Associations of early changes in lung ultrasound aeration scores and mortality in invasively ventilated patients: a post hoc analysis.

BACKGROUND: Lung ultrasound (LUS) in an emerging technique used in the intensive care unit (ICU). The derivative LUS aeration score has been shown to have associations with mortality in invasively ventilated patients. This study assessed the predictive value of baseline and early changes in LUS aeration scores in critically ill invasively ventilated patients with and without ARDS (Acute Respiratory Distress Syndrome) on 30- and 90-day mortality. METHODS: This is a post hoc analysis of a multicenter prospective observational cohort study, which included patients admitted to the ICU with an expected duration of ventilation for at least 24 h. We restricted participation to patients who underwent a 12-region LUS exam at baseline and had the primary endpoint (30-day mortality) available. Logistic regression was used to analyze the primary and secondary endpoints. The analysis was performed for the complete patient cohort and for predefined subgroups (ARDS and no ARDS). RESULTS: A total of 442 patients were included, of whom 245 had a second LUS exam. The baseline LUS aeration score was not associated with mortality (1.02 (95% CI: 0.99 - 1.06), p = 0.143). This finding was not different in patients with and in patients without ARDS. Early deterioration of the LUS score was associated with mortality (2.09 (95% CI: 1.01 - 4.3), p = 0.046) in patients without ARDS, but not in patients with ARDS or in the complete patient cohort. CONCLUSION: In this cohort of critically ill invasively ventilated patients, the baseline LUS aeration score was not associated with 30- and 90-day mortality. An early change in the LUS aeration score was associated with mortality, but only in patients without ARDS. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT04482621.

Breath metabolomics for diagnosis of acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) poses challenges in early identification. Exhaled breath contains metabolites reflective of pulmonary inflammation. AIM: To evaluate the diagnostic accuracy of breath metabolites for ARDS in invasively ventilated intensive care unit (ICU) patients. METHODS: This two-center observational study included critically ill patients receiving invasive ventilation. Gas chromatography and mass spectrometry (GC-MS) was used to quantify the exhaled metabolites. The Berlin definition of ARDS was assessed by three experts to categorize all patients into "certain ARDS", "certain no ARDS" and "uncertain ARDS" groups. The patients with "certain" labels from one hospital formed the derivation cohort used to train a classifier built based on the five most significant breath metabolites. The diagnostic accuracy of the classifier was assessed in all patients from the second hospital and combined with the lung injury prediction score (LIPS). RESULTS: A total of 499 patients were included in this study. Three hundred fifty-seven patients were included in the derivation cohort (60 with certain ARDS; 17%), and 142 patients in the validation cohort (47 with certain ARDS; 33%). The metabolites 1-methylpyrrole, 1,3,5-trifluorobenzene, methoxyacetic acid, 2-methylfuran and 2-methyl-1-propanol were included in the classifier. The classifier had an area under the receiver operating characteristics curve (AUROCC) of 0.71 (CI 0.63-0.78) in the derivation cohort and 0.63 (CI 0.52-0.74) in the validation cohort. Combining the breath test with the LIPS does not significantly enhance the diagnostic performance. CONCLUSION: An exhaled breath metabolomics-based classifier has moderate diagnostic accuracy for ARDS but was not sufficiently accurate for clinical use, even after combination with a clinical prediction score.

Lung Ultrasound Prediction Model for Acute Respiratory Distress Syndrome: A Multicenter Prospective Observational Study.

