Efficacy and Safety of Different Norepinephrine Regimens for Prevention of Spinal Hypotension in Cesarean Section: A Randomized Trial

Daili Chen, Xiaofei Qi, Xiaolei Huang, Yang Xu, Feilong Qiu, Yuting Yan, Yuantao Li, Daili Chen, Xiaofei Qi, Xiaolei Huang, Yang Xu, Feilong Qiu, Yuting Yan, Yuantao Li

Abstract

The aim of this paper is to evaluate the efficacy and safety of three different norepinephrine dosing regimens for preventing spinal hypotension in cesarean section. In this randomized double-blinded controlled study, 120 parturients scheduled for elective section delivery under spinal anesthesia were assigned to 1 of 4 groups. In the control group, patients received saline infusion. In three norepinephrine groups, the infusion dosage regimens were 5, 10, and 15 μg/kg/h, respectively. Hypotension was treated with a rescue bolus of 10 μg norepinephrine. The study protocol was continued until the end of surgery. The primary outcome was the proportion of participants that underwent hypotension. The proportion of hypotension participants was significantly reduced in the norepinephrine groups (37.9%, 20%, and 25%, respectively) compared to that in the control group (86.7%). However, the highest dose of norepinephrine (15 μg/kg/h) resulted in more hypertension episodes. In addition, blood pressure was better maintained in the norepinephrine 5 μg/kg/h and 10 μg/kg/h groups than in the control group and 15 μg/kg/h group. No significant differences in other hemodynamic variables, adverse effects, maternal and neonatal blood gases, or Apgar scores were observed among the groups. In summary, for patients who undergo cesarean delivery under spinal anesthesia, infusion of 5-10 μg/kg/h norepinephrine was effective to reduce hypotension incidence without significant adverse effects on maternal and neonatal outcomes. Clinical Trial Registration Number is ChiCTR-INR-16009452.

Figures

Figure 1
Figure 1
CONSORT flow chart.
Figure 2
Figure 2
Hemodynamic changes. Data are shown for five timepoints: baseline (T1), the highest level of sensory block (T2), delivery (T3), oxytocin administration (T4), and end of surgery (T5). Data are presented as mean (SD). Asterisks in the upper blank indicate overall significance of each timepoint. ∗p < 0.05; ∗∗p < 0.01. Post hoc multiple comparison results are shown in supplementary Table S2.

