Cobra Envenomation 

Updated: Jun 15, 2018
Author: Robert L Norris, MD; Chief Editor: Joe Alcock, MD, MS 

Overview

Background

To many people, the cobra is the quintessential venomous snake. Cobras discussed in this article include species in the genus Naja and other similar venomous snakes, such as Ophiophagus hannah (king cobra), Hemachatus haemachatus (ringhals), Walterinnesia aegyptia (desert black snake), Boulengerina species (water cobras), and Pseudohaje species (tree cobras).

Most cobras are large snakes, 1.2-2.5 m in length. The king cobra, which may reach 5.2 m, is the largest venomous snake in the world. Cobras live throughout most of Africa and southern Asia. Their habitats vary, and some species adapt readily to life in cultivated areas and around villages.

When encountered, cobras usually try to escape but occasionally defend themselves boldly and may appear aggressive. Most of these snakes elevate the head and spread the neck as a threat gesture. However, a number of other snakes, venomous and nonvenomous, use this defense as well.

Most snakebites are inflicted on body extremities. Because cobras are popular as show snakes, bites on the hands and fingers are common.

By far, rural agricultural workers and other people in Asia and Africa receive most bites while working outdoors without protective footwear or when cutting tall grass with a hand blade. In North America and Europe, captive cobras may cause bites to zookeepers or amateur collectors.[1, 2]

Not all snakebites result in envenomation. In the case of cobras, the percentage of dry bites may be quite high, 45% in one series of 47 cases from Malaysia. In another series, 1 of 3 snake charmers bitten by large king cobras showed no signs of envenomation.

In addition to biting, some cobra species have a unique defense; they eject or spit jets of venom toward an aggressor, usually and accurately directly at the eyes. The fangs of these species are specially modified with the discharge orifice on the anterior face rather than at the tip. The effective discharge range of a large snake is at least 3 m. The ringhals and certain African species of Naja are the most effective spitters, but the spitting behavior also is observed among some Asian Naja species.

Pathophysiology

Cobra envenomation is an extremely variable process. The envenomations of some species cause profound neurological abnormalities (eg, cranial nerve dysfunction, abnormal mental status, muscle weakness, paralysis, and respiratory arrest). With other cobras, local tissue damage is of primary concern.

Necrosis is typical of bites by the African spitting cobras (Naja nigricollis, Naja mossambica, Naja pallida, and Naja katiensis), the Chinese cobra (Naja atra), the Monocellate cobra (Naja kaouthia), and the Sumatran spitting cobra (Naja sumatrana). Although the venoms of these cobras contain neurotoxins, necrosis often is the chief or only manifestation of envenoming in humans. Occasionally, a combination of neurologic dysfunction and tissue necrosis may occur as with the Indian cobra (Naja naja). The images below depict several species.


Naja atra (Chinese cobra). Photo by Sherman Minto Naja atra (Chinese cobra). Photo by Sherman Minton, MD.

Naja kaouthia (Monocellate cobra). Photo by Sherm Naja kaouthia (Monocellate cobra). Photo by Sherman Minton, MD.

Naja naja (Indian Cobra). Photo by Robert Norris, Naja naja (Indian Cobra). Photo by Robert Norris, MD.

Cobra venoms have been studied extensively. As with all snake venoms, they are multicomponent products whose toxins are mostly proteins and polypeptides.

Venoms can be divided into the following categories:

  • With most species, excluding some of the African spitting cobras, the most clinically significant toxins are postsynaptic neurotoxins that competitively bind to nicotinic acetylcholine receptors to produce depolarizing neuromuscular blockade. One group in this category has 60-62 amino acids and 4 disulfide bridges. Another has 71-74 amino acids and 5 disulfide bridges.

  • The second venom category comprises so-called cardiotoxins, which are actually generalized cell-membrane poisons that produce irreversible cell depolarization. Such depolarization may cause dysrhythmia, hypotension, and death.