Rationale: Lung ultrasound (LUS) is a promising tool for diagnosis of acute respiratory distress syndrome (ARDS), but adequately sized studies with external validation are lacking. Objectives: To develop and validate a data-driven LUS score for diagnosis of ARDS and compare its performance with that of chest radiography (CXR). Methods: This multicenter prospective observational study included invasively ventilated ICU patients who were divided into a derivation cohort and a validation cohort. Three raters scored ARDS according to the Berlin criteria, resulting in a classification of "certain no ARDS," or "certain ARDS" when experts agreed or "uncertain ARDS" when evaluations conflicted. Uncertain cases were classified in a consensus meeting. Results of a 12-region LUS exam were used in a logistic regression model to develop the LUS-ARDS score. Measurements and Main Results: Three hundred twenty-four (16% certain ARDS) and 129 (34% certain ARDS) patients were included in the derivation cohort and the validation cohort, respectively. With an ARDS diagnosis by the expert panel as the reference test, the LUS-ARDS score, including the left and right LUS aeration scores and anterolateral pleural line abnormalities, had an area under the receiver operating characteristic (ROC) curve of 0.90 (95% confidence interval [CI], 0.85-0.95) in certain patients of the derivation cohort and 0.80 (95% CI, 0.72-0.87) in all patients of the validation cohort. Within patients who had imaging-gold standard chest computed tomography available, diagnostic accuracy of eight independent CXR readers followed the ROC curve of the LUS-ARDS score. Conclusions: The LUS-ARDS score can be used to accurately diagnose ARDS also after external validation. The LUS-ARDS score may be a useful adjunct to a diagnosis of ARDS after further validation, as it showed performance comparable with that of the current practice with experienced CXR readers but more objectifiable diagnostic accuracy at each cutoff.

Biomarkers of alveolar epithelial injury and endothelial dysfunction are associated with scores of pulmonary edema in invasively ventilated patients.

Pulmonary edema is a central hallmark of acute respiratory distress syndrome (ARDS). Endothelial dysfunction and epithelial injury contribute to alveolar-capillary permeability but their differential contribution to pulmonary edema development remains understudied. Plasma levels of surfactant protein-D (SP-D), soluble receptor for advanced glycation end products (sRAGE), and angiopoietin-2 (Ang-2) were measured in a prospective, multicenter cohort of invasively ventilated patients. Pulmonary edema was quantified using the radiographic assessment of lung edema (RALE) and global lung ultrasound (LUS) score. Variables were collected within 48 h after intubation. Linear regression was used to examine the association of the biomarkers with pulmonary edema. In 362 patients, higher SP-D, sRAGE, and Ang-2 concentrations were significantly associated with higher RALE and global LUS scores. After stratification by ARDS subgroups (pulmonary, nonpulmonary, COVID, non-COVID), the positive association of SP-D levels with pulmonary edema remained, whereas sRAGE and Ang-2 showed less consistent associations throughout the subgroups. In a multivariable analysis, SP-D levels were most strongly associated with pulmonary edema when combined with sRAGE (RALE score: ßSP-D = 6.79 units/log10 pg/mL, ßsRAGE = 3.84 units/log10 pg/mL, R2 = 0.23; global LUS score: ßSP-D = 3.28 units/log10 pg/mL, ßsRAGE = 2.06 units/log10 pg/mL, R2 = 0.086), whereas Ang-2 did not further improve the model. Biomarkers of epithelial injury and endothelial dysfunction were associated with pulmonary edema in invasively ventilated patients. SP-D and sRAGE showed the strongest association, suggesting that epithelial injury may form a final common pathway in the alveolar-capillary barrier dysfunction underlying pulmonary edema.

Biological Subphenotypes of Acute Respiratory Distress Syndrome Show Prognostic Enrichment in Mechanically Ventilated Patients without Acute Respiratory Distress Syndrome.

Rationale: Recent studies showed that biological subphenotypes in acute respiratory distress syndrome (ARDS) provide prognostic enrichment and show potential for predictive enrichment. Objectives: To determine whether these subphenotypes and their prognostic and potential for predictive enrichment could be extended to other patients in the ICU, irrespective of fulfilling the definition of ARDS. Methods: This is a secondary analysis of a prospective observational study of adult patients admitted to the ICU. We tested the prognostic enrichment of both cluster-derived and latent-class analysis (LCA)-derived biological ARDS subphenotypes by evaluating the association with clinical outcome (ICU-day, 30-day mortality, and ventilator-free days) using logistic regression and Cox regression analysis. We performed a principal component analysis to compare blood leukocyte gene expression profiles between subphenotypes and the presence of ARDS. Measurements and Main Results: We included 2,499 mechanically ventilated patients (674 with and 1,825 without ARDS). The cluster-derived "reactive" subphenotype was, independently of ARDS, significantly associated with a higher probability of ICU mortality, higher 30-day mortality, and a lower probability of successful extubation while alive compared with the "uninflamed" subphenotype. The blood leukocyte gene expression profiles of individual subphenotypes were similar for patients with and without ARDS. LCA-derived subphenotypes also showed similar profiles. Conclusions: The prognostic and potential for predictive enrichment of biological ARDS subphenotypes may be extended to mechanically ventilated critically ill patients without ARDS. Using the concept of biological subphenotypes for splitting cohorts of critically ill patients could add to improving future precision-based trial strategies and lead to identifying treatable traits for all critically ill patients.

