Early Versus Late Initiation of Renal Replacement Therapy in Critically Ill Patients: Systematic Review and Meta-Analysis

Objective: Early initiation of renal replacement therapy (RRT) effect on survival and renal recovery of critically ill patients is still uncertain. We aimed to systematically review current evidence comparing outcomes of early versus late initiation of RRT in critically ill patients. Methods: We searched the Medline (via Pubmed), LILACS, Science Direct, and CENTRAL databases from inception until November 2016 for randomized clinical trials (RCTs) or observational studies comparing early versus late initiation of RRT in critically ill patients. The primary outcome was mortality. Duration of mechanical ventilation, intensive care unit (ICU) length of stay (LOS), hospital LOS, and renal function recovery were secondary outcomes. Meta-analysis and trial sequential analysis (TSA) were used for the primary outcome. Results: Sixty-two studies were retrieved and analyzed, including 11 RCTs. There was no difference in mortality between early and late initiation of RRT among RCTs (odds ratio [OR] = 0.78; 95% confidence interval [CI]: 0.52-1.19; I2 = 63.1%). Trial sequential analysis of mortality across all RCTs achieved futility boundaries at both 1% and 5% type I error rates, although a subgroup analysis of studies including only acute kidney injury patients was not conclusive. There was also no difference in time on mechanical ventilation, ICU and hospital LOS, or renal recovery among studies. Early initiation of RRT was associated with reduced mortality among prospective (OR = 0.69; 95% CI: 0.49-0.96; I2 = 85.9%) and retrospective (OR = 0.61; 95% CI: 0.41-0.92; I2 = 90.9%) observational studies, both with substantial heterogeneity. However, subgroup analysis excluding low-quality observational studies did not achieve statistical significance. Conclusion: Pooled analysis of randomized trials indicates early initiation of RRT is not associated with lower mortality rates. The potential benefit of reduced mortality associated with early initiation of RRT was limited to low-quality observational studies.

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Timing of renal replacement therapy initiation for acute kidney injury in critically ill patients: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis

Critical Care ◽

10.1186/s13054-020-03451-y ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Xiaoming Li ◽

Chao Liu ◽

Zhi Mao ◽

Qinglin Li ◽

Feihu Zhou

Keyword(s):

Systematic Review ◽

Acute Kidney Injury ◽

Critically Ill ◽

Critically Ill Patients ◽

Sequential Analysis ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Kidney Injury ◽

Early Initiation ◽

Trial Sequential Analysis

Abstract Background Acute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical prognosis. Renal replacement therapy (RRT) has been widely used in critically ill patients with AKI. However, in patients without urgent indications such as acute pulmonary edema, severe acidosis, and severe hyperkalemia, the optimal timing of RRT initiation is still under debate. We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of early RRT initiation versus delayed RRT initiation. Methods We searched databases (PubMed, EMBASE and Cochrane Library) from inception through to July 20, 2020, to identify eligible RCTs. The primary outcome was 28-day mortality. Two authors extracted the data independently. When the I2 values < 25%, we used fixed-effect mode. Otherwise, the random effects model was used as appropriate. TSA was performed to control the risk of random errors and assess whether the results in our meta-analysis were conclusive. Results Eleven studies involving 5086 patients were identified. Two studies included patients with sepsis, one study included patients with shock after cardiac surgery, and eight others included mixed populations. The criteria for the initiation of RRT, the definition of AKI, and RRT modalities existed great variations among the studies. The median time of RRT initiation across studies ranged from 2 to 7.6 h in the early RRT group and 21 to 57 h in the delayed RRT group. The pooled results showed that early initiation of RRT could not decrease 28-day all-cause mortality compared with delayed RRT (RR 1.01; 95% CI 0.94–1.09; P = 0.77; I2 = 0%). TSA result showed that the required information size was 2949. The cumulative Z curve crossed the futility boundary and reached the required information size. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients and was associated with a higher incidence of hypotension (RR 1.42; 95% CI 1.23–1.63; P < 0.00001; I2 = 8%) and RRT-associated infection events (RR 1.34; 95% CI 1.01–1.78; P = 0.04; I2 = 0%). Conclusions This meta-analysis suggested that early initiation of RRT was not associated with survival benefit in critically ill patients with AKI. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients, resulting in a waste of health resources and a higher incidence of RRT-associated adverse events. Maybe, only critically ill patients with a clear and hard indication, such as severe acidosis, pulmonary edema, and hyperkalemia, could benefit from early initiation of RRT.

