Prevention of Myocardial Injury in Non-cardiac Surgery

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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Prevention of Myocardial Injury by Remote Ischemic Preconditioning in Emergent or Urgent Non-cardiac Surgery: a Randomized Clinical Trial

Conditions
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Myocardial Injury, Myocardial Infarction

Intervention / Treatment
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* Procedure: Remote ischemic preconditioning


Participation Criteria
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Eligibility Criteria
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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: Ischemic heart disease, defined by any of the following criteria A. angina pectoris B. prior myocardial infarction C. prior percutaneous coronary intervention D. prior coronary artery bypass graft Peripheral arterial disease, defined by any of the following criteria A. intermittent claudication B. reduced peripheral arterial blood flow C. prior vascular surgery due to peripheral arterial disease Prior stroke OR any 1 of 7 risk criteria A. age ≥70 years; B. congestive heart failure C. prior transient ischemic attack; D. diabetes and currently taking an oral hypoglycemic agent or insulin E. hypertension G. preoperative serum creatinine >175 µmol/L (>2.0 mg/dl) H. smoking within 2 years of surgery Exclusion Criteria: History of peripheral arterial disease affecting both upper limbs Renal failure with eGRF<30ml/min/1.73m2 Cardiogenic shock or cardiac arrest during the current hospital admission Reoperation after elective surgery carried out during the current hospital admission Not capable of giving informed consent after oral and written information Other conditions that prevent the performance of remote ischemic preconditioning. Previously included in this trial

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br>Remote ischemic preconditioning, 4 cycles of 5 minutes ischemia and 5 minutes reperfusion of the forearm before surgery. | Procedure: Remote ischemic preconditioning<br>* 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.<br>|
| No Intervention: Control<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with myocardial injury in non-cardiac surgery |  | during surgery or the first 4 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perioperative, Postoperative Complications/prevention & control