Propafenone versus amiodarone for supraventricular arrhythmias in septic shock: a randomised controlled trial.

PURPOSE: Acute onset supraventricular arrhythmias can contribute to haemodynamic compromise in septic shock. Both amiodarone and propafenone are available interventions, but their clinical effects have not yet been directly compared. METHODS: In this two-centre, prospective controlled parallel group double blind trial we recruited 209 septic shock patients with new-onset arrhythmia and a left ventricular ejection fraction above 35%. The patients were randomised in a 1:1 ratio to receive either intravenous propafenone (70 mg bolus followed by 400-840 mg/24 h) or amiodarone (300 mg bolus followed by 600-1800 mg/24 h). The primary outcomes were the proportion of patients who had sinus rhythm 24 h after the start of the infusion, time to restoration of the first sinus rhythm and the proportion of patients with arrhythmia recurrence. RESULTS: Out of 209 randomized patients, 200 (96%) received the study drug. After 24 h, 77 (72.8%) and 71 (67.3%) were in sinus rhythm (p = 0.4), restored after a median of 3.7 h (95% CI 2.3-6.8) and 7.3 h (95% CI 5-11), p = 0.02, with propafenone and amiodarone, respectively. The arrhythmia recurred in 54 (52%) patients treated with propafenone and in 80 (76%) with amiodarone, p < 0.001. Patients with a dilated left atrium had better rhythm control with amiodarone (6.4 h (95% CI 3.5; 14.1) until cardioversion vs 18 h (95% CI 2.8; 24.7) in propafenone, p = 0.05). CONCLUSION: Propafenone does not provide better rhythm control at 24 h yet offers faster cardioversion with fewer arrhythmia recurrences than with amiodarone, especially in patients with a non-dilated left atrium. No differences between propafenone and amiodarone on the prespecified short- and long-term outcomes were observed.

Internal jugular vein collapsibility does not predict fluid responsiveness in spontaneously breathing patients after cardiac surgery.

PURPOSE: The objective of our study was to evaluate the diagnostic accuracy of internal jugular vein (IJV) collapsibility as a predictor of fluid responsiveness in spontaneously breathing patients after cardiac surgery. METHODS: In this prospective observational study, spontaneously breathing patients were enrolled on the first postoperative day after coronary artery bypass grafting. Hemodynamic data coupled with simultaneous ultrasound assessment of the IJV were collected at baseline and after passive leg raising test (PLR). Continuous cardiac index (CI), stroke volume (SV), and stroke volume variation (SVV) were assessed with FloTracTM/EV1000™. Fluid responsiveness was defined as an increase in CI ≥ 10% after PLR. We compared the differences in measured variables between fluid responders and non-responders and tested the ability of ultrasonographic IJV indices to predict fluid responsiveness. RESULTS: Fifty-four patients were included in the study. Seventeen (31.5%) were fluid responders. The responders demonstrated significantly lower inspiratory and expiratory diameters of the IJV at baseline, but IJV collapsibility was comparable (P = 0.7). Using the cut-off point of 20%, IJV collapsibility predicted fluid responsiveness with a sensitivity of 76.5% and specificity of 38.9%, ROC AUC 0.55. CONCLUSION: In spontaneously breathing patients after surgical coronary revascularisation, collapsibility of the internal jugular vein did not predict fluid responsiveness.

Prediction of Fluid Responsiveness Using Combined End-Expiratory and End-Inspiratory Occlusion Tests in Cardiac Surgical Patients.

End-expiratory occlusion (EEO) and end-inspiratory occlusion (EIO) tests have been successfully used to predict fluid responsiveness in various settings using calibrated pulse contour analysis and echocardiography. The aim of this study was to test if respiratory occlusion tests predicted fluid responsiveness reliably in cardiac surgical patients with protective ventilation. This single-centre, prospective study, included 57 ventilated patients after elective coronary artery bypass grafting who were indicated for fluid expansion. Baseline echocardiographic measurements were obtained and patients with significant cardiac pathology were excluded. Cardiac index (CI), stroke volume and stroke volume variation were recorded using uncalibrated pulse contour analysis at baseline, after performing EEO and EIO tests and after volume expansion (7 mL/kg of succinylated gelatin). Fluid responsiveness was defined as an increase in cardiac index by 15%. Neither EEO, EIO nor their combination predicted fluid responsiveness reliably in our study. After a combined EEO and EIO, a cut-off point for CI change of 16.7% predicted fluid responsiveness with a sensitivity of 61.8%, specificity of 69.6% and ROC AUC of 0.593. In elective cardiac surgical patients with protective ventilation, respiratory occlusion tests failed to predict fluid responsiveness using uncalibrated pulse contour analysis.

