Snakebites worldwide: Management

INTRODUCTION — Snakebites account for significant morbidity and mortality worldwide, especially in South and Southeast Asia, sub-Saharan Africa, and Latin America [1]. Venomous snakes are widely distributed around the world and clinical effects from envenomation can overlap to a great degree even among different families of snakes. This topic will discuss the management of snakebites that occur worldwide, other than those by snakes found in the United States.

The clinical manifestations and diagnosis of snakebites worldwide and the principles of management of snakebites within the United States are discussed separately. (See "Snakebites worldwide: Clinical manifestations and diagnosis" and "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Clinical manifestations, evaluation, and diagnosis" and "Evaluation and management of coral snakebites".)

TERMINOLOGY — Although common names are used to describe snakes throughout this topic, the genus and species that correlate with the common names can be found in the following tables for Africa (table 1), Asia (table 2), Central and South America (table 3), Australia and the Pacific Islands (table 4), Europe (table 5), and the Middle East (table 6) and at the Clinical Toxinology Resources website.

FIRST AID — Initial first aid of snake envenomation is directed at reducing the spread of venom and expediting transfer to an appropriate medical center.

General principles — Although evidence is limited, generally agreed-upon principles for first aid of snakebite victims are as follows [2-5]:

●Remove the patient from the snake's territory. Keep the patient calm and at rest, remaining as still as possible.

●Attempt to identify the snake only if it is safe for the patient and the rescuer, and it will not delay transport of the patient to definitive medical care. Snake parts should not be handled directly. The bite reflex may remain intact in recently killed snakes and permit further biting [3]. A photograph taken at a safe distance may be useful.

●Remove any jewelry or footwear from the affected extremity. Clothing that is not tight and does not cause circulatory compromise can be left in place.

●Immobilize the injured part of the body in a functional position (table 7 and figure 1). Limited evidence exists regarding the recommended height of the bite wound relative to the level of the heart. Expert recommendations vary according to the expected degree of local injury compared with systemic toxicity. In regions where venomous snakebites result in significant local tissue damage with important but less common systemic effects (eg, North America), the bite wound may be placed at the level of the heart to manage local swelling but not encourage systemic absorption. However, in settings where neurotoxicity is likely and local tissue effects are of secondary concern (eg, Australia), the bite wound should be kept below the level of the heart to slow lymphatic venom absorption.

●Fashion a splint out of any rigid object (eg, padded piece of wood or tree branch, rolled newspaper, sleeping bag pad, or backpack frame) and apply to the extremity as follows:

•Splint the leg posteriorly in extension immobilizing the ankle and the knee.

•Splint the arm to the elbow and apply a sling.

●Transport the patient to the nearest medical facility as quickly as possible.

●Do not allow the victim to walk because exertion and, with bite wounds on the lower extremity, local muscle contraction may increase snake venom absorption.

●Do not manipulate the wound except to permit gentle bandaging or, if indicated, pressure immobilization or placement of a pressure pad. If transport to definitive care will be prolonged and a venom detection kit will not be used (countries other than Australia and Papua New Guinea), gentle cleansing may be performed. (See 'Pressure immobilization' below and "Snakebites worldwide: Clinical manifestations and diagnosis", section on 'Venom identification'.)

●Withhold alcohol and any drugs (such as aspirin and nonsteroidal anti-inflammatory medications) that may confound clinical assessment or interfere with treatment.

Pressure immobilization — We suggest that patients with snakebites from species with venoms that cause paralysis with little to no local tissue damage (eg, Australian elapids, kraits (picture 1), some purely neurotoxic cobras, coral snakes, or South American rattlesnakes) in whom transportation to definitive medical treatment will be prolonged, should receive pressure immobilization (figure 2) rather than immobilization alone. Pressure bandage immobilization (PBI) is not suggested following bites by snake species whose venom is associated with significant local tissue necrosis (eg, many cobras, adders, pit vipers, and rattle snakes). In these patients, localization of toxin may worsen tissue damage and could possibly raise compartment pressures. (See "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Management", section on 'First aid'.)

Application of a pressure bandage and immobilization (PBI) to the extremity consists of the following steps (figure 2) [6]:

●Do not remove clothing.

●Avoid excessive movement of the affected limb.

●With the patient at rest and the affected extremity below the heart, wrap the extremity with an elastic bandage from the lower to the upper portion of the limb.

●If an elastic bandage is not available, use pantyhose or other clothing torn into wide strips.

●Ensure that the bandage is firm and has the same tightness as for wrapping of a sprained ankle but just permits passage of two fingers underneath. Check that distal pulses remain palpable.

●Fashion a splint out of any rigid object (eg, padded piece of wood or tree branch, rolled newspaper, sleeping bag pad, or backpack frame) and apply to the extremity as follows:

•Splint the leg posteriorly in extension immobilizing the ankle and the knee.

•Splint the arm to the elbow and apply a sling.

●Do not remove the pressure bandage and immobilization until the patient has reached the hospital and a clinical assessment regarding the need for antivenom has occurred [7].

One exception to this rule occurs if it is evident that the bandage is so tight that it is hampering circulation (ie, distal pulses are markedly decreased or not palpable). This situation may occur if pressure immobilization is improperly applied or local swelling has increased the tightness of the bandage. If time to definitive care will exceed the likely ability of the distal limb to survive prolonged anoxia, the bandage should be carefully loosened to permit distal circulation but to avoid systemic venom absorption.

The pressure bandage and immobilization technique has wide support in Australia, where elapid snake toxins primarily cause neurotoxicity and/or coagulopathy without tissue necrosis and where there may be significant delays in transfer to medical facilities [4,8].

Its potential efficacy was first demonstrated in studies on monkeys using tiger snake venom (Notechis scutatus) with high systemic toxicity [9]. Immobilization of the envenomed limb and application of pressure of approximately 55 mmHg resulted in a significant delay in systemic absorption of venom. Dramatic benefits have also been described with delays of up to six hours for systemic absorption of venom in human case reports [10,11]. However, definitive evidence that pressure immobilization improves the outcomes of snakebites in humans is lacking [4,8].

Overall use and proper technique are both major considerations when assessing the potential benefit of pressure bandage and immobilization. Case series indicate that only 30 to 70 percent of patients treated for snakebite in Australia have pressure bandage and immobilization applied, despite heavy emphasis on its use in this region [12,13]. In addition, studies that evaluated intensive training of lay volunteers and healthcare providers indicate that proper bandage pressures are only achieved about 25 to 50 percent of the time [14,15].

Nevertheless, when used correctly for bites by snake species that do not cause local tissue damage, pressure immobilization is unlikely to be harmful and may be helpful.

Methods to avoid — The following methods, while used widely in the past and advocated by some, cause more harm than good and should be avoided [3,16,17]:

●Incision and oral suction

●Mechanical suction devices

●Cryotherapy

●Surgery

●Electric shock therapy

●Tourniquets

Tourniquets and oral suction are strongly discouraged, because, together, they can damage nerves, tendons, and blood vessels and lead to infection [3,18,19]. Furthermore, venom removal by suction is minimal, as illustrated in a study of mock venom extraction with a mechanical suction device in human volunteers that reduced the total body burden by only 2 percent [20]. Local suction devices exert significant negative pressure, which can disrupt adjacent tissues and may potentially enhance venom absorption with increased local tissue injury.

