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Canadian Journal of Anesthesia/Journal canadien d'anesthésie

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01-08-2014 | Reports of Original Investigations

The effects of epidural/spinal opioids in labour analgesia on neonatal outcomes: a meta-analysis of randomized controlled trials

Authors: Kai Wang, MSc, Liang Cao, MSc, Qian Deng, BSc, Li-Qiang Sun, MSc, Tian-Yu Gu, MSc, Jie Song, MD, Dun-Yi Qi, MD

Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Issue 8/2014

Abstract

Purpose

Epidural/spinal opioids are increasingly used to relieve parturients’ pain in labour. Some studies indicate that opioids can induce side effects in neonates, such as respiratory depression and neurobehavioural changes. This meta-analysis aimed to clarify the effects of opioids in labour analgesia on neonates.

Source

PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE™ were searched for relevant randomized controlled trials (RCTs). The neonatal data of Apgar scores, Neurological and Adaptive Capacity Scores (NACS), and umbilical cord pH values were extracted. Statistical analyses were carried out using Review Manager 5.2 and Stata^® 10.

Principal findings

Twenty-one trials with 2,859 participants were included in our meta-analysis. No difference in the incidence of Apgar scores < 7 was shown between the opioid and control groups at one minute (risk difference [RD] 0.0%, 95% confidence interval [CI]: −3.0 to 2.0, P = 0.78; I ² = 0%, 95% CI: 0 to 50) and at five minutes (RD −1.0%, 95% CI: −2.0 to 1.0, P = 0.31; I ² = 0%, 95% CI: 0 to 50). No significant differences were found in the NACS at two hours (mean difference [MD] −0.35, 95% CI: −1.70 to 1.01, P = 0.62; I ² = 0%, 95% CI: 0 to 79) and at 24 hr (MD −0.45, 95% CI: −1.36 to 0.46, P = 0.33; I ² = 3%, 95% CI: 0 to 26). Also, no significant differences were found in umbilical cord artery pH (MD −0.02, 95% CI: −0.06 to 0.03, P = 0.48; I ² = 80%, 95% CI: 46 to 92) and vein pH (MD −0.03, 95% CI: −0.07 to 0.00, P = 0.08; I ² = 77%, 95% CI: 36 to 91). No significant publication bias was found.

Conclusion

The common doses of fentanyl and sufentanil used with an epidural/spinal technique in labour analgesia are safe for neonates up to 24 hr after delivery. In future studies, more attention should be paid to the long-term side effects in neonates.

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Melzack R. The myth of painless childbirth (the John J. Bonica lecture). Pain 1984; 19: 321-37.PubMedCrossRef

Lavand’homme P. Chronic pain after vaginal and cesarean delivery: a reality questioning our daily practice of obstetric anesthesia. Int J Obstet Anesth 2010; 19: 1-2.PubMedCrossRef

Anim-Somuah M, Smyth RM, Jones L. Epidural versus non-epidural or no analgesia in labour. Cochrane Database Syst Rev 2011; 12: CD000331.

George RB, Allen TK, Habib AS. Intermittent epidural bolus compared with continuous epidural infusions for labor analgesia: a systematic review and meta-analysis. Anesth Analg 2013; 116: 133-44.PubMedCrossRef

Kane KM, Percival N, Please NW, Roberts H, Snow P. Effects of some analgesic drugs used in childbirth; with special reference to variation in respiratory minute volume of the newborn. Lancet 1957; 272: 128-32.PubMed

Hamza J, Benlabed M, Orhant E, et al. Neonatal pattern of breathing during active and quiet sleep after maternal administration of meperidine. Pediatr Res 1992; 32: 412-6.PubMedCrossRef

Koch G, Wendel H. The effect of pethidine on the postnatal adjustment of respiration and acid base balance. Acta Obstet Gynecol Scand 1968; 47: 27-37.PubMedCrossRef

Hodgkinson R, Bhatt M, Wang CN. Double-blind comparison of the neurobehaviour of neonates following the administration of different doses of meperidine to the mother. Can Anaesth Soc J 1978; 25: 405-11.PubMedCrossRef

Kariniemi V, Ammala P. Effects of intramuscular pethidine on fetal heart rate variability during labour. Br J Obstet Gynaecol 1981; 88: 718-20.PubMedCrossRef

10.

