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Background Arterial hyperoxia may induce vasoconstriction and reduce cardiac output, which is particularly undesirable in patients who already have compromised perfusion of vital organs. Due to the inaccessibility of vital organs in humans, vasoconstrictive effects of hyperoxia have primarily been studied in animal models. However, the results of these studies vary substantially. Here, we investigate the variation in magnitude of the hyperoxia effect among studies and explore possible sources of heterogeneity, such as vascular region and animal species. Method Pubmed and Embase were searched for eligible studies up to November 2017. In vivo and ex vivo animal studies reporting on vascular tone changes induced by local or systemic normobaric hyperoxia were included. Experiments with co-interventions (e.g. disease or endothelium removal) or studies focusing on lung, brain or fetal vasculature or the ductus arteriosus were not included. We extracted data pertaining to species, vascular region, blood vessel characteristics and method of hyperoxia induction. Overall effect sizes were estimated with a standardized mean difference (SMD) random effects model. Results We identified a total of 60 studies, which reported data on 67 in vivo and 18 ex vivo experiments. In the in vivo studies, hyperoxia caused vasoconstriction with an SMD of − 1.42 (95% CI − 1.65 to − 1.19). Ex vivo, the overall effect size was SMD − 0.56 (95% CI − 1.09 to − 0.03). Between-study heterogeneity ( I 2 ) was high for in vivo (72%, 95% CI 62 to 85%) and ex vivo studies (86%, 95% CI 78 to 98%). In vivo, in comparison to the overall effect size, hyperoxic vasoconstriction was less pronounced in the intestines and skin ( P  = 0.03) but enhanced in the cremaster muscle region ( P  < 0.001). Increased constriction was seen in vessels 15–25 μm in diameter. Hyperoxic constriction appeared to be directly proportional to oxygen concentration. For ex vivo studies, heterogeneity could not be explained with subgroup analysis. Conclusion The effect of hyperoxia on vascular tone is substantially higher in vivo than ex vivo. The magnitude of the constriction is most pronounced in vessels ~ 15–25 μm in diameter and is proportional to the level of hyperoxia. Relatively increased constriction was seen in muscle vasculature, while reduced constriction was seen in the skin and intestines.

Background The sequential organ failure assessment score (SOFA) is increasingly used as an endpoint in intensive care randomized controlled trials (RCTs). Although serially measured SOFA is independently associated with mortality in observational cohorts, the association between treatment effects on SOFA vs. effects on mortality has not yet been quantified in RCTs. The aim of this study was to quantify the relationship between SOFA and mortality in RCTs and to identify which SOFA derivative best reflects between-group mortality differences. Methods The review protocol was prospectively registered (Prospero CRD42016034014). We performed a literature search (up to May 1, 2016) for RCTs reporting both SOFA and mortality, and analyzed between-group differences in these outcomes. Treatment effects on SOFA and mortality were calculated as the between-group SOFA standardized difference and log odds ratio (OR), respectively. We used random-effects meta-regression to (1) quantify the linear relationship between RCT treatment effects on mortality (logOR) and SOFA (i.e. responsiveness) and (2) quantify residual heterogeneity (i.e. consistency, expressed as I 2 ). Results Of 110 eligible RCTs, 87 qualified for analysis. Using all RCTs, SOFA was significantly associated with mortality (slope = 0.49 (95% CI 0.17; 0.82), p  = 0.006, I 2  = 5%); the overall mortality effect explained by SOFA score ( R 2 ) was 9%. Fifty-eight RCTs used Fixed-day SOFA as an endpoint (i.e. the score on a fixed day after randomization), 25 studies used Delta SOFA as an endpoint (i.e. the trajectory from baseline score) and 15 studies used other SOFA derivatives as an endpoint. Fixed-day SOFA was not significantly associated with mortality (slope = 0.35 (95% CI −0.04; 0.75), p  = 0.08, I 2  = 12%) and explained 3% of the overall mortality effect ( R 2 ). Delta SOFA was significantly associated with mortality (slope = 0.70 (95% CI 0.26; 1.14), p  = 0.004, I 2  = 0%) and explained 32% of the overall mortality effect ( R 2 ). Conclusions Treatment effects on Delta SOFA appear to be reliably and consistently associated with mortality in RCTs. Fixed-day SOFA was the most frequently reported outcome among the reviewed RCTs, but was not significantly associated with mortality. Based on this study, we recommend using Delta SOFA rather than Fixed-day SOFA as an endpoint in future RCTs.

