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AUSTRALIAN DEATH ADDERS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Death adders are front-fanged elapids with a viper-like appearance. The death adders are widely distributed throughout Australia and often found in the warmer parts of Australia; they are also widely distributed throughout the mainland of Papua New Guinea. Death adder envenomations are rare in Australia, but continue to be a significant issue in Papua New Guinea. Neurotoxicity is the primary clinical feature of envenomation.

Specific Substances

    A) AUSTRALIAN DEATH ADDERS
    1) Acanthophis antarcticus
    2) Acanthophis pyrrhus
    3) Acanthophis praelongus
    4) Australian death adder
    5) Common death adder
    6) Desert death adder
    7) Northern death adder

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) BACKGROUND: Death adders (Acanthophis species) are elapids but have a viper-like appearance that can readily distinguish them from other venomous snakes in Australia and Papua New Guinea. These snakes may also behave like a viper. Death adders have a broad, triangular head, a narrow neck and a short stout-like body with semi-mobile fangs. There are a variety of species found throughout these countries. These snakes are the most evolved of all elapids.
    B) TOXICOLOGY: Death adder snake venom has neurotoxic action. Acanthophin, a neurotoxin, has been isolated from the venom. Its physiologic action is the blockade of nicotinic acetylcholine receptors on the postsynaptic membrane of the motor end-plate. Symptoms (ie, neurotoxicity) may mimic myasthenia gravis or that of other Australian elapids. In comparison, taipan snakes and likely Papuan black snakes exert their neurotoxic effects by predominantly binding presynaptically. Of the 3 primary species (A antarcticus, A praelongus and A pyrrhus) that are likely to cause envenomation, all 3 venoms can produce rapid postsynaptic neurotoxicity.
    C) EPIDEMIOLOGY: Death adders are nocturnal and are typically active at night, although they can strike during the day. Envenomation is relatively rare in Australia but remains a significant issue in Papua New Guinea. However, death adders can produce severe neurologic symptoms of envenomation. It is considered the second most severe cause of envenomation in Australia; taipans remain the most severe cause of envenomation.
    D) WITH POISONING/EXPOSURE
    1) MILD ENVENOMATION: Nonspecific abdominal pain, nausea, vomiting and headache may develop with mild envenomation; it may be an early manifestation of severe envenomation or may be due to anxiety. Symptoms may start within a few hours of envenomation.
    2) SEVERE ENVENOMATION: Early symptoms are characterized by mild local swelling, pain and lymphadenopathy. Neurotoxicity is likely to occur and can be present within several hours or may be delayed up to 12 hours or more. Ptosis is usually the earliest sign of neurotoxicity followed by difficulty swallowing and/or talking, chest wall weakness, intercostal muscle paralysis, and respiratory difficulty. Death is usually due to respiratory paralysis.
    3) RARE or ABSENT: Blood coagulopathies have not been reported after death adder envenomation, and myotoxicity (more likely with A praelongus, A rugosus, A sp. Seram and A wellsi species) is rare and when it does develop it is generally not severe.

Laboratory Monitoring

    A) Monitor vital signs and mental status.
    B) Monitor serial neurologic exams for any evidence of ptosis, ophthalmoplegia, dysarthria, dysphagia, or respiratory or skeletal muscle weakness.
    C) Assess respiratory function; respiratory paralysis may develop secondary to neurotoxicity. Monitor pulse oximetry and ABGs in patients with early signs of systemic envenoming. Monitor for any evidence of difficulty handling secretions. Monitoring negative inspiratory force may provide early evidence of the need for endotracheal intubation and mechanical ventilation.
    D) Monitor serum electrolytes, renal function, urinalysis and urine output.
    E) Institute continuous cardiac monitoring and obtain an ECG.
    F) Monitor CK if there is evidence of myotoxicity. If there is any question about the type of snake involved monitor coagulation studies (INR, aPTT, fibrinogen), CK, and CBC.
    G) If there is any question as to the type of snake involved, obtain a swab from the bite site or a urine specimen, and use the venom detection kit to identify the species of snake if any clinical or laboratory evidence of envenomation develop. The presence of venom at the bite site does NOT mean that systemic envenomation has occurred.

