Liver cell injury in paracetamol overdose
Conditions
Interventions
Patients will be randomized 1:1:1 to the three treatments using the randomisation option in the REDCap software.
Randomisation will be done at the place where patient will be treated (in the emergenc
Sponsors
South Asian Clinical Toxicology Research Collaboration (SACTRC)
Eligibility
Inclusion criteria
Inclusion criteria: Patients >16 years of age with acute paracetamol poisoning. i.e who present within 10 hours of ingestion and whose plasma paracetamol levels falls above Prescott normogram line.
Exclusion criteria
Exclusion criteria: 1. Patients presenting more than 10 hours after poisoning. 2. Patients who have already received an antidote (possible in other hospitals prior to transfer). 3. Patients who have received charcoal (which would interfere with oral antidotes). 4. Patients under the age of 16. 5. Patients who are unable to give the amount of paracetamol ingested and the time of ingestion 6. Patients who are institutionalized for any mental health condition. 7. Patients with known cognitive impairment (e.g. dementia). 8. Patients with an unrelated life threatening illness (e.g. terminal cancer). 9. Patients who are known to be pregnant or breast feeding. (This is simply a practical decision. There are no known risks these patients will be subjected to by being treated with these antidotes) 10. Patients who have had a paracetamol overdose in the previous 4 weeks or have taken a significant dose of any other toxic substance in addition to paracetamol. 11. Patients who are on warfarin. 12. Patients who have taken a staggered dose of paracetamol (over more than a 2-hour period).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rise of ALT to more than 50% of the baseline value within 24 hours. [On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.] | — |
Secondary
| Measure | Time frame |
|---|---|
| ALT above 1000 IU/L at any time point [On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.] INR > 2 at any time point [On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.] miR122 levels. [Patients with ALT>150U/L at any time during their admission. The time points at which miR-122 levels are measured will be decided post-hoc. Paracetamol sulphate, paracetamol glucuronide and paracetamol mercaptopuric acid levels will be measured in the urine collected during the first 24 hours.] APAP-adduct concentrations: PPA – Paracetamol Protein Adduct Paracetamol cysteine (APAP – CYS) [On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.] Length of hospital stay and number of days spent in the Intensive Care Unit. [At discharge] Adverse antidote effects including nausea, vomiting, rash, hypotension, bronchospasm. [On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.] Proportion with full adherence to standard regimen in each arm for 24 hours [At 24 hours of initiating treatment ] Acute kidney injury: Serum creatinine (AKIN criteria) [On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.] Severe acute liver injury: ALT level of above 150U/L or ALT level of above 50U/L when clinical symptoms and signs of hepatotoxicity are present. The clinical symptoms and signs of hepatotoxicity which would be used in this regard are:- (i) Liver tenderness (ii) Late onset (>24 hours) vomiting (iii) Signs of liver failure (Jaundice etc.) [On admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge.] Death [Any time point.] | — |
Countries
Sri Lanka
Contacts
Public ContactProf.Indika Bandara Gawarammana
Professor in Medicine
Outcome results
None listed