March 2015 | Vol 20 | Issue 1 Journal of Mahatma Gandhi Institute of Medical Sciences

Snake bite poisoning

H. S. Bawaskar, P. H. Bawaskar

Introduction

Snake envenoming is a disease of poverty.[1] Envenoming by poisonous animals (snakes, scorpions, wasps, ants, and spiders) is an occupational hazard often faced by farmers, farm laborers, hunters, and shepherds of tropical and subtropical countries. Poisoning by venomous snake bite is a common acute life-threatening, time-limiting medical emergency. In the rural area, snake bite poisoning is a leading cause of death of young earning member of the family. More than 2,000,000 snake bites are reported in the country, and it is estimated that >50000 people die of snakebite each year.[2,3] Newly posted or inexperienced doctors and inadequate facilities at primary health center (PHC), ignorance of conventional treatment of snake bite by doctors; further delays appropriate treatment of victims and contribute to increasing morbidity and mortality.[4] It is the surprise to note that snake bite poisoning is seldom mentioned as a priority for health research in the developing country like India.

Snake-venom antigen detection Kits should be made available. Mono-specific antivenom producers in India should be encouraged to prepare antivenom from venom obtained from snakes caught from relevant areas of the country.[5,6]

Snakes

Of more than 3000 known species of snakes, only about 300 are venomous and in India there are about 216 identifiable species of snakes, of which 52 are known to be poisonous. The major families of poisonous snakes in India are Elapid which includes common cobra (Naja naja), king cobra and common krait (Bungarus caerulus, Banded krait, Sind krait), viperidae (Russell’s viper), Echis carinatus (saw-scaled or carpet viper), and pit viper and hydrophiidae (sea snakes). Recently, venomous viper called hope nosed viper is reported from Cochin region. During monsoon season, fatal snake bites are common to feature in local newspaper].[7] Table 1 highlights the risk factors predisposing to snake bites. Table 2 gives the characteristics of various snakes.

Biochemistry, Physiological, and Pathology of Envenoming

Snakes are cold-blooded, highly specialized animals. A pair of salivary glands secretes a powerful

Bawaskar Hospital and Clinical Research Center, Mahad, Raigad, Maharashtra, India

Address for correspondence:Dr. H. S. Bawaskar, Bawaskar Hospital and Clinical Research Center, Mahad, Raigad, Maharashtra, India. E-mail: himmatbawaskar@rediffmail.com

AbstrAct

Envenoming by venomous snake evokes a life-threatening response. Rapid diagnosis of acute hemorrhagic disorders, neurorespiratory, renal, and hemodynamic failure subsequent to snake bite and their rapid interventions saves life. Early administration of the appropriate dose of potent snake antivenom along with adjuvant treatment, proper care of the wound, correcting electrolyte imbalance, tissue oxygenation, and maintenance of adequate nutrition may help rapid recovery.

Keywords: Antisnake-venom, cobra, krait, snake bite, viper

Access this article online

Quick Response Code:Website: www.jmgims.co.in

DOI: 10.4103/0971-9903.151717

Toxicology symposia – Review Article

Bawaskar and Bawaskar: Snake bite poisoning6

Journal of Mahatma Gandhi Institute of Medical Sciences March 2015 | Vol 20 | Issue 1

multipurpose enzyme fluid (venom) that flow at the time of envenoming through fine channeled or grooved teeth called fangs. Venom secretion in all venomous snakes appears to vary in seasons; more in warmer

months with high morbidity and fatality. Snake is cold blooded animal. Darker the snake, it secretes more venom as compared to a light colored. Because of the rise in body temperature of dark skin (poor conductor

Table 1: Risk factors involved in accidental snake envenomingConditions Predisposed individualsBarefoot walking in the dark, sleeping on the floor, use of open toilets All but mostly farmers, cattle grazers, school childrenHandling of rubbles blindly over attic, firewood, cattle shades, near dwellings mud house with multiple groves, wattle, and daub houses

Housewives, laborers, young children

Chula (furnace made of mud use for cooking food at village) Housewives, housekeepers/cleanersThe ash remains in the Chula is warmer in winter and cold in summer a pleasant environment to attract the snake-like krait

Catching snake/handling snake Untrained, unskilled snake catchers without proper instruments and requirement

Table 2: Characteristics of different snakes [Figure 1]Species Characteristics Factors predisposing to biteCobras Cobras are fast, graceful poisonous snakes that have a hood and raise the front part

of their body off the ground in a distinctive way. The Indian cobra is favored by snake charmers and measure 1.2-1.7 m (4-5½ feet).

Cobra bite tends to occur during daytime and early darkness while going to open the toilet, while playing near the loose stones or basement of the house, searching ball in bushes, putting sticks in grooves and improper, careless handling while rescuing the cobra.

Krait Krait is 1-4 feet long with enlarged hexagonal vertebral scales, uniform white or red belly and narrow white crossbars on the back, more or less distinctly in pairs; the crossbars are typically absent near the head and neck region. The common krait resides in the vicinity of human habitation, near the wattle and daub, mud, and small hut dwelling. Krait is nocturnal, terrestrial snake that enters human dwellings in search of prey such as rats, mice, and lizards. It eats even the small snakes (cannibalism). The common krait is regarded as the most dangerous species of venomous snake in Indian subcontinentBanded krait its head is slightly broader than the neck, tail is short and round tip. Body is covered with equally spaced wide, yellow/pale brown/white and black bands. It lives in termite mounds and rodent burrow close to the waterBanded krait is seen West Bengal, Assam, Bihar, Orissa Madhya Pradesh, Andhra Pradesh, Chandrapur district of Maharashtra

Most bite occurs during cooler months of June to December, when snakes may, during the course of hunting activity, linger on a person’s bedding to take advantage of the warmth therein.Banded krait though is much active during the night, but more reluctant to bite than common krait.

