Snakes of India & ASV

Biological E.

Topics for discussion

1. Type of snakes found in India2. Geographical Availability3. Approximate death in India due to snake bite4. Venom of different snakes & their mechnism of action.5. An ideal Anti Snake preparation6. Currently available anti snake preparation7. Dosages schedule of anti snake preparation8. Polyvalent anti snake preparation and advantages and

disadvantages over monovalent ASV.9. How new ASVs scores over older ASVs.

Current therapy guidelines

Future therapy guidelines

• National survey on antisnake venom utilization & administration (2008) being conducted by the Indian society of toxicology

• To cover 500 major hospitals across India• Questionnaire-based survey

– QUESTIONNAIRES MAILED TWICE (August & October)

– RESPONSE RECEIVED: 112 HOSPITALS (as on 15 Nov)

• Findings to be published in 2009• May form basis of future use guidelines

Snake bite incidences worldwide

Snake bite deaths worldwide

Statistics of relevance

• INDIA – Records the highest annual incidence of total snake bites

as well as fatal snake bites in the world– 2,00,000 bites/year– 15,000 deaths/year

• (some estimates put this at more than 50,000 deaths per year)

• Number of Indian snake species: – 250 [ some say 272]

• Venomous species: – 52

www.wikipedia.org/snakevenom, www.mun.ca

Snake Bite and snake Venom

• When a snake bites, it may excrete venom but this is dependent on the type of snake – venomous or non venomous.

• Snake Venom is a Toxin (Hemotoxin Neurotoxin, or Cytotoxin)

• It is a varied form of saliva and excreted through a modified parotid salivary gland– Located on each side of the skull, behind the eye– Produced through a pumping mechanism from a sac that

stores the venom, proceeds through a channel, down a tubular fang, hollow in the center to project the venom.

www.wikipedia.org/snakevenom, www.mun.ca

Snake Venom

• Snake venoms are– A combination of proteins and enzymes– 90% protein by dry weight & most of these are enzymes– Have 25 different enzymes found in various venoms and

10 of these occur frequently in most venoms– Synergistic in effects: different venoms contain different

combinations of enzymes causing a more potent effect than any of the individual effects (very similar to drug synergism)

Mechanism of Toxicity of Venom

• The most common types of enzymes are proteolytic, phospholipases and hyaluronidases

– Proteolytic Enzymes: digestive properties

– Phospholipases: degrade lipids

– Hyaluronidases: speed venom spread through the body

Commonest Indian venomous snakes

The big 4 –

1. Common cobra – Naja Naja - neurotoxic venom

2. Common krait – Bungarus Caeruleus - neurotoxic venom

3. Saw scaled viper (carpet viper)– Echis carinatus - haemotoxic Venom

4. Russell’s viper– Daboia russelli - haemotoxic Venom

Commonest Indian venomous snakes – the big 4

CobraCobra KraitKrait

Russel’s viperRussel’s viper Saw-scaled viperSaw-scaled viper

The venom is synthesized by the modified salivary glands and injected through special channeled or grooved teeth called fangs

Commonly encountered venomous snakesin most parts of India

In terms of frequency of encounters -

1. Russell’s viper

2. Common cobra

3. Saw scaled viper

4. Common krait

5. Miscellaneous

Russell’s viper

• Daboia ruselii

• Koriwala

Common cobra

• Naja naja ()

• Sheesh Nag, Kala Nag, Karo

Saw scaled viper

• Echis carinatus

• Marathi - phoorsa.

• Kannada - kallu have.

• Malayalam - churuta, anali;

• Gujarati - tarachha.

• Hindi - afai.

Common krait

• Bungarus caeruleus

• Sung Choor

Other less commonly encountered venomous snakes

• Pit vipers

• Rarely encountered venomous snakes1. King cobra

2. Banded krait

3. Coral snake

4. Sea snakes

Summary of Manifestations

LOCAL NEURO BLEED MISC.

