Balanced crystalloids versus isotonic saline in critically ill patients: systematic review and meta-analysis.
ABSTRACT: Intravenous fluids are one of the most used medical therapy for patients, especially critically ill patients. We conducted a meta-analysis comparing between balanced crystalloids and normal saline in critically ill patients and its effect on various clinical outcomes.Meta-analysis and systematic review of randomized clinical trials (RCTs).Electronic search was performed using PubMed, Cochrane library, and clinical trials.gov from inception through March 1, 2018, with inclusion of prospective studies that investigated one of the primary outcomes which were acute kidney injury (AKI) and in-hospital mortality while secondary outcomes were intensive care unit (ICU) mortality and new renal replacement therapy (RRT).Six RCTs were included. Total of 19,332 patients were included in the final analysis. There was no significant difference in in-hospital mortality (11.5% vs 12.2%; OR 0.92; 95% CI 0.85-1.01; P?=?0.09; I2 =?0%), incidence of AKI (12% vs 12.7%, OR 0.92; 95% CI 0.84-1.01; P?=?0.1; I2 =?0), overall ICU mortality (OR 0.9, 95% CI 0.81-1.01, P?=?0.08, I2 =?0%), or need for new RRT (OR 0.92, 95% CI 0.67-1.28, P?=?0.65, I2 =?38%) between balanced crystalloids and isotonic saline in critically ill patients.Balanced crystalloids and isotonic saline have no difference on various clinical outcomes including in-hospital mortality, AKI, overall ICU mortality, and new RRT. Further powerful clinical trials are required to determine the relationship between crystalloid fluid type and clinical outcomes.
Project description:The appropriate timing for initiating renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI) remains unknown. This meta-analysis aims to assess the efficacy of early initiation of RRT in critically ill patients with AKI. The Pubmed, Embase and Cochrane databases were searched up to August 13, 2019. Only randomized controlled trials (RCTs) comparing the effects of early and late RRT on AKI patients were included. The primary outcome was 28-day mortality. Eleven RCTs including 1131 and 1111 AKI patients assigned to early and late RRT strategies, respectively, were enrolled in this meta-analysis. The pooled 28-day mortality was 38.1% (431/1131) and 40.7% (453/1111) in the patients assigned to early and late RRT, respectively, with no significant difference between groups (risk ratio (RR), 0.95; 95% CI, 0.78-1.15, I2?=?63%). No significant difference was found between groups in terms of RRT dependence in survivors on day 28 (RR, 0.90; 95% CI, 0.67-1.25, I2?=?0%), and recovery of renal function (RR, 1.03; 95% CI, 0.89-1.19, I2?=?56%). The early RRT group had higher risks of catheter-related infection (RR, 1.7, 95% CI, 1.01-2.97, I2?=?0%) and hypophosphatemia (RR, 2.5, 95% CI, 1.25-4.99, I2?=?77%) than the late RRT group. In conclusion, an early RRT strategy does not improve survival, RRT dependence, or renal function recovery in critically ill patients with AKI in comparison with a late RRT strategy. However, clinicians should be vigilant because early RRT can carry higher risks of catheter-related infection and hypophosphatemia during dialysis than late RRT.
Project description:BACKGROUND:Crystalloids are the most frequently prescribed drugs in intensive care medicine and emergency medicine. Thus, even small differences in outcome may have major implications, and therefore, the choice between balanced crystalloids versus normal saline continues to be debated. We examined to what extent the currently accrued information size from completed and ongoing trials on the subject allow intensivists and emergency physicians to choose the right fluid for their patients. METHODS:Systematic review and meta-analysis with random effects inverse variance model. Published randomized controlled trials enrolling adult patients to compare balanced crystalloids versus normal saline in the setting of intensive care medicine or emergency medicine were included. The main outcome was mortality at the longest follow-up, and secondary outcomes were moderate to severe acute kidney injury (AKI) and initiation of renal replacement therapy (RRT). Trial sequential analyses (TSA) were performed, and risk of bias and overall quality of evidence were assessed. Additionally, previously published meta-analyses, trial sequential analyses and ongoing large trials were analysed for included studies, required information size calculations and the assumptions underlying those calculations. RESULTS:Nine studies (n?=?32,777) were included. Of those, eight had data available on mortality, seven on AKI and six on RRT. Meta-analysis showed no significant differences between balanced crystalloids versus normal saline for mortality (P?=?0.33), the incidence of moderate to severe AKI (P?=?0.37) or initiation of RRT (P?=?0.29). Quality of evidence was low to very low. Analysis of previous meta-analyses and ongoing trials showed large differences in calculated required versus accrued information sizes and assumptions underlying those. TSA revealed the need for extremely large trials based on our realistic and clinically relevant assumptions on relative risk reduction and baseline mortality. CONCLUSIONS:Our meta-analysis could not find significant differences between balanced crystalloids and normal saline on mortality at the longest follow-up, moderate to severe AKI or new RRT. Currently accrued information size is smaller, and the required information size is larger than previously anticipated. Therefore, completed and ongoing trials on the topic may fail to provide adequate guidance for choosing the right crystalloid. Thus, physiology will continue to play an important role for individualizing this choice.
