Biomarkers, Blood Pressure and BIS: Perioperative Risk Stratification and Management Optimization of Patients at Cardiac Risk Undergoing Major Noncardiac Surgery (The BBB Study)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 458
- 试验地点
- 1
- 主要终点
- High-sensitivity cardiac Troponin I (hs-cTnI) > 0.04ng/ml and >= 35% relative increase compared to preoperative value
研究概览
简要总结
Major adverse cardiovascular events (MACE) are a leading cause of serious complications and death following major noncardiac surgery. The heart biomarkers brain-type natriuretic peptide (BNP) and high-sensitivity troponin I/T (hs-TnI/T), may aid in estimating the risk of surgery - low values may permit identifying patients at a very low risk of postoperative complications, potentially helping to avoid unnecessary tests and delays prior to surgery.
Recent studies suggest that the manner in which an anesthetic is conducted may have an important impact on postoperative outcomes. The combination of low blood pressure (BP) and a deep level of anesthesia despite a low dose of anesthetic - also known as a "triple low" - has been linked to increased complications and death following surgery. However, it is unclear whether triple lows actually cause postoperative complications or whether they are merely an indicator of a sick patient, who is in general more likely to suffer from cardiovascular events in the near future. To answer this question, in this study patients will be randomly assigned to groups with lower and higher blood pressures, and the postoperative rates of major adverse cardiovascular events and of relevant increases in hs-TnI (a marker of cardiac injury) compared.
Another important question is that of the optimal blood pressure target during surgery. Currently there are no established methods of tailoring blood pressure management to the individual patient. In the study the investigators will perform ambulatory 24h BP measurements prior to surgery to measure the patients' average BP during sleep. In the analysis of the study data, the investigators will try to determine the relationship of preoperative biomarker levels, intraoperative BP (both in relation to fixed targets and to the patient's own night-time BP) and of anesthetic depth with the occurrence of major adverse cardiovascular events after surgery.
详细描述
- Hypothesis and purpose
This study is based on the hypothesis that normal preoperative cardiac biomarkers, lack of intraoperative hypotension and BIS values between 45-60 are associated with better outcomes compared with elevated biomarkers, intraoperative hypotension and/or BIS values below 45. Additionally, the investigators hypothesize that tight blood pressure management reduces the incidence of adverse outcomes compared to liberal blood pressure management (see below for definitions). Lastly, the investigators will test the hypothesis that individualized, relative lower limits of blood pressure are a better predictor of adverse outcomes than absolute, non-individualized limits. 2. Study design
The study will be comprised of a cohort study (RISK) and a nested randomized controlled trial (RCT) [HEMODYNAMICS]. In the period between September 2015 and August 2018 all patients meeting the inclusion criteria will be included in the cohort study to assess the association of perioperative biomarkers, intraoperative blood pressure and BIS values with the occurrence of MACE. A smaller subset of patients will additionally be included in the RCT to assess the effect of tight versus liberal blood pressure management on MACE.
Cardiac risk assessment and optimization will be performed according to clinical practice in the investigators' institution, following internal guidelines (based on the 2007 ACC/AHA guidelines. In addition, preoperative cardiac biomarkers (BNP and hsTnI) will be measured. Intraoperative blood pressure management will be based on an internal hemodynamic management algorithm, however in the cohort study the intervention threshold will be left at the discretion of the anesthesiologist. The occurrence of MACE will be assessed 30 days and one year after surgery. The association of preoperative biomarker levels and the occurrence of intraoperative hypotension will be investigated.
In the RCT, patients will be assessed similarly to the protocol of the cohort study, however these patients will be randomly assigned to either tight (mean arterial pressure [MAP] > 75 mmHg) or liberal (MAP at the discretion of the anesthesiologist, but not < 60mmHg) blood pressure management using the same hemodynamic management algorithm as in the whole cohort. In a subset of the RCT patients, a nighttime blood pressure profile will be obtained additionally to define a presumed individual lower blood pressure limit (i.e. the mean MAP during natural sleep). The association of intraoperative time spent below the individual lower blood pressure limit with the occurrence of adverse outcomes will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •pregnancy
- •inclusion in another clinical trial with any endpoints in common with the BBB Study: hs-cTnI, components of MACE (acute coronary syndrome [ACS], congestive heart failure [CHF], coronary revascularization, stroke, acute kidney injury [AKI], new chronic kidney disease [CKD] or progression of CKD, mortality)
- •previously enrolled in BBB Study
- •emergent surgery
- •presence of any active cardiac conditions:
- •unstable coronary syndromes: unstable or severe (CCS III or IV) angina
- •decompensated heart failure: NYHA IV, worsening or new-onset
- •significant arrhythmias: high-grade AV-block (Mobitz II and third-degree), symptomatic bradycardia, symptomatic ventricular arrhythmias, supraventricular arrhythmias with uncontrolled ventricular rate (>100bpm at rest), newly recognized ventricular tachycardia
- •severe valvular disease: severe aortic stenosis (mean pressure gradient > 40 mmHg, aortic valve area < 1.0 cm2, symptomatic), symptomatic mitral stenosis (progressive dyspnea on exertion, externional presyncope, heart failure)
- •any transplantation
研究组 & 干预措施
Liberal blood pressure management
干预措施: Liberal blood pressure management (Drug)
Tight blood pressure management
干预措施: Tight blood pressure management (Drug)
结局指标
主要结局
High-sensitivity cardiac Troponin I (hs-cTnI) > 0.04ng/ml and >= 35% relative increase compared to preoperative value
时间窗: Postoperative days 0-3
Major adverse cardiovascular events
时间窗: 30 days postoperatively
Acute coronary syndrome, new or worsening congestive heart failure, coronary revascularization, stroke, acute kidney injury, all-cause mortality
次要结局
- Major adverse cardiovascular events(1 year postoperatively)
研究者
Miodrag Filipovic, Prof. Dr. med.
Vice-Chairman, Clinic for Anesthesiology, Intensive Care, Prehospital and Pain Medicine
Cantonal Hospital of St. Gallen