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Vasopressors for managing maternal hypotension during cesarean section under spinal anesthesia: A systematic review and network meta-analysis

  • Choongun Ryu1
  • Geun-Joo Choi1
  • Yong-Hee Park1
  • Ye-Jin Cho2
  • Hyun Kang1

1Department of Anesthesiology and Pain Medicine, Chung-Ang University College of Medicine, 06911 Seoul, Republic of Korea

2Department of Anesthesiology and Pain Medicine, Chung-Ang University Hospital, 06973 Seoul, Republic of Korea

DOI: 10.22514/sv.2020.16.0094 Vol.17,Issue 1,January 2021 pp.152-168

Published: 08 January 2021

*Corresponding Author(s): Hyun Kang E-mail: roman00@naver.com

Abstract

Introduction: Spinal anesthesia during elective cesarean section often induces maternal hypotension, and vasopressors are the most reliable agents to counteract this. We conducted a systematic review and network meta-analysis to compare and specifically evaluate the efficacy of vasopressors in preventing maternal hypotension (effectiveness) and decreasing fetal acidosis (safety) in parturients undergoing spinal anesthesia for cesarean section. Methods: We performed a systematic and comprehensive search to identify all randomized controlled studies on vasopressors to manage maternal hypotension during cesarean section under spinal anesthesia, which had been published until June 30, 2019 and updated until September 20, 2020. A network meta-analysis was conducted to combine direct and indirect comparisons of vasopressors. The primary outcomes included minimum systolic blood pressure, the incidence of hypotension, and fetal acidosis. Stata SE 15.0 was used for the meta-analysis. Results: Forty-five studies (n = 3,369) with six different vasopressors injected using various methods were included. Based on the surface under the cumulative ranking curve (SUCRA) value, intravenous (IV) continuous infusion of mephentermine (SUCRA value 83.4%) was the most efficacious vasopressor with the lowest incidence of hypotension, followed by continuous infusion of ephedrine with norepinephrine bolus (81.6%) and norepinephrine (76.4%). Compared with an IV bolus injection, all analyzed vasopressors were more effective when they were infused continuously for managing maternal hypotension. In terms of safety, only angiotensin II as an IV continuous infusion (94.7%) was efficacious in preventing fetal acidosis, resulting in a pH closer to 7.4, and there were no significant differences in umbilical arterial pH between the test and control groups. Conclusion: Clinicians should continuously infuse vasopressors to manage maternal hypotension during cesarean section under spinal anesthesia. According to SUCRA, norepinephrine administered as an IV continuous infusion was the third most efficacious vasopressor with the lowest incidence of maternal hypotension, and it could be a potential alternative to phenylephrine. Meanwhile, only angiotensin II administered as an IV continuous infusion caused less umbilical arterial acidosis than the control group.

Keywords

Spinal anesthesia; Cesarean section; Hypotension; Meta-analysis; Systematic review; Vasopressors

Cite and Share

Choongun Ryu,Geun-Joo Choi,Yong-Hee Park,Ye-Jin Cho,Hyun Kang. Vasopressors for managing maternal hypotension during cesarean section under spinal anesthesia: A systematic review and network meta-analysis. Signa Vitae. 2021. 17(1);152-168.

References

[1] Riley ET, Cohen SE, Macario A, Desai JB, Ratner EF. Spinal versus epidural anesthesia for cesarean section: a comparison of time efficiency, costs, charges, and complications. Anesthesia and Analgesia. 1995; 80: 709- 712.

[2] Fettes PD, Jansson JR, Wildsmith JA. Failed spinal anaesthesia: mechanisms, management, and prevention. The British Journal of Anaesthesia. 2009; 102: 739-748.

[3] Dyer RA, Biccard BM. Ephedrine for spinal hypotension during elective caesarean section: the final nail in the coffin? Acta Anaesthesiologica Scandinavica. 2012; 56: 807-809.

[4] Clark RB, Thompson DS, Thompson CH. Prevention of spinal hypoten-sion associated with Cesarean section. Anesthesiology. 1976; 45: 670-674.