COBRA + ++ Nil Shock +/-

KRAIT Nil + Nil Pupils –dilated, fixed

VIPER +++ + / - ++ Renal failure, Shock

Summary of Manifestations

Feature Cobras Kraits Russells Viper

Saw Scaled Viper

Hump Nosed Viper

Local Pain/ Tissue Damage YES NO YES YES YES

Ptosis/ Neurological Signs YES YES YES! NO NO

Haemostatic abnormalities NO NO! YES YES YES

Renal Complications NO NO YES NO YES

Response to Neostigmine YES NO? NO? NO NO

Response to ASV YES YES YES YES NO

Snake bites

Management

Local signs

• Fang marks

• Local pain

• Local bleeding

• Bruising

• Lymphangitis, lymph node enlargement

• Inflammation (swelling, redness, heat)

• Blistering

• Local infection, abscess formation

• Necrosis

General symptoms (0)

• Local effects: – This is related to the digestive function of the venom and

causes local tissue necrosis.– It is maximal with a viper bite and least with krait

• (so much so that the bite may go unnoticed and symptoms which follow may not be attributed to snake bite).

General symptoms (1)

• General: – Nausea, vomiting, malaise, abdominal pain, weakness,

drowsiness, prostration

• Cardiovascular (Viperidae): – Visual disturbances, dizziness, faintness, collapse, shock,

hypotension, cardiac arrhythmias, pulmonary oedema,

General symptoms (2)

• Bleeding and clotting disorders (Viperidae)– bleeding from recent wounds (including fang marks,

venepunctures etc) and from old partly-healed wounds– spontaneous systemic bleeding - from gums, epistaxis,

bleeding into the tears, haemoptysis, haematemesis, rectal bleeding or melaena, haematuria, vaginal bleeding, bleeding into the skin (petechiae, purpura, ecchymoses) and mucosae (eg conjunctivae), intracranial haemorrhage..

General symptoms (3)

• Neurological (Elapidae, Russell’s viper): – Drowsiness, paraesthesiae, abnormalities of taste and smell,

“heavy” eyelids, ptosis, external ophthalmoplegia, paralysis of facial muscles and other muscles innervated by the cranial nerves, aphonia, difficulty in swallowing secretions, respiratory and generalised flaccid paralysis

• Skeletal muscle breakdown (sea snakes, Russell’s viper): – Generalised pain, stiffness and tenderness of muscles,

trismus, myoglobinuria, hyperkalaemia, cardiac arrest, acute renal failure

General symptoms (4)

• Renal (Viperidae, sea snakes): – Loin (lower back) pain, haematuria, haemoglobinuria,

myoglobinuria, oliguria/anuria, symptoms and signs of uraemia (acidotic breathing, hiccups, nausea, pleuritic chest pain....)

• Endocrine (acute pituitary/adrenal insufficiency) (Russell’s viper)– Acute phase: shock, hypoglycaemia– Chronic phase (months to years after the bite): weakness, loss

of secondary sexual hair, amenorrhoea, testicular atrophy, hypothyroidism etc

Prognosis assesment

• Time of bite

• Activity at the time of bite

• First aid action taken since the bite

• Clinical examination

• 20 mn whole Blood Clotting Test

Management

Management

Local

Specific

Supportive

Management

• The first aid being currently recommended is based around the mnemonic: “Do it R.I.G.H.T.”

• R. =– Reassure the patient. 70% of all snakebites are from non-venomous species.

Only 50% of bites by venomous species actually envenomate the patient

• I = – Immobilise in the same way as a fractured limb. Use bandages or cloth to hold

the splints, not to block the blood supply or apply pressure. Do not apply any compression in the form of tight ligatures, they can be dangerous!

• G. H. = – Get to Hospital Immediately. Traditional remedies have NO PROVEN benefit

in treating snakebite.

• T= – Tell the doctor of any systemic symptoms such as ptosis that manifest on the

way to hospital.

Management - Local

• The local wound should be cleaned gently with normal saline. Short skin incisions and suction has been advised if the bite is less than 1 hour old.

• Immobilise the affected limb. Apply tourniquet around a single boned part of the bitten limb between the wound and the heart. – Pressure should be adequate to occlude lymphatics but

not the distal arterial pulse. – Tourniquet can be released briefly for a few seconds

every 10minutes.

• No compressive therapy if necrosis as in viper bite.

Management: Specific 1

• Use Polyvalent ASV, available in a lyophilized form (as liquid antivenin is unstable at room temperature).

• Active against the 4 common poisonous snakes in India – cobra, krait, Russel’s viper and saw scaled viper (Echis).

