Arterial Hyperoxemia During Cardiopulmonary Bypass Was Not Associated With Worse Postoperative Pulmonary Function: A Retrospective Cohort Study.

BACKGROUND: Arterial hyperoxemia may cause end-organ damage secondary to the increased formation of free oxygen radicals. The clinical evidence on postoperative lung toxicity from arterial hyperoxemia during cardiopulmonary bypass (CPB) is scarce, and the effect of arterial partial pressure of oxygen (Pa o2 ) during cardiac surgery on lung injury has been underinvestigated. Thus, we aimed to examine the relationship between Pa o2 during CPB and postoperative lung injury. Secondarily, we examined the relationship between Pa o2 and global (lactate), and regional tissue malperfusion (acute kidney injury). We further explored the association with regional tissue malperfusion by examining markers of cardiac (troponin) and liver injury (bilirubin). METHODS: This was a retrospective cohort study including patients who underwent elective cardiac surgeries (coronary artery bypass, valve, aortic, or combined) requiring CPB between April 2015 and December 2021 at a large quaternary medical center. The primary outcome was postoperative lung function defined as the ratio of Pa o2 to fractional inspired oxygen concentration (F io2 ); P/F ratio 6 hours following surgery or before extubation. The association between CPB in-line sample monitor Pa o2 and primary, secondary, and exploratory outcomes was evaluated using linear or logistic regression models adjusting for available baseline confounders. RESULTS: A total of 9141 patients met inclusion and exclusion criteria, and 8429 (92.2%) patients had complete baseline variables available and were included in the analysis. The mean age of the sample was 64 (SD = 13), and 68% were men (n = 6208). The time-weighted average (TWA) of in-line sample monitor Pa o2 during CPB was weakly positively associated with the postoperative P/F ratio. With a 100-unit increase in Pa o2 , the estimated increase in postoperative P/F ratio was 4.61 (95% CI, 0.71-8.50; P = .02). Our secondary analysis showed no significant association between Pa o2 with peak lactate 6 hours post CPB (geometric mean ratio [GMR], 1.01; 98.3% CI, 0.98-1.03; P = .55), average lactate 6 hours post CPB (GMR, 1.00; 98.3% CI, 0.97-1.03; P = .93), or acute kidney injury by Kidney Disease Improving Global Outcomes (KDIGO) criteria (odds ratio, 0.91; 98.3% CI, 0.75-1.10; P = .23). CONCLUSIONS: Our investigation found no clinically significant association between Pa o2 during CPB and postoperative lung function. Similarly, there was no association between Pa o2 during CPB and lactate levels, postoperative renal function, or other exploratory outcomes.

Video Laryngoscopy vs Direct Laryngoscopy for Endotracheal Intubation in the Operating Room: A Cluster Randomized Clinical Trial.

Importance: Endotracheal tubes are typically inserted in the operating room using direct laryngoscopy. Video laryngoscopy has been reported to improve airway visualization; however, whether improved visualization reduces intubation attempts in surgical patients is unclear. Objective: To determine whether the number of intubation attempts per surgical procedure is lower when initial laryngoscopy is performed using video laryngoscopy or direct laryngoscopy. Design, Setting, and Participants: Cluster randomized multiple crossover clinical trial conducted at a single US academic hospital. Patients were adults aged 18 years or older having elective or emergent cardiac, thoracic, or vascular surgical procedures who required single-lumen endotracheal intubation for general anesthesia. Patients were enrolled from March 30, 2021, to December 31, 2022. Data analysis was based on intention to treat. Interventions: Two sets of 11 operating rooms were randomized on a 1-week basis to perform hyperangulated video laryngoscopy or direct laryngoscopy for the initial intubation attempt. Main Outcomes and Measures: The primary outcome was the number of operating room intubation attempts per surgical procedure. Secondary outcomes were intubation failure, defined as the responsible clinician switching to an alternative laryngoscopy device for any reason at any time, or by more than 3 intubation attempts, and a composite of airway and dental injuries. Results: Among 8429 surgical procedures in 7736 patients, the median patient age was 66 (IQR, 56-73) years, 35% (2950) were women, and 85% (7135) had elective surgical procedures. More than 1 intubation attempt was required in 77 of 4413 surgical procedures (1.7%) randomized to receive video laryngoscopy vs 306 of 4016 surgical procedures (7.6%) randomized to receive direct laryngoscopy, with an estimated proportional odds ratio for the number of intubation attempts of 0.20 (95% CI, 0.14-0.28; P < .001). Intubation failure occurred in 12 of 4413 surgical procedures (0.27%) using video laryngoscopy vs 161 of 4016 surgical procedures (4.0%) using direct laryngoscopy (relative risk, 0.06; 95% CI, 0.03-0.14; P < .001) with an unadjusted absolute risk difference of -3.7% (95% CI, -4.4% to -3.2%). Airway and dental injuries did not differ significantly between video laryngoscopy (41 injuries [0.93%]) vs direct laryngoscopy (42 injuries [1.1%]). Conclusion and Relevance: In this study among adults having surgical procedures who required single-lumen endotracheal intubation for general anesthesia, hyperangulated video laryngoscopy decreased the number of attempts needed to achieve endotracheal intubation compared with direct laryngoscopy at a single academic medical center in the US. Results suggest that video laryngoscopy may be a preferable approach for intubating patients undergoing surgical procedures. Trial Registration: ClinicalTrials.gov Identifier: NCT04701762.

