BACKGROUND: Acute kidney injury (AKI) is associated with mortality after cardiac surgery. Novel risk factors may improve identification of patients at risk for renal injury. The authors evaluated the association between preoperative biomarkers that reflect cardiac, inflammatory, renal, and metabolic disorders and cardiac surgery–associated AKI (CSA-AKI) in elderly patients. METHODS: This was a secondary analysis of the 2-center prospective cohort study “Anesthesia Geriatric Evaluation.” Twelve biomarkers were determined preoperatively in 539 patients. Primary outcome was CSA-AKI. The association between biomarkers and CSA-AKI was investigated with multivariable logistic regression analysis. Secondary outcomes were 1-year mortality and patient-reported disability and were assessed with relative risks (RR) between patients with and without CSA-AKI. RESULTS: CSA-AKI occurred in 88 (16.3%) patients and was associated with increased risk of mortality (RR, 6.70 [95% confidence interval {CI}, 3.38–13.30]) and disability (RR, 2.13 [95% CI, 1.53–2.95]). Preoperative concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitive C-reactive protein (hs-CRP), hemoglobin, and magnesium had the strongest association with CSA-AKI. Identification of patients with CSA-AKI improved when a biomarker panel was used (area under the curve [AUC] 0.75 [95% CI, 0.69–0.80]) compared to when only clinical risk factors were used (European System for Cardiac Operative Risk Evaluation [EuroSCORE II] AUC 0.67 [95% CI, 0.62–0.73]). CONCLUSIONS: Preoperative cardiac, inflammatory, renal, and metabolic biomarkers are associated with CSA-AKI and may improve identification of patients at risk.
ABSTRACT Background Cardiac and inflammatory biomarkers have been associated with adverse outcome after major abdominal surgery. Remote ischemic preconditioning (RIPC) may protect organs from ischemic insults during and after cardiac surgery, but the effect in major abdominal surgery is largely unknown. Objective To study the effect of RIPC on cardiac and inflammatory biomarkers in patients undergoing pancreatic resection. Methods Single-center, double-blind, randomized controlled trial in ninety patients undergoing elective pancreatic resection between March 2017 and February 2019. Three cycles of upper-limb ischemia and reperfusion (each 5 minutes) were applied before surgery. The primary endpoint was the maximum postoperative high-sensitive cardiac troponin (hs-cTn) T concentration within 48 hours after surgery. Secondary endpoints were postoperative myocardial injury (PMI, defined as a postoperative hs-cTnT ≥14 ng L -1 ), the maximum concentration of interleukin (IL)-6 within 48 hours after surgery, and postoperative complications within 30-days of surgery. Results RIPC did not reduce the maximum hs-cTnT concentration after surgery (12.6 ng L -1 vs 16.6 ng L -1 in the control group (P=0.23), nor did it lessen the incidence of PMI (15 (33.3%) patients in the RIPC group versus 19 (42.2%) controls, P=0.93). The maximum postoperative IL-6 concentration was 239 pg mL -1 [115-360] in the RIPC group, as compared to 317 pg mL -1 [174-909] in the control group (P=0.13). A postoperative complication occurred in 23 (51%) RIPC patients and 24 (53%) controls. Conclusions Remote ischemic preconditioning did not reduce the maximum postoperative hs-cTnT concentration. Postoperative myocardial injury, IL-6 concentrations and postoperative complications were not statistically different between RIPC patients and controls. Trial Registration Clinicaltrials.gov identifier NCT03460938 Funding Funding for biomarker analysis was provided by Roche Diagnostics. Roche Diagnostics had no role in design and conduct of the study, analysis and interpretation of the data, preparation and approval of the manuscript. Article summary Strengths and limitations of this study Well-designed clinical trial in a selected group of high-risk abdominal surgery patients. Serial assessment of high-sensitive cardiac troponin T and interleukin-6 concentrations. Postoperative cardiac biomarker concentrations were relatively low. This trial was not primarily designed to detect differences in IL-6 concentrations and postoperative complications.
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 ... read more 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. show less
Background: Advanced glycation end products (AGEs) are a potential biomarker of biological age. Skin Auto Fluorescence (SAF) can assess AGEs non-invasively. We evaluated the association of SAF levels with frailty and its predictive ability for adverse outcomes in elderly cardiac surgery patients. Methods & Results: We measured SAF level in cardiac surgery patients aged ≥70 and analyzed the correlation with frailty diagnosed with geriatric assessment. A decision algorithm for frailty screening was developed using Conditional Interference Tree analysis and compared with the Frailty Phenotype (FP), a validated frailty assessment tool. We evaluated the association of SAF level with severe postoperative complications and a composite endpoint of one-year disability (defined by WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) questionnaire) and mortality with Poisson regression analyses. Among 555 enrolled patients, 122 (22%) were classified as frail. Of all frailty characteristics, SAF level was most strongly associated with dependent living status (aRR 2.61 (95% CI 1.23-5.53) and handgrip strength (aRR 1.72 (95% CI 1.28-2.32). A decision algorithm including SAF level, sex, prescription drugs, preoperative hemoglobin and EuroSCORE II resulted in a C-statistic of 0.72 (95% CI 0.67-0.77) vs 0.66 (95% CI 0.61-0.71) for the FP. SAF level was also associated with disability/death after one year (aRR 1.18 (95% CI 1.06-1.30). The RR for severe complications was 1.32 (95% CI 0.99-1.75). Conclusion: Higher SAF level is associated with frailty in elderly cardiac surgery patients, as well as an increased risk of death and disability. This biomarker could potentially optimize preoperative screening for cardiac surgery.
Abstract Background Postoperative anaemia is common in older cardiac surgery patients and often caused by iron deficiency. Anaemia may negatively affect recovery after cardiac surgery. This study aims to determine the efficacy of treatment of postoperative iron deficiency anaemia (IDA) with intravenous iron (IVI) on disability 90 days after cardiac surgery in older patients. Methods This is a randomized placebo-controlled double-blind multi-centre trial. In total, 310 patients aged ≥ 70 years with moderate IDA on postoperative day 1 (haemoglobin 85–110 g/L and ferritin concentration < 100 μg/L or iron saturation < 20%) after uncomplicated elective cardiac surgery (aortic valve repair or coronary artery bypass graft surgery) will be included. Patients will be randomly allocated to receive either IVI (ferric derisomaltose) or placebo (sodium chloride 0.9%) on postoperative day 1 in a 1:1 ratio, stratified by centre and type of cardiac surgery. The primary outcome is disability measured by the 12-item World Health Organization Disability Assessment score 2.0 after 90 days. Secondary outcome measures are the number of postoperative red blood cell (RBC) transfusions, change in reticulocyte haemoglobin content (pg) from randomization to hospital discharge, Hb levels at discharge, hospital complications, dyspnoea (assessed with the Rose Dyspnoea Scale) and health-related quality of life (HRQL) (assessed with The Older Persons and Informal Caregivers-Short Form (TOPICS-SF) questionnaire) after 90 days and days alive and out of hospital after 90 days. Lastly, the functional outcomes (e.g. steep ramp or 6-min walk test) and Hb level after 90 days will be assessed as an exploratory endpoint. Discussion The results of this study will demonstrate whether early treatment of postoperative IDA with IVI improves disability at 90 days in older cardiac surgery patients. Trial registration ClinicalTrials.gov NCT04913649. Registered on June 4, 2021.
To provide an overview and evaluate the performance of mortality prediction models for patients requiring extracorporeal membrane oxygenation (ECMO) support for refractory cardiocirculatory or respiratory failure.A systematic literature search was undertaken to identify studies developing and/or validating multivariable prediction models for all-cause mortality in adults requiring or receiving veno-arterial (V-A) or veno-venous (V-V) ECMO. Estimates of model performance (observed versus expected (O:E) ratio and c-statistic) were summarized using random effects models and sources of heterogeneity were explored by means of meta-regression. Risk of bias was assessed using the Prediction model Risk Of BiAS Tool (PROBAST).Among 4905 articles screened, 96 studies described a total of 58 models and 225 external validations. Out of all 58 models which were specifically developed for ECMO patients, 14 (24%) were ever externally validated. Discriminatory ability of frequently validated models developed for ECMO patients (i.e., SAVE and RESP score) was moderate on average (pooled c-statistics between 0.66 and 0.70), and comparable to general intensive care population-based models (pooled c-statistics varying between 0.66 and 0.69 for the Simplified Acute Physiology Score II (SAPS II), Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score). Nearly all models tended to underestimate mortality with a pooled O:E > 1. There was a wide variability in reported performance measures of external validations, reflecting a large between-study heterogeneity. Only 1 of the 58 models met the generally accepted Prediction model Risk Of BiAS Tool criteria of good quality. Importantly, all predicted outcomes were conditional on the fact that ECMO support had already been initiated, thereby reducing their applicability for patient selection in clinical practice.A large number of mortality prediction models have been developed for ECMO patients, yet only a minority has been externally validated. Furthermore, we observed only moderate predictive performance, large heterogeneity between-study populations and model performance, and poor methodological quality overall. Most importantly, current models are unsuitable to provide decision support for selecting individuals in whom initiation of ECMO would be most beneficial, as all models were developed in ECMO patients only and the decision to start ECMO had, therefore, already been made.
