Red blood cell transfusion results in adhesion of neutrophils in human endotoxemia and in critically ill patients with sepsis.

BACKGROUND: Red blood cell (RBC) transfusion is associated with adverse effects, which may involve activation of the host immune response. The effect of RBC transfusion on neutrophil Reactive Oxygen Species (ROS) production and adhesion ex vivo was investigated in endotoxemic volunteers and in critically ill patients that received a RBC transfusion. We hypothesized that RBC transfusion would cause neutrophil activation, the extent of which depends on the storage time and the inflammatory status of the recipient. STUDY DESIGN AND METHODS: Volunteers were injected with lipopolysaccharide (LPS) and transfused with either saline, fresh, or stored autologous RBCs. In addition, 47 critically ill patients with and without sepsis receiving either fresh (<8 days) or standard stored RBC (2-35 days) were included. Neutrophils from healthy volunteers were incubated with the plasma samples from the endotoxemic volunteers and from the critically ill patients, after which priming of neutrophil ROS production and adhesion were assessed. RESULTS: In the endotoxemia model, ex vivo neutrophil adhesion, but not ROS production, was increased after transfusion, which was not affected by RBC storage duration. In the critically ill, ex vivo neutrophil ROS production was already increased prior to transfusion and was not increased following transfusion. Neutrophil adhesion was increased following transfusion, which was more notable in the septic patients than in non-septic patients. Transfusion of fresh RBCs, but not standard issued RBCs, resulted in enhanced ROS production in neutrophils. CONCLUSION: RBC transfusion was associated with increased neutrophil adhesion in a model of human endotoxemia as well as in critically ill patients with sepsis.

Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy.

OBJECTIVE: We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain. PATIENTS AND METHODS: This was a pre-planned secondary analysis of Efraim, a prospective, multinational, observational study of 1611 immunocompromised patients with acute respiratory failure admitted to the intensive care unit (ICU). We compared patients with noninvasive testing only to those who had also received bronchoscopy by bivariate analysis and after propensity score matching. RESULTS: Bronchoscopy was performed in 618 (39%) patients who were more likely to have haematological malignancy and a higher severity of illness score. Bronchoscopy alone achieved a diagnosis in 165 patients (27% adjusted diagnostic yield). Bronchoscopy resulted in a management change in 236 patients (38% therapeutic yield). Bronchoscopy was associated with worsening of respiratory status in 69 (11%) patients. Bronchoscopy was associated with higher ICU (40% versus 28%; p<0.0001) and hospital mortality (49% versus 41%; p=0.003). The overall rate of undiagnosed causes was 13%. After propensity score matching, bronchoscopy remained associated with increased risk of hospital mortality (OR 1.41, 95% CI 1.08-1.81). CONCLUSIONS: Bronchoscopy was associated with improved diagnosis and changes in management, but also increased hospital mortality. Balancing risk and benefit in individualised cases should be investigated further.

The effect of red blood cell transfusion on iron metabolism in critically ill patients.

BACKGROUND: Anemia of inflammation (AI) has a high prevalence in critically ill patients. In AI, iron metabolism is altered, as high levels of inflammation-induced hepcidin reduce the amount of iron available for erythropoiesis. AI is treated with red blood cell (RBC) transfusions. The effect of RBC transfusion on iron metabolism during inflammatory processes in adults is unknown. We investigated the effect of RBC transfusion on iron metabolism in critically ill patients. METHODS: In a prospective cohort study in 61 critically ill patients who received 1 RBC unit, levels of iron variables were determined before, directly after, and 24 hours after transfusion in septic and nonseptic patients. RESULTS: Serum iron levels were low and increased after transfusion (p = 0.02). However, RBC transfusion had no effect on transferrin saturation (p = 0.14) and ferritin levels (p = 0.74). Hepcidin levels increased after RBC transfusion (p = 0.01), while interleukin-6 levels decreased (p = 0.03). In septic patients, RBC transfusion induced a decrease in haptoglobin levels compared to baseline, which did not occur in nonseptic patients (p = 0.01). The effect of RBC transfusion on other iron variables did not differ between septic and nonseptic patients. CONCLUSION: Transfusion of a RBC unit transiently increases serum iron levels in intensive care unit patients. The increase in hepcidin levels after transfusion can further decrease iron release from intracellular storage making it available for erythropoiesis. RBC transfusion is associated with a decrease in haptoglobin levels in septic compared to nonseptic patients, but did not affect other markers of hemolysis.

Hyperoxia does not affect oxygen delivery in healthy volunteers while causing a decrease in sublingual perfusion.

