The brown snake, found in Australia, belongs to the family of Elapidae and contains the following species:
Pseudonaja guttata (speckled brown snake, shown in image below)
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Pseudonaja guttata (speckled brown snake).
Pseudonaja textilis (common brown snake, also known as eastern brown snake, shown in image below)
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Pseudonaja textilis (eastern brown snake).
Pseudonaja affinis (dugite)
Pseudonaja nuchalis (western brown snake, shown in image below)
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Pseudonaja nuchalis (western brown snake).
Pseudonaja inframacula (peninsula brown snake)
Pseudonaja ingrami (Ingram's brown snake)
Pseudonaja affinis tanneri (Tanner's brown snake)
Pseudonaja modesta (ringed brown snake, shown in image below)
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Pseudonaja modesta (ringed brown snake).
Envenomation by P textilis, P nuchalis, P guttata, and P affinis has been documented, but little information is available about the toxic effects of the other species.
All of these snakes occur mainly in inland floodplains with deeply fissured soils. The snakes are active during cooler parts of the day, such as early morning and late afternoon. They exist in 5 different colors, have a highly flexible head, and can squeeze into narrow places. They feed on small animals but also can grip large prey. They may bite humans above the knee by raising their head from the ground and assuming an "S" shape when striking. Unless provoked, they are thought to be reluctant to attack humans.
Most of the literature describing the brown snake consists of case studies of people accidentally bitten and their clinical course. They have less effective dentition than other elapids and may leave little evidence of a puncture wound; however, their venom is readily diffusible and can rapidly enter the circulation.
These snakes are among the most venomous in the world. The common brown snake produces the second most toxic snakebite venom known (LD 50 0.53 mg/kg) and is the most common cause of snakebite death in Australia.[1] Common to these species' venom are neurotoxins and hemotoxins.
Brown snake envenomations are characterized by disseminated intravascular coagulation (DIC) like hemorrhage and cardiovascular depression. Other, less common, manifestations are conduction defects, thrombocytopenia, renal failure, intracranial hematomas, and paralysis.[2, 3]
The venom-induced consumptive coagulopathy (VICC) is characterized by defibrination, often accompanied by platelet counts within the reference range. The venom has the ability to convert prothrombin to thrombin and to significantly deplete factors V, VII, protein C, and plasminogen within 2 hours of the snakebite.[4] Complete VICC (defined as international normalized ratio >3) occurs in 80% of the victims, while partial VICC occurs in 20% of the victims.[5]
Cardiovascular depression may be caused by intravascular coagulation, or the venom may contain a primary myocardial depressant. The potent neurotoxins cause neurological symptoms soon after envenomation. One example is texilotoxin, a multimumeric polypeptide from the common brown snake. These neurotoxins can cause respiratory paralysis by blocking nicotinic acetylcholine receptors at the postsynaptic motor endplate and/or affect neurotransmitter release at presynaptic motor nerve endings. Convulsions may occur. Little or no myotoxicity is present.
Pseudonaja species live mainly in Australia. About 3000 bites occur per year in Australia from all species of snakes, 500 of which require antivenin. The dugite brown snake may be found in the southwestern corner of Australia, in Western Australia and along the South Australian border. The speckled brown snake can be found from central Queensland to the eastern areas of the Northern Territory. Ingram's snake may be found around Barkly Tableland of the Northern Territory, and the ringed snake may be found in the arid regions of all the mainland states. The western snake may be found throughout Australia and the common brown snake in Queensland, New South Wales, and from Victoria to the southeast of South Australia.
Snakebites tend to occur more often in the warmer months reflecting increased snake activity as well as increased human outdoor activity. The predominance of the bites occur in the lower limb.
Sex
Males are bitten more frequently than females, presumably because of the greater popularity among males of owning and handling snakes as well as greater risk of occupational and recreational exposure.
Age
Young children tend to become critically ill sooner than adults because of their smaller body weight and tendency to receive multiple bites.
