By:

Indramani Prakash(JR2)

Published in Journal of the Association of Physicians of India .2013;61:27-30

Dr. Adesh Kumar Singh(MD)

Snakebite is a major problem in rural India with morethan 2 lakh snakebites being reported in Indiaannually of which35,000-50,000 die. The only specificantidote for snakebite is administration of Anti snakevenom (ASV) with or without adjunctive treatmentsnecessary in each case. Albert Calmette introducedserum antivenin use for the treatment of envenomingin 1895 against the Indian Cobra (Naja naja) in Indiaand by Lépinay in Vietnam.

SNAKES OF INDIA

There are about 236 species of snakes in India, most of which are nonpoisonous.

However, there are 13 known species that are poisonous and of these four,

namely common cobra (Naja naja), Russell’s viper (Dabiola russelii), saw-scaled

viper (Echis carinatus) and common krait (Bungarus caeruleus) are highly

venomous and believed to be responsible for most of the poisonous bites in India.

.

Russel Viper

Saw scaled Viper

Pit Viper

COBRA

KRAIT

SEA SNAKE

-Reassure the victim that death is not imminent and medical care is available. -Control anxiety as excitement will increase heart rate and lead to spread of venom. --Make the victim lie flat with bitten limb below the heart level. -Remove shoes, rings, watches, jewelry and tight clothing from the bitten area as they can act as a tourniquet when swelling occurs. -Immobilize the victim’s bitten limb using a splint and lightly put a bandage.

Do not apply a tourniquet.Do not wash the bite site with soap or any other solution to remove the venom.Do not make cuts or incisions on or near the bitten area.Do not use electrical shock. Do not freeze or apply extreme cold to the area ofbite.Do not apply any kind of potentially harmful herbal or folk remedy.Do not attempt to suck out venom with your mouth.Do not give the victim drink, alcohol or other drugs.

Do’s…

Don’ts…

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Local symptoms and signs in the bitten part:

•fang marks, local pain, local bleeding , bruising •lymphangitis (raised red lines tracking up the bitten limb)•lymph node enlargement•inflammation (swelling, redness, heat), Blistering •local infection, abscess formation, necrosis

Generalized (systemic) symptoms and signs

GeneralNausea, vomiting, malaise, abdominal pain, weakness, drowsiness, prostration.

Cardiovascular (Viperidae)Visual disturbances, dizziness, faintness, collapse, shock, hypotension, cardiac arrhythmias, pulmonary oedema, conjunctival oedema (chemosis).

Bleeding and clotting disorders (Viperidae)Traumatic bleeding from recent wounds (including prolonged bleedingfrom the fang marks and from old partly-healed wounds. Spontaneous systemic bleeding - from gums, epistaxis, bleeding into the tears, intracranial haemorrhagerectal bleeding or melaena, haematuria, and retina.

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, nasal voice or aphonia, regurgitation through the nose, difficulty in swallowing secretions, respiratory and generalised flaccid paralysis.

Bilateral ptosis

in a patient bitten by a common krait

Russell’s viper

Subconjunctival haemorrhages in a patient bitten by a Russell’s viper

Haemoptysis from a tuberculous lung cavity in a patientbitten by a pit viper

Fatal cerebral haemorrhage in a victim of Russell’s viper bite

Treatment

ASV used in India is polyvalent and contains antivenin against cobra, Russell’s viper, krait, saw scaled viper. Each vial of ASV containing 10 ml of antivenin costs about 500 rupees. To the rural poor patients from agricultural background who are the most common victims of snake bite it is a huge burden. Another problem with ASV is that, it being a refined animal serum product some patients develop hypersensitvity reactions to it.

Anti-snake Venom Administration

Anti-snake venom should be administered only when there are definite signs of envenomation, i.e. coagulopathy or neurotoxicity. Only unbound, free flowing venom in bloodstream or tissue fluid, can be neutralized by it. It carries the risk of anaphylactic reaction and doctors should be prepared to handle such reactions.

Prophylaxis for Anti-snake Venom Reactions

Two regimens are normally recommended, i.e. hydrocortisone (100 mg) + antihistamine or 0.25–0.3 mg adrenaline subcutaneously.

Anti-snake Venom Test Dose

Test doses have not been shown to have predictive value in predicting anaphylactic reaction or late serum sickness and not recommended.

Initial Dose

• Mild envenomation (systemic symptoms manifest > 3 hours after bite) neurotoxic/hemotoxic 8–10 Vials • Severe envenomation (systemic symptoms manifest < 3 hours after bite) neurotoxicor hemotoxic 8 Vials Each vial is 10 ml of reconstituted ASV. Children should receive the same ASV dosage as adults.

