Manual vs Closed-loop Control of Mean Arterial Pressure

Physician-Directed vs Computer-Assisted Norepinephrine Administration in Patients Undergoing Major Abdominal Surgery: A Randomized Controlled Trial

Intraoperative hypotension can impact patient outcome. Vasopressors are usually used to correct hypotension and ensure adequate organ perfusion.

The investigators have recently developed an automated system (closed-loop system) to titrate vasopressor agents in surgical and intensive care patients.

The purpose of this study is to compare two strategies to correct hypotension based on an individual definition of hypotension (therefore, the target MAP used to define hypotension will differ for each patient (individualized approach):

1. Control group = standard practice ( manually adjusted norepinephrine infusion to correct hypotension and keep MAP within 90% of patient's baseline MAP
2. Intervention group = closed-loop (automated) vasopressor administration system will deliver norepinephrine using feedback from standard operating room hemodynamic monitor (EV1000 Monitor-Flotrac, Edwards Lifesciences, IRVINE, USA) to correct hypotension and keep MAP within 90% of patient's baseline MAP

Study Overview

• Status: Completed
• Conditions: Hypotension
• Intervention / Treatment: Device: Manual adjustment; Device: closed-loop system

Detailed Description

In order to prevent the known postoperative complications of intraoperative hypotension, vasopressor agents are occasionally used to ensure adequate perfusion. These vasopressors are usually administered as manually adjusted infusions, but this practice requires considerable time and attention.

To overcome this issue, the investigators have developed a closed-loop vasopressor (CLV) controller to potentially correct hypotension more efficiently. After completing extensive in-silico, in-vivo studies and a pilot human trial in a small cohort of 20 patients, the investigators aimed to conduct now a randomized control trial comparing manual vasopressor adjustment versus closed-loop vasopressor adjustment in high risk patients undergoing major abdominal surgeries in order to correct hypotension during surgery

The primary outcome will be the incidence of hypotension (defined as a reduction of > 10% from patient's MAP target, or a allowed tolerance of 10% reduction from patient's baseline MAP). This has been chosen based on the recent study of Emmanuel Futier and colleagues (Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1346-1357), even if it was originally done with systolic blood pressure

Participants in both groups will receive standard patient care in that in no way will their anesthetic or surgical procedure will be altered as part of the study, with the exception of vasopressor administration.

Fluids will be standardized in both groups and will be given as a continuous baseline infusion of 3 ml/kg/h (balanced crystalloid solution) and additional fluid boluses (mini fluid challenges of 100 ml) as a goal directed fluid therapy strategy to maintain stroke volume variation < 13%. The only difference is the way norepinephrine is delivered to the patient (manual versus closed-loop assisted)

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussel-hoofdstad
    • Brussels, Brussel-hoofdstad, Belgium, 1070
      • Erasme Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• High-risk adult patients undergoing major abdominal surgeries requiring an advanced cardiac output monitoring device (EV1000-Edwards LifeSciences, Irvine, USA) and a tight blood pressure control

Exclusion Criteria:

• Atrial Fibrillation
• Severe Arythmia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: manual group; Hypotension will be corrected by manual infusion of norepinephrine	Device: Manual adjustment; Vasopressor agents will be manually adjusted (standard practice). Fluids will be given using a goal directed strategy (EV1000 Monitor, Edwards Lifesciences, Irvine, CA, USA)
EXPERIMENTAL: closed-loop group; Hypotension will be corrected by closed-loop control of norepinephrine infusion	Device: closed-loop system; Hypotension will be corrected by an automated system for vasopressor administration. Fluids will be given using a goal directed strategy (EV1000 Monitor, Edwards Lifesciences, Irvine, CA, USA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of case Time in hypotension (MAP < 90% of the chosen MAP target).	Undertreatment. Percentage of time during surgery in hypotension. The MAP used to define hypotension will differ for each patient (individualized approach)	At postoperative day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of case time in hypotension (MAP < 65 mmHg)	Percentage of time during surgery in hypotension using the population target usually admitted and used in clinical studies (MAP < 65 mmHg)	during surgery
Percentage of case time in target (MAP +/- 10 mmHg) of the chosen MAP target	Percentage of time during surgery with a MAP +/- 10 mmHg of the chosen MAP target.	during surgery
Amount of vasopressors received	Amount of vasopressors received	during surgery
Uretral perfusion index during surgery	Mean Uretral perfusion index during surgery using the novel IKORUS urinary catheter recently available on the market	during surgery
Uretral perfusion index during the first 15 minutes of the surgery	Mean Uretral perfusion index during the first 15 minutes of the surgery	during surgery
Uretral perfusion index during the last 15 minutes of the surgery	Mean Uretral perfusion index during the last 15 minutes of the surgery	during surgery
Cardiac index during surgery	Mean cardiac index during surgery	during surgery
Stroke volume index during surgery	Mean Stroke volume index during surgery	during surgery
Stroke volume variation during surgery	Mean Stroke volume variation during surgery	during surgery
Amount of fluid received during surgery	Amount of fluid received during surgery	during surgery
Net fluid balance during surgery	Net fluid balance during surgery	during surgery

Collaborators and Investigators

• Sponsor: Erasme University Hospital
• Collaborators: University of California, Los Angeles; University of California, Irvine; Bicetre Hospital

Publications and helpful links

General Publications

• Joosten A, Chirnoaga D, Van der Linden P, Barvais L, Alexander B, Duranteau J, Vincent JL, Cannesson M, Rinehart J. Automated closed-loop versus manually controlled norepinephrine infusion in patients undergoing intermediate- to high-risk abdominal surgery: a randomised controlled trial. Br J Anaesth. 2021 Jan;126(1):210-218. doi: 10.1016/j.bja.2020.08.051. Epub 2020 Oct 8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 17, 2019
• Primary Completion (ACTUAL): March 5, 2020
• Study Completion (ACTUAL): March 5, 2020

Study Registration Dates

• First Submitted: September 12, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (ACTUAL): September 13, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 10, 2020
• Last Update Submitted That Met QC Criteria: March 6, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension
• Other Study ID Numbers: P2019/347

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