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.

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.

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.

Unraveling the mechanisms of benzo[a]pyrene degradation by Pigmentiphaga kullae strain KIT-003 using a multi-omics approach.

Polycyclic aromatic hydrocarbons (PAHs), notably benzo[a]pyrene (BaP), are environmental contaminants with multiple adverse ecological implications. Numerous studies have suggested the use of BaP biodegradation using various bacterial strains to remove BaP from the environment. This study investigates the BaP biodegradation capability of Pigmentiphaga kullae strain KIT-003, isolated from the Nak-dong River (South Korea) under specific environmental conditions. The optimum conditions of biodegradation were found to be pH 7.0, 35°C, and a salinity of 0 %. GC-MS analysis suggested alternative pathways by which KIT-003 produced catechol from BaP through several intermediate metabolites, including 4-formylchrysene-5-carboxylic acid, 5,6-dihydro-5,6-dihydroxychrysene-5-carboxylic acid (isomer: 3,4-dihydro-3,4-dihydroxychrysene-4-carboxylic acid), naphthalene-1,2-dicarboxylic acid, and 2-hydroxy-1-naphthoic acid. Proteomic profiles indicated upregulation of enzymes associated with aromatic compound degradation, such as nahAc and nahB, and of those integral to the tricarboxylic acid cycle, reflecting the strain's adaptability to and degradation of BaP. Lipidomic analysis of KIT-003 demonstrated that BaP exposure induced an accumulation of glycerolipids such as diacylglycerol and triacylglycerol, indicating their crucial role in bacterial adaptation mechanisms under BaP stress. This study provides significant scientific knowledge regarding the intricate mechanisms involved in BaP degradation by microorganisms.

Postoperative Hypoalbuminemia as a Predictor of Acute Kidney Injury After Open Repair of Ruptured Abdominal Aortic Aneurysm.

BACKGROUND: Perioperative hypoalbuminemia has a prognostic effect on mortality and morbidity in various cohorts. Patients undergoing open repair of ruptured abdominal aortic aneurysms (rAAA) are at a high risk of hypoalbuminemia due to bleeding and underlying diseases. Hence, this study aimed to investigate the predictive value of immediate postoperative hypoalbuminemia for the risk for acute kidney injury (AKI) in patients undergoing open rAAA repair. METHODS: We retrospectively reviewed 143 patients who underwent open rAAA repair between January 2008 and May 2022. The patients were divided into two groups according to the presence of postoperative AKI. The perioperative serum albumin levels of the two groups were compared. The patients were further divided into two groups based on the median immediate postoperative albumin level (2.4 g/dL). The incidence of AKI was compared between the two groups. Multivariate logistic regression analysis was performed to assess the predictors of postoperative AKI. Kaplan-Meier survival curves were used to evaluate potential of AKI and albumin level as prognostic factors for mortality. RESULTS: Immediate postoperative serum albumin was significantly lower in the AKI group than in the non-AKI group (2.11 ± 0.62 g/dL vs. 2.59 ± 0.62 g/dL, p < 0.001). The incidence of postoperative AKI was significantly higher in patients with albumin ≤ 2.4 g/dL than in patients with albumin > 2.4 g/dL (53.8% vs. 27.7%, p = 0.002). Immediate postoperative albumin level was an independent predictor of AKI (Odds ratio [OR], 0.310; 95% confidence interval [CI] 0.165-0.583, p < 0.001) and 1-year mortality (OR, 0.230; 95% CI 0.098-0.542, p = 0.001). CONCLUSIONS: Immediate postoperative hypoalbuminemia was associated with postoperative AKI and mortality in patients with rAAA.

Effect of Perioperative Intravenous Iron Supplementation for Complex Cardiac Surgery on Transfusion Requirements: A Randomized, Double-blinded Placebo-controlled Trial.

