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American Journal of Infection Control 47 (2019) 755−760

Contents lists available at ScienceDirect

American Journal of Infection Control


journal homepage: www.ajicjournal.org

Major Article

Chest physiotherapy for the prevention of ventilator-associated


pneumonia: A meta-analysis
Meng-Yang Wang BS a,*, Lei Pan MD b, Xiao-Juan Hu MD a
a
Joint Programme of Nanchang University of London, Nanchang University, Nanchang, Jiangxi, China
b
Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou, Shangdong, China

Key Words: Background: Ventilator-associated pneumonia (VAP) remains a frequent and severe complication in
Chest physiotherapy mechanically ventilated patients. We undertook a meta-analysis to evaluate the efficacy of chest physiother-
Prevention apy (CPT) for the prevention of VAP.
Ventilator-associated pneumonia Methods: A systematic literature search of PubMed and Embase databases were searched up until November
Meta-analysis
25, 2018 for published studies of mechanically ventilated patients comparing CPT with controls and report-
ing on the occurrence of VAP. Two authors independently selected studies and abstracted data on study qual-
ity and outcomes. We pooled data using random-effects models.
Results: A total of 6 randomized (n = 704) controlled trials were identified. CPT did not significantly reduce the
incidence of VAP (risk ratio = 1.02; 95% confidence interval, 0.82-1.26; P = .87), but reduced hospital mortality
(risk ratio = 0.68; 95% confidence interval, 0.48-0.95; P = .02). No significant differences were observed regard-
ing intensive care unit mortality, length of intensive care unit stay, and duration of mechanical ventilation.
Conclusions: CPT may not significantly reduce the incidence of VAP and alter other important clinical out-
comes in adult patients receiving mechanical ventilation. However, the results should be interpreted cau-
tiously owing to the heterogeneity and the limited trials. Further large-scale, well-designed randomized
controlled trials are needed.
© 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All
rights reserved.

Ventilator-associated pneumonia (VAP), defined as pneumonia most frequently performed interventions in the intensive care areas and
in patients receiving mechanical ventilation (MV) that arises >48- has been recognized as an important aspect to achieve successful wean-
72 hours after endotracheal intubation,1 is the most common hospital- ing from the ventilator.12 A variety of manual treatments—mainly
acquired infection in the intensive care unit (ICU) and affects 8%-28% including gravity-assisted drainage, chest wall percussion, chest wall
of patients receiving MV.2 Moreover, VAP has been associated with vibrations, and manual lung hyperinflation (bagging)—were developed
comparatively higher morbidity and mortality rates and higher health and were commonly used intensive care procedures.13,14 Various combi-
care costs.3-5 Given the clinical consequences attributable to VAP, pre- nations of CPT aimed at enhancing secretion clearance may assist in the
vention strategies are urgently needed to tackle the growing burden of prevention of VAP.15 Recently, some studies have evaluated the use of
VAP.6 To date, many interventions aimed at preventing VAP have been CPT in critically ill patients. However, these studies have a modest sam-
assessed, for example; oral antiseptics,7 probiotics,8 subglottic secre- ple size and convey inconclusive results. We therefore undertook a
tion drainage,9 oropharyngeal chlorhexidine,10 and others. However, meta-analysis of published studies to assess the effects of CPT on the
the role of chest physiotherapy (CPT) in preventing VAP has received incidence of VAP and other important clinical outcomes in mechanically
limited attention and remains unclear. ventilated patients.
CPT was implemented at the beginning of the 20th century, and
deep breathing exercise was 1 of the first methods.11 CPT is one of the METHODS

Data sources and searches


* Address correspondence to Meng-Yang Wang, BS, Joint Programme of Nanchang
University and Queen Mary University of London, School of Basic Medical Sciences,
Nanchang University, 461 Bayi Rd, Nanchang 330006, Jiangxi, China.
Data reported in our review are in accordance with the Preferred
E-mail address: [email protected] (M.-Y. Wang). Reporting Items for Systematic Reviews and Meta-Analyses state-
Conflicts of interest: None to report. ment.16 Relevant trials were identified by searching PubMed and

https://doi.org/10.1016/j.ajic.2018.12.015
0196-6553/© 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
756 M.-Y. Wang et al. / American Journal of Infection Control 47 (2019) 755−760