Tourniquets may cut off arterial blood flow and cause significant ischemic damage, especially when left on for a prolonged period of time [3,17].

MANAGEMENT

Approach — Emergency management of respiratory depression and shock, followed by timely antivenom administration whenever possible to patients with appropriate indications comprise the key initial interventions in patients with snakebite. (See 'Indications' below.)

Initial stabilization — Early care of snakebite victims should focus on supporting patients with life-threatening respiratory depression, cardiac failure, or shock. This may include cardiopulmonary resuscitation (CPR) if there is cardiac arrest. If pressure immobilization is in place, then it should not be removed until after initial assessment, stabilization, and if needed, antivenom are provided.

Respiratory failure — Life-threatening paralysis with respiratory depression warrants rapid securing of the airway and support of breathing as follows:

●Airway – Airway obstruction or respiratory failure caused by neurotoxic envenomation requires immediate airway support with oxygen and bag-mask ventilation followed by prompt rapid sequence intubation (RSI). Because of the potential for coagulopathy, intubation should be performed carefully to avoid traumatic bleeding. (See "Rapid sequence intubation in adults for emergency medicine and critical care" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)

Key considerations for RSI in these patients include the following [17]:

•Clinicians should provide appropriate sedation as these patients are typically fully conscious.

•The need for muscle relaxants should be assessed on a case-by-case basis, as they may be superfluous in major neurotoxic envenoming, and giving further paralytic agents may confound the clinical picture.

•Atropine administration should be assessed on a case by case basis in older patients in whom atropine for RSI is not typically given. As an example, victims of mamba envenomation may have hypersalivation due to the action of venom anticholinesterases that may require atropine during RSI to control secretions.

●Breathing – When available, concomitant end-tidal carbon dioxide measurement and frequent assessment of maximal inspiratory and expiratory forces should be performed to detect evidence of impending respiratory failure. Decrease in oxygenation, as detected by pulse oximetry or arterial blood gas measurement, is a late finding.

Oxygen should be used with caution in patients with suspected neurotoxic envenomation who do not warrant immediate airway management. Detection of respiratory failure may be impaired by oxygen therapy. Although the other clinical features of neurotoxicity usually manifest earlier (particularly bulbar palsy, usually first manifesting as bilateral ptosis). Hypoxia due to hypoventilation mandates intubation.

Shock — Hypovolemia from hemorrhage secondary to coagulopathy, fluid shift into the bitten limb, and/or direct venom effects with vasodilation or myocardial depression may cause serious shock with hypotension [21]. These patients warrant treatment with rapid infusion of balanced crystalloid solution or blood (depending upon degree of hemorrhage and to maintain the hematocrit at acceptable levels) and, if shock is not reversed and central venous pressure is not low, vasopressors.

In our experience, particularly in children, the infirm, or older adults, fluid overload and cardiorespiratory decompensation, such as pulmonary edema, may occasionally occur several hours into treatment when fluid initially sequestered in the bitten limb reenters the circulation. Thus, whenever possible, patients with snakebite and shock warrant close monitoring of central venous pressure during fluid resuscitation.

Coma — For patients with a delayed presentation after bites by any snake able to cause major neurotoxic paralysis, including many Australian elapids, some cobras, kraits, coral snakes, and some rattlesnakes from south and central America, an envenomed patient may present with severe neurotoxicity and be unable to give a history of snakebite. In this setting, the patient may show some features suggestive of catastrophic brain injury, such as fixed dilated pupils, absence of deep tendon reflexes, absence of withdrawal or other reaction to painful stimuli, and failing respiration (table 8).

In addition to support of airway, breathing, and circulation, and measurement of a rapid blood glucose to exclude hypoglycemia, these patients often require neuroimaging, when available, to assess for trauma or stroke. Despite appearing moribund, the patient may still be conscious and require appropriate sedation and pain management. (See "Snakebites worldwide: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)

Local wound care — If pressure immobilization is in place and the patient shows signs of life-threatening envenomation, hospital personnel should not remove it until monitoring, complete assessment, and, if needed, intravenous (IV) antivenom is provided. For patients without clinical evidence of serious envenomation but with signs of ischemic limb injury from the pressure immobilization, cautious removal of the overtight bandaging should occur as part of the initial assessment. However, signs of envenomation may develop, and the clinician should be prepared to treat immediately with antivenom and other therapy [16].

If antivenom is not indicated, then the first aid should be removed. If pressure immobilization first aid has been effectively applied, removal may result in severe envenomation developing rapidly or after a brief delay. This may result in sudden, potentially catastrophic collapse, including cardiac arrest (notably following bites by Australian brown snakes, genus Pseudonaja) in patients without evidence of systemic envenomation on arrival, and treating clinicians should ensure adequate monitoring is in place to immediately recognize and respond to such unexpected rapid severe deterioration in a previously well patient.

Excessive manipulation of the bitten extremity may result in increased systemic absorption of venom and should be avoided until assessment is complete or antivenom therapy is established.

Known snake species — Patients with appropriate indications should receive antivenom targeted against the most likely venomous snake species with provision to manage potential adverse effects. (See 'Indications' below and 'Administration' below and 'Allergic reactions' below.)

Where possible, the snake should be identified clinically, by examination, or in Australia and Papua New Guinea, by venom kit testing combined with use of a diagnostic algorithm. Local knowledge is vital in this regard; in Southeast Asia, for example, syndromic diagnosis has been used (algorithm 1 and table 2) [22].

In Australia and Papua New Guinea, snakes may vary widely in appearance, and identification is rarely possible by the clinician [23]. However, venom detection kits are useful in determining the appropriate monovalent antivenom in conjunction with diagnostic algorithms (table 4 and algorithm 2A-B) [24,25] (see "Snakebites worldwide: Clinical manifestations and diagnosis", section on 'Venom identification'). In Australia, rapid identification of a snake from photos of the snake or a dead specimen may be possible for a clinical toxinologist through a service currently available only through a dedicated clinical toxinology department (eg, at Women's and Children's Hospital, Adelaide, South Australia).

Unknown snake species — If there is doubt about the identity of the snake, treatment should be administered as for an unidentified snakebite and managed according to presenting symptoms, likely toxicity encountered in the region, and any presenting snake venom syndrome (table 9). For clinicians not experienced with snakebite management, decisions about antivenom administration should be made with the assistance of a clinical toxinologist, poison control center, or clinician with expertise in management of venomous snakes in the region. (See "Snakebites worldwide: Clinical manifestations and diagnosis", section on 'Additional resources'.)

Patients with local pain and swelling that is not progressive typically warrant hospital admission and close observation to ensure that signs of systemic envenomation do not develop as for an asymptomatic (dry bite). (See 'Asymptomatic (dry bite)' below.)

Repeated laboratory studies and ongoing monitoring for the primary toxicities of local snakes are also indicated. (See "Snakebites worldwide: Clinical manifestations and diagnosis", section on 'Physical examination' and "Snakebites worldwide: Clinical manifestations and diagnosis", section on 'Ancillary studies'.)

