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Objective: The right axillary artery is currently recommended for arterial cannulation in surgery for acute type A aortic dissection. However, the feasibility of cannulation on a dissected right axillary artery remains undetermined. The objective was to examine the feasibility of cannulation on a dissected right axillary artery., Methods: From 2016 to 2020, 835 patients who underwent acute type A aortic dissection repair were included in this study. Cannulation strategy and perioperative outcomes of patients who did and did not have right axillary artery dissection were compared. Propensity score matching and logistic regression were applied., Results: A total of 124 patients had right axillary artery dissection, and 711 patients did not. Direct right axillary artery cannulation was used for cardiopulmonary bypass in the majority of patients, but with a lower rate in patients with right axillary artery dissection (n = 88 [71.0%] vs n = 579 [81.4%], P = .007). Right axillary artery cannulation failure (n = 3 [2.4%] vs n = 5 [0.7%], P = .102) and related complications (n = 1 [0.8%] vs n = 6 [0.8%], P = 1.000) were rare in both groups. In-hospital mortality (n = 18 [14.5%] vs n = 59 [8.3%], P = .027) and stroke (n = 14 [11.3%] vs n = 42 [5.9%], P = .027) were significantly higher in the right axillary artery dissection group, but after propensity score matching, in-hospital outcomes were comparable. Right axillary artery dissection was not a risk factor for mortality, stroke, right axillary artery cannulation not performed, or right axillary artery cannulation failure., Conclusions: Direct right axillary artery cannulation is feasible for most patients with acute type A aortic dissection with right axillary artery dissection., (Copyright © 2022. Published by Elsevier Inc.)

ObjectiveThe objective of this study was to determine the association between preoperative nutritional status and postoperative outcomes in children undergoing surgery for congenital heart defects (CHD).MethodsSeventy-one patients with CHD were enrolled in a prospective, 2-center cohort study. We adjusted for baseline risk differences using a standardized risk adjustment score for surgery for CHD. We assigned a World Health Organization z score for each subject's preoperative triceps skin-fold measurement, an assessment of total body fat mass. We obtained preoperative plasma concentrations of markers of nutritional status (prealbumin, albumin) and myocardial stress (B-type natriuretic peptide [BNP]). Associations between indices of preoperative nutritional status and clinical outcomes were sought.ResultsSubjects had a median (interquartile range [IQR]) age of 10.2 (33) months. In the University of California at San Francisco (UCSF) cohort, duration of mechanical ventilation (median, 19 hours; IQR, 29 hours), length of intensive care unit stay (median, 5 days; IQR 5 days), duration of any continuous inotropic infusion (median, 66 hours; IQR 72 hours), and preoperative BNP levels (median, 30 pg/mL; IQR, 75 pg/mL) were associated with a lower preoperative triceps skin-fold z score (P

ObjectiveWe sought to investigate the impact of 22q11.2 deletion on perioperative outcome in tetralogy of Fallot.MethodsWe conducted a retrospective review of patients with tetralogy of Fallot who underwent complete surgical reconstruction at The Children's Hospital of Philadelphia between 1995 and 2006. Inclusion criteria included diagnosis of tetralogy of Fallot and known genotype. Fisher exact and Mann-Whitney tests were used for categoric and continuous variables, respectively. Regression analysis was used to determine whether deletion status predicts outcome.ResultsWe studied 208 subjects with tetralogy of Fallot, 164 (79%) without and 44 (20%) with 22q11.2 deletion syndrome. There were no differences in sex, race, gestational age, age at diagnosis, admission weight, and duration of mechanical ventilation. Presenting anatomy, survival, complications and reoperations were also comparable between patients with and without 22q11.2 deletion syndrome. Those with 22q11.2 deletion syndrome had more aortopulmonary shunts preceding complete surgical repair (21% vs 7%, P = .02). This association was present after adjustment for presenting anatomy (stenosis, atresia, or absence of pulmonary valve and common atrioventricular canal) and surgical era. In addition, those with 22q11.2 deletion syndrome had longer cardiopulmonary bypass time (84 vs 72 minutes, P = .02) and duration of intensive care (6 vs 4 days, P = .007).ConclusionsGenotype affects early operative outcomes in tetralogy of Fallot resulting, in particular, in longer duration of intensive care. Future studies are required to determine factors contributing to such differences in this susceptible population.

Objective: To report early outcomes of blood conservation in neonatal open-heart surgery., Methods: Ninety-nine patients undergoing neonatal open-heart surgery during the implementation of a blood conservation program between May 2021 and February 2023 were reviewed. Patients either received traditional blood management (blood prime, n = 43) or received blood conservation strategies (clear prime, n = 56). Baseline characteristics and outcomes were compared between groups., Results: There was no difference in body weight (median, 3.2 kg vs 3.3 kg; P = .83), age at surgery (median, 5 days vs 5 days; P = .37), distribution of The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Categories categories or duration of cardiopulmonary bypass. Patients in the clear prime group had higher preoperative hematocrit (median, 41% vs 38%; P < .01), shorter postoperative mechanical ventilation time (median, 48 hours vs 92 hours; P = .02) and postoperative intensive care unit length of stay (median, 6 days vs 9 days; P < .01) than patients in the blood prime group. Fourteen patients (25%) in the clear prime group, including 1 Norwood patient, were discharged without any transfusion. Among patients within the clear prime group, hospitalizations without blood exposure were associated with higher preoperative hematocrit (median, 43% vs 40%; P = .02), shorter postoperative mechanical ventilation times (median, 22 hours vs 66 hours; P = .01) and shorter postoperative hospital stays (median, 10 days vs 15 days; P = .02)., Conclusions: Bloodless surgery is possible in a significant proportion of neonates undergoing open-heart surgery, including the Norwood operation, even in the early stages of experience. Early clinical results are favorable but long-term follow-up and continued efforts are warranted to prove safety and reproducibility., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

ObjectivesTo determine the incidence, impact, etiology, and methods for prevention of stroke after surgery of the thoracic aorta.MethodsA total of 317 thoracic aortic operations on 303 patients (194 male, 109 female) aged 13 to 87 years (mean 61 years) were reviewed. There were 218 procedures on the ascending aorta and arch and 99 on the descending aorta. Of the 218 procedures on the ascending aorta and arch, 86 involved cardiopulmonary bypass, 122 involved deep hypothermic circulatory arrest, 2 involved antegrade cerebral perfusion, and 8 involved "clamp and sew" or left heart bypass. Of the 99 procedures on the descending aorta, 20 involved "clamp and sew," 69 involved left heart or full bypass, and 10 involved deep hypothermic circulatory arrest. A total of 206 cases were elective and 97 were emergency operations.ResultsTwenty-three (7.3%) of 317 patients had a stroke. Fifteen strokes occurred in operations on the ascending aorta and 8 in operations on the descending aorta (6.9% vs 8.1%; P =.703). Stroke occurred in 16 (16.5%) of 97 emergency operations and 7 (3.4%) of 206 elective operations (P =.001). In the 300 patients surviving the operation, stroke was a significant predictor of postoperative death (9/23 [39.1%] vs 23/277 [8.3%]; P =.001). Analysis of operative reports, brain images, and neurologic consultations revealed 15 of the 23 strokes were embolic, 3 were ischemic, 3 hemorrhagic, and 2 indeterminate. Patients with stroke had longer intensive care unit stays (18.4 vs 6.8 days; P =.0001), longer times to extubation (12.7 vs 3.8 days; P

Objective: Patient characteristics, risks, and outcomes associated with reoperative multivalve cardiac surgery are poorly characterized. Effect of patient variables and surgical components of each reoperation were evaluated with regard to operative mortality., Methods: From January 2008 to January 2022, 2324 patients with previous cardiac surgery underwent 2352 reoperations involving repair or replacement of multiple cardiac valves at Cleveland Clinic. Mean age was 66 ± 14 years. Number of surgical components representing surgical complexity (valve procedures, aortic surgery, coronary artery bypass grafting, and atrial fibrillation procedures) ranged from 2 to 6. Random forest for imbalanced data was used to identify risk factors for operative mortality., Results: Surgery was elective in 1327 (56%), urgent in 1006 (43%), and emergency in 19 (0.8%). First-time reoperations were performed in 1796 (76%) and 556 (24%) had 2 or more previous operations. Isolated multivalve operations comprised 54% (1265) of cases; 1087 incorporated additional surgical components. Two valves were operated on in 80% (1889) of cases, 3 in 20% (461), and 4 in 0.09% (2). Operative mortality was 4.2% (98 out of 2352), with 1.7% (12 out of 704) for elective, isolated multivalve reoperations. For each added surgical component, operative mortality incrementally increased, from 2.4% for 2 components (24 out of 1009) to 17% for ≥5 (5 out of 30). Predictors of operative mortality included coronary artery bypass grafting, surgical urgency, cardiac, renal dysfunction, peripheral artery disease, New York Heart Association functional class, and anemia., Conclusions: Elective, isolated reoperative multivalve surgery can be performed with low mortality. Surgical complexity coupled with key physiologic factors can be used to inform surgical risk and decision making., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Care and outcomes for the more than 40,000 patients undergoing pediatric and congenital heart surgery in the United States annually are known to vary widely. While consensus recommendations have been published across numerous fields as one mechanism to promote a high level of care delivery across centers, it has been more than two decades since the last pediatric heart surgery recommendations were published in the United States. More recent guidance is lacking, and collaborative efforts involving the many disciplines engaged in caring for these children have not been undertaken to date. The present initiative brings together professional societies spanning numerous care domains and congenital cardiac surgeons, pediatric cardiologists, nursing, and other healthcare professionals from diverse programs around the country to develop consensus recommendations for United States centers. The focus of this initial work is on pediatric heart surgery, and it is recommended that future efforts focus in detail on the adult congenital population. We describe the background, rationale, and methodology related to this collaborative effort, and recommendations put forth for Essential Care Centers (essential services necessary for any program), and Comprehensive Care Centers (services to optimize comprehensive and high-complexity care), encompassing structure, process, and outcome metrics across 14 domains., (Copyright © 2023 [Author/Employing Institution]. Published by Elsevier Inc. All rights reserved.)

Objective: Several human studies have associated nitric oxide administration via the cardiopulmonary bypass circuit with decreased incidence of cardiopulmonary bypass-associated acute kidney injury, but histopathologic and serologic evidence of nitric oxide efficacy for acute kidney injury attenuation are lacking., Methods: By using a survival ovine model (72 hours), acute kidney injury was induced by implementing low-flow cardiopulmonary bypass for 2 hours, followed by full-flow cardiopulmonary bypass for 2 hours. The nitric oxide cohort (n = 6) received exogenous nitric oxide through the cardiopulmonary bypass circuit via the oxygenator, and the control group (n = 5) received no nitric oxide. Serial serologic biomarkers and renal histopathology were obtained., Results: Baseline characteristics (age, weight) and intraoperative parameters (cardiopulmonary bypass time, urine output, heart rate, arterial pH, and lactate) were equivalent (P > .10) between groups. Postoperatively, urine output, heart rate, respiratory rate, and peripheral arterial saturation were equivalent (P > .10) between groups. Post-cardiopulmonary bypass creatinine elevations from baseline were significantly greater in the control group versus the nitric oxide group at 16, 24, and 48 hours (all P < .05). Histopathologic evidence of moderate/severe acute kidney injury (epithelial necrosis, tubular slough, cast formation, glomerular edema) occurred in 60% (3/5) of the control group versus 0% (0/6) of the nitric oxide group. Cortical tubular epithelial cilia lengthening (a sensitive sign of cellular injury) was significantly greater in the control group than in the nitric oxide group (P = .012)., Conclusions: In a survival ovine cardiopulmonary bypass model, nitric oxide administered with cardiopulmonary bypass demonstrated serologic and histologic evidence of renal protection from acute kidney injury. These results provide insight into 1 potential mechanism for cardiopulmonary bypass-associated acute kidney injury and supports continued study of nitric oxide via cardiopulmonary bypass circuit for prevention of acute kidney injury., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Cardioplegia and cardiopulmonary bypass dysregulate coronary vasomotor tone, which can be further affected by common comorbidities in patients undergoing cardiac surgery. This study investigates differences in coronary myogenic tone and vasomotor responses to phenylephrine before and after cardioplegia and cardiopulmonary bypass based on hypertension history., Methods: Coronary arterioles before and after cardioplegia and cardiopulmonary bypass were dissected from atrial tissue samples in patients with no hypertension, well-controlled hypertension, or uncontrolled hypertension, as determined by documented history of hypertension, antihypertensive agent use, and clinical blood pressure measurements averaged over 1 year. Myogenic tone in response to stepwise increases in intraluminal pressure was studied between pressure steps. Microvascular reactivity in response to phenylephrine was assessed via vessel myography. Protein expression was measured with immunoblotting., Results: Coronary myogenic tone was significantly increased in the uncontrolled hypertension group compared with the no hypertension and well-controlled hypertension groups before cardioplegia and cardiopulmonary bypass at higher intraluminal pressures, and after cardioplegia and cardiopulmonary bypass across all intraluminal pressures (P < .05). Contractile responses to phenylephrine were significantly enhanced in patients in the uncontrolled hypertension group compared with the well-controlled hypertension group before cardioplegia and cardiopulmonary bypass, and in the uncontrolled hypertension group compared with the no hypertension and well-controlled hyertension groups after cardioplegia and cardiopulmonary bypass (P < .05). There were no differences in myogenic tone or phenylephrine-induced reactivity between the no hypertension and well-controlled hypertension groups (P > .05). There was increased expression of phosphorylated protein kinase C alpha in the uncontrolled hypertension group after cardiopulmonary bypass compared with before cardiopulmonary bypass and increased phosphorylated extracellular signal-regulated kinase 1/2 in the uncontrolled hypertension compared with the no hypertension group after cardiopulmonary bypass (P < .05)., Conclusions: Uncontrolled hypertension is associated with increased coronary myogenic tone and vasoconstrictive response to phenylephrine that persists after cardioplegia and cardiopulmonary bypass., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Peripheral pulmonary artery stenosis (PPAS) is a relatively rare form of congenital heart disease often associated with Williams syndrome, Alagille syndrome, and elastin arteriopathy. This disease is characterized by stenoses at nearly all lobar and segmental ostia and results in systemic-level right ventricular pressures. The current study summarizes our experience with the surgical treatment of PPAS., Methods: This was a retrospective review of 145 patients who underwent surgical repair of PPAS. This included 43 patients with Williams syndrome, 39 with Alagille syndrome, and 21 with elastin arteriopathy. Other diagnoses include tetralogy of Fallot with PPAS (n = 21), truncus arteriosus (n = 5), transposition (n = 3), double-outlet right ventricle (n = 2), arterial tortuosity syndrome (n = 3), and other (n = 8)., Results: The median preoperative right ventricle to aortic peak systolic pressure ratio was 1.01 (range, 0.50-1.60) which was reduced to 0.30 (range, 0.17-0.60) postoperatively. The median number of ostial repairs was 17 (range, 6-34) and median duration of cardiopulmonary bypass was 398 minutes (range, 92-844). There were 3 in-hospital deaths (2.1%). The median duration of follow-up was 26 months (range, 1-220) with 4 late deaths (2.9%). Eighty-two patients have subsequently undergone catheterization and 74 had a pressure ratio <0.50., Conclusions: The surgical treatment of PPAS resulted in a 70% reduction in right ventricular pressures. At 3 years, freedom from death was 94% and 90% of those evaluated maintained low pressures. These results suggest that the surgical treatment of PPAS is highly effective in most patients., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Acute kidney injury (AKI) after pediatric cardiac surgery with cardiopulmonary bypass (CPB) is a frequently reported complication. In this study we aimed to determine the oxygen delivery indexed to body surface area (Do 2 i) threshold associated with postoperative AKI in pediatric patients during CPB, and whether it remains clinically important in the context of other known independent risk factors., Methods: A single-institution, retrospective study, encompassing 396 pediatric patients, who underwent heart surgery between April 2019 and April 2021 was undertaken. Time spent below Do 2 i thresholds were compared to determine the critical value for all stages of AKI occurring within 48 hours of surgery. Do 2 i threshold was then included in a classification analysis with known risk factors including nephrotoxic drug usage, surgical complexity, intraoperative data, comorbidities and ventricular function data, and vasoactive inotrope requirement to determine Do 2 i predictive importance., Results: Logistic regression models showed cumulative time spent below a Do 2 i value of 350 mL/min/m 2 was associated with AKI. Random forest models, incorporating established risk factors, showed Do 2 i threshold still maintained predictive importance. Patients who developed post-CPB AKI were younger, had longer CPB and ischemic times, and required higher inotrope support postsurgery., Conclusions: The present data support previous findings that Do 2 i during CPB is an independent risk factor for AKI development in pediatric patients. Furthermore, the data support previous suggestions of a higher threshold value in children compared with that in adults and indicate that adjustments in Do 2 i management might reduce incidence of postoperative AKI in the pediatric cardiac surgery population., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate recent practice and outcomes of reoperative cardiac surgery via re-sternotomy. Use of early versus late institution of cardiopulmonary bypass (CPB) before sternal re-entry was of particular interest., Methods: From January 2008 to July 2017, 7640 patients underwent reoperative cardiac surgery at Cleveland Clinic. The study group consisted of 6627 who had a re-sternotomy and preoperative computed tomography scans; 755 and 5872 were in the early and late institution of CPB groups, respectively. Patients were stratified into high (n = 563) or low (n = 6064) anatomic risk of re-entry on the basis of computed tomography criteria. Weighted propensity-balanced operative mortality and morbidity were compared with surgeon as a random effect., Results: Reoperative procedures most commonly incorporated aortic valve replacement (n = 3611) and coronary artery bypass grafting (n = 2029), but also aortic root (n = 1061) and arch procedures (n = 527). Unadjusted operative mortality was 3.5% (235/6627), and major sternal re-entry and mediastinal dissection injuries were uncommon (2.8%). In the propensity-weighted analysis, similar mortality (3.1% vs 4.5%; P = .6) and major morbidity, including stroke (1.8% vs 3.2%) and dialysis (0 vs 2.6%), were noted in the high anatomic risk cohort between early and late CPB groups. Similar trends were observed in the low anatomic risk cohort (mortality 3.5% vs 2.1%; P = .2)., Conclusions: Reoperative cardiac surgery is associated with low operative morbidity and mortality at an experienced center. Early and late CPB strategies have comparable outcomes in the context of an image-guided, team-based strategy., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Hemolysis, characterized by formation of free hemoglobin (Hb), occurs in patients undergoing cardiopulmonary bypass (CPB). However, there is no study of the dynamic changes in red blood cell (RBC)-derived exosomes (Exos) released during CPB, nor whether these particles mediate acute kidney injury (AKI)., Methods: This study is a comprehensive time-course analysis, at baseline, 30 minutes, to 24 hours post-crossclamp release (XCR) to determine (1) Exos Hb content; (2) free Hb/heme, haptoglobin, hemopexin; and (3) urinary markers of AKI over the same time period. In addition, we developed a model system in Sprague-Dawley rats to test for AKI after intravenous injection of Exos Hb released during CPB., Results: In 30 patients undergoing CPB, there is a significant increase in plasma Hb-positive Exos but not microvesicles 30 minutes post-XCR versus other time points, with a simultaneous decrease in the haptoglobin/Hb ratio. These changes presage a significant increase in urine neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 at 24 hours. Intravenous injection of plasma Exos (10 9-10 particles obtained 30 minutes post-XCR) into rats causes AKI at 72 hours, manifested by multifocal degeneration of proximal tubular epithelium. At 21 days, there is persistent tubular injury and interstitial fibrosis. Intravenous injection of Exos from 35-day-old stored RBCs into rats results in glomerular-tubular injury, increased kidney ferritin and hemoxygenase-1 expression, and significant elevation of kidney injury molecule-1 and proteinuria at 72 hours., Conclusions: These combined studies raise the potential for RBC-derived Exos, released during CPB, to target the kidney and mediate AKI., (Published by Elsevier Inc.)

Background: Cerebral protection remains the cornerstone of successful aortic surgery; however, there is no consensus as to the optimal strategy., Objective: To compare the safety and efficacy of innominate to axillary artery cannulation for delivering antegrade cerebral protection during proximal aortic arch surgery., Methods: This randomized controlled trial (The Aortic Surgery Cerebral Protection Evaluation CardioLink-3 Trial, ClinicalTrials.gov Identifier: NCT02554032), conducted across 6 Canadian centers between January 2015 and June 2018, allocated 111 individuals to innominate or axillary artery cannulation. The primary safety outcome was neuroprotection per the appearance of new severe ischemic lesions on the postoperative diffusion-weighted-magnetic resonance imaging. The primary efficacy outcome was the difference in total operative time. Secondary outcomes included 30-day all-cause mortality and postoperative stroke., Results: One hundred two individuals (mean age, 63 ± 11 years) were in the primary safety per-protocol analysis. Baseline characteristics between the groups were similar. New severe ischemic lesions occurred in 19 participants (38.8%) in the axillary versus 18 (34%) in the innominate group (P for noninferiority = .0009). Total operative times were comparable (median, 293 minutes; interquartile range, 222-411 minutes) for axillary versus (298 minutes; interquartile range, 231-368 minutes) for innominate (P for superiority = .47). Stroke/transient ischemic attack occurred in 4 (7.1%) participants in the axillary versus 2 (3.6%) in the innominate group (P = .43). Thirty-day mortality, seizures, delirium, and duration of mechanical ventilation were similar in both groups., Conclusions: diffusion-weighted magnetic resonance imaging assessments indicate that antegrade cerebral protection with innominate cannulation is safe and affords similar neuroprotection to axillary cannulation during aortic surgery, although the burden of new neurological lesions is high in both groups., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To clarify the relationship between the use of extracorporeal life support during lung transplantation and severe primary graft dysfunction (PGD), we developed and analyzed a novel multicenter international registry., Methods: The Extracorporeal Life Support in Lung Transplantation Registry includes double-lung transplants performed at 8 high-volume centers (>40/year). Multiorgan transplants were excluded. We defined severe PGD as grade 3 PGD (PGD3) observed 48 or 72 hours after reperfusion. Modes of support were no extracorporeal life support (off-pump), extracorporeal membrane oxygenation (ECMO), and cardiopulmonary bypass (CPB). To assess the association between mode of support and PGD3, we adjusted for demographic and intraoperative factors with a stepwise, mixed selection, multivariable regression model, ending with 10 covariates in the final model., Results: We analyzed 852 transplants performed between January 2016 and March 2020: 422 (50%) off-pump, 273 (32%) ECMO, and 157 (18%) CPB cases. PGD3 rates at time point 48-72 were 12.1% (51 out of 422) for off-pump, 28.9% for ECMO (79 out of 273), and 42.7% (67 out of 157) for CPB. The adjusted model resulted in the following risk profile for PGD3: CPB versus ECMO odds ratio, 1.89 (95% CI, 1.05-3.41; P = .033), CPB versus off-pump odds ratio, 4.24 (95% CI, 2.24-8.04; P < .001), and ECMO versus off-pump odds ratio, 2.24 (95% CI, 1.38-3.65; P = .001)., Conclusions: Venoarterial ECMO is increasingly used at high-volume centers to support complex transplant recipients during double-lung transplantation. This practice is associated with more risk of PGD3 than off-pump transplantation but less risk than CPB. When extracorporeal life support is required during lung transplantation, ECMO may be the preferable approach when feasible., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Cardioplegic ischemia-reperfusion and diabetes mellitus are correlated with coronary endothelial dysfunction and inactivation of small conductance calcium-activated potassium channels. Increased reactive oxidative species, such as mitochondrial reactive oxidative species, may contribute to oxidative injury. Thus, we hypothesized that inhibition of mitochondrial reactive oxidative species may protect coronary small conductance calcium-activated potassium channels and endothelial function against cardioplegic ischemia-reperfusion-induced injury., Methods: Small coronary arteries and endothelial cells from the hearts of mice with and without diabetes mellitus were isolated and examined by using a cardioplegic hypoxia and reoxygenation model to determine whether the mitochondria-targeted antioxidant Mito-Tempo could protect against coronary endothelial and small conductance calcium-activated potassium channel dysfunction. The microvessels or mouse heart endothelial cells were treated with or without Mito-Tempo (0-10 μM) 5 minutes before and during cardioplegic hypoxia and reoxygenation. Microvascular function was assessed in vitro by vessel myography. K + currents of mouse heart endothelial cells were measured by whole-cell patch clamp. The levels of intracellular cytosolic free calcium (Ca 2+ ) concentration, mitochondrial reactive oxidative species, and small conductance calcium-activated potassium protein expression of mouse heart endothelial cells were measured by Rhod-2 fluorescence staining, MitoSox, and Western blotting, respectively., Results: Cardioplegic hypoxia and reoxygenation significantly attenuated endothelial small conductance calcium-activated potassium channel activity, caused calcium overload, and increased mitochondrial reactive oxidative species of mouse heart endothelial cells in both the nondiabetic and diabetes mellitus groups. In addition, treating mouse heart endothelial cells with Mito-Tempo (10 μM) reduced cardioplegic hypoxia and reoxygenation-induced Ca 2+ and mitochondrial reactive oxidative species overload in both the nondiabetic and diabetes mellitus groups, respectively (P < .05). Treatment with Mito-Tempo (10 μM) significantly enhanced coronary relaxation responses to adenosine 5'-diphosphate and NS309 (P < .05), and endothelial small conductance calcium-activated potassium channel currents in both the nondiabetic and diabetes mellitus groups (P < .05)., Conclusions: Administration of Mito-Tempo improves endothelial function and small conductance calcium-activated potassium channel activity, which may contribute to its enhancement of endothelium-dependent vasorelaxation after cardioplegic hypoxia and reoxygenation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between low oxygen delivery (DO 2 ) on cardiopulmonary bypass and morbidity and mortality following cardiac surgery remains unexamined., Methods: We reviewed patients undergoing Society of Thoracic Surgeons index procedures from March 2019 to July 2020, coincident with implementation of a new electronic perfusion record that provides for continuous recording of DO 2 and flow parameters. Continuous perfusion variables were analyzed using area-over-the-curve (AOC) calculations below predefined thresholds (DO 2 <280 mL O 2 /min/m 2 , cardiac index <2.2 L/min, hemoglobin < baseline, and mean arterial pressure <65 mm Hg) to quantify depth and duration of potentially harmful exposures. Multivariable logistic regression adjusted by Society of Thoracic Surgeons predicted-risk scores were used to assess for relationship of perfusion variables with the primary composite outcome of any Society of Thoracic Surgeons index procedure, as well as individual Society of Thoracic Surgeons secondary outcomes (eg, mortality, renal failure, prolonged ventilation >24 hours, stroke, sternal wound infection, and reoperation)., Results: Eight hundred thirty-four patients were included; 42.7% (356) underwent isolated coronary artery bypass grafting (CABG), whereas 57.3% underwent nonisolated CABG (eg, valvular or combined CABG/valvular operations). DO 2 <280-AOC trended toward association with the primary outcome across all cases (P = .07), and was significantly associated for all nonisolated CABG cases (P = .02)-more strongly than for cardiac index <2.2-AOC (P = .04), hemoglobin <7-AOC (P = .51), or mean arterial pressure <65-AOC (P = .11). Considering all procedures, DO 2 <280-AOC was independently associated prolonged ventilation >24 hours (P = .04), an effect again most pronounced in nonisolated-CABG cases (P = .002), as well as acute kidney injury <72 hours (P = .04). Patients with glomerular filtration rate <65 mL/min and baseline hemoglobin <12.5 g/dL appeared especially vulnerable., Conclusions: Low DO 2 on bypass may be associated with morbidity/mortality following cardiac surgery, particularly in patients undergoing nonisolated CABG. These results underscore the importance of goal-directed perfusion strategies., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (MAPCAs) is