Adjusting Acute Kidney Injury Kidney Disease: Improving Global Outcomes Urine Output Criterion for Predicted Body Weight Improves Prediction of Hospital Mortality.

BACKGROUND: Based on the Kidney Disease: Improving Global Outcomes (KDIGO) definitions, urine output, serum creatinine, and need for kidney replacement therapy are used for staging acute kidney injury (AKI). Currently, AKI staging correlates strongly with mortality and can be used as a predictive tool. However, factors associated with the development of AKI may affect its predictive ability. We tested whether adjustment for predicted (versus actual) body weight improved the ability of AKI staging to predict hospital mortality. METHODS: A total of 3279 patients who had undergone cardiac surgery in a university hospital were retrospectively analyzed. AKI was staged according to KDIGO criteria (standard staging) and after adjustment for hourly urine output adjusted by predicted body weight for each patient and each day of their hospital stay. RESULTS: The incidence of AKI (all stages) was 43% (predicted body weight adjusted) and 50% (standard staging), respectively ( P < .001). In sensitivity-specificity analyses for predicting hospital mortality, the area under the curve was significantly higher after adjustment for predicted body weight than with standard staging ( P = .002). CONCLUSIONS: Compared to standard staging, adjustment of urine output for predicted body weight increases the specificity and improves prediction of hospital mortality in patients undergoing cardiac surgery.

Relationships between training dose and record power outputs in professional road cyclists: insights and threats to validity.

Testing short-term (4-8 weeks) correlations between training dose and performance in professional road cyclists can help improve their training and performance. Multilevel mixed-modeling was used to correlate training dose (Time, Edwards' Trimp-eTRIMP, Training Stress Score-TSS, time spent in power output zones-Z1, Z2, Z3, Polarization Index-PI) and Record Power Output (RPO) over 1 minute (RPO1), 5 (RPO5), 20 (RPO20), and 40 minutes (RPO40) across four different time periods: training dose of the previous month with RPOs of the subsequent month (Monthly-analysis); training dose of the 8 weeks preceding All, Grand tours, One-day races with RPOs of these races. In Monthly-analysis, small positive relationships between all the training dose parameters, except for PI, and RPO1, RPO5, RPO20, RPO40 were found (p ≤ 0.001). In Grand tours analysis, Z3 showed a positive association with RPO40 (r: 0.45; p = 0.007, moderate) and was positively related to RPO1 and RPO5 (r between 0.32 and 0.34; p = 0.053-0.059, moderate). PI was small positively related to RPO1 (r = 0.29, p = 0.076, small). In One-day races analysis, eTRIMP was positively related to RPO5 (r = 0.30, p = 0.035, moderate), Z1 negatively related to RPO40 (r = -0.31, p = 0.031, moderate), PI positively related to RPO5 (r = 0.24, p = 0.068, small) and Z2 was negatively related to RPO20 (r = -0.29, p = 0.051, small). A certain degree of responsiveness to training dose exists in professional road cyclists. To improve RPOs an appropriate preparation pattern seems to be increasing high intensity training for Grand Tours and fostering high intensity and overall training load (eTRIMP and TSS) in a more polarized-fashion for one-day races. Systematic and precise data collection during training and racing is highly advocated.

Full and simplified assessment of left ventricular diastolic function in covid-19 patients admitted to ICU: Feasibility, incidence, and association with mortality.

PURPOSE: Left ventricular diastolic dysfunction (LVDD) is associated with poor outcomes in the intensive care unit (ICU). Nonetheless, precise reporting of LVDD in COVID-19 patients is currently lacking and assessment could be challenging. METHODS: We performed an echocardiography study in COVID-19 patients admitted to ICU with the aim to describe the feasibility of full or simplified LVDD assessment and its incidence. We also evaluated the association of LVDD or of single echocardiographic parameters with hospital mortality. RESULTS: Between 06.10.2020 and 18.02.2021, full diastolic assessment was feasible in 74% (n = 26/35) of patients receiving a full echocardiogram study. LVDD incidence was 46% (n = 12/26), while the simplified assessment produced different results (incidence 81%, n = 21/26). Nine patients with normal function on full assessment had LVDD with simplified criteria (grade I = 2; grade II = 3; grade III = 4). Nine patients were hospital-survivors (39%); the incidence of LVDD (full assessment) was not different between survivors (n = 2/9, 22%) and non-survivors (n = 10/17, 59%; p = .11). The E/e' ratio lateral was lower in survivors (7.4 [3.6] vs. non-survivors 10.5 [6.3], p = .03). We also found that s' wave was higher in survivors (average, p = .01). CONCLUSION: In a small single-center study, assessment of LVDD according to the latest guidelines was feasible in three quarters of COVID-19 patients. Non-survivors showed a trend toward greater LVDD incidence; moreover, they had significantly worse s' values (all) and higher E/e' ratio (lateral).

