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Continuous Pneumatic Regulation of Tracheal Cuff Pressure to Decrease Ventilator-associated Pneumonia in Trauma Patients Who Were Mechanically Ventilated

The AGATE Multicenter Randomized Controlled Study

      Background

      Ventilator-associated pneumonia (VAP) is the most frequent health care-associated infection in severely ill patients, and aspiration of contaminated oropharyngeal content around the cuff of the tracheal tube is the main route of contamination.

      Research Question

      Is continuous regulation of tracheal cuff pressure using a pneumatic device superior to manual assessment three times daily using a portable manometer (routine care) in preventing VAP in patients with severe trauma?

      Study Design and Methods

      In this open-label, randomized controlled superiority trial conducted in 13 French ICUs, adults (age ≥ 18 years) with severe trauma (Injury Severity Score > 15) and requiring invasive mechanical ventilation for ≥ 48 h were enrolled. Patients were randomly assigned (1:1) via a secure Web-based random number generator in permuted blocks of variable sizes to one of two groups according to the method of tracheal cuff pressure control. The primary outcome was the proportion of patients developing VAP within 28 days following the tracheal intubation, as determined by two assessors masked to group assignment, in the modified intention-to-treat population. This study is closed to new participants.

      Results

      A total of 434 patients were recruited between July 31, 2015, and February 15, 2018, of whom 216 were assigned to the intervention group and 218 to the control group. Seventy-three patients (33.8%) developed at least one episode of VAP within 28 days following the tracheal intubation in the intervention group compared with 64 patients (29.4%) in the control group (adjusted subdistribution hazard ratio, 0.96; 95% CI, 0.76-1.20; P = .71). No serious adverse events related to the use of the pneumatic device were noted.

      Interpretation

      Continuous regulation of cuff pressure of the tracheal tube using a pneumatic device was not superior to routine care in preventing VAP in patients with severe trauma.

      Clinical Trial Registration

      ClinicalTrials.gov; No.: NCT02534974; URL: www.clinicaltrials.gov.

      Graphical abstract

      Key Words

      Abbreviations:

      aSHR (adjusted subdistribution hazard ratio), HR (hazard ratio), VAP (ventilator-associated pneumonia)
      FOR EDITORIAL COMMENT, SEE PAGE 393
      Severe trauma is the leading cause of death worldwide and the third highest cause of death in France following cardiovascular disease and cancer. Most deaths occur within the first 24 h following the trauma and are directly related to hemorrhagic shock or intractable neurologic injuries. About one-quarter of deaths occur later and are mainly due to health care-associated infections.
      • Osborn T.M.
      • Tracy J.K.
      • Dunne J.R.
      • Pasquale M.
      • Napolitano L.M.
      Epidemiology of sepsis in patients with traumatic injury.
      ,
      • Esnault P.
      • Nguyen C.
      • Bordes J.
      • et al.
      Early-onset ventilator-associated pneumonia in patients with severe traumatic brain injury: incidence, risk factors, and consequences in cerebral oxygenation and outcome.
      Neurologic disorders, need for mechanical ventilation, and the early posttraumatic immune suppression are major factors contributing to the high incidence of health care-associated infections, particularly ventilator-associated pneumonia (VAP).
      • Hershman M.J.
      • Cheadle W.G.
      • Wellhausen S.R.
      • Davidson P.F.
      • Polk H.C.
      Monocyte HLA-DR antigen expression characterizes clinical outcome in the trauma patient.
      • Dirnagl U.
      • Klehmet J.
      • Braun J.S.
      • et al.
      Stroke-induced immunodepression: experimental evidence and clinical relevance.
      • Cavalcanti M.
      • Ferrer M.
      • Ferrer R.
      • Morforte R.
      • Garnacho A.
      • Torres A.
      Risk and prognostic factors of ventilator-associated pneumonia in trauma patients.
      VAP occurs in 35% to 60% of patients with severe trauma
      • Reizine F.
      • Asehnoune K.
      • Roquilly A.
      • et al.
      Effects of antibiotic prophylaxis on ventilator-associated pneumonia in severe traumatic brain injury. A post hoc analysis of two trials.
      ,
      • Asehnoune K.
      • Seguin P.
      • Allary J.
      • et al.
      Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial.
      and contributes to increased morbidity and mortality.
      • Rello J.
      • Ramírez-Estrada S.
      • Romero A.
      • et al.
      Factors associated with ventilator-associated events: an international multicenter prospective cohort study.
      Moreover, VAPs are responsible for more than one-half of antibiotic prescriptions in the ICUs and therefore contribute significantly to the spread of bacterial resistance.
      American Thoracic Society, Infectious Diseases Society of America
      Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.
      Aspiration of bacterial-contaminated oropharyngeal or gastric contents plays a major role in the development of VAP.
      • Estes R.J.
      • Meduri G.U.
      The pathogenesis of ventilator-associated pneumonia: I. Mechanisms of bacterial transcolonization and airway inoculation.
      Maintaining the tracheal cuff pressure at an optimal level is therefore of critical importance. Cuff under-inflation increases the risk of bacterial aspiration and then VAP. Cuff over-inflation increases the risk of ischemia of the tracheal mucosa and, upon removal, tracheal edema and later tracheal stenosis.
      • Kastanos N.
      • Estopa Miro R.
      • Marin Perez A.
      • Xaubet Mir A.
      • Agustí-Vidal A.
      Laryngotracheal injury due to endotracheal intubation: incidence, evolution, and predisposing factors. A prospective long-term study.
      Regular control of tracheal cuff pressure is therefore recommended, but the optimal method has yet to be clearly established. Intermittent manual control using a portable manometer is the reference method, but it requires fine tuning and is frequently accompanied by episodes of under-inflation and/or over-inflation.
      • Nseir S.
      • Brisson H.
      • Marquette C.H.
      • et al.
      Variations in endotracheal cuff pressure in intubated critically ill patients: prevalence and risk factors.
      Indeed, the diameter of the trachea around the cuff frequently varies in different situations, such as patient mobilization, swallowing movements, respiratory efforts, and coughing. Use of automatic devices allows the cuff pressure to be continuously maintained in the target values,
      • Rouzé A.
      • Jonckheere J De
      • Zerimech F.
      • et al.
      Efficiency of an electronic device in controlling tracheal cuff pressure in critically ill patients: a randomized controlled crossover study.
      but few studies showing a decline in the incidence of complications are available.
      The impact of continuous control of cuff pressure in preventing VAP has only been evaluated in three small prospective studies. All were conducted in single centers,
      • Nseir S.
      • Zerimech F.
      • Fournier C.
      • et al.
      Continuous control of tracheal cuff pressure and microaspiration of gastric contents in critically ill patients.
      • Valencia M.
      • Ferrer M.
      • Farre R.
      • et al.
      Automatic control of tracheal tube cuff pressure in ventilated patients in semirecumbent position: a randomized trial.
      • Lorente L.
      • Lecuona M.
      • Jiménez A.
      • et al.
      Continuous endotracheal tube cuff pressure control system protects against ventilator-associated pneumonia.
      one was observational,
      • Lorente L.
      • Lecuona M.
      • Jiménez A.
      • et al.
      Continuous endotracheal tube cuff pressure control system protects against ventilator-associated pneumonia.
      and another one used VAP as secondary outcome only.
      • Nseir S.
      • Zerimech F.
      • Fournier C.
      • et al.
      Continuous control of tracheal cuff pressure and microaspiration of gastric contents in critically ill patients.
      Few surgical patients were included, and none were trauma patients, although they represent the most at-risk population for VAP among critically ill patients.
      • Rello J.
      • Allegri C.
      • Rodriguez A.
      • et al.
      Risk factors for ventilator-associated pneumonia by Pseudomonas aeruginosa in presence of recent antibiotic exposure.
      One study showed no benefit of using a continuous control device of tracheal cuff pressure on VAP, whereas the two others reported a lower VAP incidence with the use of such devices.
      • Nseir S.
      • Zerimech F.
      • Fournier C.
      • et al.
      Continuous control of tracheal cuff pressure and microaspiration of gastric contents in critically ill patients.
      • Valencia M.
      • Ferrer M.
      • Farre R.
      • et al.
      Automatic control of tracheal tube cuff pressure in ventilated patients in semirecumbent position: a randomized trial.
      • Lorente L.
      • Lecuona M.
      • Jiménez A.
      • et al.
      Continuous endotracheal tube cuff pressure control system protects against ventilator-associated pneumonia.
      A meta-analysis of the three trials suggested a benefit of continuous control of tracheal cuff pressure in reducing the risk of VAP (hazard ratio [HR], 0.47; 95% CI, 0.31-0.71) without any significant impact on other outcomes, such as antibiotic usage, duration of mechanical ventilation, or ICU length of stay.
      • Nseir S.
      • Lorente L.
      • Ferrer M.
      • et al.
      Continuous control of tracheal cuff pressure for VAP prevention: a collaborative meta-analysis of individual participant data.
      Therefore, the real impact of these automatic devices remains uncertain,
      • Colombo S.M.
      • Palomeque A.C.
      • Li Bassi G.
      The zero-VAP sophistry and controversies surrounding prevention of ventilator-associated pneumonia.
      ,
      • Papazian L.
      • Klompas M.
      • Luyt C.E.
      Ventilator-associated pneumonia in adults: a narrative review.
      and learned societies do not recommend their systematic implementation for the purpose of VAP prevention.
      • Leone M.
      • Bouadma L.
      • Bouhemad B.
      • et al.
      Brief summary of French guidelines for the prevention, diagnosis and treatment of hospital-acquired pneumonia in ICU.
      ,
      • Torres A.
      • Niederman M.S.
      • Chastre J.
      • et al.
      International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia. European Respiratory Society.
      Given these concerns, we designed a multicenter randomized trial to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device is superior to intermittent control of tracheal cuff pressure using a portable manometer in reducing the incidence of VAP in patients with severe trauma.

      Patients and Methods

       Study Design

      The AGATE trial was an investigator-initiated, multicenter, randomized, controlled, open-label superiority trial. Patients were recruited from 13 ICUs in 13 French university hospitals. The study protocol has been previously published.
      • Marjanovic N.
      • Frasca D.
      • Asehnoune K.
      • et al.
      Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol.

       Participants

      Adult patients (age ≥ 18 years) with severe trauma (Injury Severity Score > 15)
      • Copes W.S.
      • Champion H.R.
      • Sacco W.J.
      • Lawnick M.M.
      • Keast S.L.
      • Bain L.W.
      The Injury Severity Score revisited.
      and requiring invasive mechanical ventilation for ≥ 48 h were enrolled in this study. The expected time on mechanical ventilation was based on the physician’s experience and initial assessment of injuries. Patients were included as soon as possible following ICU admission and no later than 24 h following trauma and 15 h following tracheal intubation. We excluded patients likely to die within 48 h following admission, having their trachea intubated via the nasal route, being ventilated with a tracheotomy, or having any contraindication to the head-up position.

       Randomization and Blinding

      A statistician, who was neither involved in screening patients nor in assessing outcomes, provided a computer-generated numbered list. Randomization was conducted by the attending physician through a secure Web-based randomization system with stratification according to center and neurologic compromise (Glasgow Coma Scale score < 8 or ≥ 8) at the time of inclusion, to account for differences in patient treatment between centers and the heightened VAP risk in patients with altered consciousness.
      • Bronchard R.
      • Albaladejo P.
      • Brezac G.
      • et al.
      Early onset pneumonia: risk factors and consequences in head trauma patients.
      Patients were randomly assigned (1:1) in permuted blocks of variable size to one of the two treatment groups based on the method used to monitor the tracheal cuff pressure.
      Blinding of the participants and medical staff was not feasible due to the nature of the intervention. However, the microbiologists who tested the pulmonary and blood samples in each center, the outcome assessors (N. M. and O. M.) and the statistician (D. F.) were blinded to group assignment.

       Procedures

      According to the randomized group assignment, the cuff pressure of the tracheal tube was monitored either manually every 8 h (control group) using a portable manometer
      • Leone M.
      • Bouadma L.
      • Bouhemad B.
      • et al.
      Brief summary of French guidelines for the prevention, diagnosis and treatment of hospital-acquired pneumonia in ICU.
      or automatically and continuously (intervention group) through the use of a pneumatic device (Nosten, Leved), aiming at keeping tracheal tube cuff pressure between 25 and 30 cm H2O.
      • Jaillette E.
      • Zerimech F.
      • De Jonckheere J.
      • et al.
      Efficiency of a pneumatic device in controlling cuff pressure of polyurethane-cuffed tracheal tubes: a randomized controlled study.
      The Nosten device is a CE-labeled mechanical device consisting of a 200-mL sterile, single-use, cylindrical cuff connected to the tracheal tube cuff by a plastic tube (e-Fig 1). A weight mounted on an articulated arm exerts a constant pressure on this cuff, which is adjustable by moving another weight along the arm. Any pressure variation in the tracheal tube cuff due to a change in tracheal diameter is immediately compensated for by the disproportion between the volumes of both cuffs to immediately adjust the cuff volume of the tracheal tube, keeping the cuff pressure constant. ICU teams were trained by the manufacturer prior to beginning the study, and training reminders were issued regularly throughout the study to ensure that the pneumatic device was used appropriately, according to the manufacturer’s recommendations.
      We required all study centers to follow French recommendations,
      • Leone M.
      • Bouadma L.
      • Bouhemad B.
      • et al.
      Brief summary of French guidelines for the prevention, diagnosis and treatment of hospital-acquired pneumonia in ICU.
      similar to the Centers for Disease Control and Prevention recommendations regarding VAP prevention.
      Centers for Disease Control and Prevention
      Ventilator-associated pneumonia (VAP) events.
      These recommendations are described in detail elsewhere
      • Marjanovic N.
      • Frasca D.
      • Asehnoune K.
      • et al.
      Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol.
      ; specifically, patients added regular decontamination of the nasal and oropharyngeal cavities through suitable oral care, following each ICU protocol. Prophylactic antibiotic treatments were administered by attending physicians and followed the French recommendations of 2017.
      • Martin C.
      • Auboyer C.
      • Boisson M.
      • et al.
      Antibioprophylaxis in surgery and interventional medicine (adult patients). Update 2017.
      Most often, the duration was limited to the operating period but could be extended to 48 h for fractures operated on within the first 6 h following trauma. Curative antibiotic therapy should be limited to infections for which the bacterial origin was documented, or probable, and in cases in which other anti-infectious measures were insufficient, in accordance with the 2008 recommendations of the official French health authority on the proper use of antibiotics.
      French Health Authority
      Antibiotic therapy and prevention of bacterial resistance in healthcare organisations.
      None of the patients received polyurethane-cuffed, tapered-cuff shaped tracheal tubes or with subglottic secretion drainage. No modification was allowed during the study duration.
      The patients were monitored from randomization through to their discharge from the ICU without exceeding 60 days following inclusion. Any patient who left the ICU was considered having exited the study. Any readmission into the ICU (even within 60 days following the trauma) was not taken into account. Attempted detection of VAP signs were performed on a daily basis while the patient was being mechanically ventilated. A thoracic radiograph aimed at detecting VAP was required within a few hours whenever at least two of the following clinical signs of VAP were observed in the same clinical examination: fever ≥ 38.0°C or hypothermia ≤ 36.0°C, purulent endotracheal secretions, or either hyperleukocytosis (≥ 12,000/mL) or leukopenia (≤ 4,000/mL). Whenever the patient met the clinical and radiologic criteria on the same day, the modified clinical pulmonary infection score was calculated,
      • Schurink C.A.M.
      • Nieuwenhoven CA Van
      • Jacobs J.A.
      • et al.
      Clinical pulmonary infection score for ventilator-associated pneumonia: accuracy and inter-observer variability.
      and bacterial analysis of the respiratory tract was performed. The type of sampling (BAL, blind protected telescoping catheter, or tracheal aspirates) was left to the discretion of the attending physician. We routinely obtained sets of aerobic and anaerobic blood cultures in patients with fever (body temperature ≥ 38.5°C), hypothermia (≤ 36.5°C), or other symptoms such as chills (a sensation of cold, with convulsive shaking of the body) or sudden shock (systolic BP < 90 mm Hg or decrease of 40 mm Hg or more in systolic BP compared with baseline in patients with arterial hypertension), and when VAP was suspected.

       Outcomes

      The primary outcome was the proportion of patients who developed VAP at day 28 in the ICU. The diagnosis of VAP was based on the American Thoracic Society definition
      American Thoracic Society, Infectious Diseases Society of America
      Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.
      and centralized by two outcome assessors (N. M. and O. M.) blinded to group assignment because current definitions may result in misdiagnosis.
      • Fernando S.M.
      • Tran A.
      • Cheng W.
      • et al.
      Diagnosis of ventilator-associated pneumonia in critically ill adult patients—a systematic review and meta-analysis.
      In case of disagreements, conflicts were discussed between the two experts to reach a consensus.
      Additional prespecified outcomes were: (1) the proportion of patients who developed VAP in the ICU; (2) the proportion of patients who developed bacteremic VAP in the ICU; (3) the proportion of patients who developed early (≤ 7 days) or late (> 7 days) VAP in the ICU; (4) the time until the first diagnosis of VAP; (5) the proportion of patients who developed ventilator-associated events according to the Centers for Disease Control and Prevention definition
      Centers for Disease Control and Prevention
      Ventilator-associated pneumonia (VAP) events.
      ; (6) the number of ventilator-free days; (7) the number of antibiotic-free days; (8) the length of stay in the ICU; (9) the proportion of patients who died during their ICU stay; and (10) the proportion of patients who required corticosteroids or bronchodilators within 48 h of tracheal extubation. Definitions are available in e-Appendix 1.

       Statistical Analysis

      The sample size of 440 (n = 220 in each group) was computed on an estimated 20% VAP incidence in the control group and a 50% reduction in the intervention group, with a two-sided α risk of 5% and a power of 80%, and a maximum patient loss of 10%. The VAP incidence in the control group was estimated on unpublished analysis of the AtlanRea database, a French research network dedicated to trauma patients to which several participating study centers belong. The 50% reduction in VAP in the experimental group was based on the finding of previous studies.
      • Nseir S.
      • Zerimech F.
      • Fournier C.
      • et al.
      Continuous control of tracheal cuff pressure and microaspiration of gastric contents in critically ill patients.
      ,
      • Lorente L.
      • Lecuona M.
      • Jiménez A.
      • et al.
      Continuous endotracheal tube cuff pressure control system protects against ventilator-associated pneumonia.
      Data were analyzed on a modified intention-to-treat principle (all randomized patients except those who withdrew consent). No interim analysis was planned. Continuous variables are expressed as mean ± SD or median and interquartile range and were compared by using the Student t test or Mann-Whitney U test for normally and nonnormally distributed continuous variables, respectively. Categorical variables are given as number (percentage) and were compared by using the χ2 or Fisher exact tests. Treatment effects on time until VAP occurrence were assessed by using competing risks regression (Fine and Gray model), with mortality and tracheal extubation prior to VAP occurrence being considered as competing risks, and expressed as an adjusted subdistribution hazard ratio (aSHR) with 95% CIs. The proportionality of VAP occurrence hazard risk was tested by using Schoenfeld residuals. Treatment effects on other outcomes were assessed by using logistic regression models and expressed as adjusted OR with 95% CI. Mortality between study groups was compared by using a Cox regression model and expressed as adjusted hazard ratio with 95% CI. The proportionality of mortality hazard risk was tested by using Schoenfeld residuals. Treatment effects were adjusted for stratification factors (center and Glasgow Coma Scale score < 8 or ≥ 8) and unbalanced variables.
      All tests were two-tailed, with no adjustment for multiple testing. Analyses were performed by using SAS version 9.3 (SAS Institute, Inc.) and R statistical package version 3.6.2 or later (The R Foundation for Statistical Computing, https://www.R-project.org/).

       Ethical Approval

      The study protocol was approved by the ethics committee of Poitiers University hospital (France) and was performed according to the principles of the Declaration of Helsinki and the Clinical Trials Directive 2001/20/EC of the European Parliament.

       Study Registration

      The study is registered with ClinicalTrials.gov.
      National Institutes of Health Clinical Center. Impact of the addition of a device providing continuous pneumatic regulation of tube cuff pressure to an overall strategy aimed at preventing ventilator-associated pneumonia in the severe trauma patient. A multicentre, randomised, controlled study. (AGATE).

      Results

      Between July 31, 2015, and February 15, 2018, we screened 711 potentially eligible patients and randomly assigned 437 to one of the study groups (Fig 1). Two patients assigned to the experimental group and one patient assigned to the control group withdrew consent and were subsequently excluded from analyses. Therefore, 434 patients were included in the modified intention-to-treat analysis (216 in the experimental group and 218 in the control group). Baseline characteristics (e-Table 1, Table 1), number of patients under mechanical ventilation for ≥ 48 h (191 [88%] vs 182 [83%] in the experimental and control groups, respectively), and therapeutics received during the ICU stay (e-Table 2) were overall comparable between study groups. Antibiotic prophylaxis was more frequent in the control group than in the experimental group and was included in the multivariate model (e-Table 3).
      Table 1Baseline Characteristics of the Modified Intention-to-Treat Population
      CharacteristicIntervention Group (n = 216)Control Group (n = 218)
      Age, y45 ± 2044 ± 20
      Male sex171 (79%)166 (76%)
      BMI, kg/m225 ± 525 ± 4
      Medical history
       Diabetes mellitus6 (3%)7 (3%)
       Obesity (BMI > 30 kg/m2)22 (11%)21 (10%)
       Malnutrition (BMI < 20 kg/m2)4 (2%)7 (3%)
       Alcoholism31 (16%)34 (18%)
       Smoking42 (24%)46 (25%)
       Cirrhosis2 (1%)1 (0%)
       Gastro-esophageal reflux2 (1%)3 (1%)
      Glasgow Coma Scale score on the scene7 (4-13)7 (4-12)
      Injury Severity Score29 (21-34)27 (22-35)
      Trauma to tracheal intubation time, min62 (36-167)66 (35-147)
      Trauma to randomization time, h10 (6-14)10 (6-13)
      Etomidate use for tracheal intubation132 (61%)124 (57%)
      Thiopental use for tracheal intubation6 (3%)2 (1%)
      Gastric tube123 (57%)116 (53%)
      Orotracheal route104 (85%)93 (80%)
      Nasotracheal route19 (15%)23 (20%)
      Aspiration prior to tracheal intubation37 (17%)35 (16%)
      Antibiotic prophylaxis120 (56%)140 (64%)
      Data are expressed as mean ± SD or median (interquartile range) unless otherwise indicated.
      Investigators declared 248 events (127 [51.2%] in the experimental group and 121 [48.8%] in the control group) as possible VAP. After blinded adjudication, only 159 (64.1%) of them (82 of 216 [38.0%] in the experimental group and 77 of 218 [35.3%] in the control group) met all American Thoracic Society criteria for VAP. The clinical pulmonary infection score at the day of VAP diagnosis (7 [6-8] in the experimental group compared with 7 [7-8] in the control group; P = .63) was comparable between the study groups. Microbiologic methods used to diagnose VAPs were similar between study groups (e-Table 4). Twenty-two patients developed at least two VAPs while on mechanical ventilation. Overall, 73 (33.8%) of 216 patients in the experimental group and 64 (29.4%) of 218 patients in the control group developed at least one episode of VAP within 28 days of mechanical ventilation (aSHR, 0.96; 95% CI, 0.76-1.20) (Fig 2, Table 2), with no difference between centers (e-Table 5). The proportionality of hazard was respected for VAP occurrence and for mortality (e-Figs 2, 3).
      Figure thumbnail gr2
      Figure 2Cumulative incidence (with 95% CI) and aSHR for ventilator-associated pneumonia according to study group allocation. aSHR, adjusted subdistribution hazard ratio.
      Table 2Primary and Secondary Outcomes
      VariableIntervention Group (n = 216)Control

      Group (n = 218)
      Treatment Effect [95% CI]P Value
      VAP
       At day 2873 (34%)64 (29%)0.96 [0.76-1.20].71
       At day 6073 (34%)65 (30%)0.96 [0.76-1.20].73
       Early (≤ 7 d)52 (24%)55 (25%)0.97 [0.66-1.45].90
       Late (> 7 d) at day 2827 (12%)18 (8%)1.05 [0.63-1.74].85
       With bacteremia, at day 282 (1%)4 (2%).69
       Time until first diagnosis, d5 (4-8)5 (4-6).25
      Ventilator associated events
       Ventilator-associated condition66 (31%)56 (26%)1.26 [0.83-1.92].28
       Infection-related VAC63 (29%)54 (25%)1.24 [0.81-190].33
       Possible VAP30 (14%)31 (14%)0.96 [0.55-1.67].89
      Steroids or beta2-agonist after scheduled tracheal extubation22/174 (13%)18/168 (11%)1.26 [0.65-2.46].57
      Duration of mechanical ventilation, h9 (4-17)9 (3-18).50
      Ventilator-free days at day 2814 (0-23)12 (0-23).54
      Ventilator-free days at day 6046 (27-55)44 (0-55).44
      Antibiotic-free days at day 2820 (12-28)20 (5-28).66
      Antibiotic-free days at day 6052 (44-60)52 (40-60).60
      ICU length of stay, days14 (8-26)14 (6-22).38
      Hospital length of stay, days25 (13-46)24 (12-43).45
      ICU mortality at day 2842 (19%)52 (24%)0.78 [0.52-1.18].24
      ICU Mortality at day 6044 (21%)57 (26%)0.72 [0.46-1.13].16
      Data are expressed as median (interquartile range) unless otherwise indicated. VAC = ventilator-associated complication; VAP = ventilator-associated pneumonia.
      The proportion of patients developing VAP prior to or following day 8 of mechanical ventilation and the proportion of bacteremic VAP were comparable between the two study groups (Table 2), as were the pathogens isolated in microbiologic cultures (Table 3). Similarly, the number of patients presenting ventilator-associated events, ventilator-free days, antibiotic-free days, length of stay in the ICU or hospital, and in-ICU mortality were comparable between the study groups.
      Table 3Microbiologic Documentation of the 159 VAP Occurrences
      VariableIntervention Group (n = 82 VAP)Control Group (n = 77 VAP)
      Early VAP (n = 52)Late VAP (n = 30)Early VAP (n = 55)Late VAP (n = 22)
      Staphylococcus aureus21 (30%)9 (22%)27 (32%)6 (21%)
      Streptococcus pneumoniae6 (9%)2 (5%)3 (4%)1 (4%)
      Haemophilus influenzae9 (13%)3 (7%)14 (17%)1 (4%)
      Escherichia coli13 (19%)6 (15%)6 (7%)3 (11%)
      Proteus species3 (4%)1 (2%)5 (6%)1 (4%)
      Klebsiella pneumoniae1 (0%)4 (10%)9 (11%)2 (7%)
      Enterobacter cloacae7 (10%)6 (15%)7 (8%)3 (11%)
      Serratia marcescens2 (3%)1 (2%)3 (4%)2 (7%)
      Pseudomonas aeruginosa4 (6%)5 (12%)6 (7%)5 (18%)
      Acinetobacter baumannii3 (4%)3 (7%)1 (1%)1 (4%)
      Stenotrophomonas species0 (0%)0 (0%)2 (2%)1 (4%)
      Total69408326
      More than one microorganism was recorded in some cases. VAP = ventilator-associated pneumonia.
      No serious issues were reported with the use of the pneumatic device. Median time of device interruption was 3 h (1-8) overall, corresponding to 1.4% (0.5-3.7) of mechanical ventilation time. These interruptions were mainly for patient transfer to the radiology department or the operating room. Use of steroids and/or beta2-agonists following scheduled tracheal extubation was comparable between the two study groups (22 of 174 [13%] patients in the experimental group compared with 18 of 168 [11%] in the control group; P = .57) (e-Table 2, Table 2). The numbers of patients having a tracheostomy were comparable between groups (38 of 216 [18%] in the experimental group compared with 33 of 218 [15%] in the control group; P = .49).

      Discussion

      We report the first large-scale study comparing the efficacy of two modalities of tracheal cuff pressure control in reducing ventilator-associated complications in patients with severe trauma. Continuous control of tracheal cuff pressure using a pneumatic device failed to reduce the incidence of VAP compared with routine care.
      We included patients with severe trauma requiring prolonged (> 48 h) mechanical ventilation because they represent the most vulnerable ICU population for developing VAP. These health care-associated infections typically occur at the end of the first week, when the decline in immune defenses in response to the post-traumatic antiinflammatory reaction is maximal.
      • Mannick J.A.
      • Rodrick M.L.
      • Lederer J.A.
      The immunologic response to injury.
      ,
      • Ward N.S.
      • Casserly B.
      • Ayala A.
      The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients.
      In the intervention group, we chose a pneumatic rather than an electronic device because the former has several advantages, including a shorter response time with fewer periods of insufficient or excessive tracheal cuff pressure and therefore a reduced risk of microbial aspiration and tracheal injury, no need for electronic supply, lower acquisition costs, and easier handling. The number of patients who developed VAP in the control group was greater than the number used to determine the sample size for the study. This could be explained by the exclusion of patients with a high probability of death or of having their trachea extubated within 48 h of enrollment in the study. This resulted in an increased probability of showing a benefit of the intervention.
      Devices that automatically control tracheal cuff pressure are expected to keep pressure in the target range longer, but their impact on preventing VAP was mixed prior to starting the current study. In a single French medical ICU,
      • Nseir S.
      • Zerimech F.
      • Fournier C.
      • et al.
      Continuous control of tracheal cuff pressure and microaspiration of gastric contents in critically ill patients.
      122 patients were randomly assigned to receive continuous control of cuff pressure using a pneumatic device similar to the one used in the current study (n = 61) or routine care (n = 61). The percentage of patients with abundant micro-aspiration defined as the primary outcome (18% vs 46%; OR, 0.25; 95% CI, 0.11-0.59), bacterial concentration in tracheal aspirates (mean ± SD, 1.6 ± 2.4 log10 CFU/mL vs 3.1 ± 3.7 log10 CFU/mL; P = .01), and VAP rate (9.8% vs 26.2%; OR, 0.30; 95% CI [0.11-0.84]) were significantly lower in the intervention group compared with the control group. By contrast, in a second randomized study of 142 patients from two medical ICUs of a single hospital,
      • Valencia M.
      • Ferrer M.
      • Farre R.
      • et al.
      Automatic control of tracheal tube cuff pressure in ventilated patients in semirecumbent position: a randomized trial.
      VAP rate with clinical criteria (22% vs 29%) and microbiologic confirmation (15% vs 15%), distribution of early and late onset, and causative microorganisms were comparable for the automatic and control groups, respectively. In a last observational single-center study involving 284 patients, the use of an electronic device was associated with fewer occurrences of VAP than an intermittent control protocol (11% vs 22%; P = .02).
      • Lorente L.
      • Lecuona M.
      • Jiménez A.
      • et al.
      Continuous endotracheal tube cuff pressure control system protects against ventilator-associated pneumonia.
      Unfortunately, all these studies suffered from several limitations. They were single-center studies, thus limiting the external validity of their findings. The diagnosis of VAP was not assessed blindly to the intervention, leading to potential interpretation bias. Among the two studies showing a decrease in VAP incidence in the intervention group, one was not randomized and the other did not include VAP as the primary outcome.
      To the best of our knowledge, the AGATE trial is the first multicenter randomized study adequately powered to evaluate the potential benefit of an automatic device for continuous cuff pressure monitoring in reducing VAP. Despite inclusion of > 400 critical care patients, we were unable to show any reduction in VAP with the use of a pneumatic automatic device. This resulted in the absence of positive impact in the number of days without antibiotics or mechanical ventilation, length of stay, and mortality. Several factors may explain our findings. First, we cannot exclude the possibility that significant aspiration of contaminated oropharyngeal or gastric contents may have occurred prior to insertion of the tracheal tube. Indeed, severe trauma is generally associated with immediate neurologic disorders, a major risk factor for aspiration,
      • Bronchard R.
      • Albaladejo P.
      • Brezac G.
      • et al.
      Early onset pneumonia: risk factors and consequences in head trauma patients.
      ,
      • Hadjibashi A.A.
      • Berry C.
      • Ley E.J.
      • et al.
      Alcohol is associated with a lower pneumonia rate after traumatic brain injury.
      whereas delay between trauma and insertion of the tracheal tube was > 1 h in > 50% of included patients, and possible up to 24 h as per study protocol. Second, similarly, we cannot rule out significant aspiration of contaminated oropharyngeal or gastric contents prior to pneumatic device placement, as the assessment of trauma and the frequent need for surgery may have delayed admission to the ICU and therefore inclusion of patients in the study, up to a maximum of 15 h following tracheal intubation as per study protocol. Third, despite randomization, the number of patients receiving antibiotic prophylaxis was higher in the control group than in the intervention group. Because antibiotic administration is a well-known protective factor for early-onset VAP, this variable was included in our multivariate analyses to account for this imbalance between study groups. Finally, patients were provided with recommended VAP prevention measures,
      • Leone M.
      • Bouadma L.
      • Bouhemad B.
      • et al.
      Brief summary of French guidelines for the prevention, diagnosis and treatment of hospital-acquired pneumonia in ICU.
      including the semi-recumbent position, a protective lung ventilation strategy, early enteral nutrition, extubation as early as possible, and adherence to hygiene guidelines. Tracheal tubes with subglottic secretion drainage were not used in any of the study participants because this device was not recommended in France at the beginning of the study, and most patients had their trachea intubated prior to being admitted to the ICU. Use of a device to continuously control cuff pressure may become useless in patients when a care bundle approach, including regular control of cuff pressure, is adequately applied.
      • Roquilly A.
      • Chanques G.
      • Lasocki S.
      • et al.
      Implementation of French recommendations for the prevention and the treatment of hospital-acquired pneumonia: a cluster-randomized trial.
      Periods of over-inflation of the tracheal cuff may cause edema of the tracheal mucosa,
      • Loeser E.A.
      • Hodges M.
      • Gliedman J.
      • Stanley T.H.
      • Johansen R.K.
      • Yonetani D.
      Tracheal pathology following short-term intubation with low- and high-pressure endotracheal tube cuffs.
      reducing the diameter of the airway and possibly resulting in respiratory failure after scheduled tracheal extubation. In our study, use of the pneumatic device was not associated with a reduction in steroid or beta2-agonist administration following a scheduled tracheal intubation. These unexpected results could be explained by periods of over-inflation in the control group not being frequent or long enough to cause damage to the tracheal mucosa.
      Our study suffers from several limitations. First, we only included patients with severe trauma and requiring prolonged mechanical ventilation. As previously discussed, it is possible that, in these patients, aspiration of contaminated oropharyngeal or gastric contents occurs very early following the trauma, prior to tracheal intubation and/or placement of the pneumatic device, accounting for the absence of any impact on early-onset VAP incidence. A study will have to be conducted in nontrauma patients to confirm our findings in other severely ill populations. Second, because of the device evaluated, the investigators could not be blinded to the treatment received, resulting in an open-label clinical trial suffering from its inherent methodologic bias. Nevertheless, all centers were already implementing recommended measures to prevent VAP prior to starting the study, and the diagnosis of VAP was made by two assessors blinded to group assignment. Third, compliance with French recommendations on VAP prevention (eg, head-up elevation) was not systematically sought. However, adherence to these guidelines was observed in 42% to 47% of the 1,856 patients enrolled in the Pneumocare study, a randomized cluster trial conducted in 35 French ICUs, many of which participated in this study.
      • Roquilly A.
      • Chanques G.
      • Lasocki S.
      • et al.
      Implementation of French recommendations for the prevention and the treatment of hospital-acquired pneumonia: a cluster-randomized trial.
      Four, we did not record cuff pressure values in the control group at each evaluation. Therefore, it is impossible to determine whether pressure adjustments were frequent. Nevertheless, episodes of under- or over-inflation of the tracheal tube cuff frequently occur between two assessments, resulting in an under-evaluation of these events in the absence of continuous monitoring.
      • Nseir S.
      • Brisson H.
      • Marquette C.H.
      • et al.
      Variations in endotracheal cuff pressure in intubated critically ill patients: prevalence and risk factors.
      Five, cuff pressure values were not recorded in the experimental group either. Studies that recorded cuff pressure continuously over 24 to 48 h with the use of a pneumatic device observed episodes of under- or over-inflation in < 5% of the recording time.
      • Nseir S.
      • Zerimech F.
      • Fournier C.
      • et al.
      Continuous control of tracheal cuff pressure and microaspiration of gastric contents in critically ill patients.
      ,
      • Jaillette E.
      • Zerimech F.
      • De Jonckheere J.
      • et al.
      Efficiency of a pneumatic device in controlling cuff pressure of polyurethane-cuffed tracheal tubes: a randomized controlled study.
      Although unlikely, we cannot totally rule out the possibility that episodes of under-inflation were more frequent in our study. To evaluate the device as real life to facilitate the generalizability of our findings, caregivers were asked to follow the manufacturer’s recommendations. These recommendations require checking the device at each nursing round and, in case of anomaly detection, to measure the cuff pressure and, as usual, to check the cuff pressure every 8 h or sooner if an air leak is detected on the ventilator. Finally, the impact of the intervention on late-onset VAP related to multidrug-resistant micro-organisms was not sought. However, because late-onset VAP were uncommon, the study was underpowered to address this issue.

      Interpretation

      Continuous regulation of tracheal cuff pressure using a pneumatic device was not superior to intermittent control of tracheal cuff pressure using a manual manometer in reducing the incidence of VAP in patients with severe trauma. Further studies taking into account the limitations of the current study are required to make definite conclusions regarding the absence of benefit of the intervention.
      Study Question: Is continuous regulation of tracheal cuff pressure superior to manual assessment every 8 h using a portable manometer (routine care) in preventing VAP?
      Results: Seventy-three patients (33.8%) in the experimental group and 64 patients (29.4%) in the control group developed at least one episode of VAP within 28 days of mechanical ventilation (aSHR, 0.96; 95% CI, 0.76-1.20).
      Interpretation: In this large multicenter, randomized controlled study with severe trauma patients, continuous monitoring of tracheal cuff pressure using a pneumatic device did not prevent VAP compared with routine care. Further studies taking into account the limitations of the current study are required to make definite conclusions regarding the absence of benefit of the intervention.

      Acknowledgments

      Author contributions: O. M. is the guarantor of the content of the manuscript, including data and analysis. N. M. and O. M. conceived the study; J. K. and D. F. performed the statistical analyses; and O. M., N. M., and D. F. drafted the first version of the manuscript. All the investigators mentioned as co-authors helped collect the data, amended the first version of the manuscript, and read and approved the final manuscript.
      Financial/nonfinancial disclosures: None declared.
      Role of sponsors: Neither the sponsor nor the funder had a role in the trial initiation, study design, choice of devices, data collection, data analysis, data interpretation, writing of the report, or the decision to submit. The corresponding author had full access to all of the data in the study and had final responsibility for the decision to submit for publication.
      AGATE Study Group collaborators: Guillaume Besch, PhD; Bélaid Bouhemad, PhD; Elodie Caumon, MSc; Thien-Nga Chamaraux-Tran, PhD; Raphael Cinotti, MD; Thomas Gaillard, MD; Soizic Gergaud, MD; Marc Ginet, MD; Philippe Gouin, MD; Florian Grimaldi, MD; Pierre-Gildas Guitard, MD; Emmanuelle Hammad; Lilit Kelesyan, MD; Sébastien Leduc; Maxime Leger, MD; Pierre-Olivier Ludes, MD; Laurent Muler, PhD; Abdelouaid Nadji, MD; Catherine Paugam-Burtz, PhD; Marie-Héléne Po, MD; Hervé Quintard, PhD; Claire Roger, PhD; Antoine Roquilly, PhD.
      Other contributions: The authors thank all the physicians and nurses in charge of the patients during the study for their support.
      Data sharing: The study protocol is available at https://pubmed.ncbi.nlm.nih.gov/28790042/. Individual participant data will not be available directly to external users, but will be available after de-identification to researchers who provide a methodologically sound proposal, three months following article publication and up to five years later. Proposals should be sent to olivier.mimoz@chu-poitiers.fr. To gain access, data requestors will be asked to sign a data access agreement. The request form will include defining the planned use of the data, and agreement to limit the use to the provided purpose. In addition, a processing fee will be assessed for all requested analyses to cover costs related to time and effort to respond to the request.
      Additional information: The e-Appendix, e-Figures, and e-Tables can be found in the Supplemental Materials section of the online article.

