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Blood Safety and Laboratory Technology The Clinical Management of Snake Bites in the South East Asian Region Management of Snake bites in South East Asia - Part -1 The following steps or stages are often involved Management of Snake bite First aid treatment Transport to hospital Rapid clinical assessment and resuscitation Detailed clinical assessment and species diagnosis Investigations/laboratory tests Antivenom treatment Observation of the response to antivenom: decision about the need for further dose(s) of antivenom Supportive/ancillary treatment Treatment of the bitten part Rehabilitation Treatment of chronic complications 5.1 First aid treatment First aid treatment is carried out immediately or very soon after the bite, before the patient reaches a dispensary or hospital. It can be performed by the snake bite victim himself/herself or by anyone else who is present. Aims of first aid attempt to retard systemic absorption of venom preserve life and prevent complications before the patient can receive medical care (at a dispensary or hospital) control distressing or dangerous early symptoms of envenoming arrange the transport of the patient to a place where they can receive medical care (5.2) ABOVE ALL, DO NO HARM! Unfortunately, most of the traditional, popular, available and affordable first aid methods have proved to be useless or even frankly dangerous. These methods include: making local incisions or pricks/punctures ("tattooing") at the site of the bite or in the bitten limb, attempts to suck the venom out of the wound, use of (black) snake stones, tying tight bands (tourniquets) around the limb, electric shock, topical instillation or application of chemicals, herbs or ice packs. Local people may have great confidence in traditional (herbal) treatments, but they must not be allowed to delay medical treatment or to do harm. MOST TRADITIONAL FIRST AID METHODS SHOULD BE DISCOURAGED : THEY DO MORE HARM THAN GOOD Recommended first aid methods Reassure the victim who may be very anxious Immobilise the bitten limb with a splint or sling (any movement or muscular contraction increases absorption of venom into the bloodstream and lymphatics) Consider pressure-immobilisation (Fig 39) for some elapid bites Avoid any interference with the bite wound as this may introduce infection, increase absorption of the venom and increase local bleeding As far as the snake is concerned - do not attempt to kill it as this may be dangerous. However, if the snake has already been killed, it should be taken to the dispensary or hospital with the patient in case it can be identified. However, do not handle the snake with your bare hands as even a severed head can bite! 5.1.1 The special danger of rapidly developing paralytic envenoming after bites by some elapid snakes: use of pressure-immobilisation Bites by cobras, king cobras, kraits or sea snakes may lead, on rare occasions, to the rapid development of life-threatening respiratory paralysis. This paralysis might be delayed by slowing down the absorption of venom from the site of the bite. The following technique is currently recommended: Pressure immobilisation method (Fig 39). Ideally, an elasticated, stretchy, crepe bandage, approximately 10 cm wide and at least 4.5 metres long should be used. If that it not available, any long strips of material can 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 tightly as for a sprained ankle, but not so tightly that the peripheral pulse (radial, posterior tibial, dorsalis pedis) is occluded or that a finger cannot easily be slipped between its layers. Figure 39Pressure immobilisation method. Recommended first-aid for bites by neurotoxic elapid snakes (by courtesy of the Australian Venom Research Unit, University of Melbourne) Pressure immobilisation is recommended for bites by neurotoxic elapid snakes, including sea snakes but should not be used for viper bites because of the danger of increasing the local effects of the necrotic venom. Ideally, compression bandages should not be released until the patient is under medical care in hospital, resuscitation facilities are available and antivenom treatment has been started (see Caution below). 