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BACKGROUND - Conservative fluid management increases ventilator-free days without influencing overall mortality in acute respiratory distress syndrome. Plasma concentrations of B-type natriuretic peptide (a marker of ventricular filling) or aldosterone (a marker of effective circulating volume) may identify patients for whom fluid management impacts survival.
METHODS - This was a retrospective analysis of the Fluid and Catheter Treatment Trial (FACTT), a randomized trial comparing conservative with liberal fluid management in acute respiratory distress syndrome. Using plasma collected at study enrollment, we measured B-type natriuretic peptide and aldosterone by immunoassay. Multivariable analyses examined the interaction between B-type natriuretic peptide or aldosterone concentration and fluid strategy with regard to 60-day in-hospital mortality.
RESULTS - Among 625 patients with adequate plasma, median B-type natriuretic peptide concentration was 825 pg/mL (interquartile range, 144-1,574 pg/mL), and median aldosterone was 2.49 ng/dL (interquartile range, 1.1-4.3 ng/dL). B-type natriuretic peptide did not predict overall mortality, correlate with fluid balance, or modify the effect of conservative vs liberal fluid management on outcomes. In contrast, among patients with lower aldosterone concentrations, conservative fluid management increased ventilator-free days (17.1 ± 9.8 vs 12.5 ± 10.3, P < .001) and decreased mortality (19% vs 30%, P = .03) (P value for interaction = .01).
CONCLUSIONS - In acute respiratory distress syndrome, B-type natriuretic peptide does not modify the effect of fluid management on outcomes. Lower initial aldosterone appears to identify patients for whom conservative fluid management may improve mortality.
Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
BACKGROUND - Currently, guidelines recommend initial resuscitation with intravenous (IV) crystalloids during severe sepsis/septic shock. Albumin is suggested as an alternative. However, fluid mixtures are often used in practice, and it is unclear whether the specific mixture of IV fluids used impacts outcomes. The objective of this study is to test the hypothesis that the specific mixture of IV fluids used during initial resuscitation, in severe sepsis, is associated with important in-hospital outcomes.
METHODS - Retrospective cohort study includes patients with severe sepsis who were resuscitated with at least 2 l of crystalloids and vasopressors by hospital day 2, patients who had not undergone any major surgical procedures, and patients who had a hospital length of stay (LOS) of at least 2 days. Inverse probability weighting, propensity score matching, and hierarchical regression methods were used for risk adjustment. Patients were grouped into four exposure categories: recipients of isotonic saline alone ("Sal" exclusively), saline in combination with balanced crystalloids ("Sal + Bal"), saline in combination with colloids ("Sal + Col"), or saline in combination with balanced crystalloids and colloids ("Sal + Bal + Col"). In-hospital mortality was the primary outcome, and hospital LOS and costs per day (among survivors) were secondary outcomes.
RESULTS - In risk-adjusted Inverse Probability Weighting analyses including 60,734 adults admitted to 360 intensive care units across the United States between January 2006 and December 2010, in-hospital mortality was intermediate in the Sal group (20.2%), lower in the Sal + Bal group (17.7%, P < 0.001), higher in the Sal + Col group (24.2%, P < 0.001), and similar in the Sal + Bal + Col group (19.2%, P = 0.401). In pairwise propensity score-matched comparisons, the administration of balanced crystalloids by hospital day 2 was consistently associated with lower mortality, whether colloids were used (relative risk, 0.84; 95% CI, 0.76 to 0.92) or not (relative risk, 0.79; 95% CI, 0.70 to 0.89). The association between colloid use and in-hospital mortality was inconsistent, and survival was not uniformly affected, whereas LOS and costs per day were uniformly increased. Results were robust in sensitivity analyses.
CONCLUSIONS - During the initial resuscitation of adults with severe sepsis/septic shock, the types of IV fluids used may impact in-hospital mortality. When compared with the administration of isotonic saline exclusively during resuscitation, the coadministration of balanced crystalloids is associated with lower in-hospital mortality and no difference in LOS or costs per day. When colloids are coadministered, LOS and costs per day are increased without improved survival. A large randomized controlled trial evaluating crystalloid choice is warranted. Meanwhile, the use of balanced crystalloids seems reasonable. (Anesthesiology 2015; 123:1385-93).
INTRODUCTION - Intravenous (IV) fluids may be associated with complications not often attributed to fluid type. Fluids with high chloride concentrations such as 0.9 % saline have been associated with adverse outcomes in surgery and critical care. Understanding the association between fluid type and outcomes in general hospitalized patients may inform selection of fluid type in clinical practice. We sought to determine if the type of IV fluid administered to patients with systemic inflammatory response syndrome (SIRS) is associated with outcome.
METHODS - This was a propensity-matched cohort study in hospitalized patients receiving at least 500 mL IV crystalloid within 48 hours of SIRS. Patient data was extracted from a large multi-hospital electronic health record database between January 1, 2009, and March 31, 2013. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, readmission, and complications measured by ICD-9 coding and clinical definitions. Outcomes were adjusted for illness severity using the Acute Physiology Score. Of the 91,069 patients meeting inclusion criteria, 89,363 (98%) received 0.9% saline whereas 1706 (2%) received a calcium-free balanced solution as the primary fluid.
RESULTS - There were 3116 well-matched patients, 1558 in each cohort. In comparison with the calcium-free balanced cohort, the saline cohort experienced greater in-hospital mortality (3.27% vs. 1.03%, P <0.001), length of stay (4.87 vs. 4.38 days, P = 0.016), frequency of readmission at 60 (13.54 vs. 10.91, P = 0.025) and 90 days (16.56 vs. 12.58, P = 0.002) and frequency of cardiac, infectious, and coagulopathy complications (all P < 0.002). Outcomes were defined by administrative coding and clinically were internally consistent. Patients in the saline cohort received more chloride and had electrolyte abnormalities requiring replacement more frequently (P < 0.001). No differences were found in acute renal failure.
