Impact of intravenous exenatide infusion for perioperative blood glucose control on myocardial ischemia-reperfusion injuries after coronary artery bypass graft surgery: sub study of the phase II/III ExSTRESS randomized trial.

BACKGROUND: The aim of the study was to investigate whether intravenous (iv) infusion of exenatide, a synthetic GLP-1 receptor agonist, could provide a protective effect against myocardial ischemia-reperfusion injury after coronary artery bypass graft (CABG) surgery. METHODS: A sub study analysis of patients > 18 years admitted for elective CABG and included in the ExSTRESS trial was conducted. Patients were randomized to receive either iv exenatide (1-h bolus of 0.05 µg min-1 followed by a constant infusion of 0.025 µg min-1) (exenatide group) or iv insulin therapy (control group) for blood glucose control (target range 100-139 mg dl-1) during the first 48 h after surgical incision. All serum levels of troponin I measured during routine care in the Cardiac Surgery ICU were recorded. The primary outcome was the highest value of plasma concentration of troponin I measured between 12 and 24 h after ICU admission. The proportion of patients presenting an echocardiographic left ventricular ejection fraction (LVEF) > 50% at the follow-up consultation was compared between the two groups. RESULTS: Finally, 43 and 49 patients were analyzed in the control and exenatide groups, respectively {age: 69 [61-76] versus 71 [63-75] years; baseline LVEF < 50%: 6 (14%) versus 16 (32%) patients; on-pump surgery: 29 (67%) versus 33 (67%) patients}. The primary outcome did not significantly differ between the two groups (3.34 [1.06-6.19] µg l-1 versus 2.64 [1.29-3.85] µg l-1 in the control and exenatide groups, respectively; mean difference (MD) [95% confidence interval (95% CI)] 0.16 [- 0.25; 0.57], p = 0.54). The highest troponin value measured during the first 72 h in the ICU was 6.34 [1.36-10.90] versus 5.04 [2.39-7.18] µg l-1, in the control and exenatide groups respectively (MD [95% CI] 0.20 [- 0.22; 0.61], p = 0.39). At the follow-up consultation, 5 (12%) versus 8 (16%) patients presented a LVEF < 50% in the control and in the exenatide groups respectively (relative risk [95% CI] 0.68 [0.16; 2.59], p = 0.56). CONCLUSIONS: Postoperative iv exenatide did not provide any additional cardioprotective effect compared to iv insulin in low-risk patients undergoing scheduled CABG surgery. Trial registration ClinicalTrials.gov Identifier NCT01969149, date of registration: January 7th, 2015; EudraCT No. 2009-009254-25 A, date of registration: January 6th, 2009.

Kinetics of endocan in patients undergoing cardiac surgery with and without cardiopulmonary bypass.

BACKGROUND: Endocan plays an important role in the processes of inflammation and infection. The use of cardiopulmonary bypass (CPB) during cardiac surgery can induce an inflammatory response. We aimed to describe the kinetics of endocan in patients undergoing cardiac surgery with and without the use of CPB. METHODS: Single-centre, observational study with retrospective analysis of prospectively collected data, to compare the kinetics of endocan in patients undergoing isolated coronary artery bypass graft (CABG) surgery. Endocan was measured at induction of general anesthesia (baseline), and at 6, 24, 48 and 72 h after the end of surgery. Patients were classified into two groups, namely those undergoing CPB (CPB group) and those without CPB (off-pump group). RESULTS: In total, 91 patients were included in this analysis: 61 patients in the CPB group and 30 in the off-pump group. There were no major significant differences between groups. Patients with CPB had a significantly higher level of endocan at 6 h (9.7 ±â€¯6.7 ng/ml vs 6.9 ±â€¯3.3 ng/ml, p = 0.03), but the difference was no longer statistically significant at subsequent timepoints. Endocan values were not significantly correlated with the duration of CPB (p = 0.53). CONCLUSION: Endocan levels in patients undergoing isolated CABG surgery with CPB are significantly higher at 6 h than in patients with off-pump surgery, and peaks earlier in those with CPB (6 h) than in those undergoing off-pump surgery (24 h).

Protective ventilation during anaesthesia reduces major postoperative complications after lung cancer surgery: A double-blind randomised controlled trial.

