Hypotension Prediction 2 Study in Cardiac Surgery and Postoperative ICU Admission

Study Overview
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Brief Summary
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This trial registration serves as an amendment incorporating the IPD Sharing Statement. This study already has a trial registration (2021 April 30) in the Netherlands Trial Registry (Reference number NL9449, https://trialsearch.who.int/). However, the NTR register is subject to a merger with another Dutch register. This means that existing registrations are still visible, but can no longer be adjusted. Study summary: Hypotension in the operating room (OR) and during post-operative ICU admission is common in surgical patients and even more prevalent in cardiac surgery patients. It is associated with adverse outcomes and while these events are preventable, current management is predominantly reactive. Edwards Lifesciences (Irvine, CA) has developed the Hypotension Prediction Index (HPI), an early warning system that predicts an hypotensive event, defined as MAP below 65 mmHg, with high accuracy minutes before it occurs. At the time of writing the protocol this model has not been tested in a clinical trial in cardiac surgery patients or ICU admitted patients. The aim of the HYPE-2 trial is to assess whether the HPI-algorithm can reduce the time-weighted average (TWA) of intra- and postoperative hypotension in elective on-pump coronary artery bypass graft (CABG) surgery patients.

Detailed Description
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Population studied: All adult patients undergoing elective on-pump CABG surgery or CABG with additional single heart valve surgery (e.g. valve repair or replacement), requiring a radial arterial line and an intended target MAP of 65 mmHg or above during both surgery (excluding cardiopulmonary bypass pump time (CBP)) and during mechanically ventilated phase of duration of ICU admission.

Official Title
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Effect of a Machine Learning-Derived Early Warning System for Hypotension vs Standard Care on Depth and Duration of Intra- and Postoperative Hypotension in Elective Cardiac Surgery

Conditions
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Intraoperative Hypotension, Postoperative Hypotension, Hypotension

Intervention / Treatment
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* Other: HPI guided treatment advice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older at inclusion Planned for elective on-pump CABG surgery or CABG with additional single heart valve surgery (e.g. valve repair or replacement) Planned to receive standard monitoring for cardiac surgery Target MAP of 65 mmHg or above during surgery Target MAP of 65 mmHg or above during the mechanically ventilated phase of ICU admission Exclusion Criteria: Known cardiac shunts (significant) Severe cardiac arrhythmias (including but not limited to persistent atrial fibrillation prior to surgery) Expected to receive an hemodynamic assist device (e.g. intra-aortic balloon pump) during surgery Dialysis dependent kidney failure prior to surgery Planned to receive Perioperative Goal Directed Therapy (PGDT) other than standard intraoperative care Previous cardiac surgery in medical history

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study has two arms in which patients are allocated in a 1:1 randomization ratio.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control group<br>Objective to maintain a mean arterial blood pressure (MAP) above or equal to 65 mm Hg, as is standard care in out institution. This is done using standard hemodynamic monitoring, which in our center consists of continuous arterial blood pressure monitoring and the pulse pressure variation parameter. The clinician will administer either fluids, inotropes, vasopressors, or a combination, or apply positional changes to maintain the set MAP threshold. | |
| Experimental: Additional HPI guided treatment<br>Objective to maintain a mean arterial blood pressure (MAP) above or equal to 65 mm Hg, as is standard care in out institution. This is done using standard hemodynamic monitoring (as described for the control group) but is assisted by the Hypotension Prediction Index (HPI). This parameter is made available to the clinicians with the HemoSphere Advanced Monitoring Platform (HemoSphere) and is used to initiate treatment when the HPI values is ≥ 75. It also provides additional advanced hemodynamic variables (e.g. cardiac output, systemic vascular resistance). The treating clinicians are trained to use these variables and are provided with a diagnostic flowchart to determine the cause (preload, contractility and afterload) of the upcoming hypotensive (MAP < 65 mmHg) event. Timing of treatment and choice of treatment is then left to the discretion of the attending clinician. | Other: HPI guided treatment advice<br>* Administer hemodynamic altering intervention aimed at either a preload, contractility, or afterload problem to prevent impending hypotension. Treatment options include: administering either fluids, inotropes, vasopressors, positional changes, or a combination.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The overall time-weighted average (TWA) of hypotension (severity of hypotension) | TWA is a calculation of the depth (in mmHg) of hypotension below the 'threshold' MAP of 65 mmHg x the time spent in hypotension in minutes, this resulting in an 'area'. To better compare this value between different patients the 'area' can be divided by the total duration of the measurement. | During both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of hypotension | number of hypotensive events during study phases | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| Time spent in hypotension | amount of time in minutes spent in hypotension during study phases | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| The percentage of time in hypotension | amount of time in hypotension expressed in percentage of the total study phases' duration | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| The AUT of a MAP < 65 mmHg | AUT is a calculation of the depth (in mmHg) of hypotension below the 'threshold' MAP of 65 mmHg x the time spent in hypotension in minutes, this resulting in an 'area'. | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| Incidence of hypertension | number of hypertensive events during study phases | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| Time spent in hypertension | amount of time in minutes spent in hypertension during study phases | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| The percentage of time in hypertension | amount of time in hypertension expressed in percentage of the total study phases' duration | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| The AAT of a MAP > 100 mmHg | AAT is a calculation of the depth (in mmHg) of hypertension above the 'threshold' MAP of 100 mmHg x the time spent in hypertension in minutes, this resulting in an 'area'. | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| TWA of hypertension | TWA is a calculation of the depth (in mmHg) of hypertension above the 'threshold' MAP of 100 mmHg x the time spent in hypertension in minutes, this resulting in an 'area'. This 'area' is divided by the total duration of the measurement. | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| Incidence of HPI alarm (HPI ≥ 75) | number of HPI alarms during study phases | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| Time spent in HPI alarm | amount of time in minutes spent in HPI alarms during study phases | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| The percentage of time in HPI alarm | amount of time in HPI alarms expressed in percentage of the total study phases' duration | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| The AAT of a HPI ≥ 75 | AAT is a calculation of the depth of HPI above or equal to the 'threshold' of 75 x the time spent in HPI alarm in minutes, this resulting in an 'area'. | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| TWA of HPI alarm | TWA is a calculation of the depth of HPI above or equal to the 'threshold' of 75 x the time spent in HPI alarm in minutes, this resulting in an 'area'. This 'area' is divided by the total duration of the measurement. | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| Treatment choice | vasopressors, blood transfusions, fluids, inotropes, position changes, decrease in anesthetics | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| Treatment dose | Dosage of medication or volume of fluids | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| Time to treatment | If an alarm or hypotensive event had more than 1 treatment, the time to first treatment will be used. | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 
| Number of treatments | amount of treatments (e.g., administered fluids, vasopressors, inotropes, anesthetics) given to alter the hemodynamics (increase of reduce the blood pressure) | Will be analyzed for the overall duration of both the off-pump phases of on-pump CABG surgery and the mechanically ventilated phase of post-operative ICU admission (or 8 hours maximum) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intensive Care Unit, Cardiac surgery, Coronary Artery Bypass Grafting