5.1.2 Tight (arterial) tourniquets are not recommended! Traditional tight (arterial) tourniquets. To be effective, these had to be applied around the upper part of the limb, so tightly that the peripheral pulse was occluded. This method was extremely painful and very dangerous if the tourniquet was left on for too long (more than about 40 minutes), as the limb might be damaged by ischaemia. Many gangrenous limbs resulted! ARTERIAL TOURNIQUETS ARE NOT RECOMMENDED Caution: Release of a tight tourniquet or compression bandage may result in the dramatic development of severe systemic envenoming 5.1.3 Viper and cobra bites The pressure-immobilisation method as described above will increase intracompartmental pressure and, by localising the venom, might be expected to increase the locally-necrotic effects of viper venoms and some cobra venoms. Pressure bandaging is not recommended for bites by vipers and cobras whose venoms cause local necrosis. The use of a local compression pad applied over the wound, without pressure bandaging of the entire bitten limb, has produced promising results in Myanmar and deserves further study. 5.2 Transport to hospital The patient must be transported to a place where they can receive medical care (dispensary or hospital) as quickly, but as safely and comfortably as possible. Any movement, but especially movement of the bitten limb, must be reduced to an absolute minimum to avoid increasing the systemic absorption of venom. Any muscular contraction will increase this spread of venom from the site of the bite. A stretcher, bicycle, cart, horse, motor vehicle, train or boat should be used, or the patient should be carried. 5.3 Treatment in the dispensary or hospital 5.3.1 Rapid clinical assessment and resuscitation Cardiopulmonary resuscitation may be needed, including administration of oxygen and establishment of intravenous access. Airway, respiratory movements (Breathing) and arterial pulse (Circulation) must be checked immediately. The level of consciousness must be assessed. The following are examples of clinical situations in which snake bite victims might require urgent resuscitation: Profound hypotension and shock resulting from direct cardiovascular effects of the venom or secondary effects such as hypovolaemia or haemorrhagic shock. Terminal respiratory failure from progressive neurotoxic envenoming that has led to paralysis of the respiratory muscles. Sudden deterioration or rapid development of severe systemic envenoming following the release of a tight tourniquet or compression bandage (see Caution above). Cardiac arrest precipitated by hyperkalaemia resulting from skeletal muscle breakdown (rhabdomyolysis) after sea snake bite. Late results of severe envenoming such as renal failure and septicaemia complicating local necrosis. 5.4 Detailed clinical assessment and species diagnosis 5.4.1 History A precise history of the circumstances of the bite and the progression of local and systemic symptoms and signs is very important. Three useful initial questions are: "In what part of your body have you been bitten?" The doctor can see immediately evidence that the patient has been bitten by a snake (eg fang marks) and the nature and extent of signs of local envenoming. "When were you bitten?" Assessment of the severity of envenoming depends on how long ago the patient was bitten. If the patient has arrived at the hospital soon after the bite, there may be few symptoms and signs even though a large amount of venom may have been injected. "Where is the snake that bit you?" If the snake has been killed and brought, its correct identification can be very helpful. If it is obviously a harmless species (or not a snake at all!), the patient can be quickly reassured and discharged from hospital. Early clues that a patient has severe envenoming: Snake identified as a very dangerous one Rapid early extension of local swelling from the site of the bite Early tender enlargement of local lymph nodes, indicating spread of venom in the lymphatic system Early systemic symptoms: collapse (hypotension, shock), nausea, vomiting, diarrhoea, severe headache, "heaviness" of the eyelids, inappropriate (pathological) drowsiness or early ptosis/ophthalmoplegia Early spontaneous systemic bleeding Passage of dark brown urine Patients who become defibrinogenated or thrombocytopenic may begin to bleed from old, partially-healed wounds as well as bleeding persistently from the fang marks. The patient should be asked how much urine has been passed since the bite and whether it was a normal colour. An important early symptom of sea snake envenoming that may develop as soon as 30 minutes after the bite is generalised pain, tenderness and stiffness of muscles and trismus. 5.4.2 Physical examination This should start with careful assessment of the site of the bite and signs of local envenoming. 5.4.2.1 Examination of the bitten part The extent of swelling, which is usually also the extent of tenderness to palpation, should be recorded. Lymph nodes draining the limb should be palpated and overlying ecchymoses and lymphangitic lines noted. A bitten limb may be tensely oedematous, cold, immobile and with impalpable arterial pulses. These appearances may suggest intravascular thrombosis, which is exceptionally rare after snake bite, or a compartmental syndrome, which is uncommon. If possible, intracompartmental pressure should be measured (see Annex 5) and the blood flow and patency of arteries and veins assessed (eg by doppler ultrasound). Early signs of necrosis may include blistering, demarcated darkening (easily confused with bruising) or paleness of the skin, loss of sensation and a smell of putrefaction (rotting flesh). 