  • Toxins in the third category activate complement via the alternative pathway (C3-C9 sequence).

  • The fourth category is composed of enzyme toxins, such as phospholipase A2 (variable toxicity), hyaluronidase (facilitates tissue dispersion of other toxins), L -amino acid oxidase (gives many venoms a characteristic yellow coloration), and acetylcholine acetylhydrolase (unknown toxicity). Other proteolytic enzymes are found in the venom of the king cobra.

Naja philippinensis (Philippine cobra) venom is the most toxic, with a subcutaneous median lethal dose (LD50) of 0.14 mg/kg in mice. In comparison, the corresponding LD50 for Naja naja (Indian cobra) venom is 0.29 mg/kg, for Naja haje (Egyptian cobra) venom is 1.75 mg/kg, for king cobra venom is 1.73 mg/kg, and for Naja nigricollis (black-necked spitting cobra) venom is 3.05 mg/kg.

An additional, unique form of toxicity with some Asian and African species is acute ophthalmia, which occurs when venom is spit into the eyes. Spitting cobras can spit venom into a person's eyes from up to 3 m away. Immediate and intense pain results, with blepharospasm, tearing, and blurring of vision. Systemic toxicity does not occur with eye exposure, but corneal ulcerations, uveitis, and permanent blindness have been reported in untreated cases. Occasionally, ocular exposure occurs when a person has venom on their hands (as following laboratory venom extraction from a snake) and rubs his or her eyes.[3]

About half of the cases ascribed to the African spitting cobras (N nigricollis, N mossambica, N pallida, N katiensis) showed corneal ulceration, and some patients experienced permanent visual impairment or blindness. Cases ascribed to the Asian spitting cobras and the African ringhals are usually less severe.

Epidemiology

Frequency

United States

Envenomations result from human interaction with cobras in zoos, research laboratories, and private collections in the United States and other countries where cobras lack natural habitat. In a series of 54 consultations regarding bites by non-native snakes in the United States, 23 involved cobras. One fatality occurred, and 7 other cases involved serious envenoming. In Russell's 1980 series, cobras inflicted 18 of the 85 bites by non-native snakes.[4] No comparable data are available for other nations, though it was reported that only 3 cobra bites among 32 bites inflicted by non-native venomous snakes occurred in Britain (rattlesnakes were implicated most often in this series).

International

Snakebites are a significant medical problem in parts of Africa and Asia. In West Africa, the annual bite incidence is 40-120 bites per 100,000 population. Two rural Congolese regions report an annual incidence of 430 bites per 100,000 population. In a 7-year survey, the Natalese incidence was 24 bites per 100,000 population.

Sex

Because of increased exposure to snakes, men are bitten more often than women.

Mortality/Morbidity

In India, the annual mortality incidence is 5.6-12.6 per 100,000 population. At one time, Burma listed snakebite as its fifth leading cause of death. More recently, the annual mortality incidence was 3.3 per 100,000 population.[5] Data from Thailand and Malaysia in the 1980s demonstrate an annual mortality incidence of 0.1 per 100,000 population.[6, 7]

Determining the exact contribution of cobras to overall snakebite morbidity and mortality is difficult. In most cases, bitten individuals are unable to identify the snake. In India, the tendency is to ascribe all fatal or serious bites to cobras. Physicians are also likely to attribute all bites with neurotoxic symptoms to cobras.

In a Thai survey, cobras made up 17% of the 1145 snakes identified in bites and were responsible for 25% of the fatalities associated with those bites.[8] In northern Malaysia, cobras accounted for 23 of 854 bites in which the snake was identified. In a survey in Taiwan, cobras were blamed for 100 of 851 bites in which the snake was identified; none was fatal.[9] Cobras accounted for 2 of 95 bites on a Liberian rubber plantation.[10] The ringhals was responsible for 18 of 314 envenomations in Natal. Based on patients' symptoms alone, 18 other bites in this series were ascribed to cobras.