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777-P: Enteral Nutrition in Critically Ill Patients with Hyperglycemia: A Meta-analysis of Randomized Controlled Trials with Trial Sequential Analysis

Diabetes ◽

10.2337/db19-777-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 777-P

Author(s):

MAGALI KUMBIER ◽

FLAVIA MORAES SILVA ◽

LANA C. PINTO ◽

JUSSARA ALMEIDA ◽

FRANZOSI OELLEN

Keyword(s):

Enteral Nutrition ◽

Randomized Controlled Trials ◽

Critically Ill ◽

Critically Ill Patients ◽

Sequential Analysis ◽

Meta Analysis ◽

Trial Sequential Analysis ◽

Controlled Trials ◽

Randomized Controlled

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The impact of tracheotomy timing in critically ill patients undergoing mechanical ventilation: A meta-analysis of randomized controlled clinical trials with trial sequential analysis

Heart & Lung ◽

10.1016/j.hrtlng.2018.09.005 ◽

2019 ◽

Vol 48 (1) ◽

pp. 46-54 ◽

Cited By ~ 22

Author(s):

Ruohui Wang ◽

Changkun Pan ◽

Xiaokun Wang ◽

Feng Xu ◽

Shuang Jiang ◽

...

Keyword(s):

Mechanical Ventilation ◽

Clinical Trials ◽

Critically Ill Patients ◽

Sequential Analysis ◽

Meta Analysis ◽

Trial Sequential Analysis ◽

Controlled Clinical Trials ◽

Randomized Controlled Clinical Trials ◽

Randomized Controlled ◽

The Impact

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Postpyloric feeding in critically ill patients: Updated systematic review, meta-analysis and trial sequential analysis of randomized trials

Saudi Critical Care Journal ◽

10.4103/2543-1854.208928 ◽

2017 ◽

Vol 1 (1) ◽

pp. 6 ◽

Cited By ~ 1

Author(s):

Waleed Alhazzani ◽

Fayez Alshamsi ◽

Rucha Utgikar ◽

Saleh Almenawer ◽

Mustafa Alquraini ◽

...

Keyword(s):

Systematic Review ◽

Critically Ill ◽

Critically Ill Patients ◽

Sequential Analysis ◽

Randomized Trials ◽

Meta Analysis ◽

Trial Sequential Analysis

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Stress ulcer prophylaxis with proton pump inhibitors or histamine 2 receptor antagonists in critically ill adults - a meta-analysis of randomized controlled trials with trial sequential analysis

BMC Gastroenterology ◽

10.1186/s12876-019-1105-y ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Xiaoyang Zhou ◽

Hanyuan Fang ◽

Jianfei Xu ◽

Peifu Chen ◽

Xujun Hu ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Sequential Analysis ◽

