This prospective randomized controlled crossover study was performed during a 1-year period, in a 10-bed ICU at the university hospital of Lille (France), in accordance with the Helsinki Declaration.
Inclusion and exclusion criteria
Inclusion criteria were: age >18 years and mechanical ventilation through a tracheal tube for a predicted duration of at least 48 h. Exclusion criteria were: mechanical ventilation through a tracheostomy, enrollment in another study that might interfere with the current study results, pregnancy, and contraindication for enteral nutrition.
Randomization
Patients were randomly assigned to receive continuous control of P
cuff with the electronic device (Mallinckrodt electronic cuff pressure controller®, VBM Medizintechnik GmbH, Sulz am Neckar, Germany) for 24 h, followed by discontinuous control (every 8 h) with a manual manometer (Hi-Lo Hand Pressure Gauge®, Mallinckrodt, Medtronic TM) for 24 h (Fig. 1), or the reverse sequence (Fig. 2). The target of P
cuff was 25 cmH2O during the two periods. Randomization was performed using a computer‐generated random assignment list in balanced blocs of six. Treatment assignments were contained in sealed opaque envelopes sequentially numbered.
Study objectives and outcome measurement
The primary objective was to determine the efficiency of the electronic device in reducing percentage of time spent with underinflation or overinflation of tracheal cuff, compared with routine care using a manometer. The secondary objectives included the impact of the electronic device on percentage of patients with underinflation or overinflation of tracheal cuff, percentage of time spent with underinflation of tracheal cuff, percentage of time spent with overinflation of tracheal cuff, percentage of time spent with normal (20–30 cmH2O) tracheal cuff, P
cuff, and coefficient of variation of P
cuff, compared with routine care, and its impact on microaspiration of gastric and oropharyngeal secretions.
P
cuff and airway pressure were continuously recorded at a digitizing frequency of 100 Hz for 48 h (Physiotrace®; Estaris, Lille, France) [24], including 24 h of continuous control of P
cuff using the mechanical device and 24 h of manual control of P
cuff using the manometer (Fig. 3). Pepsin and alpha amylase were quantitatively measured in all tracheal aspirates during the two study periods [25, 26]. In order to avoid interference between the two periods regarding pepsin and alpha amylase levels, tracheal aspirate performed during the first 2 h of each study period was not analyzed. The engineer who analyzed the data (JDJ) and the physicians who measured pepsin and alpha amylase (FZ, PM, and MB) were blinded to study group assignment.
Study population
All patients were intubated with a high-volume low-pressure PVC standard-cuffed tracheal tube. Tracheal tube size was 8 and 7.5 in men and women, respectively. During the manometer period, nurses adjusted P
cuff every 8 h. Tracheal suctioning was performed, using open suction system, 6 times a day, or more frequently if clinically indicated. Semi-recumbent position was used during mechanical ventilation. During routine care period, P
cuff was adjusted, using the manometer, before turning and oral care.
Definitions
The primary outcome was the percentage of time spent with underinflation or with overinflation of tracheal cuff. Secondary outcomes included mean P
cuff, coefficient of variation of P
cuff, percentage of patients with underinflation of tracheal cuff, percentage of patients with overinflation of tracheal cuff, percentage of time spent with normal (20–30 cmH2O) cuff pressure, percentage of time spent with underinflation of tracheal cuff, percentage of time spent with overinflation of tracheal cuff, mean pepsin and alpha amylase level, percentage of tracheal aspirates positive for pepsin, and percentage of tracheal aspirates positive for alpha amylase.
Underinflation of tracheal cuff was defined as P
cuff <20 cmH2O for >5 min over the 24-h period of recording. Overinflation of tracheal cuff was defined as P
cuff >30 cmH2O for >5 min over the 24-h period of recording [14]. The coefficient of variation of P
cuff was calculated as standard deviation/mean P
cuff × 100.
Microaspiration of gastric contents was defined by the presence of pepsin at significant level (>200 ng/mL) in tracheal aspirate. Microaspiration of oropharyngeal secretions was defined by the presence of alpha amylase at significant level (>1685 UI/L) in tracheal aspirate [26].
Statistical analyses
Sample size calculation
Based on previous results [14, 15], the mean percentage of time spent with underinflation or overinflation of tracheal cuff was 30 % [standard deviation (SD) = 20 %] in patients intubated with a PVC‐cuffed tracheal tube receiving routine care of P
cuff using a manual manometer. The expected mean percentage of time with underinflation or overinflation of tracheal cuff using the mechanical device was 10 % (expected difference of 20 %). In a parallel-group design, n = 22 patients per group will be required to detect this difference with a two-sided test, a power of 90 %, an alpha risk of 5 %, and a SD of 20 %. In a crossover design, the sample size determination is based on SD within subject difference, which can be derived from SD of measure and coefficient correlation (r) between the two measures on the same subject [27]. The sample size can therefore be derived from the number of patients to be included in parallel-group design, as follows: n * (1 − r). Thus, assuming a conservative value of 0.2 for r, the number of patients to include is 18.
Result analysis
All analyses were performed in an intention-to-treat manner. Distribution of quantitative variables was tested using Shapiro–Wilk test. Normally and non-normally distributed variables were expressed as mean ± SD and median (25th, 75th interquartile), respectively. The statistical significance was set at p < 0.05.
The primary outcome was compared using a mixed linear model, adjusting for the period effect. Interaction between study period and assigned treatment, i.e., continuous control of P
cuff or routine care, was tested. Qualitative and quantitative patient characteristics and secondary outcomes were compared between the two 24-h periods using McNemar and Wilcoxon tests, respectively.