BackgroundThe effect of loop diuretic use in critically ill patients on vasopressor support or in shock is unclear. This study aimed to explore the relationship between loop diuretic use and hospital mortality in critically ill patients with vasopressor support.MethodsData were extracted from the Medical Information Mart for Intensive Care III database. Adult patients with records of vasopressor use within 48h after intensive care unit admission were screened. Multivariable logistic regression and propensity score matching was used to investigate any association.ResultsData on 7828 patients were included. The crude hospital mortality was significantly lower in patients with diuretic use (166/1469 vs. 1171/6359, p<0.001). In the extended multivariable logistic models, the odds ratio (OR) of diuretic use was consistently significant in all six models (OR range 0.56-0.75, p<0.05 for all). In the subgroup analysis, an interaction effect was detected between diuretic use and fluid balance (FB). In the positive FB subgroup, diuretic use was significantly associated with decreased mortality (OR 0.64, 95% confidence interval (CI) 0.51-0.78) but was insignificant in the negative FB subgroup. In the other subgroups of mean arterial pressure, maximum sequential organ failure assessment score, and lactate level, the association between diuretic use and mortality remained significant and no interaction was detected. After propensity score matching, 1463 cases from each group were well matched. The mortality remained significantly lower in the diuretic use group (165/1463 vs. 231/1463, p<0.001).ConclusionsAlthough residual confounding cannot be excluded, loop diuretic use is associated with lower mortality.
The concept of net ultrafiltration (UFNET) mentioned in the paper by Murugan et al. in a recent issue of Critical Care does not equate to the real UFNET in patients with renal replacement therapy initiation. Furthermore, the baseline blood pressure among the groups had a statistically significant difference. Both of these two factors may affect the final results. Thus, we should be cautious interpreting the conclusions.
BackgroundRegional citrate anticoagulation (RCA) is a widely used strategy for continuous renal replacement therapy (CRRT). Most of the current guidelines recommend liver failure as one of the contraindications for citrate anticoagulation. However, some studies suggested that the use of citrate for CRRT in liver failure patients did not increase the risk of citrate-related complications. The purpose of this systematic review is to summarize the current evidences on the safety and efficacy of RCA for CRRT in liver failure patients.MethodsWe performed a comprehensive search on PubMed, Embase, and the Cochrane Library databases from the inception to March 1, 2018. Studies enrolled adult (age>18years) patients with various levels of liver dysfunction underwent RCA-CRRT were included in this systematic review.ResultsAfter the study screening, 10 observational studies with 1241 liver dysfunction patients were included in this systematic review. The pooled rate of citrate accumulation and bleeding was 12% [3%, 22%] and 5% [2%, 8%], respectively. Compared with the baseline data, the serum pH, bicarbonate, and base excess (BE), the rate of metabolic alkalosis, the serum ionized calcium (ionCa) and total calcium (totCa) level, and the ratio of total calcium/ionized calcium (totCa/ionCa) significantly increased at the end of observation. However, no significant increase was observed in serum citrate (MD -65.82 [-194.19, 62.55]), lactate (MD 0.49 [-0.27, 1.26]) and total bilirubin concentration (MD 0.79 [-0.70, 2.29]) at the end of CRRT. Compared with non-liver failure patients, the live failure patients showed no significant difference in the pH (MD -0.04 [-0.13, 0.05]), serum lactate level (MD 0.69 [-0.26, 1.64]), and totCa/ionCa ratio (MD 0.03 [-0.12, 0.18]) during CRRT. The median of mean filter lifespan was 55.9h, with a range from 22.7 to 72h.ConclusionsRegional citrate anticoagulation seems to be a safe anticoagulation method in liver failure patients underwent CRRT and could yield a favorable filter lifespan. Closely monitoring the acid base status and electrolyte balance may be more necessary during RCA-CRRT in patients with liver failure.
BackgroundPublished data revealed that host genetic variants have a substantial influence on sepsis susceptibility. However, the results have been inconsistent. We aimed to systematically review the published studies and quantitatively evaluate the effects of these variants on the risk of sepsis.MethodsWe searched the PubMed, EMBASE, Medline, Web of Knowledge, and HuGE databases to identify studies that investigated the associations between genetic variants and sepsis risk. Then, we conducted meta-analyses of the associations for genetic variants with at least three study populations and applied the Venice criteria to assess the association result credibility.ResultsA literature search identified 349 eligible articles that investigated 405 variants of 172 distinct genes. We performed 204 primary and 185 subgroup meta-analyses for 76 variants of 44 genes. The results showed that 29 variants of 23 genes were significantly associated with the risk of sepsis, including 8 variants of pattern recognition receptors (PRRs), 14 variants of cytokines, one variant of an immune-related gene and 6 variants of other genes. Furthermore, the cumulative epidemiological evidence of a significant association between each variant and the risk of sepsis was classified as strong or moderate for 18 variants. For the 329 variants with fewer than three study populations, 63 variants of 48 genes have been reported to be significantly associated with the risk of sepsis in a systematic review.ConclusionWe identified several genetic variants that could influence the susceptibility to sepsis by systematic review and meta-analysis. This study provides a comprehensive overview of the genetic architecture of variants involved in sepsis susceptibility and novel insight that may affect personalized targeted treatment in the future clinical management of sepsis.
Background: With the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in pulmonary disease diagnosis. We aimed to review and summarize lung fluid biomarkers associated with acute respiratory distress syndrome diagnosis and mortality. Methods: After searching PubMed, Embase, Web of Science, and the Cochrane Library for articles published prior to January 11, 2018, we performed a meta-analysis on biomarkers for acute respiratory distress syndrome diagnosis in at-risk patients and those related to disease mortality. From the included studies, we then extracted the mean and standard deviation of the biomarker concentrations measured in the lung fluid, acute respiratory distress syndrome etiologies, sample size, demographic variables, diagnostic criteria, mortality, and protocol for obtaining the lung fluid. The effect size was measured by the ratio of means, which was then synthesized by the inverse-variance method using its natural logarithm form and transformed to obtain a pooled ratio and 95% confidence interval. Results: In total, 1156 articles were identified, and 49 studies were included. Increases in total phospholipases A2 activity, total protein, albumin, plasminogen activator inhibitor-1, soluble receptor for advanced glycation end products, and platelet activating factor-acetyl choline were most strongly associated with acute respiratory distress syndrome diagnosis. As for biomarkers associated with acute respiratory distress syndrome mortality, interleukin-1, interleukin-6, interleukin-8, Kerbs von Lungren-6, and plasminogen activator inhibitor-1 were significantly increased in the lung fluid of patients who died. Decreased levels of Club cell protein and matrix metalloproteinases-9 were associated with increased odds for acute respiratory distress syndrome diagnosis, whereas decreased levels of Club cell protein and interleukin-2 were associated with increased odds for acute respiratory distress syndrome mortality. Conclusions: This meta-analysis provides a ranking system for lung fluid biomarkers, according to their association with diagnosis or mortality of acute respiratory distress syndrome. The performance of biomarkers among studies shown in this article may help to improve acute respiratory distress syndrome diagnosis and outcome prediction.
