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AUSTRALIAN BROWN SNAKES

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Brown snakes are front-fanged elapids; they are the most common cause of both snakebites and of lethal snake envenomation in Australia.

Specific Substances

    A) AUSTRALIAN BROWN SNAKES
    1) Australian brown snake
    2) Brown snake
    3) Common brown snake
    4) Dugite
    5) Eastern brown snake
    6) Gwardar
    7) Ingram's brown snake
    8) Peninsula brown snake
    9) Pseudonaja affinis
    10) Pseudonaja guttata
    11) Pseudonaja inframacula
    12) Pseudonaja ingrami
    13) Pseudonaja modesta
    14) Pseudonaja nuchalis
    15) Pseudonaja textilis
    16) Ringed brown snake
    17) Spotted brown snake
    18) Speckled brown snake
    19) Western brown snake

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) GENERAL: Brown snakes are front fanged elapids; they are found throughout Australia.
    B) TOXICOLOGY: Brown snake venom contains a potent prothrombin activator that causes rapid consumption of essential clotting factors with a resulting severe coagulopathy. Some venom components have nephrotoxic or neurotoxic effects, but these are not dominant clinical manifestations of most envenomations.
    C) EPIDEMIOLOGY: Brown snakes are the most common cause of both snakebites and of lethal snake envenomation in Australia.
    D) WITH POISONING/EXPOSURE
    1) MILD ENVENOMATION: A significant number of brown snake bites do not result in envenomation. Nonspecific abdominal pain, nausea, vomiting, and headache may develop with mild envenomation, may be an early manifestation of what develops into a more severe envenomation, or may be due to anxiety.
    2) SEVERE ENVENOMATION: Early on patients may develop mild local swelling and lymphadenopathy. Early collapse after the bite suggests severe envenomation. Venom-induced consumptive coagulopathy is a hallmark of severe envenomation. It is characterized by very low concentrations of fibrinogen, increased INR and aPTT, prolonged whole blood clotting time, increased concentrations of fibrin degradation products, elevated D-dimer, and the potential for widespread and life-threatening hemorrhage. Coagulopathy is usually evident within 12 hours (much faster in severe cases) and takes 12 to 18 hours after antivenom administration to resolve. A smaller number of patients develop thrombotic microangiopathy with severe thrombocytopenia, hemolysis, anemia, and renal failure. The onset of thrombotic microangiopathy is generally delayed for several days after the bite and it is at its most severe after recovery from the initial coagulopathy. Fatalities are usually secondary to bleeding complications (most often intracranial) or multi-organ-system failure.

Laboratory Monitoring

    A) Monitor vital signs and mental status.
    B) Monitor serum electrolytes, renal function, urinalysis and urine output.
    C) Monitor coagulation studies on presentation, after removing pressure immobilization if it has been used, and approximately every 6 hours thereafter including: CBC with platelet count, INR, and aPTT. Fibrinogen, fibrin degradation products, and D-dimer can be monitored but may not be necessary in most patients. The whole blood clotting time can also be used to assess for coagulation abnormalities.
    D) Monitor for clinical evidence of bleeding (eg, hematuria, GI bleeding, epistaxis, bruising, bleeding from venipuncture sites or gums, altered mentation suggesting intracranial bleeding).
    E) 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) Obtain an head CT if altered mentation develops, or there is any clinical concern for intracranial bleeding.