O’Sullivan G. Analgesia and anaesthesia in labour. Curr Obstet Gynaecol 2005; 15: 9-17.CrossRef

11.

Evron S, Ezri T. Options for systemic labor analgesia. Curr Opin Anaesthesiol 2007; 20: 181-5.PubMedCrossRef

12.

Rayburn WF, Smith CV, Parriott JE, Woods RE. Randomized comparison of meperidine and fentanyl during labor. Obstet Gynecol 1989; 74: 604-6.PubMed

13.

Tian F, Wang K, Hu J, et al. Continuous spinal anesthesia with sufentanil in labor analgesia can induce maternal febrile responses in puerperas. Int J Clin Exp Med 2013; 6: 334-41.PubMedCentralPubMed

14.

Akkamahadevi P, Srinivas H, Siddesh A, Kadli N. Comparision of efficacy of sufentanil and fentanyl with low-concentration bupivacaine for combined spinal epidural labour analgesia. Indian J Anaesth 2012; 56: 365-9.PubMedCentralPubMedCrossRef

15.

Nakamura G, Ganem EM, Rugolo LM, Castiglia YM. Effects on mother and fetus of epidural and combined spinal-epidural techniques for labor analgesia. Rev Assoc Med Bras 2009; 55: 405-9.PubMedCrossRef

16.

Loftus JR, Hill H, Cohen SE. Placental transfer and neonatal effects of epidural sufentanil and fentanyl administered with bupivacaine during labor. Anesthesiology 1995; 83: 300-8.PubMedCrossRef

17.

Porter J, Bonello E, Reynolds F. Effect of epidural fentanyl on neonatal respiration. Anesthesiology 1998; 89: 79-85.PubMedCrossRef

18.

Douma MR, Middeldorp JM, Verwey RA, Dahan A, Stienstra R. A randomised comparison of intravenous remifentanil patient-controlled analgesia with epidural ropivacaine/sufentanil during labour. Int J Obstet Anesth 2011; 20: 118-23.PubMedCrossRef

19.

Malvasi A, Tinelli A, Brizzi A, et al. Intrapartum sonography for occiput posterior detection in early low dose combined spinal epidural analgesia by sufentanil and ropivacaine. Eur Rev Med Pharmacol Sci 2010; 14: 799-806.PubMed

20.

Kalra S, Saraswat N, Agnihotri GS. Comparison of efficacy of bupivacaine and fentanyl with bupivacaine and sufentanil for epidural labor analgesia. Saudi J Anaesth 2010; 4: 178-81.PubMedCentralPubMedCrossRef

21.

Salim R, Nachum Z, Moscovici R, Lavee M, Shalev E. Continuous compared with intermittent epidural infusion on progress of labor and patient satisfaction. Obstet Gynecol 2005; 106: 301-6.PubMedCrossRef

22.

Beilin Y, Bodian CA, Weiser J, et al. Effect of labor epidural analgesia with and without fentanyl on infant breast-feeding: a prospective, randomized, double-blind study. Anesthesiology 2005; 103: 1211-7.PubMedCrossRef

23.

Nikkola EM, Jahnukainen TJ, Ekblad UU, Kero PO, Salonen MA. Neonatal monitoring after maternal fentanyl analgesia in labor. J Clin Monit Comput 2000; 16: 597-608.PubMedCrossRef

24.

Gambling D, Berkowitz J, Farrell TR, Pue A, Shay D. A randomized controlled comparison of epidural analgesia and combined spinal-epidural analgesia in a private practice setting: pain scores during first and second stages of labor and at delivery. Anesth Analg 2013; 116: 636-43.PubMedCrossRef

25.

Lilker S, Rofaeel A, Balki M, Carvalho JC. Comparison of fentanyl and sufentanil as adjuncts to bupivacaine for labor epidural analgesia. J Clin Anesth 2009; 21: 108-12.PubMedCrossRef

26.

Amiel-Tison C, Barrier G, Shnider SM, Levinson G, Hughes SC, Stefani SJ. A new neurologic and adaptive capacity scoring system for evaluating obstetric medications in full-term newborns. Anesthesiology 1982; 56: 340-50.PubMedCrossRef

27.

Jones L, Othman M, Dowswell T, et al. Pain management for women in labour: an overview of systematic reviews. Cochrane Database Syst Rev 2012; 3: CD009234.

28.

