Rapid screening of critically ill patients for low plasma vitamin C concentrations using a point-of-care oxidation-reduction potential measurement.

BACKGROUND: Hypovitaminosis C and vitamin C deficiency are common in critically ill patients and associated with organ dysfunction. Low vitamin C status often goes unnoticed because determination is challenging. The static oxidation reduction potential (sORP) reflects the amount of oxidative stress in the blood and is a potential suitable surrogate marker for vitamin C. sORP can be measured rapidly using the RedoxSYS system, a point-of-care device. This study aims to validate a model that estimates plasma vitamin C concentration and to determine the diagnostic accuracy of sORP to discriminate between decreased and higher plasma vitamin C concentrations. METHODS: Plasma vitamin C concentrations and sORP were measured in a mixed intensive care (IC) population. Our model estimating vitamin C from sORP was validated by assessing its accuracy in two datasets. Receiver operating characteristic (ROC) curves with areas under the curve (AUC) were constructed to show the diagnostic accuracy of sORP to identify and rule out hypovitaminosis C and vitamin C deficiency. Different cut-off values are provided. RESULTS: Plasma vitamin C concentration and sORP were measured in 117 samples in dataset 1 and 43 samples in dataset 2. Bias and precision (SD) were 1.3 ± 10.0 µmol/L and 3.9 ± 10.1 µmol/L in dataset 1 and 2, respectively. In patients with low plasma vitamin C concentrations, bias and precision were - 2.6 ± 5.1 µmol/L and - 1.1 ± 5.4 µmol in dataset 1 (n = 40) and 2 (n = 20), respectively. Optimal sORP cut-off values to differentiate hypovitaminosis C and vitamin C deficiency from higher plasma concentrations were found at 114.6 mV (AUC 0.91) and 124.7 mV (AUC 0.93), respectively. CONCLUSION: sORP accurately estimates low plasma vitamin C concentrations and can be used to screen for hypovitaminosis C and vitamin C deficiency in critically ill patients. A validated model and multiple sORP cut-off values are presented for subgroup analysis in clinical trials or usage in clinical practice.

Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial.

BACKGROUND: High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients. METHODS: This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations. DISCUSSION: Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest. TRIAL REGISTRATION: ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662 European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL.

Observational Research for Therapies Titrated to Effect and Associated With Severity of Illness: Misleading Results From Commonly Used Statistical Methods.

OBJECTIVES: In critically ill patients, treatment dose or intensity is often related to severity of illness and mortality risk, whereas overtreatment or undertreatment (relative to the individual need) may further increase the odds of death. We aimed to investigate how these relationships affect the results of common statistical methods used in observational studies. DESIGN: Using Monte Carlo simulation, we generated data for 5,000 patients with a treatment dose related to the pretreatment mortality risk but with randomly distributed overtreatment or undertreatment. Significant overtreatment or undertreatment (relative to the optimal dose) further increased the mortality risk. A prognostic score that reflects the mortality risk and an outcome of death or survival was then generated. The study was analyzed: 1) using logistic regression to estimate the effect of treatment dose on outcome while controlling for prognostic score and 2) using propensity score matching and inverse probability weighting of the effect of high treatment dose on outcome. The data generation and analyses were repeated 1,500 times over sample sizes between 200 and 30,000 patients, with an increasing accuracy of the prognostic score and with different underlying assumptions. SETTING: Computer-simulated studies. MEASUREMENTS AND MAIN RESULTS: In the simulated 5,000-patient observational study, higher treatment dose was found to be associated with increased odds of death (p = 0.00001) while controlling for the prognostic score with logistic regression. Propensity-matched analysis led to similar results. Larger sample sizes led to equally biased estimates with narrower CIs. A perfect risk predictor negated the bias only under artificially perfect assumptions. CONCLUSIONS: When a treatment dose is associated with severity of illness and should be dosed "enough," logistic regression, propensity score matching, and inverse probability weighting to adjust for confounding by severity of illness lead to biased results. Larger sample sizes lead to more precisely wrong estimates.

Coronary Angiography After Cardiac Arrest Without ST Segment Elevation: One-Year Outcomes of the COACT Randomized Clinical Trial.

