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Influence of Airway Management on Ventilator-Associated Pneumonia
Evidence From Randomized Trials
Deborah Cook, MD;
Bernard De Jonghe, MD;
Laurent Brochard, MD;
Christian Brun-Buisson, MD
JAMA. 1998;279:781-787.
ABSTRACT
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Objective.— Ventilator-associated pneumonia (VAP) is a serious complication of critical illness, conferring increased morbidity and mortality. Many interventions have been studied to reduce the risk of VAP. We systematically reviewed the influence of airway management on VAP in critically ill patients.
Data Sources.— Studies were identified through searching MEDLINE and EMBASE from 1980 through July 1997 and by searching SCISEARCH, the Cochrane Library, bibliographies of primary and review articles, personal files, and contact with authors of the randomized trials.
Study Selection.— We selected randomized trials evaluating ventilator circuit and secretion management strategies on the rate of VAP.
Data Extraction.— Two investigators independently abstracted key data on design features, the population, intervention, and outcome of the studies.
Data Synthesis.— The frequency of ventilator circuit changes and the type of endotracheal suction system do not appear to influence VAP rates (3 trials, none with significant difference; range of relative risks [RRs], 0.84-0.91). However, lower VAP rates may be associated with avoidance of heated humidifiers and use of heat and moisture exchangers (5 trials, only 1 showing a significant difference; range of RRs, 0.34-0.86), use of oral vs nasal intubation (1 trial; RR, 0.52; 95% confidence interval, 0.24-1.13), subglottic secretion drainage vs standard endotracheal tubes (2 trials, 1 showing a significant difference; range of RRs, 0.46-0.57), and kinetic vs conventional beds (5 trials, only 1 showing a significant difference; range of RRs, 0.35-0.78).
Conclusions.— Some ventilator circuit and secretion management strategies may influence VAP rates in critically ill patients. Whether these strategies are adopted in practice depends on several factors such as the magnitude and precision of estimates of benefit and harm, as well as access, availability, and costs.
INTRODUCTION
IN CRITICALLY ILL patients, the development of nosocomial pneumonia may confer an increased morbidity and mortality.1 The largest intensive care unit (ICU) prevalence study conducted to date revealed that ventilator-associated pneumonia (VAP) accounted for almost half of ICU infections in Europe.2 In the last decade, there has been a profusion of informative studies on the epidemiology, risk factors, diagnosis, treatment, cost, and clinical sequelae of this serious condition. Several prophylactic interventions hold the promise of decreasing the burden of illness caused by nosocomial pneumonia.
These strategies can be classified as mechanical, focusing on the ventilator circuit (eg, frequency of tubing changes and gas humidification strategies), the endotracheal tube (eg, intubation orifice, suctioning, and secretion drainage), and patient placement (eg, body position and kinetic bed therapy); or interventions directed at the gastrointestinal tract (eg, enteral feeding strategies); or pharmacologic approaches (eg, selective digestive decontamination, endotracheal antibiotics, and stress ulcer prophylaxis); or the influences of the ICU environment.
Randomized trials have evaluated the influence of some of these interventions on surrogates of VAP. Craven et al3 allocated patients to receive ventilator tubing changes every 24 or 48 hours and found no difference in inspiratory-phase gas cultures or tubing colonization. In another study, a trend toward decreased tracheal colonization was observed in patients ventilated with heat and moisture exchangers vs heated humidifiers.4 Rouby and colleagues5 randomized patients to nasal or oral intubation and found that radiologic evidence of maxillary sinusitis was markedly higher in the nasal group. The relationship between body position and tracheobronchial aspiration has been highlighted by 3 randomized trials showing that scintigraphic evidence of aspiration occurs more often in patients placed in the semirecumbent than in the supine position.6-8 The foregoing studies represent prominent contributions to the experimental evidence regarding VAP prevention strategies, though a direct, confirmed causal relationship between these surrogate end points and VAP would strengthen the inferences we draw from them.
The goal of this systematic review is to evaluate the influence of ventilator circuit and secretion management strategies on nosocomial pneumonia as studied in randomized clinical trials.