Serratus anterior and pectoralis plane blocks for robotically assisted mitral valve repair: a randomised clinical trial.

BACKGROUND: Minimally invasive cardiac surgery provokes substantial pain and therefore analgesic consumption. The effect of fascial plane blocks on analgesic efficacy and overall patient satisfaction remains unclear. We therefore tested the primary hypothesis that fascial plane blocks improve overall benefit analgesia score (OBAS) during the initial 3 days after robotically assisted mitral valve repair. Secondarily, we tested the hypotheses that blocks reduce opioid consumption and improve respiratory mechanics. METHODS: Adults scheduled for robotically assisted mitral valve repairs were randomised to combined pectoralis II and serratus anterior plane blocks or to routine analgesia. The blocks were ultrasound-guided and used a mixture of plain and liposomal bupivacaine. OBAS was measured daily on postoperative Days 1-3 and were analysed with linear mixed effects modelling. Opioid consumption was assessed with a simple linear regression model and respiratory mechanics with a linear mixed model. RESULTS: As planned, we enrolled 194 patients, with 98 assigned to blocks and 96 to routine analgesic management. There was neither time-by-treatment interaction (P=0.67) nor treatment effect on total OBAS over postoperative Days 1-3 with a median difference of 0.08 (95% confidence interval [CI]: -0.50 to 0.67; P=0.69) and an estimated ratio of geometric means of 0.98 (95% CI: 0.85-1.13; P=0.75). There was no evidence of a treatment effect on cumulative opioid consumption or respiratory mechanics. Average pain scores on each postoperative day were similarly low in both groups. CONCLUSIONS: Serratus anterior and pectoralis plane blocks did not improve postoperative analgesia, cumulative opioid consumption, or respiratory mechanics during the initial 3 days after robotically assisted mitral valve repair. CLINICAL TRIAL REGISTRATION: NCT03743194.

Derivation and Validation of Clinical Phenotypes of the Cardiopulmonary Bypass-Induced Inflammatory Response.

BACKGROUND: Precision medicine aims to change treatment from a "one-size-fits-all" approach to customized therapies based on the individual patient. Applying a precision medicine approach to a heterogeneous condition, such as the cardiopulmonary bypass (CPB)-induced inflammatory response, first requires identification of homogeneous subgroups that correlate with biological markers and postoperative outcomes. As a first step, we derived clinical phenotypes of the CPB-induced inflammatory response by identifying patterns in perioperative clinical variables using machine learning and simulation tools. We then evaluated whether these phenotypes were associated with biological response variables and clinical outcomes. METHODS: This single-center, retrospective cohort study used Cleveland Clinic registry data from patients undergoing cardiac surgery with CPB from January 2010 to March 2020. Biomarker data from a subgroup of patients enrolled in a clinical trial were also included. Patients undergoing emergent surgery, off-pump surgery, transplantation, descending thoracoabdominal aortic surgery, and planned ventricular assist device placement were excluded. Preoperative and intraoperative variables of patient baseline characteristics (demographics, comorbidities, and laboratory data) and perioperative data (procedural data, CPB duration, and hemodynamics) were analyzed to derive clinical phenotypes using K-means-based consensus clustering analysis. Proportion of ambiguously clustered was used to assess cluster size and optimal cluster numbers. After clusters were formed, we summarized perioperative profiles, inflammatory biomarkers (eg, interleukin [IL]-6 and IL-8), kidney biomarkers (eg, urine neutrophil gelatinase-associated lipocalin [NGAL] and IL-18), and clinical outcomes (eg, mortality and hospital length of stay). Pairwise standardized difference was reported for all summarized variables. RESULTS: Of 36,865 eligible cardiac surgery cases, 25,613 met inclusion criteria. Cluster analysis derived 3 clinical phenotypes: α, ß, and γ. Phenotype α (n = 6157 [24%]) included older patients with more comorbidities, including heart and kidney failure. Phenotype ß (n = 10,572 [41%]) patients were younger and mostly male. Phenotype γ (n = 8884 [35%]) patients were 58% female and had lower body mass index (BMI). Phenotype α patients had worse outcomes, including longer hospital length of stay (mean = 9 days for α versus 6 for both ß [absolute standardized difference {ASD} = 1.15] and γ [ASD = 1.08]), more kidney failure, and higher mortality. Inflammatory biomarkers (IL-6 and IL-8) and kidney injury biomarkers (urine NGAL and IL-18) were higher with the α phenotype compared to ß and γ immediately after surgery. CONCLUSIONS: Deriving clinical phenotypes that correlate with response biomarkers and outcomes represents an initial step toward a precision medicine approach for the management of CPB-induced inflammatory response and lays the groundwork for future investigation, including an evaluation of the heterogeneity of treatment effect.

Procedure-Specific Relationships Between Postoperative Troponin T and a Composite of Mortality and Low Cardiac Output Syndrome: A Retrospective Cohort Analysis.