Asymptomatic (dry bite) — A significant proportion of snakebites do not result in envenomation. Patients without clinical features of local or systemic envenomation should be closely observed before discharge from medical attention. The time required for observation in hospital before discharge of an asymptomatic patient with possible envenomation depends upon the venom properties of the local snake fauna and the level of clinical and laboratory expertise available [26]. Clinicians who are unfamiliar with the management of snakebite should seek expert consultation with a clinical toxinologist, poison control center, or physician experienced in management of snakebites in the region. (See 'Additional resources' below.)

Important considerations include the following [16,17]:

●Patients with unknown snakebites in regions with neurotoxic snake species may warrant prolonged observation (up to 24 hours post-bite).

●Snake venoms that cause isolated coagulopathy will usually do so within 12 hours.

●In locations where snakebite can cause systemic myolysis, observation up to 24 hours and pre-discharge measurement of creatine kinase may be warranted.

●In general, it is wise to observe suspected snakebite patients overnight, rather than discharge them in the evening or at night, as local resources allow.

Antivenom — Despite limited evidence and no placebo controlled trials of antivenom for most snake species [27], antivenom remains the primary treatment for any patient with serious snake envenomation and in most patients should be used whenever available (table 9) [16,17]. Although high rates of adverse reactions occur for some antivenoms, patients generally benefit from antivenom and, for many, antivenom is life-saving. All patients who receive antivenom warrant appropriate measures to manage an adverse reaction. (See 'Indications' below and 'Allergic reactions' below.)

Antivenoms consist of animal immunoglobulins developed against whole venom [17]. The process involves immunizing animals (commonly horse, sheep, goats, or rabbits) with the venom and extracting the antivenom from the animal serum. Alternatively, IgY (immunoglobulin present in birds, reptiles, and amphibians but not mammals) may be raised against snake venoms using chicken eggs [17]. However, there are concerns that IgY-based antivenoms may contain antibodies against only some classes of toxins and therefore may not offer the broad spectrum neutralization offered by IgG-based antivenoms. Antivenoms may be provided as whole immunoglobulin (IgG or IgY) or as Fab fragments; either F(ab)₂ or Fab fragments.

Antivenoms vary with respect to the number of venoms against which they are raised as follows [16,17]:

●Monovalent – Most monovalent antivenoms are raised against a single genus or species of snake and should only be considered effective for bites by that snake or group of snakes [17,28].

●Polyvalent – Polyvalent antivenoms are developed against venoms from multiple different snakes that typically share a geographical region and can be used to treat envenomations by any of the included species [17].

Indications — When deciding whether to administer antivenom, clinicians who are unfamiliar with the management of snakebite should seek expert consultation with a clinical toxinologist, poison control center, or physician experienced in management of snakebites in the region. (See 'Additional resources' below.)

The decision to administer antivenom is based upon clinical findings and the risk of adverse reactions specific to the particular antivenom.

The decision on whether to use a monovalent or a polyvalent antivenom is determined by individual clinical circumstances, the nature of the local snake fauna, and the characteristics of the antivenoms under consideration. There is no clear "rule" that monovalent is better than polyvalent, but where the snake identity is established and the monovalent is of lower volume and risk (and potentially of lower cost), then it is clearly preferable to the polyvalent antivenom [17]. However, if an appropriate monovalent antivenom is either not available in a timely manner or the quantity available is suboptimal, a relevant polyvalent antivenom may be used in addition or instead. (See 'Antivenom' above.)

Effectiveness of antivenom may be reduced by clinical factors (eg, late presentation), a mismatch between envenoming species and the antivenom administered (eg, misdiagnosis), pharmacokinetic factors (failure to reach target sites) and irreversible venom binding. (See 'Failure to respond' below.)

●Life-threatening envenomation – We recommend that patients with confirmed snakebite and evidence of life-threatening systemic envenomation (table 9) (eg, collapse, convulsions, weakness, paralysis, respiratory failure, shock, coagulopathy or bleeding, or venom-induced/associated acute kidney injury) receive antivenom, when possible rather than supportive care alone [16,17]. The decision to administer antivenom must balance the potential benefit with the risk of adverse reactions, but in cases of severe envenomation when the antivenom is associated with relatively low rates of anaphylaxis, then treatment is appropriate.

Patients receiving antivenom require frequent monitoring and should have resuscitation equipment and medications to treat anaphylaxis, most importantly, epinephrine (drawn up in a syringe or prepared for continuous IV infusion) ready prior to commencing antivenom. Antivenom administration should occur in an acute care setting (eg, emergency department or intensive care unit) whenever possible. (See 'Allergic reactions' below.)

Particularly for snakes with presynaptic neurotoxins (eg, kraits (picture 1), most Australian elapid snakes, mambas (picture 2), some coral snakes, South American rattlesnakes, some populations of Russell's vipers (picture 3), or some European adders), but also for some species with only postsynaptic neurotoxins, it is important to commence antivenom early, as soon as first signs become apparent (eg, ptosis or partial or lateral gaze ophthalmoplegia). (See 'Neurotoxicity' below.)

On the other hand, although delays in administration result in lowered effectiveness, anecdotal evidence suggests that some improvement is possible even days after envenomation with some snakes [29].

Although specific data vary by region, snake species, and available antivenom, the evidence to support the benefit of antivenom relies mainly on indirect epidemiological evidence of lower mortality worldwide after the introduction of antivenom against local venomous snake species, in vitro studies of venom neutralization, animal studies, and observational series in humans [1,27,30-32]. The average death rate from snake envenomation in India has fallen from approximately 5.4 to 15.9 deaths per 100,000 persons in the 1940s to 1950s [31] to an estimated 1.1 to 4.7 deaths per 100,000 more recently [1,33]. In 1914, prior to the availability of antivenom raised against indigenous species and wider availability of acute medical care facilities, the mortality among undifferentiated snakebite victims in India was approximately 8 percent [31]. By the 1980s, the lowest case fatality rate in this region was 1.7 percent [1]. Given that many snakebite victims in India still do not have timely access to medical care and that most Indian antivenoms have high rates of allergic reactions (up to 80 percent of patients [2]), this improvement in mortality is significant. However, in some regions of India, the death rate still remains as high as 9 percent with approximately 46,000 people dying from snakebites in India annually [33,34].

More dramatic improvement in outcomes after the introduction of antivenom for snakebite has been seen in other countries. The following are selected examples with similar trends noted in other countries where data are available:

•Antivenom use in Nigeria after carpet viper bites (Echis species) resulted in no deaths among 400 patients as compared with a historical mortality of 10 to 20 percent among untreated Echis snakebite victims [35].

•In the United States, after the introduction of antivenom in the 1950s and the development of widespread availability of emergency and critical care medicine starting in the 1960s, mortality from snakebite dropped from as high as 36 percent to 0.06 percent. (See "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Management", section on 'Antivenom therapy'.)

Given such trends, most experts feel that performing placebo controlled trials of antivenom administration in patients with severe envenomation is unethical.

●Rhabdomyolysis — Antivenom may attenuate but does not reverse rhabdomyolysis after a snakebite. The recommended approach to snakebite-induced rhabdomyolysis is extrapolated from crush injuries and is discussed in detail separately. Initial therapy consists of rapid infusion of isotonic saline to establish urine output of 200 to 300 mL/hour (4 ml/kg per hour in children). (See "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)", section on 'Volume administration'.)

