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SPIDER-FUNNEL WEB

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) ROBUSTOXIN: The sole lethal toxin, robustoxin (also known as atracotoxin), has been isolated from the venom of the male funnel web spider, A. robustus, and determined the molecular weight of the lethal polypeptide neurotoxin to be 4,887. The complete sequence of 42 amino acids has been determined. It acts as a presynaptic neurotoxin, causing repetitive firing of action potentials.

Specific Substances

    A) SPIDER-FUNNEL WEB
    1) Atracinae
    2) Atrax robustus
    3) Sydney funnel-web spider
    4) Hadronyche infensa
    5) Toowoomba funnel-web spider
    6) Darling Downs funnel-web spider
    7) Hadronyche versuta
    8) Blue Mountains funnel-web spider
    9) Hadronyhce formidabilis
    10) Northern tree funnel-web spider
    11) Hadronyche cerberea
    12) Southern tree funnel-web spider
    13) Hadronyche venenata
    14) Tasmanian funnel-web spider
    15) Hadronyche species
    16) Bermagui funnel-web spider
    17) Illawarra funnel-web spider
    18) Hunter Region funnel-web spider
    19) Port Macquaire funnel-web spider
    20) Black spiders
    21) Brisbane funnel-web
    22) Dark brown spiders
    23) Funnel web spider
    24) Funnel-web spiders
    25) Male funnel web spider
    26) Spiders (funnel web)
    27) Sydney funnel-web Atrax robustus

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) DESCRIPTION: These are large, black or dark brown spiders (body 3 to 3.5 cm long). Cephalothorax is oval, smooth, and shiny with closely grouped eyes; abdomen similar size to thorax, dull and hairy with spinnerets. Their habitat is limited to the eastern portions of Queensland and New South Wales in Australia. Males are more toxic than females. Deaths have only been reported after envenomation by Atrox robustus, which is found within a 160 km radius of Sydney.
    B) TOXICOLOGY: Venom components cause excessive neurotransmitter release at autonomic and somatic nerve terminals. It acts as a presynaptic neurotoxin, causing repetitive firing of action potentials, initially enhancing and then inhibiting autonomic and skeletal muscle response.
    C) EPIDEMIOLOGY: Envenomation is rare. Most funnel web spider bites do not result in systemic envenomation. It is estimated that 10% to 20% of bites cause systemic effects. However, the rates of severe envenomation can vary widely depending on the species.
    D) WITH POISONING/EXPOSURE
    1) MILD ENVENOMATION: Bites are extremely painful (hours to days duration). A bite mark may be visible on the skin. Bleeding from the wound may also occur. Local necrosis does not occur. Patients with mild envenomation may develop headache, nausea, lethargy, malaise, local or regional paresthesia.
    2) SEVERE ENVENOMATION: Onset may be within 10 minutes. In severe envenomation, early effects include numbness around the mouth and lips, tongue spasms, nausea, vomiting, abdominal pain, tachycardia, muscle fasciculations, sweating, brisk salivation, lacrimation, dyspnea, piloerection, and agitation. Death during this phase is usually due to pulmonary edema. A delayed phase may follow the early phase, occurring on average 11 hours later. Overt cholinergic and adrenergic effects resolve and the patient may appear to be improving only to develop refractory hypotension, apnea and cardiac arrest.

Laboratory Monitoring

    A) Monitor vital signs and institute continuous cardiac monitoring. Monitor pulse oximetry and/or arterial blood gases, ECG, and chest radiograph in patients with respiratory signs or symptoms.
    B) Monitor for clinical evidence of pulmonary edema.
    C) Monitor electrolytes, renal function, and CK in patients with significant envenomation.
    D) There is no specific clinical assay for funnel web spider venom.

