SNAKE BITE

PROF. SUBHASH RANJAN

INTRODUCTIONIndia estimates approx 2,00,000 bites and 35-

50,000 snake bite deaths/year

No reliable national statistics are available.

Males bitten almost twice as often as females

Majority of the bites being on the lower extremities.

50% of bites by venomous snakes are dry bites, result in negligible envenomation.

What are Indian FAB FOUR?

FAB FOUR In India, >200 species of snakes; only 52 are poisonous.

Saw-scaled viper (Echis carinatus) Russell’s viper (Daboia russelii) Common krait (Bungarus caeruleus) Indian cobra (Naja naja)

Neurotoxic 20-30%

1 2 43

Majority of bites 70-80% Hemotoxin / Vasculotoxin

COMMON INDIAN SNAKES

COBRA (Naja naja)

King Cobra (Ophiophagus hannah)

Saw-scaled Viper (Echis carinatus)

Green Vine Snake (Ahaetulla nasuta)

Mild Venomous; ASV not required

Indian Russell's Viper

Russell’s Viper

Green Pit Viper

TRPA1/Wasabi Receptor

Infrared Vision

Indian Green Pit Viper

Asian Sand Viper (Eristicophis macmahonii)

Hump Nosed Viper

Hump Nosed Viper

Common Indian Krait (Bungarus caeruleus)

Common Indian Krait (Bungarus caeruleus)

The Greater Black Krait (Bungarus niger)

The Greater Black Krait (Bungarus niger)

Indian Cat Snake Mild Venomous; ASV not required

Wolf SnakeMild Venomous; ASV not required

Sea Snake

Trinket Snake (Elaphe helena monticollaris)

Mild Venomous; ASV not required

Montane TrinketMild Venomous; ASV not required

Indian Rat SnakeNon Venomous; ASV not required

Indian Rock Python

Variegated Kukri (Oligodon taeniolatus)

Non Venomous; ASV not required

KEELBACK

http://animalrescuesquadgoa.com/Non%20venemous.html

Non Venomous; ASV not required

Snake bite

Venomous snakes

Majority (80%) is by non-venomous snakes

About 50% of bites are dry

FACTS

Is there any medical implication for snake

identification?

Species: Medical Implications Signs/Symptoms and Potential Treatments

Cobra Krait Russell’s Viper Saw Scaled

Viper Other Vipers

Local pain/ Tissue Damage Yes No Yes Yes Yes

Ptosis/Neurotoxicity Yes Yes Yes! NO No

Coagulation No No Yes Yes Yes

Renal Problems No No Yes NO Yes

Neostigmine & Atropine Yes No? No? NO No

What is syndromic approach & its significance in Indian

scenario?

Desired when snake is unidentified

SYNDROMIC APPROACHSyndrome 1Local envenoming (swelling etc) with bleeding/clotting disturbances = Viperidae (all species)

Syndrome 2Local envenoming (swelling etc) with bleeding/clotting disturbances, shock or renal failure = Russell’s viper (and possibly saw-scaled viper – Echis species)With conjunctival oedema (chemosis) and acute pituitary insufficiency = Russell’s viperWith ptosis, external ophthalmoplegia, facial paralysis etc and dark brown urine = Russell’s viper

SYNDROMIC APPROACHSyndrome 3Local envenoming (swelling etc) with paralysis = cobra or king cobra

Syndrome 4 : Paralysis with minimal or no local envenomingBite on land while sleeping= kraitBite in the sea = sea snake

Syndrome 5 : Paralysis with dark brown urine and renal failure:-Bite on land (with bleeding/clotting disturbance) = Russell’s viperBite in the sea (no bleeding/clotting disturbances) = sea snake

Composition of Snake Venom

Procoagulant enzymes (Viperidae) Russell’s viper

Haemorrhagins (zinc metalloproteinases)

damage the endothelial lining.

Cytolytic or necrotic toxins

Haemolytic and myolytic phospholipases A2 damage cell membranes, endothelium, skeletal muscle, nerve and red blood cells.

Pre-synaptic neurotoxins (Elapidae and some Viperidae)

Post-synaptic neurotoxins (Elapidae)

Snake Bite Toxicity Profile ?

