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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.

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 (rSO 2 ) value as a marker of its adequacy. This prospective observational trial examined the predictive value of MCA MFV and rSO 2 , 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 rSO 2 (< 60%) showed association with delirium occurrence in univariable analysis. After multivariable analysis, only the low preoperative rSO 2 (< 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 rSO 2 value was associated with a sevenfold increased risk of delirium.

Degradation of endothelial glycocalyx (EG) is associated with inflammation and endothelial dysfunction, which may contribute to the development of acute kidney injury (AKI). We investigated the association between a marker of EG degradation and AKI after valvular heart surgery. Serum syndecan-1 concentrations were measured at induction of anesthesia and discontinuation of cardiopulmonary bypass in 250 patients. Severe AKI was defined as Kidney Disease: Improving Global Outcomes Criteria Stage 2 or 3. Severe AKI occurred in 13 patients (5%). Receiver operating characteristic analysis of preoperative syndecan-1 to predict severe AKI showed area under curve of 0.714 (95% confidence interval (CI), 0.575-0.853; p = 0.009). The optimal cut-off value was 90 ng/mL, with a sensitivity of 61.5% and specificity of 78.5%. In multivariable analysis, both preoperative syndecan-1 ≥ 90 ng/mL and Cleveland Clinic Foundation score independently predicted severe AKI. Severe tricuspid regurgitation was more frequent (42.4% vs. 17.8%, p < 0.001), and baseline right ventricular systolic pressure (41 (33-51) mmHg vs. 33 (27-43) mmHg, p = 0.001) and TNF-α (1.85 (1.37-2.43) pg/mL vs. 1.45 (1.14-1.92) pg/mL, p <0.001) were higher in patients with high preoperative syndecan-1. Patients with high preoperative syndecan-1 had longer hospital stay (16 (12-24) days vs. 13 (11-17) days, p = 0.001). In conclusion, a high preoperative syndecan-1 concentration greater than 90 ng/mL was able to predict severe AKI after valvular heart surgery and was associated with prolonged hospitalization.

Indications of non-vitamin K antagonist oral anticoagulants (NOACs), consisting of two types: direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitor (rivaroxaban, apixaban, and edoxaban), have expanded over the last few years. Accordingly, increasing number of patients presenting for surgery are being exposed to NOACs, despite the fact that NOACs are inevitably related to increased perioperative bleeding risk. This review article contains recent clinical evidence-based up-to-date recommendations to help set up a multidisciplinary management strategy to provide a safe perioperative milieu for patients receiving NOACs. In brief, despite the paucity of related clinical evidence, several key recommendations can be drawn based on the emerging clinical evidence, expert consensus, and predictable pharmacological properties of NOACs. In elective surgeries, it seems safe to perform high-bleeding risk surgeries 2 days after cessation of NOAC, regardless of the type of NOAC. Neuraxial anesthesia should be performed 3 days after cessation of NOACs. In both instances, dabigatran needs to be discontinued for an additional 1 or 2 days, depending on the decrease in renal function. NOACs do not require a preoperative heparin bridge therapy. Emergent or urgent surgeries should preferably be delayed for at least 12 h from the last NOAC intake (better if > 24 h). If surgery cannot be delayed, consider using specific reversal agents, which are idarucizumab for dabigatran and andexanet alfa for rivaroxaban, apixaban, and edoxaban. If these specific reversal agents are not available, consider using prothrombin complex concentrates., Competing Interests: CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © the Korean Society of Anesthesiologists, 2020.)

Outcomes of cardiac surgery are influenced by systemic inflammation. High mobility group box 1 (HMGB1), a pivotal inflammatory mediator, plays a potential role as a prognostic biomarker in cardiovascular disease. The aim of this prospective, observational study was to investigate the relationship between serum HMGB1 concentrations and composite of morbidity endpoints in cardiac surgery. Arterial blood samples for HMGB1 measurement were collected from 250 patients after anaesthetic induction (baseline) and 1 h after weaning from cardiopulmonary bypass (post-CPB). The incidence of composite of morbidity endpoints (death, myocardial infarction, stroke, renal failure and prolonged ventilator care) was compared in relation to the tertile distribution of serum HMGB1 concentrations. The incidence of composite of morbidity endpoints was significantly different with respect to the tertile distribution of post-CPB HMGB1 concentrations (p = 0.005) only, and not to the baseline. Multivariable analysis revealed post-CPB HMGB1 concentration (OR, 1.072; p = 0.044), pre-operative creatinine and duration of CPB as independent risk factors of adverse outcome. Accounting for its prominent role in mediating sterile inflammation and its relation to detrimental outcome, HMGB1 measured 1 h after weaning from CPB would serve as a useful biomarker for accurate risk stratification in cardiac surgical patients and may guide tailored anti-inflammatory therapy.

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)., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

While both baseline regional cerebral oxygen saturation (rSO 2 ) and intraoperative rSO 2 decreases have prognostic importance in cardiac surgery, evidence is limited in patients who received interventions to correct rSO 2 decreases. The primary aim was to examine the association between rSO 2 values (both baseline rSO 2 and intraoperative decrease in rSO 2 ) with the composite of morbidity endpoints. We retrospectively analyzed 356 cardiac surgical patients having continuously recorded data of intraoperative rSO 2 values. Per institutional guidelines, patients received interventions to restore the rSO 2 value to ≥80% of the baseline value. Analyzed rSO 2 variables included baseline value, and area under the threshold below an absolute value of 50% (AUT50). Their association with outcome was analyzed with multivariable logistic regression. AUT50 (odds ratio, 1.05; 95% confidence interval; 1.01-1.08; p = 0.015) was shown to be an independent risk factor (along with age, chronic kidney disease, and cardiopulmonary bypass time) of adverse outcomes. In cardiac surgical patients who received interventions to correct decreases in rSO 2 , increased severity of intraoperative decrease in rSO 2 as reflected by AUT below an absolute value of 50% was associated with a composite of adverse outcomes, implicating the importance of cerebral oximetry to monitor the brain as an index organ.

