Is early ventricular dysfunction or dilatation associated with lower mortality rate in adult severe sepsis and septic shock? A meta-analysis

Huang et al. Critical Care Is early ventricular dysfunction or dilatation associated with lower mortality rate in adult severe sepsis and septic shock? A meta-analysis Stephen J Huang 0 Marek Nalos 0 Anthony S McLean 0 0 Department of Intensive Care Medicine, Nepean Hospital, Nepean Clinical School, University of Sydney , Penrith NSW 2750 , Australia Introduction: Reversible myocardial depression occurs early in severe sepsis and septic shock. The question of whether or not early ventricular depression or dilatation is associated with lower mortality in these patients remains controversial. Most studies on this topic were small in size and hence lacked statistical power to answer the question. This meta-analysis attempted to answer the question by increasing the sample size via pooling relevant studies together. Methods: PubMed, Embase (and Medline) databases and conference abstracts were searched to July 2012 for primary studies using well-defined criteria. Two authors independently screened and selected studies. Eligible studies were appraised using defined criteria. Additional information was sought the corresponding authors if necessary. Study results were pooled using random effects models. Standardized mean differences (SMD) between survivor and non-survivor groups were used as the main effect measures. Results: A total of 62 citations were found. Fourteen studies were included in the analysis. The most apparent differences between the studies were sample sizes and exclusion criteria. All studies, except four pre-1992 studies, adopted the Consensus definition of sepsis. Altogether, there were >700 patients available for analysis of the left ventricle and >400 for the right ventricle. There were no significant differences in left ventricular ejection fractions, right ventricular ejection fractions, and right ventricular dimensions between the survivor and non-survivor groups. When indexed against body surface area or body height, the survivors and non-survivors had similar left ventricular dimensions. However, the survivors had larger non-indexed left ventricular dimensions. Conclusion: This meta-analysis failed to find any evidence to support the view that the survivors from severe sepsis or septic shock had lower ejection fractions. However, non-indexed left ventricular dimensions were mildly increased in the survivor group but the indexed dimensions were similar between the groups. Both survivors and non-survivors had similar right ventricular dimensions. - Introduction The phenomenon of sepsis related myocardial dysfunction has been recognized for over three decades [1]. One of the earliest studies by Weisel et al. in 1977, using pulmonary artery catheter thermodilution method measured left ventricular stroke work index, observed that not only was left ventricular depression common in patients with sepsis, but was also potentially reversible [2]. They also found that the left ventricular systolic function was reduced in non-survivor. Six years later, Hoffman et al., using gated cardiac scintigraphy, documented that right ventricular ejection fraction (RVEF) was depressed in patients with septic shock compared to normal [3]. It was unclear from this study whether the survivors exhibited a better baseline right ventricular function. The most quoted study on this subject is Parker and co-authors 1984 landmark paper which reported approximately half of the 20 patients with septic shock in the study had severely reduced baseline left ventricular ejection fraction (LVEF), and that the mean LVEF was paradoxically lower in survivors [4]. Using radionuclide cineagiography, they also showed that survivors had dilated left ventricles (LV). In a subsequent study, Parker et al. further found that survivors of septic shock also had depressed initial RVEF, a finding that was not shared by Vincent et al., who noted that survivors from septic shock had markedly higher initial RVEF in two studies [5,6]. While many physicians believe poor LVEF have better outcome in patients with sepsis, some conflicting data have started to emerge in recent years. For example, Vieillard-Baron et al., by examining the hemodynamic parameters in septic shock patients, found that the initial LVEF were similar in survivors and non-survivors [7]. Pulido et al. also failed to find any association between 30- or 100-day mortality with initial ventricular dysfunction [8]. Some studies also casted doubts about the earlier claims that survivors from severe sepsis or septic shock have larger ventricular size [7,9]. Despite all these studies, the debates of whether or not ventricular dysfunction or dilatation (increased ventricular cavity size) is associated with lower mortality in severe sepsis or septic shock continue. One of the main reasons is the small sample size in majority of these studies lacked the statistical power to detect genuine differences in effect sizes. In light of this continuing uncertainty, we conducted this meta-analysis to assist in clarifying the situation. The goals of this meta-analysis are: (1) to critically appraise the best available observational studies that correlated venticular function and/or dimension with mortality in adult patients with severe sepsis or septic shock; (2) to synthesize the relevant data and determine if ventricular dysfunction or dilatation is associated with lower mortality rate; and (3) to list the main difficulties encountered in past studies and to propose some suggestions for future studies on this subject. Methods Study identification Our search strategy began by breaking the research question down to: (1) patient type (study population); (2) indicator or indices; and (3) outcomes. For patient type, we included only severe sepsis or septic shock; for indicator, we used myocardial depression and any synonyms; for outcomes, we looked for mortality and any synonyms. Primary studies dated July 2012 and earlier were searched using PubMed and Embase (including Medline). The following terms (some with truncation) were searched as key and text words: Sepsis OR septic shock [title] AND ((Ventricular OR cardiac OR myocardial) AND (failure OR depression OR dysfunction OR function OR impairment OR dimension OR dilat*)) OR (ejection fraction) [title] AND (death OR mortality OR surviv* OR outcome OR predict* OR prognos*). We limited the search to human studies, English language, clinical study, outcome study, clinical trials, article, article in press, conference abstract, or conference paper. The reference lists of all eligible studies were examined to search for other relevant studies. Study eligibility Two investigators (SJH and MN) independently reviewed the titles and abstracts of all relevant studies; all potential relevant studies were retrieved. When disagreement occurred, the reviewers resolved the discrepancies by consensus. Selection criteria used to identify studies were: prospective or retrospective observational studies; adult patients (...truncated)