Cobra Envenomation

Practice Essentials

Cobra envenomation is an extremely variable process. The lethality of the venom itself varies significantly - depending on the species, age of the individual snake, suspected seasonal variation in venom composition, route of enoculation (intravenous, intradermal, subcutaneous, etc), and many more factors.

Prognosis

Many patients recover with no specific treatment.

The neurotoxic effects of cobra venom are reversible, though motor recovery may take up to 7 days - and as many as 10 weeks.^[1]

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

Digit or limb amputation may result with secondary infections following an initial bite. Marjolin ulcers may also form from chronic lesions.

Corneal erosions can develop secondary infections which may lead to permanent blindness with venom introduced into the eyes.

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.

Signs and symptoms

Signs and symptoms following a cobra bite can be extremely variable:

• Immediate, local pain (almost always present)
• Soft tissue swelling (may be progressive)
• Tissue necrosis with surrounding blistering and regional lymphadenopathy
• Nausea and vomiting (earliest sign of systemic envenomination, typically within 6 hours)^[1]
• Early neurologic findings: contraction of frontalis muscle causing elevation of brows, ptosis, ophthalmoplegia, blurred vision (ocular muscles highly sensitive to neuromuscular blockade), loss of visual accommodation due to mydriasis, perioral paresthesia
• Later neurologic findings: dysphagia, dysphasia, paralysis of palate and jaw muscles, tongue paralysis, neck paralysis, respiratory arrest. Despite occuring later, findings may be rapidly progressive within minutes to hours.^[1]
• Autonomic dysfunction: profuse salivation, nausea, vomiting, abdominal pain, blood pressure and heart rate abnormalities
• Alteration of mental status (eg, drowsiness, occasionally with euphoria)
• Chest pain or tightness, shortness of breath
• Eye pain, tearing, blurred vision (with eye exposure to venom from spitting cobras)

Diagnostics

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).

An arterial or venous blood gas may be helpful in gauging respiratory status.

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.

Consider a chest radiograph for patients requiring intubation or showing evidence of cardiorespiratory failure.

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

Treatment

For a full discussion, see Treatment and Medication.

The definitive therapy for cobra envenomation is antivenom administration. This should be started as soon as possible if evidence of systemic envenomation is present. Supportive care should be provided throughout the patient's course - from pre-hospital until discharge with follow-up.

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Background

Venomous snakes are divided into families, of which the major ones are elapidae and viperidae. Physically, elapidae have shorter fangs, smaller heads, and smooth scales. Viperidae have stockier triangular heads wider than their necks, hingeable fangs that fold against the roof of their mouths, and ridged scales. However the distinction of interest for this article is venom. As a general rule-of-thumb, elapidae venom causes neuromuscular deficits - mainly flaccid paralysis - while viperidae venom focuses on local effects, including tissue necrosis, rhabdomyolysis, coagulopathy, and bleeding. As a disclaimer, these descriptors are generalized and individual species may differ from them. For example, venom of African spitting cobras primarily cytotoxic and coagulopathic effects with significantly less neurologic impact.

Cobras belong to the elapidae family and is the common name for snakes belonging to the Naja genus. Although primarily found in Africa and southern Asia, they are well recognized around the world - in large part due to its unique neck hood but also because of its debilitating venom. They have long held importance in their respective local cultures as creatures of danger but have permeated beyond into literature, media, folklore, etc. To many people, the cobra is the quintessential venomous snake.

As for physical attributes, cobras are generally large snakes, measuring 1.2 to 2.5 meters in length. The king cobra, which may reach 5.2m, is the longest of the cobras - and in fact, they are the longest venomous snake in the world. When encountered, cobras usually try to escape but occasionally defend themselves boldly and may appear aggressive. Cobras will elevate their head and spread their characterstic neck hood, typically only seen in a defensive mode. They are also said to produce a growl-like sound.

Most snakebites are inflicted on body extremities. By far, rural agricultural workers and other people in Asia and Africa receive most bites while working outdoors without protective wear. Children and young people tend to suffer more morbidity and mortality. In North America and Europe, captive cobras may cause bites to zookeepers or amateur collectors.^{[2, 3]}

Not all snakebites result in envenomation, that is the introduction of venom into a victim typically via injection by fangs. Reports of dry bites is skewed given difficulties in accurately determining if venom was injected and in general lack of reporting of bites. Given this however, a literature review showed a wide incidence of dry bites based on snake species, ranging from 4% to 50%.^[4]

In addition to biting, some cobra species have the ability to eject or spit jets of venom toward an aggressor, usually directed at the eyes in an effort to temporarily blind it in order to stage an escape. 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 is 1 meter but can reach up to 3 meters. This ability is found in African and Asian spitting cobras as well as South African ringhals, belonging to the Elapidae family that appear very similar to but are not true cobras.