Treatment Overview

    0.4.7) BITES/STINGS
    A) NO OR MILD ENVENOMATION
    1) Patients who are asymptomatic or only have mild symptoms and no laboratory evidence of envenomation should be monitored for a minimum of 12 hours.
    B) SEVERE ENVENOMATION
    1) Patients with severe symptoms, or laboratory evidence of venom-induced consumptive coagulopathy or renal injury should be treated with antivenom and if coagulopathy is severe fresh frozen plasma, or cryoprecipitate.
    C) ANTIVENOM
    1) Treat patients with venom-induced consumptive coagulopathy or renal insufficiency secondary to brown snake envenomation with brown snake antivenom. If specific antivenom is not available, or the species of snake responsible is not known , polyvalent antivenom may be used. The optimum dose of antivenom is not known. For patients with mild coagulopathy, the manufacturer recommends an initial dose of 2 ampoules of brown snake antivenom (diluted 1 to 10 in crystalloid, each ampoule infused over 15 to 30 minutes). For patients with severe coagulopathy, the initial dose is 4 ampoules (diluted 1 to 10 in crystalloid, each ampoule infused over 15 to 30 minutes) with subsequent doses of 2 to 6 ampoules likely to be necessary over the subsequent few hours. Some authors advocate an initial dose of 10 ampoules in patients with severe brown snake envenomation. Monitor patient carefully and be prepared to treat anaphylaxis.
    D) VENOM INDUCED CONSUMPTIVE COAGULOPATHY
    1) In addition to antivenom, fresh frozen plasma and/or cryoprecipitate should be considered early in patients with severe consumptive coagulopathy.
    E) 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.
    F) MONITORING OF PATIENT
    1) Monitor vital signs and mental status. Monitor serum electrolytes, renal function, urinalysis and urine output. Monitor coagulation studies on presentation and approximately every 6 hours thereafter, including: CBC with platelet count, INR, and aPTT. Fibrinogen, fibrin degradation products, and D-dimer can be monitored, but may not be necessary in most patients. The whole blood clotting time can also be used to assess for coagulation abnormalities. Monitor for clinical evidence of bleeding (eg, hematuria, GI bleeding, epistaxis, bruising, bleeding from venipuncture sites or gums, altered mentation suggesting intracranial bleeding). 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. Obtain an head CT if altered mentation develops, or there is any clinical concern for intracranial bleeding.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: There is no role for home management of possible snake bite.
    2) OBSERVATION CRITERIA: All patients with suspected snake bite should be observed for at least 12 hours, with serial laboratory studies (ie, coagulation studies, serum electrolytes, renal function) on admission and every 6 hours thereafter, and careful clinical evaluation. If there is no clinical or laboratory evidence of envenomation, coagulopathy, or renal insufficiency after this time, 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 coagulopathy, bleeding, or renal insufficiency, 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.
    H) TOXICOKINETICS
    1) ONSET: Onset of envenomation can be quite rapid, with some patients collapsing shortly after being bitten. The vast majority of patients who develop systemic envenomation have evidence of coagulopathy on laboratory testing within 12 hours of the bite (generally sooner in patients with severe envenomation). DURATION: Once venom-induced consumptive coagulopathy has developed, recovery of normal coagulation generally does not occur until 12 to 18 hours after the administration of antivenom.
    I) PITFALLS
    1) The presence of brown snake 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 or laboratory evidence of envenomation. The onset of clinical evidence of envenomation may be delayed; all patients with suspected snakebite should be observed for a minimum of 12 hours. 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 or laboratory evidence of envenomation.
    J) DIFFERENTIAL DIAGNOSIS
    1) Envenomation by tiger snakes, taipan or mulga snakes can cause coagulation abnormalities. Disseminated intravascular coagulation. Overdose of anticoagulants such as warfarin or brodifacoum.

Range Of Toxicity

    A) TOXICITY: A single bite from a brown snake can be lethal. Children often develop more severe effects. Some definite bites by brown snakes do not result in envenomation, but the percent of "dry" bites is unknown.

Clinical Effects

Summary Of Exposure

    A) GENERAL: Brown snakes are front fanged elapids; they are found throughout Australia.
    B) TOXICOLOGY: Brown snake venom contains a potent prothrombin activator that causes rapid consumption of essential clotting factors with a resulting severe coagulopathy. Some venom components have nephrotoxic or neurotoxic effects, but these are not dominant clinical manifestations of most envenomations.
    C) EPIDEMIOLOGY: Brown snakes are the most common cause of both snakebites and of lethal snake envenomation in Australia.
    D) WITH POISONING/EXPOSURE
    1) MILD ENVENOMATION: A significant number of brown snake bites do not result in envenomation. Nonspecific abdominal pain, nausea, vomiting, and headache may develop with mild envenomation, may be an early manifestation of what develops into a more severe envenomation, or may be due to anxiety.
    2) SEVERE ENVENOMATION: Early on patients may develop mild local swelling and lymphadenopathy. Early collapse after the bite suggests severe envenomation. Venom-induced consumptive coagulopathy is a hallmark of severe envenomation. It is characterized by very low concentrations of fibrinogen, increased INR and aPTT, prolonged whole blood clotting time, increased concentrations of fibrin degradation products, elevated D-dimer, and the potential for widespread and life-threatening hemorrhage. Coagulopathy is usually evident within 12 hours (much faster in severe cases) and takes 12 to 18 hours after antivenom administration to resolve. A smaller number of patients develop thrombotic microangiopathy with severe thrombocytopenia, hemolysis, anemia, and renal failure. The onset of thrombotic microangiopathy is generally delayed for several days after the bite and it is at its most severe after recovery from the initial coagulopathy. Fatalities are usually secondary to bleeding complications (most often intracranial) or multi-organ-system failure.