Sea snakes Sea snake bite cases are reported from the coastal region. Fishermen accidentally handle the sea snake result in envenoming

Russell’s viper or Daboia or viper Russell siamensis

It is 3-5 feet long snake. Head is covered with small scales and without shields. Body is massive, cylindrical, narrowing at both ends. Head is flat, triangular with a short snout, large gold-flecked eyes with a vertical pupil and large open nostrils. Round belly with constricted neck. Typical rows of oval (Rudraksha) arranged in two rows is characteristic of Russell’s viper. Its natural prey includes mice, rats, frogs, lizards, snakes and birds. Young are cannibalistic. Female produces 20-60 young’s usually around June or July. Length of fangs in adult snake is 16 mm long and curved. The amount of venom injected at the time of the bite is 63+ - 7 mg. It inhabits 10 South Asian countries. In Pakistan, India, Sri Lanka, Bangladesh, Burma and Thailand, it ranks amongst the most important causes of snakebite mortality.

While protecting the paddy, wheat by containing the rodent (rats) population, it kills many farmers unlucky enough to tread on it during harvest.Bite occurs while reaping or handling rice or Jawar or sugar cane husk bundles. At times, snake is trodden while walking in growing grass. Snake catcher often gets snake bite because of careless handling. Long sharp curve fangs can bite through a simple cloth bag in which temporarily caught snake is kept.

Echis cariniatus or saw scaled viper or carpet viper

It is of size 1-3 feet long. Head of this snake is sub ovate with short rounded snout. Body is cylindrical, short and snout. Body is covered with rough, serrated flank scales, neck is distinctly constricted. Its color is pale brown, tawny with dark brown. A cruciform or trident or arrow type or just like the bird footprint shaped mark seen on the head. It flourishes in hot and humid climate all over the coastal region of India. It is an alert, active, diurnal in habit and capable of quick movement when necessary. It hibernates in the winter. It often climbs onto shrubs and other low vegetation. Readiness with which it bites on the smallest provocation with extremely rapid strike makes it is one of the dangerous snakes. It forms a double coil in the form of the figure of 8 with its head in the center a striking position. The coils keep moving against each other, and serrated keels on the flank scales produce a hissing noise by friction. It is viviparous producing 3-15 young at a time. It injects 0.0046 g venom at the time of the bite

Farmers, hunters, laborers, and person walking barefoot at peddler or in the jungle and rocky areas often bitten by this snake

Green pit viper and bamboo pit (Trimeresurus)

Pit viper victims report during the monsoon season.

Bawaskar and Bawaskar: Snake bite poisoning 7

March 2015 | Vol 20 | Issue 1 Journal of Mahatma Gandhi Institute of Medical Sciences

of heat) snake, the venom is in more fluid state and injected rapidly with high speed and maximum quantity in a short time during envenoming. As oppose to light colored skin because of low body temperature, the venom is thick and hence less amount is injected at the time of envenoming.[8]

It is quite clear that snake venom is not a substance evolved to attack man or any big vertebrates. Snake can bite and continue to secrete venom a number of times in succession. Most snakes inject 10% of the available venom in a single strike except the Russell’s viper which injects 75% of stored venom in one bite due to big long sharp curved fangs.[7] At times snake only bite without envenoming called as “defence bite or dry bite” ;while the bite with envenoming is called as the “professional bite”.

Venom is a cocktail of 20 or more components including proteins, enzymes, nonenzymatic polypeptide toxins, nontoxic nerve growth factors,

hyaluronidase, metalase, lipids, free amino acids, nucleotides, carbohydrates, biogenic amines, and various activators and in activators of physiological processes.[6] Krait and cobra venom contains acetylcholine (Ach) esterase, phospholipase B, and glycerophosphatase. Phospholipase A2 is found in the majority of venom and is extensively studied. It destroys mitochondria, red blood cells (RBCs), leukocytes, platelets, peripheral nerve endings, skeletal muscles, vascular endothelium, presynaptic neurotoxicity, opiate-like sedative effects, and auto pharmacological release of histamine (anaphylaxis). Hyaluronidase promotes the spread of venom through the tissue. Proteolytic enzymes are responsible for local changes in permeability leading to edema, blistering, bruising, and local necrosis.[6,7]

Cobra venomCobra venom is of smaller molecular size and rapidly absorbed into circulation. Absorption is further accelerated by threat of death, running and hence the liberated catecholamine and running due to fear can kill the victim within 8 min. Cobras unlike the krait deposit its venom deeply. This in combination with hyaluronidase allows spreading of the venom to occur rapidly and symptoms to arise abruptly. Interestingly, this rapidity of onset of symptoms prompts the rural victim in India to seek care quickly after cobra bite.[9] Severe, irreparable local tissue is lost at the bite site of cobra envenoming due to myocytolysis. Cobra venom is rich in postsynaptic neurotoxins called alpha-bungarotoxin and cobratoxin. Cobra venom binds especially to Ach receptors, prevents the interaction between Ach and receptors on postsynaptic membrane result in neuromuscular blockade. Cardio- toxin content of cobra venom has direct action on skeletal, cardiac, smooth muscles, nerves and neuromuscular junction causes paralysis, circulatory, respiratory failure, cardiac arrhythmias, various heart block and cardiac arrest because the venom releases calcium ions from the surface membrane to the myocardium.

