Different Noradrenaline Protocols in Post Spinal Hypotension in CS

Comparison of Different Noradrenaline Protocols to Prevent Post Spinal Hypotension During Elective Caesarean Delivery: A Randomised, Double-blind Clinical Trial

The incidence of hypotension after spinal anesthesia is approximately 60% in parturients undergoing cesarean section. As a consequence of hypotension, nausea-vomiting, dyspnea and neurological deterioration in patients and low Apgar scores in newborns may occur. Therefore, there is an increasing interest to prevent maternal post spinal hypotension by using several drugs including noradrenaline given in different protocols to the patients undergoing spinal anesthesia for cesarean section. However, there is no conclusive answer to the question of which dosage is the best to prevent the maternal post spinal hypotension in literature.

In this prospective randomized study, we aimed to compare different noradrenaline protocols for preventing maternal post spinal hypotension during elective cesarean delivery.

Study Overview

• Status: Completed
• Conditions: Hypotension; Cesarean Section; Anesthesia, Spinal
• Intervention / Treatment: Drug: Noradrenalin 10 microgram bolus; Drug: Noradrenaline 0.05 microgram/kg/minute infusion; Procedure: Spinal anesthesia; Drug: Noradrenaline 5 microgram bolus; Drug: Infusion dosage: 0.075 microgram/kg/minute infusion; Drug: Noradrenaline 0.1 microgram/kg/minute infusion

Detailed Description

One of the most important and frequent adverse effects of spinal anesthesia is post procedure hypotension. The emerging hypotension does not affect only the pregnant, it also does harm to the newborn. Therefore, an anesthesiologist should avoid and take precautions to prevent maternal post spinal hypotension. There is a growing body of evidence about noradrenalin application in the management of hemodynamic optimization of patients undergoing cesarean section with spinal anesthesia. However, there is no conclusive decision about the dosage and application protocol of noradrenaline in this patient population. In a study comparing the incidence of post spinal maternal hypotension given noradrenaline versus phenylephrine, the authors reported that both of drugs effectively controlled maternal blood pressure. The incidence of maternal hypotension was 30% and 32% (p= 0.8) in noradrenaline and phenylephrine study arms, respectively. Therefore, one can speculate that the incidence of maternal post spinal hypotension remains high even in patients receiving noradrenaline or phenylephrine. In the noradrenaline arm, only noradrenaline infusion with a dosage of 0.05 microgram/kg/minute without any bolus was applied to the patients. In another study, the effects of different noradrenaline infusion dosages with 5 microgram bolus dosage on maternal post spinal hypotension were investigated. The frequencies of maternal hypotension were 42.1%, 24.7% and 26% in patients receiving 0.025, 0.05 and 0.075 microgram/kg/minute with a bolus 5 microgram noradrenaline, respectively. As a conclusion of this study, addition of a bolus dose of 5 microgram noradrenaline may lower the incidence of post spinal hypotension. However, as in the previous study, approximately one fourth of patients still may have a post spinal hypotension episode. Regarding these results, the present study is planned to answer the question of which approach including increasing infusion or bolus dosage of noradrenaline is superior to ameliorate the incidence of hypotension in this population.

In conclusion, the aim of this study is to compare three different noradrenaline protocols including different bolus and infusion dosages to decrease the rate of hypotension in patients undergoing cesarean section with spinal anesthesia.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey
  • Ankara, Turkey
    • Ankara University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• ASA 2
• 38 +4 gestational age parturient

Exclusion Criteria:

