri Lanka, where antivenom reactions are particularly common:

• A landmark 2011 factorial trial (n=1,007 patients) demonstrated that prophylactic adrenaline reduced severe reactions to antivenom by 43% at 1 hour and 38% at 48 hours compared to placebo 1

• An earlier 1999 trial (n=105 patients) showed even more dramatic results, with only 11% of adrenaline-pretreated patients developing acute adverse reactions compared to 43% in the placebo group (P=0.0002) 2

• Both studies used the same dose: 0.25 ml of 1:1000 adrenaline given subcutaneously immediately before antivenom administration 1, 2

• Importantly, no significant adverse effects were attributable to this low-dose prophylactic adrenaline in either study 1, 2

Critical Context: Why This Matters

Acute adverse reactions to snake antivenom are extremely common in many regions:

• In the 2011 trial, 75% of patients developed acute reactions to antivenom, with 43% classified as severe 1

• 89% of reactions occurred within the first hour of antivenom administration 1

• 40% of all patients required rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour, indicating the severity and frequency of these reactions 1

• Both anaphylactic and pyrogenic acute reactions can occur, with severe systemic anaphylaxis potentially developing within an hour of antivenom exposure 3

What NOT to Use for Prophylaxis

Do not use hydrocortisone or promethazine for prophylaxis:

• The 2011 factorial trial definitively showed that hydrocortisone and promethazine did not reduce severe reactions to antivenom 1

• More concerning, adding hydrocortisone actually negated the protective benefit of adrenaline 1

• This is a critical pitfall to avoid—combining these medications eliminates the proven benefit of adrenaline alone 1

Practical Administration Protocol

Dosing and timing:

• Administer 0.25 ml of 1:1000 adrenaline subcutaneously 1, 2
• Give immediately before starting the antivenom infusion 1, 2
• This is a much lower dose than used for treating anaphylaxis (which is 0.3-0.5 mg intramuscularly in adults) 4

Monitoring requirements:

• Patients must still be monitored closely for at least the first hour, as reactions can still occur despite prophylaxis 1
• Have full resuscitation equipment and rescue doses of intramuscular adrenaline (0.3-0.5 mg for adults) immediately available 4
• Monitor for at least 96 hours, as delayed serum sickness reactions can occur 5-14 days after antivenom 3

Special Considerations for Hemodynamically Stable Patients

The question specifically addresses hemodynamically stable patients, which is the appropriate population for this intervention:

• Prophylactic subcutaneous adrenaline is given to stable patients BEFORE antivenom to prevent reactions 1, 2

• If a patient is already hemodynamically unstable from the snakebite itself, they require immediate antivenom without delay, and standard anaphylaxis protocols apply if reactions occur 5

• The 2024 AHA/Red Cross guidelines emphasize that definitive treatment for snakebite is antivenom, which must not be delayed 5

Important Caveats

This recommendation applies primarily to regions where antivenom quality is suboptimal:

• The evidence comes from South Asian countries where acute adverse reactions to antivenom are extremely common (75% reaction rate) 1

• In regions with higher-quality antivenom, reaction rates may be lower, though prophylactic adrenaline remains safe and potentially beneficial 3

• Ultimately, prevention of reactions depends mainly on improving antivenom quality, but until these improvements occur, prophylactic adrenaline is the best available intervention 3

No contraindications in this setting:

• There are no contraindications to epinephrine use in life-threatening situations, even in patients with cardiovascular disease or those taking beta-blockers 5, 4

• The low prophylactic dose (0.25 ml of 1:1000 subcutaneously) is even safer than therapeutic doses 1, 2

What to Do If Reactions Occur Despite Prophylaxis

Even with prophylaxis, some patients will still develop reactions:

• Treat breakthrough anaphylaxis with intramuscular adrenaline 0.3-0.5 mg in the anterolateral thigh (not the subcutaneous prophylactic dose) 4

• Be prepared to repeat every 5 minutes if symptoms persist 4

• Administer IV fluids, oxygen, antihistamines, and corticosteroids as adjuncts 4

• Position supine with legs elevated if hypotension develops 4