OBJECTIVES: We investigated whether routine perioperative intravenous iron replenishment reduces the requirement for packed erythrocytes (pRBC) transfusion. SUMMARY OF BACKGROUND DATA: Patients undergoing complex cardiac surgery are at high risk of developing postoperative iron deficiency anemia, thus requiring transfusion, which is associated with adverse outcomes. METHODS: Patients were randomized to receive either ferric derisomaltose 20 mg/kg (n = 103) or placebo (n = 101) twice during the perioperative period: 3 days before and after the surgery. The primary endpoint was the proportion of patients who received pRBC transfusion until postoperative day (POD) 10. Hemoglobin, reticulocyte count, serum iron profile, hepcidin, and erythropoietin were serially measured. RESULTS: pRBC was transfused in 60.4% and 57.2% of patients in the control and iron group, respectively (P = 0.651). Hemoglobin concentration at 3 weeks postoperatively was higher in the iron group than in the control group (11.6 ± 1.5 g/dL vs 10.9 ± 1.4 g/dL, P < 0.001). The iron group showed higher reticulocyte count [205 (150-267)×103/µL vs 164 (122-207)×103/µL, P = 0.003] at POD 10. Transferrin saturation and serum ferritin were significantly increased in the iron group than in the control group (P < 0.001). Serum hepcidin was higher in the iron group than in the control group at POD 3 [106.3 (42.9-115.9) ng/mL vs 39.3 (33.3-43.6) ng/mL, P < 0.001]. Erythropoietin concentration increased postoperatively in both groups (P = 0.003), with no between-group difference. CONCLUSIONS: Intravenous iron supplementation during index hospitalization for complex cardiac surgery did not minimize pRBC transfusion despite replenished iron store and augmented erythropoiesis, which may be attributed to enhanced hepcidin expression.

Sirtuin 1 and endothelial glycocalyx.

Sirtuin1 deficiency or reduced activity comprises one of the hallmarks of diseases as diverse as chronic cardiovascular, renal, and metabolic, some malignancies, and infections, as well as aging-associated diseases. In a mouse model of endothelium-limited defect in sirtuin 1 deacetylase activity, we found a dramatic reduction in the volume of endothelial glycocalyx. This was associated with the surge in the levels of one of key scaffolding heparan sulfate proteoglycans of endothelial glycocalyx, syndecan-4, and specifically, its extracellular domain (ectodomain). We found that the defect in endothelial sirtuin 1 deacetylase activity is associated with (a) elevated basal and stimulated levels of superoxide generation (via the FoxO1 over-acetylation mechanism) and (b) increased nuclear translocation of NF-kB (via p65 over-acetylation mechanism). These findings laid the foundation for the proposed novel function of sirtuin 1, namely, the maintenance of endothelial glycocalyx, particularly manifest in conditions associated with sirtuin 1 depletion. In the forthcoming review, we summarize the emerging conceptual framework of the enhanced glycocalyx degradation in the states of defective endothelial sirtuin 1 function, thus explaining a broad footprint of the syndrome of endothelial dysfunction, from impaired flow-induced nitric oxide production, deterrent leukocytes infiltration, increased endothelial permeability, coagulation, and pro-inflammatory changes to development of microvascular rarefaction and progression of an underlying disease.

Perioperative Nadir Hemoglobin Concentration and Outcome in Off-Pump Coronary Artery Bypass Surgery　- A Retrospective Review.

BACKGROUND: Emerging evidence advocates the use of restrictive transfusion strategies at hemoglobin (Hb) levels of approximately 7-8 g/dL in cardiac surgeries using cardiopulmonary bypass. Yet, it is unclear whether the same thresholds can be applied to off-pump coronary bypass (OPCAB) that accompanies cardiac displacement and warm regional ischemia-reperfusion injury without the aid of a bypass machine. The aim of this study is to investigate the relationship between perioperative nadir Hb level and outcome following OPCAB.Methods and Results:Medical records of 1,360 patients were reviewed. Hb levels were serially assessed during and after surgery. The incidence of composite endpoints was 35%, which included myocardial infarction, stroke, acute kidney injury, sternal infection, reoperation, prolonged mechanical ventilation, and in-hospital mortality. The nadir Hb level was significantly lower in the morbidity group than in the non-morbidity group (8.1 [7.4-9.1] vs. 8.8 [7.9-9.8] g/dL, P<0.001). Multivariable logistic regression analysis revealed nadir Hb as an independent risk factor of adverse outcome (odds ratio: 0.878, 95% confidence intervals: 0.776-0.994, P=0.04), whereas preoperative anemia and perioperative transfusion were not. The critical value of Hb for predicting detrimental outcome was 8.05 g/dL. CONCLUSIONS: A significant association is found between perioperative nadir Hb and adverse outcome after OPCAB. Although preoperative anemia was not associated with poor prognosisper se, it was the only modifiable risk factor that was closely linked to nadir Hb.