NEUROTOXICITY Starts early- many die before

they reach hospitals Many reverse very well with

ASV if started early Less number of cases

HEMOTOXICITY Starts late hence most of them

reach hospitals Many organ involvement hence

MV is mostly supportive to buy time for organs to recover

More number of cases

70-80%

20-30%

Overlap: Neurohemat

What is the mode of Neurotoxicity in Krait Bite?

Krait- Pre-synaptic action

Beta-bungarotoxin- Phospholipases A2

1) Inhibiting the release of Ach from the presynaptic membrane

2) Presynaptic nerve terminals exhibited signs of irreversible physical damage and are devoid of synaptic vesicles

3) ASV & anticholinesterases have no effect

Paralysis lasts several weeks and frequently requires prolonged MV. Recovery is dependent upon regeneration of the terminal axon.

What is the mode of Neurotoxicity in Cobra Bite?

Cobra – post-synaptic alpha-neurotoxins “Curare -mimetic toxins’’

Bind specifically to Ach receptors, preventing the interaction between Ach and receptors on postsynaptic membrane.

Prevents the opening of the sodium channel associated with the Ach receptor and results in neuromuscular blockade.

ASV -rapid reversal of paralysis.

Dissociation of the toxin-receptor complex, which leads to a reversal of Paralysis

Anticholinesterases reverse the neuromuscular blockade

Neuroparalytic Manifestations Study

Ptosis

RSinvolvementBulbar

weakness

N Sharma, S Chauhan, S Faruqi, P Bhat, S Varma, Emerg Med J 2005;22:118–120

Ophthalmoplegia

Quick Neurological Examination !

Neurotoxic Envenoming-Examination

Ask the patient to look up and observe whether the

upper lids retract fully.

Test eye movements for evidence of early external

ophthalmoplegia .

Check the size and reaction of the pupils.

The muscles flexing the neck may be paralysed, giving

the “broken neck sign

Bungarus niger envenoming

20 hr post-bite

Neurotoxic Envenoming-Examination

Krait can cause fixed, dilated non reactive pupils

simulating brain stem death – however, it can recover

fully

Ask the patient to open their mouth wide and protrude

their tongue; early restriction often due to paralysis of

pterygoid muscles.

How to identify for bulbar palsy & early resp failure?

Bulbar & Resp Paralysis Can the patient swallow or are secretions accumulating

in the pharynx- an early sign of bulbar paralysis.

Ask the patient to take deep breaths in and out. “Paradoxical respiration”.

Objective measurement of ventilatory capacity is very useful. Use a peak flow metre, spirometer (FEV1 and FVC)

Ask the patient to blow into the tube of a sphygmomanometer to record the maximum expiratory pressure (mmHg).

Paradoxical Respiration This is an abnormal pattern of breathing in which the

abdominal wall is sucked in during inspiration (it is usually pushed out).

Paradoxical respiration is due to paralysis of the diaphragm.

Hematological Side Effects

Venom induces bleeding

Venom induces clotting

Venom induces haemolysis

Haemorrhagin – causes direct endothelial damage by loosening the gap between endothelial cells

Procoagulant factors

Anticoagulant factors

Fibrinonolytic factors

Snake Venom and the Coagulation Cascade

RVV – Russel’s Viper Venom ECV – Echis

carinatus Venom

PTT

PT

20 min Whole Blood Clotting Test (20-WBCT)

Place a few ml of freshly sampled venous blood in a small glass vessel

Leave undisturbed for 20 minutes at ambient temp & tip the vessel once

If the blood is still unclotted and runs out, the patient has hypofibrinogenaemia/DIC

In the SE Asia, incoagulable blood is diagnostic of a viper bite and rules out an elapid bite

Local Symptoms & Signs in the Bitten Part

Fang marks Local pain Local bleeding Bruising Lymphangitis Lymph node enlargement Inflammation (swelling, redness, heat) Blistering Local infection, abscess formation Necrosis

Russell’s Viper Bite

Venomous Non-venomous

LOCAL NECROSIS

What are the systemic manifestations of the

envenomation ?

