Individualized Blood Pressure Management in Patients Undergoing Cardiac Surgery (PRECISE)

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Cardiac Surgery
• Intervention / Treatment: Other: Individualized intraoperative BP management; Other: Standard intraoperative BP management

Detailed Description

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.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Novosibirsk, Russian Federation, 630055
    • Meshalkin Research Institute of Pathology of Circulation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Individualized BP group; Individualized intraoperative BP management	Other: Individualized intraoperative BP management; 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.
Placebo Comparator: Standard treatment group; Standard intraoperative BP management	Other: Standard intraoperative BP management; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Meshalkin Research Institute of Pathology of Circulation
• Investigators: Principal Investigator: Vladimir Lomivorotov, MD, PhD, Meshalkin Research Institute of Pathology of Circulation

Publications and helpful links

General Publications

• Sun LY, Chung AM, Farkouh ME, van Diepen S, Weinberger J, Bourke M, Ruel M. Defining an Intraoperative Hypotension Threshold in Association with Stroke in Cardiac Surgery. Anesthesiology. 2018 Sep;129(3):440-447. doi: 10.1097/ALN.0000000000002298. Erratum In: Anesthesiology. 2019 Feb;130(2):360.
• Walsh M, Devereaux PJ, Garg AX, Kurz A, Turan A, Rodseth RN, Cywinski J, Thabane L, Sessler DI. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013 Sep;119(3):507-15. doi: 10.1097/ALN.0b013e3182a10e26.
• Bijker JB, van Klei WA, Vergouwe Y, Eleveld DJ, van Wolfswinkel L, Moons KG, Kalkman CJ. Intraoperative hypotension and 1-year mortality after noncardiac surgery. Anesthesiology. 2009 Dec;111(6):1217-26. doi: 10.1097/ALN.0b013e3181c14930.
• Monk TG, Saini V, Weldon BC, Sigl JC. Anesthetic management and one-year mortality after noncardiac surgery. Anesth Analg. 2005 Jan;100(1):4-10. doi: 10.1213/01.ANE.0000147519.82841.5E.
• Sessler DI, Khanna AK. Perioperative myocardial injury and the contribution of hypotension. Intensive Care Med. 2018 Jun;44(6):811-822. doi: 10.1007/s00134-018-5224-7. Epub 2018 Jun 4.
• Gold JP, Charlson ME, Williams-Russo P, Szatrowski TP, Peterson JC, Pirraglia PA, Hartman GS, Yao FS, Hollenberg JP, Barbut D, et al. Improvement of outcomes after coronary artery bypass. A randomized trial comparing intraoperative high versus low mean arterial pressure. J Thorac Cardiovasc Surg. 1995 Nov;110(5):1302-11; discussion 1311-4. doi: 10.1016/S0022-5223(95)70053-6.

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2019
• Primary Completion (Anticipated): March 10, 2020
• Study Completion (Anticipated): April 10, 2020

Study Registration Dates

• First Submitted: October 3, 2018
• First Submitted That Met QC Criteria: December 21, 2018
• First Posted (Actual): December 24, 2018

Study Record Updates

• Last Update Posted (Actual): November 22, 2019
• Last Update Submitted That Met QC Criteria: November 20, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Myocardial infarction; Hypotension; Acute kidney injury; Cardiopulmonary bypass; Intraoperative blood pressure
• Other Study ID Numbers: 19

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