Ventilator Associated Pneumonia Systematic Review and Meta Analysis

Ventilator Associated Pneumonia Systematic Review and Meta Analysis ORDER NOW FOR CUSTOMIZED AND ORIGINAL ESSAY PAPERS ON Ventilator Associated Pneumonia Systematic Review and Meta Analysis Select a systematic review with meta-analysis from a peer reviewed journal. This systematic review with meta-analysis must have relevance to your PICOT question . Address the following for the discussion based on this study (post your response with numbers for clarity). Be thorough in your responses. Ventilator Associated Pneumonia Systematic Review and Meta Analysis Give the study reference in APA format. What was the aim of the systematic review? Was the validity of studies addressed appropriately? Explain? Describe how the studies were combined and were they combined appropriately? How large was the intervention of treatment effect? Based on your area of clinical practice uncertainty and PICOT question, what clinical recommendations would be supported by the data from this systematic review? 1 page single paced, no cover sheet, only reference page. Intext Citations and I am providing the article. attachment_1 Fan et al. Critical Care (2016) 20:338 DOI 10.1186/s13054-016-1506-z RESEARCH Open Access Does ventilator-associated event surveillance detect ventilator-associated pneumonia in intensive care units? A systematic review and meta-analysis Yunzhou Fan†, Fang Gao†, Yanyan Wu, Jie Zhang, Ming Zhu and Lijuan Xiong* Abstract Background: Ventilator-associated event (VAE) is a new surveillance paradigm for monitoring complications in mechanically ventilated patients in intensive care units (ICUs). The National Healthcare Safety Network replaced traditional ventilator-associated pneumonia (VAP) surveillance with VAE surveillance in 2013. The objective of this study was to assess the consistency between VAE surveillance and traditional VAP surveillance. Methods: We systematically searched electronic reference databases for articles describing VAE and VAP in ICUs. Pooled VAE prevalence, pooled estimates (sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)) of VAE for the detection of VAP, and pooled estimates (weighted mean difference (WMD) and odds ratio ([OR)) of risk factors for VAE compared to VAP were calculated. Results: From 2191 screened titles, 18 articles met our inclusion criteria, representing 61,489 patients receiving mechanical ventilation at ICUs in eight countries. The pooled prevalence rates of ventilator-associated conditions (VAC), infection-related VAC (IVAC), possible VAP, probable VAP, and traditional VAP were 13.8 %, 6.4 %, 1.1 %, 0.9 %, and 11.9 %, respectively. Pooled sensitivity and PPV of each VAE type for VAP detection did not exceed 50 %, while pooled specificity and NPV exceeded 80 %. Compared with VAP, pooled ORs of in-hospital death were 1.49 for VAC and 1.76 for IVAC; pooled WMDs of hospital length of stay were ?4.27 days for VAC and ?5.86 days for IVAC; and pooled WMDs of ventilation duration were ?2.79 days for VAC and ?2.89 days for IVAC. Conclusions: VAE surveillance missed many cases of VAP, and the population characteristics identified by the two surveillance paradigms differed. VAE surveillance does not accurately detect cases of traditional VAP in ICUs. Keywords: Ventilator-associated events VAE, Ventilator-associated pneumonia VAP, Surveillance, Meta-analysis Background Mechanical ventilation (MV) is a widely used intervention for critically ill patients in intensive care units (ICUs). Ventilator-associated pneumonia (VAP) is a clinically important, potentially preventable complication of mechanical ventilation [1–3]. Prior to 2013, the National Healthcare Safety Network (NHSN) monitored MV complications by VAP * Correspondence: [email protected] † Equal contributors Department of Nosocomial Infection Management, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan 430022, China surveillance. The clinical diagnosis of VAP is based on clinical signs, chest radiography, and microbiological data. Clinical signs include: changes in sputum or tracheal secretions in terms of purulence, color, and/or increasing production; cough; temperature >38 or <36 °C; rales or bronchial breath sounds on examination, and worsening oxygenation. Laboratory findings include non-specific indicators of infection including leukocytosis (>12 × 109 white blood cells (WBC)/L) or leukopenia (<4.0 × 109 WBC/L). Ventilator Associated Pneumonia Systematic Review and Meta Analysis Signs on chest radiography include the development of new infiltrates or the presence of persistent and/or worsening infiltrates [4]. © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Fan et al. Critical Care (2016) 20:338 However, VAP surveillance relying on clinical criteria has proven highly problematic in practice, because most of these diagnostic criteria are not objective or specific [5–7], leaving a wide margin in the surveillance of infection for subjective diagnosis of VAP. Under strong pressure on hospitals to minimize VAP, these subjective criteria have been applied with increasing stringency, resulting