INTRODUCTION
The Indian subcontinent is home to more than 230 species of snakes of which some are poisonous. In 4 families of venomous snakes, 6 species are responsible for snakebites & are medically important in India.
They are :-
1.Elapidae. Represented by * Cobras a. King Cobra (Ophiphagushannah)
b. Common Cobra (Naja Naja)
* Krait. (Bungarus ceruleus)
2. Hydrophilidae - Seasnakes.
3. Viperidae - Russel viper/Saw scaled vipers.
4. Atractasipidae.
Here the epidemiology, pathogenesis, clinical features and managements are discussed.
EPIDEMIOLOGY
It is widely agreed that India contributes the largest share to the annual worldwide mortality due to snake bite. Figures of mortality range from 15000,to 40,000/year in India. Hospital records the sole source of most snakebite likely to over represent the more seriously envenomed patients. As in developing countries like India 80% of victims first consult traditional healers, so population survey gives most accurate picture of diagnosis than hospital record. First of all it was SWAROOP STUDY which reported about 200,000 bites/yr and 15,000 deaths as far as back in 1954. based on epidemiologic survey of 26 villages with a total population of 19,000 in Burdwan Dist. of W.B. HARI et all worked out an annual incidence of 0.16% and mortality of 0.061%. Myanmar has the highest snake bite mortality in the world. Maharastra has highest incidence of snakebites i.e 70bites per 100,000 population/year, with mortality of 2.4/ 100,000 per year. Bengal, Tamilnadu , UP & Kerala, are other states with large no of snake bites. Chippaux study shows marked increased frequency of - illegitimate bite in Developed countries and hazardous bite in developing countries.

Age & Sex
Though all age groups of both sexes are the victims majority are 11-50 years of male suggesting special risk in outdoor activities. Males are victimized twice or thrice than females.

Time & Seasonal variation:-
Maximum incidence between 4.00pm to midnight (varies with outdoor activities). During rainfall & epidemics after floods and natural disaster.
Site of bite:-
Most frequent site of bite � Lowerlimb(2/3rd ) of which 50% occur in feet alone.
Host factors:-
Occupational hazards- for farmers, harder, hunter & fisherman.
Morbidity & mortality:-
Depends upon the species of snake involved as estimated fatal dose of the venom varies with species.
Average Yield/bite Fataldose is much smaller
1.Cobra - 60mg 12mg.
2.Russelviper � 63mg 15mg.
3. Krait � 20mg 6 mg.
4. Saw scaled viper � 13 mg 8 mg.
Severity of Envenoming:-
Depends upon the dose of venom injected, composition & potency of venom, number & depth of bites, age of the victim, site of bite, nature, timing & quality of first aid & medical treatment.

PATHOPHYSIOLOGY OF OPHITOXEMIA:-
Most complex of all poisons are mixture of enzymatic & nonenzymatic compound, nontoxic proteins including carbohydrates & metals.
Enzymes � It is a constitute of 20 different enzymes including phospholipase. A2 B, C, D, hydrolases, phosphatases, proteases, esterase, Acetyl choline esterase, transaminase, hyaluronidase, phosphodiesterase DNAse RNAse etc.

Nonenzymatic compounds are - Neurotoxins
- Haemorrhagins.
Different species have different proportion of most of it. So they are formerly categorized as neurotoxic, haemotoxic, myotoxic but strict categorization is not essential
� Neurotoxins
Cobra � Cobrotoxin & bungarotoxin causes postsynaptic blokage (at moter end plate release of Ach).
Krait � B bungarotoxin causes pre synaptic blockage
Viper � Acetylcholine esterase causes breaksdown of Ach.
� Cardiotoxins
Cobra & Taipan � cardiotoxins causes myocardial depression and cardiac arrythmias.
� Vasculotoxins
Viper � Viper venom � affects coagulation pathways at several points. Activates factors V, IX, X, XII, platelets & protein C & fibrinolysins.
Haemorrahgins � damages endothelium to produce spontaneous bleeding, potentiates platelet aggregation & favours vasodilation.
� Myotoxins
Sea snake - Myotoxins produces muscle necrosis, myoglobinuria, hyperkalaemia.
� Nephrotoxins
Vipers � Indirectly damage renal system and causes prolonged hypotension, hypovolumia and hyperkalaemia/DIC/direct damage/rhabdomyolysis.
� Locally affecting toxins are protease, phoshpolipase 2, polypeptide toxins, hyaluronidase, histamine/brady kinin, hydrolanse
� Proteolysis
(Damages RBC, leucocytes & platelet membranes & vascular endothelium & other membranes.)