Age and acute hyperglycemia are known risk factors of myocardial ischemia-reperfusion injury. We investigated age-related difference in the effect of acute hyperglycemia on myocardial ischemia-reperfusion injury in Sprague-Dawley rats (young, 3 months; middle-aged, 10-12 months; and old, 22-24 months). The rats received 1.2 g/kg dextrose or normal saline and were subjected to coronary artery occlusion for 45 minutes followed by reperfusion for 240 minutes. Infarct size and ejection fraction were measured. The levels of apoptosis-related proteins (C-PARP, Bcl-2, Bax, and cytochrome c) and autophagy-related proteins (Bnip3, Beclin-1, Atg5, and LC3B-II) were evaluated. Infarct size increased with acute hyperglycemia in young and middle-aged rats but not in old rats, whereas the reduction of ejection fraction after ischemia-reperfusion was aggravated by acute hyperglycemia in all age groups. Acute hyperglycemia increased Bnip3 and Beclin-1 expressions after ischemia-reperfusion in young and middle-aged rats but not in old rats, whereas it increased the expression of Bax, cytochrome c, Atg5, and LC3B-II only in young or middle-aged rats. Conclusively, acute hyperglycemia does not aggravate myocardial ischemia-reperfusion injury in old rats, unlike in young and middle-aged rats. This heterogeneity may be due to attenuated changes in protein signaling after ischemia-reperfusion injury under acute hyperglycemia in old rats., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: There seem to be modifiable components of diabetes in terms of glycemic control to improve surgical outcome. The aim of the study was to evaluate impact of preoperative glycated hemoglobin (HbA1c) level in patients with diabetes mellitus undergoing off-pump coronary bypass (OPCAB) on perioperative glycemic variability and short-term outcome., Methods: Medical records of 703 patients with diabetes mellitus who underwent OPCAB from 2005 to 2017 were reviewed. The perioperative goal of glycemic control was <180 mg/dL. Patients were divided into 2 groups according to HbA1c level (<7.0% or ≥7.0%). Glycemic variability during surgery and up to 24 hours after surgery was assessed by coefficient of variation (CV). Primary outcome was defined as composite of postoperative permanent stroke, prolonged ventilation, deep sternal wound infection, renal failure, reoperation, and 30-day mortality., Results: Incidence of composite of postoperative morbidity and mortality endpoints was greater in patients with HbA1c ≥7.0% (21% vs 15%, P = .041). Perioperative time-weighted average glucose concentration was also greater in patients with HbA1c ≥7.0%, whereas the CV did not show any difference. Multivariable logistic regression analysis revealed that congestive heart failure, chronic kidney disease, moderate mitral regurgitation or greater, preoperative hemoglobin level, and preoperative HbA1c ≥7.0% were independently associated with composite of postoperative morbidity and mortality, but perioperative CV and time-weighted average glucose ≥200 mg/dL were not., Conclusions: Increased preoperative HbA1c (≥7.0%) level reflecting long-term glycemic control seems to exert an adverse influence on outcome, whereas the influence of perioperative glycemic variables appear to be abrogated using a target glucose level of <180 mg/dL in patients with diabetes mellitus undergoing OPCAB., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Anesthesia for percutaneous transluminal angioplasty (PTA) involves a high-risk population having a broad spectrum of pain character and intensity. This study delved the anesthetic efficacy of dexmedetomidine versus midazolam, when used with remifentanil. Seventy patients scheduled for femoropopliteal PTA were randomized into two groups receiving either intermittent midazolam boluses (0.03⁻0.05 mg/kg) (MR group) or dexmedetomidine 0.2⁻0.7 μg/kg/h after a loading dose of 1.0 μg/kg for 10 min (DR group), both with remifentanil. The primary endpoint was the patients' satisfaction (1⁻5, 5; extremely satisfied). Secondary endpoints included postprocedural pain scores (0⁻10, 10; worst imaginable pain) and adverse events. The satisfaction level of patients was significantly greater in the DR group compared with the MR group (4.0 [3.0, 5.0] versus 4.0 [2.0, 5.0] p = 0.021). The number of patients having a postprocedural pain score of at least 3 was significantly greater in the MR group compared with the DR group (10 [29%] versus 2 [6%], p = 0.013). The number of patients with hypotensive episodes was higher in the DR group (5 [14.7%] versus 0, p = 0.025), which could all be restored with ephedrine. The use of dexmedetomidine in conjunction with remifentanil may be a safe option that provides excellent patient satisfaction while potentially attenuating postprocedural pain.

Emerging evidence indicates the pronounced role of inflammasome activation linked to reactive oxygen species (ROS) in the sterile inflammatory response triggered by ischemia/reperfusion (I/R) injury. Ethyl pyruvate (EP) is an antioxidant and conveys myocardial protection against I/R injury, while the exact mechanisms remain elusive. We aimed to investigate the effect of EP on myocardial I/R injury through mechanisms related to ROS and inflammasome regulation. The rats were randomly assigned to four groups: (1) sham, (2) I/R-control (IRC), (3) EP-pretreatment + I/R, and (4) I/R + EP-posttreatment. I/R was induced by a 30 min ligation of the left anterior descending artery followed by 4 h of reperfusion. EP (50 mg/kg) was administered intraperitoneally at 1 h before ischemia (pretreatment) or upon reperfusion (posttreatment). Both pre- and post-EP treatment resulted in significant reductions in myocardial infarct size (by 34% and 31%, respectively) and neutrophil infiltration. I/R-induced myocardial expressions of NADPH oxidase-4, carnitine palmitoyltransferase 1A, and thioredoxin-interacting protein (TXNIP) were mitigated by EP. EP treatment was associated with diminished inflammasome activation (NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like protein, and caspase-1) and interleukin-1 β induced by I/R. I/R-induced phosphorylation of ERK and p38 were also mitigated with EP treatments. In H9c2 cells, hypoxia-induced TXNIP and NLRP3 expressions were inhibited by EP and to a lesser degree by U0126 (MEK inhibitor) and SB203580 (p38 inhibitor) as well. EP's downstream protective mechanisms in myocardial I/R injury would include mitigation of ROS-mediated NLRP3 inflammasome upregulation and its associated pathways, partly via inhibition of hypoxia-induced phosphorylation of ERK and p38.

Background: Repeated remote ischaemic conditioning (RIC) during weaning from cardiopulmonary bypass and in the early postoperative period may confer protection against acute kidney injury (AKI). We evaluated the effect of repeated RIC on the incidence of AKI in patients undergoing valvular heart surgery., Methods: Patients were randomised into either the RIC (n=120) or control (n=124) group. A pneumatic tourniquet was placed on each patient's thigh. Upon removal of the aortic cross-clamp, three cycles of inflation for 5 min at 250 mm Hg (with 5 min intervals) were applied in the RIC group. Additionally, three cycles of RIC were repeated at postoperative 12 and 24 h. AKI was diagnosed based on the Kidney Disease: Improving Global Outcomes guideline. The incidences of renal replacement therapy, permanent stroke, sternal wound infection, newly developed atrial fibrillation, mechanical ventilation >24 h, and reoperation for bleeding during hospitalisation were recorded., Results: The incidences of AKI were not significantly different between the control (19.4%) and RIC (15.8%) groups (a difference of 3.5 percentage points; 95% confidence interval: -6.8%-13.9%; P=0.470). Perioperative serum creatinine concentrations were similar in the control and RIC groups (P=0.494). Fluid balance, urine output, blood loss, transfusion, and vasopressor/inotropic requirements were not significantly different between the groups (all P>0.05). The occurrences of a composite of morbidity and mortality endpoints were not significantly different between the control (46.0%) and RIC (39.2%) groups (a difference of 6.8 percentage points; 95% confidence interval: -6.4%-20.0%; P=0.283)., Conclusions: The results of our study do not support repeated RIC to decrease the incidence of AKI after valvular heart surgery., Clinical Trial Registration: NCT02720549., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Carotid intima-media thickness (IMT) is a well-known predictor of adverse outcomes in the ischemic heart disease patients; however, evidence is lacking in patients undergoing off-pump coronary artery bypass surgery (OPCAB). Data from 407 patients who underwent OPCAB between April 2013 and August 2016 were retrospectively reviewed. A composite of cardiovascular morbidity endpoints was defined as the presence of stroke, acute myocardial infarction, new cardiac arrhythmia (newly developed atrial fibrillation, atrial flutter, or atrioventricular block), cardiovascular death, or cerebrovascular death within 30 days after surgery. Increased carotid IMT was defined as ≥0.9 mm on one or both sides. The incidence of a composite of cardiovascular morbidity endpoints was 24.0% in the normal IMT group (n = 221) and 34.4% in the increased IMT group (n = 186) (p = 0.021). Multivariable analysis revealed increased IMT (odds ratio 1.719, 95% confidence interval 1.108 to 2.666, p = 0.016) and preoperative renal replacement therapy (odds ratio 4.264, 95% confidence interval 1.679 to 10.829, p = 0.002) as independent predictors of a composite of cardiovascular morbidity endpoints. In patients undergoing OPCAB, preoperative assessment of carotid IMT may help predicting the development of a postoperative composite of cardiovascular morbidity endpoints.

