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Meta-Analysis
. 2018 May 21;5(5):CD000331.
doi: 10.1002/14651858.CD000331.pub4.

Epidural versus non-epidural or no analgesia for pain management in labour

Millicent Anim-Somuah  1 , Rebecca Md Smyth, Allan M Cyna, Anna Cuthbert
Affiliations
Meta-Analysis

Epidural versus non-epidural or no analgesia for pain management in labour

Millicent Anim-Somuah et al. Cochrane Database Syst Rev. .

Abstract

Background: Epidural analgesia is a central nerve block technique achieved by injection of a local anaesthetic close to the nerves that transmit pain, and is widely used as a form of pain relief in labour. However, there are concerns about unintended adverse effects on the mother and infant. This is an update of an existing Cochrane Review (Epidural versus non-epidural or no analgesia in labour), last published in 2011.

Objectives: To assess the effectiveness and safety of all types of epidural analgesia, including combined-spinal-epidural (CSE) on the mother and the baby, when compared with non-epidural or no pain relief during labour.

Search methods: We searched Cochrane Pregnancy and Childbirth's Trials Register (ClinicalTrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (30 April 2017), and reference lists of retrieved studies.

Selection criteria: Randomised controlled trials comparing all types of epidural with any form of pain relief not involving regional blockade, or no pain relief in labour. We have not included cluster-randomised or quasi-randomised trials in this update.

Data collection and analysis: Two review authors independently assessed trials for inclusion and risks of bias, extracted data and checked them for accuracy. We assessed selected outcomes using the GRADE approach.

Main results: Fifty-two trials met the inclusion criteria and we have included data from 40 trials, involving over 11,000 women. Four trials included more than two arms. Thirty-four trials compared epidural with opioids, seven compared epidural with no analgesia, one trial compared epidural with acu-stimulation, one trial compared epidural with inhaled analgesia, and one trial compared epidural with continuous midwifery support and other analgesia. Risks of bias varied throughout the included studies; six out of 40 studies were at high or unclear risk of bias for every bias domain, while most studies were at high or unclear risk of detection bias. Quality of the evidence assessed using GRADE ranged from moderate to low quality.Pain intensity as measured using pain scores was lower in women with epidural analgesia when compared to women who received opioids (standardised mean difference -2.64, 95% confidence interval (CI) -4.56 to -0.73; 1133 women; studies = 5; I2 = 98%; low-quality evidence) and a higher proportion were satisfied with their pain relief, reporting it to be "excellent or very good" (average risk ratio (RR) 1.47, 95% CI 1.03 to 2.08; 1911 women; studies = 7; I2 = 97%; low-quality evidence). There was substantial statistical heterogeneity in both these outcomes. There was a substantial decrease in the need for additional pain relief in women receiving epidural analgesia compared with opioid analgesia (average RR 0.10, 95% CI 0.04 to 0.25; 5099 women; studies = 16; I2 = 73%; Tau2 = 1.89; Chi2 = 52.07 (P < 0.00001)). More women in the epidural group experienced assisted vaginal birth (RR 1.44, 95% CI 1.29 to 1.60; 9948 women; studies = 30; low-quality evidence). A post hoc subgroup analysis of trials conducted after 2005 showed that this effect is negated when trials before 2005 are excluded from this analysis (RR 1.19, 95% CI 0.97 to 1.46). There was no difference between caesarean section rates (RR 1.07, 95% CI 0.96 to 1.18; 10,350 women; studies = 33; moderate-quality evidence), and maternal long-term backache (RR 1.00, 95% CI 0.89 to 1.12; 814 women; studies = 2; moderate-quality evidence). There were also no clear differences between groups for the neonatal outcomes, admission to neonatal intensive care unit (RR 1.03, 95% CI 0.95 to 1.12; 4488 babies; studies = 8; moderate-quality evidence) and Apgar score less than seven at five minutes (RR 0.73, 95% CI 0.52 to 1.02; 8752 babies; studies = 22; low-quality evidence). We downgraded the evidence for study design limitations, inconsistency, imprecision in effect estimates, and possible publication bias.Side effects were reported in both epidural and opioid groups. Women with epidural experienced more hypotension, motor blockade, fever, and urinary retention. They also had longer first and second stages of labour, and were more likely to have oxytocin augmentation than the women in the opioid group. Women receiving epidurals had less risk of respiratory depression requiring oxygen, and were less likely to experience nausea and vomiting than women receiving opioids. Babies born to women in the epidural group were less likely to have received naloxone. There was no clear difference between groups for postnatal depression, headache, itching, shivering, or drowsiness. Maternal morbidity and long-term neonatal outcomes were not reported.Epidural analgesia resulted in less reported pain when compared with placebo or no treatment, and with acu-stimulation. Pain intensity was not reported in the trials that compared epidural with inhaled analgesia, or continuous support. Few trials reported on serious maternal side effects.

Authors' conclusions: Low-quality evidence shows that epidural analgesia may be more effective in reducing pain during labour and increasing maternal satisfaction with pain relief than non-epidural methods. Although overall there appears to be an increase in assisted vaginal birth when women have epidural analgesia, a post hoc subgroup analysis showed this effect is not seen in recent studies (after 2005), suggesting that modern approaches to epidural analgesia in labour do not affect this outcome. Epidural analgesia had no impact on the risk of caesarean section or long-term backache, and did not appear to have an immediate effect on neonatal status as determined by Apgar scores or in admissions to neonatal intensive care. Further research may be helpful to evaluate rare but potentially severe adverse effects of epidural analgesia and non-epidural analgesia on women in labour and long-term neonatal outcomes.

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Conflict of interest statement

Millicent Anim‐Somuah: None known

Rebecca MD Smyth: None known

Allan M Cyna: None known

Anna Cuthbert: I am a research associate working in the editorial base of Cochrane Pregnancy and Childbirth. I am employed by the University of Liverpool to work as a research associate in Cochrane Pregnancy and Childbirth (who receives infrastructure funding from the NIHR, UK).

