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ANTI SNAKE VENOM COMPLICATIONS AND MANAGEMENT

 
 

Dr. MABEL VASNAIK
Prof & Head, Dept of Emergency Medicine
St Johns Medical College Hospital, Bangalore

 

Anti Snake Venom (ASV) The"polyvalent anti-snake venom serum" is raised in horses using the venoms of the four most important venomous snakes in India

Indian cobra,Naja naja

Indian krait, Bungarus caeruleus

Russell’s viper, Daboia russelii

Saw -scaled viper, Echis carinatus

The polyvalent ASV is ineffective against Humpnosed pit viper.

 

Indications for administration of ASV

ASV should be administered only in the presence of envenomation as evidenced by Coagulopathy, Neurotoxicity, Hypotension, shock, arrhythmias, Acute renal failure, Local envenomation

The unbound, free flowing venom,is neutralised when in bloodstream or in tissue fluid.

ASV should not be used indiscriminately because antivenom treatment carries a risk of severe anaphylactic reactions and in most countries it is costly and may be in limited supply.

The approximate amount of venom injected in a Russels viper bite averages around 63mg (Range of venom 5mg to 147 mg).One vial polyvalent ASV neutralises 6mg of venom, so a snakebite victim needs around 10 to 25 vials of ASVonly.

 

Antivenom Reactions

Reactions to ASV occurs in about 20%of patients. These reactions can be -Early (within 10 to 180 mins)

-Late ( 5 days or more)

Anaphylaxis

It is an acute, life-threatening, multisystem response to a variety of triggers which affects multiple organ systems

   o cutaneous

   o pulmonary

   o cardiovascular

   o gastrointestinal

 

Two pathways

   1. IgE mediated

   2. Immune complex mediated via the complement pathway, C3a and C5a

Stimulates mast cell or basophil degranulation leading to a release of

biologically active chemical mediators

 

 

CLINICAL FEATURES

Signs and symptoms begin within 60 min.

Faster the onset of symptoms , greater the severity of reaction.

Biphasic phenomenon- recurrence(3-20%) usually 4-8 hrs after initial exposure.

 

SIGNS AND SYMPTOMS

 • pruritus more on scalp

 • flushing

 • urticaria

 • angioedema- edema of lips,

larynx (“lump in throat”,

hoarseness)

periorbital,

extremities

 

The clinical presentation of early anaphylactic reactions are

Dry cough Fever

Nausea, vomiting, diarrhea Abdominal colic and cramps

Rhinorrhea Conjunctivitis

Lightheadedness

 

In case of Life threatening anaphylaxis

Tachycardia, Hypotension Arrhythmias

Bronchospasm, tightness of chest Angio oedema

Fatal reactions have probably been under reported

 

Pyrogenic (endotoxin) Reactions

Due to pyrogen contamination during the manufacturing process

Usually seen 1-2 hrs after treatment, characterized by

 • Chills, rigors, Fever,Vasodilatation, hypotension

 • Febrile convulsions in children

 

Immediate Management Airway and Breathing Oxygenate with mask

Intubate and ventilate if necessary

 

Treatment of early anaphylactic and pyrogenic reactions

Adrenaline should be kept loaded before starting the ASV. Stop the ASV temporarily and give adrenaline at the first sign of a reaction -0.5mg IM in adults &

0.01mg/kg IM in children. This can be repeated every 5 to 10 mins till symptoms subside

In case of persistent hypotension, Life threatening anaphylaxis, Adrenaline-can be given IV -0.1mg(100ug) of 1:10,000 dilution IV bolus given over 5 minutes.

This dose can be repeated if necessary.

If hypotension refractory to bolus dose start an adrenaline infusion.Add 1 mg adrenaline to 500 ml of 5 % Dextrose (2 µg/ml).Infuse at 1ml / min. Titrate upwards to 4 ml/min. Cardiac monitoring is needed in case of IV administration of Adrenalin as it can cause life threatening arrhythmias. Be cautious when administering adrenalin in elderly patients, patients with hypertension, arteriopathies, known IHD

 

Adrenaline- Mechanism of Action

 • Stimulation of alpha, B1, B2 adrenoceptors

 • ↑PVR, BP, CPP, CO

 • ↓angioedema

 • Bronchodilation

 • ↑intracellular Cyclic AMP in mast cells and basophils, ↓ release of inflammatory mediators

 

Treatment of Hypotension

Crystalloids –Normal saline bolus 1-2L (10 to 20ml/kg in children)

 

SECOND- LINE THERAPY

Corticosteroids

Hydrocortisone 200 – 500mg IV (5-10mg/kg in children)

Methylprednisolone 125mg IV (2mg/kg in children)

Prevents recurrent anaphylaxis

 

For allergic bronchospasm

Nebulization - Salbutamol + ipratopium bromide

Nebulised adrenaline if required

 

Additional Treatment

H1 antihistamine,

10mg chlorpheniramine maleate IV, (0.2mg/kg children) or

22.5mg pheniramine maleate IV or

25mg promethazine HCl IV

H2 antihistamines,

Ranitidine 50mg IV

Pyrogenic reactions

Paracetamol- oral or rectal

Cool patient by tepid sponging

 

