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Status unknownNCT04951167Updated Jul 6, 2021

EFFECT OF DIFFERENT NOREPINPHRINE APPLICATION METHODS IN CAESARIANES ON HYPOTENSION AFTER SPINAL ANESTHESIA

An interventional study of Norepinephrine and Norepinephrine in HYPOTENSION AFTER SPINAL ANESTHESIA,IN PREGNANCY, sponsored by Inonu University. Status unknown at 1 site in Turkey. Open to female participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-07-06.

Sponsored by Inonu University · Not applicable, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Jul 2021), so the status shown — last known as Active, not recruiting — may be out of date.
Phase
Not applicable
Study type
Interventional
Enrollment
208
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study summary

There are previous studies in which norepinephrine was administered only as a prophylactic or only infusion to prevent hypotension after spinal anesthesia in cesarean sections. However, there are not enough studies reporting which of these application methods are more effective. Therefore, in our study, cesarean section under spinal anesthesia was planned; We aimed to investigate the effectiveness of norepinephrine differential administration methods on preventing maternal hypotension.

Read the detailed description

EFFECT OF DIFFERENT NOREPINPHRINE APPLICATION METHODS IN CAESARIANES ON HYPOTENSION AFTER SPINAL ANESTHESIA INTRODUCTION Spinal anesthesia in cesarean sections is a frequently used anesthesia technique today. The most common complication associated with spinal anesthesia is hypotension. Systemic vascular resistance and cardiac output decrease due to sympathetic blockade, and when this is accompanied by bradycardia and contractility, hypotension develops(1,2,3).

Maternal hypotension is a condition that can cause negative consequences such as nausea, vomiting, and dizziness in pregnant women who undergo spinal anesthesia. In addition, it increases the likelihood of fetal acidosis, hypoxia, and neonatal neurological damage. Therefore, it is necessary to treat maternal hypotension effectively. In the current treatment of maternal hypotension, intravenous fluid administration, treatments such as ephedrine, phenylephrine, and norepinephrine are used (4,5,7). Among these drugs, ephedrine is the first preferred vasopressor (4). For this reason, its efficacy and safety, and the use of different doses have been extensively studied (5,7). Ephedrine is a vasopressor with both direct and indirect effects in the treatment of hypotension due to neuraxial block in obstetrics with its alpha and beta agonist effects. The most important disadvantage of ephedrine is that it has a slow onset and weak effect, difficulty in titration, development of tachyphylaxis, causing maternal tachy-arrhythmias and fetal acidosis (9). Ephedrine easily crosses the placenta and causes fetal tachycardia, an increase in noradrenaline concentration in the umbilical artery (UA), and a decrease in pH and base excess (BE). An increase in fetal metabolic rate, an increase in fetal O2 consumption and CO2 production, and an increase in lactate level are observed through beta-adrenergic stimulation (9). Phenylephrine, on the other hand, is a pure alpha-agonist agent that is more potent (phenylephrine/ephedrine: 80:1), easy to titrate, effectively treats hypotension and nausea-vomiting, has minimal placental transfer, and does not cause fetal acidosis and changes (10-11). However, the disadvantage of phenylephrine is that it decreases maternal heart rate and cardiac output (12). Another vasopressor drug used in the treatment of hypotension in recent years is norepinephrine. Norepinephrine is both an α-receptor agonist and a weak β-receptor agonist (7,8). Theoretically, it lowers heart rate and cardiac output less.

There are previous studies in which norepinephrine was administered only as a prophylactic or only infusion to prevent hypotension after spinal anesthesia in cesarean sections. However, there are not enough studies reporting which of these application methods are more effective. Therefore, in our study, cesarean section under spinal anesthesia was planned; We aimed to investigate the effectiveness of norepinephrine differential administration methods on preventing maternal hypotension.

WORKING PROTOCOL After the approval of the faculty ethics committee, the written and verbal consent of the patients will be obtained, and a double-blind randomized study will be initiated.

Pregnant women over the age of 18, with ASA (American Society of Anesthesiologists physical status) ≤ III, body weight 50-100 kg and height 150-180 cm, with a single pregnancy planned for cesarean section under elective conditions under spinal anesthesia, will be included in the study.

Pregnant women with allergy or hypersensitivity to norepinephrine, pre-existing hypertension or pregnancy-induced hypertension, cardiovascular or cerebrovascular disease, renal failure, history of thrombosis in the mesenteric or peripheral vessels, history of diabetes with known fetal anomalies, users of monoaminooxidase inhibitors, tricyclic antidepressants and those who refused to study were excluded.

Pregnant women will be randomly divided into 4 groups using the closed envelope method. The person who prepares the study drugs and follows the study will be different and unaware of the study. Following standard aspiration prophylaxis and monitoring, peripheral vascular access will be established with an 18-G catheter and 1 ml/kg/hour Ringer Lactate solution will be started. Basal systolic blood pressure will be determined by measuring heart rate values every 2 minutes and averaging the 3 values.

