Perioperative Personalized Blood Pressure Management: IMPROVE-multi (IMPROVE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Complications; Blood Pressure; Surgery; Anesthesia; Intraoperative Hypotension
• Intervention / Treatment: Other: Personalized blood pressure management

• Study Type: Interventional
• Enrollment (Estimated): 1272
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bernd Saugel, M.D.; Phone Number: 004940741052415; Email: b.saugel@uke.de
• Study Contact Backup: Name: Karim Kouz, M.D.; Phone Number: 004940741052415; Email: k.kouz@uke.de

Study Locations

• Germany
  • Hamburg, Germany, 20246
    • Recruiting
    • Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf
    • Contact: Karim Kouz, Dr; Phone Number: +49 40 7410 52415; Email: k.kouz@uke.de

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Routine management (control) group; 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; 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; 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.

What is the study measuring?

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
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
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 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 endometritis	Incidence of endometritis 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 sepsis	Incidence of sepsis within 7 days after surgery	Postoperative Day 7
Unplanned hospital re-admission	Incidence of unplanned hospital re-admission within 30 days after surgery	Postoperative Day 30
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 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
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 colitis or infection with Clostridium difficile	Incidence of colitis or infection with Clostridium difficile within 7	Postoperative Day 7
Postoperative surgical site infection	Incidence of 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
Hospital discharge	Time-to-event outcome with the event "hospital discharge"	Postoperative Day 90

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Collaborators: The Cleveland Clinic; Jena University Hospital
• Investigators: Principal Investigator: Bernd Saugel, M.D., Department of Anesthesiology, University Medical Center Hamburg-Eppendorf

Publications and helpful links

General Publications

• Bergholz A, Meidert AS, Flick M, Krause L, Vettorazzi E, Zapf A, Brunkhorst FM, Meybohm P, Zacharowski K, Zarbock A, Sessler DI, Kouz K, Saugel B. Effect of personalized perioperative blood pressure management on postoperative complications and mortality in high-risk patients having major abdominal surgery: protocol for a multicenter randomized trial (IMPROVE-multi). Trials. 2022 Nov 17;23(1):946. doi: 10.1186/s13063-022-06854-0.

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2023
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: June 12, 2022
• First Posted (Actual): June 14, 2022

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: July 1, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Hypotension; Postoperative Complications
• Other Study ID Numbers: ZKSJ0147

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No