Performance of Lung Ultrasound for Monitoring Interstitial Lung Disease.

OBJECTIVES: In this study, we sought to assess the validity of lung ultrasound (LUS) during the follow-up of patients with a wide spectrum of interstitial lung diseases (ILDs). METHODS: Twenty-four patients (13 males, 11 females; mean age ± SD, 65.4 ± 14.3 years; age range, 40-84 years) with a diagnosis of ILDs who were admitted to the Interstitial Lung Disease Unit were prospectively enrolled. Patients were examined with a 56-lung intercostal space LUS protocol in lateral decubitus position, at baseline, 6-months, and 1-year. The LUS score was defined as the sum of B-lines counted in each intercostal space. All patients underwent complete pulmonary function tests at baseline and follow-up time-points. High-resolution computed tomography (HRCT) was performed at baseline and during follow-up, according to personalized patients' needs. All HRCT studies were graded according to the Warrick scoring system (WS). RESULTS: Pooled data analysis showed a significant correlation between WS and LUS scores (P < .001). For separate time-point analysis, a significant correlation between LUS scores and WS was found at baseline (P < .001) and 1 year (P = .005). LUS scores negatively correlated with alveolar volume (VA) (P < .046) and diffusing capacity for carbon monoxide (DLCO) (P < .001) at 6 months and with transfer coefficient of the lung for carbon monoxide (KCO) (P < .031) and DLCO (P = .002) at 12-months. A multivariate regression model showed DLCO to be an independent predictor of LUS score at 1 year (P = .026). CONCLUSIONS: Our results highlight the validity and potential applicability of LUS for disease monitoring in a wide spectrum of ILDs.

A Model Predicting the 6-Month Disability of Patients With Traumatic Brain Injury to Assess the Quality of Care in Intensive Care Units: Results from the CREACTIVE Study.

Assessing quality of care is essential for improving the management of patients experiencing traumatic brain injury (TBI). This study aimed at devising a rigorous framework to evaluate the quality of TBI care provided by intensive care units (ICUs) and applying it to the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) consortium, which involved 83 ICUs from seven countries. The performance of the centers was assessed in terms of patients' outcomes, as measured by the 6-month Glasgow Outcome Scale-Extended (GOS-E). To account for the between-center differences in the characteristics of the admitted patients, we developed a multinomial logistic regression model estimating the probability of a four-level categorization of the GOS-E: good recovery (GR), moderate disability (MD), severe disability (SD), and death or vegetative state (D/VS). A total of 5928 patients admitted to the participating ICUs between March 2014 and March 2019 were analyzed. The model included 11 predictors and demonstrated good discrimination (area under the receiver operating characteristic [ROC] curve in the validation set for GR: 0.836, MD: 0.802, SD: 0.706, D/VS: 0.890) and calibration, both overall (Hosmer-Lemeshow test p value: 0.87) and in several subgroups, defined by prognostically relevant variables. The model was used as a benchmark for assessing quality of care by comparing the observed number of patients experiencing GR, MD, SD, and D/VS to the corresponding numbers expected in each category by the model, computing observed/expected (O/E) ratios. The four center-specific ratios were assembled with polar representations and used to provide a multidimensional assessment of the ICUs, overcoming the loss of information consequent to the traditional dichotomizations of the outcome in TBI research. The proposed framework can help in identifying strengths and weaknesses of current TBI care, triggering the changes that are necessary to improve patient outcomes.

Comparative Effectiveness of Intracranial Pressure Monitoring on 6-Month Outcomes of Critically Ill Patients With Traumatic Brain Injury.