King cobra bites are considered more serious than bites from other cobra species because of the greater volumes of injected venom and the more rapid onset of neurotoxic symptoms. Mortality is also higher. In a series of 35 cases, 10 deaths occurred. Ringhals bites are similar to other cobra bites but are less serious both locally and systemically. Deaths are rare. A medical report of 4 bites by the desert black snake described relatively mild symptoms and reported recovery without specific treatment. Anecdotal reports of fatal bites exist. No medical accounts of bites by water cobras or tree cobras exist. Anecdotal evidence suggests both are dangerous.[11]

Prognosis

Many patients recover with no specific treatment.

The neurotoxic effects of cobra venom are completely reversible, though recovery may take up to 6 days.

Reports of death within 1 hour of cobra bite exist, but a timeframe of 2-6 hours is more typical of fatal cases.

With sound supportive care (eg, prevention of aspiration and respiratory support) and appropriate, prompt antivenom administration, anticipate recovery from cobra envenomation.

Patient Education

Advise amateur herpetoculturists bitten by a venomous snake in their collection to not keep such animals. If they previously have received antivenom, their risk for an allergic reaction may be increased should antivenom use be required again in the future.

For patient education resources, visit the First Aid and Injuries Center. Also, see the patient education article Snakebite.

 

Presentation

History

The onset of symptoms and signs following a cobra bite can be extremely variable, as follows:

  • Immediate, local pain (almost always present)

  • Soft tissue swelling (may be progressive)

  • Neurologic findings, which may begin early and be rapidly progressive (in anecdotal cases, victims have suffered respiratory arrest in a matter of minutes) or may be delayed in onset as long as 24 hours

  • Alteration of mental status (eg, drowsiness, occasionally with euphoria)

  • Complaints related to cranial nerve dysfunction, such as ptosis (often one of the earliest neurotoxic findings), ophthalmoplegia, dysphagia, and dysphasia

  • Profuse salivation, nausea, vomiting, and abdominal pain

  • Paresis of neck and jaw muscles and generalized muscular weakness followed by flaccid paralysis

  • Shortness of breath, respiratory failure (muscular paresis and accumulated secretions)

  • Chest pain or tightness

  • Eye pain, tearing, blurred vision (with eye exposure to venom from spitting cobras)

Physical Examination

Impending respiratory failure may be heralded by respiratory distress or weakness and cyanosis.

Neurologic dysfunction may be heralded by altered mental status, ptosis (may be the earliest sign of systemic toxicity), and/or generalized weakness or paralysis.

Cardiovascular collapse may be heralded by hypotension and/or tachycardia or bradycardia.

Soft tissue edema may be noted.

Signs of necrosis usually appear within 48 hours of the bite. The area around the fang punctures darkens.

See the image below.

Necrosis from a Naja atra (Chinese cobra) bite. Th Necrosis from a Naja atra (Chinese cobra) bite. This resulted in a severe deformity. The patient had few systemic signs or symptoms. Photo by Sherman Minton, MD.

Blistering may follow.

Necrosis is usually confined to the skin and subcutaneous tissue but may be quite extensive. See the image below.

Necrosis from a cobra bite. Photo by Sherman Minto Necrosis from a cobra bite. Photo by Sherman Minton, MD.

A putrid smell is characteristic.

Acute inflammation of the eye follows venom-spitting exposure and is characterized by ocular congestion, edema of the conjunctiva and cornea, and a whitish discharge.

Complications

Complications of cobra envenomation may include the following:

  • Respiratory failure/arrest

  • Cardiovascular collapse

  • Prolonged neuromuscular weakness

  • Tissue necrosis

  • Antivenom-related complications - Nonallergic anaphylactic (anaphylactoid) reactions, delayed serum sickness
  • Venom-induced ophthalmia (spitting cobras)

 

DDx

 

Workup

Laboratory Studies

Laboratory studies offer no diagnostic benefit for snake envenomation. Baseline labs (eg, complete blood count [CBC], electrolyte tests, renal function studies, coagulopathy panels) may be reasonable in severe bites or if the patient has significant underlying medical problems. Coagulopathy is not an expected feature of bites by most cobras, though prolonged bleeding and failure of clot retraction have been reported following bites by African spitting cobras and anticoagulant proteins have been identified in the venom of the African ringhals (Hemachatus haemachatus).