OBJECTIVE: To determine the human dose-response relationship between a stepwise increase in arterial oxygen tension and its associated changes in DO2 and sublingual microcirculatory perfusion. METHODS: Fifteen healthy volunteers breathed increasing oxygen fractions for 10 minutes to reach arterial oxygen tensions of baseline (breathing air), 20, 40, 60 kPa, and max kPa (breathing oxygen). Systemic hemodynamics were measured continuously by the volume-clamp method. At the end of each period, the sublingual microcirculation was assessed by SDF. RESULTS: Systemic DO2 was unchanged throughout the study (Pslope  = .8). PVD decreased in a sigmoidal fashion (max -15% while breathing oxygen, SD18, Pslope  = .001). CI decreased linearly (max -10%, SD10, Pslope  < .001) due to a reduction in HR (max -10%, SD7, Pslope  = .009). There were no changes in stroke volume or MAP. Most changes became apparent above an arterial oxygen tension of 20 kPa. CONCLUSIONS: In healthy volunteers, supraphysiological arterial oxygen tensions have no effect on systemic DO2 . Sublingual microcirculatory PVD decreased in a dose-dependent fashion. All hemodynamic changes appear negligible up to an arterial oxygen tension of 20 kPa.

Respiratory Viruses in Invasively Ventilated Critically Ill Patients-A Prospective Multicenter Observational Study.

OBJECTIVES: The presence of respiratory viruses and the association with outcomes were assessed in invasively ventilated ICU patients, stratified by admission diagnosis. DESIGN: Prospective observational study. SETTING: Five ICUs in the Netherlands. PATIENTS: Between September 1, 2013, and April 30, 2014, 1,407 acutely admitted and invasively ventilated patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nasopharyngeal swabs and tracheobronchial aspirates were collected upon intubation and tested for 14 respiratory viruses. Out of 1,407 patients, 156 were admitted because of a severe acute respiratory infection and 1,251 for other reasons (non-severe acute respiratory infection). Respiratory viruses were detected in 28.8% of severe acute respiratory infection patients and 17.0% in non-severe acute respiratory infection (p < 0.001). In one third, viruses were exclusively detected in tracheobronchial aspirates. Rhinovirus and human metapneumovirus were more prevalent in severe acute respiratory infection patients (9.6% and 2.6% vs 4.5 and 0.2%; p = 0.006 and p < 0.001). In both groups, there were no associations between the presence of viruses and the number of ICU-free days at day 28, crude mortality, and mortality in multivariate regression analyses. CONCLUSIONS: Respiratory viruses are frequently detected in acutely admitted and invasively ventilated patients. Rhinovirus and human metapneumovirus are more frequently found in severe acute respiratory infection patients. Detection of respiratory viruses is not associated with worse clinically relevant outcomes in the studied cohort of patients.

Vitamin C: should we supplement?

PURPOSE OF REVIEW: Hypovitaminosis C and vitamin C deficiency are very common in critically ill patients due to increased needs and decreased intake. Because vitamin C has pleiotropic functions, deficiency can aggravate the severity of illness and hamper recovery. RECENT FINDINGS: Vitamin C is a key circulating antioxidant with anti-inflammatory and immune-supporting effects, and a cofactor for important mono and dioxygenase enzymes. An increasing number of preclinical studies in trauma, ischemia/reperfusion, and sepsis models show that vitamin C administered at pharmacological doses attenuates oxidative stress and inflammation, and restores endothelial and organ function. Older studies showed less organ dysfunction when vitamin C was administered in repletion dose (2-3 g intravenous vitamin C/day). Recent small controlled studies using pharmacological doses (6-16 g/day) suggest that vitamin C reduces vasopressor support and organ dysfunction, and may even decrease mortality. SUMMARY: A short course of intravenous vitamin C in pharmacological dose seems a promising, well tolerated, and cheap adjuvant therapy to modulate the overwhelming oxidative stress in severe sepsis, trauma, and reperfusion after ischemia. Large randomized controlled trials are necessary to provide more evidence before wide-scale implementation can be recommended.

Making sense of early high-dose intravenous vitamin C in ischemia/reperfusion injury.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

Effects of hyperoxia on vascular tone in animal models: systematic review and meta-analysis.

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 (I2) 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.

Hemodynamic effects of acute hyperoxia: systematic review and meta-analysis.

