Different Noradrenaline Protocols in Post Spinal Hypotension in CS

• ClinicalTrials.gov Identifier: NCT04701190
• Recruitment Status: Completed
• First Posted: January 8, 2021
• Last Update Posted: February 1, 2022
• Sponsor: Ankara University
• Information provided by (Responsible Party): Menekse Ozcelik, Ankara University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hypotension; Cesarean Section; Anesthesia, Spinal	Drug: Noradrenalin 10 microgram bolus; Drug: Noradrenaline 5 microgram bolus; Drug: Noradrenaline 0.1 microgram/kg/minute infusion; Drug: Noradrenaline 0.05 microgram/kg/minute infusion; Drug: Infusion dosage: 0.075 microgram/kg/minute infusion; Procedure: Spinal anesthesia	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)

Masking Description

The hypotension will be recognized by the participants due to feeling unwell of theirselves. However they will not have any information about the dosage of the study drug. So they will be blinded to the study group which they will be included by the investigator of the study.

The investigator will collect the data coming from the monitors, patients and the newborn. Therefore, the investigator will not be aware of the intervention about the dosing of noradrenaline made by the anesthesiologist.

• Primary Purpose: Prevention
• Official Title: Comparison of Different Noradrenaline Protocols to Prevent Post Spinal Hypotension During Elective Caesarean Delivery: A Randomised, Double-blind Clinical Trial
• Actual Study Start Date: February 1, 2021
• Actual Primary Completion Date: December 15, 2021
• Actual Study Completion Date: December 15, 2021

Arms and Interventions

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 Name: 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 Name: 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.	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 Name: 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 Name: NA 0.075I; Procedure: Spinal anesthesia; Spinal anesthesia using 0.5% 10 milligram heavy bupivacaine plus 12.5 microgram fentanyl
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.	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 Name: NA 0.1I; Procedure: Spinal anesthesia; Spinal anesthesia using 0.5% 10 milligram heavy bupivacaine plus 12.5 microgram fentanyl

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. The incidence of post delivery maternal hypotension [ Time Frame: Between 5th minute after delivery and the end of surgery ]
   The secondary outcome of this study is to compare the incidences of maternal post delivery hypotension in patients administered three different noradrenaline protocols.
2. The incidence of post delivery maternal severe hypotension [ Time Frame: Between 5 minute of delivery and the end of surgery ]
   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.
3. The incidence of intervention applied by an anesthesiologist [ Time Frame: Between the start of patient monitoring and the end of surgery ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Parturient
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Turkey

Ankara University School of Medicine

Ankara, Turkey

Sponsors and Collaborators

Ankara University

Investigators

• Principal Investigator: Menekse Ozcelik, M.D; Associate Professor

More Information

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.

• Responsible Party: Menekse Ozcelik, Associate Professor, Ankara University
• ClinicalTrials.gov Identifier: NCT04701190
• Other Study ID Numbers: 05
• First Posted: January 8, 2021
• Last Update Posted: February 1, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Menekse Ozcelik, Ankara University:

Apgar Score; Pregnancy; Blood Pressure; Heart Rate; adult; female; Hypotension; Noradrenaline; Cesarean Section; Anesthesia, Spinal

Additional relevant MeSH terms:

Hypotension; Vascular Diseases; Cardiovascular Diseases; Norepinephrine; Physiological Effects of Drugs; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Sympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Vasoconstrictor Agents