• Average potency of the ASV available is such that – 1 ml will neutralize

• 0.6mg cobra, • 0.45mg krait, • 0.6mg Russel’s viper and • 0.45mg saw scaled viper venom

Management: Specific 2

• Reconstitution involves the addition of 10ml of distilled water to an ampoule and shaking till the solution is clear.

• It should be administered intravenously as early as possible.

• It is essential to enquire about allergy (specially to horse serum).

• It is well to be prepared for an anaphylactic reaction during the antivenin administration.

Criteria for giving ASV

• ASV’s only role is to neutralize unbound free flowing venom

• 50% of Cobra bites inject no venom to the victim• Criteria :

– Incoagulable blood (20WBCT)

– Visible neurological signs (ptosis, ophtalmoplegia, descending paralysis, inability to lift the head)

– Clear evidence of current systemic bleeding

• ASV to be given only if one or more of these signs are present, but purely local swelling, even if accompanied by a bite mark from an apparently venomous snake, is not grounds for administering ASV.

20WBCT - 20 Minute Whole Blood Clotting Test

• Few ml of fresh venous blood placed in a NEW, CLEAN, DRY, GLASS test tube– Left undisturbed for 20 mn– Gently tilted to 45° and examined

• If it has remained liquid: – consumption coagulopathy ASV required

• Clotted: – ASV not necessary (at this stage)

• Done every 30 minutes from admission for 3 hours and then hourly after that.

• If incoagulable blood is there, 6 hourly cycle will then be adopted to test for the requirement for repeat doses of ASV.

Prevention of adverse reactions to ASV

• No intradermal test is indicative: – Because intradermal allergy testing is targeted at IgE

mediated reaction whereas ASV reactions are complement mediated

– Risk of pre sensitizing the patient and making the reaction more likely

– Waste of precious time

• Premedication with – hydrocortsisone, anti-histamine or Sc adrenaline: only for

the first dose, efficacy unproven

Therapy of adverse reactions to ASV

• Anaphylaxis can be rapid onset, usually within 20 mn from start of ASV and can deteriorate into a life-threatening emergency very rapidly. Adrenaline should always be immediately available.

• Urticaria, itching, fever, chills, nausea, vomiting, diarrhoea, abdominal cramps, hypotension, bronchospasm and angio-oedema

• ASV will be discontinued and Treatment and drugs of choice – Adrenaline, 0.5 mg IM, to be repeated if symptoms do not improve

within 15 mn– 100 mg hydrocortisone + 25 mg Promethazine IM / – 10 mg chlorphenimarine IV

• Children are given 0.01mg/kg body weight of adrenaline IM.

Management: Supportive 1

• Analgesics for pain - Prefer paracetamol to aspirin• Antibiotics for infection, only if necrosis

– choice to cover anaerobes.

• Antitetanus prophylaxis• Avoid heparin.• Replacement of coagulation factors / platelets if there is

active significant bleeding or bleeding into a vital organ.– Primary mean of restoring clotting factors is by ASV

– Once venom has been adequately neutralized, liver will begin to restore factors to normal levels

– Blood products are used exceptionally in case of severe bleeding, after coagulation has been restored

Referral criteria for indoor management

• Transportation of the patient: NPA + bag mask ventilation

• Occult systemic bleeding / renal failure

• Neurotoxic envinemation – Inability to perform neck lift suggests imminent

respiratory failure– Requiring longer term mechanical ventilation

• Surgical cases – requiring debridement of necrotic tissue

Antisnake venom

ASV

Types of ASV available

• Liquid ASV– Requires no reconstitution but problem of cold chain

• Lyophilized– Requires no refrigeration but time required for

reconstitution with distilled water

AntiSnakevenoms available in India

• Polyvalent Snake Antivenom I.P– 4 Antivenoms effective against the Big 4, mixed

together

• Manufacturers: 1. VINS Bioproducts Ltd, AP

2. Serum Institute of India Ltd, Pune

3. Haffkine Institute, Mumbai

4. Bharat Serums of India, Mumbai

• Owing to reports of significant bites by pit vipers, there is a move to add a 5th antivenom!

Polyvalent antisnakevenom

Advantages• No need to waste time or

effort at identifying the exact nature of venomous snake

• Less expensive• Easy distribution to all

parts of the country

Disadvantages• Decreased efficacy (?)• Increased incidence of

allergic reactions

Why not a monovalent antisnakevenom?