Treatment Overview

    0.4.7) BITES/STINGS
    A) NO OR MILD ENVENOMATION
    1) Patients who are asymptomatic or only have mild symptoms of neurotoxicity should be monitored for a minimum of 12 hours.
    B) SEVERE ENVENOMATION
    1) Patients with severe or progressive neurotoxic symptoms should be treated with antivenom. Patients may require respiratory support including intubation and mechanical ventilation secondary to respiratory paralysis.
    C) ANTIVENOM
    1) SUMMARY: Treat patients with evidence of systemic envenoming (ie, neurotoxicity) following a bite by a death adder. If the death adder antivenom is not available, or the species of snake responsible is not known, polyvalent antivenom may be used.
    2) DEATH ADDER (CSL) ANTIVENOM: DOSE: ADULTS and CHILDREN: The contents of one vial (6000 units) should be administered slowly by the IV route after being diluted 1 to 10 in crystalloid. The dose is the same for adults and children. In young children, a dilution of 1 to 5 may be used to avoid fluid overload. Do NOT administer by the IM route. MONITORING: The patient should be monitored for at least 6 hours after antivenom therapy. Monitor patient carefully and be prepared to treat anaphylaxis. Serum sickness is common about 1 to 2 weeks after treatment.
    3) POLYVALENT (CSL) ANTIVENOM: DOSE: ADULTS and CHILDREN: The contents of one vial (40,000 units) should be administered slowly by the IV route after being diluted 1 to 10 in crystalloid. The dose is the same for adults and children. In young children, a dilution of 1 to 5 may be used to avoid fluid overload. Do NOT administer by the IM route. PRECAUTIONS: The same considerations for monitoring and patient care associated with the death adder antivenom apply to polyvalent antivenom administration.
    D) ACUTE ALLERGIC REACTION
    1) Antihistamines, inhaled beta agonists, intramuscular epinephrine as needed for mild to moderate reactions, intravenous epinephrine and endotracheal intubation for severe reactions.
    E) MONITORING OF PATIENT
    1) Monitor vital signs and mental status. Monitor serial neurologic exams for any evidence of ptosis, ophthalmoplegia, dysarthria, dysphagia, or respiratory or skeletal muscle weakness. Assess respiratory function; respiratory paralysis may develop secondary to neurotoxicity. Monitor pulse oximetry and ABGs in patients with early signs of systemic envenoming. Monitor for any evidence of difficulty handling secretions. Monitoring negative inspiratory force may provide early evidence of the need for endotracheal intubation and mechanical ventilation. Monitor serum electrolytes, renal function, urinalysis and urine output. Institute continuous cardiac monitoring and obtain an ECG. Monitor CK if there is evidence of myotoxicity. If there is any question about the type of snake involved monitor coagulation studies (INR, aPTT, fibrinogen), CK, and CBC. If there is any question as to the type of snake involved, obtain a swab from the bite site or a urine specimen, and use the venom detection kit to identify the species of snake if any clinical or laboratory evidence of envenomation develop. The presence of venom at the bite site does NOT mean that systemic envenomation has occurred.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: There is no role for home management of a possible snake bite.
    2) OBSERVATION CRITERIA: All patients with suspected snake bite should be observed for at least 12 hours; patients should also not be discharged at night to allow for appropriate observation. In some cases, early symptoms of paralysis can begin 2 to 3 hours after envenomation followed by progressive paralysis over the next few hours. However, paralysis can be delayed for many hours (12 or more hours) in some patients. If there is no clinical or laboratory evidence of envenomation following the observation period, the patient can be discharged.
    3) ADMISSION CRITERIA: Any patient who develops more than mild clinical signs and symptoms or who develops ANY evidence of neurotoxicity should be admitted to an intensive care setting.
    4) CONSULT CRITERIA: Consult a clinical toxinologist, medical toxicologist or poison center for any patient with severe envenomation.
    G) TOXICOKINETICS
    1) Death adder venom has neurotoxic action. Acanthophin, a neurotoxin, has been isolated from the venom. Its physiologic action is the blockade of nicotinic acetylcholine receptors on the postsynaptic membrane of the motor end-plate. Symptoms may mimic myasthenia gravis.
    H) PITFALLS
    1) The presence of death adder venom at the bite site does not necessarily mean that systemic envenomation has occurred and is not an indication for antivenom treatment in the absence of systemic envenomation. The onset of clinical evidence (ie, ptosis, blurred vision) of envenomation can occur 2 to 3 hours after envenomation followed by progressive paralysis over the next few hours. However, signs of paralysis may be delayed 12 or more hours in some cases. Release of pressure bandages applied as a first aid measure has been associated with abrupt rises in serum venom concentrations and abrupt clinical worsening. Pressure immobilization should not be removed until the patient is at a hospital where antivenom can be administered, and the patient should be stabilized and antivenom should generally be administered before the bandage is removed if there is clinical evidence of envenomation.
    I) DIFFERENTIAL DIAGNOSIS
    1) Envenomation by other Australian elapids (eg, tiger snakes or taipan) can also produce neurotoxicity. Myasthenia gravis.