The global inhomogeneity index assessed by electrical impedance tomography overestimates PEEP requirement in patients with ARDS: an observational study.

BACKGROUND: Electrical impedance tomography (EIT) visualises alveolar overdistension and alveolar collapse and enables optimisation of ventilator settings by using the best balance between alveolar overdistension and collapse (ODCL). Besides, the global inhomogeneity index (GI), measured by EIT, may also be of added value in determining PEEP. Optimal PEEP is often determined based on the best dynamic compliance without EIT at the bedside. This study aimed to assess the effect of a PEEP trial on ODCL, GI and dynamic compliance in patients with and without ARDS. Secondly, PEEP levels from "optimal PEEP" approaches by ODCL, GI and dynamic compliance are compared. METHODS: In 2015-2016, we included patients with ARDS using postoperative cardiothoracic surgery patients as a reference group. A PEEP trial was performed with four consecutive incremental followed by four decremental PEEP steps of 2 cmH2O. Primary outcomes at each step were GI, ODCL and best dynamic compliance. In addition, the agreement between ODCL, GI, and dynamic compliance was determined for the individual patient. RESULTS: Twenty-eight ARDS and 17 postoperative cardiothoracic surgery patients were included. The mean optimal PEEP, according to best compliance, was 10.3 (±2.9) cmH2O in ARDS compared to 9.8 (±2.5) cmH2O in cardiothoracic surgery patients. Optimal PEEP according to ODCL was 10.9 (±2.5) in ARDS and 9.6 (±1.6) in cardiothoracic surgery patients. Optimal PEEP according to GI was 17.1 (±3.9) in ARDS compared to 14.2 (±3.4) in cardiothoracic surgery patients. CONCLUSIONS: Currently, no golden standard to titrate PEEP is available. We showed that when using the GI, PEEP requirements are higher compared to ODCL and best dynamic compliance during a PEEP trial in patients with and without ARDS.

Development and validation of a point-of-care breath test for octane detection.

BACKGROUND: There is a demand for a non-invasive bedside method to diagnose Acute Respiratory Distress Syndrome (ARDS). Octane was discovered and validated as the most important breath biomarker for diagnosis of ARDS using gas-chromatography and mass-spectrometry (GC-MS). However, GC-MS is unsuitable as a point-of-care (POC) test in the intensive care unit (ICU). Therefore, we determined if a newly developed POC breath test can reliably detect octane in exhaled breath of invasively ventilated ICU patients. METHODS: Two developmental steps were taken to design a POC breath test that relies on gas-chromatography using air as carrier gas with a photoionization detector. Calibration measurements were performed with a laboratory prototype in healthy subjects. Subsequently, invasively ventilated patients were included for validation and assessment of repeatability. After evolving to a POC breath test, this device was validated in a second group of invasively ventilated patients. Octane concentration was based on the area under the curve, which was extracted from the chromatogram and compared to known values from calibration measurements. RESULTS: Five healthy subjects and 53 invasively ventilated patients were included. Calibration showed a linear relation (R2 = 1.0) between the octane concentration and the quantified octane peak in the low parts per billion (ppb) range. For the POC breath test the repeatability was excellent (R2 = 0.98, ICC = 0.97 (95% CI 0.94-0.99)). CONCLUSION: This is the first study to show that a POC breath test can rapidly and reliably detect octane, with excellent repeatability, at clinically relevant levels of low ppb in exhaled breath of ventilated ICU patients. This opens possibilities for targeted exhaled breath analysis to be used as a bedside test and makes it a potential diagnostic tool for the early detection of ARDS.

Clamshell in a Heartbeat.

There is a restrained attitude toward the implementation and performance of resuscitative thoracotomy as a last resort procedure in patients with cardiac arrest after penetrating thoracic trauma. We present a case with a remarkable recovery and hope to boost morality in the use of this procedure in the prehospital setting. A disoriented 25-year-old woman stabbed multiple times was found next to the highway. Her clinical situation deteriorated swiftly upon arrival of the helicopter emergency medical services. They were able to perform a clamshell thoracotomy and fly the patient out to the nearest trauma center. She awoke with good neurologic function. Her hospital admission was complicated by mediastinitis. A routine cardiac ultrasound showed mitral valve insufficiency due to combined perforation of the anterior leaflet and ventricular septum. Both lesions were in the trajectory of the primary stab wound. Successful outcome in our case was due to the following: little delay between clinical deterioration and the arrival of the helicopter emergency medical services physician (signs of life on arrival of paramedics are an independent predictor of survival), young age and penetrating injury are associated with a good neurologic outcome in case of traumatic cardiac arrest, and extensive follow-up cardiac ultrasound as part of tertiary survey after resuscitative emergency thoracotomy is advised.

Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteria: a proof-of-concept study.

Volatile organic compounds in breath can reflect host and pathogen metabolism and might be used to diagnose pneumonia. We hypothesized that rats with Streptococcus pneumoniae (SP) or Pseudomonas aeruginosa (PA) pneumonia can be discriminated from uninfected controls by thermal desorption-gas chromatography-mass-spectrometry (TD-GC-MS) and selected ion flow tube-mass spectrometry (SIFT-MS) of exhaled breath. Male adult rats (n = 50) received an intratracheal inoculation of 1) 200 µl saline, or 2) 1 × 107 colony-forming units of SP or 3) 1 × 107 CFU of PA. Twenty-four hours later the rats were anaesthetized, tracheotomized, and mechanically ventilated. Exhaled breath was analyzed via TD-GC-MS and SIFT-MS. Area under the receiver operating characteristic curves (AUROCCs) and correct classification rate (CCRs) were calculated after leave-one-out cross-validation of sparse partial least squares-discriminant analysis. Analysis of GC-MS data showed an AUROCC (95% confidence interval) of 0.85 (0.73-0.96) and CCR of 94.6% for infected versus noninfected animals, AUROCC of 0.98 (0.94-1) and CCR of 99.9% for SP versus PA, 0.92 (0.83-1.00), CCR of 98.1% for SP versus controls and 0.97 (0.92-1.00), and CCR of 99.9% for PA versus controls. For these comparisons the SIFT-MS data showed AUROCCs of 0.54, 0.89, 0.63, and 0.79, respectively. Exhaled breath analysis discriminated between respiratory infection and no infection but with even better accuracy between specific pathogens. Future clinical studies should not only focus on the presence of respiratory infection but also on the discrimination between specific pathogens.

Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy.

OBJECTIVE: We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain. PATIENTS AND METHODS: This was a pre-planned secondary analysis of Efraim, a prospective, multinational, observational study of 1611 immunocompromised patients with acute respiratory failure admitted to the intensive care unit (ICU). We compared patients with noninvasive testing only to those who had also received bronchoscopy by bivariate analysis and after propensity score matching. RESULTS: Bronchoscopy was performed in 618 (39%) patients who were more likely to have haematological malignancy and a higher severity of illness score. Bronchoscopy alone achieved a diagnosis in 165 patients (27% adjusted diagnostic yield). Bronchoscopy resulted in a management change in 236 patients (38% therapeutic yield). Bronchoscopy was associated with worsening of respiratory status in 69 (11%) patients. Bronchoscopy was associated with higher ICU (40% versus 28%; p<0.0001) and hospital mortality (49% versus 41%; p=0.003). The overall rate of undiagnosed causes was 13%. After propensity score matching, bronchoscopy remained associated with increased risk of hospital mortality (OR 1.41, 95% CI 1.08-1.81). CONCLUSIONS: Bronchoscopy was associated with improved diagnosis and changes in management, but also increased hospital mortality. Balancing risk and benefit in individualised cases should be investigated further.

Clinical implementation of electric impedance tomography in the treatment of ARDS: a single centre experience.