a relatively rare and complex form of congenital heart disease. Unifocalization of MAPCAs has been advocated by some groups for the treatment of this condition. The purpose of this study was to assess the midterm fate of unifocalized MAPCAs in a cohort of patients with retroesophageal MAPCAs., Methods: This was a retrospective review of 37 patients who underwent a unifocalization procedure. All patients in this study had 1 or more retroesophageal MAPCAs, and detailed mapping of the MAPCAs was made based on a combination of the cardiac catheterization and surgical findings., Results: The 37 patients had a total of 166 MAPCAs, or 4.5 MAPCAs per patient. One hundred twenty-nine (78%) MAPCAs were unifocalized, whereas 37 (22%) were ligated because they were dual supply. Median follow-up was 69 months. At follow-up cardiac catheterization, evaluation of the 129 unifocalized MAPCAs demonstrated that 123 (95%) had antegrade flow, whereas 6 were occluded. For the 123 MAPCAs with antegrade flow, 97 (80%) were widely patent, whereas 26 were stenotic. Thirteen of the 37 patients have subsequently undergone reintervention on MAPCAs that were determined to be stenotic following unifocalization. Seven of these patients had mild disease and had complete resolution with balloon (n = 5) or surgical revision (n = 2). Six patients with moderate or severe disease underwent surgical revision with confirmed resolution in 4 of 6., Conclusions: The data demonstrate that the majority of unifocalized MAPCAs remain widely patent following unifocalization. However, one-quarter of unifocalized MAPCAs develop stenoses or occlusion. These results suggest the fate for most unifocalized MAPCAs is favorable but highlight the need for close vigilance., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Acute kidney injury (AKI) is a serious complication of cardiac surgery with cardiopulmonary bypass (CPB). The aim of this study was to evaluate the effects of nitric oxide (NO) supplementation to the CPB circuit on the development of cardiac surgery-associated AKI., Methods: This prospective randomized controlled study included 96 patients with moderate risk of renal complications who underwent elective cardiac surgery with CPB. The study protocol was registered at ClinicalTrials.gov (identifier NCT03527381). Patients were randomly allocated to either NO supplementation to the CPB bypass circuit (NO treatment group; n = 48) or usual care (control group; n = 48). In the NO treatment group, 40-ppm NO was administered during the entire CPB period. The primary outcome was the incidence of AKI., Results: NO treatment was associated with a significant decrease in AKI incidence (10 cases [20.8%] vs 20 cases [41.6%] in the control group; relative risk, 0.5; 95% confidence interval, 0.26-0.95; P = .023) and a higher median urine output during CPB (2.6 mL/kg/h [interquartile range (IQR), 2.1-5.08 mL/kg/h] vs 1.7 mL/kg/h [IQR, 0.80-2.50 mL/kg/h]; P = .0002). The median urinary neutrophil gelatinase-associated lipocalin level at 4 hours after surgery was significantly lower in the NO treatment group (1.12 ng/mL [IQR, 0.75-5.8 ng/mL] vs 4.62 ng/mL [IQR, 2.02-34.55 ng/mL]; P = .005). In the NO treatment group, concentrations of NO metabolites were significantly increased at 5 minutes postclamping, at 5 minutes after declamping, and at the end of the operation. Concentrations of proinflammatory and anti-inflammatory mediators and free plasma hemoglobin did not differ significantly between the 2 groups., Conclusions: NO administration in patients at moderate risk of renal complications undergoing elective cardiac surgery with CPB was associated with a lower incidence of AKI., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Oliguria after cardiac surgery remains of uncertain clinical significance. Therefore, we investigated the relationship of acute kidney injury severity across urine output and creatinine domains with the risk for major adverse kidney events at 180 days. We aimed to determine the impact of acute kidney injury after cardiac surgery., Methods: In a retrospective multicenter study, we investigated the relationship of acute kidney injury severity across urine output and creatinine categories with the risk for major adverse kidney events at 180 days-the composite of death, dialysis, and persistent renal dysfunction-using a large database of patients undergoing cardiac surgery at 1 of 5 hospitals within the regional medical system. We analyzed electronic records from 6637 patients treated between 2008 and 2014, of whom 5389 (81.2%) developed any acute kidney injury within 72 hours of surgery. We stratified patients by levels of urine output or serum creatinine according to Kidney Disease Improving Global Outcomes criteria for acute kidney injury., Results: Major adverse kidney events at 180 days increased from 4.5% for no acute kidney injury to 61.3% for stage 3 acute kidney injury (P < .001). Death or dialysis by day 180 was 2.4% for those with no acute kidney injury and 46.7% for those with acute kidney injury stage 3 (P < .001). Isolated oliguria was common (42.6%), and isolated azotemia was rare (6.1%). Even stage 1 acute kidney injury by oliguria alone was associated with an increased risk of major adverse kidney events at 180 days (odds ratio, 1.76; 1.20-2.57; P = .004), mainly driven by persistent renal dysfunction (odds ratio, 2.01; 1.26-3.18; P = .003)., Conclusions: Acute kidney injury is common in patients undergoing cardiac surgery, and even milder forms of acute kidney injury, including isolated stage 1 oliguria, are associated with adverse long-term consequences., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the altitude differences in the optimal perfusate oxygenation (PpO 2 ) in patients who underwent cardiac surgery., Methods: We included children (aged 1 month to 18 years) with congenital heart diseases surgically repaired between 2012 and 2018. We included only patients who underwent cardiac surgery with arrested heart cardiopulmonary bypass. Primary outcome was severe systemic inflammatory response syndrome (SIRS). Logistic regression was used to evaluate the association between arterial PpO 2 on continuous and categorical scales and severe SIRS by altitude. We established PpO 2 thresholds that equated to a risk probability of roughly 0.185 or greater for developing severe SIRS in each group of altitude., Results: Among 3918 patients from low altitudes and 2384 from high altitudes, high-altitude patients were older (median, 42.3 [interquartile range 22.8-75.8] vs 37.1 [17.7-69.1] months, P < .001) and had lower arterial PpO 2 (289 [237-342] vs 301 [246-362] mm Hg, P < .001). Greater PpO 2 was associated with increased risk of severe SIRS overall (adjusted odds ratio, 1.221 [95% confidence interval, 1.167-1.278] per standard deviation increase), with