Individualized Blood Pressure Management in Patients Undergoing Cardiac Surgery

Study Overview
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Brief Summary
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This pilot randomized-controlled study will determine the feasibility of large study comparing individualized versus standard blood pressure (BP) management in patients undergoing cardiac surgery under cardiopulmonary bypass (CPB). Our hypothesis is that maintaining higher BP levels based on preoperative measurements will reduce the incidence of major complications (composite outcome).

Detailed Description
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Adequate hemodynamic control is a cornerstone in management in patients undergoing different types of surgery. Among all perioperative risk factors, the association between perioperative hypotension and adverse clinical outcomes in noncardiac and cardiac surgery patients is well defined. Numerous factors are responsible for development of perioperative hypotension. They include but not limited to perioperative use of renin-angiotensin-aldosterone system and calcium channel blockers, hypovolemia, hemodilution, bleeding and inflammatory response syndrome. To date, several evidence has been accumulated indicating that intraoperational hypertension can be hazardous. It was shown that even short durations (1 to 5 min) of an intraoperative mean arterial pressure < 55 mmHg were associated with myocardial injuries and acute kidney injury (AKI). Results of recent large retrospective cohort study conducted in adult patients who underwent cardiac surgery requiring CPB showed that postoperative stroke was strongly associated with sustained mean arterial pressure of less than 64 mmHg during cardiopulmonary bypass. In patients undergoing CABG the overall incidence of combined cardiac and neurologic complications was significantly lower in the group where MAP during CPB was relatively high (80-110 mmHg) than in the low pressure group (MAP 50-60 mmHg) (p = 0.026). For each of the individual outcomes the trend favored the high pressure group. Therefore, MAP may be an important intraoperative therapeutic hemodynamic target to reduce the incidence of complications in patients undergoing CPB.

Official Title
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Individualized Blood Pressure Management in Patients Undergoing Cardiac Surgery. A Pilot, Randomized Controlled Study

Conditions
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Cardiac Surgery

Intervention / Treatment
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* Other: Individualized intraoperative BP management
* Other: Standard intraoperative BP management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years old Signed informed consent Elective cardiac surgery under CPB (CABG or valve surgery) Exclusion Criteria: Unstable Coronary Artery Disease: Recent (< 6 weeks) myocardial infarction, unstable angina, severe (> 70%) left main coronary artery stenosis Uncontrolled hypertension preoperatively (SBP > 160 mm Hg) Critical preoperative state (ventricular tachycardia or ventricular fibrillation or aborted sudden death, preoperative cardiac massage, preoperative ventilation before anesthetic room, hemodynamic instability, preoperative inotropes or intraaortic balloon pumping, preoperative severe acute renal failure (anuria or oliguria <10ml/hr) Planned surgery on aorta Emergency surgery Pregnancy Current enrollment into another randomized controlled trial (in the last 30 days) Previous enrollment and randomization into current study Glomerular filtration rate ≤59 ml/min/1.73m2 (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation)

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individualized BP group<br>Individualized intraoperative BP management | Other: Individualized intraoperative BP management<br>* In the treatment group, the nurse will measure resting blood pressure three times in the ward one day before surgery (after a 5-min rest while lying supine). Average measurement will be used to calculate mean arterial pressure (MAP). Before and after CPB patients will receive continuous infusion of norepinephrine to maintain MAP within ± 10% of patients resting MAP. If targeted MAP during CPB could not be achieved after increasing pump-flow (not more than 130%), infusion of norepinephrine will used. After CPB, the choice of vasopressors/inotropes to maintain predefined MAP will be left on attending anesthesiologists based on patient status.<br>|
| Placebo Comparator: Standard treatment group<br>Standard intraoperative BP management | Other: Standard intraoperative BP management<br>* Standard treatment strategy will be used aiming to maintain pre-bypass and post-bypass MAP at 65-75 mm Hg. MAP during CPB will be maintained at 50-60 mm Hg. If MAP of 50-60 mm Hg during CPB could not be achieved after increasing pump-flow (not more than 130%), infusion of norepinephrine will be started. No vasodilators will be used if MAP will exceed predefined range.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compliance with the protocol | Successful compliance with protocol is defined as ≥ 90% of prescribed intervention being administered across all patients. | Operative day 1 | 
| Successful recruitment rate | Successful recruitment rate will be defined as recruitment of 2 patients per week. | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative creatinine concentration | Plasma creatinine level will be measured daily during 3 postoperative days. | 3 days after surgery | 
| Postoperative cardiac troponin I level | Cardiac troponin I level wil be measured in the time frame from 6 to 12 hours postoperatively. | 12 hours after surgery | 
| Intraoperative blood pressure | Intraoperative blood pressure (mean, systolic and diastolic) will be registered every 5 minutes intraoperatively using invasive blood pressure monitoring system. | Operative day 1 | 
| Rate of postoperative complications | Postoperative complications (myocardial infarction, atrial fibrillation, stroke, delirium, need for renal replacement therapy, infection, reexploration for bleeding) will be defined according to standard European Society of Anaesthesiology/European Society of Intensive Care Medicine definitions where possible. | 30 days after surgery | 
| Postoperative blood loss | Drainage volume (ml/kg) will be measured in the next morning after surgery. | Postoperative day 1 | 
| Daily Sequential Organ Failure Assessment (SOFA) score | Organ failure will be assessed by using Sequential Organ Failure Assessment (SOFA) score which will be recorded daily until patient discharge from the ICU. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). The score ranges from 0 to 24 points (the higher the score, the higher the mortality). | 30 days after surgery | 
| Peak concentration of lactate during CPB and up to 24 hours after surgery | Lactate values (mmol/l) will be measured every 6 hours during the first 24 postoperative hours. | Postoperative day 1 | 
| Oxygen delivery during CPB | Oxygen delivery during CPB will be calculated according to the standard formula (pump flow x O2 arterial content). | Operative day 1 | 
| Cerebral oxygenation (near infrared spectroscopy) | Number of cerebral desaturations will be recorded intraoperatively. | Operative day1 | 
| Ventilation > 24 hours | Number of patients with duration of ventilation more than 24 h. | 30 days after surgery | 
| Duration of ICU stay and hospitalization | Number of postoperative days spent in the ICU and in the hospital will be counted. | 30 days after surgery | 
| 30-day all-cause mortality | Number of patients who will die within 30-day after surgery from any cause | 30 days after surgery | 
| Need for blood transfusions | Number of patients who will need transfusions of any blood products (RBC, fresh frozen plasma, platelets, cryoprecipitate). | 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypotension, Intraoperative blood pressure, Cardiopulmonary bypass, Myocardial infarction, Acute kidney injury