Range Of Toxicity

    A) TOXICITY: The venom is very toxic. Human envenomation by death adders (Acanthophis spp) are rare; however, death adders can cause serious envenomations and death due to respiratory paralysis.

Clinical Effects

Summary Of Exposure

    A) BACKGROUND: Death adders (Acanthophis species) are elapids but have a viper-like appearance that can readily distinguish them from other venomous snakes in Australia and Papua New Guinea. These snakes may also behave like a viper. Death adders have a broad, triangular head, a narrow neck and a short stout-like body with semi-mobile fangs. There are a variety of species found throughout these countries. These snakes are the most evolved of all elapids.
    B) TOXICOLOGY: Death adder snake venom has neurotoxic action. Acanthophin, a neurotoxin, has been isolated from the venom. Its physiologic action is the blockade of nicotinic acetylcholine receptors on the postsynaptic membrane of the motor end-plate. Symptoms (ie, neurotoxicity) may mimic myasthenia gravis or that of other Australian elapids. In comparison, taipan snakes and likely Papuan black snakes exert their neurotoxic effects by predominantly binding presynaptically. Of the 3 primary species (A antarcticus, A praelongus and A pyrrhus) that are likely to cause envenomation, all 3 venoms can produce rapid postsynaptic neurotoxicity.
    C) EPIDEMIOLOGY: Death adders are nocturnal and are typically active at night, although they can strike during the day. Envenomation is relatively rare in Australia but remains a significant issue in Papua New Guinea. However, death adders can produce severe neurologic symptoms of envenomation. It is considered the second most severe cause of envenomation in Australia; taipans remain the most severe cause of envenomation.
    D) WITH POISONING/EXPOSURE
    1) MILD ENVENOMATION: Nonspecific abdominal pain, nausea, vomiting and headache may develop with mild envenomation; it may be an early manifestation of severe envenomation or may be due to anxiety. Symptoms may start within a few hours of envenomation.
    2) SEVERE ENVENOMATION: Early symptoms are characterized by mild local swelling, pain and lymphadenopathy. Neurotoxicity is likely to occur and can be present within several hours or may be delayed up to 12 hours or more. Ptosis is usually the earliest sign of neurotoxicity followed by difficulty swallowing and/or talking, chest wall weakness, intercostal muscle paralysis, and respiratory difficulty. Death is usually due to respiratory paralysis.
    3) RARE or ABSENT: Blood coagulopathies have not been reported after death adder envenomation, and myotoxicity (more likely with A praelongus, A rugosus, A sp. Seram and A wellsi species) is rare and when it does develop it is generally not severe.