References

    1. Mercier F. J., Augè M., Hoffmann C., Fischer C., Le Gouez A. Maternal hypotension during spinal anesthesia for caesarean delivery. Minerva Anestesiologica. 2013;79(1):62–73.
    1. Fratelli N., Prefumo F., Andrico S., et al. Effects of epidural analgesia on uterine artery Doppler in labour. British Journal of Anaesthesia. 2011;106(2):221–224. doi: 10.1093/bja/aeq317.
    1. Valentin M., Ducarme G., Ceccaldi P.-F., Bougeois B., Luton D. Uterine artery, umbilical, and fetal cerebral Doppler velocities after epidural analgesia during labor. International Journal of Gynecology and Obstetrics. 2012;118(2):145–148. doi: 10.1016/j.ijgo.2012.03.034.
    1. Antoine C., Young B. K. Fetal lactic acidosis with epidural anesthesia. American Journal of Obstetrics & Gynecology. 1982;142(1):55–59. doi: 10.1016/S0002-9378(16)32284-0.
    1. Ngan Kee W. D., Khaw K. S., Lau T. K., Ng F. F., Chui K., Ng K. L. Randomised double-blinded comparison of phenylephrine vs ephedrine for maintaining blood pressure during spinal anaesthesia for non-elective Caesarean section. Anaesthesia. 2008;63(12):1319–1326. doi: 10.1111/j.1365-2044.2008.05635.x.
    1. Cooper D. W., Carpenter M., Mowbray P., Desira W. R., Ryall D. M., Kokri M. S. Fetal and maternal effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology. 2002;97(6):1582–1590. doi: 10.1097/00000542-200212000-00034.
    1. Stewart A., Fernando R., McDonald S., Hignett R., Jones T., Columb M. The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia. Anesthesia & Analgesia. 2010;111(5):1230–1237. doi: 10.1213/ANE.0b013e3181f2eae1.
    1. Langesæter E., Rosseland L. A., 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(5):856–863. doi: 10.1097/ALN.0b013e31818a401f.
    1. Dyer R. A., Reed A. R., Van Dyk D., et al. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology. 2009;111(4):753–765. doi: 10.1097/ALN.0b013e3181b437e0.
    1. Ngan Kee W. D., Lee S. W. Y., Ng F. F., Tan P. E., Khaw K. S. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology. 2015;122(4):736–745. doi: 10.1097/ALN.0000000000000601.
    1. Vallejo M. C. 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. doi: 10.1016/j.ijoa.2016.08.005.
    1. Onwochei D. N., Ngan Kee W. D., Fung L., Downey K., Ye X. Y., Carvalho J. C. A. Norepinephrine intermittent intravenous boluses to prevent hypotension during spinal anesthesia for cesarean delivery: A sequential allocation dose-finding study. Anesthesia & Analgesia. 2017;125(1):212–218. doi: 10.1213/ANE.0000000000001846.
    1. Ngan Kee W. D., Lee S. W. Y., Ng F. F., Khaw K. S. Prophylactic Norepinephrine Infusion for Preventing Hypotension During Spinal Anesthesia for Cesarean Delivery. Anesthesia & Analgesia. 2017 doi: 10.1213/ANE.0000000000002243.
    1. Poterman M., Vos J. J., Vereecke H. E. M., et al. Differential effects of phenylephrine and norepinephrine on peripheral tissue oxygenation during general anaesthesia. European Journal of Anaesthesiology. 2015;32(8):571–580. doi: 10.1097/EJA.0000000000000247.
    1. Allen T. K., et al. A double-blind placebo-controlled trial of four fixed rate infusion regimens of phenylephrine for hemodynamic support during spinal anesthesia for cesarean delivery. Anesthesia & Analgesia. 2010;111(5):1221–1229. doi: 10.1213/ANE.0b013e3181e1db21.
    1. Ilies C., Grudev G., Hedderich J., et al. Comparison of a continuous noninvasive arterial pressure device with invasive measurements in cardiovascular postsurgical intensive care patients: A prospective observational study. European Journal of Anaesthesiology. 2015;32(1):20–28. doi: 10.1097/EJA.0000000000000136.
    1. Rosseland L. A., Hauge T. H., Grindheim G., Stubhaug A., Langesæter E. Changes in blood pressure and cardiac output during cesarean delivery: The effects of oxytocin and carbetocin compared with placebo. Anesthesiology. 2013;119(3):541–551. doi: 10.1097/ALN.0b013e31829416dd.
    1. Rumboll C. K., Dyer R. A., Lombard C. J. The use of phenylephrine to obtund oxytocin-induced hypotension and tachycardia during caesarean section. International Journal of Obstetric Anesthesia. 2015;24(4, article no. 2402):297–302. doi: 10.1016/j.ijoa.2015.08.003.
    1. Connolly C. C., Steiner K. E., Stevenson R. W., et al. Regulation of glucose metabolism by norepinephrine in conscious dogs. American Journal of Physiology-Endocrinology and Metabolism. 1991;261(6):E764–E772. doi: 10.1152/ajpendo.1991.261.6.E764.
    1. Kang Y. J. Involvement of alpha(2)-adrenergic receptor in the regulation of the blood glucose level induced by immobilization stress. Archives of Pharmacal Research. 2015;38(5):921–929. doi: 10.1007/s12272-014-0430-5.
    1. Barth E., Albuszies G., Baumgart K., et al. Glucose metabolism and catecholamines. Critical Care Medicine. 2007;35(9):S508–S518. doi: 10.1097/01.CCM.0000278047.06965.20.
    1. Coore H. G., Randle P. J. Regulation of insulin secretion studied with pieces of rabbit pancreas incubated in vitro. Biochemical Journal. 1964;93(1):66–78. doi: 10.1042/bj0930066.
    1. Porte D., Jr. A receptor mechanism for the inhibition of insulin release by epinephrine in man. The Journal of Clinical Investigation. 1967;46(1):86–94. doi: 10.1172/JCI105514.
    1. Reverte M., Garcia-Barrado M., Moratinos J. Changes in plasma glucose and lactate evoked by α and β. Fundamental & Clinical Pharmacology. 1991;5(8):663–676. doi: 10.1111/j.1472-8206.1991.tb00756.x.
    1. Bonamigo R., Razera F., Cartell A. Extensive skin necrosis following use of noradrenaline and dopamine. Journal of the European Academy of Dermatology and Venereology. 2007;21(4):565–566. doi: 10.1111/j.1468-3083.2006.01963.x.
    1. Simman R., Phavixay L. Bilateral toe necrosis resulting from norepinephrine bitartrate usage. Advances in Skin & Wound Care. 2013;26(6):254–256. doi: 10.1097/01.ASW.0000431083.77517.fd.
    1. Lecoq J.-P. H., Brichant J.-F., Lamy M. L., Joris J. L. Norepinephrine and ephedrine do not counteract the increase in cutaneous microcirculation induced by spinal anaesthesia. British Journal of Anaesthesia. 2010;105(2):214–219. doi: 10.1093/bja/aeq145.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться