Evaluation and management of coral snakebites

INTRODUCTION — Coral snakebites are rare. Successful treatment requires prompt transfer of the snakebite victim to definitive medical care, careful clinical assessment, and timely administration of antivenom in selected patients. Consultation with a medical toxicologist or other physician with experience in managing venomous snakebites is recommended prior to antivenom administration. Phone consultation with a medical toxicologist is available through a United States regional poison control center by calling 1-800-222-1222. Contact information for poison centers around the world is provided separately. (See 'Additional resources' below.)

The clinical evaluation and management of coral snakebites are reviewed here. The principles of management of Crotalinae (eg, "pit vipers," including rattlesnakes, water moccasin [cottonmouth], or copperhead) snakebites and snakebites outside the United States are discussed separately. (See "Bites by Crotalinae snakes (rattlesnakes, water moccasins [cottonmouths], or copperheads) in the United States: Clinical manifestations, evaluation, and diagnosis" and "Snakebites worldwide: Clinical manifestations and diagnosis" and "Snakebites worldwide: Management".)

EPIDEMIOLOGY — Coral snakes are native to a large portion of the Americas from the southern United States through Mexico, Central America, and South America to southern Argentina (figure 1) [1]. Throughout the Americas, coral snakebites are uncommon, ranging from two bites per year in Argentina to fewer than 100 bites per year in the United States [1,2]. In Central America, Colombia, and Brazil, coral snakes comprise <1 to 2 percent of all snakebites [1,3]. Most bites involve Micrurus species [1,3,4], and Micrurus fulvius (eastern coral snake) (picture 1) and Micrurus tener (Texas coral snake) account for almost all bites reported in the United States (table 1) [5]. Envenomation usually causes neurologic symptoms. Envenomations, which are less common than total snakebites, including "dry bites" (in which no venom is transferred), occur approximately 75 to 80 times per year [4]. Fatalities from coral snake envenomation are rare but have been described [6,7].

Coral snakes are also found outside of the Americas, including Asia and southern Africa. Neurotoxicity with bites by these snakes is possible but rarely described [8,9].

CORAL SNAKE CHARACTERISTICS — Appearance, venom apparatus, and venom actions for coral snakes are as follows:

●Appearance – Coral snakes have small, oblong heads; lack a pit; and have very short, hollow fangs [1,10]. They can be identified by their brightly colored bands. Banding patterns can sometimes help distinguish coral snakes from similar nonvenomous snakes but should never be relied on for exclusion of diagnosis without the offending snake or a reliable photograph. As an example, venomous coral snakes within the United States and northern Mexico have red and yellow bands adjacent to each other (remembered by the phrase "red on yellow, kill a fellow; red on black, friend of Jack" or "venom lack") (picture 1). However, color intensity and banding patterns are variable and in other parts of the Americas can be reversed (red bands adjacent to black bands). In Mexico (south of Mexico City), Central America, and South America, some coral snakes are red and black, and several species of snakes without neurotoxic venom closely mimic the banding of coral snakes. Rarely, coral snakes can be all black or albino.

Misidentification (particularly in an emergency) may have potentially serious outcomes if a coral snake is mistaken for a nonvenomous snake. Thus, patients bitten by a banded snake in the geographic regions where coral snakes reside should be observed closely for an extended period of time before envenomation is excluded. (See 'Disposition' below.)

●Venom apparatus and requirements for envenomation – Coral snakes deliver venom through very small, fixed, hollow fangs located in the anterior maxilla. Envenomation usually requires that the snake chews on its victim [11]. Because the other teeth in the snake's mouth are rear-facing, once the snake becomes attached, it can be difficult to remove.

Most coral snakes play dead or retreat as a first response to a threat. Thus, a coral snakebite typically results from harassment by a human or companion animal such as a curious dog, or excessive handling of a snake.

●Venom mechanism of toxicity – Phospholipases A₂ (PLA₂) and "three finger" toxins (3FTx) are the most abundant toxins found in coral snake venom. The PLA₂s produce neurotoxicity by inhibiting presynaptic release of neurotransmitters at the neuromuscular junction (NMJ), while the 3FTxs act by blocking postsynaptic nicotinic acetylcholine receptors [12]. Both are present in the venom of North American Micrurus spp, though the PLA₂s appear to predominate.

Rarely, local tissue damage, direct muscle toxicity, and coagulopathy in addition to neurotoxicity have been reported with bites by selected species of coral snakes (eg, Micrurus lemniscatus halleri) [1,13]. However, pain at the bite site is frequently reported immediately after the bite even if neurotoxic signs and symptoms are delayed.