Increase Vascular permeability � Local effects, (swelling, edema inflammation, gangrene).

Systemic effects.

(Hypoalbuminemia) (hypotension) (shock)
CLINICAL FEATURES
I. Snake bites with no manifestations:
Confirmed bites with no manifestations � Drybites by poisonous snakes and bite by non poisonous snakes, Large no of studies show that a lot of poisonous bites do not cause symptoms, Banerjee � noted 80% of victims have no evidence of envenomations. Reid also states that over 50% of individual bitten by poisonous snakes escape with hardly any feature of poisoning, Stainly�s 117 out of 200 cases showed envenomation, Lamb states that 30% of cobra bites are superficial.

II. Local manifestations :-
Physiological trauma is the earliest. Local reactions are marked in both families of elapidae and viperadae ( krait is the exception). Local reactions are noted within 6-8 mins but may have onset upto 30min & develop upto 24 hrs. Local pain , with radiation & tenderness and the development of small reddish wheal are first to occur followed by oedema, swelling & appearance of bullae progressing rapidly involving trunk. Tingling, numbness over tongue, parasthesia around wound local bleeding including petechial & purpuric rash � more common in viperbites. Regional lymphadenopathy is an early & reliable sign. Intercompartmental syndrome- occur in 10% of cases. Necrosis of skin, subcutaneous tissue & muscle causes increased intercompartmental pressure which leads to pain & anasthesia on stretching of intercompartmental muscles. Severe pain, absence of arterial pulses and cold segment of limbs is due to thrombosis of major arteries which may lead to dry gangrene. All the above features of local reactions are evident in elapidae but the gangrene is mostly wet gangrene. In rare instances patients may have � Raynaud�s phenomenon/ secondary infection/ tetanus/ gas gangrene.
III. Systemic Menisfestations:
The most common and earliest symptom following snake bite is fright of unpleasant & rapid death. Victim attempts flight which unfortunately results in enhanced systematic absorption of venom leading to psychological shock & even death . Fear may cause transient pallor, sweating & vomiting.
Time of onset of systemic poisoning in cobra � 5 min to 10 hrs, Viper � 20 min to several hrs and Sea snake � almost always within 2 hrs.
Systemic manifestations depend predominantly on the constituents of the venom of that particular species as neurotoxin (cobras & kraits) haemorrhagin(vipers) myotoxin(sea snake), but strict categorization is not valid.
a) Neurotoxic features
Usually within 6 hrs but may be delayed. Symptoms are usually preceded by preparalytic syndromes which includes vomiting, blurred vision, drowsiness , heaviness of head, tingling sensation of mouth. Paralysis first appears as bilateral ptosis followed by bilateral opthalmoplegia, followed by paralysis of muscles of palate jaw, tongue , larynx , neck & muscles of deglutition . Muscles innervated by cranial nerves are involved earlier. Pupils react to light till terminal stage. Reflexes are not affected usually & preserved till late stages. Muscles of diaphragm are involves late which accounts for terminal respiratory paralysis. Onset of coma is variable ( may progress to coma in 2hrs).

