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Management of Snake bite :

Management of Snake bite Dr. Sanjib Ghosh

Snake Venom:

Snake Venom More than 20 different constituents •Mainly proteins, enzymes polypeptide toxins • Procoagulation • Haemorrhagins enzymes & polypeptide toxins • Cytolytic or necrotic toxins • Haemolytic and myolytic phospholipases A2 • Pre synaptic neurotoxins - kraits, sea snakes • Post synaptic neurotoxins - cobra

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Cobra (Naja naja)

Cobra bite:

Cobra bite Local effects - Extensive • pain • swelling • blister formation • Systemic effects neurological effects • ptosis, diplopia, external ophthalmoplegia • dysphagia • respiratory paralysis

Krait bite:

Krait bite Local signs very minimal, paraesthesia at the site of bite • Abdominal pain, cramps, vomiting • Visual difficulties blurred vision, double vision (diplopia), Drooping of the eye lids (ptosis), external ophthalmoplegia • Dysphasia • Difficulty in speech ,breathing/ Respiratory paralysis

Viper bite :

Viper bite

Severity of Envenomation :

Severity of Envenomation Grade 0 —No envenomation—No local signs by six hours and no systemic signs by 24 hours. Grade 1 —Minimal envenomation—Local swelling and pain without progression, no systemic or lab abnormalities. Needs only pain control and careful observation. Grade 2 —Moderate envenomation—Swelling, pain, or ecchymosis progressing beyond site of injury; mild systemic signs of nausea, vomiting, perioral and scalp parasthesias and fasciculations, or lab manifestations in the form of evidence of coagulopathy. Antivenom should be given. Grade 3 —Severe envenomation—Marked local response with development of vesicles and bullae, systemic findings as in moderate plus hypotension, shock, bleeding diathesis and respiratory distress and evidence of coagulopathy plus anaemia and metabolic acidosis. Antivenom should be given. A progression of local swelling is best recognised if the circumference of bitten limb is taken every 15 minutes and a demarcation line is drawn on the upper limit of the initial swelling or the fang marks. Most envenomations become symptomatic in minutes and almost always within six hours. Delayed signs of envenomation have been reported in some species of snakes, especially kraits, so all patients with presumed dry snake bite should be admitted to hospital and observed for at least 24 hours

Management of snake bite:

Management of snake bite First aid treatment • Transport to hospital • Rapid clinical assessment and resuscitation • Detailed clinical assessment and species diagnosis • Investigations/ laboratory tests

Non poisonous snake:

Non poisonous snake

Poisonous snake:

Poisonous snake

First aid:“Do Nots”:

First aid:“Do Nots” Do not panic • Do not make any cut, scratch or incision • Do not suck at the wound • Do not apply ice packs to the bitten areas • Do not use a conventional very tight constricting band or tourniquet • Do not drink alcohol, take herbal medicine or asprin

First aid:“Dos”:

First aid:“Dos” "do it 'RIGHT'": r eassure the victim, i mmobilize the extremity, g et to the h ospital, and inform the physician of t elltale symptoms and signs Lympho-occlusive bandages or tourniquets may limit spread only at the cost of greater local tissue damage, particularly with necrotic venoms. Because tourniquets lead to higher rates of amputation and loss of function, they absolutely should not be used. Elapid venoms that are primarily neurotoxic and have no significant local tissue effects may be localized by pressure-immobilization, in which the entire limb is immediately wrapped with a bandage (e.g., crepe or elastic) and then splinted

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Pressure-Immobilization

mnemonic RIGHT:

mnemonic RIGHT R—Reassure the patient. Snake bite understandably causes great fear in the patient. Seventy per cent of all snake bites are non-venomous. Even in bites by venomous snakes, envenomation occurs in only 50% of cases. I—Immobilise in the same way as you would a fractured limb, using splint and bandage. This goes a long way in slowing the spread of the venom in the body. G—Grade the degree of envenomation (see below). This will help in assessing the need for dose of antivenom and the quantity of the initial dose. H—Admit the patient to hospital even if your hospital is not equipped for such cases. Correct initial steps will ensure stabilisation of the patient while transport is being organised. T—Take a blood sample. After the initial stabilisation, which also includes assessment of the airway, breathing, and circulation, locally clean the wound, give tetanus toxoid vaccine if the immunisation is incomplete, and insert a large bore intravenous line. A sample should be collected for: Blood grouping —This should be done immediately before coagulopathy starts after which typing may be impossible.