Animal models suggest that venom absorption from subcutaneous injection into the central circulation is primarily via the lymphatic system [14]. Intravenous antivenom does not rapidly or completely neutralize lymphatic venom; the lymph then functions as a depot for ongoing systemic absorption. Similarly, intravenous antivenom is unable to bind venom retained at the injection site, which may be subsequently absorbed [15]. Antivenom has no ability to reverse presynaptic toxicity at the NMJ. Giving antivenom early may prevent those components from being taken into the presynaptic membrane. Postsynaptic venom components may still be accessible to antivenom, meaning that there is a possible role for late administration even with established symptoms.

EVALUATION

History — When a coral snakebite is reported or suspected, the clinician should determine the following:

●Where and when the bite occurred

●A description of the snake if the snake has not been brought in or photographed

●How the bite occurred and whether there was more than one bite

●Any signs or symptoms and the timing of onset

●Initial treatment and first aid that was provided, including timing of first aid

●Any recent ethanol or recreational drug use that may modify the patient's presentation

●Pertinent past medical history, such as current medications (especially anticoagulants or beta blockers), any prior snakebites for which antivenom was given, or allergy to animals used in antivenom production (eg, horses, sheep, rabbits)

Coral snakebites frequently occur after intentional handling of the snake [6,16]. Most victims are male, and many patients are intoxicated at the time of the bite. In some cases, the coral snake is mistaken for other banded snakes (eg, king snake or milk snake) [17]. In other instances, the patient is bitten while trying to kill the snake. In tropical regions, snakebites may also occur when farmers encounter snakes in fields [1].

Patients may report pain and swelling or paresthesias at the bite site [1,3,6,16-18]. Initial systemic symptoms can include nausea, vomiting, abdominal pain, myalgia, or dizziness. Patients with neurotoxicity may complain of double vision, difficulty swallowing, difficulty speaking, or generalized weakness [3,16,19].

Physical examination — Neuromuscular signs of coral snake envenomation typically develop four to six hours after the snakebite but can be delayed for more than 12 hours [16,17]. Findings include salivation, drowsiness, and a descending muscle weakness that usually begins with ocular and bulbar signs including ptosis, ophthalmoplegia, dysarthria, and dysphagia (table 1) [16,18]. Generalized muscle weakness can cause respiratory depression or failure.

In most patients, pain at the bite site is minimal or absent. Although swelling at the bite site may be present, it is usually less pronounced than in patients with pit viper envenomations. Significant local tissue damage and coagulopathy are not typical of coral snake envenomation in the United States [1]. However, severe local pain, myolysis, thrombocytopenia, and coagulopathy in addition to delayed neurotoxicity have been described after envenomation by Micrurus lemniscatus halleri, which is found in Central and South America [1,13,20].

Ancillary studies — All patients with suspected or confirmed coral snakebites require serial assessment of respiratory function.

Respiratory function — Although the decision to perform endotracheal intubation and institute mechanical ventilation should be made on clinical grounds (including the need for airway protection associated with bulbar palsy), ancillary studies may provide additional objective information to augment serial clinical assessment in some patients:

●Pulmonary function testing – Serial measurements of pulmonary function, especially maximal inspiratory pressure (MIP, sometimes called negative inspiratory force [NIF]), maximal expiratory pressure (MEP), and forced vital capacity (FVC), can identify the presence and degree of respiratory muscle weakness. Serial measures of pulmonary function (instead of using one measure at one point in time) can be used as rough guidelines, especially when the respiratory decline is acute in children under six years of age. MIP can be obtained even when a lack of cooperation does not allow measurement of MEP or FVC. (See "Tests of respiratory muscle strength", section on 'Interpretation (PImax, PEmax, SNIP)' and "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Chronic ventilatory support'.)

Ventilatory support is indicated when the FVC is less than 50 percent of predicted, when the MIP is less negative than -30 cmH2O (eg, -20 cmH2O), or when the MEP is below -40 cmH2O. The diminished MIP indicates a high risk for hypercapnia, while the low MEP indicates inadequate cough strength and risk for secretion retention.

●Capnography – Capnography measures end-tidal CO₂ (EtCO₂) and respiratory rate with each breath in spontaneously breathing patients. Continuous capnography provides instantaneous feedback on the clinical status of the patient and can provide early detection of hypercarbia in victims of coral snake envenomation. (See "Carbon dioxide monitoring (capnography)", section on 'Acute respiratory distress'.)

●Blood gas measurement – Arterial or venous blood gas may also be used to assess the degree of respiratory acidosis in patients with weakness or declining clinical status. (See "Simple and mixed acid-base disorders", section on 'Response to respiratory acidosis'.)

Continuous pulse oximetry is also appropriate but is insensitive for the detection of respiratory failure.