Background: Anemia is a frequent complication after cardiac surgery especially following reoperation due to previous prosthetic valve failure or multiple valve surgery (including combined coronary artery bypass grafting). This trial explores whether intravenously administered iron isomaltoside 1000 (Monofer®) results in better clinical outcomes in patients undergoing complex heart valve surgery who are expected to receive transfusion., Methods/design: In this prospective, single-center, double-blinded, randomized controlled trial, 214 patients undergoing reoperation or multiple valve surgery are randomly allocated to either the iron isomaltoside 1000 (IVFe) or the control group from August 2016 to August 2018. The IVFe group receives iron isomaltoside 1000 mg (maximum dose 20 mg/kg) intravenously 3 days before and after the surgery. The control group receives an equivalent volume of normal saline. The primary endpoint is transfusion requirement (more than 1 unit of packed erythrocytes) for postoperative care until discharge and secondary endpoint are major complications, such as delayed ventilator therapy, acute kidney injury, and mortality. Reticulocyte count, plasma hepcidin, iron profiles (serum iron, serum ferritin, total iron-binding capacity, transferrin, transferrin saturation), coagulation profiles, urinary analysis, and chemical profiles are measured for three preoperative baseline-data days and just before surgery, except for hepcidin. After surgery, daily routine basic laboratory tests are measured just before discharge and reticulocyte count, iron profiles, and hepcidin are repeatedly checked for three postoperative days., Discussions: From our study, we can clarify the following points: the first is the perioperative IVFe effect on the demand for transfusion, and clinical outcomes in reoperation or complex valve surgery and the second is the role of hepcidin in the effect of IVFe on the hemoglobin level increase., Trial Registration: ClinicalTrials.gov , Identifier: NCT02862665 . Registered on August 2016.

Even after recovery from acute kidney injury, glomeruli remain vulnerable to further injury by way of interstitial fibrosis. This study is aimed at elucidating the effects of post ischemia-reperfusion (I/R) treatment with trimetazidine on the progression to renal fibrosis as well as short- and intermediate-term aspects. Trimetazidine 3 mg/kg or 0.9% saline was given intraperitoneally once upon reperfusion or daily thereafter for 5 d or 8 w. Renal histologic changes and related signaling proteins were assessed. After 24 h, post I/R treatment with trimetazidine significantly reduced serum blood urea nitrogen and creatinine levels and tubular injury accompanied with upregulation of hypoxia-inducible factor- (HIF-) 1 α , vascular endothelial growth factor (VEGF), and Bcl-2 expression. After 5 d, post I/R treatment with trimetazidine reduced renal tubular cell necrosis and apoptosis with upregulation of HIF-1 α -VEGF and tissue inhibitors of metalloproteinase activities, attenuation of matrix metalloproteinase activities, and alteration of the ratio of Bax to Bcl-2 levels. After 8 w, however, post I/R treatment with trimetazidine did not modify the progression of renal fibrosis. In conclusion, post I/R treatment with trimetazidine allows ischemic kidneys to regain renal function and structure more rapidly compared to nontreated kidneys, but not enough to resolute renal fibrosis in long-term aspect.

Background: Spinal surgery in the prone position is accompanied by increased intrathoracic pressure and decreased respiratory compliance. This study investigated whether intraoperative lung protective mechanical ventilation improved lung function evaluated with pulmonary function tests in patients at risk of postoperative pulmonary complications (PPCs) after major spinal surgery in the prone position., Methods: Seventy-eight patients at potential risk of PPCs were randomly assigned to the protective group (tidal volume; 6 mL/kg predicted body weight, 6 cm H2O positive end-expiratory pressure with recruitment maneuvers) or the conventional group (10 mL/kg predicted body weight, no positive end-expiratory pressure). The primary efficacy variables were assessed by pulmonary function tests, performed before surgery, and 3 and 5 days afterward., Results: Postoperative forced vital capacity (2.17±0.1 L vs. 1.91±0.1 L, P=0.213) and forced expiratory volume in 1 second (1.73±0.08 L vs. 1.59±0.08 L, P=0.603) at postoperative day (POD) 3 in the protective and conventional groups, respectively, were similar. Trends of a postoperative decrease in forced vital capacity (P=0.586) and forced expiratory volume in 1 second (P=0.855) were similar between the groups. Perioperative blood-gas analysis variables were comparable between the groups. Patients in the protective and conventional groups showed similar rates of clinically significant PPCs (8% vs. 10%, P>0.999)., Conclusions: In patients at potential risk of developing PPCs undergoing major spinal surgery, we did not find evidence indicating any difference between the lung protective and conventional ventilation in postoperative pulmonary function and oxygenation.

Background: Anesthetic care for termination of atrial fibrillation with catheter ablation poses significant challenges due to significant pain and lengthy procedure. A delicate polypharmacy combining anesthetic agents to minimize respiratory depression and hemodynamic changes and to provide satisfactory sedation and analgesia is needed., Methods: Ninety-eight patients were randomized into two groups receiving either two grams of propacetamol or normal saline intravenously for 20 minutes before anesthesia. Monitored anesthesia care was provided with midazolam and remifentanil., Results: Total amounts of remifentanil infused were similar between the groups (626±251 vs. 597±315 μg, P=0.606). Accounting for the mean duration of the procedure and the elimination half-life of propacetamol, remifentanil requirements were significantly less among patients whose procedure ended within 180 minutes (N.=56) in the propacetamol group than those in the control group (540±194 vs. 421±164 μg, P=0.017). In the control group, the incidence of analgesics usage 24 hours after the procedure was significantly greater (43% vs. 23%, P=0.038), and patients exhibited a higher pain score (3.1±2.1 vs. 1.9±2.1, P=0.007), compared to the propacetamol group., Conclusions: The addition of a single dose of pre-emptive propacetamol showed promising results in terms of opioid consumption in patients whose procedure ended within 180 minutes. It provided better post-procedural pain control, compared with midazolam plus remifentanil alone.