[5] Hall PA, Bennett A, Wilkes MP, Lewis M. Spinal anaesthesia for caesarean section: comparison of infusions of phenylephrine and ephedrine. The British Journal of Anaesthesia. 1994; 73: 471-474. Kang

[6] YG, Abouleish E, Caritis S. Prophylactic intravenous ephedrine infusion during spinal anesthesia for cesarean section. Anesthesia and Analgesia. 1982; 61: 839-842.

[7] Cyna AM, Andrew M, Emmett RS, Middleton P, Simmons SW. Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Cochrane Database of Systematic Reviews. 2006; 4: Cd002251.

[8] Ralston DH, Shnider SM, DeLorimier AA. Effects of equipotent ephedrine, metaraminol, mephentermine, and methoxamine on uterine blood flow in the pregnant ewe. Anesthesiology. 1974; 40: 354-370.

[9] Cooper DW, Carpenter M, Mowbray P, Desira WR, Ryall DM, Kokri MS. Fetal and maternal effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology. 2002; 97: 1582-1590.

[10] Veeser M, Hofmann T, Roth R, Klöhr S, Rossaint R, Heesen M. Vasopressors for the management of hypotension after spinal anesthesia for elective caesarean section. Systematic review and cumulative meta-analysis. Acta Anaesthesiologica Scandinavica. 2012; 56: 810-816.

[11] Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesthesia and Analgesia. 2002; 94: 920-926.

[12] Heesen M, Kolhr S, Rossaint R, Traube S. Prophylactic phenylephrine for caesarean section under spinal anaesthesia: systematic review and meta-analysis. Anaesthesia. 2014; 69: 143-165.

[13] Ngan Kee WD, Lee SW, Ng FF, Tan PE, Khaw KS. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology. 2015; 122: 736-745.

[14] Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. PRISMA-P Group: Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. British Medical Journal (Clinical Research Edition). 2015; 350: g7647.

[15] Ryu C, Choi GJ, Park YH, Kang H. Vasopressors for the management of maternal hypotension during cesarean section under spinal anesthesia: A systematic review and network meta-analysis protocol. Medicine. 2019; 98: e13947.

[16] Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions. Chichester, England, Wiley-Blackwell, 2008.

[17] Cornell JE. The PRISMA extension for network meta-analysis: bringing clarity and guidance to the reporting of systematic reviews incorporating network meta-analyses. Annals of Internal Medicine. 2015; 162: 797-798.

[18] Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS One. 2013; 8: e76654.

[19] White IR, Barrett JK, Jackson D, Higgins JP. Consistency and incon- sistency in network meta-analysis: model estimation using multivariate meta-regression. Research Synthesis Methods. 2012; 3: 111-125.

[20] Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. Journal of Clinical Epidemiology. 2011; 64: 163-171.

[21] Riley RD, Higgins JP, Deeks JJ. Interpretation of random effects meta-analyses. British Medical Journal (Clinical Research Edition). 2011; 342: d549.

[22] Gutsche BB. Prophylactic ephedrine preceding spinal analgesia for cesarean section. Anesthesiology. 1976; 45: 462-465.

[23] Moran DH, Perillo M, LaPorta RF, Bader AM, Datta S. Phenylephrine in the prevention of hypotension following spinal anesthesia for cesarean delivery. Journal of Clinical Anesthesia. 1991; 3: 301-305.

[24] Alahuhta S, Räsänen J, Jouppila P, Jouppila R, Hollmén AI. Ephedrine and phenylephrine for avoiding maternal hypotension due to spinal anaesthesia for caesarean section. Effects on uteroplacental and fetal haemodynamics. The International Journal of Obstetric Anesthesia. 1992; 1: 129-134.

[25] Pierce ET, Carr DB, Datta S. Effects of ephedrine and phenylephrine on maternal and fetal artrial natriuretic peptide levels during elective cesarean section. Acta Anaesthesiologica Scandinavica. 1994; 38: 48-51.

