Modeling and estimating a threshold effect: An application to improving cardiac surgery practices.

Estimating thresholds when a threshold effect exists has important applications in biomedical research. However, models/methods commonly used in the biomedical literature may lead to a biased estimate. For patients undergoing coronary artery bypass grafting (CABG), it is thought that exposure to low oxygen delivery (DO2) contributes to an increased risk of avoidable acute kidney injury. This research is motivated by estimating the threshold of nadir DO2 for CABG patients to help develop an evidence-based guideline for improving cardiac surgery practices. We review several models (sudden-jump model, broken-stick model, and the constrained broken-stick model) that can be adopted to estimate the threshold and discuss modeling assumptions, scientific plausibility, and implications in estimating the threshold. Under each model, various estimation methods are studied and compared. In particular, under a constrained broken-stick model, a modified two-step Newton-Raphson algorithm is introduced. Through comprehensive simulation studies and an application to data on CABG patients from the University of Michigan, we show that the constrained broken-stick model is flexible, more robust, and able to incorporate scientific knowledge to improve efficiency. The two-step Newton-Raphson algorithm has good computational performances relative to existing methods.

Nontechnical Skills for Intraoperative Team Members.

Nontechnical skills, defined as the set of cognitive and social skills used by individuals and teams to reduce error and improve performance in complex systems, have become increasingly recognized as a key contributor to patient safety. Efforts to characterize, quantify, and teach nontechnical skills in the context of perioperative care continue to evolve. This review article summarizes the essential behaviors for safety, described in taxonomies for nontechnical skills assessments developed for intraoperative clinical team members (eg, surgeons, anesthesiologists, scrub practitioners, perfusionists). Furthermore, the authors describe emerging methods to advance understanding of the impact of nontechnical skills on perioperative outcomes.

Oxygen Delivery Thresholds During Cardiopulmonary Bypass and Risk for Acute Kidney Injury.

BACKGROUND: Postoperative acute kidney injury (AKI) in cardiac surgery patients is multifactorial and associated with low oxygen delivery (DO2) during cardiopulmonary bypass. METHODS: Cardiac surgical patients undergoing full cardiopulmonary bypass between May 1, 2016 and December 31, 2021 were included, whereas those on preoperative dialysis, undergoing circulatory arrest procedures, or lacking minute-to-minute physiologic data were excluded. A 5-minute running average of indexed DO2 (DO2i, mL/min/m2) was calculated ([pump flow] × [hemoglobin] × 1.36 [hemoglobin saturation] + 0.003 [arterial oxygen tension]/body surface area). AKI was defined using established Kidney Disease: Improving Global Outcomes criteria. The threshold of nadir DO2i on the effect of AKI was estimated using risk-adjusted Constrained Broken-Stick models. RESULTS: Postoperative AKI occurred among 1155 patients (29.4%), with 276 (7.0%) having stage 2 to 3 AKI. The median nadir DO2i was lower for those with (vs without) AKI (197.9 mL/min/m2 [interquartile range {IQR}, 166.3-233.2] vs 217.2 mL/min/m2 [IQR, 184.5-252.2], P < .001) and stage 2 to 3 AKI relative to stage 1 or none (186.9 mL/min/m2 [IQR, 160.1-220.5] vs 213.8 mL/min/m2 [IQR, 180.4-249.4]). In risk-adjusted analyses the estimated threshold for nadir DO2i was 231.2 mL/min/m2 (95% CI, 173.6-288.8) for any AKI and 103.3 (95% CI, 68.4-138.3) for stage 2 to 3 AKI. CONCLUSIONS: Decreasing nadir DO2i was associated with an increased risk of AKI. The identified nadir DO2i thresholds suggest management and treatment of nadir DO2i during cardiopulmonary bypass may decrease a patient's postoperative AKI risk.

Evaluating Changes in del Nido Cardioplegia Practices in Adult Cardiac Surgery.

There has been a rapid adoption of the use of del Nido cardioplegia (DC) among adults undergoing cardiac surgery. We leveraged a multicenter database to evaluate differences over time in the choice and impact of cardioplegia type (DC vs. blood) among patients undergoing cardiac surgery. We evaluated 26,373 patients undergoing non-emergent coronary artery bypass and/or valve surgery between 2014-2015 (early period) and 2017-2018 (late period) at 31 centers. DC was compared with blood-based cardioplegia (BC: 1:1, 2:1, 4:1, 8:1, and variable ratio). We evaluated whether treatment choice differed across prespecified patient characteristics, procedure type, and perfusion practices by time period. We evaluated increased DC use with clinical outcomes (major morbidity and mortality, prolonged intubation, and renal failure), after adjusting for baseline characteristics, procedure type, center, and year. DC use increased from 19.6% in 2014-2015 to 41.5% in 2017-2018, p < .001. Increased DC use occurred among coronary artery bypass grafting (CABG), valve, and CABG + valve procedures, all p < .001. Differences in median procedural duration increased over time (DC vs. BC): 1) bypass duration was 11.0 minutes shorter with DC in the early period and 27.0 minutes shorter in the late period, and 2) cross-clamp duration was 7.0 minutes shorter with DC in the early period and 17.0 minutes shorter in the late period, all p < .001. There were no statistical differences in adjusted odds of major morbidity and mortality (odds ratio [OR]adj: 1.01), prolonged intubation (ORadj: .99), or renal failure (ORadj: .80) by DC use (p > .05). In this large multicenter experience, DC use increased over time and was associated with reduced bypass and ischemic time absent any significant differences in adjusted outcomes.