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot of comparison: 1 Epidural versus opioids, outcome: 1.12 Assisted vaginal birth.
5
5
Funnel plot of comparison: 1 Epidural versus opioids, outcome: 1.13 Caesarean section.
6
6
Funnel plot of comparison: 1 Epidural versus opioids, outcome: 1.35 Apgar score less than 7 at 5 minutes.
1.1
1.1. Analysis
Comparison 1 Epidural versus opioids, Outcome 1 Pain score in labour.
1.2
1.2. Analysis
Comparison 1 Epidural versus opioids, Outcome 2 Pain intensity severe or intolerable.
1.3
1.3. Analysis
Comparison 1 Epidural versus opioids, Outcome 3 Woman's perception of pain relief in labour.
1.4
1.4. Analysis
Comparison 1 Epidural versus opioids, Outcome 4 Woman's perception of pain relief during first stage of labour.
1.5
1.5. Analysis
Comparison 1 Epidural versus opioids, Outcome 5 Woman's perception of pain relief during the second stage of labour.
1.6
1.6. Analysis
Comparison 1 Epidural versus opioids, Outcome 6 Satisfaction with pain relief in labour ‐ proportion rating excellent or very good.
1.7
1.7. Analysis
Comparison 1 Epidural versus opioids, Outcome 7 Satisfaction with pain relief in labour ‐ continuous data.
1.8
1.8. Analysis
Comparison 1 Epidural versus opioids, Outcome 8 Time of administration of pain relief to time pain relief was satisfactory (minutes).
1.9
1.9. Analysis
Comparison 1 Epidural versus opioids, Outcome 9 Perceived feeling of poor control in labour.
1.10
1.10. Analysis
Comparison 1 Epidural versus opioids, Outcome 10 Satisfaction with childbirth experience ‐ proportion rating satisfied to very satisfied.
1.11
1.11. Analysis
Comparison 1 Epidural versus opioids, Outcome 11 Need for additional means of pain relief.
1.12
1.12. Analysis
Comparison 1 Epidural versus opioids, Outcome 12 Assisted vaginal birth.
1.13
1.13. Analysis
Comparison 1 Epidural versus opioids, Outcome 13 Caesarean section.
1.14
1.14. Analysis
Comparison 1 Epidural versus opioids, Outcome 14 Long‐term backache.
1.15
1.15. Analysis
Comparison 1 Epidural versus opioids, Outcome 15 Hypotension as defined by trial authors.
1.16
1.16. Analysis
Comparison 1 Epidural versus opioids, Outcome 16 Postnatal depression (authors definition, on medication, or self‐reported).
1.17
1.17. Analysis
Comparison 1 Epidural versus opioids, Outcome 17 Motor blockade.
1.18
1.18. Analysis
Comparison 1 Epidural versus opioids, Outcome 18 Respiratory depression requiring oxygen administration.
1.19
1.19. Analysis
Comparison 1 Epidural versus opioids, Outcome 19 Headache.
1.20
1.20. Analysis
Comparison 1 Epidural versus opioids, Outcome 20 Perineal trauma requiring suturing.
1.21
1.21. Analysis
Comparison 1 Epidural versus opioids, Outcome 21 Nausea and vomiting.
1.22
1.22. Analysis
Comparison 1 Epidural versus opioids, Outcome 22 Itch.
1.23
1.23. Analysis
Comparison 1 Epidural versus opioids, Outcome 23 Fever > 38 º C.
1.24
1.24. Analysis
Comparison 1 Epidural versus opioids, Outcome 24 Shivering.
1.25
1.25. Analysis
Comparison 1 Epidural versus opioids, Outcome 25 Drowsiness.
1.26
1.26. Analysis
Comparison 1 Epidural versus opioids, Outcome 26 Urinary retention.
1.27
1.27. Analysis
Comparison 1 Epidural versus opioids, Outcome 27 Catheterisation during labour.
1.28
1.28. Analysis
Comparison 1 Epidural versus opioids, Outcome 28 Malposition.
1.29
1.29. Analysis
Comparison 1 Epidural versus opioids, Outcome 29 Surgical amniotomy.
1.30
1.30. Analysis
Comparison 1 Epidural versus opioids, Outcome 30 Acidosis defined by cord arterial pH < 7.2 at delivery.
1.31
1.31. Analysis
Comparison 1 Epidural versus opioids, Outcome 31 Acidosis defined by cord arterial pH < 7.15.
1.32
1.32. Analysis
Comparison 1 Epidural versus opioids, Outcome 32 Naloxone administration.
1.33
1.33. Analysis
Comparison 1 Epidural versus opioids, Outcome 33 Meconium staining of liquor.
1.34
1.34. Analysis
Comparison 1 Epidural versus opioids, Outcome 34 Neonatal intensive care unit admission.
1.35
1.35. Analysis
Comparison 1 Epidural versus opioids, Outcome 35 Apgar score less than 7 at 5 minutes.
1.36
1.36. Analysis
Comparison 1 Epidural versus opioids, Outcome 36 Length of first stage of labour (minutes).
1.37
1.37. Analysis
Comparison 1 Epidural versus opioids, Outcome 37 Length of second stage of labour (minutes).
1.38
1.38. Analysis
Comparison 1 Epidural versus opioids, Outcome 38 Oxytocin augmentation.
1.39
1.39. Analysis
Comparison 1 Epidural versus opioids, Outcome 39 Caesarean section for fetal distress.
1.40
1.40. Analysis
Comparison 1 Epidural versus opioids, Outcome 40 Caesarean section for dystocia.
1.41
1.41. Analysis
Comparison 1 Epidural versus opioids, Outcome 41 Sensitivity analysis ‐ allocation concealment: Maternal satisfaction with pain relief in labour ‐ proportion rating excellent or very good.
1.42
1.42. Analysis
Comparison 1 Epidural versus opioids, Outcome 42 Sensitivity analysis ‐ incomplete outcome data: Maternal satisfaction with pain relief in labour ‐ proportion rating excellent or very good.
1.43