Arterial blood gas (ABG) determinations may be helpful if the patient's respiratory status is questionable.

In some regions of the world, researchers are developing immunologic tools, such as enzyme-linked immunosorbent assays (ELISAs), to aid in species identification and possibly in severity grading.

Imaging Studies

A chest radiograph benefits patients who have severe envenomations, require intubation, or show evidence of cardiorespiratory failure.

Other Tests

An electrocardiogram (ECG) should be obtained if the victim complains of chest pain or if there is evidence of dysrhythmia.

 

Treatment

Prehospital Care

Prompt movement of the victim to a medical facility capable of rendering advanced care, including airway support and antivenom administration, is critical.

Make every effort to specifically identify the envenoming species; this aids further management and determination of the proper antivenom to be administered.

If the patient is bitten by a wild snake, identification may be equally problematic and important, particularly if there is more than one antivenom option for the region. Attempts to capture or kill the snake could result in additional bites or delay in transporting the victim to medical care. If possible, a digital photo of the snake may be a better choice. If the snake is killed, it must be handled with care as it may have a prolonged bite reflex after death that could lead to additional envenomation. Knowledge of the snake fauna of an area and habits of the various species may help in identification. If available antivenom is polyspecific, covering all cobras in the region, precise species identification becomes much less important.

Fairly accurate ELISA tests for identification of snake venoms in wound aspirate, serum, urine, and other body fluids have been developed but are not generally available in regions where cobras live.

If the bite occurs in a research or zoo setting, the cage identification card should be brought to the hospital. If available, species-specific antivenom should be sent with the patient.

If a captive cobra in a private collection inflicts the bite, identification may be more straightforward. Unfortunately, tremendous controversy exists among experts regarding taxonomy of cobra species and becomes amplified in the lay herpetoculturist community. A private collector who presents after being bitten by his or her captive "Thai cobra" may have been envenomed by any 1 of at least 3 different species, each with different clinical consequences. Thus, expect a variety of physiologic abnormalities and enlist professional help (eg, from a local zoo) to obtain prompt, accurate identification of the snake.

In some regions of the world, clothing is wrapped around a bitten extremity proximal to the bite site. However, prolonged use of arterial tourniquets is unwise and has caused loss of limb function. A completely occlusive tourniquet might be considered when a victim has been bitten by a highly toxic snake, such as a cobra, and is a very short distance from medical care (though efficacy is unproven and additional harm may occur).

An alternative first aid procedure is the Australian pressure immobilization technique (see the images below). This technique has been shown to be helpful in delaying systemic absorption of some elapid venoms, but its use in cobra bites, particularly those that may result in local tissue necrosis, remains controversial.

The Australian pressure immobilization technique. The Australian pressure immobilization technique. This technique has been shown to be helpful in delaying systemic absorption of elapid venoms, but its use in cobra bites remains controversial. A broad pressure bandage is immediately wrapped, beginning distally (illustration 1 of 5), around as much of the extremity as possible (illustrations 2 and 3). No effort should be spent removing clothing prior to bandage application. The bandage is wrapped snugly, as for a severely sprained ligament. A splint (or sling when applied to the upper extremity) is then placed (illustrations 4 and 5), and the victim is carried from the scene. The victim should expend no effort in getting to definitive care. Pressure immobilization should remain in place until the victim has reached medical care. The doctor will decide when to remove the bandages. If venom has been injected, it will move into the bloodstream quickly once the bandages are removed. The doctor should leave the bandages and splint in position until appropriate antivenom is available. Used with permission from Commonwealth Serum Laboratories.
The Australian pressure immobilization technique, The Australian pressure immobilization technique, illustration 2 of 5. A broad pressure bandage is immediately wrapped, beginning distally (as shown above), around as much of the extremity as possible. No effort should be spent removing clothing prior to bandage application. The bandage is wrapped snugly, as for a severely sprained ligament. Used with permission from Commonwealth Serum Laboratories.
The Australian pressure immobilization technique, The Australian pressure immobilization technique, illustration 3 of 5. A broad pressure bandage is immediately wrapped, beginning distally (as shown above), around as much of the extremity as possible. No effort should be spent removing clothing prior to bandage application. The bandage is wrapped snugly, as for a severely sprained ligament. Used with permission from Commonwealth Serum Laboratories.
The Australian pressure immobilization technique, The Australian pressure immobilization technique, illustration 4 of 5. A splint (or sling when applied to the upper extremity) is then placed and the victim is carried from the scene. The victim should expend no effort in getting to definitive care. Pressure immobilization should remain in place until the victim has reached medical care. Used with permission from Commonwealth Serum Laboratories.
The Australian pressure immobilization technique, The Australian pressure immobilization technique, illustration 5 of 5. A splint (or sling when applied to the upper extremity) is then placed and the victim is carried from the scene. The victim should expend no effort in getting to definitive care. Pressure immobilization should remain in place until the victim has reached medical care. Used with permission from Commonwealth Serum Laboratories.

An elastic compress (eg, Ace wrap, clothing, crepe bandage) is wrapped rapidly around the bitten extremity, beginning distally and progressing proximally to encompass the entire limb. The compress is as tight as one used for immobilization of a severe ligamentous sprain. Then, the extremity is splinted and kept at heart level while the victim is carried from the scene. Research shows, however, that, in simulated snakebite scenarios, individuals usually underestimate the degree of tension required for the wrap to be effective, and, even with intensive training, are usually unable to apply the technique correctly.[12]

This technique should not be used in any situation in which the snake responsible for the bite is known to cause local necrosis (such as with African spitting cobras), as local tissue damage may be increased with its use.

Incisions are not helpful. Using a mechanical suction device is unlikely to return any significant amount of venom, and it could increase local tissue damage when a necrotizing venom is involved. Suction should, therefore, be avoided.

Avoid cooling measures and ice application. They have been associated with increased necrotic complications.

If venom is spit into the eyes, immediately and copiously irrigate them with any bland fluid, such as water, saline solution, or milk.[13]

Emergency Department Care

Assess the patient's airway and breathing. Aggressively manage any signs of impending respiratory failure with endotracheal intubation to prevent aspiration.

Immediately institute cardiac and pulse oximetry monitoring and closely monitor the patient's vital signs.

Start, at an appropriate rate, at least 1 large-bore line with normal saline or Ringer's lactate.

All persons who have been bitten by a cobra should be presumed to have received a severe envenomation and should be managed accordingly (close monitoring of cardiorespiratory status and expedited efforts to locate and procure appropriate antivenom for the offending species).[14]

Antivenom is the only proven therapy for significant snakebites.[15] About 20 laboratories in Africa, Asia, and Europe produce cobra antivenoms. Some are monovalent, but most are polyvalent against venoms of all the important snakes of a nation or region. However, the quality varies, and no international standards of purity or effectiveness exist. In the United States, no cobra antivenom has FDA approval. All are considered experimental drugs. Antivenoms are largely ineffective in preventing or ameliorating the necrosis caused by many cobra venoms.

Table of antivenom choices for cobra bites. As ant Table of antivenom choices for cobra bites. As antivenom manufacturers come and go in the market, choices in this list may or may not be available. Consultation with regional poison control centers, which have access to the Antivenin Index, may help identify and locate an appropriate product for use.