BACKGROUND: In clinical practice, oxygen is generally administered to patients with the intention of increasing oxygen delivery. Supplemental oxygen may, however, cause arterial hyperoxia, which is associated with hemodynamic alterations. We performed a systematic review and meta-analysis of the literature to determine the effect of hyperoxia on central hemodynamics and oxygen delivery in healthy volunteers and cardiovascular-compromised patients. METHODS: PubMed and EMBASE were searched up to March 2017. Studies with adult humans investigating changes in central hemodynamics or oxygen delivery induced by acute normobaric hyperoxia were included. Studies focusing on lung, retinal, or brain parameters were not included. We extracted subject and oxygen exposure characteristics, indexed and unindexed values for heart rate, stroke volume, cardiac output, mean arterial pressure (MAP), systemic vascular resistance, and oxygen delivery during normoxia and hyperoxia. For quantitative synthesis of the data, a random-effects ratio of means (RoM) model was used. RESULTS: We identified 33 studies with 42 datasets. Study categories included healthy volunteers (n = 22 datasets), patients with coronary artery disease (CAD; n = 6), heart failure (HF; n = 6), coronary artery bypass graft (CABG; n = 3) and sepsis (n = 5). Hyperoxia (arterial oxygen tension of 234-617 mmHg) reduced cardiac output (CO) by 10-15% in both healthy volunteers (-10.2%, 95% confidence interval (CI) -12.9% to -7.3%) and CAD (-9.6%, 95% CI -12.3% to -6.9%) or HF patients (-15.2%, 95% CI -21.7% to -8.2%). No significant changes in cardiac output were seen in CABG or septic patients (-3%). Systemic vascular resistance increased remarkably in patients with heart failure (24.6%, 95% CI 19.3% to 30.1%). In healthy volunteers, and those with CAD and CABG, the effect was smaller (11-16%) and was virtually absent in patients with sepsis (4.3%, 95% CI -3.2% to 12.3%). No notable effect on MAP was found in any group (2-3%). Oxygen delivery was not altered by hyperoxia. Considerable heterogeneity existed between study results, likely due to methodological differences. CONCLUSIONS: Hyperoxia may considerably decrease cardiac output and increase systemic vascular resistance, but effects differ between patient categories. Heart failure patients were the most sensitive while no hemodynamic effects were seen in septic patients. There is currently no evidence supporting the notion that oxygen supplementation increases oxygen delivery.

Low Transmission of Airway Pressures to the Abdomen in Mechanically Ventilated Patients With or Without Acute Respiratory Failure and Intra-Abdominal Hypertension.

PURPOSE: Intra-abdominal pressure, measured at end expiration, may depend on ventilator settings and transmission of intrathoracic pressure. We determined the transmission of positive intrathoracic pressure during mechanical ventilation at inspiration and expiration into the abdominal compartment. METHODS AND RESULTS: We included 9 patients after uncomplicated cardiac surgery and 9 with acute respiratory failure. Intravesical pressures were measured thrice (reproducibility of 1.8%) and averaged, at the end of each inspiratory and expiratory hold maneuvers of 5 seconds. Transmission, the change in intra-abdominal over intrathoracic pressures from end inspiration to end expiration, was about 8%. End-expiratory intra-abdominal pressure was lower than "total" intra-abdominal pressure over the entire respiratory cycle by 0.34 cm H2O. It was 0.73 cm H2O higher than "true" intra-abdominal pressure over the entire respiratory cycle, taking transmission into account. The percentage error was 3% for total and 10% for true pressure. Results did not differ among patients with or without acute respiratory failure and decreased respiratory compliance or between those with (≥12 mm Hg, n = 5) or without intra-abdominal hypertension. CONCLUSIONS: Transmitted airway pressure only slightly affects intra-abdominal pressure in mechanically ventilated patients, irrespective of respiratory compliance and baseline intra-abdominal pressure values. End-expiratory measurements referenced against atmospheric pressure may suffice for clinical practice.

Moderate hyperoxic versus near-physiological oxygen targets during and after coronary artery bypass surgery: a randomised controlled trial.

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 (PaO2) 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 PaO2 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 PaO2 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.

Diaphragm muscle fiber weakness and ubiquitin-proteasome activation in critically ill patients.