Stress Ulcer ◽

Meta Analysis ◽

Trial Sequential Analysis ◽

Gi Bleeding ◽

Ulcer Prophylaxis ◽

Critically Ill Adults ◽

Ill Adults

Abstract Background Proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) have been widely used as stress ulcer prophylaxis (SUP) in critically ill patients, however, its efficacy and safety remain unclear. This study aimed to assess the effect of SUP on clinical outcomes in critically ill adults. Methods Literature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane database of clinical trials for randomized controlled trials (RCTs) that investigated SUP, with PPI or H2RA, versus placebo or no prophylaxis in critically ill patients from database inception through 1 June 2019. Study selection, data extraction and quality assessment were performed in duplicate. The primary outcomes were clinically important gastrointestinal (GI) bleeding and overt GI bleeding. Conventional meta-analysis with random-effects model and trial sequential analysis (TSA) were performed. Results Twenty-nine RCTs were identified, of which four RCTs were judged as low risk of bias. Overall, SUP could reduce the incident of clinically important GI bleeding [relative risk (RR) = 0.58; 95% confidence intervals (CI): 0.42–0.81] and overt GI bleeding (RR = 0.48; 95% CI: 0.36–0.63), these results were confirmed by the sub-analysis of trials with low risk of bias, TSA indicated a firm evidence on its beneficial effects on the overt GI bleeding (TSA-adjusted CI: 0.31–0.75), but lack of sufficient evidence on the clinically important GI bleeding (TSA-adjusted CI: 0.23–1.51). Among patients who received enteral nutrition (EN), SUP was associated with a decreased risk of clinically important GI bleeding (RR = 0.61; 95% CI: 0.44–0.85; TSA-adjusted CI: 0.16–2.38) and overt GI bleeding (RR = 0.64; 95% CI: 0.42–0.96; TSA-adjusted CI: 0.12–3.35), but these benefits disappeared after adjustment with TSA. Among patients who did not receive EN, SUP had only benefits in reducing the risk of overt GI bleeding (RR = 0.37; 95% CI: 0.25–0.55; TSA-adjusted CI: 0.22–0.63), but not the clinically important GI bleeding (RR = 0.27; 95% CI: 0.04–2.09). Conclusions SUP has benefits on the overt GI bleeding in critically ill patients who did not receive EN, however, its benefits on clinically important GI bleeding still needs more evidence to confirm.

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Impact of Early versus Late Initiation of Renal Replacement Therapy in Patients with Cardiac Surgery-Associated Acute Kidney Injury: Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials

BioMed Research International ◽

10.1155/2018/6942829 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13

Author(s):

Jie Cui ◽

Da Tang ◽

Zhen Chen ◽

Genglong Liu

Keyword(s):

Acute Kidney Injury ◽

Cardiac Surgery ◽

Sequential Analysis ◽

Meta Analysis ◽

Kidney Injury ◽

Early Initiation ◽

Trial Sequential Analysis ◽

Initiation Time ◽

Late Initiation ◽

The Impact

Background. Previous studies have examined the effect of the initiation time of renal replacement therapy (RRT) in patients with cardiac surgery-associated acute kidney injury (CSA-AKI), but the findings remain controversial. The aim of this meta-analysis was to systematically and quantitatively compare the impact of early versus late initiation of RRT on the outcome of patients with CSA-AKI.Methods. Four databases (PubMed, the Cochrane Library, ISI Web of Knowledge, and Embase) were systematically searched from inception to June 2018 for randomized clinical trials (RCTs). Two investigators independently performed the literature search, study selection, data extraction, and quality evaluation. Meta-analysis and trial sequential analysis (TSA) were used to examine the impact of RRT initiation time on all-cause mortality (primary outcome). The Grading of Recommendations Assessment Development and Evaluation (GRADE) was used to evaluate the level of evidence.Results. We identified 4 RCTs with 355 patients that were eligible for inclusion. Pooled analyses indicated no difference in mortality for patients receiving early and late initiation of RRT (relative risk [RR] = 0.61, 95% confidence interval [CI] = 0.33 to 1.12). However, the results were not confirmed by TSA. Similarly, early RRT did not reduce the length of stay (LOS) in the intensive care unit (ICU) (mean difference [MD] = -1.04; 95% CI = -3.34 to 1.27) or the LOS in the hospital (MD = -1.57; 95% CI = -4.62 to 1.48). Analysis using GRADE indicated the certainty of the body of evidence was very low for a benefit from early initiation of RRT.Conclusion. Early initiation of RRT had no beneficial impacts on outcomes in patients with CSA-AKI. Future larger and more adequately powered prospective RCTs are needed to verify the benefit of reduced mortality associated with early initiation of RRT.Trial Registration. This trial is registered with PROSPERO registration number CRD42018084465, registered on 11 February 2018.

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