a stronger monotonic associations for low-altitude patients than for high-altitude patients (adjusted odds ratio, 1.302 [95% confidence interval, 1.229-1.379] vs adjusted odds ratio, 1.083 [95% confidence interval, 1.003-1.170] per standard deviation increase) (P interaction = .0003). A PpO 2 level of 310 mm Hg identified low-altitude patients with a risk probability of roughly 0.185 or greater of severe SIRS, whereas the cutoffs ranged from 200 mm Hg to 325 mm Hg for high-altitude patients., Conclusions: This study suggests altitude differences in the association of arterial PpO 2 with inflammatory response following pediatric cardiac surgery., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Severe acute kidney injury (AKI) is a known risk factor for infection and mortality. However, whether stage 1 AKI is a risk factor for infection has not been evaluated in adults. We hypothesized that stage 1 AKI following cardiac surgery would independently associate with infection and mortality., Methods: In this retrospective propensity score-matched study, we evaluated 1620 adult patients who underwent nonemergent cardiac surgery at the University of Colorado Hospital from 2011 to 2017. Patients who developed stage 1 AKI by Kidney Disease Improving Global Outcomes creatinine criteria within 72 hours of surgery were matched to patients who did not develop AKI. The primary outcome was an infection, defined as a new surgical-site infection, positive blood or urine culture, or development of pneumonia. Secondary outcomes included in-hospital mortality, stroke, and intensive care unit (ICU) and hospital length of stay (LOS)., Results: Stage 1 AKI occurred in 293 patients (18.3%). Infection occurred in 20.9% of patients with stage 1 AKI compared with 8.1% in the no-AKI group (P < .001). In propensity-score matched analysis, stage 1 AKI independently associated with increased infection (odds ratio [OR]; 2.24, 95% confidence interval [CI], 1.37-3.17), ICU LOS (OR, 2.38; 95% CI, 1.71-3.31), and hospital LOS (OR, 1.30; 95% CI, 1.17-1.45)., Conclusions: Stage 1 AKI is independently associated with postoperative infection, ICU LOS, and hospital LOS. Treatment strategies focused on prevention, early recognition, and optimal medical management of AKI may decrease significant postoperative morbidity., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To compare outcomes of single (intervention group: del Nido [DN], and histamine-tryptophan-ketoglutarate) versus multidose (control group) cardioplegia in the adult cardiac surgery patients., Methods: Medical search engines were interrogated to identify relevant randomized controlled trials and propensity-score matched cohorts. Meta-analysis was conducted for primary (in-hospital/30-day mortality) and secondary (ischemic and cardiopulmonary bypass [CPB] times, reperfusion fibrillation, peak of cardiac enzymes, myocardial infarction) endpoints. Subgroup analyses were conducted for study design and type of intervention, and meta-regression for primary outcome included type of surgery and left ventricular ejection fraction as moderators., Results: Ten randomized controlled trials and 13 propensity-score matched cohorts were included, reporting on 5516 patients. Estimates are expressed as (parameter value [OR, odds ratio; MD, mean difference; SMD, standardized mean difference]/unit of measure [95% confidence interval], P value). DN reduced ischemic time (MD, -7.18 minutes [-12.52 to -1.84], P < .01), CPB time (MD, -10.44 minutes [-18.99 to -1.88], P .01), reperfusion fibrillation (OR, 0.16 [0.05-0.54], P < .01), and cardiac enzymes (SMD -0.17 [-0.29, 0.05], P < .01) compared with multidose cardioplegia. None of these beneficial effects were reproduced by histamine-tryptophan-ketoglutarate, which instead increased CPB time (MD, 2.04 minutes [0.73-3.37], P < .01) and reperfusion fibrillation (OR, 1.80 [1.20-2.70], P < .01). There was no difference in mortality and myocardial infarction between single and multidose, independently of type of surgery or left ventricular ejection fraction., Conclusions: DN decreases operative times, reperfusion fibrillation, and surge of cardiac enzymes compared with multidose cardioplegia., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Long-axis right ventricular (RV) function, which provides nearly 80% of RV ejection, acutely decreases during cardiac surgery. RV dysfunction increases risk for perioperative morbidity and mortality. Our objective was to characterize the change in perioperative RV long-axis and global function by determining the influence of procedure type, surgical approach, and reoperative status and examining its temporal relationship to pericardiotomy versus cardiopulmonary bypass (CPB) and cardioplegia., Methods: Standardized transesophageal echocardiographic examinations (TEEs) were prospectively performed in 109 patients undergoing coronary artery bypass grafting, mitral or aortic valve surgery, and/or aortic surgery via full sternotomy, mini-sternotomy, or right thoracotomy. Mid-esophageal, 4-chamber views centered on the RV were recorded at 4 intraoperative time points, following: (1) anesthetic induction; (2) pericardiotomy; (3) CPB; and (4) chest closure. Long-axis RV function was assessed by tricuspid annular plane systolic excursion and 2-dimensional longitudinal RV strain, and global RV function by fractional area change (FAC), calculated off-line from 2-dimensional TEE images., Results: TEE measures of RV function were significantly reduced after CPB compared with baseline (baseline vs after CPB: TAPSE 2.2 [Q1, Q3: 1.8, 2.5] vs 1.5 [1.1, 1.7] mm; RV strain -22 [-24, -18] vs -16 [-20, -14] %; FAC 45 [35, 51] vs 42 [34, 49] %), but not after pericardiotomy. Reduced RV function persisted after chest closure: tricuspid annular plane systolic excursion 1.3 [1.0, 1.6] mm, RV strain -16 [-18, -13]%, FAC 38 [31, 46] %. Reduced function was demonstrated across cardiac surgical procedures, approaches, and primary and reoperative surgery., Conclusions: Acute intraoperative reduction in RV function occurs following CPB, independent of procedural characteristics and pericardiotomy. Etiology and clinical implications of reduced perioperative RV function remain to be determined., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Prolonged cardiopulmonary bypass (CPB) is recognized as a risk factor for acute renal failure (ARF), but the dose effect of time on bypass is unknown. We therefore examined the risk of ARF associated with increasing CPB time stratified by preoperative renal function., Methods: A retrospective analysis was performed on 3889 patients undergoing cardiac surgery on CPB without circulatory arrest between 2011 and 2017 excluding those with a diagnosis of dialysis-dependent renal failure and those who had an intra-aortic balloon pump. Postoperative ARF was defined