Abstract

Background: In this review, we aimed to analyze the risk factors of mediastinitis after open cardiac surgery.

Methods: The literature screening was performed at Pubmed, Ovid, and Sciencedirect databases without date limitation. Studies investigating the co-existing diseases were included. The results of trials were evaluated with random or fixed effect model according to the heterogeneity.

Results: A total of 5009 articles were attained after database searching. Thirty five articles were included to the metaanalysis including 131.158 patients who met inclusion criteria. The most possible preoperative risk factors for mediastinitis were atrial fibrillation, pulmonary disease, diabetes mellitus, renal disease, peripheral vascular disease and systemic hypertension (p<0.05). Pulmonary hypertension, malignancy, hepatic and neurological diseases, heart failure and dyslipidemia were not found to be risk factors (p>0.05). Heterogeneity was not observed for four (renal, hepatic, neurological and peripheral vascular diseases) of 12 factors (I2<25%).

Conclusion: The results of our meta-analysis showed that preoperative co-existing diseases such as pulmonary hypertension, malignancy, heart failure, hepatic and neurological diseases, and dyslipidemia may not be risk factors for the development of mediastinitis following cardiac surgery.

Mediastinitis, also know as deep sternal wound infection (DSWI), is a rare, serious complication often seen after open cardiac surgery which may increase the length of intensive care unit (ICU) and/or hospital stays and also may cause a higher mortality rate. Researchers have reviewed the preoperative, intraoperative and postoperative variables for predicting postoperative mediastinitis development,[1-5] and coexisting diseases, such as diabetes mellitus (DM) and systemic hypertension (HT) along with pulmonary, renal, hepatic, and neurological diseases, were generally examined in those studies. However, we found controversy regarding the association between postoperative mediastinitis and those diseases. Therefore, in this study, we aimed to review and analyze the literature to determine which preoperative variables can be used to predict mediastinitis.

Methods

Search strategy
We performed the database search and analyzed the article in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).[6] Two authors searched the PubMed electronic database to determine whether or not coexisting diseases could predict the development of mediastinitis after cardiac surgery. The search concluded on January 5^th, 2014, and there were no limitations related to this date.

The search was conducting using the following English keywords or a combination of these words: cardiac surgery, heart surgery, valve surgery, coronary artery bypass grafting (CABG), mediastinitis, and DSWI. The search was limited to English, with articles in other languages being excluded from the study. In addition, the study was limited to clinical trials, comparative studies, multicenter studies, observational studies, randomized controlled trials, controlled clinical trials, and evaluation studies.

Selection of studies
The studies, regardless of sample size, included both retrospective and prospective clinical studies. Inclusion criteria were that it was a clinical study that involved open cardiac surgery with off-pump or extracorporeal circulation and that the article was in English. Experimental studies, articles not in English, and those that focused on non-cardiac surgery were excluded from the study. Furthermore, articles that were associated with our review topic but did not contain information concerning the rate of mediastinitis according to preoperative coexisting diseases were also excluded as well as those that contained data with figures but no numerical values.

Data extraction
Two reviewers independently extracted data from the relevant studies, and any disagreements were resolved by consensus using a third reviewer. At first, we gathered the publication information (first author's name, publication year, patient population, and type of surgery), characteristics of the participants (sample size and type of study methods), and outcome information (mediastinitis rate, number of diseases, number of control cases, and definition of mediastinitis) and then recorded the number of patients with and without mediastinitis (controls).

Statistical analysis
Statistical analysis was carried out using the Comprehensive Meta-Analysis (CMA) Version 2.0 (Biostat, Englewood, New Jersey, USA), and the odds ratio (OR) and 95% confidence interval (CI) (lower-upper limit) was utilized for this analysis. The heterogeneity was evaluated using the statistics of I², with it being accepted as significant if I² >25%. In addition, the heterogeneity was classified as low (25% < I² > 50%.), moderate (50% < I² > 75%.), or high (I² >75%) and was evaluated by analyzing subgroups and moderators. The meta-analysis was performed by using fixed or random effect models, with the latter being conducted in the presence of heterogeneity (I² > 25%) and the former without heterogeneity (I² <25%). The overall e ffect was analyzed via a Z score, and potential publication bias was evaluated using the Begg test.

Results

A flow diagram of the database search is shown in Figure 1. We identified 5,009 records and filtered these down to 999 articles. After duplicates were removed, 374 records remained, and 255 of these were excluded after screening because they were deemed to be unrelated to our topic. Then the full text of 119 articles were assessed for their eligibility, and 83 were excluded because of the absence of detailed data regarding gender in each group. This left 36 articles that were included in the quantitative synthesis.[1-5,7-36] The demographic features of these studies are summarized in Table 1. The ratio of development of mediastinitis was 1.99% (2,619 cases out of 131,158). Results of analysis, heterogeneity and publication bias are shown in Table 2-14.

