Association of serum creatinine trajectories with one-year mortality after valvular heart surgery: a retrospective cohort study.

BACKGROUND: Acute renal dysfunction is defined by the maximum increase in serum creatinine (sCr) without considering the pattern of change in sCr. We aimed to identify longitudinal patterns (trajectories) of postoperative sCr concentrations and investigate their association with long-term outcomes in patients undergoing valvular heart surgery. MATERIALS AND METHODS: In this retrospective review of 3,436 patients who underwent valvular heart surgery, we applied trajectory projection cluster analysis to identify the trajectories of sCr changes from baseline during the seven postoperative days. Primary and secondary endpoints were to investigate the associations of sCr trajectories with mortality using Kaplan-Meier curves and Cox proportional hazards regression analysis, and a composite of major adverse kidney events (MAKEs) at one year after surgery, respectively. RESULTS: Four clusters were identified: Clusters 1 and 2, a minimal change in sCr (90.1% of patients); Cluster 3, a significant and persistent increase in sCr (4.1% of patients); and Cluster 4, a significant but transient increase in sCr (5.8% of patients). The one-year postoperative mortality rate was higher in Cluster 3 (18.4%) and Cluster 4 (11.6%) than in Cluster 1+2 (2.7%). The Kaplan-Meier survival curve demonstrated significant differences in mortality rates among the clusters (log-rank test, P<0.001). In the multivariable Cox analysis, the sCr trajectory cluster was an independent prognostic factor for mortality. Cluster 3 had a higher prevalence of MAKEs (37.6%) compared with Cluster 1+2 (6.8%, P<0.001) and Cluster 4 (24.1%, P=0.045). The cluster was an independent prognostic factor for MAKEs. CONCLUSION: The sCr trajectory clusters exhibited significantly different risks of mortality and MAKEs at one year after surgery. Through these sCr trajectories, we confirmed that both the extent of sCr increase and its sustainability during the first seven postoperative days were closely associated with the long-term prognosis after valvular heart surgery.

Influence of acute kidney injury and its recovery subtypes on patient-centered outcomes after lung transplantation.

This study aimed to investigate the association between acute kidney injury (AKI) recovery subtypes and days alive out of hospital within the first 3 months (DAOH-90) in patients undergoing lung transplantation. Patients who underwent lung transplantation from January 2012 to December 2021 were retrospectively analyzed and stratified into three groups: no-AKI, early recovery AKI (within 7 days), and non-early recovery AKI group. AKI occurred in 86 (35%) of patients, of which 40 (16%) achieved early recovery, and the remaining 46 (19%) did not. The median DAOH-90 was 21 days shorter in the AKI than in the no-AKI (P = 0.002), and 29 days shorter in the non-early recovery AKI group than in the no-AKI group (P < 0.001). Non-early recovery AKI and preoperative tracheostomy status were independently associated with shorter DAOH-90. The prevalence of CKD (76%), and 1-year mortality (48%) were highest in the non-early recovery AKI group. Postoperative AKI was associated with an adverse patient-centered quality measure for perioperative care, and shorter DAOH-90. The non-early recovery AKI group exhibited the worst prognosis in terms of DAOH-90, CKD progression, and 1-year mortality, highlighting the important role of AKI and early-recovery AKI on both the quality of life and clinical outcomes after lung transplantation.

Effects of dexmedetomidine on renal function after cardiac surgery for infective endocarditis: An interim analysis of a randomized controlled trial.

BACKGROUND: Patients undergoing cardiac surgery for infective endocarditis (IE) are at a high risk of postoperative acute kidney injury (AKI) owing to heightened systemic inflammation. Therefore, we aimed to investigate the effect of dexmedetomidine on postoperative AKI in patients who underwent cardiac surgery for IE. METHODS: A total of 63 patients who underwent cardiac surgery for IE were randomly assigned to receive either intravenous dexmedetomidine infusion of 0.4 µg kg-1 h-1 (DEX group) or normal saline infusion (control group) for 24 h after induction of anesthesia. The occurrence of AKI within seven days postoperation, epinephrine, norepinephrine, and interleukin-6 levels, as well as postoperative morbidities, were assessed. An intertrim analysis was conducted using Pocock's alpha spending function at α = 0.05 and ß = 0.2. RESULTS: This trial was early terminated according to the results of interim analysis performed when 60 % of the pre-set number of patients have been collected. The incidence of AKI was significantly lower in the DEX group than in the control group (32.3 % vs. 9.4 %, p = 0.025). Patients in the DEX group had significantly lower epinephrine levels than those in the control group, whereas norepinephrine and interleukin-6 levels were similar. Perioperative mean arterial pressure or heart rate did not differ between the groups. CONCLUSIONS: Dexmedetomidine administration for 24 h starting from induction of anesthesia significantly reduced the incidence of postoperative AKI after cardiac surgery for IE (by 29 % vs. control) without hemodynamic side effects. This was accompanied by a significant attenuation of postoperative increase in serum epinephrine levels.

Effect of high-dose vitamin C on renal ischemia-reperfusion injury.