Clinical assessment :

Clinical assessment At least 24 hours of observation. Local swelling is usually detectable within 15 min of pit viper envenom. and within 2 h of enven. by most other vipers, but may not develop in enven. by neurotoxic species. Fang marks are sometimes invisible. Tender enlargement of regional lymph nodes is an early sign of envenom. by Viperidae, some Elapidae. All tooth sockets should be examined as this is usually the first site of spontaneous bleeding : other common sites are nose, conjunctivas, skin, and gastrointestinal tract. Persistent bleeding from venepuncture sites and other wounds implies incoagulable blood. Hypotension and shock are signs of hypovolaemia or cardiotoxicity.Ptosis is the earliest sign of neurotoxic envenom. Respiratory muscle power should be assessed objectively and repeatedly, for example by measuring vital capacity. Trismus and generalized muscle tenderness suggest rhabdomyolysis. If a procoagulant venom is suspected, coagulability of whole blood should be checked using the 20WBCT.

Treatment in hospital:

Treatment in hospital Closely monitor: (vital signs, cardiac rhythm, oxygen saturation, urine output) & a Hx is quickly obtained and a rapid, thorough physical examination is performed. All patients should be observed for 12-24 hours, as the initial manifestations may be delayed, especially with elapid bites. Pain and vomiting should be managed symptomatically. Aspirin should not be used for analgesia since this may aggravate bleeding. In severe coagulopathy with thrombocytopenia causing disseminated intravascular coagulation, large quantities of fresh frozen plasma, cryoprecipitate and platelets are required if the response to antivenin is poor

Investigations:

Investigations 20WBCT (20 minutes Whole Blood Clotting Test) • Blood urea • Serum creatinine • Serum electrolytes • Full blood count • Blood film • UFR • ECG • Respiratory rate / Tidal volume / Blood gas tensions •Input-output chart should be done daily

20WBCT (20min. Whole Blood Clotting Test):

20WBCT (20min. Whole Blood Clotting Test) 20-min. whole blood-clotting test is a useful bedside tool in remote areas → a 2-3 ml of venous blood from the victim is left undisturbed at ambient temperature for at least 20 min. The vessel containing the blood is then tipped once and may be compared with a normal control. If it has not clotted, there is haemostatic disturbance from systemic envenomation

INDICATIONS FOR ANTIVENIN:

INDICATIONS FOR ANTIVENIN Hypotension and shock, abnormal ECG, or other evidence of cardiovascular dysfunction Spontaneous systemic bleeding Incoagulable blood Neurotoxicity Haematuria Other evidence of haemolysis/rhabdomyolysis Rapidly progressive extensive local swelling Bites on digits by snakes with known necrotic venoms

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Supporting evidence of severe envenoming is a neutrophil leucocytosis, ↑ serum enzymes such as CK and aminotransferase,haemoconcentration, severe anaemia, myoglobinuria, haemoglobinuria, methaemoglobinuria, hypoxaemia, and acidosis. In the absence of systemic envenomation, local swelling involving > 1/2 the bitten limb, extensive blistering or bruising, bites on digits, and rapid progression of swelling are indications for antivenom, especially in patients bitten by species whose venoms are known to cause local necrosis

Antivenom :

