Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy-analysis of registry data.

AIMS: To estimate the effect of prophylactic angiotensin-converting enzyme inhibitors (ACEi) on survival in Duchenne muscular dystrophy (DMD). METHODS AND RESULTS: We analysed the data from the French multicentre DMD Heart Registry (ClinicalTrials.gov: NCT03443115). We estimated the association between the prophylactic prescription of ACEi and event-free survival in 668 patients aged 8 to 13 years, with normal left ventricular function, using (i) a Cox model with intervention as a time-dependent covariate, (ii) a propensity-based analysis comparing ACEi treatment vs. no treatment, and (iii) a set of sensitivity analyses. The study outcomes were overall survival and hospitalizations for heart failure (HF) or acute respiratory failure. Among the 668 patients included in the DMD Heart Registry, 576 (mean age 6.1 ± 2.8 years) were eligible for this study, of whom 390 were treated with ACEi prophylactically. Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with ACEi, respectively. In a Cox model with intervention as a time-dependent variable, the hazard ratio (HR) associated with ACEi treatment was 0.49 [95% confidence interval (CI) 0.34-0.72] and 0.47 (95% CI 0.31-0.17) for overall mortality after adjustment for baseline variables. In the propensity-based analysis, 278 patients were included in the treatment group and 834 in the control group, with 18.5% and 30.4% 12-year estimated probability of death, respectively. ACEi were associated with a lower risk of death (HR 0.39; 95% CI 0.17-0.92) and hospitalization for HF (HR 0.16; 95% CI 0.04-0.62). All other sensitivity analyses yielded similar results. CONCLUSION: Prophylactic ACEi treatment in DMD was associated with a significantly higher overall survival and lower rates of hospitalization for HF.

Almitrine Infusion in Severe Acute Respiratory Syndrome Coronavirus 2-Induced Acute Respiratory Distress Syndrome: A Single-Center Observational Study.

OBJECTIVES: Treating acute respiratory failure in patients with coronavirus disease 2019 is challenging due to the lack of knowledge of the underlying pathophysiology. Hypoxemia may be explained in part by the loss of hypoxic pulmonary vasoconstriction. The present study assessed the effect of almitrine, a selective pulmonary vasoconstrictor, on arterial oxygenation in severe acute respiratory syndrome coronavirus 2-induced acute respiratory distress syndrome. DESIGN: Single-center retrospective observational study. SETTING: ICU of Lille Teaching Hospital, France, from February 27, 2020, to April 14, 2020. PATIENTS: Patients with coronavirus disease 2019 pneumonia confirmed by positive reverse transcriptase-polymerase chain reaction for severe acute respiratory syndrome-coronavirus 2 and acute respiratory distress syndrome according to Berlin definition. Data focused on clinicobiological features, ventilator settings, therapeutics, outcomes, and almitrine-related adverse events. INTERVENTIONS: Almitrine was considered in patients with severe hypoxemia (Pao2/Fio2 ratio < 150 mm Hg) in addition to the recommended therapies, at an hourly IV delivery of 10 µg/kg/min. Comparative blood gases were done before starting almitrine trial and immediately after the end of the infusion. A positive response to almitrine was defined by an increase of Pao2/Fio2 ratio greater than or equal to 20% at the end of the infusion. MEASUREMENTS AND MAIN RESULTS: A total of 169 patients were enrolled. Thirty-two patients with acute respiratory distress syndrome received an almitrine infusion trial. In most cases, almitrine was infused in combination with inhaled nitric oxide (75%). Twenty-one patients (66%) were responders. The median Pao2/Fio2 ratio improvement was 39% (9-93%) and differs significantly between the responders and nonresponders (67% [39-131%] vs 6% [9-16%], respectively; p < 0.0001). The 28-day mortality rates were 47.6% and 63.6% (p = 0.39) for the responders and nonresponders, respectively. Hemodynamic parameters remained similar before and after the trial, not suggesting acute cor pulmonale. CONCLUSIONS: Almitrine infusion improved oxygenation in severe acute respiratory syndrome coronavirus 2-induced acute respiratory distress syndrome without adverse effects. In a multistep clinical approach to manage severe hypoxemia in this population, almitrine could be an interesting therapeutic option to counteract the loss of hypoxic pulmonary vasoconstriction and redistribute blood flow away from shunting zones.

Impact of nutrition route on microaspiration in critically ill patients with shock: a planned ancillary study of the NUTRIREA-2 trial.