RATIONALE: The clinical significance of diaphragm weakness in critically ill patients is evident: it prolongs ventilator dependency, and increases morbidity and duration of hospital stay. To date, the nature of diaphragm weakness and its underlying pathophysiologic mechanisms are poorly understood. OBJECTIVES: We hypothesized that diaphragm muscle fibers of mechanically ventilated critically ill patients display atrophy and contractile weakness, and that the ubiquitin-proteasome pathway is activated in the diaphragm. METHODS: We obtained diaphragm muscle biopsies from 22 critically ill patients who received mechanical ventilation before surgery and compared these with biopsies obtained from patients during thoracic surgery for resection of a suspected early lung malignancy (control subjects). In a proof-of-concept study in a muscle-specific ring finger protein-1 (MuRF-1) knockout mouse model, we evaluated the role of the ubiquitin-proteasome pathway in the development of contractile weakness during mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Both slow- and fast-twitch diaphragm muscle fibers of critically ill patients had approximately 25% smaller cross-sectional area, and had contractile force reduced by half or more. Markers of the ubiquitin-proteasome pathway were significantly up-regulated in the diaphragm of critically ill patients. Finally, MuRF-1 knockout mice were protected against the development of diaphragm contractile weakness during mechanical ventilation. CONCLUSIONS: These findings show that diaphragm muscle fibers of critically ill patients display atrophy and severe contractile weakness, and in the diaphragm of critically ill patients the ubiquitin-proteasome pathway is activated. This study provides rationale for the development of treatment strategies that target the contractility of diaphragm fibers to facilitate weaning.

Effect of transfusion of fresh frozen plasma on parameters of endothelial condition and inflammatory status in non-bleeding critically ill patients: a prospective substudy of a randomized trial.

INTRODUCTION: Much controversy exists on the effect of a fresh frozen plasma (FFP) transfusion on systemic inflammation and endothelial damage. Adverse effects of FFP have been well described, including acute lung injury. However, it is also suggested that a higher amount of FFP decreases mortality in trauma patients requiring a massive transfusion. Furthermore, FFP has an endothelial stabilizing effect in experimental models. We investigated the effect of fresh frozen plasma transfusion on systemic inflammation and endothelial condition. METHODS: A prospective predefined substudy of a randomized trial in coagulopathic non-bleeding critically ill patients receiving a prophylactic transfusion of FFP (12 ml/kg) prior to an invasive procedure. Levels of inflammatory cytokines and markers of endothelial condition were measured in paired samples of 33 patients before and after transfusion. The statistical tests used were paired t test or the Wilcoxon signed-rank test. RESULTS: At baseline, systemic cytokine levels were mildly elevated in critically ill patients. FFP transfusion resulted in a decrease of levels of TNF-α (from 11.3 to 2.3 pg/ml, P = 0.01). Other cytokines were not affected. FFP also resulted in a decrease in systemic syndecan-1 levels (from 675 to 565 pg/ml, P = 0.01) and a decrease in factor VIII levels (from 246 to 246%, P <0.01), suggestive of an improved endothelial condition. This was associated with an increase in ADAMTS13 levels (from 24 to 32%, P <0.01) and a concomitant decrease in von Willebrand factor (vWF) levels (from 474 to 423%, P <0.01). CONCLUSIONS: A fixed dose of FFP transfusion in critically ill patients decreases syndecan-1 and factor VIII levels, suggesting a stabilized endothelial condition, possibly by increasing ADAMTS13, which is capable of cleaving vWF. TRIAL REGISTRATIONS: Trialregister.nl NTR2262, registered 26 March 2010 and Clinicaltrials.gov NCT01143909, registered 14 June 2010.

NT-proBNP in cardiopulmonary resuscitated patients treated with mild therapeutic hypothermia is not independently associated with mortality: a retrospective observational study.