Background: Hyperglycemia (HG) is common in cardiovascular surgeries due to diabetes, inflammation, and the neuroendocrine stress response. HG aggravates renal ischemia-reperfusion (I/R) injury through an increased inflammatory response, and blunts the protective effect of various measures. Ethyl pyruvate (EP) provides anti-inflammatory effects against I/R injury via inhibition of high-mobility group box 1 protein (HMGB1) release. This study aimed to determine the renoprotective effect of EP against I/R injury under HG., Methods: Sprague-Dawley rats were randomly assigned at random to 8 groups: normoglycemia (NG)-sham, NG-I/R-control, NG-EP-I/R (pretreatment), NG-I/R-EP (posttreatment), HG-sham, HG-I/R-control, HG-EP-I/R, and HG-I/R-EP. Renal I/R was induced by 45 minutes of ischemia (clamping of renal arteries), followed by 24 hours of reperfusion. EP (50 mg/kg) was administered intraperitoneally at 1 h before ischemia (pretreatment) or on reperfusion (posttreatment)., Results: I/R injury under HG significantly aggravated the degree of renal tubular apoptosis and damage compared with the NG groups, which could be attenuated by both pretreatment and posttreatment of EP. I/R-induced increases in HMGB1 and Toll-like receptors (TLRs), activation of NF-kB, and resultant alterations in interleukin-1β, tumor necrosis factor-α, proapoptotic Bax, and antiapoptotic Bcl-2 were all favorably modulated by EP treatment in both the NG and HG groups compared with their corresponding control groups., Conclusions: Despite aggravation of renal I/R injury by HG through amplified inflammation, EP administration showed similar suppression of the HMGB1-TLR-NF-kB pathway in the HG and NG groups. EP retained anti-inflammatory, antiapoptotic, and renoprotective effects in the HG groups, whether administered before ischemia or on reperfusion., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Hyperglycemia (HG) exacerbates myocardial ischemia/reperfusion (I/R) injury and renders protective strategies ineffective by amplified inflammatory response via enhanced high-mobility group box-1 (HMGB1) release. This study investigated the role of ethyl pyruvate (EP) against myocardial I/R injury under a clinically relevant HG condition., Methods: Sprague-Dawley rats (n=76) were randomly assigned to 6 groups: normoglycemia (NG)-Sham, NG-I/R-control (C, saline), NG-I/R-EP treatment (50mg/kg) upon reperfusion, HG-Sham, HG-I/R-C, and HG-I/R-EP treatment upon reperfusion. HG was induced by 1.2g/kg dextrose. I/R was induced by ligation of the left anterior descending artery for 30min followed by 4h of reperfusion., Results: HG resulted in exacerbation of myocardial infarct size by 19% with amplified activation of HMGB1-receptors of advanced glycation end products/toll like receptors-NF-κB pathway compared to NG following I/R, which all could be attenuated by EP. EP treatment was associated with diminished tumor necrosis factor-α, interleukin-1β, and interleukin-6 expressions. It also served to normalize the increase in pro-apoptotic Bax and the decrease in anti-apoptotic Bcl-2 protein levels. These effects were associated with decreased myocardial apoptosis and infarct size (by 30% and 36% in the NG and HG groups, respectively) regardless of the glycemic condition., Conclusion: HG exacerbated myocardial I/R injury through amplified inflammatory response via increased HMGB1 level. EP treatment upon reperfusion conveyed significant myocardial protection against the I/R injury under both NG and HG conditions. Common to both glycemic conditions, associated mechanisms involved attenuated increase in HMGB1 level and suppression of its down-stream pathways., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Efficacy of remote ischemic preconditioning (RIPC) for cardioprotection in cardiac surgery is controversial. We aimed to evaluate the clinical and molecular effects of RIPC on the concentrically hypertrophied myocardium., Methods: Seventy-two aortic stenosis patients receiving aortic valve replacement (AVR) under sevoflurane anesthesia were randomly allocated to RIPC (3cycles of 5-min inflation [300mmHg] and deflation on the left arm) or control (deflated cuff placement) group. The primary endpoints were 24-h area under the curve (AUC) for serum creatine kinase (CK)-MB and troponin (Tn)-T levels. The secondary endpoints were myocardial activation of cell signaling pathways, including reperfusion injury salvage kinases (RISK), signal transducer and activator of transcription (STAT), nitric oxide synthase (NOS), and apoptosis related molecules, obtained from right atrial tissue before and after cardiopulmonary bypass (CPB)., Results: There were no intergroup differences in 24-h AUCs of CK-MB and Tn-T. Phosphorylations of RISK pathway molecules were not enhanced by RIPC before and after CPB. Phosphorylation of STAT5 was significantly lower in the RIPC group before and after CPB. Phosphorylations of STAT3 and endothelial NOS were not enhanced by RIPC before and after CPB. Expression level of cleaved caspases-3/caspase-3 was significantly higher in the RIPC group before CPB., Conclusions: RIPC did not provide clinical benefits or activate protective signaling in patients with concentric left ventricular hypertrophy undergoing AVR., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: In fasting cardiac surgery patients, preoperative carbohydrate (CHO) drink intake attenuated insulin resistance and improved cardiac metabolism, although its beneficial effects were not evident after cardiac surgery possibly due to cardiopulmonary bypass-related extreme systemic inflammation., Objective: We aimed to evaluate whether preoperative CHO intake affected insulin resistance and free-fatty acid (FFA) concentrations in off-pump coronary revascularisation., Design: A randomised controlled trial., Setting: Primary care in a university hospital in Korea from January 2015 to July 2016., Patients: Sixty patients who underwent elective multi-vessel off-pump coronary revascularisation were randomised into two groups. Three patients were excluded from analysis and 57 patients completed study., Intervention: The CHO group received oral CHO (400 ml) the prior evening and 2 to 3 h before surgery, and the control group was fasted from food and water according to standard protocol., Main Outcome Measures: Insulin resistance was assessed twice, after anaesthetic induction and after surgery via short insulin tolerance test. FFA, C-reactive protein and creatine kinase-myocardial band concentrations were determined serially for 48 h after surgery., Results: Insulin sensitivity was greater (P = 0.002) and plasma FFA concentrations were lower (P = 0.001) after anaesthetic induction in the CHO group compared with the Control group, although there were no intergroup differences after surgery. The postoperative peak creatine kinase-myocardial band concentration was significantly lower in the CHO group compared with the Control group [8.8 (5.4 to 18.2) vs. 6.4 (3.5 to 9.7) ng ml, P = 0.031]., Conclusion: A preoperative CHO supplement significantly reduced insulin resistance and FFA concentrations compared with fasting at the beginning of the surgery, but these benefits were lost after off-pump coronary revascularisation. Despite their transient nature, these beneficial effects resulted in less myocardial injury, mandating further studies focused on the impact of preoperative CHO on myocardial ischaemia and cardiac function after coronary revascularisation., Trial Registration: Clinicaltrials.gov identifier: NCT 02330263.