Acute kidney injury frequently occurs after cardiac surgery, and is primarily attributed to renal ischemia-reperfusion (I/R) injury and inflammation from surgery and cardiopulmonary bypass. Vitamin C, an antioxidant that is often depleted in critically ill patients, could potentially mitigate I/R-induced oxidative stress at high doses. We investigated the effectiveness of high-dose vitamin C in preventing I/R-induced renal injury. The ideal time and optimal dosage for administration were determined in a two-phase experiment on Sprague-Dawley rats. The rats were assigned to four groups: sham, IRC (I/R + saline), and pre- and post-vitC (vitamin C before and after I/R, respectively), with vitamin C administered at 200 mg/kg. Additional groups were examined for dose modification based on the optimal timing determined: V100, V200, and V300 (100, 200, and 300 mg/kg, respectively). Renal I/R was achieved through 45 min of ischemia followed by 24 h of reperfusion. Vitamin C administration during reperfusion significantly reduced renal dysfunction and tubular damage, more than pre-ischemic administration. Doses of 100 and 200 mg/kg during reperfusion reduced oxidative stress markers, including myeloperoxidase and inflammatory responses by decreasing high mobility group box 1 release and nucleotide-binding and oligomerization domain-like receptor 3 inflammasome. Overall beneficial effect was most prominent with 200 mg/kg. The 300 mg/kg dose, however, showed no additional benefits over the IRC group regarding serum blood urea nitrogen and creatinine levels and histological evaluation. During reperfusion, high-dose vitamin C administration (200 mg/kg) significantly decreased renal I/R injury by effectively attenuating the major triggers of oxidative stress and inflammation.

Effect of Retrograde Autologous Priming on Coagulation Assessed by Rotation Thromboelastometry in Patients Undergoing Valvular Cardiac Surgery.

OBJECTIVES: To investigate the effect of retrograde autologous priming (RAP) on coagulation function using rotation thromboelastometry (ROTEM) in patients undergoing valvular cardiac surgery. DESIGN: A prospective, randomized, patient- and outcome assessor-blinded study. SETTING: At a single-center university hospital. PARTICIPANTS: Patients aged 20 years or older undergoing valvular cardiac surgery. INTERVENTIONS: A total of 104 patients were allocated to the RAP or control group (1:1 ratio). In the RAP group, the prime was displaced into the collection bag before bypass initiation. ROTEM was performed at the induction of anesthesia, at the beginning of rewarming, and after the reversal of heparinization. Allogeneic plasma products and platelet concentrates were transfused according to ROTEM-based algorithms. MEASUREMENTS AND MAIN RESULTS: An average volume of 635 ± 114 mL was removed using RAP (from the 1,600 mL initial prime volume). The hematocrit 10 minutes after cardiopulmonary bypass (CPB) was 24.7 ± 3.5% in the control group, and 26.1 ± 4.1% in the RAP group (p = 0.330). ROTEM, including EXTEM, INTEM, and FIBTEM, showed prolonged clotting time and decreased maximal clot firmness after CPB in both groups without intergroup differences. The number of patients who received intraoperative erythrocytes (27% v 25%, control versus RAP, p = 0.823), fresh frozen plasma (14% v 8%, control versus RAP, p = 0.339), cryoprecipitate (21% v 12%, control versus RAP, p = 0.185), or platelet concentrate transfusion (19% v 12%, control versus RAP, p = 0.277) did not differ between the groups. CONCLUSIONS: Cardiopulmonary bypass induced impaired coagulation function on ROTEM. However, RAP did not improve coagulation function when compared with conventional priming in patients undergoing valvular cardiac surgery.

Risk stratification model integrating nutritional and inflammatory factors for predicting 1-year mortality after valvular heart surgery: a retrospective cohort study.

INTRODUCTION: Existing risk-scoring systems for cardiac surgery include only standard preoperative factors without considering nutritional and inflammatory status or intraoperative factors. The objective of this study was to develop a comprehensive prediction model for mortality incorporating nutritional, inflammatory, and perioperative factors in patients undergoing valvular heart surgery. MATERIALS AND METHODS: In this retrospective review of 2046 patients who underwent valvular heart surgery, Cox and LASSO regression analyses were performed to identify independent prognostic factors for 1-year postoperative mortality among various perioperative factors known to affect prognosis, including objective nutritional and inflammatory indices. A novel nomogram model incorporating selected prognostic factors was developed, and its discrimination ability was evaluated using the C-index. The model was validated in internal and external cohorts. RESULTS: The 1-year mortality rate after valvular heart surgery was 5.1% (105 of 2046 patients) and was significantly associated with several preoperative objective inflammatory and nutritional indices. Cox and LASSO analyses identified the following five independent prognostic factors for mortality: monocyte-to-lymphocyte ratio (an objective inflammatory index), EuroSCORE II, Controlling Nutritional Status score, cardiopulmonary bypass time, and number of erythrocyte units transfused intraoperatively. The nomogram model incorporating these five factors had a C-index of 0.834 (95% CI: 0.791-0.877), which was higher than that of EuroSCORE II alone (0.744, 95% CI: 0.697-0.791) ( P <0.001). The nomogram achieved good discrimination ability, with C-indices of 0.836 (95% CI: 0.790-0.878) and 0.727 (95% CI: 0.651-0.803) in the internal and external validation cohorts, respectively, and showed well-fitted calibration curves. CONCLUSIONS: A nomogram model incorporating five inflammatory, nutritional, and perioperative factors, as well as EuroSCORE II, was a better predictor of 1-year mortality after valvular heart surgery than EuroSCORE II alone, with good discrimination and calibration power for predicting mortality in both internal and external validation cohorts.