BackgroundMost of the previous studies focused on central line-associated bloodstream infection (CLABSI), while non-central line-associated bloodstream infection (N-CLABSI) was poorly studied. This study was performed to investigate the clinical impacts and risk factors for N-CLABSI in intensive care unit (ICU) patients.MethodsAn observational study was conducted in an adult general ICU. The electronic medical records from 2013 to 2017 of all patients aged 18years admitted to the ICU >2days were analyzed retrospectively. Patients with N-CLABSI and without N-CLABSI or with CLABSI were compared for clinical features and outcomes. Predicted death in ICU included death in ICU and discharging from ICU against medical advice because of critical conditions and the desire to pass away at home. Propensity score (PS) matching was used to ensure that both two groups had similar baseline characteristics. Multivariate regression models were used to confirm whether N-CLABSI was an independent risk factor for each of the outcomes and to analyze the risk factors for N-CLABSI in ICU patients.ResultsOf 5046 patients included, 155 developed 168 ICU-acquired N-CLABSI episodes (2.1 episodes per 1000 patient-days) in the ICU, accounted for the majority of nosocomial bloodstream infections (NBSIs; 71.8%). After PS matching, patients with N-CLABSI had prolonged length of stay (LOS) in ICU (median 15days, p<0.001) and LOS in hospital (median 13days, p<0.001), excess hospitalization costs (median, $27,668 [in US dollar 2017, 1:6.75], p<0.001), and increased mortality in ICU (8.8%, p=0.013) and predicted mortality in ICU (22.7%, p<0.001), compared with those without N-CLABSI. There were no significant differences in all the outcomes between N-CLABSI and CLABSI. N-CLABSI was an independent risk factor for each of the outcomes. Gastrointestinal bleeding (adjusted odds ratio [aOR] 2.30), trauma (aOR 2.52), pancreatitis (aOR 3.45), surgical operation (aOR 1.82), intravascular catheters (aOR 2.93), sepsis (aOR 1.69), pneumonia (aOR 1.53), intraabdominal infection (IAI, aOR 8.37), or healthcare-associated infections other than NBSI, pneumonia, and IAI (aOR 3.89) were risk factors for N-CLABSI in ICU patients.ConclusionsN-CLABSI was associated with similar poor outcomes with CLABSI, including prolonged LOS in ICU and in hospital and increased hospitalization costs and predicted mortality in ICU. The risk factors for N-CLABSI identified in this study provide further insight in preventing N-CLABSI.
BackgroundRecent studies have reported that preadmission metformin users had lower mortality than non-metformin users in patients with sepsis and diabetes mellitus; however, these results are still controversial. Therefore, we conducted a systematic review and meta-analysis of published observational cohort data to determine the association between preadmission metformin use and mortality in septic adult patients with diabetes mellitus.MethodsThe MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched from their inception to September 30, 2018. Cohort studies that evaluated the use of metformin in septic adult patients with diabetes mellitus were included. The quality of outcomes was evaluated using the Newcastle-Ottawa Scale (NOS). The inverse variance method with random effects modelling was used to calculate the pooled odds ratios (ORs) and 95% CIs.ResultsFive observational cohort studies (1282 patients) that were all judged as having a low risk of bias were included. In this meta-analysis, metformin use was associated with a significantly lower mortality rate (OR, 0.59; 95% CI, 0.43-0.79, P=0.001).ConclusionsThis meta-analysis indicated an association between metformin use prior to admission and lower mortality in septic adult patients with diabetes mellitus. This finding suggested that the possible effect of metformin should be evaluated in future clinical trials.
Background The optimal timing of lactate measurement for septic patients in the intensive care unit (ICU) remains controversial, and whether initiating and repeating the lactate measurement earlier could make a difference for septic patients with an elevated lactate level remains unexplored. Methods This was a retrospective observational study that included septic patients with an initial lactate level > 2.0 mmol/L after ICU admission, and all data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The main exposure of interest was the early lactate measurement, which was defined as an initial lactate level measurement within 1 h after ICU admission. The primary outcome was 28-day mortality. Results A total of 2642 eligible subjects were enrolled, including 738 patients who had initial lactate measurements completed within 1 h (EL group) and 1904 patients who had initial lactate measurements completed more than 1 h after ICU admission (LL group). A significant beneficial effect of early lactate measurement in terms of 28-day mortality was observed: the adjusted odds ratio (OR) was 0.69 (95% CI 0.55-0.87; p = 0.001), and the mediation effect of the time to initial vasopressor administration was significant (average causal mediation effect (ACME) - 0.018; 95% CI - 0.005 approximately to - 0.036; p < 0.001). A strong relationship between delayed initial lactate measurement and risk-adjusted 28-day mortality was noted (OR 1.04; 95% CI 1.02-1.05; p < 0.001). Each hour of delay in remeasuring the lactate level was associated with an increase in 28-day mortality in the EL group (OR 1.09; 95% CI 1.04-1.15; p < 0.001). Further analysis demonstrated that repeating the measurement 3 h after the initial lactate measurement led to a significant difference. Conclusions Early lactate measurement is associated with a lower risk-adjusted 28-day mortality rate in septic patients with lactate levels > 2.0 mmol/L. A shorter time to the initial vasopressor administration may contribute to this relationship. Repeating the lactate measurement within 3 h after the initial measurement is appropriate for patients whose lactate levels were measured within 1 h of admission.