Anesthesia, Cardiac Output, Postoperative Complications, Surgery
Conditions
Brief summary
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.
Detailed description
not provided
Interventions
OTHERPersonalized hemodynamic management
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.
Sponsors
Universitätsklinikum Hamburg-Eppendorf
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
In patients in the routine management group, the treating anesthesiologists will be blinded to data of preoperative baseline cardiac output measurements to avoid performance bias. Participanting patients, outcome assessors, and data analysts are blinded to group allocation.
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite outcome of major postoperative complications | Postoperative Day 7 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite outcome of major postoperative complications | Postoperative Day 3 | 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. |
| Postoperative acute kidney injury | Postoperative Day 3 | Incidence of acute kidney injury within 3 days after surgery |
| Postoperative acute myocardial injury | Postoperative Day 3 | Incidence of acute myocardial injury within 3 days after surgery |
| Postoperative severe infectious complications | Postoperative Day 3 | 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. |
| Postoperative non-fatal cardiac arrest | Postoperative Day 3 | Incidence of postoperative non-fatal cardiac arrest within 3 days after surgery |
| Postoperative death | Postoperative Day 3 | Incidence of postoperative death within 3 days after surgery |
| Composite outcome of long-term postoperative complications | Postoperative Day 30 | Collapsed incidence of need for renal replacement therapy, myocardial infarction, non-fatal cardiac arrest, and death within 30 days after surgery |
| Postoperative need for renal replacement therapy | Postoperative Day 30 | Incidence of need for renal replacement therapy within 30 days after surgery |
| Postoperative myocardial infarction | Postoperative Day 30 | Incidence of myocardial infarction within 30 days after surgery |
| Postoperative fever | Postoperative Day 7 | Incidence of fever within 7 days after surgery |
| Postoperative respiratory infection | Postoperative Day 7 | Incidence of respiratory infection within 7 days after surgery |
| Postoperative neurological infection | Postoperative Day 7 | Incidence of neurological infection within 7 days after surgery |
| Postoperative urinary system infection | Postoperative Day 7 | Incidence of urinary system infection within 7 days after surgery |
| Postoperative colitis or infection with Clostridium difficile | Postoperative Day 7 | Incidence of colitis or infection with Clostridium difficile within 7 days after surgery |
| Postoperative endometritis | Postoperative Day 7 | Incidence of endometritis within 7 days after surgery |
| Postoperative deep incisional surgical site infection | Postoperative Day 7 | Incidence of deep incisional surgical site infection within 7 days after surgery |
| Postoperative organ or space surgical site infection | Postoperative Day 7 | Incidence of organ or space surgical site infection (including anastomotic leak) within 7 days after surgery |
| Postoperative unknown infection with pathogenic organisms in tissue or fluid | Postoperative Day 7 | Incidence of unknown infection with pathogenic organisms in tissue or fluid within 7 days after surgery |
| Postoperative sepsis | Postoperative Day 7 | Incidence of sepsis within 7 days after surgery |
| Transfer from intensive care unit to normal ward | Postoperative Day 90 | Time-to-event endpoint with the event "transfer from intensive care unit to normal ward" within 90 days after surgery |
| Hospital discharge | Postoperative Day 90 | Time-to-event endpoint with the event "hospital discharge" within 90 days after surgery |
| Unplanned hospital re-admission | Postoperative Day 30 | Incidence of unplanned hospital re-admission within 30 days after surgery |
Countries
Austria, Czechia, Denmark, Germany, Spain
Contacts
PRINCIPAL_INVESTIGATORBernd Saugel, M.D.
Universitätsklinikum Hamburg-Eppendorf
Outcome results
None listed