1.43. Analysis
Comparison 1 Epidural versus opioids, Outcome 43 Sensitivity analysis ‐ allocation concealment: Need for additional means of pain relief.
1.44
1.44. Analysis
Comparison 1 Epidural versus opioids, Outcome 44 Sensitivity analysis ‐ incomplete outcome data: Need for additional means of pain relief.
2.1
2.1. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 1 Pain score in labour.
2.2
2.2. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 2 Woman's perception of pain relief during first stage of labour.
2.3
2.3. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 3 Woman's perception of pain relief during the second stage of labour.
2.4
2.4. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 4 Pain intensity.
2.5
2.5. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 5 Satisfaction with pain relief in labour ‐ proportion rating excellent or very good.
2.6
2.6. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 6 Perceived feeling of poor control in labour.
2.7
2.7. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 7 Need for additional means of pain relief.
2.8
2.8. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 8 Instrumental delivery.
2.9
2.9. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 9 Caesarean section.
2.10
2.10. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 10 Motor blockade.
2.11
2.11. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 11 Headache.
2.12
2.12. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 12 Perineal trauma requiring suturing.
2.13
2.13. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 13 Nausea and vomiting.
2.14
2.14. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 14 Itch.
2.15
2.15. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 15 Fever > 38 º C.
2.16
2.16. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 16 Shivering.
2.17
2.17. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 17 Drowsiness.
2.18
2.18. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 18 Urinary retention.
2.19
2.19. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 19 Apgar score less than 7 at 5 minutes.
2.20
2.20. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 20 Length of first stage of labour (minutes).
2.21
2.21. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 21 Length of second stage of labour (minutes).
2.22
2.22. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 22 Oxytocin augmentation.
2.23
2.23. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 23 Caesarean section for fetal distress.
2.24
2.24. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 24 Caesarean section for dystocia.
2.25
2.25. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 25 Sensitivity analysis ‐ allocation concealment: Need for additional means of pain relief.
2.26
2.26. Analysis
Comparison 2 Epidural versus placebo/no treatment, Outcome 26 Sensitivity analysis ‐ incomplete outcome data: Need for additional means of pain relief.
3.1
3.1. Analysis
Comparison 3 Epidural versus TENS, Outcome 1 Maternal pain score in labour.
3.2
3.2. Analysis
Comparison 3 Epidural versus TENS, Outcome 2 Instrumental delivery.
3.3
3.3. Analysis
Comparison 3 Epidural versus TENS, Outcome 3 Caesarean section.
3.4
3.4. Analysis
Comparison 3 Epidural versus TENS, Outcome 4 Hypotension as defined by trial authors.
3.5
3.5. Analysis
Comparison 3 Epidural versus TENS, Outcome 5 Urinary retention.
3.6
3.6. Analysis
Comparison 3 Epidural versus TENS, Outcome 6 Nausea and vomiting.
3.7
3.7. Analysis
Comparison 3 Epidural versus TENS, Outcome 7 Length of second stage of labour (minutes).
3.8
3.8. Analysis
Comparison 3 Epidural versus TENS, Outcome 8 Oxytocin augmentation.
4.1
4.1. Analysis
Comparison 4 Epidural versus inhaled analgesia, Outcome 1 Maternal satisfaction with pain relief in labour ‐ proportion rating excellent or very good.
4.2
4.2. Analysis
Comparison 4 Epidural versus inhaled analgesia, Outcome 2 Caesarean section.
5.1
5.1. Analysis
Comparison 5 Epidural versus continuous support, Outcome 1 Satisfaction with pain relief in labour ‐ proportion rating excellent or very good.
5.2
5.2. Analysis
Comparison 5 Epidural versus continuous support, Outcome 2 Need for additional means of pain relief.
5.3
5.3. Analysis
Comparison 5 Epidural versus continuous support, Outcome 3 Instrumental delivery.
5.4
5.4. Analysis
Comparison 5 Epidural versus continuous support, Outcome 4 Caesarean section.
5.5
5.5. Analysis
Comparison 5 Epidural versus continuous support, Outcome 5 Long‐term backache.
5.6
5.6. Analysis
Comparison 5 Epidural versus continuous support, Outcome 6 Headache.
5.7
5.7. Analysis
Comparison 5 Epidural versus continuous support, Outcome 7 Nausea and vomiting.
5.8
5.8. Analysis
Comparison 5 Epidural versus continuous support, Outcome 8 Cathetherisation during labour.
5.9
5.9. Analysis
Comparison 5 Epidural versus continuous support, Outcome 9 Apgar score less than 7 at 5 minutes.
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References