Effect of 5% albumin on endothelial glycocalyx degradation during off-pump coronary artery bypass.

PURPOSE: The integrity of the endothelial glycocalyx (EG), a critical player in vascular homeostasis, reportedly influences the outcomes of critically ill patients. We investigated the effect of 5% albumin, which preserved EG integrity in preclinical studies, vs balanced crystalloid solution on EG degradation in patients undergoing off-pump coronary surgery. METHODS: Patients were randomized to receive either 5% albumin (N = 51) or balanced crystalloid solution (Plasma-Lyte [Baxter Incorporated, Seoul, Republic of Korea]; N = 53) for intravenous volume replacement during surgery (double-blinded). The primary outcome was plasma syndecan-1 concentration, a marker of EG degradation, measured after anesthetic induction (baseline), completion of grafting, and sternal closure. Secondary outcomes were atrial natriuretic peptide (ANP), tumour necrosis factor (TNF)-α, soluble thrombomodulin, and perioperative fluid balance. RESULTS: The mean (standard deviation) fluid requirements were 833 (270) mL and 1,323 (492) mL in the albumin and Plasma-Lyte group, respectively (mean difference, -489 mL; 95% confidence interval [CI], -643 to -335; P < 0.001). Plasma syndecan-1 concentration increased after completion of grafting (median difference, 116 ng·mL-1; 95% CI, 67 to 184; P < 0.001) and sternal closure (median difference, 57 ng·mL-1; 95% CI, 36 to 80; P < 0.001) compared with those at baseline, without any intergroup differences. Atrial natriuretic peptide, TNF-α, and soluble thrombomodulin concentrations were similar between the two groups. The amount of chest tube drainage was greater in the albumin group than that in the Plasma-Lyte group (median difference, 190 mL; 95% CI, 18 to 276; P = 0.03). CONCLUSION: Off-pump coronary surgery was associated with significant EG degradation. Yet, intraoperative fluid therapy with 5% albumin could not ameliorate EG degradation when compared with balanced crystalloid solution. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03699462); first posted 9 October 2018.

RéSUMé: OBJECTIF: L'intégrité du glycocalyx endothélial (GE), un acteur essentiel de l'homéostasie vasculaire, influencerait le devenir des patient·es gravement malades. Nous avons étudié l'effet de l'albumine à 5 %, qui préservait l'intégrité du GE dans les études précliniques, par rapport à une solution cristalloïde équilibrée sur la dégradation du GE chez les patient·es bénéficiant d'une chirurgie coronarienne à cœur battant. MéTHODE: Les patient·es ont été randomisé·es à recevoir soit de l'albumine à 5 % (N = 51) ou de la solution cristalloïde équilibrée (Plasma-Lyte [Baxter Incorporated, Séoul, République de Corée]; N = 53) pour le remplacement du volume intraveineux pendant la chirurgie (en double aveugle). Le critère d'évaluation principal était la concentration plasmatique de syndécan-1, un marqueur de la dégradation du GE, mesurée après l'induction de l'anesthésie (ligne de base), la fin de la greffe et la fermeture du sternum. Les critères d'évaluation secondaires étaient le peptide natriurétique auriculaire (ANP), le facteur de nécrose tumorale (TNF)-α, la thrombomoduline soluble et le bilan hydrique périopératoire. RéSULTATS: Les besoins liquidiens moyens (écart type) étaient de 833 (270) mL et 1323 (492) mL dans les groupes albumine et Plasma-Lyte, respectivement (différence moyenne, −489 mL; intervalle de confiance [IC] à 95 %, −643 à −335; P < 0,001). La concentration plasmatique de syndécan-1 a augmenté après la fin de la greffe (différence médiane, 116 ng·mL−1; IC 95 %, 67 à 184; P < 0,001) et la fermeture du sternum (différence médiane, 57 ng·mL−1; IC 95 %, 36 à 80; P < 0,001) par rapport aux concentrations au départ, sans différences intergroupe. Les concentrations de peptide natriurétique auriculaire, de TNF-α et de thrombomoduline soluble étaient similaires entre les deux groupes. La quantité de drainage du drain thoracique était plus importante dans le groupe albumine que dans le groupe Plasma-Lyte (différence médiane, 190 mL; IC 95 %, 18 à 276; P = 0,03). CONCLUSION: La chirurgie coronarienne à cœur battant a été associée à une dégradation significative du glycocalyx endothélial. Pourtant, la fluidothérapie peropératoire avec 5 % d'albumine n'a pas pu améliorer la dégradation du GE par rapport à une solution cristalloïde équilibrée. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT03699462); enregistrée pour la première fois le 9 octobre 2018.

Inhaled iloprost in off-pump coronary artery bypass surgery: a randomized controlled trial.

PURPOSE: Mechanical cardiac constraint during off-pump coronary artery bypass surgery (OPCAB) causes right ventricle (RV) compression and increased pulmonary artery pressure (PAP), which may further compromise RV dysfunction. We aimed to assess the effect of inhaled iloprost, a potent selective pulmonary vasodilator, on the cardiac index (CI) during mechanical constraint. The secondary aim was to determine the resultant changes in the hemodynamic and respiratory parameters. METHODS: A total of 100 adult patients with three-vessel coronary artery disease who had known risk factors for hemodynamic instability (congestive heart failure, mean PAP ≥ 25 mm Hg, RV systolic pressure ≥ 50 mm Hg on preoperative echocardiography, left ventricular ejection fraction < 50%, myocardial infarction within one month of surgery, redo surgery, and left main disease) were enrolled in a randomized controlled trial. The patients were randomly allocated to the control or iloprost groups at a 1:1 ratio, in which saline and iloprost (20 µg) were inhaled for 15 min after internal mammary artery harvesting, respectively. Cardiac index was measured by pulmonary artery catheterization. RESULTS: There were no significant intergroup differences in CI during grafting (P = 0.36). The mean PAP had a significant group-time interaction (P = 0.04) and was significantly lower in the iloprost group at circumflex grafting (mean [standard deviation], 26 [3] mm Hg vs 24 [3] mm Hg; P = 0.01). The remaining hemodynamic parameters were similar between the groups. CONCLUSION: Inhaled iloprost showed a neutral effect on hemodynamic parameters, including the CI and pulmonary vascular resistance index, during OPCAB. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04598191); first submitted 12 October 2020.

RéSUMé: OBJECTIF: La contrainte cardiaque mécanique lors d'un pontage aortocoronarien à cœur battant (OPCAB) provoque une compression du ventricule droit (VD) et une augmentation de la pression artérielle pulmonaire (PAP), ce qui peut compromettre davantage le dysfonctionnement du VD. Notre objectif était d'évaluer l'effet de l'iloprost inhalé, un puissant vasodilatateur pulmonaire sélectif, sur l'index cardiaque (IC) au cours de la contrainte mécanique. L'objectif secondaire était de déterminer les modifications résultantes des paramètres hémodynamiques et respiratoires. MéTHODE: Au total, 100 patient·es adultes atteint·es d'une coronaropathie à trois vaisseaux qui présentaient des facteurs de risque connus d'instabilité hémodynamique (insuffisance cardiaque congestive, PAP moyenne ≥ 25 mm  Hg, pression systolique du VD ≥ 50 mm Hg à l'échocardiographie préopératoire, fraction d'éjection ventriculaire gauche < 50 %, infarctus du myocarde dans le mois précédant la chirurgie, chirurgie de reprise et maladie principale gauche) ont été inclus·es dans une étude randomisée contrôlée. Les patient·es ont été réparti·es au hasard dans les groupes témoin ou iloprost dans un rapport de 1:1, dans lequel la solution saline et l'iloprost (20 µg) ont été inhalés pendant 15 minutes après le prélèvement de l'artère mammaire interne, respectivement. L'indice cardiaque a été mesuré par cathétérisme de l'artère pulmonaire. RéSULTATS: Il n'y a eu aucune différence significative entre les groupes en matière d'IC pendant le pontage (P = 0,36). La PAP moyenne présentait une interaction significative groupe-temps (P = 0,04) et était significativement plus faible dans le groupe iloprost au pontage de l'artère circonflexe (moyenne [écart type], 26 [3] mm Hg vs 24 [3] mm Hg; P = 0,01). Les autres paramètres hémodynamiques étaient similaires entre les groupes. CONCLUSION: L'iloprost inhalé a montré un effet neutre sur les paramètres hémodynamiques, y compris sur l'IC et l'indice de résistance vasculaire pulmonaire, pendant un pontage aortocoronarien à cœur battant. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04598191); soumis pour la première fois le 12 octobre 2020.

Effects of dexmedetomidine on A549 non-small cell lung cancer growth in a clinically relevant surgical xenograft model.

