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• There are two important groups of venomous snake

  • Elapidae : They have short and permanently erected fangs. They include cobras, king cobras, kraits, coral snakes and sea snakes.

  • Viperidae: They have long fangs which are normally folded up against the upper jaw but, when snake strikes they are erected. They include two subgroups

    • Vipers (Viperinae)

    • Pit vipers (Crotalinae)

Composition Of Venom

• Procoagulant enzymes : Venom of snakes like russells viper has several different procoagulant which activate different steps of the clotting cascade. The result is formation of fibrin in the blood stream. Most of them are destroyed by the bodys own fibrinolytic system resulting in consumption coagulopathy.

• Haemorrhagins : That damage endothelial lining of blood vessel walls causing spontaneous systemic haemorrhage.

• Cytolytic or necrotic toxins : these digestive hydrolases ,polypeptide toxins and other factors increase permeability increase in local swelling.

• Hemolytic and myolytic phospholipase A: These enzymes damage cell membranes, endothelium, skeletal muscle, nerves and red blood cells.

• Pre synaptic neurotoxins (Elapidae): These are phospholipase A2 , that damage nerve endings , initially realsing acetylcholine transmitter, then interfering with release.

• Post synaptic neurotoxins: These polypeptide compete with acetylcholine for receptors in the neuromuscular junction and lead to curare like paralysis.

SIGNS & SYMPTOMS

Early Symptoms & Signs

• Initially there will be pain due to penetration fangs followed by increasing pain(Burning, bursting, thrombing) at the site of bite.

• Local swelling that extends proximally up the bitten limb.

• Tender, painful enlargement of the regional lymph node (Femoral/inguinal : lower limbs; at elbow/axilla : Upper limb )

• Krait bites may not have any fangs.

Local Symptoms And Signs In Bite

• Fang marks

• Local pain

• Local bleeding

• Bruising

• Lymphangits

• Lymph node enlargement

• Inflammation (Swelling, redness)

• Blistering

• Local infection, abcess formation

• Necrosis.

Systemic Symptoms & Sign

• General : Nausea, vomiting,malaise, abdominal pain, weakness, drowsiness, prostration.

• Cardiovascular (viper): Visual disturbance, dizziness, faintness, collapse, shock, hypoperfusion, cardiac arrythmias, pulmonary oedema, conjuntival oedema.

• Bleeding and clotting diorders (viperidae)

  • Bleeding from fang marks, venepuncture site

  • Spontaneous bleeding from gums , epistaxis, bleeding into the tears, hemoptysis, haematemesis, rectal bleeding or malena, haematuria, vaginal bleeding, bleeding into skin (petechiae purpura, ecchymoses) , intracerebral bleed.

• Neurological (Elapidae, Russell's viper) : Drowsiness, parasthesiae, abnormalities of taste and smell, heavy eyelids , ptosis, external opthalmoplegia, 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, hyperkalemia, cardiac arrest, acute renal failure.

• Renal (Viperidae, sea snakes) : Low back pain, haematuria, haemoglobinuria, myoglobinuria, oliguria/anuria, symptoms & signs of uremia(acidotic breathing, hiccups, nausea, pleuritc chest pain)

• Endocrine (Acute pitutary/ adrenal insufficency)

  • Acute phase : Shock, hypoglycemia

  • Chronic phase : Weakness, loss of secondary sexual hair, amenorrhea, testicular atrophy, hypothyroidism.

Neurotoxic envenoming

• Ask the patient to look up and observe fully whether upper lids retract fully.

• Test eye movements for evidence of early external opthalmoplegia

• Check the size and reaction of the pupils .

• Ask the patient to open the mouth and protrude the tongue, any early restriction of mouth opening may indicate trismus (sea snake)

• Check facial muscles, gag reflex, tongue.

• The muscle flexing the neck may be paralysed producing a “ broken neck sign”.

Bulbar and respiratory paralysis

• Early signs of bulbar palsy: asses the swallowing, accumulation of secretions are an early signs of bulbar paralysis.

• Paradoxical breathing: Indicates that diaphragm is contracting but accessory muscles and intercostal muscles are paralysed (abdomen expands rather than chest on attempt inspiration)

INVESTIGATION

20 MINUTE WHOLE BLOOD CLOTTING TEST

• Place 2 ml of freshly sampled venous blood in a small, new, dry glass vessel.

• Leave the tube undisturbed for 20 minutes at ambient temperature.

• Tip the vessel once.

• If at the end of 20min the blood is not clotted then it means that patient has hypofibrinogenemia due to venom induced consumption coagulopathy.

• If the vessel used for test is not made of ordinary glass or if it has been cleaned with detergent, its wall may not stimulate clotting of the blood sample (surface activation factor XII-Hageman factor) and the test will be invalid .

• Glass antibiotic bottles can be used as an alternative after cleaning with 0.9% Saline for IV infusion without any added detergent of other cleansing agent, followed by hot air drying.

• PT & aPTT : They more sensitive laboratory test that are rapid and relatively simple to perform . An INR >1.2 is suggestive of coagulopathy .