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) PHOTOPHOBIA
    a) Photophobia can be an early neurologic manifestation of brown snake envenomation, but it is not common (Herrmann et al, 1972; Brimacombe & Murray, 1995).
    3.4.5) NOSE
    A) WITH POISONING/EXPOSURE
    1) EPISTAXIS
    a) Epistaxis can be a manifestation of venom induced consumptive coagulopathy (Brimacombe & Murray, 1995; Henderson et al, 1993).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) BLEEDING GUMS
    a) Bleeding from the gums is often an early manifestation of venom-induced consumptive coagulopathy (Johnston et al, 2002).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) TACHYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia may develop early in patients with severe brown snake envenomation (Barrett & Little, 2003).
    B) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension may develop early in patients with severe brown snake envenomation (Barrett & Little, 2003).
    C) CARDIAC ARREST
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: There is one report of successful resuscitation from cardiac arrest after severe brown snake envenomation.
    b) CASE REPORT: A 44-year-old man was bitten on the finger trying to catch what was later identified as a Pseudonaja nuchalis (gwardar) that was in his house. He applied a compression bandage from fingers to elbow and drove to his general practitioner. On arrival he felt unwell and had chest tightness, and then became unresponsive. He was transferred to a hospital. On arrival 2 hours and 15 minutes after the bite he was unresponsive with tonic-clonic activity and no pulse, but narrow complexes on ECG. CPR was started, he was intubated, given two 0.5 mg doses of epinephrine IV, 1 liter normal saline, and an undiluted bolus of antivenom consisting of 1 ampule polyvalent antivenom, and 2 ampules each brown snake and tiger snake antivenom. Shortly after that, another ampule of polyvalent antivenom and 3 ampules of brown snake antivenom were administered. There was a return of spontaneous circulation one minute after this second dose of antivenom, with a total CPR time of 11 minutes. He developed severe coagulopathy, was treated with reinforcement of the compression bandage and more brown snake antivenom (an additional 15 vials were used in the first 5 hours after the bite). His coagulopathy resolved, cranial CT was normal, and he was extubated and neurologically intact. Angiography 4 days after envenomation revealed normal left ventricular function and coronary arteries. He was treated with a 5-day course of prednisone, but developed mild serum sickness (flu-like illness with rash and sore joints) 17 to 21 days after the bite (Johnston et al, 2002).
    D) ELECTROCARDIOGRAM ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) ECG changes have been reported in patients with severe brown snake envenomation. The etiology and significance is unclear.
    b) CASE REPORT: A 42-year-old woman was bitten on the heel by Pseudonaja nuchalis (western brown snake). She became diaphoretic and collapsed. She developed severe coagulopathy, was treated with a total of 9 ampules of brown snake antivenom. At 24 hours after the bite she developed anterolateral T-wave inversion with a troponin of 0.5 mcg/L (normal: 0 to 0.5 mcg/L) and a CK-MB of 13 units/L (normal 0 to 4.4 units/L). Echocardiography and CT angiogram were normal and ECG changes resolved on day 5 (Isbister & Currie, 2003).
    c) CASE REPORT: A 23-year-old man was bitten by an unknown snake. On arrival to the hospital one hour later, brown snake venom was detected at the bite site, and he had severe coagulopathy. He was treated with brown snake antivenom, but delayed hemolysis, thrombocytopenia and acute renal failure developed, which resolved over 11 days. On admission, prior to administration of antivenom, his ECG showed QRS widening (150 msec in the precordial leads and 130 msec in the limb leads) which resolved over 11 days to 110 msec and 90 msec, respectively (Buckley & Dawson, 1993).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) HEMOPTYSIS
    1) WITH POISONING/EXPOSURE
    a) Hemoptysis can be a manifestation of venom-induced consumptive coagulopathy (Brimacombe & Murray, 1995).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) INTRACRANIAL HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) Intracranial hemorrhage can occur, and is a common cause of death. It should be suspected in any patient with altered mental status or severe headache in the setting of venom-induced consumptive coagulopathy.
    b) CASE REPORTS
    1) A 57-year-old woman was bitten by a brown snake. Within about 30 minutes she was confused and agitated, with vomiting and decreasing mental status. She was treated with polyvalent and brown snake antivenom, and fresh frozen plasma, and was intubated. She developed multiple bilateral intracranial hemorrhages, which progressed to transtentorial herniation and brain death. Life support was discontinued 24 hours after the bite (Midyett, 1998).
