Personalized Hemodynamic Management in High-risk Major Abdominal Surgery

Universitätsklinikum Hamburg-Eppendorf1,128 enrolled

Overview

Postoperative mortality within 30 days after surgery is around 2% in patients having major noncardiac surgery in Europe and the USA. In fact, if the first 30 days after surgery were considered a disease, it would be the third leading cause of death globally. Postoperative deaths are a consequence of postoperative organ injury and complications - including acute myocardial injury, acute kidney injury, and severe infectious complications. To avoid postoperative deaths, it is thus crucial to reduce postoperative organ injury and complications. To reduce postoperative organ injury and complications, modifiable risk factors need to be addressed. These modifiable risk factors for postoperative organ injury include low blood flow states and intraoperative hypotension. Optimizing blood flow (i.e., cardiac index) during surgery may thus be effective in reducing postoperative organ injury and complications. However, the optimal hemodynamic treatment strategy for high-risk surgical patients remains unclear. Cardiac index varies substantially between individuals. However, current intraoperative hemodynamic treatment strategies mainly aim to maximize cardiac index instead of using personalized cardiac index targets for each individual patient. A single-center pilot trial suggests that using individualized cardiac index targets during surgery may reduce postoperative organ injury and complications compared to routine hemodynamic management. However, large robust trials investigating the effect of personalized hemodynamic management targeting preoperative baseline cardiac index on postoperative complications are missing. The investigators, therefore, propose a multicenter randomized trial to test the hypothesis that personalized intraoperative hemodynamic management targeting preoperative baseline cardiac index reduces the incidence of a composite outcome of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, severe infectious complications, and death within 7 days after surgery compared to routine hemodynamic management in high-risk patients having elective major abdominal surgery.

not provided

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Interventions

Personalized hemodynamic managementOTHER

Personalized hemodynamic management: Intraoperative cardiac index will be maintained at least at the preoperative baseline cardiac index. Preoperative baseline cardiac index will be determined one day before surgery with the patient being awake and resting in the supine position using the Starling Fluid Management System (Baxter, Deerfield, IL, USA) Preoperative baseline cardiac index will be determined with the patient being awake and resting in supine position using the Starling Fluid Management System (Baxter, Deerfield, IL, USA) (usually at least one day before surgery). We will define the individual preoperative baseline cardiac index as the average value over a 5 min period at rest (minimum cardiac index threshold: 2.2 L min-1 m-2). Intraoperative cardiac index will be measured using the Baxter Starling Fluid Management System.

Eligibility

Sex: ALLMin age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria: Consenting patients ≥45 years scheduled for elective major abdominal surgery (involving visceral organs) 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-1 or estimated glomerular filtration rate \<90 mL min-1 (1.73 m2)-1 within the last 6 months * coronary artery disease * 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) or therapy (e.g., immunosuppressants, chemotherapy, radiation, steroids \[above Cushing threshold\]) * liver cirrhosis (any Child-Pugh class) * body mass index ≥30 kg m-2 * history of smoking within two years of surgery * age ≥65 years * expected surgery 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 * ambulatory surgery * planned surgery: nephrectomy, liver or kidney transplantation surgery * 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 * impossibility to perform cardiac index monitoring using the Starling Fluid Management System (Baxter, Deerfield, IL, USA) * current participation in another clinical trial or treatment with a similar biological mechanism or primary outcome measure

Locations (12)

Medical University of Graz

Graz, Austria

University Hospital Plzen

Pilsen, Czechia

Hvidovre Hospital

Copenhagen, Denmark

Rigshospitalet

Copenhagen, Denmark

University Medical Center Copenhagen Bispebjerg and Frederiksberg

Copenhagen, Denmark

University Hospital RWTH Aachen

Aachen, Germany

University Hospital Düsseldorf

Düsseldorf, Germany

University Medical Center Hamburg

Hamburg, Germany

University Medical Center Schleswig Holstein, Lübeck

Lübeck, Germany

University Hospital Marburg

Marburg, Germany

...and 2 more locations

Outcomes

Primary Outcomes

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, severe infectious complications, and death within 7 days after surgery.

Time frame: Postoperative Day 7

Secondary Outcomes

Composite outcome of major postoperative complications

Collapsed incidence of acute kidney injury, acute myocardial injury (including myocardial infarction), non-fatal cardiac arrest, severe infectious complications, and death within 3 days after surgery.