Impact of chronic use of heat-not-burn cigarettes on oxidative stress, endothelial dysfunction and platelet activation: the SUR-VAPES Chronic Study.

Tobacco habit still represents the leading preventable cause of morbidity and mortality worldwide. Heat-not-burn cigarettes (HNBCs) are considered as an alternative to traditional combustion cigarettes (TCCs) due to the lack of combustion and the absence of combustion-related specific toxicants. The aim of this observational study was to assess the effect of HNBC on endothelial function, oxidative stress and platelet activation in chronic adult TCC smokers and HNBC users. The results showed that both HNBC and TCC display an adverse phenotype in terms of endothelial function, oxidative stress and platelet activation. Future randomised studies are strongly warranted to confirm these data.

Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study.

BACKGROUND: Several studies have shown that heart rate control with selective beta-1 blockers in septic shock is safe. In these trials, esmolol was administered 24 h after onset of septic shock in patients who remained tachycardic. While an earlier use of beta-blockers might be beneficial, such use remains challenging due to the difficulty in distinguishing between compensatory and non-compensatory tachycardia. Therefore, the Esmosepsis study was designed to study the effects of esmolol aimed at reducing the heart rate by 20% after the initial resuscitation process in hyperkinetic septic shock patients on (1) cardiac index and (2) systemic and regional hemodynamics as well as inflammatory patterns. METHODS: Nine consecutive stabilized tachycardic hyperkinetic septic shock patients treated with norepinephrine for a minimum of 6 h were included. Esmolol was infused during 6 h in order to decrease the heart rate by 20%. The following data were recorded at hours H0 (before esmolol administration), H1-H6 (esmolol administration) and 1 h after esmolol cessation (H7): systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, central venous pressure, heart rate, PICCO transpulmonary thermodilution, sublingual and musculo-cutaneous microcirculation, indocyanine green clearance and echocardiographic parameters, diuresis, lactate, and arterial and venous blood gases. RESULTS: Esmolol was infused 9 (6.4-11.6) hours after norepinephrine introduction. Esmolol was ceased early in 3 out of 9 patients due to a marked increase in norepinephrine requirement associated with a picture of persistent cardiac failure at the lowest esmolol dose. For the global group, during esmolol infusion, norepinephrine infusion increased from 0.49 (0.34-0.83) to 0.78 (0.3-1.11) µg/min/kg. The use of esmolol was associated with a significant decrease in heart rate from 115 (110-125) to 100 (92-103) beats/min and a decrease in cardiac index from 4.2 (3.1-4.4) to 2.9 (2.5-3.7) l/min/m-2. Indexed stroke volume remained unchanged. Cardiac function index and global ejection fraction also markedly decreased. Using echocardiography, systolic, diastolic as well as left and right ventricular function parameters worsened. After esmolol cessation, all parameters returned to baseline values. Lactate and microcirculatory parameters did not change while the majority of pro-inflammatory proteins decreased in all patients. CONCLUSION: In the very early phase of septic shock, heart rate reduction using fast esmolol titration is associated with an increased risk of hypotension and decreased cardiac index despite maintained adequate tissue perfusion (NCT02068287).

Association of weaning failure from mechanical ventilation with transthoracic echocardiography parameters: a systematic review and meta-analysis.