b) Cardiotoxic features:-
Include tachycardia, hypotension, & ECG changes. 25% of viperbite include rate/rhythm/bloodpressure fluctuation. Sudden cardiac arrests may occur due to dyselectrolytemia. Though nondyselectrolytemia MI has also been seen.
c) Haemostatic abnormalities:-
One case of nonbacterial thrombotic endocarditis-reported from, PGI Chandigarh. Bleeding from the punctured wound is the earliest feature, Blood do not coagulate due to consumption coagulopathy &haemorrhagins produce widespread bleeding detected as bleeding gum, nose, GIT (haematemesis & melaena), Urinary bladder (haematuria). Consequent to bleeding hypotension & shock occurs. Intracerebral haemorrhage may occur. Subarachnoid haemorrhage is reported in 5 in 200 cases of Saini�s series in Jammu,(most were elderly).
d) Nephrotoxicity:-
In a series of study of Clarke out of 40 viper bites renal failure was detected in 3. The extent of renal abnormalities is correlated with the amount of coagulation defect . However renal defect persisted for several days after coagulation defect normalized, suggesting that multiple factors are involved in venom induced ARF.
e) Hypotension syndromes :-
Due to increased capillary permeability � menifested by serous effusions/ pulmonary edema/ haemoconcentration/hypoalbuminemia/shock.
f) Pregnency outcomes:-
Almost all pregnant abort or present with APH/PPH.
g) Rare outcomes-
Hypopitutarism, bilateral thalamichaematoma, hysteric paralysis.
LABORATORY DIAGNOSIS:-
� History- Patient usually gives history of snakebite but it may be absent in kraitbite (painless). Although fangmarks are essential fatal envenoming do occur without identifiable marks.
� Cell counts � Neutrophillic Leucolytosis
- Anaemia
- Thrombocytopenia
- Haematocrit � Initially ( haemoconcentration), Later ( haemolysis).
� Coagulation profile - Prolonged clotting time
- Prolonged prothrombin time.
- Fibrin Degradation products ( >80 mg/dl).

� Simple bedside test
(1) Tourniquet test � Torniquet pressure of 100 � 120 mm of Hg is applied for 5 minutes � (+ve) if >5purpuric spots.
(2) Whole blood clotting test :- 5ml of blood taken in clean, dry test tube- undisturbed for 20 min � seen for clotting.
(3) Clot quality observation test (Clot retraction test):- seen for clotting after one hour

� Urine Analysis
All snake bite patients should be advised to evacuate bladder at first aid & urine examined for microscopic haematuria. It could also reveal proteinuria, haemoglobinuria or myoglobinuria.
� Features of Azotemia S.Urea , S.creatinire may be raised.
� Metabolic parameters:- Hyperkalaemia, Hypoxemia, Respiratory acidosis may occur
� Myotoxicity is evidenced by � Raised Sr.CPK, & transaminase .
� ECG shows � Nonspecific alteration in rate, rhythm, predominently bradycardia, menifestation of hyperkalemia.
� X-ray chest � To rule out pulmonary edema/Infarction/bronchopneumonia/pleural effusion
� CT scan - May be required if suspision of Intracerebral bleeding,
� Immunodiagnosis

Detection of venom antigens in bodyfluids �
Used for - Pathophysiology
- Assessment of first aid
- Antivenom dose monitoring.
ELISA test � (venom detection kits) - Highly sensitive but not specific.


MANAGEMENT
1. First aid:-
Reassurance (to flight & fright response), Immobilisation of bitten limb, No tampering of the wound is best (Reid). Aim should be to transfer the patient to nearest hospital as quickly as passively as comfortably as possible.

Controversial first aid methods which are :-
� Local incision, excision of bitten skin , cauterization, amputation of digits
It has been proved from animal studies that all these methods do not decrease systemic envenomation, rather potentates bleeding introduces infection damage tissues.
� Suction by mouth as shown in Indian cinema has been rejected by its questionable efficacy while some advocate large amount of venom can be aspirated by this method if approached within seconds.
� Introduction of chemicals are worthless ( Nowhere recommended in any textbooks& therapeutics, rather rejected by Mansoon)

2. Use of tourniquets, compressionpads, bandages (controversial):-
Manson � Tight tourniquets have been responsible for terrible morbidity & mortality in snake bite victims & should not be used .
Sautherland (Australia)- advocated a pressure immobilization method by crepe bandaging proved effective in limiting absorption of venom ( applies p.of 55of hg). It is just tightly as sprained ankle starting from toes & fingers & incorporating a splint. It should be binded so tightly that only lymphatic circulation is obliterated not arterial. One finger should be introducible between the affected part & tourniquet. Use of tourniquets may be dangerous as they can cause gangrene, fibrinolysis, bleeding from occluded limbs, peripheral nerve palsy, compartmental ischaemia , intensification of local reaction. So general consensus in Western countries is to use crepebandage & splints in Elapidae and Sea snakes bites and to be avoided in Viperbites, which are responsible of intense local reactions. Clinical trials are needed to prove the efficacy of tourniquets & Compression bandage. The patient should be transferred in Lt. Lateral decubitus position to prevent aspiration.
3. Drugs :-
Reid advocated pain relief with placebo was as effective as NSAIDS. Gellert- experienced that codeine sulfate should be given to calm the patient & to reduce autonomic hyperactivity. Vomiting � can be treated with chlorphromazine ( 25-50mg IV infusion.) Others symptoms like syncope , shock, angioedema if supervene 0.1% adrenaline S/C can be given as first aid .