Antivenom In settings with scarce antivenom, poor transport facilities, and inadequate laboratories, administration of antivenom is guided by the 20 minute whole blood clotting test and clinical symptoms. Perform the test every six hours. The protocol in the table is best suited for primary care facilities. Frequency of evaluationClotting time and neurotoxicityAntivenom in 1 hour (ml)Hourly>20 min or presence of neurotoxicity or both80-100 (first dose)Second hour from first doseWorsening neurotoxicity80-100Sixth hour from first dose and subsequently every six hoursStill >20 min80-100 and subsequently every six hours till clotting time is normalDilute antivenom in 100-500 ml of isotonic fluid or 5% dextrose. In case of neurotoxic bites, further worsening after two doses will require mechanical ventilation. Antivenom may not help at this stage. In viperine bites repeat antivenom every six hours until coagulopathy is corrected

General indications for antivenom:

General indications for antivenom Antivenom is indicated if there are signs of systemic envenom. such as: 1. haemostatic abnormalities: spontaneous systemic bleeding, incoagulable blood, or thrombocytopenia; 2. neurotoxicity; 3. hypotension and shock, abnormal ECG, or other evidence of cardiovascular dysfunction; 4. generalized rhabdomyolysis. Supporting evidence of severe envenom. is a neutrophil leucocytosis, elevated serum enzymes such as CK and aminotransferases,haemoconcentration, severe anaemia, myoglobinuria, haemoglobinuria, methaemoglobinuria, hypoxaemia, and acidosis. In the absence of systemic envenom. local swelling involving > 1/2 the bitten limb, extensive blistering or bruising, bites on digits, and rapid progression of swelling are indications for antivenom, especially in patients bitten by species whose venoms are known to cause local necrosis

Prediction of antivenom reactions :

Prediction of antivenom reactions Skin and conjunctival tests do not predict early (anaphylactic) or late (serum sickness type) antivenom reactions and should not be used. Contraindications to antivenom Atopic patients and those who have reacted previously to equine antiserum are at increased risk of developing severe antivenom reactions. In such cases, antivenomshould be given only if there is severe envenoming. Reactions may be prevented or ameliorated by pretreatment with subcutaneous adrenaline (epinephrine), antihistamine, and hydrocortisone, or a continuous intravenous infusion of 1:1 000 000 adrenaline while antivenom is being given. However, this prophylaxis is not safe enough to be recommended for routine use. Rapid desensitization is not recommended. Prior to antivenin therapy, any Hx of allergy and an intradermal sensitivity test by injecting 0.02 ml of saline-diluted antiserum at a site distant from the bite.

Starting dose, and need (if any) for re-dosing :

Starting dose, and need (if any) for re-dosing 1.Initial dose is 4-6 vials with each reconstituted and then diluted to reach a 250ccvol.incrystalloid fluid. First dose is given over 10 min. Additional doses are infused as 2 vial doses at 6, 12, and 18-hour intervals until appropriate end point has been reached.

End point of antivenom therapy:

End point of antivenom therapy Arrest of progression or improvement of clinical findings. In most cases, infusion of 8-12 vials is sufficient. However, extremely close observation for worsening systemic involvement, worsening of the patient.s condition, or increasing limb circumference with development of compartment syndrome is essential as this would require further antivenom therapy.

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2.a dosing schedule requires the administration of a loading dose of FabAV and, once initial control has been achieved, three maintenance doses 6, 12, and 18 hours later

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3. For viperid bites, antivenom administration should generally be continued as needed until the victim shows definite improvement (e.g., stabilized vital signs, reduced pain, restored coagulation). Neurotoxicity from elapid bites may be harder to reverse with antivenom. Once neurotoxicity is established and endotracheal intubation is required, further doses of antivenom are unlikely to be beneficial.

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4.Additional antivenin (e.g. the contents of 1-5 vials) should be administered if swelling progresses or if systemic features of envenoming increase in severity and new manifestations such as hypotension or reduced haematocrit appear.