Treatment Overview

    0.4.7) BITES/STINGS
    A) FIRST AID
    1) If a pressure bandage has not been applied prehospital and it is less than 2 hours since the bite, or if there is clinical evidence of envenomation, it should be applied when the patient reaches the hospital. The bandage should be applied with the tightness of a bandage applied for a sprain, should cover the bitten area and should be applied from distal to proximal. The limb should then be immobilized with a splint or sling. The patient should remain as still as possible, even if the above measures are done appropriately, exercise will increase the proximal lymphatic flow of venom to the systemic circulation.
    B) NO OR MILD ENVENOMATION
    1) Patients who are asymptomatic or only have mild symptoms should be monitored for a minimum of 4 hours if the type of spider is unknown, 18 hours if it is a known funnel web spider bite. If a compression bandage has been applied it may be removed when intravenous access is established and the patient is in a facility where antivenom can be administered if needed.
    C) SEVERE ENVENOMATION
    1) Patients with severe symptoms of systemic envenomation should be treated with antivenom. If a compression bandage has been applied to a patient who already has symptoms, it should not be removed until the patient has received antivenom and signs and symptoms have improved.
    D) ANTIVENOM
    1) Patients with evidence of systemic envenomation should receive 2 vials of funnel web spider antivenom, and may need an additional 2 to 4 vials. Patients with severe systemic envenomation should receive 4 vials initially. Antivenom is generally diluted 1:10 with isotonic fluid and each vial infused over 15 to 30 minutes. The dose is the same for adults and children. Be prepared to treat anaphylaxis.
    E) AIRWAY MANAGEMENT
    1) Early endotracheal intubation should be considered in patients with hypoxia, respiratory distress, pulmonary edema or mental status depression. Bilevel positive airway pressure noninvasive ventilation (BIPAP) or endotracheal intubation and mechanical ventilation with positive end expiratory pressure (PEEP) may be necessary in patients who develop pulmonary edema.
    F) HYPERTENSIVE EPISODE
    1) If antivenom is not rapidly available, other modalities may be necessary to treat severe hypertension while antivenom is obtained. Severe hypertension should be treated with an alpha blocker such as phentolamine, or a short acting, titratable agent such as nitroprusside or nitroglycerin.
    G) ATROPINE
    1) If antivenom is not rapidly available, atropine may be used to dry secretions while antivenom is being obtained.
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: There is no role for home management. A patient bitten by any of the large species of Atrax (or Hadronyche) should be evaluated at a medical facility. A pressure immobilization bandage should be applied at the scene as soon as possible.
    2) OBSERVATION CRITERIA: Patients with bites from a spider identified as or strongly suspected of being a funnel web spider should be observed for 18 hours and discharged if asymptomatic. If the offending spider is not known, a 4 hour period of observation (after removal of the pressure bandage) is probably sufficient.
    3) ADMISSION CRITERIA: Patients who develop signs or symptoms of systemic envenomation should receive antivenom and be admitted to an intensive care setting.
    4) CONSULT CRITERIA: Consult a clinical toxinologist, toxicologist or poison center for patients with significant envenomation or in whom the diagnosis is unclear.
    5) TRANSFER CRITERIA: Patients with evidence of systemic envenomation will require transfer to a facility that has antivenom and intensive care capability if these are not available at the facility where they initially present.
    I) TOXICOKINETICS
    1) Onset of systemic evidence of envenomation is generally quite rapid (minutes to a few hours) unless a pressure immobilization bandage is applied immediately. Severe effects generally resolve over the first 24 to 48 hours, although mild persistent effects such as intermittent diaphoresis or weakness may persist for several weeks.
    J) PITFALLS
    1) The spider may not be seen, so a high index of suspicion is necessary, especially in young children. Abrupt onset or worsening of severe systemic envenomation has been reported after removal of pressure immobilization bandages; they should only be removed after intravenous access is obtained and antivenom is immediately available.
    K) DIFFERENTIAL DIAGNOSIS
    1) Scorpion sting (similar manifestations but not native to Australia). Organophosphate poisoning, or poisoning from various direct and indirect acting cholinergic agonists used to treat urinary retention, myasthenia gravis, and Alzheimer's disease.

Range Of Toxicity

    A) Most bites cause no effects or mild systemic effects. A single spider bite can cause severe, potentially lethal, envenomation; however, there have been no confirmed deaths since the introduction of antivenom in 1981.

Clinical Effects

Summary Of Exposure

    A) DESCRIPTION: These are large, black or dark brown spiders (body 3 to 3.5 cm long). Cephalothorax is oval, smooth, and shiny with closely grouped eyes; abdomen similar size to thorax, dull and hairy with spinnerets. Their habitat is limited to the eastern portions of Queensland and New South Wales in Australia. Males are more toxic than females. Deaths have only been reported after envenomation by Atrox robustus, which is found within a 160 km radius of Sydney.
    B) TOXICOLOGY: Venom components cause excessive neurotransmitter release at autonomic and somatic nerve terminals. It acts as a presynaptic neurotoxin, causing repetitive firing of action potentials, initially enhancing and then inhibiting autonomic and skeletal muscle response.
    C) EPIDEMIOLOGY: Envenomation is rare. Most funnel web spider bites do not result in systemic envenomation. It is estimated that 10% to 20% of bites cause systemic effects. However, the rates of severe envenomation can vary widely depending on the species.
    D) WITH POISONING/EXPOSURE
    1) MILD ENVENOMATION: Bites are extremely painful (hours to days duration). A bite mark may be visible on the skin. Bleeding from the wound may also occur. Local necrosis does not occur. Patients with mild envenomation may develop headache, nausea, lethargy, malaise, local or regional paresthesia.
    2) SEVERE ENVENOMATION: Onset may be within 10 minutes. In severe envenomation, early effects include numbness around the mouth and lips, tongue spasms, nausea, vomiting, abdominal pain, tachycardia, muscle fasciculations, sweating, brisk salivation, lacrimation, dyspnea, piloerection, and agitation. Death during this phase is usually due to pulmonary edema. A delayed phase may follow the early phase, occurring on average 11 hours later. Overt cholinergic and adrenergic effects resolve and the patient may appear to be improving only to develop refractory hypotension, apnea and cardiac arrest.