Effect of dexmedetomidine on acute kidney injury after aortic surgery: a single-centre, placebo-controlled, randomised controlled trial.

BACKGROUND: Acute kidney injury (AKI) is a frequent and serious complication after aortic surgery requiring cardiopulmonary bypass (CPB). Dexmedetomidine, a selective α-2 adrenoreceptor agonist, may reduce AKI because of its sympatholytic and anti-inflammatory effects against ischaemia-reperfusion injury. We investigated the effect of dexmedetomidine administration on AKI after aortic surgery requiring CPB in a placebo-controlled randomised controlled trial. METHODS: A total of 108 patients were randomly assigned to an infusion of dexmedetomidine or saline at a rate of 0.4 µg kg-1 h-1 for 24 h starting after anaesthetic induction. The primary outcome was the incidence of AKI, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The secondary outcomes included delirium and major morbidity. Safety outcomes were drug-related adverse events (bradycardia, hypotension). RESULTS: AKI occurred in 7/54 (13%) subjects randomised to dexmedetomidine, compared with 17/54 (31%) subjects randomised to saline infusion (odds ratio=0.32; 95% confidence interval [CI], 0.12-0.86; P=0.026). Secondary outcomes, including stroke, mortality, and delirium, were similar between subjects randomised to dexmedetomidine (16/54 [30%] or saline control (22 [41%]; odds ratio=0.61 [95% CI, 0.28-1.36]). The incidence of bradycardia and hypotension was similar between groups (14/54 (26%) vs. 17/54 (32%) (odds ratio:0.76 (95%CI:0.33-1.76) and 29/54 (54%) vs. 36/54 (67%) (odds ratio:0.58 (95%CI:0.27-1.26), respectively). The length of hospital stay was shorter in the dexmedetomidine group (12 [10-17] days) vs saline control (15 [11-21] days; P=0.039). CONCLUSIONS: Pre-emptive dexmedetomidine administration for 24 h starting after induction of anaesthesia reduced the incidence of AKI after aortic surgery requiring CPB, without any untoward side-effects related to its sedative or sympatholytic effects. CLINICAL TRIAL REGISTRATION: NCT02607163 (www.ClinicalTrials.gov).

Preoperative transcranial Doppler and cerebral oximetry as predictors of delirium following valvular heart surgery: a case-control study.

Delirium is a frequent and serious complication after cardiac surgery with cerebral hypoperfusion as one from the key pathophysiological mechanisms. Middle cerebral artery (MCA) mean blood flow velocity (MFV) measured by transcranial Doppler has been used as a marker of cerebral perfusion, and cerebral oximetry (rSO2) value as a marker of its adequacy. This prospective observational trial examined the predictive value of MCA MFV and rSO2, measured immediately before induction of anesthesia, for delirium after valvular heart surgery in elderly patients. In 113 patients, delirium was evaluated for 7 days postoperatively, using the confusion assessment method for the intensive care unit. The primary endpoint was the occurrence of postoperative delirium. Overall, 16 patients (14%) exhibited delirium. MCA MVF values could not predict the development of delirium. Preoperative statin use, geriatric depression scale score, and low preoperative rSO2 (< 60%) showed association with delirium occurrence in univariable analysis. After multivariable analysis, only the low preoperative rSO2 (< 60%) (OR 6.748, 95% CI 1.647-27.652, P = 0.008) remained as an independent predictor of delirium. Preoperative MCA MFV was not significantly associated with delirium after valvular heart surgery in elderly patients, while a low baseline rSO2 value was associated with a sevenfold increased risk of delirium.

The Importance of Porins and ß-Lactamase in Outer Membrane Vesicles on the Hydrolysis of ß-Lactam Antibiotics.