Effect of sex on nadir hematocrit and rates of acute kidney injury in coronary artery bypass.

OBJECTIVE: Findings from a large multicenter experience showed that sex influenced the relationship between low nadir hematocrit and increased risk of acute kidney injury after cardiac surgery. We explored whether sex-related differences persisted among patients undergoing isolated coronary artery bypass grafting. METHODS: We undertook a prospective, observational study of 17,363 patients without dialysis (13,137 male: 75.7%; 4226 female: 24.3%) undergoing isolated coronary artery bypass grafting between 2011 and 2016 across 41 institutions in the Perfusion Measures and Outcomes registry. Odds ratios between nadir hematocrit and stage 2 or 3 acute kidney injury were calculated, and the interaction of sex with nadir hematocrit was tested. The multivariable, generalized, linear mixed-effect model adjusted for preoperative and intraoperative factors and institution. RESULTS: Median nadir hematocrit was 22% among women and 27% among men (P < .001). Women were administered a greater median net prime volume indexed to body surface area (407 vs 363 mL/m2) and more red blood cell transfusions (55.5% vs 24.3%; both P < .001). Acute kidney injury was higher among women (6.0% vs 4.3%, P < .001). There was no effect of sex on the relationship between nadir hematocrit and acute kidney injury (P = .67). Low nadir hematocrit was inversely associated with acute kidney injury (adjusted odds ratios per 1-unit increase in nadir hematocrit 0.96; 95% confidence interval, 0.93-0.98); this effect was similar across sexes and independent of red blood cell transfusions. CONCLUSIONS: We found no sex-related differences in the effect of nadir hematocrit on acute kidney injury after isolated coronary artery bypass grafting. However, the strong inverse relationship between anemia and acute kidney injury across sexes suggests the importance of reducing exposure to low nadir hematocrit.

Net Prime Volume Is Associated with Increased Odds of Blood Transfusion.

Hemodilutional anemia has been cited as a contributing factor to red blood cell (RBC) transfusions in cardiac surgery patients. Accordingly, efforts have been made to minimize hemodilution by reducing cardiopulmonary bypass (CPB) prime volume. We sought to assess the impact of these efforts on intraoperative RBC transfusions. We evaluated 21,360 patients undergoing coronary artery bypass with or without aortic valve surgery between July 2011 through December 2016 at any of 42 centers participating in the Perfusion Measures and Outcomes registry. The primary exposure was net CPB prime volume (total prime volume minus retrograde autologous prime volume) indexed to body surface area (mL/m2), which was further divided into quartiles (Q1: <262 mL/m2, Q2: 262-377 mL/m2, Q3: 377-516 mL/m2, and Q4: >516 mL/m2). The primary outcome was intraoperative RBC transfusion. We modeled the effect of index net prime volume on transfusion, adjusting for patient (age, gender, race, diabetes, vascular disease, previous myocardial infarction, ejection fraction, creatinine, preoperative hematocrit (HCT), total albumin, status, aspirin, and antiplatelet agents), procedural (procedure types) characteristics, surgical year, and hospital. The median net prime volume was 378 mL/m2 (25th percentile: 262 mL/m2, 75th percentile: 516 mL/m2). Relative to patients in Q1, patients in Q4 were more likely to be older, female, nondiabetic, have higher ejection fraction, have more ultrafiltration volume removed, and undergo more elective and aortic valve procedures (all p < .05). Patients in Q4 relative to Q1 were exposed to lower nadir HCTs on bypass, p < .05. The net prime volume was associated with an increased risk of transfusion (8.9% in Q1 vs. 22.6% in Q4, p < .001). After adjustment, patients in Q4 (relative to Q1) had a 2.9-fold increased odds (ORadj = 2.9, 95% CI [2.4, 3.4]) of intraoperative RBC transfusion. In this large, multicenter experience, patients exposed to larger net prime volumes were associated with greater adjusted odds of receiving intraoperative transfusions. Our findings reinforce the importance of efforts to reduce the net CPB prime volume. Based on these findings and other supporting evidence, the net prime volume should be adopted as a national quality measure.

Recent innovations in perfusion and cardiopulmonary bypass for neonatal and infant cardiac surgery.

The development and refinement of cardiopulmonary bypass (CPB) has made the repair of complex congenital heart defects possible in neonates and infants. In the past, the primary goal for these procedures was patient survival. Now that substantial survival rates have been achieved for even the most complex of repairs in these patients, focus has been given to the reduction of morbidity. Although a necessity for these complex neonatal and infant heart defect repairs, CPB can also be an important source of perioperative complications. Recent innovations have been developed to mitigate these risks and is the topic of this review. Specifically, we will discuss improvements in minimizing blood transfusions, CPB circuit design, monitoring, perfusion techniques, temperature management, and myocardial protection, and then conclude with a brief discussion of how further systematic improvements can be made in these areas.