BACKGROUND: Thoracic surgery for lung resection is associated with a high incidence of postoperative pulmonary complications. Controlled ventilation with a large tidal volume has been documented to be a risk factor for postoperative respiratory complications after major abdominal surgery, whereas the use of low tidal volumes and positive end-expiratory pressure (PEEP) has a protective effect. OBJECTIVE: To evaluate the effects of ventilation with low tidal volume and PEEP on major complications after thoracic surgery. DESIGN: A double-blind, randomised controlled study. SETTING: A multicentre trial from December 2008 to October 2011. PATIENTS: A total of 346 patients undergoing lobectomy or pneumonectomy for lung cancer. MAIN OUTCOME MEASURES: The primary outcome was the occurrence of major postoperative complications (pneumonia, acute lung injury, acute respiratory distress syndrome, pulmonary embolism, shock, myocardial infarction or death) within 30 days after surgery. INTERVENTIONS: Patients were randomly assigned to receive either lung-protective ventilation (LPV group) [tidal volume 5 ml kg ideal body weight + PEEP between 5 and 8 cmH2O] or nonprotective ventilation (control group) (tidal volume 10 ml kg ideal body weight without PEEP) during anaesthesia. RESULTS: The trial was stopped prematurely because of an insufficient inclusion rate. Major postoperative complications occurred in 23/172 patients in the LPV group (13.4%) vs. 38/171 (22.2%) in the control group (odds ratio 0.54, 95% confidence interval, 0.31 to 0.95, P = 0.03). The incidence of other complications (supraventricular cardiac arrhythmia, bronchial obstruction, pulmonary atelectasis, hypercapnia, bronchial fistula and persistent air leak) was also lower in the LPV group (37.2 vs. 49.4%, odds ratio 0.60, 95% confidence interval, 0.39 to 0.92, P = 0.02).The duration of hospital stay was shorter in the LPV group, 11 [interquartile range, 9 to 15] days vs. 12 [9 to 16] days, P = 0.048. CONCLUSION: Compared with high tidal volume and no PEEP, LPV combining low tidal volume and PEEP during anaesthesia for lung cancer surgery seems to improve postoperative outcomes. TRIALS REGISTRATION: ClinicalTrials.gov number: NCT00805077.

Clinical Effectiveness of Intravenous Exenatide Infusion in Perioperative Glycemic Control after Coronary Artery Bypass Graft Surgery: A Phase II/III Randomized Trial.

BACKGROUND: We aimed to assess the clinical effectiveness of intravenous exenatide compared to insulin in perioperative blood glucose control in coronary artery bypass grafting surgery patients. METHODS: Patients more than 18 yr old admitted for elective coronary artery bypass grafting were included in a phase II/III nonblinded randomized superiority trial. Current insulin use and creatinine clearance of less than 60 ml/min were exclusion criteria. Two groups were compared: the exenatide group, receiving exenatide (1-h bolus of 0.05 µg/min followed by a constant infusion of 0.025 µg/min), and the control group, receiving insulin therapy. The blood glucose target range was 100 to 139 mg/dl. The primary outcome was the proportion of patients who spent at least 50% of the study period within the target range. The consumption of insulin (Cinsulin) and the time to start insulin (Tinsulin) were compared between the two groups. RESULTS: In total, 53 and 51 patients were included and analyzed in the exenatide and control groups, respectively (age: 70 ± 9 vs. 68 ± 11 yr; diabetes mellitus: 12 [23%] vs. 10 [20%]). The primary outcome was observed in 38 (72%) patients in the exenatide group and in 41 (80%) patients in the control group (odds ratio [95% CI] = 0.85 [0.34 to 2.11]; P = 0.30). Cinsulin was significantly lower (60 [40 to 80] vs. 92 [63 to 121] U, P < 0.001), and Tinsulin was significantly longer (12 [7 to 16] vs. 7 [5 to 10] h, P = 0.02) in the exenatide group. CONCLUSIONS: Exenatide alone at the dose used was not enough to achieve adequate blood glucose control in coronary artery bypass grafting patients, but it reduces overall consumption of insulin and increases the time to initiation of insulin.

High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic Patients After Cardiothoracic Surgery: A Randomized Clinical Trial.