Background: We aimed to investigate the ability of rotational thromboelastometry (ROTEM) thresholds for coagulopathy to predict increased perioperative blood loss in off-pump coronary artery bypass graft surgery (OPCABG) and its association with transfusion requirement., Methods: The data of 303 patients undergoing OPCABG were retrospectively analyzed. Perioperative blood loss and transfusion requirement were compared according to the presence of abnormal ROTEM thresholds, which were tested after anesthesia induction and heparin reversal. Logistic regression analyses were performed to predict significant perioperative blood loss (more than 20% of estimated blood volume)., Results: After graft completion, 92 patients (30%) exhibited abnormal ROTEM thresholds and showed significantly higher perioperative blood loss (median 840 mL [interquartile range: 646 to 1,102 mL] versus median 690 [interquartile range: 530 to 850 mL], p < 0.001) and greater transfusion requirement (both in the number of patients receiving transfusion and the median number of transfused units) of packed erythrocytes and fresh frozen plasma than patients exhibiting no ROTEM thresholds. After multivariate analysis of preoperative anemia, postoperative international normalized ratio greater than 1.3, and ROTEM thresholds, only ROTEM threshold (odds ratio 3.45, 95% confidence interval: 2.00 to 5.97, p < 0.001) remained an independent predictor of significant perioperative blood loss, which occurred in 79 patients (26%)., Conclusions: Abnormal ROTEM thresholds after heparin reversal were found to be associated with significant perioperative bleeding and transfusion requirement in OPCABG. Rotational thromboelastometry may allow timely hemostatic interventions to reduce blood loss and transfusion in OPCABG., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) polymorphisms may influence 5-hydroxytryptamine receptor antagonist efficacy by altering their efflux transportation. We evaluated the influence of ABCB1 polymorphisms on the efficacy of ramosetron compared with palonosetron in managing postoperative nausea and vomiting (PONV) in patients who received intravenous patient-controlled analgesia after spinal surgery., Methods: Patients were randomly allocated to receive 2 boluses (20 min before the end of surgery and 24 h after surgery) of either ramosetron 0.3 mg (n=150) or palonosetron 0.075 mg (n=146). The incidence and severity of PONV, fentanyl consumption, and pain intensity were serially assessed for postoperative 48 hours. ABCB1 3435C>T and 2677G>T/A polymorphisms were assessed., Results: The incidences of nausea were similar between the 2 groups in patients with the 3435TT (50% vs. 56%, ramosetron and palonosetron group, respectively, P>0.999) or 2677TT (50% vs. 56%, ramosetron and palonosetron group, respectively, P>0.999). Mild PONV were more frequent in the ramosetron group than in the palonosetron group among patients with 3435TT (91% vs. 33%, P=0.034) and 2677TT (92% vs. 20%, P=0.002) genotypes. The intensity of nausea experienced by ramosetron-group TT genotype patients (1 [1 to 2], 3435TT; 1 [1 to 2.5], 2677TT) was lower than that experienced by ramosetron-group non-TT genotype patients (3 [1 to 6], 3435 non-TT, P=0.030; 3 [1 to 6], 2677 non-TT, P=0.038) and palonosetron-group TT genotype patients (6 [2 to 7], 3435TT, P=0.010; 6 [4 to 7], 2677TT, P=0.002)., Conclusions: Compared with palonosetron, ramosetron may be superior for reducing PONV severity, especially in patients with ABCB1 3435TT or 2677TT genotype.

Background: Perioperative cerebral hypoperfusion/ischemia is a major inciting factor of postoperative delirium, which is coupled with adverse outcome in elderly patients. Cerebral oximetry enables noninvasive assessment of the regional cerebral oxygen saturation (rSO2). This study aimed to investigate whether perioperative rSO2 variations were linked to delirium in elderly patients after spinal surgery., Materials and Methods: Postoperative delirium was assessed for 48 hours postsurgery in 109 patients aged over 60 years without a prior history of cerebrovascular or psychiatric diseases by the Confusion Assessment Method for the intensive care unit and the intensive care delirium screening checklist. The rSO2 values immediately before and throughout surgery were acquired. The preoperative cognitive functions, patient characteristics, and perioperative data were recorded., Results: During the 48-h postoperative period, 9 patients (8%) exhibited delirium. The patients with delirium showed similar perioperative rSO2 values as those without, in terms of the median lowest rSO2 values (55% vs. 56%; P=0.876) and incidence (22%, both) and duration of decline of rSO2<80% of the baseline values. The serially assessed hemodynamic variables, hematocrit levels, and blood gas analysis variables were also similar between the groups, except for the number of hypotensive events per patient, which was higher in the patients with delirium than in those without (4, interquartile range [IQR] 3 to 6 vs. 2, IQR: 1to 3; P=0.014)., Conclusions: The degree and duration of decrease of the perioperative rSO2 measurements were not associated with delirium in elderly patients after spinal surgery.

Hemodynamic management aims to provide adequate tissue perfusion, which is often altered during cardiac surgery with cardiopulmonary bypass (CPB). We evaluated whether skin perfusion pressure (SPP) can be used for monitoring of adequacy of tissue perfusion in patients undergoing valvular heart surgery. Seventy-two patients undergoing valve replacement were enrolled. SPP and serum lactate level were assessed after anaesthesia induction (baseline), during CPB, after CPB-off, end of surgery, arrival at intensive care unit, and postoperative 6 h. Lactate was further measured until postoperative 48 h. Association of SPP with lactate and 30-day morbidity comprising myocardial infarction, acute kidney injury, stroke, prolonged intubation, sternal infection, reoperation, and mortality was assessed. Among the lactate levels, postoperative 6 h peak value was most closely linked to composite of 30-day morbidity. The SPP value during CPB and its % change from the baseline value were significantly associated with the postoperative 6 h peak lactate (r = -0.26, P = 0.030 and r = 0.47, P = 0.001, respectively). Optimal cut-off of % decrease in SPP during CPB from baseline value for the postoperative 6 h hyperlactatemia was 48% (area under curve, 0.808; 95% confidence interval (CI), 0.652-0.963; P = 0.001). Decrease in SPP >48% during CPB from baseline value was associated with a 12.8-fold increased risk of composite endpoint of 30-day morbidity (95% CI, 1.48-111.42; P = 0.021) on multivariate logistic regression. Large decrease in SPP during CPB predicts postoperative 6 h hyperlactatemia and 30-day morbidity, which implicates a promising role of SPP monitoring in the achievement of optimal perfusion during CPB.

Hyperglycemia, which reduces the efficacy of treatments and worsens clinical outcomes, is common in stroke. Ability of pregabalin to reduce neuroexcitotoxicity may provide protection against stroke, even under hyperglycemia. We investigated its protective effect against hyperglycemic stroke and its possible molecular mechanisms. Male Wistar rats administered dextrose to cause hyperglycemia, underwent middle cerebral artery occlusion for 1 h and subsequent reperfusion. Rats were treated with an intraperitoneal injection of 30 mg/kg pregabalin or an equal amount of normal saline at the onset of reperfusion (n = 16 per group). At 24 h after reperfusion, neurological deficit, infarct volume, and apoptotic cell count were assessed. Western blot analysis was performed to determine protein expression of high-mobility group box 1 (HMGB1), toll-like receptor-4 (TLR-4), phosphorylated nuclear factor-kappa B (p-NF-κB), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), phosphorylated inducible and endothelial nitric oxide synthase (p-iNOS, p-eNOS), Bcl-2, Bax, Cytochrome C, and caspase-3 in the brain. Pregabalin-treated rats showed significantly improved neurological function (31% decrease in score), reduced infarct size (by 33%), fewer apoptotic cells (by 63%), and lower expression levels of HMGB1, TLR4, p-NF-κB, IL-1β, and TNF- α, compared with control rats. Decreased p-iNOS and increased p-eNOS expressions were also observed. Expression of Bax, Cytochrome C, and cleaved caspase-3/caspase3 was significantly downregulated, while Bcl-2 expression was increased by pregabalin treatment. Pregabalin administration upon reperfusion decreased neuronal death and improved neurological function in hyperglycemic stroke rats. Cogent mechanisms would include attenuation of HMGB1/TLR-4-mediated inflammation and favorable modulation of the NOS., Competing Interests: Pfizer Inc. (New York, NY, USA) have provided pregabalin via their compound transfer program. This does not alter adherence to PLOS ONE policies on sharing data and materials.