Vital Signs

    3.3.2) RESPIRATIONS
    A) WITH POISONING/EXPOSURE
    1) Dyspnea and acute lung injury have been well described (Browne, 1997; Miller et al, 2000).
    3.3.3) TEMPERATURE
    A) MONKEY studies have shown a rise in core temperature (Sutherland, 1983).
    3.3.4) BLOOD PRESSURE
    A) WITH POISONING/EXPOSURE
    1) Hypertension is common early in the course of envenomation (minutes to a few hours) (Isbister & Warner, 2003; Miller et al, 2000; Sutherland, 1992; Grant & Loxton, 1992; Torda et al, 1980). Later in the course of severe envenomation refractory hypotension may develop (Isbister & Warner, 2003; White et al, 1995; Torda et al, 1980).
    3.3.5) PULSE
    A) WITH POISONING/EXPOSURE
    1) Tachycardia is common early in significant envenomation, and may be quite severe (heart rates of 170 to 200 beats/minute have been reported in children) (Isbister & Warner, 2003; Miller et al, 2000; Browne, 1997; Sutherland, 1992; Torda et al, 1980).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) EARLY SYMPTOMS include may lacrimation and blurred vision (Harrington et al, 1999; Miller et al, 2000; Isbister & Warner, 2003).
    2) DIPLOPIA and MIOSIS have been reported (Harrington et al, 1999; Dieckmann et al, 1989).
    3) MYDRIASIS has also been described (Miller et al, 2000).
    4) CASE REPORT: Bradycardia, hypertension, miosis, diaphoresis, hypersalivation and lacrimation, abdominal pain, oral paresthesia, and fasciculations occurred in a 38-year-old man following envenomation by H. cerberea. The patient recovered within an hour after receiving 2 vials of antivenom, except for persistent abdominal pain which required atropine administration (Isbister & Gray, 2004).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) EARLY SYMPTOMS include numbness around mouth and lips, and tongue spasms and/or fasciculations (Isbister & Warner, 2003; Miller et al, 2000; Harrington et al, 1999; Sutherland, 1992).
    2) INCREASED SALIVATION is a common early finding (Isbister & Warner, 2003; Miller et al, 2000; Harrington et al, 1999; Browne, 1997; Sutherland, 1992; Dieckmann et al, 1989).
    a) INCIDENCE: In a systematic review of 59 patients with severe envenomation, 44% had increased salivation (Isbister et al, 2005).
    3) CASE REPORT: Bradycardia, hypertension, miosis, diaphoresis, hypersalivation and lacrimation, abdominal pain, oral paresthesia, and fasciculations occurred in a 38-year-old man following envenomation by H. cerberea. The patient recovered within an hour after receiving 2 vials of antivenom, except for persistent abdominal pain which required atropine administration (Isbister & Gray, 2004).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia is common early in significant envenomation, and may be quite severe (heart rates of 170 to 200 bpm reported in children) (Isbister & Warner, 2003; Miller et al, 2000; Browne, 1997; Sutherland, 1992; Torda et al, 1980).
    b) INCIDENCE: In a series of 13 patients with Hadronyche envenomation, 9 (69%) developed sinus tachycardia (Miller et al, 2000). In another larger series, 59% of patients with severe envenomation developed tachycardia (Isbister et al, 2005).
    B) CARDIAC ARREST
    1) WITH POISONING/EXPOSURE
    a) Cardiac arrest early in the course of envenomation is generally secondary to hypoxia, especially in children (White et al, 1995; Sutherland, 1983). Death late in the course of envenomation (on average 11 hours after envenomation) may develop from refractory hypotension or end organ complications (White et al, 1995; Torda et al, 1980).
    C) CONDUCTION DISORDER OF THE HEART
    1) WITH POISONING/EXPOSURE
    a) Atrial fibrillation, sinus tachycardia (Browne, 1997), and ventricular tachycardia have all occurred following envenomation by funnel web spiders (Dieckmann et al, 1989).
    D) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Bradycardia, hypertension, miosis, diaphoresis, hypersalivation and lacrimation, abdominal pain, oral paresthesia, and fasciculations occurred in a 38-year-old man following envenomation by H. cerberea. The patient recovered within an hour after receiving 2 vials of antivenom, except for persistent abdominal pain which required atropine administration (Isbister & Gray, 2004).
    b) INCIDENCE: In a systematic review of 59 patients with severe envenomation, 10% developed bradycardia (Isbister et al, 2005).
    E) HYPERTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypertension is common early in the course of envenomation (minutes to a few hours), and may be quite severe (Isbister & Warner, 2003; Miller et al, 2000; Sutherland, 1992; Grant & Loxton, 1992; Torda et al, 1980; Rosengren et al, 2008).
    b) INCIDENCE: In a series of 13 patients with Hadronyche envenomation, 9 (69%) developed hypertension (Miller et al, 2000). In a systematic review of 59 cases of severe envenomation, 75% developed hypertension (Isbister et al, 2005).
    c) CASE REPORT: Bradycardia, hypertension, miosis, diaphoresis, hypersalivation and lacrimation, abdominal pain, oral paresthesia, and fasciculations occurred in a 38-year-old man following envenomation by H. cerberea. The patient recovered within an hour after receiving 2 ampules of antivenom, except for persistent abdominal pain which required atropine administration (Isbister & Gray, 2004).
    F) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Later in the course of severe envenomation (on average 11 hours after envenomation) refractory hypotension may develop (Isbister & Warner, 2003; White et al, 1995; Torda et al, 1980).
    b) INCIDENCE: In a series of 13 patients with Hadronyche envenomation, 4 (31%) developed hypotension (Miller et al, 2000). A lower incidence of hypotension (10%) was noted in a larger series (Isbister et al, 2005).
    G) MYOCARDIAL INFARCTION
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 67-year-old woman with a history of diabetes and hypercholesterolemia was bitten on her right hand by a large male Sydney funnel-web spider (Atrax robustus). Thirty minutes later, she developed drooling, profuse diaphoresis and lacrimation, shaking, paresthesias in the feet, hands, and lips, vomiting, tachycardia (HR 114 bpm), and hypertension (146/100 mmHg). An ECG showed sinus tachycardia with more than 2 mm ST elevation in leads V3 to V6.
