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 1 Service 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) guidelines. We searched MEDLINE and the Cochrane Controlled Trials Register (through 10 June 2014) as well as reference 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, silver-coated endotracheal tubes) or oropharyngeal prophylactic methods (selective oropharyngeal decontamination, patient position, sinusitis prophylaxis, subglottic secretion drainage, tracheal cuff monitoring). One reviewer extracted 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; I 2 = 33%) in trials investigating SDD with systemic antimicrobial therapy and 1.00 (.84–1.21; P = .96; I 2 = 0%) without 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 ventilator-associated pneumonia, developing as a consequence of lung bacterial colonization, alters clinically Received 22 January 2014; accepted 4 August 2014; electronically published 24 September 2014. Correspondence: Karim Asehnoune, MD, PhD, CHU de Nantes, Service d’Anesthésie Réanimation, 1 Pl Alexis Ricordeau, 44093 Nantes Cedex 1, France (karim. ). Clinical Infectious Diseases® 2015;60(1):64–75 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: . DOI: 10.1093/cid/ciu740 64 • CID 2015:60 (1 January) • Roquilly et al important outcomes, including duration of mechanical ventilation, length of stay in the intensive care unit (ICU), and mortality rates [1–3]. HAP is associated with use of antibiotics that may increase the risk of multiple-drug-resistant bacteria in ICUs, and the increase in medical costs is estimated to be to $20 000 per episode of HAP [4]. Given HAP-associated morbidity, the prevention of HAP has been the focus of numerous studies in critically ill patients and remains a controversial issue. Bacterial colonization of the oropharynx and subsequent microaspirations are initial events that lead to HAP [5–7]. The prevention of such events was therefore proposed as a method for reducing the rate of HAP and presumably for reducing associated morbidity and mortality. Three main approaches have been evaluated: (1) diminishing the microaspiration of digestive flora; (2) reducing the volume of oropharyngeal secretions aspirated into the lungs; and (3) inhibiting overgrowth or alterations in the microbiome in the oropharynx or larynx. Several meta-analyses of approaches to reducing the incidence of HAP conclude to a reduction in the risk of infection of such strategies. However, international recommendations for the prevention of HAP provide different conclusions [8–11] and do not state which intervention is mandatory or superior to the others. The combination of several strategies for preventing HAP failed to improve mortality rates [12], and nonadherence to international guidelines for HAP prevention is common [13]. We have hypothesized that all the preventive strategies do not equally alter the risk of death. Because many interventions are often poorly applied in clinical practice, it is important to determine the most effective interventions that should be implemented in critically ill patients. We thus performed a systematic review to determine which method is the most effective for decreasing mortality rates. The rates of HAP, duration of mechanical ventilation, and ICU length of stay were also evaluated as secondary criteria. MATERIALS AND METHODS Data Source and Searches We followed PRISMA (Preferred Reported Items for Systemic Reviews and Meta-Analyses) guidelines were followed during the design and implementation of this meta-analysis (Supplementary Table 1). We attempted to identify all relevant studies published in English regardless of publication status ( published or in press). We considered abstracts presented at scientific meetings <3 years earlier (Society Of Critical Care Medicine, European Society of Intensive Care Medicine, Societé Française d’Anesthesie Reanimation, Societé de Reanimation de Langue Française). PubMed (MEDLINE/Index Medicus) and the Cochrane Controlled Trials Register were searched for studies published from January 1969 through 10 June 2014. The Medical Subject Heading terms used for the search were pneumonia and intensive care units with the limit “adult 19+ years.” The “related articles” hyperlinks in MEDLINE were explored for additional references. The reference lists of all selected trials and previous published meta-analysis were checked for additional references. We contacted authors to identify unpublished data. Study Selection The authors selected all randomized trials that evaluated any of the following strategies in adult patients (aged ≥18 years) hospitalized in ICUs: acidified enteral feeding, selective digestive decontamination (SDD), early enteral feeding, postpyloric enteral feeding, decreased gastric retention, probiotic/symbiotic therapies, ulcer prophylaxis, aerosolized antibiotics, closed suctioning systems, early tracheotomy, humidification, phytotherapy (ginger extract), physiother (...truncated)