Background: Patients with infective endocarditis (IE) have an elevated risk of renal dysfunction because of extensive systemic inflammation and use of nephrotoxic antibiotics. In this randomized, placebo-controlled trial, we investigated whether perioperative sodium bicarbonate administration could attenuate postoperative renal dysfunction in patients with IE undergoing cardiac surgery., Methods: Seventy patients randomly received sodium chloride (n = 35) or sodium bicarbonate (n = 35). Sodium bicarbonate was administered as a 0.5 mmol/kg loading dose for 1 h commencing with anesthetic induction, followed by a 0.15 mmol/kg/h infusion for 23 h. The primary outcome was peak serum creatinine (SCr) level during the first 48 h postoperatively. The incidence of acute kidney injury, SCr level, estimated glomerular filtration rate, and major morbidity endpoints were assessed postoperatively., Results: The peak SCr during the first 48 h postoperatively (bicarbonate vs., Control: 1.01 (0.74, 1.37) mg/dl vs. 0.88 (0.76, 1.27) mg/dl, P = 0.474) and the incidence of acute kidney injury (bicarbonate vs., Control: 29% vs. 23%, P = 0.584) were similar in both groups. The postoperative increase in SCr above baseline was greater in the bicarbonate group than in the control group on postoperative day 2 (0.21 (0.07, 0.33) mg/dl vs. 0.06 (0.00, 0.23) mg/dl, P = 0.028) and postoperative day 5 (0.23 (0.08, 0.36) mg/dl vs. 0.06 (0.00, 0.23) mg/dl, P = 0.017)., Conclusions: Perioperative sodium bicarbonate administration had no favorable impact on postoperative renal function and outcomes in patients with IE undergoing cardiac surgery. Instead, it was associated with possibly harmful renal effects, illustrated by a greater increase in SCr postoperatively, compared to control., Trial Registration: ClinicalTrials.gov, NCT01920126 . Registered on 31 July 2013.

Background: This randomized trial evaluated the effect of intravenous patient-controlled analgesia (IV-PCA) based on fentanyl mixed with either propacetamol or an equivalent volume of normal saline on postoperative nausea and vomiting (PONV) in highly susceptible patients undergoing spinal surgery., Materials and Methods: One hundred eight nonsmoking female patients were randomly and evenly allocated to receive IV-PCA with either propacetamol (4 g) or normal saline mixed to fentanyl (20 μg/kg). Primary study outcome was PONV incidence at 24 hours postsurgery. Secondary outcomes were nausea severity, pain intensity (100-mm visual analog scale), use of rescue antiemetics and analgesics, patient satisfaction, and adverse events at 6, 12, and 24 hours postsurgery., Results: Postsurgery, the propacetamol versus normal saline group had lower PONV incidence at 24 hours (41% vs. 66%, P=0.011); pain intensity at rest and rescue analgesic requirements at 6 to 12 hours (30±15 vs. 41±19, P=0.008; and 25% vs. 49%, P=0.036, respectively) and at 12 to 24 hours (25±15 vs. 35±17, P=0.008; and 19% vs. 42%, P=0.044, respectively); and higher patient satisfaction score (6.4±1.4 vs. 5.7±1.8, P=0.028)., Conclusions: In patients undergoing spinal surgery and at risk of developing PONV, continuous IV-PCA based on propacetamol mixed to fentanyl, relative to fentanyl alone, effectively reduced the incidence of PONV, pain intensity at rest, and additional use of rescue analgesics with higher patient satisfaction.

Background: Acute kidney injury (AKI) is a common morbidity after off-pump coronary revascularization. We investigated whether perioperative administration of sodium bicarbonate, which might reduce renal injury by alleviating oxidative stress in renal tubules, prevents postoperative AKI in off-pump coronary revascularization patients having renal risk factors., Methods: Patients (n=162) having at least one of the following AKI risk factors were enrolled: (i) age >70 yr; (ii) diabetes mellitus; (iii) chronic renal disease; (iv) congestive heart failure or left ventricular ejection fraction <35%; and (v) reoperation or emergency. Patients were evenly randomized to receive either sodium bicarbonate (0.5 mmol kg -1 for 1 h upon induction of anaesthesia followed by 0.15 mmol kg -1 h -1 for 23 h) or 0.9% saline. Acute kidney injury within 48 h after surgery was assessed using the Acute Kidney Injury Network criteria., Results: The incidences of AKI were 21 and 26% in the bicarbonate and control groups, respectively (P=0.458). Serially measured serum creatinine concentrations and perioperative fluid balance were also comparable between the groups. The length of postoperative hospitalization and incidence of morbidity end points were similar between the groups, whereas significantly more patients in the bicarbonate group required prolonged mechanical ventilation (>24 h) relative to the control group (20 vs 6, P=0.003)., Conclusions: Perioperative sodium bicarbonate administration did not decrease the incidence of AKI after off-pump coronary revascularization in high-risk patients and might even be associated with a need for prolonged ventilatory care., Clinical Trial Registration: NCT01840241., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have the potential to reduce acute kidney injury (AKI) after cardiac surgery through their pleiotropic properties. Here we studied the preventive effect of atorvastatin on AKI after valvular heart surgery., Methods: Two-hundred statin-naïve patients were randomly allocated to receive either statin or placebo. Atorvastatin was administered orally to the statin group according to a dosage schedule (80 mg single dose on the evening prior to surgery; 40 mg on the morning of surgery; three further doses of 40 mg on the evenings of postoperative days 0, 1, and 2). AKI incidence was assessed during the first 48 postoperative hours on the basis of Acute Kidney Injury Network criteria., Results: The incidence of AKI was similar in the statin and control groups (21 vs. 26 %, respectively, p = 0.404). Biomarkers of renal injury including plasma neutrophil gelatinase-associated lipocalin and interleukin-18 were also similar between the groups. The statin group required significantly less norepinephrine and vasopressin during surgery, and fewer patients in the statin group required vasopressin. There were no significant differences in postoperative outcomes., Conclusions: Acute perioperative statin treatment was not associated with a lower incidence of AKI or improved clinical outcome in patients undergoing valvular heart surgery. (ClinicalTrials.gov NCT01909739).

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.

Urine output is closely associated with renal function and has been used as a diagnostic criterion for acute kidney injury (AKI). However, urine output during cardiopulmonary bypass (CPB) has never been identified as a predictor of postoperative AKI. Considering altered renal homeostasis during CPB, we made a comprehensible approach to CPB urine output and evaluated its predictability for AKI.Patients undergoing cardiovascular surgery with the use of CPB, between January 2009 and December 2011, were retrospectively reviewed. AKI was defined as an increase in serum creatinine ≥0.3 mg/dL in the first postoperative 48 hours. We extrapolated a possible optimal amount of urine output from the plot of probability of AKI development according to CPB urine output. After separating patients by the predicted optimal value, we performed stepwise logistic regression analyses to find potential predictors of AKI in both subgroups.A total of 696 patients were analyzed. The amount of CPB urine output had a biphasic association with the incidence of AKI using 4 mL/kg/h as a boundary value. In a multivariate logistic regression to find predictors for AKI in entire patients, CPB urine output did not show statistical significance. After separating patients into subgroups with CPB urine output below and over 4 mL/kg/h, it was identified as an independent predictor for AKI with the odds ratio of 0.43 (confidence interval 0.30-0.61) and 1.11 (confidence interval 1.02-1.20), respectively.The amount of urine output during CPB with careful analysis may serve as a simple and feasible method to predict the development of AKI after cardiac surgery at an early time point.