Gram-negative bacteria have an outer membrane inhibiting the entry of antibiotics. Porins, found within the outer membrane, are involved in regulating the permeability of ß-lactam antibiotics. ß-lactamases are enzymes that are able to inactivate the antibacterial properties of ß-lactam antibiotics. Interestingly, porins and ß-lactamase are found in outer membrane vesicles (OMVs) of ß-lactam-resistant Escherichia coli and may be involved in the survival of susceptible strains of E. coli in the presence of antibiotics, through the hydrolysis of the ß-lactam antibiotic. In this study, OMVs isolated from ß-lactam-resistant E. coli and from mutants, lacking porin or ß-lactamase, were evaluated to establish if the porins or ß-lactamase in OMVs were involved in the degradation of ß-lactam antibiotics. OMVs isolated from E. coli deficient in ß-lactamase did not show any degradation ability against ß-lactam antibiotics, while OMVs lacking OmpC or OmpF showed significantly lower levels of hydrolyzing activity than OMVs from parent E. coli. These data reveal an important role of OMVs in bacterial defense mechanisms demonstrating that the OmpC and OmpF proteins allow permeation of ß-lactam antibiotics into the lumen of OMVs, and antibiotics that enter the OMVs can be degraded by ß-lactamase.

Endothelial glycocalyx-the battleground for complications of sepsis and kidney injury.

After briefly discussing endothelial glycocalyx and its role in vascular physiology and renal disease, this overview focuses on its degradation very early in the course of microbial sepsis. We describe our recently proposed mechanism for glycocalyx degradation induced by exocytosis of lysosome-related organelles and release of their cargo. Notably, an intermediate in nitric oxide synthesis, NG-hydroxy-l-arginine, shows efficacy in curtailing exocytosis of these organelles and improvement in animal survival. These data not only depict a novel mechanism responsible for very early glycocalyx degradation, but may also outline a potential preventive therapy. The second issue discussed in this article is related to the therapeutic acceleration of restoration of already degraded endothelial glycocalyx. Here, using as an example our recent findings obtained with sulodexide, we illustrate the importance of the expedited repair of degraded endothelial glycocalyx for the survival of animals with severe sepsis. These two focal points of the review on glycocalyx may not only have broader disease applicability, but they may also provide additional evidence to buttress the idea of the importance of endothelial glycocalyx and its maintenance and repair in the prevention and treatment of an array of renal and nonrenal diseases.

Postoperative Cognitive Dysfunction and the Change of Regional Cerebral Oxygen Saturation in Elderly Patients Undergoing Spinal Surgery.

BACKGROUND: In this study, we examined the relationship between postoperative cognitive dysfunction (POCD) and intraoperative regional cerebral oxygen saturation (rSO2) in elderly patients undergoing spinal surgery. METHODS: We enrolled 87 patients older than 65 years. All patients were tested using a battery of cognitive function tests (Korean Mini-Mental State Examination and visuomotor test of Dynamic Lowenstein Occupational Therapy Cognitive Assessment-Geriatric Version) the day before their surgical operation and on the seventh postoperative day. Our threshold for defining POCD for a given patient was a Reliable Change Index score of <-1.96 occurring on 2 tests. RESULTS: POCD was detected in 20 patients (23%) at the seventh postoperative day. Between-patient baseline characteristics, surgical data, and baseline cognitive function were similar for both those who developed POCD and those who did not. A univariate analysis that included age, female sex, education level, presence of diabetes, and duration of intraoperative decline in rSO2 to a level of <60% of baseline revealed that only diabetes and duration of rSO2 <60% (odds ratio, 1.01; 95% confidence interval [CI], 1.005-1.010) were found to be risk factors for POCD. After multivariate logistic regression analysis of these 2 variables, only the duration of rSO2 <60% (odds ratio, 1.006; 95% CI, 1.00-1.01, P = 0.014) remained as an independent risk factor for POCD. The area under the receiver operation characteristic of the duration of rSO2 <60% was 0.70 (95% CI, 0.57-0.82; P = 0.008). The optimal cutoff value was 157 minutes with a sensitivity of 75% and specificity of 72%. CONCLUSIONS: This study showed that the duration of decline in rSO2 <60% during lumbar spinal surgery was correlated with the development of POCD at the seventh postoperative day in elderly patients.

