Effects of perioperative fluid management on postoperative outcomes in liver transplantation: a systematic review protocol.
ABSTRACT: BACKGROUND:Liver transplant recipients suffer many complications, but few intraoperative interventions supported by high-quality evidence have been found effective to reduce their incidence or severity. Fluid balance has been proposed as an important aspect of perioperative care in high-risk recipients. We will conduct a systematic review aimed at evaluating the effects of restrictive perioperative fluid management strategies compared to liberal ones on clinically significant postoperative outcomes. METHODS:We will search through major databases (CINAHL Complete, EMB Reviews, EMBASE, MEDLINE, PubMed, and the gray literature (CADTH, Clinical Trials, National Guideline Clearing House, NICE, MedNar, Google Scholar and Open Grey)), from inception up to a date close to the review submission for publication, for eligible studies. Randomized controlled trials and comparative non-randomized studies (prospective or retrospective) comparing two fluid management strategies (or two outcomes with available data on fluid volume received for observational studies) on adult liver recipients will be included. Eligible studies will have to report at least one postoperative complication or mortality. Our primary outcome will be acute renal failure and our secondary exploratory outcomes will be all other postoperative complications and mortality. Study selection and data abstraction using an electronic standardized form will be performed by three authors. Risk of bias will be evaluated and data will be pooled if limited clinical diversity is observed. DISCUSSION:Human organs available for transplantation are scarce resources. Strategies to improve recipients' survival are needed. We hypothesize that restrictive fluid management strategies will be associated with better postoperative outcomes than liberal fluid management strategies. This systematic review will improve our understanding of the available evidence and help us better inform future clinical trials. SYSTEMATIC REVIEW REGISTRATION:This systematic review protocol is registered in PROSPERO ( CRD42017054970 ).
Project description:BACKGROUND:Intraoperative restrictive fluid management strategies might improve postoperative outcomes in liver transplantation. Effects of vasopressors within any hemodynamic management strategy are unclear. METHODS:We conducted an observational cohort study on adult liver transplant recipients between July 2008 and December 2017. We measured the effect of vasopressors infused at admission in the intensive care unit (ICU) and total intraoperative fluid balance. Our primary outcome was 48-hour acute kidney injury (AKI) and our secondary outcomes were 7-day AKI, need for postoperative renal replacement therapy (RRT), time to extubation in the ICU, time to ICU discharge and survival up to 1 year. We fitted models adjusted for confounders using generalized estimating equations or survival models using robust standard errors. We reported results with 95% confidence intervals. RESULTS:We included 532 patients. Vasopressors use was not associated with 48-hour or 7-day AKI but modified the effects of fluid balance on RRT and mortality. A higher fluid balance was associated with a higher need for RRT (OR = 1.52 [1.15, 2.01], p<0.001 for interaction) and lower survival (HR = 1.71 [1.26, 2.34], p<0.01 for interaction) only among patients without vasopressors. In patients with vasopressors, higher doses of vasopressors were associated with a higher mortality (HR = 1.29 [1.13, 1.49] per 10 ?g/min of norepinephrine). CONCLUSION:The presence of any vasopressor at the end of surgery was not associated with AKI or RRT. The use of vasopressors might modify the harmful association between fluid balance and other postoperative outcomes. The liberal use of vasopressors to implement a restrictive fluid management strategy deserves further investigation.
Project description:OBJECTIVES:The aim of this study was to determine whether a restrictive compared to a liberal fluid therapy will increase postoperative acute kidney injury (AKI) in patients with severe preeclampsia. METHODS:A total of 46 patients (mean age, 32 years; standard deviation, 6.8 years) with severe preeclampsia were randomized to liberal (1500 ml of lactated Ringer's, n=23) or restrictive (250 ml of lactated Ringer's, n=23) intravenous fluid regimen during cesarean section. The primary outcome was the development of a postoperative renal dysfunction defined by AKI Network stage ?1. Serum cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated at postoperative days 1 and 2. ClinicalTrials.gov: NCT02214186. RESULTS:The rate of postoperative AKI was 43.5% in the liberal fluid group and 43.5% in the restrictive fluid group (p=1.0). Intraoperative urine output was higher in the liberal (116 ml/h, IQR 69-191) than in the restrictive fluid group (80 ml/h, IQR 37-110, p<0.05). In both groups, serum cystatin C did not change from postoperative day 1 compared to the preoperative period and significantly decreased on postoperative day 2 compared to postoperative day 1 (p<0.05). In the restrictive fluid group, NGAL levels increased on postoperative day 1 compared to the preoperative period (p<0.05) and decreased on postoperative day 2 compared to postoperative day 1 (p<0.05). CONCLUSION:Among patients with severe preeclampsia, a restrictive fluid regimen during cesarean section was not associated with increased postoperative AKI.