BACKGROUND: Weaning from mechanical ventilation is a challenging step during recovery from critical illness. Weaning failure or early reintubation are associated with increased morbidity and mortality, exposing patients to life-threatening complications. Cardiac dysfunction represents the most common cause of weaning failure. We conducted a systematic review and meta-analysis to evaluate the association between transthoracic echocardiographic parameters and weaning failure. METHODS: We performed a systematic search of MEDLINE and EMBASE screening for prospective studies providing echocardiographic data collected just before the beginning of spontaneous breathing trial and outcome of the weaning attempt. We primarily focused on parameters currently recommended for evaluation of left ventricular (LV) systolic or diastolic dysfunction. RESULTS: We included 11 studies in our primary analysis, which included data on LV ejection fraction (LVEF, n=10 studies) and parameters recommended for the assessment of LV diastolic function (E/e' ratio n=10; E/A ratio n=9; E wave n=8; and e' wave n=7). Weaning failure was significantly associated to a higher E/e' ratio (standardised mean difference [SMD]=1.70, 95% confidence interval [CI; 0.78-2.62]; P<0.001), lower e' wave (SMD=-1.22, 95% CI [-2.33 to -0.11]; P=0.03), and higher E wave (SMD=0.97, 95% CI [0.29-1.65]; P=0.005). We found no association between weaning failure and LVEF (SMD=-0.86, 95% CI [-1.92-0.20]; P=0.11) and E/A ratio (SMD=0.00, 95% CI [-0.30-0.31]; P=0.98). CONCLUSIONS: Weaning failure is associated with parameters indicating worse LV diastolic function (E/e', e' wave, E wave) and increased LV filling pressure (E/e' ratio). The association between weaning failure and LV systolic dysfunction as evaluated by LVEF is more unclear. More studies are needed to clarify this aspect and regarding the role of right ventricular function.

How temperature can alter the combined effects of carbon nanotubes and caffeine in the clam Ruditapes decussatus?

Nowadays, multi-walled carbon nanotubes are considered to be emerging contaminants and their impact in ecosystem has drawn special research attention, while other contaminants, such as caffeine, have more coverage in literature. Despite this, the effects of a combination of the two has yet to be evaluated, especially considering predicted temperature rise. In the present study a typical bioindicator species for marine environment, the clam Ruditapes decussatus, and classical tools, such as biomarkers and histopathological indices, were used to shed light on the species' response to these contaminants, under actual and predicted warming scenarios. The results obtained showed that both contaminants have a harmful effect at tissue level, as shown by higher histopathological index, especially in digestive tubules. Temperatures seemed to induce greater biochemical impacts than caffeine (CAF) and -COOH functionalized multi-walled carbon nanotubes (f-MWCNTs) when acting alone, namely in terms of antioxidant defences and energy reserves content, which were exacerbated when both contaminants were acting in combination (MIX treatment). Overall, the present findings highlight the complex response of clams to both pollutants, evidencing the role of temperature on clams' sensitivity, especially to mixture of pollutants.

Resuscitation with Hydroxyethyl Starch Maintains Hemodynamic Coherence in Ovine Hemorrhagic Shock.

BACKGROUND: Fluid resuscitation in hemorrhagic shock aims to restore hemodynamics and repair altered microcirculation. Hemodynamic coherence is the concordant performance of macro- and microcirculation. The present study on fluid therapy in hemorrhagic shock hypothesized that the choice of fluid (0.9% sodium chloride [saline group] or balanced 6% hydroxyethyl starch 130/0.4 [hydroxyethyl starch group]) impacts on hemodynamic coherence. METHODS: After instrumentation, 10 sheep were bled up to 30 ml/kg body weight of blood stopping at a mean arterial pressure of 30 mmHg to establish hemorrhagic shock. To reestablish baseline mean arterial pressure, they received either saline or hydroxyethyl starch (each n = 5). Hemodynamic coherence was assessed by comparison of changes in mean arterial pressure and both perfused vessel density and microvascular flow index. RESULTS: Bleeding of 23 ml/kg blood [21; 30] (median [25th; 75th percentile]) in the saline group and 24 ml/kg [22; 25] (P = 0.916) in the hydroxyethyl starch group led to hemorrhagic shock. Fluid resuscitation reestablished baseline mean arterial pressure in all sheep of the hydroxyethyl starch group and in one sheep of the saline group. In the saline group 4,980 ml [3,312; 5,700] and in the hydroxyethyl starch group 610 ml [489; 615] of fluid were needed (P = 0.009). In hemorrhagic shock perfused vessel density (saline from 100% to 83% [49; 86]; hydroxyethyl starch from 100% to 74% [61; 80]) and microvascular flow index (saline from 3.1 [2.5; 3.3] to 2.0 [1.6; 2.3]; hydroxyethyl starch from 2.9 [2.9; 3.1] to 2.5 [2.3; 2.7]) decreased in both groups. After resuscitation both variables improved in the hydroxyethyl starch group (perfused vessel density: 125% [120; 147]; microvascular flow index: 3.4 [3.2; 3.5]), whereas in the saline group perfused vessel density further decreased (64% [62; 79]) and microvascular flow index increased less than in the hydroxyethyl starch group (2.7 [2.4; 2.8]; both P < 0.001 for saline vs. hydroxyethyl starch). CONCLUSIONS: Resuscitation with hydroxyethyl starch maintained coherence in hemorrhagic shock. In contrast, saline only improved macro- but not microcirculation. Hemodynamic coherence might be influenced by the choice of resuscitation fluid.