Importance: While the relationship between persistent elevations in intracranial pressure (ICP) and poorer outcomes is well established for patients with traumatic brain injury (TBI), there is no consensus on how ICP measurements should drive treatment choices, and the effectiveness of ICP monitoring remains unknown. Objective: To evaluate the effectiveness of ICP monitoring on short- and mid-term outcomes of patients with TBI. Design, Setting, and Participants: CREACTIVE was a prospective cohort study that started in March 2014 and lasted 5 years. More than 8000 patients with TBI were enrolled at 83 intensive care units (ICUs) from 7 countries who joined the CREACTIVE Consortium. Patients with TBI who met the Brain Trauma Foundation guidelines for ICP monitoring were selected for the current analyses, which were performed from January to November 2022. Exposure: Patients who underwent ICP monitoring within 2 days of injury (exposure group) were propensity score-matched to patients who were not monitored or who underwent monitoring 2 days after the injury (control group). Main Outcome and Measure: Functional disability at 6 months as indicated by Glasgow Outcome Scale-Extended (GOS-E) score. Results: A total of 1448 patients from 43 ICUs in Italy and Hungary were eligible for analysis. Of the patients satisfying the ICP-monitoring guidelines, 503 (34.7%) underwent ICP monitoring (median [IQR] age: 45 years [29-61 years]; 392 males [77.9%], 111 females [22.1%]) and 945 were not monitored (median [IQR] age: 66 years [48-78 years]; 656 males [69.4%], 289 females [30.6%]). After matching to balance the variables, worse 6-month recovery was observed for monitored patients compared with nonmonitored patients (death/vegetative state: 39.2% vs 40.6%; severe disability: 33.2% vs 25.4%; moderate disability: 15.7% vs 14.9%; good recovery: 11.9% vs 19.1%, respectively; P = .005). Monitored patients received medical therapies significantly more frequently. Conclusions and Relevance: In this cohort study, ICP monitoring was associated with poorer recovery and more frequent medical interventions with their relevant adverse effects. Optimizing the value of ICP monitoring for TBI requires further investigation on monitoring indications, clinical interventions, and management protocols.

Effect of albuterol on expiratory resistance in mechanically ventilated patients.

BACKGROUND: In mechanically ventilated patients with COPD, the response of the expiratory resistance of the respiratory system (expiratory R(RS)) to bronchodilators is virtually unknown. OBJECTIVE: To examine the effect of inhaled albuterol on expiratory R(RS), and the correlation of albuterol-induced changes in expiratory R(RS) with end-inspiratory resistance and the expiratory flow-volume relationship. METHODS: We studied 10 mechanically ventilated patients with COPD exacerbation, before and 30 min after administration of albuterol. We obtained flow-volume curves during passive expiration, divided the expired volume into 5 equal volume slices, and then calculated the time constant and dynamic effective deflation compliance of the respiratory system (effective deflation C(RS)) of each slice via regression analysis of the volume-flow and post-occlusion volume-tracheal pressure relationships, respectively. For each slice we calculated expiratory R(RS) as the time constant divided by the effective deflation C(RS). RESULTS: Albuterol significantly decreased the expiratory R(RS) (mean expiratory R(RS) 42.68 ± 17.8 cm H(2)O/L/s vs 38.08 ± 16.1 cm H(2)O/L/s) and increased the rate of lung emptying toward the end of expiration (mean time constant 2.51 ± 1.2 s vs 2.21 ± 1.2 s). No correlation was found between the albuterol-induced changes in expiratory R(RS) and that of end-inspiratory resistance. Only at the end of expiration did albuterol-induced changes in the expiratory flow-volume relationship correlate with changes in expiratory R(RS) in all patients. CONCLUSIONS: In patients with COPD, albuterol significantly decreases expiratory resistance at the end of expiration. In mechanically ventilated patients, neither inspiratory resistance nor the whole expiratory flow-volume curve may be used to evaluate the bronchodilator response of expiratory resistance.

Prognostic Value of a Combination of Circulating Biomarkers in Critically Ill Patients with Traumatic Brain Injury: Results from the European CREACTIVE Study.