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Liu 2015 {published data only}
    1. Liu Y, Xu M, Che X, He J, Guo D, Zhao G, et al. Effect of direct current pulse stimulating acupoints of JiaJi (T10‐13) and Ciliao (BL 32) with Han's Acupoint Nerve Stimulator on labour pain in women: a randomized controlled clinical study. Journal of Traditional Chinese Medicine 2015;35(6):620‐5. - PubMed
Logtenberg 2017 {published data only}
    1. Logtenberg A, Oude Rengerink K, Verhoeven C, Mol BW. Remifentanil patient controlled analgesia versus epidural analgesia during labour: a randomised trial (NTR3687). Regional Anesthesia and Pain Medicine 2014;39(5 Suppl 1):E241‐E242.
    1. Logtenberg SL, Oude Rengerink K, Post JA, Verhoeven CJ, Freeman LM, Middeldorp JM, et al. Labour pain with remifentanil patient‐controlled analgesia versus epidural analgesia: a randomised equivalence trial. BJOG: an international journal of obstetrics and gynaecology 2017;124(4):652‐60. - PubMed
Long 2003 {published data only}
    1. Long J, Yue Y. Patient controlled intravenous analgesia with tramadol for pain relief. Chinese Medical Journal 2003;116(11):1752‐5. - PubMed
Loughnan 2000 {published data only}
    1. Loughnan B, Carli F, Romney M, Dore C, Gordon H. A large randomised controlled trial comparing epidural bupivacaine with intramuscular pethidine for pain relief in labour in primiparous women. Acta Obstetricia et Gynecologica Scandinavica 1997;76(167):44.
    1. Loughnan B, Carli F, Romney M, Dore C, Gordon H. A large randomised controlled trial comparing epidural bupivacaine with intramuscular pethidine for pain relief in labour in primiparous women. British Journal of Anaesthesia 1998;80(5 Suppl):151‐2.
    1. Loughnan B, Carli F, Romney M, Dore C, Gordon H. Epidural analgesia and backache: a randomized comparison with intramuscular meperidine for analgesia during labour. British Journal of Anaesthesia 2002;89(3):466‐72. - PubMed
    1. Loughnan BA, Carli F, Romney M, Dore C, Gordon H. The influence of epidural analgesia on the development of new backache in primiparous women: report of a randomized controlled trial. International Journal of Obstetric Anesthesia 1997;6:203‐4.
    1. Loughnan BA, Carli F, Romney M, Dore CJ, Gordon H. Randomized controlled comparison of epidural bupivacaine versus pethidine for analgesia in labour. British Journal of Anaesthesia 2000;84(6):715‐9. - PubMed
Lucas 2001 {published data only}
    1. Lucas M, Sharma S, Leveno K, Ramin S, Wiley J, Sidawi J. A randomized trial of labor epidural analgesia in women with preeclampsia. Anesthesiology 1998;88(4 Suppl):A25.
    1. Lucas M, Sharma S, McIntire D, Sidawi E, Ramin S, Leveno K, et al. A randomized trial of epidural analgesia on pregnancy‐induced hypertension. American Journal of Obstetrics and Gynecology 1999;180(1 Pt 2):S18. - PubMed
    1. Lucas M, Sharma S, McIntire D, Wiley J, Sidawi J, Ramin S, et al. A randomized trial of labor analgesia in women with pregnancy‐induced hypertension. American Journal of Obstetrics and Gynecology 2001;185(4):970‐5. - PubMed
Morgan‐Ortiz 1999 {published data only}
    1. Morgan‐Ortiz F, Quintero‐Ledezma J, Pérez‐Sotelo JA, Trapero‐Morales M. Evolution and quality care of labour and delivery in primiparous patients who underwent early obstetric analgesia. Ginecologia y Obstetricia de Mexico 1999;67:522‐6. - PubMed
Morris 1994 {published data only}
    1. Morris GF, Gore‐Hickman W, Lang SA, Yip RW. Can parturients distinguish between intravenous and epidural fentanyl?. Canadian Journal of Anaesthesia 1994;41(8):667‐72. - PubMed
Muir 1996 {published data only}
    1. Muir HA, Shukla R, Liston R, Writer D. Randomised trial of labor analgesia: a pilot study to compare patient‐controlled epidural analgesia to determine if analgesic method affects delivery outcome. Canadian Journal of Anaesthesia 1996;43(5):A60.
Muir 2000 {published data only}
    1. Halpern S, Breen T, Campbell DC, Blanchard W. Epidural PCA fentanyl/bupivacaine vs IV PCA fentanyl: neonatal effects. Anesthesiology 1999;90(4 Suppl):A19.
    1. Halpern S, Muir H, Breen T, Campbell DC. Randomised controlled trials in obstetrical anesthesia‐what did the patients think?. Anesthesiology 1999;91(3A):A1068.
    1. Muir HA, Breen T, Campbell DC, Halpern S, Blanchard W. Is intravenous PCA fentanyl an effective method for providing labor analgesia?. Anesthesiology 1999;90(4 Suppl):A28.
    1. Muir HD, Breen T, Campbell D, Halpern S, Liston R, Blanchard W. A multi centre study of the effects of analgesia on the progress of labour (abstract). Anesthesiology 2000;92 Suppl:A23.
Nikkola 1997 {published data only}
    1. Nikkola EM, Ekblad UU, Kero PO, Alihanka JJ, Salonen MA. Intravenous fentanyl PCA during labour. Canadian Journal of Anaesthesia 1997;44(12):1248‐55. - PubMed
Philipsen 1989 {published data only}
    1. Philipsen T, Jensen NH. A randomised study comparing epidural block and pethidine as analgesic in labour. World Congress of Gynecology and Obstetrics; 1988 Oct 23‐28; Brazil. 1988:378‐9.
    1. Philipsen T, Jensen NH. Epidural block or parenteral pethidine as analgesic in labour; a randomized study concerning progress in labour and instrumental deliveries. European Journal of Obstetrics & Gynecology and Reproductive Biology 1989;30(1):27‐33. - PubMed
    1. Philipsen T, Jensen NH. Maternal opinion about analgesia in labour and delivery. A comparison of epidural blockade and intramuscular pethidine. European Journal of Obstetrics & Gynecology and Reproductive Biology 1990;34(3):205‐10. - PubMed
Rabie 2006 {published data only}
    1. Rabie ME, Negmi HH, Moustafa AM, Al Oufi H. Remifentanil by patient controlled analgesia compared with epidural analgesia for pain relief in labour [abstract]. Regional Anesthesia and Pain Management 2006;31(5 Suppl 1):52.
Ramin 1995 {published data only}
    1. Ramin S, Gambling DR, Lucas MJ, Sharma SK, Sidawi JE, Leveno KJ. Randomised trial of epidural versus intravenous analgesia during labour. Obstetrics & Gynecology 1995;86(5):783‐9. - PubMed