Importance: Ischemic heart disease is a common cause of cardiac arrest. However, randomized data on long-term clinical outcomes of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients successfully resuscitated from cardiac arrest in the absence of ST segment elevation myocardial infarction (STEMI) are lacking. Objective: To determine whether immediate coronary angiography improves clinical outcomes at 1 year in patients after cardiac arrest without signs of STEMI, compared with a delayed coronary angiography strategy. Design, Setting, and Participants: A prespecified analysis of a multicenter, open-label, randomized clinical trial evaluated 552 patients who were enrolled in 19 Dutch centers between January 8, 2015, and July 17, 2018. The study included patients who experienced out-of-hospital cardiac arrest with a shockable rhythm who were successfully resuscitated without signs of STEMI. Follow-up was performed at 1 year. Data were analyzed, using the intention-to-treat principle, between August 29 and October 10, 2019. Interventions: Immediate coronary angiography and PCI if indicated or coronary angiography and PCI if indicated, delayed until after neurologic recovery. Main Outcomes and Measures: Survival, myocardial infarction, revascularization, implantable cardiac defibrillator shock, quality of life, hospitalization for heart failure, and the composite of death or myocardial infarction or revascularization after 1 year. Results: At 1 year, data on 522 of 552 patients (94.6%) were available for analysis. Of these patients, 413 were men (79.1%); mean (SD) age was 65.4 (12.3) years. A total of 162 of 264 patients (61.4%) in the immediate angiography group and 165 of 258 patients (64.0%) in the delayed angiography group were alive (odds ratio, 0.90; 95% CI, 0.63-1.28). The composite end point of death, myocardial infarction, or repeated revascularization since the index hospitalization was met in 112 patients (42.9%) in the immediate group and 104 patients (40.6%) in the delayed group (odds ratio, 1.10; 95% CI, 0.77-1.56). No significant differences between the groups were observed for the other outcomes at 1-year follow-up. For example, the rate of ICD shocks was 20.4% in the immediate group and 16.2% in the delayed group (odds ratio, 1.32; 95% CI, 0.66-2.64). Conclusions and Relevance: In this trial of patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, a strategy of immediate angiography was not found to be superior to a strategy of delayed angiography with respect to clinical outcomes at 1 year. Coronary angiography in this patient group can therefore be delayed until after neurologic recovery without affecting outcomes. Trial Registration: trialregister.nl Identifier: NTR4973.

Gastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda proposed by the Section of Metabolism, Endocrinology and Nutrition of the European Society of Intensive Care Medicine.

BACKGROUND: Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. METHODS: This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. RESULTS: Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. CONCLUSIONS: Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.

Fluid balance and phase angle as assessed by bioelectrical impedance analysis in critically ill patients: a multicenter prospective cohort study.

BACKGROUND: Bioelectrical 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. METHODS: A 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. RESULTS: One 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). CONCLUSIONS: Our results show that during critical illness, changes in phase angle and vector length partially reflect changes in hydration.

Identifying critically ill patients with low muscle mass: Agreement between bioelectrical impedance analysis and computed tomography.

BACKGROUND & AIMS: Low muscle mass and -quality on ICU admission, as assessed by muscle area and -density on CT-scanning at lumbar level 3 (L3), are associated with increased mortality. However, CT-scan analysis is not feasible for standard care. Bioelectrical impedance analysis (BIA) assesses body composition by incorporating the raw measurements resistance, reactance, and phase angle in equations. Our purpose was to compare BIA- and CT-derived muscle mass, to determine whether BIA identified the patients with low skeletal muscle area on CT-scan, and to determine the relation between raw BIA and raw CT measurements. METHODS: This prospective observational study included adult intensive care patients with an abdominal CT-scan. CT-scans were analysed at L3 level for skeletal muscle area (cm2) and skeletal muscle density (Hounsfield Units). Muscle area was converted to muscle mass (kg) using the Shen equation (MMCT). BIA was performed within 72 h of the CT-scan. BIA-derived muscle mass was calculated by three equations: Talluri (MMTalluri), Janssen (MMJanssen), and Kyle (MMKyle). To compare BIA- and CT-derived muscle mass correlations, bias, and limits of agreement were calculated. To test whether BIA identifies low skeletal muscle area on CT-scan, ROC-curves were constructed. Furthermore, raw BIA and CT measurements, were correlated and raw CT-measurements were compared between groups with normal and low phase angle. RESULTS: 110 patients were included. Mean age 59 ± 17 years, mean APACHE II score 17 (11-25); 68% male. MMTalluri and MMJanssen were significantly higher (36.0 ± 9.9 kg and 31.5 ± 7.8 kg, respectively) and MMKyle significantly lower (25.2 ± 5.6 kg) than MMCT (29.2 ± 6.7 kg). For all BIA-derived muscle mass equations, a proportional bias was apparent with increasing disagreement at higher muscle mass. MMTalluri correlated strongest with CT-derived muscle mass (r = 0.834, p < 0.001) and had good discriminative capacity to identify patients with low skeletal muscle area on CT-scan (AUC: 0.919 for males; 0.912 for females). Of the raw measurements, phase angle and skeletal muscle density correlated best (r = 0.701, p < 0.001). CT-derived skeletal muscle area and -density were significantly lower in patients with low compared to normal phase angle. CONCLUSIONS: Although correlated, absolute values of BIA- and CT-derived muscle mass disagree, especially in the high muscle mass range. However, BIA and CT identified the same critically ill population with low skeletal muscle area on CT-scan. Furthermore, low phase angle corresponded to low skeletal muscle area and -density. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02555670).