Methylene blue administration in patients with refractory distributive shock - a retrospective study.

Hemodynamic effectiveness of methylene blue (MB) was tested in patients with refractory distributive shock. A retrospective analysis of 20 critically-ill patients who developed refractory shock was performed. Patients were divided into two study groups as responders with positive hemodynamic response to MB administration (defined as 10% decrease of norepinephrine dose) and non-responders. Hemodynamic, outcome data and baseline tissue hypoxia-related parameters including ratio of central venous-to-arterial carbon dioxide tension to arterio-venous oxygen content (P(v-a)CO2/C(a-v)O2) were compared between the groups. There were 9 (45%) responders and 11 (55%) non-responders to single bolus of MB administration. Dose of MB did not differ between responders and non-responders (1.3 ± 0.5 vs. 1.3 ± 0.4 mg/kg respectively, P = 0.979). MB responders had lower baseline P(v-a) CO2/C(a-v)O2 (1.79 ± 0.73 vs. 3.24 ± 1.18, P = 0.007), higher pH (7.26 ± 0.11 vs. 7.16 ± 0.10, P = 0.037) and lower lactate levels at 12 hours post MB administration (3.4 ± 2.7 vs. 9.9 ± 2.2 mmol/L, P = 0.002) compared to non-responders. Methylene blue represents a non-adrenergic vasopressor with only limited effectiveness in patients with refractory distributive shock. Profound tissue hypoxia with high degree of anaerobic metabolism was associated with the loss of hemodynamic responsiveness to its administration.

Dendritic Cells in Subcutaneous and Epicardial Adipose Tissue of Subjects with Type 2 Diabetes, Obesity, and Coronary Artery Disease.

Dendritic cells (DCs) are professional antigen-presenting cells contributing to regulation of lymphocyte immune response. DCs are divided into two subtypes: CD11c-positive conventional or myeloid (cDCs) and CD123-positive plasmacytoid (pDCs) DCs. The aim of the study was to assess DCs (HLA-DR+ lineage-) and their subtypes by flow cytometry in peripheral blood and subcutaneous (SAT) and epicardial (EAT) adipose tissue in subjects with (T2DM, n = 12) and without (non-T2DM, n = 17) type 2 diabetes mellitus undergoing elective cardiac surgery. Subjects with T2DM had higher fasting glycemia (8.6 ± 0.7 vs. 5.8 ± 0.2 mmol/l, p < 0.001) and glycated hemoglobin (52.0 ± 3.4 vs. 36.9 ± 1.0 mmol/mol, p < 0.001) and tended to have more pronounced inflammation (hsCRP: 9.8 ± 3.1 vs. 5.1 ± 1.9 mg/ml, p = 0.177) compared with subjects without T2DM. T2DM was associated with reduced total DCs in SAT (1.57 ± 0.65 vs. 4.45 ± 1.56% for T2DM vs. non-T2DM, p = 0.041) with a similar, albeit insignificant, trend in EAT (0.996 ± 0.33 vs. 2.46 ± 0.78% for T2DM vs. non-T2DM, p = 0.171). When analyzing DC subsets, no difference in cDCs was seen between any of the studied groups or adipose tissue pools. In contrast, pDCs were increased in both SAT (13.5 ± 2.0 vs. 4.6 ± 1.9% of DC cells, p = 0.005) and EAT (29.1 ± 8.7 vs. 8.4 ± 2.4% of DC, p = 0.045) of T2DM relative to non-T2DM subjects as well as in EAT of the T2DM group compared with corresponding SAT (29.1 ± 8.7 vs. 13.5 ± 2.0% of DC, p = 0.020). Neither obesity nor coronary artery disease (CAD) significantly influenced the number of total, cDC, or pDC in SAT or EAT according to multiple regression analysis. In summary, T2DM decreased the amount of total dendritic cells in subcutaneous adipose tissue and increased plasmacytoid dendritic cells in subcutaneous and even more in epicardial adipose tissue. These findings suggest a potential role of pDCs in the development of T2DM-associated adipose tissue low-grade inflammation.

Coronary Artery Disease Is Associated with an Increased Amount of T Lymphocytes in Human Epicardial Adipose Tissue.

Immunocompetent cells including lymphocytes play a key role in the development of adipose tissue inflammation and obesity-related cardiovascular complications. The aim of the study was to explore the relationship between epicardial adipose tissue lymphocytes and coronary artery disease (CAD). To this end, we studied the content and phenotype of lymphocytes in peripheral blood, subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT) in subjects with and without CAD undergoing elective cardiac surgery. Eleven subjects without CAD (non-CAD group) and 22 age-, BMI-, and HbA1C-matched individuals with CAD were included into the study. Blood, SAT, and EAT samples were obtained at the beginning of surgery. Lymphocyte populations were quantified as % of CD45+ cells using flow cytometry. Subjects with CAD had a higher total lymphocyte amount in EAT compared with SAT (32.24 ± 7.45 vs. 11.22 ± 1.34%, p = 0.025) with a similar trend observed in non-CAD subjects (29.68 ± 7.61 vs. 10.13 ± 2.01%, p = 0.067). T (CD3+) cells were increased (75.33 ± 2.18 vs. 65.24 ± 4.49%, p = 0.032) and CD3- cells decreased (21.17 ± 2.26 vs. 31.64 ± 4.40%, p = 0.028) in EAT of CAD relative to the non-CAD group. In both groups, EAT showed an elevated percentage of B cells (5.22 ± 2.43 vs. 0.96 ± 0.21%, p = 0.039 for CAD and 12.49 ± 5.83 vs. 1.16 ± 0.19%, p = 0.016 for non-CAD) and reduced natural killer (NK) cells (5.96 ± 1.32 vs. 13.22 ± 2.10%, p = 0.012 for CAD and 5.32 ± 1.97 vs. 13.81 ± 2.72%, p = 0.022 for non-CAD) relative to SAT. In conclusion, epicardial adipose tissue in subjects with CAD shows an increased amount of T lymphocytes relative to non-CAD individuals as well as a higher number of total and B lymphocytes and reduced NK cells as compared with corresponding SAT. These changes could contribute to the development of local inflammation and coronary atherosclerosis.

Immature granulocytes as a sepsis predictor in patients undergoing cardiac surgery.

OBJECTIVES: Usefulness of immature granulocyte percentage (IG%) to discriminate between postoperative non-infective systemic inflammatory response syndrome (SIRS) and sepsis was tested in cardiac surgical patients. METHODS: A retrospective analysis of 124 patients who developed non-infective SIRS and sepsis after elective cardiac surgery was performed. Predictive ability of IG% to predict sepsis was compared to procalcitonin (PCT), white blood cell count, temperature and different biomarker combinations using receiver operating characteristic and logistic regression analysis. The optimal cut-off points, diagnosis sensitivity and specificity were calculated. RESULTS: There were 44 patients diagnosed with sepsis and 80 patients with non-infective SIRS. In receiver operating characteristic analysis, area under the curve was higher for IG% (0.71) and PCT (0.72) compared to white blood cell count (0.62) and temperature (0.58). The best cut-off value for IG% was 1.45% (sensitivity 70.5%, specificity 60%) and 1.43 µg/l for PCT (sensitivity 65.9%, specificity 75%). The combination of IG% and PCT provided the best sepsis prediction (area under the curve of 0.8, sensitivity 63.6% and specificity 88.8%). CONCLUSIONS: In cardiac surgical patients, IG% is a helpful marker with the moderate ability to discriminate between sepsis and non-infective SIRS, comparable to serum PCT. A combination of these parameters increased the test's overall predictive ability by improving its specificity.

Effect of continuous exenatide infusion on cardiac function and peri-operative glucose control in patients undergoing cardiac surgery: A single-blind, randomized controlled trial.