Embase databases—up until November 25, 2018. The structured Statistical analysis
search strategies used the following format of search terms: (chest
physiotherapy OR CPT OR manual hyperinflation OR chest vibrations OR Differences were expressed as relative risks (RRs) with 95% confi-
respiratory physiotherapy) AND pneumonia. The search was limited to dence intervals (CIs) for dichotomous outcomes, and weighted mean
human subjects. No language restriction was imposed. We also man- differences (WMDs) with 95% CIs for continuous outcomes. Heteroge-
ually checked the reference lists of randomized controlled trials neity across studies was tested by using the I2 statistic, which was a
(RCTs) to include other potentially eligible trials. This process was quantitative measure of inconsistency across studies. Studies with
performed iteratively until no additional articles could be identified. an I2 statistic of 25%-50% were considered to have low heterogeneity,
The following inclusive selection criteria were applied: (1) those with an I2 statistic of 50%-75% were considered to have moder-
study design: RCTs reported in a full article; (2) study population: ate heterogeneity, and those with an I2 statistic of >75% were consid-
adult critically ill patients receiving MV; (3) intervention: CPT with ered to have a high degree of heterogeneity.18 If I2 >50%, potential
or without other preventive measures; (4) comparison interven- sources of heterogeneity were identified by sensitivity analyses con-
tion: other preventive measures; and (5) outcome measure: the ducted by omitting 1 study in each turn and investigating the influ-
incidence of VAP. ence of a single study on the overall pooled estimate. Publication bias
was not assessed because of the limited number (<10) of studies
Data extraction and outcome measures included in each analysis. A P value of <.05 was considered statisti-
cally significant. All statistical analyses were performed using STATA
Two authors independently extracted the following data from version 11.0 (Stata Corporation, College Station, TX).
each trial: first author, publication year, number of patients (inter-
vention and control), type of ICU and study population, severity of RESULTS
illness at ICU admission (intervention and control), study design,
intervention group, control group, definition of VAP, the incidence Eligible studies and baseline characteristics
of VAP, and other important clinical outcomes data. Extracted data
were entered into a standardized Excel file (Microsoft, Redmond, The initial search yielded 410 articles of which 400 were excluded
WA) and were checked by a second author (X.J.H.). Any disagree- for duplicate studies and various reasons based on the titles and
ments were resolved by discussion and consensus. The primary abstracts (Fig 1). Finally, 6 RCTs were included in the final analysis.19-24
outcome was the incidence of VAP, while the secondary outcomes The main characteristics of studies included in the meta-analysis
included ICU mortality, hospital mortality, length of ICU stay, and are presented in Table 1, and the outcome data of each included trial
duration of MV. are described in Table 2. These studies were published between 1998
and 2017. The size ranged from 46-173 (total 704) patients. Among
Quality assessment the 6 studies included here, all reported VAP events and length of ICU
stay, 3 reported ICU mortality events,19-21 and 5 trials reported dura-
The methodological quality of each study was assessed using the tion of MV19,21-24 and hospital mortality.19-23 The quality of the
Cochrane Handbook for Systematic Reviews of Interventions.17 Two included studies are shown in Table 3.
authors subjectively reviewed all studies and assigned a value of The selected trials examined various populations in ICUs, including
‘high’, ‘low’, or ‘unclear’ to the following: (1) sequence generation; (2) trauma patients,19 medical-surgical,20,21 and mixed (medical, surgical
allocation concealment; (3) blinding; (4) incomplete data addressed; and trauma, and neuroscience).22-24 All of these patients were aged
(5) selective data reporting; and (6) free of other bias. >16 years and received MV for >24 hours, with no current pneumonia.