Project description:INTRODUCTION: Acute kidney injury (AKI) increases mortality and morbidity of critically ill patients. Mortality of patients treated with renal replacement therapy (RRT) is high. We aimed to evaluate the nationwide incidence of RRT-treated AKI in Finland, hospital and six-month mortality, and health-related quality of life (HRQoL) of these patients. METHODS: We performed a retrospective cohort study including all general intensive care unit (ICU) admissions in Finland in 2007 through 2008. We identified patients who had received RRT due to AKI (RRT patients) and compared these patients to ICU patients who were not treated with RRT (non-RRT patients). The HRQoL was assessed by the EQ-5D index and visual analogue scale (VAS). RESULTS: We analysed the final cohort of 24,904 patients, of whom 1,686 received RRT due to AKI. The incidence of RRT-treated AKI was 6.8% (95% confidence interval (CI) 6.5 to 7.1%) among ?15-year-old general ICU patients, which corresponds to a yearly population-based incidence of 19.2 per 100,000 (95% CI 17.9 to 20.5/100,000). According to RIFLE (Risk, Injury, Failure) classification 26.6% (95% CI 26.0 to 27.2%) of patients had AKI (RIFLE R-F). Hospital and six-month mortality of RRT patients were 35.0% and 49.4%. At six-months, RRT patients perceived their health as good as non-RRT patients by VAS. CONCLUSIONS: The population-based incidence of AKI treated with RRT was 19.2 per 100,000 in Finland and 6.8% of all general ICU patients. The hospital and six-month mortality rates were lower than previously reported for ICU-treated RRT patients.
Project description:To investigate the impact of timing the initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI), focusing on the randomized controlled trials (RCTs) in this field.The PubMed, EMBASE and Cochrane databases were searched between January 1, 1985, and June 30, 2016, to identify randomized trials that assessed the timing of initiation of RRT in patients with AKI.Nine RCTs, with a total of 1636 patients, were enrolled in this meta-analysis. A pooled analysis of the studies indicated no mortality benefit with "early" RRT, with an RR of 0.98 (95% CI 0.78 to 1.23, P = 0.84). There was no significant difference in intensive care unit (ICU) length of stay (LOS) or hospital LOS between the early and late RRT groups for survivors or nonsurvivors. Pooled analysis also demonstrated no significant change in renal function recovery (RR 1.02, 95% CI 0.88 to 1.19, I2 = 59%), RRT dependence (RR 0.76, 95% CI 0.42 to 1.37, I2 = 0%), duration of RRT (Mean difference 1.43, 95% CI -1.75 to 4.61, I2 = 78%), renal recovery time (Mean difference 0.73, 95% CI -2.09 to 3.56, I2 = 70%) or mechanical ventilation time (Mean difference - 0.95, 95% CI -3.54 to 1.64, I2 = 64%) between the early and late RRT groups. We found no significant differences in complications between the groups.Our meta-analysis revealed that the "early" initiation of RRT in critically ill patients did not result in reduced mortality. Pooled analysis of secondary outcomes also showed no significant difference between the early and late RRT groups. More well-designed and large-scale trials are expected to confirm the result of this meta-analysis.
Project description:Catalytic iron has been hypothesized to be a key mediator of AKI. However, the association between plasma catalytic iron levels and AKI has not been well studied in humans.A single-center, prospective, nonconsecutive cohort study of 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012 was performed. Plasma catalytic iron, free hemoglobin, and other iron markers were measured on ICU days 1 and 4. The primary end point was in-hospital mortality or AKI requiring RRT. Secondary end points included mortality (assessed during hospitalization, at 30 days, and 1 year) and incident AKI, defined by modified Kidney Disease Improving Global Outcomes criteria.ICU day 1 plasma catalytic iron levels were higher among patients who reached the primary end point (median, 0.74 µmol/l [interquartile range, 0.31-3.65] versus 0.29 µmol/l [0.22-0.46]; P<0.01). ICU day 1 plasma catalytic iron levels were associated with number of packed red blood cell transfusions before ICU arrival (rs=0.29; P<0.001) and plasma free hemoglobin levels on ICU day 1 (rs=0.32; P<0.001). Plasma catalytic iron levels on ICU day 1 were significantly associated with in-hospital mortality or AKI requiring RRT, even after adjusting for age, enrollment eGFR, and number of packed red blood cell transfusions before ICU arrival (13 events; adjusted odds ratio per 1-SD higher ln[catalytic iron], 3.33; 95% confidence interval, 1.79 to 6.20). ICU day 1 plasma catalytic iron levels were also significantly associated with incident AKI, RRT, hospital mortality, and 30-day mortality.Among critically ill patients, elevated plasma catalytic iron levels on arrival to the ICU are associated with a greater risk of incident AKI, RRT, and hospital mortality.