If no systemic symptoms are present, recovery is expected.
Since the development of antivenin and the use of compression bandages, fatalities from brown snake bites have become rare. However, in spite of prompt medical care and antivenin administration, the potency of the venom has produced fatalities.
Of all the cases of snakebites in Australia, only 2-3 fatalities occur per year. As many as 60% of fatalities from snake envenomations may be attributed to the brown snake. Early deaths (within hours) are thought to result from the venom's cardiotoxic effect as well as anaphylaxis to the venom. Delayed deaths appear to result from secondary complications, such as intracranial hemorrhage, from the venom's hemotoxins.
Approximately 30% of brown snake bites cause systemic envenomation; 60% of bites with systemic involvement produce altered mental status, loss of consciousness, or seizures; and approximately 33% of these present with defibrination syndrome.
The subcutaneous median lethal dose (LD50) for the common brown snake in 18- to 21-gram mice is 0.053 mg/kg. The average yield of a venom milking is 4 mg, and the highest recorded yield is 67 mg. The LD50 for other species of brown snake for 18- to 21-gram mice are as follows: 0.47 mg/kg for P nuchalis, 0.66 mg/kg for P affinis, and 0.36 mg/kg for P guttata.
The bites of Pseudonaja frequently occur on the extremities, mostly on the fingers and feet, because collectors handle them or people accidentally step on them. Unfortunately, unless the patient gives a history of being bitten by a snake, local clues to the evidence of a bite may be subtle or absent because brown snake bites cause little or no local swelling or pain. After giving a history of being bitten by a brown-colored snake, the patient may complain of neurological symptoms within an hour; the symptomatology within a few hours may manifest with a coagulopathy and signs of diaphragmatic paralysis and cardiovascular compromise. The following symptoms may be present:
Prothrombin time (PT)/activated partial thromboplastin time (aPTT)/international normalized ratio (INR) - Mild envenomation INR greater than 2; complete defibrination INR greater than 12[9]
Fibrinogen - Severe envenomation associated with afibrinogenemia (<0.3 g/L)
Fibrin degradation products
D-dimer
Electrolytes
Blood urea nitrogen (BUN) and creatinine
Urinalysis
Arterial blood gas (ABG)
Type and crossmatch for packed red blood cells (PRBCs), fresh frozen plasma (FFP), and platelets
Enzyme immunoassays (EIAs) for quantifying venom concentration[10] : A small study of 27 brown snake envenomed patients showed the median venom concentration was 20 ng/mL. The EIA test is able to detect down to concentrations of 3 ng/mL.[11]
The goals of prehospital treatment include implementing basic and advanced life support algorithms and ensuring an adequate airway. Consider immobilization of the cervical spine if trauma to the cervical spine is suspected.
Assess if breathing is adequate. Consider endotracheal intubation if indicated.
Provide fluid support for hypotension, as well as cardiopulmonary resuscitation (CPR), and administer chemical adjuncts for cardiovascular compromise if necessary.
Remove patient from further potential harm and institute local wound care. This includes immobilizing the affected limb and maintaining it at the level of the heart. Do not tamper with the bite and avoid potentially harmful procedures such as mouth suction, local application of electrical shock or ice, or cauterization or incision of the bite. Possible complications of these techniques may result in ischemia, gangrene, damage to nerves, congestion, edema, or increased bleeding.
An elastic bandage placed at the bite site and wrapped proximally to include the entire limb may delay absorption of the neurotoxin into the systemic circulation. Care should be taken not to remove the compression bandage until antivenin therapy is instituted. The bandage should not compromise arterial circulation.
Attempt to identify the snake, but avoid protracted attempts to locate or capture the snake. If the snake is from a research center or zoo, send specific antivenin with the patient if possible.
Stabilization of airway, breathing, and circulation
Oxygen
Avoid nasotracheal intubation to prevent epistaxis.