Dexmedetomidine added to an opioid-based analgesic regimen for the prevention of postoperative nausea and vomiting in highly susceptible patients: A randomised controlled trial.

BACKGROUND: Dexmedetomidine, an α2 adrenergic receptor agonist, has analgesic, sedative and sympatholytic properties, with a lack of respiratory depression. It is licensed only for intensive care sedation. OBJECTIVE: The objective of this study is to investigate whether intravenous (i.v.) patient-controlled analgesia (PCA) with dexmedetomidine added to a fentanyl-based drug mixture could reduce postoperative nausea and vomiting (PONV) in highly susceptible patients undergoing lumbar spinal surgery. DESIGN: A randomised, double-blinded study. SETTING: At a tertiary university hospital between September 2012 and September 2013. PATIENTS: One hundred and eight patients undergoing level 1 or 2 posterior lumbar spinal fusion who had at least three risk factors for PONV (female, nonsmoker, use of postoperative opioids) were randomised into two groups. Three patients were excluded from analysis and 105 patients completed the study. METHODS: Patients received either dexmedetomidine 0.5 µg kg⁻¹ i.v. (dexmedetomidine group) or 0.9% normal saline (control group) 30 min before the completion of surgery followed by fentanyl 0.5 µg kg⁻¹ and 4 mg ondansetron. Postoperatively, the PCA (fentanyl 10 µg kg⁻¹ with 120 mg ketorolac, with or without dexmedetomidine 10 µg kg⁻¹ made up to a total volume of 100 ml) was programmed to deliver 1 ml bolus (lockout 15 min) with a continuous background infusion of 2 ml h⁻¹. The PCA was used for the first 48 h postoperatively. MAIN OUTCOME MEASURES: The incidence and severity of PONV, cumulative dose of PCA fentanyl consumed and pain scores were assessed for 48 h. RESULTS: The dexmedetomidine group experienced less nausea during the time interval 1 to 3 h postoperatively compared with the control group [odds ratio (OR) 0.32; 95% confidence interval (CI) 0.13 to 0.77; P = 0.019]. The intensity of nausea between the groups during the first 48 h was comparable, but the dexmedetomidine group had a lower incidence of moderate to severe nausea (OR 0.28; 95% CI 0.12 to 0.67; P < 0.003). Pain scores were not significantly different between the groups, but patients in the dexmedetomidine group required less fentanyl and less rescue analgesia in the first 12 h. Compared with the control group, patients in the dexmedetomidine group experienced almost twice as many episodes of hypotension and bradycardia, but this failed to reach statistical significance. CONCLUSION: Adding dexmedetomidine to a fentanyl-based PCA drug mixture reduces the frequency and severity of acute postoperative nausea in highly susceptible patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01840254.

A Randomized, Double-blind, Non-inferiority Trial of Magnesium Sulphate versus Dexamethasone for Prevention of Postoperative Sore Throat after Lumbar Spinal Surgery in the Prone Position.

BACKGROUND: Postoperative sore throat (POST) is a frequent complication of tracheal intubation, particularly after surgery in the prone position. We designed this study to validate the non-inferiority of magnesium sulphate against dexamethasone for prevention of POST after lumbar spinal surgery. METHODS: One hundred and forty-six patients were randomly allocated to receive either magnesium or dexamethasone. Before anesthetic induction, the magnesium group (n = 73) received magnesium sulphate 30 mg/kg followed by 10 mg/kg/h by continuous infusion until the end of surgery. The dexamethasone group (n = 73) received dexamethasone 8 mg. The primary endpoint was the overall incidence of POST, which was assessed serially over 48 hr postoperatively. The predefined margin of non-inferiority for magnesium against dexamethasone was 15%. RESULTS: Overall incidences of POST at rest (50.7% versus 49.3% in the magnesium and dexamethasone group, respectively, p = 0.869) and swallowing (65.8% versus 61.6% in the magnesium and dexamethasone group, respectively, p = 0.606) were not different between the groups. The upper limit of the 90% confidence interval, which must be lower than the predefined margin of non-inferiority to prove the non-inferiority of magnesium sulphate against dexamethasone, for at rest and swallowing were 14.97% (p = 0.0496) and 17.19% (p = 0.0854), respectively. The incidences and severities of POST and hoarseness were also not different between the groups throughout the study period. CONCLUSIONS: Prophylactic magnesium sulphate appears to be non-inferior to dexamethasone for the prevention of POST at rest in patients undergoing lumbar spinal surgery in the prone position.

