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Mid-regional pro-adrenomedullin (MR-proADM), a marker of positive fluid balance in critically ill patients: results of the ENVOL study.

ABSTRACT: The optimal control of blood volume without fluid overload is a main challenge in the daily care of intensive care unit (ICU) patients. Accordingly this study focused on the identification of biomarkers to help characterize fluid overload status.Sixty-seven patients were studied from ICU admission to day 7 (D7). Blood and urine samples were taken daily and sodium and water balance strictly calculated resulting in a total cumulative assessment of ?Na+ and ?H2O. Furthermore, plasmatic biomarkers (cortisol, epinephrine, norepinephrine, renin, angiotensin II, aldosterone, pro-endothelin, copeptine, atrial natriuretic peptide, erythropoietin, mid-regional pro-adrenomedullin (MR-proADM)) and Sequential Organ Failure Assessment (SOFA) scores were measured at D2, D5 and D7. Blood volumes were measured with 51Cr fixed on red blood cells at D2 and D7.The ?Na+ or ?H2O were increased in all patients but never related to blood volumes at D2 nor D7. Total blood volumes were at normal values with constantly low red blood cell volumes and normal or decreased plasmatic volume. Weight, plasmatic proteins, and hemoglobin were weakly related to ?Na+ or ?H2O. Amongst all tested biomarkers, only MR-proADM was related to sodium and fluid overload. This biomarker was also a predictor of SOFA scores.Plasmatic concentration in MR-proADM seems to be a good surrogate for evaluation of ?Na+ or ?H2O and predicts sodium and extracellular fluid overload.ClinicalTrials.gov: NCT01858675 in May 13, 2013.

SUBMITTER: Vigue B

PROVIDER: S-EPMC5101658 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Mid-regional pro-adrenomedullin (MR-proADM), a marker of positive fluid balance in critically ill patients: results of the ENVOL study.

Vigué Bernard B Leblanc Pierre-Etienne PE Moati Frédérique F Pussard Eric E Foufa Hussam H Rodrigues Aurore A Figueiredo Samy S Harrois Anatole A Mazoit Jean-Xavier JX Rafi Homa H Duranteau Jacques J

Critical care (London, England) 20161109 1

<h4>Background</h4>The optimal control of blood volume without fluid overload is a main challenge in the daily care of intensive care unit (ICU) patients. Accordingly this study focused on the identification of biomarkers to help characterize fluid overload status.<h4>Methods</h4>Sixty-seven patients were studied from ICU admission to day 7 (D<sub>7</sub>). Blood and urine samples were taken daily and sodium and water balance strictly calculated resulting in a total cumulative assessment of ∆Na< ...[more]

PMID: 27825364

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Project description:In the Fluid and Catheter Treatment Trial (NCT00281268), adults with acute lung injury randomized to a conservative vs. liberal fluid management protocol had increased days alive and free of mechanical ventilator support (ventilator-free days). Recruiting sufficient children with acute lung injury into a pediatric trial is challenging. A Bayesian statistical approach relies on the adult trial for the a priori effect estimate, requiring fewer patients. Preparing for a Bayesian pediatric trial mirroring the Fluid and Catheter Treatment Trial, we aimed to: 1) identify an inverse association between fluid balance and ventilator-free days; and 2) determine if fluid balance over time is more similar to adults in the Fluid and Catheter Treatment Trial liberal or conservative arms.Multicentered retrospective cohort study.Five pediatric intensive care units.Mechanically ventilated children (age?1 month to <18 yrs) with acute lung injury admitted in 2007-2010.None.Fluid intake, output, and net fluid balance were collected on days 1-7 in 168 children with acute lung injury (median age 3 yrs, median PaO2/FIO2 138) and weight-adjusted (mL/kg). Using multivariable linear regression to adjust for age, gender, race, admission day illness severity, PaO2/FIO2, and vasopressor use, increasing cumulative fluid balance (mL/kg) on day 3 was associated with fewer ventilator-free days (p=.02). Adjusted for weight, daily fluid balance on days 1-3 and cumulative fluid balance on days 1-7 were higher in these children compared to adults in the Fluid and Catheter Treatment Trial conservative arm (p<.001, each day) and was similar to adults in the liberal arm.Increasing fluid balance on day 3 in children with acute lung injury at these centers is independently associated with fewer ventilator-free days. Our findings and the similarity of fluid balance patterns in our cohort to adults in the Fluid and Catheter Treatment Trial liberal arm demonstrate the need to determine whether a conservative fluid management strategy improves clinical outcomes in children with acute lung injury and support a Bayesian trial mirroring the Fluid and Catheter Treatment Trial.

Project description:Biomarkers are widely used to confirm the presence of infection. However, it would be of the greatest importance to predict in advance the occurrence or worsening of organ dysfunction in infected patients allowing timely antibiotic escalation. This study investigates the ability of procalcitonin (PCT) and MR-proADM to predict the transition to sepsis in infected patients. The study was conducted in a neurointensive care unit over a three-month period. We included both patients with and without infection to investigate the specificity of organ dysfunction prediction in infected patients. Daily measurement of PCT and MR-proADM, SOFA, Pitt, and CPIS were performed. To measure the correlation between each biomarker and each severity score, linear mixed-effects models were developed. For each biomarker-score combination we tested the correlation of the score with the biomarker measured one and two days before, the same day, and the day after. Sixty-four critically ill patients, 31 with infection, were enrolled. The statistically significant biomarker-score combinations were PCT-SOFA, MR-proADM-SOFA, MR-proADM-Pitt, and MR-proADM-CPIS. The MR-proADM models predicting Pitt and CPIS variations with 24-hour anticipation showed the best fit. The scores increased by 0.6 ± 0.3 and 0.4 ± 0.2 for each unitary biomarker increase, respectively. The MR-proADM-SOFA combinations were equivalent when the biomarker was measured the day before or the same day (score increases were 1.5 ± 0.4 and 1.9 ± 0.4, respectively). The PCT-SOFA model had the best fit when PCT was measured the same day of the score. There was no difference in the predictive ability of the biomarker in infected and non-infected patients. This was a pivotal study conducted in a single neurointensive centre on a limited number of patients, and as such it does not provide definitive conclusions. PR-proADM predicted occurrence and worsening of organ failure in critically ill patients with and without infection. The combination with infection diagnostic biomarkers such as PCT would allow predicting evolution to sepsis in infected patients.