We performed a randomized controlled trial with the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide as add-on to standard peri-operative insulin therapy in patients undergoing elective cardiac surgery. The aims of the study were to intensify peri-operative glucose control while minimizing the risk of hypoglycaemia and to evaluate the suggested cardioprotective effects of GLP-1-based treatments. A total of 38 patients with decreased left ventricular systolic function (ejection fraction ≤50%) scheduled for elective coronary artery bypass grafting (CABG) were randomized to receive either exenatide or placebo in a continuous 72-hour intravenous (i.v.) infusion on top of standard peri-operative insulin therapy. While no significant difference in postoperative echocardiographic variables was found between the groups, participants receiving exenatide showed improved peri-operative glucose control as compared with the placebo group (average glycaemia 6.4 ± 0.5 vs 7.3 ± 0.8 mmol/L; P < .001; percentage of time in target range of 4.5-6.5 mmol/L 54.8% ± 14.5% vs 38.6% ± 14.4%; P = .001; percentage of time above target range 39.7% ± 13.9% vs 52.8% ± 15.2%; P = .009) without an increased risk of hypoglycaemia (glycaemia <3.3 mmol/L: 0.10 ± 0.32 vs 0.21 ± 0.42 episodes per participant; P = .586). Continuous administration of i.v. exenatide in patients undergoing elective CABG could provide a safe option for intensifying the peri-operative glucose management of such patients.

A rationale for early extracorporeal membrane oxygenation in patients with postinfarction ventricular septal rupture complicated by cardiogenic shock.

AIMS: Ventricular septal rupture (VSR) became a rare mechanical complication of myocardial infarction in the era of percutaneous coronary interventions but is associated with extreme mortality in patients who present with cardiogenic shock (CS). Promising outcomes have been reported with the use of circulatory support allowing haemodynamic stabilization, followed by delayed repair. Therefore, we analysed our experience with an early use of Veno-Arterial Extracorporeal Membrane Oxygenation (V-A ECMO) for postinfarction VSR. METHODS AND RESULTS: We conducted a retrospective search of institutional database for patients presenting with postinfarction VSR from January 2007 to June 2016. Data from 31 consecutive patients (mean age 69.5 ± 9.1 years) who were admitted to hospital were analysed. Seven out of 31 patients with VSR who were in refractory CS received V-A ECMO support preoperatively. ECMO improved end-organ perfusion with decreased lactate levels 24 hours after implantation (7.9 mmol/L vs. 1.6 mmol/L, p = 0.01), normalized arterial pH (7.25 vs. 7.40, p < 0.04), improved mean arterial pressure (64 mmHg vs. 83 mmHg, p < 0.01) and lowered heart rate (115/min vs. 68/min, p < 0.01). Mean duration of ECMO support was 12 days, 5 out of 7 patients underwent surgical repair, 4 were weaned from ECMO, 3 survived 30 days and 2 survived more than 1 year. The most frequent complication (5 patients) and the cause of death (3 patients) was bleeding. CONCLUSIONS: Our experience suggests that early V-A ECMO in patients with VSR and refractory CS might prevent irreversible multiorgan failure by improved end-organ perfusion. Bleeding complications remain an important limitation of this approach.

Catastrophic Left Ventricular Thrombosis Complicating Extra-corporeal Membrane Oxygenation: A Case Report.

A massive left ventricular thrombosis represents a rare however, catastrophic complication of a central veno-arterial extra-corporeal membrane oxygenation. We report a case of such complication in a patient with severe left ventricular dysfunction after cardiac surgery. Its management and preventive measures are described and discussed.

Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials.