The perioperative milieu following curative lung cancer surgery is accompanied by a stress response. Inflammasomes mediate inflammation resulting in the unfavorable immunomodulation of natural killer (NK) cell activity, thus promoting cancer progression. This study aimed to investigate the effects of dexmedetomidine (DEX) on the innate immune system, chronic inflammation, and lung cancer progression in a clinically relevant human-to-mouse xenograft model. The human lung cancer cell line A549-luc was subcutaneously injected into BALB/c nude mice. Saline or dexmedetomidine was administered for 2 weeks via an implanted osmotic minipump. After 4 weeks, the tumor size and weight were measured. NK cell activity, serum interferon-γ, interleukin (IL)-1ß and tumor necrosis factor (TNF)-α levels were also measured. IL-10, IL-18, and inflammasome expression levels were assessed in the tumor tissues. DEX caused a decrease in tumor size, tumor weight, and IL-1ß and TNF-α levels and an increase in NK cell activity and IFN-γ level. IL-10 and IL-18 expression was significantly decreased in the DEX-treated group. NLRP3, CTP1A, TXNIP, ASC, IL-1ß, and caspase-1 protein levels were decreased in the DEX-treated group. In conclusion, the use of DEX for 2 weeks inhibited lung cancer progression by suppressing inflammasome- and IL-1ß signaling-induced inflammation and enhancing NK cell activity.

Effects of intraoperative inspired oxygen fraction (FiO2 0.3 vs 0.8) on patients undergoing off-pump coronary artery bypass grafting: the CARROT multicenter, cluster-randomized trial.

BACKGROUND: To maintain adequate oxygenation is of utmost importance in intraoperative care. However, clinical evidence supporting specific oxygen levels in distinct surgical settings is lacking. This study aimed to compare the effects of 30% and 80% oxygen in off-pump coronary artery bypass grafting (OPCAB). METHODS: This multicenter trial was conducted in three tertiary hospitals from August 2019 to August 2021. Patients undergoing OPCAB were cluster-randomized to receive either 30% or 80% oxygen intraoperatively, based on the month when the surgery was performed. The primary endpoint was the length of hospital stay. Intraoperative hemodynamic data were also compared. RESULTS: A total of 414 patients were cluster-randomized. Length of hospital stay was not different in the 30% oxygen group compared to the 80% oxygen group (median, 7.0 days vs 7.0 days; the sub-distribution hazard ratio, 0.98; 95% confidence interval [CI] 0.83-1.16; P = 0.808). The incidence of postoperative acute kidney injury was significantly higher in the 30% oxygen group than in the 80% oxygen group (30.7% vs 19.4%; odds ratio, 1.94; 95% CI 1.18-3.17; P = 0.036). Intraoperative time-weighted average mixed venous oxygen saturation was significantly higher in the 80% oxygen group (74% vs 64%; P < 0.001). The 80% oxygen group also had a significantly greater intraoperative time-weighted average cerebral regional oxygen saturation than the 30% oxygen group (56% vs 52%; P = 0.002). CONCLUSIONS: In patients undergoing OPCAB, intraoperative administration of 80% oxygen did not decrease the length of hospital stay, compared to 30% oxygen, but may reduce postoperative acute kidney injury. Moreover, compared to 30% oxygen, intraoperative use of 80% oxygen improved oxygen delivery in patients undergoing OPCAB. Trial registration ClinicalTrials.gov (NCT03945565; April 8, 2019).

Predictive Value of the Changes in Neutrophil-Lymphocyte Ratio for Outcomes After Off-Pump Coronary Surgery.

Purpose: The neutrophil-to-lymphocyte ratio (NLR) is an extensively analyzed prognostic inflammatory index in cardiac patients. The degree of change in NLR values before and after surgery (delta-NLR) can represent the inflammatory response induced by surgery and serve as a meaningful prognostic biomarker in surgical patients; however, this has not been well investigated. We aimed to investigate the predictive value of the perioperative NLR and delta-NLR for outcomes of off-pump coronary artery bypass (OPCAB) surgery by evaluating "days alive and out of hospital (DAOH)", a novel patient-centered outcome. Patients and Methods: In this single-center retrospective study, perioperative data, including NLR data, from 1322 patients were analyzed. The primary endpoint was DOAH at 90 days postoperatively (DAOH 90), and the secondary endpoint was long-term mortality. Linear regression analysis and Cox regression analysis were performed to identify independent risk factors for the endpoints. In addition, Kaplan-Meier survival curves were plotted to assess long-term mortality. Results: The median NLR values significantly increased from 2.2 (1.6-3.1) at baseline to 7.4 (5.4-10.3) postoperatively, with median delta-NLR values of 5.0 (3.2-7.6). Preoperative NLR and delta-NLR were independent risk factors for short DAOH 90 in the linear regression analysis. In Cox regression analysis, delta-NLR, but not preoperative NLR, was an independent risk factor for long-term mortality. When patients were divided into two groups according to delta-NLR, the high delta-NLR group had a shorter DAOH 90 than the low delta-NLR group. Kaplan-Meier curves showed higher long-term mortality in the high delta-NLR group than in the low delta-NLR group. Conclusion: In OPCAB patients, preoperative NLR and delta-NLR were significantly associated with DAOH 90, and delta-NLR was an independent risk factor for long-term mortality, indicating their role in risk assessment, which is essential for perioperative management.

Hemodynamic management during off-pump coronary artery bypass surgery: a narrative review of proper targets for safe execution and troubleshooting.