    1) Fifteen minutes later, despite IV administration of atropine and 2 ampules (500 units) of funnel-web spider antivenom, the patient's heart rate and blood pressure increased to 148 bpm and 180/98 mmHg, respectively, and ABGs revealed metabolic acidosis (pH 7.33, PCO2 30 mmHg, PO2 72 mmHg, HCO3 17 mmol/L). Over the next hour, following administration of another 2 ampules of antivenom, the patient's blood pressure was 83/45 mmHg, her heart rate was 125 bpm, and her ABGs began to normalize; however, she continued to experience hypersalivation, lacrimation and fasciculations.
    2) Following another 2 ampules of antivenom (a cumulative total dose of 6 ampules), her blood pressure increased to 146/80 mmHg and her heart rate decreased to 119 bpm, although she develop worsening pulmonary edema necessitating intubation.
    3) A repeat ECG, performed 3.5 hours post envenomation, showed 2 to 3 mm of ST elevation in leads V3 to V6; troponin T level was 1.3 (normal less than 1). Echocardiogram showed apical hypokinesia and mild hypokinesia of the basal, anterior and posterior left ventricular walls. No coronary angiography was performed . Nuclear stress testing revealed only mild atherosclerotic disease. Over the next 12 hours, the patient's condition gradually improved following supportive care, she was extubated, and had no signs of cardiac failure 2 days post envenomation (Isbister & Warner, 2003).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPOTENSION
    a) Animals may experience hypotension (Mylecharane et al, 1989).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) PULMONARY EDEMA
    1) WITH POISONING/EXPOSURE
    a) Severe dyspnea and pulmonary edema are well described in serious envenomation, usually developing within the first few hours in untreated patients (Miller et al, 2000; Dieckmann et al, 1989; Sutherland, 1983; Torda et al, 1980).
    b) INCIDENCE: In a series of 13 patients with Hadronyche envenomation, 7 (54%) developed pulmonary edema (Miller et al, 2000). In another review, the overall rate of pulmonary edema was 54%, with the rate higher among children (70%) as compared to adults (44%) (Isbister et al, 2005).
    c) CASE REPORT: Pulmonary edema (clinical and radiographic evidence) and dyspnea (60 breaths/minute) developed in a 9-month-old within 30 minutes of exposure despite immediate application of a pressure immobilization bandage and splinting of the extremity that was bitten (Browne, 1997).
    d) CASE REPORT: A 6-year-old boy developed pulmonary edema requiring intubation two hours following a bite by Hadronyche sp. 14 (Port Macquarie funnel-web spider). Pulmonary edema developed despite immediate application of a compression bandage as well as administration of a total of 4 vials of antivenom (Miller et al, 2000).
    e) CASE REPORT: A 67-year-old woman developed an acute myocardial infarction and respiratory insufficiency following envenomation from a Sydney funnel-web spider (Atrax robustus). Approximately 45 minutes post envenomation, SpO2 was 93% (on 50% O2) and bibasilar crepitations were present on auscultation. Over the next hour, respiratory function continued to worsen, requiring 70% O2 by a non-rebreather mask and then continuous positive airway pressure (CPAP). As the patient continued to deteriorate, intubation was necessary. A chest radiograph revealed interstitial pulmonary edema. With supportive care, the patient gradually improved and was extubated approximately 20 hours post envenomation (Isbister & Warner, 2003).
    B) STRIDOR
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 49-year-old man was bitten on the right foot by a male Atrax robustus. A pressure immobilization bandage was applied. He rapidly developed diaphoresis, piloerection and pain in the leg, followed by fasciculations of the arm muscles which progressed to severe spasms. At 40 minutes after the bite he had severe hypertension (240/140 mmHg) and at 50 minutes after envenomation he was uncooperative, cyanotic and had stridor. He was intubated, mechanically ventilated and transferred to a hospital with an ICU. On arrival he was hypertensive (220/130 mmHg), tachycardic (155 beats/min), had increased muscle tone and metabolic acidosis. He was treated with 2 vials of funnel web antivenom and improved. He continued to report weakness and bouts of diaphoresis for the next 3 weeks (Fisher et al, 1981).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) ALTERED MENTAL STATUS
    1) WITH POISONING/EXPOSURE
    a) Altered mental status may develop, either primarily or secondary to hypoxia. Agitation and confusion are fairly common, and may progress to drowsiness, sedation and rarely coma (Miller et al, 2000; Harrington et al, 1999; White et al, 1995; Sutherland, 1992). Monkey studies have suggested death due to raised intracranial pressure (Duncan et al, 1980).
    b) CASE REPORT: A 9-month-old girl was unresponsive 25 minutes after being bitten on the hand by a male A. robustus, despite immediate first aid (hand immobilization) by the parent (Browne, 1997).
    c) INCIDENCE; In a series of 13 patients with Hadronyche envenomation, 5 (54%) developed altered mentation (Miller et al, 2000).
    B) COMA
    1) WITH POISONING/EXPOSURE
    a) The overall rate of coma in a series of 59 severe envenomations was 8%. However, all cases of coma were limited to pediatric patients; 22% of 23 children in the study developed coma (Isbister et al, 2005).
    C) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache has been reported (Dieckmann et al, 1989; Sutherland, 1992), and may be a manifestation of mild envenomation (Isbister & White, 2004).
    D) HYPERREFLEXIA
    1) WITH POISONING/EXPOSURE
    a) Hyperreflexia has been reported (Dieckmann et al, 1989).
    E) PARESTHESIA
    1) WITH POISONING/EXPOSURE
    a) Paresthesias and numbness are common early symptoms of envenomation, usually starting around the mouth, less commonly this progresses to generalized paresthesias (Isbister & Gray, 2004; Isbister & Warner, 2003; Miller et al, 2000; Harrington et al, 1999).
    b) Local or regional paresthesias may be the only manifestation in mild envenomation (Isbister & White, 2004).
