Department of Anaesthesiology, Zealand University Hospital, Køge, Denmark.
Department of Anaesthesiology, Næstved-Slagelse-Ringsted Hospitals, Næstved, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Lancet Rheumatol. 2024 Apr;6(4):e205-e215. doi: 10.1016/S2665-9913(24)00020-1. Epub 2024 Mar 5.
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.
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.
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.
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.
The Novo Nordisk Foundation and Næstved-Slagelse-Ringsted Hospitals' Research Fund.
全髋关节置换术后多模式术后镇痛是推荐的，但药物的最佳组合仍不确定。RECIPE 试验的目的是研究不同组合的对乙酰氨基酚、布洛芬和镇痛佐剂地塞米松在全髋关节置换术后治疗术后疼痛的相对益处和危害。
RECIPE 试验是一项在丹麦九家医院进行的随机、双盲、安慰剂对照试验。计划接受全髋关节置换术的成年人被随机分配（1:1:1:1），使用计算机生成的列表，按部位分层，接受以下组合的口服给药：每 6 小时口服对乙酰氨基酚 1000 毫克、每 6 小时口服布洛芬 400 毫克或单次静脉注射地塞米松 24 毫克：对乙酰氨基酚加布洛芬、布洛芬加地塞米松、对乙酰氨基酚加地塞米松和对乙酰氨基酚加布洛芬加地塞米松。主要结局是 24 小时静脉内吗啡消耗量，在改良意向治疗人群中进行分析，定义为所有接受全髋关节置换术的随机分配参与者。预先确定的最小重要差异为 8 毫克。安全性结局包括 90 天内和 24 小时内的严重和非严重不良事件。该试验在 ClinicalTrials.gov 注册，NCT04123873。
2020 年 3 月 5 日至 2022 年 11 月 15 日期间，我们随机分配了 1060 名参与者，其中 1043 名（589 名[56%]女性和 454 名[44%]男性）被纳入改良意向治疗人群。261 名分配到对乙酰氨基酚加布洛芬组，262 名分配到布洛芬加地塞米松组，262 名分配到对乙酰氨基酚加地塞米松组，258 名分配到对乙酰氨基酚加布洛芬加地塞米松组。在对乙酰氨基酚加布洛芬组，24 小时吗啡消耗量中位数为 24 毫克（IQR 12-38），在对乙酰氨基酚加地塞米松组为 20 毫克（12-32），在布洛芬加地塞米松组为 16 毫克（10-30），在对乙酰氨基酚加布洛芬加地塞米松组为 15 毫克（8-26）。与对乙酰氨基酚加布洛芬组相比，对乙酰氨基酚加布洛芬加地塞米松组的 24 小时吗啡消耗量显著降低（Hodges-Lehmann 中位数差异-6 毫克[99%CI-10 至-3]；p<0·0001）和对乙酰氨基酚加地塞米松组（-4 毫克[-8 至-1]；p=0·0013），但没有任何比较达到 8 毫克的最小重要阈值。与布洛芬加地塞米松组（91[35%]）相比，对乙酰氨基酚加布洛芬加地塞米松组（258 名参与者中的 91 名）中有一人或多人发生不良事件，对乙酰氨基酚加地塞米松组（262 名参与者中的 99 名），对乙酰氨基酚加地塞米松组（262 名参与者中的 103 名）和对乙酰氨基酚加布洛芬组（261 名参与者中的 165 名）。
在接受全髋关节置换术的成年人中，对乙酰氨基酚、布洛芬和地塞米松的组合在手术后 24 小时内吗啡消耗量最低，且不良事件的发生情况最有利，与对乙酰氨基酚加布洛芬相比，严重和非严重不良事件的发生率较低（主要由恶心、呕吐和头晕的差异驱动）。
诺和诺德基金会和 Næstved-Slagelse-Ringsted 医院的研究基金。