Signs of hemo- or myotoxicity — Hemo- or myotoxicity has only been described after envenomation by the South American coral snake (Micrurus lemniscatus helleri) [1,13]. When a bite by this snake is confirmed or when the patient is bitten by a banded snake but is displaying signs of significant local pain, muscle pain, or bleeding that is atypical for most coral snakes, then the following studies should be obtained:

●Coagulopathy – Clotting parameters should be measured as follows:

•Complete blood count with platelets

•Prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPTT)

•Fibrinogen (only direct fibrinogen measurement is reliable; derived fibrinogen is not reliable in snakebites)

•Fibrin/fibrinogen degradation products or D-dimer

●Rhabdomyolysis – Studies helpful in identifying rhabdomyolysis and associated renal impairment include:

•Rapid urine dipstick for blood

•Urine for myoglobin

•Microscopic urinalysis

•Serum creatine kinase

•Serum electrolytes, calcium, phosphate, uric acid, blood urea nitrogen, and creatinine

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS — The diagnosis of a coral snakebite is typically straightforward because it often results from direct handling of a banded snake that must often be forcibly removed, as coral snakes frequently adhere tightly to the bite site. A digital photograph or verified snake specimen helps to confirm the diagnosis.

Coral snake envenomation causes a descending flaccid paralysis that often begins with ocular and bulbar signs, including ptosis, diplopia, dysphagia, and drooling and may occur more than 12 hours after the bite.

Descending paralysis is also seen with:

●Other neurotoxic snakes (see "Snakebites worldwide: Clinical manifestations and diagnosis", section on 'Neurotoxicity')

●Myasthenia gravis (see "Clinical manifestations of myasthenia gravis", section on 'Presenting symptoms')

●Botulism (see "Botulism", section on 'Clinical manifestations')

●Paralytic shellfish poisoning (see "Overview of shellfish, pufferfish, and other marine toxin poisoning", section on 'Paralytic shellfish poisoning')

Food history, for example, ingestion of shellfish (especially noncommercially harvested bivalve mollusks) or home canned foods, helps to differentiate these toxic causes of paralysis from a coral snakebite. (See "Overview of shellfish, pufferfish, and other marine toxin poisoning", section on 'Paralytic shellfish poisoning' and "Botulism", section on 'Clinical manifestations' and "Clinical manifestations of myasthenia gravis", section on 'Presenting symptoms'.)

The approach to muscle weakness caused by a variety of medical conditions is discussed in detail separately. (See "Etiology and evaluation of the child with weakness" and "Evaluation of the adult with acute weakness in the emergency department" and "Approach to the patient with muscle weakness".)

FIRST AID — Initial first aid of snakebites is directed at reducing the spread of venom and expediting transfer to an appropriate medical center according to the following general principles:

●Remove the patient from the snake's territory and keep them warm, at rest, and calm.

●Immobilize the injured body part in a functional position, preferably using pressure immobilization techniques. For bites on the extremities, keep the affected limb at the level of the heart. Do not apply constrictive/tourniquet dressings.

Pressure immobilization is used to delay systemic absorption of snake venom in areas where neurotoxic elapids are common. It is not used routinely in the United States, where local tissue toxicity from pit viper envenomation is most common. However, it may be useful to delay systemic absorption of neurotoxic venom after bites by coral snakes, especially when antivenom administration is delayed (figure 2). (See "Snakebites worldwide: Management", section on 'Pressure immobilization'.)

●Cleanse the wound.

●Withhold alcohol and drugs that may cause altered mental status.

●Attempt to identify the snake without endangering the patient or rescuer. A digital photo taken at a safe distance may be useful. Snake parts should not be handled directly.

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

INITIAL MANAGEMENT

Eastern or Texas coral snakebite

Asymptomatic or minor local symptoms — Coral snake envenomation can cause delayed neurotoxicity and respiratory failure [16,18]. Thus, all patients with confirmed or suspected coral snakebites warrant observation for 24 hours in a setting where antivenom administration and advanced respiratory support can be safely performed if the patient should deteriorate.

Patients with mild to moderate pain may receive oral analgesia (eg, acetaminophen or, since eastern or Texas coral snakes do not cause hemotoxicity, ibuprofen).

During observation, these patients require:

●Frequent assessment for motor weakness with an emphasis on ocular and bulbar findings (eg, ptosis, diplopia, ophthalmoplegia, dysphagia, and dysarthria)

●Continuous capnography

●Serial measures of pulmonary function, especially maximal inspiratory pressure (MIP, sometimes called negative inspiratory force [NIF]), and in cooperative patients, maximal expiratory pressure (MEP) and forced vital capacity (FVC)

A reasonable approach is to assess motor weakness and pulmonary function hourly for the first 12 hours and then, if no progression, decrease to every two hours for the remaining 12 hours of observation.