Off-pump coronary surgery requires mechanical cardiac displacement, which results in bi-ventricular systolic and diastolic dysfunction. Although transient, subsequent hemodynamic deterioration can be associated with poor prognosis and, in extreme cases, emergency conversion to on-pump surgery, which is associated with high morbidity and mortality. Thus, appropriate decision-making regarding whether the surgery can be proceeded based on objective hemodynamic targets is essential before coronary arteriotomy. For adequate hemodynamic management, avoiding myocardial oxygen supply-demand imbalance, which includes maintaining mean arterial pressure above 70 mmHg and preventing an increase in oxygen demand beyond the patient's coronary reserve, must be prioritized. Maintaining mixed venous oxygen saturation above 60%, which reflects the lower limit of adequate global oxygen supply-demand balance, is also essential. Above all, severe mechanical cardiac displacement incurring compressive syndromes, which cannot be overcome by adjusting major determinants of cardiac output, should be avoided. An uncompromising form of cardiac constraint can be ruled out as long as the central venous pressure is not equal to or greater than the pulmonary artery diastolic (or occlusion) pressure, as this would reflect tamponade physiology. In addition, transesophageal echocardiography should be conducted to rule out mechanical cardiac displacement-induced ventricular interdependence, dyskinesia, severe mitral regurgitation, and left ventricular outflow tract obstruction with or without systolic motion of the anterior leaflet of the mitral valve, which cannot be tolerated during grafting. Finally, the ascending aorta should be carefully inspected for gas bubbles to prevent hemodynamic collapse caused by a massive gas embolism obstructing the right coronary ostium.

Low Intraoperative Cerebral Oxygen Saturation Is Associated with Acute Kidney Injury after Off-Pump Coronary Artery Bypass.

By monitoring the brain as the index organ of global oxygen supply-demand balance including major organs, regional cerebral oxygen saturation (rScO2) may indicate adequacy of renal perfusion. The aim of this study was to investigate the relationship between perioperative rScO2 and acute kidney injury (AKI) after off-pump coronary artery bypass (OPCAB). AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes criteria. Collected rScO2 variables were baseline, mean, and lowest value during surgery, maximal percentage decrease from baseline, and areas under the threshold below an absolute value of 50% (AUT50) and of 80% of baseline (AUT80%base). Among 580 patients, AKI developed in 143 (24.7%) patients. Patients with AKI had lower baseline, mean, and lowest rScO2 and higher AUT50 and AUT80%base than those without AKI despite routine efforts to restore the rScO2 values within 20% of the baseline. Among the rScO2 variables, the area under the receiver operating characteristic curve of mean rScO2 was the highest (0.636), which was used for the multivariable logistic regression. Multivariable logistic regression revealed mean rScO2 as an independent predictor of AKI (odds ratio, 0.964; 95% confidence interval, 0.937-0.990; p = 0.008), along with chronic kidney disease and emergency surgery. Low intraoperative mean rScO2 was independently associated with AKI after OPCAB, which may serve as an early marker of renal injury.

Impact of transient decrease in mixed venous oxygen saturation on prognosis in off-pump coronary artery bypass surgery: a retrospective cohort study.

BACKGROUND: The prognostic consequences of transient hemodynamic deterioration due to cardiac displacement, which is most severe during left circumflex artery (LCX) grafting in off-pump coronary artery bypass surgery (OPCAB) are unknown. This study aimed to investigate the association between mixed venous oxygen saturation (SvO2) < 60% during LCX grafting and the occurrence of composite of morbidity endpoints. METHODS: Data of patients who underwent elective OPCAB between January 2010 and December 2019 were reviewed. Logistic regression analysis was performed to detect risk factors for the composite of morbidity endpoints, defined as 30-day or in-hospital mortality, postoperative myocardial infarction, prolonged mechanical ventilation > 24 h, cerebrovascular accident, and acute kidney injury. RESULTS: Among 1,071 patients, the composite of morbidity endpoints occurred in 303 (28%) patients. SvO2 < 60% during LCX grafting was significantly associated with the composite of morbidity (OR: 2.72, 95% CI [1.60, 4.61], P < 0.001) along with advanced age, chronic kidney disease, ratio of early mitral inflow velocity to mitral annular early diastolic velocity, and EuroSCORE II. Other major hemodynamic variables including the cardiac index were not associated with the outcome. Additional regression analysis revealed pre-operative anemia as a predictor of SvO2 < 60% during LCX grafting (OR: 2.09, 95% CI [1.33, 3.29], P = 0.001). CONCLUSIONS: A decrease in SvO2 < 60%, albeit confined to the period of cardiac displacement, was associated with a 2.7-fold increased risk of detrimental outcomes after OPCAB, implying the prognostic importance of this transient deterioration in oxygen supply-demand balance.

Regulators impeding erythropoiesis following iron supplementation in a clinically relevant rat model of iron deficiency anemia with inflammation.

