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Pneumonia Prevention to Decrease Mortality in Intensive Care Unit: a Systematic Review and Meta-Analysis

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Pneumonia Prevention to Decrease Mortality in Intensive Care Unit: a Systematic Review and Meta-Analysis MAJOR ARTICLE Pneumonia Prevention to Decrease Mortality in Intensive Care Unit: A Systematic Review and Meta-analysis Antoine Roquilly,1 Emmanuel Marret,3 Edward Abraham,4 and Karim Asehnoune1,2 1Service d’Anesthésie Réanimation Hôtel-Dieu, Nantes University Hospital, 2UPRES EA3826, Faculty of Médecine of Nantes, and 3Department of Anesthesiology and Critical Care, Tenon University Hospital, University Pierre et Marie Curie, Paris, France; and 4Wake Forest School of Medicine, Winston-Salem, North Carolina (See the Editorial Commentary by Klompas on pages 76–8.) Background. To determine the strategies of prevention of hospital-acquired pneumonia that reduce mortality in intensive care unit (ICU). Methods. We followed PRISMA (Preferred Reported Items for Systemic Reviews and Meta-Analyses) guide- lines. We searched MEDLINE and the Cochrane Controlled Trials Register (through 10 June 2014) as well as refer- ence lists of articles. We included all randomized controlled trials conducted in critically ill adult patients hospitalized in ICUs and evaluating digestive prophylactic methods (selective digestive decontamination [SDD], acidification of gastric content, early enteral feeding, prevention of microinhalation); circuit prophylactic methods (closed suctioning systems, early tracheotomy, aerosolized antibiotics, humidification, lung secretion drainage, sil- ver-coated endotracheal tubes) or oropharyngeal prophylactic methods (selective oropharyngeal decontamination, patient position, sinusitis prophylaxis, subglottic secretion drainage, tracheal cuff monitoring). One reviewer extract- ed data that were checked by 3 others. The primary outcome was the mortality rate in the ICU. Results. We identified 157 randomized trials to pool in a meta-analysis. The primary outcome was available in 145 studies (n = 37 156). The risk ratio (RR) for death was 0.95 (95% confidence interval [CI], .92–.99; P = .02) in the intervention groups. In subgroup analysis, only SDD significantly decreased mortality compared with control (n = 10 227; RR, 0.84 [95% CI, .76–.92; P < .001]). The RR for in-ICU death was 0.78 (95% CI, .69–.89; P <.001; I2 = 33%) in trials investigating SDD with systemic antimicrobial therapy and 1.00 (.84–1.21; P = .96; I2 = 0%) with- out systemic antimicrobial therapy. Conclusions. Selective digestive decontamination with systemic antimicrobial therapy reduced mortality and should be considered in critically ill patients at high risk for death. Keywords. hospital-acquired pneumonia/prevention; mortality; selective digestive decontamination; mechanical ventilation. Hospital-acquired pneumonia (HAP), and notably ven- important outcomes, including duration of mechanical tilator-associated pneumonia, developing as a conse- ventilation, length of stay in the intensive care unit quence of lung bacterial colonization, alters clinically (ICU), and mortality rates [1–3]. HAP is associated with use of antibiotics that may increase the risk of mul- tiple-drug-resistant bacteria in ICUs, and the increase in Received 22 January 2014; accepted 4 August 2014; electronically published 24 medical costs is estimated to be to $20 000 per episode of September 2014. Correspondence: Karim Asehnoune, MD, PhD, CHU de Nantes, Service d’Anes- HAP [4]. Given HAP-associated morbidity, the preven- thésie Réanimation, 1 Pl Alexis Ricordeau, 44093 Nantes Cedex 1, France (karim. tion of HAP has been the focus of numerous studies in [email protected]). ® critically ill patients and remains a controversial issue. Clinical Infectious Diseases 2015;60(1):64–75 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Bacterial colonization of the oropharynx and subse- Diseases Society of America. All rights reserved. For Permissions, please e-mail: quent microaspirations are initial events that lead to [email protected]. DOI: 10.1093/cid/ciu740 HAP [5–7]. The prevention of such events was therefore 64 • CID 2015:60 (1 January) • Roquilly et al proposed as a method for reducing the rate of HAP and presum- therapies, ulcer prophylaxis, aerosolized antibiotics, closed suc- ably for reducing associated morbidity and mortality. Three main tioning systems, early tracheotomy, humidification, phytotherapy approaches have been evaluated: (1) diminishing the microaspi- (ginger extract), physiotherapy, positive end-expiratory pressure ration of digestive flora; (2) reducing the volume of oropharyn- (PEEP), tracheal saline instillation, silver-coated endotracheal geal secretions aspirated into the lungs; and (3) inhibiting tubes), selective oropharyngeal decontamination (SOD), patient overgrowth or alterations in the