The ‘2G’ study: High dose oral paracetamol in emergency department patients - A Pilot Randomised Control Trial

Background: Paracetamol is a relatively safe & common analgesic used for many types of pain in the emergency department (ED). Current dosing guidelines for adult patients recommend a maximum dose of 1000mg four times a day, regardless of administration route. Data suggests that quicker and more effective analgesia can be achieved with either intravenous administration or a higher oral dose, such as 2000mg. This effect has been correlated with higher serum concentrations of paracetamol that reach a therapeutic range ( > 10mg/L) more rapidly. There is also extensive data indicating that in patients with normal metabolism and liver function, a single dose of 2000mg does not risk paracetamol toxicity, or any other adverse outcome. Given the above information, we propose that a loading dose of 2000mg paracetamol may provide more effective analgesia than the standard 1000mg dose in treating acute pain. This could potentially have a wide variety of benefits, including improved patient experience, reduced suffering from pain, reduced length of hospital stay and a lower reliance on hazardous opioid medications, such as oxycodone. Methods/Design: We propose a prospective, randomised, controlled and double-blinded trial of adults aged > 18 with acute moderate to severe pain and no contraindications to oral paracetamol administration. Standard pain scores (0-10 scale), adverse effects and need for rescue analgesia will be measured at 20-minute intervals for one hour post ingestion. Medication packets containing either: (i) 2000mg paracetamol (4 tablets total) OR (ii) 1000mg paracetamol, 5mg oxycodone and one sugar tablet (4 tablets total) will be prepared by pharmacy and placed in the drug cupboard with non-descript labels. These medication packets will be provided to patients by medical or nursing staff. The primary outcome will be the median improvement in pain rating after 1 hour, with need for additional analgesia and associated side effects (e.g. nausea) as secondary measures. The sample size required for a statistically significant outcome will be determined by a literature review. Discussion: This trial will evaluate the efficacy and safety of a loading dose of oral paracetamol, which we propose to be a safe and more effective analgesic option than standard dosing with opioid supplementation. If there is a significant improvement in pain scores, and no adverse effects are detected, this could potentially allow for quicker, easier and cheaper analgesia in a wide array of ED populations. This would in turn reduce dependence on opioid analgesia and improve patient care.