    2) A 72-year-old woman was bitten on the foot by a brown snake. She developed severe coagulopathy, that persisted despite brown snake antivenom and fresh frozen plasma. She developed a headache and lost consciousness 13 hours after the bite. CT showed intraparenchymal and subdural hematomas, and she died 22 hours after the bite (Sprivulis & Jelinek, 1995).
    3) A 31-year-old man was bitten on the finger by a brown snake. He collapsed 15 minutes later, sustaining an occipital scalp laceration. He had severe coagulopathy on presentation to hospital 1 hour after the bite. The snake was initially misidentified, and he was treated with black snake antivenom and polyvalent antivenom. He became confused, and developed diplopia and ptosis 4 hours after the bite. His condition further deteriorated, and he was endotracheally intubated. He was then given brown snake antivenom. Cranial CT showed large bilateral occipitotemporal hematomas and edema. The hematomas were surgically drained, but he died 23 hours after the bite (Sprivulis & Jelinek, 1995).
    B) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache has been reported with mild brown snake envenomation (White et al, 1987).
    b) Headache and irritability can be early neurologic manifestations of more severe brown snake envenomation (Herrmann et al, 1972; Brimacombe & Murray, 1995). These symptoms can also develop secondary to anxiety (White, 1995).
    C) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizure may be a rare manifestation of severe envenomation.
    b) CASE REPORT: A 3-year-old boy was bitten at least twice by a brown snake. A compression bandage was applied and he was taken to a medical clinic. The bandage was removed, and the child began shaking all over with spasmodic movements, became pale, clammy, and limp with his jaw clenched tight, and urinary and fecal incontinence. The child was transported to a hospital, where a coagulopathy was noted and the child was treated with brown snake antivenom. He recovered completely (White & Williams, 1989).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) Gastrointestinal bleeding can develop as a complication of venom-induced consumptive coagulopathy (Sprivulis & Jelinek, 1995).(Henderson et al, 1993).
    B) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea and abdominal pain have been reported with mild brown snake envenomation (White et al, 1987).
    b) Nausea, vomiting and abdominal pain can be early manifestations of more severe brown snake envenomation (Herrmann et al, 1972; White & Williams, 1989). These symptoms can also develop secondary to anxiety (White, 1995).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) Acute renal failure can develop after brown snake envenomation, but is not as common as consumptive coagulopathy. It generally happens in patients who develop evidence of hemolysis (anemia, fragmented red cells, elevated LDH and bilirubin) and severe thrombocytopenia. Hemodialysis may be required for several weeks, but renal function usually recovers (Isbister et al, 2007a; Buckley & Dawson, 1993; Acott, 1988; White & Fassett, 1983).
    B) BLOOD IN URINE
    1) WITH POISONING/EXPOSURE
    a) Hematuria can develop in patients with venom-induced consumptive coagulopathy (Johnston et al, 2002).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) BLOOD COAGULATION DISORDER
    1) WITH POISONING/EXPOSURE
    a) Brown snake venom induces a consumptive coagulopathy that is characterized by very low concentrations of fibrinogen, increased INR and aPTT, prolonged whole blood clotting time, increased concentrations of fibrin degradation products, elevated D-dimer, and the potential for widespread and life-threatening hemorrhage (Barrett & Little, 2003; Masci et al, 1990).
    b) ONSET: Coagulopathy is usually evident by 12 hours (Ireland et al, 2010), but generally occurs much more rapidly in patients with severe envenomation.
    c) DURATION: Once venom induced consumptive coagulopathy has developed, recovery of normal coagulation generally does not occur until 12 to 18 hours after the administration of antivenom (Isbister, 2010).
    d) MANIFESTATIONS: Can include bleeding from almost any site including: skin hematomas, bleeding from venipuncture sites, bleeding from the mouth and gums, epistaxis, hemoptysis, hematemesis, melena or hematochezia, hematuria, and intracranial hemorrhage (Barrett & Little, 2003; Johnston et al, 2002; Henderson et al, 1993).
    B) THROMBOTIC MICROANGIOPATHY
    1) WITH POISONING/EXPOSURE
    a) A thrombotic microangiopathy, characterized by severe thrombocytopenia, hemolysis, anemia, and renal failure has been reported after brown snake envenomation, but is not common (Isbister et al, 2007a).
    b) ONSET: If thrombotic microangiopathy develops, severe thrombocytopenia generally reaches its nadir 3 to 4 days after the bite, anemia with red cell fragmentation and elevated LDH develops over several days, and acute renal failure follows, which may require 2 to 8 weeks to resolve completely (Isbister et al, 2007a).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) PALE - SYMPTOM