Sabry 2011 {published data only}
    1. NCT01290289. Analgesia in labor, a prospective parallel single blind study to compare regional analgesia (combined spinal epidural analgesia (cse), epidural analgesia (e)) and intravenous (iv) pethidine analgesia. clinicaltrials.gov/show/NCT01290289 (first received 4 Feb 2011).
    1. Sweed N, Sabry N, Azab T, Nour S. Regional versus IV analgesics in labor. Minerva Medica 2011;102(5):353‐61. - PubMed
Scavone 2002 {published data only}
    1. Scavone BM, Sullivan JT, Peaceman AM, Strauss‐Hoder TP, Wong CA. Fetal heart rate and uterine contraction pattern abnormalities after combined spinal/epidural vs systemic labor analgesia [abstract]. Anesthesiology 2002;96 Suppl:Abstract no: A1049.
Sharma 1997 {published data only}
    1. Alexander JM, Sharma SK, McIntire DD, Wiley J, Leveno KJ. Intensity of labor pain and cesarean delivery. Anesthesia & Analgesia 2001;92(1):1524‐8. - PubMed
    1. Alexander JM, Sharma SK, McIntire DD, Wiley J, Leveno KJ. The effect of parity on labour pain. American Journal of Obstetrics and Gynecology 2000;182:S134.
    1. Philip J, Alexander J, Ramin S, Sharma S, McIntire D, Leveno K. Epidural analgesia during labor may be an independent source of maternal fever. American Journal of Obstetrics and Gynecology 1998;178(1 Pt 2):S175.
    1. Philip J, Alexander JM, Sharma SK, Leveno KJ, McIntire DD, Wiley J. Epidural analgesia during labour and maternal fever. Anesthesiology 1999;90(5):1271‐5. - PubMed
    1. Sharma SK, Sidawi JE, Ramin SM, Lucas MJ, Leveno KJ, Cunningham FG. A randomised trial of epidural versus patient‐controlled meperidine analgesia during labour. Anesthesiology 1997;87(3):487‐94. - PubMed
Sharma 2002 {published data only}
    1. Alexander JM, Sharma SK, McIntire DD, Leveno KJ. Epidural analgesia lengthens the friedman active phase of labor [abstract]. Anesthesiology 2002;96(Suppl 1):P40. - PubMed
    1. Alexander JM, Sharma SK, McIntire DD, Leveno KJ. Epidural analgesia lengthens the friedman active phase of labour. Obstetrics & Gynecology 2002;100(1):46‐50. - PubMed
    1. Hill J, Alexander J, Sharma S, McIntire D, Leveno K. The effects of low‐dose epidural technique for labor analgesia on fetal heart rate (fhr) [abstract]. American Journal of Obstetrics and Gynecology 2001;185(6 Suppl):S206.
    1. Hill JB, Alexander JM, Sharma SK, McIntire DD. A comparison of the effects of epidural and meperidine analgesia during labor on fetal heart rate. Obstetrics & Gynecology 2003;102(2):333‐7. - PubMed
    1. Sharma S, Leveno K, Messick G, Alexander J, Sidawi J, Wiley J. A randomized trial of patient‐controlled epidural versus patient‐controlled intravenous analgesia during labor [abstract]. Anesthesiology 2000;92 Suppl:A22.
Shifman 2007 {published data only}
    1. Shifman EM, Butrov AV, Floka SE, Got IB. Transient neurological symptoms in puerperas after epidural analgesia during labor. Anesteziologiia i Reanimatologiia 2007, issue 6:17‐20. - PubMed
Stocki 2011 {published data only}
    1. Stocki D, Matot I, Einav S, Eventov‐Friedman S, Ginosar Y, Weiniger CF. A randomized controlled trial of the efficacy and respiratory effects of patient‐controlled intravenous remifentanil analgesia and patient‐controlled epidural analgesia in laboring women. Anesthesia & Analgesia 2014;118(3):589‐97. - PubMed
Sullivan 2002 {published data only}
    1. Stocki D, Matot I, Weiniger CF. A prospective randomized controlled trial to compare the efficacy and safety of remifentanil IV PCA to epidural PECA in labor analgesia. European Journal of Anaesthesiology 2011;28 Suppl:164‐5.
    1. Sullivan JT, Scavone BM, McCarthy RJ, Wong CA. Does type of labor analgesia alter the pattern of oxytocin use? [abstract]. Anesthesiology 2002;96(Suppl 1):Abstract no: P48.
    1. Sullivan JT, Scavone BM, McCarthy RJ, Wong CA. Neuraxial labor analgesia is associated with an altered pattern of oxytocin use [abstract]. Anesthesiology 2002;96 Suppl:Abstract no: A1039.
Thalme 1974 {published data only}
    1. Thalme B, Belfrage P, Raabe N. Lumbar epidural analgesia in labour: I. Acid‐base balance and clinical condition of mother, fetus and newborn child. Acta Obstetricia et Gynecologica Scandinavica 1974;53(1):27‐35. - PubMed
Thorp 1993 {published data only}
    1. Thorp JA, Hu D, Albin R, McNitt J, Meyer BA, Cohen GR, et al. The effect of intrapartum epidural analgesia on nulliparous labor: a randomized controlled prospective trial. American Journal of Obstetrics and Gynecology 1993;168:319. - PubMed
    1. Thorp JA, Hu DH, Albin RM, McNitt J, Meyer BA, Cohen GR, et al. The effect of intrapartum epidural analgesia on nulliparous labor: a randomized, controlled, prospective trial. American Journal of Obstetrics and Gynecology 1993;169(4):851‐8. - PubMed
Tveit 2012 {published data only}
    1. Tveit TO, Seiler S, Halvorsen A, Rosland JH. Labour analgesia: A randomised, controlled trial comparing intravenous remifentanil and epidural analgesia with ropivacaine and fentanyl. European Journal of Anaesthesiology 2012;29(3):129‐36. - PubMed
Volmanen 2008 {published data only}
    1. Volmanen P, Sarvela J, Akural EI, Raudaskoski T, Korttila K, Alahuhta S. Intravenous remifentanil vs. epidural levobupivacaine with fentanyl for pain relief in early labour: a randomised, controlled, double‐blinded study. Acta Anaesthesiologica Scandinavica 2008;52(2):249‐55. - PubMed
Witoonpanich 1984 {published data only}
    1. Witoonpanich P, Surapong K. Control of hypertension in labouring preeclamptics. 4th World Congress of the International Society for the study of Hypertension in Pregnancy; 1984 June 18‐21; Amsterdam, The Netherlands. 1984:230.
Xing 2015 {published data only}
    1. Xing JJ, Liu XF, Xiong XM, Huang L, Lao CY, Yang M, et al. Effects of combined spinal‐epidural analgesia during labor on postpartum electrophysiological function of maternal pelvic floor muscle: a randomized controlled trial. Plos One 2015;10(9):e0137267. - PMC - PubMed