Common Indian krait (Bungarus caeruleus) — (Local names — Kala gandait, kala taro, kandar, manyar, chitti, kattu viriyan, valla pamboo)Common Indian krait venom contains both presynaptic beta bungarotoxin and alpha bungarotoxin. These toxins initially release Ach at the nerve endings, at neuromuscular junction and then damage it subsequently preventing the release of Ach. Irrespective of Krait, its venom is 10 times more lethal than cobra.

Figure 1: Different types of snakes, (a) and (b) Cobra, (c) and (d) krait, (e) Russell’s Viper, (f) and (g) is saw scaled viper and its fangs

a

c

f

e

b

d

g

Bawaskar and Bawaskar: Snake bite poisoning8

Journal of Mahatma Gandhi Institute of Medical Sciences March 2015 | Vol 20 | Issue 1

But unfortunately unlike as in cobra bite, the victim reports too late due to delayed clinical manifestations. Krait is nocturnal in habit. Its fangs are small size like that of insulin needle. It injects the venom into skin or skin deep. It accidentally bites a person sleeping on floor bed.[8,10-12] Though venom is of small molecular size it is absorbed slowly as skin has poor circulation and reflexes are blunted during sleep.[11] Neuromuscular blockade by the short chain neurotoxin (cobra toxin, alpha bungarotoxin) is more readily reversible than with a long chain toxin (beta bungarotoxin). Beta bungarotoxin in the krait venom bears similarity to botulinum toxin.[6,9,13] Preserved tendon reflexes in botulism differentiates it from krait bite. Krait venom has a great affinity towards presynaptic Ach receptors. Thus, the tissue having high concentration of this receptors are affected in the following order, such as sphincter pupillae, levator palpebral superioris, neck muscles, bulbar muscles, subsequently limbs and lastly the diaphragm and intercostals muscles. Venom acts as early as 30 min and till 18 h.[9] Envenoming by krait has an early phase profound paralysis which lasts for 30 to 60 minutes, followed by deep paralysis phase which lasts for 2 to3 days and then recovery phase ranging from 2 to 3 weeks.

Viper (Russel viper)Viper venom interferes with blood clotting. Venoms contain serine proteases, metalloproteinases, C-type lectins, disintegrins, and phospholipases, and it exhibits both anticoagulant and procoagulant effects on blood clotting mechanism resulting in defibrination syndrome or disseminated intravascular fibrino-coagulopathy.[14,15] Russell’s venom is a rich source of enzymes that activates factor X to convert prothrombin to thrombin in presence of calcium factor V and platelets thus Russell’s venom contains several different “pro-coagulants” which activate different steps in the clotting cascade.[14-16] The fibrinolytic activity of the viper venom is so fast that sometimes within 30 min of the bite, the coagulation factors are so depleted that blood does not clot. Russell’s venom activates the clotting system of the snake’s natural prey with such speed that Macfarlane a brilliant hematologist was “left feeling it is almost too clever to be true.”[17] Haemorrhagins-1, 2 and metallo-endopeptidase causes acute rapid bleeding in brain, lungs, kidney, heart, and gastrointestinal tract.[16,18] It causes severe vasoconstriction followed by vasodilatation of the microvessels. Endothelial gaps due to disintegration of the endothelial cells within intracellular edema, swollen mitochondria, dilated

endoplasmic reticulum, and separation of intracellular junction of the endothelial cells. Local loss of basement membrane of the vessels leads to capillary leaking syndrome and a resistant shock [Table 3].[14-16,18]

Management of Snake Bite

First aid (to be given at the time when bite occurs)1. If one can locate the bite site, remove the surface

deposited venom by clean cloth or cotton.2. Keep the bitten part below heart level.3. Crepe bandage from the distal end of the bite site

with a pressure equal to that one can easily put and remove the finger underneath the bandage.

4. One should not kill the time in search of the snake. If the snake is found or killed take it to hospital, it may help to doctor for diagnosis.

5. Victim should not be allowed to walk.6. Do not incise at the site of the bite.7. If the victim is found unconscious without

respiration, the relatives should start mouth to mouth respiration and chest compressions.

First response at the healthcare facility (primary health center, hospital etc.)1. History — site of the bite, activity at the time of the

bite, time of bite, visualization/recognition of the snake.

2. Symptoms suggestive of neuromuscular palsy (ptosis, respiratory difficulty, dysphagia, weakness of limbs, etc.) should be specifically asked for.

3. Initial clinical signs should be noted in detail such as heart rate, blood pressure, respiratory rate, one min counting test, oxygen saturation, bulbar palsy, muscle power, tendon reflexes, pooling of saliva, broken neck sign. These signs to be closely monitored every hour till clinical improvement. Electrocardiogram should be recorded for arrhythmias. Serum electrolytes and renal profile should be done.