If the envenomating species has been determined, a resource, such as the Antivenom Index (published and maintained by the American Association of Zoological Parks and Aquariums and the American Association of Poison Control Centers), can be accessed by calling a regional poison control center or the Arizona Poison and Drug Information Center (from outside Arizona, 520-626-6016; from Arizona only, 800-362-0101). This document lists the preferred antivenoms available for most medically important venomous snakes around the world and has information about where these sera can be obtained in the United States (usually zoos or serpentariums). Once the antivenom is located, the physician may need assistance from the police or military to facilitate its rapid transport.

If possible, the antivenom should have antibodies against venom of the cobra species that inflicted the bite. However, shared venom antigens among cobra species exist, and heterologous antivenoms may be effective. Venoms of the African spitting cobras are among the most difficult to neutralize by nonspecific antivenoms. Notechis (Australian tiger snake) antivenom proved effective in animal experiments against 9 of 11 cobra venoms, exceptions being ringhals and Chinese cobra venoms. Apparent effectiveness of tiger snake antivenom in clinically treating cobra bites has been shown in a few cases.

If the patient arrives with some device applied in an attempt to limit spread of the venom, such as a tourniquet, constriction band, or pressure device, quickly assess the patient to determine if any evidence of systemic toxicity is present.

Assess the presence of distal pulses below the ligature. If symptoms are present and antivenom is available, start the antivenom before removing the device. If symptoms are absent and antivenom is available, remove the device and observe the patient closely for symptoms or signs of toxicity. If signs of envenoming occur, administer antivenom promptly.

If the tourniquet is totally occluding arterial flow, and there will be a delay in obtaining antivenom, apply a more loosely fitting device, such as the Australian pressure immobilization technique (see Prehospital Care), and then remove the tourniquet. A more loosely fitting device is appropriate to prevent the release of acidotic, hyperkalemic blood and venom into the central circulation as the tourniquet is released.

When applicable, initiate and continue irrigation of the eyes with saline. Applying several drops of a topical ophthalmic anesthetic agent may reduce pain and aid in irrigation. The topical use of 1:1000 epinephrine solution is reported to relieve pain promptly. A fluorescein-aided slit lamp examination helps to find evidence of corneal damage. A brief course of topical ophthalmic antibiotics and preservative-free lubricating drops may be prescribed.

Inpatient Care

Admit all cobra snakebite patients to closely monitored settings, whether or not antivenom is given.

Observe asymptomatic patients for at least 24 hours. Delayed signs and symptoms may occur.

If signs or symptoms of envenomation progress after first administration of antivenom, a second dose of antivenom may be required. If two doses of antivenom are given and the victim still requires airway intubation and ventilatory support, further antivenom administration will be unhelpful.

Continue to administer epinephrine, antihistamines, and steroids to a patient experiencing an acute allergic reaction to antivenom until the patient is stable.

If necrosis occurs, initiate standard, conservative wound care (eg, cleansing, splinting, debridement as necessary). Secondary bacterial infections may occur and are usually caused by gram-negative bacilli, such as Proteus, Pseudomonas, and Enterobacter species.[16] Initial antibiotics should cover gram-positive and gram-negative organisms. Culture results should determine use of further antibiotics. Occasionally, debridement, amputation, or grafting of tissue is required.

Warn patients who have received antivenom about the signs and symptoms of delayed serum sickness. If these signs or symptoms develop after discharge, evaluate the patient promptly for initiation of systemic steroids and diphenhydramine as outlined above.

People bitten by cobras should be cared for in a facility capable of intensive monitoring.

Consultations

See the list of consultations below:

  • Toxicologist or expert in snake envenomation

  • Regional poison control center

  • A local zoo or museum - May be able to assist in species identification and may have appropriate antivenom in stock

  • Ophthalmologist  - Should evaluate any patient who has eye exposure to spitting cobra venom

  • General surgeon or plastic surgeon for follow-up care of necrotic wounds

Prevention

Professional snake keepers should use standard safety techniques (eg, locked cages, trap boxes, protective eyewear) when dealing with cobras and other species that spit venom.