Double-blinded, randomized controlled trial of N-acetylcysteine for prevention of acute kidney injury in high risk patients undergoing off-pump coronary artery bypass.

AIM: The aim of this study was to investigate the influence of perioperative N-acetylcysteine (NAC) administration, a known antioxidant, on the incidence of acute kidney injury (AKI) after off-pump coronary bypass surgery (OPCAB) in patients with known risk factors of AKI. METHODS: One hundred and seventeen patients with ≥1 of the following risk factors of AKI were randomized into either the control (n = 57) or the NAC (n = 60) group; (i) preoperative serum creatinine >1.4 mg/dL; (ii) left ventricular ejection fraction <35% or congestive heart failure (iii) age >70 years (iv) diabetes or (v) re-operation. Patients in the NAC group received 150 mg/kg of NAC IV bolus at anaesthetic induction followed by a continuous infusion at 150 mg/kg per day for 24 h. AKI was diagnosed based on Acute Kidney Injury Network criteria during 48 h postoperatively. RESULTS: The incidence of AKI was 32% (19/60) and 35% (20/57) in the control and the NAC group, respectively (P = 0.695). The serum concentrations of creatinine and cystatin C were similar between the groups throughout the study period. Fluid balance including the amount of blood loss and transfusion requirement were similar between the groups except the amount of postoperative urine output, which was higher in the control group compared with the NAC group (5528 ± 1247 mL vs. 4982 ± 1185 mL, control vs. NAC, P = 0.017). CONCLUSION: Perioperative administration of NAC did not prevent the development of postoperative AKI after OPCAB in highly susceptible patients to AKI.

Effect of glucose-insulin-potassium on hyperlactataemia in patients undergoing valvular heart surgery: A randomised controlled study.

BACKGROUND: Hyperlactataemia represents oxygen imbalance in the tissues and its occurrence during cardiac surgery is associated with adverse outcomes. Glucose-insulin-potassium (GIK) infusion confers myocardial protection against ischaemia-reperfusion injury and has the potential to reduce lactate release while improving its clearance. OBJECTIVES: The objective of this study is to compare the effect of GIK on the incidence of hyperlactataemia in patients undergoing valvular heart surgery. DESIGN: A randomised controlled study. SETTING: Single university teaching hospital. PATIENTS: One hundred and six patients scheduled for elective valvular heart surgery with at least two of the known risk factors for hyperlactataemia. INTERVENTION: Patients were randomly allocated to receive either GIK solution (insulin 0.1 IU kg(-1) h(-1) and an infusion of 30% dextrose and 80 mmol l(-1) potassium at 0.5 ml kg(-1) h(-1)) or 0.9% saline (control) throughout surgery. MAIN OUTCOME MEASURES: The primary outcome was the incidence of hyperlactataemia (lactate ≥ 4 mmol l(-1)) during the operation and until 24 h after the operation. Secondary outcomes included haemodynamic parameters, use of vasopressor or inotropic drugs, and fluid balance until 24 h postoperatively. Postoperative morbidity endpoints were also assessed. RESULTS: The incidences of hyperlactataemia were similar in the groups (32/53 patients in each of the control and GIK groups, P > 0.999). There were no intergroup differences in haemodynamic parameters, use of vasopressor and inotropic drugs, or fluid balance. The incidences of postoperative morbidity endpoints were similar in both groups. CONCLUSION: Despite its theoretical advantage, GIK did not provide beneficial effects in terms of the incidence of hyperlactataemia or outcome in patients undergoing valvular heart surgery. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01825720.

Association of carotid arterial circumferential strain with left ventricular function and hemodynamic compromise during off-pump coronary artery bypass surgery.