BACKGROUND: Microaspiration of gastric and oropharyngeal secretions is the main mechanism of entry of bacteria into the lower respiratory tract in intubated critically ill patients. The aim of this study is to determine the impact of enteral nutrition, as compared with parenteral nutrition, on abundant microaspiration of gastric contents and oropharyngeal secretions. METHODS: Planned ancillary study of the randomized controlled multicenter NUTRIREA2 trial. Patients with shock receiving invasive mechanical ventilation were randomized to receive early enteral or parenteral nutrition. All tracheal aspirates were collected during the 48 h following randomization. Abundant microaspiration of gastric contents and oropharyngeal secretions was defined as the presence of significant levels of pepsin (> 200 ng/ml) and salivary amylase (> 1685 UI/ml) in > 30% of tracheal aspirates. RESULTS: A total of 151 patients were included (78 and 73 patients in enteral and parenteral nutrition groups, respectively), and 1074 tracheal aspirates were quantitatively analyzed for pepsin and amylase. Although vomiting rate was significantly higher (31% vs 15%, p = 0.016), constipation rate was significantly lower (6% vs 21%, p = 0.010) in patients with enteral than in patients with parenteral nutrition. No significant difference was found regarding other patient characteristics. The percentage of patients with abundant microaspiration of gastric contents was significantly lower in enteral than in parenteral nutrition groups (14% vs 36%, p = 0.004; unadjusted OR 0.80 (95% CI 0.69, 0.93), adjusted OR 0.79 (0.76, 0.94)). The percentage of patients with abundant microaspiration of oropharyngeal secretions was significantly higher in enteral than in parenteral nutrition groups (74% vs 54%, p = 0.026; unadjusted OR 1.21 (95% CI 1.03, 1.44), adjusted OR 1.23 (1.01, 1.48)). No significant difference was found in percentage of patients with ventilator-associated pneumonia between enteral (8%) and parenteral (10%) nutrition groups (HR 0.78 (0.26, 2.28)). CONCLUSIONS: Our results suggest that enteral and parenteral nutrition are associated with high rates of microaspiration, although oropharyngeal microaspiration was more common with enteral nutrition and gastric microaspiration was more common with parenteral nutrition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03411447 . Registered 18 July 2017. Retrospectively registered.

Hyperoxemia as a risk factor for ventilator-associated pneumonia.

BACKGROUND: Consequences of hyperoxemia, such as acute lung injury, atelectasis, and reduced bacterial clearance, might promote ventilator-associated pneumonia (VAP). The aim of our study was to determine the relationship between hyperoxemia and VAP. METHODS: This retrospective observational study was performed in a 30-bed mixed ICU. All patients receiving invasive mechanical ventilation for more than 48 hours were eligible. VAP was defined using clinical, radiologic, and quantitative microbiological criteria. Hyperoxemia was defined as PaO2 > 120 mmHg. All data, except those related to hyperoxemia, were prospectively collected. Risk factors for VAP were determined using univariate and multivariate analysis. RESULTS: VAP was diagnosed in 141 of the 503 enrolled patients (28 %). The incidence rate of VAP was 14.7 per 1000 ventilator days. Hyperoxemia at intensive care unit admission (67 % vs 53 %, OR = 1.8, 95 % CI (1.2, 29), p <0.05) and number of days spent with hyperoxemia were significantly more frequent in patients with VAP, compared with those with no VAP. Multivariate analysis identified number of days spent with hyperoxemia (OR = 1.1, 95 % CI (1.04, 1.2) per day, p = 0.004), simplified acute physiology score (SAPS) II (OR = 1.01, 95 % CI (1.002, 1.024) per point, p < 0 .05), red blood cell transfusion (OR = 1.8, 95 % CI (1.2, 2.7), p = 0.01), and proton pomp inhibitor use (OR = 1.9, 95 % CI (1.03, 1.2), p < 0.05) as independent risk factors for VAP. Other multiple regression models also identified hyperoxemia at ICU admission (OR = 1.89, 95 % CI (1.23, 2.89), p = 0.004), and percentage of days with hyperoxemia (OR = 2.2, 95 % CI (1.08, 4.48), p = 0.029) as independent risk factors for VAP. CONCLUSION: Hyperoxemia is independently associated with VAP. Further studies are required to confirm our results.

Assessing alcohol versus baclofen withdrawal syndrome in patients treated with baclofen for alcohol use disorder.