METHODS
Data Sources
We searched computerized databases from 1980 to July 1997 using the following text words and key words for MEDLINE: critical care, intensive care units, pneumomia, respiratory tract infection, cross infection, respiration, artificial ventilators, mechanical ventilation, randomized controlled trials, and prospective studies; and the following terms for EMBASE: pneumonia, prevention, and control. Frequently cited articles were identified and SCISEARCH (Science Citation Index online) was used to locate any additional relevant randomized trials. We also used the Cochrane Library, searching the Clinical Trials Registry for randomized trials. We examined the Cochrane Database of Systematic Reviews as well as the Database of Abstracts of Reviews (DARE) for systematic reviews. We had no language restrictions. The titles (and the abstracts, when available) in the MEDLINE and EMBASE printouts and the reference lists of all primary articles and review articles were reviewed independently in duplicate. Any additional relevant articles were identified and retrieved. We also developed a comprehensive list of relevant trials and wrote to the first author of each to identify any other relevant unpublished trials in this field.
Study Selection
The following selection criteria were applied to the full articles by 2 of us independently (D.C. and B.A.J.): population: critically ill adults including trauma patients; interventions: ventilator circuit and secretion management strategies; outcomes: VAP; and design: published human clinical studies with random or alternate treatment allocation.
A priori, we excluded populations of seriously but not necessarily critically ill patients, neutropenic patients, those with human immunodeficiency virus infection, and children. We omitted studies with a before-after study design.9-10 We excluded pharmacologic approaches to VAP prevention, whether mediated through the endotracheal tube such as intratracheal antibiotics11-12 or the gastrointestinal tract such as selective digestive decontamination,13-17 stress ulcer prophylaxis,18 and enteral nutrition.19-28 We also excluded strategies that evaluated surrogate VAP end points.3-8
Data Extraction
In duplicate, we abstracted data from the trials to describe the population, the method of treatment allocation, the proportion of patients who were excluded after randomization, whether cointerventions were described, whether the outcome of VAP was made by investigators blinded to the intervention, and the definition of pneumonia used. Disagreements between reviewers on design characteristics and raw data abstraction were resolved by discussion and consensus.
Analysis
We measured agreement between reviewers on the selection of articles for inclusion in the review. We standardized presentation of the VAP rates using relative risk reduction and calculated 95% confidence intervals using a natural log transformation. When the relative risk reduction was significant at the P<.05 level, we calculated the number of patients we would need to treat to prevent 1 case of VAP.29 Since study designs and the definitions of pneumonia differed, we did not statistically pool results of these trials, or subgroups of them, in a meta-analysis. Other clinical outcomes reported in the individual trials were recorded qualitatively. Significant differences (P<.05) were noted. Readers are referred to the original publications for details.
Data Synthesis
Study Identification and Selection
These multiple search strategies yielded 3 trials on ventilator circuit changes,30-32 5 comparing heated humidifiers vs heat and moisture exchangers,33-37 1 trial of oral vs nasal endotracheal intubation,38 2 trials of subglottic secretion drainage,39-40 2 trials of closed vs open system suctioning,41-42 and 5 trials of kinetic bed therapy.43-47 Agreement was 100% for selection of these studies.
Study Characteristics
Study characteristics are reported in Table 1. All were randomized trials except 3 that used alternate treatment allocation according to year of birth,30 medical record number,32 or room assignment.42 The mechanical nature of these interventions precluded blinding of the patients and caregivers. Therefore, care delivered by bedside nurses, respiratory therapists, and intensivists could have differed among groups and influenced the development of VAP; accordingly, potential cointerventions are important to consider (Table 1). The chest radiograph was assessed blinded to group assignment in 9 studies.30-31,35, 37, 40-41,44, 46-47 Six studies included invasive bronchoscopic tests as criteria for the diagnosis of VAP.30, 32, 35, 38-40 Two studies adjudicated VAP events by investigators blinded to group assignment.31, 41 Most trials described whether there were any withdrawals after randomization.
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Table 1.—Ventilator Circuit and Secretion Management Trials: Design Characteristics*
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Outcomes
The results of these studies are presented in Table 2. Of 2677 patients in these 18 randomized trials, a total of 458 had a diagnosis of VAP. The relative risk reduction in VAP associated with these 6 interventions ranged from 0.34 (favoring heat and moisture exchangers over heated humidifiers) to 0.95 (suggesting no difference between closed vs open suction systems).
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Table 2.—Ventilation Circuit and Secretion Management Trials: Results
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Considering VAP risk, there is no apparent advantage to changing ventilator circuits frequently. This holds true whether circuits are changed every 2 days30 or every 7 days31 compared with no change at all and whether they are changed weekly as opposed to 3 times per week.32 Other measures of potential benefit and harm recorded in these trials appear similar using different circuit management strategies.