4. Specific Therapy :-
A. ANTIVENOM :-
Decision � In the management of snakebite, the most important clinical decision is whether to give antivenom therapy. For only a minority of snakebite patient need it. It may produce severe reactions & it is expensive & often in short supply.
Preparation:- They are prepared by immunizing horses with venom of poisonous snakes & extracting serum & purifying it . They may be species specific monovalent form/ poly valent form . Supplied as dry powder & reconstituted with DW or NS.
INDIA � C.R.I. Kasaulli � Antivenom against 4 medically important species are available.
Hopkins institute Pune � Against 30 species are available.

INDICATIONS OF ANTIVENOM TREATMENTS
a) Systemic envenoming
Neurotoxicity (ptosis, opthalmoplegia), incoagulable blood indicating consumption coagulopathy / DIC, spontaneous systemic bleeding ( from gingival sulci , nose), hypotension ( shock), generalised rhabdomyolysis. ( stiff tender painful muscles darkurine, myoglobinuria), impaired consciousness.
b) Severe local envenoming
Extensive local swelling ( > � of bitten limb), rapidly evolving local swelling, bites on fingers and toes, wider range of indication are prescribed in wealthy countries.
Contraindications Atopic patients & those previously had reaction with equine antiserum.
Prediction of antivenom reaction :- Hypersensitivity testing by intradermal or S.C. injection of diluted antivenom have no predictive value for early and late antivenom reactions. However these tests delay the start of treatment & are not without risk.
Prevention of antivenom reactions:-
Desert et all advocated in their trial that significant reduction in ASV reactions (from 12.5 to 30%) if the patients are given adrenaline subcutaneously (0.1% of adrenaline).
It is a dictum that it is never too late to give antivenom as long as signs of venom persists (it can be given from 2 days of seasnake bite to many days after viperbite proved by Saini�s study) .

Average requirements of dose in various studies:-
1. Bhat(1974)[Jammu] Intermittent Bolus Dose
Initial � 20 ml
Repeat � 20 ml every 4to 6 hrs till clotting time (CT) normal Total Dose
80ml-in mild
100 ml � moderate
250 ml � severe.
2. Thomas & Jacob (1985) [Kerala] Continuous IV infusion 153 ml � Traditional
79 ml � modified
3. JIPMER (1994)
( Pondichery) Local envenomation :_
Systemic envenomation:-
Initial � mild to moderate
Severe defect �
Repeatdose - 50 ml Iv bolus (single)

100 ml
50-200ml
50 ml every 4 to 6 hrs till CT - normal
4. Tariang et al (1996)
( CMC Vellore)
High Dose ( 31 pts)
2 vials IV infusion over 2hrs followed by 2 vials over 4hrs 4hrly till CT becomes normal then 2vials infusion over 24hrs.
Total �89 ml Low Dose(29pts)
2vias over 1hr followed by 1vial every 4 hrly IV infusion over 24hr


Total � 47ml
5. Das et al (1999)
(JIPMER)
Despite of high dose 44.4% developed ARF and dialysis required. Total � 183.3ml(4patient)
70 ml - Bolus
30 ml over 6 hr/6hrly till CT becomes normal 153.8 ml(5pts)
30 ml bolus
30ml over 6 hr/6hrly till CT becomes normal

Suggestive tentative schedule:-
� Over various parts of the country recommended doses are:-
Viper � Initial dose � 20 to 100 ml
Repeat dose � 20 to 50 ml every (4-6) hr till CT is normal
Recurrence of coagulation defect � 20 to 50 ml.
Cobra/Krait � Initial dose � 200 ml preferred (100 ml effective)
Repeat dose � (50-100)ml 4 to 6 hrly - Until neurotropic sign disappear
King Cobra � (100-150) ml Monospecific ASV

