Bites Sept 2014 Epidemiology 1000-300 snake bites/ye, 1-4 deaths/yr in Australia. 5-10% envenomation rate Most deaths due to haematological problems Clinical envenoming Local effects (pain, swelling, bruising) Systemic symptoms Major toxin syndromes Venom-induced consumption coagulopathy (VICC) Neurotoxicity Myotoxicity Clinical examination Bite site: fang marks, bruising, local necrosis, draining lymph nodes Neurological: cranial nerves (ptosis, ophthalmoplegia, bulbar weakness), limb weakness, resp muscle weakness Haematological: evidence of abnormal coagulation (bleeding from bite site, cannula site, oral cavity, occult sites GI/GU/intracranial) Increased risk of severity 1. LOC 2. Multiple bites 3. Alcohol 4. Fast onset of symptoms 5. Brown worse than Tiger Investigations Coagulation studies INR and aptt Fibrinogen and D-dimer differentiate between VICC and anticoagulant effect D-dimer 100-1000x increase Point of care INR devices give false negatives FBC and film Thrombocytopenia and red cell fragmentation = thrombotic microangiopathy Platelets fall within 24 hrs Non-specific leucocytosis and lymphopenia in systemic envenoming Biochem Serial measurements to assess renal function Elevated CK in myotoxicity but test may lag symptoms by up to 24 hrs Elevated LDH = thrombotic microangiopathy Venom Detection Kit (SVDK) Result must not be used to diagnose or exclude envenoming High rates of inaccuracy (>10% wrong identity, >25% false negatives) Assists in antivenom selection only once diagnosis of envenoming made Results must be considered with local snake geographical distributions Venom Detection Kit (SVDK) used to determine which antivenom, not if envenomed. Take swab early but don t use SVDK unless signs/symptoms of envenomation www.shakem.co.nz 1
Clinical syndromes in snake bite Sudden collapse Collapse or syncope occurring within an hour of the bite Collapse is associated with hypotension and loss of consciousness Spontaneous recovery usually occurs within minutes Minority of patients (about 5%) have a cardiac arrest or seizure Venom-induced consumption coagulopathy (VICC) Activation of the clotting pathway by prothrombin activator toxins and consumption of clotting factors (fibrinogen, factor V and factor VIII) lead to a consumptive coagulopathy Procoagulant (like DIC) Rapid onset 15-60mins, recovery 12-18hrs INR is high or unrecordable and aptt is prolonged Fibrinogen level is low or undetectable and D-dimer level is very high Complete or severe VICC is defined as: Undetectable fibrinogen, INR > 3.0 (most often unrecordable), abnormal aptt, very high D-dimer Partial VICC (less severe changes) is defined as: Low but detectable fibrinogen level (< 1.5 g/l) and INR < 3.0 Neurotoxicity A descending flaccid paralysis that classically first involves the eye muscles (ptosis, diplopia and blurred vision), followed by bulbar muscles, respiratory muscle/limb paralysis Myotoxicity Local or generalised myalgia and/or muscle tenderness CK level is usually normal (within the laboratory s reference interval) on admission and rapidly rises over 24 48 hours (1000 U/L in mild cases to > 100 000 U/L in severe cases) Potassium level may be elevated (> 5.0 mmol/l), renal impairment may develop Anticoagulant coagulopathy Provides a good marker of envenoming by all black snakes, including mulga snakes aptt is moderately abnormal (1.5 2.5 laboratory s reference interval), with or without mild elevation of INR (> 1.3) D-dimer and fibrinogen levels are generally normal (D-dimer < 1.0 mg/l and fibrinogen > 1.5 g/l [or > 2.0 g/l in some laboratories]) Thrombotic microangiopathy Presence of fragmented red blood cells on blood film (microangiopathic haemolytic anaemia), thrombocytopenia and a rising creatinine level (> 120 mmol/l), which may lead to acute renal failure requiring dialysis Systemic symptoms Non-specific systemic symptoms: N/V, abdominal pain, diarrhoea, diaphoresis and headache First Aid Pressure bandage with immobilisation (PBI) wide elastic bandage Mark site of bite allows window to be cut Management A: keep patent B: 02, be aware weakness affecting resp muscles, may req BVM C: Monitor/shock/IV/fluid (generous iv hydration to prevent ARF in rhabdo) D: PRESSURE IMMOBILISATION, GCS<8?ETT Don t remove bandage ADT www.shakem.co.nz 2
Diagnostic Process - Need hospital with staff able to assess and treat anaphylaxis, lab for INR 24hrs, AV stocks 1. Establish clinical/lab evidence of envenoming (bloods and neurological exam) 2. Determine most likely snake 3. Cut hole in PIB and swab 4. If any concerns re envenoming give most appropriate antivenom 5. If well and labs normal, remove PIB in critical care area 6. If deteriorates, replace PIB 7. If no symptoms 1 hour after PIB removal admit for observation 8. Repeat bloods and neuro exam at 1hr/6hr/12hr post bite 9. If at any time any suggestion of envenomation give antivenom 10. Observe all patients for at least 12 hours Antivenom have full resus facilities available safe in children, pregnancy and lactation usually given IM; if given IV, dilute in 500ml N saline and give over 20-30mins (can stop if allergy) when discharge, give advice Re: serum sickness Polyvalent contains brown, black, tiger, taipan and death adder Absolute and Relative Indications for Antivenom Absolute indications Reported sudden collapse, seizure or cardiac arrest Abnormal INR Any evidence of paralysis, with ptosis and/or ophthalmoplegia being the earliest signs Relative indications Systemic symptoms (vomiting, headache, abdominal