Physicians should also acquire North American coral snake antivenom as soon as possible and have it immediately available for administration if evidence of envenomation develops, including neuromuscular effects, systemic effects such as vomiting, or local effects beyond minor swelling and pain due to traumatic bite injury (see 'North American coral snake antivenom' below). In the United States, regional poison control centers are available to assist with locating and procuring snake antivenom. Coral snake antivenom production has resumed after a period of scarcity, and in-date product is available for purchase and shipping [21].

The benefit of empiric administration of North American coral snake antivenom to asymptomatic patients before clinical signs of envenomation develop is unclear. For asymptomatic patients with suspected or confirmed eastern coral snakebite, we suggest against empiric antivenom administration. However, some experts still advocate for empiric coral snake antivenom treatment for these patients.

In past years, prior to shortages of North American coral snake antivenom, asymptomatic patients with suspected eastern coral snakebites routinely received empiric antivenom treatment. When antivenom was scarce, observation of patients for onset of symptoms prior to administering antivenom became a more common practice in the United States. Subsequent experience suggests that the risk of empiric antivenom administration may outweigh the benefits in most asymptomatic patients. For example, in a retrospective observational study of 240 patients with eastern coral snakebites reported to the Florida Poison Information Network and who were asymptomatic at presentation, only 6 of 106 patients (5.7 percent) who had antivenom initially withheld ultimately received antivenom; one of these patients went on to require endotracheal intubation and mechanical ventilation for 24 days [18]. In the 134 asymptomatic patients who received antivenom empirically, three underwent endotracheal intubation and mechanical ventilation for an average of six days. Of the 252 symptomatic and asymptomatic patients who received antivenom in this study, 18 percent had adverse reactions including shortness of breath (8 percent), hypotension (2 percent), and angioedema (1 percent). Thus, serious neurotoxicity can still occur despite administering North American coral snake antivenom before symptoms develop, and serious adverse effects occur in a significant proportion of patients receiving antivenom.

Neuromuscular or other systemic signs of envenomation — Symptomatic patients are at risk for progressive neuromuscular weakness and respiratory failure after an eastern or Texas coral snakebite. Neurotoxicity may also progress despite administration of antivenom [16-18].

In addition to antivenom, severe pain warrants treatment with intravenous (IV) opioid medications (eg, fentanyl or morphine).

Neurologic assessment and respiratory support — Symptomatic patients should have serial, detailed neurologic examinations hourly for at least 24 hours [16,22]. Important clinical findings include the presence of motor weakness, particularly involving cranial nerves and resulting in ptosis, diplopia, ophthalmoplegia, dysphagia, and dysarthria. The clinician should also assess the patient's ability to swallow, strength of the gag, and maintain adequate respiratory ventilation. Once neurologic signs of motor weakness occur, progression to respiratory paralysis can be rapid, and more frequent monitoring of respiratory function and physical examination may be necessary. (See 'Respiratory function' above.)

Patients with clinical evidence of ventilatory failure or who are in danger of aspiration due to inability to handle oral secretions warrant prompt endotracheal intubation. The clinician should intervene with endotracheal intubation by rapid sequence intubation and mechanical ventilation once signs of respiratory failure develop, regardless of whether they have received antivenom or not. (See "Rapid sequence intubation in adults for emergency medicine and critical care" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach" and 'North American coral snake antivenom' below.)

North American coral snake antivenom — When administering antivenom, clinicians who are unfamiliar with the management of snakebites should seek expert consultation with a medical toxicologist or experienced physician or contact a regional poison control center. (See 'Additional resources' below.)

●Indications – For patients with weakness or other evidence of envenomation beyond minor pain and swelling at the bite site (eg, salivation, vomiting, or paresthesias) after a suspected or confirmed eastern or Texas coral snakebite, we recommend antivenom rather than supportive care alone. Antivenom is most effective when given as soon as possible after the onset of symptoms. In addition to antivenom, severe pain warrants treatment with IV opioid medications (eg, fentanyl or morphine).

For asymptomatic patients with suspected or confirmed eastern coral snakebites, we suggest against empiric administration of antivenom, although some experts do advocate for empiric administration to patients with confirmed bites. (See 'Asymptomatic or minor local symptoms' above.)

●Precautions – There are no absolute contraindications to North American coral snake antivenom administration. Relative contraindications include:

•Known allergy to horse products or horse serum

•Prior allergic reaction to North American coral snake antivenom

•Lack of medical resources to manage a potential allergic reaction

In most instances of serious envenomation, the benefit of antivenom administration outweighs the risk for patients with known allergy or prior allergic reactions. Whenever possible, the clinician should consult with a regional poison control center or physician with experience providing antivenom to such patients prior to antivenom administration.

In patients with a history of allergic reactions to horse or other animal serums, other chemical or food allergies, atopy or similar conditions, the clinician should make pre-antivenom administration preparations to manage an acute allergic reaction, should it develop (see 'Treatment of hypersensitivity reactions' below and "Snakebites worldwide: Management", section on 'Premedication'):

•Epinephrine should be readily available and pre-mixed.