Systolic-dicrotic notch pressure difference can identify tachycardic patients with septic shock at risk of cardiovascular decompensation following pharmacological heart rate reduction.

BACKGROUND: During sepsis, heart rate (HR) reduction could be a therapeutic target, but identification of responders (non-compensatory tachycardia) and non-responders (compensatory for 'fixed' stroke volume [SV]) is challenging. We tested the ability of the difference between systolic and dicrotic pressure (SDPdifference), which reflects the coupling between myocardial contractility and a given afterload, in discriminating the origin of tachycardia. METHODS: In this post hoc analysis of 45 patients with septic shock with persistent tachycardia, we characterised features of haemodynamic response focusing on SDPdifference, classifying patients according to variations in arterial dP/dtmax after 4 h of esmolol administration to maintain HR <95 beats min-1. A cut-off value of 0.9 mm Hg ms-1 was used for group allocation. RESULTS: After reducing HR, arterial dP/dtmax remained above the cut-off in 23 patients, whereas it decreased below the cut-off in 22 patients (from 0.99 [0.37] to 0.63 [0.16] mm Hg ms-1; mean [SD], P<0.001). At baseline, patients with decreased dP/dtmax after esmolol had lower SDPdifference than those with higher dP/dtmax (40 [19] vs 53 [16] mm Hg, respectively; P=0.01). The SDPdifference remained unchanged after esmolol in the higher dP/dtmax group (49 [16] mm Hg), whereas it decreased significantly in patients with lower dP/dtmax (29 [11] mm Hg; P<0.001). In the latter, the HR reduction resulted in a significant cardiac output reduction with unchanged SV, whereas in patients with higher dP/dtmax SV increased (from 48 [12] to 67 [14] ml; P<0.001) with maintained cardiac output. CONCLUSIONS: A decrease in SDPdifference could discriminate between compensatory and non-compensatory tachycardia, revealing a covert loss of myocardial contractility not detected by conventional echocardiographic parameters and deteriorating after HR reduction with esmolol. CLINICAL TRIAL REGISTRATION: NCT02188888.

Renewable Polysaccharides Micro/Nanostructures for Food and Cosmetic Applications.

The worldwide diffusion of nanotechnologies into products nowadays has completely revolutionized human life, providing novel comfort and benefits. Their inclusion in food and cosmetic has a heavy impact over the market, allowing the development of higher value products with enhanced properties. Natural origin polymers and in particular polysaccharides represent a versatile platform of materials for the development of micro/nanostructured additives for food and cosmetic products due to their chemical versatility, biocompatibility, and abundance. Here, we review the current applications of polysaccharides-based micro/nanostructures, taking into consideration the precursors' production, isolation, and extraction methods and highlighting the advantages, possible drawbacks, and market diffusion.

The Effect of Propofol and Dexmedetomidine Sedation on Norepinephrine Requirements in Septic Shock Patients: A Crossover Trial.