BACKGROUND: Myocardial injury after coronary artery bypass grafting (CABG) is defined as troponin concentrations >10 times 99th percentile upper reference limit (URL) according to the Fourth Universal Definition. However, troponin concentrations after non-CABG cardiac surgery which indicate greater-than-expected myocardial injury and increased risk for complications remain unclear. Our goal was to assess procedure-specific relationships between troponin T and a composite outcome of low cardiac output syndrome and in-hospital mortality in cardiac surgical patients. METHODS: Patients having cardiac surgery between January 2010 and December 2017 were categorized into 4 groups by procedure: (1) CABG; (2) mitral valve repair; (3) aortic valve repair/replacement (AVR); (4) mitral valve replacement (MVR) or CABG + valve surgeries. Exclusion criteria were elevated preoperative troponin T, preoperative kidney failure, circulatory arrest, or preoperative/planned mechanical circulatory support. Logistic regression was used to assess the association between troponin T and composite outcome, both overall and by procedure, including assessment of the interaction between procedure and troponin T on outcome. RESULTS: Among 10,253 patients, 37 (0.4%) died and 393 (3.8%) developed the primary outcome. Troponin T concentrations differed by procedure (P < .001). Compared to CABG, AVR had 0.53 (99.2% confidence interval [CI], 0.50-0.56; unadjusted P < .001) times lower troponin T concentrations, while MVR/CABG + valve were 1.54 (99.2% CI, 1.45-1.62, unadjusted P < .001) times higher. There were linear relationships between log2 troponin T concentration and log odds mortality/low cardiac output syndrome. The (unadjusted) relationships were parallel for various types of surgery (interaction P = .59), but at different levels of the outcome. CONCLUSIONS: The relative increase in odds for mortality/low cardiac output syndrome per a similar increase in troponin T concentrations did not differ among cardiac surgical procedures, but the absolute troponin T concentrations did. Troponin concentrations should thus be interpreted in context of surgical procedure.

Incidence, Outcomes, and Risk Factors for Preincision Cardiac Arrest in Cardiac Surgery Patients.

BACKGROUND: We examined the incidence, postoperative outcomes, and patient-related factors associated with preincision cardiac arrest in patients undergoing cardiac surgery. METHODS: We retrospectively examined adult patients undergoing elective or urgent cardiac surgery at the Cleveland Clinic between 2008 and 2019. The incidence of preincision cardiac arrest, defined as arrest between induction of general anesthesia and surgical incision, was reported. In a secondary analysis, we assessed the association between preincision cardiac arrest and major postoperative outcomes. In a tertiary analysis, we used adjusted linear regression models to explore the association between preincision cardiac arrest and prespecified patient risk factors, including severe left main coronary artery stenosis, left ventricular ejection fraction, moderate/severe right ventricular dysfunction, low-flow low-gradient aortic stenosis, and moderate/severe pulmonary hypertension. RESULTS: Preincision cardiac arrests occurred in 75 of 41,238 (incidence of 0.18%; 95% CI, 0.17-0.26) patients who had elective or urgent cardiac surgery. Successful cardiopulmonary resuscitation with return of spontaneous circulation or bridge to cardiopulmonary bypass occurred in 74 of 75 (98.6%) patients. Patients who experienced preincision cardiac arrest had significantly higher in-hospital mortality than those who did not (11% vs 2%; odds ratio [OR] (95% CI), 4.14 (1.94-8.84); P < .001). They were also more likely to suffer postoperative respiratory failure (46% vs 13%; OR [95% CI], 3.94 [2.40-6.47]; P < .001), requirement for renal replacement therapy (11% vs 2%; OR [95% CI], 3.90 [1.82-8.35]; P < .001), neurologic deficit (7% vs 2%; OR [95% CI], 2.49 (1.00-6.21); P = .05), and longer median hospital stay (15 vs 8 days; hazard ratio (HR) [95% CI], 0.68 [0.55-0.85]; P < .001). Reduced left ventricular ejection fraction (per 5% decrease) (OR [95% CI], 1.13 [1.03-1.22]; P = .006) and moderate/severe pulmonary hypertension (OR [95% CI], 3.40 [1.95-5.90]; P < .001) were identified as independent risk factors for cardiac arrest. CONCLUSIONS: Cardiac arrest after anesthetic induction is rare in cardiac surgical patients in our investigation. Though most patients are rescued, morbidity and mortality remain higher. Reduced left ventricular ejection fraction and moderate/severe pulmonary hypertension are associated with greater risk for preincision cardiac arrest.

Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial.

