Freeman Liv M, Bloemenkamp Kitty W, Franssen Maureen T, Papatsonis Dimitri N, Hajenius Petra J, Hollmann Markus W, Woiski Mallory D, Porath Martina, van den Berg Hans J, van Beek Erik, Borchert Odette W H M, Schuitemaker Nico, Sikkema J Marko, Kuipers A H M, Logtenberg Sabine L M, van der Salm Paulien C M, Oude Rengerink Katrien, Lopriore Enrico, van den Akker-van Marle M Elske, le Cessie Saskia, van Lith Jan M, Struys Michel M, Mol Ben Willem J, Dahan Albert, Middeldorp Johanna M
Obstetrics, Leiden University Medical Centre, Leiden, Netherlands
Obstetrics, Leiden University Medical Centre, Leiden, Netherlands.
BMJ. 2015 Feb 23;350:h846. doi: 10.1136/bmj.h846.
To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour.
Multicentre randomised controlled equivalence trial.
15 hospitals in the Netherlands.
Women with an intermediate to high obstetric risk with an intention to deliver vaginally. To exclude a clinically relevant difference in satisfaction with pain relief of more than 10%, we needed to include 1136 women. Because of missing values for satisfaction this number was increased to 1400 before any analysis. We used multiple imputation to correct for missing data.
Before the onset of active labour consenting women were randomised to a pain relief strategy with patient controlled remifentanil or epidural analgesia if they requested pain relief during labour.
Primary outcome was satisfaction with pain relief, measured hourly on a visual analogue scale and expressed as area under the curve (AUC), thus providing a time weighted measure of total satisfaction with pain relief. A higher AUC represents higher satisfaction with pain relief. Secondary outcomes were pain intensity scores, mode of delivery, and maternal and neonatal outcomes. Analysis was done by intention to treat. The study was defined as an equivalence study for the primary outcome.
1414 women were randomised, of whom 709 were allocated to patient controlled remifentanil and 705 to epidural analgesia. Baseline characteristics were comparable. Pain relief was ultimately used in 65% (447/687) in the remifentanil group and 52% (347/671) in the epidural analgesia group (relative risk 1.32, 95% confidence interval 1.18 to 1.48). Cross over occurred in 7% (45/687) and 8% (51/671) of women, respectively. Of women primarily treated with remifentanil, 13% (53/402) converted to epidural analgesia, while in women primarily treated with epidural analgesia 1% (3/296) converted to remifentanil. The area under the curve for total satisfaction with pain relief was 30.9 in the remifentanil group versus 33.7 in the epidural analgesia group (mean difference -2.8, 95% confidence interval -6.9 to 1.3). For who actually received pain relief the area under the curve for satisfaction with pain relief after the start of pain relief was 25.6 in the remifentanil group versus 36.1 in the epidural analgesia group (mean difference -10.4, -13.9 to -7.0). The rate of caesarean section was 15% in both groups. Oxygen saturation was significantly lower (SpO2 <92%) in women who used remifentanil (relative risk 1.5, 1.4 to 1.7). Maternal and neonatal outcomes were comparable between both groups.
In women in labour, patient controlled analgesia with remifentanil is not equivalent to epidural analgesia with respect to scores on satisfaction with pain relief. Satisfaction with pain relief was significantly higher in women who were allocated to and received epidural analgesia.
Netherlands Trial Register NTR2551.
比较分娩期间患者自控瑞芬太尼镇痛与硬膜外镇痛时女性对疼痛缓解的满意度。
多中心随机对照等效性试验。
荷兰的15家医院。
有中度至高度产科风险且打算经阴道分娩的女性。为排除疼痛缓解满意度方面超过10%的临床相关差异，我们需要纳入1136名女性。由于满意度存在缺失值，在进行任何分析之前，该数字增加到了1400。我们使用多重填补法来校正缺失数据。
在活跃期分娩开始前，同意参与的女性若在分娩期间要求缓解疼痛，将被随机分配至患者自控瑞芬太尼镇痛策略或硬膜外镇痛。
主要结局是对疼痛缓解的满意度，通过视觉模拟量表每小时测量一次，并以曲线下面积（AUC）表示，从而提供对疼痛缓解总体满意度的时间加权测量。AUC越高表示对疼痛缓解的满意度越高。次要结局包括疼痛强度评分、分娩方式以及母婴结局。分析采用意向性分析。该研究针对主要结局被定义为等效性研究。
1414名女性被随机分组，其中709名被分配至患者自控瑞芬太尼组，705名被分配至硬膜外镇痛组。基线特征具有可比性。瑞芬太尼组65%（447/687）最终使用了镇痛，硬膜外镇痛组为52%（347/671）（相对风险1.32，95%置信区间1.18至1.48）。分别有7%（45/687）和8%（51/671）的女性发生了交叉。在主要接受瑞芬太尼治疗的女性中，13%（53/402）转为硬膜外镇痛，而在主要接受硬膜外镇痛治疗的女性中，1%（3/296）转为瑞芬太尼。瑞芬太尼组疼痛缓解总体满意度的曲线下面积为30.9，硬膜外镇痛组为33.7（平均差值-2.8，95%置信区间-6.9至1.3）。对于实际接受了疼痛缓解的女性，疼痛缓解开始后疼痛缓解满意度的曲线下面积，瑞芬太尼组为25.6，硬膜外镇痛组为36.1（平均差值-10.4，-13.9至-7.0）。两组剖宫产率均为15%。使用瑞芬太尼的女性血氧饱和度显著更低（SpO2<92%）（相对风险1.5，1.4至1.7）。两组母婴结局具有可比性。
在分娩女性中，就疼痛缓解满意度评分而言，患者自控瑞芬太尼镇痛与硬膜外镇痛不等效。被分配并接受硬膜外镇痛的女性对疼痛缓解的满意度显著更高。
荷兰试验注册NTR2551。