BACKGROUND: In phase 2 trials, lebrikizumab, an anti-interleukin-13 monoclonal antibody, reduced exacerbation rates and improved FEV1 in patients with uncontrolled asthma, particularly in those with high concentrations of type 2 biomarkers (eg, periostin or blood eosinophils). We undertook replicate phase 3 studies to assess the efficacy and safety of lebrikizumab in patients with uncontrolled asthma despite inhaled corticosteroids and at least one second controller medication. METHODS: Adult patients with uncontrolled asthma, pre-bronchodilator FEV1 40-80% predicted, and stable background therapy were randomly assigned (1:1:1) with an interactive voice-web-based response system to receive lebrikizumab 37·5 mg or 125 mg, or placebo subcutaneously, once every 4 weeks. Randomisation was stratified by screening serum periostin concentration, history of asthma exacerbations within the last 12 months, baseline asthma medications, and country. The primary efficacy endpoint was the rate of asthma exacerbations over 52 weeks in biomarker-high patients (periostin ≥50 ng/mL or blood eosinophils ≥300 cells per µL), analysed with a Poisson regression model corrected for overdispersion with Pearson χ2 that included terms for treatment group, number of asthma exacerbations within the 12 months before study entry, baseline asthma medications, geographic region, screening periostin concentration, and blood eosinophil counts as covariates. Both trials are registered at ClinicalTrials.gov, LAVOLTA I, number NCT01867125, and LAVOLTA II, number NCT01868061. FINDINGS: 1081 patients were treated in LAVOLTA I and 1067 patients in LAVOLTA II. Over 52 weeks, lebrikizumab reduced exacerbation rates in biomarker-high patients in the 37·5 mg dose group (rate ratio [RR] 0·49 [95% CI 0·34-0·69], p<0·0001) and in the 125 mg dose group (RR 0·70 [0·51-0·95], p=0·0232) versus placebo in LAVOLTA I. Exacerbation rates were also reduced in biomarker-high patients in both dose groups versus placebo in LAVOLTA II (37·5 mg: RR 0·74 [95% CI 0·54-1·01], p=0·0609; 125 mg: RR 0·74 [0·54-1·02], p=0·0626). Pooling both studies, the proportion of patients who experienced treatment-emergent adverse events (79% [1125 of 1432 patients] for both lebrikizumab doses vs 80% [576 of 716 patients] for placebo), serious adverse events (8% [115 patients] for both lebrikizumab doses vs 9% [65 patients] for placebo), and adverse events leading to study drug discontinuation (3% [49 patients] for both lebrikizumab doses vs 4% [31 patients] for placebo) were similar between lebrikizumab and placebo. The following serious adverse events were reported in the placebo-controlled period: one event of aplastic anaemia and five serious adverse events related to raised concentrations of eosinophils in patients treated with lebrikizumab and one event of eosinophilic pneumonia in the placebo group. INTERPRETATION: Lebrikizumab did not consistently show significant reduction in asthma exacerbations in biomarker-high patients. However, it blocked interleukin-13 as evidenced by the effect on interleukin-13-related pharmacodynamic biomarkers, and clinically relevant changes could not be ruled out. FUNDING: F Hoffmann-La Roche.

High thoracic anesthesia offers no major benefit over general anesthesia in on-pump cardiac surgery patients: a retrospective study.

BACKGROUND: Thoracic epidural anesthesia (TEA) has been proposed to improve and facilitate early postoperative outcome in cardiac surgery. The aim of our study was to analyze early postoperative outcome data of patients undergoing cardiac surgery under general anesthesia (GA) with comparison to patients receiving combined TEA and GA. METHODS: Medical records data from 288 patients who underwent elective on-pump cardiac surgery were retrieved and analyzed. Patients were divided into two study groups according to the type of anesthesia used: GA group (n = 141) and TEA group (n = 147). Early postoperative outcome data including quality of analgesia and major organ outcome parameters were compared between the study groups. RESULTS: There was no major difference in early postoperative outcome data between the study groups, except for shorter time to extubation (6.0 ± 10.0 vs. 6.9 ± 8.8 h, respectively, P < 0.05) and hospital stay (10.7 ± 5.9 vs. 12.9 ± 8.8 days, respectively, P < 0.05) in TEA group compared to GA group. Also TEA group as compared to GA group had lower pain numeric rating scale scores (1 ± 1.1 vs. 1.4 ± 1.5 at 24 h, respectively, P < 0.05) and morphine requirements during the first 24 h after surgery (148.2 vs. 193 ± 85.4 µg/kg, respectively, P < 0.05). CONCLUSION: Both anesthetic methods were equivalent in most postoperative outcome measures. Thoracic epidural analgesia provided superior pain relief, shorter time to extubation and earlier hospital discharge.

Space GlucoseControl system for blood glucose control in intensive care patients--a European multicentre observational study.

