In a randomized trial, 506 patients requiring perioperative hemodynamic support after cardiac surgery were assigned to receive levosimendan or placebo in addition to standard care. There was no ...significant between-group difference in 30-day mortality.
Every year, more than 1 million patients undergo cardiac surgery in the United States and Europe.
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Acute perioperative left ventricular dysfunction is a major complication affecting up to 20% of such patients
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,
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and is associated with increased mortality.
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Inotropic drugs (catecholamines and phosphodiesterase type 3 PDE-3 inhibitors) are the cornerstone of postoperative hemodynamic support.
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,
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However, no randomized, controlled trials have shown the superiority of any inotropic agent in terms of major clinical outcomes. Furthermore, meta-analyses and observational studies suggest that catecholamines and PDE-3 inhibitors may increase mortality.
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,
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Levosimendan (Simdax, Orion) is an inotropic agent that has been . . .
Epidurals provide excellent analgesia for cardiac surgery and may reduce complications. However, their use has been tempered because of concern of the rare, but serious complication of epidural ...haematoma. The aim of this meta-analysis was to assess the effect of epidural on survival and the risk estimate of epidural haematoma.
A systematic review of the literature (Pubmed, Embase, Scopus and the Cochrane Register) and a meta-analysis of the available randomized and case-matched studies were performed to estimate the effect on survival. An international, directed and viral anonymous survey was performed to identify the incidence of haematomas with a corresponding estimate of the number of epidurals performed.
Of 66 randomized and case-matched studies, 57 trials including 6383 patients reported the incidence of all-cause mortality at the longest follow up available, with a significant reduction with epidurals (59/3123 1.9% vs 108/3260 3.3% in the control arm, RR 0.65 95% CI 0.48–0.86, P=0.003, NNT=70). No epidural haematoma was reported in these 66 trials (3320 epidurals). All other literature revealed nine haematomas in 13 100 patients. Through the anonymous, web-based, viral, international survey, we identified 16 further, non-published, epidural haematomas from 72 400 positioned epidurals. Therefore, a total of 25 haematomas have been identified from an estimate of 88 820 positioned epidurals, producing an estimated risk of 1:3552 (95% CI 1:2552–1:5841).
The use of epidural analgesia in cardiac surgery is associated with a reduction in mortality (NNT=70), and with an estimated risk of epidural haematoma of 1:3552.
Inotropes and vasopressors are frequently administered to critically ill patients in order to improve haemodynamic function and restore adequate organ perfusion. However, some studies have suggested ...a possible association between inotrope administration and increased mortality. We therefore performed a meta-analysis of randomized trials published in the last 20 yr to investigate the effect of these drugs on mortality.
BioMedCentral, PubMed, Embase and the Cochrane Central Register were searched (all updated April 8th, 2015). Inclusion criteria were: random allocation to treatment, at least one group receiving an inotropic or vasopressor drug compared with at least one group receiving a non-inotropic/vasopressor treatment, study published after 1st January 1994, and systemic drug administration. Exclusion criteria were overlapping populations, studies published as abstract only, crossover studies, paediatric studies and lack of data on mortality.
A total of 28 280 patients from 177 trials were included. Overall, pooled estimates showed no difference in mortality between the group receiving inotropes/vasopressors and the control group 4255/14 036 (31.7%) vs 4277/14 244 (31.8%), risk ratio=0.98 (0.96–1.01), P for effect=0.23, P for heterogeneity=0.30, I2=6%. A reduction in mortality was associated with inotrope/vasopressor therapy use in settings of vasoplegic syndromes, sepsis and cardiac surgery. Levosimendan was the only drug associated with improvement in survival. Subgroup analysis did not identify any groups with increased mortality associated with inotrope/vasopressor therapy.
Our systematic review found that inotrope/vasopressor therapy is not associated with differences in mortality in the overall population and in the majority of subsettings.
Inodilators are commonly used in critically ill patients, but their effect on survival has not been properly studied to date. The objective of this work was to conduct a network meta-analysis on the ...effects of inodilators on survival in adult cardiac surgery patients, and to compare and rank drugs that have not been adequately compared in head-to-head trials.