To report on our clinical experience using EIT in individualized PEEP titration in ARDS. Using EIT assessment, we optimized PEEP settings in 39 ARDS patients. The EIT PEEP settings were compared with the physicians' PEEP settings and the PEEP settings according to the ARDS network. We defined a PEEP difference equal to or greater than 4 cm H2O as clinically relevant. Changes in lung compliance and PaO2/FiO2-ratio were compared in patients with EIT-based PEEP adjustments and in patients with unaltered PEEP. In 28% of the patients, the difference in EIT-based PEEP and physician-PEEP was clinically relevant; in 36%, EIT-based PEEP and physician-PEEP were equal. The EIT-based PEEP disagreed with the PEEP settings according to the ARDS network. Adjusting PEEP based upon EIT led to a rapid increase in lung compliance and PaO2/FiO2-ratio. However, this increase was also observed in the group where the PEEP difference was less than 4 cm H2O. We hypothesize that this can be attributed to the alveolar recruitment during the PEEP trial. EIT based individual PEEP setting appears to be a promising method to optimize PEEP in ARDS patients. The clinical impact, however, remains to be established.

Increased Dicarbonyl Stress as a Novel Mechanism of Multi-Organ Failure in Critical Illness.

Molecular pathological pathways leading to multi-organ failure in critical illness are progressively being unravelled. However, attempts to modulate these pathways have not yet improved the clinical outcome. Therefore, new targetable mechanisms should be investigated. We hypothesize that increased dicarbonyl stress is such a mechanism. Dicarbonyl stress is the accumulation of dicarbonyl metabolites (i.e., methylglyoxal, glyoxal, and 3-deoxyglucosone) that damages intracellular proteins, modifies extracellular matrix proteins, and alters plasma proteins. Increased dicarbonyl stress has been shown to impair the renal, cardiovascular, and central nervous system function, and possibly also the hepatic and respiratory function. In addition to hyperglycaemia, hypoxia and inflammation can cause increased dicarbonyl stress, and these conditions are prevalent in critical illness. Hypoxia and inflammation have been shown to drive the rapid intracellular accumulation of reactive dicarbonyls, i.e., through reduced glyoxalase-1 activity, which is the key enzyme in the dicarbonyl detoxification enzyme system. In critical illness, hypoxia and inflammation, with or without hyperglycaemia, could thus increase dicarbonyl stress in a way that might contribute to multi-organ failure. Thus, we hypothesize that increased dicarbonyl stress in critical illness, such as sepsis and major trauma, contributes to the development of multi-organ failure. This mechanism has the potential for new therapeutic intervention in critical care.

Antibiotic-Induced Within-Host Resistance Development of Gram-Negative Bacteria in Patients Receiving Selective Decontamination or Standard Care.

OBJECTIVE: To quantify antibiotic-associated within-host antibiotic resistance acquisition rates in Pseudomonas aeruginosa, Klebsiella species, and Enterobacter species from lower respiratory tract samples of ICU patients receiving selective digestive decontamination, selective oropharyngeal decontamination, or standard care. DESIGN: Prospective cohort. SETTING: This study was nested within a cluster-randomized crossover study of selective digestive decontamination and selective oropharyngeal decontamination in 16 ICUs in The Netherlands. PATIENTS: Eligible patients were those colonized in the respiratory tract with P. aeruginosa, Klebsiella species, or Enterobacter species susceptible to one of the marker antibiotics and with at least two subsequent microbiological culture results from respiratory tract samples available. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Antibiotic resistance acquisition rates were defined as the number of conversions from susceptible to resistant for a specific antibiotic per 100 patient-days or 100 days of antibiotic exposure within an individual patient. The hazard of antibiotic use for resistance development in P. aeruginosa was based on time-dependent Cox regression analysis. Findings of this study cohort were compared with those of a previous cohort of patients not receiving selective digestive decontamination/selective oropharyngeal decontamination. Numbers of eligible patients were 277 for P. aeruginosa, 174 for Klebsiella species, and 106 for Enterobacter species. Resistance acquisition rates per 100 patient-days ranged from 0.2 (for colistin and ceftazidime in P. aeruginosa and for carbapenems in Klebsiella species) to 3.0 (for piperacillin-tazobactam in P. aeruginosa and Enterobacter species). For P. aeruginosa, the acquisition rates per 100 days of antibiotic exposure ranged from 1.4 for colistin to 4.9 for piperacillin-tazobactam. Acquisition rates were comparable for patients receiving selective digestive decontamination/selective oropharyngeal decontamination and those receiving standard care. Carbapenem exposure had the strongest association with resistance development (adjusted hazard ratio, 4.2; 95% CI, 1.1-15.6). CONCLUSION: Within-host antibiotic resistance acquisition rates for systemically administered antibiotics were comparable between patients receiving selective decontamination and those receiving standard care and were highest during carbapenem use.