Project description:Liberal fluid strategies in critically ill patients are associated with harm, thought to be due to endothelial and glycocalyx injury. As the restrictive versus liberal fluid therapy for major abdominal surgery trial not only failed to report survival benefit with restrictive fluids but was associated with a higher rate of acute kidney injury, we hypothesized that factors other than endothelial and glycocalyx injury were likely to account for these findings. Consequently, we measured injury biomarkers in a cohort of the restrictive versus liberal fluid therapy for major abdominal surgery trial.<h4>Design</h4>The restrictive versus liberal fluid therapy for major abdominal surgery trial was an international, randomized, assessor-blinded trial comparing restrictive with liberal IV fluid regimens that represented traditional care in patients undergoing major abdominal surgery.<h4>Setting and patients</h4>Cohort of restrictive versus liberal fluid therapy for major abdominal surgery bloods was collected at a single major site (161 patients) prior to, day 1 and day 3 after surgery.<h4>Intervention</h4>Bloods were blindly and randomly batch analyzed for plasma markers of endothelial/glycocalyx injury-angiopoietin-1, angiopoietin-2, soluble tyrosine-protein kinase-2 receptor, soluble intracellular adhesion molecule-1, syndecan, and tumor necrosis factor-?. Data were examined as restrictive versus liberal enrollment groups and high versus low (± 5,000?mL) fluid groups. Differences were examined by linear mixed modeling.<h4>Measurement and main results</h4>There were no significant differences in any biomarkers between the restrictive (<i>n</i> = 75) and liberal (<i>n</i> = 86) groups. When examined as low (<i>n</i> = 81) and high (<i>n</i> = 79) fluid groups, plasma angiopoietin-2 (<i>p</i> = 0.009) and soluble intracellular adhesion molecule-1 (<i>p</i> = 0.01) were elevated in the high fluid group. There were no differences in other biomarkers.<h4>Conclusions</h4>Although these results are consistent with previous findings of vascular injury following liberal fluid therapy, they suggest alternative mechanisms underlie the clinical outcomes from restrictive versus liberal fluid therapy for major abdominal surgery study.<h4>Clinicaltrialsgov identifier</h4>NCT01424150.
Project description:Most non-oncologic clinical practice guidelines recommend restrictive allogeneic blood transfusion practices; however, there is a lack of consensus regarding the best transfusion practice in oncology. We conducted a systematic review of the literature to compare the efficacy and safety of restrictive versus liberal transfusion strategies in patients with cancer.A literature search using MEDLINE, PUBMED and EMBASE identified all controlled studies comparing the use of restrictive with liberal transfusion in adult oncology participants up to August 10, 2015. Two review authors independently assessed studies for inclusion, extracted data and appraised the quality of the included studies. The primary outcomes of interest were blood utilization and all-cause mortality.Out of 4241 citations, six studies (3 randomized and 3 non-randomized) involving a total of 983 patients were included in the final review. The clinical context of the studies varied with 3 chemotherapy and 3 surgical studies. The overall risk of bias in all studies was moderate to high. Restrictive transfusion strategies were associated with a 36% reduced risk of receiving a perioperative transfusion (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.49-0.83). There was no difference in mortality between the strategies (RR 1.00, 95% CI 0.32-3.18). There were no differences in adverse events reported between the restrictive and liberal transfusion strategies.Restrictive strategy appears to decrease blood utilization without increasing morbidity or mortality in oncology. This review is limited by a paucity of high quality studies on this topic. Better designed studies are warranted.
Project description:<h4>Objective</h4>To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions.<h4>Design</h4>Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.<h4>Data sources</h4>Cochrane central register of controlled trials, SilverPlatter Medline (1950 to date), SilverPlatter Embase (1980 to date), and Science Citation Index Expanded (1900 to present). Reference lists of identified trials and other systematic reviews were assessed, and authors and experts in transfusion were contacted to identify additional trials.<h4>Trial selection</h4>Published and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding procedure, publication status, or sample size.<h4>Data extraction</h4>Two authors independently screened titles and abstracts of trials identified, and relevant trials were evaluated in full text for eligibility. Two reviewers then independently extracted data on methods, interventions, outcomes, and risk of bias from included trials. random effects models were used to estimate risk ratios and mean differences with 95% confidence intervals.<h4>Results</h4>31 trials totalling 9813 randomised patients were included. The proportion of patients receiving red blood cells (relative risk 0.54, 95% confidence interval 0.47 to 0.63, 8923 patients, 24 trials) and the number of red blood cell units transfused (mean difference -1.43, 95% confidence interval -2.01 to -0.86) were lower with the restrictive compared with liberal transfusion strategies. Restrictive compared with liberal transfusion strategies were not associated with risk of death (0.86, 0.74 to 1.01, 5707 patients, nine lower risk of bias trials), overall morbidity (0.98, 0.85 to 1.12, 4517 patients, six lower risk of bias trials), or fatal or non-fatal myocardial infarction (1.28, 0.66 to 2.49, 4730 patients, seven lower risk of bias trials). Results were not affected by the inclusion of trials with unclear or high risk of bias. Using trial sequential analyses on mortality and myocardial infarction, the required information size was not reached, but a 15% relative risk reduction or increase in overall morbidity with restrictive transfusion strategies could be excluded.<h4>Conclusions</h4>Compared with liberal strategies, restrictive transfusion strategies were associated with a reduction in the number of red blood cell units transfused and number of patients being transfused, but mortality, overall morbidity, and myocardial infarction seemed to be unaltered. Restrictive transfusion strategies are safe in most clinical settings. Liberal transfusion strategies have not been shown to convey any benefit to patients.<h4>Trial registration</h4>PROSPERO CRD42013004272.
