Prophylactic norepinephrine infusion for postspinal anesthesia hypotension in patients undergoing cesarean section: A randomized, controlled, dose‐finding trial

Chen, Yi; Zou, Lili; Li, Zhenzhou; Guo, Lei; Xue, Wei; He, Ling; Ma, Shuqin; Ni, Xinli

doi:10.1002/phar.2514

Cited by 18 publications

(16 citation statements)

References 23 publications

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“…Of the remaining 333 studies, 315 were removed based on the title and abstract screening; six were further excluded because the up-and-down method was used for dose finding; and another two were also excluded as NE was used for rescuing instead of preventing hypotension. Therefore, 10 RCTs were finally included in this systematic review ( Chen et al, 2018 ; Hasanin et al, 2019 ; Choudhary et al, 2020 ; Fu et al, 2020 ; Wei et al, 2020 ; Chen et al, 2021 ; Sheng et al, 2021 ; Wakhloo et al, 2021 ; Xu et al, 2021 ; Lyu et al, 2022 ). The flow diagram for study selection is shown in Figure 1 , and the risk of bias for each included study is shown in Figure 2 .…”

Section: Resultsmentioning

confidence: 99%

Prophylactic intravenous norepinephrine for the prevention of hypotension during spinal anesthesia for elective cesarean section: a systematic review and dose–response meta-analysis of randomized controlled trials

Li,

Shuai,

Huang

2023

Front. Pharmacol.

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Introduction: In this study, we aimed to evaluate the potential dose–response relationship between prophylactic norepinephrine (NE) infusion rates and the risks of hypotension during cesarean section following spinal anesthesia.Methods: Randomized controlled trials with two or more NE doses for post-spinal hypotension prophylaxis during cesarean section were systematically searched in the MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and US Clinical Trials Registry databases until 31 July 2022. The primary outcome was the relative risk of maternal hypotension with different NE regimens (infusion rates or bolus doses). Secondary outcomes included the relative risks of maternal and fetal adverse events with different NE regimens.Results: Ten studies with 1,144 parturients were included for final analysis using restricted cubic splines and random-effects dose–response meta-analysis models. A significant dose–response relationship existed between NE infusion rates and the relative risks of maternal hypotension. Every 0.01 μg/kg/min increment in the NE infusion rate was associated with a 14% decrease in the incidence of post-spinal hypotension. ED50 and ED95 of NE infusion rates for post-spinal hypotension prophylaxis were estimated to be 0.046 (95% CI from 0.032 to 0.085) and 0.2 (95% CI from 0.14 to 0.37) μg/kg/min, respectively. However, a higher NE infusion rate was associated with a higher incidence of maternal hypertension.Conclusion: An increased NE infusion rate was associated with a decreased incidence of post-spinal hypotension but an increased incidence of hypertension. Therefore, 0.07 μg/kg/min was recommended as the initial NE infusion rate for clinical practice, as it was associated with the lowest risk of physician intervention for unstable hemodynamics after spinal anesthesia for cesarean delivery.Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=349934), identifier (CRD42022349934).

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Section: Resultsmentioning

confidence: 99%

Prophylactic intravenous norepinephrine for the prevention of hypotension during spinal anesthesia for elective cesarean section: a systematic review and dose–response meta-analysis of randomized controlled trials

Li,

Shuai,

Huang

2023

Front. Pharmacol.

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“… 6 , 19 Our previous randomized, controlled, dose-finding trial indicated that the norepinephrine prophylactic infusion effectively reduced the incidence of hypotension induced by spinal anesthesia and maintained the SBP closer to the baseline. 20 Because norepinephrine better maintains CO, reduces the incidence of bradycardia, and improves hemodynamic stability, it was recently put forward as an advantageous alternative to phenylephrine. 21 We found that the incidence of bradycardia was significantly lower in the norepinephrine group relative to the PE group.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic Norepinephrine and Phenylephrine Boluses to Prevent Postspinal Anesthesia Hypotension During Cesarean Section: A Randomized Sequential Allocation Dose-Finding Study