AIMS: While elevated hepcidin levels with inflammation have been postulated as a putative mechanism hindering effective erythropoiesis after intravenous (IV) iron therapy in anemic patients undergoing surgery, little is known about the concomitant changes in other major regulators affecting erythropoiesis. This study investigated the activities of relevant regulators after iron replenishment in a rat model of iron deficiency anemia with inflammation. MAIN METHODS: Inflammation was induced by administration of complete Freund's adjuvant (CFA) in male Sprague-Dawley rats. After 2 weeks of CFA treatment, the rats received IV iron (CFA­iron) or saline (CFA-saline). The control group received saline instead of CFA and iron (saline-saline). At 1, 3, and 10 days after iron or saline treatment, inflammatory cytokines, oxidative markers, iron profiles, hepcidin, erythropoietin (EPO), erythroferrone (ERFE), fibroblast growth factor 23 (FGF 23), and expression of mRNA and proteins in the liver involved in hepcidin signaling pathways were measured. KEY FINDINGS: CFA treatment and iron restriction decreased hemoglobin and serum iron levels, significantly increasing inflammatory and oxidative markers. Iron supplementation did not restore hemoglobin levels despite improved iron profiles. CFA injections increased hepcidin and FGF 23 levels and decreased EPO and ERFE levels, which further intensified after iron supplementation with concomitantly elevated levels of oxidative stress and inflammatory markers. SIGNIFICANCE: Under inflammatory conditions, IV iron administration exacerbated inflammatory and oxidative stress and did not resolve anemia, even under iron deficiency conditions. Iron therapy exerted adverse influences on the changes in key regulators toward impeding erythropoiesis that was already impeded by inflammation.

Perioperative Doppler ultrasound assessment of portal vein flow pulsatility in high-risk cardiac surgery patients: a multicentre prospective cohort study.

BACKGROUND: Portal vein Doppler ultrasound pulsatility measured by transoesophageal echocardiography is a marker of the haemodynamic impact of venous congestion in cardiac surgery. We investigated whether the presence of abnormal portal vein flow pulsatility is associated with a longer duration of invasive life support and postoperative complications in high-risk patients. METHODS: In this multicentre cohort study, pulsed-wave Doppler ultrasound assessments of portal vein flow were performed during anaesthesia before initiation of cardiopulmonary bypass (before CPB) and after separation of cardiopulmonary bypass (after CPB). Abnormal pulsatility was defined as portal pulsatility fraction (PPF) ≥50% (PPF50). The primary outcome was the cumulative time in perioperative organ dysfunction (TPOD) requiring invasive life support during 28 days. Secondary outcomes included major postoperative complications. RESULTS: 373 patients, 71 (22.0%) had PPF50 before CPB and 77 (24.9%) after CPB. PPF50 was associated with longer duration of TPOD (median [inter-quartile range]; before CPB: 27 h [11-72] vs 19 h [8.5-42], P=0.02; after CPB: 27 h [11-61] vs 20 h [8-42], P=0.006). After adjusting for confounders, PPF50 before CPB showed significant association with TPOD. PPF50 after CPB was associated with a higher rate of major postoperative complications (36.4% vs 20.3%, P=0.006). CONCLUSIONS: Abnormal portal vein flow pulsatility before cardiopulmonary bypass was associated with longer duration of life support therapy after cardiac surgery in high-risk patients. Abnormal portal vein flow pulsatility after cardiopulmonary bypass separation was associated with a higher risk of major postoperative complications although this association was not independent of other factors. CLINICAL TRIAL REGISTRATION: NCT03656263.

Influence of Mild Thyroid Dysfunction on Outcomes after Off-Pump Coronary Artery Bypass Surgery.

We retrospectively evaluated the association between preoperative mild thyroid dysfunction (subclinical hypothyroidism [SCH] or low triiodothyronine [T3] syndrome) and outcomes in patients who underwent off-pump coronary surgery (OPCAB). Further, 800 patients (2015−2020) were divided into euthyroid, low T3, and SCH groups. The primary outcome assessed the association with composite endpoints (myocardial infarction, prolonged mechanical ventilation [>24 h], acute kidney injury, and 30-day/in-hospital mortality). The secondary outcome assessed the association with long-term mortality and 10% and 8% of the patients exhibited low T3 and SCH, respectively. Incidences of composite endpoints were significantly higher in the low T3 and SCH groups versus the euthyroid group (50.6%, 45.2%, 17.4%, respectively, p < 0.001). Multivariable regression analysis revealed chronic kidney disease, anemia, EuroSCORE, low T3, and SCH as independent risk factors of composite endpoints. The long-term mortality rate (median follow-up, 30 months) was higher in the low T3 and SCH groups than in the euthyroid group (9.6%, 11.3%, 2.4%, respectively, p < 0.001). In the absence of overt thyroid dysfunction, low T3 and SCH were associated with increased risk of adverse outcomes after OPCAB. Moreover, the adverse influences of low T3 and SCH seem to extend to long-term mortality, implying that routine thyroid function tests may enhance accurate risk stratification.

Platelet Reactivity and Outcomes after Off-Pump Coronary Surgery in Acute Coronary Syndrome Patients.