Amateurs should refrain from keeping exotic venomous snakes in their collections. If they keep such snakes, they should know the specific species they keep, the appropriate antivenom type, and where it can be obtained in an emergency. Preferably, amateurs should maintain their own supply of appropriate antivenom, but this may be difficult (due to regulations related to importing foreign antivenoms into the country) and expensive.

Travelers in regions where cobras are indigenous should wear protective clothing (long pants and footwear), avoid areas where snakes seek cover, and know the location of the nearest source of medical care in case they are bitten.

Long-Term Monitoring

Patients with necrosis need continued outpatient management of their wounds and should be warned about the signs and symptoms of infection. Continued outpatient physical therapy may be necessary.

Patients who received antivenom should be aware of the signs and symptoms of delayed serum sickness and should return if they develop.

Patients who have experienced acute ophthalmia following spitting cobra venom exposure should have outpatient ophthalmologic follow-up to monitor for complications such as uveitis or corneal ulceration.

 

Medication

Medication Summary

The definitive therapy for cobra envenomation is antivenom administration, which should be started as soon as possible if evidence of systemic envenoming is present. If specific antivenom is not rapidly available, the patient must be supported using conservative measures alone. Measures include securing the airway and supporting respirations as necessary. Hypotension should be treated initially with intravenous fluids (initially crystalloids but if blood pressure/tissue perfusion fails to improve, then albumin). If hypotension persists after the intravascular volume is replete, vasopressor agents may be necessary.

Evidence supports the trial of cholinesterase-inhibiting drugs, such as edrophonium or neostigmine, as a temporizing measure in a situation of severe cobra venom poisoning with significant neurologic abnormalities until antivenom can be obtained.[17, 18]   These temporizing drugs should not, however, delay securing the airway of a victim who is developing respiratory distress or inability to handle secretions.

As with any form of bite, update the tetanus status as necessary. Antibiotic prophylaxis is not necessary.

Antivenom

Antivenom can be started according to the manufacturer's instructions regarding route and dose.  Although some manufacturers advise use of an intradermal skin test to predict an acute reaction to antivenom, this procedure is terribly unreliable and only serves to waste precious time.  Such recommendations for skin testing should be ignored.

Several different cobra antivenoms are produced by various countries. They are of variable purity and efficacy. The most appropriate agent for the species involved should be determined and obtained. Given venom variability, antivenom produced in the country of origin of the offending species is preferred. An intradermal skin test for potential acute sensitivity is often recommended by manufacturers before administration. Such skin tests are, however, completely unreliable predictors of anaphylactic/anaphylactoid reactions, and should be omitted. Before administration, intravascular volume should be expanded using crystalloids such as normal saline or Ringer's lactate unless some contraindication (eg, congestive heart failure) is present. Pretreatment with antihistamines (H1 and H2 blockers) can be considered, though their efficacy at preventing adverse reactions to antivenom is unproven. Epinephrine should be immediately available for treatment of an anaphylactoid response to the heterologous serum.

Antihistamines

Class Summary

Antihistamines (H1 and H2 blockers) may blunt or prevent an acute allergic reaction when given before the administration of antivenom. If an anaphylactic/anaphylactoid reaction occurs despite pretreatment, further antihistamine dosing may be required. These agents are useful in managing pruritus in cases of delayed serum sickness, which may appear days to weeks following antivenom treatment.

Diphenhydramine (Benadryl)

Diphenhydramine can be administered parenterally. It is often the H1 blocker of choice in treating or preventing anaphylactoid reactions. It is also effective orally in treating itching associated with serum sickness. If an acute allergic reaction subsequently occurs, further administration may be required.

Cimetidine (Tagamet)

Cimetidine is an H2 antagonist coadministered with an H1 antagonist if there is no response to the H1 antagonist alone; it treats itching and flushing in anaphylaxis, pruritus, urticaria, and contact dermatitis.

