Clinical trial NCT04089644: Manual vs Closed-loop Control of Mean Arterial Pressure
Official title: Physician-Directed vs Computer-Assisted Norepinephrine Administration in Patients Undergoing Major Abdominal Surgery: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypotension
Lead sponsor: Erasme University Hospital
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
name: University of California, Irvine
name: Bicetre Hospital
First posted: 2019-09-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single center prospective randomized controlled trial
Primary purpose: TREATMENT

Brief summary: 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

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)

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of case Time in hypotension (MAP < 90% of the chosen MAP target).
timeFrame: At postoperative day 1
Secondary outcomes:
measure: Percentage of case time in hypotension (MAP < 65 mmHg)
timeFrame: during surgery
measure: Percentage of case time in target (MAP +/- 10 mmHg) of the chosen MAP target
timeFrame: during surgery
measure: Amount of vasopressors received
timeFrame: during surgery
measure: Uretral perfusion index during surgery
timeFrame: during surgery
measure: Uretral perfusion index during the first 15 minutes of the surgery
timeFrame: during surgery
measure: Uretral perfusion index during the last 15 minutes of the surgery
timeFrame: during surgery
measure: Cardiac index during surgery
timeFrame: during surgery
measure: Stroke volume index during surgery
timeFrame: during surgery
measure: Stroke volume variation during surgery
timeFrame: during surgery
measure: Amount of fluid received during surgery
timeFrame: during surgery
measure: Net fluid balance during surgery
timeFrame: during surgery
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Erasme Hospital
state: Brussel-hoofdstad
Study officials:
affiliation: ERASME
name: Alexandre Joosten, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.