4. Give injection tetanus toxoid to all patients provided blood is clotted in 20WBCT.

5. Intramuscular injection to be avoided in viper bite envenoming may result in huge hematoma.

20 Minutes Whole Blood Clotting Time

Before the injection of anti-snake-venom (ASV) take 2-3 ml of patients’ blood in a new dry glass test tube which is not irrigated by any detergents. Keep the tube undisturbed for 20 minutes and then tip it off, if blood

Bawaskar and Bawaskar: Snake bite poisoning 9

March 2015 | Vol 20 | Issue 1 Journal of Mahatma Gandhi Institute of Medical Sciences

Table 3: Signs and symptoms of different snakesSnake Signs and symptomsCobra [Figure 2] Regional lymphadenopathy is often absent

Victim experiences severe pain at bite site having a fangs marksRapid progression of swellingSkin at and around the bite site is ecchymosed. Subsequently developed tense blebs and massive damage of skin and subcutaneous tissue due to myocytolysis result in huge nonhealing ulcersVictim may die of cardiac lethal ventricular arrhythmias or cardiogenic shock due to massive myocardial infarction, due to a surge of catecholamines because of the threat of deathSinus bradycardia, A-V block and hypotension due to cardio-depressant action of venomSudden respiratory arrest without any other neurological manifestations can occur resulting in anoxic cardiac arrest. Rapid ptosis and bulbar palsy accompanied with respiratory depression can occurRarely hematotoxic effects are seenBlurring of vision and loss of accommodation is earliest most sign of neurological envenoming[4,11,19-21]

Common Indian krait

Acute abdominal pain (due to cholecystokinin release),[8,9,22] vomiting, staring look, blurring of vision, gooseflesh, salivation, hypertension, pulmonary edema (autonomic symptoms)A syndrome of neuromuscular paralysis that falls into three distinct phases. The first phase is rapid onset phase leading profound paralysis within 30-60 min. The second phase is a stable phase of deep paralysis lasting 2-3 days. The third phase is a recovery phase 2-3 weeks.[13] This explains the prolonged period of ventilators support and intensive care requirements essential for recovery[10-12]

Envenoming by different species of krait in addition can cause resistant neuroparalysis[23] hyponatremia[24] renal failure,[25] hyperkalemia, myocytolysis, myocardial damage with lethal arrhythmias, pulmonary edema, hypertension.[26-28]

T wave inversion in electrocardiograph due to hypoxia, accompanied with vague chest discomfort due to respiratory muscle weakness and dysphasiaBradycardia, sweating, raised blood pressure, pulmonary edema, starring look, blurring of vision or at times photophobiaPtosis, pulling of saliva, difficult to protrude the tongue beyond teeth margin, slurred or nasal twang speech, aphasia dysphagia, dyspnea, external ophthalmoplegia, weakness of neck muscle, respiratory muscle and lastly the diaphragmQuadriplegia with aphasia and dilated pupils locked in syndrome may be diagnosed as brain death. Patient can only communicate by flicker of toes and fingers or pelvic girdle. Frontalis muscle has dual nerve supply may be spared in locked in syndrome, patient attempt to move this muscle on command movement can be felt by putting palm over forehead confirm patient is conscious hence it is called pseudo-coma. Venom induced paralysis of pupillary muscle causing nonreactive dilated pupils should not be taken as a sign of irreversible brain damage

Viper (Russell’s viper) [Figure 3]

Acute renal failure due to viper bite is attributed to hypotension due to raised circulating bradykinin, hypovolemia due to blood loss either by external bleed or accumulation in compartment severe ongoing edema. Renal tubular blockade by free hemoglobin, myoglobulin, hyperkalemia, tubular damage, interstitial nephritisVictim experience severe local pain at the site of the biteWithin 6-8 h rapid swelling progresses to the whole limb may extend to abdominal or chest wallLocal ecchymosis and tense blebs over bitten partWithin 1 h, there is regional lymphangitisRapid development of edema of muscles, bleeding result in the development of compartment syndrome, characterized by swelling, pain full passive movements, and loss of sensation over the nerve areas passing through the compartment. Subsequently, the development of wet gangrene or nonhealing ulcer. If untreated the bitten part usually toe or finger results in auto amputationsLymph nodes proximal to the bite become enlarged and tender. Tenderness along hunter’s canal often noted, over bitten lower limbHemostatic failurePro-coagulant content of venom causes initiate rapid thrombosis, hypofirbinogenelmia as result of consumption coagulopathyHematuria, bleeding in the skin, and pituitary hemorrhageRussell’s bite victims subsequently developed amenorrhea, Sheehan’s syndrome, loss of libido due hypopituitarism reported from south part of India.[29-31]

Enhanced capillary permeability seen in the form of pleural, pericardial effusion, ascites and conjunctival hemorrhage or congestions resistant shock syndrome responsible for a high fatality (capillary leaking syndrome)Ptosis, bulbar palsy, internuclear ophthalmoplegia and respiratory paralysis due to presynaptic neuromuscular block in a Russell’s viper bite poisoning often seen and reported from Kerala and Sri Lanka[32]

Sea snakes Headache, sweating, vomiting tingling numbness, foreign body sensation in the throat and swelling of the tongueWithin 30 min to 3 h after bite victim experience severe muscle pain, marked tenderness all over muscles, trismus, muscular paralysis, respiratory arrest, without local manifestations at the site of the biteDue to myotoxic effects of the venom resulting in liberation of potassium into circulation followed by tented T waves, widened QRS complexes and diastolic cardiac arrestMassive liberation myoglobin into circulation, it blocks the renal tubules, and acute renal shut down. Brown colored urine a diagnostic of myoglobinuria

Echis cariniatus or saw scaled viper or carpet viper [Figure 4]

