National ICU Registries as Enablers of Clinical Research and Quality Improvement.

OBJECTIVES: Clinical quality registries (CQRs) have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. This narrative review describes the challenges, proposed solutions, and evidence generated by National ICU registries as facilitators for research and quality improvement. DATA SOURCES: English language articles were identified in PubMed using phrases related to ICU registries, CQRs, outcomes, and case-mix. STUDY SELECTION: Original research, review articles, letters, and commentaries, were considered. DATA EXTRACTION: Data from relevant literature were identified, reviewed, and integrated into a concise narrative review. DATA SYNTHESIS: CQRs have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. The initial experience in European countries and in Oceania ensured that through locally generated data, ICUs could assess their performances by using risk-adjusted measures and compare their results through fair and validated benchmarking metrics with other ICUs contributing to the CQR. The accomplishment of these initiatives, coupled with the increasing adoption of information technology, resulted in a broad geographic expansion of CQRs as well as their use in quality improvement studies, clinical trials as well as international comparisons, and benchmarking for ICUs. CONCLUSIONS: ICU registries have provided increased knowledge of case-mix and outcomes of ICU patients based on real-world data and contributed to improve care delivery through quality improvement initiatives and trials. Recent increases in adoption of new technologies (i.e., cloud-based structures, artificial intelligence, machine learning) will ensure a broader and better use of data for epidemiology, healthcare policies, quality improvement, and clinical trials.

Cerebellar phenotypes in germline PTEN mutation carriers.

PTEN hamartoma tumour syndrome (PHTS) comprises different hereditary conditions caused by germline PTEN mutations, predisposing to the development of multiple hamartomas in many body tissues and also increasing the risk of some types of cancer. Cerebellar involvement in PHTS patients has been long known due to the development of a pathognomonic cerebellar hamartoma (known as dysplastic gangliocytoma of the cerebellum or Lhermitte-Duclos disease). Recently, a crucial role of the cerebellum has been highlighted in the pathogenesis of autism spectrum disorders, now recognised as a phenotype expressed in a variable percentage of PHTS children. In addition, rare PTEN variants are indeed identified in medulloblastoma as well, even if they are less frequent than other germline gene mutations. The importance of PTEN and its downstream signalling enzymatic pathways, PI3K/AKT/mTOR, has been studied at different levels in both human clinical settings and animal models, not only leading to a better understanding of the pathogenesis of different disorders but, most importantly, to identify potential targets for specific therapies. In particular, PTEN integrity makes an important contribution to the normal development of tissue architecture in the nervous system, including the cerebellum. Thus, in patients with PTEN germline mutations, the cerebellum is an affected organ that is increasingly recognised in different disorders, whereas, in animal models, cerebellar Pten loss causes a variety of functional and histological alterations. In this review, we summarise the range of cerebellar involvement observed in PHTS and its relationships with germline PTEN mutations, along with the phenotypes expressed by murine models with PTEN deficiency in cerebellar tissue.

Epidemiology, ventilation management and outcomes of COVID-19 ARDS patients versus patients with ARDS due to pneumonia in the Pre-COVID era.

BACKGROUND: Ventilation management may differ between COVID-19 ARDS (COVID-ARDS) patients and patients with pre-COVID ARDS (CLASSIC-ARDS); it is uncertain whether associations of ventilation management with outcomes for CLASSIC-ARDS also exist in COVID-ARDS. METHODS: Individual patient data analysis of COVID-ARDS and CLASSIC-ARDS patients in six observational studies of ventilation, four in the COVID-19 pandemic and two pre-pandemic. Descriptive statistics were used to compare epidemiology and ventilation characteristics. The primary endpoint were key ventilation parameters; other outcomes included mortality and ventilator-free days and alive (VFD-60) at day 60. RESULTS: This analysis included 6702 COVID-ARDS patients and 1415 CLASSIC-ARDS patients. COVID-ARDS patients received lower median VT (6.6 [6.0 to 7.4] vs 7.3 [6.4 to 8.5] ml/kg PBW; p < 0.001) and higher median PEEP (12.0 [10.0 to 14.0] vs 8.0 [6.0 to 10.0] cm H2O; p < 0.001), at lower median ΔP (13.0 [10.0 to 15.0] vs 16.0 [IQR 12.0 to 20.0] cm H2O; p < 0.001) and higher median Crs (33.5 [26.6 to 42.1] vs 28.1 [21.6 to 38.4] mL/cm H2O; p < 0.001). Following multivariable adjustment, higher ΔP had an independent association with higher 60-day mortality and less VFD-60 in both groups. Higher PEEP had an association with less VFD-60, but only in COVID-ARDS patients. CONCLUSIONS: Our findings show important differences in key ventilation parameters and associations thereof with outcomes between COVID-ARDS and CLASSIC-ARDS. TRIAL REGISTRATION: Clinicaltrials.gov (identifier NCT05650957), December 14, 2022.