Patients with snake envenomation by Australian snake species (table 4) causing significant rhabdomyolysis (eg, creatine kinase [CK] >1000 IU/L, evidence of myoglobinuria, or kidney injury) without other systemic findings typically warrant antivenom. In such patients, the sooner antivenom is commenced, the more likely it will attenuate (but not reverse) rhabdomyolysis [36].

Small observational studies suggest that antivenom may improve the clinical course of patients with myotoxicity after snakebite in Australia [36,37]. In a case series of 13 patients envenomated by the Mulga snake (Pseudechis australis), early antivenom administration less than three hours after the bite was associated with no myotoxicity in three patients compared with elevated CK (3000 to about 7000 IU/L) among seven patients who received antivenom after three hours. However, CK <1000 IU/L was also seen in three patients who did not receive antivenom.

Evidence is lacking to guide the use of antivenom for snake species associated with isolated myotoxicity outside of Australia. Antivenom use in this situation should be guided by whether other forms of systemic envenomation (eg, neurotoxicity or coagulopathy) are present.

●Local effects only — Many snake species may cause medically significant or even severe local tissue damage around the bite site. The role of antivenom in reducing or preventing such tissue injury remains uncertain, but in general, antivenom is considered to have at least some beneficial effect in this setting. It is therefore necessary to weigh the benefits and risks of giving antivenom to treat purely local effects, on a case by case basis and consultation with a clinician with expertise managing snakebites in the region is advised. Potential candidates include patients with rapid development of obviously severe local effects (such as blistering, bruising, hemorrhagic blebs, necrosis), or rapid progression of effects (eg, over one to two hours) to involve a substantial part of the bitten limb. Such patients typically also have some evidence of systemic envenomation although findings may be nonspecific (eg, nausea, vomiting, or headache).

Obtaining antivenom — A listing of available antivenoms by region is available at www.toxinology.com and on the snakebite section of the World Health Organization (WHO) website. Be aware that antivenom producers may change types, characteristics, and availability of their antivenoms without notice, and such changes may not be reflected on global websites such as those listed above.

Availability of antivenom varies significantly by region. In general, appropriate antivenoms are more easily obtained in the Americas (North, Central, and South America), Europe, the Middle East, Asia, and Australia than in sub-Saharan Africa and Papua New Guinea. Although there are good antivenoms available for Papua New Guinea, they are typically in short supply in hospitals there [16].

Often antivenom is available on a regional or national basis through the producer. However, clinicians in many regions with significant numbers of dangerous snake envenomations have little or no access to antivenom because of short supply, cost, or lack of antivenom available for the specific snake species [17].

For patients with envenomations by non-native exotic snakes, the clinician should contact the regional poison control center to determine if antivenom is available. Frequently, major zoos in North America, Europe, and Australia stock a range of antivenoms for exotic snakes in their collections. To obtain emergency consultation with a medical toxicologist, in the United States, call 1-800-222-1222, or the nearest international regional poison center. (See 'Additional resources' below.)

Administration — Preparation, dosing, and administration of antivenom varies by specific product. Clinicians with limited experience should seek consultation with toxinologists, regional poison control centers, or clinicians with expertise in the management of snake envenomations in their region. (See "Snakebites worldwide: Clinical manifestations and diagnosis", section on 'Additional resources'.)

Key aspects of snake antivenom administration include:

●Choice of antivenom – A list of available antivenoms by snake species can be found at www.toxinology.com and on the snakebite section of the World Health Organization (WHO) website. Be aware that antivenom producers may change types, characteristics, and availability of their antivenoms without notice, and such changes may not be reflected on global websites such as those listed above.

●Dose – Dosing is determined by the snake species and individual patient characteristics. It is based on the average amount of venom expected from the snakebite, so the size and weight of the patient may be irrelevant. The dose of antivenom does not differ between adults and children; there is no "pediatric dose" for antivenom.

●Route of administration – The IV route of administration is preferred to intramuscular (IM) injection whenever possible to ensure the most effective and rapid neutralization of snake venom. In small children, if IV access is not possible, intraosseous infusion is appropriate if life-threatening envenomation is likely. (See "Intraosseous infusion", section on 'Indications'.)

The clinician may administer IV antivenom in one of two ways:

•Antivenom diluted in a compatible solution (eg, normal saline) and infused over 30 to 60 minutes

•Reconstituted (if required; eg, lyophilized antivenoms; not required for liquid antivenoms) and given by slow IV injection over 10 to 20 minutes

Preliminary evidence suggests that the IV injection does not increase the risk of allergic reaction over IV infusion. As an example, in a trial of 198 patients receiving antivenom in Sri Lanka, the frequency of severe hypersensitivity reactions was not different in patients receiving IV injection over 20 minutes versus IV infusion over two hours (32 versus 35 percent, respectively) [38].

In general, IV infusion of diluted antivenom is still preferred because it permits slower administration with an ability to hold the infusion if an adverse reaction occurs and to restart the infusion at a slower rate after the reaction is treated. (See 'Allergic reactions' below.)

However, in some circumstances, such as under-resourced developing nation local health facilities, equipment for safe use of a diluted IV infusion may not be available, or of suspect quality and safety, and in this setting a slow IV push of antivenom by the physician may be a better option. However, in such cases, the full dose of antivenom may be administered before an adverse reaction is clinically apparent.

The patient should be monitored carefully for signs of adverse reactions during and for at least one hour following antivenom administration, regardless of route. Resuscitation equipment and medications to treat anaphylaxis, most importantly, epinephrine (drawn up in a syringe or prepared for continuous IV infusion) should be immediately available. The tables provide treatment recommendations for anaphylaxis (table 10 and table 11).

Premedication with subcutaneous epinephrine is suggested when the administered antivenom is known to be associated with high rates of anaphylaxis. (See 'Premedication' below.)

Based on case series of patients envenomed by Russell's viper, IM routes of antivenom administration can be effective for systemic envenomation if IV administration is not possible [39]. However, animal models indicate that the efficacy of IM antivenom may vary by snake species [40,41]. Thus, IM administration of antivenom should only be performed when IV or intraosseous (IO) administration cannot be achieved and for snake envenomations in which human or animal experience indicates that IM administration will be effective.

Response to treatment — The effect of the antivenom should be monitored carefully. Lack of response is usually caused by administration of inadequate amounts of antivenom or use of the wrong antivenom but may also occur if it is too late for the antivenom to be effective, such as in patients with advanced paralysis due to presynaptic neurotoxins in the venom. (See 'Failure to respond' below and 'Neurotoxicity' below.)

The typical timing to reversal of toxic effects when adequate amounts of antivenom have been given varies by type of envenomation as follows [16]:

●Coagulopathy – Spontaneous bleeding ceases by about 20 minutes. Coagulation tests often normalize or whole blood clotting is restored by about six to eight hours.

For some snakes (eg, Australian snakes (table 4)) the coagulopathy may take longer than six hours to show evidence of reversal after adequate antivenom treatment. If formal coagulation tests are used to assess antivenom response to toxicity from these species (recommended whenever possible), then a response is generally defined as an improvement in coagulation parameters, not a return to normal values, which may take 24 hours or more.