Systemic Symptoms & Signs General Nausea, vomiting, malaise, abdominal pain, weakness, drowsiness,

prostration, conjunctival oedema

Cardiovascular (Viperidae) Visual disturbances, dizziness, faintness, collapse, shock, hypotension,

cardiac arrhythmias, pulmonary oedema

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

Systemic Symptoms & Signs

Bleeding & Clotting Disorders Bleeding from recent wounds (including fang marks), venepunctures

and from old partly-healed wounds

Spontaneous systemic bleeding – from gums, epistaxis, bleeding into the tears

haemoptysis, haematemesis, hematochezia or melaena, haematuria, bleeding P/V, bleeding into the skin (petechiae, purpura, ecchymoses) and mucosae (eg conjunctivae)

Intracranial haemorrhage (meningism from SAH, lateralising signs and/or coma from cerebral haemorrhage)

Systemic Symptoms & Signs Skeletal muscle breakdown (sea snakes, Russell’s viper)

Generalised pain, stiffness and tenderness of muscles, trismus, myoglobinuria hyperkalaemia, cardiac arrest, acute renal failure

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

Myoglobinuria after Bungarus niger envenoming

Pleuropericardial Haemorrhagic Effusion

Manoj Lakhotia et al JIACM 2002; 3(4): 392-4

Treatment

First AidPrimary/Secondary Care LevelTertiary Care Level

First AidReassure the victim

Immobilise the bitten limb with a splint or sling

Consider pressure-immobilisation for some elapid bites; AVOID IN COBRA

Avoid any interference with the bite wound as this may introduce infection, increase venom absorption & local bleeding

All rings, watches, constricting clothing should be removed.

Pressure Immobilization(Elapidae bite)

Developed in 1970 by late Struan Sutherland, Australia

Bandaging entire limb using a long crepe bandage – starting from toe or finger as tightly as for a sprained ankle incorporating a splint.

Pressure Immobilisation

Pr immobilisation is recommended for bites by neurotoxic elapid snakes, including sea snakes.

Caries risk of sudden envenomation after release – neurotoxic snakes.

Should not be used for viper bites because of the danger of increasing the local effects of the necrotic venom.

COMPLICATIONS OF ARTERIAL TOURNIQUET

Congestion & swelling Ischaemia & gangrene Damage to peripheral nerves Increased bleeding from bite site

Tourniquet Gangrene

INCISION & SUCTION

No!

TREATMENT

CRYOTHERAPY:No!Increases tendency to necrosis

TREATMENTHOSPITAL MEASURES FOR ASYMPTOMATIC PTSa) OBSERVATION FOR 24 HOURS

b) MONITOR: PR, RR, BP CBC-TLC ↑, Platelets ↓ Urine output BUN, Creatinine PT, aPTTK, INR CPK (>600 IU/L) Vomiting, diarrhoea Abnormal bleeds Local swelling necrosis ECG Blood gas analysis

MEDICOLEGAL 39 Code of Criminal Procedure under

 Constitution of India Article 21

MLC to be initiated

Hospital mngt, if tourniquet is a already in place

•Limb is ischemic – remove immediately

•Limb is not ischemic:-1) Snake (unknown) or neurotoxic – Don’tremove until definite treatment (ASV) is initiated

2) Snake is viper – remove the tourniquet

What is ASV?

ASV ASV is Ig (usually the enzyme refined F(ab)2 fragment of

IgG) purified from the serum/plasma of a horse/sheep immunised with the venoms of one or more species of snake.

Monovalent/Polyvalent

The ASV in India is a polyvalent type which is active against the commonly found snakes in India including the FAB Four.

Antivenom

Polyvalent antivenoms from India raised against venom from:•Bungarus caeruleus•Naja naja•Echis carinatus•Daboia russelii

No monovalent vaccine in India

ASV Average dry weight of venom injected = 63

+/- 7mg by Russell’s Viper or Cobra.

Each vial neutralises venoms of 6 mg Cobra

6 mg Russell's Viper4.5 mg of Krait 4.5 mg of Saw Scaled Viper

Initial dose should be 8-12 vials.

Snake inject same amount of venom into children, dose of ASV is same as adult .

http://cbcreatures.webs.com/snakeantivenom.htm

What are the indications for ASV use?