Individualized patient care is essential to reduce the global burden of traumatic brain injury (TBI). This pilot study focused on TBI patients admitted to intensive care units (ICUs) and aimed at identifying patterns of circulating biomarkers associated with the disability level at 6 months from injury, measured by the extended Glasgow Outcome Scale (GOS-E). The concentration of 107 biomarkers, including proteins related to inflammation, innate immunity, TBI, and central nervous system, were quantified in blood samples collected on ICU admission from 80 patients. Patients were randomly selected among those prospectively enrolled in the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) observational study. Six biomarkers were selected to be associated with indicators of primary or secondary brain injury: three glial proteins (glial cell-derived neurotrophic factor, glial fibrillary acidic protein, and S100 calcium-binding protein B) and three cytokines (stem cell factor, fibroblast growth factor [FGF] 23 and FGF19). The subjects were grouped into three clusters according to the expression of these proteins. The distribution of the 6-month GOS-E was significantly different across clusters (p < 0.001). In two clusters, the number of 6-month deaths or vegetative states was significantly lower than expected, as calculated according to a customization of the corticosteroid randomization after significant head injury (CRASH) scores (observed/expected [O/E] events = 0.00, 95% confidence interval [CI]: 0.00-0.90 and 0.00, 95% CI: 0.00-0.94). In one cluster, less-than-expected unfavorable outcomes (O/E = 0.50, 95% CI: 0.05-0.95) and more-than-expected good recoveries (O/E = 1.55, 95% CI: 1.05-2.06) were observed. The improved prognostic accuracy of the pattern of these six circulating biomarkers at ICU admission upon established clinical parameters and computed tomography results needs validation in larger, independent cohorts. Nonetheless, the results of this pilot study are promising and will prompt further research in personalized medicine for TBI patients.

Hospitals with and without neurosurgery: a comparative study evaluating the outcome of patients with traumatic brain injury.

BACKGROUND: We leveraged the data of the international CREACTIVE consortium to investigate whether the outcome of traumatic brain injury (TBI) patients admitted to intensive care units (ICU) in hospitals without on-site neurosurgical capabilities (no-NSH) would differ had the same patients been admitted to ICUs in hospitals with neurosurgical capabilities (NSH). METHODS: The CREACTIVE observational study enrolled more than 8000 patients from 83 ICUs. Adult TBI patients admitted to no-NSH ICUs within 48 h of trauma were propensity-score matched 1:3 with patients admitted to NSH ICUs. The primary outcome was the 6-month extended Glasgow Outcome Scale (GOS-E), while secondary outcomes were ICU and hospital mortality. RESULTS: A total of 232 patients, less than 5% of the eligible cohort, were admitted to no-NSH ICUs. Each of them was matched to 3 NSH patients, leading to a study sample of 928 TBI patients where the no-NSH and NSH groups were well-balanced with respect to all of the variables included into the propensity score. Patients admitted to no-NSH ICUs experienced significantly higher ICU and in-hospital mortality. Compared to the matched NSH ICU admissions, their 6-month GOS-E scores showed a significantly higher prevalence of upper good recovery for cases with mild TBI and low expected mortality risk at admission, along with a progressively higher incidence of poor outcomes with increased TBI severity and mortality risk. CONCLUSIONS: In our study, centralization of TBI patients significantly impacted short- and long-term outcomes. For TBI patients admitted to no-NSH centers, our results suggest that the least critically ill can effectively be managed in centers without neurosurgical capabilities. Conversely, the most complex patients would benefit from being treated in high-volume, neuro-oriented ICUs.

PROSAFE: a European endeavor to improve quality of critical care medicine in seven countries.

BACKGROUND: Long-lasting shared research databases are an important source of epidemiological information and can promote comparison between different healthcare services. Here we present PROSAFE, an advanced international research network in intensive care medicine, with the focus on assessing and improving the quality of care. The project involved 343 ICUs in seven countries. All patients admitted to the ICU were eligible for data collection. METHODS: The PROSAFE network collected data using the same electronic case report form translated into the corresponding languages. A complex, multidimensional validation system was implemented to ensure maximum data quality. Individual and aggregate reports by country, region, and ICU type were prepared annually. A web-based data-sharing system allowed participants to autonomously perform different analyses on both own data and the entire database. RESULTS: The final analysis was restricted to 262 general ICUs and 432,223 adult patients, mostly admitted to Italian units, where a research network had been active since 1991. Organization of critical care medicine in the seven countries was relatively similar, in terms of staffing, case mix and procedures, suggesting a common understanding of the role of critical care medicine. Conversely, ICU equipment differed, and patient outcomes showed wide variations among countries. CONCLUSIONS: PROSAFE is a permanent, stable, open access, multilingual database for clinical benchmarking, ICU self-evaluation and research within and across countries, which offers a unique opportunity to improve the quality of critical care. Its entry into routine clinical practice on a voluntary basis is testimony to the success and viability of the endeavor.