Inadequate antivenom dosing is the first consideration in patients with persistent bleeding [42].

●Hypotension and cardiotoxicity – Marked improvement should occur within 20 to 30 minutes.

●Neurotoxicity – Detectable improvement within 30 minutes with complete reversal within several hours is seen in responsive patients (venom with only post-synaptic neurotoxins).

Failure to respond — Failure of response to antivenom may be due to the following reasons:

●Insufficient antivenom

●Wrong antivenom

●Inactive or poor quality antivenom

●Excessive delay in administration after envenomation

●A venom effect not reversible by antivenom (eg, presynaptic neurotoxic paralysis)

Expired antivenom may retain its potency for some time following its use-by date [43]. The risk-benefit ratio may still support its use if no "in date" antivenom is available. However, liquid antivenoms that are opaque or have visible precipitants should not be given because these findings indicate protein denaturation with loss of potency and increased potential for adverse reactions [16].

Allergic reactions — Reactions to most antivenoms are common and may be divided into three types:

●Early allergic reactions

●Pyrogenic reactions

●Late allergic reactions (serum sickness)

Given the risk of significant acute allergic reactions, including anaphylaxis following the administration of snake antivenom, resuscitation equipment and medications to treat anaphylaxis should be immediately available. The most important of these is epinephrine (drawn up in a syringe or prepared for continuous IV infusion). The tables provide treatment recommendations for anaphylaxis (table 10 and table 11). (See "Anaphylaxis: Emergency treatment", section on 'Immediate management'.)

The rate of early and late allergic reactions varies with different antivenom preparations and depends upon the method of purification, the total foreign protein load and the composition of the antivenom (whole immunoglobulin compared with Fab fragments) [44]. Rates for early major adverse reactions to antivenom (anaphylaxis) can be very high, up to 80 percent for some antivenoms raised against Indian snakes (table 2) [2], and in this setting the risk-benefit of use must be carefully considered before recommending use. For some other antivenoms (eg, CroFab, ViperaTAb, or Australian CSL/Seqirus antivenoms) the rate of anaphylaxis can be below 5 percent. However, the risk of adverse reactions is still significant for all antivenoms. Thus, antivenom administration should be avoided for trivial levels of envenomation.

On the other hand, antivenom should not be withheld when severe or life-threatening envenomation has occurred. In some situations, the balance of benefit and risk of antivenom administration is very close. In such cases, consultation with a clinical toxinologist, poison control center, or physician experienced in the local management of snakebite should be sought. (See 'Additional resources' below.)

Treatment of anaphylaxis or serum sickness is discussed in detail separately. (See "Anaphylaxis: Emergency treatment", section on 'Immediate management' and "Serum sickness and serum sickness-like reactions".)

Premedication — We suggest that patients treated in the following settings receive premedication with subcutaneous epinephrine [45]:

●Use of antivenom is associated with high rates of allergic reactions.

●There is a significant risk of allergic reaction associated with antivenom use and the management of acute allergic reactions is problematic because of limited staffing or facilities.

Limited evidence suggests that the use of prophylactic subcutaneous epinephrine prior to the administration of IV antivenoms in such settings is beneficial. As an example, in a placebo-controlled trial of 105 Sri Lankan patients who received IV polyvalent antivenom, fewer adverse reactions occurred in those patients who received pretreatment with 0.25 mg subcutaneous epinephrine when compared with placebo (11 versus 43 percent, respectively) [46].

By contrast, evidence does not support routine pretreatment with either antihistamines or corticosteroids:

●Pretreatment with IV antihistamines has had mixed effects on the frequency of allergic reactions following antivenom administration:

•In a trial of 52 Sri Lankan patients who received polyvalent antivenom, the frequency of mild-to-moderate early reactions was modestly reduced with the combination of an IV chlorpheniramine bolus and hydrocortisone infusion when compared with placebo or hydrocortisone alone (52 versus 80 to 81 percent, respectively) [47]. However, the high rate of acute reactions to the polyvalent antivenom in the control arms makes this study only generalizable to antivenoms with very high rates of adverse reactions.

•In a trial of 101 Brazilian children and adults receiving antivenom for Bothrops snakebite (picture 4), the frequency of allergic reactions was approximately 25 percent regardless of whether patients received IV promethazine or placebo [48].

●Corticosteroids are often used with early and late allergic reactions although their benefit is not well documented. As noted in the small trial from Sri Lanka above, IV hydrocortisone was not better than placebo in preventing allergic reactions [47].

Contraindications — There are no absolute contraindications to antivenom administration. However, antivenom should be used with greater restraint and special caution in the following situations [16,17]:

●Prior allergic reaction to antivenom or one of its components – Prior reaction to antivenom with the same animal component (eg, equine, ovine, or rabbit serum). However, if the likely effect of envenomation is life threatening, then withholding antivenom because of a past adverse reaction to antivenom is rarely appropriate. Particular care should be taken while administering antivenom to ensure any adverse reaction can be promptly managed. This may involve, in selected cases, having an IV epinephrine infusion prepared and immediately available prior to giving the antivenom (table 12 and table 13 and table 14).

●Patients with asthma – These patients may be at higher risk for immediate allergic reactions with severe respiratory distress. However, such patients with major envenomation (eg, serious systemic signs) should still receive antivenom with precautions in place to immediately treat an allergic reaction.

●Patients receiving beta adrenergic blockers or angiotensin-converting enzyme inhibitors –These drugs may reduce the effectiveness of treatment of anaphylaxis, specifically the effectiveness of epinephrine. Glucagon may be effective for treating anaphylaxis in patients taking beta adrenergic blockers who do not respond to epinephrine. (See "Anaphylaxis: Emergency treatment", section on 'Glucagon for patients taking beta blockers'.)

In general, if a patient is at serious risk of dying from envenomation, then the benefit of giving antivenom likely outweighs the risk of these adverse reactions.

Treatment other than antivenom — The timely administration of adequate amounts of antivenom is the key therapy for all significant systemic complications of venomous snakebites. (See 'Indications' above.)

This section discusses adjunctive therapies that may also be needed for the management of specific conditions (table 9).

Local effects — The clinician should gently clean the bite area with soap and water. If a venom detection kit will be used, cleansing should occur only after the wound site is swabbed. The wound should then be bandaged and checked once to twice daily for signs of infection, but prophylactic antibiotics are usually not indicated. Snakebites are considered tetanus prone wounds. (See 'Other therapies' below.)

Evidence is lacking to guide positioning of an affected extremity after snakebite and the following suggestions are based upon experience and regional considerations as follows:

●Once antivenom has been given and is judged to be effective, local swelling may be treated with elevation of the affected extremity.

●If antivenom is not available or has not been given, positioning of the affected limb depends upon the degree of swelling, the type of venomous snake, and the envenomation syndrome the patient is exhibiting.

•In regions where venomous snakebites result in significant local tissue damage with important but less common systemic effects (eg, North America), the bite wound may be placed at the level of the heart to manage local swelling but not encourage systemic absorption.