      Supplementary Data

      References

        • Osborn T.M.
        • Tracy J.K.
        • Dunne J.R.
        • Pasquale M.
        • Napolitano L.M.
        Epidemiology of sepsis in patients with traumatic injury.
        Crit Care Med. 2004; 32: 2234-2240
        • Esnault P.
        • Nguyen C.
        • Bordes J.
        • et al.
        Early-onset ventilator-associated pneumonia in patients with severe traumatic brain injury: incidence, risk factors, and consequences in cerebral oxygenation and outcome.
        Neurocrit Care. 2017; 27: 187-198
        • Hershman M.J.
        • Cheadle W.G.
        • Wellhausen S.R.
        • Davidson P.F.
        • Polk H.C.
        Monocyte HLA-DR antigen expression characterizes clinical outcome in the trauma patient.
        Br J Surg. 1990; 77: 204-207
        • Dirnagl U.
        • Klehmet J.
        • Braun J.S.
        • et al.
        Stroke-induced immunodepression: experimental evidence and clinical relevance.
        Stroke. 2007; 38: 770-773
        • Cavalcanti M.
        • Ferrer M.
        • Ferrer R.
        • Morforte R.
        • Garnacho A.
        • Torres A.
        Risk and prognostic factors of ventilator-associated pneumonia in trauma patients.
        Crit Care Med. 2006; 34: 1067-1072
        • Reizine F.
        • Asehnoune K.
        • Roquilly A.
        • et al.
        Effects of antibiotic prophylaxis on ventilator-associated pneumonia in severe traumatic brain injury. A post hoc analysis of two trials.
        J Crit Care. 2019; 50: 221-226
        • Asehnoune K.
        • Seguin P.
        • Allary J.
        • et al.
        Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial.
        Lancet Respir Med. 2014; 2: 706-716
        • Rello J.
        • Ramírez-Estrada S.
        • Romero A.
        • et al.
        Factors associated with ventilator-associated events: an international multicenter prospective cohort study.
        Eur J Clin Microbiol Infect Dis. 2019; 38: 1693-1699
        • American Thoracic Society, Infectious Diseases Society of America
        Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.
        Am J Respir Crit Care Med. 2005; 171: 388-416
        • Estes R.J.
        • Meduri G.U.
        The pathogenesis of ventilator-associated pneumonia: I. Mechanisms of bacterial transcolonization and airway inoculation.
        Intensive Care Med. 1995; 21: 365-383
        • Kastanos N.
        • Estopa Miro R.
        • Marin Perez A.
        • Xaubet Mir A.
        • Agustí-Vidal A.
        Laryngotracheal injury due to endotracheal intubation: incidence, evolution, and predisposing factors. A prospective long-term study.
        Crit Care Med. 1983; 11: 362-367
        • Nseir S.
        • Brisson H.
        • Marquette C.H.
        • et al.
        Variations in endotracheal cuff pressure in intubated critically ill patients: prevalence and risk factors.
        Eur J Anaesthesiol. 2009; 26: 229-234
        • Rouzé A.
        • Jonckheere J De
        • Zerimech F.
        • et al.
        Efficiency of an electronic device in controlling tracheal cuff pressure in critically ill patients: a randomized controlled crossover study.
        Ann Intensive Care. 2016; 6: 93
        • Nseir S.
        • Zerimech F.
        • Fournier C.
        • et al.
        Continuous control of tracheal cuff pressure and microaspiration of gastric contents in critically ill patients.
        Am J Respir Crit Care Med. 2011; 184: 1041-1047
        • Valencia M.
        • Ferrer M.
        • Farre R.
        • et al.
        Automatic control of tracheal tube cuff pressure in ventilated patients in semirecumbent position: a randomized trial.
        Crit Care Med. 2007; 35: 1543-1549
        • Lorente L.
        • Lecuona M.
        • Jiménez A.
        • et al.
        Continuous endotracheal tube cuff pressure control system protects against ventilator-associated pneumonia.
        Crit Care. 2014; 18: R77
        • Rello J.
        • Allegri C.
        • Rodriguez A.
        • et al.
        Risk factors for ventilator-associated pneumonia by Pseudomonas aeruginosa in presence of recent antibiotic exposure.
        Anesthesiology. 2006; 105: 709-714
        • Nseir S.
        • Lorente L.
        • Ferrer M.
        • et al.
        Continuous control of tracheal cuff pressure for VAP prevention: a collaborative meta-analysis of individual participant data.
        Ann Intensive Care. 2015; 5: 43
        • Colombo S.M.
        • Palomeque A.C.
        • Li Bassi G.
        The zero-VAP sophistry and controversies surrounding prevention of ventilator-associated pneumonia.
        Intensive Care Med. 2020; 46: 368-371
        • Papazian L.
        • Klompas M.
        • Luyt C.E.
        Ventilator-associated pneumonia in adults: a narrative review.
        Intensive Care Med. 2020; 46: 888-906
        • Leone M.
        • Bouadma L.
        • Bouhemad B.
        • et al.
        Brief summary of French guidelines for the prevention, diagnosis and treatment of hospital-acquired pneumonia in ICU.
        Ann Intensive Care. 2018; 8: 104
        • Torres A.
        • Niederman M.S.
        • Chastre J.
        • et al.
        International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia. European Respiratory Society.
        (Accessed February 13, 2021)
        • Marjanovic N.
        • Frasca D.
        • Asehnoune K.
        • et al.
        Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol.
        BMJ Open. 2017; 7
        • Copes W.S.
        • Champion H.R.
        • Sacco W.J.
        • Lawnick M.M.
        • Keast S.L.
        • Bain L.W.
        The Injury Severity Score revisited.
        J Trauma. 1988; 28: 69-77
        • Bronchard R.
        • Albaladejo P.
        • Brezac G.
        • et al.
        Early onset pneumonia: risk factors and consequences in head trauma patients.
        Anesthesiology. 2004; 100: 234-239
        • Jaillette E.
        • Zerimech F.
        • De Jonckheere J.
        • et al.
        Efficiency of a pneumatic device in controlling cuff pressure of polyurethane-cuffed tracheal tubes: a randomized controlled study.
        BMC Anesthesiology. 2013; 13: 50
        • Centers for Disease Control and Prevention
        Ventilator-associated pneumonia (VAP) events.
        • Martin C.
        • Auboyer C.
        • Boisson M.
        • et al.
        Antibioprophylaxis in surgery and interventional medicine (adult patients). Update 2017.
        Anaesth Crit Care Pain Med. 2019; 38: 549-562
        • French Health Authority
        Antibiotic therapy and prevention of bacterial resistance in healthcare organisations.
        • Schurink C.A.M.
        • Nieuwenhoven CA Van
        • Jacobs J.A.
        • et al.
        Clinical pulmonary infection score for ventilator-associated pneumonia: accuracy and inter-observer variability.
        Intensive Care Med. 2004; 30: 217-224
        • Fernando S.M.
        • Tran A.
        • Cheng W.
        • et al.
        Diagnosis of ventilator-associated pneumonia in critically ill adult patients—a systematic review and meta-analysis.
        Intensive Care Med. 2020; 46: 1170-1179
      1. National Institutes of Health Clinical Center. Impact of the addition of a device providing continuous pneumatic regulation of tube cuff pressure to an overall strategy aimed at preventing ventilator-associated pneumonia in the severe trauma patient. A multicentre, randomised, controlled study. (AGATE).
        (NCT02534974. ClinicalTrials.gov. National Institutes of Health; 2015. Updated April 25, 2019)
        • Mannick J.A.
        • Rodrick M.L.
        • Lederer J.A.
        The immunologic response to injury.
        J Am Coll Surg. 2001; 193: 237-244
        • Ward N.S.
        • Casserly B.
        • Ayala A.
        The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients.
        Clin Chest Med. 2008; 29: 617-625
        • Hadjibashi A.A.
        • Berry C.
        • Ley E.J.
        • et al.
        Alcohol is associated with a lower pneumonia rate after traumatic brain injury.
        J Surg Res. 2012; 173: 212-215
        • Roquilly A.
        • Chanques G.
        • Lasocki S.
        • et al.
        Implementation of French recommendations for the prevention and the treatment of hospital-acquired pneumonia: a cluster-randomized trial.
        Clin Infect Dis. 2020; (ciaa1441)
        • Loeser E.A.
        • Hodges M.
        • Gliedman J.
        • Stanley T.H.
        • Johansen R.K.
        • Yonetani D.
        Tracheal pathology following short-term intubation with low- and high-pressure endotracheal tube cuffs.
        Anesth Analg. 1978; 57: 577-579

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      • Response
        CHESTVol. 160Issue 2
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          We thank Lakhal et al for their great interest in our study.1 The authors suggest frequent disconnection of the pneumatic device from the tracheal cuff to explain failure of the intervention. Overall, 778 device interruptions were recorded during the study (three per patient on average), which corresponds to only 1.4% of mechanical ventilation time, mainly (65%) for patient transfer to the radiology department or the operating room. These short periods of disconnection could have led to episodes of under-inflation of the tracheal cuff and thus aspiration of the oropharyngeal content; however, we do not believe that they alone can explain the lack of benefit of the intervention.
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      • Regulation of Tracheal Cuff Pressure: Get Connected, Stay Connected
        CHESTVol. 160Issue 2
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          The study by Marjanovic et al1 published in this issue of CHEST is the first multicenter randomized controlled study to address the efficacy of a device for the continuous regulation of tracheal cuff pressure. Therefore, its authors should be commended. In trauma patients who are ventilated mechanically, there was no added value as compared with standard care (ie, manual intermittent adjustment of tracheal cuff pressure at least tid) of the use of such a device: neither the primary outcome (the incidence of ventilator-associated pneumonia [VAP]) nor secondary outcomes were positively impacted by the device.
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