Polyvalent Snake Antivenin in the ICU

 Occasionally we come across a case of snake bite in ICU. Here in this Blog Post I'll discuss in brief about the SNAKE ANTIVENIN (POLYVALENT) I.P. - the antidote we commonly use

Antivenin is a injectable medication made from antibodies which is used to treat certain venomous snake bites. The mechanism of action of this drug is based on that of vaccines developed by Edward Jenner but, in this case immunity is induced in a host animal ( like horse) and the hyperimmunized serum is then transfused into the patient who has been bitten.



Antivenins are of two types:

1. Monovalent (effective against a single snake species)
2. Polyvalent (effective against many snake species) - MOST COMMONLY USED IN INDIA

The SNAKE ANTIVENIN (POLYVALENT) I.P. is supplied in a liquid preparation containing Phenol (0.25% w/v) as preservative. It contains refined globulins, processed by enzyme digestion.It has to be stored between 2 to 8 degrees Celsius and should not be allowed to freeze.

Commercially, antivenin can be produced both in liquid and lyophilized forms. There is no evidence to suggest which form is more effective. Liquid Preparation requires a reliable cold chain and has 2-year shelf life. Lyophilized ASV, in powder form, has 5-year shelf life and requires only to be kept cool.

The antivenin is a preparation from equine plasma of Hyperimmunised Horses and is effective against the four common poisonous snakes found in India:

1. Cobra (Naja naja)
2. Common Krait (Bungarus caeruleus)
3. Russells Viper (Vipera russelli)
4. Sawscaled Viper (Echis carinatus)

It must be noted here that polyvalent antivenin is ineffective against species like Humpnosed Pit Viper (Hypnale hypnale) and also in case of region specific species like Sochurek’s Saw-scaled Viper (Echis carinatus sochureki) in Rajasthan, where the effectiveness of polyvalent antivenin is questionable.
Each ml of the serum neutralizes the following amount of standard venoms:

1. Cobra - 0.6mg
2. Common Krait - 0.45mg
3. Russells Viper - 0.6mg
4. Sawscaled Viper - 0.45mg

PROCEDURE FOR ADMINISTRATION OF ANTIVENIN

Precautions
Before drug administration ask for:

1. History of previous serum administration (if any) before the patient was shifted to the ICU
2. Any history of Asthma, Eczema, Known drug allergy or any other atopic/hypersensitivity disorder

Pre-administration Sensitivity testing:
0.1 ml of Antivenin in 1:10 dilution is injected subcutaneously and the patient is kept under observation for 30 mins for any local and/or generalized reaction.

In allergic and sensitive patients, it is better to administer the serum with antihistamines.

However, the administration of serum in sensitive patients must be weighed against the severity of the Patient's condition and urgency of treatment must over-ride the risk of anaphylaxis. Sensitive cases may the co-administered intravenous antivenin along with 1:1000 adrenaline intramuscularly to reduce the risk of anaphylaxis. Half dose of adrenaline may be repeated after 15mins if required.


Severity of evenomation can be indicated by appearance of systemic symptoms:

• Mild envenomation - (systemic symptoms manifest > 3 hours after bite) neurotoxic/hemotoxic
• Severe envenomation -(systemic symptoms manifest < 3 hours after bite) neurotoxic/hemotoxic 

There is no universal agreement on exact dose of antivenin. Only the polyvalent antivenin can neutralise the venom in circulation. As a first dose, 20ml of antivenin can be administered intravenously at a rate of 5ml/min or diluted in Isotonic Fluid and run over 30-60mins.

Second dose can be repeated 2 hours after the first dose or even earlier if symptoms persist. Further dose can be given depending on the condition of the patient.

In case of viper bite, local infiltration of the antivenin in and around bitten area can be done to prevent gangrene formation - however this has been debated and is controversial.


Response to antivenin
If adequate dose of antivenin has been administered the following responses my be seen:

• A general improvement in patients condition. Nausea, vomiting and ache/pain may disappear quickly - however may be a placebo effect
• Spontaneous systemic bleeding (bleeding gums) stop within 15-30mins.
• Blood coagulability (as measured by 20WBCT) is usually restored in 3 - 9 hours. 
• In shocked patients, BP may increase within 30-60 mins and arrhythmias like Brady-arrhythmia may disappear. 
• Neurotoxic envenoming of the post-synaptic type (cobra bites) may begin to improve as early
  as 30 minutes after antivenom, but usually take several hours. Envenoming with presynaptic toxins (kraits and sea snakes) is unlikely to respond in this way.
  
  
  

Criteria for giving more antivenom:

• Persistence or recurrence of blood incoagulability after 6 hr of bleeding after 1-2 hr
• Deteriorating neurotoxic or cardiovascular signs after 1-2 hr 

 If the blood remains incoagulable (as measured by 20WBCT) six hours after the initial dose of antivenom, the same dose should be repeated. This is based on the observation that, if a large dose of antivenin (more than enough to neutralise the venom procoagulant enzymes) is given initially, the time taken for the liver to restore coagulable levels of fibrinogen and other clotting factors is 3-9 hours. In patients who continue to bleed briskly, the dose of antivenom should be repeated within 1-2 hours. In case of deteriorating neurotoxicity or cardiovascular signs, the initial dose of antivenom should be repeated after 1-2 hours, and full supportive treatment must be considered.