Acute kidney injury (AKI) following cardiac surgery is closely interrelated with hemodynamic instability and sympathetic activity, and adversely influences prognosis. Here, we investigated in a randomized placebo-controlled trial whether dexmedetomidine, an α2 adrenoreceptor agonist, could prevent AKI after valvular heart surgery. Two hundred patients undergoing valvular heart surgery were randomly assigned to equal placebo or treatment groups. Dexmedetomidine was infused at a rate of 0.4 μg/kg/h starting immediately after anesthetic induction and continuing for 24 h after surgery. We then assessed the incidence of AKI during the first 48 postoperative hours, hemodynamic variables, and a composite of major morbidity end points. The incidence of AKI, based on Acute Kidney Injury Network criteria, was significantly lower in the treatment group compared with the control group (14 vs. 33%). The dexmedetomidine group exhibited a significantly lower incidence of a composite of major morbidity end points (21 vs. 38%) and a significantly shorter length of intensive care unit stay (3 [2, 3] days vs. 3 [2, 4] days) compared with the control group. Thus, perioperative infusion of dexmedetomidine effectively reduced both the incidence and severity of AKI, and improved outcome in patients undergoing valvular heart surgery without untoward hemodynamic side effects.

Background: Positive end-expiratory pressure (PEEP)-induced increase in central venous pressure (CVP) has been suggested to be a robust indicator of fluid responsiveness, with heart rhythm having minimal influence. We compared the ability of PEEP-induced changes in CVP with passive leg raising (PLR)-induced changes in stroke volume index (SVI) in patients with atrial fibrillation after valvular heart surgery., Methods: In 43 patients with atrial fibrillation after cardiac surgery, PEEP was increased from 0 to 10 cm H2O for 5 min and changes in CVP were assessed. After returning the PEEP to 0 cm H2O, PLR was performed for 5 min and changes in SVI were recorded. Finally, 300 ml of colloid was infused and haemodynamic variables were assessed 5 min after completion of a fluid challenge. Fluid responsiveness was defined as an increase in SVI ≥10% measured by a pulmonary artery catheter., Results: Fifteen (35%) patients were fluid responders. There was no correlation between PEEP-induced increases in CVP and changes in SVI after a fluid challenge (β coefficient -0.052, P=0.740), whereas changes in SVI during PLR showed a significant correlation (β coefficient 0.713, P<0.001). The area under the receiver operating characteristic curve of the PEEP-induced increase in CVP and changes in SVI during PLR for fluid responsiveness was 0.556 [95% confidence interval (CI) 0.358-0.753, P=0.549) and 0.771 (95% CI 0.619-0.924, P=0.004), respectively., Conclusions: A PEEP-induced increase in CVP did not predict fluid responsiveness in patients with atrial fibrillation after cardiac surgery, but increases in SVI during PLR seem to be a valid predictor of fluid responsiveness in this subset of patients., (© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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.

Activation of peroxisome proliferator-activated receptor α (PPARα) confers cardioprotection, while its mechanism remains elusive. We investigated the protective effect of PPARα activation against cardiac ischemia-reperfusion injury in terms of the expression of uncoupling protein (UCP). Myocardial infarct size and UCP expression were measured in rats treated with WY-14643 20 mg/kg, a PPARα ligand, or vehicle. WY-14643 increased UCP3 expression in vivo. Myocardial infarct size was decreased in the WY-14643 group (76 ± 8% versus 42 ± 12%, P<0.05). During reperfusion, the incidence of arrhythmia was higher in the control group compared with the WY-14643 group (9/10 versus 3/10, P<0.05). H9c2 cells were incubated for 24 h with WY-14643 or vehicle. WY-14643 increased UCP3 expression in H9c2 cells. WY-14643 decreased hypoxia-stimulated ROS production. Cells treated with WY-14643 were more resistant to hypoxia-reoxygenation than the untreated cells. Knocking-down UCP3 by siRNA prevented WY-14643 from attenuating the production of ROS. UCP3 siRNA abolished the effect of WY-14643 on cell viability against hypoxia-reoxygenation. In summary, administration of PPARα agonist WY-14643 mitigated the extent of myocardial infarction and incidence of reperfusion-induced arrhythmia. PPARα activation conferred cytoprotective effect against hypoxia-reoxygenation. Associated mechanisms involved increased UCP3 expression and resultant attenuation of ROS production.

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.

Introduction: In multi-level lumbar spinal fusion surgery yielding a large amount of blood loss, choice of fluid for volume resuscitation is an important issue since it can influence acid-base status, coagulation, and patients' outcome. This study compared the effect of plasmalyte to 0.9% saline on coagulation assessed by rotation thromboelastometry (ROTEM) and acid-base balance in the aforementioned patients., Methods: Fifty patients were randomly allocated to receive either 0.9% saline or plasmalyte during operation and until postoperative 12 h. ROTEM was performed at 10 min after anesthetic induction and end of surgery. Arterial blood gas analyses were serially performed from 10 min after anesthetic induction until postoperative 12 h. Fluid balance, blood loss, and transfusion requirement were assessed., Results: ROTEM variables showed sporadic deterioration in both groups after surgery without intergroup differences. Intraoperatively, arterial pH, base excess, and bicarbonate concentrations were lower and serum chloride concentrations were higher in the 0.9% saline group compared with the plasmalyte group. The differences in base excess and bicarbonate concentrations persisted until postoperative 12 h. Fluid balance, blood loss, and transfusion requirement were similar between the groups while urine output was greater in the plasmalyte group compared with the 0.9% saline group (3.2 ± 1.6 ml/kg/h vs. 1.8 ± 1.1 ml/kg/h, p = 0.001)., Conclusion: In contrast to plasmalyte, fluid therapy with 0.9% saline resulted in transient hyperchloremic acidosis in patients undergoing multi-level lumbar spinal fusion, while coagulation assessed by ROTEM analysis and the amount of blood loss were similar between the groups., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

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.

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., (© 2014 Asian Pacific Society of Nephrology.)