Indications for Antivenom Use Shock

Resp distress /failure

Extensive Local Swelling

Ptosis

Generalized myalgias

Trismus

Mod-to-severe pain with passive movement of extremities

Severe GI Symptoms

Myoglobinuria

Elevated creatine kinase level (>600 IU/l)

Altered level of consciousness

Hyperkalemia

ECG Changes

Leukocytosis.

Antivenom Reconstitution Freeze-dried (lyophilised) ASV is reconstituted with

10 ml of sterile DW per vial.

TREATMENT OF SNAKEBITEPROCEDURE OF ADMINISTRATION

Test Dose?No!

Has no predictive value in detecting anaphylactoid or late serum reactions and should not be used.

Not IgE mediated, but complement - activated. May also pre-sensitise the patient, and create greater risk.

Methods of Administration

IV “push” injection: recons freeze-dried ASV is given by slow iv inj (not more than 2ml/min).

IV infusion: recons freeze - dried ASV is diluted in approx 5-10 ml of isotonic fluid per kg BW (ie 250-500 ml of N/S or 5% Dex in adult pt) and infused at a constant rate over a period of about 1h.

Antivenom Administration

Adrenaline drawn up in readiness before ASV is administered.

ASV should be given by the IV route whenever possible.

I/M may be given when no i/v access, expeditions with limited med facilities.

Prophylaxis in High Risk patients

Pre-treated empirically with s/c epinephrine (adrenaline)

IV antihistamines anti-H1 + anti- H2 (Ranitidine)

IV Hydrocortisone 100 mg

IM Antivenom A maximum of 5-10 ml should be given at each

site by deep IM inj followed by massage to aid absorption

ASV should never be injected into the gluteal region (upper outer quadrant of the buttock) as absorption is exceptionally slow and unreliable and there is always the danger of sciatic N damage by an inexperienced operator.

Dose

5 vials(50ml)

5-10 vials(50-100ml)

10-20 vials(100-200ml)

Large vs Small dose

Low dose of snake antivenom is as effective as high dose inpatients with severe neurotoxic snake envenomingAgarwal, Aggarwal, Gupta, et al Emerg Med J 2005;22:397–399.

•High dose group 100ml stat and 100 ml every 6 hrs•Low dose group 100ml stat and 50 ml every 6 hrsUntil recovery of neurological signs

Timing of ASV

There is no consensus as to the window period of administration of ASV.

Best effects are observed within 4 h of bite .

It has been noted to be effective in symptomatic pts even when administered up to 48 h after bite.

ASV is efficacious even 6-7 days after the bite from vipers

At the Earliest Sign of a Reaction:

ASV administration must be temporarily suspended

Adrenaline (0.1% solution, 1 in 1,000; 1 mg/ml) is the effective treatment for early anaphylactic and pyrogenic ASV reactions

Early reaction to ASV Anaphylaxis

Adrenaline (SC or IM) 0.3 to 0.5ml 1:1000 (1mg/ml). Repeated at 5 to 20 min interval if severe.

Adrenaline (IV) - in intractable reaction 2.5 ml iv; 1:10,000 (0.1mg/ml).

Volume resuscitation

Case scenario……. 34 yr old male shifted from Periph Hosp with H/O snake

bite 6 hrs back has ptosis, respiratory distress, RR 35/mt, BP 120/60, oral secretions present, absent gag and cough reflex shifted to ICU for tertiary care.

On ASV 100ml stat, & 50ml in NS over 6 hrs Oxygen 3l/mt

Patient received in casualty: 2 situations

Patient is comfortable, vitals stable

No ptosis, distress

Patient is dead –what do you think went wrong ?

What could have been done better ? Bulbar signs-probably aspirated and died Endotracheal intubation could have been placed on T-

piece Ambuing or Transport Ventilator Anticholienesterases Neostigmine with atropine

Patient is dead –what do you think went wrong ?

