Levosimendan for Hemodynamic Support after Cardiac Surgery Landoni, Giovanni; Lomivorotov, Vladimir V; Alvaro, Gabriele ...
New England journal of medicine/The New England journal of medicine,
05/2017, Letnik:
376, Številka:
21
Journal Article
Recenzirano
Odprti dostop
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.
1
Acute perioperative left ventricular dysfunction is a major complication affecting up to 20% of such patients
2
,
3
and is associated with increased mortality.
4
Inotropic drugs (catecholamines and phosphodiesterase type 3 PDE-3 inhibitors) are the cornerstone of postoperative hemodynamic support.
3
,
5
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.
6
,
7
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.
Essentials
The optimal management of patients with platelet dysfunction undergoing surgery is unclear.
This meta‐analysis compared perioperative administration of desmopressin to placebo.
...Desmopressin reduced red cell transfusions, blood loss and risk of re‐operation due to bleeding.
There were too few events to determine if there was a change in the risk of thrombotic events.
Summary
Background
Platelet dysfunction, including that caused by antiplatelet agents, increases the risk of perioperative bleeding. The optimal management of patients with platelet dysfunction undergoing surgery is unclear.
Objectives
To assess whether desmopressin reduces perioperative allogeneic red cell transfusion and bleeding in patients with platelet dysfunction.
Patients/Methods
We searched for randomized controlled trials in The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, the Transfusion Evidence Library and the ISI Web of Science to 7th July 2016. Data were pooled using mean difference (MD), relative risks or Peto odds ratios (pOR) using a random‐effects model.
Results
Ten trials with 596 participants were identified, all in the setting of cardiac surgery. Platelet dysfunction was due to antiplatelet agents in six trials and cardiopulmonary bypass in four trials. Patients treated with desmopressin were transfused with fewer red cells (MD, −0.65 units; 95% Confidence Interval CI, −1.16 to −0.13 units), lost less blood (MD, −253.93 mL; 95% CI, −408.01 to −99.85 mL) and had a lower risk of re‐operation due to bleeding (pOR, 0.39; 95% CI, 0.18–0.84). The GRADE quality of evidence was very low to moderate, suggesting considerable uncertainty over the results
Conclusions
Desmopressin may be a useful agent to reduce bleeding and transfusion requirements for people with platelet dysfunction or with a history of recent antiplatelet drug administration undergoing cardiac surgery.
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.
After a comprehensive review and meta-analysis, radiotherapy and chemotherapy appeared to be similarly effective overall in clinical stage (CS) IIA and IIB seminoma, but chemotherapy demonstrated a ...trend toward lower incidence of side-effects and RR in CS IIB disease.
Outcomes of radiotherapy (RT) compared with chemotherapy (CT) remain poorly defined for clinical stage (CS) IIA and IIB seminoma. We aimed to evaluate the current role of the two treatment modalities in this setting of testicular seminoma.
A systematic review and meta-analysis (MA) was carried out to identify all evaluable studies. Search was limited to studies published after 1990 and included the Medline, Embase databases, and abstracts from ASCO (GU), ESMO, AUA, and ASTRO meetings up to April 2014. Sensitivity analyses were applied including the following: CSIIA and CSIIB, paraortic + iliac RT only in both stages, RT dose (≥30 versus <30 Gy), and PEB/EP regimens only.
Thirteen studies have been selected for MA on relapse outcome. No randomized trials compared RT and CT. There were 4 prospective and 9 retrospective studies, with a total of 607 patients receiving RT and 283 patients CT. The pooled relapse rate (RR) was similar between the RT 0.11, 95% confidence interval (CI) 0.08–0.14, P for heterogeneity = 0.096, I2 = 38% and CT groups (0.08, 95% CI 0.01–0.15, P for heterogeneity <0.001, I2 = 82.5%). However, in the sensitivity analysis, the pooled RR for RT in CSIIB was 0.12 (95% CI 0.06–0.17) while it was 0.05 (95% CI 0–0.11) for CT. Long-term side-effects and incidence of second cancers were more frequently reported following RT. The overall incidence of nontesticular second malignancies was 0.04 (95% CI 0.01–0.02) in the RT group and 0.02 (95% CI 0.003–0.04) in the CT group.
Although RT and CT appeared to be equal options in CSIIA and IIB seminoma, a trend in favor of CT for a lower incidence of side-effects and RR in CSIIB was found. This evidence is limited by the retrospective quality of studies and their small sample size.
PDF