    1) WITH POISONING/EXPOSURE
    a) Patients with severe brown snake envenomation may develop pale, dusky, or clammy grey skin soon after the bite (Barrett & Little, 2003; White & Williams, 1989).
    B) BLEEDING
    1) WITH POISONING/EXPOSURE
    a) Bruising or bleeding from venipuncture sites is often one of the early manifestations of venom-induced consumptive coagulopathy (Herrmann et al, 1972; Schapel et al, 1971).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) LYMPHADENOPATHY
    1) WITH POISONING/EXPOSURE
    a) Enlarged, tender lymph nodes can develop after brown snake envenomation (Isbister & Currie, 2003a; Schapel et al, 1971).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and mental status.
    B) Monitor serum electrolytes, renal function, urinalysis and urine output.
    C) Monitor coagulation studies on presentation, after removing pressure immobilization if it has been used, and approximately every 6 hours thereafter including: CBC with platelet count, INR, and aPTT. Fibrinogen, fibrin degradation products, and D-dimer can be monitored but may not be necessary in most patients. The whole blood clotting time can also be used to assess for coagulation abnormalities.
    D) Monitor for clinical evidence of bleeding (eg, hematuria, GI bleeding, epistaxis, bruising, bleeding from venipuncture sites or gums, altered mentation suggesting intracranial bleeding).
    E) 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) Obtain an head CT if altered mentation develops, or there is any clinical concern for intracranial bleeding.
    4.1.2) SERUM/BLOOD
    A) Monitor serum electrolytes and renal function.
    B) COAGULATION STUDIES
    1) The primary effect of brown snake envenomation is coagulopathy. Monitor coagulation studies on presentation, after removing pressure immobilization if it has been used, and approximately every 6 hours thereafter (Ireland et al, 2010) including: CBC with platelet count, INR, and aPTT. While fibrinogen, fibrin degradation products, and D-dimer are monitored in some settings, INR and aPTT appear to provide a good assessment of coagulation status in patients with brown sake envenomation (Isbister et al, 2006).
    2) WHOLE BLOOD CLOTTING TIME (WBCT): A method to determine whole blood clotting can be done at the bedside with a few millimeters of venous blood placed in a new, clean, dry, glass tube (or bottle), if the patient has no history of coagulopathies. The steps are as follows and may be useful in a setting where laboratory studies are limited (Anon, 1999):
    a) Place a few millimeters of venous blood in a GLASS tube
    b) Leave undisturbed for 20 minutes at room temperature
    c) Tip the vessel once:
    1) If blood is still liquid and runs out it is indicative of a venom-induced coagulopathy
    2) Inaccurate results may occur if the vessel had been cleaned previously with detergent
    d) FALSE NEGATIVE results could occur if clot identification is read beyond 20 minutes (Stone et al, 2006).
    e) FALSE POSITIVE results could occur if polypropylene or polyethylene tubes are used instead of glass (Stone et al, 2006).
    4.1.3) URINE
    A) Monitor urinalysis for hematuria. Monitor urine output.
    4.1.4) OTHER
    A) OTHER
    1) CLINICAL EXAMINATION
    a) Monitor vital signs and mental status. Monitor for clinical evidence of bleeding (eg, hematuria, GI bleeding, epistaxis, bruising, bleeding from venipuncture sites or gums, altered mentation suggesting intracranial bleeding).
    2) VENOM DETECTION
    a) If there is any question as to the type of snake involved, use the venom detection kit on the bite site and/or urine to identify the species involved. The presence of venom at the bite site does NOT mean that systemic envenomation has occurred. Many centers advocate obtaining a swab of the bite site or specimen of urine to be held on presentation, and only using the venom detection kit if there is clinical or laboratory evidence of envenomation develops (Jelinek et al, 2004; Isbister & Currie, 2003a; Jelinek et al, 1991).
    b) Venom detection in urine usually is associated with systemic envenomation, but a few cases have been reported where venom was detected in urine or blood in the absence of clinical or laboratory evidence of significant envenomation (Jelinek et al, 1991). Blood samples have been found to be unreliable for testing for the presence of venom and should not be used (White, 1995).
    c) In an in vitro study, the venom or saliva of other Australian snakes that are considered venomous, mildly venomous, and non-venomous were not found to yield positive results for brown snake venom on the venom detection kit (Jelinek et al, 2004).
    3) COMPUTERIZED TOMOGRAPHY
    a) Intracranial hemorrhage is a common cause of fatality after brown snake envenomation. Obtain a cranial CT if there is altered mental status or any other suggestion of intracranial bleeding.

