Advertisement

Induction opioids for caesarean section under general anaesthesia: a systematic review and meta-analysis of randomised controlled trials

      Highlights

      • Opioids are effective agents to suppress the pressor response to laryngoscopy.
      • Remifentanil and alfentanil did not impact Apgar scores.
      • Remifentanil and alfentanil did not impact neonatal respiratory support requirement.

      Abstract

      Introduction

      The adverse effects of induction opioids on the neonate are poorly characterised. The study aim was to investigate whether induction opioids can be used in caesarean section without adversely affecting the neonate.

      Methods

      Six databases were systematically searched from inception until January 2019. Included studies compared induction opioids and placebo in caesarean section. Results were presented as odds ratios (95% confidence intervals) for dichotomous outcomes and weighted mean difference for continuous outcomes. An I2 statistic of >50% was significant for heterogeneity. The primary outcome was Apgar score (1 and 5 min). Secondary outcomes included neonatal adverse events, cord blood gas analyses, maternal haemodynamic parameters (systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR) and catecholamine concentrations.

      Results

      Seventeen studies (n=987) were included in the meta-analysis. Remifentanil 0.5–1 μg/kg or 2–3 μg/kg/h, alfentanil 7.5–10 μg/kg and fentanyl 0.5–1 μg/kg were compared to placebo. There was no significant difference in Apgar scores at 1 min (P=0.25, 0.58 and 0.89 respectively) for all three opioids or at 5 min for remifentanil and alfentanil (P=0.08 and 0.21 respectively). Fentanyl significantly reduced 5 min Apgar scores (P=0.002). There was no difference in neonatal airway interventions with remifentanil or alfentanil (P <0.05). All three induction opioids caused a significant reduction in maximum SBP (P <0.0001), MAP (P <0.00001) and HR (P <0.00001).

      Conclusion

      Induction opioids are effective sympatholytic agents. Remifentanil and alfentanil appear to be safe, with no significant effect on Apgar scores or neonatal airway intervention, but a well-powered trial is required to confirm these findings.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to International Journal of Obstetric Anesthesia
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • McGlennan A.
        • Mustafa A.
        General anaesthesia for caesarean section.
        BJA Educ. 2009; 9: 148-151
        • Shribman A.J.
        • Smith G.
        • Achola K.J.
        Cardiovascular and catecholamine responses to laryngoscopy with and without tracheal intubation.
        Br J Anaesth. 1987; 59: 295-299
        • Khan F.A.
        • Ullah H.
        Pharmacological agents for preventing morbidity associated with the haemodynamic response to tracheal intubation.
        Cochrane Database Syst Rev. 2013; 7: CD004087
        • Desborough J.P.
        The stress response to trauma and surgery.
        Br J Anaesth. 2000; 85: 109-117
        • Gin T.
        • O'Meara M.E.
        • Kan A.F.
        • Leung R.K.
        • Tan P.
        • Yau G.
        Plasma catecholamines and neonatal condition after induction of anaesthesia with propofol or thiopentone at caesarean section.
        Br J Anaesth. 1993; 70: 311-316
        • McDonald R.K.
        • Evans F.T.
        • Weise V.K.
        • Patrick R.W.
        Effect of morphine and nalorphine on plasma hyrocortisone levels in man.
        J Pharmacol Exp Ther. 1959; 125: 241-247
        • Maghsoudloo M.
        • Eftekhar N.
        • Ashraf M.A.
        • Khan Z.H.
        • Sereshkeh H.P.
        Does intravenous fentanyl affect Apgar scores and umbilical vessel blood gas parameters in cesarean section under general anesthesia?.
        Acta Med Iran. 2011; 49: 517-522
        • Gin T.
        • Ngan-Kee W.D.
        • Siu Y.K.
        • Stuart J.C.
        • Tan P.E.
        • Lam K.K.
        Alfentanil given immediately before the induction of anesthesia for elective cesarean delivery.
        Anesth Analg. 2000; 90: 1167-1172
        • Dann W.
        • Hutchinson A.
        • Cartwright D.
        Maternal and neonatal responses to alfentanil administered before induction of general anaesthesia for caesarean section.
        Br J Anaesth. 1987; 59: 1392-1396
        • Ngan Kee W.D.
        • Khaw K.S.
        • Ma K.C.
        • Wong A.S.
        • Lee B.B.
        • Ng F.F.
        Maternal and neonatal effects of remifentanil at induction of general anesthesia for cesarean delivery: a randomized, double-blind, controlled trial.
        Anesthesiology. 2006; 104: 14-20
        • Heesen M.
        • Klöhr S.
        • Hofmann T.
        • et al.
        Maternal and foetal effects of remifentanil for general anaesthesia in parturients undergoing caesarean section: a systematic review and meta-analysis.
        Acta Anaesthesiol Scand. 2013; 57: 29-36
      1. Howick J, Chalmers I, Greenhalgh T, Heneghan C, Liberati A. The 2011 Oxford CEBM Levels of Evidence (Introductory Document). Available at: https://www.cebm.net/wp-content/uploads/2014/06/CEBM-Levels-of-Evidence-Introduction-2.1.pdf. Published 2011. Accessed December 20, 2018.