Relevant studies were independently searched in BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Central Register of clinical trials (updated on May 1, 2014). The criteria for inclusion were: random allocation to treatment with at least one group receiving dobutamine, enoximone, levosimendan, or milrinone and at least another group receiving the above inodilators or placebo, performed in cardiac surgical patients. The endpoint was to identify differences in mortality at longest follow-up available.
The 46 included trials were published between 1995 and 2014 and randomised 2647 patients. The Bayesian network meta-analysis found that only the use of levosimendan was associated with a decrease in mortality when compared with placebo (posterior mean of OR=0.48, 95% CrI 0.28 to 0.80). The posterior distribution of the probability for each inodilator to be the best and the worst drug showed that levosimendan is the best agent to improve survival after cardiac surgery. The sensitivity analyses performed did not produce different interpretative result.
Levosimendan seems to be the most efficacious inodilator to improve survival in cardiac surgery.
Meta-analysis: pitfalls and hints Greco, T; Zangrillo, A; Biondi-Zoccai, G ...
Heart, lung and vessels,
2013, Letnik:
5, Številka:
4
Journal Article
Odprti dostop
The present work is an overview of the main pitfalls which may occur when a researcher performs a meta-analysis. The main goal is to help clinicians evaluate published research results. Organizing ...and carrying out a meta-analysis is hard work, but the findings can be significant. Meta-analysis is a powerful tool to cumulate and summarize the knowledge in a research field, and to identify the overall measure of a treatment's effect by combining several conclusions. However, it is a controversial tool, because even small violations of certain rules can lead to misleading conclusions. In fact, several decisions made when designing and performing a meta-analysis require personal judgment and expertise, thus creating personal biases or expectations that may influence the result. Meta-analysis' conclusions should be interpreted in the light of various checks, discussed in this work, which can inform the readers of the likely reliability of the conclusions. Specifically, we explore the principal steps (from writing a prospective protocol of analysis to results' interpretation) in order to minimize the risk of conducting a mediocre meta-analysis and to support researchers to accurately evaluate the published findings.
Many studies have compared desflurane, isoflurane, sevoflurane, total i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on patient survival.
We performed standard pairwise ...and Bayesian network meta-analyses; the latter allows indirect assessments if any of the anaesthetic agents were not compared in head-to-head trials. Pertinent studies were identified using BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Library (last updated in June 2012).
We identified 38 randomized trials with survival data published between 1991 and 2012, with most studies (63%) done in coronary artery bypass grafting (CABG) patients with standard cardiopulmonary bypass. Standard meta-analysis showed that the use of a volatile agent was associated with a reduction in mortality when compared with TIVA at the longest follow-up available 25/1994 (1.3%) in the volatile group vs 43/1648 (2.6%) in the TIVA arm, odds ratio (OR)=0.51, 95% confidence interval (CI) 0.33–0.81, P-value for effect=0.004, number needed to treat 74, I2=0% with results confirmed in trials with low risk of bias, in large trials, and when including only CABG studies. Bayesian network meta-analysis showed that sevoflurane (OR=0.31, 95% credible interval 0.14–0.64) and desflurane (OR=0.43, 95% credible interval 0.21–0.82) were individually associated with a reduction in mortality when compared with TIVA.
Anaesthesia with volatile agents appears to reduce mortality after cardiac surgery when compared with TIVA, especially when sevoflurane or desflurane is used. A large, multicentre trial is warranted to confirm that long-term survival is significantly affected by the choice of anaesthetic.
Guidelines support the use of a restrictive strategy in blood transfusion management in a variety of clinical settings. However, recent randomized controlled trials (RCTs) performed in the ...perioperative setting suggest a beneficial effect on survival of a liberal strategy. We aimed to assess the effect of liberal and restrictive blood transfusion strategies on mortality in perioperative and critically ill adult patients through a meta-analysis of RCTs.
We searched PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, Transfusion Evidence Library, and Google Scholar up to 27 March 2015, for RCTs performed in perioperative or critically ill adult patients, receiving a restrictive or liberal transfusion strategy, and reporting all-cause mortality. We used a fixed or random-effects model to calculate the odds ratio (OR) and 95% confidence interval (CI) for pooled data. We assessed heterogeneity using Cochrane's Q and I2 tests. The primary outcome was all-cause mortality within 90-day follow-up.