Baclofen is a γ-aminobutyric acid B (GABA-B) receptor agonist that is approved for spasticity. Recently, the off-label use of baclofen for alcohol use disorder (AUD) has increased. However, baclofen is known to induce a neuroadaptation process, which may be identified by the occurrence of a specific baclofen withdrawal syndrome (BWS), that is, confusion, agitation, seizures, and delirium. The same set of symptoms characterizes alcohol withdrawal syndrome (AWS), which could lead to mistaking BWS for AWS in some situations. We report the cases of 3 patients under a chronic baclofen treatment for AUD. The patients emergently presented with a clinical state of confusion that was initially diagnosed and treated as AWS, with limited effect of benzodiazepines. Retrospectively, using a validated algorithm for assessing drug-induced withdrawal, we determined that all of these clinical cases were consistent with BWS. Both AWS and BWS should be considered in the case of acute confusion or delirium occurring in patients treated with baclofen for AUD. Moreover, further research should investigate to what extent GABA-A and GABA-B induce shared or distinct neuroadaptation processes and withdrawal syndromes.

Continuous control of tracheal cuff pressure: an effective measure to prevent ventilator-associated pneumonia?

In a previous issue of Critical Care, Lorente and colleagues reported the results of a prospective observational study aiming at evaluating the effect of continuous control of cuff pressure (Pcuff ) on the incidence of ventilator-associated pneumonia (VAP). The results suggest a beneficial impact of this intervention on VAP prevention, which is in line with the results of a recent randomized controlled study. However, another randomized controlled study found no significant impact of continuous control of Pcuff on VAP incidence. Several differences regarding the device used to control Pcuff, study population, and design might explain the different reported results. Future randomized multicenter studies are needed to confirm the beneficial effect of continuous control of Pcuff on VAP incidence. Furthermore, the efficiency and cost-effectiveness of different available devices should be compared. Meanwhile, given the single-center design and the limitations of the available studies, no strong recommendation can be made regarding continuous control of Pcuff as a preventive measure of VAP.

Impact of appropriate antimicrobial treatment on transition from ventilator-associated tracheobronchitis to ventilator-associated pneumonia.

INTRODUCTION: Two small randomized controlled trials have suggested beneficial effects of antibiotic treatment in patients with ventilator-associated tracheobronchitis (VAT). The primary aim of this study is to determine the impact of appropriate antibiotic treatment on transition from VAT to ventilator-associated pneumonia (VAP) in critically ill patients. The secondary objective was to determine the incidence of VAP in patients with VAT. METHODS: This was a prospective observational multicenter study. All patients with a first episode of VAT were eligible. Patients with tracheostomy at intensive care unit (ICU) admission, and those with VAP prior to VAT were excluded. VAT was defined using all the following criteria: fever > 38 °C with no other cause, purulent tracheal secretions, positive tracheal aspirate (≥ 10(5) cfu/mL), and absence of new infiltrate on chest X ray. Only VAP episodes diagnosed during the 96 h following VAT, and caused by the same bacteria, were taken into account. Antibiotic treatment was at the discretion of attending physicians. Risk factors for transition from VAT to VAP were determined using univariate and multivariate analysis. All variables from univariate analysis with P values <0.1 were incorporated in the multivariate logistic regression analysis. RESULTS: One thousand seven hundred and ten patients were screened for this study. Eighty-six, and 123 patients were excluded for tracheostomy at ICU admission, and VAP prior to VAT; respectively. One hundred and twenty two (7.1%) patients were included. 17 (13.9%) patients developed a subsequent VAP. The most common microorganisms in VAT patients were Pseudomonas aeruginosa (30%), Staphylococcus aureus (18%), and Acinetobacter baumannii (10%). Seventy-four (60%) patients received antimicrobial treatment, including 58 (47.5%) patients who received appropriate antimicrobial treatment. Appropriate antibiotic treatment was the only factor independently associated with reduced risk for transition from VAT to VAP (OR [95% CI] 0.12[0.02-0.59], P = 0.009). The number of patients with VAT needed to treat to prevent one episode of VAP, or one episode of VAP related to P. aeruginosa was 5, and 34; respectively. CONCLUSIONS: Appropriate antibiotic treatment is independently associated with reduced risk for transition from VAT to VAP.

Efficiency of a pneumatic device in controlling cuff pressure of polyurethane-cuffed tracheal tubes: a randomized controlled study.

BACKGROUND: The primary objective of this study was to determine the efficiency of a pneumatic device in controlling cuff pressure (Pcuff) in patients intubated with polyurethane-cuffed tracheal tubes. Secondary objectives were to determine the impact of continuous control of Pcuff, and cuff shape on microaspiration of gastric contents. METHODS: Prospective randomized controlled study. All patients requiring intubation and mechanical ventilation ≥48 h were eligible. The first 32 patients were intubated with tapered polyurethane-cuffed, and the 32 following patients were intubated with cylindrical polyurethane-cuffed tracheal tubes. Patients randomly received 24 h of continuous control of Pcuff using a pneumatic device (Nosten®), and 24 h of routine care of Pcuff using a manometer. Target Pcuff was 25 cmH2O. Pcuff was continuously recorded, and pepsin was quantitatively measured in all tracheal aspirates during these periods. RESULTS: The pneumatic device was efficient in controlling Pcuff (med [IQ] 26 [24, 28] vs 22 [20, 28] cmH2O, during continuous control of Pcuff and routine care, respectively; p = 0.017). In addition, percentage of patients with underinflation (31% vs 68%) or overinflation (53% vs 100%) of tracheal cuff, and percentage of time spent with underinflation (0.9 [0, 17] vs 14% [4, 30]) or overinflation (0 [0, 2] vs 32% [9, 54]) were significantly (p < 0.001) reduced during continuous control of Pcuff compared with routine care.No significant difference was found in microaspiration of gastric content between continuous control of Pcuff compared with routine care, or between patients intubated with tapered compared with cylindrical polyurethane-cuffed tracheal tubes. CONCLUSION: The pneumatic device was efficient in controlling Pcuff in critically ill patients intubated with polyurethane-cuffed tracheal tubes. TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry (NCT01351259).

Are Cirrhotic Patients Receiving Invasive Mechanical Ventilation at Risk of Abundant Microaspiration.

Previous studies have identified cirrhosis as a risk factor for ventilator-associated pneumonia (VAP). The aim of our study was to determine the relationship between cirrhosis and abundant gastric-content microaspiration in intubated critically ill patients. We performed a matched cohort study using data from three randomized controlled trials on abundant microaspiration in patients under mechanical ventilation. Each cirrhotic patient was matched with three to four controls for gender, age ± 5 years and simplified acute physiology score II (SAPS II) ± 5 points. Abundant microaspiration was defined by significant levels of pepsin and alpha-amylase in >30% of tracheal aspirates. All tracheal aspirates were collected for the first 48 h of the study period. The percentage of patients with abundant gastric-content microaspiration was the primary outcome. The abundant microaspiration of oropharyngeal secretions, VAP incidence, the duration of mechanical ventilation, length of intensive care unit (ICU) stay and mortality were the secondary outcomes. A. total of 39 cirrhotic patients were matched to 138 controls. The percentage of patients with abundant gastric-content microaspiration did not differ between the two groups (relative risk: 0.91 (95% CI: 0.75 to 1.10)). There was no significant difference between the two groups in terms of the abundant microaspiration of oropharyngeal secretions, VAP, the duration of mechanical ventilation, the length of ICU stay and mortality. Our results suggest that cirrhosis is not associated with abundant gastric-content microaspiration.

Relationship between inhaled ß2-agonists and ventilator-associated pneumonia: a cohort study.

OBJECTIVE: To determine the impact of aerosolized bronchodilators on ventilator-associated pneumonia. DESIGN: Prospective cohort study. SETTING: A 30-bed medical and surgical intensive care unit. METHODS: All intubated patients requiring mechanical ventilation for >48 hrs were eligible during a 13-month period. Nebulized ß2-agonists were administered at the intensive care unit physician's discretion. Ventilator-associated pneumonia definition included clinical and quantitative microbiological criteria. Only first ventilator-associated pneumonia episodes were analyzed. Risk factors for ventilator-associated pneumonia were determined using univariate and multivariate analyses. The influence of inhaled ß2-agonists on ventilator-associated pneumonia occurrence was also adjusted for confounding factors using Cox's proportional-hazards model. RESULTS: Ventilator-associated pneumonia was diagnosed in 137 (31%) of the 439 enrolled patients. Ventilator-associated pneumonia was early-onset in 14 (10%) patients. The incidence rate of ventilator-associated pneumonia was 20 per 1,000 ventilator days. Ventilator-associated pneumonia was polymicrobial in 16 (11%) patients, and related to multidrug-resistant bacteria in 42 (28%) patients. Most cases of ventilator-associated pneumonia were caused by Gram-negative bacteria. Inhaled ß2-agonists were significantly more frequently used in patients with ventilator-associated pneumonia compared with those without ventilator-associated pneumonia (49% vs. 34%, odds ratio [95% confidence interval] = 1.9 [1.2-2.8], p = .003). Multivariate analysis identified aerosolized ß2-agonists (odds ratio [95% confidence interval] = 1.7 [1.1-2.6], p = .012), Simplified Acute Physiology Score II at intensive care unit admission (odds ratio [95% confidence interval] = 1.01 [1.001-1.02] per point, p = .031), and red blood cell transfusion (odds ratio [95% confidence interval] = 2 [1.3-3.1], p = .001) as independent risk factors for ventilator-associated pneumonia. Cox's proportional-hazards model also identified inhaled ß2-agonists as a risk factor for ventilator-associated pneumonia (odds ratio [95% confidence interval] = 1.52 [1.06-2.19], p = .021). CONCLUSION: Use of aerosolized bronchodilators in intensive care unit mechanically ventilated patients is an independent risk factor for ventilator-associated pneumonia.

One Outbreak Could Hide Another.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a major worldwide concern. Guidelines have been issued regarding precautions for healthcare workers caring for SARS-CoV-2-infected patients. Despite accurate observance of infection control measures, including contact precautions, we encountered an OXA-23-producing Acinetobacter baumannii outbreak in 5 intensive care units of 10 beds each in our tertiary care teaching hospital.

Is COPD associated with increased risk for microaspiration in intubated critically ill patients?

BACKGROUND: Although COPD patients are at higher risk for aspiration when breathing spontaneously, no information is available on the risk for microaspiration in invasively ventilated COPD patients. The aim of our study was to determine the relationship between COPD and abundant microaspiration in intubated critically ill patients. METHODS: This was a retrospective analysis of prospectively collected data, provided by 3 randomized controlled trials on microaspiration in critically ill patients receiving invasive mechanical ventilation for more than 48 h. Abundant microaspiration was defined as the presence of pepsin and or alpha-amylase at significant levels in tracheal aspirates. In all study patients, pepsin and alpha-amylase were quantitatively measured in all tracheal aspirates collected during a 48-h period. COPD was defined using spirometry criteria. RESULTS: Among the 515 included patients, 70 (14%) had proven COPD. Pepsin and alpha-amylase were quantitatively measured in 3873 and 3764 tracheal aspirates, respectively. No significant difference was found in abundant microaspiration rate between COPD and non-COPD patients (62 of 70 patients (89%) vs 366 of 445 (82%) patients, p = 0.25). Similarly, no significant difference was found in abundant microaspiration of gastric contents (53% vs 45%, p = 0.28), oropharyngeal secretions (71% vs 71%, p = 0.99), or VAP (19% vs 22%, p = 0.65) rates between the two groups. No significant difference was found between COPD and non-COPD patients in duration of mechanical ventilation, ICU length of stay, or ICU mortality. CONCLUSIONS: Our results suggest that COPD is not associated with increased risk for abundant microaspiration in intubated critically ill patients.

Relationship between digestive tract colonization and subsequent ventilator-associated pneumonia related to ESBL-producing Enterobacteriaceae.

BACKGROUND: Ventilator-associated pneumonia (VAP) is the most common ICU-acquired infection. Recently, the incidence of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBLE) has substantially increased in critically ill patients. Identifying patients at risk for VAP related to ESBLE could be helpful to improve the rate of appropriate initial antibiotic treatment, and to reduce unnecessary exposure to carbapenems. The primary objective was to identify risk factors for VAP related to ESBLE. Secondary objective was to determine the impact of ESBLE on outcome in VAP patients. METHODS: This retrospective study was conducted in a single mixed intensive care unit (ICU), during a 4-year period. All patients with confirmed VAP were included. VAP was defined using clinical, radiologic and quantitative microbiological data. VAP first episodes were prospectively identified using the continuous surveillance data. Exposure to different risk factors was taken into account until the diagnosis of ESBLE VAP or until ICU discharge, in patients with ESBLE VAP and VAP related to other bacteria, respectively. In all patients, routine screening for ESBLE (rectal swab) was performed at ICU admission and once a week. Patients with ESBLE VAP were compared with those with VAP related to other bacteria using univariate analysis. All significant factors were included in the multivariate logistic regression model. RESULTS: Among the 410 patients with VAP, 43 (10.5%) had ESBLE VAP, 76 (19%) patients had polymicrobial VAP and 189 (46%) had VAP related to multidrug resistant bacteria. Multivariate analysis identified prior ESBLE colonization of the digestive tract as the only independent risk factor for ESBLE VAP (OR [95% CI] = 23 [10-55], p < 0.001). Whilst the positive predictive value of ESBLE digestive colonization was low (43.6%), its negative predictive value was excellent (97.3%) in predicting ESBLE VAP. Duration of mechanical ventilation (median [IQR], 28 [18,42] vs 23 [15,42] d, p = 0.4), length of ICU stay (31 [19,53] vs 29 [18,46] d, p = 0.6), and mortality rates (55.8% vs 50%, p = 0.48) were similar in ESBLE VAP, compared with VAP related to other bacteria. CONCLUSION: Digestive tract colonization related to ESBLE is independently associated with ESBLE VAP. Its excellent negative predictive value suggests that patients without ESBLE colonization should not receive carbapenems as part of their initial empirical treatment to cover ESBLE.

Tracheal Tube Design and Ventilator-Associated Pneumonia.

Microaspiration of contaminated oropharyngeal and gastric secretions is the main mechanism for ventilator-associated pneumonia (VAP) in critically ill patients. Improving the performance of tracheal tubes in reducing microaspiration is one potential means to prevent VAP. The aim of this narrative review is to discuss recent findings on the impact of tracheal tube design on VAP prevention. Several randomized controlled studies have reported that subglottic secretion drainage (SSD) is efficient in VAP prevention. Meta-analyses have reported conflicting results regarding the impact of SSD on duration of mechanical ventilation, and one animal study raised concern about SSD-related tracheal lesions. However, this measure appears to be cost-effective. Therefore, SSD should probably be used in all patients with expected duration of mechanical ventilation > 48 h. Three randomized controlled trials have shown that tapered-cuff tracheal tubes are not useful to prevent VAP and should probably not be used in critically ill patients. Further studies are required to confirm the promising effects of continuous control of cuff pressure, polyurethane-cuffed, silver-coated, and low-volume low-pressure tracheal tubes. There is moderate evidence for the use of SSD and strong evidence against the use of tapered-cuff tracheal tubes in critically ill patients for VAP prevention. However, more data on the safety and cost-effectiveness of these measures are needed. Other tracheal tube-related preventive measures require further investigation.

Impact of tapered-cuff tracheal tube on microaspiration of gastric contents in intubated critically ill patients: a multicenter cluster-randomized cross-over controlled trial.

PURPOSE: Studies on the impact of tapered-cuff tracheal tubes on rates of microaspiration and ventilator-associated pneumonia (VAP) in intubated patients have reported conflicting results. The aim of this study was to determine the influence of this shape of tracheal cuff on abundant microaspiration of gastric contents in critically ill patients. METHODS: All patients intubated in the intensive care unit (ICU) and requiring mechanical ventilation for at least 48 h were eligible for this multicenter cluster-randomized controlled cross-over open-label study. The primary outcome was abundant microaspiration of gastric contents, defined by the presence of pepsin at significant level in >30% of tracheal aspirates. Quantitative measurement of pepsin and salivary amylase was performed in all tracheal aspirates during the 48 h following enrollment. RESULTS: A total of 326 patients were enrolled in the ten participating ICUs (162 in the PVC tapered-cuff group and 164 in the standard-cuff group). Patient characteristics were similar in the two study groups. The proportion of patients with abundant microaspiration of gastric contents was 53.5% in the tapered-cuff and 51.0% in the standard-cuff group (odds ratio 1.14, 95% CI 0.72-1.82). While abundant microaspiration of oropharyngeal secretions was not significantly different (77.4 vs 68.6%, p = 0.095), the proportion of patients with tracheobronchial colonization was significantly lower (29.6 vs 43.3%, p = 0.01) in the tapered-cuff than in the standard-cuff group. No significant difference between the two groups was found for other secondary outcomes, including ventilator-associated events and VAP. CONCLUSIONS: This trial showed no significant impact of tapered-cuff tracheal tubes on abundant microaspiration of gastric contents. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01948635.