[26] Ramin SM, Ramin KD, Cox K, Magness RR, Shearer VE, Gant NF. Comparison of prophylactic angiotensin II versus ephedrine infusion for prevention of maternal hypotension during spinal anesthesia. American Journal of Obstetrics and Gynecology. 1994; 171: 734-739.

[27] LaPorta RF, Arthur GR, Datta S. Phenylephrine in treating maternal hypotension due to spinal anaesthesia for caesarean delivery: effects on neonatal catecholamine concentrations, acid base status and Apgar scores. Acta Anaesthesiologica Scandinavica. 1995; 39: 901-905.

[28] Shearer VE, Ramin SM, Wallace DH, Dax JS, Gilstrap LC 3rd. Fetal effects of prophylactic ephedrine and maternal hypotension during regional anesthesia for cesarean section. Journal of Maternal-Fetal & Neonatal Medicine. 1996; 5: 579-584.

[29] Thomas DG, Robson SC, Redfern N, Hughes D, Boys RJ. Randomized trial of bolus phenylephrine or ephedrine for maintenance of arterial pressure during spinal anaesthesia for Caesarean section. British Journal of Anaesthesia. 1996; 76: 61-65.

[30] Chan WS, Irwin MG, Tong WN, Lam YH. Prevention of hypotension during spinal anaesthesia for caesarean section: ephedrine infusion versus fluid preload. Anaesthesia. 1997; 52: 908-913.

[31] Vincent RD Jr, Werhan CF, Norman PF, Shih GH, Chestnut DH, Ray T, et al. Prophylactic angiotensin II infusion during spinal anesthesia for elective cesarean delivery. Anesthesiology. 1998; 88: 1475-1479.

[32] Webb AA, Shipton EA. Re-evaluation of i.m. ephedrine as prophylaxis against hypotension associated with spinal anaesthesia for Caesarean section. Canadian Journal of Anesthesia. 1998; 45: 367-369.

[33] Tsen LC, Boosalis P, Segal S, Datta S, Bader AM. Hemodynamic effects of simultaneous administration of intravenous ephedrine and spinal anesthesia for cesarean delivery. Journal of Clinical Anesthesia. 2000; 12: 378-382.

[34] Vercauteren MP, Coppejans HC, Hoffmann VH, Mertens E, Adriaensen HA. Prevention of hypotension by a single 5-mg dose of ephedrine during small-dose spinal anesthesia in prehydrated cesarean delivery patients. Anesthesia and Analgesia. 2000; 90: 324-327.

[35] Mercier FJ, Riley ET, Frederickson WL, Roger-Christoph S, Benhamou D, Cohen SE. Phenylephrine added to prophylactic ephedrine infusion during spinal anesthesia for elective cesarean section. Anesthesiology. 2001; 95: 668-674.

[36] Ngan Kee WD, Lau TK, Khaw KS, Lee BB. Comparison of metaraminol and ephedrine infusions for maintaining arterial pressure during spinal anesthesia for elective cesarean section. Anesthesiology. 2001; 95: 307-313.

[37] Cooper DW, Jeyaraj L, Hynd R, Thompson R, Meek T, Ryall DM, et al. Evidence that intravenous vasopressors can affect rostral spread of spinal anesthesia in pregnancy. Anesthesiology. 2004; 101: 28-33.

[38] Turkoz A, Togal T, Gokdeniz R, Toprak HI, Ersoy O. Effectiveness of intravenous ephedrine infusion during spinal anaesthesia for caesarean section based on maternal hypotension, neonatal acid-base status and lactate levels. Anaesthesia and Intensive Care Medicine. 2002; 30: 316-320.

[39] Cooper DW, Gibb SC, Meek T, Owen S, Kokri MS, Malik AT, et al. Effect of intravenous vasopressor on spread of spinal anaesthesia and fetal acid-base equilibrium. British Journal of Anaesthesia. 2007; 98: 649-656.