Antibacterial humidification strategies that minimize tubing condensate show clinically important trends in 4 studies33-36 and a significant difference in a fifth study37 suggesting that heat and moisture exchangers are at least comparable to heated humidifiers and may be associated with lower rates of VAP than heated humidifiers. Kirton et al37 found that 10 patients would need to be managed using heat and moisture exchangers instead of heated humidifiers to prevent 1 case of VAP. However, 2 of these 5 trials show significantly more endotracheal occlusions33 causing asphyxiation,34 and more tenacious secretions33 in the heat and moisture exchanger groups.
The site of endotracheal intubation may influence the risk of VAP, and sinusitis is a particular concern in nasally intubated patients. Holzapfel and colleagues38 found that the incidence of lung infection in patients who were orally intubated was approximately half that found in those who were nasally intubated, though this difference was not significant. Other physiologic and clinical outcomes were similar between the 2 groups.
Aspiration of contaminated oropharyngeal and upper respiratory tract secretions pooled above inflated endotracheal cuffs may be an important factor predisposing to VAP. Endotracheal tubes furnished with a separate lumen open to the subglottic area above the endotracheal cuff allow continuous aspiration of subglottic secretions and have been studied in 2 randomized trials, both suggesting a 50% decrease in VAP rates.39-40 In 1 of these trials, this difference was significant, suggesting that 7 patients would need to be managed using subglottic secretion drainage instead of a standard endotracheal tube to prevent 1 case of VAP.39 Additional outcomes appear comparable between these 2 groups.
To avoid hypoxia, hypotension, and contamination of suction catheters entering the endotracheal tube, investigators have examined closed suctioning systems. The 2 published trials suggest a similar VAP rate in patients managed with either a closed or open suction system.41-42 However, increased tracheal colonization in the closed system group was noted in 1 study.41
Sequelae of prolonged immobility such as impaired mucociliary clearance, decreased tracheal secretion removal, and suboptimal gas exchange prompted evaluation of rotational bed therapy. Four studies show a trend toward lower VAP rates in patients receiving kinetic bed treatment.43-44,46-47 In the remaining trial,48 the VAP rate was significantly reduced, implying that 4 patients would need to be nursed on a kinetic bed rather than a standard bed to prevent 1 episode of VAP. While physiologic and clinical outcomes appear otherwise comparable between these bed management strategies (Table 2), several patients were withdrawn from these studies because of discomfort46-47 or possible adverse physiologic effects43-45 (Table 1).
COMMENT
Practitioners are faced with multiple potential pneumonia prevention strategies that have been evaluated in randomized controlled trials over the last decade. We have critically appraised and summarized the interventions related to ventilator circuit and secretion management that may influence the risk of acquired lung infection in critically ill patients. Three of the 6 interventions among these 18 studies demonstrated significantly lower rates of VAP, including avoidance of heated humidifiers,37 use of subglottic secretion drainage,41 and kinetic bed therapy.45 Whether and how to encode trial results into practice requires consideration of patient risk, the availability and cost of the intervention, adaptation to local circumstances, and integration of the results of observational research. Interpreting data from systematic reviews in this light is central to evidence-based practice and highlights the distinction between evidence and recommendations.48 Given the modest number of trials evaluating each strategy, their modest sample sizes, variable cointerventions, and the different pneumonia definitions used, cautious interpretation of their results is warranted.
In terms of ventilator management, infrequent circuit changes are associated with a similar, or modestly lower, rate of VAP than frequent changes and no apprent serious adverse outcomes. Though the optimal exchange schedule is uncertain, a policy of no circuit changes or infrequent circuit changes is simple to implement, and the costs are likely lower than those generated by regular, frequent circuit changes. Avoidance of heated humidifiers by using heat and moisture exchangers may also be worthwhile. Heat and moisture exchangers are associated with either similar or lower VAP rates than heated humidifiers. The mechanism for their apparent benefit is unclear and could be related to minimal circuit condensate compared with heated humidifiers, could be related to the bacterial filtration properties of the filters themselves, or could be due to other mechanisms. Preliminary results of a randomized trial comparing heated humidification using a heated wire circuit aimed at minimizing tubing condensate vs an extended use hygroscopic condenser humidifier showed similar VAP rates.49 Nevertheless, despite the administrative ease of heat and moisture exchangers, which require no change in the ventilator tubing or circuit, observational studies have documented an increased resistive load associated with exchangers.50-52 A randomized crossover trial of spontaneous breathing using heat and moisture exchangers vs heated humidifiers in patients able to tolerate a weaning trial identified a larger dead space, higher PaCO2, and increased minute ventilation in the former group,53 which could hinder weaning from mechanical ventilation. Another 3-arm randomized trial of hot water humidification vs heat and moisture exchanger with either a hydrophobic or hygroscopic filter54 suggested that hygroscopic but not hydrophobic heat and moisture exchangers minimize endotracheal tube obstruction and offer a satisfactory alternative to the more cumbersome hot water humidifiers.