Intravenous access, cardiac monitoring, and continuous pulse oximetry
Tetanus prophylaxis
Administer antivenin therapy as soon as possible if any signs of systemic involvement are present because the antivenin may reverse coagulopathy. Skin testing before administration of antivenin is not recommended because it delays treatment of this very toxic venom. Furthermore, larger initial doses should be considered if severe envenomation from multiple bites is evident. The dose of antivenom for children should not be reduced since the amount of venom injected by the snake is independent of the victim's size. The improvement of fibrinogen levels, coagulation parameters, and the patient's condition function as surrogate indicators of venom neutralization. A recent study suggests that 5 ampules will adequately treat two thirds of the patients with severe envenomation, but 10 ampules will adequately treat 89% of these patients.[12] For mild envenomation, two vials may be used to start.
Before the antivenin is given, premedicate the patient with an antihistamine, and continue the antihistamine for 5 days to prevent anaphylaxis.
Administer corticosteroids if any history of previous serum sickness or allergic reaction to the antivenin is present or for administration of large doses of antivenin.
Pregnancy is not a contraindication to giving antivenin.
Edrophonium, neostigmine, and atropine may be given to temporarily reverse respiratory weakness until antivenin is obtained, but it should not delay necessary intubation.
In the treatment of venom-induced consumptive coagulopathy, administration of FFP and/or cryoprecipitate is controversial; it has been associated with faster resolution of coagulopathy but no change in outcomes.[13]
The most common reasons for antivenom administration were coagulopathy, neurotoxicity, myotoxicity, and nonspecific systemic effects.[14]
Hypersensitivity reaction to antivenom occurred in 25% cases, with nearly half the hypersensitivity cases considered to be anaphylaxis to the antivenom.[14] . Serum sickness reaction to antivenom occurred in 17%.[15]
Swab the bite for analysis with a CSL Venom Detection Kit, if available.
Warn the patient of potential serum sickness. Instruct the patient to return if serum sickness develops. Follow up with the patient closely.
Admit any person who has been bitten by a brown snake to an intensive care unit.
Because of the potential lethality of this toxin and since symptoms may be delayed, observe asymptomatic patients in an ICU setting for at least 24 hours.
Corticosteroids and antihistamines should be continued for at least 5 days.
Transfer patient to facility capable of intensive care monitoring; and, in case patient develops renal failure and hemodialysis, arrange for transportation to facility with dialysis capabilities.
The antidote for systemic envenomations by the brown snake is the equine-derived antivenin. In a study of 35 patients with severe brown snake envenomation, two thirds of the cases were neutralized with 5 ampules and 89% were neutralized with 10 ampules.[12] As with all equine-derived antivenins, anaphylaxis should be anticipated and treated if any allergic reactions occur. Pretreatment with antihistamines and corticosteroids should be included.[16]
Hypotension should be treated with isotonic crystalloid infusions and vasopressors if blood pressure is refractory to fluids alone.
Tetanus toxoid should be given when indicated.
Cholinesterase inhibitors, such as edrophonium and neostigmine, may be given to palliate the neurological sequelae of the venom but should not replace definitive airway control.
Clinical Context:
According to the Antivenin Index, the monovalent form is not carried in the US but may be found in Australia (Commonwealth Serum Laboratories, Melbourne, Australia). The polyvalent antivenin may be obtained at the Bronx Zoo, but a local zoo may be contacted.
Skin testing before antivenin administration is not recommended because it may sensitize the individual to future antivenin use and will delay the administration of the antivenin. Antihistamines and subcutaneous epinephrine should be administered (if no contraindications are present) before giving the antivenin.
Clinical Context:
Cimetidine is an H2 antagonist that, when combined with an H1 type, may be useful in treating itching and flushing in anaphylaxis, pruritus, urticaria, and contact dermatitis that do not respond to H1 antagonists alone. Use this medication in addition to H1 antihistamines.
H1 and H2 blockers should be given to prevent immune mediated responses and may be continued for an additional 5 days or for as long as symptoms persist.