•In settings where neurotoxicity is likely and local tissue effects are of secondary concern (eg, Australia), the bite wound should be kept below the level of the heart to slow lymphatic venom absorption.

Compartment syndromes may be confused with the appearance of local necrosis following envenomation but are rare. Fasciotomies should only be performed following confirmation of raised intracompartmental pressure and the correction of coagulopathy. Fasciotomy performed in patients with uncorrected coagulopathy may result in catastrophic bleeding and poorer outcomes in the affected limb [49].

In the setting of major swelling due to envenoming, fasciotomy can be expected to result in significant long term functional and cosmetic problems and this known risk should be carefully considered as part of the risk-benefit analysis prior to any contemplated surgery.

The measurement of compartment pressures and treatment of compartment syndrome are discussed in detail separately. (See "Acute compartment syndrome of the extremities", section on 'Measurement of compartment pressures' and "Acute compartment syndrome of the extremities", section on 'Management'.)

Neurotoxicity — All patients with confirmed bites by neurotoxic snakes warrant hospital admission and frequent assessment of respiratory function. If signs of paralysis develop, including early signs such as ptosis, then there is a substantial risk that the paralysis may progress to a life-threatening extent. Thus, it is important to commence antivenom administration early, as soon as first signs become apparent (eg, ptosis or partial or lateral gaze ophthalmoplegia). (See 'Indications' above.)

Furthermore, the effectiveness of antivenom depends upon the site of action of the snake venom as follows:

●Presynaptic toxicity – In patients with paralysis caused by presynaptic neuromuscular junction (NMJ) toxicity (eg, kraits (picture 1), most Australian elapid snakes, mambas (picture 2), some coral snakes, South American rattlesnakes, some Russell's vipers, and some European adders), response depends upon timely administration of antivenom. Antivenom cannot reverse established presynaptic neurotoxic paralysis [50,51]. Once presynaptic venom is systemically absorbed, there is a latency of about an hour for the binding of neurotoxins at the NMJ and subsequent paralysis as the toxins enter and damage the terminal axon, resulting in inability to produce neurotransmitters. While antivenom can neutralize unbound toxins, once the presynaptic neurotoxins have entered the nerve cell, they are inaccessible to antivenom, which also cannot repair intracellular damage caused by these toxins. If antivenom therapy is delayed awaiting progression of paralysis beyond early signs of ptosis or gaze paralysis, it may then be too late to prevent major paralysis.

Intubation and ventilation are required for airway protection or respiratory support if bulbar palsy, increasing dyspnea, or respiratory failure is present. Regeneration of the NMJ may take up to several weeks. Thus the need for ventilation can be prolonged in such patients. (See 'Respiratory failure' above.)

However, it should be noted that snake venoms containing presynaptic neurotoxins will also contain postsynaptic neurotoxins, and in some cases, the neurotoxic effects may be principally mediated by the latter, with implications for treatment. (See 'Anticholinesterases' below.)

●Postsynaptic toxicity – In patients with paralysis caused by postsynaptic NMJ toxicity (eg, some death adder [Acanthophis spp] bites (picture 5), Philippine cobra [Naja philippinensis], and some other Asian and African cobras [Naja species]), anticholinesterase, such as edrophonium, if available, or neostigmine may be of benefit, especially if antivenom is not available or is associated with high rates of adverse reactions [52-54].

Anticholinesterases — Clinicians with limited experience using anticholinesterases for neurotoxic snakebites should consult with a poison control center or physician experienced with anticholinesterase treatment of neurotoxic snakebites, if possible. Patients receiving anticholinesterase therapy warrant close monitoring in an emergency department or intensive care unit whenever available. Atropine should be given prior to neostigmine to prevent a cholinergic crisis.

We recommend that when antivenom is not available or not effective for weakness or paralysis secondary to envenomation by a snake capable of causing postsynaptic neurotoxicity, patients undergo a neostigmine trial to determine if anticholinesterase therapy may be beneficial. (See "Snakebites worldwide: Clinical manifestations and diagnosis", section on 'Trial of anticholinesterase (neostigmine or edrophonium)'.)

In patients with neurotoxic snakebite for whom antivenom is not available or is ineffective and who have a positive neostigmine trial, we recommend treatment with an anticholinesterase. Neostigmine is the anticholinesterase that has primarily been used in snakebite victims [54-63]. It has a longer duration of action than edrophonium, is widely available, and inexpensive. It can be given IV or IM. Successful use of subcutaneous neostigmine has been reported for the management of severe myasthenia gravis but not neurotoxic snakebite [64]. Given the potential for compromised circulation in snakebite victims, we prefer the IV route for treatment of severe neurotoxicity.

●IV dose – One small trial, case series, and case reports suggest that neostigmine be given to snakebite victims at an initial IV or IM dose of 0.5 mg (0.025 to 0.04 mg/kg up to 0.5 mg in children) with co-administration of IV or IM atropine 0.5 mg (0.02 mg/kg up to 0.5 mg in children) [54-62]. Although glycopyrrolate (0.2 mg IV, IM, or subcutaneous for every 1 mg of neostigmine for adults and children) has been used as an alternative to atropine because glycopyrrolate does not cross the blood-brain barrier and therefore does not caused altered mental status [65-67], we suggest atropine over glycopyrrolate based upon greater observational evidence supporting atropine coadministration with neostigmine for snakebite.

Neostigmine is repeated every 20 minutes, as needed, until muscular strength is recovered. Subsequently, neostigmine can be given IV every two to four hours, as needed, to maintain muscle strength. Although reported regimens vary, atropine may be repeated prior to every fourth dose of neostigmine, regardless of the intervals between doses.

Based upon reported experience, the response to neostigmine varies significantly. Some patients may only need two or three doses of neostigmine to achieve and maintain full recovery of muscle strength while others may need ongoing treatment for several days [54-62]. In one small trial, patients were maintained with a continuous infusion of neostigmine (starting dose of 0.025 mg/kg per hour of neostigmine titrated to response) although it is unclear whether interval dosing would have been equally efficacious [54].

●Oral dosing – For patients who can swallow tablets, oral therapy may be given with neostigmine 15 mg every six hours or pyridostigmine 60 mg every six hours with atropine 0.6 mg every 12 hours [16].

Coagulopathy — Antivenom is the primary treatment for snakebite-induced coagulopathy with hemorrhage. It is not possible to correct coagulation defects without sufficient antivenom. Thus, persistent bleeding despite antivenom administration should prompt treatment with additional antivenom, provided the identification of the snake or choice of antivenom is secure. Although spontaneous bleeding may resolve rapidly after antivenom administration (eg, within 20 to 30 minutes), laboratory abnormalities may resolve more slowly (approximately six hours). Thus, evidence of clinical bleeding rather than laboratory measurement should be used to determine if sufficient antivenom has been provided.

The optimal management of asymptomatic patients with laboratory evidence of snakebite-induced coagulopathy is unclear. Extrapolation from other medical conditions (eg, disseminated intravascular coagulopathy) has led to the suggestion that a multicomponent coagulopathy with parameters exceeding critical thresholds (international normalized ratio (INR) >3.0, activated thromboplastin time (aPTT) >50 seconds, platelets <50,000/microL, and fibrinogen <75 mg/dL) is associated with a major bleeding risk of 1 percent over a few days [68]. Antivenom administration may be appropriate in such patients if the expected frequency of adverse reactions is low or antivenom is given in a setting where anaphylaxis can be readily managed. Consultation with a clinical toxinologist, poison control center, or physician experienced in the management of local snakebites is advised. (See 'Additional resources' below.)