•Premedication with H1 and/or H2 blockers is suggested by some experts, although evidence for benefit is mixed.

•A slower rate of administration may be helpful to reduce the incidence and severity of adverse reactions.

•Should a reaction occur, administration of parenteral epinephrine and/or steroids is indicated.

●Dose and administration – North American coral snake antivenom is the only approved antivenom available in the United States. Coral snake antivenom production has resumed after a period of scarcity, and in-date product is available for purchase and shipping. Per manufacturer instructions, the suggested initial dose of North American coral snake antivenom is three to five vials by slow intravenous push with the same dose given regardless of age [21].

North American coral snake antivenom can cause severe allergic reactions [18]; clinicians should only administer it in a continuously monitored emergency or intensive care unit setting.

Although the manufacturer instructions recommend skin testing, we recommend against it. Skin testing is not sufficiently sensitive or specific to determine the risk of allergic reaction. If antivenom is indicated, it should be given without skin testing, and the physician should be prepared to treat allergic reactions.

North American coral snake antivenom does not neutralize venoms of the Arizona or Sonoran coral snake. However, clinically significant bites from these snakes have not been reported.

●Efficacy and adverse reactions – Based upon case series and observational studies, early antivenom administration at the onset of neurotoxicity may prevent or reverse muscle paralysis, decrease the number of patients requiring endotracheal intubation, and/or shorten the duration of intubation [1,17,18,23]. However, despite receiving antivenom, muscle weakness and paralysis may still develop or, if present at the time of antivenom administration, worsen [16,18]. Thus, patients who receive antivenom require hospital admission and close monitoring for progression of neurotoxicity in an intensive care setting. For example, in a retrospective observational study of symptomatic patients, 7 of 112 patients who received antivenom still required endotracheal intubation and mechanical ventilation [18]. Adverse reactions occurred in 18 percent of patients who received antivenom. Of these, 1 to 2 percent were life-threatening (hypotension or angioedema).

Taken together, evidence indicates that coral snake antivenom might prevent or reverse neurotoxicity, especially when given soon after the bite. Although mild allergic reactions are relatively common, life-threatening reactions are rare, occurring in approximately 1 to 2 percent of patients receiving antivenom, depending upon the specific product given. This risk/benefit profile of treatment is likely superior to that of prolonged endotracheal intubation and mechanical ventilation that would result if no antivenom is given.

The empiric use of North American coral snake antivenom for asymptomatic patients is discussed separately. (See 'Asymptomatic or minor local symptoms' above.)

Therapies of uncertain benefit

Expired or alternative antivenoms — If US Food and Drug Administration (FDA)-approved antivenom is not available, no data exist concerning the benefits or risks of giving expired, alternative, or experimental antivenom for the treatment of neurotoxicity or systemic effects (eg, pain, paresthesia, nausea, or emesis) after an eastern or Texas coral snakebite. Use of expired medications or biological agents in the United States is specifically prohibited by regulatory authorities, including the US FDA and by law in some states. When giving an alternative antivenom that has not undergone US FDA approval, the clinician should notify the US FDA Office of Vaccines, Blood and Biologics (301-827-3524) and the local institutional review board in accordance with the hospital policy for experimental administration of a biologic on a compassionate basis before, or as soon as possible after administering the antivenom.

Administration of expired or alternative antivenoms to patients with neurotoxicity or systemic effects should only occur after consultation with a regional poison control center and a medical toxicologist. (See 'Additional resources' below.)

Prompt supportive care for respiratory failure, including endotracheal intubation and mechanical ventilation, without antivenom administration, should result in complete recovery in most patients, although duration of mechanical ventilation may be prolonged [24].

●Expired antivenom – Compassionate release of expired North American coral snake antivenom may be appropriate for the treatment of neurotoxicity or systemic effects (eg, pain, paresthesia, nausea, or emesis) after a suspected Texas or eastern coral snakebite when the benefits outweigh the risks in an individual patient and only if an adequate supply of in-date, North American coral snake antivenom is not available. Whenever possible, preapproval from the US FDA Office of Vaccines, Blood and Biologics (301-827-3524) should be obtained before administering an expired product. In addition, informed consent should be obtained from the patient and/or parent or guardian.

●Alternative antivenoms – If no North American coral snake antivenom is available, the clinician may attempt to obtain an alternative antivenom to treat patients with neurotoxicity. However, there is typically a significant delay (eg, 24 to 48 hours) in locating and transporting the antivenom to the patient. In the meantime, for patients with neurotoxicity, a trial of neostigmine is a reasonable option. (See 'Neostigmine' below.)