Clinical Context:
Methylprednisolone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Clinical Context:
Prednisone is used for the treatment of a variety of diseases including serum sickness in the outpatient setting. Prednisone is inactive and must be metabolized to the active metabolite prednisolone. The conversion may be impaired in patients with liver disease.
Corticosteroids should be used when evidence of an allergy-mediated event is present. However, the onset of action is approximately 4-6 hours and has limited benefit in the initial acute treatment of the rapidly deteriorating anaphylactic patient. Nonetheless, corticosteroids may benefit patients with persistent bronchospasm or hypotension.
Clinical Context:
Epinephrine is the drug of choice for treating anaphylactoid reactions. The alpha-agonist effects of epinephrine increase peripheral vascular resistance and reverse peripheral vasodilatation, vascular permeability, and systemic hypotension. Conversely, the beta-agonist effects produce bronchodilatation, positive inotropic and chronotropic cardiac activity, and result in an increased production of intracellular cAMP.
Clinical Context:
Albuterol is a beta-agonist useful in the treatment of bronchospasm that is refractory to epinephrine. It relaxes bronchial smooth muscle by action on beta 2-receptors and has little effect on cardiac muscle contractility
Clinical Context:
Theophylline potentiates exogenous catecholamines. It stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation. For bronchodilation, near toxic (>20 mg/dL) levels are usually required.
Clinical Context:
Ipratropium is chemically related to atropine. It has antisecretory properties and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa.
These agents have combined alpha- and beta-adrenergic agonist action and are the agents of first choice in the treatment of anaphylaxis.
An additional option in the management of persistent bronchospasm may be anticholinergic agents. These agents block the action of acetylcholine at parasympathetic sites in bronchial smooth muscle.
Clinical Context:
Edrophonium is a short active cholinesterase inhibitor that inhibits the destruction of acetylcholine by acetylcholinesterase and may palliate weakness. It facilitates the transmission of impulses across the myoneural junction and results in increased cholinergic responses (eg, miosis, increased tonus of intestinal and skeletal muscles, bronchial and ureteral constriction, bradycardia, and increased salivary and sweat gland secretions). It is usually administered intravenously, but, if this is not possible, an intramuscular or subcutaneous route may be used.
Clinical Context:
Neostigmine is a longer-acting cholinesterase inhibitor that can be used when edrophonium is ineffective. It inhibits the destruction of acetylcholine by acetylcholinesterase, which facilitates the transmission of impulses across the myoneural junction.
Cholinesterase inhibitors may be useful in reversing neurological complications of the venom; however, they should not be a substitute for airway management.
David Cheng, MD, Associate Professor of Emergency Medicine, Education Director, Associate Emergency Medicine Residency Director, Case Medical Center
Disclosure: Nothing to disclose.
Specialty Editors
John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals
Disclosure: Nothing to disclose.
David Eitel, MD, MBA, Associate Professor, Department of Emergency Medicine, York Hospital; Physician Advisor for Case Management, Wellspan Health System, York
Disclosure: Nothing to disclose.
Chief Editor
Joe Alcock, MD, MS, Associate Professor, Department of Emergency Medicine, University of New Mexico Health Sciences Center
Disclosure: Nothing to disclose.
Additional Contributors
Daniel J Dire, MD, FACEP, FAAP, FAAEM, Clinical Professor, Department of Emergency Medicine, University of Texas Medical School at Houston; Clinical Professor, Department of Pediatrics, University of Texas Health Sciences Center San Antonio
Disclosure: Nothing to disclose.
Acknowledgements
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Shaun J Chun, MD, to the development and writing of this article.
References
Clinical Toxinology Resources. Pseudonaja textilis. Available at http://www.toxinology.com/fusebox.cfm?fuseaction=main.snakes.display&id=SN0533. Accessed: May 12, 2016.
CSL Antivenom Handbook. CSL Brown Snake Antivenom. Available at http://www.toxinology.com/generic_static_files/cslavh_antivenom_brown.html. Accessed: May 12, 2016.
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