pain, diarrhoea) Leukocytosis Abnormal aptt CK > 1000 U/L Risks of antivenom Anaphylaxis Serum sickness Therefore give in critical area, prepare to treat for anaphylaxis (2 lines) Premedication with steroids etc not recommended Hypersensitivity reactions in 20-25% patients, more common with larger-volume antivenoms Severe anaphylaxis in 3-5% patients Serum sickness in ~1/3 patients: flu-like symptoms 4-14 days post administration Treat with prednisone 25mg OD for 5-7/7 Determining appropriate antivenom Local knowledge of snakes in area experts/snake handlers Observation of specific clinical syndromes Most parts south/central-eastern Australia one vial of each of brown and tiger snakes Smaller volume and cheaper than polyvalent antivenom, lower risk anaphylaxis Black snake, death adder and taipan rare use polyvalent antivenom One vial for both children and adults, no evidence to support further doses Black, Death Adder, Polyvalent AV - 1 ampule Brown, Taipan, Tiger AV - 2 ampules www.shakem.co.nz 3
Management of immediate reactions to antivenom 1. Stop antivenom infusion. Many reactions will resolve, and infusion then restarted at slower rate. 2. Lie patient flat, commence high-flow oxygen, support airway and ventilation if required. 3. For hypotension, give rapid infusion of 1 L normal saline (20 ml/kg in children). 4. For hypotension, hypoxaemia, wheeze or upper airway obstruction, give intramuscular adrenaline 5. Consider a cautious intravenous infusion of adrenaline avoid blood pressure surges. Patients with envenoming may be severely coagulopathic, and high blood pressure may cause or worsen intracerebral haemorrhage. Some patients can have exaggerated, hypertensive responses to intramuscular bolus adrenaline, especially to second doses. Use 1 mg in 100 ml by infusion pump: start at 0.5 ml/kg/h and titrate according to response; monitor blood pressure every 3 5 min (using the arm opposite to the infusion). Be aware that as the reaction resolves, adrenaline requirements will fall, BP will rise and the infusion rate will need to be rapidly reduced. 6. For bronchospasm, consider nebulised salbutamol. 7. For upper airway obstruction, consider nebulised adrenaline. 8. Seek further advice from a National Poisons Information Centre consultant. Other management Role of clotting factor replacement in VICC contentious FFP still given after antivenom in active bleeding/life threatening envenoming Risk of rhabdomyolysis and late neuromuscular paralysis Local Coagulopathy Neurotoxicity Myotoxicity Nephrotoxicity Life threat Sx Brown No Early (pro-c, low plt) ++ Rare No Yes Hypotension, VICC Tiger Mild Early (pro-c, low plt) Late (pre-s) Late Yes Hypotension, VICC, late paralysis + Mulga Marked Mild (anti-c) Mild Yes + Yes None Taipan Mild Early (pro-c) + Early (pre-s) + Early (mild) Yes Hypotension, VICC, paralysis (early), seizures Death Maybe No Early (post-s) + Sea No No Early Yes Yes No No Desc flaccid paralysis, hypotension www.shakem.co.nz 4
Distribution Local Symptoms Systemic Symptoms Treatment Brown Early coag Nephro LIFE THREAT Tiger Early coag Late neuro Late myo Late renal LIFE THREAT Mainland Australia Inurban areas Most common cause of severe envenoming and fatality (causes 60% snake deaths; 70% bites) Many bites don t result in systemic envenomation SE Australia Wet areas 2 nd most common cause of snake bite death (25% snake deaths) Most bites result in systemic envenomation Trivial local features Ooze at bite site Mild local redness, swelling +/- bruising over 3hrs Pain in 50% Rapid onset symptoms early collapse; maybe death <1hr due to cardiotoxicity Non-specific (N+V+H+AP), tender regional lymphadenopathy Early severe coagulopathy (pro-c, decr plt, decr FDP, VICC) may occur despite minimal Sx; risk of major haemorrhage) Thrombotic microangiopathy (10%) decr plt ARF (lasting 2-8/52) haemolytic anaemia Maybe renal failure (direct nephrotoxic effect) Rhabdo and neurotox rare May be early collapse / death due to cardiotoxicity Non-specific (as above), tender regional lymphadenopathy Early coagulopathy (pro-c, decr plt, VICC) Gradual onset neurotoxicity (pres) (over 1-2hrs) Late severe myotoxicity and renal failure (over hrs) Brown AV Hypotension VICC -uncontrolled haemorrhage FFP if actively bleeding Tiger AV VICC with uncontrolled haemorrhage, paralysis with resp failure, hypotension Black (Mulga) Black Taipan N Australia Dry areas Marked local pain redness, swelling +/- bruising over 3hrs Tender regional LN s (60%) Investigation: incr INR, decr fib, incr D-dimer, incr FDP Non-specific - headache, nausea, abdo pain, vomiting Myotoxicity (onset in 6hrs, lasts days, incr CK) and renal failure Coagulopathy (mild; anti-c, incr APTT and INR) usually not clinically significant Neurotoxicity (mild, occurs in 15%) If refractory GI Sx or rhabdo (CK >5000) PIB - Yes Black AV SE Australian coast Local pain Rare; minor myolysis only Rarely requires AV Tiger AV N and E Australia Dry areas 10% deaths Mild local redness, swelling +/- bruising over 3hrs Rapid severe systemic symptoms: most deadly snake in the world Non-specific Collapse Early Coagulopathy (pro-c, VICC) Early neurotoxicity (paralysis 1-2hrs, seizures) Early mild myotoxicity Life threatening Taipan AV Hypotension Paralysis VICC Seizures Death Adder All Australia Nocturnal 5% deaths Mod-severe local pain; little local signs Early neurotoxicity progressive symmetrical descending flaccid paralysis within 6hrs resp arrest Risk of delayed symptoms Life threatening Death Adder AV 24hrs www.shakem.co.nz 5