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.

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

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

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.

Effects of intraoperative dexmedetomidine infusion on renal function in elective living donor kidney transplantation: a randomized controlled trial.

PURPOSE: Ischemia-reperfusion injury is inevitable during donor organ harvest and recipient allograft reperfusion in kidney transplantation, and affects graft outcomes. Dexmedetomidine, an α2-adrenoreceptor agonist, has renoprotective effects against ischemia-reperfusion injury. We investigated the effects of intraoperative dexmedetomidine infusion on renal function and the development of delayed graft function after elective living donor kidney transplantation in a randomized controlled trial. METHODS: A total of 104 patients were randomly assigned to receive either an intraoperative infusion of dexmedetomidine 0.4 µg·kg-1·hr-1 or 0.9% saline. The primary outcome was the serum creatinine level on postoperative day (POD) 7. Secondary outcomes were renal function and the degree of inflammation and included the following variables: serum creatinine level and estimated glomerular filtration rate up to six months; incidence of delayed graft function; and levels of serum cystatin C, plasma interleukin (IL)-1ß, and IL-18 during the perioperative period. RESULTS: The mean (standard deviation) serum creatinine level on POD 7 was comparable between the groups (dexmedetomidine vs control: 1.11 [0.87] mg·dL-1 vs 1.06 [0.73] mg·dL-1; mean difference, 0.05; 95% confidence interval, -0.27 to 0.36; P = 0.77). Delayed graft function occurred in one patient in each group (odds ratio, 1.020; P > 0.99). There were no significant differences in the secondary outcomes between the groups (all P > 0.05). CONCLUSIONS: Intraoperative dexmedetomidine infusion did not produce any beneficial effects on renal function or delayed graft function in patients undergoing elective living donor kidney transplantation. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT03327389); registered 31 October 2017.

RéSUMé: OBJECTIF: Les lésions d'ischémie-reperfusion sont inévitables lors du prélèvement d'organes du donneur et de la reperfusion de l'allogreffe chez le receveur pour une transplantation rénale, et affectent le devenir du greffon. La dexmédétomidine, un agoniste des adrénorécepteurs de type α2, a des effets néphroprotecteurs sur les lésions d'ischémie-reperfusion. Nous avons réalisé une étude randomisée contrôlée afin d'examiner les effets d'une perfusion peropératoire de dexmédétomidine sur la fonction rénale et l'apparition d'un retard de fonctionnement du greffon après une transplantation rénale élective issue de donneurs vivants. MéTHODE: Au total, 104 patients ont été aléatoirement répartis pour recevoir une perfusion peropératoire de 0,4 µg·kg-1·r-1 de dexmédétomidine ou une solution saline à 0,9 %. Le critère d'évaluation principal était la créatininémie au jour postopératoire (JPO) 7. Les critères d'évaluation secondaires étaient la fonction rénale et le degré d'inflammation et comprenaient les variables suivantes : créatininémie et infiltration glomérulaire estimée jusqu'à six mois; incidence de retard de fonctionnement du greffon; et taux sériques de cystatine C, d'interleukine plasmatique (IL)-1ß et d'IL-18 pendant la période périopératoire. RéSULTATS: Le taux moyen (écart type) de créatinine sérique au JPO 7 était comparable entre les groupes (dexmédétomidine vs témoin : 1,11 [0,87] mg·dL-1 vs 1,06 [0,73] mg·dL-1; différence moyenne, 0,05; intervalle de confiance à 95 %, -0,27 à 0,36; P = 0,77). Un patient de chaque groupe a subi un retard de fonctionnement du greffon (rapport de cotes, 1,020; P > 0.99). Aucune différence intergroupe significative n'a été observée en ce qui concerne les critères d'évaluation secondaires. CONCLUSION: La perfusion peropératoire de dexmédétomidine n'a produit aucun effet bénéfique sur la fonction rénale ou le retard de fonctionnement du greffon chez les patients bénéficiant d'une transplantation rénale élective issue de donneur vivant. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03327389); enregistrée le 31 octobre 2017.

The immunomodulatory effect of ketamine in colorectal cancer surgery: a randomized-controlled trial.