[40] Ngan Kee WD, Khaw KS, Ng FF, Lee BB. Prophylactic phenylephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery. Anesthesia and Analgesia. 2004; 98: 815-821.

[41] Desalu I, Kushimo OT. Is ephedrine infusion more effective at preventing hypotension than traditional prehydration during spinal anaesthesia for caesarean section in African parturients? International Journal of Obstetric Anesthesia. 2005; 14: 294-299.

[42] Kansai A, Mohta M, Sethi AK, yagi A, Kumar P. Randomised trial of intravenous infusion of ephedrine or mephentermine for management of hypotension during spinal anaesthesia for Caesarean section. Anaesthe-sia. 2005; 60: 28-34.

[43] Loughrey JP, Yao N, Datta S, Segal S, Pian-Smith M, Tsen LC. Hemodynamic effects of spinal anesthesia and simultaneous intravenous bolus of combined phenylephrine and ephedrine versus ephedrine for cesarean delivery. International Journal of Obstetric Anesthesia. 2005; 14: 43-47.

[44] Saravanan S, Kocarev M, Wilson RC, Watkins E, Columb MO, Lyons G. Equivalent dose of ephedrine and phenylephrine in the prevention of post-spinal hypotension in Caesarean section. British Journal of Anaesthesia. 2006; 96: 95-99.

[45] Langesaeter E, Rosseland LA, Stubhaug A. Continuous invasive blood pressure and cardiac output monitoring during cesarean delivery: a randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion. Anesthesiology. 2008; 109: 856-863.

[46] Ngan Kee WD, Khaw KS, Lau TK, Ng FF, Chui K, Ng KL. Randomised double-blinded comparison of phenylephrine vs ephedrine for maintaining blood pressure during spinal anaesthesia for non-elective Caesarean section. Anaesthesia. 2008; 63: 1319-1326.

[47] Dyer RA, Reed AR, van Dyk D, Arcache MJ, Hodges O, Lombard CJ, et al. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology. 2009; 111: 753-765.

[48] Magalhães E, Govêia CS, de Araúdio Ladeira LC, Nascimento BG, Kluthcouski SM. Ephedrine versus phenylephrine: prevention of hypotension during spinal block for cesarean section and effects on the fetus. Brazilian Journal of Anesthesiology. 2009; 59: 11-20.

[49] Ngan Kee WD, Khaw KS, Tan PE, Ng FF, Karmakar MK. Placental transfer and fetal metabolic effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology. 2009; 111: 506-512.

[50] Adigun TA, Amanor-Boadu SD, Soyannwo OA. Comparison of intra-venous ephedrine with phenylephrine for the maintenance of arterial blood pressure during elective caesarean section under spinal anaesthesia. African Journal of Medicine and Medical Sciences. 2010; 39: 13-20.

[51] Guillon A, Leyre S, Remérand F, Taihlan B, Perrotin F, Fusciardi J, et al. Modification of Tp-e and QTc intervals during caesarean section under spinal anaesthesia. Anaesthesia. 2010; 65: 337-342.

[52] Mohta M, Janani SS, Sethi AK, Agarwal D, Tyagi A. Comparison of phenylephrine hydrochloride and mephentermine sulphate for prevention of post spinal hypotension. Anaesthesia. 2010; 65: 1200-1205.

[53] Prakash S, Pramanik V, Chellani H, Salhan S, Gogia AR. Maternal and neonatal effects of bolus administration of ephedrine and phenylephrine during spinal anaesthesia for caesarean delivery: a randomized study. International Journal of Obstetric Anesthesia. 2010; 19: 24-30.

[54] Das S, Mukhopadhyay S, Mandal M, Mandal S, Basu SR. A comparative study of infusions of phenylephrine, ephedrine and phenylephrine plus ephedrine on maternal haemodynamics in elective caesarean section. Indian Journal of Anaesthesia. 2011; 55: 578-583.