OBJECTIVES: Propofol-based sedation may increase hemodynamic instability by decreasing vascular tone and venous return. Incremental exogenous catecholamines doses may be required to counteract such effects, aggravating the deleterious effects of sympathetic overstimulation. α-2 adrenergic agonists have been reported to decrease norepinephrine requirements in experimental septic shock. The aim of the present study is to test the hypothesis that switching from sedation with propofol to the α-2 agonist dexmedetomidine may decrease norepinephrine doses in septic shock. DESIGN: Prospective open-label crossover study. SETTINGS: University hospital, ICU. PATIENTS: Thirty-eight septic shock patients requiring norepinephrine to maintain adequate mean arterial pressure and needing deep sedation with propofol and remifentanil to maintain a Richmond Agitation-Sedation Scale score between -3 and -4. INTERVENTIONS: An initial set of measurements including hemodynamics, norepinephrine doses, and depth of sedation were obtained during sedation with propofol. Propofol was then replaced by dexmedetomidine and a second set of data was obtained after 4 hours of dexmedetomidine infusion. Sedation was switched back to propofol, and a final set of measurements was obtained after 8 hours. A Richmond Agitation-Sedation Scale score between -3 and -4 was maintained during the study period. MEASUREMENTS AND MAIN RESULTS: Norepinephrine requirements decreased from 0.69 ± 0.72 µg/kg/min before dexmedetomidine to 0.30 ± 0.25 µg/kg/min 4 hours after dexmedetomidine infusion, increasing again to 0.42 ± 0.36 µg/kg/min while on propofol 8 hours after stopping dexmedetomidine (p < 0.005). Dexmedetomidine dosage was 0.7 ± 0.2 µg/kg/hr. Before and after dexmedetomidine infusion, sedative doses remained unchanged (propofol 2.6 ± 1.2 vs 2.6 ± 1.2 mg/kg/hr; p = 0.23 and remifentanil 1.27 ± 0.17 vs 1.27 ± 0.16 µg/kg/hr; p = 0.52, respectively). Richmond Agitation-Sedation Scale was -4 (-4 to -3) before, -4 (-4 to -3) during, and -4 (-4 to -4) after dexmedetomidine (p = 0.07). CONCLUSIONS: For a comparable level of sedation, switching from propofol to dexmedetomidine resulted in a reduction of catecholamine requirements in septic shock patients.

Targeting Pseudomonas aeruginosa in the Sputum of Primary Ciliary Dyskinesia Patients with a Combinatorial Strategy Having Antibacterial and Anti-Virulence Potential.

In primary ciliary dyskinesia (PCD) patients, Pseudomonas aeruginosa is a major opportunistic pathogen, frequently involved in chronic infections of the lower airways. Infections by this bacterial species correlates with a worsening clinical prognosis and recalcitrance to currently available therapeutics. The antimicrobial peptide, lin-SB056-1, in combination with the cation chelator ethylenediaminetetraacetic acid (EDTA), was previously demonstrated to be bactericidal against P. aeruginosa in an artificial sputum medium. The purpose of this study was to validate the anti-P. aeruginosa activity of such a combination in PCD sputum and to evaluate the in vitro anti-virulence effects of EDTA. In combination with EDTA, lin-SB056-1 was able to significantly reduce the load of endogenous P. aeruginosa ex vivo in the sputum of PCD patients. In addition, EDTA markedly reduced the production of relevant bacterial virulence factors (e.g., pyocyanin, proteases, LasA) in vitro by two representative mucoid strains of P. aeruginosa isolated from the sputum of PCD patients. These results indicate that the lin-SB056-1/EDTA combination may exert a dual antimicrobial and anti-virulence action against P. aeruginosa, suggesting a therapeutic potential against chronic airway infections sustained by this bacterium.

A new complimentary web-based tool for manual analysis of microcirculation videos: Validation of the Capillary Mapper against the current gold standard AVA 3.2.

OBJECTIVE: The aim of the current study was to compare a newly developed web-based freely accessible software program for manual analysis of the microcirculation, the Capillary Mapper (CM), with AVA 3.2 software (AVA; MicroVision Medical B.V., Amsterdam, The Netherlands), which is the current gold standard for analysis of microcirculation videos. METHODS: A web-based software program was developed, which enables manual analysis of videos of the microcirculation to be carried out according to recommendations of the 2018 consensus conference. A set of 50 high quality microcirculation videos was analyzed with AVA and CM with respect to total vessel density, perfused vessel density, proportion of perfused vessels, and the microvascular flow index. RESULTS: Comparison of the mean values derived from manual analysis with CM and AVA revealed no significant differences in microcirculatory variables. Analysis according to Bland and Altman revealed an acceptable bias between manual analysis with the CM and AVA for all variables tested with sufficient limits of agreement. The analysis of intraclass correlation showed "excellent" agreement for all microcirculatory variables analyzed. CONCLUSIONS: The newly developed CM was successfully validated for manual analyses of microcirculation videos against the current gold standard, the software AVA 3.2.

Landiolol for managing atrial fibrillation in intensive care.

Landiolol is an injectable ultrashort acting beta-blocker with high beta1 selectivity indicated for heart rate control of atrial fibrillation in the emergency and critical care setting. Accordingly, landiolol is associated with a significantly reduced risk of arterial hypotension and negative inotropic effects. Based on this particular profile along with the clinical experience in Japan for more than a decade landiolol represents a promising agent for the management of elevated heart rate and atrial fibrillation in intensive care patients even with catecholamine requirements. This article provides a review and perspective of landiolol for heart rate control in intensive care patients based on the current literature.

