Effects of Mechanical Insufflation-Exsufflation on Sputum Volume in Mechanically Ventilated Critically Ill Subjects.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) is a noninvasive technique performed to simulate cough and remove sputum from proximal airways. To date, the effects of MI-E on critically ill patients on invasive mechanical ventilation are not fully elucidated. In this randomized crossover trial, we evaluated the efficacy and safety of MI-E combined to expiratory rib cage compressions (ERCC). METHODS: Twenty-six consecutive subjects who were sedated, intubated, and on mechanical ventilation > 48 h were randomized to perform 2 sessions of ERCC with or without additional MI-E before tracheal suctioning in a 24-h period. The primary outcome was sputum volume following each procedure. Secondary end points included effects on respiratory mechanics, hemodynamics, and safety. RESULTS: In comparison to ERCC alone, median (interquartile range) sputum volume cleared was significantly higher during ERCC+MI-E (0.42 [0-1.39] mL vs 2.29 [1-4.67] mL, P < .001). The mean ± SD respiratory compliance improved in both groups immediately after the treatment, with the greater improvement in the ERCC+MI-E group (54.7 ± 24.1 mL/cm H2O vs 73.7 ± 35.8 mL/cm H2O, P < .001). Differences between the groups were not significant (P = .057). Heart rate increased significantly in both groups immediately after each intervention (P < .05). Additionally, a significant increase in oxygenation was observed from baseline to 1 h post-intervention in the ERCC+MI-E group (P < .05). Finally, several transitory hemodynamic variations occurred during both interventions, but these were nonsignificant and were considered clinically irrelevant. CONCLUSIONS: In mechanically ventilated subjects, MI-E combined with ERCC increased the sputum volume cleared without causing clinically important hemodynamic changes or adverse events. (ClinicalTrials.gov registration: NCT03316079.).

Pain evaluation after day-surgery using a mobile phone application.

INTRODUCTION: Few studies assess postoperative outcomes after discharge in the ambulatory setting. The aim of this study was to investigate postoperative pain and adverse effects at 24 h and at 7 days after day surgery using an e-health follow-up smartphone-based application named SATELIA®. MATERIALS AND METHODS: This retrospective, observational and monocentric cohort study was conducted at the University Hospital of Bordeaux. All eligible patients for SATELIA® follow-up between May 2018 and June 2019 were screened for the analysis. Data were extracted from two databases. Those with a missing primary outcome were excluded from the analysis. The main outcome was the worst pain score on POD 1, self-reported via SATELIA®. The secondary outcomes were the incidence of adverse effects on POD1, as well as the worst pain score and adverse effects on POD7. Quantitative data were reported by the median (IQR) and categorical data were presented as absolute numbers (%). RESULTS: A total of 2283 patients were screened for analysis, from which 592 were excluded due to missing data for the main outcome; 1691 patients were thus finally included. The median worst pain score at POD 1 was 3.0 (1.0-5.0); 35.5% (n = 601/1691) and 29.1% (n = 492/1691) of the patients reported moderate-to-severe pain at POD1 and POD7, respectively. CONCLUSION: This retrospective study shows that 35.5% of patients experience moderate-to-severe pain after day surgery. Even if SATELIA® should be further developed and evaluated, it also demonstrates the interest of using phone based software to follow patients after discharge and ensure a better personalised management.

Outcome of patients treated with molecular adsorbent recirculating system albumin dialysis: A national multicenter study.

BACKGROUND AND AIM: The molecular adsorbent recirculating system (MARS) is the most widely used device to treat liver failure. Nevertheless, data from widespread real-life use are lacking. METHODS: This was a retrospective multicenter study conducted in all French adult care centers that used MARS between 2004 and 2009. The primary objective was to evaluate patient survival according to the liver disease and listing status. Factors associated with mortality were the secondary objectives. RESULTS: A total of 383 patients underwent 393 MARS treatments. The main indications were acute liver failure (ALF, 32.6%), and severe cholestasis (total bilirubin >340 µmol/L) (37.2%), hepatic encephalopathy (23.7%), and/or acute kidney injury-hepatorenal syndrome (22.9%) most often among patients with chronic liver disease. At the time of treatment, 34.4% of the patients were listed. Overall, the hospital survival rate was 49% (95% CI: 44-54%) and ranged from 25% to 81% depending on the diagnosis of the liver disease. In listed patients versus those not listed, the 1-year survival rate was markedly better in the setting of nonbiliary cirrhosis (59% vs 15%), early graft nonfunction (80% vs 0%), and late graft dysfunction (72% vs 0%) (all P < 0.001). Among nonbiliary cirrhotic patients, hospital mortality was associated with the severity of liver disease (HE and severe cholestasis) and not being listed for transplant. In ALF, paracetamol etiology and ≥3 MARS sessions were associated with better transplant-free survival. CONCLUSION: Our study suggests that MARS should be mainly used as a bridge to liver transplantation. Survival was correlated with being listed for most etiologies and with the intensity of treatment in ALF.

Lysis Timer: a new sensitive tool to diagnose hyperfibrinolysis in liver transplantation.

AIMS: Diagnosis of hyperfibrinolysis in orthotopic liver transplantation (OLT) remains challenging. Euglobulin clot lysis time (ECLT) is not adapted to clinical situations. ROTEM is specific but seldom sensitive to hyperfibrinolysis. The Lysis Timer assesses 'Global Fibrinolytic Capacity' in citrated plasma (GFC/LT). GFC/LT associates reagents for in vitro triggering of the clot (thrombin and calcium) and its lysis (tissue-plasminogenactivator (t-PA)), turbidity signal acquisition by the Lysis Timer, and dedicated software converting the digital signal into an optical curve. A visual check of the curves was systematic to ascertain the lysis time values calculated by the software. The primary aim of this prospective observational study was to evaluate the ability of GFC/LT to recognise hyperfibrinolysis during OLT. The secondary aim was to compare its results with ROTEM maximum lysis (EXTEM ML) and with standard laboratory tests. METHODS: Thirty consecutive adult patients undergoing OLT were included (NCT03012633). Standard laboratory tests, ROTEM, GFC/LT, ECLT and fibrinolysis parameters were assayed at five sample times. RESULTS: GFC/LT was correlated with ECLT, plasmin activator inhibitor 1 antigen and activity and t-PA activity (r=0.490, 0.681, 0.643 and -0.359, respectively). Hyperfibrinolysis was defined as ECLT ≤60 min. Receiver operating characteristic curve analysis showed that GFC/LT with a threshold of 31 min detected hyperfibrinolysis with a sensitivity of 0.88 (95% CI 0.73 to 0.96), a specificity of 0.68 (95% CI 0.56 to 0.78) and an area under the curve (AUC) of 0.85 (95% CI 0.74 to 0.94). EXTEM ML >12% did not detect hyperfibrinolysis (sensitivity 0.38 (95% CI 0.24 to 0.55), specificity 0.95 (95% CI 0.86 to 0.99) and AUC 0.60 (95% CI 0.46 to 0.75)). CONCLUSIONS: GFC/LT recognised hyperfibrinolysis during OLT with a significant agreement with the other tests of fibrinolysis. TRIAL REGISTRATION NUMBER: NCT03012633.

Liver transplantation in patients with liver failure related to exertional heatstroke.

BACKGROUND & AIMS: Severe acute liver injury is a grave complication of exertional heatstroke. Liver transplantation (LT) may be a therapeutic option, but the criteria for LT and the optimal timing of LT have not been clearly established. The aim of this study was to define the profile of patients who require transplantation in this context. METHODS: This was a multicentre, retrospective study of patients admitted with a diagnosis of exertional heatstroke-related severe acute liver injury with a prothrombin time (PT) of less than 50%. A total of 24 male patients were studied. RESULTS: Fifteen of the 24 patients (median nadir PT: 35% [29.5-40.5]) improved under medical therapy alone and survived. Nine of the 24 were listed for emergency LT. At the time of registration, the median PT was 10% (5-12) and all had numerous dysfunctional organs. Five patients (nadir PT: 12% [9-12]) were withdrawn from the list because of an elevation of PT values that mainly occurred between day 2 and day 3. Ultimately, 4 patients underwent transplantation as their PT persisted at <10%, 3 days (2.75-3.25) after the onset of exertional heatstroke, and they had more than 3 organ dysfunctions. Of these 4 patients, 3 were still alive 1 year later. Histological analysis of the 4 explanted livers demonstrated massive or sub-massive necrosis, and little potential for effective mitoses, characterised by a "mitonecrotic" appearance. CONCLUSION: The first-line treatment for exertional heatstroke-related severe acute liver injury is medical therapy. LT is only a rare alternative and such a decision should not be taken too hastily. A persistence of PT <10%, without any signs of elevation after a median period of 3  days following the onset of heatstroke, was the trigger that prompted LT, was the trigger adopted in order to decide upon LT. LAY SUMMARY: Acute liver injury due to heatstroke can progress to acute liver failure with organ dysfunction despite medical treatment; in such situations, liver transplantation (LT) may offer a therapeutic option. The classic criteria for LT appear to be poorly adapted to heatstroke-related acute liver failure. We confirmed thatmedication is the first-line therapy acute liver injury caused by heatstroke, with LT only rarely necessary. A decision to perform LT should not be made hastily. Fluctuations in prothrombin time and the patient's clinical status should be considered even in the event of severe liver failure.

Impact of Systemic Vascular Resistance on the Accuracy of the Pulsioflex Device.

BACKGROUND: The accuracy of currently available devices using pulse contour analysis without external calibration for cardiac index (CI) estimation is negatively impacted by hyperdynamic states, low systemic vascular resistance (SVR), and abrupt changes in SVR. The aim of this study was to evaluate the accuracy of a new device, the Pulsioflex (Pulsion Medical System), in patients undergoing liver transplantation. METHODS: Thirty consecutive patients scheduled for liver transplantation were included. CI was monitored using pulmonary arterial catheter (CI-PAC) and Pulsioflex (CI-Pulsio). Simultaneous CI measurements were made intraoperatively at 9 different stages of the procedure. RESULTS: Two hundred seventy pairs of measurements were analyzed. The median CI-Pulsio values (3.3; interquartile range, 2.8-3.8 L·min·m) were significantly different from the median CI-PAC (4.1; interquartile range, 3.1-5.0 L·min·m; P < .0001). Bland and Altman analysis showed a mean bias of 0.8 L·min·m and 95% limit of agreement from -2.5 to 4.1 L·min·m. Percentage error was 65% (95% confidence interval, 60%-71%). Considering the variations in CI between 2 stages, the comparison between changes in CI-PAC and changes in CI-Pulsio showed a mean bias of 0.1 L·min·m and 95% limit of agreement of -2.1 to 2.2 L·min·m. When excluding changes in CI <0.5 L·min·m (154 paired analyzed), the concordance rate was 62% (95% confidence interval, 54%-70%). The bias between CI-PAC and CI-Pulsio was negatively correlated with SVR (r = -0.67, P < .0001). The bias between changes in CI-PAC and changes in CI-Pulsio was also negatively correlated with changes in SVR (r = -0.52, P < .0001). CONCLUSIONS: In patients undergoing liver transplantation, Pulsioflex does not accurately estimate CI. Its accuracy is highly impacted by SVR, and it is not able to track changes in CI when large variations in SVR occur.

Automated, continuous and non-invasive assessment of pulse pressure variations using CNAP® system.

Non-invasive respiratory variations in arterial pulse pressure using infrared-plethysmography (PPVCNAP) are able to predict fluid responsiveness in mechanically ventilated patients. However, they cannot be continuously monitored. The present study evaluated a new algorithm allowing continuous measurements of PPVCNAP (PPVCNAPauto) (CNSystem, Graz, Austria). Thirty-five patients undergoing vascular surgery were studied after induction of general anaesthesia. Stroke volume was measured using the VigileoTM/FloTracTM. Invasive pulse pressure variations were manually calculated using an arterial line (PPVART) and PPVCNAPauto was continuously displayed. PPVART and PPVCNAPauto were simultaneously recorded before and after volume expansion (500 ml hydroxyethylstarch). Subjects were defined as responders if stroke volume increased by ≥15 %. Twenty-one patients were responders. Before volume expansion, PPVART and PPVCNAPauto exhibited a bias of 0.1 % and limits of agreement from -7.9 % to 7.9 %. After volume expansion, PPVART and PPVCNAPauto exhibited a bias of -0.4 % and limits of agreement from -5.3 % to 4.5 %. A 14 % baseline PPVART threshold discriminated responders with a sensitivity of 86 % (95 % CI 64-97 %) and a specificity of 100 % (95 % CI 77-100 %). Area under the receiver operating characteristic (ROC) curve for PPVART was 0.93 (95 % CI 0.79-0.99). A 15 % baseline PPVCNAPauto threshold discriminated responders with a sensitivity of 76% (95 % CI 53-92 %) and a specificity of 93 % (95 % CI 66-99 %). Area under the ROC curves for PPVCNAPauto was 0.91 (95 % CI 0.76-0.98), which was not different from that for PPVART. When compared with PPVART, PPVCNAPauto performs satisfactorily in assessing fluid responsiveness in hemodynamically stable surgical patients.

Evolution of serum and intra-graft donor-specific anti-HLA antibodies in a patient with two consecutive liver transplantations.

The current literature suggests that anti-HLA donor-specific antibodies (DSA) may have deleterious effects on liver grafts but there is no proof that they are directly involved in the graft lesions. We report the case of a donor HLA-sensitized patient who needed a second graft 6 months after the first transplantation owing to a progressive cholestatic disease that we could finally attribute to antibody-mediated rejection (AMR). We describe the longitudinal evolution of graft function, tissue histology, serum DSA and, for the first time, intra-graft DSA after elution from biopsies.

Noninvasive assessment of macrovesicular liver steatosis in cadaveric donors based on computed tomography liver-to-spleen attenuation ratio.

Fatty liver disease, including liver steatosis, is a major health problem worldwide. In liver transplantation, macrovesicular steatosis in donor livers is a major cause of graft failure and remains difficult to assess. On one hand, several imaging modalities can be used for the assessment of liver fat, but liver biopsy, which is still considered the gold standard, may be difficult to perform in this context. On the other hand, computed tomography (CT) is commonly used by teams managing cadaveric donors to assess donors and to minimize the risk of complications in recipients. The purpose of our study was to validate the use of CT as a semiquantitative method for assessing macrovesicular steatosis in cadaveric donors with liver biopsy as a reference standard. A total of 109 consecutive cadaveric donors were included between October 2009 and May 2011. Brain death was diagnosed according to French legislation. Liver biopsy and then CT were performed on the same day to determine the degree of macrovesicular steatosis. All liver biopsies and CT scans were analyzed in a double-blinded fashion by a senior pathologist and a senior radiologist, respectively. For CT, we used the liver-to-spleen (L/S) attenuation ratio, which is a validated method for determining 30% or greater steatosis in living liver donors. Fourteen of 109 biopsies exhibited macrovesicular steatosis > 30% upon histologic analysis. A receiver operating characteristic curve was generated for the L/S ratio to identify its ability to predict significant steatosis, which was defined as >30%. A cutoff value of 0.9 for the CT L/S ratio provided a sensitivity of 79% and a specificity of 97% to detect significant steatosis.

Management of bleeding and transfusion during liver transplantation before and after the introduction of a rotational thromboelastometry-based algorithm.

Orthotopic liver transplantation (OLT) remains a potentially hemorrhagic procedure. Rotational thromboelastometry (ROTEM) is a point-of-care device used to monitor coagulation during OLT. Whether it allows blood loss and transfusions to be reduced during OLT remains controversial. Excellent correlations and predictive values have been found between ROTEM parameters and fibrinogen. We hypothesized that the use of a ROTEM-based transfusion algorithm during OLT would lead to more fibrinogen transfusion and decreased bleeding and blood transfusion. Sixty adult patients were consecutively included in a prospective, without-versus-with study: 30 in the group without ROTEM results and 30 in the group with the ROTEM-based algorithm. A small and nonsignificant increase in median fibrinogen transfusions was found for the with group (6.0 g versus 4.5 g, P = 0.50). It was not associated with a decrease in blood transfusions or in the number of patients exposed to blood products.

