Diastolic Performance and Norepinephrine in Spinal-Induced Hypotension for Cesarean Delivery (NORA-CS)

Influence of Diastolic Performance on the Response to Norepinephrine for Prevention of Spinal Anesthesia-Induced Hypotension for Cesarean Delivery and Fetal Wellbeing

Background and rationale: The best agent to prevent spinal-induced hypotension is still uncertain but norepinephrine showed fewer effects on heart rate and cardiac output. In septic patients norepinephrine has been shown to produce an "endogenous fluid challenge".

Objective: We aim to assess if patients with impaired diastolic function (46% of pregnant women at term) are less able to maintain indexed cardiac output in response to norepinephrine infusion during spinal-induced vasoplegia. We also aim to assess if fetal wellbeing is related to maternal cardiac output during spinal anesthesia for cesarean delivery.

Methods: We will assess by echocardiogram the diastolic function before surgery and will then start continuous non-invasive hemodynamic monitoring with a ClearSight® monitor (ClearSight®, Edwards Lifescience, Irvine, CA) and perform a fluid challenge to relate diastolic disfunction with fluid responsiveness. Hemodynamic monitoring will continue throughout the surgery. Norepinephrine infusion will start concomitantly to beginning of spinal anesthesia and will stop 5 minutes after uterotonic medication.

Outcome: We aim to assess if patients with diastolic disfunction are less able to maintain cardiac output in response to norepinephrine infusion during spinal anesthesia induced vasoplegia. We also aim to assess if fetal wellbeing is related to maternal cardiac output during spinal anesthesia for cesarean delivery.)

Study Overview

• Status: Completed
• Conditions: Hypotension
• Intervention / Treatment: Drug: Norepinephrine; Device: ClearSight®, Edwards Lifescience, Irvine, CA

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00168
    • IRCCS Fondazione Policlinico Universitario Agostino Gemelli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

All pregnant women scheduled for elective C-section at our Institution willing to participate.

Description

Inclusion Criteria:

Pregnant women between the 36th and the 40th week of gestation undergoing spinal anesthesia for elective caesarian delivery.

Exclusion Criteria:

1. age < 18 yo;
2. preeclampsia;
3. eclampsia;
4. atrial fibrillation and sinus tachycardia;
5. cardiovascular diseases;
6. neuromuscular disease;
7. emergent or urgent cesarean delivery;
8. coagulopathies;
9. contraindications to spinal anesthesia.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal Diastolic Function; Diastolic Function within normal values (defined in terms of E wave and A wave velocity and Deceleration Time according to the American Society of Echocardiography and the European Association of Echocardiography)	Drug: Norepinephrine; Norepinephrine is administered as a continuous infusion at 0.05 mcg/kg/min and is kept to maintain systolic blood pressure within 90-120% of baseline during spinal anaesthesia. The infusion is started at the same time cerebrospinal fluid is obtained, immediately before injection of spinal medications, through a small-bore tubing connected directly to the peripheral intravenous catheter. It is stopped 5 minutes; Device: ClearSight®, Edwards Lifescience, Irvine, CA; All patients are connected to a ClearSight® monitor (ClearSight®, Edwards Lifescience, Irvine, CA) by an inflatable finger cuff placed on the midphalanx of hand middle or ring finger with no radial artery catheter and its heart reference system (HRS) is zeroed at the level of the patient's midaxillary line. The ClearSight® monitoring is started in the pre-anaesthesia room and calibrated for 5 minutes before recording. The monitoring continues throughout the procedure until patient transfer in the recovery room. All data are anonymously collected on a USB pen for statistical analysis.
Impaired Diastolic Function; Diastolic Function with pseudonormal pattern or impaired values (defined in terms of E wave and A wave velocity and Deceleration Time according to the American Society of Echocardiography and the European Association of Echocardiography)	Drug: Norepinephrine; Norepinephrine is administered as a continuous infusion at 0.05 mcg/kg/min and is kept to maintain systolic blood pressure within 90-120% of baseline during spinal anaesthesia. The infusion is started at the same time cerebrospinal fluid is obtained, immediately before injection of spinal medications, through a small-bore tubing connected directly to the peripheral intravenous catheter. It is stopped 5 minutes; Device: ClearSight®, Edwards Lifescience, Irvine, CA; All patients are connected to a ClearSight® monitor (ClearSight®, Edwards Lifescience, Irvine, CA) by an inflatable finger cuff placed on the midphalanx of hand middle or ring finger with no radial artery catheter and its heart reference system (HRS) is zeroed at the level of the patient's midaxillary line. The ClearSight® monitoring is started in the pre-anaesthesia room and calibrated for 5 minutes before recording. The monitoring continues throughout the procedure until patient transfer in the recovery room. All data are anonymously collected on a USB pen for statistical analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indexed Cardiac Output	We aim to study if the diastolic performance of the heart measured by transthoracic echocardiography in healthy pregnant women at term undergoing spinal anesthesia for caesarean delivery influences the effects of norepinephrine on indexed cardiac output (CI) measured by non-invasive continuous hemodynamic monitoring.	Baseline/after spinal anesthesia/after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indexed Stroke Volume	We will correlate diastolic performance measured by transthoracic echocardiography with the response to norepinephrine of indexed stroke volume (SVI) in ml, blood pressure (BP) in mmHg and heart rate (HR) in bpm measured by non-invasive continuous hemodynamic monitoring.	Baseline/after spinal anesthesia/after delivery
Systolic Blood Pressure	We will correlate diastolic performance measured by transthoracic echocardiography with the response to norepinephrine of blood pressure (BP) in mmHg measured by non-invasive continuous hemodynamic monitoring.	Baseline/after spinal anesthesia/after delivery
Heart Rate	We will correlate diastolic performance measured by transthoracic echocardiography with the response to norepinephrine of heart rate (HR) in bpm measured by non-invasive continuous hemodynamic monitoring.	Baseline/after spinal anesthesia/after delivery
Apgar Scores	We ought to correlate the reduction of neonatal Apgar Scores with decreases of indexed cardiac output measured by non-invasive continuous hemodynamic monitoring.	Decreases of Indexed Cardiac Output after spinal anesthesia

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 14, 2020
• Primary Completion (ACTUAL): December 15, 2020
• Study Completion (ACTUAL): December 15, 2020

Study Registration Dates

• First Submitted: September 11, 2020
• First Submitted That Met QC Criteria: September 17, 2020
• First Posted (ACTUAL): September 23, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 25, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Cesarean section; norepinephrine; spinal anesthesia
• 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: 30865/19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No