When venom contacts the eye, acute ophthalmia occurs with symptoms of immediate and intense pain, blepharospasm, tearing, and blurring of vision. Systemic toxicity does not occur with eye exposure, but corneal ulcerations, uveitis, and permanent visual impairment or blindness have been reported in untreated cases. About half of the cases ascribed to the African spitting cobras (N nigricollis, N mossambica, N pallida, N katiensis) showed corneal ulceration, and some resulted in permanent blindness. 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.^[5]  Cases ascribed to the Asian spitting cobras and the African ringhals are usually less severe.

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Pathophysiology

The envenomation of some cobra species causes profound neurological abnormalities (eg, cranial nerve dysfunction, abnormal mental status, muscle weakness, paralysis, and respiratory arrest). However with other cobras, cytotoxicity and local tissue damage is the primary concern and presentation - especially regarding bites from 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) - despite their venoms also containing some amount of neurotoxins. Occasionally, a combination of neurologic dysfunction and tissue necrosis may occur as with the Indian cobra (Naja naja).

Venom Composition

As with all snake venoms, cobra venoms are multicomponent products. Variations in composition occur between species as a result of evolutionary adaptions. Some of cobra venom components include:

• α-neurotoxins (or α-cobratoxins). Also called three-fingered toxins due to their molecular shape, this family of neurotoxins competitively binds to post-synaptic nicotinic acetylcholine receptors to produce block depolarization, resulting in paralysis. The most concerning outcomes are bulbar and respiratory muscle paralysis resulting in death.^[1]
• Cardiotoxins. These cause a host of issues - including irreversible cell depolarization and contraction of muscular cells, cellular lysis,  dysfunction of platelet aggregation, inhibition of protein kinase C and Na+/K+ ATPase, and more - leading to dysarrhythmias and hemodynamic instability.^[6]
• Complement-activating proteins. Complement-depleting cobra venom factor (CVF) activates the alternative complement pathway without the standard antigen-antibody complex. It also dysregulates the pathway’s ability to halt the activation, overall leading to a depletion of complement factors and proteins and ultimately hindering the complement system from opsonizing and neutralizing venom.^[7]
• Enzymes. The major enzymatic toxins include phospholipase A2 (damages mitochondria, hematocytes, skeletal muscles, and vascular endothelium), hyaluronidase (facilitates tissue dispersion of other toxins by degrading extracellular matrix at bite site), L -amino acid oxidase (gives many venoms a characteristic yellow coloration), and acetylcholinesterase (terminates cholingeric neurotransmission impairing muscle contraction).^{[1, 7]}

Lethality

Naja philippinensis (Philippine cobra) venom is the most toxic of the cobra venoms, 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.

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

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

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

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Epidemiology

Frequency

About 5.4 millions snake bites occur every year, according to the World Health Organization. Of these, envenomations account for 1.8 to 2.7 million - resulting in 81,000 to 138,000 fatalities and nearly three times this in terms of permanent sequelae and amputations. Under-reporting of snake bites, resulting complications, and death is likely ubiquitous. Countries in which bites occur often have less developed healthcare infrastructure and reporting and data collecting systems in place.^[8]

International

Snakebites are a significant medical problem in parts of Africa and Asia. The majority of envenomations, up to 2 million, occur in Asia. Roughly half a million occur in Africa yearly resulting in 20,000 deaths. 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.^[8]

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.^[9] 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).

Sex

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

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Mortality/Morbidity

Determining the exact contribution of cobras to overall snakebite morbidity and mortality is difficult. This stems from a larger issue of having reliable  counts of snake bites in general, as community and government based reporting grossly undercounts numbers while population-based surveys likely more accurately reflect morbidity and mortality.^{[1, 8]} In most cases, bitten individuals are unable to identify the snake. Physicians are may by default attribute bites with neurotoxic symptoms to cobras without substantiation.

In India, the annual mortality incidence is 5.6-12.6 per 100,000 population from overall snake bites. 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.^[10] Data from Thailand and Malaysia in the 1980s demonstrate an annual mortality incidence of 0.1 per 100,000 population.^{[11, 12]}

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.^[13] 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 were fatal.^[14] Cobras accounted for 2 of 95 bites on a Liberian rubber plantation.^[15] 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.^[1] King cobras are also reputed for their short bite-to-death times, ranging from minutes to hours, while other envenominations can take days. Ringhals bites are similar to other cobra bites but are less serious both locally and systemically with deaths being 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.^[16]

Prevalance of chronic and permanent morbidity (such as amputations and physical disfigurement resulting in handicap) due to snake bites is unknown.

