Patients Undergoing General Anesthesia
Conditions
Brief summary
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.
Interventions
PROCEDUREBlood pressure
Blood pressure targets during general anesthesia and 2 hours after
PROCEDUREPositive end expiratory pressure
Positive end expiratory pressure during general anesthesia
PROCEDURETidal volume
Tidal volume during general anesthesia
PROCEDUREFraction of inspired oxygen
Fraction of inspired oxygen during general anesthesia and 2 hours after
Sponsors
Lars Wiuff Andersen
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * American Society of Anesthesiologists (ASA) classification 3 to 5 * Planned endotracheal intubation with positive pressure ventilation * Expected operating time ≥ 90 minutes * Certain types of surgery
Exclusion criteria
* Inability to obtain consent (e.g., patient is unconscious, hyperacute surgery) * Known or suspected pregnancy * Out-patient/same-day surgery * Intubated prior to surgery * Clinical judgement by the anesthesiologist that any of the interventions could be potentially harmful to the patient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility: Proportion of eligible patients randomized | Up to 90 days | Eligible patients will be defined as those meeting all inclusion criteria and none of the exclusion criteria 1 to 4. |
| Feasibility: Proportion of patient with adherence to the assigned interventions | During surgery | 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. |
| Feasibility: Proportion of patients with separation of mean arterial pressure | During surgery | 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. |
| Feasibility: Proportion of patients lost to follow-up | Up to 90 days | We aim to obtain data from more than 90% of patients still alive at 30- and 90-days follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patient with pneumonia | 30 days | Based on the United States of America Centers for Disease Control and Prevention (CDC) definition of pneumonia |
| Proportion of patient with pulmonary embolism | 30 days | 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. |
| Proportion of patient with acute kidney injury | 30 days | Composite of post-operative renal complications using Kidney Disease Improving Global Outcomes (KDIGO) criteria |
| Creatinine | 2 hours after the surgery | Measured in umol/L |
| Proportion of patient with major adverse cardiac events | 30 days | 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. |
| Troponin-I | 2 hours after the surgery | Measured in ng/L |
| Proportion of patients with myocardial injury after non-cardiac surgery | 3 days | Post-operative troponin-I above the 99% percentile for the respective assay. |
| Alanine transaminase | 2 hours after the surgery | Measured in U/L |
| Proportion of patients with emergence delirium | 2 hours after the surgery | Based on the nursing delirium screening scale to evaluate emergence delirium 90-120 minutes after admission to the post-aesthesia care unit. |
| Proportion of patients with post-operative delirium | 7 days | 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 |
| Health related quality of life | 30 days | Based on the EQ-5D-5L questionnaire |
| Opioid administered | 24 hours | Total opioid administered using morphine equivalent units. |
| Proportion of patients with post-operative nausea and vomiting | 2 hours after the surgery | Highest numeric rating scale (NRS) score (from 0 to 10 with higher scores indicating worse nausea and vomiting) documented |
| Antiemetic treatment | 24 hours | Administered antiemetic treatment (ondansetron, dexamethasone, cyclizine, droperidol, metoclopramide) within the first 24 hours after the operation. |
| Proportion of patients with surgical site infections | 30 days | Based on the United States of America Centers for Disease Control and Prevention (CDC) definition. |
| Clavien-Dindo grading of complications | 30 days | 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. |
| Proportion of patients with intensive care unit admission | 30 days | Both planned and unplanned stays at the intensive care unit. |
| Length of hospital stay | Up to 90 days | Reported in days. |
| Days alive and out of the hospital | Within 30 days | 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. |
| Proportion of patients with who die | 30 days | — |
| Post-operative pain | 2 hours after the surgery | Highest numeric rating scale (NRS) score (from 0 to 10 with higher scores indicating worse pain) documented |
| Proportion of patients with intraoperative complications | During surgery | Specific complications occurring during the surgery: Bleeding, need of blood product transfusions, arrhythmia, pneumothorax, cardiac arrest, mortality. |
| Quality of recovery | 30 days | Based on the quality of recovery-15 (QoR-15) score. The score ranges from 0-150 with higher scores indicating better recovery. |
| Proportion of patients with pulmonary post-operative complications (composite) | 30 days | A composite of the following based on European Perioperative Clinical Outcome definitions: Respirator infection, respirator failure, pleural effusion, atelectasis, pneumothorax, bronchospasms, and aspiration pneumonitis. |
Countries
Denmark
Outcome results
None listed