This trial is an investigator-initiated, multicenter, randomized, factorial, single-blind trial of multiple hemodynamic and respiratory targets during general anesthesia. These targets include blood pressure, positive end expiratory pressure, tidal volume, and fraction of inspired oxygen. Patients will be randomized to different targets using a factorial design, i.e., each patient is simultaneously randomized to four interventions. There will be five enrolling sites in the Central Denmark Region. 480 high-risk patients will be enrolled.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
485
Blood pressure targets during general anesthesia and 2 hours after
Positive end expiratory pressure during general anesthesia
Tidal volume during general anesthesia
Aalborg University Hospital
Aalborg, Denmark
Aarhus University Hospital
Aarhus, Denmark
Gødstrup Regional Hospital
Gødstrup, Denmark
Horsens Regional Hospital
Horsens, Denmark
Feasibility: Proportion of eligible patients randomized
Eligible patients will be defined as those meeting all inclusion criteria and none of the exclusion criteria 1 to 4.
Time frame: Up to 90 days
Feasibility: Proportion of patient with adherence to the assigned interventions
Adherence will be defined as follows: The allocated positive end expiratory pressure (± 1 cm H2O), tidal volume (± 1 ml/kg), and FiO2 (± 5%) is used in a minimum of 90% of the randomized patients for the duration of the surgery. Vasopressors/inotropes are only initiated and continued if the blood pressure declines below the allocated target in at least 60% of the patients and at least 60% of time during general anesthesia, i.e., 60% of the registered blood pressures should be within +/- 10 mmHg of the target when vasopressor/inotropes are administered.
Time frame: During surgery
Feasibility: Proportion of patients with separation of mean arterial pressure
We aim to achieve at least 5 mmHg separation in mean/median mean arterial pressure for the three blood pressure groups targeting mean arterial pressure.
Time frame: During surgery
Feasibility: Proportion of patients lost to follow-up
We aim to obtain data from more than 90% of patients still alive at 30- and 90-days follow-up.
Time frame: Up to 90 days
Proportion of patients with pulmonary post-operative complications (composite)
A composite of the following based on European Perioperative Clinical Outcome definitions: Respirator infection, respirator failure, pleural effusion, atelectasis, pneumothorax, bronchospasms, and aspiration pneumonitis.
Time frame: 30 days
Proportion of patient with pneumonia
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Fraction of inspired oxygen during general anesthesia and 2 hours after
Randers Regional Hospital
Randers, Denmark
Viborg Regional Hospital
Viborg, Denmark
Based on the United States of America Centers for Disease Control and Prevention (CDC) definition of pneumonia
Time frame: 30 days
Proportion of patient with pulmonary embolism
Presence of pulmonary embolus on computerized tomography (CT) or magnetic resonance (MR) imaging, or a high probability of pulmonary embolus based on ventilation perfusion scan.
Time frame: 30 days
Proportion of patient with acute kidney injury
Composite of post-operative renal complications using Kidney Disease Improving Global Outcomes (KDIGO) criteria
Time frame: 30 days
Creatinine
Measured in umol/L
Time frame: 2 hours after the surgery
Creatinine
Measured in umol/L
Time frame: The day after the surgery
Proportion of patient with major adverse cardiac events
A composite of the following based on European Perioperative Clinical Outcome definitions: Non-fatal cardiac arrest, acute myocardial infarction, congestive heart failure, new cardiac arrhythmia, and angina.
Time frame: 30 days
Troponin-I
Measured in ng/L
Time frame: 2 hours after the surgery
Troponin-I
Measured in ng/L
Time frame: The day after the surgery
Proportion of patients with myocardial injury after non-cardiac surgery
Post-operative troponin-I above the 99% percentile for the respective assay.
Time frame: 3 days
Alanine transaminase
Measured in U/L
Time frame: 2 hours after the surgery
Alanine transaminase
Measured in U/L
Time frame: The day after the surgery
Proportion of patients with emergence delirium
Based on the nursing delirium screening scale to evaluate emergence delirium 90-120 minutes after admission to the post-aesthesia care unit.
Time frame: 2 hours after the surgery
Proportion of patients with post-operative delirium
We will categorize delirium as delirium if this is either stated in the medical journal or retrospectively categorized as delirium if it meets pre-defined criteria based on the diagnostic and statistical manual of mental disorders, fifth edition from the American psychiatric association
Time frame: 7 days
Post-operative pain
Highest numeric rating scale (NRS) score (from 0 to 10 with higher scores indicating worse pain) documented
Time frame: 2 hours after the surgery
Opioid administered
Total opioid administered using morphine equivalent units.
Time frame: 24 hours
Proportion of patients with post-operative nausea and vomiting
Highest numeric rating scale (NRS) score (from 0 to 10 with higher scores indicating worse nausea and vomiting) documented
Time frame: 2 hours after the surgery
Antiemetic treatment
Administered antiemetic treatment (ondansetron, dexamethasone, cyclizine, droperidol, metoclopramide) within the first 24 hours after the operation.
Time frame: 24 hours
Proportion of patients with surgical site infections
Based on the United States of America Centers for Disease Control and Prevention (CDC) definition.
Time frame: 30 days
Clavien-Dindo grading of complications
In addition to reporting the individual post-operative complications, we will use the validated Clavien-Dindo classification to grade post-operative complications by the interventions needed.
Time frame: 30 days
Proportion of patients with intensive care unit admission
Both planned and unplanned stays at the intensive care unit.
Time frame: 30 days
Length of hospital stay
Reported in days.
Time frame: Up to 90 days
Days alive and out of the hospital
Reported in days. Patients that die during the 30 days, will receive a value of 0. All admissions at acute care hospitals in Denmark will be included in this outcome.
Time frame: Within 30 days
Proportion of patients with who die
Time frame: 30 days
Proportion of patients with who die
Time frame: 90 days
Health related quality of life
Based on the EQ-5D-5L questionnaire
Time frame: 30 days
Health related quality of life
Based on the EQ-5D-5L questionnaire
Time frame: 90 days
Proportion of patients with intraoperative complications
Specific complications occurring during the surgery: Bleeding, need of blood product transfusions, arrhythmia, pneumothorax, cardiac arrest, mortality.
Time frame: During surgery
Quality of recovery
Based on the quality of recovery-15 (QoR-15) score. The score ranges from 0-150 with higher scores indicating better recovery.
Time frame: 30 days
Quality of recovery
Based on the quality of recovery-15 (QoR-15) score. The score ranges from 0-150 with higher scores indicating better recovery.
Time frame: 90 days