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Physical Examination

Abnormal heart rate and hypotension can result from autonomic dysfunction. Respiratory distress may lead to respiratory failure due to muscular paralysis.

Patient may present with altered mental status, ptosis (often the earliest sign of systemic toxicity), mydriasis, and/or generalized weakness or paralysis. Bulbar muscular dysfunction may result in slurred speech and drooling.

With venom into the eye, acute inflammation is present with ocular congestion, edema of the conjunctiva and cornea, and a whitish discharge. Slip-lamp or fluorescein tests may show corneal erosions.

Around the bite site, soft tissue edema with surrounding blistering may be noted. Necrosis may result, usually appearing within 48 hours of the bite.

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

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Complications

Complications of cobra envenomation may include the following:

• Respiratory failure/arrest
• Cardiovascular collapse
• Prolonged neuromuscular weakness
• Tissue necrosis, potentially resulting in limb loss / amputation
• Venom-induced ophthalmia (spitting cobras)
• Anaphylaxis, non-allergic anaphylactoid reaction, delayed serum sickness (if and after antivenom administration)

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Prehospital Care

Prompt movement of a victim to a medical facility capable of rendering advanced care, including airway support and antivenom administration, is critical. The following are additional pre-hospital considerations. Addressing these should be weighed with delays in obtaining a higher level of medical care.

Species Identification

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

• Wild snake bite. 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.
• Captive snake bite. 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. Expect a variety of physiologic abnormalities and enlist professional help (eg, from a local zoo) to obtain prompt, accurate identification of the snake.

Pressure Immobilization

Arterial tourniquets is generally not recommended 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 travel time to medical care is short. The efficiacy of however is unproven and additional harm may occur.

An alternative wrap is the pressure immobilization technique, developed in Australia. Similar techniques has been shown to be helpful in delaying systemic absorption of venoms primarily by reducing lymphatic spread of venom (main mechniasm of spread), although high quality studies are lacking to substantiating efficacy. An appropriate approach to studyiung efficacy requires measurement of blood venom levels before and after removal of wrap to suggest the intervention limited systemic spread of venom. One small prospective study of bites in Burma demonstrated efficacy, however in Russell viper bites.^[17]

An elastic compress (eg, Ace wrap, clothing, crepe bandage) is wrapped rapidly around the affected 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. The extremity can also be splinted to limit movement and kept at heart level. The patient should limit movement as much as possible. Some studies show that individuals often 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. Bandages and wraps often become loose as well.^{[18, 17]}  Defer this technique for venomous bites known to cause local necrosis (such as with African spitting cobras) with cytotoxic and hemotoxic effects, as local tissue damage may be increased with its use.^[19]

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The Australian pressure immobilization technique. This technique has been shown to be helpful in delaying systemic absorption of elapid venoms, but it....

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The Australian pressure immobilization technique, illustration 2 of 5. A broad pressure bandage is immediately wrapped, beginning distally (as shown a....

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The Australian pressure immobilization technique, illustration 3 of 5. A broad pressure bandage is immediately wrapped, beginning distally (as shown a....

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The Australian pressure immobilization technique, illustration 4 of 5. A splint (or sling when applied to the upper extremity) is then placed and the ....

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The Australian pressure immobilization technique, illustration 5 of 5. A splint (or sling when applied to the upper extremity) is then placed and the ....

Local Wound Considerations

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

Use of a mechanical suction device is unlikely to return any significant amount of venom and should be avoided. It may also increase local tissue damage if a necrotizing venom is involved. 

Eye Irrigation

If venom is spit into the eyes, immediately and copiously irrigate them with any bland fluid, such as water, saline solution, or milk.^[20]

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Emergency Department Care

Initial Evaluation

All persons who have been bitten by a cobra should be presumed to have received a severe envenomation and should be managed accordingly. This includes close monitoring of cardiorespiratory status and expedited efforts to locate and procure appropriate antivenom for the offending species.^[21]  Assess the patient's airway and breathing. Aggressively manage any signs of impending respiratory failure with endotracheal intubation to prevent aspiration. Institute cardiac and pulse oximetry monitoring and closely monitor the patient's vital signs. Consider starting at least 1 large-bore line with normal saline or Ringer's lactate.