BACKGROUND: Glycaemia control (GC) remains an important therapeutic goal in critically ill patients. The enhanced Model Predictive Control (eMPC) algorithm, which models the behaviour of blood glucose (BG) and insulin sensitivity in individual ICU patients with variable blood samples, is an effective, clinically proven computer based protocol successfully tested at multiple institutions on medical and surgical patients with different nutritional protocols. eMPC has been integrated into the B.Braun Space GlucoseControl system (SGC), which allows direct data communication between pumps and microprocessor. The present study was undertaken to assess the clinical performance and safety of the SGC for glycaemia control in critically ill patients under routine conditions in different ICU settings and with various nutritional protocols. METHODS: The study endpoints were the percentage of time the BG was within the target range 4.4 - 8.3 mmol.l(-1), the frequency of hypoglycaemic episodes, adherence to the advice of the SGC and BG measurement intervals. BG was monitored, and insulin was given as a continuous infusion according to the advice of the SGC. Nutritional management (enteral, parenteral or both) was carried out at the discretion of each centre. RESULTS: 17 centres from 9 European countries included a total of 508 patients, the median study time was 2.9 (1.9-6.1) days. The median (IQR) time-in-target was 83.0 (68.7-93.1) % of time with the mean proposed measurement interval 2.0 ± 0.5 hours. 99.6% of the SGC advices on insulin infusion rate were accepted by the user. Only 4 episodes (0.01% of all BG measurements) of severe hypoglycaemia <2.2 mmol.l(-1) in 4 patients occurred (0.8%; 95% CI 0.02-1.6%). CONCLUSION: Under routine conditions and under different nutritional protocols the Space GlucoseControl system with integrated eMPC algorithm has exhibited its suitability for glycaemia control in critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01523665.

Perioperative Tight Glucose Control Reduces Postoperative Adverse Events in Nondiabetic Cardiac Surgery Patients.

CONTEXT: Tight glucose control (TGC) reduces morbidity and mortality in patients undergoing elective cardiac surgery, but only limited data about its optimal timing are available to date. OBJECTIVE: The purpose of this article was to compare the effects of perioperative vs postoperative initiation of TGC on postoperative adverse events in cardiac surgery patients. DESIGN: This was a single center, single-blind, parallel-group, randomized controlled trial. SETTINGS: The setting was an academic tertiary hospital. PARTICIPANTS: Participants were 2383 hemodynamically stable patients undergoing major cardiac surgery with expected postoperative intensive care unit treatment for at least 2 consecutive days. INTERVENTION: Intensive insulin therapy was initiated perioperatively or postoperatively with a target glucose range of 4.4 to 6.1 mmol/L. MAIN OUTCOME MEASURES: Adverse events from any cause during postoperative hospital stay were compared. RESULTS: In the whole cohort, perioperatively initiated TGC markedly reduced the number of postoperative complications (23.2% vs 34.1%, 95% confidence interval [CI], 0.60-0.78) despite only minimal improvement in glucose control (blood glucose, 6.6 ± 0.7 vs 6.7 ± 0.8 mmol/L, P < .001; time in target range, 39.3% ± 13.7% vs 37.3% ± 13.8%, P < .001). The positive effects of TGC on postoperative complications were driven by nondiabetic subjects (21.3% vs 33.7%, 95% CI, 0.54-0.74; blood glucose 6.5 ± 0.6 vs 6.6 ± 0.8 mmol/L, not significant; time in target range, 40.8% ± 13.6% vs 39.7% ± 13.8%, not significant), whereas no significant effect was seen in diabetic patients (29.4% vs 35.1%, 95% CI, 0.66-1.06) despite significantly better glucose control in the perioperative group (blood glucose, 6.9 ± 1.0 vs 7.1 ± 0.8 mmol/L, P < .001; time in target range, 34.3% ± 12.7% vs 30.8% ± 11.5%, P < .001). CONCLUSIONS: Perioperative initiation of intensive insulin therapy during cardiac surgery reduces postoperative morbidity in nondiabetic patients while having a minimal effect in diabetic subjects.

Successful use of extra-corporeal membrane oxygenation in a patient with streptococcal sepsis: a case report and review of literature.

A young patient with streptococcal sepsis due to the phlegmon of his left thigh was admitted to the general intensive care unit. He developed a multi-organ failure and septic cardiomyopathy with subsequent cardiogenic shock. This resulted in hemodynamic instability unresponsive to conservative medical treatment. We report a successful application of veno-arterial extra-corporeal membrane oxygenation, which was used to overcome the period of critically low cardiac output caused by severe septic myocardial dysfunction.