Bauer ME, Kountanis JA, Tsen LC, Greenfield ML, Mhyre JM. Risk factors for failed conversion of labor epidural analgesia to cesarean delivery anesthesia: a systematic review and meta-analysis of observational trials. Int J Obstet Anesth 2012; 21: 294-309.PubMedCrossRef

29.

Fleet J, Jones M, Belan I. Non-axial administration of fentanyl in childbirth: a review of the efficacy and safety of fentanyl for mother and neonate. Midwifery 2011; 27: e106-13.PubMedCrossRef

30.

Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration: Wiley Online Library; 2008 .

31.

Friedrich JO, Adhikari NK, Beyene J. Inclusion of zero total event trials in meta-analyses maintains analytic consistency and incorporates all available data. BMC Med Res Methodol 2007; 7: 5.PubMedCentralPubMedCrossRef

32.

Greenland S, Robins JM. Estimation of a common effect parameter from sparse follow-up data. Biometrics 1985; 41: 55-68.PubMedCrossRef

33.

Vettermann J, Thomas H, Lischke V, Asskali F. Repeated addition of fentanyl to bupivacaine peridural analgesia in labor. Clinical action and fentanyl plasma level (German). Anaesthesist 1996; 45: 428-36.PubMedCrossRef

34.

Melchor JC, Ruiz A, Santos C, et al. Comparative study of peridural anesthesia with bupivacaine alone and combined with fentanyl during vaginal delivery (Spanish). Rev Esp Anestesiol Reanim 1991; 38: 80-2.PubMed

35.

Desprats R, Mandry J, Grandjean H, Amar B, Pontonnier G, Lareng L. Peridural analgesia during labor: comparative study of a fentanyl-marcaine combination and marcaine alone (French). J Gynecol Obstet Biol Reprod (Paris) 1983; 12: 901-5.

36.

Pace MC, Aurilio C, Bulletti C, Iannotti M, Passavanti MB, Palagiano A. Subarachnoid analgesia in advanced labor: a comparison of subarachnoid analgesia and pudendal block in advanced labor: analgesic quality and obstetric outcome. Ann N Y Acad Sci 2004; 1034: 356-63.PubMedCrossRef

37.

Lee BB, Ngan Kee WD, Lau WM, Wong AS. Epidural infusions for labor analgesia: a comparison of 0.2% ropivacaine, 0.1% ropivacaine, and 0.1% ropivacaine with fentanyl. Reg Anesth Pain Med 2002; 27: 31-6.PubMedCrossRef

38.

Ruban P, Sia AT, Chong JL. The effect of adding fentanyl to ropivacaine 0.125% on patient-controlled epidural analgesia during labour. Anaesth Intensive Care 2000; 28: 517-21.PubMed

39.

Olofsson C, Ekblom A, Ekman-Ordeberg G, Irestedt L. Obstetric outcome following epidural analgesia with bupivacaine-adrenaline 0.25% or bupivacaine 0.125% with sufentanil—a prospective randomized controlled study in 1000 parturients. Acta Anaesthesiol Scand 1998; 42: 284-92.

40.

Claes B, Soetens M, Van Zundert A, Datta S. Clonidine added to bupivacaine-epinephrine-sufentanil improves epidural analgesia during childbirth. Reg Anesth Pain Med 1998; 23: 540-7.PubMed

41.

Steinberg RB, Dunn SM, Dixon DE, Rehm KL, Pastides H, Xu X. Comparison of sufentanil, bupivacaine, and their combination for epidural analgesia in obstetrics. Reg Anesth 1992; 17: 131-8.PubMed

42.

Vertommen JD, Vandermeulen E, Van Aken H, et al. The effects of the addition of sufentanil to 0.125% bupivacaine on the quality of analgesia during labor and on the incidence of instrumental deliveries. Anesthesiology 1991; 74: 809-14.PubMedCrossRef

43.

Murphy JD, Henderson K, Bowden MI, Lewis M, Cooper GM. Bupivacaine versus bupivacaine plus fentanyl for epidural analgesia: effect on maternal satisfaction. BMJ 1991; 302: 564-7.PubMedCentralPubMedCrossRef

44.

Viscomi CM, Hood DD, Melone PJ, Eisenach JC. Fetal heart rate variability after epidural fentanyl during labor. Anesth Analg 1990; 71: 679-83.PubMedCrossRef

45.