PURPOSE: Ketamine's inhibitory action on the N-methyl-D-aspartate receptor and anti-inflammatory effects may provide beneficial immunomodulation in cancer surgery. We investigated the effect of subanesthetic-dose ketamine as an adjunct to desflurane anesthesia on natural killer (NK) cell activity and inflammation in patients undergoing colorectal cancer surgery. METHODS: A total of 100 patients were randomly assigned to a control or ketamine group. The ketamine group received a bolus of 0.25 mg·kg-1 ketamine five minutes before the start of surgery, followed by an infusion 0.05 mg·kg-1·hr-1 until the end of surgery; the control group received a similar amount of normal saline. We measured NK cell activity and proinflammatory cytokines (interleukin-6 [IL-6] and tumour necrosis factor-α [TNF-α]) before surgery and one, 24, and 48 hr after surgery. C-reactive protein (CRP) was measured before surgery and one, three, and five days after surgery. Carcinoembryonic antigen and cancer recurrence/metastasis were assessed two years after surgery. RESULTS: The NK cell activity was significantly decreased after surgery in both groups, but the change was not different between groups in the linear mixed model analysis (P = 0.47). Changes in IL-6, TNF-α, CRP, and carcinoembryonic antigen levels were not different between groups (P = 0.27, 0.69, 0.99, and 0.97, respectively). Cancer recurrence within 2 years after surgery was similar between groups (10% vs 8%, P = 0.62). CONCLUSIONS: Intraoperative low-dose ketamine administration did not convey any favourable impacts on overall postoperative NK cell activity, inflammatory responses, and prognosis in colorectal cancer surgery patients. TRIAL REGISTRATION: www.clinicaltrial.gov (NCT03273231); registered 6 September 2017.

RéSUMé: OBJECTIF: L'action inhibitrice de la kétamine sur le récepteur du N-méthyle-D-aspartate et ses effets anti-inflammatoires pourraient procurer une immunomodulation bénéfique lors d'une chirurgie oncologique. Nous avons étudié l'effet de la kétamine en dose sous-anesthésique en complément à une anesthésie au desflurane sur l'activité des cellules tueuses naturelles (NK) et l'inflammation chez les patients subissant une chirurgie de cancer colorectal. MéTHODE: Au total, 100 patients ont été randomisés à un groupe témoin ou kétamine. Le groupe kétamine a reçu un bolus de 0,25 mg·kg−1 de kétamine cinq minutes avant le début de la chirurgie, suivi d'une perfusion de 0,05 mg·kg−1·h−1 jusqu'à la fin de la chirurgie; le groupe témoin a reçu une quantité similaire de solution physiologique salée. Nous avons mesuré l'activité des cellules NK et des cytokines pro-inflammatoires (interleukine-6 [IL-6] et facteur de nécrose tumorale α [TNF-α]) avant la chirurgie et une, 24 et 48 heures après la chirurgie. La protéine C réactive (CRP) a été mesurée avant la chirurgie puis un, trois et cinq jours après la chirurgie. L'antigène carcinoembryonnaire et la récurrence du cancer ou les métastases ont été évalués deux ans après la chirurgie. RéSULTATS: L'activité des cellules NK a été significativement réduite après la chirurgie dans les deux groupes, mais le changement ne différait pas entre les groupes dans l'analyse de modèle mixte linéaire (P = 0,47). Les changements dans les taux d'IL-6, de TNF-α, de CRP, et d'antigène carcinoembryonnaire n'étaient pas différents entre les groupes (P = 0,27, 0,69, 0,99 et 0,97, respectivement). La récidive du cancer au cours des deux années suivant la chirurgie était similaire entre les groupes (10 % vs 8 %, P = 0,62). CONCLUSION: L'administration peropératoire de kétamine de faible dose ne s'est pas traduite par un quelconque impact favorable sur l'activité postopératoire g des cellules NK, la réaction inflammatoire, et le pronostic chez les patients de chirurgie de cancer colorectal. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03273231); enregistrée le 6 septembre 2017.

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.

Effect of perioperative sodium bicarbonate administration on renal function following cardiac surgery for infective endocarditis: a randomized, placebo-controlled trial.

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.

Evaluation of preoperative oral carbohydrate administration on insulin resistance in off-pump coronary artery bypass patients: A randomised trial.

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.

Perioperative dexmedetomidine reduces the incidence and severity of acute kidney injury following valvular heart surgery.

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.

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.

Anesthetics influence the incidence of acute kidney injury following valvular heart surgery.

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.

Improved sedation with dexmedetomidine-remifentanil compared with midazolam-remifentanil during catheter ablation of atrial fibrillation: a randomized, controlled trial.

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.