Clinical trial NCT05416944: Perioperative Personalized Blood Pressure Management: IMPROVE-multi
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Blood Pressure
Intraoperative Hypotension
Postoperative Complications
Surgery
Anesthesia
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: Jena University Hospital
name: The Cleveland Clinic
First posted: 2022-06-14
Enrollment: 1272
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Composite outcome of major postoperative complications
timeFrame: Postoperative Day 7
Secondary outcomes:
measure: Composite outcome of major postoperative complications
timeFrame: Postoperative Day 3
measure: Postoperative acute kidney injury
timeFrame: Postoperative Day 3
measure: Postoperative acute kidney injury
timeFrame: Postoperative Day 7
measure: Postoperative acute myocardial injury (including myocardial infarction)
timeFrame: Postoperative Day 3
measure: Postoperative acute myocardial injury (including myocardial infarction)
timeFrame: Postoperative Day 7
measure: Postoperative non-fatal cardiac arrest
timeFrame: Postoperative Day 3
measure: Postoperative non-fatal cardiac arrest
timeFrame: Postoperative Day 7
measure: Postoperative death
timeFrame: Postoperative Day 3
measure: Postoperative death
timeFrame: Postoperative Day 7
measure: Composite outcome of long-term postoperative complications
timeFrame: Postoperative Day 30
measure: Composite outcome of long-term postoperative complications
timeFrame: Postoperative Day 90
measure: Postoperative need for renal replacement therapy
timeFrame: Postoperative Day 30
measure: Postoperative need for renal replacement therapy
timeFrame: Postoperative Day 90
measure: Postoperative myocardial infarction
timeFrame: Postoperative Day 30
measure: Postoperative myocardial infarction
timeFrame: Postoperative Day 90
measure: Postoperative non-fatal cardiac arrest
timeFrame: Postoperative Day 30
measure: Postoperative non-fatal cardiac arrest
timeFrame: Postoperative Day 90
measure: Postoperative death
timeFrame: Postoperative Day 30
measure: Postoperative death
timeFrame: Postoperative Day 90
measure: Postoperative infectious complications
timeFrame: Postoperative Day 7
measure: Postoperative fever
timeFrame: Postoperative Day 7
measure: Postoperative respiratory infection
timeFrame: Postoperative Day 7
measure: Postoperative neurological infection
timeFrame: Postoperative Day 7
measure: Postoperative urinary system infection
timeFrame: Postoperative Day 7
measure: Postoperative colitis or infection with Clostridium difficile
timeFrame: Postoperative Day 7
measure: Postoperative endometritis
timeFrame: Postoperative Day 7
measure: Postoperative surgical site infection
timeFrame: Postoperative Day 7
measure: Postoperative deep incisional surgical site infection
timeFrame: Postoperative Day 7
measure: Postoperative organ or space surgical site infection
timeFrame: Postoperative Day 7
measure: Postoperative unknown infection with pathogenic organisms in tissue or fluid
timeFrame: Postoperative Day 7
measure: Postoperative sepsis
timeFrame: Postoperative Day 7
measure: Hospital discharge
timeFrame: Postoperative Day 90
measure: Unplanned hospital re-admission
timeFrame: Postoperative Day 30
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf
Study officials:
affiliation: Department of Anesthesiology, University Medical Center Hamburg-Eppendorf
name: Bernd Saugel, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.