BACKGROUND: Atrial fibrillation and delirium are common consequences of cardiac surgery. Dexmedetomidine has unique properties as sedative agent and might reduce the risk of each complication. This study coprimarily aimed to establish whether dexmedetomidine reduces the incidence of new-onset atrial fibrillation and the incidence of delirium. METHODS: A randomised, placebo-controlled trial was done at six academic hospitals in the USA. Patients who had had cardiac surgery with cardiopulmonary bypass were enrolled. Patients were randomly assigned 1:1, stratified by site, to dexmedetomidine or normal saline placebo. Randomisation was computer generated with random permuted block size 2 and 4, and allocation was concealed by a web-based system. Patients, caregivers, and evaluators were all masked to treatment. The study drug was prepared by the pharmacy or an otherwise uninvolved research associate so that investigators and clinicians were fully masked to allocation. Participants were given either dexmedetomidine infusion or saline placebo started before the surgical incision at a rate of 0·1 µg/kg per h then increased to 0·2 µg/kg per h at the end of bypass, and postoperatively increased to 0·4 µg/kg per h, which was maintained until 24 h. The coprimary outcomes were atrial fibrillation and delirium occurring between intensive care unit admission and the earlier of postoperative day 5 or hospital discharge. All analyses were intention-to-treat. The trial is registered with ClinicalTrials.gov, NCT02004613 and is closed. FINDINGS: 798 patients of 3357 screened were enrolled from April 17, 2013, to Dec 6, 2018. The trial was stopped per protocol after the last designated interim analysis. Among 798 patients randomly assigned, 794 were analysed, with 400 assigned to dexmedetomidine and 398 assigned to placebo. The incidence of atrial fibrillation was 121 (30%) in 397 patients given dexmedetomidine and 134 (34%) in 395 patients given placebo, a difference that was not significant: relative risk 0·90 (97·8% CI 0·72, 1·15; p=0·34). The incidence of delirium was non-significantly increased from 12% in patients given placebo to 17% in those given dexmedetomidine: 1·48 (97·8% CI 0·99-2·23). Safety outcomes were clinically important bradycardia (requiring treatment) and hypotension, myocardial infarction, stroke, surgical site infection, pulmonary embolism, deep venous thrombosis, and death. 21 (5%) of 394 patients given dexmedetomidine and 8 (2%) of 396 patients given placebo, had a serious adverse event as determined by clinicians. 1 (<1%) of 391 patients given dexmedetomidine and 1 (<1%) of 387 patients given placebo died. INTERPRETATION: Dexmedetomidine infusion, initiated at anaesthetic induction and continued for 24 h, did not decrease postoperative atrial arrhythmias or delirium in patients recovering from cardiac surgery. Dexmedetomidine should not be infused to reduce atrial fibrillation or delirium in patients having cardiac surgery. FUNDING: Hospira Pharmaceuticals.

Association between In-hospital Mortality and Low Cardiac Output Syndrome with Morning versus Afternoon Cardiac Surgery.

BACKGROUND: Recent work suggests that having aortic valve surgery in the morning increases risk for cardiac-related complications. This study therefore explored whether mortality and cardiac complications, specifically low cardiac output syndrome, differ for morning and afternoon cardiac surgeries. METHODS: The study included adults who had aortic and/or mitral valve repair/replacement and/or coronary artery bypass grafting from 2011 to 2018. The components of the in-hospital composite outcome were in-hospital mortality and low cardiac output syndrome, defined by requirement for at least two inotropic agents at 24 to 48 h postoperatively or need for mechanical circulatory support. Patients who had aortic cross-clamping between 8 and 11 am (morning surgery) versus between 2 and 5 pm (afternoon surgery) were compared on the incidence of the composite outcome. RESULTS: Among 9,734 qualifying operations, 0.4% (29 of 6,859) died after morning, and 0.7% (20 of 2,875) died after afternoon surgery. The composite of in-hospital mortality and low cardiac output syndrome occurred in 2.8% (195 of 6,859) of morning patients and 3.4% (97 of 2,875) of afternoon patients: morning versus afternoon confounder-adjusted odds ratio, 0.96 (95% CI, 0.75 to 1.24; P = 0.770). There was no evidence of interaction between morning versus afternoon and surgery type (P = 0.965), and operation time was statistically nonsignificant for surgery subgroups. CONCLUSIONS: Patients having aortic valve surgery, mitral valve surgery, and/or coronary artery bypass grafting with aortic cross-clamping in the morning and afternoon did not have significantly different outcomes. No evidence was found to suggest that morning or afternoon surgical timing alters postoperative risk.

Effect of 6% Hydroxyethyl Starch 130/0.4 on Inflammatory Response and Pulmonary Function in Patients Having Cardiac Surgery: A Randomized Clinical Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass induces a profound inflammatory response that, when severe, can lead to multiorgan system dysfunction. Preliminary data suggest that administration of hydroxyethyl starch (HES) solutions may mitigate an inflammatory response and improve pulmonary function. Our goal was to examine the effect of 6% HES 130/0.4 versus 5% human albumin given for intravascular plasma volume replacement on the perioperative inflammatory response and pulmonary function in patients undergoing cardiac surgery. METHODS: This was a subinvestigation of a blinded, parallel-group, randomized clinical trial of patients undergoing elective aortic valve replacement surgery at the Cleveland Clinic main campus, titled "Effect of 6% Hydroxyethyl Starch 130/0.4 on Kidney and Haemostatic Function in Cardiac Surgical Patients." Of 141 patients who were randomized to receive either 6% HES 130/0.4 or 5% human albumin for intraoperative plasma volume replacement, 135 patients were included in the data analysis (HES n = 66, albumin n = 69). We assessed the cardiopulmonary bypass-induced inflammatory response end points by comparing the 2 groups' serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF), measured at baseline and at 1 and 24 hours after surgery. We also compared the 2 groups' postoperative pulmonary function end points, including the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2:Fio2 ratio), dynamic lung compliance, oxygenation index (OI), and ventilation index (VI) at baseline, within 1 hour of arrival to the intensive care unit, and before tracheal extubation. The differences in the postoperative levels of inflammatory response and pulmonary function between the HES and albumin groups were assessed individually in linear mixed models. RESULTS: Serum concentrations of the inflammatory markers (TNF-α, IL-6, MIF) were not significantly different (P ≥ .05) between patients who received 6% HES 130/0.4 or 5% albumin, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). The results of pulmonary function parameters (Pao2:Fio2 ratio, dynamic compliance, OI, VI) were not significantly different (P ≥ .05) between groups, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). CONCLUSIONS: Our investigation found no significant difference in the concentrations of inflammatory markers and measures of pulmonary function between cardiac surgical patients who received 6% HES 130/0.4 versus 5% albumin.

Prognostic Utility of KDIGO Urine Output Criteria After Cardiac Surgery.

OBJECTIVES: Kidney Disease: Improving Global Outcomes (KDIGO) guidelines include assessment of creatinine and urine output to identify acute kidney injury (AKI). Whether urine output is an accurate indicator of AKI after cardiac surgery, however, is unclear. The authors' goal was to examine whether cardiac surgery patients who fulfilled criteria for AKI by KDIGO urine output criteria also demonstrated kidney injury by elevated creatinine, other kidney biomarkers, or had worse clinical outcomes. DESIGN: Secondary analysis of prospectively collected data from a clinical trial, "6% Hydroxyethyl starch 130/0.4 in Cardiac Surgery (NCT02192502)." SETTING: Academic, quaternary care hospital. PARTICIPANTS: Patients undergoing elective aortic valve replacement INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: One hundred forty-one patients were classified into AKI stage by KDIGO urine output criteria within 24 hours after surgery. Kidney biomarkers (serum creatinine, urinary neutrophil gelatinase-associated lipocalin [NGAL], urinary interleukin-18 [IL-18]) and hospital and intensive care unit length of stay were analyzed across AKI stages. Urine output criteria classified four times as many patients with AKI than creatinine criteria (95 [67%] v 21 [15%]). Most patients meeting KDIGO urine output criteria for AKI postoperatively did not satisfy KDIGO creatinine criteria for AKI within one week (77 of 95 [81%]) or six-to-12 months (27 of 29 [93%]). Higher AKI stage assessed by urine output was not associated with higher NGAL, IL-18, or longer hospital or intensive care unit stays. CONCLUSIONS: Acute kidney injury classified by KDIGO urine output criteria was not associated with other biomarkers of kidney injury or worse patient outcomes. These data suggested that KDIGO urine output criteria after cardiac surgery may overclassify AKI stage; further research is needed.

Intercostal Blocks with Liposomal Bupivacaine in Thoracic Surgery: A Retrospective Cohort Study.

OBJECTIVE: Assess the efficacy of adding liposomal bupivacaine (LB) to bupivacaine-containing intercostal nerve blocks (ICNBs) to improve analgesia and decrease opioid consumption and hospital length of stay compared with bupivacaine-only ICNBs. DESIGN: This retrospective, observational investigation compared pain intensity scores and cumulative opioid consumption within the first 72 postoperative hours in patients who received ICNBs with bupivacaine plus LB (LB group) versus bupivacaine only (control group) after minimally invasive anatomic pulmonary resection. LB was tested for noninferiority on pain scores and opioid consumption. If LB was noninferior, superiority of LB was tested on both outcomes. SETTING: Academic tertiary care medical center. PARTICIPANTS: Adult patients undergoing minimally invasive anatomic pulmonary resection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the secondary analysis, hospital length of stay was compared through the Cox regression model. Of 396 patients, 178 (45%) received LB and 218 (55%) did not. The mean (standard deviation) pain score was three (one) in the LB group and three (one) in the control group, with a difference of -0.10 (97.5% confidence interval [-0.39 to 0.18]; p = 0.41). The mean (standard deviation) cumulative opioid consumption (intravenous morphine equivalents) was 198 (208) mg in the LB group and 195 (162) mg in the control group. Treatment effect in opioid consumption was estimated at a ratio of geometric mean of 0.94 (97.5% confidence interval [0.74-1.20]; p = 0.56). Pain control and opioid consumption were noninferior with LB but not superior. Hospital discharge was not different between groups. CONCLUSIONS: LB with bupivacaine in ICNBs did not demonstrate superior postoperative analgesia or affect the rate of hospital discharge.

Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery.

BACKGROUND: Levosimendan is an inotropic agent that has been shown in small studies to prevent or treat the low cardiac output syndrome after cardiac surgery. METHODS: In a multicenter, randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of levosimendan in patients with a left ventricular ejection fraction of 35% or less who were undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients were randomly assigned to receive either intravenous levosimendan (at a dose of 0.2 µg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1 µg per kilogram per minute for 23 hours) or placebo, with the infusion started before surgery. The two primary end points were a four-component composite of death through day 30, renal-replacement therapy through day 30, perioperative myocardial infarction through day 5, or use of a mechanical cardiac assist device through day 5; and a two-component composite of death through day 30 or use of a mechanical cardiac assist device through day 5. RESULTS: A total of 882 patients underwent randomization, 849 of whom received levosimendan or placebo and were included in the modified intention-to-treat population. The four-component primary end point occurred in 105 of 428 patients (24.5%) assigned to receive levosimendan and in 103 of 421 (24.5%) assigned to receive placebo (adjusted odds ratio, 1.00; 99% confidence interval [CI], 0.66 to 1.54; P=0.98). The two-component primary end point occurred in 56 patients (13.1%) assigned to receive levosimendan and in 48 (11.4%) assigned to receive placebo (adjusted odds ratio, 1.18; 96% CI, 0.76 to 1.82; P=0.45). The rate of adverse events did not differ significantly between the two groups. CONCLUSIONS: Prophylactic levosimendan did not result in a rate of the short-term composite end point of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device that was lower than the rate with placebo among patients with a reduced left ventricular ejection fraction who were undergoing cardiac surgery with the use of cardiopulmonary bypass. (Funded by Tenax Therapeutics; LEVO-CTS ClinicalTrials.gov number, NCT02025621 .).

Neither Preoperative Pulse Pressure nor Systolic Blood Pressure Is Associated With Cardiac Complications After Coronary Artery Bypass Grafting.

BACKGROUND: Increased pulse pressure has been associated with adverse cardiovascular events, cardiac and all-cause mortality in surgical and nonsurgical patients. Whether increased pulse pressure worsens myocardial injury and dysfunction after cardiac surgery, however, has not been fully characterized. We examined whether cardiac surgical patients with elevated pulse pressure are more susceptible to myocardial injury, dysfunction, cardiac-related complications, and mortality. Secondarily, we examined whether pulse pressure was a stronger predictor of the outcomes than systolic blood pressure. METHODS: This retrospective observational study included adult cardiac surgical patients having elective isolated on-pump coronary artery bypass grafting (CABG) between 2010 and 2017 at the Cleveland Clinic. The association between elevated pulse pressure and (1) perioperative myocardial injury, measured by postoperative troponin-T concentrations, (2) perioperative myocardial dysfunction, assessed by the requirement for perioperative inotropic support using the modified inotropic score (MIS), and (3) cardiovascular complications assessed by the composite outcome of postoperative mechanical circulatory assistance or in-hospital mortality were assessed using multivariable linear regression models. Secondarily, the association between pulse pressure versus systolic blood pressure and the outcomes were compared. RESULTS: Of 2704 patients who met the inclusion/exclusion criteria, complete data were available for 2003 patients. Increased pulse pressure over 40 mm Hg was associated with elevated postoperative troponin-T level, estimated to be 1.05 (97.5% confidence interval [CI], 1.02-1.09; P < .001) times higher per 10 mm Hg increase in pulse pressure. The association between pulse pressure and myocardial dysfunction and the composite outcome of cardiovascular complications and death were not significant. There was no difference in the association with pulse pressure versus systolic blood pressure and troponin-T concentrations. CONCLUSIONS: Elevated preoperative pulse pressure was associated with a modest increase in postoperative troponin-T concentrations, but not postoperative cardiovascular complications or in-hospital mortality in patients having CABG. Pulse pressure was not a better predictor than systolic blood pressure.

Low Tidal Volumes Are Associated With Slightly Improved Oxygenation in Patients Having Cardiac Surgery: A Cohort Analysis.

BACKGROUND: Mechanical ventilation with low tidal volumes appears to provide benefit in patients having noncardiac surgery; however, whether it is beneficial in patients having cardiac surgery is unclear. METHODS: We retrospectively examined patients having elective cardiac surgery requiring cardiopulmonary bypass through a median sternotomy approach who received mechanical ventilation with a single lumen endotracheal tube from January 2010 to mid-August 2016. Time-weighted average tidal volume (milliliter per kilogram predicted body weight [PBW]) during the duration of surgery excluding cardiopulmonary bypass was analyzed. The association between tidal volumes and postoperative oxygenation (measured by arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen ratio [PaO2/FIO2]), impaired oxygenation (PaO2/FIO2 <300), and clinical outcomes were examined. RESULTS: Of 9359 cardiac surgical patients, larger tidal volumes were associated with slightly worse postoperative oxygenation. Postoperative PaO2/FIO2 decreased an estimated 1.05% per 1 mL/kg PBW increase in tidal volume (97.5% confidence interval [CI], -1.74 to -0.37; PBon = .0005). An increase in intraoperative tidal volumes was also associated with increased odds of impaired oxygenation (odds ratio [OR; 97.5% CI]: 1.08 [1.02-1.14] per 1 mL/kg PBW increase in tidal volume; PBon = .0029), slightly longer intubation time (5% per 1 mL/kg increase in tidal volume (hazard ratio [98.33% CI], 0.95 [0.93-0.98] per 1 mL/kg PBW; PBon < .0001), and increased mortality (OR [98.33% CI], 1.34 [1.06-1.70] per 1 mL/kg PBW increase in tidal volume; PHolm = .0144). An increase in intraoperative tidal volumes was also associated with acute postoperative respiratory failure (OR [98.33% CI], 1.16 [1.03-1.32] per 1 mL/kg PBW increase in tidal volume; PHolm = .0146), but not other pulmonary complications. CONCLUSIONS: Lower time-weighted average intraoperative tidal volumes were associated with a very modest improvement in postoperative oxygenation in patients having cardiac surgery.

Predicting Right Ventricular Failure After LVAD Implantation: Role of Tricuspid Valve Annulus Displacement.

