Hiller Arja, Meretoja Olli A, Korpela Reijo, Piiparinen Satu, Taivainen Tomi
Department of Anesthesia, Hospital for Children and Adolescents, University of Helsinki, Finland.
Anesth Analg. 2006 May;102(5):1365-71. doi: 10.1213/01.ane.0000204278.71548.bf.
The combined use of acetaminophen and a nonsteroidal antiinflammatory drug has been shown to provide better postoperative analgesia than either drug alone in several adult studies. However, there are no pediatric studies analyzing similar effects when the currently recommended doses of acetaminophen are used. In a double-blind, placebo-controlled design we randomized 120 children, aged 1-9 yr, undergoing orthopedic or soft tissue surgery, into 3 groups to receive either acetaminophen 60 mg/kg rectally and 40 mg/kg orally, ketoprofen 2 mg/kg IV twice, or the combination of the active drugs. The first drug doses were given at anesthetic induction and the second doses 8 h thereafter. During anesthesia all children received sevoflurane and a continuous infusion of remifentanil. Postoperative pain was evaluated by the behavioral objective pain scale (0-9) for 24 h. The rescue medication was morphine 0.05 mg/kg IV. The primary outcome variable was morphine consumption. For statistical analysis, analysis of variance, chi2 test and Kaplan-Meier survival analysis were used. Morphine requirement was less in the combination than in the acetaminophen group both in the postanesthesia care unit (2.5 +/- 1.7 versus 3.9 +/- 2.1 morphine doses) and during the 24-h postoperative follow-up (4.1 +/- 2.5 versus 5.9 +/- 2.9 morphine doses) (P < 0.05). No differences existed between the ketoprofen and the acetaminophen groups. The objective pain scale scores were lowest in the combination group both in the postanesthesia care unit and in the postoperative ward (P < 0.05). When children were divided based on their surgery, opioid requirement and pain scores were less in the combination than in the parent drug groups only after orthopedic surgery. The combination of acetaminophen 100 mg/kg and ketoprofen 4 mg/kg in a day provided better analgesia and lower pain scores after orthopedic, but not soft tissue, surgery in children.
在多项针对成年人的研究中，已表明对乙酰氨基酚与非甾体抗炎药联合使用，比单独使用任何一种药物都能提供更好的术后镇痛效果。然而，尚无儿科研究分析使用当前推荐剂量对乙酰氨基酚时的类似效果。在一项双盲、安慰剂对照设计中，我们将120名年龄在1至9岁、接受骨科或软组织手术的儿童随机分为3组，分别接受直肠给予对乙酰氨基酚60mg/kg及口服40mg/kg、静脉注射酮洛芬2mg/kg两次，或两种活性药物联合使用。首次给药在麻醉诱导时进行，第二次给药在8小时后。麻醉期间，所有儿童均接受七氟醚和瑞芬太尼持续输注。术后24小时通过行为客观疼痛量表（0 - 9分）评估疼痛情况。急救药物为静脉注射吗啡0.05mg/kg。主要结局变量为吗啡消耗量。统计分析采用方差分析、卡方检验和Kaplan-Meier生存分析。在麻醉后护理单元（对乙酰氨基酚组为3.9±2.1剂吗啡，联合用药组为2.5±1.7剂吗啡）以及术后24小时随访期间（对乙酰氨基酚组为5.9±2.9剂吗啡，联合用药组为4.1±2.5剂吗啡），联合用药组的吗啡需求量均低于对乙酰氨基酚组（P < 0.05）。酮洛芬组与对乙酰氨基酚组之间无差异。联合用药组在麻醉后护理单元和术后病房的客观疼痛量表评分均最低（P < 0.05）。根据手术类型对儿童进行分组后，仅在骨科手术后，联合用药组的阿片类药物需求量和疼痛评分低于单一药物组。儿童接受骨科手术而非软组织手术后，每日使用100mg/kg对乙酰氨基酚与4mg/kg酮洛芬联合用药可提供更好的镇痛效果并降低疼痛评分。