Acetylcholinesterase Inhibitors in Neurotoxic Snake Envenomation :

Acetylcholinesterase Inhibitors in Neurotoxic Snake Envenomation 1. Clear, objective evidence of neurotoxicity (e.g., ptosis or inability to maintain upward gaze) should receive a trial of edrophonium (if available) or neostigmine. a.Pretreat with atropine: 0.6 mg IV (children, 0.02 mg/kg; minimum of 0.1 mg) b. Follow with: Edrophonium: 10 mg IV (children, 0.25 mg/kg) or Neostigmine: 1.5–2.0 mg IM (children, 0.025–0.08 mg/kg) 2. If objective improvement is evident at 5 min, continue neostigmine at a dose of 0.5 mg (children, 0.01 mg/kg) every 30 min as needed, with continued administration of atropine by continuous infusion of 0.6 mg over 8 h (children, 0.02 mg/kg over 8 h). 3. Maintain vigilance regarding aspiration risk, and secure the airway with endotracheal intubation as needed. Neostigmine methyl sulphate (50–100 μg/kg) and atropine, every 4 hours by continuous infusion.

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Dilute antivenom in 100-500 ml of isotonic fluid or 5% dextrose. In case of neurotoxic bites,further worsening after two doses will require mechanical ventilation. Antivenom may not help at this stage. In viperine bites repeat antivenom every six hours until coagulopathy is corrected.

Observation of the response to antivenom:

Observation of the response to antivenom General: feels better, nausea, headache etc. may disappear very quickly Spontaneous systemic bleeding: stops within 15-30 min. Blood coagulability: usually restored in 3--9 hrs Neurotoxic envenoming – post synaptic type may begin to improve 30 min to severall hrs, - pre synaptic type unlikelly to respond in this way Active haemolysis & rhabdomyolysis: in few hrs & urine returns to normall colour In shocked patients: BP may increase within the first 30-60 min

Antivenom reactions:

Antivenom reactions Early (anaphylactic) reactions: develop within 10 to 180 min of starting antivenom in between 3 and 84 per cent of patients. The incidence increases with dose and decreases when more highly refined antivenom is used, and when administration is by intramuscular rather than intravenous injection. Symptoms are itching,urticaria,cough,nausea,vomiting, other autonomic manifestations, fever, and tachycardia. Up to 40 per cent of patients with early reactions develop systemic anaphylaxis: hypotension,bronchospasm, and angio-oedema.

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Pyrogenic reactions Pyrogenic reactions result from contamination of the antivenom with endotoxin-like compounds. Fever, rigors, vasodilatation, and a fall in blood pressure develop 1 to 2 h after treatment. In children, febrile convulsions may be precipitated. Late reactions Late reactions of serum sickness type may develop between 5 and 24 days after antivenom therapy. The incidence of these reactions and the speed of their development increases with the dose of antivenom. Clinical features include fever, itching, urticaria, arthralgia (sometimes involving the temporomandibular joint),lymphadenopathy, periarticular swellings, mononeuritis multiplex, albuminuria, and, rarely, encephalopathy. This is a classical immune complex disease

Treatment of antivenom reactions :

Treatment of antivenom reactions Adrenaline is the effective treatment for early reactions; 0.5 to 1.0 ml of 0.1 per cent (1 in 1000, 1 mg/ml) is given by intramuscular injection to adults (children 0.01 ml/kg) at the first signs of a reaction. The dose may be repeated if the reaction is not controlled. Patients with profound hypotension, severe bronchospasm, or laryngeal oedema may be given adrenaline by slow intravenous injection (0.5 mg diluted in 20 ml of isotonic saline over 10–15 min). H1 blocker, such as chlorpheniramine (10 mg for adults; 0.2 mg/kg for children) should be given by intravenous injection. Pyrogenic reactions are treated by cooling the patient and giving antipyretics. Late reactions respond to an oral antihistamine such as chlorphenamine (2 mg every 6 hours for adults; 0.25 mg/kg per day in divided doses for children) or to oral prednisolone (5 mg every 6 hours for 5 to 7 days for adults; 0.7 mg/kg per day in divided doses for children).

