Infections, Hospital, Mechanical Ventilation Complication, Ventilator-Associated Pneumonia
Conditions
Keywords
Nosocomial (Hospital-Acquired) Infections, Ventilator-Associated Pneumonia, Mechanical ventilation, Endotracheal intubation
Brief summary
Ventilator-associated pneumonia (VAP) is a serious complication in mechanically ventilated critically ill patients. The intervention tested in this project (swabbing the mouth with chlorhexidine before the endotracheal tube is inserted) could reduce the risk of ventilator-associated pneumonia.
Detailed description
Ventilator-associated pneumonia (VAP) is an acute care complication with high morbidity and mortality, which is costly in length of stay and resources used. Application of chlorhexidine (CHX) to the mouths of critically ill adults after intubation reduces risk of VAP. During intubation, organisms may be dragged by the tube from the contaminated mouth to the sterile lung, and the endotracheal tube (ET) provides a pathway for direct entry of bacteria from the mouth to the lower respiratory tract. However, procedures to decontaminate the mouth before intubation are not routine and little is known about the effects of pre-intubation CHX in critically ill patients. Thus, this project focuses on evaluating the benefit of adding a pre-intubation CHX dose to the known benefit of post-intubation CHX to reduce the risk of VAP. In order to examine the effect of pre-intubation CHX on early ET colonization, we will perform microbial cultures of ETs of subjects who are extubated in the first 24 hours of study participation. We will also explore selected biomarkers (procalcitonin, cytokines) as indicators of development of VAP in a subset of subjects. The project will add to knowledge about the relationships among oral health, ET intubation and VAP, and addresses an important clinical outcome. Pre-intubation oral decontamination could reduce risk of VAP and its associated morbidity and mortality.
Interventions
PROCEDUREPre-intubation CHX
Oral application of 5 ml CHX gluconate 0.12% solution pre-intubation, and 5 ml CHX gluconate 0.12% solution twice a day following intubation.
PROCEDUREControl
No pre-intubation intervention, 5 ml CHX gluconate 0.12% solution twice a day following intubation
Sponsors
National Institute of Nursing Research (NINR)
University of South Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Need for intubation
Exclusion criteria
* Pneumonia at the time of intubation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Development of VAP (Clinical Pulmonary Infection Score) | Baseline up to 5 days | Change between post-intervention CPIS and baseline CPIS. Serial prospective evaluation of VAP risk. 6 elements of CPIS (tracheal secretions, temperature, white blood count, oxygenation, chest radiograph, and tracheal aspirate culture) summed to yield total score of 0-12 daily; higher score reflects greater likelihood of VAP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endotracheal Tube Colonization | 24 hours | semiquantitative swab culture for potentially pathogenic organisms of distal end of the endotracheal tube (ETT) interior lumen at extubation. Results were collapsed into two categories: colonization (moderate or many organisms) or no colonization. |
| Serum Cytokines | 5 days | — |
| Serum Procalcitonin | 5 days | — |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled from two large urban teaching medical centers (VCU Health System, Tampa General Hospital). Subjects were recruited in multiple clinical areas just prior to intubation, including critical care units, emergency departments, pre-operative areas, procedural areas, and medical-surgical units during rapid response or code calls.
Participants by arm
| Arm | Count |
|---|---|
| 1: Preintubation Oral Chlorhexidine Intervention: Oral application of 5 ml CHX gluconate 0.12% solution pre-intubation, and 5 ml CHX gluconate 0.12% solution twice a day following intubation. | 157 |
| 2: Control Control: No pre-intubation intervention, 5 ml CHX gluconate 0.12% solution twice a day following intubation | 157 |
| Total | 314 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | extubated | 110 | 110 |
Baseline characteristics
| Characteristic | 1: Preintubation Oral Chlorhexidine | Total | 2: Control |
|---|---|---|---|
| Age, Continuous | 58.08 years STANDARD_DEVIATION 15.85 | 58.12 years STANDARD_DEVIATION 16.01 | 58.20 years STANDARD_DEVIATION 16.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 9 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 152 Participants | 305 Participants | 153 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 45 Participants | 101 Participants | 56 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 106 Participants | 202 Participants | 96 Participants |
| Region of Enrollment United States | 157 participants | 314 participants | 157 participants |
| Sex: Female, Male Female | 66 Participants | 164 Participants | 98 Participants |
| Sex: Female, Male Male | 91 Participants | 150 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 157 | 0 / 157 |
| serious Total, serious adverse events | 0 / 157 | 0 / 157 |
Outcome results
Primary
Development of VAP (Clinical Pulmonary Infection Score)
Change between post-intervention CPIS and baseline CPIS. Serial prospective evaluation of VAP risk. 6 elements of CPIS (tracheal secretions, temperature, white blood count, oxygenation, chest radiograph, and tracheal aspirate culture) summed to yield total score of 0-12 daily; higher score reflects greater likelihood of VAP.
Time frame: Baseline up to 5 days
Population: Subjects who had complete CPIS data on admission to the study (Day 0) and subsequent complete CPIS data from day 2, 3, 4 or 5 (47 CHX \& 47 control, 438 observations) were included in the analysis in accordance with intent to treat analysis principles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1: Preintubation Intervention | Development of VAP (Clinical Pulmonary Infection Score) | 4.13 units on a scale | Standard Error 0.28 |
| 2: COntrol | Development of VAP (Clinical Pulmonary Infection Score) | 4.45 units on a scale | Standard Error 0.31 |
Comparison: We compared groups in a single analytical model using a mixed effects linear model with CPIS as the response variable. For this model, group (CHX, control), day, group by day interaction, APACHE III score and hospital (VCU, USF) were modeled as fixed effects and subject was modeled as a random effect.p-value: 0.1763mixed effects linear model
Comparison: A logistic regression analysis was performed using the binary response variable of colonization or no colonization and dependent variables for group, length of intubation, and group-by-length-of-intubation interaction. The probability of a type 1 error ( a ) was set to 0.05.p-value: 0.8656Regression, Logistic
Secondary
Endotracheal Tube Colonization
semiquantitative swab culture for potentially pathogenic organisms of distal end of the endotracheal tube (ETT) interior lumen at extubation. Results were collapsed into two categories: colonization (moderate or many organisms) or no colonization.
Time frame: 24 hours
Population: The subjects analyzed were a subset of subjects enrolled in the study from whom endotracheal tunes were obtainable for microbial culture post-intubation. Subset analysis was planned a priori.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: Preintubation Intervention | Endotracheal Tube Colonization | 18.6 percentage of ET tubes colonized |
| 2: COntrol | Endotracheal Tube Colonization | 17.5 percentage of ET tubes colonized |
Secondary
Serum Cytokines
Time frame: 5 days
Secondary
Serum Procalcitonin
Time frame: 5 days