BACKGROUND: Considering the importance of ventricular-vascular coupling, a measure of arterial stiffness may reflect global myocardial performance. We evaluated the predictive value of common carotid arterial circumferential strain (CCA CirS), measured with ultrasound speckle tracking, for hemodynamic deterioration during off-pump coronary artery bypass (OPCAB) and assessed its association with echocardiographic indices of myocardial function. METHODS AND RESULTS: Patients with left ventricular ejection fraction (LVEF) ≥50% were enrolled. Intraoperative hemodynamic variables were compared in relation to CCA CirS tertiles. A total of 96 patients were analyzed. Mixed venous oxygen saturation (SvO2) during left circumflex artery grafting and sternum closure were lower in the first tertile than in the third tertile. On univariate logistic regression female gender, ratio of early transmitral velocity to annular velocity, pulse pressure, and CCA CirS were predictors of hemodynamic deterioration (defined as decrease in SvO2≥20%), while only CCA CirS remained as an independent predictor after multivariate analysis (OR, 0.27; 95% CI: 0.11-0.68). Area under the curve of CCA CirS for its prediction was 0.730 (95% CI: 0.608-0.852). CCA CirS was strongly associated with tissue Doppler-derived parameters of LV function. CONCLUSIONS: CCA CirS is a comprehensive marker reflecting LV function, and a predictor for hemodynamic deterioration during OPCAB in patients with preserved LVEF.

Impact of preoperative fibrinogen concentration on postoperative outcome in patients who received dual antiplatelet therapy in proximity to off-pump coronary bypass surgery.

BACKGROUND: Preoperative fibrinogen concentration is associated with increased blood loss at the lower end, and with hypercoagulability-related ischemic event at the higher end in cardiac patients. We evaluated the influence of preoperative fibrinogen concentration on blood loss and outcome in patients who received clopidogrel in proximity to off-pump coronary artery bypass surgery (OPCAB). METHODS AND RESULTS: Medical records of 538 patients who received clopidogrel within 5 days of OPCAB (April 2007 to March 2012) were retrospectively reviewed. Perioperative bleeding and composite of morbidity endpoints including myocardial infarction were compared in relation to the tertile distribution of the fibrinogen concentration. The amount of blood loss was significantly larger in the first tertile, whereas the incidence of composite of morbidity endpoints was significantly higher in the third tertile. In multivariate analysis for risk factors of perioperative blood loss, body mass index and duration of surgery were identified as independent risk factors but not the fibrinogen level. And hypertension and preoperative fibrinogen level were identified as independent risk factors about composite of morbidity. The third tertile was associated with a 2-fold increased risk of developing composite of morbidity endpoints. CONCLUSIONS: In patients who received dual antiplatelet therapy in proximity to OPCAB, increased preoperative fibrinogen concentration could serve as a valuable predictor for composite of morbidity endpoints, whereas low fibrinogen concentration was not found to be a risk factor of bleeding.

Machine Learning with Clinical and Intraoperative Biosignal Data for Predicting Cardiac Surgery-Associated Acute Kidney Injury.

Early identification of patients at high risk of cardiac surgery-associated acute kidney injury (CSA-AKI) is crucial for its prevention. We aimed to leverage perioperative clinical and intraoperative biosignal data to develop machine learning models that predict CSA-AKI. We introduced a novel approach for extracting relevant features from high-resolution intraoperative biosignals to reflect the patient's baseline status, the extent of unfavorable conditions encountered intraoperatively, and data variability. We developed XGBoost models from 2,003 patients across three consecutive perioperative phases using: 1) only preoperative, 2) pre- and intraoperative, and 3) pre-, intra-, and postoperative variables. The predictive performance progressively improved throughout the three consecutive perioperative phases (e.g., AUROC of 0.767 to 0.797 and 0.840), all surpassing the Thakar Score's performance. According to the SHAP method, intraoperative perfusion pressure was most important in the prediction, highlighting the importance of intraoperative patient management and the use of high-resolution biosignal data in predictive modeling to analyze hemodynamic fluctuations during surgery. Early postoperative biomarkers were also important predictors, highlighting the importance of intensified monitoring early after surgery.