Erythropoietin (EPO), an essential hormone for erythropoiesis, provides protection against myocardial ischemia/reperfusion (I/R) injury. Hyperglycemia during acute myocardial infarction aggravates organ damage and attenuates the efficacies of various protective measures. This study aimed to investigate the protective role of EPO against myocardial I/R injury under a clinically relevant moderate hyperglycemic condition and its associated mechanisms. Eighty-two Sprague-Dawley rats were randomly assigned to six groups: normoglycemia-Sham, normoglycemia-I/R-control-saline (IRC), normoglycemia-I/R-EPO (IRE), hyperglycemia-Sham, hyperglycemia-IRC, and hyperglycemia-IRE. The rats received 1.2 g/kg dextrose or same volume of normal saline depending on the group. I/R was induced by a 30 min period of ischemia followed by reperfusion for 4 h. For 1 h before I/R injury, intravenous 4000 IU/kg of EPO was administered. EPO pretreatment significantly reduced the number of apoptotic cells and the infarct size compared with those of the control groups. EPO increased GATA-4 phosphorylation and acetylation against I/R in hyperglycemic myocardium. It also enhanced ERK induced GATA-4 post-translational modifications such as increased GATA-4 phosphorylation and acetylation, and decreased GATA-4 ubiquitination following hypoxia-reoxygenation in H9c2 cells in hyperglycemic medium. Increased GATA-4 stability by EPO diminished I/R-related down-regulation of Bcl-2 and reduction of caspase-3 activities in hyperglycemic myocardium. In conclusion, EPO pretreatment before I/R injury conveyed significant myocardial protection under moderate hyperglycemic condition through mechanisms involved in reduction of caspase-3 activity and up-regulation of Bcl-2 in association with enhanced ERK-induced GATA-4 stability., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to test the hypothesis that the predictive ability of pulse pressure variation (PPV) for fluid responsiveness would be altered in patients with elevated left ventricular (LV) filling pressure., Materials and Methods: According to the preoperative echocardiographic assessment of the ratio of early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/E'), patients undergoing surgical coronary revascularization were classified into normal (n=34, E/E'<8) and high (n=34, E/E'>15) LV filling pressure group. After anesthetic induction, PPV and hemodynamic data were measured before and after 6 mL/kg of colloid administration. Fluid responsiveness was defined as 12% or more increase in stroke volume index assessed by pulmonary artery catheter and tested by the area under the receiver operating characteristic curve (AUROC)., Results: The AUROCs of PPV in the normal and high filling pressure group were 0.829 (95% confidence interval [CI], 0.661-0.963; P<.001) and 0.583 (95% CI, 0.402-0.749; P=.110), respectively. The AUROCs of cardiac filling pressures and right ventricular end-diastolic volume index did not show statistical significance in both groups., Conclusions: None of the assessed preload indices including PPV were able to predict fluid responsiveness in patients with elevated LV filling pressure., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: We sought to evaluate the clinical usefulness of decision making by a multidisciplinary heart team for identifying potential candidates for transcatheter aortic valve implantation (TAVI) in patients with symptomatic severe aortic stenosis., Materials and Methods: The multidisciplinary team consisted of two interventional cardiologists, two cardiovascular surgeons, one cardiac imaging specialist, and two cardiac anesthesiologists., Results: Out of 60 patients who were screened as potential TAVI candidates, 31 patients were initially recommended as appropriate for TAVI, and 20 of these 31 eventually underwent TAVI. Twenty-two patients underwent surgical aortic valve replacement (AVR), and 17 patients received only medical treatment. Patients who underwent TAVI and medical therapy were older than those who underwent surgical AVR (p<0.001). The logistic Euroscore was significantly highest in the TAVI group and lowest in the surgical AVR group (p=0.012). Most patients in the TAVI group (90%) and the surgical AVR group (91%) had severe cardiac symptoms, but only 47% in the medical therapy group had severe symptoms. The cumulative percentages of survival without re-hospitalization or all-cause death at 6 months for the surgical AVR, TAVI, and medical therapy groups were 84%, 75%, and 28%, respectively (p=0.007, by log-rank)., Conclusion: TAVI was recommended in half of the potential candidates following a multidisciplinary team approach and was eventually performed in one-third of these patients. One-third of the patients who were initially considered potential candidates received surgical AVR with favorable clinical outcomes.

Propofol has been shown to provide protection against renal ischemia/reperfusion injury experimentally, but clinical evidence is lacking. Here we studied the effect of propofol anesthesia on the occurrence of acute kidney injury following heart surgery with cardiopulmonary bypass. One hundred and twelve patients who underwent valvular heart surgery were randomized to receive either propofol or sevoflurane anesthesia, both with sufentanil. Using Acute Kidney Injury Network criteria, significantly fewer patients developed acute kidney injury postoperatively in the propofol group compared with the sevoflurane group (6 compared with 21 patients). The incidence of severe renal dysfunction was significantly higher in the sevoflurane group compared with the propofol group (5 compared with none). The postoperative cystatin C was significantly lower in the propofol group at 24 and 48 h. Serum interleukin-6 at 6 h after aorta cross-clamp removal, C-reactive protein at postoperative day 1, and segmented neutrophil counts at postoperative day 3 were also significantly lower in the propofol group. Thus, propofol anesthesia significantly reduced the incidence and severity of acute kidney injury in patients undergoing valvular heart surgery with cardiopulmonary bypass compared with sevoflurane. This beneficial effect of propofol may be related to its ability to attenuate the perioperative increase in proinflammatory mediators.

Aims: Anaesthesia is required for catheter ablation of atrial fibrillation (A-fib) to achieve patient comfort and immobilization to avoid map shifts. This study compared the analgesic and sedative efficacies of dexmedetomidine-remifentanil with those of midazolam-remifentanil for catheter ablation of A-fib., Methods and Results: Ninety patients were randomized to receive either intermittent midazolam boluses (1-2 mg) with 3.6-7.2 µg/kg/h of remifentanil (MR group) or dexmedetomidine 0.2-0.7 µg/kg/h after a loading dose of 1 µg/kg with 1.2-2.4 µg/kg/h of remifentanil (DR group). The sedation level assessed by the Ramsay sedation and bispectral index scores, haemodynamic variables, pain score (10-point numerical scale), and satisfaction levels of the patients and cardiologists (5-point numerical scale) were recorded. The Ramsay sedation score was significantly higher, and the bispectral index score was lower in the DR group (P< 0.001) compared with the MR group starting 10 min after drug administration. The incidence of desaturation (SpO2 < 90%) was significantly greater in the MR group compared with the DR group (15 vs. 1, P < 0.001). The pain score was significantly lower (1.72 ± 1.65 vs. 0.95 ± 1.10, P = 0.021), and the satisfaction levels of interventionists were significantly higher (2.50 ± 0.71 vs. 3.00 ± 0.63, P = 0.001) in the DR group compared with the MR group., Conclusion: The combination of dexmedetomidine and remifentanil provided deeper sedation, less respiratory depression, better analgesia, and higher satisfaction for the interventionist during catheter ablation of A-fib compared with midazolam plus remifentanil, even at a lower dose of remifentanil., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com.)

Background: We studied respirophasic variation in carotid artery blood flow peak velocity (ΔVpeak-CA) measured by pulsed wave Doppler ultrasound as a predictor of fluid responsiveness in mechanically ventilated patients with coronary artery disease., Methods: Forty patients undergoing elective coronary artery bypass surgery were enrolled. Subjects were classified as responders if stroke volume index (SVI) increased ≥15% after volume expansion (6 ml kg(-1)). The ΔVpeak-CA was calculated as the difference between the maximum and minimum values of peak velocity over a single respiratory cycle, divided by the average. Central venous pressure, pulmonary artery occlusion pressure, pulse pressure variation (PPV), and ΔVpeak-CA were recorded before and after volume expansion., Results: PPV and ΔVpeak-CA correlated significantly with an increase in SVI after volume expansion. Area under the receiver-operator characteristic curve (AUROC) of PPV and ΔVpeak-CA were 0.75 [95% confidence interval (CI) 0.59-0.90] and 0.85 (95% CI 0.72-0.97). The optimal cut-off values for fluid responsiveness of PPV and ΔVpeak-CA were 13% (sensitivity and specificity of 0.74 and 0.71) and 11% (sensitivity and specificity of 0.85 and 0.82), respectively. In a subgroup analysis of 17 subjects having pulse pressure hypertension (≥ 60 mm Hg), PPV failed to predict fluid responsiveness (AUROC 0.70, P=0.163), whereas the predictability of ΔVpeak-CA remained unchanged (AUROC 0.90, P=0.006)., Conclusions: Doppler assessment of respirophasic ΔVpeak-CA seems to be a highly feasible and reliable method to predict fluid responsiveness in mechanically ventilated patients undergoing coronary revascularization., Clinical Trial Registration: NCT 01836081., (© The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)