Diagnostic accuracy of lung ultrasound in diagnosis of ARDS and identification of focal or non-focal ARDS subphenotypes: a systematic review and meta-analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory condition with high mortality rates, accounting for 10% of all intensive care unit admissions. Lung ultrasound (LUS) as diagnostic tool for acute respiratory failure has garnered widespread recognition and was recently incorporated into the updated definitions of ARDS. This raised the hypothesis that LUS is a reliable method for diagnosing ARDS. OBJECTIVES: We aimed to establish the accuracy of LUS for ARDS diagnosis and classification of focal versus non-focal ARDS subphenotypes. METHODS: This systematic review and meta-analysis used a systematic search strategy, which was applied to PubMed, EMBASE and cochrane databases. Studies investigating the diagnostic accuracy of LUS compared to thoracic CT or chest radiography (CXR) in ARDS diagnosis or focal versus non-focal subphenotypes in adult patients were included. Quality of studies was evaluated using the QUADAS-2 tool. Statistical analyses were performed using "Mada" in Rstudio, version 4.0.3. Sensitivity and specificity with 95% confidence interval of each separate study were summarized in a Forest plot. RESULTS: The search resulted in 2648 unique records. After selection, 11 reports were included, involving 2075 patients and 598 ARDS cases (29%). Nine studies reported on ARDS diagnosis and two reported on focal versus non-focal ARDS subphenotypes classification. Meta-analysis showed a pooled sensitivity of 0.631 (95% CI 0.450-0.782) and pooled specificity of 0.942 (95% CI 0.856-0.978) of LUS for ARDS diagnosis. In two studies, LUS could accurately differentiate between focal versus non-focal ARDS subphenotypes. Insufficient data was available to perform a meta-analysis. CONCLUSION: This review confirms the hypothesis that LUS is a reliable method for diagnosing ARDS in adult patients. For the classification of focal or non-focal subphenotypes, LUS showed promising results, but more research is needed.

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.

The Impact of Thoracic Ultrasound on Clinical Management of Critically Ill Patients (UltraMan): An International Prospective Observational Study.

OBJECTIVES: To investigate the impact of thoracic ultrasound (TUS) examinations on clinical management in adult ICU patients. DESIGN: A prospective international observational study. SETTING: Four centers in The Netherlands and Italy. PATIENTS: Adult ICU patients (> 18 yr) that received a clinically indicated lung ultrasound examination. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinicians performing TUS completed a pre- and post-examination case report form. Patient characteristics, TUS, and resulting clinical effects were recorded. First, change of management, defined as a TUS-induced change in clinical impression leading to a change in treatment plan, was reported. Second, execution of intended management changes within 8 hours was verified. Third, change in fluid balance after 8 hours was calculated. A total of 725 TUS performed by 111 operators across 534 patients (mean age 63 ± 15.0, 70% male) were included. Almost half of TUS caused a change in clinical impression, which resulted in change of management in 39% of cases. The remainder of TUS confirmed the clinical impression, while a minority (4%) did not contribute. Eighty-nine percent of management changes indicated by TUS were executed within 8 hours. TUS examinations that led to a change in fluid management also led to distinct and appropriate changes in patient's fluid balance. CONCLUSIONS: In this international observational study in adult ICU patients, use of TUS had a major impact on clinical management. These results provide grounds for future randomized controlled trials to determine if TUS-induced changes in decision-making also lead to improved health outcomes.

Clinical benefit of AI-assisted lung ultrasound in a resource-limited intensive care unit.

