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

Effets des opioïdes en péridurale/rachi pour l’analgésie du travail sur les aboutissements des nouveau-nés: une méta-analyse des études randomisées et contrôlées

Canadian Journal of Anesthesia/Journal canadien d'anesthésie volume 61, pages 695–709 (2014)Cite this article

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.

Résumé

Objectif

Les opioïdes administrés par péridurale/rachi sont de plus en plus souvent utilisés pour soulager la douleur du travail chez les parturientes. Quelques études indiquent que les opioïdes peuvent induire des effets indésirables chez les nouveau-nés, tels qu’une dépression respiratoire et des changements neurocomportementaux. Cette méta-analyse visait à clarifier les effets des opioïdes administrés pour l’analgésie du travail sur les nouveau-nés.

Source

Les essais cliniques randomisés pertinents ont été recherchés dans les bases de données Cochrane Central Register of Controlled Trials (CENTRAL) et EMBASE™. Les données néonatales des scores d’Apgar, les scores NACS (Neurological and Adaptive Capacity Scores) et les valeurs du pH du cordon ombilical en ont été extraits. Les analyses statistiques ont été réalisées à l’aide de Review Manager v.5.2 et de Stata® 10.

Constatations principales

Vingt et une études regroupant 2 859 participantes ont été incluses dans notre méta-analyse. Aucune différence dans l’incidence des scores d’Apgar < 7 n’a été montrée entre le groupe opioïdes et le groupe contrôle à une minute (différence de risque [DR] 0,0 %, intervalle de confiance [IC] à 95 %: −3,0 à 2,0, P = 0,78; I 2 = 0 %, IC à 95 %: 0 à 50) et à cinq minutes (DR −1,0 %, IC à 95 %: −2,0 à 1,0, P = 0,31; I 2 = 0 %, IC à 95 %: 0 à 50). Il n’y a pas eu de différence significative pour le NACS à 2 heures (différence moyenne [DM] −0,35, IC à 95 %: −1,70 à 1,01, P = 0,62; I 2 = 0 %, IC à 95 %: 0 à 79) et à 24 h (DM −0,45, IC à 95 %: −1,36 à 0,46, P = 0,33; I 2 = 3 %, IC à 95 %: 0 à 26). De même, aucune différence significative n’a été trouvée pour le pH artériel du cordon ombilical (DM −0,02, IC à 95 %: −0,06 à 0,03, P = 0,48; I 2 = 80 %, IC à 95 %: 46 à 92) et pour le pH veineux (DM −0,03, IC à 95 %: −0,07 à 0,00, P = 0,08; I 2 = 77 %, IC à 95 %: 36 à 91). Aucun biais significatif de publication n’a été identifié.

Conclusion

Les doses habituelles de fentalyl et sufentanil utilisées dans les techniques péridurales/rachi pour l’analgésie du travail sont sécuritaires pour les nouveau-nés jusqu’à 24 heures après l’accouchement. Davantage d’intérêt devra être porté aux effets secondaires à long terme chez les nouveau-nés au cours des futures études.

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Conflicts of interest

None declared.

Author information

Affiliations

  1. Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical College, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, 99 West Huaihai Road, Xuzhou, 221006, PR China

    Kai Wang MSc & Dun-Yi Qi MD

  2. Department of Intensive Care Unit, The Second Affiliated Hospital of Nantong University, Nantong University, Nantong, PR China

    Liang Cao MSc

  3. Department of Nursing, Xuzhou Stomatological Hospital, Xuzhou Medical College, Xuzhou, PR China

    Qian Deng BSc

  4. Department of Gynecology and Obstetrics, Affiliated Hospital of Xuzhou Medical College, Xuzhou, PR China

    Li-Qiang Sun MSc

  5. Department of Anesthesiology, The Second Affiliated Hospital of Nantong University, Nantong University, 6 North Haierxiang Road, Nantong, 226001, PR China

    Tian-Yu Gu MSc & Jie Song MD

Authors
  1. Kai Wang MSc
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  2. Liang Cao MSc
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  3. Qian Deng BSc
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  4. Li-Qiang Sun MSc
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  5. Tian-Yu Gu MSc
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  6. Jie Song MD
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  7. Dun-Yi Qi MD
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Correspondence to Jie Song MD or Dun-Yi Qi MD.

Additional information

This article is accompanied by an editorial. Please see Can J Anesth 2014; 61: this issue.

Author contributions

Kai Wang, Liang Cao, Jie Song, and Dun-Yi Qi helped design the study. Kai Wang, Liang Cao, and Dun-Yi Qi helped conduct the study. Kai Wang, Liang Cao, Qian Deng, and Tianyu Gu helped analyze the data. Kai Wang, Liang Cao, and Tianyu Gu helped write the manuscript. Kai Wang and Liang Cao contributed equally to this work. Li-Qiang Sun helped with the literature collection.

Appendix

Appendix

The formulas used to calculate standard deviation (SD) in this meta-analysis are listed below:

(1) The formula can be used to estimate the SD from the standard error of the mean (SEM) and the sample size (n).

$${\text{SD }} = {\text{ SEM}} \times \sqrt n$$

(2) The formula can be used to estimate the mean using the median (m) and the low and high end of the range (a and b, respectively).60

$$\overline{x} \approx \frac{a + 2m + b}{4}$$

The SD (S) can be estimated by

$$S^{2} \approx \frac{1}{12}\left( {\frac{(a - 2m + b)}{4}^{2} + (b - a)^{2} } \right)$$

(3) The formula can be used to estimate pooled SD (S) from separate SD1 (S1), n1 and SD2 (S2), n2 …

$$s^{2} \frac{{(n - 1)s^{2} + (n_{2} - 1)s_{2}^{2} + \cdots + (n_{k} - 1)s_{k}^{2} }}{{n_{1} + n_{2} + \cdots + n_{k} - k}}$$

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Wang, K., Cao, L., Deng, Q. et al. The effects of epidural/spinal opioids in labour analgesia on neonatal outcomes: a meta-analysis of randomized controlled trials. Can J Anesth/J Can Anesth 61, 695–709 (2014). https://doi.org/10.1007/s12630-014-0185-y

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Keywords

  • Remifentanil
  • Ropivacaine
  • Epidural Analgesia
  • Sufentanil
  • Apgar Score