Methods

    A) ENZYME IMMUNOASSAY
    1) An enzyme immunoassay has been developed to detect brown snake venom, antivenom and venom-antivenom complex (O'Leary et al, 2006). It is used primarily for research, and not to guide patient care.

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 coagulopathy, bleeding, or renal insufficiency, 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 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, with serial laboratory studies (coagulation studies, serum electrolytes, renal function) on admission and every 6 hours thereafter and careful clinical evaluation. If there is no clinical or laboratory evidence of envenomation, coagulopathy or renal insufficiency after this time, the patient can be discharged (Ireland et al, 2010).

Monitoring

    A) Monitor vital signs and mental status.
    B) Monitor serum electrolytes, renal function, urinalysis and urine output.
    C) Monitor coagulation studies on presentation, after removing pressure immobilization if it has been used, and approximately every 6 hours thereafter including: CBC with platelet count, INR, and aPTT. Fibrinogen, fibrin degradation products, and D-dimer can be monitored but may not be necessary in most patients. The whole blood clotting time can also be used to assess for coagulation abnormalities.
    D) Monitor for clinical evidence of bleeding (eg, hematuria, GI bleeding, epistaxis, bruising, bleeding from venipuncture sites or gums, altered mentation suggesting intracranial bleeding).
    E) 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) Obtain an head CT if altered mentation develops, or there is any clinical concern for intracranial bleeding.

Range Of Toxicity

Summary

    A) TOXICITY: A single bite from a brown snake can be lethal. Children often develop more severe effects. Some definite bites by brown snakes do not result in envenomation, but the percent of "dry" bites is unknown.

Minimum Lethal Exposure

    A) SUMMARY
    1) Fatalities are usually from bleeding complications (most often intracranial) or multi-organ-system failure (Isbister et al, 2007). Children are more likely to develop severe envenomation (White, 1995) and seem to have a higher mortality than adults(Currie, 2006). Patients who sustain multiple bite, have underlying medical problems or advanced age, and those who are physically active after the bite are at greater risk of severe envenomation (White, 1995).
    B) CASE REPORTS
    1) A 42-year-old man was bitten by an eastern brown sake on the foot. He developed dyspnea, called an ambulance a few minutes after the bite, and was unconscious when the ambulance arrived 7 minutes later. He was transported to hospital but sustained a cardiac arrest just prior to arrival, about 60 minutes after the arrival of the ambulance. He was resuscitated with return of spontaneous circulation, developed severe coagulopathy and bleeding and was treated with brown snake antivenom (7 hours after the bite), fresh frozen plasma and whole blood. He died of anoxic brain injury 2 days after envenomation (Henderson et al, 1993).
    2) A 39-year-old man was bitten by an eastern brown snake on the hand and foot. He lost consciousness within 10 minutes and was hypotensive and hypoventilating about 15 minutes after the bite. He was intubated, treated with epinephrine, promethazine, brown snake antivenom and polyvalent antivenom, fresh frozen plasma, cryoprecipitate, and platelets. He developed severe coagulopathy, epistaxis, hematuria, anuria, and pulmonary edema. He was also treated with plasma exchange and continuous venovenous hemofiltration. He developed refractory hypotension and died 17 hours after the bite (Henderson et al, 1993).
    3) A 57-year-old woman was bitten by a brown snake. Within about 30 minutes she was confused and agitated, with vomiting and decreasing mental status. She was treated with polyvalent and brown snake antivenom, and fresh frozen plasma and was intubated. She developed multiple bilateral intracranial hemorrhages which progressed to transtentorial herniation and brain death. Life support was discontinued 24 hours after the bite (Midyett, 1998).
    4) A 72-year-old woman was bitten on the foot by a brown snake. She developed severe coagulopathy, that persisted despite brown snake antivenom and fresh frozen plasma. She developed a headache and lost consciousness 13 hours after the bite. CT showed intraparenchymal and subdural hematomas and she died 22 hours after the bite (Sprivulis & Jelinek, 1995).
    5) A 31-year-old man was bitten on the finger by a brown snake. He collapsed 15 minutes later, sustaining an occipital scalp laceration. He had severe coagulopathy on presentation to hospital 1 hour after the bite. The snake was initially misidentified, and he was treated with black snake antivenom and polyvalent antivenom. He became confused, and developed diplopia and ptosis 4 hours after the bite. His condition further deteriorated, and he was endotracheally intubated. He was then given brown snake antivenom about 7 hours after the bite. Cranial CT showed large bilateral occipitotemporal hematomas and edema. The hematomas were surgically drained, but he died 23 hours after the bite (Sprivulis & Jelinek, 1995).