Proportional assist ventilation with load-adjustable gain factors in critically ill patients: comparison with pressure support.

OBJECTIVES: It is not known if proportional assist ventilation with load-adjustable gain factors (PAV+) may be used as a mode of support in critically ill patients. The aim of this study was to examine the effectiveness of sustained use of PAV+ in critically ill patients and compare it with pressure support ventilation (PS). DESIGN AND SETTING: Randomized study in the intensive care unit of a university hospital. METHODS: A total of 208 critically ill patients mechanically ventilated on controlled modes for at least 36 h and meeting certain criteria were randomized to receive either PS (n = 100) or PAV+ (n = 108). Specific written algorithms were used to adjust the ventilator settings in each mode. PAV+ or PS was continued for 48 h unless the patients met pre-defined criteria either for switching to controlled modes (failure criteria) or for breathing without ventilator assistance. RESULTS: Failure rate was significantly lower in PAV+ than that in PS (11.1 vs. 22.0%, P = 0.040, OR 0.443, 95% CI 0.206-0.952). The proportion of patients exhibiting major patient-ventilator dyssynchronies at least during one occasion and after adjusting the initial ventilator settings, was significantly lower in PAV+ than in PS (5.6 vs. 29.0%, P < 0.001, OR 0.1, 95% CI 0.06-0.4). The proportion of patients meeting criteria for unassisted breathing did not differ between modes. CONCLUSIONS: PAV+ may be used as a useful mode of support in critically ill patients. Compared to PS, PAV+ increases the probability of remaining on spontaneous breathing, while it considerably reduces the incidence of patient-ventilator asynchronies.

Diagnostic value of interleukin-1alpha, interleukin-6, and tumor necrosis factor in pleural effusions.

STUDY OBJECTIVES: Interleukin (IL)-1alpha, IL-6, and tumor necrosis factor (TNF)-alpha were measured in pleural fluid from 57 patients with pleural effusion in order to evaluate the diagnostic utility of these cytokines. We studied 20 patients with malignant pleural effusion, 11 patients with parapneumonic pleural effusion, 9 patients with tuberculous pleural effusion, and 17 patients with transudative pleural effusion. Cytokines were measured by radioimmunoassay. SETTING: University tertiary hospital. RESULTS: The mean values of the three cytokines measured in pleural fluid or in serum were significantly higher in patients with exudates than with transudates (p < 0.05). The ratio of IL-6 in pleural fluid to serum was significantly higher in exudates than in transudates (p < 0.05). The level of IL-6 in pleural fluid was significantly higher in tuberculous than malignant (p < 0.007) or parapneumonic pleural effusions (p < 0.04). No significant difference between the three types of exudates was found in pleural fluid levels of IL-1alpha or TNF-alpha. CONCLUSIONS: Serum levels of IL-1alpha, TNF-alpha, and in particular IL-6 can distinguish exudates from transudates, while pleural fluid IL-6 levels could be useful as an additional marker in the differential diagnosis of tuberculous, malignant, and parapneumonic exudates. Finally, our results suggest that there is local cytokine production in exudative pleural effusions.

Impact of lung ultrasound on clinical decision making in critically ill patients.