Guo,

Xu,

Qin

et al. 2023

DDDT

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Background Norepinephrine and phenylephrine are widely used for obstetric anesthesia. Our central objective was to determine the ED (effective dose) 90 and potency ratio of prophylactic norepinephrine and phenylephrine boluses for preventing postspinal anesthesia hypotension during cesarean section. Methods Patients scheduled for elective cesarean section (n = 80) were randomly allocated to receive prophylactic norepinephrine (NE) or phenylephrine (PE) boluses immediately after induction of spinal anesthesia. An initial dose of NE (3 μg) and PE (37.5 μg) was given to the first patient, and an up-and-down sequential allocation method was used to determine the next dose level according to the responses (the effectiveness for preventing postspinal anesthesia hypotension [defined as SBP < 80% of baseline value]). Primary outcomes were ED90 and the potency ratio of prophylactic norepinephrine and phenylephrine boluses. Secondary outcomes were the incidence of postspinal anesthesia hypotension, severe postspinal anesthesia hypotension, nausea, vomiting, bradycardia, hypertension, umbilical artery blood gas values, and Apgar scores. Results The ED90 values for prophylactic norepinephrine and phenylephrine boluses were 8.0 μg (95% CI 7.1–11.0 μg) and 90.9 μg (95% CI 82.0–123.9 μg), respectively. The estimated relative potency ratio was 11.4:1. The incidence of bradycardia was lower in the NE group (2.5% vs 20%, P = 0.034). Other outcomes were comparable between the two groups. Conclusion An 8-μg prophylactic bolus of norepinephrine and a 90-μg prophylactic bolus of phenylephrine can effectively prevent postspinal anesthesia hypotension in patients during cesarean section.

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“…In another dose-finding study conducted by Wei et al [ 54 ], the ED50 and ED95 values were 0.029 (95% CI, 0.008–0.042) and 0.105 (95% CI, 0.082–0.172) μg/kg/min, respectively. Subsequent dose-finding studies reported comparable ED50 and ED95 values of 0.029 (95% CI, 0.002–0.043) and 0.080 (95% CI, 0.065–0.116), respectively [ 55 , 56 ].…”

Section: Administration Methods and Optimal Dosementioning

confidence: 99%

Use of vasopressors to manage spinal anesthesia-induced hypotension during cesarean delivery

Park,

Choi

2024

Anesth Pain Med

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Cesarean sections are commonly performed under spinal anesthesia, which can lead to hypotension, adversely affecting maternal and fetal outcomes. Hypotension following spinal anesthesia is generally defined as a blood pressure of 80–90% below the baseline value. Various strategies have been implemented to reduce the incidence of spinal anesthesia-induced hypotension. The administration of vasopressors is a crucial method for preventing and treating hypotension. In the past decade, phenylephrine, a primarily alpha-adrenergic agonist, has been the preferred vasopressor for cesarean sections. Recently, norepinephrine, a potent alpha-agonist with modest beta-agonist activity, has gained popularity owing to its advantages over phenylephrine. Vasopressors can be administered via a bolus or continuous infusion. Although administering boluses alone is simpler in a clinical setting, continuous prophylactic infusion initiated immediately after spinal anesthesia is more effective in reducing the incidence of hypotension. Tailoring the infusion dose based on the patient’s body weight and adjusting the rate in response to blood pressure changes, in addition to using a prophylactic or rescue bolus, helps reduce blood pressure variability during cesarean sections under spinal anesthesia until neonatal delivery.

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Prophylactic norepinephrine infusion for postspinal anesthesia hypotension in patients undergoing cesarean section: A randomized, controlled, dose‐finding trial

Cited by 18 publications

References 23 publications

Prophylactic intravenous norepinephrine for the prevention of hypotension during spinal anesthesia for elective cesarean section: a systematic review and dose–response meta-analysis of randomized controlled trials

Prophylactic intravenous norepinephrine for the prevention of hypotension during spinal anesthesia for elective cesarean section: a systematic review and dose–response meta-analysis of randomized controlled trials

Prophylactic Norepinephrine and Phenylephrine Boluses to Prevent Postspinal Anesthesia Hypotension During Cesarean Section: A Randomized Sequential Allocation Dose-Finding Study

Use of vasopressors to manage spinal anesthesia-induced hypotension during cesarean delivery

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