Two Norepinephrine Rescue Bolus Doses for Management of Severe Post-spinal Hypotension During Elective Cesarean Delivery

Comparison of Two Norepinephrine Rescue Bolus Doses for Management of Severe Post-spinal Hypotension During Elective Cesarean Delivery: A Randomized, Controlled Trial

Maternal hypotension after spinal block is a common complication after subarachnoid block in this population whose incidence reached 60% in many reports. Hypotension is associated with maternal and neonatal complications; therefore, it is highly recommended to use vasopressors, prophylactically and interactively, for prompt control maternal blood pressure. Despite the presence of various preventive regimens (fluid loading, maternal positioning, and vasopressors), many mothers develop intraoperative episodes of hypotension which requires the use of a vasopressor bolus.

Norepinephrine (NE) is an alpha adrenergic agonist with weak beta adrenergic agonistic activity; and is increasingly used in obstetric anesthesia with acceptable maternal and neonatal outcomes. NE bolus could be used for rapid correction of maternal blood pressure in a dose which variedranged between 3.7-10 mcg. Till date, al the available data for the management of maternal hypotension did not differentiate between severe and non-severe hypotension. The incidence of severe maternal hypotension (systolic blood pressure ≤60% of baseline) ranged between 7-20%. In a recent report, Hassabelnaby et al compared 6 mcg and 10 mcg NE boluses in management of maternal hypotension and found that the doses had the same success rate (≈90%); however, most of the participants in the mentioned study had non-severe hypotension. Therefore, we hypothesize that severe hypotension should be separately investigated for the possible superiority of the higher over the lower dose of NE bolus.

Insufficient NE bolus would lead to failed management and prolonged hypotensive episode, whereas a higher dose might lead to reactive hypertension and/or bradycardia, which is sometimes severe. Therefore, determining the optimum dose for NE bolus would enable proper control of maternal hemodynamic profile

Study Overview

• Status: Completed
• Conditions: Cesarean Delivery; Norepinephrine; Postspinal Hypotension
• Intervention / Treatment: Drug: Norepinephrine 5 mcg; Drug: Norepinephrine 10 mcg

Detailed Description

Upon arrival to the operating room, the patient will be in supine position with left uterine displacement using a wedge below the right buttock. Routine monitoring will be applied (electrocardiography, pulse oximetry, and non-invasive blood pressure monitor). An 18G-cannula will be inserted, and the patients will receive 10 mg metoclopramide. Baseline heart rate and systolic blood pressure will be recorded as the average of three consecutive readings with 2-minutes interval.

Lactated Ringer's solution will be infused at rate of 15 mL/Kg over 10 minutes as a co-load; spinal anesthesia will be achieved by injecting 10 mg of hyperbaric bupivacaine and 20 mcg fentanyl into the subarachnoid space at L3-L4 or L4-L5 interspace using 25G spinal needle.

After subarachnoid block, mothers will be placed in the supine position with left-lateral tilt. The decision to give prophylactic vasopressor infusion will be according to the attending anesthetist preferences.

Block success will be assessed after 5 minutes from intrathecal injection of local anesthetic; and will be confirmed if sensory block level is at T4.

The patient would receive the study drug only if she developed severe post-spinal hypotension (defined as systolic blood pressure ≤60% of the baseline reading) as her first hypotensive episode or after 10 minutes from the last successfully managed hypotensive episode and before the delivery. .

The management of the hypotensive episode will be considered successful if the systolic blood pressure is > 80% of the baseline within 2 mins of the bolus. If the bolus failed, NE bolus of 5 mcg will be given.

Any other hypotensive episode (systolic blood pressure <80% of baseline) will be managed with NE bolus of 5 mcg.

Intraoperative bradycardia (defined as heart rate less than 55 bpm) will be managed by IV atropine bolus (0.5 mg) will be administered.

Fluid administration will be continued up to a maximum of 1.5 liters. An oxytocin bolus (0.5 IU) will be delivered over five seconds after delivery then infused at a rate of 2.5 IU/hour.

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11562
    • Kasr Alaini hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• full-term singleton pregnant women
• American society of anesthesiologist physical status of I or II,
• scheduled for elective cesarean delivery

Exclusion Criteria:

• Patients with uncontrolled cardiac morbidities (patients with tight valvular lesion, impaired contractility with ejection fraction < 50%, heart block, and arrhythmias),
• hypertensive disorders of pregnancy,
• peripartum bleeding, coagulation disorders (patients with INR >1.4 and or platelet count < 80000 /dL) or
• any contraindication to regional anesthesia, and
• baseline systolic blood pressure (SBP) < 100 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: group B	Drug: Norepinephrine 10 mcg; norepinephrine bolus of 10 mcg for treatment of sever postspinal hypotension
Active Comparator: group A	Drug: Norepinephrine 5 mcg; norepinephrine bolus of 5 mcg for treatment of sever postspinal hypotension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of successful management of severe post-spinal hypotension	systolic blood pressure >80% of baseline within 2 min of drug injection	2 minutes after drug injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to severe postspinal hypotension	minutes	1 minute after subarachnoid local anesthetic injection till 1 min after baby delivery
incidence of reactive bradycardia	heart rate heart rate less than 55 beat per minute	2 minutes after drug injection
incidence of reactive hypertension	systolic blood pressure >120% of baseline	2 minutes after drug injection
incidence of nausea and vomiting	unpleasant painless subjective feeling that one will imminently vomit or vomiting	1 minute after subarachnoid local anesthetic injection till 5 minute after baby delivery
fetal umbilical blood pH	pH	at 5 minutes post delivery
baby Apgar score	score with 0, 1, or 2, depending on the observed condition.	at 5 minutes post delivery

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2022
• Primary Completion (Actual): July 25, 2022
• Study Completion (Actual): July 25, 2022

Study Registration Dates

• First Submitted: February 22, 2022
• First Submitted That Met QC Criteria: March 11, 2022
• First Posted (Actual): March 22, 2022

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 15, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• 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: MS-657-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: protocol and data of this research could be available from the PI upon reasonable request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No