      2. Julian PT, Altman DG. Chapter 8: Assessing risk of bias in included studies. Cochrane Database Syst Rev Web site. Available at: http://hiv.cochrane.org/sites/hiv.cochrane.org/files/uploads/Ch08_Bias.pdf. Published 2008. Accessed December 20, 2018.

        • Liberati A.
        • Altman D.G.
        • Tetzlaff J.
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.
        BMJ. 2009; 339b2700
        • Ashton W.B.
        • James M.F.
        • Janicki P.
        • Uys P.C.
        Attenuation of the pressor response to tracheal intubation by magnesium sulphate with and without alfentanil in hypertensive proteinuric patients undergoing caesarean section.
        Br J Anaesth. 1991; 67: 741-747
        • Behdad S.
        • Ayatollahi V.
        • Harrazi H.
        • Nazemian N.
        • Heiranizadeh N.
        • Baghianimoghadam B.
        Remifentanil at induction of general anesthesia for cesarean section: Double blind randomized clinical trial.
        Colombia Medica. 2013; 44: 87-91
        • Deogaonkar G.
        • Lakhe J.
        • Singla J.
        • Shidaye R.V.
        Comparison of different doses of Fentanyl for prevention of hemodynamic changes during induction and intubation in parturients undergoing caesarian section under general anesthesia.
        Sri Lankan J Anaesthesiol. 2016; 24: 28-31
        • Draisci G.
        • Valente A.
        • Suppa E.
        • et al.
        Remifentanil for cesarean section under general anesthesia: effects on maternal stress hormone secretion and neonatal well-being: a randomized trial.
        Int J Obstet Anesth. 2008; 17: 130-136
        • Karbasy S.H.
        • Derakhshan P.
        The effect of low dose fentanyl as a premedication before induction of general anesthesia on the neonatal Apgar score in cesarean section delivery: randomized, double-blind controlled trial.
        Med J Islam Repub Iran. 2016; 30: 361
        • Noskova P.
        • Blaha J.
        • Bakhouche H.
        • et al.
        Neonatal effect of remifentanil in general anaesthesia for caesarean section: a randomized trial.
        BMC Anesthesiol. 2015; 15: 38
        • Valami S.M.H.
        • Jahromi S.A.H.
        • Masoodi N.
        The effect of alfentanil on maternal haemodynamic changes due to tracheal intubation in elective caesarean sections under general anaesthesia.
        Indian J Anaesth. 2015; 59: 728
        • Yoo K.Y.
        • Jeong C.W.
        • Park B.Y.
        • et al.
        Effects of remifentanil on cardiovascular and bispectral index responses to endotracheal intubation in severe pre-eclamptic patients undergoing Caesarean delivery under general anaesthesia.
        Br J Anaesth. 2009; 102: 812-819
        • Lee E.M.
        • Kim D.Y.
        • Chung R.K.
        • Lee G.Y.
        The maternal and neonatal effect of remifentanil in general anesthesia for cesarean section.
        Reg Anesth Pain Med. 2006; 1: 48-52
        • Hasannasab B.
        • Banihashem N.
        • Matloob M.
        • Toliyat Abolhasani V.
        Effect of remifentanil on blood pressure and pulse rate of mothers and Apgar score of neonates during general anesthesia in elective cesarean section.
        J Babol Univ Med Sci. 2009; 11: 5
        • Bouattour L.
        • Ben Amar H.
        • Bouali Y.
        • et al.
        Maternal and neonatal effects of remifentanil for general anaesthesia for caesarean delivery.
        Ann Fr Anesth Reanim. 2007; 26: 299-304
        • Orhan Sungur M.
        • Ozkan Seyhan T.
        • Parlak H.
        • Altuntas E.
        • Tugrul M.
        The effects of remifentanil during general anaesthesia induction for caesarean delivery of severe preeclamptic patients.
        Euro J Anaesthesiol. 2009; 26: 151
        • Kart K.
        • Hanci A.
        Effects of remifentanil and dexmedetomidine on the mother's awareness and neonatal Apgar scores in caesarean section under general anaesthesia.
        J Int Med Res. 2018; 46: 1846-1854
        • Rout C.
        • Rocke D.
        Effects of alfentanil and fentanyl on induction of anaesthesia in patients with severe pregnancy induced hypertension.
        Br J Anaesth. 1990; 65: 468-474
        • Moore R.
        • Gavaghan D.
        • Tramer M.
        • Collins S.
        • McQuay H.
        Size is everything–large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects.
        Pain. 1998; 78: 209-216
        • Straube S.
        • Moore R.
        • Derry S.
        • Wiffen P.
        Small studies in meta-analyses. Making the best of a little.
        BMJ (Clinical Research Ed). 2010; 341c4463
        • Esler M.
        • Jennings G.
        • Lambert G.
        • Meredith I.
        • Horne M.
        • Eisenhofer G.
        Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions.
        Physiol Rev. 1990; 70: 963-985
        • Halter J.B.
        • Pflug A.E.
        • Porte Jr, D.
        Mechanism of plasma catecholamine increases during surgical stress in man.
        J Clin Endocrinol Metab. 1977; 45: 936-944