Heent

    3.4.2) HEAD
    A) WITH POISONING/EXPOSURE
    1) DYSARTHRIA
    a) Dysarthria is likely to occur as part of the clinical events associated with neurotoxic symptoms. It is likely to follow symptoms of ptosis (earliest evidence of neurotoxicity) (White, 1995a; Lalloo et al, 1996).
    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) PTOSIS
    a) Ptosis is the earliest sign of neurotoxicity after death adder envenomation (Lalloo et al, 1996; White, 1995a; Hudson, 1988; Currie et al, 1988).
    2) DIPLOPIA
    a) Diplopia and blurred vision are early symptoms of neurotoxicity after envenomation. Symptoms usually follow ptosis (earliest evidence of toxicity) (White, 1995a; Lalloo et al, 1996).
    3) OPHTHALMOPLEGIA
    a) In a study of 18 patients with death adder envenomation, 10 (55.6%) developed ophthalmoplegia (Lalloo et al, 1996).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) ELECTROCARDIOGRAM ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) In a prospective study of envenomation of species found in Australia, ECG changes were observed in 36 of 69 patients (52%) following taipan envenomation, 2 of 6 patients (33%) following death adder envenomation, and 1 case following brown snake envenomation. Dysrhythmias and septal T-wave inversions were equally common (Lalloo et al, 1995).
    B) ATRIOVENTRICULAR BLOCK
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A patient developed second-degree atrioventricular block with a ventricular rate of 36 bpm after a death adder envenomation. This may have been due to a preexisting condition but that seems unlikely as the patient had an initial heart rate of 100 bpm at the time of admission (Lalloo et al, 1996).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) RESPIRATORY INSUFFICIENCY
    1) WITH POISONING/EXPOSURE
    a) Respiratory paralysis is the progressive development of descending neurotoxic events following envenomation by Acanthophis species. Intubation and mechanical ventilation have been necessary. In most cases, antivenom therapy if given early can rapidly improve respiratory effort and strength (Lalloo et al, 1996).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) NEUROTOXICITY
    1) WITH POISONING/EXPOSURE
    a) Neurotoxicity is the primary clinical feature of death adder envenomation (Currie, 2004). Systemic paralysis is a common finding of death adder envenomation (White, 1995a).
    b) ONSET: Most patients will have clinical evidence (ie, ptosis, blurred vision) of envenomation (in some cases severe symptoms) within 2 to 3 hours followed by progressive paralysis over the next few hours. However, signs of paralysis may be delayed 12 or more hours in some cases (White, 1995a).
    c) INCIDENCE: In a study of 18 patients with death adder envenomation, 17 (94.4%) patients had evidence of neurotoxicity at the time of arrival to the hospital. Clinical symptoms ranged from mild ptosis (n=15; 88.2%) to complete respiratory paralysis requiring intubation and ventilation (n=5; 27.8%). Thirteen patients received antivenom. All patients recovered (Lalloo et al, 1996).
    1) CASE REPORT: A 7-year-old girl had evidence of systemic envenomation at the time of admission. The child had been bitten about 3.5 hours earlier by a death adder. Signs and symptoms included ptosis, partial ophthalmoplegia, difficulty swallowing, weakness of the respiratory muscles, vomiting and tender lymph nodes. Neurotoxic symptoms had reportedly begun about 1.5 hours after being bitten. Treatment included 1 vial of death adder antivenom, 0.45 mg neostigmine and 0.6 mg atropine with rapid clinical improvement over 2 hours with the patient being extubated. Fourteen hours after admission neurotoxic symptoms resolved and the child recovered completely (Lalloo et al, 1996).
    2) CASE REPORT: A 30-year-old man was admitted to the hospital 12 hours after being bitten by a death adder and was complaining of lymph node pain and vomiting. He had moderate ptosis and severe ophthalmoplegia and dysarthria with shallow respirations requiring intubation. A vial of antivenom was given and respiratory and peripheral muscle strength improved within 30 minutes. Six hours after being treated the patient was extubated. At 18 hours, the only symptoms remaining were mild ptosis and ophthalmoplegia. The patient recovered completely (Lalloo et al, 1996).
    d) In a prospective study of snakebites in the Northern Territory of Australia, 8 (n=21; 38%) patients developed neurotoxicity following death adder envenomation. It was suggested that variations in the death adder species may occur in the Top End of the Northern Territory (Currie, 2004).
    B) PARALYSIS
    1) WITH POISONING/EXPOSURE
    a) Neuromuscular paralysis is likely due to post-synaptic neurotoxins (White, 1995a), which can resemble myasthenia gravis (Hudson, 1988a). In one case symptoms improved by the administration of edrophonium and atropine (Hudson, 1988a).