Levosimendan for patients with severely reduced left ventricular systolic function and/or low cardiac output syndrome undergoing cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Previous studies have shown beneficial effects of levosimendan in high-risk patients undergoing cardiac surgery. Two large randomized controlled trials (RCTs), however, showed no advantages of levosimendan. METHODS: We performed a systematic review and meta-analysis (MEDLINE and Embase from inception until March 30, 2017), investigating whether levosimendan offers advantages compared with placebo in high-risk cardiac surgery patients, as defined by preoperative left ventricular ejection fraction (LVEF) ≤ 35% and/or low cardiac output syndrome (LCOS). The primary outcomes were mortality at longest follow-up and need for postoperative renal replacement therapy (RRT). Secondary postoperative outcomes investigated included myocardial injury, supraventricular arrhythmias, development of LCOS, acute kidney injury (AKI), duration of mechanical ventilation, intensive care unit and hospital lengths of stay, and incidence of hypotension during drug infusion. RESULTS: Six RCTs were included in the meta-analysis, five of which investigated only patients with LVEF ≤ 35% and one of which included predominantly patients with LCOS. Mortality was similar overall (OR 0.64 [0.37, 1.11], p = 0.11) but lower in the subgroup with LVEF < 35% (OR 0.51 [0.32, 0.82], p = 0.005). Need for RRT was reduced by levosimendan both overall (OR 0.63 [0.42, 0.94], p = 0.02) and in patients with LVEF < 35% (OR 0.55 [0.31, 0.97], p = 0.04). Among secondary outcomes, we found lower postoperative LCOS in patients with LVEF < 35% receiving levosimendan (OR 0.49 [0.27, 0.89], p = 0.02), lower overall AKI (OR 0.62 [0.42, 0.92], p = 0.02), and a trend toward lower mechanical support, both overall (p = 0.07) and in patients with LVEF < 35% (p = 0.05). CONCLUSIONS: Levosimendan reduces mortality in patients with preoperative severely reduced LVEF but does not affect overall mortality. Levosimendan reduces the need for RRT after high-risk cardiac surgery.

Provision of physiological data and reference values in awake and anaesthetized female sheep aged 6-12 months.

OBJECTIVE: To provide physiological data and reference values in awake and anaesthetized sheep aged 6-12 months. STUDY DESIGN: Descriptive study. ANIMALS: Data from 260 female sheep of the species Ovis orientalis aries aged 6-12 months were extracted from 10 experimental trials. METHODS: Data from pulmonary arterial thermodilution in awake (cohort 1; n = 109) and anaesthetized animals (cohort 2; n = 81), and transpulmonary thermodilution in anaesthetized animals (cohort 3; n = 70) were analysed. General anaesthesia was induced by intramuscular injection of S-ketamine and midazolam and maintained by inhaled isoflurane. Standard laboratory variables (blood gas and clinical chemistry) were assessed. RESULTS: A total of 7553 single data entries from 260 healthy sheep were included. Measurement errors or invalid data documentation meant that 313 data entries (4.1%) were excluded. A small confidence interval for median values was calculated for nearly all variables. The median body weight was 39.8 kg (2.5-97.5th percentile 30.6-48.1 kg). A set of reference values (2.5-97.5th percentiles) is provided for common cardiopulmonary and laboratory variables. Compared to awake animals, haemodynamic variables were markedly influenced by anaesthesia, as reflected by a considerably lower stroke volume index in anaesthetized sheep. There were also differences in stroke volume index between the cohorts of pulmonary artery and transpulmonary thermodilution. CONCLUSIONS AND CLINICAL RELEVANCE: The present work presents a large and consistent database of a variety of physiological variables measured in healthy juvenile female sheep. The data appear to be robust and allow the establishment of standardized inclusion criteria for experimental studies and may help to better evaluate past, present and future research. Differences between pulmonary artery and transpulmonary thermodilution should be assessed in future studies.

Comparison Between Doppler-Echocardiography and Uncalibrated Pulse Contour Method for Cardiac Output Measurement: A Multicenter Observational Study.