Project description:BACKGROUND:Acute kidney injury (AKI) commonly occurs in intensive care units (ICUs), leading to adverse clinical outcomes and increasing costs. However, there are limited epidemiological data of AKI in the critically ill in Beijing, China. METHODS:In this prospective cohort study in 30 ICUs, we screened the patients up to 10?days after ICU admission. Characteristics and outcomes were compared between AKI and non-AKI, renal replacement therapy (RRT) and non-RRT patients. Nomograms of logistic regression and Cox regression were performed to examine potential risk factors for AKI and mortality. RESULTS:A total of 3107 patients were included in the final analysis. The incidence of AKI was 51.0%; stages 1 to 3 accounted for 23.1, 11.8, and 15.7%, respectively. The majority (87.6%) of patients with AKI developed AKI on the first 4 days after admission to the ICU. A total of 281 patients were treated with RRT. Continuous RRT with predilution, citrate for anticoagulation and femoral vein for vascular access was the most common RRT pattern (29.9%, 84 of 281). Patients with AKI were associated with longer ICU-LOS and higher mortality and costs (P<0.001). In patients treated with RRT, 78.6 and 28.5% of RRTs were dependent on the 7th and 28th days, respectively. The 28?day mortalities of non-AKI, AKI stages 1-3, and septic shock patients were 6.83, 15.04, 27.99, 45.18 and 36.5%, respectively. CONCLUSIONS:Approximately half of our ICU patients experienced AKI. The majority of patients with AKI developed AKI during the first 4 days after admission to the ICU. Continuous RRT with predilution, citrate for anticoagulation and femoral vein for vascular access was the most common RRT pattern in our ICUs. AKI was associated with a higher mortality and costs, incomplete kidney recovery and s series of adverse outcomes.
Project description:Purpose: The results from randomized controlled trials (RCTs) concerning the timing of initiation of renal replacement therapy (RRT) for patients with acute kidney injury (AKI) are still inconsistent.Materials and methods: We searched for RCTs, as well as relevant references, focusing on the timing of RRT for AKI patients in the Medline, Embase, Cochrane Library, Google Scholar and Chinese databases from their inception to December 2018.Results: We included 18 RCTs from 1997 to 2018 involving 2856 patients. Pooled analyses of all RCTs showed no significant difference in mortality between early initiation and delayed initiation of RRT (RR 0.98, 95% CI: 0.89 to 1.08, p?=?.7) (I2?=?2%), and similar results were found in critically ill and community-acquired AKI patients, as well as in a subgroup of patients with sepsis and in cardiac surgery recipients. There was also no difference in the incidence of dialysis independence (RR 0.75, 95% CI: 0.47 to 1.2, p?=?.2) (I2?=?0). However, an early RRT strategy was associated with a significantly higher incidence of the need for RRT for AKI patients (RR 1.24, 95% CI: 1.13 to 1.36, p?<?.01) (I2?=?34%).Conclusions: As no life-threatening complications occurred, there was no evidence to show any benefit of an early RRT strategy for critically ill or community-acquired AKI patients; in contrast, a delayed strategy might avert the need for RRT.
Project description:Rationale & Objective:Uric acid is excreted by the kidney and accumulates in acute kidney injury (AKI). Whether higher plasma uric acid level predisposes to AKI or its complications is not known. Study Design:Prospective observational cohort study. Setting & Participants:2 independent cohorts of critically ill patients: (1) 208 patients without AKI admitted to the intensive care unit (ICU) at Brigham & Women's Hospital between October 2008 and December 2016; and (2) 250 participants with AKI requiring renal replacement therapy (RRT) who had not yet initiated RRT enrolled in the Acute Renal Failure Trial Network (ATN) Study. Exposure:Plasma uric acid level upon ICU admission and before RRT initiation in the ICU and ATN Study cohorts, respectively. Outcomes:Incident AKI and 60-day mortality in the ICU and ATN Study cohorts, respectively. Analytical Approach:Logistic regression models were used to test the association of plasma uric acid level with incident AKI and 60-day mortality. Results:In the ICU cohort, median plasma uric acid level was 4.7 (interquartile range [IQR], 3.6-6.4) mg/dL, and 40 patients (19.2%) developed AKI. Higher plasma uric acid levels associated with incident AKI, but this association was confounded by serum creatinine level and was not significant after multivariable adjustment (adjusted OR per doubling of uric acid, 1.50; 95% CI, 0.80-2.81). In the ATN Study cohort, median plasma uric acid level was 11.1 (IQR, 8.6-14.2) mg/dL, and 125 participants (50.0%) died within 60 days. There was no statistically significant association between plasma uric acid levels and 60-day mortality in either unadjusted models or after multivariable adjustment for demographic, severity-of-illness, and kidney-specific covariates (adjusted OR per doubling of uric acid, 1.15; 95% CI, 0.71-1.86). Limitations:Heterogeneity of ICU patients. Conclusions:Plasma uric acid levels upon ICU admission or before RRT initiation are not independently associated with adverse clinical outcomes in critically ill patients.
