High Early Fluid Input After Aneurysmal Subarachnoid Hemorrhage: Combined Report of Association With Delayed Cerebral Ischemia and Feasibility of Cardiac Output-Guided Fluid Restriction.

BACKGROUND: Guidelines on the management of aneurysmal subarachnoid hemorrhage (aSAH) recommend euvolemia, whereas hypervolemia may cause harm. We investigated whether high early fluid input is associated with delayed cerebral ischemia (DCI), and if fluid input can be safely decreased using transpulmonary thermodilution (TPT). METHODS: We retrospectively included aSAH patients treated at an academic intensive care unit (2007-2011; cohort 1) or managed with TPT (2011-2013; cohort 2). Local guidelines recommended fluid input of 3 L daily. More fluids were administered when daily fluid balance fell below +500 mL. In cohort 2, fluid input in high-risk patients was guided by cardiac output measured by TPT per a strict protocol. Associations of fluid input and balance with DCI were analyzed with multivariable logistic regression (cohort 1), and changes in hemodynamic indices after institution of TPT assessed with linear mixed models (cohort 2). RESULTS: Cumulative fluid input 0 to 72 hours after admission was associated with DCI in cohort 1 (n=223; odds ratio [OR] 1.19/L; 95% confidence interval 1.07-1.32), whereas cumulative fluid balance was not. In cohort 2 (23 patients), using TPT fluid input could be decreased from 6.0 ± 1.0 L before to 3.4 ± 0.3 L; P = .012), while preload parameters and consciousness remained stable. CONCLUSION: High early fluid input was associated with DCI. Invasive hemodynamic monitoring was feasible to reduce fluid input while maintaining preload. These results indicate that fluid loading beyond a normal preload occurs, may increase DCI risk, and can be minimized with TPT.

Targeting urine output and 30-day mortality in goal-directed therapy: a systematic review with meta-analysis and meta-regression.

BACKGROUND: Oliguria is associated with a decreased kidney- and organ perfusion, leading to organ damage and increased mortality. While the effects of correcting oliguria on renal outcome have been investigated frequently, whether urine output is a modifiable risk factor for mortality or simply an epiphenomenon remains unclear. We investigated whether targeting urine output, defined as achieving and maintaining urine output above a predefined threshold, in hemodynamic management protocols affects 30-day mortality in perioperative and critical care. METHODS: We performed a systematic review with a random-effects meta-analyses and meta-regression based on search strategy through MEDLINE, EMBASE and references in relevant articles. We included studies comparing conventional fluid management with goal-directed therapy and reporting whether urine output was used as target or not, and reporting 30-day mortality data in perioperative and critical care. RESULTS: We found 36 studies in which goal-directed therapy reduced 30-day mortality (OR 0.825; 95% CI 0.684-0.995; P = 0.045). Targeting urine output within goal-directed therapy increased 30-day mortality (OR 2.66; 95% CI 1.06-6.67; P = 0.037), but not in conventional fluid management (OR 1.77; 95% CI 0.59-5.34; P = 0.305). After adjusting for operative setting, hemodynamic monitoring device, underlying etiology, use of vasoactive medication and year of publication, we found insufficient evidence to associate targeting urine output with a change in 30-day mortality (goal-directed therapy: OR 1.17; 95% CI 0.54-2.56; P = 0.685; conventional fluid management: OR 0.74; 95% CI 0.39-1.38; P = 0.334). CONCLUSIONS: The principal finding of this meta-analysis is that after adjusting for confounders, there is insufficient evidence to associate targeting urine output with an effect on 30-day mortality. The paucity of direct data illustrates the need for further research on whether permissive oliguria should be a key component of fluid management protocols.

Neutrophil Gelatinase-Associated Lipocalin as a Diagnostic Marker for Acute Kidney Injury in Oliguric Critically Ill Patients: A Post-Hoc Analysis.