BACKGROUND: Interpreting point-of-care lung ultrasound (LUS) images from intensive care unit (ICU) patients can be challenging, especially in low- and middle- income countries (LMICs) where there is limited training available. Despite recent advances in the use of Artificial Intelligence (AI) to automate many ultrasound imaging analysis tasks, no AI-enabled LUS solutions have been proven to be clinically useful in ICUs, and specifically in LMICs. Therefore, we developed an AI solution that assists LUS practitioners and assessed its usefulness in  a low resource ICU. METHODS: This was a three-phase prospective study. In the first phase, the performance of four different clinical user groups in interpreting LUS clips was assessed. In the second phase, the performance of 57 non-expert clinicians with and without the aid of a bespoke AI tool for LUS interpretation was assessed in retrospective offline clips. In the third phase, we conducted a prospective study in the ICU where 14 clinicians were asked to carry out LUS examinations in 7 patients with and without our AI tool and we interviewed the clinicians regarding the usability of the AI tool. RESULTS: The average accuracy of beginners' LUS interpretation was 68.7% [95% CI 66.8-70.7%] compared to 72.2% [95% CI 70.0-75.6%] in intermediate, and 73.4% [95% CI 62.2-87.8%] in advanced users. Experts had an average accuracy of 95.0% [95% CI 88.2-100.0%], which was significantly better than beginners, intermediate and advanced users (p < 0.001). When supported by our AI tool for interpreting retrospectively acquired clips, the non-expert clinicians improved their performance from an average of 68.9% [95% CI 65.6-73.9%] to 82.9% [95% CI 79.1-86.7%], (p < 0.001). In prospective real-time testing, non-expert clinicians improved their baseline performance from 68.1% [95% CI 57.9-78.2%] to 93.4% [95% CI 89.0-97.8%], (p < 0.001) when using our AI tool. The time-to-interpret clips improved from a median of 12.1 s (IQR 8.5-20.6) to 5.0 s (IQR 3.5-8.8), (p < 0.001) and clinicians' median confidence level improved from 3 out of 4 to 4 out of 4 when using our AI tool. CONCLUSIONS: AI-assisted LUS can help non-expert clinicians in an LMIC ICU improve their performance in interpreting LUS features more accurately, more quickly and more confidently.

Impact and burden of sickle cell disease in critically ill obstetric patients in a high dependency unit in Sierra Leone-a registry based evaluation.

INTRODUCTION: Sickle cell disease (SCD) in pregnancy is associated with worse maternal and neonatal outcomes. There is limited available data describing the burden and outcomes of critically ill obstetric patients affected by SCD in low-income settings. OBJECTIVES: We aimed to define SCD burden and impact on mortality in critically-ill obstetric patients admitted to an urban referral hospital in Sierra Leone. We hypothesized that SCD burden is high and independently associated with increased mortality. METHODS: We performed a registry-based cross-sectional study from March 2020 to December 2021 in the high-dependency unit (HDU) of Princess Christian Maternity Hospital PCMH, Freetown. Primary endpoints were the proportion of patients identified in the SCD group and HDU mortality. Secondary endpoints included frequency of maternal direct obstetric complications (MDOCs) and the maternal early obstetric warning score (MEOWS). RESULTS: Out of a total of 497 patients, 25 (5.5%) qualified to be included in the SCD group. MEOWS on admission was not different between patients with and without SCD and SCD patients had also less frequently reported MDOCs. Yet, crude HDU mortality in the SCD group was 36%, compared to 9.5% in the non SCD group (P < 0.01), with an independent association between SCD group exposure and mortality when accounting for severity on admission (hazard ratio 3.40; 95%CI 1.57-7.39; P = 0.002). Patients with SCD had a tendency to longer HDU length of stay. CONCLUSIONS: One out of twenty patients accessing a HDU in Sierra Leone fulfilled criteria for SCD. Despite comparable severity on admission, mortality in SCD patients was four times higher than patients without SCD. Optimization of intermediate and intensive care for this group of patients should be prioritized in low-resource settings with high maternal mortality.

Latent class analysis of imaging and clinical respiratory parameters from patients with COVID-19-related ARDS identifies recruitment subphenotypes.

BACKGROUND: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) require respiratory support with invasive mechanical ventilation and show varying responses to recruitment manoeuvres. In patients with ARDS not related to COVID-19, two pulmonary subphenotypes that differed in recruitability were identified using latent class analysis (LCA) of imaging and clinical respiratory parameters. We aimed to evaluate if similar subphenotypes are present in patients with COVID-19-related ARDS. METHODS: This is the retrospective analysis of mechanically ventilated patients with COVID-19-related ARDS who underwent CT scans at positive end-expiratory pressure of 10 cmH2O and after a recruitment manoeuvre at 20 cmH2O. LCA was applied to quantitative CT-derived parameters, clinical respiratory parameters, blood gas analysis and routine laboratory values before recruitment to identify subphenotypes. RESULTS: 99 patients were included. Using 12 variables, a two-class LCA model was identified as best fitting. Subphenotype 2 (recruitable) was characterized by a lower PaO2/FiO2, lower normally aerated lung volume and lower compliance as opposed to a higher non-aerated lung mass and higher mechanical power when compared to subphenotype 1 (non-recruitable). Patients with subphenotype 2 had more decrease in non-aerated lung mass in response to a standardized recruitment manoeuvre (p = 0.024) and were mechanically ventilated longer until successful extubation (adjusted SHR 0.46, 95% CI 0.23-0.91, p = 0.026), while no difference in survival was found (p = 0.814). CONCLUSIONS: A recruitable and non-recruitable subphenotype were identified in patients with COVID-19-related ARDS. These findings are in line with previous studies in non-COVID-19-related ARDS and suggest that a combination of imaging and clinical respiratory parameters could facilitate the identification of recruitable lungs before the manoeuvre.