as a 3-fold increase in creatinine level, creatinine level > 4 mg/dL, or requirement for dialysis. A logistic regression model was built to identify predictors of ARF and to determine the probability of ARF., Results: Postoperative ARF occurred in 72 patients (2%) overall. Of 100 patients with an estimated glomerular filtration rate <30 mL/min/1.73 m 2 , 22% developed ARF, of which 16 required dialysis. Thirty-day mortality was 31% for those with ARF compared with <1% for those without ARF (P < .01). Risk factors for ARF included obesity (odds ratio, 3.03; P < .01), increasing preoperative creatinine level (odds ratio, 4.21; P < .01), CPB time scaled by a factor of 10 minutes (odds ratio, 1.06; P = .04), and postoperative transfusion (odds ratio, 11.94; P < .01). The adjusted probability of ARF as a function of CPB time was determined and stratified by preoperative glomerular filtration rate., Conclusions: Increasing CPB duration is associated with postoperative ARF, particularly among those with preoperative renal impairment. For patients with an estimated glomerular filtration rate <30 mL/min/1.73 m 2 the risk increases exponentially with time., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Cardiac surgery demands highly effective cardioprotective regimens. We previously demonstrated improved cardioprotection with "polarized" compared with "depolarized" arrest. This study uses a clinically relevant porcine model of cardiopulmonary bypass to compare the efficacy of blood-based St Thomas' Hospital polarizing cardioplegia (STH-Pol-B) with blood-based St Thomas' Hospital hyperkalemic cardioplegia (STH2-B)., Methods: Pigs were monitored and subjected to normothermic cardiopulmonary bypass, cardiac arrest via antegrade cold (4°C) blood cardioplegia (STH2-B, control group: n = 6 or STH-Pol-B, study group: n = 7), and global ischemia (60 minutes) followed by on-pump reperfusion (60 minutes) and subsequent off-pump reperfusion (90 minutes). At termination, tissue samples were taken for analysis of high-energy phosphates, ultrastructure, and microRNAs. The primary endpoint of this study was creatine kinase-muscle/brain release during reperfusion., Results: Creatine kinase-muscle/brain was comparable in both groups. After pigs were weaned from cardiopulmonary bypass, hemodynamic parameters such as mean arterial pressure (P = .007), left ventricular systolic pressure (P < .001), external heart work (P = .012), stroke volume (P = .015), as well as dp/dt max (P = .027), were improved with polarizing cardioplegia. Wedge pressure was significantly lower in the study group (P < .01). Energy charge was comparable between groups. MicroRNA-708-5p was significantly lower (P = .019) and microRNA-122 expression significantly (P = .046) greater in STH-Pol-B hearts., Conclusions: Polarized cardiac arrest offers similar myocardial protection and enhances functional recovery in a porcine model of cardiopulmonary bypass. Differential expression of microRNAs may indicate possible new ischemia-reperfusion markers. These results confirm the noninferiority and potential of polarized versus depolarized arrest., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

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/m 2 ) 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., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the possible overlooked causes of early postoperative paraplegia, a severe complication of acute Stanford type A aortic dissection (ATAAD) after total arch replacement and frozen elephant trunk (FET)., Methods: We reviewed the clinical data and perioperative aortic computed tomography angiography records of 110 consecutive patients with ATAAD who underwent total arch replacement and FET (12 cm) between December 2014 and September 2017 and investigated the possible risk factors related to early postoperative paraplegia., Results: Paraplegia occurred in 5 (4.5%) patients. No significant differences were found between patients with and without paraplegia in terms of sex, age, medical history, cardiopulmonary bypass time, antegrade cerebral perfusion time, rectal temperature during antegrade cerebral perfusion, postoperative hypotension, maximum first 24-hour vasoactive-inotropic score, upper-lower pressure gradient, or false lumen thrombosis. Postoperative aortic computed tomography angiography showed a "cutoff" phenomenon in the lower descending aorta in 4 of the 5 patients. Univariate logistical analysis showed that paraplegia was associated with the "cutoff" phenomenon (P < .05). The patients with a distance ≥30 mm from the distal end of the stent to the first untreated intimal tear had significantly greater rates of the "cutoff" phenomenon and paraplegia than those with the distance <30 mm (P < .05)., Conclusions: Total arch replacement and FET is safe and feasible for ATAAD involving the descending aorta. Early postoperative paraplegia is associated with the "cutoff" phenomenon in the lower descending aorta. The position of the first untreated intimal tear may be related with the occurrence of the "cutoff" phenomenon and paraplegia., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Previous studies have reported that nadir oxygen delivery during cardiopulmonary bypass is associated with the occurrence of postoperative acute kidney injury (AKI). However, these measurements only considered the bottom point of the oxygen delivery (DO 2 ) but did not consider the duration of DO 2 . We aimed to examine whether the time-dose response of DO 2 during cardiopulmonary bypass can be used to estimate the risk for postoperative AKI., Methods: We evaluated 112 patients who underwent cardiac surgeries with cardiopulmonary bypass. We analyzed the perfusion parameters recorded every 20 seconds. To obtain time-dose response of DO 2 index (DO 2 i), the area under the curve was calculated as below the 300 mL/min/m 2 threshold, which accounts for depth and duration of cumulative oxygen debt. In addition, the cumulative time below DO 2 i 300 mL/min/m 2 was also calculated. Receiver operating characteristic analysis, univariate regression analysis, and multivariate regression analysis were used to evaluate associations between perioperative variables and postoperative AKI., Results: Patients who developed AKI had larger area under the curve below the 300 mL/min/m 2 threshold (1581 vs 632; P < .01) and cumulative time below DO 2 i 300 mL/min/m 2 (34.7 vs 15.3 minutes; P < .01). Nadir DO 2 i was not significantly different between the non-AKI and AKI groups (263.4 vs 247.0 mL/min/m 2 ; P = .291)., Conclusions: The time-dose response of DO 2 i during cardiopulmonary bypass is a better indicator than nadir DO 2 i in evaluating AKI risk. Maintaining DO 2 i levels >300 mL/min/m 2 may result in decreased risk for postoperative AKI., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)