Soon after the bite within 1 h there is development of swelling over the bitten partSwelling progress more than one segmentsWithin 60-120 min victim experience a painful lymphadenopathy at drainage area of the bitten partIf untreated swelling progressed to the whole limb or the chest wallEcchymosis seen over the bitten part or may spread over lymphatic drainage areasAcute bleeding in the form of gum bleeds or bleeding from abrasion on the other part of the body or from the venipuncture site seen within 90-120 min of bite. At times, patient remains untreated bleeding persisted for 1-2 weeks in the form of blood stain sputum, hematuria and disappeared of its ownNatural immunity against the echis carinatus venom developed in cases of repeated bite by same species in an endemic areas as minimum clinical involvement in subsequent bite reported in Jammu regionRenal failure due to echis carinatus reported from Pondicherry and Jammu areas but not from Maharashtra.[33]

Green pit viper/bamboo viper

Rarely victim manifests external bleeding or renal failure. Snake bite cases are reported from Kerala characterized by local edema and rarely a systemic bleeding disorderCoagulopathy and renal failure due to hump-nosed pit viper snakebite have been reported from Kerala state which was previously thought of a nonvenomous snake

Bawaskar and Bawaskar: Snake bite poisoning10

Journal of Mahatma Gandhi Institute of Medical Sciences March 2015 | Vol 20 | Issue 1

did not clot, it confirms hypofibrinogenemia and that the venom action is persisting. This test should not be repeated before 6 h of the last dose of ASV as liver takes 6 h for regeneration of clotting factors.[34]

Antisnake-venom

In India, we have polyvalent antivenom available which acts against krait, cobra, Russell’s viper and

Echis. It accelerates the dissociation of the toxin — receptors complexes and reverses the paralysis. On arrival of the patient, 100 ml (10 vials) ASV is added to 200 cc of normal saline and given to the patient over 30-50 min. One should sit by the side of the victim for early diagnosis and treatment of anaphylaxis. Within 30 min after initial dose of ASV if there is no improvement of neurological manifestations one can repeat dose of ASV and no more than total 20 vials of ASV to be administered. ASV neutralizes circulating venom and it has no action once the venom is attached to the receptor site. In krait bite, its venom destroys receptors thus neurological manifestation may persist for 2 to 3 weeks till there is regeneration of receptors. At this stage, administration of ASV is merely a waste. No amount of antivenom is going to reverse the ptosis or neuroparalysis till regeneration of receptors.

Antivenom should be administered as soon as signs of systemic or severe local swelling are noted. The mean times between envenoming and death are 8 h (12 min to 120 h) in cobra, 18 h (3-63 h) in Bungarus caeruleus, 3 days (15 min to 264 h) in Russell’s viper and 5 days (25-41 days) for Echis cariniatus. The approximate serum half-life of antivenom in envenomed victims ranges from 26 to 95 h. Before discharge, envenomed victims should be closely observed daily for minimum 3-4 days.[6,9]

Antivenom Reaction and its Management

No skin test should be performed before giving ASV as it does not give any surety regarding reaction. It is merely killing vital time. Antivenom should not be given intramuscularly. It should be administered by a qualified person who has knowledge of the anaphylaxis reaction and its management. However, snake catchers or trekkers should take with them few ampoules of ASV in case of an accident, so as to make is readily available to a doctor.[4]

Reaction of ASV can develop within 10-180 min. The incidence is increased with dose of antivenom and speed of administered. Bolus dose may give rapid reaction. A turbid solution of ASV may precipitate severe reaction and hence should be thrown away

Earliest symptoms are hotness in ears, scalp, itching over scalp, urticaria, sudden onset of intractable cough, nausea, vomiting, goose skin, giddiness often complained of uneasiness, suffocation, and irrelevant

Figure 2: Characteristics of cobra bite (a) severe tissue damage at bite site (b) bilateral ptosis

a b

Figure 3: Characteristics of Russell’s vipers bite (a) oedema with blood oozing from site of bite, (b) wet gangrene, (c) extensive oedema upto the groin, (d) gum bleed

a

c

b

d

Figure 4: Characteristics of Echis carinatus bite (a) tense bleb at the site of bite, (b) active gum bleed, (c) active epistaxis

a

b c

Bawaskar and Bawaskar: Snake bite poisoning 11

March 2015 | Vol 20 | Issue 1 Journal of Mahatma Gandhi Institute of Medical Sciences

behavior. Febrile reactions due to contamination of ASV with endotoxin like compounds may cause fever, rigors, vasodilatation, and hypotension which can occur within 1-2 h of treatment. Children get febrile convulsions.

Systemic anaphylaxisSudden onset of projectile profound vomiting, sphincter relaxation, hypotension, bronchospasm, foreign body sensation in throat and angioedema. These reactions are due to complement activation by immune complexes or aggregates of immune globulin.

Delayed reaction serum sickness can develop between 5 and 24 days of ASV therapy. Incidence of this depends upon the dose of ASV but is rare. This delayed reaction is clinically characterized by pyrexia of unknown origin, itching, arthralgia, lymphadenopathy, joint swellings, mononeuritis multiplex, albuminuria, and rarely encephalopathy. Low dose of adrenaline, promethazine, and hydrocortisone can be used as prophylaxis against anaphylaxis reaction.[35]

Management of Reaction

In case of reaction, injection adrenalin 0.5 ml of 0.1% to be administered by intramuscular route on the lateral aspect of the thigh. Dose can be repeated if not controlled. In a situation where life is at stake, that is, severe hypotension, bronchospasm, laryngeal edema adrenalin to be given in the dose of 1000 µg (1 ml) diluted in 9 cc of normal saline. A total of 10 cc of this solution can be given 1 ml intravenously every 3-5 min till reaction is reduced. In addition to this, intravenous aminophylline, head low position, intravenous normal saline, H1 blocker, chlorpheniramine maleate, intravenous methyl prednisolone, nasal oxygen may be helpful. Sometimes, patient may require endotracheal intubation and ventilation. Irrespective of due care and when reaction is over; during re-administration of ASV, the patient can develop re-reaction. In such situation, one can select ASV from another batch and try. Patient should not die of reaction and so also not due to snake bite envenoming. One should not be afraid of administration of ASV in a severe venomous bite provided one is fully prepared to treat any severe reaction. Many victims are referred from PHC to rural or district hospital without giving ASV and succumb on way to the hospital.