When to restart the ASV after a reaction

 • Once the patient has stabilized

 • Once the BP is under control

 • Once the manifestations of the reaction have subsided

 • In severe reactions ASV can be restarted under cover of an adrenaline infusion

 • Rate of ASV infusion can be decreased initially

 • Patient should be under strict monitoring

 

Late (serum sickness type) reactions

Usually occurs1-12 days after treatment .Characterised by fever, arthralgia, myalgia, nausea, vomiting, diarrhoea, recurrent urticaria, lymphadenopathy, periarticular swellings, mononeuritis multiplex, proteinuria, with immune complex nephritis, encephalopathy.More common when early reactions not treated

Treatment of Serum Sickness reactions

 • Tab Chlorpheniramine Maleate 2mg q6H. Children 0.25 mg/kg/day in divided doses

 • Tab Prednisolone 5mg q6h.Children 0.7 mg/kg/day in divided doses

 

No role for test dose of ASV

Skin/conjunctival sensitivity, tests IgE mediated type 1 hypersensitivity to sheep/ horse proteins.Do not predict early anaphylactic or late serum sickness type antivenom reactions as these are complement activated . Sensitivity testing may lead to unnecessary delay in treatment . Furthermore test doses can even be sensitizing.

 

No absolute contraindications to antivenom

There is no absolute contraindication to antivenom treatment, but patients who have reacted to horse (equine) or sheep (ovine) serum in the past (for example after treatment with equine anti-tetanus serum, equine anti-rabies serum or equine or ovine antivenom) and those with a strong history of atopic diseases (especially severe asthma) should be given antivenom only if they have signs of systemic envenoming.

 

Prophylaxis in high risk patients

In the absence of any prophylactic regimen that has proved effective in clinical trials, these high risk patients may be pre-treated empirically with subcutaneous epinephrine (adrenaline), intravenous antihistamines (both anti-H1, such as promethazine or chloramphenicol; and anti- H2, such as cimetidine or ranitidine) and corticosteroid. In asthmatic patients, prophylactic use of an inhaled adrenergic ß2 agonist such as salbutamol may prevent bronchospasm.

 

Prevention of ASV Reactions – Prophylactic Regimes

 • 100mg of hydrocortisone and

 • H1antihistamine (10mg chlorpheniramine maleate IV or

22.5mg pheniramine maleate IV or 25mg promethazine HCl IV )

5 minutes before ASV administration.

Children

 • 0.1-0.3mg/kg of antihistamine IV and 2mg/kg of hydrocortisone IV.

 • Antihistamine should be used with caution in pediatric patients.

 

2nd Prophylactic regime

 • 0.25-0.3mg adrenaline 1:1000 subcut 5 minutes before administration of ASV

 

Prophylaxis with hydrocortisone and chlorpheniramine bolus reduces incidence of anaphylactic reactions

52 patients were randomised into 3 groups

Group 1: 1000mg hydrocortisone in 300ml NS

infusion 5 mins before and continued 30 mins

after ASV

Group 2: Chlorpheniramine 10mg IV bolus was given

5min after ASV infusion was started in addition

to the hydrocortisone

Group 3: Placebo

 

{Gawarammana IB, Kularatne M et al, Parallel infusion of hydrocortisone ± chlorpheniramine bolus injection to prevent acute adverse reactions antivenom for snakebites Med Journal of Australia. 2004;180(1):20-3}

 

Efficacy of subcut adrenaline in prevention of anaphylaxis

0.25 ml of subcut adrenaline vs placebo immediately before infusion of ASV in 101 patients and observed for anaphylactic reactions within 24 hrs.

The incidence of anaphylaxis was 11% in the study group and 43% in the control group, showing a statistically significant difference.

 

{Premawardhena A, de Silva CE et al, Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in people bitten by snakes: randomised, placebo controlled trial BMJ. 1999; 318: 1041-1043}

 

Efficacy of Promethazine prophylaxis against anaphylaxis

25 mg promethazine in adults (0.5mg/kg child) vs placebo 20 min before infusion of ASV in 101 patients and observed for anaphylactic reactions within 24 hrs.

The incidence of anaphylaxis was 24% in the study group and 25% in the control group, showing no difference.

 

{Wen Fan H, Marcopito LF et al Sequential randomised and double blind trial of Promethazine prophylaxis against early anaphylactic reactions to antivenom for Bothrops snake bites. BMJ. 1999; (318):1451-1453}

 

St. Johns Medical College Hospital Study

 • Randomised, double blind controlled trial

 • Group 1: Hydrocortisone100mg IV + Chlorpheniramine maleate 10mg IV

 • Group 2: Placebo 5mins before the administration of ASV

 • To study the efficacy of the above regime on reducing anaphylaxis after ASV

 

Summary

ASV is polyvalent

No role for test dose to predict anaphylaxis

Prophylactic regimes available

Early and late reactions

Important to recognize as soon as possible

Adrenaline is the mainstay of treatment

Restart the ASV once symptoms subside

 

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