References to studies excluded from this review

Abboud 1982 {published data only}
    1. Abboud TK, Sarkis F, Goebelsmann U, Hung TT, Henriksen EH. Effects of epidural anesthesia during labor on maternal plasma B‐endorphin levels. Anesthesiology 1982;57:A382. - PubMed
Anwar 2015 {published data only}
    1. Anwar S, Anwar MW, Ayaz A, Danish N, Ahmad S. Effect of epidural analgesia on labor and its outcomes. Journal of Ayub Medical College, Abbottabad: JAMC 2015;27(1):146‐50. - PubMed
Buchan 1973 {published data only}
    1. Buchan PC, Milne MK, Browning MC. The effect of continuous epidural blockade on plasma 11‐hydroxy‐corticosteroid concentrations in labour. Journal of Obstetrics and Gynaecology of the British Commonwealth 1973;80:974‐7. - PubMed
Chen 2000 {published data only}
    1. Chen LK, Hsu HW, Lin CJ, Huang CH, Tsai SK, Lee CN, et al. Effects of epidural fentanyl on labor pain during the early period of the first stage of induced labor in nulliparous women. Journal of the Formosan Medical Association 2000;99(7):549‐53. - PubMed
Cutura 2011 {published data only}
    1. Cutura N, Soldo V, Milovanovic SR, Orescanin‐Dusic Z, Curkovic A, Tomovic B, et al. Optimal dose of an anesthetic in epidural anesthesia and its effect on labor duration and administration of vacuum extractor and forceps. Clinical & Experimental Obstetrics & Gynecology 2011;38(3):247‐50. - PubMed
Ginosar 2002 {published data only}
    1. Ginosar Y, Columb M, Cohen SE, Mirikatani E, Tingle MS, Ratner EF, et al. Epidural fentanyl infusions in the presence of local anesthetics exert segmental analgesia: an MLAC infusion study in nulliparous labour [abstract]. Anesthesiology 2002;96(Suppl 1):P‐62. - PubMed
Ginosar 2003 {published data only}
    1. Ginosar Y, Columb MO, Cohen SE, Mirikatani E, Tingle MS, Ratner EF, et al. The site of action of epidural fentanyl infusions in the presence of local anesthetics: a minimum local analgesic concentration infusion study in nulliparous labor. Anesthesia & Analgesia 2003;97:1439‐45. - PubMed
Gupta 2013 {published data only}
    1. CTRI/2013/09/003968. Intravenous paracetamol as an adjunct to patient‐controlled epidural analgesia with levobupivacaine and fentanyl in labour: a randomised controlled trial. ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=6573&EncHid=&amp... (first received 11 September 2011).
    1. Gupta N, Gupta S, Agarwal A, Agarwal S, Dwivedi S, Singh A. To study the painless labour by epidural analgesia and its effects on cardiotocographic parameters and labour. International Journal of Reproduction, Contraception, Obstetrics and Gynecology 2013;2(4):666‐70.
Hood 1993 {published data only}
    1. Hood DD, Parker RL, Meis PJ. Epidural bupivacaine does not effect fetal heart rate tracing. Anesthesiology 1993;79:3A.
John 2013 {published data only}
    1. John C, Fyneface‐Ogan S, Enyindah C. A comparison of the effect of spinal analgesia and sedo‐analgesia on maternal cortisol levels during labour. 1st FIGO African Regional Conference of Gynecology and Obstetrics; 2013 Oct 2‐5; Addis Ababa, Ethiopia. 2013.
Jouppila 1976 {published data only}
    1. Joupila R, Hollmen A. The effect of segmental analgesia on maternal and foetal acid‐base balance, lactate, serum potassium and creatinine phosphokinase. Acta Anaesthesiologica Scandinavica 1976;20:259‐68. - PubMed
    1. Jouppila R. The effect of segmental epidural analgesia on maternal growth hormone, insulin, glucose and free fatty acids during labour. Annales Chirurgiae et Gynaecologiae 1976;65(6):398‐404. - PubMed
Jouppila 1980 {published data only}
    1. Jouppila R, Jouppila P, Moilanen K, Pakarinen A. The effect of segmental epidural analgesia on maternal prolactin during labour. British Journal of Obstetrics and Gynaecology 1980;87:234‐8. - PubMed
Justins 1983 {published data only}
    1. Justins DM, Knott C, Luthman J, Reynolds F. Epidural vs intramuscular fentanyl; anaesthesia and pharmacokinetics in labour. Anaesthesia 1983;38(10):937‐42. - PubMed
Kujansuu 1987 {published data only}
    1. Kujansuu E. Paracervical and epidural anaesthesia in labour pain [Paraservikaali‐ ja epiduraalipuudutus synnytyskivun lievityksessä]. Suomen Lääkärilehti 1987;42:2038‐9.
Kurjak 1974 {published data only}
    1. Kurjak A, Beazley JM. The effect of continuous lumbar epidural analgesia on the fetus, newborn child and the acid‐base status of maternal blood. Acta Medica Iugoslavica 1974;28:15‐26. - PubMed
Lassner 1981 {published data only}
    1. Lassner J, Barrier G, Talafre ML, Durupty D. Failure of extradural morphine to provide adequate pain relief in labour. British Journal of Anaesthesia 1981;53:112P.
Leong 2000 {published data only}
    1. Leong EW, Sivanesaratnam V, Oh LL, Chan YK. Epidural analgesia in primigravidae in spontaneous labour at term: a prospective study. Journal of Obstetrics & Gynaecology Research 2000;26(4):271‐5. - PubMed
MacKenzie 1996 {published data only}
    1. MacKenzie P, James K, Bower S, McGrady E, Patrick A. Plasma fentanyl levels during epidural and intravenous fentanyl infusion for labour analgesia [abstract]. International Journal of Obstetric Anesthesia 1996;5:218‐9.
Manninen 2000 {published data only}
    1. Manninen T, Aantaa R, Salonen M, Pirhonen J, Palo P. A comparison of the hemodynamic effects of paracervical block and epidural anesthesia for labor analgesia. Acta Anaesthesiologica Scandinavica 2000;44(4):441‐5. - PubMed
Martin 2003 {published data only}
    1. Martin GC, Beilin Y, Holzman IR, Ekwa‐Ekoko C. Is there an effect of giving epidural fentanyl during labor on breastfeeding? [abstract]. Pediatric Research 2003;53 Suppl:93.
McGrath 1992 {published data only}
    1. McGrath J, Chestnut D, Debruyn C. The effect of epidural bupivacaine versus intravenous nalbuphine on fetal heart rate during labor. Anesthesiology 1992;77(3A):A984.
Moreno 1997 {published data only}
    1. Moreno I, Puertas A, Mino M, Lopez JC, Manzanares S, Carrillo MP, et al. Influence of epidural analgesia on the labour induced by premature rupture of membranes. Acta Ginecologica 1997;54:211‐4.
    1. Puertas A, Mino M, Moreno M, Rodriguez C, Miranda J, Herruzo A. Influence of the epidural anaesthesia in the oxytocin labour induction of premature rupture of membranes. Prenatal and Neonatal Medicine 1996;1(Suppl 1):88.
Nafisi 2006 {published data only}
    1. Nafisi S. Effects of epidural lidocaine analgesia on labor and delivery: a randomized, prospective, controlled trial. BMC Anesthesiology 2006;6:15. - PMC - PubMed