CONCLUSIONS - In this large electronic health record, the predominant use of 0.9% saline in patients with SIRS was associated with significantly greater morbidity and mortality compared with predominant use of balanced fluids. The signal is consistent with that reported previously in perioperative and critical care patients. Given the large population of hospitalized patients receiving IV fluids, these differences may confer treatment implications and warrant corroboration via large clinical trials.
TRIAL REGISTRATION - NCT02083198 clinicaltrials.gov; March 5, 2014.
BACKGROUND - The objective of this systematic review and meta-analysis was to assess the relationship between the chloride content of intravenous resuscitation fluids and patient outcomes in the perioperative or intensive care setting.
METHODS - Systematic searches were performed of PubMed/MEDLINE, Embase and Cochrane Library (CENTRAL) databases in accordance with PRISMA guidelines. Randomized clinical trials, controlled clinical trials and observational studies were included if they compared outcomes in acutely ill or surgical patients receiving either high-chloride (ion concentration greater than 111 mmol/l up to and including 154 mmol/l) or lower-chloride (concentration 111 mmol/l or less) crystalloids for resuscitation. Endpoints examined were mortality, measures of kidney function, serum chloride, hyperchloraemia/metabolic acidosis, blood transfusion volume, mechanical ventilation time, and length of hospital and intensive care unit stay. Risk ratios (RRs), mean differences (MDs) or standardized mean differences (SMDs) and confidence intervals were calculated using fixed-effect modelling.
RESULTS - The search identified 21 studies involving 6253 patients. High-chloride fluids did not affect mortality but were associated with a significantly higher risk of acute kidney injury (RR 1.64, 95 per cent c.i. 1.27 to 2.13; P < 0.001) and hyperchloraemia/metabolic acidosis (RR 2.87, 1.95 to 4.21; P < 0.001). High-chloride fluids were also associated with greater serum chloride (MD 3.70 (95 per cent c.i. 3.36 to 4.04) mmol/l; P < 0.001), blood transfusion volume (SMD 0.35, 0.07 to 0.63; P = 0.014) and mechanical ventilation time (SMD 0.15, 0.08 to 0.23; P < 0.001). Sensitivity analyses excluding heavily weighted studies resulted in non-statistically significant effects for acute kidney injury and mechanical ventilation time.
CONCLUSION - A weak but significant association between higher chloride content fluids and unfavourable outcomes was found, but mortality was unaffected by chloride content.
© 2014 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.
Fluid management during critical illness is a dynamic process that may be conceptualized as occurring in four phases: rescue, optimization, stabilization, and de-escalation (mobilization). The selection and administration of resuscitation fluids is one component of this complex physiological sequence directed at restoring depleted intravascular volume. Presently, the selection of i.v. fluid is usually dictated more by local practice patterns than by evidence. The debate on fluid choice has primarily focused on evaluating outcome differences between 'crystalloids vs colloids'. More recently, however, there is interest in examining outcome differences based on the chloride content of crystalloid solutions. New insights into the conventional Starling model of microvascular fluid exchange may explain that the efficacy of colloids in restoring and maintaining depleted intravascular volume is only moderately better than crystalloids. A number of investigator-initiated, high-quality, randomized controlled trials have demonstrated that modest improvements in short-term physiological endpoints with colloids have not translated into better patient-centred outcomes. In addition, there is substantial evidence that certain types of fluids may independently worsen patient-centred outcomes. These include hydroxyethyl starch and albumin solutions in selected patient populations. There is no evidence to support the use of other colloids. The use of balanced salt solutions in preference to 0.9% saline is supported by the absence of harm in large observational studies. However, there is no compelling randomized trial-based evidence demonstrating improved clinical outcomes with the use of balanced salt solutions compared with 0.9% saline at this time.
© The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: email@example.com.
PURPOSE - Recent data suggest that both elevated serum chloride levels and volume overload may be harmful during fluid resuscitation. The purpose of this study was to examine the relationship between the intravenous chloride load and in-hospital mortality among patients with systemic inflammatory response syndrome (SIRS), with and without adjustment for the crystalloid volume administered.
METHODS - We conducted a retrospective analysis of 109,836 patients ≥ 18 years old that met criteria for SIRS and received fluid resuscitation with crystalloids. We examined the association between changes in serum chloride concentration, the administered chloride load and fluid volume, and the 'volume-adjusted chloride load' and in-hospital mortality.
RESULTS - In general, increases in the serum chloride concentration were associated with increased mortality. Mortality was lowest (3.7%) among patients with minimal increases in serum chloride concentration (0-10 mmol/L) and when the total administered chloride load was low (3.5% among patients receiving 100-200 mmol; P < 0.05 versus patients receiving ≥ 500 mmol). After controlling for crystalloid fluid volume, mortality was lowest (2.6%) when the volume-adjusted chloride load was 105-115 mmol/L. With adjustment for severity of illness, the odds of mortality increased (1.094, 95% CI 1.062, 1.127) with increasing volume-adjusted chloride load (≥ 105 mmol/L).
CONCLUSIONS - Among patients with SIRS, a fluid resuscitation strategy employing lower chloride loads was associated with lower in-hospital mortality. This association was independent of the total fluid volume administered and remained significant after adjustment for severity of illness, supporting the hypothesis that crystalloids with lower chloride content may be preferable for managing patients with SIRS.