Trial of AnticholinesteraseAnticholinesterase (“Tensilon”/Edrophonium) test Record baseline parameters Give atropine IV Give anticholinesterase drug edrophonium chloride

(adults 10 mg, children 0.25 mg/kg body weight) given intravenously over 3 or 4 minutes

Observe

Improvement in ptosis, Respiratory distress, better cough effort, decrease in RR

Tearing, salivation,muscle fasciculation, abdominal cramp,bronchospasm, bradycardia, cardiac arrest

Neostigmine

Positive response

Atropine IV

Negative response

Dose of Neostigmine

Neostigmine 25µg/kg/hr Neostigmine 0.5 mg / 6 hr IV atropine 0.5 mg / 12 hr

34 yr old male shifted from Periph Hosp with H/O snake bite 6 hrs back has ptosis, respiratory distress, RR 35/mt, BP 120/60, oral secretions present, absent gag and cough reflex shifted to ICU for tertiary care.

On ASV 100ml stat, & 50ml in NS over 6 hrsOxygen 3l/mtRecd neostigmine 0.6mg and 0.6 mg atropine iv

You can have alive but a sicker patient

You can have dead patient

Cobra

Krait

Case scenario…….

Alive but a sicker patient

Shifted to ICU placed on a Ventilator lot of secretions

Do we continue anticholinesterases ?

Issues to consider

Increased secretions

Increased incidence of VAP ?

We rarely use these drugs once the patient is in the ICU under observation

Observation of the Response to Antivenom

Cobra bites-Post synaptic

May begin to improve as early as 30 minutes after anti-venom, but usually take several hours.

Krait and sea snakes- Pre synaptic

Depends on the timing of ASV administrationIf delayed may not produce any action or Minimal delayed action

Repeat Dose

Signs of systemic envenoming may recur within 24-48 hrs Criteria for repeating the initial dose of antivenom Persistence/recurrence of blood incoagulability after 1-2 h Deteriorating neurotoxic or cardiovascular signs after 1-2 h

Continuing absorption- due to improved blood supply following correction of shock, hypovolaemia etc

After elimination of antivenom a redistribution of venom from the tissues into the vascular space.

Causes

How to Know ASV Dose Administered is Sufficient?

a) Spontaneous systemic bleeding stops in 15-30 min.

b) Blood coagulability is usually restored in 6 hours.

c) Post synaptic neurotoxic envenoming begins to improve in 30 min, but can take several hours.

How to Know ASV Dose Administered is Sufficient?

d) Presynaptic neurotoxic envenoming usually takes a considerably more time to improve.

e) Active haemolysis & rhabdomyolysis may cease within a few hours & urine returns to its normal colour.

f) In shocked pts, BP may improve in 30 min.

What is the Max Dose of ASV?

25 – 30 vials

Q. If symptoms persist despite giving max Q. If symptoms persist despite giving max dose, what must be done?dose, what must be done?Ans. Supportive measures & treatment of complications:

Ventilation – Elapid bite Dialysis, transfusions, etc – Viperid bite Fasciotomy, wound surgery, amputation,

etc, as per need.

Pregnancy and Snake Bite

Pregnant pt is treated the same manner as the nonpregnant .

Spontaneous abortion, bleeding, fetal death & malformations are common.

Lactating mothers can continue lactating

A 25 yr old male with snake bite has signs of compartment syndrome and the pressure is 60 mmHg, is undergoing surgery, has a Hb of 6 gm%, is hypotensive 100/60, on noradrenalin, acidotic, coagulation profile is normal

Blood is started After 15 mts of surgical time patient develops Dark colored urine BP drops to 80/60 with ARF What are the possibilities ?

Rhabdomyolysis

(Viper Bite)

Treatment Fluids, Mannitol,Alkalinize the urine, Manage electrolytesFasciotomyRRT

Other Rx

Antibiotics

Hydration

Tetanus prophylaxis

Wound debridement

Fasciotomy for compartment syndrome

Haemodialysis for acute renal failure

Mechanical ventilation

DIC; related mngt

Criteria for Fasciotomy in Snake-Bitten Limbs

Clinical evidence of an intracompartmental syndrome

Intracompartmental pr >40 mmHg (in adults)

Disposition (Dry bite)* Viper BiteNo local and systemic envenomationat 8 to 12h by repeated lab tests – ‘Dry Bite’.

* Neurotoxic snakeObservation period 12-24hr.Neurotoxicity can be delayed .

References N Engl J Med, Vol. 347, No. 5 August 1, 2002

www.nejm.org Page 347-356

WHO Guidelines for the Clinical Management of Snake Bites in the South-East Asia Region

THANK YOU

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