Neri 1986 {published data only}
    1. Neri A, Nitke S, Lachman E, Ovadia J. Lumbar epidural analgesia in hypertensive patients during labour. European Journal of Obstetrics & Gynecology and Reproductive Biology 1986;22(1‐2):1‐6. - PubMed
Noble 1971 {published data only}
    1. Noble AD, Craft IL, Bootes JA, Edwards PA, Thomas DJ, Mills KL. Continuous lumbar epidural analgesia using bupivacaine: a study of the fetus and newborn child. Journal of Obstetrics and Gynaecology of the British Commonwealth 1971;78(6):559‐63. - PubMed
Polley 2000 {published data only}
    1. Polley LS, Columb MO, Naughton NN, Wagner DS, Dorantes DM, Ven CJ. Effect of intravenous versus epidural fentanyl on the minimum local analgesic concentration of epidural bupivacaine in labor. Anesthesiology 2000;93(1):122‐8. [PUBMED: 10861155] - PubMed
Revill 1979 {published data only}
    1. Revill S. Pain relief in labour: what the patient requires. First European Congress of Obstetrical Anaesthesia and Analgesia; 1979; Birmingham, UK. 1979:1‐16.
Robinson 1980 {published data only}
    1. Robinson JO, Rosen M, Evans JM, Revill SI, David H, Rees GA. Maternal opinion about analgesia for labour. A controlled trial between epidural block and intramuscular pethidine combined with inhalation. Anaesthesia 1980;35(12):1173‐81. - PubMed
Robinson 1997 {published data only}
    1. Robinson PN, Romney M, Gordon H, Loughnan BA. Outcome of labour using low dose extradural bupivacaine compared with intramuscular pethidine. British Journal of Anaesthesia 1997;79(5):675P.
Ryhanen 1984 {published data only}
    1. Ryhanen P, Jouppila R, Lanning M, Jouppila P, Hollmen A, Kouvalainen K. Effect of segmental epidural analgesia on changes in peripheral blood leucocyte counts, lymphocyte subpopulations, and in vitro transformation in healthy parturients and their newborns. Gynecologic and Obstetric Investigation 1984;17(4):202‐7. - PubMed
Solek‐Pastuszka 2009 {published data only}
    1. Solek‐Pastuszka J, Kepinski S, Makowski A, Celewicz Z, Zukowski M, Safranow K, et al. Patient‐controlled continuous epidural analgesia vs intravenous remifentanil infusion for labour anaesthesia. Anestezjologia Intensywna Terapia 2009;41(2):84‐8. - PubMed
Stourac 2014 {published data only}
    1. Stourac P, Suchomelova H, Stodulkova M, Huser M, Krikava I, Janku P, et al. Comparison of parturient‐controlled remifentanil with epidural bupivacain and sufentanil for labour analgesia: randomised controlled trial. Biomedical Papers: Journal of the Palacky University 2014;158(2):227‐32. - PubMed
Swanström 1981 {published data only}
    1. Bratteby LE. Short‐ and long‐term effects on the infant of obstetric regional anesthesia. Acta Anaesthesiologica Scandinavica 1983;27:36.
    1. Bratteby LE, Andersson L, Swanström S. Effect of obstetrical regional analgesia on the change in respiratory frequency in the newborn. British Journal of Anaesthesia 1979;51:41‐5.
    1. Swanström S, Bratteby LE. Metabolic effects of obstetric regional analgesia and of asphyxia in the newborn infant during the first two hours after birth. I. Arterial blood glucose concentrations. Acta Paediatrica Scandinavica 1981;70(6):791‐800. - PubMed
    1. Swanström S, Bratteby LE. Metabolic effects of obstetric regional analgesia and of asphyxia in the newborn infant during the first two hours after birth. II. Arterial plasma concentrations of glycerol, free fatty acids and beta‐hydroxybutyrate. Acta Paediatrica Scandinavica 1981;70(6):801‐9. - PubMed
    1. Swanström S, Bratteby LE. Metabolic effects of obstetric regional analgesia and of asphyxia in the newborn infant during the first two hours after birth. III. Adjustment of arterial blood gases and acid‐base balance. Acta Paediatrica Scandinavica 1981;70(6):811‐8. - PubMed
Tugrul 2006 {published data only}
    1. Tugrul S, Oral O, Bakacak M, Uslu H, Pekin O. Effects of epidural analgesia using ropivacaine on the mother and the newborn during labor. Saudi Medical Journal 2006;27(12):1853‐8. - PubMed
Wassen 2015 {published data only}
    1. Bonouvrie K, Bosch A, Roumen FJ, Kuijk SM, Nijhuis JG, Evers SM, et al. Epidural analgesia during labour, routinely or on request: a cost‐effectiveness analysis. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2016;207:23‐31. - PubMed
    1. Bosch AA, Goossens M, Bonouvrie K, Grimm B, Nijhuis JG, Roumen FJ, et al. Maternal quality of life in routine labor epidural analgesia versus labor analgesia on request, results of a randomized trial. Journal of Maternal‐Fetal and Neonatal Medicine 2016;29(Suppl 1):186‐7. - PubMed
    1. Wassen M, Smits L, Scheepers H, Marcus M, Neer J, Nijhuis J, et al. Routine labour epidural analgesia versus labour analgesia on request: a randomised non‐inferiority trial. BJOG: an International Journal of Obstetrics and Gynaecology 2015;122(3):344‐50. - PubMed
Wong 2005 {published data only}
    1. Scavone BM, McCarthy RJ, Wong CA, Sullivan JT. The influence of time of day of administration on duration of opioid labor analgesia. Anesthesia & Analgesia 2010;111(4):986‐91. - PubMed
    1. Wong CA, Scavone BM, Peaceman AM, McCarthy RJ, Sullivan JT, Diaz NT, et al. The risk of caesarean delivery with neuroaxial analgesia given early versus late in labour. New England Journal of Medicine 2005;352(7):655‐65. - PubMed
    1. Wong CA, Scavone BM, Sullivan JT, Strauss‐Hoder TP, McCarthy RJ. Randomized trial of neuraxial vs systemic analgesia for latent phase labor: effect on incidence of cesarean delivery [abstract]. Anesthesiology 2002;96 Suppl:Abstract no: A1047.
Wong 2009 {published data only}
    1. Wong CA, McCarthy RJ, Sullivan JT, Scavone BM, Gerber SE, Yaghmour EA. Early compared with late neuraxial analgesia in nulliparous labor induction: a randomized controlled trial. Obstetrics & Gynecology 2009;113(5):1066‐74. - PubMed
    1. Wong CA, Scavone BM, Sullivan JT, Ebarvia MJ, McCarthy RJ. The risk of cesarean delivery with early neuraxial analgesia in nulliparous induction of labor. Anesthesiology 2007;107:Abstract no: A1204.
    1. Wong CA, Sullivan JT, McCarthy RJ, Scavone BM, Patel R, Ebarvia MJ. Randomized trial of neuraxial vs. systemic analgesia for labor induction: effect on incidence of cesarean delivery [abstract]. Anesthesiology 2007;106(Suppl 1):21.
Zakowski 1994 {published data only}
    1. Zakowski MI, Ramanathan S, Sutin KM, Grant GJ, Turndorf H. Pharmacokinetic profile of morphine in parturients following intravenous or epidural administration. Regional Anesthesia 1994;19:119‐25.