5.4.2.2 General examination Measure the blood pressure (sitting up and lying to detect a postural drop indicative of hypovolaemia) and heart rate. Examine the skin and mucous membranes for evidence of petechiae, purpura, ecchymoses and, in the conjunctivae, chemosis. Thoroughly examine the gingival sulci, using a torch and tongue depressor, as these may show the earliest evidence of spontaneous systemic bleeding. Examine the nose for epistaxis. Abdominal tenderness may suggest gastrointestinal or retroperitoneal bleeding. Loin (low back) pain and tenderness suggests acute renal ischaemia (Russell’s viper bites). Intracranial haemorrhage is suggested by lateralising neurological signs, asymmetrical pupils, convulsions or impaired consciousness (in the absence of respiratory or circulatory failure). 5.4.2.3 Neurotoxic envenoming To exclude early neurotoxic envenoming, ask the patient to look up and observe whether the upper lids retract fully (Fig 40). Test eye movements for evidence of early external ophthalmoplegia. Check the size and reaction of the pupils. Ask the patient to open their mouth wide and protrude their tongue; early restriction in mouth opening may indicate trismus (sea snake envenoming) or more often paralysis of pterygoid muscles (Fig 41). Check other muscles innervated by the cranial nerves (facial muscles, tongue, gag reflex etc). The muscles flexing the neck may be paralysed, giving the "broken neck sign" (Fig 42). 5.4.2.4 Bulbar and respiratory paralysis Can the patient swallow or are secretions accumulating in the pharynx, an early sign of bulbar paralysis? Ask the patient to take deep breaths in and out. "Paradoxical respiration" (abdomen expands rather than the chest on attempted inspiration) indicates that the diaphragm is still contracting but that the intercostal muscles and accessory muscles of inspiration are paralysed. Objective measurement of ventilatory capacity is very useful. Use a peak flow metre, spirometer (FEV1 and FVC) or ask the patient to blow into the tube of a sphygmomanometer to record the maximum expiratory pressure (mmHg). Remember that, provided their lungs are adequately ventilated, patients with profound generalised flaccid paralysis from neurotoxic envenoming are fully conscious. Because their eyes are closed and they do not move or speak, they are commonly assumed to be unconscious. They may still be able to flex a finger or toe and so simple communication is possible. Figure 40Examination for ptosis, usually the earliest sign of neurotoxic envenoming (Copyright DA Warrell) Figure 41 Inability to open the mouth and protrude the tongue in a patient with neurotoxic envenoming from the Malayan krait (Copyright DA Warrell) Figure 42Broken neck sign in a child envenomed by a cobra in Malaysia (Copyright the late HA Reid) 5.4.2.5 Generalised rhabdomyolysis In victims of envenoming by sea snakes and Russell’s vipers in Sri Lanka and South India, muscles, especially of the neck, trunk and proximal part of the limbs, may become tender and painful on active or passive movement and later may become paralysed. In sea snake bite there is pseudotrismus that can be overcome by sustained pressure on the lower jaw. Myoglobinuria may be evident 3 hours after the bite. 5.4.2.6 Examination of pregnant women There will be concern about fetal distress (revealed by fetal bradycardia), vaginal bleeding and threatened abortion. Monitoring of uterine contractions and fetal heart rate is useful. Lactating women who have been bitten by snakes should be encouraged to continue breast feeding. 5.4.3 Species diagnosis If the dead snake has been brought, it can be identified. Otherwise, the species responsible can be inferred indirectly form the patient’s description of the snake and the clinical syndrome of symptoms and signs (see above and Annex 1 & 2). This is specially important in Thailand where only monospecific antivenoms are available. 5.5 Investigations/laboratory tests 5.5.1 20 minute whole blood clotting test (20WBCT) This very useful and informative bedside test requires very little skill and only one piece of apparatus - a new, clean, dry, glass vessel (tube or bottle). 