Figure 1: Flow diaphragm of database search.

Table 1: Studies included in the analysis

Table 1: (continued)

Table 2: Results of analysis

Table 3: Pulmonary hypertension and mediastinitis

Table 4: Malignancy and mediastinitis

Table 5: Hepatic disease and mediastinitis

Table 6: Dyslipidemia and mediastinitis

Table 7: Neurological disease and mediastinitis

Table 8: Atrial fibrillation and mediastinitis

Table 9: Peripheral vascular disease and mediasitinitis

Table 10: Heart failure and mediastinitis

Table 11: Renal disease and mediastinitis

Table 12: Systemic hypertension and mediastinitis

Table 13: Diabetes mellitus and mediastinitis

Table 14: Pulmonary disease and mediastinitis

Discussion

Cardiac surgery is special because of both the individual properties of the patients and the operative procedures. Advanced age and coexisting diseases are common causes of morbidity, with invasive interventions [e.g., arterial cannulation, central venous catheterization, cardiopulmonary bypass (CPB), intra-aortic balloon pumps (IABPs), blood transfusions, and ICU stays being other possible sources of infection. In addition, invasive interventions may lead to the entry of bacterial pathogens.[37]

Kansy et al.[38] found that the ratio of major infections (septicemia, endocarditis, and mediastinitis) was 3.1% after cardiac surgery, and Chen et al.[39] also found a similar ratio for major infections (3.2%), with the risk factors being a high body mass index (BMI), previous CABG, emergency surgery, renal impairment, heart failure, peripheral and cerebrovascular diseases, and immunsuppression.

Many of the coexisting diseases, such as DM,[40] heart failure,[41] pulmonary disease,[23] and malignancy,[42] may decrease a patient’s resistance against infection while longer treatment durations of other conditions (AF and systemic HT) can increase the duration of ICU and hospital stays. Hence, the possibility of infection is also higher.

In our meta-analysis, some of the diseases occurred less frequently. Three studies featured pulmonary HT, two focused on malignancy, four had cases of hepatic disease, four included patients with dyslipidemia, three featured neurological disease, and three had cases of AF. The most studied diseases were DM (29 studies), renal disease (16 studies), systemic HT (15 studies), heart failure (12 studies), and peripheral vascular disease (10 studies). We did not observe heterogeneity for the studies that focused on peripheral vascular and renal disease (I² < 25%). F urthermore, t he heterogeneity of the studies that featured DM and systemic HT was low (25%< I2 < 50%), but it was high for those that included patients with heart failure (I² >75%).

The ratio of mediastinitis development was approximately 2%. However, future studies are needed because only nine of the 35 studies had a large sample size (>5,000) (23,499 in Baillot et al.,[9] 15,406 in Braxton et al.,[10] 11,848 in Robinson et al.,[28] 11,748 in Elenbaas et al.,[15] 10,713 in Eklund et al.,[14] 9,303 i n Gummert e t a l.,[19] 7,583 in Hallam et al.,[20] 5,798 in Filsoufi et al.,[16] and 5,649 in Floros et al.[5] However, none of these included the majority of the factors we wanted to assess in their analyses. When we excluded[5,9,10,14-16,19,20,28] those results from our analysis, the present results changed as opposite for pulmonary HT, hepatic and neurological disease, AF, and heart failure.

We used the definition of mediastinitis, type of surgery, and study design as moderators to analyze the reason for heterogeneity and found that the heterogeneity did not change based on the definition of mediastinitis or type of surgery. However, study design was a primary cause of heterogeneity.

In the literature, there were many studies that discussed the presence of mediastinitis after cardiac surgery. However, the main limitation of our metaanalysis was that we excluded studies because of their design and the absence of needed data. Another limitation was that we excluded the patients’ individual demographic characteristics, such as age and gender, along with the intraoperative variables (e.g., the presence or absence of CPB and aortic cross-clamp time) because we focused on coexisting diseases.

Conclusion

The results of our meta-analysis showed that preoperative coexisting diseases, such as pulmonary HT, malignancy, heart failure, hepatic and neurological diseases, and dyslipidemia, may not be risk factors for the development of mediastinitis after cardiac surgery. However, there is still a need for large, randomized, controlled studies to decrease the heterogeneity of analysis.

Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The authors received no financial support for the research and/or authorship of this article.

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