The effect of adjusting tracheal tube cuff pressure during deep hypothermic circulatory arrest: a randomised trial.

BACKGROUND: Regular endotracheal tube cuff monitoring may prevent silent aspiration. OBJECTIVES: We hypothesised that active management of the cuff of the tracheal tube during deep hypothermic cardiac arrest would reduce silent subglottic aspiration. We also determined to study its effect on postoperative mechanical ventilation and the incidence of postoperative positive tracheal cultures. DESIGN: A randomised clinical trial. SETTING: The study was conducted in a University Teaching Hospital from September 2008 to November 2009. PATIENTS: Twenty-four patients undergoing elective pulmonary endarterectomy were included in the study. INTERVENTION: After induction of general anaesthesia and tracheal intubation, the cuff of the tracheal tube was inflated to 25 cmH2O. Following this, 1 ml of methylene blue dye diluted in 2 ml of physiological saline was injected into the hypopharynx. Patients were randomly assigned to active cuff management during cooling and warming (where cuff pressure was monitored and the cuff was reinflated if it dropped below 20 cmH2O, or deflated if pressure exceeded 30 cmH2O) or passive monitoring (where cuff pressure was monitored but volume was not altered). Before weaning from cardiopulmonary bypass, fibreoptic bronchoscopy was performed. Silent aspiration was then diagnosed if blue dye was seen in the trachea below the cuff of the tube. MAIN OUTCOME MEASURES: The primary aim of this study was to determine the incidence of silent aspiration. Secondary outcomes included duration of postoperative mechanical ventilation of the lungs and incidence of positive culture of tracheal aspirate. RESULTS: Active cuff management patients were younger than controls (51.2 ±â€Š11.6 vs. 63.2 ±â€Š9 years, P = 0.028), but otherwise the two groups were similar. The primary endpoint was reached because we showed that silent aspiration was significantly less frequent in the study group (0/12 vs. 8/12 patients, P = 0.001). Significantly lower intracuff pressures were measured in the control group patients at several timepoints during cooling, just before hypothermic arrest and at all timepoints during rewarming. CONCLUSION: We recommend that the cuff of the tracheal tube should be checked regularly during surgery under deep hypothermia, and the cuff pressure adjusted as required.

Glucose control in the ICU: is there a time for more ambitious targets again?

During the last 2 decades, the treatment of hyperglycemia in critically ill patients has become one of the most discussed topics in the intensive medicine field. The initial data suggesting significant benefit of normalization of blood glucose levels in critically ill patients using intensive intravenous insulin therapy have been challenged or even neglected by some later studies. At the moment, the need for glucose control in critically ill patients is generally accepted yet the target glucose values are still the subject of ongoing debates. In this review, we summarize the current data on the benefits and risks of tight glucose control in critically ill patients focusing on the novel technological approaches including continuous glucose monitoring and its combination with computer-based algorithms that might help to overcome some of the hurdles of tight glucose control. Since increased risk of hypoglycemia appears to be the major obstacle of tight glucose control, we try to put forward novel approaches that may help to achieve optimal glucose control with low risk of hypoglycemia. If such approaches can be implemented in real-world practice the entire concept of tight glucose control may need to be revisited.

The influence of deep hypothermia on inflammatory status, tissue hypoxia and endocrine function of adipose tissue during cardiac surgery.

Changes in endocrine function of adipose tissue during surgery, such as excessive production of proinflammatory cytokines, can significantly alter metabolic response to surgery and worsen its outcomes and prognosis of patients. Therapeutic hypothermia has been used to prevent damage connected with perioperative ischemia and hypoperfusion. The aim of our study was to explore the influence of deep hypothermia on systemic and local inflammation, adipose tissue hypoxia and adipocytokine production. We compared serum concentrations of proinflammatory markers (CRP, IL-6, IL-8, sIL-2R, sTNFRI, PCT) and mRNA expression of selected genes involved in inflammatory reactions (IL-6, TNF-α, MCP-1, MIF) and adaptation to hypoxia and oxidative stress (HIF1-α, MT3, GLUT1, IRS1, GPX1, BCL-2) in subcutaneous and visceral adipose tissue and in isolated adipocytes of patients undergoing cardiosurgical operation with hypothermic period. Deep hypothermia significantly delayed the onset of surgery-related systemic inflammatory response. The relative gene expression of the studied genes was not altered during the hypothermic period, but was significantly changed in six out of ten studied genes (IL-6, MCP-1, TNF-α, HIF1-α, GLUT1, GPX1) at the end of surgery. Our results show that deep hypothermia suppresses the development of systemic inflammatory response, delays the onset of local adipose tissue inflammation and thus may protect against excessive expression of proinflammatory and hypoxia-related factors in patients undergoing elective cardiac surgery procedure.