Benefits of intravenous lidocaine on post-operative pain and acute rehabilitation after laparoscopic nephrectomy.

BACKGROUND AND AIMS: Intravenous (I.V.) lidocaine has analgesic, antihyperalgesic and anti-inflammatory properties and is known to accelerate the return of bowel function after surgery. We evaluated the effects of I.V. lidocaine on pain management and acute rehabilitation protocol after laparoscopic nephrectomy. MATERIALS AND METHODS: A total of 47 patients scheduled to undergo laparoscopic nephrectomy were included in a two-phase observational study where I.V. lidocaine (1.5 mg/kg/h) was introduced, in the second phase, during surgery and for 24 h post-operatively. All patients underwent the same post-operative rehabilitation program. Post-operative pain scores, opioid consumption and extent of hyperalgesia were measured. Time to first flatus and 6 min walking test (6MWT) were recorded. RESULTS: Patient demographics were similar in the two phases (n = 22 in each group). Lidocaine significantly reduced morphine consumption (median [25-75% interquartile range]; 8.5 mg[4567891011121314151617] vs. 25 mg[1920212223242526272829303132]; P < 0.0001), post-operative pain scores (P < 0.05) and hyperalgesia extent on post-operative day 1-day 2-day 4 (mean ± standard deviation (SD); 1.5 ± 0.9 vs. 4.3 ± 1.2 cm (P < 0.001), 0.6 ± 0.5 vs. 2.8 ± 1.2 cm (P < 0.001) and 0.13 ± 0.3 vs. 1.2 ± 1 cm (P < 0.001), respectively). Time to first flatus (mean ± SD; 29 ± 7 h vs. 48 ± 15 h; P < 0.001) and 6MWT at day 4 (189 ± 50 m vs. 151 ± 53 m; P < 0.001) were significantly enhanced in patients with i.v. lidocaine. CONCLUSION: Intravenous (I.V.) lidocaine could reduce post-operative morphine consumption and improve post-operative pain management and post-operative recovery after laparoscopic nephrectomy. I.V. lidocaine could contribute to better post-operative rehabilitation.

Evaluation of stroke volume variations obtained with the pressure recording analytic method.

OBJECTIVE: To investigate whether stroke volume variations obtained with the pressure recording analytic method can predict fluid responsiveness in mechanically ventilated patients with circulatory failure. DESIGN: Prospective study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Thirty-five mechanically ventilated patients with circulatory failure for whom the decision to give fluid was taken by the physician were included. Exclusion criteria were: Arrhythmia, tidal volume <8 mL/kg, left ventricular ejection fraction<50%, right ventricular dysfunction, and heart rate/respiratory rate ratio <3.6. INTERVENTIONS: Fluid challenge with 500 mL of saline over 15 mins. MEASUREMENTS AND MAIN RESULTS: Stroke volume variations and cardiac output obtained with a pressure recording analytic method, pulse pressure variations, and cardiac output estimated by echocardiography were recorded before and after volume expansion. Patients were defined as responders if stroke volume obtained using echocardiography increased by ≥15% after volume expansion. Nineteen patients responded to the fluid challenge. Median [interquartile range, 25% to 75%] stroke volume variation values at baseline were not different in responders and nonresponders (10% [8-16] vs. 14% [12-16]), whereas pulse pressure variations were significantly higher in responders (17% [13-19] vs. 7% [5-10]; p < .0001). A 12.6% stroke volume variations threshold discriminated between responders and nonresponders with a sensitivity of 63% (95% confidence interval 38% to 84%) and a specificity of 69% (95% confidence interval 41% to 89%). A 10% pulse pressure variation threshold discriminated between responders and nonresponders with a sensitivity of 89% (95% confidence interval 67% to 99%) and a specificity of 88% (95% confidence interval 62% to 98%). The area under the receiver operating characteristic curves was different between pulse pressure variations (0.95; 95% confidence interval 0.82-0.99) and stroke volume variations (0.60; 95% confidence interval 0.43-0.76); p < .0001). Volume expansion-induced changes in cardiac output measured using echocardiography or pressure recording analytic method were not correlated (r = 0.14; p > .05) and the concordance rate of the direction of change in cardiac output was 60%. CONCLUSION: Stroke volume variations obtained with a pressure recording analytic method cannot predict fluid responsiveness in intensive care unit patients under mechanical ventilation. Cardiac output measured by this device is not able to track changes in cardiac output induced by volume expansion.

The ability of pulse pressure variations obtained with CNAP™ device to predict fluid responsiveness in the operating room.

BACKGROUND: Respiratory-induced pulse pressure variations obtained with an arterial line (ΔPP(ART)) indicate fluid responsiveness in mechanically ventilated patients. The Infinity® CNAP™ SmartPod® (Dräger Medical AG & Co. KG, Lübeck, Germany) provides noninvasive continuous beat-to-beat arterial blood pressure measurements and a near real-time pressure waveform. We hypothesized that respiratory-induced pulse pressure variations obtained with the CNAP system (ΔPP(CNAP)) predict fluid responsiveness as well as ΔPP(ART) predicts fluid responsiveness in mechanically ventilated patients during general anesthesia. METHODS: Thirty-five patients undergoing vascular surgery were studied after induction of general anesthesia. Stroke volume (SV) measured with the Vigileo™/FloTrac™ (Edwards Lifesciences, Irvine, CA), ΔPP(ART), and ΔPP(CNAP) were recorded before and after intravascular volume expansion (VE) (500 mL of 6% hydroxyethyl starch 130/0.4). Subjects were defined as responders if SV increased by ≥15% after VE. RESULTS: Twenty patients responded to VE and 15 did not. The correlation coefficient between ΔPP(ART) and ΔPP(CNAP) before VE was r = 0.90 (95% confidence interval [CI] = 0.84-0.96; P < 0.0001). Before VE, ΔPP(ART) and ΔPP(CNAP) were significantly higher in responders than in nonresponders (P < 0.0001). The values of ΔPP(ART) and ΔPP(CNAP) before VE were significantly correlated with the percent increase in SV induced by VE (respectively, r(2) = 0.50; P < 0.0001 and r(2) = 0.57; P < 0.0001). Before VE, a ΔPP(ART) >10% discriminated between responders and nonresponders with a sensitivity of 90% (95% CI = 69%-99%) and a specificity of 87% (95% CI = 60%-98%). The area under the receiver operating characteristic (ROC) curve was 0.957 ± 0.035 for ΔPP(ART). Before VE, a ΔPP(CNAP) >11% discriminated between responders and nonresponders with a sensitivity of 85% (95% CI = 62%-97%) and a specificity of 100% (95% CI = 78%-100%). The area under the ROC curve was 0.942 ± 0.040 for ΔPP(CNAP). There was no significant difference between the area under the ROC curve for ΔPP(ART) and ΔPP(CNAP). CONCLUSIONS: A value of ΔPP(CNAP) >11% has a sensitivity of at least 62% in predicting preload-dependent responders to VE in mechanically ventilated patients during general anesthesia.

Uncalibrated stroke volume variations are able to predict the hemodynamic effects of positive end-expiratory pressure in patients with acute lung injury or acute respiratory distress syndrome after liver transplantation.

