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Original Investigation |

Reappraisal of Routine Oral Care With Chlorhexidine Gluconate for Patients Receiving Mechanical Ventilation:  Systematic Review and Meta-Analysis

Michael Klompas, MD1,2; Kathleen Speck, MPH3; Michael D. Howell, MD4; Linda R. Greene, RN5; Sean M. Berenholtz, MD3,6,7
[+] Author Affiliations
1Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts
2Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
3Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
4Department of Medicine, University of Chicago, Chicago, Illinois
5Highland Hospital, University of Rochester Medical Center Affiliate, Rochester, New York
6Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
7Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
JAMA Intern Med. 2014;174(5):751-761. doi:10.1001/jamainternmed.2014.359.
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Importance  Regular oral care with chlorhexidine gluconate is standard of care for patients receiving mechanical ventilation in most hospitals. This policy is predicated on meta-analyses suggesting decreased risk of ventilator-associated pneumonia, but these meta-analyses may be misleading because of lack of distinction between cardiac surgery and non–cardiac surgery studies, conflation of open-label vs double-blind investigations, and insufficient emphasis on patient-centered outcomes such as duration of mechanical ventilation, length of stay, and mortality.

Objective  To evaluate the impact of routine oral care with chlorhexidine on patient-centered outcomes in patients receiving mechanical ventilation.

Data Sources  PubMed, Embase, CINAHL, and Web of Science from inception until July 2013 without limits on date or language.

Study Selection  Randomized clinical trials comparing chlorhexidine vs placebo in adults receiving mechanical ventilation. Of 171 unique citations, 16 studies including 3630 patients met inclusion criteria.

Data Extraction and Synthesis  Eligible trials were independently identified, evaluated for risk of bias, and extracted by 2 investigators. Differences were resolved by consensus. We stratified studies into cardiac surgery vs non–cardiac surgery and open-label vs double-blind investigations. Eligible studies were pooled using random-effects meta-analysis.

Main Outcomes and Measures  Ventilator-associated pneumonia, mortality, duration of mechanical ventilation, intensive care unit and hospital length of stay, antibiotic prescribing.

Results  There were fewer lower respiratory tract infections in cardiac surgery patients randomized to chlorhexidine (relative risk [RR], 0.56 [95% CI, 0.41-0.77]) but no significant difference in ventilator-associated pneumonia risk in double-blind studies of non–cardiac surgery patients (RR, 0.88 [95% CI, 0.66-1.16]). There was no significant mortality difference between chlorhexidine and placebo in cardiac surgery studies (RR, 0.88 [95% CI, 0.25-2.14]) and nonsignificantly increased mortality in non–cardiac surgery studies (RR, 1.13 [95% CI, 0.99-1.29]). There were no significant differences in mean duration of mechanical ventilation or intensive care length of stay. Data on hospital length of stay and antibiotic prescribing were limited.

Conclusions and Relevance  Routine oral care with chlorhexidine prevents nosocomial pneumonia in cardiac surgery patients but may not decrease ventilator-associated pneumonia risk in non–cardiac surgery patients. Chlorhexidine use does not affect patient-centered outcomes in either population. Policies encouraging routine oral care with chlorhexidine for non–cardiac surgery patients merit reevaluation.

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Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Study Flowchart
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Figure 2.
Impact of Chlorhexidine Gluconate Use vs Comparators on Nosocomial Pneumonia in Cardiac Surgery Patients and Ventilator-Associated Pneumonia in Non–Cardiac Surgery Patients

Size of the data marker corresponds to the relative weight assigned in the pooled analysis using the Mantel-Haenszel random-effects model. For open-label cardiac surgery studies, heterogeneity was not applicable; test for overall effect, z = 1.24 (P = .22). For double-blind cardiac surgery studies, heterogeneity, τ2 = 0.00; χ2 = 0.60, df = 1 (P = .44); I2 = 0%; test for overall effect, z = 3.31 (P < .001). For all cardiac surgery studies, heterogeneity, τ2 = 0.00; χ2 = 0.68, df = 2 (P = .71); I2 = 0%; test for overall effect, z = 3.52 (P < .001); test for subgroup differences, χ2 = 0.07, df = 1 (P = .78); I2 = 0%. For open-label non–cardiac surgery studies, heterogeneity, τ2 = 0.17; χ2 = 8.27, df = 5 (P = .14); I2 = 40%; test for overall effect, z = 1.80 (P = .07). For double-blind non–cardiac surgery studies, heterogeneity, τ2 = 0.06; χ2 = 10.29, df = 6 (P = .11); I2 = 42%; test for overall effect, z = 0.91 (P = .36). For all non–cardiac surgery studies, heterogeneity, τ2 = 0.10; χ2 = 21.61, df = 12 (P = .04); I2 = 44%; test for overall effect, z = 1.82 (P = .07); test for subgroup differences, χ2 = 1.39, df = 1 (P = .24); I2 = 28%. For all studies, heterogeneity, τ2 = 0.09; χ2 = 26.51, df = 15 (P = .03); I2 = 43%; test for overall effect, z = 2.66 (P = .008); test for subgroup differences, χ2 = 4.56, df = 2 (P = .10); I2 = 56%.