Fig 1. Search strategy and flow chart of screened, excluded, and eventually analyzed articles. RCT, randomized controlled trials.
M.-Y. Wang et al. / American Journal of Infection Control 47 (2019) 755−760 757

Table 1
Characteristics of included studies

Number of
First author/y/ patients Severity of illness
reference Country (CPT/control) Setting and patients (CPT vs control) Method of CPT Definition of VAP

Ntoumenopoulos Australia 46 (22/24) Trauma patients (>18 y) APACHE II: 12.3 § 3.8 vs Manual hyperinflation New pulmonary infiltrate
G, 199819 requiring MV >24 h 14.1 § 7.4 and postural drainage on the chest radiograph,
(2 sessions per d) together with at least 3
of the following: temper-
ature >38°C; white cell
count >11,000; purulent
sputum with bacteria on
Gram stain; positive
culture
Templeton M, United 172 (87/85) General ICU patients (>18 APACHE II: 49 (8-96) vs Manual hyperinflation, New chest radiograph infil-
200720 Kingdom y) requiring MV >48 h 41 (4-97) positioning, rib trates, positive microbi-
springing, and gen- ology culture from
eral mobilization tracheal aspirates, a rise
(twice per d) in white cell count and
temperature (>38°C)
Patman S, 200921 Australia 144 (72/72) Acquired brain injury APACHE II: 20.3 § 5.7 vs Manual hyperinflation, Positive nonbronchoscopic
patients (>16 y) requir- 20.5 § 5.6 positioning, and air- alveolar lavage
ing MV >24 h way suctioning
(6 sessions per d)
Pattanshetty RB, India 101 (50/51) ICU patients (>18 y) NA Manual hyperinflation, Clinical pulmonary infec-
201022 requiring MV >48 h chest vibrations, tion score
positioning, and air-
way suctioning (2
sessions per d)
Pattanshetty RB, India 173 (87/86) ICU patients (>18 y) NA Positioning, manual Clinical pulmonary infec-
201123 requiring MV >48 h hyperinflation, vibra- tion score
tions and suctioning
(2 sessions per d)
Zeng H, 201724 China 68 (37/31) Integrated ICU patients APACHE II: 18.49 § 6.43 vs Positioning, manual New pulmonary infiltrate
(>18 y) with oral 18.19 § 4.82 hyperinflation, vibra- or increased range of
indwelling endotracheal tions, and early func- original lesions on the
tube requiring MV >48 h tional exercise chest radiograph,
(2 sessions per d) together with at least 2
of the following: temper-
ature >38°C; white cell
count >10 £ 109/L or
<4.0 £ 109/L; purulent
sputum with bacteria on
Gram stain; positive
culture
APACHE, acute physiology and chronic health evaluation; CPT, chest physiotherapy; ICU, intensive care unit; MICU, medical intensive care unit; MV, mechanical ventilation; NA, not
available; SICU, surgical intensive care unit; VAP, ventilator-associated pneumonia.

Of the 6 studies included in the meta-analysis, multimodality CPT (eg, Primary outcome: VAP
positioning, chest wall vibrations, manual hyperinflation, suctioning,
manual lung inflation, vibration expectoration, and early functional All 6 trials reported VAP in study patients. The aggregated results of
exercise) was administered to patients in the experimental group in the these studies suggest that CPT was not associated with a significant
3 studies.22-24 For the other trials, usual care or same CPT was adminis- reduction in the incidence of VAP (RR = 1.02; 95% CI, 0.82-1.26; P = .87)
tered to patients in the control group. The definition of VAP varied (Fig 2). The test for heterogeneity was significant (P for heterogene-
across studies, no standard definition was used in reported studies. ity = .08; I2 = 49%). Subsequently, we still performed sensitivity analyses

Table 2
Primary and secondary outcomes of the included trials, CPT versus control

Primary outcome Secondary outcomes

First author/y/reference Incidence of VAP (n/N) Hospital mortality (n/N) ICU mortality (n/N) Length of ICU stay (d) Duration of MV (d)

