Randomised controlled trial investigating the effects of early snake antivenom administration

INTERVENTION: a)tiger snake and brown snake antivenom b)1 vial of tiger snake antivenom (3000 units), 1 vial of brown snake antivenom (1000 units) c) Administered once d) Intravenous administration e)Administration of snake antivenom will be as soon as patient presents to hospital and consents to participation CONDITION: major bleeding Myotoxicity neurotoxicity renal impairment Snake envenoming PRIMARY OUTCOME: Proportion of patients with significant envenomation defined as the development of one or more of the following effects (composite outcome): i) Myotoxicity defined as a peak CK greater than 1000U/L and local or systemic myalgia ii) Neurotoxicity: paralysis of 2 or more muscle groups (extra‐ocular + bulbar) or respiratory paralysis iii) Major bleeding: defined by the International Society on Thrombosis and Haemostasis as fatal bleeding, symptomatic bleeding in a critical organ (e.g. intracranial haemorrhage) or bleeding resulting in a drop of haemoglobin >20g/L or requiring blood transfusion iv) Acute kidney failure injury: defined by the RIFLE criteria (creatinine increasing by 2x or more; <0.5ml/kg/hr urine output over 12h) SECONDARY OUTCOME: Death ocurring prior to hospital disharge Early systemic hypersensitivity reactions graded as 1) skin only reaction i.e. generalised itch, erythema, uticaria or angloedema 2)Anaphlaxis: any of No 1 skin reactions and at least one reaction from either respiratory (wheeze, throat tightness, hypoxemia) or cardiovascular systems (new onset of absolute hypotension SBP<90mmHg) 3)Severe Anaphylaxis: Severe if hypotension or hypoxia was observed during above reactions. ; Reactions assessed thorugh clinical observation by attending physician. Proportion with acute kidney injury. Assessed by: the RIFLE criteria (creatinine increasing by 2x or more; <0.5ml/kg/hr urine output over 12h). ; Proportion with major bleeding. Assessed by: defined by the International Society on Thrombosis and Haemostasis as fatal bleeding, symptomatic bleeding in a critical organ (e.g. intracranial haemorrhage) or bleeding resulting in a drop in haemoglobin >20g/L or requiring blood transfusion. Proportion with myotoxicity. Myotoxicity is assessed through symptoms and blood test results. Proportion with neurotoxicity. Assessed by: paralysis of 2 or more muscle groups (extra‐ocular + bulbar) or respiratory paralysis. Time from randomisation to hospital discharge (hours) Time to recovery of the (International Normalised Ratio) INR to less than 2 INCLUSION CRITERIA: 1. Presents to hospital within 2 hours of snakebite 2. Definite sighting of a snake by the patient (or parent/carer of child, age >2years) and a confirmed bite. 3. Early non‐specific systemic symptoms suggesting envenoming: EITHER: collapse OR two of vomiting, headache, diarrhoea or abdominal pain.