Based upon studies in small animals, the following antivenoms have been shown to neutralize venoms from some coral snake species whose geographical range extends into the United States [25-28]:

•Mexican coral snake antivenom (Coralmyn)

•Tiger snake antivenom (produced in Australia by Seqirus)

•Australia/New Guinea polyvalent antivenom (produced in Australia by Seqirus)

•Anticoral antivenom (produced by Instituto Clodomiro Picado, Costa Rica)

However, the ability of these antivenoms to reverse symptoms after North American coral snake envenomation has not been studied. The benefits of administering such products are only theoretical, while the risks associated with the product are real. North American zoos that care for exotic snakes may have these antivenoms. A regional poison center (1-800-222-1222) can assist in locating the nearest supplies of foreign antivenom and arranging contact. The regional poison center arranging procurement of an alternative antivenom, in collaboration with its consultants in the Antivenom Index, can also assist with the necessary notifications and reporting.

Experimental antivenom (equine F(ab')2 ) — To address the past shortage of coral snake antivenom in the United States, a novel, equine F(ab')2 antivenom has been produced against M. fulvius venom and has been tested in 20 cases in Florida as part of a phase 3 clinical trial [29,30]. The patients were mostly male (18/20; 90 percent), adult (mean age 36 years; range 11 to 61), and presented for care with a mean delay of 5.7 hours (range 1.6 to 16). All patients received five vials of antivenom, and one patient received a second dose. Venom was detectable at baseline in nine (45 percent) patients and became undetectable in all cases within two hours of antivenom administration. No patients experienced respiratory failure, and all survived. Adverse effects (immune reactions) occurred in six patients. Equine F(ab')2 antivenom is currently restricted to experimental protocols and is not available for general clinical use.

Neostigmine — If antivenom is not available to treat an eastern or Texas coral snakebite, a trial of neostigmine, coadministered with atropine, is unlikely to be beneficial and should not be given. The venom of North American coral snakes contains a predominance of phospholipases A₂ (PLA₂) beta-neurotoxins, which act presynaptically, and successful use of neostigmine has not been reported after envenomation by these species [12].

Coral snakebites by other species

Antivenom — For symptomatic patients with coral snakebites by species typically found in Mexico, Central America, and South America, we suggest antivenom. Regional and international poison control centers can help locate and procure antivenom for victims of coral snakebites. A list of available antivenoms by snake species can be found at Clinical Toxinology Resources. The World Health Organization (WHO) also has a snake and antivenom search tool, although the database is not yet complete. A trial of neostigmine may be attempted if antivenom is not available. (See 'Neostigmine' below.)

Coral snake antivenom is potentially associated with severe allergic reactions; it should only be administered in a continuously monitored emergency or intensive care unit setting as described separately. (See 'North American coral snake antivenom' above and 'Treatment of hypersensitivity reactions' below.)

The initial dose of antivenom varies by manufacturer and specific type of coral snakebite being treated. The dose does not differ between adults and children. For specific antivenom dosing, the clinician should refer to the manufacturer's directions for use and local guidelines. In Brazil, an initial dose of 10 vials of antivenom Micrurus is recommended for coral snake envenomation [1,23].

Although the manufacturer instructions may recommend skin testing, it is insufficiently sensitive or specific to determine the risk of allergic reaction. If antivenom is indicated, it should be given without skin testing, and the physician should be prepared to treat allergic reactions.

Patients with signs of neurotoxicity require frequent assessment of neuromuscular and respiratory status. (See 'Neurologic assessment and respiratory support' above.)

Patients who are asymptomatic or have only minor local swelling and pain, and with confirmed or suspected coral snakebite warrant observation for 24 hours in a setting where antivenom administration and advanced respiratory support can be safely performed if the patient should deteriorate. However, we suggest against empiric administration of antivenom.

During observation, these patients require:

●Frequent assessment for motor weakness with an emphasis on ocular and bulbar findings (eg, ptosis, diplopia, ophthalmoplegia, dysphagia, and dysarthria)

●Continuous capnography

●Serial measures of pulmonary function, especially maximal inspiratory pressure (MIP), and in cooperative patients, maximal expiratory pressure (MEP) and forced vital capacity (FVC)

Physicians should also obtain species-specific antivenom as soon as possible and have it immediately available for administration if neuromuscular or other severe signs of envenomation develop.

Outside of the United States, evidence for the use of coral snake antivenom is confined to case reports and reviews [1,3,13,23,31]. In most reports, antivenom is effective in reversing toxicity [23]. In South America, antivenom is used for patients with neurotoxic findings such as ptosis or weakness after coral snakebite [20,32]. Among 150 reports of envenomation by Micrurus species in Brazil occurring over almost 150 years, 77 percent of patients received antivenom [20]. Among 10 patients with neurotoxicity who received F(ab')₂ Micrurus antivenom, only mild adverse reactions occurred (urticaria in three patients and itching in two patients).

