Perioperative Myocardial Injury, Autonomic Dysfunction, Cardiovascular (CV) Risk, Major Surgery, Beta Blocker, Myocardial Injury After Non-cardiac Surgery
Conditions
Keywords
perioperative myocardial injury, major surgery, beta blocker, myocardial injury after non-cardiac surgery, autonomic dysfunction
Brief summary
Limiting perioperative tachycardia (aiming for a heart rate \<90 beats per minute throughout the perioperative period) using the ultra-short acting beta-blocker landiolol in patients with cardiovascular risk factors undergoing major surgery might lower the incidence of perioperative myocardial injury. Feasibility of the intervention needs to be proven prior to conduction of a larger trial.
Detailed description
Despite advances in surgical and anaesthetic techniques, perioperative mortality remains high, even in developed countries. Major complications contributing almost half of all deaths after surgery are major bleeding (17%), myocardial injury after non-cardiac surgery (13%) and sepsis (12%). Myocardial injury after non-cardiac surgery occurs up to 18% in patients \>45 years and is associated with a marked increase in 30-day mortality. Additional factors posing patients at risk for perioperative myocardial injury might be autonomic dysfunction, measured as exaggerated heart rate response to exercise or impaired heart rate recovery thereafter, as perioperative tachycardia is associated with perioperative myocaridal injury. The perioperative use of beta-blockers remains controversial, but the newely marketed ultra-short acting and highly cardioselective beta-blocker landiolol offers the opportunity to reduce perioperative heart rate without affecting blood pressure. The intervention (perioperative reduction of heart rate using landiolol) in this specific patient population needs to be proven as feasible prior to conducting a larger scale trial.
Interventions
DRUGLandiolol
The main dose range is 1-40 mcg/kg/min, titrated to the effect on heart rate aiming for a heart rate of below 90 beats per minute throughout. This dose can be decreased to 0 if heart rate stays below target.
Sponsors
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients undergoing elective non-cardiac surgery defined as intermediate or high-risk by the 2022 european society of cardiology (ESC) guidelines * expected duration of surgery of at least 90 minutes; * expected length of hospital stay ≥ 24 hours; * age \> 45 years with at least two of the following risk factors (adapted from revised cardiac risk index): * ischemic heart disease (history of myocardial infarction or positive exercise test, current complaint of chest pain considered to be secondary to myocardial ischemia, use of nitrates, pathological Q waves, prior coronary revascularization); * history of congestive heart failure; * history of cerebrovascular disease; * insulin-dependent diabetes mellitus; * creatinine \> 176.8 mmol/l; * pre-operative NTproBNP \> 200 pg/ml; * excessive sympathetic outflow as proven by exercise testing: * impaired HR recovery (≤ 12 bpm within 1 minute after cessation of exercise); OR * exaggerated HR response (≥ 12 bpm after 1 minute of unloaded pedalling);
Exclusion criteria
* unable to consent or follow study procedures; * absolute contraindications for exercise testing; * pregnancy or intention to become pregnant; * active cardiac conditions (such as unstable coronary syndromes, decompensated heart failure, significant arrhythmias, severe valvular disease); * urgent / emergency surgery; * already on β-blocker (within the last 30 days prior to recruitment); * contraindication for β-blocker therapy (bradycardia (HR \< 55 bpm), hypotension (systolic blood pressure \< 100 mmHg), severe peripheral vascular disease, severe asthma, allergy, higher-degree atrioventricular block); * severe preoperative anaemia (haemoglobin \< 100 g/L) unless there is a plan set up and followed for correction prior to surgery; * planned intermediate care or intensive care admission; * prior enrolment in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time perioperative heart rate in target range | From induction of anaesthesia until discharge from postanaesthetic care unit [percent of time heart rate within target range (<90 beats per minute)] | As a marker of successful intervention, time perioperative heart rate in target range (below 90 beats per minute) will serve as primary outcome. The intervention is considered feasible if the heart rate stays at least 90% of the time within the target range during the perioperative period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose of vasopressors | Induction of anaesthesia until discharge from postanaeshetic care unit [mcg per recorded drug] | Total dose of vasopressors such as noradrenalin, ephedrine or phenylephrine will be recorded in micrograms. |
| Perioperative heart rate | From induction of anaesthesa until discharge from postanaesthetic care unit [heart rate in beats per minute * minutes ] | Perioprative heart rate will be calculated as time weighted area under the curve for the perioperative period. |
| Length of postanaesthetic care unit stay | Admission to postanaesthetic care unit until discharge from postanaesthetic care unit [minutes] | Lenght of postaenaesthetic care unit stay will be recorded in minutes. |
| Length of hospital stay | Admission to hospital until discharge from hospital [days] | Length of hospital stay will be recorded in days. |
| Perioperative myocardial injury | 72 hours after surgery | Perioperative myocardial injury (PMI) is defined as an increase of hsTroponinT ≥ 14ng/L above the preoperative value according to the Basel-PMI criteria, not meeting major adverse cardiovascular event (MACE) criteria. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of life (EQ-5D) | 30 days after surgery | Quality of life will be assessed using the EQ-5D questionnaire. The EQ-5D questionnaire is a standardised health-related quality of life questionnaire developed by the EuroQol Group. It assesses five dimensions of health and results in an utility index score ranging from 0 (death) to 1 (perfect health). |
| Comprehensive complication index | 30 days after surgery | The comprehensive complication index is calculated as a sum of all complications weighted for their severity. It results in a continuous scale ranking the severity of any combination of complications from 0 (no complication) to 100 (death). |
| All-cause death | 30 days after surgery | This parameter serves to assess postoperative mortality. |
| Major adverse cardio- and cerebrovascular events | 30 days after surgery | Major adverse cardio- and cerebrovascular events (MACCE) include diagnosis of non-fatal cardiac arrest, acute myocardial infarction, congestive heart failure, new cardiac arrhythmia or angina, non-fatal stroke. |
Countries
Switzerland
Contacts
Primary ContactChristian M Beilstein, MD
Backup ContactPatrick Y Wuethrich, Prof MD
Outcome results
None listed