Postextubation laryngeal edema and stridor resulting in respiratory failure in critically ill adult patients: updated review.

Endotracheal intubation is frequently complicated by laryngeal edema, which may present as postextubation stridor or respiratory difficulty or both. Ultimately, postextubation laryngeal edema may result in respiratory failure with subsequent reintubation. Risk factors for postextubation laryngeal edema include female gender, large tube size, and prolonged intubation. Although patients at low risk for postextubation respiratory insufficiency due to laryngeal edema can be identified by the cuff leak test or laryngeal ultrasound, no reliable test for the identification of high-risk patients is currently available. If applied in a timely manner, intravenous or nebulized corticosteroids can prevent postextubation laryngeal edema; however, the inability to identify high-risk patients prevents the targeted pretreatment of these patients. Therefore, the decision to start corticosteroids should be made on an individual basis and on the basis of the outcome of the cuff leak test and additional risk factors. The preferential treatment of postextubation laryngeal edema consists of intravenous or nebulized corticosteroids combined with nebulized epinephrine, although no data on the optimal treatment algorithm are available. In the presence of respiratory failure, reintubation should be performed without delay. Application of noninvasive ventilation or inhalation of a helium/oxygen mixture is not indicated since it does not improve outcome and increases the delay to intubation.

Ventilator-associated Pneumonia caused by commensal oropharyngeal Flora; [corrected] a retrospective Analysis of a prospectively collected Database.

BACKGROUND: The significance of commensal oropharyngeal flora (COF) as a potential cause of ventilator-associated pneumonia (VAP) is scarcely investigated and consequently unknown. Therefore, the aim of this study was to explore whether COF may cause VAP. METHODS: Retrospective clinical, microbiological and radiographic analysis of all prospectively collected suspected VAP cases in which bronchoalveolar lavage fluid exclusively yielded ≥ 10(4) cfu/ml COF during a 9.5-year period. Characteristics of 899 recent intensive care unit (ICU) admissions were used as a reference population. RESULTS: Out of the prospectively collected database containing 159 VAP cases, 23 patients were included. In these patients, VAP developed after a median of 8 days of mechanical ventilation. The patients faced a prolonged total ICU length of stay (35 days [P < .001]), hospital length of stay (45 days [P = .001]), and a trend to higher mortality (39 % vs. 26 %, [P = .158]; standardized mortality ratio 1.26 vs. 0.77, [P = .137]) compared to the reference population. After clinical, microbiological and radiographic analysis, COF was the most likely cause of respiratory deterioration in 15 patients (9.4 % of all VAP cases) and a possible cause in 2 patients. CONCLUSION: Commensal oropharyngeal flora appears to be a potential cause of VAP in limited numbers of ICU patients as is probably associated with an increased length of stay in both ICU and hospital. As COF-VAP develops late in the course of ICU admission, it is possibly associated with the immunocompromised status of ICU patients.

Endotracheal aspirate and bronchoalveolar lavage fluid analysis: interchangeable diagnostic modalities in suspected ventilator-associated pneumonia?

Authoritative guidelines state that the diagnosis of ventilator-associated pneumonia (VAP) can be established using either endotracheal aspirate (ETA) or bronchoalveolar lavage fluid (BALF) analysis, thereby suggesting that their results are considered to be in accordance. Therefore, the results of ETA Gram staining and semiquantitative cultures were compared to the results from a paired ETA-BALF analysis. Different thresholds for the positivity of ETAs were assessed. This was a prospective study of all patients who underwent bronchoalveolar lavage for suspected VAP in a 27-bed university intensive care unit during an 8-year period. VAP was diagnosed when ≥ 2% of the BALF cells contained intracellular organisms and/or when BALF quantitative culture revealed ≥ 10(4) CFU/ml of potentially pathogenic microorganisms. ETA Gram staining and semiquantitative cultures were compared to the results from paired BALF analysis by Cohen's kappa coefficients. VAP was suspected in 311 patients and diagnosed in 122 (39%) patients. In 288 (93%) patients, the results from the ETA analysis were available for comparison. Depending on the threshold used and the diagnostic modality, VAP incidences varied from 15% to 68%. For the diagnosis of VAP, the most accurate threshold for positivity of ETA semiquantitative cultures was moderate or heavy growth, whereas the optimal threshold for BALF Gram staining was ≥ 1 microorganisms per high power field. The Cohen's kappa coefficients were 0.22, 0.31, and 0.60 for ETA and paired BALF Gram stains, cultures, and BALF Gram stains, respectively. Since the ETA and BALF Gram stains and cultures agreed only fairly, they are probably not interchangeable for diagnosing VAP.