BACKGROUND: Oliguria occurs frequently in critically ill patients, challenging clinicians to distinguish functional adaptation from serum-creatinine-defined acute kidney injury (AKIsCr). We investigated neutrophil gelatinase-associated lipocalin (NGAL)'s ability to differentiate between these 2 conditions. METHODS: This is a post-hoc analysis of a prospective cohort of adult critically ill patients. Patients without oliguria within the first 6 h of admission were excluded. Plasma and urinary NGAL were measured at 4 h after admission. AKIsCr was defined using the AKI network criteria with pre-admission serum creatinine or lowest serum creatinine value during the admission as the baseline value. Hazard ratios for AKIsCr occurrence within 72 h were calculated using Cox regression and adjusted for risk factors such as sepsis, pre-admission serum creatinine, and urinary output. Positive predictive values (PPV) and negative predictive values (NPV) were calculated for the optimal cutoffs for NGAL. RESULTS: Oliguria occurred in 176 patients, and 61 (35%) patients developed AKIsCr. NGAL was a predictor for AKIsCr in univariate and multivariate analysis. When NGAL was added to a multivariate model including sepsis, pre-admission serum creatinine and lowest hourly urine output, it outperformed the latter model (plasma p = 0.001; urinary p = 0.048). Cutoff values for AKIsCr were 280 ng/ml for plasma (PPV 80%; NPV 79%), and 250 ng/ml for urinary NGAL (PPV 58%; NPV 78%). CONCLUSIONS: NGAL can be used to distinguish oliguria due to the functional adaptation from AKIsCr, directing resources to patients more likely to develop AKIsCr.

Targeting oliguria reversal in perioperative restrictive fluid management does not influence the occurrence of renal dysfunction: A systematic review and meta-analysis.

BACKGROUND: Interest in perioperative fluid restriction has increased, but it could lead to hypovolaemia. Urine output is viewed as a surrogate for renal perfusion and is frequently used to guide perioperative fluid therapy. However, the rationale behind targeting oliguria reversal - achieving and maintaining urine output above a previously defined threshold by additional fluid boluses - is often questioned. OBJECTIVE: We assessed whether restrictive fluid management had an effect on oliguria, acute renal failure (ARF) and fluid intake. We also investigated whether targeting oliguria reversal affected these parameters. DESIGN: Systematic review of randomised controlled trials with meta-analyses. We used the definitions of restrictive and conventional fluid management as provided by the individual studies. DATA SOURCES: We searched MEDLINE (1966 to present), EMBASE (1980 to present), and relevant reviews and articles. ELIGIBILITY CRITERIA: We included randomised controlled trials with adult patients undergoing surgery comparing restrictive fluid management with a conventional fluid management protocol and also reporting the occurrence of postoperative ARF. RESULTS: We included 15 studies with a total of 1594 patients. There was insufficient evidence to associate restrictive fluid management with an increase in oliguria [restrictive 83/186 vs. conventional 68/230; odds ratio (OR) 2.07; 95% confidence interval (CI), 0.97 to 4.44; P = 0.06; I = 23.7%; Nstudies = 5]. The frequency of ARF in restrictive and conventional fluid management was 20/795 and 20/799, respectively (OR 1.07; 95% CI, 0.60 to 1.92; P = 0.8; I = 17.5%; Nstudies = 15). There was no statistically significant difference in ARF occurrence between studies targeting oliguria reversal and not targeting oliguria reversal (OR 0.31; 95% CI, 0.08 to 1.22; P = 0.088). Intraoperative fluid intake was 1.89 l lower in restrictive than in conventional fluid management when not targeting oliguria reversal (95% CI, -2.59 to -1.20 l; P < 0.001; I = 96.6%; Nstudies = 7), and 1.63 l lower when targeting oliguria reversal (95% CI, -2.52 to -0.74 l; P < 0.001; I = 96.6%; Nstudies = 6). CONCLUSION: Our data suggest that, even though event numbers are small, perioperative restrictive fluid management does not increase oliguria or postoperative ARF while decreasing intraoperative fluid intake, irrespective of targeting reversal of oliguria or not.