• WBC : Neutrophil leucocytosis can be seen

• Peripheral smear :Microagiopathic hemolysis

• Platelet count: May be decreased.

• RFT

• Creatinine kinase may be elevated particularly in sea snake bites.

• ECG : Abnormlaities like bradyacardia, ST-T wave changes, varying AV Block & evidence of hyperkalemia .

MANAGEMENT

• Reassure the victim who may be very anxious .

• Immobilise the bitten limb with a splint or sling because any movement or muscular contraction may increase absorption into the blood stream and lymphatics.

• Consider pressure immobilisation for some elapid bites.

• Avoid any interference with bite wound as it may introduce infection , increase absorption of venom, increase bleeding.

PRESSURE IMMOBILISATION

• It is recommended for bites by neurotoxic elapid snakes, including sea snakes but should not be used for for viper bites because it may increase local effect of necrotic venom.

• An elasticated, strechy, crepe bandage approx 10cm wide and atleast 4.5m long should be used.

• The bandage is bound firmly around the entire bitten limb, starting distally around the fingers or toes and moving proximally to include a rigid splint.

• The bandage is bound as tight as for a sprained ankle, but not so tight that pulses are occluded.

ANTIVENOM

• It is a immunoglobulin purified from the serum or plasma of a horse or sheep that has been immunised with the venoms of one or more species of snake.

• Two types : Monovalent/ Polyvalent

• Polyvalent venom : Indian cobra, Indian krait, Russels viper, Saw scaled viper

• Antibodies raised against one species may have cross neutralizing activity against other venoms.

• Polyvanlent antivenom is the antivenom available in India.

• This is known as paraspecific activity.

INDICATION

• Systemic Envenoming

• Hemostatic abnormalities : Positive 20 WBCT , INR >1.2 or PT >4.5econds above laboratory value , spontaneous systemic bleeding from distant site, Thrombocytopenia<10000

• Neurotoxic sign : Ptosis, external opthalmoplegia, paralysis

• Cardiovascular sign : Hypotension, shock cardiac arrythmia

• Acute renal failure, oliguria/anuria, rising blood creatinine/ urea

• Haemoglobinuria/myoglobinuria, generalised rhabdomyolysis

• Local Envenoming

• Local swelling involving > half of the bitten limb within 48 hours of bite.

• Swelling after bites on digits.

• Rapid extension of swelling (beyond wrist or ankle within few hours of bites on hand or feet)

• Enlarged lymph node draining the region.

Contraindication

• No absolute contraindication to antivenom treatment

• Person who had history of reaction to treatment with Anti tetanus serum, Anti rabies and those with severe atopic disease should be given antivenom only if systemic enevnomation is present.

• Subcutaneous epinephrine adult dose 0.25mg of 0.1% solution is given just before antivenom treatment is started, followed by IV antihistamines. Prophylatic B2 agonist inhalation may be given for asthmatic .

Storage and forms of antivenoms

• They available as lyophilized antivenoms has half life of 5 yrs should be stored below 25 Cand liquid antivenoms has half life of 2-3 yrs and stored at 2-8C and not frozen.

Administration

• Freeze dried (lyophilised antivenom) are reconstituted , usually with 10ml of sterile water for injection per ampoule. It can be administrated as

1. IV push 2ml/min. It is economical, saving IV fluid, cannula,

2. IV infusion : It is diluted in 5-10ml of isotonic fluid per kg body weight (5% dextrose or NS)and is infused at a constant rate over 30-60 minutes.

• Adrenaline should always be available at bed side, ideally drawn up in readiness before antivenom is administrated.

DOSE : It is actually variable according to the company and their strength of the venom. There is no proper standard guidelines .

WHO has put up some guidelines depending on the manufactures and species,

ANTIVENOM REACTION

• Early Anaphylatic reactions : Usually within 10 – 180 min of starting antivenom patient may develop itching , utricaria, dry cough, fever, nausea, vomiting, abdominal colic, diarrhea & tachycardia. Minority of the patient may develop severe life threatening anaphylaxsis: hypotension, bronchospsasm & angioedema.

• Pyrogenic reaction : they usually develop 1-2 hrs after treatment. Symptoms include rigors, fever, vasodilatation & fall in BP. They are due to pyrogen contamination during manufacturing.

• Late serum sickness type reaction: They develop 1-12 days after treatment. They include fever, nausea, vomiting, diarrhea, itching, recurrent utricaria, athralgia, myalgia, lymphadenopathy, periarticulr swelling, mononeuritis multiplex, proteinuria with immune complex nephritis.

Treatment of early anaphylatic & pyrogenic reaction

• Antivenom to be suspended temporarily

• Adrenaline is given 0.5mg IM (Deltoid/Upper lateral aspect of thigh) child :0.01mg/kg

• Adrenaline is administrated even on initial signs of utricaria, itching, tachycardia, restlessness .