Jones G, Paul DL, Elton RA, McClure JH. Comparison of bupivacaine and bupivacaine with fentanyl in continuous extradural analgesia during labour. Br J Anaesth 1989; 63: 254-9.PubMedCrossRef

46.

Van Steenberge A, Debroux HC, Noorduin H. Extradural bupivacaine with sufentanil for vaginal delivery. A double-blind trial. Br J Anaesth 1987; 59: 1518-22.PubMedCrossRef

47.

Marcos Vidal JM, Gutierrez Fernandez A, Ceron Pena L, Baticon Escudero PM, Gutierrez Fernandez J, Mourad MM. Comparison of intrathecal fentanyl and bupivacaine in combined spinal-epidural obstetric analgesia (Spanish). Rev Esp Anestesiol Reanim 2008; 55: 341-7.

48.

Jorrot JC, Lirzin JD, Dailland P, Jacquinot P, Conseiller C. A combination of sufentanil and 0.25% bupivacaine administered epidurally for obstetrical analgesia. Comparison with fentanyl and placebo (French). Ann Fr Anesth Reanim 1989; 8: 321-5.PubMedCrossRef

49.

Milon D, Lavenac G, Noury D, et al. Epidural anesthesia during labor: comparison of 3 combinations of fentanyl-bupivacaine and bupivacaine alone (French). Ann Fr Anesth Reanim 1986; 5: 18-23.PubMedCrossRef

50.

Chong DS, Karlberg J. Refining the Apgar score cut-off point for newborns at risk. Acta Paediatr 2004; 93: 53-9.PubMedCrossRef

51.

Apgar V. A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg 1953; 32: 260-7.PubMedCrossRef

52.

Scanlon JW, Brown WU Jr, Weiss JB, Alper MH. Neurobehavioral responses of newborn infants after maternal epidural anesthesia. Anesthesiology 1974; 40: 121-8.PubMedCrossRef

53.

Leong WL, Sng BL, Sia AT. A comparison between remifentanil and meperidine for labor analgesia: a systematic review. Anesth Analg 2011; 113: 818-25.PubMed

54.

Fahey J, King TL. Intrauterine asphyxia: clinical implications for providers of intrapartum care. J Midwifery Womens Health 2005; 50: 498-506.PubMedCrossRef

55.

Malin GL, Morris RK, Khan KS. Strength of association between umbilical cord pH and perinatal and long term outcomes: systematic review and meta-analysis. BMJ 2010; 340: c1471.PubMedCentralPubMedCrossRef

56.

Schnabel A, Hahn N, Broscheit J, et al. Remifentanil for labour analgesia: a meta-analysis of randomised controlled trials. Eur J Anaesthesiol 2012; 29: 177-85.PubMedCrossRef

57.

Landau R, Liu SK, Blouin JL, Carvalho B. The effect of OPRM1 and COMT genotypes on the analgesic response to intravenous fentanyl labor analgesia. Anesth Analg 2013; 116: 386-91.PubMedCrossRef

58.

Jaskot B, Czeszynska Maria B, Konefal H, Pastuszka J. Method of analgesia for labor in relation to newborn condition, cord blood cortisol and interleukin-6 levels (Polish). Ginekol Pol 2011; 82: 767-74.PubMed

59.

Capogna G, Camorcia M, Stirparo S, Farcomeni A. Programmed intermittent epidural bolus versus continuous epidural infusion for labor analgesia: the effects on maternal motor function and labor outcome. A randomized double-blind study in nulliparous women. Anesth Analg 2011; 113: 826-31.PubMed

60.

Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005; 5: 13.PubMedCentralPubMedCrossRef

Title: The effects of epidural/spinal opioids in labour analgesia on neonatal outcomes: a meta-analysis of randomized controlled trials
Authors: Kai Wang, MSc
Liang Cao, MSc
Qian Deng, BSc
Li-Qiang Sun, MSc
Tian-Yu Gu, MSc
Jie Song, MD
Dun-Yi Qi, MD
Publication date: 01-08-2014
Publisher: Springer US
Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Issue 8/2014
Print ISSN: 0832-610X
Electronic ISSN: 1496-8975
DOI: https://doi.org/10.1007/s12630-014-0185-y

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

The effects of epidural/spinal opioids in labour analgesia on neonatal outcomes: a meta-analysis of randomized controlled trials

Abstract

Purpose

Source

Principal findings

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Source

Principal findings

Conclusion

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