Neostigmine — For patients with neurotoxicity after a coral snakebite outside of the United States and for whom coral snake antivenom is not rapidly available, it is reasonable to perform a trial of neostigmine with coadministration of atropine. However, evidence for benefit in patients with coral snakebite is inconsistent. Neostigmine therapy should not delay respiratory support for patients who cannot maintain their airway or who develop respiratory failure. For patients with clinical improvement, continued neostigmine therapy may be provided [33]. Dosing for neostigmine and atropine to treat snake venom-induced neurotoxicity is provided separately. (See "Snakebites worldwide: Management", section on 'Anticholinesterases'.)

In patients with neurotoxicity after snakebites, clinical improvement after administration of the anticholinesterase neostigmine primarily results from reversal of postsynaptic inhibition. Coral snake venoms contain toxins that have actions at both presynaptic and postsynaptic receptors, and venom composition varies by coral snake species [12]. Thus, the potential for neostigmine to successfully counteract neurotoxicity after a coral snakebite is inconsistent [12,20]. Case series and case reports indicate that neostigmine has reversed skeletal muscle weakness and paralysis in some patients after bites by Micrurus frontalis [20,31]. However, for other coral snake species such as M. lemniscatus and M. laticollaris, neostigmine may not have a beneficial effect based on in vitro studies and failure to reverse neurotoxicity in two human case reports [20].

Treatment of hypersensitivity reactions — The clinician should immediately stop antivenom infusion in patients who experience signs of acute hypersensitivity (eg, urticaria, bronchospasm, angioedema, or shock). These patients should receive treatment for anaphylaxis as outlined in the rapid overviews for anaphylaxis in adults (table 2) and in children (table 3).

As a proportion of acute hypersensitivity is probably due to nonimmunologic mechanisms, recurrent reactions are not inevitable, and the clinician may attempt to resume antivenom. A reassessment of the potential risks and benefits should be made prior to readministration of antivenom, particularly where severe hypersensitivity reactions have occurred.

Most coral snake antivenoms are derived from horse serum. In the United States, North American coral snake antivenom (Lot L67530) is an equine IgG antivenom. Mild allergic reactions and serum sickness are common complications; life-threatening reactions (eg, angioedema or hypotension) are less frequent, but may occur. Outside of the United States, fractionated antivenoms are available (eg, F(ab')₂ antivenom in Brazil). Data are limited regarding the frequency of adverse reactions with these antivenoms. However, urticaria and itching seem to occur frequently, and life-threatening reactions are still possible and warrant proper preparation before administering antivenom. A serum sickness reaction has been reported four days following the administration of an equine, Central American coral snake antivenom (Clodomiro Picado, Costa Rica) [34].

The relative frequency of adverse reactions was described in one case series of 240 patients with coral snakebites reported in the United States, who received North American coral snake antivenom [18]:

●Hives – 12 percent

●Itching – 9 percent

●Shortness of breath – 8 percent

●Hypotension – 2 percent

●Angioedema – 1 percent

Wound management — Tetanus prophylaxis should be administered to snakebite patients according to the recommended immunization schedule (table 4). In the rare instance of coral snake envenomation with coagulopathy, tetanus prophylaxis should be postponed until after antivenom therapy and normalization of clotting function. (See "Tetanus-diphtheria toxoid vaccination in adults" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Wound management'.)

We discourage the use of prophylactic antibiotics in coral snakebite victims. Although snakebites may result in the inoculation of bacteria, infection following most coral snakebites is rare [17,18,20,35]. Antibiotics (such as ampicillin-sulbactam or amoxicillin-clavulanate) should only be administered for established infections or for heavily contaminated wounds.

DISPOSITION — All patients who have required treatment with antivenom require hospital admission for further observation and supportive care.

Asymptomatic patients with a coral snakebite should be observed for 24 hours because neurotoxicity may be delayed [22].

OUTCOMES — Most victims of coral snakebites fully recover, and death is rare [36].

ADDITIONAL RESOURCES

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".)

A listing of available antivenoms by region is available at Clinical Toxinology Resources. The World Health Organization (WHO) also has a snake and antivenom search tool, although the database is not yet complete.

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

●Epidemiology – Coral snakes (Elapidae) are native to the southern United States (picture 1), Mexico, Central America, and portions of South America. Bites are uncommon but can be life-threatening. Coral snake venom produces weakness and paralysis via toxins that target the neuromuscular junction. (See 'Epidemiology' above and 'Coral snake characteristics' above.)

●Evaluation – Findings of coral snake envenomation are provided in the table (table 1). Important history includes (see 'History' above):

•When the bite occurred

•When symptoms began

•Prior history of snakebite treated with antivenom

•Allergy to horses or sheep

Neuromuscular signs of coral snake envenomation are characterized by ptosis, ophthalmoplegia, dysarthria, and/or dysphagia with potential progression to respiratory failure (see 'Physical examination' above). These findings may be delayed more than 12 hours after the snakebite.