20 minute whole blood clotting test (20WBCT) Place a few mls of freshly sampled venous blood in a small glass vessel Leave undisturbed for 20 minutes at ambient temperature Tip the vessel once If the blood is still liquid (unclotted) and runs out, the patient has hypofibrinogenaemia ("incoagulable blood") as a result of venom-induced consumption coagulopathy In the South East Asian region, incoagulable blood is diagnostic of a viper bite and rules out an elapid bite Warning! If the vessel used for the test is not made of ordinary glass, or if it has been used before and cleaned with detergent, its wall may not stimulate clotting of the blood sample in the usual way and test will be invalid If there is any doubt, repeat the test in duplicate, including a "control" (blood from a healthy person) 5.5.2 Other tests Haemoglobin concentration/haematocrit: a transient increase indicates haemoconcentration resulting from a generalised increase in capillary permeability (eg in Russell’s viper bite). More often, there is a decrease reflecting blood loss or, in the case of Indian and Sri Lankan Russell’s viper bite, intravascular haemolysis. Platelet count:this may be decreased in victims of viper bites. White blood cell count: an early neutrophil leucocytosis is evidence of systemic envenoming from any species. Blood film: fragmented red cells ("helmet cell", schistocytes) are seen when there is micro-angiopathic haemolysis. Plasma/serum may be pinkish or brownish if there is gross haemoglobinaemia or myo-globinaemia. Biochemical abnormalities: aminotransferases and muscle enzymes (creatine kinase, aldolase etc) will be elevated if there is severe local damage or, particularly, if there is generalised muscle damage (Sri Lankan and South Indian Russell’s viper bites, sea snake bites). Mild hepatic dysfunction is reflected in slight increases in other serum enzymes. Bilirubin is elevated following massive extravasation of blood.Creatinine, urea or blood urea nitrogen levels are raised in the renal failure of Russell’s viper and saw-scaled viper bites and sea snake bites.Early hyperkalaemia may be seen following extensive rhabdomyolysis in sea snake bites. Bicarbonate will be low in metabolic acidosis (eg renal failure). Arterial blood gases and pH may show evidence of respiratory failure (neurotoxic envenoming) and acidaemia (respiratory or metabolic acidosis). Warning : arterial puncture is contraindicated in patients with haemostatic abnormalities (Viperidae) Desaturation: arterial oxygen desaturation can be assessed non-invasively in patients with respiratory failure or shock using a finger oximeter. Urine examination: the urine should be tested by dipsticks for blood/haemoglobin/myoglobin. Standard dipsticks do not distinguish blood, haemoglobin and myoglobin.Haemoglobin and myoglobin can be separated by immunoassays but there is no easy or reliable test. Microscopy will confirm whether there are erythrocytes in the urine. Red cell casts indicate glomerular bleeding. Massive proteinuria is an early sign of the generalised increase in capillary permeability in Russell’s viper envenoming. 5.6 Antivenom treatment Antivenom is the only specific antidote to snake venom. A most important decision in the management of a snake bite victim is whether or not to give antivenom. 5.6.1 What is antivenom? Antivenom is immunoglobulin (usually the enzyme refined F(ab0)2 fragment of IgG) 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. "Specific" antivenom, implies that the antivenom has been raised against the venom of the snake that has bitten the patient and that it can therefore be expected to contain specific antibody that will neutralise that particular venom. Monovalent or monospecific antivenom neutralises the venom of only one species of snake. Polyvalent or polyspecific antivenom neutralises the venoms of several different species of snakes, usually the most important species, from a medical point of view, in a particular geographical area. For example, Haffkine, Kasauli, Serum Institute of India and Bengal "polyvalent anti-snake venom serum" is raised in horses using the venoms of the four most important venomous snakes in India (Indian cobra, Naja naja; Indian krait, Bungarus caeruleus; Russell’s viper, Daboia russelii; saw-scaled viper, Echis carinatus). Antibodies raised against the venom of one species may have cross-neutralising activity against other venoms, usually from closely related species. This is known as paraspecific activity. For example, the manufacturers of Haffkine polyvalent anti-snake venom serum claim that this antivenom also neutralises venoms of two Trimeresurus species. 