Spinal anesthesia will be provided in the sitting position with a 25-gauge Quinke spinal needle through the L3-L4 or L4-L5 spacing with 2-2.2 ml of hyperbaric bupivacaine and 15 mcg of fentanyl. Immediately after spinal anesthesia, the pregnant woman will be placed in the supine position, with a pillow placed under the right hip (30 tilts to the left) and rapid coloading with 10 ml/kg Ringer Lactate at a maximum of 1 L with the help of a pump. Afterwards, the mai rate will be reduced to 1 ml/kg/hour again. For the study, norepinephrine will be prepared at 4 mcg/ml.

In Group PB, an IV bolus of 4 mcg will be administered immediately after spinal anesthesia, and then SF infusion will be started at 1 ml/min.

In Group PI, 1ml of saline is administered immediately after spinal anesthesia, and then infusion will be started with the study drugat 1 ml/min.(4mcg/min) In Group TB, immediately after spinal anesthesia, 1 ml of saline, followed by 1 ml/min infusion of SF, and when the blood pressure decreases by 20%, 1 ml of working solution and then 1 ml/min of saline infusion will be started.

In Group TBI, 1 ml of study drug and 1 ml/min of study drug infusion will be started immediately after spinal anesthesia, after 1 ml of saline followed by 1 ml/min of SF infusion when blood pressure decreases by 20% of the entry. Heart rate and blood pressure and pulse oximetry will be recorded every 2 minutes from intrathecal drug administration until delivery. When systolic blood pressure drops more than 20% compared to baseline, it will be considered as hypotension and an additional 4 mcg (1 ml) norepinephrine will be administered in all groups, and if it continues in the next measurement, a second dose of 4 mcg norepinephrine will be administered. Hypotension that does not improve despite two measurements will be treated with an IV bolus of 10 mg of ephedrine. According to entry, 40% or more will be considered severe hypotension and treated with 15 mg of ephedrine. If the heart rate drops to 50 beats/minute, bradycardia will be considered and treated with 0.5 mg of atropine. Hypertension will be considered as a 20% increase in systolic blood pressure from baseline and treated with a 0.1 mg bolus of nitroglycerin iv. The study protocol will be terminated after the delivery of the fetus, but anesthetist bolus norepinephrine administration will be continued for the treatment of hypotension. The number of episodes of hypotension and hypertension, bradycardia, nausea, vomiting, tremor, sensory block level, Apgar score, umbilical artery and vein values, time from intrathecal injection to delivery, uterine incision delivery times will be recorded.

RESOURCES Morgan GE, Mikhail MS, Murray MJ, Larson CP: Clinical Anesthesiology (LANGE), Güneş Bookstore, Third Edition, Ankara, 2004.P:260-269.

  1. Kayhan Z: Clinical Anesthesia. Logos Yay.Tic.A.Ş., Second Edition, Istanbul: 1997. P:482-489.
  1. Edirne S, Özyalçın SN, Raj PP, Heavner J, Aldemir T, Yücel A: Regional Anesthesia. Nobel Medicine Bookstores, Istanbul 2005. P:159-184.
  1. Kinsella S, Carvalho B, Dyer R, et al. International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia. Anaesthesia 2018;73:71-92.
  1. 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. Anesth Analg 2002;94:920-6.
  1. Habib AS. A review of the impact of phenylephrine administration on maternal hemodynamics and maternal and neonatal outcomes in women undergoing cesarean delivery under spinal anesthesia. Anesth Analg 2012;114:377-90.
  1. Chen D, Qi X, Huang X, et al. Efficacy and safety of different norepinephrine regimens for prevention of spinal hypotension in cesarean section: a randomized trial. Biomed Res Int 2018;2018:2708175.
  1. Onwochei DN, Ngan Kee WD, Fung L, et al. Norepinephrine intermittent intravenous boluses to prevent hypotension during spinal anesthesia for cesarean delivery: a sequential allocation dose-finding study. Anesth Analg 2017;125:212-8.
  1. 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;111:506-12.
  1. 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;111:506-12.
  1. 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. Br J Anaesth 2006;96:95-9.
  1. Cooper D.W. Caesarean delivery vasopressor management. Curr Opin Anaesthesiol 2012; 25:300-8.
02

Conditions studied

  • HYPOTENSION AFTER SPINAL ANESTHESIA,IN PREGNANCY

Browse trials for

Keywords

  • NOREPINPHRINE
  • SPINAL ANESTHESIA
  • HYPOTENSION
  • pregnancy
03

In context

Hypotension

1,003 studies on the registry are indexed under Hypotension; 173 are open to participants now.

This study's enrollment of 208 is above the median of 80 across 675 interventional studies indexed under Hypotension.