• ASA 3-6
• Parturients with any kind of contraindication to spinal anesthesia
• Hypertensive parturients (basal systolic blood pressure above 140 mmHg)
• Parturients having basal systolic blood pressure below 100 mmHg
• Parturients having peripartum hemorrhage
• Parturients having body mass index above 40
• Parturients with a known allergic reaction to one of the study drugs
• Parturients not willing to be included into the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Noradrenaline 0.05/10; Study drug will be prepared as follows:4 milligram noradrenaline will be administered into 100 milliliter 5% dextrose solution. The basal blood pressure of the parturient will be recorded as an arithmetic sum of the sequential three measurements of noninvasive blood pressure. Maternal hypotension and severe hypotension will be described as a decrease of noninvasive systolic blood pressure according to basal systolic blood pressure by 20% and 40%, respectively. If the heart rate of parturient will be under 60 beat/minute, this will be recorded as maternal bradycardia. The noradrenaline bolus dosage of 10 microgram will be administered to the patient at the same time of obtaining cerebrospinal fluid running freely. After the end of the injection of heavy marcaine 0.5% to the subarachnoid space, the infusion of noradrenaline with a 0.05 microgram/kg/minute dosage will be started. Noradrenaline will be continued until 5 minutes after delivery of fetus.	Drug: Noradrenalin 10 microgram bolus; The noradrenaline bolus dosage of 10 microgram will be administered to the patient at the same time of obtaining cerebrospinal fluid running freely.; Other Names: NA 10B; Drug: Noradrenaline 0.05 microgram/kg/minute infusion; Infusion dosage: 0.05 microgram/kg/minute After the end of the injection of heavy marcaine 0.5% to the subarachnoid space, the infusion of noradrenaline with a 0.05 microgram/kg/minute dosage will be started. Noradrenaline will be continued until 5 minutes after delivery of fetus.; Other Names: NA 0.05I; Procedure: Spinal anesthesia; Spinal anesthesia using 0.5% 10 milligram heavy bupivacaine plus 12.5 microgram fentanyl
Active Comparator: Noradrenaline 0.075/5; Study drug will be prepared as follows:4 milligram noradrenaline will be administered into 100 milliliter 5% dextrose solution. The basal blood pressure of the parturient will be recorded as an arithmetic sum of the sequential three measurements of noninvasive blood pressure. Maternal hypotension and severe hypotension will be described as a decrease of noninvasive systolic blood pressure according to basal systolic blood pressure by 20% and 40%, respectively. If the heart rate of parturient will be under 60 beat/minute, this will be recorded as maternal bradycardia. The noradrenaline bolus dosage of 5 microgram will be administered to the patient at the same time of obtaining cerebrospinal fluid running freely. After the end of the injection of heavy marcaine 0.5% to the subarachnoid space, the infusion of noradrenaline with a 0.075 microgram/kg/minute dosage will be started. Noradrenaline will be continued until 5 minutes after delivery of fetus.	Procedure: Spinal anesthesia; Spinal anesthesia using 0.5% 10 milligram heavy bupivacaine plus 12.5 microgram fentanyl; Drug: Noradrenaline 5 microgram bolus; The noradrenaline bolus dosage of 5 microgram will be administered to the patient at the same time of obtaining cerebrospinal fluid running freely.; Other Names: NA 5B; Drug: Infusion dosage: 0.075 microgram/kg/minute infusion; nfusion dosage: 0.075 microgram/kg/minute After the end of the injection of heavy marcaine 0.5% to the subarachnoid space, the infusion of noradrenaline with a 0.075 microgram/kg/minute dosage will be started. Noradrenaline will be continued until 5 minutes after delivery of fetus.; Other Names: NA 0.075I
Active Comparator: Noradrenaline 0.1/0; Study drug will be prepared as follows:4 milligram noradrenaline will be administered into 100 milliliter 5% dextrose solution. The basal blood pressure of the parturient will be recorded as an arithmetic sum of the sequential three measurements of noninvasive blood pressure. Maternal hypotension and severe hypotension will be described as a decrease of noninvasive systolic blood pressure according to basal systolic blood pressure by 20% and 40%, respectively. If the heart rate of parturient will be under 60 beat/minute, this will be recorded as maternal bradycardia. After the end of the injection of heavy marcaine 0.5% to the subarachnoid space, the infusion of noradrenaline with a 0.1 microgram/kg/minute without bolus dosage will be started. Noradrenaline will be continued until 5 minutes after delivery of fetus.	Procedure: Spinal anesthesia; Spinal anesthesia using 0.5% 10 milligram heavy bupivacaine plus 12.5 microgram fentanyl; Drug: Noradrenaline 0.1 microgram/kg/minute infusion; Infusion dosage: 0.1 microgram/kg/minute After the end of the injection of heavy marcaine 0.5% to the subarachnoid space, the infusion of noradrenaline with a 0.1 microgram/kg/minute dosage will be started. Noradrenaline will be continued until 5 minutes after delivery of fetus.; Other Names: NA 0.1I