    c) INCIDENCE: The reported incidence of perioral paresthesia ranges from 23% to 32% (Miller et al, 2000; Isbister et al, 2005).
    F) MUSCLE FASCICULATION
    1) WITH POISONING/EXPOSURE
    a) Muscle fasciculations are common within minutes to hours of significant envenomation (Isbister & Warner, 2003; Miller et al, 2000; Fisher et al, 1981). Fasciculation are often first noticed in the tongue, but may progress to more generalized fasciculations, spasms and myoclonus (Harrington et al, 1999; Grant & Loxton, 1992; Sutherland, 1992). Spasm of the tongue, neck and jaw may rarely cause airway compromise, especially if hypersalivation is also present.
    b) INCIDENCE: The reported incidence of fasciculations ranges from 54% to 69% (Miller et al, 2000; Isbister et al, 2005). Large muscle spasm occurred in 17% of severely envenomated patients (Isbister et al, 2005).
    c) Fasciculations occurred in 3 of 16 patients (19%) following Atracinae envenomation (Isbister & Gray, 2004).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea, vomiting, and abdominal pain are common early signs and symptoms (Isbister & Warner, 2003; Miller et al, 2000; Harrington et al, 1999; Dieckmann et al, 1989).
    b) INCIDENCE: In a series of 13 patients with Hadronyche envenomation, 9 (69%) developed nausea and/or vomiting and 3 (23%) developed abdominal pain (Miller et al, 2000). Another study noted vomiting in 41% and abdominal pain in 10% of severely envenomated patients (Isbister et al, 2005).
    B) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) Nausea, vomiting, and abdominal pain are common early signs and symptoms (Miller et al, 2000; Harrington et al, 1999; Dieckmann et al, 1989).
    b) INCIDENCE: In a series of 13 patients with Hadronyche envenomation, 3 (23%) developed abdominal pain (Miller et al, 2000).
    c) CASE REPORT: Bradycardia, hypertension, miosis, diaphoresis, hypersalivation and lacrimation, abdominal pain, oral paresthesia, and fasciculations occurred in a 38-year-old man following envenomation by H. cerberea. The patient recovered within an hour after receiving 2 vials of antivenom, except for persistent abdominal pain which required atropine administration (Isbister & Gray, 2004).
    C) EXCESSIVE SALIVATION
    1) WITH POISONING/EXPOSURE
    a) Increased salivation is a common early effect, usually developing minutes to a few hours after the bite (Isbister & Warner, 2003; Miller et al, 2000; Harrington et al, 1999; Browne, 1997; Sutherland, 1992).
    b) INCIDENCE: In a series of 13 patients with Hadronyche envenomation, 7 (54%) developed excessive salivation (Miller et al, 2000). In another series of 59 severely envenomated patients, 44% of patients developed increased salivation (Isbister et al, 2005).
    c) CASE REPORT: Bradycardia, hypertension, miosis, diaphoresis, hypersalivation and lacrimation, abdominal pain, oral paresthesia, and fasciculations occurred in a 38-year-old man following envenomation by H. cerberea. The patient recovered within an hour after receiving 2 vials of antivenom, except for persistent abdominal pain which required atropine administration (Isbister & Gray, 2004).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) Renal failure is described rarely as a complication of severe envenomation (Torda et al, 1980).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) RESPIRATORY ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) Respiratory acidosis may develop (White et al, 1995).
    B) ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) Mild metabolic acidosis has been reported (Isbister & Warner, 2003; Dieckmann et al, 1989; Fisher et al, 1981). Combined metabolic and respiratory acidosis developed in a 9-month-old bitten on the hand by a male A. robustus (Browne, 1997).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) BLOOD COAGULATION PATHWAY FINDING
    1) WITH POISONING/EXPOSURE
    a) Delayed onset consumption coagulopathy has been described as a rare complication of severe envenomation. It was likely secondary to prolonged peripheral circulatory failure (Torda et al, 1980).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) EXCESSIVE SWEATING
    1) WITH POISONING/EXPOSURE
    a) Severe diaphoresis is a common early symptom (Isbister & Gray, 2004; Isbister & Warner, 2003; Miller et al, 2000; Harrington et al, 1999; Browne, 1997; Dieckmann et al, 1989).
    b) INCIDENCE: In a series of 13 patients with Hadronyche envenomation, 12 (92%) developed diaphoresis (Miller et al, 2000). In another series of 59 severely envenomated patients, 78% of patients developed diaphoresis (Isbister et al, 2005) .
    c) CASE REPORT: Bradycardia, hypertension, miosis, diaphoresis, hypersalivation and lacrimation, abdominal pain, oral paresthesia, and fasciculations occurred in a 38-year-old man following envenomation by H. cerberea. The patient recovered within an hour after receiving 2 vials of antivenom, except for persistent abdominal pain which required atropine administration (Isbister & Gray, 2004).
    B) PILOERECTION
    1) WITH POISONING/EXPOSURE
    a) Generalized piloerection is a common early finding (Miller et al, 2000; Harrington et al, 1999; Sutherland, 1992; Dieckmann et al, 1989; Fisher et al, 1981).
    b) INCIDENCE: In a series of 13 patients with Hadronyche envenomation, 7 (54%) developed piloerection (Miller et al, 2000). In another series of 59 severely envenomated patients, 31% of patients developed piloerection (Isbister et al, 2005).
    C) PAIN
    1) WITH POISONING/EXPOSURE
    a) Local pain at the bite site is typical. In a series of 13 patients with Hadronyche envenomation, 9 (69%) reported local pain (Miller et al, 2000).
    b) DURATION: In a series of 16 patients with funnel web spider bites, the mean duration of pain was 120 minutes (ranging from 33 to 210 minutes) (Isbister & Gray, 2004).
    D) SOFT TISSUE INJURY
    1) WITH POISONING/EXPOSURE
    a) A bite mark may be visible on the skin. Bleeding from the wound may also occur. The presence of bleeding may help differentiate the likelihood of funnel-web spider bite versus other bites when a spider is not identified. Local necrosis does not occur.