It is available in

Several countries abroad

Monovalent antisnakevenom

Advantages• Increased efficacy• Lower incidence of allergic

reactions

Disadvantages• Identifying the exact nature

of venomous snake mandatory

• More expensive if all snakes need to be covered

• Difficulties in distribution of exact antisnakevenom required in various regions of India.

Anti snake venom

Dosing criteria and details

Dose of ASV - basis

• Logic suggests that our initial dose should be calculated to neutralise the average dose of venom injected.

• This ensures that the majority of victims should be covered by the initial dose and keeps the cost of ASV to acceptable levels.

• The range of venom injected is 5mg – 147 mg. • Average potency of the polyvalent ASV available is such

that 1 ml will neutralize • 0.6mg cobra,

• 0.6mg Russel’s viper

• 0.45mg krait, and

• 0.45mg saw scaled viper venom

Dose of ASV - basis

• Initial dose 8-10 vials and exact dosing amount depends on the amount of venom injected by the snake

• Cobra and Russel’s viper 60mg – Krait inject less venom but neurological symptoms

similar to Cobra.

• Saw scaled viper bite = around 15 mg of venom– On average, 15 vials required to restore coagulation

• In cases other than confirmed SSV bite, 8-10 vials

Dose of ASV - basis

• If confirmed SSV– give 4 vials if 20WBCT un coagulable– monitor coagulation and repeat ASV 6 hourly – Check series of patient

• if 50-60% restore their coagulation, 4 vials is the correct starting dose

• If 10-20% restore their coagulation after 6 hours increase the starting dose to all patients by one vial and monitor

Repeat doses of ASV

• ASV should be given as long as blood is shown incoagulable on 20WBCT – performed 6 hourly (time required by the liver to restore

clotting factors)

• Neurotoxic: patient review 1 hour after initial dose:– if worsening, give 2nd dose of ASV– if not worsened, review again after 2 hours, – if not improved, give 2nd dose of ASV– After 2 doses, ASV should be stopped, no role for very

large dose in neurotoxic bites

Dosing

• All ASV to be administered over 1 hour at constant speed, either by IV injection or continuous infusion

• SC, IM, around bite site : no• Each vial is 10ml of reconstituted ASV.• ASV can be administered in two ways:

– Intravenous Injection: reconstituted or liquid ASV is administered by slow intravenous injection. (2ml/ minute). Each vial is 10ml of reconstituted ASV.

– Infusion: liquid or reconstituted ASV is diluted in 5-10ml/kg body weight of isotonic saline or glucose.

• No change in dose for children as the amount of venom injected may be the same as in an adult.

Dosing in patients arriving late

• Victims who arrive several days after the bite, usually have acute renal failure.

• The key determining factor to administer ASV is there are any signs of current venom activity

• Venom can only be neutralised if it is unattached! Perform a 20WBCT and determine if any coagulopathy is present.

• If coagulopathy is present, administer ASV. • If no coagulopathy is evident treat any renal failure by

reference to a nephrologist and dialysis.• In the case of neurotoxic symptoms such as ptosis,

respiratory failure etc, it is probably wise to administer 1 dose of 8-10 vials of ASV to ensure that no unbound venom is present.

Neurotoxic Envenomation

• Cobra venom is a post synaptic neurotoxin and blocks the nicotinic receptor causing acetylcholine to be unable to bind

• Neostigmine prolongs the life of acetylcholine by inhibiting cholinesterase, increasing the likelywood of acetylcholine binding with unblocked receptor

• Baseline test: single breath count, time upward gaze• 1.5 mg neostigmine + 0.6 mg Atropine [Repeat tests]

• If objective improvement, repeat neostigmine + atropine every 30 min.

Research options ahead

Anti snake venoms

Possible solution for India

• Bivalent (or trivalent) antivenom– After all, there are only 2 main categories of venomous

snakes

• ELAPIDS– Neurotoxic venom

• VIPERIDS– Vasculotoxic venom

• So, why not have one bivalent antisnakevenom for common elapids?

• And, one trivalent antisnakevenom for common viperids?

Advantages of bivalent/ trivalent antisnakevenom

• Almost as effective as monovalent antivenom

• Lower incidence of allergic reactions as compared to polyvalent antivenom

• Less expensive than polyvalent antivenom

• No need of exact identification of venomous snake

• This proposal has already been put forth at the

Thank you