OBJECTIVES: Echocardiography and pulse contour methods allow, respectively, noninvasive and less invasive cardiac output estimation. The aim of the present study was to compare Doppler echocardiography with the pulse contour method MostCare for cardiac output estimation in a large and nonselected critically ill population. DESIGN: A prospective multicenter observational comparison study. SETTING: The study was conducted in 15 European medicosurgical ICUs. PATIENTS: We assessed cardiac output in 400 patients in whom an echocardiographic evaluation was performed as a routine need or for cardiocirculatory assessment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One echocardiographic cardiac output measurement was compared with the corresponding MostCare cardiac output value per patient, considering different ICU admission categories and clinical conditions. For statistical analysis, we used Bland-Altman and linear regression analyses. To assess heterogeneity in results of individual centers, Cochran Q, and the I statistics were applied. A total of 400 paired echocardiographic cardiac output and MostCare cardiac output measures were compared. MostCare cardiac output values ranged from 1.95 to 9.90 L/min, and echocardiographic cardiac output ranged from 1.82 to 9.75 L/min. A significant correlation was found between echocardiographic cardiac output and MostCare cardiac output (r = 0.85; p < 0.0001). Among the different ICUs, the mean bias between echocardiographic cardiac output and MostCare cardiac output ranged from -0.40 to 0.45 L/min, and the percentage error ranged from 13.2% to 47.2%. Overall, the mean bias was -0.03 L/min, with 95% limits of agreement of -1.54 to 1.47 L/min and a relative percentage error of 30.1%. The percentage error was 24% in the sepsis category, 26% in the trauma category, 30% in the surgical category, and 33% in the medical admission category. The final overall percentage error was 27.3% with a 95% CI of 22.2-32.4%. CONCLUSIONS: Our results suggest that MostCare could be an alternative to echocardiography to assess cardiac output in ICU patients with a large spectrum of clinical conditions.

Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial.

Importance: Despite suggestions of potential harm from unnecessary oxygen therapy, critically ill patients spend substantial periods in a hyperoxemic state. A strategy of controlled arterial oxygenation is thus rational but has not been validated in clinical practice. Objective: To assess whether a conservative protocol for oxygen supplementation could improve outcomes in patients admitted to intensive care units (ICUs). Design, Setting, and Patients: Oxygen-ICU was a single-center, open-label, randomized clinical trial conducted from March 2010 to October 2012 that included all adults admitted with an expected length of stay of 72 hours or longer to the medical-surgical ICU of Modena University Hospital, Italy. The originally planned sample size was 660 patients, but the study was stopped early due to difficulties in enrollment after inclusion of 480 patients. Interventions: Patients were randomly assigned to receive oxygen therapy to maintain Pao2 between 70 and 100 mm Hg or arterial oxyhemoglobin saturation (Spo2) between 94% and 98% (conservative group) or, according to standard ICU practice, to allow Pao2 values up to 150 mm Hg or Spo2 values between 97% and 100% (conventional control group). Main Outcomes and Measures: The primary outcome was ICU mortality. Secondary outcomes included occurrence of new organ failure and infection 48 hours or more after ICU admission. Results: A total of 434 patients (median age, 64 years; 188 [43.3%] women) received conventional (n = 218) or conservative (n = 216) oxygen therapy and were included in the modified intent-to-treat analysis. Daily time-weighted Pao2 averages during the ICU stay were significantly higher (P < .001) in the conventional group (median Pao2, 102 mm Hg [interquartile range, 88-116]) vs the conservative group (median Pao2, 87 mm Hg [interquartile range, 79-97]). Twenty-five patients in the conservative oxygen therapy group (11.6%) and 44 in the conventional oxygen therapy group (20.2%) died during their ICU stay (absolute risk reduction [ARR], 0.086 [95% CI, 0.017-0.150]; relative risk [RR], 0.57 [95% CI, 0.37-0.90]; P = .01). Occurrences were lower in the conservative oxygen therapy group for new shock episode (ARR, 0.068 [95% CI, 0.020-0.120]; RR, 0.35 [95% CI, 0.16-0.75]; P = .006) or liver failure (ARR, 0.046 [95% CI, 0.008-0.088]; RR, 0.29 [95% CI, 0.10-0.82]; P = .02) and new bloodstream infection (ARR, 0.05 [95% CI, 0.00-0.09]; RR, 0.50 [95% CI, 0.25-0.998; P = .049). Conclusions and Relevance: Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy vs conventional therapy resulted in lower ICU mortality. These preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of this approach. Trial Registration: clinicaltrials.gov Identifier: NCT01319643.