Acetaminophen (Paracetamol) or Opioid Analgesia Added to Ibuprofen for Children's Musculoskeletal Injury: Two Randomized Clinical Trials.

However, two-thirds of children experience inadequate pain relief with ibuprofen monotherapy, and the efficacy of additive medications for moderate to severe musculoskeletal pain is unclear.

然而，三分之二的儿童在使用布洛芬单药治疗时经历不充分的疼痛缓解，且对于中度至重度肌肉骨骼疼痛，添加药物的疗效尚不明确。

Background

To determine whether treatment with an opioid (hydromorphone) plus ibuprofen or nonopioid (acetaminophen [paracetamol]) plus ibuprofen decreased pain scores compared with ibuprofen alone.

确定使用阿片类药物（氢吗啡酮）加布洛芬或非阿片类药物（对乙酰氨基酚[扑热息痛]）加布洛芬是否比单独使用布洛芬更能降低疼痛评分。

DESIGN, SETTING, AND PARTICIPANTS: Two randomized, double-masked, placebo-controlledtrials were conducted from April 2019 to March 2023 in 6 university-affiliated, tertiary care Canadian pediatric emergency departments.

设计、环境和参与者：从2019年4月到2023年3月，在6个加拿大大学附属的三级儿科急诊部门进行了两项随机、双盲、安慰剂对照试验。

Children aged 6 to 17 years presenting with a nonoperative acute limb injury (<24 hours) and a verbal numerical rating scale (vNRS) pain score of 5 or more out of 10 were enrolled.

年龄在6至17岁之间，出现非手术性急性肢体损伤（<24小时）且口头数字评分（vNRS）疼痛评分为10分中的5分或以上者被纳入研究。

Date of final follow-up was March 22, 2023.

最终随访日期为2023年3月22日。

Methods

The opioid trial randomized participants to a single oral dose of ibuprofen plus hydromorphone, ibuprofen plus acetaminophen, or ibuprofen alone.

阿片类药物试验将参与者随机分配到单次口服剂量的布洛芬加氢吗啡酮、布洛芬加对乙酰氨基酚或仅布洛芬的组别。

The nonopioid trial randomized participants to a single oral dose of ibuprofen plus acetaminophen or ibuprofen alone.

非阿片类药物试验将参与者随机分配到单次口服剂量的布洛芬加对乙酰氨基酚或仅布洛芬的组别。

In all groups, ibuprofen was dosed at 10 mg/kg (maximum, 600 mg).

在所有组别中，布洛芬的剂量为10 mg/kg（最大剂量，600 mg）。

The acetaminophen dose was 15 mg/kg (maximum, 1000 mg), and the hydromorphone dose was 0.05 mg/kg (maximum, 5 mg).

对乙酰氨基酚的剂量为15 mg/kg（最大剂量，1000 mg），而氢吗啡酮的剂量为0.05 mg/kg（最大剂量，5 mg）。

main_outcomes_and_measures

The primary efficacy outcome was self-reported vNRS pain score at 60 minutes post medication administration (score range, 0 [no pain] to 10 [worst pain]; minimal clinically important difference, 1.5).

主要疗效结果是用药后60分钟患者自报的视觉模拟疼痛评分（评分范围，0 [无痛]至10 [最痛]；最小临床重要差异，1.5）。

The primary safety end point was the proportion of children with any adverse eventrelated to study drug administration.

主要安全性终点是与研究药物使用相关的任何不良事件发生比例的儿童。

Results

A total of 8098 children were screened for eligibility; 699 were randomized and 653 were included in the efficacy analyses.

共有8098名儿童接受了资格筛查；699名被随机分配，653名被纳入疗效分析。

The opioid trial included 249 children: 110 randomized to ibuprofen plus hydromorphone, 70 to ibuprofen plus acetaminophen, and 69 to ibuprofen alone.

阿片类药物试验包括249名儿童：110名随机分配至布洛芬加氢吗啡酮组，70名至布洛芬加对乙酰氨基酚组，69名至单独布洛芬组。

The nonopioid trial included 450 children: 225 randomized to a single oral dose of ibuprofen plus acetaminophen and 225 randomized to ibuprofen alone.

非阿片类试验包括450名儿童：其中225名随机接受单剂口服布洛芬加对乙酰氨基酚，另外225名随机接受单独布洛芬。

The mean (SD) age of children in the 2 trials was 11.5 (3.5) years and 47.4% were female.

两项试验中儿童的平均年龄（标准差）为11.5（3.5）岁，女性占47.4%。

The mean (SD) vNRS score at recruitment was 6.4 (1.8).

招募时的平均（标准差）视觉模拟疼痛评分（vNRS）为6.4（1.8）分。

In pooled analyses, mean (SD) vNRS scores 60 minutes after drug administration were 4.8 (2.6) in the ibuprofen plus hydromorphone group, 4.6 (2.4) in the ibuprofen plus acetaminophen group, and 4.6 (2.3) in the ibuprofen alone group (P = .78).

在汇总分析中，药物给药后60分钟，布洛芬联合氢吗啡酮组的平均（标准差）视觉模拟疼痛评分（vNRS）为4.8（2.6），布洛芬联合对乙酰氨基酚组为4.6（2.4），仅布洛芬组为4.6（2.3）（P = .78）。

Any adverse eventoccurred at higher rates in the ibuprofen plus hydromorphone group (28.2%) compared with the ibuprofen plus acetaminophen (6.1%) or ibuprofen alone groups (5.8%).

在使用布洛芬加氢吗啡酮组中，任何不良事件的发生率（28.2%）均高于布洛芬加对乙酰氨基酚组（6.1%）或单独使用布洛芬组（5.8%）。

No serious adverse events occurred.

没有发生严重不良事件。

conclusions_and_relevance

For children with acute nonoperative musculoskeletal injury, pain scores at 60 minutes after drug administration did not improve with ibuprofen plus acetaminophen or ibuprofen plus hydromorphone compared with ibuprofen alone.

对于急性非手术性肌肉骨骼损伤的儿童，在药物给药后60分钟，使用布洛芬加对乙酰氨基酚或布洛芬加氢吗啡酮的疼痛评分与单独使用布洛芬相比没有改善。

Adverse events were 4-fold more frequent with hydromorphone.

与布洛芬相比，使用氢吗啡酮的不良事件发生率高出4倍。

trial_registration

Clinicaltrials.gov Identifier: NCT03767933.

临床试验注册号：NCT03767933。