Project description:BACKGROUND:There are no overviews of systematic reviews investigating haemoglobin thresholds for transfusion. This is important as the literature on transfusion thresholds has grown considerably in recent years. Our aim was to synthesise evidence from systematic reviews and meta-analyses of the effects of restrictive and liberal transfusion strategies on mortality. METHODS:This was a systematic review of systematic reviews (overview). We searched MEDLINE, Embase, Web of Science Core Collection, PubMed, Google Scholar, and the Joanna Briggs Institute EBP Database, from 2008 to 2018. We included systematic reviews and meta-analyses of randomised controlled trials comparing mortality in patients assigned to red cell transfusion strategies based on haemoglobin thresholds. Two independent reviewers extracted data and assessed methodological quality. We assessed the methodological quality of included reviews using AMSTAR 2 and the quality of evidence pooled using an algorithm to assign GRADE levels. RESULTS:We included 19 systematic reviews reporting 33 meta-analyses of mortality outcomes from 53 unique randomised controlled trials. Of the 33 meta-analyses, one was graded as high quality, 15 were moderate, and 17 were low. Of the meta-analyses presenting high- to moderate-quality evidence, 12 (75.0%) reported no statistically significant difference in mortality between restrictive and liberal transfusion groups and four (25.0%) reported significantly lower mortality for patients assigned to a restrictive transfusion strategy. We found few systematic reviews addressed clinical differences between included studies: variation was observed in haemoglobin threshold concentrations, the absolute between group difference in haemoglobin threshold concentration, time to randomisation (resulting in transfusions administered prior to randomisation), and transfusion dosing regimens. CONCLUSIONS:Meta-analyses graded as high to moderate quality indicate that in most patient populations no difference in mortality exists between patients assigned to a restrictive or liberal transfusion strategy. TRIAL REGISTRATION:PROSPERO CRD42019120503.
Project description:Restrictive red blood cell transfusion strategies remain controversial in patients undergoing cardiac surgery. We performed a meta-analysis to assess the prognostic benefits of restrictive red blood cell transfusion strategies in patients undergoing cardiac surgery.We identified randomized clinical trials through the 9th of December 2017 that investigated a restrictive red blood cell transfusion strategy versus a liberal transfusion strategy in patients undergoing cardiac surgery. Individual patient data from each study were collected. Meta-analyses were performed for the primary and secondary outcomes. The risk of bias was assessed using the Cochrane Risk of Bias Tool. A trial sequential analysis (TSA)-adjusted random-effects model was used to pool the results from the included studies for the primary outcomes.Seven trials involving a total of 8886 patients were included. The TSA evaluations suggested that this meta-analysis could draw firm negative results, and the data were sufficient. There was no evidence that the risk of 30-day mortality differed between the patients assigned to a restrictive blood cell transfusion strategy and a liberal transfusion strategy (odds ratio (OR) 0.98; 95% confidence interval (CI) 0.77 to 1.24; p?=?0.87). Furthermore, the study suggested that the restrictive transfusion strategy was not associated with significant increases in pulmonary morbidity (OR 1.09; 95% CI 0.88 to 1.34; p?=?0.44), postoperative infection (OR 1.11; 95% CI 0.95 to 1.3; p?=?0.58), acute kidney injury (OR 1.03; 95% CI 0.92 to 1.14; p?=?0.71), acute myocardial infarction (OR 1.01; 95% CI 0.80 to 1.27; p?=?0.78), or cerebrovascular accidents (OR 0.97; 95% CI 0.72 to 1.30; p?=?0.66).Our meta-analysis demonstrates that the restrictive red blood cell transfusion strategy was not inferior to the liberal strategy with respect to 30-day mortality, pulmonary morbidity, postoperative infection, cerebrovascular accidents, acute kidney injury, or acute myocardial infarction, and fewer red blood cells were transfused.
