Perioperative Personalized Blood Pressure Management: IMPROVE-multi

Study Overview
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Brief Summary
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Rates of major complications and mortality in the first weeks after surgery remain very high: postoperative mortality is still around 2% in central Europe and the United States. Postoperative deaths are a consequence of postoperative complications. Postoperative complications that are most strongly associated with postoperative death include acute kidney injury and acute myocardial injury. To avoid postoperative complications it is thus crucial to identify and address modifiable risk factors for complications. One of these modifiable risk factors may be intraoperative hypotension. Intraoperative hypotension is associated with major postoperative complications including acute kidney injury, acute myocardial injury, and death. It remains unknown which blood pressure value should be targeted in the individual patient during surgery to avoid physiologically important intraoperative hypotension. In current clinical practice, an absolute mean arterial pressure threshold of 65mmHg is used as a lower one-size-fits-all intervention threshold. This population harm threshold is based on the results of retrospective studies. However, using this population harm threshold for all patients ignores the obvious fact that blood pressure varies considerably among individuals. In contrast to current one-size-fits-all perioperative blood pressure management, the investigators propose the concept of personalized perioperative blood pressure management. Specifically, the investigators propose to test the hypothesis that personalized perioperative blood pressure management reduces the incidence of a composite outcome of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery. The investigators will perform preoperative automated blood pressure monitoring for one night to define individual intraoperative blood pressure targets. Automated blood pressure monitoring is the clinical reference method to assess blood pressure profiles. The mission of the trial is to reduce postoperative morbidity and mortality after major surgery. The vision is to achieve this improvement in patient outcome by using the innovative concept of personalized perioperative blood pressure management. This trial is expected to change and improve current clinical practice and will have a direct impact on perioperative blood pressure management guidelines.

Official Title
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Effect of Personalized Perioperative Blood Pressure Management on Postoperative Complications and Mortality in High-risk Patients Having Major Abdominal Surgery: a Multicenter Prospective Randomized Controlled Interventional Clinical Trial

Conditions
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Blood Pressure, Intraoperative Hypotension, Postoperative Complications, Surgery, Anesthesia

Intervention / Treatment
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* Other: Personalized blood pressure management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consenting patients ≥45 years scheduled for elective major abdominal surgery under general anesthesia that is expected to last ≥90 minutes AND Presence of ≥1 of the following high-risk criteria: exercise tolerance <4 metabolic equivalents as defined by the guidelines of the American College of Cardiology/American Heart Association renal impairment (serum creatinine ≥1.3 mg/dL or estimated glomerular filtration rate <90 mL/min/1.73 m2 within the last 6 months) coronary artery disease (any stage) chronic heart failure (New York Heart Association Functional Classification ≥II) valvular heart disease (moderate or severe) history of stroke peripheral arterial occlusive disease (any stage) chronic obstructive pulmonary disease (any stage) or pulmonary fibrosis (any stage) diabetes mellitus requiring oral hypoglycemic agent or insulin immunodeficiency due to a disease (e.g., HIV, leukemia, multiple myeloma, solid organ cancer) or therapy (e.g., immunosuppressants, chemotherapy, radiation, steroids [above Cushing threshold]) liver cirrhosis (any Child-Pugh class) body mass index ≥30 kg/m2 current smoking or 15 pack-year history of smoking age ≥65 years expected anesthesia duration >180 minutes B-type natriuretic peptide (BNP) >80 ng/L or N-terminal B-type natriuretic peptide (NT-proBNP) >200 ng/L within the last 6 months Exclusion Criteria: emergency surgery surgery: nephrectomy, liver or kidney transplantation status post transplantation of kidney, liver, heart, or lung sepsis (according to current Sepsis-3 definition) American Society of Anesthesiologists physical status classification V or VI pregnancy patients on renal replacement therapy impossibility of preoperative automated blood pressure monitoring