Cardiovascular agents

Class Summary

Useful in treating acute allergic reactions that may occur with antivenom administration and in supporting the blood pressure and tissue perfusion of hypotensive patients with shock unresponsive to IV fluids and antivenom.

Epinephrine (Epi-Pen)

With its combined alpha- and beta-adrenergic effects, Epinephrine is the drug of choice for the treatment of an acute anaphylactoid reaction because it halts and reverses the major abnormalities associated with such reactions (eg, hypotension, laryngospasm, bronchospasm, edema, urticaria); it must be available immediately for administration if such a reaction to antivenom occurs.

Dopamine (Intropin)

Dopamine may be required to support blood pressure in the face of hypotension caused by an anaphylactic/anaphylactoid reaction (unresponsive to fluids, epinephrine) or by direct snake venom effects (unresponsive to fluids, antivenom).

Norepinephrine (Levophed)

Norepinephrine may be used as an alternative to dopamine to support blood pressure in the face of hypotension caused by an anaphylactic/anaphylactoid reaction that is unresponsive to fluids and epinephrine.

Corticosteroids

Class Summary

Used in management of both acute and delayed allergic phenomena following antivenom administration. Corticosteroids, however, have no primary role in the management of snake venom poisoning.

Methylprednisolone (Solu-Medrol, Depo-Medrol)

Steroids ameliorate the delayed effects of anaphylactoid reactions and may limit biphasic anaphylaxis. In severe cases of serum sickness, parenteral steroids may be beneficial to reduce the inflammatory effects of this immune-complex mediated disease.

Prednisone (Deltasone, Orasone, Sterapred)

Prednisone is useful orally in managing mild-to-moderate serum sickness treated on an outpatient basis.

Cholinesterase inhibitors

Class Summary

Cholinesterase inhibitors may be effective in temporarily reversing muscle weakness until antivenom can be obtained. Their use might obviate intubation, but airway protection should not be delayed if there is any doubt of the patient's respiratory status or ability to protect the airway.

Edrophonium (Enlon, Reversol)

Edrophonium is a short-acting anticholinesterase agent; it may provide significant improvement in muscle strength (eg, ability to open eyes) within 2 minutes and its effect peaks in 5 minutes. Weakness rapidly returns, however, and can be subsequently treated with a longer-acting agent, such as neostigmine.

Neostigmine (Prostigmin)

Neostigmine is a longer-acting cholinesterase inhibitor that can be used if a trial of edrophonium is effective; it inhibits the destruction of acetylcholine by acetylcholinesterase, which facilitates the transmission of impulses across the myoneural junction.

Immune globulins

Class Summary

Consists of administration of immunoglobulin pooled from serum of immunized subjects.

Tetanus immune globulin (TIG)

Tetanus immune globulin is used for passive immunization of any person with a wound that might be contaminated with tetanus spores when the person has not previously completed a primary tetanus immunization series.

Toxoids

Class Summary

Toxoids are used to induce active immunity against the respective antigens.

Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Adacel, Boostrix)

This is a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine. It promotes active immunity to diphtheria, tetanus, and pertussis by inducing the production of specific neutralizing antibodies and antitoxins. It is indicated for active booster immunization for tetanus, diphtheria, and pertussis prevention for persons aged 10-64 years (Adacel approved for 11-64 y, Boostrix approved for 10-18 y). It is the preferred vaccine for adolescents scheduled for booster.

Tetanus toxoid adsorbed or fluid

The immunizing agent of choice for most adults and children older than 7 years is tetanus and diphtheria toxoids. It is necessary to administer booster doses to maintain tetanus immunity throughout life. Pregnant patients should receive only tetanus toxoid, not a diphtheria antigen-containing product. In children and adults, it may be administered into the deltoid or midlateral thigh muscles. In infants, the preferred site of administration is the mid thigh laterally.