Time frame: Postoperative Day 3

Postoperative acute kidney injury

Incidence of acute kidney injury within 3 days after surgery

Time frame: Postoperative Day 3

Postoperative acute kidney injury

Incidence of acute kidney injury within 7 days after surgery

Time frame: Postoperative Day 7

Postoperative acute myocardial injury

Incidence of acute myocardial injury within 3 days after surgery

Time frame: Postoperative Day 3

Postoperative acute myocardial injury

Incidence of acute myocardial injury within 7 days after surgery

Time frame: Postoperative Day 7

Postoperative severe infectious complications

Incidence of a composite outcome 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 (including anastomotic leak), unknown infection with pathogenic organisms in tissue or fluid, and sepsis within 3 days after surgery.

Time frame: Postoperative Day 3

Postoperative severe infectious complications

Time frame: Postoperative Day 7

Postoperative non-fatal cardiac arrest

Incidence of postoperative non-fatal cardiac arrest within 3 days after surgery

Time frame: Postoperative Day 3

Postoperative non-fatal cardiac arrest

Incidence of postoperative non-fatal cardiac arrest within 7 days after surgery

Time frame: Postoperative Day 7

Postoperative death

Incidence of postoperative death within 3 days after surgery

Time frame: Postoperative Day 3

Postoperative death

Incidence of postoperative death within 7 days after surgery

Time frame: 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

Time frame: 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

Time frame: Postoperative Day 90

Postoperative need for renal replacement therapy

Incidence of need for renal replacement therapy within 30 days after surgery

Time frame: Postoperative Day 30

Postoperative need for renal replacement therapy

Incidence of need for renal replacement therapy within 90 days after surgery

Time frame: Postoperative Day 90

Postoperative myocardial infarction

Incidence of myocardial infarction within 30 days after surgery

Time frame: Postoperative Day 30

Postoperative myocardial infarction

Incidence of myocardial infarction within 90 days after surgery

Time frame: Postoperative Day 90

Postoperative non-fatal cardiac arrest

Incidence of non-fatal cardiac arrest within 30 days after surgery

Time frame: Postoperative Day 30

Postoperative non-fatal cardiac arrest

Incidence of non-fatal cardiac arrest within 90 days after surgery

Time frame: Postoperative Day 90

Postoperative death

Incidence of death within 30 days after surgery

Time frame: Postoperative Day 30

Postoperative death

Incidence of death within 90 days after surgery

Time frame: Postoperative Day 90

Postoperative fever

Incidence of fever within 7 days after surgery

Time frame: Postoperative Day 7

Postoperative respiratory infection

Incidence of respiratory infection within 7 days after surgery

Time frame: Postoperative Day 7

Postoperative neurological infection

Incidence of neurological infection within 7 days after surgery

Time frame: Postoperative Day 7

Postoperative urinary system infection

Incidence of urinary system infection within 7 days after surgery

Time frame: Postoperative Day 7

Postoperative colitis or infection with Clostridium difficile

Incidence of colitis or infection with Clostridium difficile within 7 days after surgery

Time frame: Postoperative Day 7

Postoperative endometritis

Incidence of endometritis within 7 days after surgery

Time frame: Postoperative Day 7

Postoperative deep incisional surgical site infection

Incidence of deep incisional surgical site infection within 7 days after surgery

Time frame: Postoperative Day 7

Postoperative organ or space surgical site infection

Incidence of organ or space surgical site infection (including anastomotic leak) within 7 days after surgery

Time frame: Postoperative Day 7

Postoperative unknown infection with pathogenic organisms in tissue or fluid

Incidence of unknown infection with pathogenic organisms in tissue or fluid within 7 days after surgery

Time frame: Postoperative Day 7

Postoperative sepsis

Incidence of sepsis within 7 days after surgery

Time frame: Postoperative Day 7

Transfer from intensive care unit to normal ward

Time-to-event endpoint with the event "transfer from intensive care unit to normal ward" within 90 days after surgery

Time frame: Postoperative Day 90

Hospital discharge

Time-to-event endpoint with the event "hospital discharge" within 90 days after surgery

Time frame: Postoperative Day 90

Unplanned hospital re-admission

Incidence of unplanned hospital re-admission within 30 days after surgery

Time frame: Postoperative Day 30

Personalized Hemodynamic Management in High-risk Major Abdominal Surgery

Overview

Conditions

Interventions

Eligibility

Locations (12)

Outcomes

Primary Outcomes

Secondary Outcomes