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Routine management (control) group<br>Routine intraoperative blood pressure management with a lower intervention threshold of 65 mmHg. In contrast to the patients assigned to the personalized management group, the individual mean nighttime MAP assessed using preoperative automated blood pressure monitoring is not taken into account and the treating anesthesiologists are blinded to the data of preoperative automated blood pressure monitoring. | |
| Experimental: Personalized management (intervention) group<br>In patients randomized to the personalized management group, intraoperative mean arterial pressure will be maintained at least at the mean nighttime mean arterial pressure (assessed using preoperative automated blood pressure monitoring) with a minimum mean arterial pressure of 65 mmHg, and maximum mean arterial pressure of 110 mmHg. The perioperative trial intervention period starts with the beginning of the induction of general anesthesia and ends two hours after surgery ends. | Other: Personalized blood pressure management<br>* Personalized blood pressure management: Intraoperative mean arterial pressure will be maintained at least at the mean nighttime mean arterial pressure (assessed using preoperative automated blood pressure monitoring) with a minimum mean arterial pressure of 65 mmHg, and maximum mean arterial pressure of 110 mmHg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome of major postoperative complications | Collapsed composite (any event versus none) of acute kidney injury, acute myocardial injury (including myocardial infarction), non-fatal cardiac arrest, and death within 7 days after surgery | Postoperative Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome of major postoperative complications | Collapsed incidence of acute kidney injury, acute myocardial injury (including myocardial infarction), non-fatal cardiac arrest, and death within 3 days after surgery | Postoperative Day 3 | 
| Postoperative acute kidney injury | Incidence of acute kidney injury within 3 days after surgery | Postoperative Day 3 | 
| Postoperative acute kidney injury | Incidence of acute kidney injury within 7 days after surgery | Postoperative Day 7 | 
| Postoperative acute myocardial injury (including myocardial infarction) | Incidence of acute myocardial injury (including myocardial infarction) within 3 days after surgery | Postoperative Day 3 | 
| Postoperative acute myocardial injury (including myocardial infarction) | Incidence of acute myocardial injury (including myocardial infarction) within 7 days after surgery | Postoperative Day 7 | 
| Postoperative non-fatal cardiac arrest | Incidence of non-fatal cardiac arrest within 3 days after surgery | Postoperative Day 3 | 
| Postoperative non-fatal cardiac arrest | Incidence of non-fatal cardiac arrest within 7 days after surgery | Postoperative Day 7 | 
| Postoperative death | Incidence of death within 3 days after surgery | Postoperative Day 3 | 
| Postoperative death | Incidence of death within 7 days after surgery | Postoperative Day 7 | 
| Composite outcome of long-term postoperative complications | Collapsed incidence of need for renal replacement therapy, myocardial infarction, non-fatal cardiac arrest, and death within 30 days after surgery | Postoperative Day 30 | 
| Composite outcome of long-term postoperative complications | Collapsed incidence of need for renal replacement therapy, myocardial infarction, non-fatal cardiac arrest, and death within 90 days after surgery | Postoperative Day 90 | 
| Postoperative need for renal replacement therapy | Incidence of need for renal replacement therapy within 30 days after surgery | Postoperative Day 30 | 
| Postoperative need for renal replacement therapy | Incidence of need for renal replacement therapy within 90 days after surgery | Postoperative Day 90 | 
| Postoperative myocardial infarction | Incidence of myocardial infarction within 30 days after surgery | Postoperative Day 30 | 
| Postoperative myocardial infarction | Incidence of myocardial infarction within 90 days after surgery | Postoperative Day 90 | 
| Postoperative non-fatal cardiac arrest | Incidence of non-fatal cardiac arrest within 30 days after surgery | Postoperative Day 30 | 
| Postoperative non-fatal cardiac arrest | Incidence of non-fatal cardiac arrest within 90 days after surgery | Postoperative Day 90 | 
| Postoperative death | Incidence of death within 30 days after surgery | Postoperative Day 30 | 
| Postoperative death | Incidence of death within 90 days after surgery | Postoperative Day 90 | 
| Postoperative infectious complications | Collapsed incidence of fever, respiratory infection, neurological infection, urinary system infection, colitis or infection with Clostridium difficile, endometritis, surgical site infection, deep incisional surgical site infection, organ or space surgical site infection, unknown infection with pathogenic organisms in tissue or fluid, and sepsis within 7 days after surgery | Postoperative Day 7 | 
| Postoperative fever | Incidence of fever within 7 days after surgery | Postoperative Day 7 | 
| Postoperative respiratory infection | Incidence of respiratory infection within 7 days after surgery | Postoperative Day 7 | 
| Postoperative neurological infection | Incidence of neurological infection within 7 days after surgery | Postoperative Day 7 | 
| Postoperative urinary system infection | Incidence of urinary system infection within 7 days after surgery | Postoperative Day 7 | 
| Postoperative colitis or infection with Clostridium difficile | Incidence of colitis or infection with Clostridium difficile within 7 | Postoperative Day 7 | 
| Postoperative endometritis | Incidence of endometritis within 7 days after surgery | Postoperative Day 7 | 
| Postoperative surgical site infection | Incidence of surgical site infection within 7 days after surgery | Postoperative Day 7 | 
| Postoperative deep incisional surgical site infection | Incidence of deep incisional surgical site infection within 7 days after surgery | Postoperative Day 7 | 
| Postoperative organ or space surgical site infection | Incidence of organ or space surgical site infection within 7 days after surgery | Postoperative Day 7 | 
| Postoperative unknown infection with pathogenic organisms in tissue or fluid | Incidence of unknown infection with pathogenic organisms in tissue or fluid | Postoperative Day 7 | 
| Postoperative sepsis | Incidence of sepsis within 7 days after surgery | Postoperative Day 7 | 
| Hospital discharge | Time-to-event outcome with the event hospital discharge | Postoperative Day 90 | 
| Unplanned hospital re-admission | Incidence of unplanned hospital re-admission within 30 days after surgery | Postoperative Day 30 |