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      Hemodynamic goal-directed therapy and postoperative kidney injury: an updated meta-analysis with trial sequential analysis

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          Abstract

          Background

          Perioperative goal-directed therapy (GDT) reduces the risk of renal injury. However, several questions remain unanswered, such as target, kind of patients and surgery, and role of fluids and inotropes. We therefore update a previous analysis, including all studies published in the meanwhile, to clarify the clinical impact of this strategy on acute kidney injury.

          Main body

          Randomized controlled trials enrolling adult patients undergoing major surgery were considered. GDT was defined as perioperative monitoring and manipulation of hemodynamic parameters to reach normal or supranormal values by fluids alone or with inotropes. Trials comparing the effects of GDT and standard hemodynamic therapy were considered. Primary outcome was acute kidney injury, whichever definition was used. Meta-analytic techniques (analysis software RevMan, version 5.3) were used to combine studies, using random-effect odds ratios (OR) and 95% confidence intervals (CI). Trial sequential analyses were performed including all trials and considering only low risk of bias trials. Sixty-five trials with an overall sample of 9308 patients were included. OR for the development of renal injury was 0.64 (95% CI, 0.62–0.87; p = 0.0003), with no statistical heterogeneity. Trial sequential analyses and sensitivity analysis including studies with low risk of bias confirmed the main results. A significant decrease in renal injury rate was observed in studies that adopted cardiac output and oxygen delivery as hemodynamic target and that used both fluids and inotropes. The postoperative kidney injury rate was significantly lower in trials enrolling “high-risk” patients and major abdominal and orthopedic surgery.

          Short conclusion

          The present meta-analysis suggests that targeting GDT to perioperative systemic oxygen delivery, by means of fluids and inotropes, can be the best way to improve renal perfusion and oxygenation in high-risk patients undergoing major abdominal and orthopedic surgery.

          Electronic supplementary material

          The online version of this article (10.1186/s13054-019-2516-4) contains supplementary material, which is available to authorized users.

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          Most cited references38

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          The hazards of scoring the quality of clinical trials for meta-analysis.

          Although it is widely recommended that clinical trials undergo some type of quality review, the number and variety of quality assessment scales that exist make it unclear how to achieve the best assessment. To determine whether the type of quality assessment scale used affects the conclusions of meta-analytic studies. Meta-analysis of 17 trials comparing low-molecular-weight heparin (LMWH) with standard heparin for prevention of postoperative thrombosis using 25 different scales to identify high-quality trials. The association between treatment effect and summary scores and the association with 3 key domains (concealment of treatment allocation, blinding of outcome assessment, and handling of withdrawals) were examined in regression models. Pooled relative risks of deep vein thrombosis with LMWH vs standard heparin in high-quality vs low-quality trials as determined by 25 quality scales. Pooled relative risks from high-quality trials ranged from 0.63 (95% confidence interval [CI], 0.44-0.90) to 0.90 (95% CI, 0.67-1.21) vs 0.52 (95% CI, 0.24-1.09) to 1.13 (95% CI, 0.70-1.82) for low-quality trials. For 6 scales, relative risks of high-quality trials were close to unity, indicating that LMWH was not significantly superior to standard heparin, whereas low-quality trials showed better protection with LMWH (P<.05). Seven scales showed the opposite: high quality trials showed an effect whereas low quality trials did not. For the remaining 12 scales, effect estimates were similar in the 2 quality strata. In regression analysis, summary quality scores were not significantly associated with treatment effects. There was no significant association of treatment effects with allocation concealment and handling of withdrawals. Open outcome assessment, however, influenced effect size with the effect of LMWH, on average, being exaggerated by 35% (95% CI, 1%-57%; P= .046). Our data indicate that the use of summary scores to identify trials of high quality is problematic. Relevant methodological aspects should be assessed individually and their influence on effect sizes explored.
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            POSSUM: a scoring system for surgical audit.

            POSSUM, a Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity, is described. This system has been devised from both a retrospective and prospective analysis and the present paper attempts to validate it prospectively. Logistic regression analysis yielded statistically significant equations for both mortality and morbidity (P less than 0.001). When displayed graphically zones of increasing morbidity and mortality rates could be defined which could be of value in surgical audit. The scoring system produced assessments for morbidity and mortality rates which did not significantly differ from observed rates.
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              Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study.

              Postoperative acute deterioration in renal function, producing oliguria and/or increase in serum creatinine, is one of the most serious complication in surgical patients. Most cases are due to renal hypoperfusion as a consequence of systemic hypotension, hypovolemia, and cardiac dysfunction. Although some evidence suggests that perioperative monitoring and manipulation of oxygen delivery by volume expansion and inotropic drugs may decrease mortality in surgical patients, no study analyzed this approach on postoperative renal dysfunction. The objective of this investigation is to perform a meta-analysis on the effects of perioperative hemodynamic optimization on postoperative renal dysfunction. DATA SOURCES, STUDY SELECTION, DATA EXTRACTION: A systematic literature review, using MEDLINE, EMBASE, and The Cochrane Library databases through January 2008 was conducted and 20 studies met the inclusion criteria (4220 participants). Data synthesis was obtained by using odds ratio (OR) with 95% confidence interval (CI) by random-effects model. Postoperative acute renal injury was significantly reduced by perioperative hemodynamic optimization when compared with control group (OR 0.64; CI 0.50-0.83; p = 0.0007). Perioperative optimization was effective in reducing renal injury defined consistently with risk, injury, failure, and loss and end-stage kidney disease and Acute Kidney Injury Network classifications, and in studies defining renal dysfunction by serum creatinine and/or need of renal replacement therapy only (OR 0.66; CI 0.50-0.88; p = 0.004). The occurrence of renal dysfunction was reduced when treatment started both preoperatively and intraoperatively or postoperatively, was performed in high-risk patients, and was obtained by fluids and inotropes. Mortality was significantly reduced in treatment group (OR 0.50; CI 0.31-0.80; p = 0.004), but statistical heterogeneity was observed. Surgical patients receiving perioperative hemodynamic optimization are at decreased risk of renal impairment. Because of the impact of postoperative renal complications on adverse outcome, efforts should be aimed to identify patients and surgery that would most benefit from perioperative optimization.
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                Author and article information

                Contributors
                00 39 080 5595153 , mariateresagiglio@gmail.com
                lidia.dalfino@yahoo.com
                filomena.puntillo@uniba.it
                nicola.brienza@uniba.it
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                26 June 2019
                26 June 2019
                2019
                : 23
                : 232
                Affiliations
                ISNI 0000 0001 0120 3326, GRID grid.7644.1, Anesthesia and Intensive Care Unit, Department of Emergency and Organ Transplantation, , University of Bari, ; Piazza G. Cesare, 11, 70124 Bari, Italy
                Author information
                http://orcid.org/0000-0002-4901-0045
                Article
                2516
                10.1186/s13054-019-2516-4
                6593609
                31242941
                bf748d14-29a7-459c-8200-0f032552bbc1
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 February 2019
                : 13 June 2019
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Emergency medicine & Trauma
                postoperative acute renal injury,perioperative hemodynamic optimization,high-risk patients,fluid therapy,oxygen delivery,cardiac output

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