Further Doses It will depend on the response to the initial dose. ASV should be administered either as intravenous infusion (5–10 mL/kg body weight) or as slow intravenous (IV) injection i.e. 2 mL/min). ASV should be administered over 1 hour at constant speed and patient should be closely monitored for 2 hours. In victims requiring life saving surgery a higher initial dose of ASV is justified (up to 25 vials) solely on the presumption that coagulation will be restored in 6 hours..

Neostigmine is an anticholinesterase, which is particularly effective in postsynaptic neurotoxins such as those of cobra and is not useful against presynaptic neurotoxin i.e. common Krait and the Russell’s viper.

Neostigmine test should be performed by administering 0.5–2 mg IV and if neurological improvement occurs, it should be continued 1/2 hourly over next 8 hours.

Neostigmine

ObjectiveTo demonstrate that use of lower doses of anti-snake venom is as effective as high doses and is associated with less complications and lower mortality especially in the wake of rising cost of medical treatment , the people most affected by snakebites being the poor farmers.

Materials and MethodsA Prospective descriptive cohort study consisting of 54 snakebite patients was undertaken to study the efficacy of low dose anti snake venom in the treatment of patients with poisonous snake bites. Signs and symptoms of systemic envenomation which included hemostatic abnormalities in the form of spontaneous GI bleeding, uncontrolled bleeding from external wounds, prolonged CT (>10 min), PT (INR>1.5), aPTT (> 2x control), neurotoxic signs such as ptosis, external ophthalmoplegia, falling single breath count, respiratory muscle paralysis – falling SpO2,hypotension (B.P<90/60 mm of Hg), shock (requiring ionotropic support),cardiac arrhythmia, abnormal ECG, Acute renal failure evidenced by oliguria, anuria, rising creatinine (>1.5 mg/dl), albuminuria, hemoglobinuria / myoglobinuria, dark brown urine were found eligible for the study.

All patients fulfilling the inclusion criteria were admittedto the ICU and were given ASV in 100ml 0.9 Normal Saline asfollows: 2 vials of ASV in 100 ml NS over 1 hr and then clottingtime repeated half an hour after completion of the ASV, if CTwas prolonged 1 vial of ASV in 100 ml NS was given over 4 hrsand CT repeated but if CT was normal 1 vial of ASV in 500ml NSwas given over 24 hrs and then CT repeated after completion. Ifrepeat CT was again prolonged 1 vial of ASV was given and CTrepeated and the same continued till CT was normal after a 24hr dose of ASV. All patients were given Tetanus toxoid and werepremedicated with Inj. Pheneramine and Inj. Hydrocortisone100 mg intravenously. Any other supportive measures asnecessary

Observation and ResultIn this study the average dose of ASV required was only 6.70±3.24 vials. The complications - 12.9% patientshad ARF, and another 12.9 % patients had neuropraralysis severe enough to require ventilatory support. Therewere 2 deaths (mortality of 3.7%) in the study.

DiscussionThere is evidence for smaller doses from past studies though small in number. But many centres are still using large doses.Guidelines also suggest high doses of ASV probably because of the small number of studies hence obviating the need for more to prove the same.

In this study the average dose of ASV required has only been6.70±3.24 vials and the maximum that was used was 19 vials inonly one patient. The complications (12.9% patients had ARF,and another 12.9 % patients had neuropraralysis severe enoughto require ventilatory support) and hard outcomes (mortality of3.7%) have been much better than studies using high doses (26% had ARF and there was 14 % mortality in the high dose groupin the study by Paul et al; 60% had ARF and there was 30 %mortality in the high dose group in the study by Srimannarayanaet al.

Also the quantity of anti venom used was independent of thebite to needle time and is more closely related to the severity ofenvenomation probably because the neutralizing dose dependson the type and quantity of venom injected.The adverse reaction to ASV has also been low (5.6%)as against 26.6% in the high dose group in the study bySrimannarayana et al. Also since the dose ASV is much smallerthan conventional regimes which use 10-25 vials of ASV it ismuch more economical while being equally efficacious, and haslesser adverse reactions and is more economical when comparedto higher doses.

ConclusionThis study has thus demonstrated that low dose ASV regime in poisonous snake bites irrespective of the severity along with supportive treatment as necessary is as efficacious as high dose regime, and has lesser adverse effects. It also lowers the cost of treatment as each vial of ASV costs about 500 rupees and a reduction in requirement of 5-10 vials of ASV reduces the drug cost alone by 2500 to 5000 rupees. Hence low dose regime can be used with beneficial results in poisonous snake bites.

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