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCLE FASCICULATION
    1) WITH POISONING/EXPOSURE
    a) Muscle fasciculations are common within minutes to hours of significant envenomation (Isbister & Warner, 2003; Miller et al, 2000; Fisher et al, 1981). Fasciculation are often first noticed in the tongue, but may progress to more generalized fasciculations, spasms and myoclonus (Harrington et al, 1999; Grant & Loxton, 1992; Sutherland, 1992). Spasm of the tongue, neck and jaw may rarely cause airway compromise, especially if hypersalivation is also present.
    b) INCIDENCE: The reported incidence of fasciculations ranges from 54% to 69% (Miller et al, 2000; Isbister et al, 2005). Large muscle spasm occurred in 17% of severely envenomated patients (Isbister et al, 2005).
    c) Fasciculations occurred in 3 of 16 patients (19%) following Atracinae envenomation (Isbister & Gray, 2004).
    B) SPASM
    1) WITH POISONING/EXPOSURE
    a) Muscle spasms have been reported with envenomation (Fisher et al, 1981; Harrington et al, 1999).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and institute continuous cardiac monitoring. Monitor pulse oximetry and/or arterial blood gases, ECG, and chest radiograph in patients with respiratory signs or symptoms.
    B) Monitor for clinical evidence of pulmonary edema.
    C) Monitor electrolytes, renal function, and CK in patients with significant envenomation.
    D) There is no specific clinical assay for funnel web spider venom.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor serum electrolytes and CK in patients with significant envenomation (White et al, 1995).
    2) Monitor renal function tests and INR and PTT in patients with severe envenomation. Renal failure and coagulopathy are rare effects that have been reported secondary to circulatory collapse (White et al, 1995).
    4.1.4) OTHER
    A) OTHER
    1) POSTMORTEM
    a) Postmortem studies have revealed no significant pathology (Sutherland, 1983).