microbiome in the oropharynx position, sinusitis prophylaxis, subglottic secretion drainage, and or larynx. Several meta-analyses of approaches to reducing the in- tracheal cuff monitoring. Studies using a cluster-randomization cidence of HAP conclude to a reduction in the risk of infection of procedure were included in the main analysis, but a sensitive such strategies. However, international recommendations for the analysis with exclusion of such studies was planned a priori. prevention of HAP provide different conclusions [8–11]anddo Pediatric patients were excluded from the study. not state which intervention is mandatory or superior to the oth- ers. The combination of several strategies for preventing HAP Data Extraction and Quality Assessment failed to improve mortality rates [12],and nonadherence to inter- One author (A. R.) checked all titles and abstracts of the articles national guidelines for HAP prevention is common [13]. identified from the database research and examined in full all We have hypothesized that all the preventive strategies do not randomized trials potentially eligible for the review. Quality as- equally alter the risk of death. Because many interventions are sessment for each study was performed by 2 unblinded investi- often poorly applied in clinical practice, it is important to deter- gators (A. R. and K. A.). Any disagreement among the 2 authors mine the most effective interventions that should be implemented was resolved by discussion. Persistent disagreement was settled in critically ill patients. We thus performed a systematic review to by discussion with other authors (E. M. and E. A.) after separate determine which method is the most effective for decreasing mor- review of the report. tality rates. The rates of HAP, duration of mechanical ventilation, One author (A. R.) designed a standard data extraction form, and ICU length of stay were also evaluated as secondary criteria. and other authors (E. M., E. A., and K. A.) amended and vali- dated the design of the form before abstraction of data. One au- MATERIALS AND METHODS thor (A. R.) extracted the following data from each eligible study: first author, year of publication, quality assessment by Data Source and Searches the Cochrane Collaboration’s risk of bias tool, type of interven- We followed PRISMA (Preferred Reported Items for Systemic tion, inclusion criteria, criteria used for HAP diagnosis, number Reviews and Meta-Analyses) guidelines were followed during of patients, number of HAP cases, duration of mechanical ven- the design and implementation of this meta-analysis (Supple- tilation and of ICU stay, and ICU mortality rate. Data were ex- mentary Table 1). We attempted to identify all relevant studies tracted from the tables, figures, text of the manuscript, and/or published in English regardless of publication status (published from previous meta-analysis that included the selected trial. or in press). We considered abstracts presented at scientific meetings <3 years earlier (Society Of Critical Care Medicine, Data Synthesis and Analysis European Society of Intensive Care Medicine, Societé Française The primary evaluation criterion was the rate of in-ICU deaths, that d’Anesthesie Reanimation, Societé de Reanimation de Langue is, the ICU mortality rate. When no information was available on Française). PubMed (MEDLINE/Index Medicus) and the in-ICU deaths, the rate of in-hospital death was considered if pro- Cochrane Controlled Trials Register were searched for studies vided. When trials had 2 control arms, the numbers of deaths in the published from January 1969 through 10 June 2014. The Med- control arms were pooled. The other end points analyzed included ical Subject Heading terms used for the search were pneumonia the incidence of HAP, the duration of mechanical ventilation, and and intensive care units with the limit “adult 19+ years.” The the ICU length of stay (or duration of hospitalization, as provided). “related articles” hyperlinks in MEDLINE were explored for ad- ditional references. The reference lists of all selected trials and Statistical Analyses previous published meta-analysis were checked for additional All statistical analyses were performed using Review Manager references. We contacted authors to identify unpublished data. software (version 5.1.6; Cochrane Collaboration; Nordic Cochrane Centre) or Stata software (version 10.1; StataCorp). Study Selection For dichotomous data (mortality and HAP), we calculated the The authors selected all randomized trials that evaluated any of risk ratio (RR) with 95% confidence intervals (CIs). To estimate the following strategies in adult patients (aged ≥18 years) hos- the clinical relevance of a beneficial effect on mortality, we cal- pitalized in ICUs: acidified enteral feeding, selective digestive culated the number needed to treat with 95% CIs, using RR and decontamination
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