Maximum Tolerated Exposure

    A) SUMMARY
    1) Not all brown snake bites result in envenomation, although the percent of dry bites is not known. In a series of 70 patients evaluated for possible snakebite, 45 patients had definite bites (clear history of a bite, subject saw the snake at the time of the bite and had objective evidence of fang or teeth marks at the bite site). There were 4 patients with definite bites by brown snakes (Pseudonaja nuchalis); 2 developed severe envenomation and 2 had no evidence of envenomation (Isbister & Currie, 2003).
    2) In another series of 141 patients with brown snake bites, 13 patients (9%) had no evidence of envenomation, 12 (9%) had minor envenomation, and 116 (82%) had severe envenomation (Ireland et al, 2010).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) In a series of 27 patients with severe brown snake envenomation, the mean venom concentration prior to the administration of antivenom was 20 nanograms/mL with a range of 4 to 95 nanograms/mL (Isbister et al, 2007).

Pharmacology Toxicology

Toxicologic Mechanism

    A) Brown snake venom contains a potent prothrombin activator that is a procoagulant in vitro. In vivo, this causes rapid consumption of essential clotting factors with a resulting coagulopathy (Isbister et al, 2007). This venom-induced consumptive coagulopathy is characterized by very low concentrations of fibrinogen, increased INR and aPTT, prolonged whole blood clotting time, increased concentrations of fibrin degradation products, elevated D-dimer, and the potential for widespread and life-threatening hemorrhage (Barrett & Little, 2003; Masci et al, 1990).
    B) Brown snake antivenom does contain neurotoxic components, but neurotoxicity is rarely seen clinically (Isbister et al, 2007).
    C) A thrombotic microangiopathy, characterized by severe thrombocytopenia, hemolysis, anemia, and renal failure has been reported after brown snake envenomation, but is not as common as venom-induced consumptive coagulopathy (Isbister et al, 2007a).
    D) Fatalities are usually do to severe hemorrhage or multi-organ-system failure (Isbister et al, 2007).