Project description:<h4>Background</h4>Acute kidney injury (AKI) is a common yet possibly fatal complication among critically ill patients in intensive care units (ICU). Although renal replacement therapy (RRT) is an important supportive management for severe AKI patients, the optimal timing of RRT initiation for these patients is still unclear.<h4>Methods</h4>In this systematic review, we searched all relevant randomized controlled trials (RCTs) that directly compared accelerated with standard initiation of RRT from PUBMED, MEDLINE, EMBASE, and Cnki.net published prior to July, 20, 2020. We extracted study characteristics and outcomes of being free of dialysis, dialysis dependence and mortality. We rated the certainty of evidence according to Cochrane methods and the GRADE approach.<h4>Results</h4>We identified 56 published relevant studies from 1071 screened abstracts. Ten RCTs with 4753 critically ill AKI patients in intensive care unit (ICU) were included in this meta-analysis. In our study, accelerated and standard RRT group were not associated with all-cause mortality (log odds-ratio [OR]:?-?0.04, 95% confidence intervals [CI]?-?0.16 to 0.07, p?=?0.46) and free of dialysis (log OR:?-?0.03, 95% CI?-?0.14 to 0.09, p?=?0.65). In the subgroup analyses, accelerated RRT group was significantly associated with lower risk of all-cause mortality in the surgical ICU and for those who received continuous renal replacement therapy (CRRT). In addition, patients in these two subgroups had higher chances of being eventually dialysis-free. However, accelerated initiation of RRT augmented the risk of dialysis dependence in the subgroups of patients treated with non-CRRT modality and whose Sequential Organ Failure Assessment (SOFA) score were more than 11.<h4>Conclusions</h4>In this meta-analysis, critically ill patients with severe AKI would benefit from accelerated RRT initiation regarding all-cause mortality and being eventually free of dialysis only if they were surgical ICU patients or if they underwent CRRT treatment. However, the risk of dialysis dependence was increased in the accelerated RRT group when those patients used non-CRRT modality or had high SOFA scores. All the literatures reviewed in this study were highly heterogeneous and potentially subject to biases. Trial registration CRD42020201466, Sep 07, 2020. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=201466 .
Project description:Neutrophil gelatinase-associated lipocalin (NGAL) is a promising novel biomarker that correlates with the severity and outcome of acute kidney injury (AKI). However, its prognostic utility during the late course of AKI, especially in patients that require renal replacement therapy (RRT) remains unknown. The aim of this study was to evaluate the predictive value of serum NGAL in patients with established AKI at inception of RRT in the intensive care unit (ICU).Serum NGAL (ELISA methodology) was measured in 109 critically ill patients with AKI at inception of RRT in 7 ICUs of a tertiary care university hospital. The primary outcome studied was 28-day mortality. Secondary outcome measures were ICU length of stay, ventilator-free days, and renal recovery at day 28.There was a significant difference in serum NGAL between healthy subjects (median [interquartile range] 39.0 [37.5-42.75] ng/mL), critically ill patients with systemic inflammatory response syndrome (SIRS) (297 [184-490] ng/mL), and critically ill patients with sepsis (708 [365-1301] ng/mL; P < 0.0001), respectively. Multiple linear regression showed that NGAL levels were independently related to the severity of AKI and the extent of systemic inflammation. NGAL levels were higher in non-survivors (430 [303-942] ng/mL) compared to survivors (298 [159-506] ng/mL; P = 0.004). Consistently, Cox proportional hazards regression analysis identified NGAL as a strong independent predictor for 28-day survival (hazard ratio 1.6 (95% confidence interval [CI] 1.15 - 2.23), P = 0.005).This is the first prospective evaluation of serum NGAL as an outcome-specific biomarker in critically ill patients at initiation of RRT. The results from this study indicate that serum NGAL is as an independent predictor of 28-day mortality in ICU patients with dialysis-dependent AKI.