Patients in the perioperative period receiving a liberal transfusion strategy had lower all-cause mortality when compared with patients allocated to receive a restrictive transfusion strategy (OR 0.81; 95% CI 0.66−1.00; P=0.05; I2=25%; Number needed to treat=97) with 7552 patients randomized in 17 trials. There was no difference in mortality among critically ill patients receiving a liberal transfusion strategy when compared with the restrictive transfusion strategy (OR 1.10; 95% CI 0.99−1.23; P=0.07; I2=34%) with 3469 patients randomized in 10 trials.
According to randomized published evidence, perioperative adult patients have an improved survival when receiving a liberal blood transfusion strategy.
Background
Percutaneous dilatational tracheostomy (PDT) is a common procedure in intensive care units and the identification of the best technique is very important. We performed a systematic review ...and meta‐analysis of randomized studies comparing different PDT techniques in critically ill adult patients to investigate if one technique is superior to the others with regard to major and minor intraprocedural complications.
Methods
BioMedCentral and other database of clinical trials were searched for pertinent studies. Inclusion criterion was random allocation to at least two PDT techniques. Exclusion criteria were duplicate publications, nonadult studies, and absence of outcome data.
Study Design
Population, clinical setting, and complications were extracted.
Results
Data from 1130 patients in 13 randomized trials were analyzed. Multiple dilators, single‐step dilatation, guide wire dilating forceps, rotational dilation, retrograde tracheostomy, and balloon dilation techniques were always performed in the intensive care unit. The different techniques and devices appeared largely equivalent, with the exception of retrograde tracheostomy, which was associated with more severe complications and more frequent need of conversion to other techniques when compared with guide wire dilating forceps and single‐step dilatation techniques. Single‐step dilatation technique was associated with fewer failures than rotational dilation, and fewer mild complications in comparison with balloon dilation and guide wire dilating forceps (all P < 0.05).
Conclusions
Among the six analyzed techniques, single‐step dilatation technique appeared the most reliable in terms of safety and success rate. However, the number of available randomized trials was insufficient to confidently assess the best PDT technique.
Summary
More than one million peri‐operative patients die each year. Thus, small improvements in peri‐operative care may save thousands of lives. However, clinicians need confidence in the robustness ...of trial findings. The Fragility Index may complement frequentist analysis and provide quantitative assessment of robustness. We searched MEDLINE for peri‐operative critical care randomised controlled trials that reported a statistically significant difference in mortality. We identified 46 trials with 37,347 participants. The median (IQR range) Fragility Index was 2 (1–3 0–49). Eleven trials had a Fragility Index of zero (changing from the Chi‐square test to Fisher's exact test removed significance) and seven trials had a Fragility Index of 1. Only 23/46 trials had a Fragility Index greater than the number of patients lost to follow‐up. There was a strong positive correlation between the Fragility Index and: the number of participants, R2 = 0.97, p < 0.0001; the number of centres that recruited participants, R2 = 0.96, p < 0.0001; the number of nations that recruited participants, R2 = 0.93, p < 0.0001; and the number of deaths, R2 = 0.97, p < 0.0001. As measured by the Fragility Index, the effect of peri‐operative interventions on mortality in individual randomised controlled trials are not robust.
The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients. Retrospective analysis on patients admitted to the ...San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs. The primary outcome was the time to nasopharyngeal swab negativization. A multivariable Cox model was fitted to determine factors associated with nasopharyngeal swab negativization. Of 280 patients included, 59 (21.1%) patients were treated with steroids. Differences observed between steroid users and non-users included the proportion of patients with a baseline PaO
/FiO
≤ 200 mmHg (45.8% vs 34.4% in steroids and non-steroids users, respectively; p = 0.023) or ≤ 100 mmHg (16.9% vs 12.7%; p = 0.027), and length of hospitalization (20 vs 14 days; p < 0.001). Time to negativization of nasopharyngeal swabs was similar in steroid and non-steroid users (p = 0.985). According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤ 70 years, a shorter duration of symptoms at admission, a baseline PaO
/FiO
> 200 mmHg, and a lymphocyte count at admission > 1.0 × 10
/L. SARS-CoV-2 clearance was not associated with corticosteroid use. Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with an early use of corticosteroids.
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