    1) Death adder venoms are predominantly postsynaptic and the various acanthophis species exhibit a range of neurotoxicity. Early symptoms of paralysis can occur within 2 to 3 hours of envenomation and can progress over the next few hours to produce descending muscular paralysis leading to respiratory failure (Fry et al, 2001; Currie, 2006). In a child, neurotoxic symptoms including evidence of difficulty swallowing and respiratory muscle weakness were present 3.5 hours after being bitten by a death adder. It was reported that early symptoms of neurotoxicity (ie, ptosis) had begun 1.5 after envenomation (Lalloo et al, 1996).
    C) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache is common early finding of death adder envenomation (Lalloo et al, 1996).
    b) In a study of 18 patients with death adder envenomation, 10 (58.8%) patients developed headache (Lalloo et al, 1996).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Vomiting (usually mild) and abdominal pain have been reported with death adder envenomation and are usually early findings (Lalloo et al, 1996; Hudson, 1988; Campbell, 1966).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) Acute renal failure has been reported infrequently after death adder envenomation (Lalloo et al, 1996).
    b) CASE REPORT: Five days after a death adder bite, a patient was admitted with a creatinine level of 175 micromol/L. The patient improved with conservative therapy (Lalloo et al, 1996).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) BLEEDING
    1) WITH POISONING/EXPOSURE
    a) LACK OF EFFECT
    1) Blood coagulopathies are not expected to occur with a death adder envenomation. Coagulation times are usually normal. Local wounds may bleed following an envenomation but the effects are minor, if persistent bleeding occurs another species should be considered (Currie, 2004; Campbell, 1966).
    2) In a study of 18 patients with death adder envenomation, there was no evidence of systemic bleeding in any patient. One patient developed localized bleeding from the mouth (Lalloo et al, 1996). In another study there were also no reports of coagulopathy following death adder envenomation (Currie, 2004).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) EDEMA
    1) WITH POISONING/EXPOSURE
    a) Localized swelling is common following a death adder snakebite (White, 1995a).
    b) INCIDENCE: In a prospective study of snakebites in the Northern Territory of Australia, 13 (n=21; 62%) patients bitten by a death adder developed swelling at the bite-site (Currie, 2004).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCLE WEAKNESS
    1) WITH POISONING/EXPOSURE
    a) Progressive peripheral muscle weakness can develop following death adder envenomation secondary to neurotoxicity (White, 1995a; Hudson, 1988).
    B) RHABDOMYOLYSIS
    1) WITH POISONING/EXPOSURE
    a) LACK OF EFFECT
    1) Rhabdomyolysis and myotoxicity are unlikely to occur following death adder envenomation. However, a myotoxin has been found in one death adder species (Currie, 2004).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) LYMPHADENOPATHY
    1) WITH POISONING/EXPOSURE
    a) Enlarged, painful, tender lymph node pain are frequently observed after death adder envenomation (Lalloo et al, 1996).
    b) INCIDENCE: In a prospective study of snakebites in the Northern Territory of Australia, 13 (n=21) patients developed lymphadenitis following death adder envenomation (Currie, 2004). In another study of 18 patients with death adder envenomation, 12 (70%) patients had lymph node pain and 11 (61.1%) had tender enlarged lymph nodes (Lalloo et al, 1996).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and mental status.
    B) Monitor serial neurologic exams for any evidence of ptosis, ophthalmoplegia, dysarthria, dysphagia, or respiratory or skeletal muscle weakness.
    C) Assess respiratory function; respiratory paralysis may develop secondary to neurotoxicity. Monitor pulse oximetry and ABGs in patients with early signs of systemic envenoming. Monitor for any evidence of difficulty handling secretions. Monitoring negative inspiratory force may provide early evidence of the need for endotracheal intubation and mechanical ventilation.
    D) Monitor serum electrolytes, renal function, urinalysis and urine output.
    E) Institute continuous cardiac monitoring and obtain an ECG.
    F) Monitor CK if there is evidence of myotoxicity. If there is any question about the type of snake involved monitor coagulation studies (INR, aPTT, fibrinogen), CK, and CBC.
    G) If there is any question as to the type of snake involved, obtain a swab from the bite site or a urine specimen, and use the venom detection kit to identify the species of snake if any clinical or laboratory evidence of envenomation develop. The presence of venom at the bite site does NOT mean that systemic envenomation has occurred.