in progressively lower prevalence of VAP. Indeed, previous NHSN reports indicate zero prevalence of VAP in more than 50 % of non-teaching ICUs in the USA [8, 9]. To a certain extent, this decrease reflects artifacts of VAP surveillance methods rather than true improvements in care [10]. As VAP surveillance has limited accuracy, the Centers for Disease Control (CDC) recommended a new surveillance paradigm based on ventilation-associated events (VAE) to assess complications in patients receiving MV. The ventilator-associated event paradigm includes a hierarchy of surveillance targets – ventilation-associated condition (VAC), infection-related ventilated-associated condition (IVAC), and possible and probable VAP. VAC is defined as at least two calendar days of stable or decreasing daily minimum positive end-expiratory pressure (PEEP) or daily minimum fraction of inspired oxygen (FiO2) followed by an increase in daily minimum PEEP by at least 3 cm H2O sustained for at least two calendar days or an increase in daily minimum FiO2 by at least 20 points sustained for at least two calendar days. IVAC is the subset of VAC that may be infection-related based on concurrent inflammatory signs and at least 4 days of new antibiotics. Possible VAP requires either Gram stain evidence of purulence or a pathogenic culture; probable pneumonia requires Gram stain evidence of purulence and quantitative or semi-quantitative growth of a pathogenic organism beyond defined thresholds [11]. The VAE paradigm broadens the focus of surveillance beyond the infectious etiology of respiratory failure to other physiological changes associated with suboptimal ventilator care or progression of underlying diseases, such as pulmonary edema, acute respiratory distress syndrome (ARDS), atelectasis, mucus plugging, pulmonary embolus, and radiation pneumonitis [12]. The NHSN replaced VAP surveillance with VAE surveillance in 2013, because the VAE paradigm makes surveillance more objective to facilitate automation and comparability [10]. Although VAE surveillance shifts the focus away from pneumonia and toward common complications that occur in critically ill patients receiving mechanical ventilation, VAP continues to play a major role in morbidity and length of stay (LOS) and is an important component of VAE. However, whether there are differences between VAP identified by the new VAE surveillance method compared with conventional VAP surveillance remains controversial. Some researchers Page 2 of 13 report good correlation between the two surveillance paradigms [13], while others have claim that VAE surveillance does not accurately reflect VAP [14, 15]. Ventilator Associated Pneumonia Systematic Review and Meta Analysis Understanding the difference between VAE and VAP surveillance is valuable, because the change of surveillance paradigm may ultimately affect strategies for VAP prevention and control. Accordingly, we conducted a systematic review and meta-analysis of studies reporting consistency between VAE and VAP. Our objectives were primarily to quantitatively determine the consistency of VAP identification between the two surveillance paradigms, and secondarily to explore the differences in population characteristics between VAE and VAP surveillance. Methods Selection of studies We electronically searched literature that reported prevalence of or risk factors for VAE in the PubMed, EMBASE, ScienceDirect, and Cochrane Database on 2 February 2016 for original articles published after 1 January 2010 in peer-reviewed journals. Relevant articles were identified according to the following Boolean expression: (ventilator-associated events [Title/Abstract] OR ventilator-associated conditions [Title/Abstract] OR ventilator-associated complications [Title/Abstract]) AND (prevalence [Mesh] OR risk factors [Mesh]). A reference list of key reviews was also searched for additional studies. Selection criteria Studies that assessed VAE, including VAC, IVAC, possible VAP, and probable VAP, among adult patients who received mechanical ventilation in an ICU were included in our meta-analysis. We included eligible studies that met at least one of the following criteria: 1. Studies providing original data that could be used to calculate the prevalence rate of VAE, odds ratio (OR), or weighted mean difference (WMD) of risk factors for VAE compared to VAP. 2. Studies reporting VAE and VAP in the same population that could be used to calculate relevant indicators of VAE surveillance for the detection of VAP (sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Studies of paediatric patients or patients from the emergency department were excluded in our analysis. Conference proceedings, reviews, editorials, commentaries, letters and publications in abstract form only were also excluded. In the case of duplicate studies involving the same subject, we chose the most recent one study. Fan et al. Critical Care (2016) 20:338 Page 3 of 13 Study identification Statistical analyses All titles and abstracts of the citations that were generated by the literature search were screened independently by two reviewers. Relevant publications