Secretion management represents another approach to VAP prevention. Oral intubation appears more beneficial than nasal intubation and may confer the added advantage of a decreased risk of sinusitis; costs are similar and there are few impediments to implementation. Subglottic secretion drainage seems to be a promising method of VAP prevention without serious adverse effects. Barriers to the use of these endotracheal tubes include their lack of availability at most institutions and the need to secure them wherever patients may be intubated (eg, the emergency department, operating suite, on the wards). Adoption of closed rather than open suction systems may provide some safety in terms of fewer arrhythmias and desaturation episodes at the expense of increased tracheal colonization; however, these studies are inconclusive. Kinetic bed therapy, while potentially effective at VAP prevention, may interfere with nursing care and cause patient discomfort that is difficult to measure in the critically ill population. While many decisions to acquire new ICU technology or exchange existing equipment for new equipment are made without the need for or benefit of a formal economic evaluation,55 initial capital equipment costs for kinetic beds and some of the other interventions included in this review need to be considered in cost-effectiveness studies comparing the clinical and fiscal consequences of competing preventive approaches.
The 1994 Centers for Disease Control and Prevention (CDC) guidelines56 on pneumonia prevention strongly recommend infrequent ventilator circuit changes for all hospitals, but consider the other interventions included in this review as unresolved, for which no recommendations are made.37 The 1995 American Thoracic Society (ATS) statement57 classifies the interventions in this review as probably effective and used widely in some clinical settings.38 Other strategies cataloged in these documents have been summarized elsewhere in systematic reviews13-18,58 and are beyond the scope of this article. Reasons for different recommendations found in the CDC and ATS position papers may be attributable to different approaches to searching, selecting, and interpreting the literature and synthesizing it with expert opinion. Although systematic reviews and evidence-based guidelines can help to assimilate and appraise research, they represent only aids to decision making, which warrant updating as new evidence emerges. Ideally, these aids are critically appraised and integrated with clinical expertise, which evolves as experience grows.
Subsequent randomized trials might usefully stratify patients according to risk profile.59 The diverse mechanical, gastrointestinal, and pharmacologic interventions that may influence VAP rates suggest that explicit protocols for cointerventions, or at least faithful reporting of ancillary management such as antimicrobial therapy, would be helpful.60-61 Transparent, reproducible VAP definitions, whether based on clinical criteria62 or invasive bronchoscopic techniques,63 would aid practitioners in interpreting results. Relevant end points include measures of both benefit and safety, mortality, and economic outcomes such as length of ICU stay and direct and indirect costs.
Strategies to prevent VAP continue to undergo evaluation; for example, several trials of subglottic secretion drainage are ongoing. Preliminary results of trials of composite interventions are also being conducted; Girou and colleagues64 randomized patients to subglottic secretion drainage and semirecumbency or to intubation with a standard endotracheal tube and the supine position. A recent multimodality trial65 evaluated selective aerodigestive tract decontamination, sucralfate administration, and kinetic therapy compared with no decontamination, ranitidine administration, and repositioning every 2 hours and found a trend toward a lower rate of pneumonia in the former group. Complementary lines of future investigation might include factorial designs examining the unique effect as well as the interaction of 2 or more interventions. If strategies to prevent VAP were evaluated through multicenter collaboration, more precise and generalizable estimates of their impact may become available.
AUTHOR INFORMATION
This work was partly funded by the Ontario Ministry of Health (Dr Cook).
We are grateful to Francois Feihl, MD, Orlando Kirton, MD, and Brian DeHaven, MD, for help interpreting their studies. We thank Jill Randall for her comments on early drafts, and we appreciate the help of Barbara Hill with manuscript preparation.
Reprints: Deborah Cook, MD, Department of Medicine, St Joseph's Hospital, 50 Charlton Ave E, Hamilton, Ontario, Canada L8N 4A6 (e-mail: debcook{at}fhs.csu.mcmaster.ca).
From the Department of Medicine, St Joseph's Hospital and McMaster University, Hamilton, Ontario (Dr Cook); Service de Reanimation Medicale, Hôpital de Poissy, Poissy, France (Dr De Jonghe); and Service de Reanimation Medicale, Hôpital Henri Mondor, Universite Paris-Val de Marne, Creteil, France (Drs Brochard and Brun-Buisson).
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