Manual vs Closed-loop Control of Mean Arterial Pressure

Study Overview
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Brief Summary
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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): Control group = standard practice ( manually adjusted norepinephrine infusion to correct hypotension and keep MAP within 90% of patient's baseline MAP 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
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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)

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

Conditions
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Hypotension

Intervention / Treatment
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* Device: closed-loop system
* Device: Manual adjustment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single center prospective randomized controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: manual group<br>Hypotension will be corrected by manual infusion of norepinephrine | Device: Manual adjustment<br>* Vasopressor agents will be manually adjusted (standard practice). Fluids will be given using a goal directed strategy (EV1000 Monitor, Edwards Lifesciences, Irvine, CA, USA)<br>|
| Experimental: closed-loop group<br>Hypotension will be corrected by closed-loop control of norepinephrine infusion | Device: closed-loop system<br>* 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)<br>|

What is the study measuring?
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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 |