Emergency Management

Basic cardiopulmonary resuscitationAll patients found unconscious at home and not breathing should start receiving chest compressions and mouth to mouth respiration en-route to the hospital.

Endotracheal intubation and ventilationIndicated if victim has pooling of saliva, unable to lift the neck from pillow, muscle power <3/5, reduction in oxygen saturation, signs of respiratory failure like abdominal-thoracic respiration, signs of cerebral hypoxia. At the periphery, one can do endotracheal intubation, or if not possible a laryngeal mask can be put directly over larynx and ambu bag ventilation.

Management of Specific Snake Bites

Cobra biteCobra venom is reversibly attached to postsynaptic receptors. Acetylcholinesterase inhibitor (AChEI) like neostigmine 50 µg/kg over 1st h and then 25 µg/kg next four hours preceded by atropine (to counter the muscarinic action of AChEI). Or alternatively, 0.5 mg neostigmine half hourly proceeded by atropine, may help the majority of victim to recover within 24 h. This cycle may not be required more than 5-6 times.[4,5,8,9,19-21,36] In our experience, a victim diagnosed “dead” by the peripheral doctor only by absence of respiration and nonreacting pupils was recovered with artificial ventilation, cardiopulmonary resuscitation, and AChEI.[4,37] Local wound care is done by intravenous antibiotic, daily dressing and may require plastic surgery. One should always rule out diabetes mellitus in a non-healing wound in any snake bite.

Krait biteIndian common krait venom contains both pre and postsynaptic blocker. Whether the victim will respond to AChEI or not can be tested by putting an ice-filled glove finger over eyelid. Hypothermia sensitizes the Ach receptors.[38] If there is a slight improvement in ptosis, one can try AChEI.[39-42] Recently, we found envenoming by kokan krait (light coppery color) respond to AChEI.[4]

Sea snakesPatient may require a ventilator for respiratory failure. Electrolyte imbalance especially hyperkalemia needs to be corrected (diuretic, glucose-insulin, salbutamol inhalation, calcium gluconate). In case of resistant

Bawaskar and Bawaskar: Snake bite poisoning12

Journal of Mahatma Gandhi Institute of Medical Sciences March 2015 | Vol 20 | Issue 1

hyperkalemia, one can try potassium channel drug oral glibenclamide provided one takes care of hypoglycemia.

Russell’s viper or Daboia or viper Russell siamensisOne of the most common and dreaded complication of Russell’s vipers bite is DIC, which can be diagnosed by thrombocytopenia, abnormal crenated RBCs in peripheral blood smear. In addition to ASV, one has to try plasma products and whole blood transfusion which is rare required if ASV is administered in time with an adequate dose. Hypotension can be managed with fluid and inotropic agents. Severe hypotension due to bleeding in adrenal and pituitary glands and abdominal bleed and endothelial dysfunction with capillary leak may need heavy doses of intravenous methylprednisolone.[4,6,7] One should keep in mind and look for renal failure from time of admission. Risk factors such as hypotension, hypovolemia should be corrected. There are lot of controversies regarding early introduction of diuretic, acetylcysteine or allopurinol in renal failure. However, in our experience, intravenous frusemide 80-100 mg and oral acetylcysteine 600 mg 3 times a day may help to arrest the renal damage, but this needs a randomized controlled trial. In a situation of renal failure with raised serum potassium, it may be treated with frusemide drip at rural areas or peritoneal dialysis or referred to higher center for hemodialysis.[4,18] Irrespective of the standard dose of ASV many victims develop renal failure. This is particularly reported from Marathwada region. Thus venom procured from this region should be used to prepare antivenom against Russell’ s viper which kills many farmers, sugarcane labors and deserts many families.

Local wound care is most important to avoid disability. Once the clotting mechanism is reversing (20 min whole blood clotting time), the edematous limb can be elevated with rest on the pillow below the knee. Glycerin Magsulf dressing, aspiration of tense blebs by sterile needle and syringe, debridement of dead tissues, intravenous antibiotics and avoiding surgical decompression unless absolute essential remain the mainstay of treatment here.

Echis cariniatus or saw-scaled viper or carpet viperDue to the possibility of renal failure and bleeding due to this snake envenomation more ASV is required in states of Jammu and Pondicherry (ASV >100 ml) to correct bleeding disorder as compared to Maharashtra (ASV approx 30-50 ml).[43] This snake runs rapidly in a

grown up grass hence victim may feel injury by thorn prick and failure of administration of ASV on wrong history result in many amputation of limb,..Thus a farmer or labourer with rapid development of swelling within one hour while walking bare feet in grown of grass or bund, attributed to a thorn, is often a case of Echis bite envenoming.