5.6.2 Indications for antivenom treatment (see also Annex 1 & 2) Antivenom treatment carries a risk of severe adverse reactions and in most countries it is costly and may be in limited supply. It should therefore be used only in patients in whom the benefits of antivenom treatment are considered to exceed the risks. Indications for antivenom vary in different countries. Indications for antivenom Antivenom treatment is recommended if and when a patient with proven or suspected snake bite develops one or more of the following signs Systemic envenoming Haemostatic abnormalities: spont aneous systemic bleeding (clinical), coagulopathy (20WBCT or other laboratory) or thrombocytopenia (<100 x 109/litre) (laboratory) Neurotoxic signs: ptosis, external ophthalmoplegia, paralysis etc (clinical) Cardiovascular abnormalities: hypotension, shock, cardiac arrhythmia (clinical), abnormal ECG Acute renal failure: oliguria/anuria (clinical), rising blood creatinine/ urea (laboratory) (Haemoglobin-/myoglobin-uria:) dark brown urine (clinical), urine dipsticks, other evidence of intravascular haemolysis or generalised rhabdomyolysis (muscle aches and pains, hyperkalaemia) (clinical, laboratory) Supporting laboratory evidence of systemic envenoming (see 5.5, page __) Local envenoming Local swelling involving more than half of the bitten limb (in the absence of a tourniquet) Swelling after bites on the digits (toes and especially fingers) Rapid extension of swelling (for example beyond the wrist or ankle within a few hours of bites on the hands or feet) Development of an enlarged tender lymph node draining the bitten limb 5.6.3 Inappropriate use of antivenom In some parts of the world, antivenom is given to any patient claiming to have been bitten by a snake, irrespective of symptoms or signs of envenoming. Sometimes the local community are so frightened of snake bite that they compel the doctor to give antivenom against medical advice. These practices should be strongly discouraged as they expose patients who may not need treatment to the risks of antivenom reactions; they also waste valuable and scarce stocks of antivenom. 5.6.4 How long after the bite can antivenom be expected to be effective? Antivenom treatment should be given as soon as it is indicated. It may reverse systemic envenoming even when this has persisted for several days or, in the case of haemostatic abnormalities, for two or more weeks. However, when there are signs of local envenoming, without systemic envenoming, antivenom will be effective only if it can be given within the first few hours after the bite. 5.6.5 Prediction of antivenom reactions Skin and conjunctival "hypersensitivity" tests may reveal IgE mediated Type I hypersensitivity to horse or sheep proteins but do not predict the large majority of early (anaphylactic) or late (serum sickness type) antivenom reactions. Since they may delay treatment and can in themselves be sensitizing, these tests should not be used. 5.6.6 Contraindications to antivenom There is no absolute contraindication to antivenom treatment, but patients who have reacted to horse (equine) or sheep (ovine) serum in the past (for example after treatment with equine anti-tetanus serum, equine anti-rabies serum or equine or ovine antivenom) and those with a strong history of atopic diseases (especially severe asthma) should be given antivenom only if they have signs of systemic envenoming. 5.6.6.1 Prophylaxis in high risk patients In the absence of any prophylactic regimen that has proved effective in clinical trials, these high risk patients may be pre-treated empirically with subcutaneous epinephrine (adrenaline), intravenous antihistamines (both anti-H1, such as promethazine or chloramphenicol; and anti- H2, such as cimetidine or ranitidine) and corticosteroid. In asthmatic patients, prophylactic use of an inhaled adrenergic $2 agonist such as salbutamol may prevent bronchospasm. 5.6.7 Selection of antivenom Antivenom should be given only if its stated range of specificity includes the species known or thought to have been responsible for the bite. Liquid antivenoms that have become opaque should not be used as precipitation of protein indicates loss of activity and an increased risk of reactions. Expiry dates quoted by manufacturers are often very conservative. Provided that antivenom has been properly stored, it can be expected to retain useful activity for many months after the stated "expiry date". If the biting species is known, the ideal treatment is with a monospecific/monovalent antivenom, as this involves administration of a lower dose of antivenom protein than with a polyspecific/ polyvalent antivenoms. Polyspecific/polyvalent antivenoms are preferred in many countries because of the difficulty in identifying species responsible for bites. Polyspecific antivenoms can be just as effective as monospecific ones, but since they contain specific antibodies against several different venoms, a larger dose of antivenom protein must be administered to neutralise a particular venom.