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

July 1, 2021 updated by: Nurşen Seyhun, Inonu University
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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

2. Kayhan Z: Clinical Anesthesia. Logos Yay.Tic.A.Ş., Second Edition, Istanbul: 1997. P:482-489.

3. Edirne S, Özyalçın SN, Raj PP, Heavner J, Aldemir T, Yücel A: Regional Anesthesia. Nobel Medicine Bookstores, Istanbul 2005. P:159-184.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. Cooper D.W. Caesarean delivery vasopressor management. Curr Opin Anaesthesiol 2012; 25:300-8.

Study Type

Interventional

Enrollment (Actual)

208

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Turkey
      • Malatya, Turkey, 44280
        • inonu universitesi

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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:

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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Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
in the form of infusion
Drug: Norepinephrine
in the form of bolus
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
in the form of infusion
Drug: Norepinephrine
in the form of bolus
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
in the form of infusion
Drug: Norepinephrine
in the form of bolus
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
in the form of infusion
Drug: Norepinephrine
in the form of bolus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
systolic blood pressure
Time Frame: every 2 mins from intrathecal drug administration until delivery
When systolic blood pressure drops more than 20% compared to baseline, it will be considered as hypotension
every 2 mins from intrathecal drug administration until delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inonu University

Investigators

  • Principal Investigator: Nurcin Gulhas, Prof, inonu universitesi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 15, 2021

Primary Completion (ANTICIPATED)

May 15, 2022

Study Completion (ANTICIPATED)

August 1, 2022

Study Registration Dates

First Submitted

July 1, 2021

First Submitted That Met QC Criteria

July 1, 2021

First Posted (ACTUAL)

July 6, 2021

Study Record Updates

Last Update Posted (ACTUAL)

July 6, 2021

Last Update Submitted That Met QC Criteria

July 1, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-120

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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