IMPORTANCE: Noninvasive ventilation delivered as bilevel positive airway pressure (BiPAP) is often used to avoid reintubation and improve outcomes of patients with hypoxemia after cardiothoracic surgery. High-flow nasal oxygen therapy is increasingly used to improve oxygenation because of its ease of implementation, tolerance, and clinical effectiveness. OBJECTIVE: To determine whether high-flow nasal oxygen therapy was not inferior to BiPAP for preventing or resolving acute respiratory failure after cardiothoracic surgery. DESIGN AND SETTING: Multicenter, randomized, noninferiority trial (BiPOP Study) conducted between June 15, 2011, and January 15, 2014, at 6 French intensive care units. PARTICIPANTS: A total of 830 patients who had undergone cardiothoracic surgery, of which coronary artery bypass, valvular repair, and pulmonary thromboendarterectomy were the most common, were included when they developed acute respiratory failure (failure of a spontaneous breathing trial or successful breathing trial but failed extubation) or were deemed at risk for respiratory failure after extubation due to preexisting risk factors. INTERVENTIONS: Patients were randomly assigned to receive high-flow nasal oxygen therapy delivered continuously through a nasal cannula (flow, 50 L/min; fraction of inspired oxygen [FiO2], 50%) (n = 414) or BiPAP delivered with a full-face mask for at least 4 hours per day (pressure support level, 8 cm H2O; positive end-expiratory pressure, 4 cm H2O; FiO2, 50%) (n = 416). MAIN OUTCOMES AND MEASURES: The primary outcome was treatment failure, defined as reintubation, switch to the other study treatment, or premature treatment discontinuation (patient request or adverse effects, including gastric distention). Noninferiority of high-flow nasal oxygen therapy would be demonstrated if the lower boundary of the 95% CI were less than 9%. Secondary outcomes included mortality during intensive care unit stay, changes in respiratory variables, and respiratory complications. RESULTS: High-flow nasal oxygen therapy was not inferior to BiPAP: the treatment failed in 87 of 414 patients with high-flow nasal oxygen therapy (21.0%) and 91 of 416 patients with BiPAP (21.9%) (absolute difference, 0.9%; 95% CI, -4.9% to 6.6%; P = .003). No significant differences were found for intensive care unit mortality (23 patients with BiPAP [5.5%] and 28 with high-flow nasal oxygen therapy [6.8%]; P = .66) (absolute difference, 1.2% [95% CI, -2.3% to 4.8%]. Skin breakdown was significantly more common with BiPAP after 24 hours (10% vs 3%; 95% CI, 7.3%-13.4% vs 1.8%-5.6%; P < .001). CONCLUSIONS AND RELEVANCE: Among cardiothoracic surgery patients with or at risk for respiratory failure, the use of high-flow nasal oxygen therapy compared with intermittent BiPAP did not result in a worse rate of treatment failure. The findings support the use of high-flow nasal oxygen therapy in similar patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01458444.

Is Endocan a Diagnostic Marker for Pneumonia After Cardiac Surgery? The ENDOLUNG Study.

BACKGROUND: Postoperative pneumonia is frequent after cardiac surgery and is associated with increased morbidity and mortality. We tested the hypothesis that endocan is an early biomarker for the detection of pneumonia after cardiac surgery. METHODS: Between January and May 2016, 155 patients scheduled to undergo elective cardiac surgery with cardiopulmonary bypass were prospectively included in the study. Serum level of endocan was measured at five timepoints (preoperative, and at 6, 24, 48, and 72 hours after the end of surgery). Procalcitonin and C-reactive protein were measured at 24 and 72 hours. The preoperative and postoperative characteristics of the patients were recorded. Independent predictors of postoperative pneumonia were identified by logistic regression. Threshold values of endocan predictive of postoperative pneumonia were determined using receiver-operating characteristics curve analysis. RESULTS: Seventeen patients (11%) had pneumonia after surgery. Endocan greater than 3.7 ng/mL before induction of anesthesia, or greater than 12.1 ng/mL at 6 hours after surgery, as well body mass index higher than 27 kg/m2 and duration of surgery were independent predictors of postoperative pneumonia. At induction of anesthesia, an endocan cutoff value of 3.7 ng/mL had 65% sensitivity and 72% specificity for the prediction of postoperative pneumonia; whereas at 6 hours, with a cutoff value of 12.1 ng/mL, these values were 71% and 75%, respectively. The time saved by endocan dosage compared with clinical diagnosis of postoperative pneumonia was 96 hours. CONCLUSIONS: This study shows that endocan is an early marker of postoperative pneumonia in patients after cardiac surgery.

Relevance of Endothelial Cell-Specific Molecule 1 (Endocan) Plasma Levels for Predicting Pulmonary Infection after Cardiac Surgery in Chronic Kidney Disease Patients: The Endolung Pilot Study.

OBJECTIVES: This pilot study aimed to evaluate the relevance of endocan plasma levels for predicting pulmonary infection after cardiac surgery in patients with chronic kidney disease (CKD). METHODS: Serum collected in a previous prospective cohort study (from 166 patients with preoperative CKD who underwent cardiac surgery) was used. Five patients with postoperative pulmonary infection were compared with 15 randomly selected CKD patients with an uneventful outcome. Blood samples were tested at 4 time points (preoperatively and 6, 12, and 24 h after the end of surgery). Endocan, procalcitonin, and C-reactive protein plasma levels were compared between the two groups. RESULTS: At 6 h, the patients with pulmonary infection had significantly higher levels of endocan than the patients without pulmonary infection (24.2 ± 15.6 vs. 6.4 ± 3.2 ng/mL; p = 0.03). A receiver operating characteristic curve analysis showed 80% sensitivity and 100% specificity for endocan to predict pulmonary infection (area under the curve 0.84), with a cutoff value of 15.9 ng/mL. The time saved by assessment of the endocan dosage compared to a clinical diagnosis of pulmonary infection was 47 h. CONCLUSION: This pilot study showed that a specific study to assess the link between endocan plasma levels and pulmonary infection after cardiac surgery in CKD patients is of potential utility.