Perioperative Inflammatory Response Assessment in High-risk Patients Undergoing Noncardiac Surgery

Study Overview
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Brief Summary
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Postoperative cardiovascular complications are common after noncardiac surgery. The association between perioperative inflammation and the occurrence of cardiovascular complications after surgery is still unknown. Therefore, we will evaluate as our primary aim the association between patients with increased postoperative inflammation, assessed with C-reactive protein measurements, and the occurrence of major cardiovascular complications after noncardiac surgery. We will further evaluate the influence of perioperative inflammation on the occurrence of postoperative acute kidney injury. We will also evaluate the association between inflammation and the influence on Days-At-Home within 30 days. Furthermore, we will evaluate the association between increased inflammatory biomarkers and postoperative N-terminal pro brain natriuretic peptide (NT-proBNP) concentration.

Official Title
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Perioperative Inflammatory Response Assessment in High-risk Patients Undergoing Noncardiac Surgery - a Prospective Non-interventional Observational Study

Conditions
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Postoperative Complications, Cardiovascular Complication, Myocardial Ischemia, Inflammation

Intervention / Treatment
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* Diagnostic Test: Laboratory measurements


Participation Criteria
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Eligibility Criteria
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All patients need to meet all of the following criteria for inclusion (1-4): Surgery planned for more than two hours ≥ 45 years of age Provide written informed consent AND Fulfill ≥ 1 of the following criteria (A-K) Inclusion Criteria: NT-proBNP ≥ 200 ng/L Troponin T > 25 ng/L History of coronary artery disease History of peripheral artery disease (PAD) 75 years or older History of transient ischemic attack (TIA) or stroke Current smoking or cessation of smoking within 2 years Diabetes or currently taking anti-diabetic drug Hyperlipidemia History of hypertension or currently taking an antihypertensive drug Atrial fibrillation Exclusion Criteria: Patients on immune-suppressive therapy ICU patients undergoing surgery Preoperative Sepsis/systemic inflammatory syndrome (SIRS) needing ICU treatment Preoperative hemodynamically instable patients, who require vasopressor or inotropic support History of severe heart failure (defined as left ventricular ejection fraction (LVEF) < 30%) Liver cirrhosis Chronic inflammatory bowel diseases (CIBD) Severe rheumatic diseases requiring immunosuppressive treatment

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients at least 45 years at-risk for cardiovascular complications<br> | Diagnostic Test: Laboratory measurements<br>* Inflammatory and cardiac biomarkers will be measured before surgery, and on the first, second, third and fifth postoperative day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of cardiovascular complications | The primary aim of the study is to investigate the influence of the maximum C-reactive protein value (over the first 3 days after surgery) on the incidence of major cardiovascular complications within 30 days after surgery. The composite binary endpoint is defined as myocardial infarction, myocardial injury after noncardiac surgery, new onset of atrial fibrillation, stroke or death. | within 30 days after surgery and one year after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-reactive protein | Secondary goals of the study are to investigate the influence of the C-reactive protein on day 5 on the incidence of cardiovascular complications within 30 days after surgery (combined binary endpoint). | within 30 days after surgery | 
| Acute Kidney Injury - C-reactive proteint | We will evaluate the influence C-reactive protein on the occurrence of postoperative acute kidney injury. | within 5 days after surgery | 
| Acute Kidney Injury - Interleukin 6 | We will evaluate the influence of Interleukin 6 on the occurrence of postoperative acute kidney injury. | within 5 days after surgery | 
| Acute Kidney Injury - Procalcitonin | We will evaluate the influence of Procalcitonin on the occurrence of postoperative acute kidney injury. | within 5 days after surgery | 
| Acute Kidney Injury - Copeptin | We will evaluate the influence of Copeptin on the occurrence of postoperative acute kidney injury. | within 5 days after surgery | 
| Days at home within 30 days (DAH 30) | We will evaluate the correlation between perioperative inflammation (C-reactive protein, Interleukin 6, Procalcitonin, Copeptin) and the number of days patient spend at home after surgery within 30 days (DAH30). Outcomes measure: Hospital discharge data will be used to calculate hospital length of stay. DAH30 will be calculated using mortality and hospitalization data from the date of the index surgery (day 0). For example, if a patient will die on day 2 after surgery, they were assigned 0 DAH30. If a patient will be discharged from hospital at day 6 after surgery but will be readmitted for 4 days before the second hospital discharge, we will assign 20 DAH30. If a patient will die within 30 days after surgery, irrespective of whether they will spend time at home, DAH30 will be scored as 0. | within 30 days after surgery | 
| NT-proBNP | We will evaluate the correlation of each of the following inflammatory parameters including C-reactive protein, Interleukin 6, Procalcitonin, Copeptin on postoperative NT-proBNP concentration. NT-proBNP will be measured before surgery, and on the first, second and third postoperative day. | within 5 days after surgery | 
| Interleukin 6 | We investigate the influence of the Interleukin 6 ,measured within the first five days after surgery, on the incidence of cardiovascular complications within 30 days after surgery (combined binary endpoint). | within 30 days after surgery | 
| Copeptin | We investigate the influence of the copeptin ,measured within the first five days after surgery, on the incidence of cardiovascular complications within 30 days after surgery (combined binary endpoint). | within 30 days after surgery | 
| Procalcitonin | We investigate the influence of the procalcitonin ,measured within the first five days after surgery, on the incidence of cardiovascular complications within 30 days after surgery (combined binary endpoint). | within 30 days after surgery |