Ntoumenopoulos G, 199819 4/22 vs 8/24 0/22 vs 2/24 0/22 vs 0/24 7.4 § 5.7 vs 6.8 § 4.6 6.1 § 5.4 vs 5.2 § 3.5
Templeton M, 200720 35/87 vs 25/85 46/87 vs 46/85 40/87 vs 42/85 13 (3-82) vs 12 (4-76) NA
Patman S, 200921 14/72 vs 19/72 13/72 vs 21/72 7/72 vs 14/72 9.3 § 5.1 vs 10.7 § 7.7 7.2 § 5.0 vs 8.6 § 6.5
Pattanshetty RB, 201022 48/50 vs 47/51 12/50 vs 25/51 NA 13.9 § 9.77 vs 11.3 § 5.73 8.7 § 5.6 vs 8.5 § 5.21
Pattanshetty RB, 201123 55/87 vs 48/86 24/87 vs 39/86 NA 11.4 § 9.75 vs 9.3 § 5.92 7.6 § 3.97 vs 6.8 § 4.46
Zeng H, 201724 2/37 vs 8/31 NA NA 5.6 § 3.0 vs 8.6 § 7.4 3.2 § 1.7 vs 5.6 § 4.9
NOTE. Data are mean § SD, or median (range).
CPT, chest physiotherapy; ICU, intensive care unit; MV, mechanical ventilation; n, number of events; N, total number of patients; NA, not available; VAP, ventilator-associated
pneumonia.
758 M.-Y. Wang et al. / American Journal of Infection Control 47 (2019) 755−760

Table 3
Assessing risk of bias

Sequence Allocation Incomplete data Selective data


First author/y/reference generation concealment Blinding addressed reporting Free of other bias

Ntoumenopoulos G, 199819 Yes Yes No No No Unclear


Templeton M, 200720 No No Yes Yes Yes Unclear
Patman S, 200921 No No Yes No No Unclear
Pattanshetty RB, 201022 Yes Yes No Yes Yes Unclear
Pattanshetty RB, 201123 Yes Yes No Yes Yes Unclear
Zeng H, 201724 Yes Yes No Yes Yes Unclear
NOTE. Yes = low risk of bias; No = high risk of bias.

to explore potential source of heterogeneity. Exclusion of the trial The principal findings of our study seem to be contrary with the
conducted by Zeng et al24 significantly reduced the heterogeneity but previous study on the topic. In detail, the present meta-analysis
did not change the results (RR = 1.06; 95% CI, 0.93-1.21; P = .38; P for het- included 6 RCTs involving 704 patients and indicated that CPT might
erogeneity = .31; I2 = 16%). Further exclusion of any single study did not be associated with reduction in the incidence of VAP and other
not materially alter the overall combined RR, with a range from important clinical endpoints including ICU mortality, length of ICU
0.89 (95% CI, 0.60-1.32; P = .56) to 1.06 (95% CI, 0.85-1.32; P = .63). stay, and duration of MV in critically ill patients receiving MV regard-
less of sensitivity analyses. The previous study suggested that CPT
contributes to the early recovery of the patient in the ICU, reducing
Secondary outcomes
length of stay on MV and hospitalization, as well as the incidence of
respiratory infection and mortality.25 However, the main limitation
Table 4 outlines secondary outcomes. CPT significantly decreased the
of this study was that the authors designed their study as a cohort so
hospital mortality (5 trials19-23; RR = 0.68; 98% CI, 0.48-0.95; P = .02; P for
they did not control the recruitment to avoid bias, which was pointed
heterogeneity = .09; I2 = 50%). CPT was not associated with decreases in
out in the previous study.25
ICU mortality (3 trials19-21; RR = 0.77; 98% CI, 0.43-1.37; P = .38; P for het-
In addition, relatively low heterogeneity (I2 = 49%) for the incidence
erogeneity = .17; I2 = 48%), length of ICU stay (5 RCTs19,21-24; WMD = 0.12
of VAP was observed among these studies included in the current meta-
days; 98% CI, −1.93-2.16; P = .91; P for heterogeneity = .02; I2 = 66%), and
analysis. Our sensitivity analyses suggested that 1 trial conducted by
duration of MV (5 RCTs19,21-24; WMD = −0.41 days; 95% CI, −1.76-0.94;
Zeng et al24 contributed to the heterogeneity, which was not surprising
P = .55; P for heterogeneity = .03; I2 = 62%). Subsequently, exclusion of
given the differences in characteristics of CPT protocols and participants.
any single study did not materially alter the overall combined effects
Although the whole results of CPT were very disappointing; however,
regarding length of ICU stay and duration of MV.
CPT has a trend of reducing the incidence of VAP. Further well-designed
RCTs are needed to investigate the points described earlier.
DISCUSSION Next, our results suggested that CPT might not be associated with a
markedly reduced ICU mortality, length of ICU stay, and duration of
The current findings of our study suggested that CPT could fail MV except hospital mortality. Subsequently, substantial heterogeneity
to reduce the incidence of VAP in adult critically ill patients with MV. was observed in analyzing length of ICU stay and duration of MV. How-
In addition, CPT might not be associated with a markedly reduced ever, exclusion of any single study did not materially alter the overall
ICU mortality, length of ICU stay, and duration of MV except hospital combined effects regarding length of ICU stay and duration of MV. In
mortality. detail, simple CPT including manual hyperinflation and suctioning