Methods

    A) LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY
    1) ACANTHOPHIS GENUS: Liquid chromatography/mass spectrometry has been used to evaluate various species of death adders. Variations were found among the different species in regards to venom composition (Fry et al, 2002).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.6) DISPOSITION/BITE-STING EXPOSURE
    6.3.6.1) ADMISSION CRITERIA/BITE-STING
    A) Any patient who develops more than mild clinical signs and symptoms or who develops ANY evidence of neurotoxicity should be admitted to an intensive care setting.
    6.3.6.2) HOME CRITERIA/BITE-STING
    A) There is no role for home management of a possible snake bite.
    6.3.6.3) CONSULT CRITERIA/BITE-STING
    A) Consult a clinical toxinologist, medical toxicologist or poison center for any patient with severe envenomation.
    6.3.6.5) OBSERVATION CRITERIA/BITE-STING
    A) All patients with suspected snake bite should be observed for at least 12 hours; patients should also not be discharged at night to allow for appropriate observation (Johnston et al, 2012). In some cases, early symptoms of paralysis can begin 2 to 3 hours after envenomation followed by progressive paralysis over the next few hours. However, paralysis can be delayed for many hours (12 or more hours) in some patients. If there is no clinical or laboratory evidence of envenomation following the observation period, the patient can be discharged.

Monitoring

    A) Monitor vital signs and mental status.
    B) Monitor serial neurologic exams for any evidence of ptosis, ophthalmoplegia, dysarthria, dysphagia, or respiratory or skeletal muscle weakness.
    C) Assess respiratory function; respiratory paralysis may develop secondary to neurotoxicity. Monitor pulse oximetry and ABGs in patients with early signs of systemic envenoming. Monitor for any evidence of difficulty handling secretions. Monitoring negative inspiratory force may provide early evidence of the need for endotracheal intubation and mechanical ventilation.
    D) Monitor serum electrolytes, renal function, urinalysis and urine output.
    E) Institute continuous cardiac monitoring and obtain an ECG.
    F) Monitor CK if there is evidence of myotoxicity. If there is any question about the type of snake involved monitor coagulation studies (INR, aPTT, fibrinogen), CK, and CBC.
    G) If there is any question as to the type of snake involved, obtain a swab from the bite site or a urine specimen, and use the venom detection kit to identify the species of snake if any clinical or laboratory evidence of envenomation develop. The presence of venom at the bite site does NOT mean that systemic envenomation has occurred.

Range Of Toxicity

Summary

    A) TOXICITY: The venom is very toxic. Human envenomation by death adders (Acanthophis spp) are rare; however, death adders can cause serious envenomations and death due to respiratory paralysis.

Minimum Lethal Exposure

    A) Prior to antivenom therapy, the estimated mortality rate was 50% following death adder envenomation (Swindells et al, 2006).

Maximum Tolerated Exposure

    A) CASE SERIES: In a study of 18 patients with death adder envenomation, 17 (94.4%) patients had evidence of neurotoxicity at the time of arrival to the hospital. Clinical symptoms ranged from mild ptosis (n=15; 88.2%) to complete respiratory paralysis requiring intubation and ventilation (n=5; 27.8%). Thirteen patients received antivenom. All patients recovered (Lalloo et al, 1996).
    1) CASE REPORT: A 7-year-old girl had evidence of systemic envenomation at the time of admission. The child had been bitten about 3.5 hours earlier by a death adder. Symptoms included ptosis, partial ophthalmoplegia, difficulty swallowing, weakness of the respiratory muscles, vomiting and tender lymph nodes. Neurotoxic symptoms had reportedly begun about 1.5 hours after being bitten. Treatment included 1 vial of death adder antivenom, 0.45 mg neostigmine and 0.6 mg atropine with rapid clinical improvement over 2 hours with the patient being extubated. Fourteen hours after admission neurotoxic symptoms resolved and the child recovered completely (Lalloo et al, 1996).
    2) CASE REPORT: A 30-year-old man was admitted to the hospital 12 hours after being bitten by a death adder and was complaining of lymph node pain and vomiting. He had moderate ptosis and severe ophthalmoplegia and dysarthria with shallow respirations requiring intubation. A vial of antivenom was given and respiratory and peripheral muscle strength improved within 30 minutes. Six hours after being treated the patient was extubated. At 18 hours, the only symptoms remaining were mild ptosis and ophthalmoplegia. The patient recovered completely (Lalloo et al, 1996).
    B) CASE SERIES: In a prospective study of snakebites in the Northern Territory of Australia, 8 (n=21; 38%) patients developed neurotoxicity following death adder envenomation. It was suggested that variations in the death adder species may occur in the Top End of the Northern Territory (Currie, 2004).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) A large volume of venom can be produced by death adders, with an mean yield of 84.7 mg (Swindells et al, 2006). Death adders can deliver an estimated 35 to 42 mg of venom with one bite. The approximate venom dose per bite can range from 0.46 to 0.56 mg/kg in an average adult (75 kg) (Flachsenberger & Mirtschin, 1994).