Of note, isolated coagulation abnormalities (eg, prolonged aPTT or INR in the absence of thrombocytopenia and low fibrinogen) that are not associated with clinical bleeding do not fit the pattern for snakebite-induced coagulopathy, except for snakes known to cause isolated "anticoagulant" type coagulopathy (eg, Australian Mulga and black snakes, genus Pseudechis). In such cases, a previously undetected hereditary coagulation defect should be suspected.

Blood products — Of the blood products available, whole blood or fresh frozen plasma (FFP) or similar products (eg, PF24) best addresses coagulopathy caused by snakebites and, as noted above, is primarily indicated in cases of life-threatening hemorrhage in conjunction with antivenom administration or, when antivenom is not available and the patient has major bleeding.

As in other patients with consumptive coagulopathy, platelet transfusions are indicated in patients with thrombocytopenia and bleeding, especially those with microangiopathic hemolytic anemia, with a target of maintaining the platelet count above 100,000/microL. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Actively bleeding patient'.)

For envenomation by selected snakes that typically produces marked coagulopathy, sometimes with hemorrhage (eg, Australian Tiger, brown, and Taipan snakes), FFP or similar products (eg, PF24) has been suggested as a routine adjunctive therapy in the past [69-71]. However, preliminary evidence indicates that while such treatment may result in more rapid return towards normal for laboratory parameters, there is no concomitant improvement in patient outcomes to offset the potential risks of blood product exposure. Therefore, we do not recommend routine use of FFP in patients bitten by these snakes and exhibiting coagulopathy. As an example, in a trial of 65 patients with venom induced consumptive coagulopathy, the 41 patients who received FFP were more likely to have an INR <2 than the control group (78 versus 25 percent) [69]. However, the only significant bleeding complication (intracranial hemorrhage with death) occurred in a patient who received FFP, and the time to discharge was not significantly different between the groups.

Other agents — In a trial of 20 patients with thrombotic complications of Russell's viper, anticoagulant therapy with heparin was not effective [72]. Thus, heparin and similar anticoagulants are not recommended to treat snakebite coagulopathy.

Fibrinolysis caused by Bothrops species (picture 4) was not responsive to aminocaproic acid in an animal model [30].

Hypotension — Central pressure monitoring may be useful in the titration of IV fluid in patients who have not responded to an initial fluid challenge. Central lines should be inserted with caution in patients with significant coagulopathy. The etiology of hypotension may be multifactorial and warrant the use of vasoactive medications in addition to rapid fluid or blood administration. (See 'Approach' above.)

Rhabdomyolysis — Antivenom may prevent the development of muscle toxicity but does not appear to reverse established rhabdomyolysis. (See 'Indications' above.)

The recommended approach to snakebite-induced rhabdomyolysis is extrapolated from crush injuries and is discussed in detail separately. Initial therapy consists of rapid infusion of isotonic saline to establish urine output of 200 to 300 mL/hour (4 ml/kg per hour in children). (See "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)", section on 'Volume administration'.)

Renal failure — The urine output should be monitored closely, as oliguria in patients who have been adequately volume repleted usually indicates renal failure. Development of proteinuria may also indicate possible emerging renal damage and is an indication of early acute kidney injury in Russell's viper (Daboia russelii and Daboia siamensis) envenomation. Central pressure monitoring may be useful in titrating further fluid therapy. Short-term dialysis may be required. Rarely, the renal damage may be permanent (usually bilateral renal cortical necrosis) requiring long term management for renal failure. (See "Overview of the management of acute kidney injury (AKI) in adults".)

Renal failure following a snakebite may be multifactorial resulting from hypotension, rhabdomyolysis and/or disseminated intravascular coagulation (DIC). As an example, in a prospective observational study of 100 patients envenomed with Crotalus durissus, 29 patients developed acute renal failure (ARF) associated with rhabdomyolysis. Independent risk factors for ARF included age less than 12 years, a delay in antivenom therapy of >2 hours, and a creatinine kinase at admission >2000 U/L [73]. By contrast, diuresis at admission >90 mL per hour was associated with better outcomes.

Cobra spit ophthalmia — The venom of the spitting cobras (Naja spp.) found in Asia and Africa can cause corneal damage. The fangs of these snakes are modified to allow accurate spitting of venom over 2 to 3 m and the eye is the common target.

Acutely, the eye should be irrigated with copious quantities of water or saline. Slit lamp examination and fluorescein staining should be performed to evaluate for corneal ulceration; topical antibiotic ointment should be applied if this is present [74]. The instillation of diluted antivenom is not recommended [22]. Systemic envenomation following venom spit ophthalmia has not been reported.

Other therapies

Tetanus prophylaxis — Snakebites are considered tetanus prone wounds and prophylaxis should be provided as needed (table 15). In patients with coagulopathy, tetanus prophylaxis should be postponed until after resolution with antivenom therapy. (See "Tetanus-diphtheria toxoid vaccination in adults" and "Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Wound management'.)

Antibiotics — Evidence does not support the use of empiric antibiotics to prevent secondary infection after snakebite, and we do not use them [3].

Although high rates of infection have been reported following snakebite in some regions (eg, Brazil) [75], trials of empiric antibiotic therapy have failed to show a benefit:

●In a trial of 251 patients following Bothrops envenomation in Brazil, oral chloramphenicol did not prevent abscess formation when compared with placebo [76].

●In a trial of 144 snakebite patients in Sri Lanka, patients who received parenteral benzylpenicillin and metronidazole did not have less local swelling or more rapid resolution of swelling when compared with placebo [77].

In patients with cellulitis or abscess after a snakebite, antibiotic therapy should be guided by wound culture and sensitivity whenever possible. Empiric therapy should target skin flora, and other Gram-negative bacteria (eg, Salmonella species) pending culture results. Consultation with an infectious disease specialist is warranted for complicated infections. (See "Zoonoses: Animals other than dogs and cats", section on 'Reptiles and amphibians'.)

Investigational therapies — Evolving pre-clinical research on other non-antivenom therapies for neurotoxicity and local envenoming effects, including necrosis, are providing possible new adjunctive treatments that still require clinical trial evidence. These are designed to find new approaches for addressing specific envenoming problems that currently are sub-optimally responsive to existing treatments, including antivenom. We do not recommend any of the following for routine use until safety and effectiveness are demonstrated in robust trials, but they ultimately may have a role as ancillary therapies.  

Photobiomodulation — Photobiomodulation (ie, low-level laser therapy [LLLT]) may modulate inflammation and enhance healing following envenoming by species that cause local tissue damage or myonecrosis [78]. However, specialized equipment is required, and evidence is limited. In a trial of 60 patients with Bothrops snakebites, compared with antivenom alone, LLLT combined with antivenom decreased pain intensity scores, extent of edema, and extremity circumference (as compared with the contralateral limb) but had no significant effect on rates of secondary infection, necrosis, or extent of disability [79]. LLLT is also being investigated for numerous other indications (eg, alopecia, tendinopathy).