[55] Bhardwaj N, Jain K, Arora S, Bharti N. A comparison of three vasopressors for tight control of maternal blood pressure during cesarean section under spinal anesthesia: Effect on maternal and fetal outcome. Journal of Anaesthesiology Clinical Pharmacology. 2013; 29: 26-31.

[56] Siddik-Sayyid SM, Taha SK, Kanazi GE, Aouad MT. A randomized controlled trial of variable rate phenylephrine infusion with rescue phenylephrine boluses versus rescue boluses alone on physician inter-ventions during spinal anesthesia for cesarean delivery. Anesthesia and Analgesia. 2014; 118: 611-618.

[57] Jain K, Makkar JK, Subramani Vp S, Gander S, Kumar P. A randomized trial comparing prophylactic phenylephrine and ephedrine infusion during spinal anesthesia for emergency cesarean delivery in cases of acute fetal compromise. Journal of Clinical Anesthesia. 2016; 34: 208-215.

[58] Mon W, Stewart A, Fernando R, Ashpole K, El-Wahab N, MacDonald S, et al. Cardiac output changes with phenhlephrine and ephedrine infusions during spinal anesthesia for cesarean section: A randomized, double-blind trial. Journal of Clinical Anesthesia. 2017; 37: 43-48.

[59] Uerpairojkit K, Anusorntanawat R, Sirisabya A, Chaichalothorn M, Charuluxananan S. Neonatal effects after vasopressor during spinal anesthesia for cesarean section: a multicenter, randomized controlled trial. International Journal of Obstetric Anesthesia. 2017; 32: 41-47.

[60] Vallejo MC, Attaallah AF, Elzamzamy OM, Cifarelli DT, Phelps AL, Hobbs GR, et al. An open-label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during cesarean delivery. International Journal of Obstetric Anesthesia. 2017; 29: 18-25.

[61] Mohta M, Garg A, Chilkoti GT, Malhotra RK. A randomised controlled trial of phenylephrine and noradrenaline boluses for treatment of postspinal hypotension during elective caesarean section. Anaesthesia. 2019; 74: 850-855.

[62] Xu S, Mao M, Zhang S, Qian R, Shen X, Shen J, et al. A randomized double-blind study comparing prophylactic norepinephrine and ephedrine infusion for preventing maternal spinal hypotension during elective caesarean section under spinal anesthesia: A CONSORT-compliant article. Medicine. 2019; 98: e18311.

[63] Chen Y, Guo L, Shi Y, Ma G, Xue W, He L, et al. Norepinephrine prophylaxis for postspinal anesthesia hypotension in parturient under-going caesarean section: a randomized, controlled trial. Archives of Gynecology and Obstetrics. 2020; 302: 829-836.

[64] Wang X, Mao M, Zhang S, Wang ZH, Xu SQ, Shen XF. Bolus norepinephrine and phenylephrine for maternal hypotension during elective caesarean section with spinal anesthesia: a randomized, double-blinded study. Chinese Medical Journal (English) 2020; 133: 509-516.

[65] Andres RL, Saade G, Gilstrap LC, Wilkins I, Witlin A, Zlatnik F, et al. Association between umbilical blood gas parameters and neonatal morbidity and death in neonates with pathologic fetal acidemia. American Journal of Obstetrics and Gynecology. 1999; 181: 867-871.

[66] Sykes GS, Molloy PM, Johnson P, Gu W, Ashworth F, Stirrat GM, et al. Do Apgar scores indicate asphyxia? Lancet 1982; 27: 494-496.

[67] Kostro M, Jacyna N, Gluszczak-Idziakowska E, Sułek-Kamas K, Jakiel G, Wilińska M. Factors affecting the differentiation of the Apgar score and the biochemical correlation of fetal well-being, a prospective observational clinical study. Developmental Period Medicine. 2018; 22: 238- 246.

[68] American College of Obstetrics and Gynecology. Task Force on Neonatal Encephalopathy: American Academy of Pediatrics. Neonatal Encephalopathy and Neurologic Oucome, 2nd edition. Washington, DC: American College of Obstetricians and Gynecologists, 2014.

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