• It can be repated after 5-10 min

• After adrenaline H1 antihistamine like chlorpheniramine malate is administrated (Adults : 10mg, childrens 0.2mg/kg IV)

• Followed Inj Hydrocortisone 100mg IV (2mg/kg childrens) : they prevent recurrence of anaphylaxis

• H2 receptor antihistamine like ranitidine has a role in treatment of anaphylaxis (Adults:50mg , childrens 1mg/kg)

• In patients who remain shocked and hypotensive should be laid supine with their legs elevated and given IV volume replacement with 0.9% saline.

• Epinephrine infusion at 1-4 mcg/minute increased to maximum of 10mcg/min in patients remaining hypotensive.

In pyrogenic reaction : External cooling, Paracetamol , IV fluid to correct hypovolemia.

Treatment of late serum sickness reaction

• They responds to 5 day course of antihistamine .

• Those who fail to respond in 24-48 hrs 5 day course of prednisolone should also be given.

• DOSE CPM: 2mg q 6h , children 0.25 mg/kg/d in divided doses

Prednisolone: 5mg q 6h, childrens 0.7mg/kg in divided doses for 5-7 days

CRITERIA FOR REPEATING ANTIVENOM

• Persistence or recurrence of blood incoagulability after 6hrs or bleeding after 1-2 hrs

• If neurotoxicity/ cardiovascular signs are worsening after 1-2 hrs.

NEUROTOXIC ENVENOMING

• Maintain Airway & Breathing

Trial of Anticholienesetarse (Tensilon test)

• A trial of anticholinesterase should be performed in every patient with neurotoxic envenoming .

1. Baseline observations or measurements are made against which to assess the effectiveness of acetylcholinesterase .

2. Atropine 0.6mg , childrens 50mcg/kg body weight is given IV to prevent muscarinic effect of cholinesterase like increased secretions, sweating , bradycardia, colic.

3. Followed by endorphonium (Adults 10mg, childrens 0.25mg/kg IV over 2-3 min); Neostigmine (Adults : 0.02mg/kg, childrens : 0.04mg/kg )

4. Patient is observed for next 10-20 min for improvement ; 30-60 min incase of neostigmine. Ptosis may disappear, FEV1 or maximum expiratory pressure may improve.

5. Patient responding convincingly are treated with Neostigmine 0.5-2.5 mg every 1-3 hours up to 10 mg/24 hours maximum for adults or 0.01-0.04 mg/kg every 2-4 hours for children by IM,IV or SC together with atropine to block muscarinic side effects. Patients tolerating oral route can be given 0.6mg atropine BD, Neostigmine 15mg q 6h

TREATMENT OF COMPLICATIONS

Hypotension & Shock

• Primary Causes : Anaphylaxsis, vasodilatation, cardiotoxicity, hypovolaemia

• Secondary cause: Antivenom reaction, respiratory failure, septicemia, acute pitutary adrenal insufficiency

• Hypotension is usually due to volume loss into the swollen limb, internal or external bleed.

• Treatment is adequate fluid replacement , CVP guided.

• Dopamine infusion for BP supports

• Hydrocortisone if pitutary insufficiency.

Renal Failure

Oliguric phase of renal failure

• CVP guided fluids

• Fluid challenge ; depending on the volume status a fluid bolus upto 250-500ml over 1 hour can be given in 1hr. Manintain a CVP of 10-12.

• Frusemide : 100mg IV can be given slowy if an output 40ml/h is not achieved then 200mg can be given or mannitol can be given.

• Mannitol: 200ml of 20% mannitol can be infused IV over 20min. Risk of fluid and electrolyte dearrangemanet.

• Dialysis :

1. Clinical uremia

2. Fluid overload

3. Creatinine >6mg/dl

4. Urea >200mg/dl

5. Potassium >7mEql

6. Symptomatic acidosis

Diuretic phase : Adequate salt and water replacement. Watch for hypokalemia.

Persisting renal failure : 25% of patients following russels viper require prolonged maitaince dialysis and sometimes renal transplantation. Renal biopsy may show renal cortical necrosis.

Hemolytic disturbance : FFP, Cryoprecipitate, Blood transfusion, Platelet transfusion.

Treatment Of Bitten Part

• The oral flora of wild snakes includes aerobic & anareobic bacteria, especially fecal gram negative rods.

• In asia, local bite wound infection may be due to single or multiple bacteria including gram positive aerobes (Staph. Aureus, coagulase negative staphylococcus& enterococcus), aerobic gram negative bacteria (E.Coli, Klebsiella, pseudomonas, enterobacter, morganella morganii), anaeorbic bacteria (Peptostreptococcus & bacteroides fragilis)

• Antibiotic coverage : Amoxycilin or cephalosporin + metronidazole+ single dose of gentamycin is recommended along with Tetanus Prophylaxis.

Compartment Syndrome

• Fasciotomy is done only if hemostatic abnormality is corrected.

• Clinical evidence of intracompartmental syndrome is present and pressure 40>mmHg.

Update on 24/6/2017

Reference: Guidelines for the management of snake bite ; 2^nd Edition : WHO south east asia region.2016

Note

• Intravascular hemolysis causing haemoglobinuria and renal failure is a frequent occurrence in rusell's viper.

• Humped nose pit viper also cause renal fialure but saw scaled usually does not.