Supportive treatment:

Supportive treatment Neurotoxic envenoming Bulbar and respiratory paralysis may lead to death from aspiration, airway obstruction, or respiratory failure. A clear airway must be maintained and, if respiratory distress develops, a cuffed endotracheal tube should be inserted or a tracheostomy performed. Provided they are adequately ventilated, patients with neurotoxic envenoming remain fully conscious with intact sensation. Anticholinesterases have a variable but potentially useful effect in patients with neurotoxic envenoming. The 'Tensilon test' should be performed in all cases of severe neurotoxic envenoming, as with suspected myasthenia gravis. Atropine sulphate (0.6 mg for adults; 50 μg/kg for children) is given by intravenous injection followed by an intravenous injection of edrophonium chloride (10 mg for adults; 0.25 mg/kg for children). Patients who respond convincingly can be maintained on neostigmine, methyl sulphate (50–100 μg/kg) and atropine, every 4 hours by continuous infusion

Hypotension and shock:

Hypotension and shock If CVP is low or there is other clinical evidence of hypovolaemia, a plasma expander, preferably fresh whole blood or fresh-frozen plasma,should be infused. If there is evidence of increased capillary permeability (e.g. facial and conjunctival edema,serous efusion,hemoconcentration, hypoalbuminaemia, etc.) it may be safer in the long term to rely on a selective vasoconstrictor such as dopamine (starting dose 2.5–5 μg/kg per min by i.v.infusion). Delayed hypotension developing about one week after bites by Burmese D. russelii may respond to intravenous hydrocortisone

Oliguria and renal failure :

Oliguria and renal failure Urine output, serum creatinine, urea, and electrolytes should be measured each day in patients with severe envenoming and in those bitten by species known to cause renal failure. If urine output drops below 400 ml in 24 h, urethral and central venous catheters should be inserted. If urine flow fails to increase after cautious rehydration, diuretics should be tried (e.g. furosemide) by slow intravenous injection, 100 mg followed by 200 mg, and then mannitol. Dopamine (2.5 μg/kg per min by intravenous infusion) has proved effective in some patients bitten by Russell's vipers. If these measures are ineffective, the patient should be placed on strict fluid balance. Peritoneal or haemodialysis will usually be required.

Local infection at the site of the bite :

Local infection at the site of the bite Bites by some species (e.g. Bothrops spp., C. rhodostoma) are likely to be complicated by local infections caused by bacteria in the snake's venom or on its fangs. This should be prevented with penicillin, chloramphenicol, or erythromycin and a booster dose of tetanus toxoid, especially if the wound has been incised or tampered with in any way. An aminoglycoside such as gentamicin should be given for 48 h if there is evidence of local necrosis.

Management of local envenoming :

Management of local envenoming Bullae are best left intact. The bitten limb should not be elevated as this increases the risk of intracompartmental ischaemia. Once definite signs of necrosis have appeared (blackened anaesthetic area with putrid odour or signs of sloughing), surgical debridement, immediate split-skin grafting, and broad-spectrum antibiotic cover are indicated.

Intracompartmental syndrome and fasciotomy :

Intracompartmental syndrome and fasciotomy Increased pressure within tight fascial compartments such as the digital pulp spaces and anterior tibial compartment may cause ischaemiaand. The signs are excessive pain,weakness of the compartmental muscles and pain when they are passively stretched, hypoaesthesia of skin supplied by nerves running through the compartment, and obvious tenseness of the compartment. Detection of arterial pulses by palpation or Doppler does not exclude intracompartmental ischaemia. Intracompartmental pressures exceeding 45 mmHg carry a high risk of ischaemic necrosis. In these circumstances, fasciotomy may be justified, but it did not prove effective in saving envenomed muscle in experimental animals. Fasciotomy is contraindicated until blood coagulability has been restored. Early adequate antivenom treatment will prevent the development of intracompartmental syndromes in most cases. Necrosis of digits is especially common.

