Intraoperative Hypotension, Postoperative Delirium (POD)
Conditions
Keywords
anesthesia, cardiovascular dynamics, hemodynamic monitoring
Brief summary
In older patients having surgery, postoperative delirium (an acute disturbance in awareness, attention, or cognition) is common and associated with short-term and long-term morbidity and mortality. The pathophysiology of postoperative delirium is multifactorial - but presumably includes inadequate brain perfusion during surgery caused by low intraoperative blood pressure. Therefore, the investigators aim to determine in a multicenter randomized-controlled trial if targeted intraoperative blood pressure management reduces postoperative delirium. The investigators will test the primary hypothesis that maintaining intraoperative mean arterial pressure at 85 mmHg or higher - compared to at 65 mmHg or higher (routine care) - reduces the incidence of postoperative delirium within the first 3 postoperative days in older patients with arterial hypertension having non-cardiac surgery. The investigators will also assess the duration of postoperative delirium, postoperative complications, and the patients' quality of life. The results of this trial will have a direct impact on guidelines and will help improve medical care for patients and the patients' health. Effective strategies to prevent postoperative delirium are missing. The hypothesis that targeted intraoperative blood pressure management can help reduce postoperative delirium is supported by previous observational studies and interventional trials. This trial is supposed to confirm the causal relationship between intraoperative blood pressure and postoperative delirium and to demonstrate the effectiveness of the therapeutic approach.
Interventions
OTHERMAP at 85 mmHg or higher (intervention group)
In patients assigned to the intervention group, clinicians will be instructed to maintain MAP at 85 mmHg or higher. The trial intervention will start at the beginning of induction of general anesthesia and ends at the end of surgery.
OTHERMAP at 65 mmHg or higher (control group)
In patients assigned to the control group, clinicians will be instructed to maintain MAP at 65 mmHg or higher. The trial intervention will start at the beginning of induction of general anesthesia and ends at the end of surgery.
Sponsors
Universitätsklinikum Hamburg-Eppendorf
Germany's Federal Ministry of Research, Technology and Space (BMFTR)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Patients, outcome assessors, outcome adjudicators, and data analysts will be blinded to treatment allocation.
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible for trial inclusion, patients must: * 1\) be able to provide informed consent, AND * 2\) be ≥65 years old, AND * 3\) be scheduled for elective non-cardiac surgery with general anesthesia that is expected to last ≥120 minutes, AND * 4\) have chronic arterial hypertension requiring antihypertensive medication OR have a systolic arterial pressure ≥140 mmHg or diastolic arterial pressure ≥90 mmHg on a measurement performed within the previous year, AND * 5\) be at high risk for postoperative delirium because: American Society of Anesthesiologists physical status class III or IV OR Charlson Comorbidity Index ≥3 points (please see Appendix 1) OR frailty (documented in medical records or clinical diagnosis)
Exclusion criteria
Patients that meet one or more of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delirium within the first 3 postoperative days (binary outcome) | within the first 3 postoperative days | Delirium will be assessed on the day of surgery after transfer from the post-anesthesia care unit to the general ward or intensive care unit and twice daily on postoperative days 1, 2, and 3. The 3-Minute Diagnostic Confusion Assessment Method will be used for patients on general wards and the Confusion Assessment Method for the Intensive Care Unit for patients in intensive care units. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days patients have delirium within the first 3 postoperative days (count outcome) | within the first 3 postoperative days | — |
| Delirium within the first 7 postoperative days (binary outcome) | within the first 7 postoperative days | Delirium will be based on systematic delirium assessments through postoperative day 3 and routine clinical screening from postoperative days 4 to 7. |
| Acute kidney injury within the first 7 postoperative days (binary outcome) | within the first 7 postoperative days | Acute kidney injury will be defined as an increase in serum creatinine of ≥50% from baseline or need for renal replacement therapy. |
| Acute myocardial injury within the first 7 postoperative days (Fourth Universal Definition 2018; binary outcome) | within the first 7 postoperative days | Acute myocardial injury (Fourth Universal Definition 2018) will be defined as an increase in high-sensitivity troponin according to the definition of "myocardial injury and infarction associated with non-cardiac procedures" set forth in the Fourth Universal Definition of Myocardial Infarction (2018). |
| Acute myocardial injury within the first 7 postoperative days (latest definition at time of analysis; binary outcome) | within the first 7 postoperative days | Acute myocardial injury (latest definition at time of analysis) will be defined according to the latest applicable universal definition available at the time of the final analysis; this definition will be prespecified in the statistical analysis plan before database lock and unblinding. |
| Stroke within the first 7 postoperative days (binary outcome) | within the first 7 postoperative | Stroke will be defined as any documented diagnosis of stroke in the medical record. |
| Days alive and out of hospital within the first 90 postoperative days (count outcome) | within the first 90 postoperative days | Days alive and out of hospital within the first 90 postoperative days will be defined as the number of days patients are alive and not hospitalized during the first 90 days after surgery. Patients who die within 90 days will be assigned 0 days alive and out of hospital. |
| Time until all-cause death within the first 90 postoperative days (time-to-event outcome) | within the first 90 postoperative days | Time to all-cause death within 90 postoperative days will be defined as the time from surgery to death from any cause. Patients alive at 90 days will be censored at 90 days. |
| Time until discharge from hospital within the first 90 postoperative days (time-to-event outcome) | within the first 90 postoperative days | Time to hospital discharge within 90 postoperative days will be defined as the time from surgery to hospital discharge; patients not discharged will be censored at death, trial withdrawal, or 90 days, whichever occurs first. |
| Long-term cognitive function at postoperative day 180 (continuous outcome) | postoperative day 180 | Long-term cognitive function will be assessed before surgery and at postoperative day 180 using the 5-minute Montreal Cognitive Assessment (minimal score: 0 points, maximal score: 15 points; with higher scores indicating better cognitive function). |
| Quality of recovery at postoperative day 2 (continuous outcome) | postoperative day 2 | Quality of recovery will be assessed before surgery and 48 hours after surgery using the Quality of Recovery-15 questionnaire (minimal score: 0 points, maximal score: 150 points; with higher scores indicating better quality of recovery). |
| Quality of life at postoperative day 180 (visual analog scale; continuous outcome) | postoperative day 180 | Quality of life will be assessed before surgery and at postoperative day 180 using the European Quality of Life 5 Dimension 5 Level (EQ-5D-5L) questionnaire (visual analog scale; minimal score: 0, maximal score: 100; with higher scores indicating better quality of life). |
| Quality of life at postoperative day 180 (index value; continuous outcome) | postoperative day 180 | Quality of life will be assessed before surgery and at postoperative day 180 using the European Quality of Life 5 Dimension 5 Level (EQ-5D-5L) questionnaire (index value using the German population value set; maximal score: 1.000; with higher scores indicating better quality of life). |
Countries
Germany
Contacts
CONTACTKarim Kouz, MD
CONTACTBernd Saugel, MD
Outcome results
None listed