Pneumonia
Conditions
Keywords
Ventilator-associated pneumonia
Brief summary
Recent studies have found that poor oral hygiene may foster the colonization of the oropharynx by potential respiratory pathogens in mechanically-ventilated (MV), intensive care unit (ICU) patients. Thus, improvements in oral hygiene in MV-ICU patients may prevent ventilator-associated pneumonia (VAP). The specific aims of this investigation are: 1) to organize the necessary infrastructure to develop and perform a pilot clinical trial to evaluate alternative oral hygiene procedures to prevent VAP; 2) to use this organization to perform a pilot clinical trial to determine if the use of oral topical chlorhexidine gluconate (CHX) will prevent dental plaque, oropharyngeal colonization by respiratory pathogens, and VAP in MV-ICU patients.
Detailed description
Recent studies have found that poor oral hygiene may foster the colonization of the oropharynx by potential respiratory pathogens in mechanically-ventilated (MV), intensive care unit (ICU) patients. Thus, improvements in oral hygiene in MV-ICU patients may prevent ventilator-associated pneumonia (VAP). The Specific Aims of this investigation are: 1) to organize the necessary infrastructure to develop and perform a pilot clinical trial to evaluate alternative oral hygiene procedures to prevent VAP; 2) to use this organization to perform a pilot clinical trial to determine if the use of oral topical chlorhexidine gluconate (CHX) will prevent dental plaque, oropharyngeal colonization by respiratory pathogens, and VAP in MV-ICU patients. This pilot longitudinal, double blind intervention study will consider the appropriate frequency of delivery of CHX to improve oral hygiene in MV-ICU patients. Preliminary data from these pilot studies will also allow accurate sample size calculations to be made for a large-scale multi-center clinical trial; and 3) to perform molecular epidemiological studies to identify and genetically type bacteria cultured from lower airway secretions of MV-ICU patients with or without VAP and compare them to isolates of the same species from their dental plaque. This pilot study will enable this multidisciplinary team of investigators to organize the infrastructure, patient recruitment and methodologic protocols, and data management and analysis procedures necessary to perform a multi-center, controlled clinical trial to assess the efficacy and generalizability of this intervention to improve oral hygiene in MV-ICU and prevent VAP.
Interventions
DRUGchlorhexidine gluconate oral rinse (0.12%)
chlorhexidine gluconate oral rinse
DRUGplacebo
Sponsors
National Institute of Dental and Craniofacial Research (NIDCR)
State University of New York at Buffalo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients included in this study will be those admitted to the trauma intensive care unit (TICU) of Erie County Medical Center (ECMC) hospital. All patients admitted to the TICU who are intubated and mechanically ventilated within 24-48 hours of admission will be eligible for study admission, with the exception of those demonstrating the following
Exclusion criteria
a) a witnessed aspiration (to eliminate patients with chemical pneumonitis); b) a confirmed diagnosis of post-obstructive pneumonia (e.g. advanced lung cancer); c) a known hypersensitivity to CHX; d) patients for whom consent can not be obtained; e) a diagnosed thrombocytopenia (platelet count less than 40 and/or a INR above 2) or other coagulopathy; f) a do not intubate order; g) children under the age of 18 years; h) Pregnant women; i) Legal incarceration; j) If transferred from another ICU; k) Those with oral mucositis; l) Those with immunosuppression (either-HIV or drug induced \[e.g. organ transplant patients or those on long term steroid therapy\]); m) Patients re-admitted to the TICU * Comatose and intubated patients will be included since they represent patients at greatest risk for respiratory infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Colonization of the Oral Cavity by Respiratory Pathogens (on Teeth/Denture/Buccal Mucosa) as Determined by Quantitative Cultures Expressed as Colony Forming Units (Cfu) Per ml (CFU/mL) of the Aerobic Cultivable Flora After 48 Hours | Every 48 hours until discharge | Samples were diluted and plated on sheep's blood agar (to isolate S. aureus), and MacConkey agar (for isolation of Gram-negative bacilli) and incubated for 72 hours at 37°C in 5% carbon dioxide. Plates were assessed for growth for the following target bacteria: S. aureus, P. aeruginosa, Acinetobacter species, and enteric organisms (Klebsiella pneumoniae, Serratia marcescens, Enterobacter species, Proteus mirabilis, Escherichia coli). Results of quantitative cultures were expressed as colony forming units (cfu) per ml of sample. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Pulmonary Infection Score (CPIS) at 48 Hours | 48 hours | The CPIS score was calculated as follows: 1) Fever: 0 (36.5 to 38.4°C), 1 (38.5 to 39), 2 (\<36.0 OR \>39.0); 2) Leukocytosis: 0 (4000 to 11,000 white blood cells per mm3 of blood), 1 (11,000 to 17,000), 2 (\>17,000); 3) New infiltrate: 0 = None, 1 = Patchy, 2 = Localized; 4) Secretions: 0 = None to minimal, 1 = moderate, 2 = large amount; and 5) PaO2/ FiO2: 0 = more than 330 and 2 = less than 330. Total scores for the subscales can range from 0-10, with lower scores indicating better outcome. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from 1 March, 2004 until 30 November, 2007. Subjects were recruited from patients admitted to the ICU of the Erie County Medical Center (ECMC) who were mechanically ventilated. This ICU provides trauma, burn care, and rehabilitation and is an affiliated teaching facility for the State University of New York at Buffalo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Vehicle control twice a day (oral rinse) | 59 |
| Chlorhexidine/Placebo Chlorhexidine oral rinse 1 oz once a day/placebo oral rinse once a day | 58 |
| Chlorhexidine chlorhexidine 1 oz oral rinse twice a day | 58 |
| Total | 175 |
Baseline characteristics
| Characteristic | Chlorhexidine/Placebo | Chlorhexidine | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants | 58 Participants | 59 Participants | 175 Participants |
| Age, Continuous | 44.8 years STANDARD_DEVIATION 19.9 | 47.6 years STANDARD_DEVIATION 19.1 | 50.0 years STANDARD_DEVIATION 22.5 | 48.0 years STANDARD_DEVIATION 20.8 |
| Region of Enrollment United States | 58 participants | 58 participants | 59 participants | 175 participants |
| Sex: Female, Male Female | 15 Participants | 14 Participants | 23 Participants | 52 Participants |
| Sex: Female, Male Male | 43 Participants | 44 Participants | 36 Participants | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 49 | 0 / 47 | 0 / 50 |
| serious Total, serious adverse events | 0 / 49 | 0 / 47 | 0 / 50 |
Outcome results
Primary
Colonization of the Oral Cavity by Respiratory Pathogens (on Teeth/Denture/Buccal Mucosa) as Determined by Quantitative Cultures Expressed as Colony Forming Units (Cfu) Per ml (CFU/mL) of the Aerobic Cultivable Flora After 48 Hours
Samples were diluted and plated on sheep's blood agar (to isolate S. aureus), and MacConkey agar (for isolation of Gram-negative bacilli) and incubated for 72 hours at 37°C in 5% carbon dioxide. Plates were assessed for growth for the following target bacteria: S. aureus, P. aeruginosa, Acinetobacter species, and enteric organisms (Klebsiella pneumoniae, Serratia marcescens, Enterobacter species, Proteus mirabilis, Escherichia coli). Results of quantitative cultures were expressed as colony forming units (cfu) per ml of sample.
Time frame: Every 48 hours until discharge
Population: All tests were carried out using intent-to-treat analysis, with two-sided tests with a significance level of 0.05. Baseline comparisons between groups were made by analysis of variance (ANOVA) and/or the chi-squared test, as appropriate.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Colonization of the Oral Cavity by Respiratory Pathogens (on Teeth/Denture/Buccal Mucosa) as Determined by Quantitative Cultures Expressed as Colony Forming Units (Cfu) Per ml (CFU/mL) of the Aerobic Cultivable Flora After 48 Hours | 7 CFU/mL | Standard Deviation 2 |
| Chlorhexidine/Placebo | Colonization of the Oral Cavity by Respiratory Pathogens (on Teeth/Denture/Buccal Mucosa) as Determined by Quantitative Cultures Expressed as Colony Forming Units (Cfu) Per ml (CFU/mL) of the Aerobic Cultivable Flora After 48 Hours | 7.1 CFU/mL | Standard Deviation 1.9 |
| Chlorhexidine | Colonization of the Oral Cavity by Respiratory Pathogens (on Teeth/Denture/Buccal Mucosa) as Determined by Quantitative Cultures Expressed as Colony Forming Units (Cfu) Per ml (CFU/mL) of the Aerobic Cultivable Flora After 48 Hours | 5.1 CFU/mL | Standard Deviation 2 |
Comparison: A mixed effect model was used to compare overall treatment effects between groups for repeated measures data. The group comparison for each time point was performed using ANOVA.p-value: 0.675ANOVA
Secondary
Clinical Pulmonary Infection Score (CPIS) at 48 Hours
The CPIS score was calculated as follows: 1) Fever: 0 (36.5 to 38.4°C), 1 (38.5 to 39), 2 (\<36.0 OR \>39.0); 2) Leukocytosis: 0 (4000 to 11,000 white blood cells per mm3 of blood), 1 (11,000 to 17,000), 2 (\>17,000); 3) New infiltrate: 0 = None, 1 = Patchy, 2 = Localized; 4) Secretions: 0 = None to minimal, 1 = moderate, 2 = large amount; and 5) PaO2/ FiO2: 0 = more than 330 and 2 = less than 330. Total scores for the subscales can range from 0-10, with lower scores indicating better outcome.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clinical Pulmonary Infection Score (CPIS) at 48 Hours | 2.5 units on a scale | Standard Deviation 1 |
| Chlorhexidine/Placebo | Clinical Pulmonary Infection Score (CPIS) at 48 Hours | 2.5 units on a scale | Standard Deviation 0.9 |
| Chlorhexidine | Clinical Pulmonary Infection Score (CPIS) at 48 Hours | 2.4 units on a scale | Standard Deviation 1 |