Browse Hypotension studies →

Lead sponsor

Inonu University is the lead sponsor of 375 studies on the registry; 86 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

Pregnant women over the age of 18, with ASA (American Society of Anesthesiologists physical status) ≤ III, body weight 50-100 kg and height 150-180 cm, with a single pregnancy planned for cesarean section under elective conditions under spinal anesthesia, will be included in the study.

Exclusion criteria

Exclusion Criteria:

Pregnant women with allergy or hypersensitivity to norepinephrine, pre-existing hypertension or pregnancy-induced hypertension, cardiovascular or cerebrovascular disease, renal failure, history of thrombosis in the mesenteric or peripheral vessels, history of diabetes with known fetal anomalies, users of monoaminooxidase inhibitors, tricyclic antidepressants and those who refused to study were excluded.

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05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
208 participants (actual)

Study arms

  • Active comparator
    PB: prophylactic bolus

    an IV bolus of 4 mcg Norepinephrine will be administered immediately after spinal anesthesia, and then SF infusion will be started at 1 ml/min.

    Drug: Norepinephrine

  • Active comparator
    PI:prophylactic infusion

    1ml of saline is administered immediately after spinal anesthesia, and then infusion will be started with the study drug at 1 ml/min.(4mcg/min)

    Drug: Norepinephrine

  • Active comparator
    TB:therapeutic bolus

    immediately after spinal anesthesia, 1 ml of saline, followed by 1 ml/min infusion of SF, and when the blood pressure decreases by 20%, 1 ml of working solution and then 1 ml/min of saline infusion will be started.

    Drug: Norepinephrine

  • Active comparator
    TBI:therapeutic bolus-infusion

    1 ml of study drug and 1 ml/min of study drug infusion will be started immediately after spinal anesthesia, after 1 ml of saline followed by 1 ml/min of SF infusion when blood pressure decreases by 20% of the entry

    Drug: Norepinephrine

Interventions

  • DrugNorepinephrine

    in the form of infusion

  • DrugNorepinephrine

    in the form of bolus

06

What researchers measure

Primary outcomes

  1. systolic blood pressure

    When systolic blood pressure drops more than 20% compared to baseline, it will be considered as hypotension

    Time frame: every 2 mins from intrathecal drug administration until delivery

07

Study locations

1 site
  • Inonu Universitesi
    Malatya, 44280, Turkey
08

References and documents

Publications

  • Kinsella SM, Carvalho B, Dyer RA, Fernando R, McDonnell N, Mercier FJ, Palanisamy A, Sia ATH, Van de Velde M, Vercueil A; Consensus Statement Collaborators. International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia. Anaesthesia. 2018 Jan;73(1):71-92. doi: 10.1111/anae.14080. Epub 2017 Nov 1. No abstract available. PubMed 29090733 ↗
  • 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. Anesth Analg. 2002 Apr;94(4):920-6, table of contents. doi: 10.1097/00000539-200204000-00028. PubMed 11916798 ↗
  • Habib AS. A review of the impact of phenylephrine administration on maternal hemodynamics and maternal and neonatal outcomes in women undergoing cesarean delivery under spinal anesthesia. Anesth Analg. 2012 Feb;114(2):377-90. doi: 10.1213/ANE.0b013e3182373a3e. Epub 2011 Nov 21. PubMed 22104076 ↗
  • Chen D, Qi X, Huang X, Xu Y, Qiu F, Yan Y, Li Y. Efficacy and Safety of Different Norepinephrine Regimens for Prevention of Spinal Hypotension in Cesarean Section: A Randomized Trial. Biomed Res Int. 2018 May 23;2018:2708175. doi: 10.1155/2018/2708175. eCollection 2018. PubMed 29951531 ↗
  • Onwochei DN, Ngan Kee WD, Fung L, Downey K, Ye XY, Carvalho JCA. Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension During Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-Finding Study. Anesth Analg. 2017 Jul;125(1):212-218. doi: 10.1213/ANE.0000000000001846. PubMed 28248702 ↗
  • 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 Sep;111(3):506-12. doi: 10.1097/ALN.0b013e3181b160a3. PubMed 19672175 ↗
  • 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. Br J Anaesth. 2006 Jan;96(1):95-9. doi: 10.1093/bja/aei265. Epub 2005 Nov 25. PubMed 16311286 ↗
  • Cooper DW. Caesarean delivery vasopressor management. Curr Opin Anaesthesiol. 2012 Jun;25(3):300-8. doi: 10.1097/ACO.0b013e3283530d62. PubMed 22473212 ↗

Individual participant data

Plan to share: Yes

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 6, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04951167
Lead sponsor
Inonu University
Responsible party
Nurşen Seyhun (M.D., Inonu University) — Principal investigator
First posted
Jul 6, 2021
Start date
May 15, 2021
Primary completion
May 15, 2022 (estimated)
Completion
Aug 2022 (estimated)
Last update
Jul 6, 2021

Study contacts

Nurcin Gulhas, Prof
principal investigator · Inonu Universitesi

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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