Non-opioid analgesic combinations following total hip arthroplasty (RECIPE): a randomised, placebo-controlled, blinded, multicentre trial.

BACKGROUND: Multimodal postoperative analgesia following total hip arthroplasty is recommended, but the optimal combination of drugs remains uncertain. The aim of the RECIPE trial was to investigate the relative benefit and harm of the different combinations of paracetamol, ibuprofen, and the analgesic adjuvant dexamethasone for treatment of postoperative pain following total hip arthroplasty. METHODS: The RECIPE trial was a randomised, blinded, placebo-controlled trial conducted at nine Danish hospitals. Adults scheduled for total hip arthroplasty were randomly assigned (1:1:1:1) using a computer-generated list with stratification by site to receive combinations of oral paracetamol 1000 mg every 6 h, oral ibuprofen 400 mg every 6 h, or a single-dose of intravenous dexamethasone 24 mg in the following groups: paracetamol plus ibuprofen, ibuprofen plus dexamethasone, paracetamol plus dexamethasone, and paracetamol plus ibuprofen plus dexamethasone. The primary outcome was 24 h intravenous morphine consumption, analysed in a modified intention-to-treat population, defined as all randomly assigned participants who underwent total hip arthroplasty. The predefined minimal important difference was 8 mg. Safety outcomes included serious and non-serious adverse events within 90 days and 24 h. The trial was registered with ClinicalTrials.gov, NCT04123873. FINDINGS: Between March 5, 2020, and Nov 15, 2022, we randomly assigned 1060 participants, of whom 1043 (589 [56%] women and 454 [44%] men) were included in the modified intention-to-treat population. 261 were assigned to paracetamol plus ibuprofen, 262 to ibuprofen plus dexamethasone, 262 to paracetamol plus dexamethasone, and 258 to paracetamol plus ibuprofen plus dexamethasone. Median 24 h morphine consumption was 24 mg (IQR 12-38) in the paracetamol plus ibuprofen group, 20 mg (12-32) in the paracetamol plus dexamethasone group, 16 mg (10-30) in the ibuprofen plus dexamethasone group, and 15 mg (8-26) in the paracetamol plus ibuprofen plus dexamethasone group. The paracetamol plus ibuprofen plus dexamethasone group had a significantly reduced 24 h morphine consumption compared with paracetamol plus ibuprofen (Hodges-Lehmann median difference -6 mg [99% CI -10 to -3]; p<0·0001) and paracetamol plus dexamethasone (-4 mg [-8 to -1]; p=0·0013), however, none of the comparisons showed differences reaching the minimal important threshold of 8 mg. 91 (35%) of 258 participants in the paracetamol plus ibuprofen plus dexamethasone group had one or more adverse events, compared with 99 (38%) of 262 in the ibuprofen plus dexamethasone group, 103 (39%) of 262 in the paracetamol plus dexamethasone group, and 165 (63%) of 261 in the paracetamol plus ibuprofen group. INTERPRETATION: In adults undergoing total hip arthroplasty, a combination of paracetamol, ibuprofen, and dexamethasone had the lowest morphine consumption within 24 h following surgery and the most favourable adverse event profile, with a lower incidence of serious and non-serious adverse events (primarily driven by differences in nausea, vomiting, and dizziness) compared with paracetamol plus ibuprofen. FUNDING: The Novo Nordisk Foundation and Næstved-Slagelse-Ringsted Hospitals' Research Fund.

Ultrasound-guided peripheral nerve blocks for preoperative pain management in hip fractures: a systematic review.

Systematic reviews associate peripheral nerve blocks based on anatomic landmarks or nerve stimulation with reduced pain and need for systemic analgesia in hip fracture patients. We aimed to investigate the effect of ultrasound-guided nerve blocks compared to conventional analgesia for preoperative pain management in hip fractures. Five databases were searched until June 2021 to identify randomised controlled trials. Two independent authors extracted data and assessed risk of bias. Data was pooled for meta-analysis and quality of evidence was evaluated using Grades of Recommendation Assessment, Development and Evaluation (GRADE). We included 12 trials (976 participants) comparing ultrasound-guided nerve blocks to conventional systemic analgesia. In favour of ultrasound, pain measured closest to two hours after block placement decreased with a mean difference of -2.26 (VAS 0 to 10); (p < 0.001) 95% CI [-2.97 to -1.55]. In favour of ultrasound, preoperative analgesic usage of iv. morphine equivalents in milligram decreased with a mean difference of -5.34 (p=0.003) 95% CI [-8.11 to -2.58]. Time from admission until surgery ranged from six hours to more than three days. Further, ultrasound-guided nerve blocks may be associated with a lower frequency of delirium: risk ratio 0.6 (p = 0.03) 95% CI [0.38 to 0.94], fewer serious adverse events: risk ratio 0.33 (p = 0.006) 95% CI [0.15 to 0.73] and higher patient satisfaction: mean difference 25.9 (VAS 0 to 100) (p < 0.001) 95% CI [19.74 to 32.07]. However, the quality of evidence was judged low or very low. In conclusion, despite low quality of evidence, ultrasound-guided blocks were associated with benefits compared to conventional systemic analgesia.