Recommended ancillary studies consist of (see 'Ancillary studies' above):

•Pulmonary function testing, especially maximal inspiratory pressure (MIP, sometimes called negative inspiratory force [NIF]), maximal expiratory pressure (MEP), and forced vital capacity (FVC); MIP alone is performed in uncooperative children.

•For patients with signs of weakness, blood gas measurement.

•For patients who are displaying signs of significant local pain, muscle pain, or bleeding (atypical for most coral snakebites), clotting parameters and studies to assess for rhabdomyolysis.

●Diagnosis – The diagnosis of a coral snakebite relies on a history of banded snakebite. It is further supported by accompanying signs of envenomation, especially muscle weakness. A digital photograph or verified coral snake specimen confirms the diagnosis. (See 'Diagnosis and differential diagnosis' above.)

●Management – Clinicians who lack experience caring for patients with coral snakebites should seek expert consultation with a medical toxicologist, regional poison control center, or physician experienced in management of coral snakes in the region. (See 'Additional resources' above.)

Management is based on the clinical presentation:

•Asymptomatic or minor local symptoms (mild pain or swelling at the bite site) – Patients with no symptoms or only minor local swelling and pain at the bite site after suspected or confirmed eastern, Texas, or other coral snakebite warrant observation for 24 hours. For these patients, we suggest against empiric antivenom administration because the risk of antivenom administration appears to exceed the risk of neurotoxicity (Grade 2C). However, some experts treat all confirmed coral snakebites with antivenom regardless of clinical findings. (See 'Asymptomatic or minor local symptoms' above and 'Coral snakebites by other species' above.)

During observation, these patients require continuous capnography and:

-Serial assessment of motor strength, especially ocular and bulbar findings such as ptosis, diplopia, ophthalmoplegia, dysphagia, and dysarthria.

-Serial measures of pulmonary function, especially MIP, NIF, and in cooperative patients, MEP and FVC.

A reasonable approach is to assess motor weakness and pulmonary function hourly for the first 12 hours and then, if no progression, decrease to every two hours for the remaining 12 hours.

•Neuromuscular or other systemic findings of envenomation – For patients with weakness or other systemic findings of envenomation (eg, salivation, vomiting, or paresthesias) beyond minor pain and swelling at the bite site after a suspected or confirmed eastern or Texas coral snakebite, we recommend the administration of antivenom rather than supportive care alone (Grade 1C). For symptomatic patients with coral snakebites by species typically found in Mexico, Central America, and South America, we suggest antivenom rather than supportive care alone (Grade 2C).

Antivenom is most effective when given as soon as possible after the onset of symptoms. Coral snake antivenoms can cause severe allergic reactions and require administration in an acute care setting. (See 'North American coral snake antivenom' above and 'Antivenom' above.)

The initial dose of antivenom does not differ between adults and children. For specific antivenom dosing, the clinician should refer to the manufacturer's directions for use and local guidelines. (See 'North American coral snake antivenom' above and 'Antivenom' above.)

If anaphylaxis occurs, stop antivenom infusion and provide emergency management as described in the rapid overviews (table 2 and table 3).

Symptomatic patients also warrant monitoring and serial assessment of motor strength and pulmonary function, as described above, but with more frequent assessment of motor weakness and pulmonary function (eg, hourly).

Patients with clinical evidence of ventilatory failure or who cannot maintain their airway warrant prompt endotracheal intubation and mechanical ventilation, regardless of whether they have received antivenom or not.

-Neostigmine – If there is a delay in obtaining species-specific antivenom and neurotoxicity is developing after a suspected South American coral snakebite, it is reasonable to perform a trial of neostigmine with coadministration of atropine. However, it should not delay endotracheal intubation and mechanical ventilation for patients who cannot maintain their airway or who develop respiratory failure. Neostigmine is unlikely to be beneficial for neurotoxicity caused by eastern or Texas coral snake envenomation. (See 'Neostigmine' above and "Snakebites worldwide: Management", section on 'Anticholinesterases'.)

If antivenom is not available to treat an eastern or Texas coral snakebite, a trial of neostigmine, coadministered with atropine, is unlikely to be beneficial and should not be given. (See 'Neostigmine' above.)

●Wound management – Administer tetanus prophylaxis according to the recommended immunization schedule (table 4). We discourage the use of prophylactic antibiotics in coral snakebite victims. (See 'Wound management' above.)

ACKNOWLEDGMENT — We are saddened by the death of Steven A Seifert, MD, FAACT, FACMT, who passed away in May 2022. UpToDate gratefully acknowledges Dr. Seifert's outstanding work as an author for this topic.