Alternative diagnosis in the putative ventilator-associated pneumonia patient not meeting lavage-based diagnostic criteria.

BACKGROUND: The clinical picture of ventilator-associated pneumonia (VAP) can be mimicked by other infectious and non-infectious diseases. The aim of this study was to determine the alternative diagnoses and to develop a diagnostic flow chart for patients suspected of having VAP not meeting the diagnostic broncho-alveolar lavage (BAL) criteria. METHODS: Adult intensive care patients with a clinical suspicion of VAP and negative BAL results were included. The clinical suspicion of VAP was based on the combination of clinical, radiological, and microbiological criteria. BAL was considered positive if cell differentiation revealed ≥ 2% cells with intracellular organisms and/or quantitative culture results of ≥ 10(4) cfu/ml. The most likely alternative diagnosis of fever and pulmonary densities was retrospectively determined by two authors independently. RESULTS: In all, 110 of 207 patients with suspected VAP did not meet the diagnostic BAL criteria and required further diagnostic evaluation. In 67 patients an alternative diagnosis for fever could be found. In 51 patients an alternative diagnosis of both fever and pulmonary densities could be established. In almost 40% of patients no alternative diagnosis could be provided. Non-bacterial pneumonia was diagnosed in 10 patients with Herpes simplex virus 1 (HSV-1) as the most common pathogen. In eight patients non-infectious pneumonitis was diagnosed. CONCLUSION: Due to the wide range of alternative diagnoses and applied tests the diagnostic work-up proved to be necessarily individualized and guided by repeated clinical assessment. The most frequently found alternative diagnoses were viral pneumonia and non-infectious pneumonitis.

Effects of decontamination of the oropharynx and intestinal tract on antibiotic resistance in ICUs: a randomized clinical trial.

IMPORTANCE: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are prophylactic antibiotic regimens used in intensive care units (ICUs) and associated with improved patient outcome. Controversy exists regarding the relative effects of both measures on patient outcome and antibiotic resistance. OBJECTIVE: To compare the effects of SDD and SOD, applied as unit-wide interventions, on antibiotic resistance and patient outcome. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, cluster randomized crossover trial comparing 12 months of SOD with 12 months of SDD in 16 Dutch ICUs between August 1, 2009, and February 1, 2013. Patients with an expected length of ICU stay longer than 48 hours were eligible to receive the regimens, and 5881 and 6116 patients were included in the clinical outcome analysis for SOD and SDD, respectively. INTERVENTIONS: Intensive care units were randomized to administer either SDD or SOD. MAIN OUTCOMES AND MEASURES: Unit-wide prevalence of antibiotic-resistant gram-negative bacteria. Secondary outcomes were day-28 mortality, ICU-acquired bacteremia, and length of ICU stay. RESULTS: In point-prevalence surveys, prevalences of antibiotic-resistant gram-negative bacteria in perianal swabs were significantly lower during SDD compared with SOD; for aminoglycoside resistance, average prevalence was 5.6% (95% CI, 4.6%-6.7%) during SDD and 11.8% (95% CI, 10.3%-13.2%) during SOD (P < .001). During both interventions the prevalence of rectal carriage of aminoglycoside-resistant gram-negative bacteria increased 7% per month (95% CI, 1%-13%) during SDD (P = .02) and 4% per month (95% CI, 0%-8%) during SOD (P = .046; P = .40 for difference). Day 28-mortality was 25.4% and 24.1% during SOD and SDD, respectively (adjusted odds ratio, 0.96 [95% CI, 0.88-1.06]; P = .42), and there were no statistically significant differences in other outcome parameters or between surgical and nonsurgical patients. Intensive care unit-acquired bacteremia occurred in 5.9% and 4.6% of the patients during SOD and SDD, respectively (odds ratio, 0.77 [95% CI, 0.65-0.91]; P = .002; number needed to treat, 77). CONCLUSIONS AND RELEVANCE: Unit-wide application of SDD and SOD was associated with low levels of antibiotic resistance and no differences in day-28 mortality. Compared with SOD, SDD was associated with lower rectal carriage of antibiotic-resistant gram-negative bacteria and ICU-acquired bacteremia but a more pronounced gradual increase in aminoglycoside-resistant gram-negative bacteria. TRIAL REGISTRATION: trialregister.nlIdentifier: NTR1780.