Haemostatic disturbances:

Haemostatic disturbances Once specific antivenom has been given to neutralize venom procoagulants, restoration of coagulability and platelet function may be accelerated by giving fresh whole blood, fresh-frozen plasma, cryoprecipitates (containing fibrinogen, factor VIII, fibronectin, and some factors V and XIII) or platelet concentrates. Heparin has been used to treat a variety of snake bites, usually with disastrous results. Heparin did not prove beneficial in patients envenomed by Echis ocellatus . Other drugs Corticosteroids, antifibrinolytic agents (aprotinin–Trasylol and e-amino-caproic acid), antihistamines, trypsin, and a variety of traditional herbal remedies have all been used, but none has proved effective and many are potentially harmful. Treatment of snake venom ophthalmia When cobra venom is 'spat' into the eyes, first aid consists of irrigation with generous volumes of water or any other bland liquid which is available. Unless a corneal abrasion can be excluded by fluorescein staining or slit-lamp examination, treatment should be the same as for any corneal injury: a topical antimicrobial such as tetracycline or chloramphenicol should be applied. Instillation of antivenom is not recommended. A 0.1 per cent adrenaline eyedrop preparation relieves the pain.

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INDIAN SCENARIO

Repeat Doses: Anti Haemostatic :

Repeat Doses: Anti Haemostatic In the case of anti haemostatic envenomation, the ASV strategy will be based around a six hour time period. When the initial blood test reveals a coagulation abnormality, the initial ASV amount will be given over 1 hour. No additional ASV will be given until the next Clotting Test is carried out. This is due to the inability of the liver to replace clotting factors in under 6 hrs. After 6 hours a further coagulation test should be performed and a further dose should be administered in the event of continued coagulation disturbance. This dose should also be given over 1 hour. CT tests and repeat doses of ASV should continue on a 6 hourly pattern until coagulation is restored, unless a species is identified as one against which Polyvalent ASV is not effective.

Anti Haemostatic Maximum ASV Dosage Guidance :

Anti Haemostatic Maximum ASV Dosage Guidance The normal guidelines are to administer ASV every 6 hours until coagulation has been restored. However, what should the clinician do after say, 30 vials have been administered and the coagulation abnormality persists? There are a number of questions that should be considered. Firstly, is the envenoming species one for which polyvalent ASV is effective? For example, it has been established that envenomation by the Hump-nosed Pitviper (Hypnale hypnale) does not respond to normal ASV. This may be a cause as, in the case of Hypnale, coagulopathy can continue for up to 3 weeks!

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The next point to consider is whether the coagulopathy is resulting from the action of the venom. The maximum venom yield from say a Russells Viper is 147 mg, which will reduce the moment the venom enters the system and starts binding to tissues. If 30 vials of ASV have been administered that represents 180 mg of neutralising capacity. This should certainly be enough to neutralise free flowing venom. At this point the clinician should consider whether the continued administration of ASV is serving any purpose, particularly in the absence of proven systemic bleeding. At this stage the use of Fresh Frozen Plasma (FFP) or factors can be considered, if available

Recurrent Envenomation :

Recurrent Envenomation When coagulation has been restored no further ASV should be administered, unless a proven recurrence of a coagulation abnormality is established. There is no need to give prophylactic ASV to prevent recurrence (Srimannarayana et al, 2004). Recurrence has been a mainly U.S. phenomenon, due to the short half-life of Crofab ASV.

Repeat Doses: Neurotoxic :

Repeat Doses: Neurotoxic The ASV regime relating to neurotoxic envenomation has caused considerable confusion. If the initial dose has been unsuccessful in reducing the symptoms or if the symptoms have worsened or if the patient has gone into respiratory failure then a further dose should be administered, after 1-2 hours. At this point the patient should be re-assessed. If the symptoms have worsened or have not improved, a second dose of ASV should be given. This dose should be the same as the initial dose, i.e. if 10 vials were given initially then 10 vials should be repeated for a second dose and then ASV is discontinued. 20 vials is the maximum dose of ASV that should be given to a neurotoxically envenometed patient.

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Once the patient is in respiratory failure, has received 20 vials of ASV and is supported on a ventilator, ASV therapy should be stopped. This is due to the assumption that all circulating venom would have been neutralised by this point. Therefore further ASV serves no useful purpose.

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