The Treatment for snakebite

The Treatment for snakebite


First help 

The aim of first help is to retard the systemic absorption of venom and prevent life-threatening complications by prompt transport to a medical facility. First help can be performed by victim himself/herself or by any person who happens to be nearby. Traditionally, first aid included making local incisions or "tattooing" at the site of the bite, attempts at suctioning venom out of the wound, use of tight bands (tourniquets) around the limb, and/or local application of ice packs. None of the traditional remedies have any proven medical benefit. They should be discouraged as they do more harm than good and delay transport to a medical facility. Incision, suction, electric shocks, cryotherapy, or washing the wound are contraindicated as any interference with the wound introduces infection, increases bleeding from the site, and hastens absorption of the venom.
The current guidelines for first help include the following:
Reassure the victim (70% of all snakebites are by nonvenomous snakes and 50% of bites by venomous species are dry bites )
Immobilize the affected limb (by bandage or clothes to hold splint, but tight arterial compression is not recommended)
quickly transfer of victim to hospital
Pressure immobilization method (PIM) was gathered by the Australian Venom Research Unit, university of Melbourne, Australia, for rapidly acting neurotoxic elapid snake venom. As per the PIM, immobilization and bandaging of the bitten part is a bit like that done in the case of a sprained ankle. Studies have shown that it's seldom applied properly in simulated environments and, moreover, mobilizing the limb for more than 10 min nullifies the benefits of even the correctly applied bandage.
In most instances, health care providers, general public, or community health workers are the first responders to come to the aid of the snakebite victim. If outcomes are to be improved, it's vital that they should all be made aware of the importance of immediate immobilization of the limb and transfer to the hospital at the earliest.
Hospital treatment Emergency care department

When the patient reaches the emergency department, evaluation should begin with the assessment of the airway, breathing, circulatory status, and consciousness.
Urgent resuscitation will be recommended in those in shock (cardiovascular toxicity), those with respiratory failure (neurotoxin), and in those who have had cardiac arrest (beacuse of hypoxia, cardiac toxicity, or hyperkalemia from rhabdomyolysis).
Oxygen should be administered to every envenomed patient and a large-bore intravenous catheter should be inserted. A bolus of normal saline or Ringer's lactate should be given to all patients with suspected envenomation. The patient may then be administered specific treatment after a precise history has been taken and thorough physical examination done.
History

Attempts should be made to determine whether a venomous snake has in fact bitten the patient and, if so, the severity of the bite. it's essential to establish that the victim has been bitten by a snake and not by some other animal; this can be cross-checked by searching for fang marks and signs of local envenomation. If the victim has brought the snake, identification of the species should be carried out carefully, since crotalids can envenomate even when dead. This is why bringing the murdered snake into the ED should be discouraged. Questions should be asked to determine the time elapsed since the snakebite and a brief medical history should be obtained (e.g., date of last tetanus immunization, use of any medication, presence of any systemic disease, and history of allergy).



Physical examination

During the initial evaluation, the bite site should be examined for signs of local envenomation (edema, petechiae, bullae, oozing from the wound, etc) and for the extent of swelling. The bite site and at the rather least two other, more proximal, locations should be marked and the circumference of the bitten limb should be measured every 15 min thereafter, until the swelling is no longer progressing. The extremity should be placed in a well-padded splint for at the very least 24 h. Serial measurement of circumference helps in estimating spread of venom and effect of antivenom. [9] Lymph nodes draining the limb should be palpated and the presence of lymphangitic lines noted.
Distal pulses should be checked and monitored if there's presence of gross swelling. The presence of a pulse does not rule out compartment syndrome however, and compartment pressure should be measured directly if there's concern that a compartment syndrome is developing. The diagnosis is established if the compartment pressure, measured directly by inserting a 22G IV cannula and connecting it with manometer, is raised above 55 cm water/saline. Direct measurement is required before resorting to fasciotomy since compartment syndrome is rare in snakebite victims and fasciotomy done without correction of hemostatic abnormality may cause the patient to bleed to death.

signals for severe snake envenomation should be sought. They consist of the following:

Snake identified is a very venomous 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 systems
Early systemic symptoms
Early spontaneous systemic bleeding (particularly bleeding from the gums)
Passage of dark brown urine



   Laboratory Investigations  


Although lab tests are of little value in the diagnosis of snake envenomation, they're useful for prognosticating and for making decisions about specific interventions.