were reviewed in their entirety, and the reviewers were blinded to the author and research institution of each study. Each reviewer made a judgment on the inclusion or exclusion of the study. In the event of disagreement, a third reviewer served as a consultant to resolve the issue. A random effects model was used to calculate pooled estimates and their 95 % confidence intervals (CIs) if there was significant heterogeneity among studies. Otherwise, a fixed effects model was chosen. The VAP detection capability was assessed by receiver operating characteristic (ROC) curves. A ROC curve was plotted using the sensitivity and 1? specificity of each study that reported original data. Heterogeneity was assessed by the Q test and I2 statistic. Egger’s test was used to estimate publication bias in meta-analyses containing more than two individual studies. Sensitivity analysis was performed by limiting the meta-analysis to studies that used the standard CDC/ NHSN definition of VAE for diagnosing VAE and the CDC/NHSN criteria for VAP with quantitative culture results in the diagnosis of VAP, in order to test the impact of the diagnosis method on the pooled results. All tests were two-tailed and statistical significance was defined by a p value <0.05. All analyses were conducted using STATA software (version 11.0, Stata corp., College Station, TX, USA). The study was reviewed and approved by the ethical committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Ventilator Associated Pneumonia Systematic Review and Meta Analysis Data extraction For each included report, the following data were extracted: publication date, region, population, baseline period, hospital, type of ICU, prevalence of VAE with number of cases (n) or corresponding denominators (N), and risk factors (including age, gender, the acute physiology and chronic health evaluation (APACHE) score, hospital length of stay, ICU length of stay, duration of ventilation, in-hospital mortality, and ICU mortality). Quality assessment The quality of the studies was assessed independently, using the Newcastle–Otawa scale (NOS) for nonrandomised observational studies [16], while the Jadad scale was used for randomised controlled trials (RCTs) [17]. The NOS scale allocates a maximum of nine stars to a study, judged on three broad perspectives: the selection of the study groups; the comparability of the groups; and the ascertainment of either the exposure or outcome of interest for case–control or cohort studies, respectively. Studies were defined as poor (0–3), fair (4– 6), or good (7–9). The Jadad scale assesses the quality of RCTs relevant to random assignment, double-blinding, and the flow of patients. It allocates a maximum of 5 points to a study. Studies were defined as poor (0–1), fair (2–3), or good (4–5). Two assessors independently evaluated the methodological quality of included studies, and disagreement was resolved through discussion with a third assessor. Outcome measures The primary outcomes were pooled prevalence rate and pooled consistency between VAE and VAP (sensitivity, specificity, PPV, and NPV). The secondary outcomes were pooled ORs and WMDs of relevant factors for VAE compared with VAP (age, sex, APACHE score, LOS, ventilation duration, and mortality). The metaanalysis comparison between VAE and VAP was limited to studies that reported VAE and VAP simultaneously. Studies that reported VAE only were not included in the comparison analysis but were included in the prevalence analysis. In the comparison analysis, continuous data were expressed as WMD and dichotomous data as OR. Results Our search identified 2192 publications. A flow diagram of the selection process is presented in Fig. 1. A total of 888 duplicate publications were removed, and of the remaining 1304 original articles, 1237 were excluded as irrelevant to the study objectives based on their titles and abstracts. Two authors independently reviewed 67 fulltext articles and excluded 49 articles that did not meet the selection criteria. Ultimately, 18 studies [18–35] (12 cohort studies, 2 nested case–control studies, 2 time-series analysis studies, 1 screening test, and 1 RCT) were selected for final analysis. One study reported a group of patients from collaborative units undergoing daily spontaneous awakening and spontaneous breathing trials and a group of patients from surveillance-only units [18], and another study reported a group of patients undergoing subglottic secretion suctioning and a group of patients not having subglottic secretion suctioning [19]. For the purpose of our analysis, these groups were treated as four separate studies. Table 1 presents a list of the included studies and their characteristics. In all, the meta-analysis included 61,489 patients who received mechanical ventilation in ICUs in eight countries. Most studies were of acceptable quality, apart from one that was rated as poor (Additional file 1: Table S1). Ventilator Associated Pneumonia Systematic Review and Meta Analysis The pooled prevalence rates of each type of VAE and VAP are shown in Table 2. Among mechanically ventilated patients, the pooled