Fab based Antivenom alt. to IgG

Dart et al 99 (1) It largely reduces the antivenom reaction
(2) Effectively reverses coagulation abnormalities.
However it requires repeated doses as � life is<12 hrs

Antivenom Reactions
Clinical features Treatment
1. Early anaphylactic reaction :-
(10 min �3 hrs) Itching, Utricaria, Vomiting, fever tachycardia
40% develop systemic hypotension bronchospasm, angioedema ( socarefull watch) -Adrenaline(0.5ml-1ml 1:1000/S.C)

Chlorpromazin 10 mg IV
(&#61613; Incidence with &#61613;dose incidence with refined antivenom and more in IM > Iv)
2. Pyrogenic reaction (1-2)hrs Fever, rigor vasodilatation Hypotension. Paracetamol(15 mg /kg)
3.Serum Sickness (7days )
(5-24 days) Fever itching arthralgia (TMJ) particular swelling mononeuritis plultiplex Albuminuria/ encephalopathy Chlorpromazin PM 2mg/4tim x5 days
Prednisolone
(5mg/4times x(5-7)days)

B. HYPOTENSION SHOCK � Fresh blood is ideal
- Ionotropic support
- I.V Hydrocortisone ( in delayed hypotension )
C. NEUROTOXICITY
� Bulbar, respiratory paralysis � cuffed endotracheal intubation / tracheostomy.
� Complete respiratory paralysis � Mechanical ventilation .
� Anticholine esterase � like Neostigmine produces a rapid useful improvement in neuromuscular transmission. Worth giving after Tensilion test
� Neostigmine � (50-100&#61549;g)/kg and atropine(0.06mg)4hrly or by continuous infusion .
D. RENAL FAILURE:
Cautious rehydration, Diureties if renal failure, Haemodialysis/ Peritoneal dialysis.
E. LOCAL INFECTION:
Tetanus toxoid, Antibiotics to prevent infection at the site of bite (chloramphenicol, erythromycin, penicillin) Bullae should be left as such, limb should not be elevated, Necrotic tissue debridgement should be done as soon as possible & denuded area should be covered with split skin graft.

F. INTERCOMPARTMENTAL SYNDROME:
Fasciotomy if I.C.P > 45mm Hg, Only after correction of coagulopathy
G. SNAKEVENOM OPTHALMIA:
Immediate wash with normal saline, Exclude corneal abrasion by slit lamp examination installation of local Antibiotic/Adrenalin to relieve pain.
H. HAEMOSTATIC DISTURBANCES:
After neutralising venom procoagulant by specific antivenom restoration of coagulability & platelet function may be achieved by giving fresh blood, fresh frozen plasma, cryoprecipitate or platelet concentrates. Heparin producing disastrous results must be avoided.
I. DRUGS:
Costicosteroids , Antitibrinolytics, Antihistaminics, trypsin and other herbal medicine have no proved efficacy rather harmful.
CLINICAL FOCUS
� As a tropical, agricultural and developing country snake bite is common in India . Few snakes are poisonous.
� Incidence is more is males with seasonal variation.
� The average yield/bite is much higher than fatal dose.
� Severity of envenoming depends on various factors.
� The venom is a complex combination of which neurotoxins haemorrhagin and myotoxins are lethal to human.
� The clinical presentation varies from local reaction (various grades) to variety of systemic manifestations.
� Diagnosis depends on history, simple bed side clot retraction test, urine analysis and other parameters depends on systemic involvement.
� Treatment protocol includes simple first aid, torniquet (controversial) symptomatic and specific antivenom (ASV) therapy.
� The antivenum has many reactions but still life saving. The dosage schedule varies in different studies and in different species of snakes.
REFERENCES
1. Mansons Textbook of Tropical diseases
2. Oxfont textbook of Medicine. Page 1; 925 � 1:935.
3. Harrisons principle of Internal medicine. Page 16th Edn 2593-2595.
4. API text book of medicine 2003, 7th Edition, 1279 � 1282.
5. www. pubmed. Com.
6. www.medfinder.com.
7. New England Jaurnal of Medicine.