Specific investigations

(a) The 20-min whole blood clotting test (20 WBCT): The 20 WBCT is a simple bedside test of coagulopathy to diagnose viper envenomation and rule out elapid bite. It requires a new clean, dry test tube made up of simple glass that has not been washed with any detergent. A few milliliters of fresh venous blood is drawn and left undisturbed in the test tube for 20 min; the tube is then tilted gently. If the blood is still liquid after 20 min, it is evidence of coagulopathy and confirms that the patient has been bitten by a viper. Cobras or kraits dont cause antihemostatic symptoms.

(b) Enzyme linked immunosorbent assay (ELISA): ELISA tests are now available to identify the species involved, based on antigens in the venom. These tests, however, are expensive and not freely available and thus have limited value in diagnosis; at present, they find use mainly in epidemiological studies.

Other nonspecific tests include

Hemogram: The hemogram may show transient elevation of hemoglobin level due to hemoconcentration (because of the increased capillary leak) or may show anemia (due to hemolysis, especially in viper bites). Presence of neutrophilic leucocytosis signifies systemic absorption of venom. Thrombocytopenia may be a feature of viper envenomation.
Serum creatinine: This is necessary to rule out renal failure after viper and sea snake bite.
Serum amylase and creatinine phosphokinase (CPK): Elevated levels of these markers implies muscle damage (caution for renal damage).
Prothrombin time (PT) and set in motion partial thromboplastin time (aPTT): Prolongation may be present in viper bite.
Fibrinogen and fibrin degradation products (FDPs): Low fibrinogen with elevated FDP is present when venom interferes with the clotting mechanism.
Arterial blood gas and electrolyte determinations: These test are necessary for patients with systemic symptoms.
Urine examination: Can reveal hematuria, proteinuria, hemoglobinuria, or myoglobinuria. (Arterial blood gases and urine examination should be repeated at frequent intervals during the acute phase to assess progressive systemic toxicity).
Electrocardiogram (ECG): Nonspecific ECG changes such as bradycardia and atrioventricular block with ST-T changes may be seen.
Electroencephalogram (EEG): Recently, EEG changes have been noted in up to 96% of patients bitten by snakes. These changes start within hours of the bite but are not associated with any features of encephalopathy. Sixty-two% showed grade I changes, 31% cases manifested grade II changes (moderate to severe abnormality), and the remaining 4% showed severe abnormality (grade III). These abnormal EEG patterns were seen mainly in the temporal lobes.


The first blood drawn from the patient should be typed and cross-matched, as the effects of both venom and antivenom can interfere with later cross-matching.


   Specific Therapy Anti-snake venom

Anti-snake venom (ASV) are immunoglobulins prepared by immunizing horses with the venom of poisonous snakes and subsequently extracting and purifying the horses' serum. they are the only effectual antidote for snake venom. Antivenoms may be species specific (monovalent/monospecific) or may be effective against multiple species (polyvalent/polyspecific). Antibodies raised against the venom of one species may have cross-neutralizing activity against other venoms, sometimes that from closely related species. This is known as paraspecific activity. As per the recommendations of WHO, the most effective treatment for snakebite is the administration of monospecific ASV  ; however, this therapy is not always available to snakebite victims because of its high cost, frequent lack of availability, and the difficulty in properly identifying the snake.
WHO recommends that if an adequate cold chain is in place, antivenoms should be prepared in the liquid form, since this reduces production costs and avoids the potential adverse physicochemical alterations to the product often brought about by lyophilization. On the other hand, if the integrity of the cold chain cannot be guaranteed, antivenoms should be lyophilized to maintain stability.
several antivenom preparations are available internationally. In India, polyvalent antivenom prepared by Central Research Institute, Kasauli (HP) is effectual against the most common Indian species  Antivenom produced at the Haffkine Corporation, Parel (Mumbai) is effective against the venom of even more species. lists ASV producers in India, both in the public along with the private sector.
ASV is supplied in dry powder form and has to be reconstituted by diluting in 10 ml of normal saline/D 5 W. Mixing is done by swirling and not by vigorous shaking.

