To determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0–3 years after cardiac surgery with cardiopulmonary bypass. Multi-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016–July 2020. Children aged 0–3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%. In total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0–432.5) mcg/kg vs 692.6 (IQR, 532.7–856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion − 3.1% (95% CI − 16.6–10.3%). In children aged 0–3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic. Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20.

中文翻译：

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间歇性静脉注射扑热息痛与连续吗啡治疗接受心胸外科手术的婴儿：一项多中心随机对照试验

确定间歇性静脉注射（IV）扑热息痛作为主要镇痛药是否会显着减少体外循环心脏手术后 0-3 岁儿童的吗啡消耗量。在荷兰和比利时的四个三级儿科重症监护病房 (PICU) 进行的多中心、随机、双盲对照试验。纳入期； 2016 年 3 月至 2020 年 7 月。0-3 岁接受体外循环心脏手术的儿童符合资格。手术结束时给予负荷剂量 100 mcg/kg 吗啡后，患者被随机分为连续吗啡或间歇性静脉注射扑热息痛作为主要镇痛药。如果数字评定量表（NRS）疼痛评分超过预定的截止值，则给予救援吗啡。主要结果是术后第一个 48 小时内经体重调整的中位累积吗啡剂量（以 mcg/kg 为单位）。为了比较组间主要结果，使用了按中心分层的非参数 Van Elteren 检验。为了比较两组之间一项或多项 NRS 疼痛评分为 4 分或更高的患者比例，使用 20% 的非劣效性界限进行非劣效性分析。总共筛查了828人，最终纳入208名患者； 315名患者的父母没有给予同意，305名患者因各种原因被排除在外。入组的 208 名儿童中有 14 名在研究药物开始前退出研究，留下 194 名患者进行最终分析。 102 名患者接受间歇性静脉注射扑热息痛，106 名患者接受连续吗啡治疗。静脉注射扑热息痛组术后前 48 小时体重调整累积吗啡消耗量中位值比吗啡组低 5 倍 (79%)（中位值 145.0 (IQR, 115.0–432.5) mcg/kg vs 692.6 (IQR, 115.0–432.5) mcg/kg IQR，532.7–856.1) 微克/千克；P < 0.001)。各组之间的救援吗啡消耗量相似 (p = 0.38)。证明静脉注射扑热息痛在 NRS 疼痛评分方面具有非劣效性；比例差异 - 3.1% (95% CI - 16.6–10.3%)。在接受心脏手术的 0-3 岁儿童中，间歇性静脉注射扑热息痛可将手术后 48 小时内经体重调整的累积吗啡消耗量中位数降低 79%，且疼痛缓解效果相同，表明静脉注射对乙酰氨基酚作为主要镇痛药的效果相当。试验注册 ClinicalTrials.gov，标识符：NCT05853263； EudraCT 编号：2015-001835-20。