prevalence of VAC Fan et al. Critical Care (2016) 20:338 Page 4 of 13 Fig. 1 Flow diagram of the selection process (13.8 %, 95 % CI 9.0, 18.6 %) was higher, and that of IVAC (6.4 %, 95 % CI 4.8, 8.1 %) lower, than that of VAP (11.9 %, 95 % CI 9.4, 14.4 %). VAE surveillance detected fewer cases of possible and probable VAP among ventilated patients, with pooled prevalence rates of 1.1 % (95 % CI 0.5, 1.7 %) and 0.9 % (95 % CI 0.6, 1.2 %), respectively. Additionally, the pooled prevalence of VAE and VAP increased with the prolongation of ventilation. In consistency analysis of VAE and VAP, pooled sensitivity was the highest for VAC at 41.8 % (95 % CI 17.7, 65.9 %) and lowest for probable VAP at 1.6 % (95 % CI 0.1, 3.2 %). Pooled PPV was the highest for IVAC at 47.2 % (95 % CI 16.1, 78.3 %) and lowest for probable VAP at 6.5 % (95 % CI 0.3, 12.6 %). Overall, the pooled estimates of sensitivity and PPV of each VAE type for the detection of VAP did not exceed 50 %. By contrast, the pooled specificity and NPV of VAC and IVAC were greater than 80 %, and those of possible VAP and probable VAP were nearly 100 % (Table 3). The ROC curve for IVAC showed a better capability of VAP detection compared with that of VAC (Fig. 2). ROC curves for possible and probable VAP were not plotted, because studies that provided original sensitivity and specificity data were scarce. The results of comparisons of population characteristics between VAE and VAP surveillance are shown in Table 4. In-hospital mortality in VAE was higher than that of VAP: the pooled OR of death in hospital was 1.49 (95 % CI 1.11, 2.01) for VAC and 1.76 (95 % CI 1.23, 2.52) for IVAC. Hospital LOS was shorter for VAE compared to VAP: the pooled WMD of hospital LOS was ?4.27 days (95 % CI ?7.00, ?1.55 days) for VAC and ?5.86 days (95 % CI ?9.46, ?2.25 days) for IVAC. Additionally, compared with VAP, the pooled WMD of ventilation duration was ?2.79 days (95 % CI ?4.79, ?0.80 days) for VAC and ?2.89 days (95 % CI ?5.58, ?0.20 days) for IVAC. On the other hand, VAE and VAP did not significantly differ by age, sex, APACHE score, or ICU LOS. In sensitivity analysis, limiting the meta-analysis to studies that employed the standard CDC/NHSN criteria for VAE [18–21, 23–32, 35] and definite VAP identified by quantitative culture of specimens from patients [19, 21, 24, 28, 35], the pooled estimates were robust except for pooled prevalence (Additional file 1: Tables S2–S4). The pooled prevalence rates of each VAE type decreased but VAP increased after limiting the analyses to these studies.Ventilator Associated Pneumonia Systematic Review and Meta Analysis The new pooled prevalence of VAC (8.0 %, 95 % CI 6.5, 9.6 %) and IVAC (4.0 %, 95 % CI 3.1, 4.9 %) were lower than that of VAP (13.0 %, 95 % CI 6.3, 19.7 %). Among all meta-analyses containing more than two individual studies, publication bias was detected only for Reference Region Units (n) ICU type Baseline period Population VAE criteria VAP criteria Design Sample size Total (n) VAE Adjusted confounders VAP [17]a USA 7 MICU, SICU, 2011.11– CICU 2013.05 Consecutive mechanical ventilation episodes from collaborative units undergoing daily SAT/SBT CDC/NHSN definition NA Interrupted time 3425 series analysis 293 NA Age, sex, reason for intubation, and SOFA score [17]b USA 6 MICU, SICU, 2011.11– CICU 2013.05 Consecutive mechanical ventilation episodes from surveillance-only units not undergoing daily SAT/SBT CDC/NHSN definition NA Interrupted time 1739 series analysis 75 NA Age, sex, reason for intubation, and SOFA score [18]a Belgium 1 ICU 2012.01– 2013.03 Adult patients ventilated for ?2 calendar days from groups undergoing subglottic secretion suctioning CDC/NHSN definition CDC/NHSN criteria and quantitative culture results of specimens Randomized controlled trial 170 37 15 NA [18]b Belgium 1 ICU 2012.01– 2013.03 Adult patients ventilated for ?2 calendar days from groups not undergoing subglottic secretion suctioning CDC/NHSN definition CDC/NHSN criteria and quantitative culture results of specimens Randomized controlled trial 182 41 32 NA [19] China 1 ICU 2010.04– 2014.02 VAP patients CDC/NHSN definition CDC/NHSN criteria Retrospective cohort 165 55 165 NA [20] USA 1 SICU, MICU 2013.01– 2013.12 Adult patients ventilated for ?2 calendar days CDC/NHSN definition CDC/NHSN criteria Prospective and quantitative cohort culture of specimens 1209 67 84 [21] France Multiple ICU centres 1996.11– 2012.10 Adult patients ventilated for ?5 calendar days from French multicentre OUTCOMEREA database Adapted definition CDC/NHSN criteria (?2 day rise in range of PEEP or a decreasing PaO2/FiO2 ratio by >50 mm Hg with the same level of PEEP or by > 100 mm Hg whatever the level of PEEP) Inception cohort 3028 2331 816 NA [22] USA 1 MICU 2012.12– 2013.04 Adult patients requiring mechanical ventilation CDC/NHSN definition NA Retrospective cohort 257 19 NA [23] USA 1 SICU 2012.09– 2013.08 All intubated patients admitted to SICU CDC/NHSN definition Criteria based on Prospective clinical pulmonary screening test … Get a 10 % discount on an order above $ 100 Use the following coupon code : NURSING10