Green pit viper and bamboo pit (Trimeresurus)The polyvalent ASV available in India does not cover for envenomation with these two vipers. However, empirical treatment with polyvalent venom should be offered as paraspecificity may sometimes help to alleviate the envenoming.[44]

When there is doubt regarding species of snake in such situation, one can manage the case on syndromic approach.[45]

Conclusion

Scientists should make attempts to prepare venomous toxoid to immunize the farmers and risky population against venomous snake toxins. Toxicologists should make an attempt to prepare the pharmacological antidote to venom actions. Antivenom producers in India should prepare ELISA kit for detection of venom antigen in blood and prepare antivenom from venoms obtained from snakes caught from relevant areas of the country. The attending doctor gets immense satisfaction when the serious poor victim of snake bite recovers.

References1. Harrison RA, Hargreaves A, Wagstaff SC, Faragher B,

Lalloo DG. Snake envenoming: A disease of poverty. PLoS Negl Trop Dis 2009;3:e569.

2. Mohapatra B, Warrell DA, Suraweera W, Bhatia P, Dhingra N, Jotkar RM, et al. Snakebite mortality in India: A nationally representative mortality survey. PLoS Negl Trop Dis 2011;5:e1018.

3. Bhaumik S. Snakebite: A forgotten problem. BMJ 2013;346:f628.

4. Bawaskar HS, Bawaskar PH, Punde DP, Inamdar MK, Dongare RB, Bhoite RR. Profile of snakebite envenoming in rural Maharashtra, India. J Assoc Physicians India 2008;56:88-95.

5. Bawaskar HS, Bawaskar PH. Profile of snakebite envenoming in western Maharashtra, India. Trans R Soc Trop Med Hyg 2002;96:79-84.

6. Williams D, Gutiérrez JM, Harrison R, Warrell DA, White J, Winkel KD, et al. The Global Snake Bite Initiative: An antidote for snake bite. Lancet 2010;375:89-91.

7. Warrell DA, Gutiérrez JM, Calvete JJ, Williams D. New approaches & technologies of venomics to meet the challenge of human envenoming by snakebites in India. Indian J Med Res 2013;138:38-59.

Bawaskar and Bawaskar: Snake bite poisoning 13

March 2015 | Vol 20 | Issue 1 Journal of Mahatma Gandhi Institute of Medical Sciences

8. Bawaskar HS, Bawaskar PH, Bawaskar PH. Premonitory signs and symptoms of envenoming by common krait (Bungarus caeruleus). Trop Doct 2014;44:82-5.

9. Warrell DA. Injuries, envenoming, poisoning, and allergic reaction caused by animals. In: Oxford Text Book of Medicine. 4th ed. p. 923-45.

10. Kularatne SA. Common krait (Bungarus caeruleus) bite in Anuradhapura, Sri Lanka: A prospective clinical study, 1996-98. Postgrad Med J 2002;78:276-80.

11. Bawaskar HS, Bawaskar PH. Envenoming by the common krait (Bungaraus caeruleus) and Aian Cobra (Naja naja): Clinical manifestations and their management in a rural setting. Wilderness Environ Med 2004;15:257-88.

12. Agrawal PN, Aggarwal AN, Gupta D, Behera D, Prabhakar S, Jindal SK. Management of respiratory failure in severe neuroparalytic snake envenomation. Neurol India 2001;49: 25-8.

13. Dixon RW, Harris JB. Nerve terminal damage by beta-bungarotoxin: Its clinical significance. Am J Pathol 1999;154:447-55.

14. Isbister GK. Procoagulant snake toxins: Laboratory studies, diagnosis, and understanding snakebite coagulopathy. Semin Thromb Hemost 2009;35:93-103.

15. Isbister GK. Snakebite doesn’t cause disseminated intravascular coagulation: Coagulopathy and thrombotic microangiopathy in snake envenoming. Semin Thromb Hemost 2010;36:444-51.

16. Myint-Lwin, Warrell DA, Phillips RE, Tin-Nu-Swe, Tun-Pe, Maung-Maung-Lay. Bites by Russell’s viper (Vipera russelli siamensis) in Burma: Haemostatic, vascular, and renal disturbances and response to treatment. Lancet 1985;2: 1259-64.

17. Macfarlane RG. Russell’s viper venom, 1934-64. Br J Haematol 1967;13:437-51.

18. Chugh KS. Snake-bite-induced acute renal failure in India. Kidney Int 1989;35:891-907.

19. Theakston RD, Phillips RE, Warrell DA, Galagedera Y, Abeysekera DT, Dissanayaka P, et al. Envenoming by the common krait (Bungarus caeruleus) and Sri Lankan cobra (Naja naja): Efficacy and complications of therapy with Haffkine antivenom. Trans R Soc Trop Med Hyg 1990;84:301-8.

20. Punde DP. Management of snake-bite in rural Maharashtra: A 10-year experience. Natl Med J India 2005;18:71-5.

21. Kularatne SA, Budagoda BD, Gawarammana IB, Kularatne WK. Epidemiology, clinical profile and management issues of cobra (Naja naja) bites in Sri Lanka: First authenticated case series. Trans R Soc Trop Med Hyg 2009;103:924-30.

22. Warrell DA. Guidelines for the Management of Snake-Bites. World Health Organization; 2010. p. 1-129.

23. Prasarnpun S, Walsh J, Awad SS, Harris JB. Envenoming bites by kraits: The biological basis of treatment-resistant neuromuscular paralysis. Brain 2005;128:2987-96.

