Abstract：
Intravenous paracetamol (acetaminophen) has not been licensed for analgesia in preterm neonates or infants < 2 years, respectively, in Europe and the United States. A variety of dosing regimens is therefore used off-label. Because evidence supports the use of the same target mean steady state paracetamol concentration (Cssmean, 9-11 mg/L) for pain relief in neonates compared to older children and adults, dosing regimens based on this Cssmean were evaluated in a two-step approach.
First, a systematic search was performed to provide pharmacokinetic (PK)-based dosing guidelines for pain in neonates (with subsequent searches on safety in these papers). Second, concentration-time profiles based on these dosing guidelines were generated to provide a dosing advice for paracetamol to treat neonatal pain.
Of 2334 potentially relevant articles, 9 studies were included. For typical term neonates, dosages specified in packaging (labels) resulted in Cssmean below target (7.65 mg/L), while dosages from investigator-initiated studies resulted in either a Cssmean above (15.31), or around the target (11.78 and 10.21) for (pre)term neonates >32 weeks. Only one study suggested a dosing resulting in a tailored concentration (8.7) in preterm neonates <32 weeks.
A loading dose 20 mg/kg, followed by 10 mg/kg/6h is recommended for 32-44 weeks\' neonates, which is supported by short-term safety. For neonates < 32 weeks, a loading dose of 12 mg/kg and a maintenance dose of 6mg/kg/6h seems to lead to the target Cssmean, though additional clinical studies are needed to support its safety.
First, a systematic search was performed to provide pharmacokinetic (PK)-based dosing guidelines for pain in neonates (with subsequent searches on safety in these papers). Second, concentration-time profiles based on these dosing guidelines were generated to provide a dosing advice for paracetamol to treat neonatal pain.
Of 2334 potentially relevant articles, 9 studies were included. For typical term neonates, dosages specified in packaging (labels) resulted in Cssmean below target (7.65 mg/L), while dosages from investigator-initiated studies resulted in either a Cssmean above (15.31), or around the target (11.78 and 10.21) for (pre)term neonates >32 weeks. Only one study suggested a dosing resulting in a tailored concentration (8.7) in preterm neonates <32 weeks.
A loading dose 20 mg/kg, followed by 10 mg/kg/6h is recommended for 32-44 weeks\' neonates, which is supported by short-term safety. For neonates < 32 weeks, a loading dose of 12 mg/kg and a maintenance dose of 6mg/kg/6h seems to lead to the target Cssmean, though additional clinical studies are needed to support its safety.
摘要：
静脉注射对乙酰氨基酚（对乙酰氨基酚）未获许可用于早产儿或<2岁的婴儿的镇痛。分别,在欧洲和美国。因此,在标签外使用多种给药方案。因为证据支持使用相同的目标平均稳态扑热息痛浓度（Cssmean，9-11mg/L）用于缓解新生儿的疼痛，与年龄较大的儿童和成人相比，以两步法评估基于该Cssmean的给药方案。
首先，我们进行了系统搜索,以提供基于药代动力学(PK)的新生儿疼痛给药指南(随后在这些论文中进行了安全性搜索).第二,根据这些给药指南生成浓度-时间曲线,为对乙酰氨基酚治疗新生儿疼痛提供给药建议.
在2334篇潜在相关文章中,包括9项研究。对于典型的足月新生儿，包装（标签）中指定的剂量导致Cssmean低于目标（7.65mg/L），虽然研究者发起的研究的剂量导致Cssmean高于（15.31），或附近的目标（11.78和10.21）对于（前）足月新生儿>32周。只有一项研究表明，在<32周的早产儿中，剂量会导致定制的浓度（8.7）。
负荷剂量为20mg/kg，其次是10mg/kg/6h建议32-44周的新生儿，这是由短期安全支持。对于<32周的新生儿，12mg/kg的负荷剂量和6mg/kg/6h的维持剂量似乎导致目标Cssmean，尽管需要更多的临床研究来支持其安全性。
首先，我们进行了系统搜索,以提供基于药代动力学(PK)的新生儿疼痛给药指南(随后在这些论文中进行了安全性搜索).第二,根据这些给药指南生成浓度-时间曲线,为对乙酰氨基酚治疗新生儿疼痛提供给药建议.
在2334篇潜在相关文章中,包括9项研究。对于典型的足月新生儿，包装（标签）中指定的剂量导致Cssmean低于目标（7.65mg/L），虽然研究者发起的研究的剂量导致Cssmean高于（15.31），或附近的目标（11.78和10.21）对于（前）足月新生儿>32周。只有一项研究表明，在<32周的早产儿中，剂量会导致定制的浓度（8.7）。
负荷剂量为20mg/kg，其次是10mg/kg/6h建议32-44周的新生儿，这是由短期安全支持。对于<32周的新生儿，12mg/kg的负荷剂量和6mg/kg/6h的维持剂量似乎导致目标Cssmean，尽管需要更多的临床研究来支持其安全性。