Phospholipase A2 inhibitors — Varespladib, an inhibitor of phospholipase A2 (PLA2), has garnered considerable attention since many snake venoms contain potent PLA2-based toxins. Varespladib was developed and studied to treat non-envenoming diseases (eg, ulcerative colitis, rheumatoid arthritis, asthma) but showed safety concerns at higher doses. An ongoing trial (Broad-spectrum Rapid Antidote: Varespladib Oral for snakebite [BRAVO]) is comparing oral varespladib with standard of care [80]. An animal study suggests that varespladib may have a role in treating snakebite paralytic neurotoxicity caused by Australian taipan venom, which contains potent pre-and post-synaptic neurotoxins that can cause severe flaccid paralysis poorly responsive to specific antivenom [81]. In vitro studies have found similar beneficial effects of varespladib against several other neurotoxic Elapid and Viperid snake venoms [82].

Metalloproteinase inhibitors — Snake venom metalloproteinases (SVMPs) contribute to local envenoming effects and systemic toxicity (eg, coagulopathy, kidney injury, vascular permeability). An animal study found that marimastat (an SVMP inhibitor) and varespladib injected intradermally reduced the extent of local tissue injury of two viper venoms (Bothrops asper and Echis ocellatus), even when administered 60 minutes post venom injection [83].

ADDITIONAL RESOURCES

Region-specific resources — Resources that provide information about specific regions or snake species include:

●African snakebites

•Guidelines for the prevention and clinical management of snakebite in Africa. World Health Organization Regional Office for Africa, Brazzaville, Mauritius, 2010.

•Target product profiles for animal plasma-derived antivenoms: antivenoms for treatment of snakebite envenoming in sub-Saharan Africa. World Health Organization, 2023.

●South-East Asian snakebites – Warrell DA. Guidelines for the management of snake-bites. World Health Organization Regional Office for South-East Asia, India, 2016.

●Australian snakebites – White J. Snakebite & spiderbite management guidelines South Australia. Department of Health, Adelaide, 2018.

●A comprehensive publication on management of envenomation in Australia ("A Clinicians Guide to Australian Venomous Bites and Stings") produced independently but with financial support of the antivenom producer, Seqirus, is available as a PDF via the link in the reference [84].

●An extensive database of the distribution for snake species, their clinical manifestations, and treatment of envenomation provided by the University of Adelaide, Australia. Available at www.toxinology.com.

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Envenomation by snakes, arthropods (spiders and scorpions), and marine animals".)

SUMMARY AND RECOMMENDATIONS

●First aid – Initial first aid of venomous snakebite is directed at reducing the spread of venom and expediting transfer to an appropriate medical center. Key aspects include (see 'General principles' above):

•Remove the patient from the snake's territory.

•Keep the patient calm and at rest.

•Remove any jewelry or footwear on the affected extremity.

•Immobilize the injured body part. We suggest that patients with snakebites from species with venoms that cause paralysis with little to no local tissue damage (eg, Australian elapids, kraits, some purely neurotoxic cobras, coral snakes, or South American rattlesnakes) and for whom transportation to definitive medical treatment will be prolonged receive pressure bandage and immobilization (figure 2) rather than immobilization alone (Grade 2C). (See 'Pressure immobilization' above.)

●Approach – Emergency management of respiratory depression and shock, followed by timely antivenom administration, if available, to patients with appropriate indications comprise the key initial interventions in patients with snakebite (table 9). If pressure immobilization is in place, then it should not be removed until initial assessment, stabilization, and, if needed, antivenom are provided. Additional management depends upon whether the biting snake is known or unknown and whether envenomation has occurred. (See 'Approach' above.)

●Antivenom – When deciding whether to administer antivenom, clinicians who are unfamiliar with the management of snakebite should seek expert consultation with a clinical toxinologist, poison control center, or physician experienced in management of snakebites in the region.

•Indications – We recommend that patients with confirmed snakebite and evidence of life-threatening systemic envenomation (table 9) (eg, collapse, convulsions, weakness, paralysis, respiratory failure, shock, coagulopathy or bleeding, or acute kidney injury [notably following bites by Russell vipers]) receive antivenom, if available, rather than supportive care alone (Grade 1A). Whenever possible, the snake should be identified clinically, by examination, or in Australia and Papua New Guinea, by venom kit testing. In certain regions, diagnostic algorithms can help with choosing the proper antivenom (algorithm 1 and table 2 and table 4 and algorithm 2A-B). (See 'Indications' above and 'Known snake species' above.)

•Contraindications and precautions – There are no absolute contraindications to antivenom administration. However, antivenom should be used with greater restraint and special caution in patients with a prior allergic reaction to antivenom or one of its components, asthma, or beta-adrenergic blockers or angiotensin converting enzyme inhibitor as current medications. In general, if a patient is at serious risk of dying from envenomation, then the benefit of antivenom administration outweighs the risk of these adverse effects. Withholding antivenom because of a past adverse reactions is rarely likely to be appropriate. (See 'Contraindications' above.)

•Premedication and monitoring for allergic reactions – Patients receiving antivenom require frequent monitoring and should have resuscitation equipment and medications immediately available to treat anaphylaxis. We suggest that patients treated with antivenom with a high rate of acute allergic reactions or who are receiving antivenom in facilities where the acute management of allergic reactions is problematic because of limited staffing or facilities receive premedication with subcutaneous epinephrine (Grade 2B). (See 'Allergic reactions' above and 'Premedication' above.)

•Dosing and administration – Preparation, dosing, and administration of antivenom varies by specific product. Dosing is determined by the snake species and individual patient characteristics. It does not differ between adults and children. A list of available antivenoms by snake species can be found at www.toxinology.com. (See 'Administration' above and 'Additional resources' above.)

●Other treatments – Treatments other than antivenom that may also be needed for the management of specific complications of venomous snakebite are provided in the table (table 9) and are discussed in detail above. (See 'Treatment other than antivenom' above.)

•Neostigmine – We recommend that, when antivenom is not available or not effective for weakness or paralysis secondary to envenomation by a snake capable of causing postsynaptic neurotoxicity, patients undergo a neostigmine trial to determine if anticholinesterase therapy may be beneficial. In patients with neurotoxic snakebite for whom antivenom is not available or is ineffective and who have a positive neostigmine trial, we recommend treatment with neostigmine (Grade 1B). (See 'Anticholinesterases' above.)

•Wound management – The clinician should gently clean the bite area with soap and water. If a venom detection kit will be used, cleansing should occur only after the wound site is swabbed. The wound should then be bandaged and checked once to twice daily for signs of infection. Evidence does not support the use of empiric antibiotics to prevent secondary infection after snakebite, and we do not use them. (See 'Antibiotics' above.)

Snakebites are considered tetanus prone wounds and prophylaxis should be provided as needed (table 15). In patients with coagulopathy, tetanus prophylaxis should be postponed until after antivenom therapy and normalization of abnormalities. (See 'Tetanus prophylaxis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Allen Cheng, MB, BS, who contributed to earlier versions of this topic review.