PURPOSE: To assess the impact of lung ultrasound (LU) on clinical decision making in mechanically ventilated critically ill patients. METHODS: One hundred and eighty-nine patients took part in this prospective study. The patients were enrolled in the study when LU was requested by the primary physician for (1) unexplained deterioration of arterial blood gases and (2) a suspected pathologic entity [pneumothorax, significant pleural effusion (including parapneumonic effusion, empyema, or hemothorax), unilateral atelectasis (lobar or total), pneumonia and diffuse interstitial syndrome (pulmonary edema)]. RESULTS: Two hundred and fifty-three LU examinations were performed; 108 studies (42.7%) were performed for unexplained deterioration of arterial blood gases, and 145 (57.3%) for a suspected pathologic entity (60 for pneumothorax, 34 for significant pleural effusion, 22 for diffuse interstitial syndrome, 15 for unilateral lobar or total lung atelectasis, and 14 for pneumonia). The net reclassification index was 85.6%, indicating that LU significantly influenced the decision-making process. The management was changed directly as a result of information provided by the LU in 119 out of 253 cases (47%). In 81 cases, the change in patient management involved invasive interventions (chest tube, bronchoscopy, diagnostic thoracentesis/fluid drainage, continuous venous-venous hemofiltration, abdominal decompression, tracheotomy), and in 38 cases, non-invasive (PEEP change/titration, recruitment maneuver, diuretics, physiotherapy, change in bed position, antibiotics initiation/change). In 53 out of 253 cases (21%), LU revealed findings which supported diagnoses not suspected by the primary physician (7 cases of pneumothorax, 9 of significant pleural effusion, 9 of pneumonia, 16 of unilateral atelectasis, and 12 of diffuse interstitial syndrome). CONCLUSION: Our study shows that LU has a significant impact on decision making and therapeutic management.

Lung ultrasound in critically ill patients: comparison with bedside chest radiography.

PURPOSE: To compare the diagnostic performance of lung ultrasound and bedside chest radiography (CXR) for the detection of various pathologic abnormalities in unselected critically ill patients, using thoracic computed tomography (CT) as a gold standard. METHODS: Forty-two mechanically ventilated patients scheduled for CT were prospectively studied with a modified lung ultrasound protocol. Four pathologic entities were evaluated: consolidation, interstitial syndrome, pneumothorax, and pleural effusion. Each hemithorax was evaluated for the presence or absence of each abnormality. RESULTS: Eighty-four hemithoraces were evaluated by the three imaging techniques. The sensitivity, specificity, and diagnostic accuracy of CXR were 38, 89, and 49% for consolidation, 46, 80, and 58% for interstitial syndrome, 0, 99, and 89% for pneumothorax, and 65, 81, and 69% for pleural effusion, respectively. The corresponding values for lung ultrasound were 100, 78, and 95% for consolidation, 94, 93, and 94% for interstitial syndrome, 75, 93, and 92% for pneumothorax, and 100, 100, and 100% for pleural effusion, respectively. The relatively low sensitivity of lung ultrasound for pneumothorax could be due to small number of cases (n = 8) and/or suboptimal methodology. CONCLUSIONS: In our unselected general ICU population lung ultrasound has a considerably better diagnostic performance than CXR for the diagnosis of common pathologic conditions and may be used as an alternative to thoracic CT.

Modulation and treatment of patient-ventilator dyssynchrony.

PURPOSE OF REVIEW: The coupling between ventilator delivered inspiratory flow and patient's demands both in terms of timing and drive is a challenging task that has become largely feasible in recent years. This review addresses the new advances to modulate and treat patient-ventilator dyssynchrony. RECENT FINDINGS: Patient-ventilator dyssynchrony is a common phenomenon with conventional modes of mechanical ventilation which influence the duration of mechanical ventilation. Inspection of pressure, volume and flow waveforms represents a valuable tool for the physician to recognize and take the appropriate action to improve patient-ventilator synchrony. New developments have been introduced aiming to improve patient ventilator synchrony by modulating the triggering function and the variables that control the flow delivery and the cycling off. SUMMARY: Patient-ventilator dyssynchrony may affect patients' outcome. New modes of assisted mechanical ventilation have been introduced and represent a major step forward in modulating patient-ventilator dyssynchrony.