Methods

    A) OTHER
    1) There is no specific clinical test specific for funnel web spider venom (White et al, 1995).

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) Patients who develop signs or symptoms of systemic envenomation should receive antivenom and be admitted to an intensive care setting.
    6.3.6.2) HOME CRITERIA/BITE-STING
    A) There is no role for home management. A patient bitten by any of the large species of Atrax (or Hadronyche) should be evaluated at a medical facility. A pressure immobilization bandage should be applied at the scene as soon as possible.
    6.3.6.3) CONSULT CRITERIA/BITE-STING
    A) Consult a clinical toxinologist, toxicologist or poison center for patients with significant envenomation or in whom the diagnosis is unclear.
    6.3.6.4) PATIENT TRANSFER/BITE-STING
    A) Patients with evidence of systemic envenomation will require transfer to a facility that has antivenom and intensive care capability if these are not available at the facility where they initially present.
    6.3.6.5) OBSERVATION CRITERIA/BITE-STING
    A) Patients with bites from a spider identified as or strongly suspected of being a funnel web spider should be observed for 18 hours and discharged if asymptomatic (Miller et al, 2000). If the offending spider is not known, a 4 hour period of observation (after removal of pressure bandage) may be sufficient (Isbister & White, 2004; Isbister & Sibbritt, 2004; Miller et al, 2000; Sutherland, 1983).

Monitoring

    A) Monitor vital signs and institute continuous cardiac monitoring. Monitor pulse oximetry and/or arterial blood gases, ECG, and chest radiograph in patients with respiratory signs or symptoms.
    B) Monitor for clinical evidence of pulmonary edema.
    C) Monitor electrolytes, renal function, and CK in patients with significant envenomation.
    D) There is no specific clinical assay for funnel web spider venom.

Abstracts

Case Reports

    A) ACUTE EFFECTS
    1) Thirteen fatalities have been reported between 1927 and 1980. Ages ranged between 15 months and 60 years (Sutherland, 1983). In children, death occurred in 15 to 90 minutes; in adults, death occurred 30 hours and later after the envenomation (Sutherland, 1983). In most bites (even by the male A. robustus), little venom is injected and no illness occurs. However, no confirmed fatalities have been reported since the introduction of antivenom in 1981.
    B) LOCAL EFFECTS
    1) Bites are extremely painful (hours to days duration). A bite mark may be visible on the skin. Bleeding from the wound may also occur (Isbister & Gray, 2004; Isbister & Sibbritt, 2004). The presence of bleeding may help differentiate the likelihood of funnel-web spider bite versus other bites when a spider is not identified (Isbister & Sibbritt, 2004). Local necrosis does not occur.
    C) SYSTEMIC EFFECTS
    1) A review of 138 funnel-web spider bites noted a 17% severe envenomation rate by A. robustus. The rate of severe envenomation was 63% for H. formidabilis and 75% for H. cerberea (Isbister et al, 2005).
    D) ADVERSE EFFECTS
    1) CASE REPORTS: Dieckmann et al (1989) reported 3 cases, all of which exhibited the characteristic symptomatology of funnel web spider envenomation, and all 3 patients required 4 to 5 vials of antivenom to reverse the symptoms completely (Dieckmann et al, 1989).
    2) CASE REPORT: A 9-month-old was bitten on the hand and received immediate immobilization of the limb, but still developed severe symptoms related to envenomation. The infant required mechanical ventilation for pulmonary edema and aggressive supportive care. Even though 4 ampules of antivenom were given over a 60 minute period, initial attempts at removing the limb immobilizer resulted in rapid deterioration in circulatory status (tachycardia, hypertension, cool, clammy skin). A total of 5 vials were required to alleviate all symptoms. Two days after exposure the patient was discharged with no sequelae (Browne, 1997).
    3) CASE REPORTS: Miller et al (2000) described 5 cases of Hadronyche envenomation and reviewed 8 other cases. Diaphoresis was the most common clinical finding (12 of 13 patients, 92%), followed by local pain, hypertension, fasciculation or spasm, sinus tachycardia, and nausea or vomiting, each of which developed in 9 of 13 patients (69%). Pulmonary edema, salivation, altered consciousness and piloerection developed in 7 of 13 patients (54%), while six patients (46%) developed either mydriasis or miosis. Hypotension developed in 4 patients (31%), and abdominal pain, dysrhythmias and perioral tingling each developed in 3 patients (23%). Lacrimation was only described in one patient (Miller et al, 2000).
    4) CASE REPORT: A 67-year-old woman developed ST segment elevations on 12 lead ECG within 30 minutes of a bite by A. robustus, along with elevations in troponin T levels. This patient also experienced hypertension, tachycardia and respiratory distress. Vital sign abnormalities improved with a total of 6 vials of antivenom. However, respiratory status did not resolve, requiring intubation. The patient fully recovered after 4 days. No coronary angiography was performed, and nuclear stress testing revealed only mild atherosclerotic disease (Isbister & Warner, 2003).
    5) CASE SERIES: In a review of 138 cases of confirmed funnel web spider bites and characterized features of the severely envenomated patients (77 of 138). Prevalent autonomic effects included diaphoresis (78%), salivation (44%), piloerection (31%), pupillary changes (32%) and lacrimation (12%). The most common cardiovascular effects were hypertension (75%) and tachycardia (59%); bradycardia or hypotension were seen in only 10% of cases. Pulmonary edema occurred in 54%. Neurologic findings included fasciculations (54%), perioral paresthesia (32%) and muscle spasm (17%); frank coma occurred in 8% of cases. Other systemic symptoms observed were agitation (47%), vomiting (41%), headache (10%) and abdominal pain (10%) (Isbister et al, 2005).

