Methods in Perioperative Medicine Research

Abstract

Every year, several million patients undergo surgery with the aim to cure disease or relieve symptoms thereby increasing life expectancy and improving quality of life. Research in the perioperative period is challenging due to e.g. large number of repeated measurements with multiple events that follow each other rapidly and the heterogeneous group of patients that enter the operating room. In this thesis, some of these methodologically challenging aspects were investigated.

Part I addresses how to summarize repeated measured intraoperative blood pressure measurements in research on hypotension. Intraoperative hypotension (IOH) is a common side effect of anaesthesia during surgery and is associated with adverse postoperative outcomes. Despite a consensus definition of IOH for clinical purposes, no standardized methodology is available on how to incorporate the severity of IOH in research. We conducted a systematic review to investigate which methods have been used to analyse the magnitude of IOH in anaesthesia literature (Chapter 2). The most frequently used category was Incidence followed by Duration and Lowest value. In Chapter 3, we examined whether using these methods to model IOH exposure (i.e. representing presence, depth, duration and area under the threshold) affected the association with postoperative adverse outcomes. Different methods to model IOH yielded effect estimates differing in size and statistical significance. Standardized definitions of IOH including clear reporting guidance for research purposes is needed to improve reproducibility and comparability among studies.

Part II investigates preoperative risk stratification of patients undergoing non-cardiac surgery at risk for postoperative cardiovascular complications. The Revised Cardiac Risk index (RCRI) is a predictive tool that estimates the probability of in-hospital major adverse cardiac events (MACE) in patients undergoing non-cardiac surgery. To improve the predictive performance of this model, different biomarkers and other prediction models were added or compared to the RCRI. We conducted a systematic review to investigate what biomarkers and prediction models have been added or compared to the RCRI and to quantify the predictive value of these biomarkers and prediction models to the RCRI to predict MACE (Chapter 4 and 5). We did not find added predictive value of biomarker(s) to the RCRI or other prediction models with better predictive performance compared to the RCRI alone. Individual patient data meta-analyses might be beneficial to identify biomarkers with added value to the RCRI.

Routine postoperative troponin monitoring is recommended by several guidelines to early identify patients with postoperative myocardial infarction (MI). In the UMC Utrecht, troponin is routinely measured in postoperative non-cardiac surgical patients ≥ 60 years old with at least one overnight hospital stay. Part III focuses on the effect of postoperative myocardial injury (PMI, i.e. elevated troponins) on disability-free survival and health care resources during hospitalization. To conduct follow-up on patients with PMI, we implemented a dedicated anesthesia team (Chapter 6). Anesthesiologists were involved in the early detection of 59% of MIs and in 12% of all complications. Improvement in patient outcomes remains to be elucidated since no long-term follow-up was available. The independent effects of PMI phenotypes and on disability-free survival following non-cardiac surgery were investigated in Chapter 7. We stratified patients based on PMI and the occurrence of postoperative complications. This resulted in five groups, i.e. no adverse events, isolated PMI, MI, and complications with or without PMI but no MI. We did not find differences in the association between PMI phenotypes and disability-free survival. However, a clinically relevant change in disability score after surgery was found for patients with MI and patients with non-MI events with PMI. Early recognition and management of cardiac and non-cardiac complications in patients at high risk might benefit disability-free survival on the long-term.