Project description:BACKGROUND:Exacerbations of COPD (ECOPD) are a frequent cause of emergency room (ER) visits. Predictors of early outcome could help clinicians in orientation decisions. In the current study, we investigated whether mid-regional pro-adrenomedullin (MR-proADM) and copeptin, in addition to clinical evaluation, could predict short-term outcomes. PATIENTS AND METHODS:This prospective blinded observational study was conducted in 20 French centers. Patients admitted to the ER for an ECOPD were considered for inclusion. A clinical risk score was calculated, and MR-proADM and copeptin levels were determined from a venous blood sample. The composite primary end point comprised 30-day death or transfer to the intensive care unit or a new ER visit. RESULTS:A total of 379 patients were enrolled in the study, of whom 277 were eventually investigated for the primary end point that occurred in 66 (24%) patients. In those patients, the median (interquartile range [IQR]) MR-proADM level was 1.02 nmol/L (0.77-1.48) versus 0.83 nmol/L (0.63-1.07) in patients who did not meet the primary end point (P=0.0009). In contrast, copeptin levels were similar in patients who met or did not meet the primary end point (P=0.23). MR-proADM levels increased with increasing clinical risk score category: 0.74 nmol/L (0.57-0.89), 0.83 nmol/L (0.62-1.12) and 0.95 nmol/L (0.75-1.29) for the low-, intermediate- and high-risk categories, respectively (P<0.001). MR-proADM was independently associated with the primary end point (odds ratio, 1.65; 95% confidence interval [CI], 1.10-2.48; P=0.015). MR-proADM predicted the occurrence of primary end point with a sensitivity of 46% (95% CI, 33%-58%) and a specificity of 79% (95% CI, 74-84). CONCLUSION:MR-proADM but not copeptin was significantly associated with outcomes at 30 days, even after adjustment for clinical risk category. Overall, MR-proADM, alone or combined with the clinical risk score, was a moderate strong predictor of short-term outcomes.

Project description:Importance:After initial resuscitation, critically ill children may accumulate fluid and develop fluid overload. Accruing evidence suggests that fluid overload contributes to greater complexity of care and worse outcomes. Objective:To describe the methods to measure fluid balance, define fluid overload, and evaluate the association between fluid balance and outcomes in critically ill children. Data Sources:Systematic search of MEDLINE, EMBASE, Cochrane Library, trial registries, and selected gray literature from inception to March 2017. Study Selection:Studies of children admitted to pediatric intensive care units that described fluid balance or fluid overload and reported outcomes of interest were included. No language restrictions were applied. Data Extraction and Synthesis:All stages were conducted independently by 2 reviewers. Data extracted included study characteristics, population, fluid metrics, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale. Narrative description of fluid assessment methods and fluid overload definitions was done. When feasible, pooled analyses were performed using random-effects models. Main Outcomes and Measures:Mortality was the primary outcome. Secondary outcomes included treatment intensity, organ failure, and resource use. Results:A total of 44 studies (7507 children) were included in this systematic review and meta-analysis. Of those, 27 (61%) were retrospective cohort studies, 13 (30%) were prospective cohort studies, 3 (7%) were case-control studies, and 1 study (2%) was a secondary analysis of a randomized trial. The proportion of children with fluid overload varied by case mix and fluid overload definition (median, 33%; range, 10%-83%). Fluid overload, however defined, was associated with increased in-hospital mortality (17 studies [n?=?2853]; odds ratio [OR], 4.34 [95% CI, 3.01-6.26]; I2?=?61%). Survivors had lower percentage fluid overload than nonsurvivors (22 studies [n?=?2848]; mean difference, -5.62 [95% CI, -7.28 to -3.97]; I2?=?76%). After adjustment for illness severity, there was a 6% increase in odds of mortality for every 1% increase in percentage fluid overload (11 studies [n?=?3200]; adjusted OR, 1.06 [95% CI, 1.03-1.10]; I2?=?66%). Fluid overload was associated with increased risk for prolonged mechanical ventilation (>48 hours) (3 studies [n?=?631]; OR, 2.14 [95% CI, 1.25-3.66]; I2?=?0%) and acute kidney injury (7 studies [n?=?1833]; OR, 2.36 [95% CI, 1.27-4.38]; I2?=?78%). Conclusions and Relevance:Fluid overload is common and is associated with substantial morbidity and mortality in critically ill children. Additional research should now ideally focus on interventions aimed to mitigate the potential for harm associated with fluid overload.

Dataset Information

Mid-regional pro-adrenomedullin (MR-proADM), a marker of positive fluid balance in critically ill patients: results of the ENVOL study.

Publications

Mid-regional pro-adrenomedullin (MR-proADM), a marker of positive fluid balance in critically ill patients: results of the ENVOL study.

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