Ethics, consent, and permissions
We conducted a controlled randomized single-blinded clinical trial (clinicaltrials.gov: NCT01912105) in the general intensive care unit (ICU) of a tertiary-care university hospital (San Gerardo Hospital, Monza, Italy). The study was approved by the local Institutional Review Board (San Gerardo Hospital Ethical Committee) and was carried out in compliance with the Helsinki Declaration. Request of written informed consent was delayed until patient recovery and family members were informed, as per local regulation.
Patients
From April 2013 to June 2014, forty patients were randomized and successfully completed the study (see Fig. 1). Inclusion criteria were as follows: age >18 years old, intubation within 24 h, expected intubation longer than 48 h, and FiO2 <80 % at the moment of patients screening. Exclusion criteria were as follows: current or past participation in another intervention trial conflicting with the present study, expected survival less than 24 h or high probability of unfavorable outcome (e.g., return of spontaneous circulation after unwitnessed cardiac arrest, no-flow >10 min or age >65), acute severe asthma, extracorporeal membrane oxygenation treatment, presence of double lumen ETT, known difficult airway management in case of ETT displacement (such as upper airway edema, or cervical spine trauma), and contraindication posed by staff physicians. Patients enrolled in the study who were extubated and required reintubation were not enrolled in the study a second time.
Study protocol
Upon enrollment, patients were randomized to receive standard care (control group) with the CSS in use in our ICU (KimVent closed suction system, Kimberly-Clark Corp., Neenah, WI USA,) or the use of a novel cleaning CSS (Airway Medix closed suctioning system, Biovo Technologies, Tel Aviv, Israel, treatment group). A computer-based random sequence was used to obtain a 1:1 randomization ratio in blocks of 10 patients. The cleaning CSS used in the treatment group is a suction catheter with aspiration holes on the side and a balloon on its tip, which normally remains deflated and can be used to perform a standard suction maneuver. When the cleaning option is activated, the same device can also be used to clean the ETT: the catheter is inserted within the ETT similarly to a standard suction maneuver, and then the activation of the suction channel occurs together with the inflation of the cleaning balloon and the activation of water jets. When the catheter is gently retracted, the inflated balloon and the water jets gather secretions from the ETT wall, which are removed by the aspirating system.
A standard CSS was used in the control group, while in the treatment group tracheal suction was performed with the study CSS with the cleaning option disabled. In the treatment group, three additional cleaning maneuvers were performed every day (once every shift). Tracheal suction maneuvers were performed by critical care nurses when needed, based on the standard protocol in use in our ICU with the aim of a secretion detector [9], both in the treatment and in the control groups. Further details about airways management can be found in the supplemental digital content (Additional file 1).
Data collection
Patient’s history and demographics were recorded, together with several clinical parameters, investigating the presence of Acute Respiratory Distress Syndrome diagnosis [10] and assessing the Simplified Acute Physiology Score II [SAPS2] [11].
We collected daily clinical data regarding ventilator parameters and signs of infection, to calculate a modified clinical pulmonary infection score (mCPIS) [12]. Nurses recorded the total number of tracheal suction maneuvers performed, along with major adverse events related to the use of the new cleaning device. These were defined as follows: desaturation (drop in SpO2 >5 %) persisting for more than 5 min after suction and requiring a change in ventilator parameters; modification of blood pressure (systolic >200 mmHg or diastolic <80 mmHg if not already present) requiring new drug therapy; persistent reduction of ETCO2 (drop >5 mmHg); persistence of tachycardia or occurrence of other arrhythmia following the cleaning maneuver; ETT displacement requiring reintubation. When planned in advance, we collected surveillance tracheal aspirate samples in the 24 h prior to extubation. At extubation, we recorded ICU length of stay, ventilator free days in the first 28 days, and patient outcome. We also assessed the incidence of VAP and ventilator-associated events (VAE). Further details about data collection are provided in the Additional file 1.
Sample processing
After extubation, an investigator blind to the randomization group performed a MicroCT scan of the collected ETTs (SkyScan 1176, Bruker, Belgium) for a length of 20 cm from the ETT tip. After image reconstruction, an automated software (CT Analyzer, Bruker, Belgium) analyzed the CT images based on densitometric criteria, to obtain the measurement of the total volume of secretions and the ETT lumen cross-sectional area reduction due to the presence of secretions. Image analyses were conducted using the MicroCT scan embedded software (CT Analyzer, Bruker, Belgium). To describe the local distribution of the secretions within the ETT, we calculated the average amount of secretions and cross-sectional area reduction every 0.5 mm. To analyze possible differences of the regional distribution of the secretions between the two groups, the same variables were also calculated dividing the ETT length in three equal parts: ventilator side, central, and tip side. After MicroCT scan, ETT microbial colonization was assessed (see Additional file 1 for details).
Statistical methods
We based our sample size estimation on previous explorative laboratory analyses (unpublished data) investigating the volume of secretions present within ETTs after extubation by CT scan. We hypothesized an average secretions volume of 2.1 ± 2.1 ml in the control group, and 0.2 ml in the treatment group. Therefore, a sample size of 20 patients per arm (total 40 enrolled patients) would provide 80 % power to detect a difference considering a p value level of 0.05 as significant.
Normality of variables’ distribution was assessed by Shapiro–Wilk’s test; normally and non-normally distributed data are presented as mean ± SD and median [inter-quartile range], respectively. Differences between the two groups were tested by Student’s t-test for normally distributed variables, and by Mann–Whitney test for non-normally distributed variables. Categorical variables’ differences were analyzed by Fisher’s exact test in case of dichotomous variables, otherwise by Chi-Square test. To evaluate differences of secretion distribution within the ETT, a Repeated Measures ANOVA model was performed, considering the randomization group as between-subject factor, and the regional distribution (three ETT parts) as within-subject factor; Tukey’s correction for post hoc tests was used. Statistical analyses were performed using SPSS software version 18.0 (Chicago, IL) and SigmaPlot 11 (Systat software Inc., Germany). A p value <0.05 was considered statistically significant.