The use of continuous glucose monitoring combined with computer-based eMPC algorithm for tight glucose control in cardiosurgical ICU.

AIM: In postcardiac surgery patients, we assessed the performance of a system for intensive intravenous insulin therapy using continuous glucose monitoring (CGM) and enhanced model predictive control (eMPC) algorithm. METHODS: Glucose control in eMPC-CGM group (n = 12) was compared with a control (C) group (n = 12) treated by intravenous insulin infusion adjusted according to eMPC protocol with a variable sampling interval alone. In the eMPC-CGM group glucose measured with a REAL-Time CGM system (Guardian RT) served as input for the eMPC adjusting insulin infusion every 15 minutes. The accuracy of CGM was evaluated hourly using reference arterial glucose and Clarke error-grid analysis (C-EGA). Target glucose range was 4.4-6.1 mmol/L. RESULTS: Of the 277 paired CGM-reference glycemic values, 270 (97.5%) were in clinically acceptable zones of C-EGA and only 7 (2.5%) were in unacceptable D zone. Glucose control in eMPC-CGM group was comparable to C group in all measured values (average glycemia, percentage of time above, within, and below target range,). No episode of hypoglycemia (<2.9 mmol) occurred in eMPC-CGM group compared to 2 in C group. CONCLUSION: Our data show that the combination of eMPC algorithm with CGM is reliable and accurate enough to test this approach in a larger study population.

Comparison of three protocols for tight glycemic control in cardiac surgery patients.

OBJECTIVE: We performed a randomized trial to compare three insulin-titration protocols for tight glycemic control (TGC) in a surgical intensive care unit: an absolute glucose (Matias) protocol, a relative glucose change (Bath) protocol, and an enhanced model predictive control (eMPC) algorithm. RESEARCH DESIGN AND METHODS: A total of 120 consecutive patients after cardiac surgery were randomly assigned to the three protocols with a target glycemia range from 4.4 to 6.1 mmol/l. Intravenous insulin was administered continuously or in combination with insulin boluses (Matias protocol). Blood glucose was measured in 1- to 4-h intervals as requested by the protocols. RESULTS: The eMPC algorithm gave the best performance as assessed by time to target (8.8 +/- 2.2 vs. 10.9 +/- 1.0 vs. 12.3 +/- 1.9 h; eMPC vs. Matias vs. Bath, respectively; P < 0.05), average blood glucose after reaching the target (5.2 +/- 0.1 vs. 6.2 +/- 0.1 vs. 5.8 +/- 0.1 mmol/l; P < 0.01), time in target (62.8 +/- 4.4 vs. 48.4 +/- 3.28 vs. 55.5 +/- 3.2%; P < 0.05), time in hyperglycemia >8.3 mmol/l (1.3 +/- 1.2 vs. 12.8 +/- 2.2 vs. 6.5 +/- 2.0%; P < 0.05), and sampling interval (2.3 +/- 0.1 vs. 2.1 +/- 0.1 vs. 1.8 +/- 0.1 h; P < 0.05). However, time in hypoglycemia risk range (2.9-4.3 mmol/l) in the eMPC group was the longest (22.2 +/- 1.9 vs. 10.9 +/- 1.5 vs. 13.1 +/- 1.6; P < 0.05). No severe hypoglycemic episode (<2.3 mmol/l) occurred in the eMPC group compared with one in the Matias group and two in the Bath group. CONCLUSIONS: The eMPC algorithm provided the best TGC without increasing the risk of severe hypoglycemia while requiring the fewest glucose measurements. Overall, all protocols were safe and effective in the maintenance of TGC in cardiac surgery patients.