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Worldwide, more than 200 million patients have major non-cardiac surgery annually and a significant proportion of these patients suffer major cardiovascular complications (e.g. nonfatal myocardial infarction, cardiac arrest, vascular death) within 30 days of their surgery. Perioperative myocardial infarction is the most common cardiovascular complication and recent clinical studies have shown that even minor myocardial injury in relation to non-cardiac surgery is associated with 30-day mortality.
Remote ischemic preconditioning is a procedure, which protects remote tissues and organs e.g. against ischemia-reperfusion injury. Cycles of forearm or leg ischemia and reperfusion by the inflation of a blood-pressure cuff for brief periods are the preferred method.The aim of this interventional clinical study is to determine whether remote ischemic preconditioning can reduce markers of myocardial injury in emergent or urgent non-cardiac surgery.
Patients with a hip fracture will be included in the study. The patients will be randomized to remote ischemic preconditioning or control (no intervention). The remote ischemic preconditioning procedure is carried out immediately after the induction of regional or general anesthesia. The blood pressure cuff is placed on the upper limb. The cuff is inflated to 200 mmHg resulting in a total occlusion of the blood flow to the limb. After 5 minutes of ischemia the cuff is deflated and the limb is reperfused for 5 minutes. The procedure is carried out 4 times in a row. For patients with systolic blood pressures >185 mmHg, the cuff will be inflated to at least 15 mmHg above the patient's systolic blood pressure.
The primary outcome is myocardial injury in noncardiac surgery within day 4 postoperatively.
We expect 15% of the patients in the placebo group to suffer myocardial injury while the incidence of myocardial injury is expected to be reduced to 7% in the intervention group. Type I error is set at 5% and type II error is set at 20%. In total 2 x 264 patients need to be included based on this power calculation. We will include patients until we have a total of 2 x 270 patients for evaluation (per-protocol).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention | Active Comparator | Remote ischemic preconditioning, 4 cycles of 5 minutes ischemia and 5 minutes reperfusion of the forearm before surgery. |
|
| Control | No Intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Remote ischemic preconditioning | Procedure | The remote ischemic preconditioning procedure is carried out immediately after the induction of regional or general anesthesia. The blood pressure cuff is placed on the upper limb. The cuff is inflated to 200 mmHg resulting in a total occlusion of the blood flow to the limb. After 5 minutes of ischemia the cuff is deflated and the limb is reperfused for 5 minutes. The procedure is carried out 4 times in a row. For patients with systolic blood pressures >185 mmHg, the cuff will be inflated to at least 15 mmHg above the patient's systolic blood pressure. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with myocardial injury in non-cardiac surgery | during surgery or the first 4 days after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Peak plasma TnI and total TnI release (area under the curve) | during surgery or the first 4 days after surgery | |
| Endothelial dysfunction (reactive hyperemia index) | Assessed by EndoPat | 24 hours after surgery |
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Inclusion Criteria:
patients ≥ 45 years undergoing in-hospital hip fracture surgery
undergoing emergent or urgent surgery (i.e. emergent or urgent visitation to the Department of Orthopedic Surgery)
fulfil 1 or more of the following 4 inclusion criteria, which are all determined during the conversation with the patient:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sarah E Busch, MD | Department of Surgery, Koge Hospital, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Depertment of Orthopedic Surgery, Holstebro Hospital | Holstebro | Central Jutland | 7500 | Denmark | ||
| Department of Anesthesia, Herlev Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37584362 | Derived | Wahlstrom KL, Ekeloef S, Gogenur I, Munster AB. Myocardial injury after non-cardiac surgery and per operative fibrin metabolism in patients undergoing hip-fracture surgery: an observational study. Scand J Clin Lab Invest. 2023 Sep;83(5):299-308. doi: 10.1080/00365513.2023.2220970. Epub 2023 Aug 16. | |
| 33440017 | Derived |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 29, 2016 | May 7, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D011183 | Postoperative Complications |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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|
| Perioperative myocardial infarction | 30 days, one year and 5 years after surgery |
| Major adverse cardiovascular events | 30 days, one year and 5 years after surgery |
| Length of postoperative hospital stay | participants will be followed for the duration of hospital stay, an expected average of 10 days |
| Length of intensive care unit stay | participants will be followed for the duration of hospital stay, an expected average of 10 days |
| All-cause mortality | 30 days, one year and 5 years after surgery |
| Biomarkers of coagulation | preoperatively, 2 hours after incision, and on days 1 and 2 after surgery |
| Plasma N-terminal Pro-Brain Natriuretic Peptide | Plasma N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) before surgery and at day 1 after surgery. | Preoperative and day 1 |
| Herlev |
| Region H |
| 2730 |
| Denmark |
| Department of Surgery, Koge Hospital | Køge | 4600 | Denmark |
| Ekeloef S, Koyuncu S, Holst-Knudsen J, Gundel O, Meyhoff CS, Homilius M, Stilling M, Ekeloef P, Munster AMB, Mathiesen O, Gogenur I. Cardiovascular events in patients undergoing hip fracture surgery treated with remote ischaemic preconditioning: 1-year follow-up of a randomised clinical trial. Anaesthesia. 2021 Aug;76(8):1042-1050. doi: 10.1111/anae.15357. Epub 2021 Jan 13. |
| 31801725 | Derived | Ekeloef S, Homilius M, Stilling M, Ekeloef P, Koyuncu S, Munster AB, Meyhoff CS, Gundel O, Holst-Knudsen J, Mathiesen O, Gogenur I. The effect of remote ischaemic preconditioning on myocardial injury in emergency hip fracture surgery (PIXIE trial): phase II randomised clinical trial. BMJ. 2019 Dec 4;367:l6395. doi: 10.1136/bmj.l6395. |
| D007238 |
| Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |