Peri-operative management of pheochromocytoma with intravenous urapidil to prevent hemodynamic instability: A 17-year experience.

BACKGROUND AND AIMS: Surgery for pheochromocytoma (PCC) can cause excessive catecholamine release with severe hypertension. Alpha blockade is the mainstay of preoperative management. The aim of this study was to evaluate the efficacy and tolerance of intra-venous (IV) urapidil, a competitive short acting α1 receptor antagonist, in the prevention of peri-operative hemodynamic instability of patients with PCC. MATERIAL AND METHODS: This retrospective observational study included 75 patients (79 PCC) for PCC removal surgery from 2001 to 2017 at the Bordeaux University Hospital. They received, 3 days before surgery, continuous intravenous infusion of urapidil with stepwise increase to the maximum tolerated dose. Urapidil was maintained during the procedure and stopped after clamping the adrenal vein. Plasma catecholamine concentrations were measured during surgery. Hypertensive peaks (SAP >160 mmHg) and tachycardia >100 beats/min were treated with boluses of nicardipine 2 mg and esmolol 0.5 mg/kg. RESULTS: We recorded 20/79 (25%) cases with systolic arterial pressure (SAP) >180 mmHg. Only 11/79 (14%) had hypotension with SAP <80 mmHg. Peaks of catecholamine secretions were observed preferentially during peritoneal insufflation and tumor dissection (P < 0.05). A correlation was found between tumor size (mm) and the highest norepinephrine levels [r = 0.288, P = 0.015], and between hypertensive peaks (mmHg) and the highest norepinephrine levels [r = 0.45, P = 0.017]. No mortality was reported. The median [range] postoperative hospital stay was 4 [2-9] days. CONCLUSION: IV urapidil limits hypertensive and hypotensive peaks during PCC surgery, and corresponds to surgical imperatives allowing a short hospital stay, due to its "on-off" effect.

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.

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.

High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial.

IMPORTANCE: Enteral administration of immune-modulating nutrients (eg, glutamine, omega-3 fatty acids, selenium, and antioxidants) has been suggested to reduce infections and improve recovery from critical illness. However, controversy exists on the use of immune-modulating enteral nutrition, reflected by lack of consensus in guidelines. OBJECTIVE: To determine whether high-protein enteral nutrition enriched with immune-modulating nutrients (IMHP) reduces the incidence of infections compared with standard high-protein enteral nutrition (HP) in mechanically ventilated critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: The MetaPlus study, a randomized, double-blind, multicenter trial, was conducted from February 2010 through April 2012 including a 6-month follow-up period in 14 intensive care units (ICUs) in the Netherlands, Germany, France, and Belgium. A total of 301 adult patients who were expected to be ventilated for more than 72 hours and to require enteral nutrition for more than 72 hours were randomized to the IMHP (n = 152) or HP (n = 149) group and included in an intention-to-treat analysis, performed for the total population as well as predefined medical, surgical, and trauma subpopulations. INTERVENTIONS: High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome measure was incidence of new infections according to the Centers for Disease Control and Prevention (CDC) definitions. Secondary end points included mortality, Sequential Organ Failure Assessment (SOFA) scores, mechanical ventilation duration, ICU and hospital lengths of stay, and subtypes of infections according CDC definitions. RESULTS: There were no statistically significant differences in incidence of new infections between the groups: 53% (95% CI, 44%-61%) in the IMHP group vs 52% (95% CI, 44%-61%) in the HP group (P = .96). No statistically significant differences were observed in other end points, except for a higher 6-month mortality rate in the medical subgroup: 54% (95% CI, 40%-67%) in the IMHP group vs 35% (95% CI, 22%-49%) in the HP group (P = .04), with a hazard ratio of 1.57 (95% CI, 1.03-2.39; P = .04) for 6-month mortality adjusted for age and Acute Physiology and Chronic Health Evaluation II score comparing the groups. CONCLUSIONS AND RELEVANCE: Among adult patients breathing with the aid of mechanical ventilation in the ICU, IMHP compared with HP did not improve infectious complications or other clinical end points and may be harmful as suggested by increased adjusted mortality at 6 months. These findings do not support the use of IMHP nutrients in these patients. TRIAL REGISTRATION: trialregister.nl Identifier: NTR2181.

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.

Subclavian central venous catheter-related thrombosis in trauma patients: incidence, risk factors and influence of polyurethane type.

INTRODUCTION: The incidence of deep venous thrombosis (DVT) related to a central venous catheter varies considerably in ICUs depending on the population included. The aim of this study was to determine subclavian central venous catheter (SCVC)-related DVT risk factors in severely traumatized patients with regard to two kinds of polyurethane catheters. METHODS: Critically ill trauma patients needing a SCVC for their usual care were prospectively included in an observational study. Depending on the month of inclusion, patients received one of the two available products in the emergency unit: either an aromatic polyurethane SCVC or an aliphatic polyurethane SCVC. Patients were screened weekly by ultrasound for SCVC-related DVT. Potential risk factors were collected, including history-related, trauma-related and SCVC-related characteristics. RESULTS: A total of 186 patients were included with a median Injury Severity Sore of 30 and a high rate of severe brain injuries (21% of high intracranial pressure). Incidence of SCVC-related DVT was 37% (95% confidence interval: 26 to 40) in patients or 20/1,000 catheter-days. SCVC-related DVT occurred within 8 days in 65% of cases. There was no significant difference in DVT rates between the aromatic polyurethane and aliphatic polyurethane SCVC groups (38% vs. 36%). SCVC-related DVT independent risk factors were age>30 years, intracranial hypertension, massive transfusion (>10 packed red blood cell units), SCVC tip position in the internal jugular or in the innominate vein, and ipsilateral jugular catheter. CONCLUSION: SCVC-related DVT concerned one-third of these severely traumatized patients and was mostly clinically silent. Incidence did not depend on the type of polyurethane but was related to age>30 years, intracranial hypertension or misplacement of the SCVC. Further studies are needed to assess the cost-effectiveness of routine screening in these patients in whom thromboprophylaxis may be hazardous.

Predicting fluid responsiveness during infrarenal aortic cross-clamping in pigs.

OBJECTIVE: Infrarenal aortic cross-clamping (ACC) induces hemodynamic disturbances that may affect respiratory-induced variations in stroke volume and, therefore, affect the ability of dynamic parameters such as pulse-pressure variation (PPV) to predict fluid responsiveness. Since this issue has not been investigated yet to authors' knowledge, the hypothesis was tested that ACC may change PPV and impair its ability to predict fluid responsiveness. DESIGN: Prospective laboratory experiment. SETTING: A university research laboratory. PARTICIPANTS: Nineteen anesthetized and mechanically ventilated pigs. INTERVENTIONS: Two courses of volume expansion were performed using 500 mL of saline before and during ACC. Animals were monitored using a systemic arterial catheter, and a pulmonary arterial catheter (stroke volume, central venous pressure, pulmonary arterial occlusion pressure). Animals were defined as responders to volume expansion if stroke volume increased ≥ 15%. RESULTS: Before ACC, 13 animals were responders. Fluid responsiveness was predicted by a PPV ≥ 14% with a sensitivity of 77% (95% CI = 46%-95%) and a specificity of 83% (95% CI = 36%-97%). The area under the receiver operating characteristic curve was 0.90(95% CI = 0.67-0.99) and was higher than those generated for central venous pressure and pulmonary arterial occlusion pressure. ACC induced an increase in PPV (p<0.0005). During ACC, 8 animals were responders. An 18% PPV threshold discriminated between responders and non-responders to volume expansion, with a sensitivity of 87% (95% CI = 47%-98%) and a specificity of 54% (95% CI = 23%-83%). The area under the receiver operating characteristic curve was 0.72 (95% CI = 0.47-0.90) and was not different from those generated for central venous pressure and pulmonary arterial occlusion pressure. CONCLUSIONS: ACC induced a significant increase in PPV and reduced its ability to predict fluid responsiveness.

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.

Impact of norepinephrine on the relationship between pleth variability index and pulse pressure variations in ICU adult patients.