BACKGROUND: Positive end-expiratory pressure (PEEP) may reduce cardiac output and total hepatic blood flow after liver transplantation. Pulse pressure variation is useful in predicting the PEEP-induced decrease in cardiac output. The aim of the study was to examine the relationships between stroke volume variations (SVV) obtained with the Vigileo monitor (Edwards Lifesciences, Irvine, CA), and the hemodynamic effects of PEEP. METHODS: Over 2 yr, patients presenting an acute lung injury or an acute respiratory distress syndrome in the 72 h after liver transplantation were prospectively enrolled. Patients were monitored with a pulmonary artery catheter (stroke volume) and with the Vigileo system (stroke volume and SVV). Measurements were performed in duplicate, first during zero end-expiratory pressure and then 10 min after the addition of 10 cm H2O PEEP. RESULTS: Twenty-six patients were included. Six patients were excluded from analysis. On PEEP, SVV and pulse pressure variation increased significantly and stroke volume decreased significantly. PEEP-induced changes in stroke volume measured by pulmonary artery catheter were significantly correlated with SVV (r = 0.69; P < 0.001) and pulse pressure variation on zero end-expiratory pressure (r = 0.66, P < 0.001). PEEP-induced decrease in stroke volume measured by pulmonary artery catheter > or = 15% was predicted by an SVV > 7% (sensitivity = 100%, specificity = 80%) and by a pulse pressure variation > 8% (sensitivity = 80%, specificity = 100%). PEEP-induced changes in stroke volume measured by pulmonary artery catheter and Vigileo device were correlated (r = 0.51, P < 0.005). CONCLUSIONS: SVV obtained with Vigileo monitor is useful to predict decrease in stroke volume induced by PEEP. Moreover, this device is able to track changes in stroke volume induced by PEEP.

A comparison of stroke volume variation measured by Vigileo/FloTrac system and aortic Doppler echocardiography.

BACKGROUND: The goal of this study was to compare stroke volume variation (SVV) assessed from a peripheral artery with the Vigileo/FloTrac system (SVV-FloTrac) with SVV derived close to the heart by aortic Doppler (SVV-Doppler). METHODS: Thirty patients undergoing liver transplantation underwent simultaneous SVV-FloTrac and SVV-Doppler measurements before and after intravascular volume expansion. RESULTS: SVV-FloTrac and SVV-Doppler comparison before intravascular volume expansion showed a mean bias of 0.7%, and 95% limits of agreement of -4.2% to 5.5%. The areas under the receiver operating characteristic curves generated to discriminate responders and nonresponders to intravascular volume expansion were not different for SVV-FloTrac and SVV-Doppler. CONCLUSIONS: SVV-FloTrac and SVV-Doppler measurements show acceptable bias and limits of agreement, and similar performance in terms of fluid responsiveness in patients undergoing liver transplantation.

Selective targeting of synthetic antioxidants to mitochondria: towards a mitochondrial medicine for neurodegenerative diseases?

Mitochondria are the major source of superoxide, and are responsible for activating apoptosis and oxidative damage during acute neuronal cell death and neurodegenerative disorders like Alzheimer and Parkinson diseases. While the molecular mechanisms by which mitochondrial oxidative stress triggers apoptosis are still investigated, attempts to achieve neuroprotection using antioxidant molecules have already been successful in several models of neuronal cell death. To increase the availability of antioxidant drugs at the mitochondrial level within cells, Michael P. Murphy recently proposed to covalently couple antioxidant molecules to a membrane-permeable lipophilic cation serving as carrier. Since mitochondria maintain at rest a potential of -180 mV, the diffusible cationic moiety drives the accumulation of the complex inside the matrix towards a diffusion equilibrium: for a monovalent cationic carrier, a thousand-fold accumulation of the complex is theoretically achievable; for a divalent cation, a million-fold accumulation is expected. Such mitochondria-targeted versions of natural antioxidants have successfully been synthesized and were found to counteract the pro-apoptotic effects of exogenous oxidative insults, while having no effects in models mimicking physiological apoptosis. Based on these observations, we carried out the synthesis of targeted variants of the artificial free radical scavengers 4-hydroxy-2,2,6,6-tetramethylpiperidin-N-oxide (TEMPOL) and Salen-Mn(III) complex of o-vanillin (EUK-134). Our preliminary results indicate that these targeted compounds, while delaying apoptosis after an exogenous oxidative insult, are not more active than their untargeted variants. This questions the general efficiency of the targeting procedure used and/or suggests that the main pro-apoptotic effector targets of exogenous oxidative insults are not located within mitochondria.