Indications for ASV
the recommended use of antivenom is essential and requires an informed evaluation of the patient. Not every poisonous snakebite merits its use. Antivenom treatment carries a risk of severe adverse reactions and in most countries it is expensive 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. Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) has recently been approved for use in the United States. CroFab is a venom-specific Fab fragment of immunoglobulin G (IgG) that works by binding and neutralizing venom toxins, facilitating their redistribution away from target tissues and their elimination from the body. It has been demonstrated that these fragments are safe and effectual, with a low incidence of sequelae; however, allergic reactions can occur when any animal protein derivatives are administered to human subjects. The overall incidence of immediate and delayed allergic reactions to this product appears so far to be lower than that reported with classic whole-IgG antivenom. Antivenom is indicated whenever there are signs of systemic envenomation or presence of severe local swelling.

Antivenom therapy
Antivenom should be ideally administered within 4 h of the bite, but is effectual even if given within 24 h. The dosage needed varies with the degree of envenomation.

Dose of ASV
Despite widespread use of antivenom, there have been virtually no clinical trials to determine the right dose.  The dosage has remained a matter of much debate. The classic dosing in our setup is based on the degree of envenomation 
WHO/SEARO recommends the dose of antivenom to be the amount required to neutralize the average venom yield when captive snakes are milked of their venom. Published research has indicated that the Russell's viper injects, on average, 63 mg (SD: ± 7 mg) of venom in the first bite.  As each vial of polyvalent ASV neutralizes 6 mg of Russell's viper venom, the initial dose should be 8-10 vials to ensure that the majority of the victims are covered by the initial dose; this will also aid keep the price of ASV down to acceptable levels.  As snakes inject identical amount of venom into young people and adults, children should receive the same dose of antivenom as adults.
Response to infusion of antivenom is marked by normalization of blood pressure. Within 15-30min bleeding stops, though coagulation disturbances may take up to 6 h to normalize. Neurotoxicity begins to improve within the first 30 min, but patients may require 24-48 h for full recovery.
A repeat dose of ASV should be given when there is persistence of blood incoagulability even after 6 h or continued bleeding after 1-2 h of the initial dose. ASV should also be repeated when there are worsening neurotoxic or cardiovascular signs even after 1-2 h.