Range Of Toxicity

Summary

    A) Most bites cause no effects or mild systemic effects. A single spider bite can cause severe, potentially lethal, envenomation; however, there have been no confirmed deaths since the introduction of antivenom in 1981.

Minimum Lethal Exposure

    A) CASE REPORTS
    1) SUMMARY: Thirteen fatalities have been reported between 1927 and 1980. Ages ranged between 15 months and 60 years (Sutherland, 1983). In children, death has occurred between 15 and 90 minutes; in adults, death may occur 30 hours and later after the envenomation (Sutherland, 1983). There are no confirmed deaths due to funnel-web spider bites after the introduction of antivenom in 1981, and decreased reports of patients with severe envenomation requiring ICU admission (Isbister, 2010).
    B) ANIMAL DATA
    1) Primates appear to be uniquely sensitive to funnel web spider venom compared with other vertebrates.
    2) Monkeys given robustoxin (5 to 30 mcg/kg IV) or male A. robustus venom (50 mcg/kg IV) exhibited the following effects: lacrimation, salivation, skeletal muscle fasciculations, elevated body temperature, increased firing in autonomic and skeletal motor nerves, severe hypotension, and death due to respiratory and circulatory failure (Mylecharane et al, 1989).

Maximum Tolerated Exposure

    A) In most bites (even by the male A. robustus), little venom is injected and either no illness occurs, or mild effects may develop (headache, nausea, malaise, paresthesia) (Isbister & White, 2004).
    B) CASE REPORTS
    1) PEDIATRIC
    a) Despite pulmonary edema and circulatory collapse a 9-month-old recovered completely from several bites on the hand by a male A. robustus. A total of 5 ampules of antivenom were required to alleviate all symptoms. The patient made a complete recovery (Browne, 1997).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) ANIMAL DATA
    a) In monkeys a dose of 5 to 30 micrograms/kilogram intravenously of robustoxin or 50 micrograms/kilogram intravenously of male A. robustus venom produced the same characteristic neurotoxic effects (Mylecharane et al, 1989).

Toxicity Information

    7.7.1) TOXICITY VALUES

Pharmacology Toxicology

Toxicologic Mechanism

    A) SUMMARY - The Sydney funnel-web spider contains a lethal neurotoxin found in the venom of the male species which initially enhances, then inhibits skeletal motor nerves (Hodgson, 1997). Only primates and new born mice have been found to be susceptible to the effects of the venom.
    B) The venom contains a high level of GABA, a spermine complex, lactic acid, and a range of other chemicals including tyramine and octopamine. The venom is acidic.
    C) Venom from the funnel web spider contains many acylpolyamine toxins (curtatoxins or agatoxins) that have paralytic and insecticidal activity. The polyamine portion rather than the acyl moiety of these toxins appears to be more crucial to the paralytic potency in insects (Quistad et al, 1991; Adams et al, 1989).
    D) Originally, the major toxin was thought to be "atraxotoxin" a protein of MW 9,800, consisting of 97 amino acids. However, Sheumack et al (1983) isolated the sole lethal toxin, "robustoxin", from the venom of the male funnel web spider, A. robustus, and determined the molecular weight of the lethal polypeptide neurotoxin to be 4,887 (Sheumack et al, 1983). The complete sequence of 42 amino acids has been determined (Sheumack et al, 1985). Depending on the author, the active toxin is also termed atraxotoxin, atraxin or delta-atracotoxin (Isbister & White, 2004; Miller et al, 2000) .
    1) It has been suggested that a pre-robustoxin molecule may be present in the venom of the male species (Collins et al, 1995). Further study is required to determine the possible significance of this finding.
    E) Experimentally, venom of the male A. robustus is at least 6 times as toxic as that of the female due to differing toxin content. Historically, of the 13 deaths positively attributed to envenomation by the funnel web spider, Atraxtobustus, all have been due to male spiders (Sutherland, 1983).
    F) Venom components cause excessive neurotransmitter release at autonomic and somatic nerve terminals (Nicholson & Graudins, 2002). It acts as a presynaptic neurotoxin, causing repetitive firing of action potentials (Isbister & White, 2004; Miller et al, 2000). The site of action appears to be at pre-synaptic tetrodotoxin-sensitive voltage-gated Na+ channels. Atracotoxins slow channel inactivation, which likely leads to the observed effects of neurologic overstimulation (Isbister & White, 2004) .

Animal Toxicology

Clinical Effects

    11.1.3) CANINE/DOG
    A) Fatalities have not been reported in domestic animals. Effects noted in dogs and cats were limited to the cardiovascular system (hypertension, tachycardia, atrial fibrillation and flutter, and ventricular irritability) (Tibballs et al, 1987).
    11.1.6) FELINE/CAT
    A) Fatalities have not been reported in domestic animals. Effects noted in dogs and cats were limited to the cardiovascular system (hypertension, tachycardia, atrial fibrillation and flutter, and ventricular irritability) (Tibballs et al, 1987).

References

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