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Figure 3.
Impact of Chlorhexidine Gluconate Use vs Comparators on Mortality

Size of the data marker corresponds to the relative weight assigned in the pooled analysis using the Mantel-Haenszel random-effects model. For open-label cardiac surgery studies, heterogeneity was not applicable; test for overall effect, z = 1.09 (P = .27). For double-blind cardiac surgery studies, heterogeneity, τ2 = 1.26; χ2 = 3.88, df = 1 (P = .05); I2 = 74%; test for overall effect, z = 0.63 (P = .53). For all cardiac surgery studies, heterogeneity, τ2 = 0.81; χ2 = 5.71, df = 2 (P = .06); I2 = 65%; test for overall effect, z = 0.19 (P = .85); test for subgroup differences, χ2 = 1.35, df = 1 (P = .24); I2 = 26%. For open-label non–cardiac surgery studies, heterogeneity, τ2 = 0.02; χ2 = 3.13, df = 2 (P = .21); I2 = 36%; test for overall effect, z = .40 (P = .69). For double-blind non–cardiac surgery studies, heterogeneity, τ2 = 0.00; χ2 = 1.44, df = 5 (P = .92); I2 = 0%; test for overall effect, z = 1.52 (P = .13). For all non–cardiac surgery studies, heterogeneity, τ2 = 0.00; χ2 = 4.36, df = 8 (P = .82); I2 = 0%; test for overall effect, z = 1.88 (P = .06); test for subgroup differences, χ2 = 0.22, df = 1 (P = .64); I2 = 0%. For all studies, heterogeneity, τ2 = 0.00; χ2 = 10.23, df = 11 (P = .51); I2 = 0%; test for overall effect, z = 1.84 (P = .07); test for subgroup differences, χ2 = 1.65, df = 3 (P = .65); I2 = 0%.

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Figure 4.
Impact of Chlorhexidine Gluconate Use vs Comparators on Mean Duration of Mechanical Ventilation

Size of the data marker corresponds to the relative weight assigned in the pooled analysis using inverse variance random-effects model. Because no open-label cardiac surgery studies measured this outcome, heterogeneity and test for overall effect were not applicable to this subgroup. For double-blind cardiac surgery studies, heterogeneity was not applicable; test for overall effect, z = 1.14 (P = .25). For all cardiac surgery studies, heterogeneity was not applicable; test for overall effect, z = 1.14 (P = .25); test for subgroup differences, heterogeneity was not applicable. For open-label non–cardiac surgery studies, heterogeneity was not applicable; test for overall effect, z = 1.17 (P = .24). For double-blind non–cardiac surgery studies, heterogeneity, τ2 = 2.28; χ2 = 6.63, df = 3 (P = .08); I2 = 55%; test for overall effect, z = 0.13 (P = .90). For all non–cardiac surgery studies, heterogeneity, τ2 = 2.49; χ2 = 8.15, df = 4 (P = .09); I2 = 51%; test for overall effect, z = 0.14 (P = .89); test for subgroup differences, χ2 = 1.37, df = 1 (P = .24); I2 = 27%. For all studies, heterogeneity, τ2 = 0.71; χ2 = 8.26, df = 5 (P = .14); I2 = 40%; test for overall effect, z = 0.02 (P = .98); test for subgroup differences, χ2 = 1.38, df = 2 (P = .50); I2 = 0%.

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Figure 5.
Impact of Chlorhexidine Gluconate Use vs Comparators on Intensive Care Length of Stay

Size of the data marker corresponds to the relative weight assigned in the pooled analysis using inverse variance random-effects model. Because no open-label cardiac surgery studies measured this outcome, heterogeneity and test for overall effect were not applicable to this subgroup. For double-blind cardiac surgery studies, heterogeneity was not applicable; test for overall effect, z = 1.28 (P = .20). For all cardiac surgery studies, heterogeneity was not applicable; test for overall effect, z = 1.28 (P = .20); test for subgroup differences, heterogeneity was not applicable. For open-label non–cardiac surgery studies, heterogeneity was not applicable; test for overall effect, z = 1.32 (P = .19). For double-blind non–cardiac surgery studies, heterogeneity, τ2 = 0.00; χ2 = 1.55, df = 3 (P = .67); I2 = 0%; test for overall effect, z = 0.34 (P = .74). For all non–cardiac surgery studies, heterogeneity, τ2 = 0.00; χ2 = 3.40, df = 4 (P = .49); I2 = 0%; test for overall effect, z = 0.11 (P = .91); test for subgroup differences, χ2 = 1.85, df = 1 (P = .17); I2 = 46%. For all studies, heterogeneity, τ2 = 0.00; χ2 = 3.46, df = 5 (P = .63); I2 = 0%; test for overall effect, z = 1.26 (P = .21); test for subgroup differences, χ2 = 1.91, df = 2 (P = .39); I2 = 0%.

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