References

General Bibliography

    1) Acott CJ: Acute renal failure after envenomation by the common brown snake. Med J Aust 1988; 149(11-12):709-710.
    2) Anon: WHO/SEARO guidelines for clinical management of snake bites. So Asian J Trop Med Pub Health 1999; 30 (S1):1-85.
    3) Barrett R & Little M : Five years of snake envenoming in far north Queensland. Emerg Med (Fremantle) 2003; 15(5-6):500-510.
    4) Brimacombe J & Murray A: Envenomation by Ingram's Brown snake (Pseudonaja ingrami). Anaesth Intensive Care 1995; 23(2):231-233.
    5) Brown SG , Caruso N , Borland ML , et al: Clotting factor replacement and recovery from snake venom-induced consumptive coagulopathy. Intensive Care Med 2009; 35(9):1532-1538.
    6) Buckley N & Dawson AH: Unusual results of brown snake envenomation. Med J Aust 1993; 158(12):866, 868.
    7) Currie BJ: Treatment of snakebite in Australia: The current evidence base and questions requiring collaborative multicentre prospective studies. Toxicon 2006; 48(7):941-956.
    8) Henderson A, Baldwin LN, & May C: Fatal brown snake (Pseudonaja textilis) envenomation despite the use of antivenom. Med J Aust 1993; 158(10):709-710.
    9) Herrmann RP , Davey MG , & Skidmore PH : The coagulation defect after envenomation by the bite of the dugite (Demansia nuchalis affinis), a Western Australian brown snake. Med J Aust 1972; 2(4):183-186.
    10) Ireland G, Brown SG, Buckley NA, et al: Changes in serial laboratory test results in snakebite patients: when can we safely exclude envenoming?. Med J Aust 2010; 193(5):285-290.
    11) Isbister GK & Currie BJ : Suspected snakebite: one year prospective study of emergency department presentations. Emerg Med (Fremantle) 2003a; 15(2):160-169.
    12) Isbister GK & Currie BJ: Suspected snakebite: One year prospective study of emergency department presentations. Emerg Med 2003; 15(2):160-169.
    13) Isbister GK , Duffull SB , & Brown SG : Failure of antivenom to improve recovery in Australian snakebite coagulopathy. QJM 2009; 102(8):563-568.
    14) Isbister GK : Antivenom efficacy or effectiveness: the Australian experience. Toxicology 2010; 268(3):148-154.
    15) Isbister GK, Little M, Cull G, et al: Thrombotic microangiopathy from Australian brown snake (Pseudonaja) envenoming. Intern Med J 2007a; 37(8):523-528.
    16) Isbister GK, O'Leary MA, Schneider JJ, et al: Efficacy of antivenom against the procoagulant effect of Australian brown snake (Pseudonaja sp.) venom: in vivo and in vitro studies. Toxicon 2007; 49(1):57-67.
    17) Isbister GK, Williams V, Brown SG, et al: Clinically applicable laboratory end-points for treating snakebite coagulopathy. Pathology 2006; 38(6):568-572.
    18) Jelinek GA , Hamilton T , & Hirsch RL : Admissions for suspected snake bite to the Perth adult teaching hospitals, 1979 to 1988. Med J Aust 1991; 155(11-12):761-764.
    19) Jelinek GA , Tweed C , Lynch D , et al: Cross reactivity between venomous, mildly venomous, and non-venomous snake venoms with the Commonwealth Serum Laboratories Venom Detection Kit. Emerg Med Australas 2004; 16(5-6):459-464.
    20) Johnston MA , Fatovich DM , Haig AD , et al: Successful resuscitation after cardiac arrest following massive brown snake envenomation. Med J Aust 2002; 177(11-12):646-649.
    21) Lieberman P, Nicklas R, Randolph C, et al: Anaphylaxis-a practice parameter update 2015. Ann Allergy Asthma Immunol 2015; 115(5):341-384.
    22) Lieberman P, Nicklas RA, Oppenheimer J, et al: The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010; 126(3):477-480.
    23) Masci PP , Rowe EA , Whitaker AN , et al: Fibrinolysis as a feature of disseminated intravascular coagulation (DIC) after Pseudonaja textilis textilis envenomation. Thromb Res 1990; 59(5):859-870.
    24) Midyett FA: Neuroradiologic findings in brown snake envenomation: computed tomography demonstration. Australas Radiol 1998; 42(3):248-249.
    25) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
    26) Nowak RM & Macias CG : Anaphylaxis on the other front line: perspectives from the emergency department. Am J Med 2014; 127(1 Suppl):S34-S44.
    27) O'Leary MA , Isbister GK , Schneider JJ , et al: Enzyme immunoassays in brown snake (Pseudonaja spp.) envenoming: detecting venom, antivenom and venom-antivenom complexes. Toxicon 2006; 48(1):4-11.
    28) Product Information: diphenhydramine HCl intravenous injection solution, intramuscular injection solution, diphenhydramine HCl intravenous injection solution, intramuscular injection solution. Hospira, Inc. (per DailyMed), Lake Forest, IL, 2013.
    29) Ryan NM , Kearney RT , Brown SG , et al: Incidence of serum sickness after the administration of Australian snake antivenom (ASP-22). Clin Toxicol (Phila) 2016; 54(1):27-33.
    30) Schapel GJ , Utley D , & Wilson GC : Envenomation by the Australian common brown snake--Pseudonaja (Demansia) textilis textilis. Med J Aust 1971; 1(3):142-144.
    31) Sprivulis P & Jelinek GA: Fatal intracranial haematomas in two patients with Brown snake envenomation. Med J Aust 1995; 162(4):215-216.
    32) Stone R, Seymour J, & Marshall O: Plastic containers and the whole-blood clotting test: glass remains the best option. Trans R Soc Trop Med Hyg 2006; 100(12):1168-1172.
    33) Toxinology Department, Women's & Children's Hospital: CSL antivenom handbook: CSL brown snake antivenom. Toxinology Department, Women's & Children's Hospital. Adelaide, Australia. 2001. Available from URL: http://www.toxinology.com/generic_static_files/cslavh_antivenom_brown.html#use. As accessed 2012-02-16.
    34) Vanden Hoek,TL; Morrison LJ; Shuster M; et al: Part 12: Cardiac Arrest in Special Situations 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. American Heart Association. Dallas, TX. 2010. Available from URL: http://circ.ahajournals.org/cgi/reprint/122/18_suppl_3/S829. As accessed 2010-10-21.
    35) White J & Fassett R : Acute renal failure and coagulopathy after snakebite. Med J Aust 1983; 2(3):142-143.
    36) White J & Williams V: Severe envenomation with convulsion following multiple bites by a common brown snake, Pseudonaja textilis. Aust Paediatr J 1989; 25(2):109-111.
    37) White J , Williams V , & Passehl JH : The five-ringed brown snake, Pseudonaja modesta (Gunther): report of a bite and comments on its venom. Med J Aust 1987; 147(11-12):603-605.
    38) White J: Clinical toxicology of snakebite in australia and new guinea, in Meier J & White J (eds): Handbook of Clinical Toxicology of Animal Venoms and Poisons, CRC Press, Boca Raton, FL, 1995, pp 595-618.
    39) White J: Envenoming and antivenom use is Australia. Toxicol 1998; 36:1483-1492.
    40) Yeung JM, Little M, Murray LM, et al: Antivenom dosing in 35 patients with severe brown snake (Pseudonaja) envenoming in Western Australia over 10 years. Med J Aust 2004; 181(11-12):703-705.