INTRODUCTION: Pleth Variability Index (PVI) is an automated and continuous calculation of respiratory variations in the perfusion index. PVI correlates well with respiratory variations in pulse pressure (ΔPP) and is able to predict fluid responsiveness in the operating room. ICU patients may receive vasopressive drugs, which modify vascular tone and could affect PVI assessment. We hypothesized that the correlation between PVI and ΔPP and the ability of PVI to identify patients with ΔPP > 13% is dependent on norepinephrine (NE) use. METHODS: 67 consecutive mechanically ventilated patients in the ICU were prospectively included. Three were excluded. The administration and dosage of NE, heart rate, mean arterial pressure, PVI and ΔPP were measured simultaneously. RESULTS: In all patients, the correlation between PVI and ΔPP was weak (r2 = 0.21; p = 0.001). 23 patients exhibited a ΔPP > 13%. A PVI > 11% was able to identify patients with a ΔPP > 13% with a sensitivity of 70% (95% confidence interval: 47%-87%) and a specificity of 71% (95% confidence interval: 54%-84%). The area under the curve was 0.80 ± 0.06. 35 patients (53%) received norepinephrine (NE(+)). In NE(+) patients, PVI and ΔPP were not correlated (r2 = 0.04, p > 0.05) and a PVI > 10% was able to identify patients with a ΔPP > 13% with a sensitivity of 58% (95% confidence interval: 28%-85%) and a specificity of 61% (95% confidence interval:39%-80%). The area under the ROC (receiver operating characteristics) curve was 0.69 ± 0.01. In contrast, NE(-) patients exhibited a correlation between PVI and ΔPP (r2 = 0.52; p < 0.001) and a PVI > 10% was able to identify patients with a ΔPP > 13% with a sensitivity of 100% (95% confidence interval: 71%-100%) and a specificity of 72% (95% confidence interval: 49%-90%). The area under the ROC curve was 0.93 ± 0.06 for NE(-) patients and was significantly higher than the area under the ROC curve for NE(+) patients (p = 0.02). CONCLUSIONS: Our results suggest that in mechanically ventilated adult patients, NE alters the correlation between PVI and ΔPP and the ability of PVI to predict ΔPP > 13% in ICU patients.

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.

Chronic hypoxia-induced alterations in mitochondrial energy metabolism are not reversible in rat heart ventricles.

Chronic hypoxia alters mitochondrial energy metabolism. In the heart, oxidative capacity of both ventricles is decreased after 3 weeks of chronic hypoxia. The aim of this study was to evaluate the reversal of these metabolic changes upon normoxia recovery. Rats were exposed to a hypobaric environment for 3 weeks and then subjected to a normoxic environment for 3 weeks (normoxia-recovery group) and compared with rats maintained in a normoxic environment (control group). Mitochondrial energy metabolism was differentially examined in both left and right ventricles. Oxidative capacity (oxygen consumption and ATP synthesis) was measured in saponin-skinned fibers. Activities of mitochondrial respiratory chain complexes and antioxidant enzymes were measured on ventricle homogenates. Morphometric analysis of mitochondria was performed on electron micrographs. In normoxia-recovery rats, oxidative capacities of right ventricles were decreased in the presence of glutamate or palmitoyl carnitine as substrates. In contrast, oxidation of palmitoyl carnitine was maintained in the left ventricle. Enzyme activities of complexes III and IV were significantly decreased in both ventricles. These functional alterations were associated with a decrease in numerical density and an increase in size of mitochondria. Finally, in the normoxia-recovery group, the antioxidant enzyme activities (catalase and glutathione peroxidase) increased. In conclusion, alterations of mitochondrial energy metabolism induced by chronic hypoxia are not totally reversible. Reactive oxygen species could be involved and should be investigated under such conditions, since they may represent a therapeutic target.

Time course of mitochondrial metabolism alterations to repeated injections of bupivacaine in rat muscle.

PURPOSE: Bupivacaine-induced myotoxicity is associated with mitochondrial bioenergetic alterations. The impact of the duration of bupivacaine treatment on mitochondrial energy production remains undetermined. Here, we assessed, in vivo, the alteration of mitochondrial metabolism following different durations of bupivacaine exposure (40, 56, or 112 hr) that correspond to 5, 7, or 14 repeated injections of 0.25% bupivacaine, respectively. METHODS: Rats were divided randomly into seven different groups: one control group (no catheter); three groups with normal saline injections (1 mL x kg(-1)) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr, respectively; and three groups with 0.25% bupivacaine injections (1 mL x kg(-1)) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr. Psoas and gracilis muscle samples located within the bupivacaine infusion-diffusion space were investigated. To estimate mitochondrial respiratory capacity, the protein content of the mitochondrial respiratory chain apparatus was evaluated by measuring citrate synthase activity. To measure mitochondrial respiratory function, adenosine diphosphate-stimulated oxygen consumption was measured by polarography in saponin-skinned muscle fibres using glutamate-malate or succinate as energy substrates. RESULTS: In psoas and gracilis muscles, saline solution had no effect on the two mitochondrial parameters. Bupivacaine induced a significant decrease in the citrate synthase activity in psoas (r(2) = 0.74; P < 0.001) and gracilis muscle (r(2) = 0.52; P < 0.001), and there was a significant decrease in the adenosine diphosphate-stimulated oxygen consumption using glutamate or succinate as substrates in both muscles (P < 0.001). CONCLUSIONS: The severity of bupivacaine-induced myotoxicity is closely linked to the duration of bupivacaine exposure in the muscle fibres located close to the catheter tip.

Clinical mortality risk factors of variceal upper gastrointestinal bleeding in a Malagasy surgical intensive care unit.

BACKGROUND: Variceal upper gastrointestinal bleeding is a dreadful complication of portal hypertension with a significant morbidity and mortality. Different prognostic scores can be used. However, in the local context of Madagascar, the completion of paraclinical investigations can be delayed by the limited financial means of patients. Hence, determining clinical mortality risk factors of variceal upper gastrointestinal bleeding could be interesting. The aim of the study was to evaluate the clinical mortality risk factors of variceal gastrointestinal bleeding (VUGIB). METHOD: An observational, cohort retrospective study was conducted over an 8-year period (2010-2017), at the surgical intensive care unit of the J.R. Andrianavalona University Hospital, Antananarivo, in patients admitted for VUGIB confirmed by upper gastrointestinal endoscopy and whose clinical examination was performed at admission. The primary endpoint was intensive care unit (ICU) mortality. Univariate analysis and multivariate logistic regression analysis were performed to identify risk factors for ICU mortality, with OR defining odds ratio. A p value <0.05 was considered significant. RESULTS: 1920 patients were admitted for gastrointestinal bleeding of any digestive causes; the source of bleeding was variceal in 269 patients (14%). The predominantly male population (sex ratio = 2.5), aged 47.1 ± 13.7 years was mostly American Society of Anesthesiologists (ASA) 1 classification (58.4%). In 56.5% of patients, the gastrointestinal bleeding had not occurred before. The mortality rate was 16.0%. Three major clinical factors of mortality were identified: previous endoscopic band variceal ligation (OR = 12.57 [2.18-72.58], p = 0.005), tachycardia >120 bpm (OR = 2.91 [1.04-8.14], p = 0.041), and ascites (OR = 3.80 [1.85-7.81], p < 0.001). CONCLUSION: Upper gastrointestinal bleeding may be life-threatening. The mortality scores are certainly useful; however, the identification of clinical factors is interesting in countries like Madagascar, pending the results of paraclinical investigations.

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.

Erythropoietin protects against local anesthetic myotoxicity during continuous regional analgesia.

BACKGROUND: Local anesthetics offer the benefits of extended analgesia with greater patient satisfaction and faster rehabilitation compared with intravenous morphine. These benefits, however, can be offset by adverse iatrogenic muscle pain caused by bupivacaine. Here, the authors describe the mechanisms of local anesthetic-induced myotoxicity and a partial protective effect of recombinant human erythropoietin (rhEPO). METHODS: The authors developed a rat analgesia model with femoral nerve catheter and a cell culture model of human skeletal muscle myoblasts to study local anesthetic effects. Rats were randomly assigned to four different groups: daily intraperitoneal injection with 5,000 U/kg rhEPO or saline coupled to a perineural catheter injection with 1 ml/kg bupivacaine, 0.25%, or saline. In psoas rat muscle, oxygen consumption rates were measured using a Clark-type electrode in saponin-skinned fibers. Mitochondrial adenosine triphosphate synthesis rates were determined by bioluminescence. Enzymatic activity of mitochondrial respiratory chain complexes was measured on tissue homogenates using spectrophotometric procedures, and mitochondrial morphology was analyzed by transmission electron microscopy. In addition, the interaction between bupivacaine and rhEPO was investigated on human skeletal muscle myoblasts by fluorescence microscopy using mitotracker green and using the lipophilic cation JC-1. RESULTS: Bupivacaine caused impairment of mitochondrial structure and bioenergetics in rats. Human myoblasts treated with bupivacaine showed a dose-dependent decrease in mitochondrial membrane potential associated with unusual morphologies. Impairment of mitochondrial bioenergetics was prevented partially by the use of rhEPO coadministered with bupivacaine. CONCLUSIONS: The authors demonstrated a dose- and time-dependent protective effect of rhEPO against bupivacaine-induced myotoxicity in regional analgesia.

Age-dependent bupivacaine-induced muscle toxicity during continuous peripheral nerve block in rats.

BACKGROUND: Regional blocks improve postoperative analgesia and postoperative rehabilitation in children and adult patients. Continuous peripheral nerve blocks have been proposed as safe and effective techniques for postoperative pain relief and chronic pain therapy, particularly in small children. Few clinical reports have described myotoxicity induced by bupivacaine in these young patients, in contrast with a larger number of observations in adults. Here, the authors addressed this issue by a comparative evaluation of bupivacaine-induced myotoxicity in young versus adult rats. METHODS: Femoral nerve block catheters were inserted in male Wistar rats. Young (3-week-old) and adult (12-week-old) rats were randomly assigned to received seven injections (1 ml/kg) of 0.25% bupivacaine (n = 6 per experiment) or isotonic saline (n = 6 per experiment) at 8-h intervals. Rats were killed 8 h after the last injection. Psoas muscle adjacent to the femoral nerve was quickly dissected. Oxygen consumption rates were measured in saponin-skinned fibers, mitochondrial adenosine triphosphate synthesis rates were determined by bioluminescence, and citrate synthase activity was determined by spectrophotometry. Muscle ultrastructural damage was also examined and scored as normal, focal disruption, moderate disruption, or extreme disruption of the sarcomeres. RESULTS: Bupivacaine caused a reduction of mitochondrial adenosine triphosphate synthesis rate, a decrease of citrate synthase activity, and muscle ultrastructural damages. Young rats treated with bupivacaine showed more severe alterations of mitochondrial bioenergetics and muscle ultrastructure. CONCLUSIONS: These findings demonstrate that bupivacaine-induced myotoxicity can be explained by mitochondrial bioenergetics alterations, which are more severe in young rats.

Changes in stroke volume induced by passive leg raising in spontaneously breathing patients: comparison between echocardiography and Vigileo/FloTrac device.

INTRODUCTION: Passive leg raising (PLR) is a simple reversible maneuver that mimics rapid fluid loading and increases cardiac preload. The effects of this endogenous volume expansion on stroke volume enable the testing of fluid responsiveness with accuracy in spontaneously breathing patients. However, this maneuver requires the determination of stroke volume with a fast-response device, because the hemodynamic changes may be transient. The Vigileo monitor (Vigileo; Flotrac; Edwards Lifesciences, Irvine, CA, USA) analyzes systemic arterial pressure wave and allows continuous stroke volume monitoring. The aims of this study were (i) to compare changes in stroke volume induced by passive leg raising measured with the Vigileo device and with transthoracic echocardiography and (ii) to compare their ability to predict fluid responsiveness. METHODS: Thirty-four patients with spontaneous breathing activity and considered for volume expansion were included. Measurements of stroke volume were obtained with transthoracic echocardiography (SV-TTE) and with the Vigileo (SV-Flotrac) in a semi-recumbent position, during PLR and after volume expansion (500 ml saline). Patients were responders to volume expansion if SV-TTE increased > or = 15%. RESULTS: Four patients were excluded. No patients received vasoactive drugs. Seven patients presented septic hypovolemia. PLR-induced changes in SV-TTE and in SV-Flotrac were correlated (r2 = 0.56, P < 0.0001). An increase in SV-TTE > or = 13% during PLR was predictive of response to volume expansion with a sensitivity of 100% and a specificity of 80%. An increase in SV-Flotrac > or =16% during PLR was predictive of response to volume expansion with a sensitivity of 85% and a specificity of 90%. There was no difference between the area under the ROC curve for PLR-induced changes in SV-TTE (AUC = 0.96 +/- 0.03) or SV-Flotrac (AUC = 0.92 +/- 0.05). Volume expansion-induced changes in SV-TTE correlated with volume expansion-induced changes in SV-Flotrac (r2 = 0.77, P < 0.0001). In all patients, the highest plateau value of SV-TTE recorded during PLR was obtained within the first 90 s following leg elevation, whereas it was 120 s for SV-Flotrac. CONCLUSIONS: PLR-induced changes in SV-Flotrac are able to predict the response to volume expansion in spontaneously breathing patients without vasoactive support.

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.