Zernikow Boris, Michel Erik, Anderson Brian
Vodafone Foundation Institute for Children's Pain Therapy and Pediatric Palliative Care, Children's Hospital, Witten/Herdecke University, Datteln, Germany.
J Pain. 2007 Mar;8(3):187-207. doi: 10.1016/j.jpain.2006.11.008.
The recently introduced fentanyl transdermal therapeutic system (TTS) with a drug release rate of 12.5 microg/h matches the lower dosing requirements of cancer pain control in children. It is likely that fentanyl TTS will be used in pediatrics with increasing frequency. We compiled the published evidence on pediatric applications of this drug formulation to help physicians get the most benefit from its use. Within this systematic review, a total of 11 observational clinical or pharmacokinetic studies were identified. There are no pediatric randomized or controlled cohort studies. Pharmacokinetic studies poorly described time-concentration profiles after application. The time to reach steady-state serum drug concentrations seems to be longer, clearance (expressed as liters per kilogram per hour) higher, and elimination half-life shorter in children than in adults. There are no fundamental differences in effect or profile of adverse effects compared with adults. Fentanyl TTS may be associated with less constipation compared with morphine use. Frequently, pediatric patients need supplemental mechanical fixation of the fentanyl TTS by means of medical tape. Younger patients tend to have a higher fentanyl requirement when referenced to body weight. Both parents and medical professionals are satisfied with fentanyl TTS to a higher degree than with individual analgesic pretreatment regimens. Fentanyl TTS is a promising option for chronic pain control in children. An approximate conversion factor of 45 mg/day oral morphine to 12.5 microg/h fentanyl TTS is used for initial therapy dose estimation in children receiving long-term morphine therapy. This is conservatively low to avoid respiratory depression. Daily oral morphine equivalent dose should be at least 30 mg/d before fentanyl TTS therapy is started with 12.5 microg/h. Evidence for superiority of fentanyl TTS treatment above conventional opioid administration is both scarce and of low quality.
The article gives a comprehensive overview of all pediatric data concerning the fentanyl TTS. Children may take longer to reach steady-state fentanyl serum concentrations than adults, and younger children may require higher doses referenced to body weight than older children or adults. Consequently, there is a need to provide sufficient medication in the phase of therapy initiation to prevent breakthrough pain. The 72-hour dosing schedule recommended by the manufacturers may not be applicable to children because of poor patch adhesiveness. The authors suggest to ensure firm fixation of the fentanyl TTS with additional medical tape if necessary and to change the fentanyl TTS after 48 hours. Transdermal fentanyl in children may exhibit fewer side effects when compared with other opioids, especially constipation. Randomized studies are urgently needed to definitively answer this question.
最近推出的药物释放速率为12.5微克/小时的芬太尼透皮治疗系统（TTS）符合儿童癌症疼痛控制较低的给药要求。芬太尼TTS在儿科的使用频率可能会越来越高。我们汇总了已发表的关于该药物制剂儿科应用的证据，以帮助医生从其使用中获得最大益处。在这项系统评价中，共确定了11项观察性临床或药代动力学研究。尚无儿科随机或对照队列研究。药代动力学研究对用药后的时间-浓度曲线描述欠佳。与成人相比，儿童达到稳态血清药物浓度的时间似乎更长，清除率（以升/千克/小时表示）更高，消除半衰期更短。与成人相比，在效果或不良反应特征方面没有根本差异。与使用吗啡相比，芬太尼TTS可能与便秘较少相关。儿科患者经常需要用医用胶带对芬太尼TTS进行额外的机械固定。与体重相关，年龄较小的患者往往需要更高剂量的芬太尼。家长和医疗专业人员对芬太尼TTS的满意度均高于单独的镇痛预处理方案。芬太尼TTS是儿童慢性疼痛控制的一个有前景的选择。对于接受长期吗啡治疗的儿童，初始治疗剂量估计时使用约45毫克/天口服吗啡换算为12.5微克/小时芬太尼TTS的换算因子。为避免呼吸抑制，该值保守设定得较低。在开始12.5微克/小时芬太尼TTS治疗前，每日口服吗啡等效剂量应至少为30毫克/天。芬太尼TTS治疗优于传统阿片类药物给药的证据既稀少且质量不高。
本文全面概述了所有关于芬太尼TTS的儿科数据。儿童达到芬太尼稳态血清浓度的时间可能比成人更长，且与年龄较大的儿童或成人相比，年龄较小的儿童按体重计算可能需要更高剂量。因此，在治疗开始阶段需要提供足够的药物以预防突破性疼痛。由于贴剂粘性差，制造商推荐的72小时给药方案可能不适用于儿童。作者建议如有必要，用额外的医用胶带确保芬太尼TTS牢固固定，并在48小时后更换芬太尼TTS。与其他阿片类药物相比，儿童经皮芬太尼可能副作用更少，尤其是便秘。迫切需要进行随机研究来明确回答这个问题。