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of maternal post spinal hypotension	The primary outcome of this study is to compare the incidences of maternal post spinal hypotension in patients administered three different noradrenaline protocols.	Between the application time of spinal anesthesia and 5th minute after delivery
Incidence of maternal post spinal severe hypotension	The other primary outcome of this study is to compare the incidences of maternal post spinal severe hypotension in patients administered three different noradrenaline protocols.	Between the application time of spinal anesthesia and 5th minute after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of post delivery maternal hypotension	The secondary outcome of this study is to compare the incidences of maternal post delivery hypotension in patients administered three different noradrenaline protocols.	Between 5th minute after delivery and the end of surgery
The incidence of post delivery maternal severe hypotension	The other secondary outcome of this study is to compare the incidences of maternal post delivery severe hypotension in patients administered three different noradrenaline protocols.	Between 5 minute of delivery and the end of surgery
The incidence of intervention applied by an anesthesiologist	The other secondary outcome is to determine and to compare the frequency of intervention applied by the anesthesiologist to stabilize the patients hemodynamic status.This interventions include changing the noradrenaline infusion status, administering atropine and ephedrine, according to the patients hemodynamic data.	Between the start of patient monitoring and the end of surgery

Collaborators and Investigators

• Sponsor: Ankara University
• Investigators: Principal Investigator: Menekse Ozcelik, M.D, Associate Professor

Publications and helpful links

General Publications

• Vallejo MC, Attaallah AF, Elzamzamy OM, Cifarelli DT, Phelps AL, Hobbs GR, Shapiro RE, Ranganathan P. An open-label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during cesarean delivery. Int J Obstet Anesth. 2017 Feb;29:18-25. doi: 10.1016/j.ijoa.2016.08.005. Epub 2016 Aug 28.
• Hasanin AM, Amin SM, Agiza NA, Elsayed MK, Refaat S, Hussein HA, Rouk TI, Alrahmany M, Elsayad ME, Elshafaei KA, Refaie A. Norepinephrine Infusion for Preventing Postspinal Anesthesia Hypotension during Cesarean Delivery: A Randomized Dose-finding Trial. Anesthesiology. 2019 Jan;130(1):55-62. doi: 10.1097/ALN.0000000000002483.
• Hasanin A, Amin S, Refaat S, Habib S, Zayed M, Abdelwahab Y, Elsayad M, Mostafa M, Raafat H, Elshall A, Fatah SAE. Norepinephrine versus phenylephrine infusion for prophylaxis against post-spinal anaesthesia hypotension during elective caesarean delivery: A randomised controlled trial. Anaesth Crit Care Pain Med. 2019 Dec;38(6):601-607. doi: 10.1016/j.accpm.2019.03.005. Epub 2019 Mar 30.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): December 15, 2021
• Study Completion (Actual): December 15, 2021

Study Registration Dates

• First Submitted: January 6, 2021
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 8, 2021

Study Record Updates

• Last Update Posted (Actual): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: adult; Pregnancy; Hypotension; Blood Pressure; female; Cesarean Section; Heart Rate; Apgar Score; Noradrenaline; Anesthesia, Spinal
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: 05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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