ASV administration
ASV can be administered either by slow intravenous injection at a rate of 2 ml/min or by intravenous infusion (antivenom diluted in 5-10 ml per kilogram body weight of normal saline or D 5 W and infused over 1 h). Slow intravenous injection has the advantage that a doctor or nurse is present during the injection period when there is a risk of some early reaction to the ASV. All patients should be strictly observed for an hour for growth of any anaphylactic reaction. Epinephrine should always be kept ready before administration of antivenom.
ASV should never be given locally at the site of the snakebite since it has not been shown to be efficient and, moreover, this route of administration is associated with very note worthy risks. For example, it's utterly painful and may increase intracompartmental pressure. Intramuscular injections are also not preferred since ASV is composed of large molecules (IgG or fragments) which are absorbed slowly via lymphatics, making the bioavailability by this route poor as compared to intravenous administration. Other disadvantages include pain on injection and risk of hematoma formation and sciatic nerve damage in patients with hemostatic abnormalities.  Intramuscular injections should only be given in settings where intravenous access cannot be obtained and/or the victim cannot be transported to a hospital immediately.
ASV sensitivity testing
ASV sensitivity testing is no longer required as a lack of response does not predict the large majority of early (anaphylactic) or late (serum sickness type) reactions.  Such testing could also presensitize the patient to the serum protein and, in addition, occassionally delays treatment.
ASV reaction
Approximately 20% patients treated with ASV develop either early or late reaction.
Early anaphylactic reactions occurs within 10-180 min of start of therapy and is characterized by itching, urticaria, dry cough, nausea and vomiting, abdominal colic, diarrhea, tachycardia, and fever. Some patients may develop severe life-threatening anaphylaxis characterized by hypotension, bronchospasm, and angioedema.
Pyrogenic reactions sometimes develop 1-2 h after treatment. Symptoms include chills and rigors, fever, and hypotension. These reactions are caused by contamination of the ASV with pyrogens during the manufacturing process.
Late (serum sickness-type) reactions develop 1-12 (mean 7) days after treatment. Clinical features include fever, nausea, vomiting, diarrhea, itching, recurrent urticaria, arthralgia, myalgia, lymphadenopathy, immune complex nephritis and, rarely, encephalopathy.
Treatment of ASV reaction
When the patient shows signs of a reaction, antivenom administration must be temporarily stopped and adrenaline (1 in 1000) given intramuscularly in an initial dose of 0.5 mg in adults or 0.01 mg/kg body weight in children. The dose can be repeated every 5-10 min if required.
After adrenaline, an anti-H1 antihistamine such as chlorpheniramine maleate (adult dose 10 mg, small people 0.2 mg/kg) should be given intravenously. it may be followed by intravenous hydrocortisone (adult dose one hundred mg, children 2 mg/kg).
Late (serum sickness-type) reactions occassionally respond to a 5-day course of oral antihistamine (e.g., chlorpheniramine 2 mg six hourly in adults and 0.25 mg/kg/day in divided doses in young people). Patients who fail to respond within 24-48 h should be given a 5-day course of prednisolone (5 mg six hourly in adults and 0.7 mg/kg/day in divided doses in young people).
   Supportive Therapy  
The patient should be moved to an appropriate area of the hospital. The ICU will be needed for patients with signs of severe envenomation (coma, respiratory paralysis, hypotension, pulmonary edema, and history of syncope). Patients with presence of fang marks, moderate pain, minimal local edema, erythema, ecchymosis, and no systemic reactions can be treated in the ward under close monitoring. Supportive therapy is required to buy time while the damaged organs recover. The varieties of supportive care that may be necessary is summarized below.
Coagulopathy with bleeding
Coagulopathy often reverses after ASV treatment. In incredible cases, when there is severe bleeding or when urgent surgery is needed, restoration of coagulability can be accelerated by giving fresh frozen plasma, cryoprecipitate (fibrinogen, factor VIII), fresh whole blood, or platelet concentrates.
Neurotoxic symptoms
Antivenom treatment alone cannot be relied upon to save the life of a patient with bulbar and respiratory paralysis. Once there's loss of the gag reflex, failure to cough, or respiratory distress, endotracheal intubation and initiation of mechanical ventilation is indicated. Tracheostomy and inclusion of a cuffed tracheostomy tube can be done whenever expertise for endotracheal intubation is not available. Since Elapid toxin result in pathophysiological changes resembling those of myasthenia gravis, anticholinesterase drugs can have a useful effect in patients with neurotoxic envenomation, particularly in those bitten by cobras. A trial of anticholinesterase should be performed in every patient with neurotoxic envenomation. Injection neostigmine can be given as 50-100 μg/kg 4 hourly or as a continuous infusion. Glycopyrrolate 0.2 mg can be given before neostigmine as, unlike atropine, glycopyrrolate does not cross the blood-brain barrier. Seneviratne and Dissanayake, in a prospective study on the neurological manifestations, disease course, and outcome in neurotoxic envenomation, demonstrated that neostigmine improved the muscle weakness. However, the number of cases in the study was too little for them to build an unequivocal recommendation. They were of the opinion that it would maybe be reasonable to offer anticholinesterase therapy to those who demonstrate a positive response to the tensilon test or a decremental response to repetitive nerve stimulation.
Care of bitten part
The appearance of an immobile, tensely-swollen, cold, and apparently pulseless snake-bitten limb may suggest to surgeons the possibility of increased intracompartmental pressure, especially if the digital pulp spaces or the anterior tibial compartment are involved. Swelling of envenomed muscle within such tight fascial compartments could result in an increase in tissue pressure above the venous pressure and result in ischemia. However, the classical signs of an intracompartmental pressure syndrome may be difficult to assess in snakebite victims. Fasciotomy should not be contemplated until hemostatic abnormalities have been corrected, otherwise the patient may bleed to death. It has also been reported that fasciotomy worsens the amount of myonecrosis in crotalid snake venom-injected tissue.
As most snakes harbor aerobic as well as anaerobic bacteria in their mouths, a prophylactic course of penicillin (or erythromycin for penicillin-hypersensitive patients) and a single dose of broad spectrum antibiotic course which will cover anaerobes together with a booster dose of tetanus toxoid is needed.