Ischemic and hemorrhagic complications are major determinants of survival in acute coronary syndrome (ACS) patients undergoing coronary surgery. We investigated the association of preoperative platelet reactivity to P2Y12 antagonists with ischemic and hemorrhagic complications after Off-Pump Coronary Artery Bypass surgery (OPCAB) in ACS patients who received dual anti-platelet therapy (DAPT) within 5 days prior to surgery. This prospective, observational study with 177 patients compared the incidence of perioperative major bleeding and major adverse cardiac events (MACEs) in relation to the tertile distribution of the % inhibitory response to P2Y12 antagonists, as measured by a thromboelastography platelet mapping assay. The incidences of perioperative major bleeding and MACEs were similar in relation to the tertile distribution of inhibitory response to P2Y12 antagonists. The % inhibitory responses to P2Y12 antagonists between patients who did or did not exhibit MACEs, and with or without major bleeding, were 58 ± 20% and 56 ± 20% (p = 0.578) and 57 ± 19% and 56 ± 21% (p = 0.923), respectively. In ACS patients who received DAPT close to OPCAB, the platelet inhibitory response to P2Y12 antagonists was not associated with ischemic or hemorrhagic complications. OPCAB may obviate the need for routine platelet function testing for ACS patients requiring DAPT and surgical revascularization. Clinical Registration Number: NCT02184884.

Increased Carotid Intima-Media Thickness was not Associated With Cognitive Dysfunction After Off-Pump Coronary Surgery in Older Adult Patients Without Carotid Stenosis.

Increased carotid intima-media thickness (C-IMT), a marker of atherosclerosis, is known to be associated with cerebrovascular and cortical abnormalities and cognitive impairment. This prospective observational study investigated the association between increased C-IMT and postoperative cognitive dysfunction (POCD) in older adult patients undergoing off-pump coronary artery bypass surgery. A total of 201 patients (57 females, 144 males; >60 years) were classified into increased (n = 105) or normal (n = 96) C-IMT groups by a cut-off value of 0.9 mm (bilateral C-IMT mean). Cognitive function was serially assessed with the Korean Mini-Mental State Examination, and Korean Montreal Cognitive Assessment scores preoperatively and at 7 days and 3 months postoperatively. POCD was defined as the deterioration of 1 standard deviation in at least one of the postoperative tests compared with their corresponding baseline scores. Independent risk factors for POCD were evaluated using multivariable analysis. Overall, POCD occurred in 46 patients (23%) over the 3 months. The incidences of POCD at 7 days and 3 months after surgery were similar, and there was no difference in both Korean Mini-Mental State Examination and Korean Montreal Cognitive Assessment test scores before and after surgery between groups. Chronic obstructive lung disease and intraoperative hyperglycemia episodes (>180 mg/dL), but not increased C-IMT, were independent risk factors for POCD. Unlike in nonsurgical cohorts, increased C-IMT was not significantly associated with the occurrence of POCD in older adult patients undergoing off-pump coronary artery bypass surgery.

Impact of preoperative nutritional scores on 1-year postoperative mortality in patients undergoing valvular heart surgery.

OBJECTIVE: Malnutrition is a well-recognized risk factor for poor prognosis and mortality. We investigated whether preoperative malnutrition diagnosed with objective nutritional scores affects 1-year mortality in patients undergoing valvular heart surgery. METHODS: In this retrospective cohort observational study, we evaluated the association among the Controlling Nutritional Status score, Prognostic Nutritional Index, and Geriatric Nutritional Risk Index with 1-year mortality in 1927 patients undergoing valvular heart surgery. We identified factors for mortality using multivariable Cox proportional hazard analysis and investigated the utility of nutritional scores for risk stratification. RESULTS: Malnutrition, as identified by a high Controlling Nutritional Status score and low Prognostic Nutritional Index and Geriatric Nutritional Risk Index, was significantly associated with higher 1-year mortality. Kaplan-Meier survival curve showed that mortality significantly increased as the severity of malnutrition increased (log-rank test, P < .001). The predicted discrimination (C-index) was 0.79 with the Controlling Nutritional Status score, 0.77 with the Prognostic Nutritional Index, and 0.73 with the Geriatric Nutritional Risk Index. Each nutritional index (Controlling Nutritional Status; hazard ratio, 1.31, 95% confidence interval, 1.21-1.42, P < .001), the European System for Cardiac Operative Risk Evaluation II (hazard ratio, 1.07, 95% confidence interval, 1.04-1.09, P < .001), and chronic kidney disease (hazard ratio, 2.26, 95% confidence interval, 1.31-3.90, P = .003) were independent risk factors for mortality. The Controlling Nutritional Status score added to the European System for Cardiac Operative Risk Evaluation II significantly increased the predictive discrimination ability for mortality (C-index 0.82, 95% confidence interval, 0.78-0.87, P = .014) compared with the Controlling Nutritional Status or European System for Cardiac Operative Risk Evaluation II alone. CONCLUSIONS: Preoperative malnutrition as assessed by objective nutritional scores was associated with 1-year mortality after valvular heart surgery. The Controlling Nutritional Status score had the highest predictive ability and, when added to the European System for Cardiac Operative Risk Evaluation II, provided more accurate risk stratification.