Early high protein intake and mortality in critically ill ICU patients with low skeletal muscle area and -density.

BACKGROUND & AIMS: Optimal nutritional support during the acute phase of critical illness remains controversial. We hypothesized that patients with low skeletal muscle area and -density may specifically benefit from early high protein intake. Aim of the present study was to determine the association between early protein intake (day 2-4) and mortality in critically ill intensive care unit (ICU) patients with normal skeletal muscle area, low skeletal muscle area, or combined low skeletal muscle area and -density. METHODS: Retrospective database study in mechanically ventilated, adult critically ill patients with an abdominal CT-scan suitable for skeletal muscle assessment around ICU admission, admitted from January 2004 to January 2016 (n = 739). Patients received protocolized nutrition with protein target 1.2-1.5 g/kg/day. Skeletal muscle area and -density were assessed on abdominal CT-scans at the 3rd lumbar vertebra level using previously defined cut-offs. RESULTS: Of 739 included patients (mean age 58 years, 483 male (65%), APACHE II score 23), 294 (40%) were admitted with normal skeletal muscle area and 445 (60%) with low skeletal muscle area. Two hundred (45% of the low skeletal muscle area group) had combined low skeletal muscle area and -density. In the normal skeletal muscle area group, no significant associations were found. In the low skeletal muscle area group, higher early protein intake was associated with lower 60-day mortality (adjusted hazard ratio (HR) per 0.1 g/kg/day 0.82, 95%CI 0.73-0.94) and lower 6-month mortality (HR 0.88, 95%CI 0.79-0.98). Similar associations were found in the combined low skeletal muscle area and -density subgroup (HR 0.76, 95%CI 0.64-0.90 for 60-day mortality and HR 0.80, 95%CI 0.68-0.93 for 6-month mortality). CONCLUSIONS: Early high protein intake is associated with lower mortality in critically ill patients with low skeletal muscle area and -density, but not in patients with normal skeletal muscle area on admission. These findings may be a further step to personalized nutrition, although randomized studies are needed to assess causality.

Metabolic support in the critically ill: a consensus of 19.

Metabolic alterations in the critically ill have been studied for more than a century, but the heterogeneity of the critically ill patient population, the varying duration and severity of the acute phase of illness, and the many confounding factors have hindered progress in the field. These factors may explain why management of metabolic alterations and related conditions in critically ill patients has for many years been guided by recommendations based essentially on expert opinion. Over the last decade, a number of randomized controlled trials have been conducted, providing us with important population-level evidence that refutes several longstanding paradigms. However, between-patient variation means there is still substantial uncertainty when translating population-level evidence to individuals. A cornerstone of metabolic care is nutrition, for which there is a multifold of published guidelines that agree on many issues but disagree on others. Using a series of nine questions, we provide a review of the latest data in this field and a background to promote efforts to address the need for international consistency in recommendations related to the metabolic care of the critically ill patient. Our purpose is not to replace existing guidelines, but to comment on differences and add perspective.

Predictors of 90-Day Restart of Renal Replacement Therapy after Discontinuation of Continuous Renal Replacement Therapy, a Prospective Multicenter Study.

BACKGROUND: Restart of renal replacement therapy (RRT) after initial discontinuation of continuous RRT (CRRT) is frequently needed. The aim of the present study was to evaluate whether renal markers after discontinuation of CRRT can predict restart of RRT within 90 days. METHODS: Prospective multicenter observational study in 90 patients, alive, still on the intensive care unit at day 2 after discontinuation of CRRT for expected recovery with urinary neutrophil gelatinase-associated lipocalin (NGAL) available. The endpoint was restart of RRT within 90 days. Baseline and renal characteristics were compared between outcome groups no restart or restart of RRT. Logistic regression and receiver operator characteristic curve analysis were performed to determine the best predictive and discriminative variables. RESULTS: Restart of RRT was needed in 32/90 (36%) patients. Compared to patients not restarting, patients restarting RRT demonstrated a higher day 2 urinary NGAL, lower day 2 urine output, and higher incremental creatinine ratio (day 2/0). In multivariate analysis, only incremental creatinine ratio (day 2/0) remained independently associated with restart of RRT (OR 5.28, 95% CI 1.45-19.31, p = 0.012). The area under curve for incremental creatinine ratio to discriminate for restart of RRT was 0.76 (95% CI 0.64-0.88). The optimal cutoff was 1.49 (95% CI 1.44-1.62). CONCLUSION: In this prospective multicenter study, incremental creatinine ratio (day 2/0) was the best predictor for restart of RRT. Patients with an incremental creatinine ratio at day 2 of 1.5 times creatinine at discontinuation are likely to need RRT within 90 days. These patients might benefit from nephrological follow-up.

Amino Acid Loss during Continuous Venovenous Hemofiltration in Critically Ill Patients.

BACKGROUND/OBJECTIVES: During continuous venovenous hemofiltration (CVVH), there is unwanted loss of amino acids (AA) in the ultrafiltrate (UF). Solutes may also be removed by adsorption to the filter membrane. The aim was to quantify the total loss of AA via the CVVH circuit using a high-flux polysulfone membrane and to differentiate between the loss by ultrafiltration and adsorption. METHODS: Prospective observational study in ten critically ill patients, receiving predilution CVVH with a new filter, blood flow 180 mL/min, and predilution flow 2,400 mL/h. Arterial blood, postfilter blood, and UF samples were taken at baseline, and 1, 8, and 24-h after CVVH initiation, to determine AA concentrations and hematocrit. Mass transfer calculations were used to determine AA loss in the filter and by UF, and the difference between these 2. RESULTS: The median AA loss in the filter was 10.4 g/day, the median AA loss by UF was 13.4 g/day, and the median difference was -2.9 g/day (IQR -5.9 to -1.4 g/day). For the individual AA, the difference ranged from -1 g/day to +0.4 g/day, suggesting that some AA were consumed or adsorbed and others were generated. AA losses did not significantly change over the 24-h study period. CONCLUSION: During CVVH with a modern polysulfone membrane, the estimated AA loss was 13.4 g/day, which corresponds to a loss of about 11.2 g of protein per day. Adsorption did not play a major role. However, individual AA behaved differently, suggesting complex interactions and processes at the filter membrane or peripheral AA production.

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.

Predictors of short-term successful discontinuation of continuous renal replacement therapy: results from a prospective multicentre study.

BACKGROUND: Prediction of successful discontinuation of continuous renal replacement therapy (CRRT) might reduce complications of over- and under-treatment. The aim of this study was to identify renal and non-renal predictors of short-term successful discontinuation of CRRT in patients in whom CRRT was stopped because renal recovery was expected and who were still in the Intensive Care Unit (ICU) at day 2 after stop CRRT. METHODS: Prospective multicentre observational study in 92 patients alive after discontinuation of CRRT for acute kidney injury (AKI), still in the ICU and free from renal replacement therapy (RRT) at day 2 after discontinuation. Successful discontinuation was defined as alive and free from RRT at day 7 after stop CRRT. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and clinical variables were collected. Logistic regression and Receiver Operator Characteristic (ROC) curve analysis were performed to determine the best predictive and discriminative variables. RESULTS: Discontinuation of CRRT was successful in 61/92 patients (66%). Patients with successful discontinuation of CRRT had higher day 2 urine output, better renal function indicated by higher creatinine clearance (6-h) or lower creatinine ratio (day 2/day 0), less often vasopressors, lower urinary NGAL, shorter duration of CRRT and lower cumulative fluid balance (day 0-2). In multivariate analysis renal function determined by creatinine clearance (Odds Ratio (OR) 1.066, 95% confidence interval (CI) 1.022-1.111, p = 0.003) or by creatinine ratio (day 2/day 0) (OR 0.149, 95% CI 0.037-0.583, p = 0.006) and non-renal sequential organ failure assessment (SOFA) score (OR 0.822, 95% CI 0.678-0.996, p = 0.045) were independently associated with successful discontinuation of CRRT. The area under the curve of creatinine clearance to predict successful discontinuation was 0.791, optimal cut-off of 11 ml/min (95% CI 6-16 ml/min) and of creatinine ratio 0.819 (95% CI 0.732-0.907) optimal cut-off of 1.41 (95% CI 1.27-1.59). CONCLUSION: In this prospective multicentre study we found higher creatinine clearance or lower creatinine ratio as best predictors of short-term successful discontinuation of CRRT, with a creatinine ratio of 1.41 (95% CI 1.27-1.59) as optimal cut-off. This study provides a practical bedside tool for clinical decision making.

