This study was conducted in adherence to the STROBE statement for observational research.(von Elm et al. 2008) The local Research Ethics Committee assessed the study protocol and waived the need for informed consent (UMC Utrecht Medical Research Ethics Committee 19-029/C).
Patients
This retrospective observational study included patients aged ³60 years with postoperative elevated troponin levels as detected by routine troponin monitoring within the first three days after noncardiac surgery between January 1st, 2017 and December 31th, 2018 at the University Medical Center Utrecht, a tertiary referral hospital. Patients admitted immediately after the procedure at the Intensive Care Unit (ICU) or the Cardiac Care Unit (CCU) for more than two days were not visited by the dedicated anesthesiologists and were therefore excluded from the analysis, because follow-up in these patients was conducted by intensivists or cardiologists as part of our local protocol. Patients who died within 24 hours or in whom further therapy was withheld directly after surgery were also excluded. Patients, who underwent surgery more than once within the study period, were included as a new case. However, in case the procedure was performed within three days after the previous procedure, only the first procedure was included in the analysis.
Postoperative care
According to our local postoperative care protocol, cardiac troponin I (TnI) is measured in all noncardiac surgical patients aged ³60 years once daily on the first three postoperative days during hospital admission. This protocol excludes ophthalmic and plastic surgery patients because of low risk of cardiac complications. Troponin elevation was defined as TnI above the clinical cut-off level, which is the lowest value measurable with a 10% coefficient of variation above the 99th percentile upper reference limit.(Thygesen et al. 2018) Two different TnI assays were used over the years. This resulted in a clinical cut-off of TnI ≥60 ng L-1 (AccuTnI assay, Beckman Coulter, Brea, California, USA) from January 1st, 2017 until May 16th, 2018 and a clinical cut-off of high-sensitive TnI ≥18 ng L-1 (Unicel DxI 800, Beckman Coulter, Brea, California, USA) from May 17th, 2018 until December 31st, 2018.
Patients with elevated TnI were consulted within the first three postoperative days, and longer if indicated. Management of these patients was left to the judgement of the attending anesthesiologist, which was based on a local protocol. This protocol advises to optimize myocardial oxygen supply and demand, and to conduct follow-up of troponin and an electrocardiogram (ECG) in patients with TnI >120 ng L-1 in case of no evident non-ischemic cause (e.g. sepsis, stress induced cardiomyopathy) to rule out myocardial ischemia. This cut-off was based on two times the clinical cut-off of the assay used at that moment. Further, this protocol advises to consider consultation of a cardiologist, follow-up at the outpatient cardiac clinic, and prescription of antiplatelet therapy, statin or beta-blockade. In patients with troponin >600 ng L-1, i.e. more than ten times the clinical cut-off, a cardiology consultation is always recommended. Patients with mild troponin elevation were per protocol frequently not visited physically by the anesthesiologist because of a low risk of serious complications, but were only followed up by TnI and ECG. A team of ten dedicated anesthesiologists with a particular interest in perioperative medicine were educated on the protocol.
Data collection
All data were collected from electronic medical files. These data included patient characteristics, comorbidities, revised cardiac risk index (RCRI) (Lee et al. 1999), American Society of Anesthesiologists (ASA) physical status classification (American Society of Anesthesiologists 2014), Metabolic Equivalent Task score (METs) (Kristensen et al. 2014), and surgical risk as defined by the RCRI, and by the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). (Kristensen et al. 2014) Additionally, data on visits by the dedicated anesthesiologist, diagnostics, in-hospital postoperative complications, severity of complications according to the Clavien-Dindo classification, (Dindo et al. 2004; Jammer et al. 2015) and in-hospital mortality were collected.
Outcome
The primary outcome was early detected (i.e. ≤ 7 days after surgery) myocardial infarction as a result of consultation by the dedicated anesthesiologist. Myocardial infarction was defined as clinically diagnosed by the attending cardiologist. Secondary outcomes were overall detected complications, additional diagnostic tests advised by the dedicated anesthesiologist, treatment advised by the anesthesiologist, consultation of another medical specialist, and advised postoperative follow-up at the outpatient cardiac clinic. Potentially, a cardiologist could already have been consulted by the ward physician in patients with an elevated troponin or other cardiac complications, as the ward physicians were aware of the protocol. Therefore, we also recorded whether a cardiologist was consulted prior to or simultaneously with the visit by the dedicated anesthesiologists.
In addition to myocardial infarction, we assessed the occurrence of the following complications within seven days after the procedure: arrhythmia diagnosed on 12-leads ECG or cardiac monitor, cardiopulmonary resuscitation, cerebrovascular accident (defined as radiologically-confirmed ischemic or hemorrhagic stroke or transient ischemic attack), radiologically-confirmed deep venous thrombosis and pulmonary embolism, sepsis as clinically diagnosed by the treating physician, pneumonia requiring antibiotics, respiratory failure requiring MCU (Medium Care Unit) or ICU admission, acute kidney injury (AKI) defined as an increase in creatinine of 26.4 mmol L-1 or 25% from the preoperative creatinine value (Jammer et al. 2015), anemia defined as hemoglobin <6.0 mmol L-1 (10 g dL-1, according to the Dutch guideline on blood transfusion(CBO 2011)), unexpected MCU or ICU admission, and unplanned reoperations. Additionally, length of hospital stay, mortality within seven days and the cause of death were assessed. Last, the Clavien-Dindo grade of the most severe complication within a week after surgery was recorded. A severe complication was defined as a Clavien-Dindo grade ≥3 as this involves complications requiring a surgical, endoscopic or radiologic intervention, life threatening complications requiring care in a high-dependency or intensive care unit, or death. (Dindo et al. 2004; Jammer et al. 2015) Additionally, we assessed the final suspected etiology of the elevated troponin as proposed by the dedicated anesthesiologist.
Statistical analyses
Baseline characteristics were compared dependent on the amount of troponin elevation (i.e. TnI 18-119 ng L-1, TnI 120-599 ng L-1 and TnI ≥ 600 ng L-1). These thresholds were chosen based on the thresholds as defined in our local protocol. The contribution of the dedicated anesthesiologist on the early detection of complications was assessed relative to the total number of complications. In addition, complications by their severity, length of stay, unexpected ICU or MCU admission and death were assessed. The consultation rates by the dedicated anesthesiologists were evaluated, as were the number of ordered diagnostics, consulted medical specialties and advised therapies. In order to determine whether care utility and complications were dependent on the height of troponin elevation, these were evaluated in subgroups of patients with different levels of troponin (i.e. TnI 18-119 ng L-1, TnI 120-599 ng L-1 and TnI ≥ 600 ng L-1).
Hemoglobin and creatinine measurements were missing in 103 and 204 patients, respectively. Since these variables were only used for descriptive statistics, we did not consider this an important source of bias and we did not impute the data. The statistical analyses were performed with R (Version 3.5.1 – © 2018-07-02, R, Inc., for Windows). (R Core Team (2016))