What is the recommended dose and administration protocol for antivenom (antivenin) in India, including IV fluid preparation?

Anti-Snake Venom Administration in India: Dosing and IV Preparation Protocol

Administer 10 vials of polyvalent anti-snake venom (ASV) as the initial dose for systemic envenomation, diluted in normal saline and given intravenously over 1 hour, with repeat doses of 5-10 vials every 4-6 hours until coagulation parameters normalize. 1, 2

Initial Assessment and Preparation

Before administering ASV, ensure the following are immediately available:

• Epinephrine (0.01 mg/kg in children up to 0.3 mg; 0.3-0.5 mg in adults) for anaphylactic reactions 1
• Airway management equipment and ventilatory support capability, especially for neurotoxic envenomation (krait, cobra) 2
• Cardiac monitoring equipment 3
• Emergency resuscitation medications including antihistamines and corticosteroids 3

Remove all rings and constricting objects from the bitten extremity immediately to prevent tissue damage from progressive swelling. 1, 2

Dosing Protocol

Initial Dose

The recommended starting dose is 10 vials of polyvalent ASV, which provides adequate neutralization without increasing adverse reaction risk compared to lower doses. 1, 2 This represents a practical single-dose approach that has replaced older recommendations.

However, evidence from a randomized controlled trial in India suggests that lower doses may be equally effective: starting with 2 vials over 1 hour, followed by 1 vial every 4 hours until coagulation normalizes (mean total: 4.7 vials), which was as effective as conventional higher dosing (mean: 8.9 vials) and saved approximately Rs. 1000 per patient. 4

Repeat Dosing

Administer additional 5-10 vials every 4-6 hours if:

• Coagulation parameters remain abnormal (prolonged clotting time, thrombocytopenia)
• Progressive local swelling continues
• Neurotoxic symptoms worsen or fail to improve
• New systemic symptoms develop 2, 4

Continue maintenance dosing until clinical improvement is sustained and laboratory parameters normalize. 4

IV Preparation and Administration

Dilution Protocol

Dilute the ASV in normal saline (0.9% sodium chloride) at a ratio of 1:5 to 1:10 (e.g., 10 vials in 50-100 mL of normal saline). 3 This dilution facilitates controlled infusion and reduces the risk of adverse reactions.

Administration Technique

Administer the diluted ASV intravenously over 1 hour via slow IV infusion. 4

• Use a dedicated IV line with appropriate vascular access 3
• Start infusion slowly for the first 10-15 minutes while monitoring closely for hypersensitivity reactions 3
• If no adverse reactions occur, continue at the prescribed rate 3

Test Dose Considerations

A test dose is traditionally recommended but controversial. Administer 0.1-0.2 mL of diluted ASV subcutaneously or as a slow IV push over 2-3 minutes, then observe for 15-20 minutes. 3 However, note that test doses have poor predictive value for anaphylaxis and should not delay definitive treatment in severe envenomation. 5

Monitoring During Administration

Continuously monitor the following throughout ASV infusion:

• Vital signs (blood pressure, heart rate, respiratory rate) every 15 minutes initially, then every 30 minutes 3
• Signs of anaphylaxis: urticaria, bronchospasm, hypotension, angioedema 1, 3
• Respiratory status, particularly for neurotoxic envenomation 2
• Cardiac rhythm via ECG monitoring 3
• Progression of local swelling 2

Managing Adverse Reactions

Acute adverse reactions occur in 10-40% of patients receiving Indian polyvalent ASV. 5

If Anaphylaxis Occurs:

1. Stop ASV infusion immediately 3
2. Administer epinephrine intramuscularly in the anterolateral thigh (0.01 mg/kg in children up to 0.3 mg; 0.3-0.5 mg in adults) 1
3. Provide airway support and supplemental oxygen 2
4. Administer IV antihistamines and corticosteroids 3
5. Once stabilized, ASV can be restarted at a slower rate with premedication 5

Premedication to Reduce Reactions:

Consider administering antihistamines (H1 and H2 blockers) and hydrocortisone 30 minutes before ASV infusion, though evidence for efficacy is limited. 5

Critical Timing Considerations

Early ASV administration is crucial for preventing irreversible effects. Antivenom is most effective when given within the first few hours after envenomation, particularly for preventing pre-synaptic neurotoxicity and myotoxicity. 6

Do not delay ASV administration while waiting for laboratory confirmation if systemic symptoms are present (nausea, vomiting, headache, abdominal pain, ptosis, difficulty swallowing). 6

Common Pitfalls and Caveats

Major issues with Indian ASV product guidelines include:

• Misinformation about first aid measures (avoid tourniquets, ice, suction, or electric shock) 2, 5
• Ambiguous dosing recommendations in package inserts 5
• Inadequate guidance on managing adverse reactions 5
• Batch-to-batch variation in antibody content and quality 7

The Indian polyvalent ASV contains antibodies against the "Big Four" snakes (Indian cobra, common krait, Russell's viper, saw-scaled viper) but shows variable neutralization capacity depending on geographic venom variation. 7 It may have limited cross-reactivity with other regional pit vipers. 8

Antivenom cannot reverse established neurotoxicity or myotoxicity but can prevent progression if given early. 6 Patients with respiratory paralysis will require mechanical ventilation regardless of ASV administration. 2

Hospital stocking recommendations suggest maintaining 12-18 vials for initial treatment capacity, though 10 vials is typically sufficient for a single patient. 9, 1