Keywords: Vitamin C, Hydrocortisone, Thiamine, Sepsis

Background The safety of perioperative hyperoxia is currently unclear. Previous studies in patients undergoing coronary artery bypass surgery suggest reduced myocardial damage when avoiding extreme perioperative hyperoxia (>400 mmHg). In this study we investigated whether an oxygenation strategy from moderate hyperoxia to a near-physiological oxygen tension reduces myocardial damage and improves haemodynamics, organ dysfunction and oxidative stress. Methods This was a single-blind, single-centre, open-label, randomised controlled trial in patients undergoing elective coronary artery bypass surgery. Fifty patients were randomised to a partial pressure of oxygen in arterial blood (P a O 2 ) target of 200–220 mmHg during cardiopulmonary bypass and 130–150 mmHg during intensive care unit (ICU) admission (control group) versus lower targets of 130–150 mmHg during cardiopulmonary bypass and 80–100 mmHg at the ICU (conservative group). Primary outcome was myocardial injury (CK-MB and Troponin-T) at ICU admission and 2, 6 and 12 hours thereafter. Results Weighted P a O 2 during cardiopulmonary bypass was 220 mmHg (interquartile range (IQR) 211–233) vs. 157 (151–162) in the control and conservative group, respectively ( P  < 0.0001). During ICU admission, weighted P a O 2 was 107 mmHg (86–141) vs. 90 (84–98) ( P  = 0.03), respectively. Area under the curve of CK-MB was median 23.5 μg/L/h (IQR 18.4–28.1) vs. 21.5 (15.8–26.6) ( P  = 0.35) and 0.30 μg/L/h (0.25–0.44) vs. 0.39 (0.24–0.43) ( P  = 0.81) for Troponin-T. Cardiac index, systemic vascular resistance index, creatinine, lactate and F2-isoprostane levels were not different between groups. Conclusions Compared to moderate hyperoxia, a near-physiological oxygen strategy does not reduce myocardial damage in patients undergoing coronary artery bypass surgery. Conservative oxygen administration was not associated with increased lactate levels or hypoxic events. Trial registration Netherlands Trial Registry NTR4375 , registered on 30 January 2014

Keywords: Vitamin C, Cardiac arrest, Pharmacokinetics, Continuous renal replacement therapy

There is increasing evidence that fluid overload and acute kidney injury (AKI) are associated but the exact cause-effect relationship remains unclear. Wang and colleagues analysed patients admitted to 30 intensive care units in China and found that fluid accumulation was independently associated with an increased risk of AKI and mortality. This commentary focuses on the close pathophysiological link between AKI and fluid overload and discusses the implications for clinical practice. It outlines some of the challenges, including the difficulty in diagnosing fluid overload reliably with current methods, and stresses the importance of personalised fluid therapy with physiological end-points to avoid the deleterious effects of fluid overload.

Background/ObjectivesA low bioelectrical impedance analysis (BIA)-derived phase angle (PA) predicts morbidity and mortality in different patient groups. An association between PA and long-term mortality in ICU patients has not been demonstrated before. The purpose of the present study was to determine whether PA on ICU admission independently predicts 90-day mortality.Subjects/ methodsThis prospective observational study was performed in a mixed university ICU. BIA was performed in 196 patients within 24 h of ICU admission. To test the independent association between PA and 90-day mortality, logistic regression analysis was performed using the APACHE IV predicted mortality as confounder. The optimal cutoff value of PA for mortality prediction was determined by ROC curve analysis. Using this cutoff value, patients were categorized into low or normal PA group and the association with 90-day mortality was tested again.ResultsThe PA of survivors was higher than of the non-survivors (5.0° ± 1.3° vs. 4.1° ± 1.2°, p < 0.001). The area under the ROC curve of PA for 90-day mortality was 0.70 (CI 0.59–0.80). PA was associated with 90-day mortality (OR = 0.56, CI: 0.38–0.77, p = 0.001) on univariate logistic regression analysis and also after adjusting for BMI, gender, age, and APACHE IV on multivariable logistic regression (OR = 0.65, CI: 0.44–0.96, p = 0.031). A PA < 4.8° was an independent predictor of 90-day mortality (adjusted OR = 3.65, CI: 1.34–9.93, p = 0.011).ConclusionsPhase angle at ICU admission is an independent predictor of 90-day mortality. This biological marker can aid in long-term mortality risk assessment of critically ill patients.

BackgroundBioelectrical impedance analysis (BIA) is a validated method to assess body composition in persons with fluid homeostasis and reliable body weight. This is not the case during critical illness. The raw BIA markers resistance, reactance, phase angle, and vector length are body weight independent. Phase angle reflects cellular health and has prognostic significance. We aimed to assess the course of phase angle and vector length during intensive care unit (ICU) admission, and determine the relation between their changes (Δ) and changes in body hydration.MethodsA prospective, dual-center observational study of adult ICU patients was conducted. Univariate and multivariable regression analyses were performed, including reactance as a marker of cellular mass and integrity and total body water according to the Biasioli equation (TBWBiasioli) and fluid balance as body weight independent markers of hydration.ResultsOne hundred and fifty-six ICU patients (mean ± SD age 62.5 ± 14.5 years, 67% male) were included. Between days 1 and 3, there was a significant decrease in reactance/m (−2.6 ± 6.0 Ω), phase angle (−0.4 ± 1.1°), and vector length (−12.2 ± 44.3 Ω/m). Markers of hydration significantly increased. Δphase angle and Δvector length were both positively related to Δreactance/m (r2 = 0.55, p < 0.01; r2 = 0.38, p < 0.01). Adding ΔTBWBiasioli as explaining factor strongly improved the association between Δphase angle and Δreactance/m (r2 = 0.73, p < 0.01), and Δvector length and Δreactance/m (r2 = 0.77, p < 0.01).ConclusionsOur results show that during critical illness, changes in phase angle and vector length partially reflect changes in hydration.

See related research by Oshima et al. http://ccforum.biomedcentral.com/articles/10.1186/s13054-016-1595-8