Coronary Angiography after Cardiac Arrest without ST-Segment Elevation.

BACKGROUND: Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography and percutaneous coronary intervention (PCI) in the treatment of patients who have been successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains uncertain. METHODS: In this multicenter trial, we randomly assigned 552 patients who had cardiac arrest without signs of STEMI to undergo immediate coronary angiography or coronary angiography that was delayed until after neurologic recovery. All patients underwent PCI if indicated. The primary end point was survival at 90 days. Secondary end points included survival at 90 days with good cerebral performance or mild or moderate disability, myocardial injury, duration of catecholamine support, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, major bleeding, occurrence of acute kidney injury, need for renal-replacement therapy, time to target temperature, and neurologic status at discharge from the intensive care unit. RESULTS: At 90 days, 176 of 273 patients (64.5%) in the immediate angiography group and 178 of 265 patients (67.2%) in the delayed angiography group were alive (odds ratio, 0.89; 95% confidence interval [CI], 0.62 to 1.27; P = 0.51). The median time to target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group (ratio of geometric means, 1.19; 95% CI, 1.04 to 1.36). No significant differences between the groups were found in the remaining secondary end points. CONCLUSIONS: Among patients who had been successfully resuscitated after out-of-hospital cardiac arrest and had no signs of STEMI, a strategy of immediate angiography was not found to be better than a strategy of delayed angiography with respect to overall survival at 90 days. (Funded by the Netherlands Heart Institute and others; COACT Netherlands Trial Register number, NTR4973.).

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.

Indirect calorimetry in critically ill mechanically ventilated patients: Comparison of E-sCOVX with the deltatrac.

BACKGROUND & AIMS: Indirect calorimetry is recommended to measure energy expenditure (EE) in critically ill, mechanically ventilated patients. The most validated system, the Deltatrac® (Datex-Ohmeda, Helsinki, Finland) is no longer in production. We tested the agreement of a new breath-by-breath metabolic monitor E-sCOVX® (GE healthcare, Helsinki, Finland), with the Deltatrac. We also compared the performance of the E-sCOVX to commonly used predictive equations. METHODS: We included mechanically ventilated patients eligible to undergo indirect calorimetry. After a stabilization period, EE was measured simultaneously with the Deltatrac and the E-sCOVX for 2 h. Agreement and precision of the E-sCOVX was tested by determining bias, limits of agreement and agreement rates compared to the Deltatrac. Performance of the E-sCOVX was also compared to four predictive equations: the 25 kcal/kg, Penn State University 2003b, Faisy, and Harris-Benedict equation. RESULTS: We performed 29 measurements in 16 patients. Mean EE-Deltatrac was 1942 ± 274 kcal/day, and mean EE-E-sCOVX was 2177 ± 319 kcal/day (p < 0.001). E-sCOVX overestimated EE with a bias of 235 ± 149 kcal/day, being 12.1% of EE-Deltatrac. Limits of agreement were -63 to +532 kcal/day. The 10% and 15% agreement rates of EE-E-sCOVX compared to the Deltatrac were 34% and 72% respectively. The bias of E-sCOVX was lower than the bias of the 25 kcal/kg-equation, but higher than bias of the other equations. Agreement rates for E-sCOVX were similar to the equations. The Faisy-equation had the highest 15% agreement rate. CONCLUSION: The E-sCOVX metabolic monitor is not accurate in estimating EE in critically ill mechanically ventilated patients when compared to the Deltatrac, the present reference method. The E-sCOVX overestimates EE with a bias and precision that are clinically unacceptable.