References to studies awaiting assessment

Antipin 2014 {published data only}
    1. Antipin EE, Uvarov DN, Nedashkovskii EV, Kushev IP. Epidural analgesia in the first stage of labor‐‐is there an alternative?. Anesteziologiia I Reanimatologiia 2014;2014(1):18‐22. - PubMed
Gupta 2016 {published data only}
    1. Gupta K, Mitra S, Kazal S, Saroa R, Ahuja V, Goel P. I.V. paracetamol as an adjunct to patient‐controlled epidural analgesia with levobupivacaine and fentanyl in labour: a randomized controlled study. British Journal of Anaesthesia 2016;117(5):617‐22. - PubMed
Kamali 2016 {published data only}
    1. IRCT2016051820258N9. Clinical trial comparison of labor phases in painless delivery with epidural analgesia and Entonox. en.search.irct.ir/view/30306 (first received 17 Nov 2016).
Marshalov 2012 {published data only}
    1. Marshalov D, Salov I, Shifman E, Petrenko A. Influence of epidural analgesia on abdominal wall pain tension and level of abdominal pressure in labor. Regional Anesthesia and Pain Medicine 2012;37(7 Suppl):E278.
Vavrinkova 2005 {published data only}
    1. Vavrinkova B, Oborna L, Binder T, Horak J. Nalbuphine in obstetrical analgesia [Nalbuphine v porodnicke analgezii]. Ceska Gynekologie 2005;70(3):180‐3. - PubMed
Weissman 2006 {published data only}
    1. NCT00296751. Epidural analgesia versus iv meperidine for labor pain control. objective evaluation of the pain intensity influence on the autonomic nervous system. clinicaltrials.gov/ct2/show/record/NCT00296751 (first received 24 Feb 2006).

Additional references

Barragán 2011
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Bohren 2017
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Bromage 1999
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