Project description:This study sought to evaluate whether restrictive blood transfusion strategies are associated with a risk of infection in orthopedic patients by conducting a meta-analysis of randomized controlled trials (RCTs). RCTs with restrictive versus liberal red blood cell (RBC) transfusion strategies were identified by searching Medline, Embase, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from their inception to December 2014. Eight RCTs with infections as outcomes were included in the final analysis. According to the Jadad scale, all studies were considered to be of high quality. The pooled risk ratio [RR] for the association between transfusion strategy and infection was 0.65 (95% CI, 0.47-0.91; p = 0.012), and the number of patients needed to treat to avoid an infection using a restrictive transfusion strategy was 62. No heterogeneity was observed. The sensitivity analysis indicated unstable results, and no significant publication bias was observed. This meta-analysis of RCTs demonstrates that restrictive transfusion strategies in orthopedic patients result in a significant reduction in infections compared with more liberal strategies.
Project description:Diabetes mellitus results in an attenuated inflammatory response, reduces pulmonary microvascular permeability, and may decrease the risk of developing acute respiratory distress syndrome (ARDS). Studies have shown that patients with ARDS are better managed by a conservative as compared to liberal fluid management strategy. However, it is not known if the same fluid management principles hold true for patients with comorbid diabetes mellitus and ARDS.As diabetes mellitus results in reduced pulmonary microvascular permeability and an attenuated inflammatory response, we hypothesize that in the setting of ARDS, diabetic patients will be able to tolerate a positive fluid balance better than patients without diabetes.The Fluid and Catheter Treatment Trial (FACTT) randomized patients with ARDS to conservative versus liberal fluid management strategies. In a secondary analysis of this trial, we calculated the interaction of diabetic status and differing fluid strategies on outcomes. Propensity score subclassification matching was used to control for the differing baseline characteristics between patients with and without diabetes.Nine hundred fifty-six patients were analyzed. In a propensity score matched analysis, the difference in the effect of a conservative as compared to liberal fluid management strategy on ventilator free days was 2.23 days (95% CI: -0.97 to 5.43 days) in diabetic patients, and 2.37 days (95% CI: -0.21 to 4.95 days) in non-diabetic patients. The difference in the effect of a conservative as compared to liberal fluid management on 60 day mortality was 2% (95% CI: -11.8% to 15.8%) in diabetic patients, and -7.9% (95% CI: -21.7% to 5.9%) in non-diabetic patients.When comparing a conservative fluid management strategy to a liberal fluid management strategy, diabetic patients with ARDS did not have a statistically significant difference in outcomes than non-diabetic patients.
Project description:<h4>Objective</h4>To compare patient outcomes of restrictive versus liberal blood transfusion strategies in patients with cardiovascular disease not undergoing cardiac surgery.<h4>Design</h4>Systematic review and meta-analysis.<h4>Data sources</h4>Randomised controlled trials involving a threshold for red blood cell transfusion in hospital. We searched (to 2 November 2015) CENTRAL, Medline, Embase, CINAHL, PubMed, LILACS, NHSBT Transfusion Evidence Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ISRCTN Register, and EU Clinical Trials Register. Authors were contacted for data whenever possible.<h4>Trial selection</h4>Published and unpublished randomised controlled trials comparing a restrictive with liberal transfusion threshold and that included patients with cardiovascular disease.<h4>Data extraction and synthesis</h4>Data extraction was completed in duplicate. Risk of bias was assessed using Cochrane methods. Relative risk ratios with 95% confidence intervals were presented in all meta-analyses. Mantel-Haenszel random effects models were used to pool risk ratios.<h4>Main outcome measures</h4>30 day mortality, and cardiovascular events.<h4>Results</h4>41 trials were identified; of these, seven included data on patients with cardiovascular disease. Data from a further four trials enrolling patients with cardiovascular disease were obtained from the authors. In total, 11 trials enrolling patients with cardiovascular disease (n=3033) were included for meta-analysis (restrictive transfusion, n=1514 patients; liberal transfusion, n=1519). The pooled risk ratio for the association between transfusion thresholds and 30 day mortality was 1.15 (95% confidence interval 0.88 to 1.50, P=0.50), with little heterogeneity (I(2)=14%). The risk of acute coronary syndrome in patients managed with restrictive compared with liberal transfusion was increased (nine trials; risk ratio 1.78, 95% confidence interval 1.18 to 2.70, P=0.01, I(2)=0%).<h4>Conclusions</h4>The results show that it may not be safe to use a restrictive transfusion threshold of less than 80 g/L in patients with ongoing acute coronary syndrome or chronic cardiovascular disease. Effects on mortality and other outcomes are uncertain. These data support the use of a more liberal transfusion threshold (>80 g/L) for patients with both acute and chronic cardiovascular disease until adequately powered high quality randomised trials have been undertaken in patients with cardiovascular disease.<h4>Registration</h4>PROSPERO CRD42014014251.