24. Trinh KX, Khac QL, Trinh LX, Warrell DA. Hyponatraemia, rhabdomyolysis, alterations in blood pressure and persistent mydriasis in patients envenomed by Malayan kraits (Bungarus candidus) in southern Viet Nam. Toxicon 2010;56:1070-5.

25. Faiz A, Ghose A, Ahsan F, Rahman R, Amin R, Hassan MU, et al. The greater black krait (Bungarus niger), a newly recognized cause of neuro-myotoxic snake bite envenoming in Bangladesh. Brain 2010;133:3181-93.

26. Agarwal R, Aggarwal AN, Gupta D. Elapid snakebite as a cause of severe hypertension. J Emerg Med 2006;30:319-20.

27. Agarwal R, Singh AP, Aggarwal AN. Pulmonary oedema complicating snake bite due to Bungarus caeruleus. Singapore Med J 2007;48:e227-30.

28. Pillai LV, Ambike D, Husainy S, Khaire A, Captain A, Kuch U. Severe neurotoxic envenoming and cardiac complications after the Bite of a ‘Sind Krait’ (Bungarus cf. sindanus) in Maharashtra, India. Trop Med Health 2012;40:103-8.

29. Krishnan MN, Kumar S, Ramamoorthy KP. Severe panhypopituitarism and central diabetes insipidus following snake bite: Unusual presentation as torsades de pointes. J Assoc Physicians India 2001;49:923-4.

30. Tun-Pe, Phillips RE, Warrell DA, Moore RA, Tin-Nu-Swe, Myint-Lwin, et al. Acute and chronic pituitary failure resembling Sheehan’s syndrome following bites by Russell’s viper in Burma. Lancet 1987;2:763-7.

31. Antonypillai CN, Wass JA, Warrell DA, Rajaratnam HN. Hypopituitarism following envenoming by Russell’s vipers (Daboia siamensis and D. russelii) resembling Sheehan’s syndrome: First case report from Sri Lanka, a review of the literature and recommendations for endocrine management. QJM 2011;104:97-108.

32. Kularatne SA. Epidemiology and clinical picture of the Russell’s viper (Daboia russelii) bite in Anuradhapura, Sri Lanka: A prospective study of 336 patients. Southeast Asian J Trop Med Public Health 2003;34:855-62.

33. Bhat RN. Viperine snake bite poisoning in Jammu. J Indian Med Assoc 1974;63:383-92.

34. Sano-Martins IS, Fan HW, Castro SC, Tomy SC, Franca FO, Jorge MT, et al. Reliability of the simple 20 minute whole blood clotting test (WBCT20) as an indicator of low plasma fibrinogen concentration in patients envenomed by Bothrops snakes. Butantan Institute Antivenom Study Group. Toxicon 1994;32:1045-50.

35. de Silva HA, Pathmeswaran A, Ranasinha CD, Jayamanne S, Samarakoon SB, Hittharage A, et al. Low-dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: A randomised, double-blind, placebo-controlled trial. PLoS Med 2011;8:e1000435.

36. Watt G, Theakston RD, Hayes CG, Yambao ML, Sangalang R, Ranoa CP, et al. Positive response to edrophonium in patients with neurotoxic envenoming by cobras (Naja naja philippinensis). A placebo-controlled study. N Engl J Med 1986;315:1444-8.

37. Agarwal R, Singh N, Gupta D. Is the patient brain-dead? Emerg Med J 2006;23:e5.

38. Golnik KC, Pena R, Lee AG, Eggenberger ER. An ice test for the diagnosis of myasthenia gravis. Ophthalmology 1999;106:1282-6.

39. Kumar S, Usgaonkar RS. Myasthenia gravis — like picture resulting from snake bite. J Indian Med Assoc 1968;50: 428-9.

40. Banerjee RN, Sahni AL, Chacko KA, Vijay K. Neostigmine in the treatment of Elapidae bites. J Assoc Physicians India 1972;20:503-9.

41. Pandey AK, Singh AN, Sinha BN. Neostigmine in the neuroparalytic effects of snake bite. J Indian Med Assoc 1979;73:86-8.

42. Anil A, Singh S, Bhalla A, Sharma N, Agarwal R, Simpson ID. Role of neostigmine and polyvalent antivenom in Indian

Bawaskar and Bawaskar: Snake bite poisoning14

Journal of Mahatma Gandhi Institute of Medical Sciences March 2015 | Vol 20 | Issue 1

common krait (Bungarus caeruleus) bite. J Infect Public Health 2010;3:83-7.

43. Ali G, Kak M, Kumar M, et al. Acute renal failure following Echis carinatus envenomation. Indian J Nephrol 2004;14: 177-81.

44. Joseph JK, Simpson ID, Menon NC, Jose MP, Kulkarni KJ, Raghavendra GB, et al. First authenticated cases of life-threatening envenoming by the hump-nosed pit viper (Hypnale hypnale) in India. Trans R Soc Trop Med Hyg 2007;101:85-90.

45. Ariaratnam CA, Sheriff MH, Arambepola C, Theakston RD, Warrell DA. Syndromic approach to treatment of snake bite in Sri Lanka based on results of a prospective national hospital-based survey of patients envenomed by identified snakes. Am J Trop Med Hyg 2009;81:725-31.

How to cite this article: Bawaskar HS, Bawaskar PH. Snake bite poisoning. J Mahatma Gandhi Inst Med Sci 2015;20:5-14.Source of Support: Nil, Conflict of Interest: None declared.