Pharmacology Toxicology

Toxicologic Mechanism

    A) SUMMARY
    1) In most Acanthophis species, neurotoxicity primarily due to the postsynaptic effects of the venom. The neurotoxins bind to the post-synaptic membrane of the motor end-plate, which blocks the acetylcholine receptors. The clinical effects may resemble myasthenia gravis. In comparison, taipan snakes and likely Papuan black snakes exert their neurotoxic effects by predominantly binding presynaptically (Currie et al, 1988).
    2) Post-synaptic neurotoxins usually act rapidly and produce paralysis that responds to antivenom therapy; after envenomation by snakes with pre-synaptic neurotoxins, it can take longer for paralysis to occur (White, 1995a).
    3) It has been suggested that acanthophis venoms may also contain presynaptic phospholipase A2 neurotoxin complexes that bind irreversibly to motor nerve terminals. This can produce irreversible neurotoxicity by depletion of the neurotransmitter, resulting in prolonged paralysis if the patient is not treated promptly with antivenom (Blacklow et al, 2010).
    B) NEUROTOXICITY
    1) Acanthophis venoms are made up of alpha postsynaptic neurotoxins and more recently phospholipase A2 toxins have been isolated (Fry et al, 2002).
    2) Death adder venom acts postsynaptically at the neuromuscular junction to reduce responses to acetylcholine causing severe flaccid paralysis and finally death from respiratory failure (Flachsenberger & Mirtschin, 1994). The most common death adders venoms (A antarcticus, A praelongus and A pyrrhyus) all contain postsynaptic neurotoxins. Individual variation in the venom may occur and can be related to geographic differences (Fry et al, 2002). In one study, A antarcticus was found to be more neurotoxic than A pyrrhus and A pyrrhus was more neurotoxic than A praelongus (Wickramaratna & Hodgson, 2001).
    C) COAGULOPATHY
    1) Death adder species (A antarcticus, A praelongus and A pyrrhus) have weak anticoagulant activity (van der Weyden et al, 2000). In a series of death adder envenomations, none of the patients developed coagulopathy (Lalloo et al, 1995).
    D) MYOTOXICITY
    1) Myotoxicity is usually not associated with Acanthophis species (Campbell, 1966). However, there have been some clinical reports of myotoxicity associated with A rugosus in Papau New Guinea (Blacklow et al, 2010).

References

General Bibliography

    1) Blacklow B, Konstantakopoulos N, Hodgson WC, et al: Presence of presynaptic neurotoxin complexes in the venoms of Australo-Papuan death adders (Acanthophis spp.). Toxicon 2010; 55(6):1171-1180.
    2) Campbell CH: The death adder (Acanthophis antarcticus): the effect of the bite and its treatment. Med J Aust 1966; 2(20):922-925.
    3) Clinical Toxinology Department, Women's & Children's Hospital: CSL Polyvalent Snake Antivenom. Clinical Toxinology Department, Women's & Children's Hospital. Adelaide, Australia. 2001. Available from URL: http://www.toxinology.com/generic_static_files/cslavh_antivenom_polyvalen.html. As accessed 2012-10-10.
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