A randomised controlled trial on the efficacy of activated charcoal in lowering blood paracetamol concentrations in paracetamol overdose patients.

INTERVENTION: 1. Study Setting: Emergency Treatment Unit and the Medical Wards of Teaching Hospital, Anuradhapura. 2. Method of Randomisation: Simple randomization. 3. Activated Charcoal 50g dissolved in 100ml water orally administered (by the patient him/her self) under the supervision of a clinical research assistant (MBBS or BSc nursing graduate) on presentation(only if less than 8h from ingestion).Activated charcoal is not given for paracetamol poisoning in the study setting as a standard practice. Only the intervention group will receive activated charcoal. Controls will receive the standard treatment in the ward setting. 4. All the patients in both arms will receive standard N‐Acetylcystine (NAC) regimen practiced in the Teaching Hospital, Anuradhapura. 5. This is an open‐labelled study. CONDITION: Paracetamol overdose PRIMARY OUTCOME: The primary outcome will be a clinically significant reduction in the Area Under Curve (AUC) of in patients receiving charcoal compared to those not receiving charcoal. Area Under the Curve (AUC) = [Dose] * [Fraction Absorbed (F)] / [Clearance (CL)]. The AUC will be estimated by first modelling the data using population analysis techniques to determine the best fit to all of the data for patients taking paracetamol in the trial. Once a final model is established this will be used to estimate the individual predicted AUC for each patient which will then be compared between those receiving and not receiving charcoal. A 20% reduction in the AUC/dose will be regarded as clinically significant based on previous pharmacokinetic‐pharmacodynamic studies [The blood samples will be collected in all patients (both groups) on following time points after the ingestion of paracetamol.; 1. Time of admission; 2. 4hours; 3. 8hours; 4. 12hours; 5. 24hours; 6. 48hours; 7. 72hours; 8. 96hours; 9. 120hours; AUC will be calculated based on the paracetamol concentration data of all the blood samples, after the trial has finished.; ]; SECONDARY OUTCOME: (1) Reduction of the apparent half‐life of elimination (t1/2?) in patients receiving charcoal compared to those not receiving charcoal.The decline of the Paracetamol plasma concentration is not due to elimination alone. Other factors such as absorption rate or distribution rate influence the declining of plasma concentration. In such conditions, the observed half‐life is not a true elimination half‐life hence called apparent half‐life of elimination (time taken for paracetamol concentration to become 50% of the initial concentration. ; ; (2) Proportion of patients with a ALT >150IU/L after 24 hours of ingestion. ; ; (3) Proportion of patients who have their on‐admission ALT values doubled by 24 hours. ; ; (4) Proportion of patients with an ALT >1000IU/L (hepatotoxicity) ; ; (5) Proportion of patients with adverse effects of charcoal such as vomiting and aspiration pneumonitis. ; ; (6) Reduction in other biomarkers of hepatotoxicity at 24 hours (miRNA‐122 and INR at 24h.) [(1) 4,8,12,24,48,72,96,120 hours post ingestion ; ; (2) 24 hours post ingestion ; ; (3) 24 hours post ingestion ; ; (4) 48 hours post ingestion ; ; (5) 24 hours post ingestion ; ; (6) 24 hours post ingestion]; INCLUSION CRITERIA: All patients (>16y) with paracetamol overdoses (>5g) presenting within 8h of ingestion.