OBJECTIVES: Right ventricular failure after left ventricular assist device implantation increases postoperative morbidity and mortality. Whether intraoperative echocardiographic and hemodynamic measurements predict right ventricular failure is unclear. Speckle-tracking-derived tricuspid annulus displacement may provide a useful, effective, and straightforward predictor of severe right ventricular failure in patients having left ventricular device implantation. The aim of this study was to determine if intraoperative tricuspid annulus displacement is a stronger discriminator compared with the global longitudinal strain and modified tricuspid annular plane systolic excursion, the Michigan risk score, and pulmonary artery pulsatility index. DESIGN: Retrospective analysis. SETTING: A tertiary-care referral center. PARTICIPANTS: Patients scheduled for left ventricular assist device implantation from January 2010 to December 2017. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: The authors examined 86 patients undergoing left ventricular assist device implantation with adequate intraoperative echocardiographic images. The analyses did not demonstrate an association between tricuspid annulus displacement and severe right ventricular failure (univariate C-statistics <0.60 for all 4 echocardiographic measures). The discrimination ability was not significantly better than strain (DeLong test p = 0.44) and modified tricuspid annular plane systolic excursion (p = 0.89). The discrimination ability of tricuspid annulus displacement measurements was not better than the Michigan risk score (p = 0.65) and pulmonary artery pulsatility index (p = 0.73). CONCLUSIONS: Intraoperative echocardiographic parameters, including tricuspid annulus displacement, modified tricuspid annular plane systolic excursion, and strain, are poor discriminators of severe right ventricular failure after left ventricular assist device implantation. The preoperative Michigan risk-scoring system and intraoperative pulmonary artery pulsatility index are equally unreliable.

A Comparison of Global Longitudinal, Circumferential, and Radial Strain to Predict Outcomes After Cardiac Surgery.

OBJECTIVE: Myocardial strain measured by speckle-tracking echocardiography detects subtle regional and global left ventricular dysfunction. Myocardial strain is measured in the longitudinal, circumferential, and radial dimensions; however, it is unclear which dimension of strain is the best predictor of postoperative outcomes. DESIGN: A secondary analysis of prospectively collected data from a clinical trial (NCT01187329). SETTING: The cardiothoracic surgical operating rooms of an academic tertiary-care center. PARTICIPANTS: Cardiothoracic surgery patients with aortic stenosis having aortic valve replacement (AVR) with or without coronary artery bypass grafting enrolled in a clinical trial. INTERVENTIONS: Myocardial deformation analysis from standardized investigative transesophageal echocardiographic examinations performed after induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: The authors compared the ability of intraoperative global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) strain to predict adverse postoperative outcomes, including prolonged hospitalization and the need for pharmacologic hemodynamic support after cardiac surgery. The association of GLS, GCS, and GRS with prolonged hospitalization (>7 days) and the need for pharmacologic hemodynamic support, with epinephrine or norepinephrine after cardiopulmonary bypass, were assessed using separate multivariable logistic regression models with adjustment for multiple comparisons. Of 100 patients, 86 had acceptable measurements for GLS analysis, 73 for GCS, and 72 for GRS. Worse GLS was associated with prolonged hospitalization [odds ratio [OR] (98.3% confidence interval [CI]) of 1.21 (1.01-1.46) per-unit worsening in strain (p = 0.01, significance criterion <0.0167)] and the need for inotropic support with epinephrine [OR (99.2% CI) of 1.81 (1.10-2.97) per-unit worsening in strain (p = 0.002, significance criterion <0.0083)], but not norepinephrine. GCS and GRS were not associated with adverse outcomes. CONCLUSION: GLS, but not GCS or GRS, predicts prolonged hospitalization and the requirement for inotropic support with epinephrine after AVR.

Hyperinsulinemic Normoglycemia during Cardiac Surgery Reduces a Composite of 30-day Mortality and Serious In-hospital Complications: A Randomized Clinical Trial.

BACKGROUND: Hyperinsulinemic normoglycemia augments myocardial glucose uptake and utilization. We tested the hypothesis that hyperinsulinemic normoglycemia reduces 30-day mortality and morbidity after cardiac surgery. METHODS: This dual-center, parallel-group, superiority trial randomized cardiac surgical patients between August 2007 and March 2015 at the Cleveland Clinic, Cleveland, Ohio, and Royal Victoria Hospital, Montreal, Canada, to intraoperative glycemic management with (1) hyperinsulinemic normoglycemia, a fixed high-dose insulin and concomitant variable glucose infusion titrated to glucose concentrations of 80 to 110 mg · dl; or (2) standard glycemic management, low-dose insulin infusion targeting glucose greater than 150 mg · dl. The primary outcome was a composite of 30-day mortality, mechanical circulatory support, infection, renal or neurologic morbidity. Interim analyses were planned at each 12.5% enrollment of a maximum 2,790 patients. RESULTS: At the third interim analysis (n = 1,439; hyperinsulinemic normoglycemia, 709, standard glycemic management, 730; 52% of planned maximum), the efficacy boundary was crossed and study stopped per protocol. Time-weighted average glucose concentration (means ± SDs) with hyperinsulinemic normoglycemia was 108 ± 20 versus 150 ± 33 mg · dl with standard glycemic management, P < 0.001. At least one component of the composite outcome occurred in 49 (6.9%) patients receiving hyperinsulinemic normoglycemia versus 82 (11.2%) receiving standard glucose management (P < efficacy boundary 0.0085); estimated relative risk (95% interim-adjusted CI) 0.62 (0.39 to 0.97), P = 0.0043. There was a treatment-by-site interaction (P = 0.063); relative risk for the composite outcome was 0.49 (0.26 to 0.91, P = 0.0007, n = 921) at Royal Victoria Hospital, but 0.96 (0.41 to 2.24, P = 0.89, n = 518) at the Cleveland Clinic. Severe hypoglycemia (less than 40 mg · dl) occurred in 6 (0.9%) patients. CONCLUSIONS: Intraoperative hyperinsulinemic normoglycemia reduced mortality and morbidity after cardiac surgery. Providing exogenous glucose while targeting normoglycemia may be preferable to simply normalizing glucose concentrations.