Fig 2. Meta-analysis of 5 trials evaluating the incidence of ventilator-associated pneumonia. Chest physiotherapy did not significantly reduce the incidence of ventilator-associated
pneumonia. CI, confidence interval; ID, identification; RR, relative risks.
M.-Y. Wang et al. / American Journal of Infection Control 47 (2019) 755−760 759

Table 4
Meta-analyses of secondary outcomes

Outcome n (N) Estimate Effect (95% CI) P value I2 (%) P heterogeneity


19-23
Hospital mortality 636 (5) RR 0.68 (0.48-0.95) .02 50 .09
ICU mortality19-21 362 (3) RR 0.77 (0.43-1.37) .38 48 .17
Length of ICU stay19,21-24 532 (5) WMD 0.12 (−1.93-2.16) .91 66 .02
Duration of MV19,21-24 532 (5) WMD −0.41 (−1.76-0.94) .55 62 .03
CI, confidence interval; ICU, intensive care unit; MV, mechanical ventilation; n, total number of patients; N, number of trials; RR, risk ratio; WMD, weighted mean difference.

were administered in the 3 studies,19-21 and multimodality CPT was included trials. The differences in performed CPT, methodological
administered in the other 3 studies,22-24 which may be the potential quality (eg, diagnosis of VAP that considerably differs among studies),
reason causing the heterogeneity in the present study. However, these and the lack of information on factors that significantly influence VAP
results are not conclusive because further adequately powered studies incidence (eg, concomitant antibiotic therapy, VAP prevention meas-
are needed. In fact, these included studies are not adequately powered ures, nutrition policy) varied greatly. Different studies defined sur-
to examine these secondary outcome measures because they were not vival in widely variant terms. Moreover, the high prevalence of acute
the primary outcomes and were the only clinically significant end- cerebral pathology in the included studies renders evaluation of out-
points consistently reported in many of the studies analyzed in the come parameters such as duration of MV or ICU length of stay irrele-
present meta-analysis. Future research should focus on these clinical vant. These factors may result in the heterogeneity and have
endpoints rather than just the incidence of VAP. potential impact on our results. Furthermore, because of the limited
Our study provides additional interesting clues that may be useful number of RCTs regarding the secondary outcomes, caution should
for future research on the topic. Remarkably, the studies conducted by be taken when interpreting the results. Finally, some missing and
Pattanshetty et al22,23 and Zeng et al24 were different trials than what unpublished data may lead to bias in effect size.
was included in our study, that is multimodality CPT including posi-
tioning, chest wall vibrations, manual hyperinflation, suctioning, man-
CONCLUSIONS
ual lung inflation, vibration expectoration, and early functional
exercise were administered to patients in the experimental group
Despite its various limitations and poor results, our study is still clini-
while manual hyperinflation and suctioning were administered to
cally valuable. CPT may not significantly reduce the incidence of VAP
patients in the control group. However, regarding the other trials, usual
and alter other important clinical outcomes in mechanically ventilated
care or same CPT was administered to patients in the control group.
patients. In addition, the individualized principle of CPT based on the
Zeng et al24 suggested that twice-daily multimodality CPT was associ-
patient’s characteristics may be crucial but is needed to be observed in
ated with a significant decrease in VAP, length of ICU stay, and duration
future research. Furthermore, heterogeneity among study designs still
of MV in mechanically ventilated patients. Therefore, whether multi-
exists; thus, further well-designed and adequately powered RCTs are
modality CPT is better than simple CPT in ICU patients requires further
urgently needed to confirm our preliminary findings. We believe that
research to confirm. We believe that the individualized principle of
research on the field is worthwhile and should be continued.
CPT based on the patient’s characteristics may be crucial and is needed
to be observed in future research. Multimodality CPT may be encour-
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