Antivenom

Antivenom is the only proven therapy for significant snakebites.^[22]  They consist of antibodies produced and collected from an animal donor (typically horse or sheep) that have been introduced to sub-lethal doses of venom. Monovalent antivenom consist of antibodies that neutralize venom from only one species, while polyvalent neutralize multiple - typically of multple regional snake species. This becomes useful when the exact species in question is unknown. As expected, treating with a monovalent antivenom specific to the biting snake species is typically more effective than treating with a polyvalent antivenom - which may have decreased antibody concentration specific for the offending venom or whose antibodies have partial cross-reactivity against the offending venom. Repeated and higher doses of less-specific polyvalent antivenom also poses a higher risk for anaphylaxis and anaphylactoid reactions.^[23]

Roughly 20 laboratories in Africa, Asia, and Europe produce antivenoms. Quality and efficacy of antivenom varies, and no international standards of purity or effectiveness exist. In the United States, none of the available cobra antivenoms have FDA approval. In general, antivenoms are largely ineffective in preventing or ameliorating necrosis caused by envenomation. Additionally, manufacturers often recommend refrigerating antivenom to improve their stability and storage duration. Costs and logistics may limit availability of antivenom in certain regions of the world.

Antivenom can be started according to the manufacturer's instructions regarding route and dose. Prior to administering, some manufacturers advise an intradermal skin test of the antivenom to gauge an acute reaction; however, this has not been substantiated and unpredictive of anaphylactic/anaphylactoid reactions and will delay administration of the antivenom. Multiple vials of antivenom may be required for effective treatment.

Given venom variability, antivenom produced in the country of origin of the offending species is preferred. 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 and steroids (eg methylprednisolone 1g) should be immediately available for treatment of an anaphylaxis or anaphylactoid response to the heterologous serum.

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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. Co....

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.

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.

Evaluation of Bite Injury

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.

Evaluation of Eye Injury

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.

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Inpatient Care

Admit cobra snakebite patients to closely monitored settings.  Monitor even asymptomatic patients for 24 hours, as delayed signs and symptoms may occur. 

Respiratory paralysis leading to mechanical ventilation may still be required, either because of the inefficacy of the administered antivenom and/or the delayed nature of the paralysis. Neurotoxic effects will however spontaneously resolve even with failed antivenom treatment. Patients requiring mechanical ventilation will typically see their respiratory paralysis resolved within 1 to 4 days, ocular muscles within 2 to 4 days, and full motor function in 3 to 7 days. Prolonged cases of paralysis resolution have been noted requiring up to 10 weeks after envenomination of mechanical ventilation.^[1]

Serum sickness may occur as a reaction to proteins in received antivenom after 5 to 10 days. Patients should be educated on signs and symptoms, and instructed to return to a medical provider if they are encountered. The patient should promptly initiate systemic corticosteroids, diphenhydramine, and analgesics.

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.^[24] 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.

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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, potentially requiring serial debridements

For a comprehensive treatment overview, from first-aid care to in-hospital medical management, review UCSD Toxicology's approach to a king cobra (Ophiophagus hannah) bite.

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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.

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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.

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Medication Summary

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.^{[25, 26]}   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.

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Diphenhydramine (Benadryl)

• Dosing, Interactions, etc.

Clinical Context:  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.

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Cimetidine (Tagamet)

• Dosing, Interactions, etc.

Clinical Context:  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.

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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.

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Epinephrine (Epi-Pen)

• Dosing, Interactions, etc.

Clinical Context:  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.

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Dopamine (Intropin)

• Dosing, Interactions, etc.

Clinical Context:  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).

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Norepinephrine (Levophed)

• Dosing, Interactions, etc.

Clinical Context:  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.

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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.

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Methylprednisolone (Solu-Medrol, Depo-Medrol)

• Dosing, Interactions, etc.

Clinical Context:  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.

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Prednisone (Deltasone, Orasone, Sterapred)

• Dosing, Interactions, etc.

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

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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.

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Edrophonium (Enlon, Reversol)

• Dosing, Interactions, etc.

Clinical Context:  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.

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Neostigmine (Prostigmin)

• Dosing, Interactions, etc.

Clinical Context:  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.

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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.

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Tetanus immune globulin (TIG)

• Dosing, Interactions, etc.

Clinical Context:  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.

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Class Summary

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

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

• Dosing, Interactions, etc.

Clinical Context:  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.

• References

Tetanus toxoid adsorbed or fluid

• Dosing, Interactions, etc.

Clinical Context:  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.

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Class Summary

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

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