Patients at High Risk for Obstructive Sleep Apnea Are at Increased Risk for Atrial Fibrillation After Cardiac Surgery: A Cohort Analysis.

BACKGROUND: Patients with obstructive sleep apnea (OSA) experience intermittent hypoxia, hypercarbia, and sympathetic activation during sleep, which increases risk for paroxysmal atrial fibrillation and other cardiac arrhythmias. Whether patients with OSA experience increased episodes of atrial fibrillation after cardiac surgery is unclear. We examined whether patients at increased risk for OSA, assessed by the STOP-BANG (snoring, tired during the day, observed stop breathing during sleep, high blood pressure, body mass index more than 35 kg/m, age more than 50 years, neck circumference more than 40 cm, and male gender) questionnaire, had a higher incidence of new-onset postoperative atrial fibrillation after cardiac surgery. Because both postoperative atrial fibrillation and OSA increase resource utilization, we secondarily examined whether patients at increased OSA risk had longer duration of postoperative mechanical ventilation and intensive care unit (ICU) length of stay. METHODS: With institutional review board approval, this retrospective observational study evaluated adult patients who underwent elective cardiac surgery requiring cardiopulmonary bypass between 2014 and 2015 with preoperative assessment of OSA risk using the STOP-BANG questionnaire. Patients with a history of atrial fibrillation were excluded. The association between the STOP-BANG score and postoperative atrial fibrillation was examined using a multivariable logistic regression model. Secondarily, we estimated the association between the STOP-BANG score and duration of initial intubation using multivariable linear regression and ICU length of stay using Cox proportional hazards regression. We also descriptively summarized the percentage of patients requiring tracheal reintubation for mechanical ventilation. RESULTS: Of 4228 cardiac surgery patients, 1593 met inclusion and exclusion criteria. An increased STOP-BANG score was associated with higher odds of postoperative atrial fibrillation (odds ratio [95% confidence interval {CI}], 1.16 [1.09-1.23] per-point increase in the STOP-BANG score; P < .001). The STOP-BANG score was not associated with ICU length of stay (estimated hazard ratio [97.5% CI], 0.99 [0.96-1.03] per-point increase in the STOP-BANG score; P = .99) or duration of initial intubation (ratio of geometric means [97.5% CI], 1.01 [1.00-1.04]; P = .03; significance criterion [Bonferroni correction] < 0.025). One percent of patients required reintubation. DISCUSSION: Increasing risk for OSA, assessed by STOP-BANG, was associated with higher odds of postoperative atrial fibrillation, but not prolonged duration of mechanical ventilation or ICU length of stay.

Reduced Left Ventricular Global Longitudinal Strain Predicts Prolonged Hospitalization: A Cohort Analysis of Patients Having Aortic Valve Replacement Surgery.

BACKGROUND: Left ventricular ejection fraction (LVEF) is often preserved in patients with aortic stenosis and thus cannot distinguish between normal myocardial contractile function and subclinical dysfunction. Global longitudinal strain and strain rate (SR), which measure myocardial deformation, are robust indicators of myocardial function and can detect subtle myocardial dysfunction that is not apparent with conventional echocardiographic measures. Strain and SR may better predict postoperative outcomes than LVEF. The primary aim of our investigation was to assess the association between global longitudinal strain and serious postoperative outcomes in patients with aortic stenosis having aortic valve replacement. Secondarily, we also assessed the associations between global longitudinal SR and LVEF and the outcomes. METHODS: In this post hoc analysis of data from a randomized clinical trial (NCT01187329), we examined the association between measures of myocardial function and the following outcomes: (1) need for postoperative inotropic/vasopressor support; (2) prolonged hospitalization (>7 days); and (3) postoperative atrial fibrillation. Standardized transesophageal echocardiographic examinations were performed after anesthetic induction. Myocardial deformation was measured using speckle-tracking echocardiography. Multivariable logistic regression was used to assess associations between measures of myocardial function and outcomes, adjusted for potential confounding factors. The predictive ability of global longitudinal strain, SR, and LVEF was assessed as area under receiver operating characteristics curves (AUCs). RESULTS: Of 100 patients enrolled in the clinical trial, 86 patients with aortic stenosis had acceptable images for global longitudinal strain analysis. Primarily, worse intraoperative global longitudinal strain was associated with prolonged hospitalization (odds ratio [98.3% confidence interval], 1.22 [1.01-1.47] per 1% decrease [absolute value] in strain; P = .012), but not with other outcomes. Secondarily, worse global longitudinal SR was associated with prolonged hospitalization (odds ratio [99.7% confidence interval], 1.68 [1.01-2.79] per 0.1 second(-1) decrease [absolute value] in SR; P = .003), but not other outcomes. LVEF was not associated with any outcomes. Global longitudinal SR was the best predictor for prolonged hospitalization (AUC, 0.72), followed by global longitudinal strain (AUC, 0.67) and LVEF (AUC, 0.62). CONCLUSIONS: Global longitudinal strain and SR are useful predictors of prolonged hospitalization in patients with aortic stenosis having an aortic valve replacement.