BACKGROUND: In spite of the introduction of mild therapeutic hypothermia (MTH), mortality rates remain high in patients with return of spontaneous circulation (ROSC) after cardiac arrest (CA). To date, no accurate and independent biomarker to predict survival in these patients exists. B-type natriuretic peptide (BNP) was found to provide both prognostic and diagnostic value in various cardiovascular diseases, including survival to hospital discharge in patients with ROSC. However, the biologically inactive counterpart of BNP, NT-proBNP, was found to be a more stable and accurate analyte. The current retrospective observational study investigates the value of NT-proBNP to predict 28-day mortality in post-CA patients treated with MTH, as well as the dynamics of NT-proBNP during MTH. METHODS: NT-proBNP levels were measured in post-CA patients cooled via cold intravenous saline infusion and water-circulating body wraps (Medi-Therm®, Gaymar). Plasma samples were obtained before cooling was started, at the start and end of the maintenance phase and at the end of rewarming. RESULTS: 250 patients, admitted between 2009 and 2013, had NT-proBNP levels measured on ICU admission and were included for the evaluation of NT-proBNP as a prognostic marker. In the 28 days following ICU admission, 114 patients died (46%). Non-survivors had significantly higher NT-proBNP (median 1448 ng/l, IQR 366-4623 vs median 567 ng/1, IQR 148-1899; P < 0.001) levels on ICU admission. Unadjusted odds ratios for 28-day mortality were 1.7 (95% CI 0.8-3.5), 1.6 (0.8-3.3) and 3.6 (1.7-7.5) for increasing quartiles of NT-proBNP as compared to the lowest quartile. Adjusted odds ratios were 1.1 (95% CI 0.5-2.5), 1.1 (0.5-2.5) and 1.6 (0.7-3.8), respectively. A cut-off value of 834 ng/l achieved a sensitivity of 58% and a specificity of 58% to predict 28-day mortality. Of 113 patients, NT-proBNP values of each MTH phase were available and grouped in decreased or increased levels in time. Both decreases and increases of NT-proBNP values were observed during the MTH phases, but presence of either was not associated with outcome. CONCLUSIONS: High NT-proBNP plasma concentrations on ICU admission are associated with high 28-day mortality in post-CA patients treated with MTH in a univariate analysis, but not in a multivariate analysis. Increases or decreases of NT-proBNP levels during MTH appear unrelated to 28 day mortality.

Estimating Vitamin C Status in Critically Ill Patients with a Novel Point-of-Care Oxidation-Reduction Potential Measurement.

Vitamin C deficiency is common in critically ill patients. Vitamin C, the most important antioxidant, is likely consumed during oxidative stress and deficiency is associated with organ dysfunction and mortality. Assessment of vitamin C status may be important to identify patients who might benefit from vitamin C administration. Up to now, vitamin C concentrations are not available in daily clinical practice. Recently, a point-of-care device has been developed that measures the static oxidation-reduction potential (sORP), reflecting oxidative stress, and antioxidant capacity (AOC). The aim of this study was to determine whether plasma vitamin C concentrations were associated with plasma sORP and AOC. Plasma vitamin C concentration, sORP and AOC were measured in three groups: healthy volunteers, critically ill patients, and critically ill patients receiving 2- or 10-g vitamin C infusion. Its association was analyzed using regression models and by assessment of concordance. We measured 211 samples obtained from 103 subjects. Vitamin C concentrations were negatively associated with sORP (R2 = 0.816) and positively associated with AOC (R2 = 0.842). A high concordance of 94-100% was found between vitamin C concentration and sORP/AOC. Thus, plasma vitamin C concentrations are strongly associated with plasma sORP and AOC, as measured with a novel point-of-care device. Therefore, measuring sORP and AOC at the bedside has the potential to identify and monitor patients with oxidative stress and vitamin C deficiency.

Renal Resistive Index: Response to Shock and its Determinants in Critically Ill Patients.

INTRODUCTION: Shock is characterized by micro- and macrovascular flow impairment contributing to acute kidney injury (AKI). Routine monitoring of the circulation regards the macrocirculation but not the renal circulation which can be assessed with Doppler ultrasound as renal resistive index (RRI). RRI reflects resistance to flow. High RRI predicts persistent AKI. Study aims were to determine whether RRI is elevated in shock and to identify determinants of RRI. MATERIALS AND METHODS: This prospective observational cohort study included two cohorts of patients, with and without shock less than 24-h after intensive care admission. Apart from routine monitoring, three study measurements were performed simultaneously: RRI, sublingual microcirculation, and bioelectral impedance analysis. RESULTS: A total of 92 patients were included (40 shock, 52 nonshock), median age was 69 [60-76] vs. 67 [59-76], P = 0.541; APACHE III was 87 [65-119] vs. 57 [45-69], P < 0.001. Shock patients had higher RRI than patients without shock (0.751 [0.692-0.788] vs. 0.654 [0.610-0.686], P < 0.001). Overall, high age, APACHE III score, lactate, vasopressor support, pulse pressure index (PPI), central venous pressure (CVP), fluid balance, and low preadmission estimated glomerular filtration rate, mean arterial pressure (MAP), creatinine clearance, and reactance/m were associated with high RRI at univariable regression (P < 0.01). Microcirculatory markers were not. At multivariable regression, vasopressor support, CVP, PPI and MAP, reactance/m, and preadmission eGFR were independent determinants of RRI (n = 92, adj. R = 0.587). CONCLUSIONS: Patients with shock have a higher RRI than patients without shock. Independent determinants of high RRI were pressure indices of the systemic circulation, low membrane capacitance, and preadmission renal dysfunction. Markers of the sublingual microcirculation were not.