Patient controlled analgesia with remifentanil versus epidural analgesia in labour: Randomised multicentre equivalence trial

Liv M. Freeman, Kitty W. Bloemenkamp, Maureen T. Franssen, Dimitri N. Papatsonis, Petra J. Hajenius, Markus W. Hollmann, Mallory D. Woiski, Martina Porath, Hans J. Van Den Berg, Erik Van Beek, Odette W.H.M. Borchert, Nico Schuitemaker, J. Marko Sikkema, A. H.M. Kuipers, Sabine L.M. Logtenberg, Paulien C.M. Van Der Salm, Katrien Oude Rengerink, Enrico Lopriore, M. Elske Van Den Akker-van Marle, Saskia Le CessieJan M. Van Lith, Michel M. Struys, Ben Willem J. Mol, Albert Dahan, Johanna M. Middeldorp

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Abstract

Objective: To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. Design: Multicentre randomised controlled equivalence trial. Setting: 15 hospitals in the Netherlands. Participants: 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. Intervention: 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. Main outcome measures: 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. Results: 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. Conclusion: 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. Trial registration Netherlands Trial Register NTR2551.

Original languageEnglish
Article numberh846
Number of pages14
JournalBMJ: British Medical Journal
Volume350
DOIs
Publication statusPublished - 23 Feb 2015
Externally publishedYes

Cite this

Freeman, L. M., Bloemenkamp, K. W., Franssen, M. T., Papatsonis, D. N., Hajenius, P. J., Hollmann, M. W., ... Middeldorp, J. M. (2015). Patient controlled analgesia with remifentanil versus epidural analgesia in labour: Randomised multicentre equivalence trial. BMJ: British Medical Journal, 350, [h846]. https://doi.org/10.1136/bmj.h846
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. ; Rengerink, Katrien Oude ; 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. / Patient controlled analgesia with remifentanil versus epidural analgesia in labour : Randomised multicentre equivalence trial. In: BMJ: British Medical Journal. 2015 ; Vol. 350.
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title = "Patient controlled analgesia with remifentanil versus epidural analgesia in labour: Randomised multicentre equivalence trial",
abstract = "Objective: To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. Design: Multicentre randomised controlled equivalence trial. Setting: 15 hospitals in the Netherlands. Participants: 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. Intervention: 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. Main outcome measures: 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. Results: 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. Conclusion: 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. Trial registration Netherlands Trial Register NTR2551.",
author = "Freeman, {Liv M.} and Bloemenkamp, {Kitty W.} and Franssen, {Maureen T.} and Papatsonis, {Dimitri N.} and Hajenius, {Petra J.} and Hollmann, {Markus W.} and Woiski, {Mallory D.} and Martina Porath and {Van Den Berg}, {Hans J.} and {Van Beek}, Erik and Borchert, {Odette W.H.M.} and Nico Schuitemaker and Sikkema, {J. Marko} and Kuipers, {A. H.M.} and Logtenberg, {Sabine L.M.} and {Van Der Salm}, {Paulien C.M.} and Rengerink, {Katrien Oude} and Enrico Lopriore and {Van Den Akker-van Marle}, {M. Elske} and {Le Cessie}, Saskia and {Van Lith}, {Jan M.} and Struys, {Michel M.} and Mol, {Ben Willem J.} and Albert Dahan and Middeldorp, {Johanna M.}",
year = "2015",
month = "2",
day = "23",
doi = "10.1136/bmj.h846",
language = "English",
volume = "350",
journal = "BMJ: British Medical Journal",
issn = "0959-535X",
publisher = "BMJ Publishing Group",

}

Freeman, LM, Bloemenkamp, KW, Franssen, MT, Papatsonis, DN, Hajenius, PJ, Hollmann, MW, Woiski, MD, Porath, M, Van Den Berg, HJ, Van Beek, E, Borchert, OWHM, Schuitemaker, N, Sikkema, JM, Kuipers, AHM, Logtenberg, SLM, Van Der Salm, PCM, Rengerink, KO, Lopriore, E, Van Den Akker-van Marle, ME, Le Cessie, S, Van Lith, JM, Struys, MM, Mol, BWJ, Dahan, A & Middeldorp, JM 2015, 'Patient controlled analgesia with remifentanil versus epidural analgesia in labour: Randomised multicentre equivalence trial', BMJ: British Medical Journal, vol. 350, h846. https://doi.org/10.1136/bmj.h846

Patient controlled analgesia with remifentanil versus epidural analgesia in labour : Randomised multicentre equivalence trial. / 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.; Rengerink, Katrien Oude; 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.

In: BMJ: British Medical Journal, Vol. 350, h846, 23.02.2015.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Patient controlled analgesia with remifentanil versus epidural analgesia in labour

T2 - Randomised multicentre equivalence trial

AU - Freeman, Liv M.

AU - Bloemenkamp, Kitty W.

AU - Franssen, Maureen T.

AU - Papatsonis, Dimitri N.

AU - Hajenius, Petra J.

AU - Hollmann, Markus W.

AU - Woiski, Mallory D.

AU - Porath, Martina

AU - Van Den Berg, Hans J.

AU - Van Beek, Erik

AU - Borchert, Odette W.H.M.

AU - Schuitemaker, Nico

AU - Sikkema, J. Marko

AU - Kuipers, A. H.M.

AU - Logtenberg, Sabine L.M.

AU - Van Der Salm, Paulien C.M.

AU - Rengerink, Katrien Oude

AU - Lopriore, Enrico

AU - Van Den Akker-van Marle, M. Elske

AU - Le Cessie, Saskia

AU - Van Lith, Jan M.

AU - Struys, Michel M.

AU - Mol, Ben Willem J.

AU - Dahan, Albert

AU - Middeldorp, Johanna M.

PY - 2015/2/23

Y1 - 2015/2/23

N2 - Objective: To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. Design: Multicentre randomised controlled equivalence trial. Setting: 15 hospitals in the Netherlands. Participants: 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. Intervention: 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. Main outcome measures: 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. Results: 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. Conclusion: 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. Trial registration Netherlands Trial Register NTR2551.

AB - Objective: To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. Design: Multicentre randomised controlled equivalence trial. Setting: 15 hospitals in the Netherlands. Participants: 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. Intervention: 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. Main outcome measures: 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. Results: 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. Conclusion: 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. Trial registration Netherlands Trial Register NTR2551.

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U2 - 10.1136/bmj.h846

DO - 10.1136/bmj.h846

M3 - Article

C2 - 25713015

AN - SCOPUS:84923872996

VL - 350

JO - BMJ: British Medical Journal

JF - BMJ: British Medical Journal

SN - 0959-535X

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