Serial electrical impedance tomography course in different treatment groups; The MaastrICCht cohort.

PURPOSE: To describe the effect of dexamethasone and tocilizumab on regional lung mechanics over admission in all mechanically ventilated COVID-19 patients. MATERIALS AND METHODS: Dynamic compliance, alveolar overdistension and collapse were serially determined using electric impedance tomography (EIT). Patients were categorized into three groups; no anti-inflammatory therapy, dexamethasone therapy, dexamethasone + tocilizumab therapy. The EIT variables were (I) visualized using polynomial regression, (II) evaluated throughout admission using linear mixed-effects models, and (III) average respiratory variables were compared. RESULTS: Visual inspection of EIT variables showed a pattern of decreasing dynamic compliance. Overall, optimal set PEEP was lower in the dexamethasone group (-1.4 cmH2O, -2.6; -0.2). Clinically applied PEEP was lower in the dexamethasone and dexamethasone + tocilizumab group (-1.5 cmH2O, -2.6; -0.2; -2.2 cmH2O, -5.1; 0.6). Dynamic compliance, alveolar overdistension, and alveolar collapse at optimal set PEEP did not significantly differ between the three groups. CONCLUSION: Optimal and clinically applied PEEP were lower in the dexamethasone and dexamethasone + tocilizumab groups. The results suggest that the potential beneficial effects of these therapies do not affect lung mechanics favorably. However, this study cannot fully rule out any beneficial effect of anti-inflammatory treatment on pulmonary function due to its observational nature.

Pulmonary response prediction through personalized basis functions in a virtual patient model.

BACKGROUND AND OBJECTIVE: Recruitment maneuvers with subsequent positive-end-expiratory-pressure (PEEP) have proven effective in recruiting lung volume and preventing alveoli collapse. However, determining a safe, effective, and patient-specific PEEP is not standardized, and this more optimal PEEP level evolves with patient condition, requiring personalised monitoring and care approaches to maintain optimal ventilation settings. METHODS: This research examines 3 physiologically relevant basis function sets (exponential, parabolic, cumulative) to enable better prediction of elastance evolution for a virtual patient or digital twin model of MV lung mechanics, including novel elements to model and predict distension elastance. Prediction accuracy and robustness are validated against recruitment maneuver data from 18 volume-controlled ventilation (VCV) patients at 7 different baseline PEEP levels (0 to 12 cmH2O) and 14 pressure-controlled ventilation (PCV) patients at 4 different baseline PEEP levels (6 to 12 cmH2O), yielding 623 and 294 prediction cases, respectively. Predictions were made up to 12 cmH2O of added PEEP ahead, covering 6 × 2 cmH2O PEEP steps. RESULTS: The 3 basis function sets yield median absolute peak inspiratory pressure (PIP) prediction error of 1.63 cmH2O for VCV patients, and median peak inspiratory volume (PIV) prediction error of 0.028 L for PCV patients. The exponential basis function set yields a better trade-off of overall performance across VCV and PCV prediction than parabolic and cumulative basis function sets from other studies. Comparing predicted and clinically measured distension prediction in VCV demonstrated consistent, robust high accuracy with R2 = 0.90-0.95. CONCLUSIONS: The results demonstrate recruitment mechanics are best captured by an exponential basis function across different mechanical ventilation modes, matching physiological expectations, and accurately capture, for the first time, distension mechanics to within 5-10 % accuracy. Enabling the risk of lung injury to be predicted before changing ventilator settings. The overall outcomes significantly extend and more fully validate this digital twin or virtual mechanical ventilation patient model.