Targeting Oliguria Reversal in Goal-Directed Hemodynamic Management Does Not Reduce Renal Dysfunction in Perioperative and Critically Ill Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: We investigated whether resuscitation protocols to achieve and maintain urine output above a predefined threshold-including oliguria reversal as a target--prevent acute renal failure (ARF). METHODS: We performed a systematic review and meta-analysis using studies found by searching MEDLINE, EMBASE, and references in relevant reviews and articles. We included all studies that compared "conventional fluid management" (CFM) with "goal-directed therapy" (GDT) using cardiac output, urine output, or oxygen delivery parameters and reported the occurrence of ARF in critically ill or surgical patients. We divided studies into groups with and without oliguria reversal as a target for hemodynamic optimization. We calculated the combined odds ratio (OR) and 95% confidence intervals (CIs) using random-effects meta-analysis. RESULTS: We based our analyses on 28 studies. In the overall analysis, GDT resulted in less ARF than CFM (OR, 0.58; 95% CI, 0.44-0.76; P < 0.001; I = 34.3%; n = 28). GDT without oliguria reversal as a target resulted in less ARF (OR, 0.45; 95% CI, 0.34-0.61; P < 0.001; I = 7.1%; n = 7) when compared with CFM with oliguria reversal as a target. The studies comparing GDT with CFM in which the reversal of oliguria was targeted in both or in neither group did not provide enough evidence to conclude a superiority of GDT (targeting oliguria reversal in both protocols: OR, 0.63; 95% CI, 0.36-1.10; P = 0.09; I = 48.6%; n = 9, and in neither protocol: OR, 0.66; 95% CI, 0.37-1.16; P = 0.14; I = 20.2%; n = 12). CONCLUSIONS: Current literature favors targeting circulatory optimization by GDT without targeting oliguria reversal to prevent ARF. Future studies are needed to investigate the hypothesis that targeting oliguria reversal does not prevent ARF in critically ill and surgical patients.

Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis.

INTRODUCTION: In Europe, vitamin D deficiency is highly prevalent varying between 40% and 60% in the healthy general adult population. The consequences of vitamin D deficiency for sepsis and outcome in critically ill patients remain controversial. We therefore systematically reviewed observational cohort studies on vitamin D deficiency in the intensive care unit. METHODS: Fourteen observational reports published from January 2000 to March 2014, retrieved from Pubmed and Embase, involving 9,715 critically ill patients and serum 25-hydroxyvitamin D3 (25 (OH)-D) concentrations, were meta-analysed. RESULTS: Levels of 25 (OH)-D less than 50 nmol/L were associated with increased rates of infection (risk ratio (RR) 1.49, 95% (confidence interval (CI) 1.12 to 1.99), P = 0.007), sepsis (RR 1.46, 95% (CI 1.27 to 1.68), P <0.001), 30-day mortality (RR 1.42, 95% (CI 1.00 to 2.02), P = 0.05), and in-hospital mortality (RR 1.79, 95% (CI 1.49 to 2.16), P <0.001). In a subgroup analysis of adjusted data including vitamin D deficiency as a risk factor for 30-day mortality the pooled RR was 1.76 (95% CI 1.37 to 2.26, P <0.001). CONCLUSIONS: This meta-analysis suggests that vitamin D deficiency increases susceptibility for severe infections and mortality of the critically ill.

Intraoperative glycemic control without insulin infusion during pediatric cardiac surgery for congenital heart disease.

BACKGROUND: Many studies are reporting that the occurrence of hyperglycemia in the postoperative period is associated with increased morbidity and mortality rates in children after cardiac surgery for congenital heart disease. This study sought to determine blood glucose levels in standard pediatric cardiac anesthesiological management without insulin infusions. METHODS: The study population consisted of 204 consecutive pediatric patients aged from 3 days to 15.4 years undergoing open cardiac surgery for congenital heart disease between June 2007 and January 2009. Glucose-containing fluids were not administrated intraoperatively, and all patients received high dose of opioids (sufentanil 10 mcg·kg(-1) ) and steroids (30 mg·kg(-1) methylprednisolone) iv. Glucose levels were measured before CPB, 10 min after initiation of CPB, every hour on CPB, post-CPB, and on arrival at intensive care unit (ICU). RESULTS: Intraoperatively, only one patient had a glucose level <50 mg·dl(-1) (=34.2 mg·dl(-1) ), 57/204 patients (27.9%) had at least one intraoperative glucose >180 mg·dl(-1) , but only 12 patients (5.8%) had a glucose level >180 mg·dl(-1) at ICU arrival. Thirty-day mortality was 1.5% (3/204). Younger age, lower body weight, and lower CPB temperature were associated with hyperglycemia at ICU arrival, as were higher RACHS and Aristotle severity scores. CONCLUSION: A conventional (no insulin, no glucose) anesthetic management seems sufficient in the vast majority of patients (96.5%). Special attention should be paid to small neonates with complex congenital heart surgery, in whom insulin treatment may be contemplated.