Flow Index: a novel, non-invasive, continuous, quantitative method to evaluate patient inspiratory effort during pressure support ventilation.

BACKGROUND: The evaluation of patient effort is pivotal during pressure support ventilation, but a non-invasive, continuous, quantitative method to assess patient inspiratory effort is still lacking. We hypothesized that the concavity of the inspiratory flow-time waveform could be useful to estimate patient's inspiratory effort. The purpose of this study was to assess whether the shape of the inspiratory flow, as quantified by a numeric indicator, could be associated with inspiratory effort during pressure support ventilation. METHODS: Twenty-four patients in pressure support ventilation were enrolled. A mathematical relationship describing the decay pattern of the inspiratory flow profile was developed. The parameter hypothesized to estimate effort was named Flow Index. Esophageal pressure, airway pressure, airflow, and volume waveforms were recorded at three support levels (maximum, minimum and baseline). The association between Flow Index and reference measures of patient effort (pressure time product and pressure generated by respiratory muscles) was evaluated using linear mixed effects models adjusted for tidal volume, respiratory rate and respiratory rate/tidal volume. RESULTS: Flow Index was different at the three pressure support levels and all group comparisons were statistically significant. In all tested models, Flow Index was independently associated with patient effort (p < 0.001). Flow Index prediction of inspiratory effort agreed with esophageal pressure-based methods. CONCLUSIONS: Flow Index is associated with patient inspiratory effort during pressure support ventilation, and may provide potentially useful information for setting inspiratory support and monitoring patient-ventilator interactions.

Flow Index accurately identifies breaths with low or high inspiratory effort during pressure support ventilation.

BACKGROUND: Flow Index, a numerical expression of the shape of the inspiratory flow-time waveform recorded during pressure support ventilation, is associated with patient inspiratory effort. The aim of this study was to assess the accuracy of Flow Index in detecting high or low inspiratory effort during pressure support ventilation and to establish cutoff values for the Flow index to identify these conditions. The secondary aim was to compare the performance of Flow index,of breathing pattern parameters and of airway occlusion pressure (P0.1) in detecting high or low inspiratory effort during pressure support ventilation. METHODS: Data from 24 subjects was included in the analysis, accounting for a total of 702 breaths. Breaths with high inspiratory effort were defined by a pressure developed by inspiratory muscles (Pmusc) greater than 10 cmH2O while breaths with low inspiratory effort were defined by a Pmusc lower than 5 cmH2O. The areas under the receiver operating characteristic curves of Flow Index and respiratory rate, tidal volume,respiratory rate over tidal volume and P0.1 were analyzed and compared to identify breaths with low or high inspiratory effort. RESULTS: Pmusc, P0.1, Pressure Time Product and Flow Index differed between breaths with high, low and intermediate inspiratory effort, while RR, RR/VT and VT/kg of IBW did not differ in a statistically significant way. A Flow index higher than 4.5 identified breaths with high inspiratory effort [AUC 0.89 (CI 95% 0.85-0.93)], a Flow Index lower than 2.6 identified breaths with low inspiratory effort [AUC 0.80 (CI 95% 0.76-0.83)]. CONCLUSIONS: Flow Index is accurate in detecting high and low spontaneous inspiratory effort during pressure support ventilation.

Non-invasive assessment of respiratory muscle activity during pressure support ventilation: accuracy of end-inspiration occlusion and least square fitting methods.

Pressure support ventilation (PSV) should be titrated considering the pressure developed by the respiratory muscles (Pmusc) to prevent under- and over-assistance. The esophageal pressure (Pes) is the clinical gold standard for Pmusc assessment, but its use is limited by alleged invasiveness and complexity. The least square fitting method and the end-inspiratory occlusion method have been proposed as non-invasive alternatives for Pmusc assessment. The aims of this study were: (1) to compare the accuracy of Pmusc estimation using the end-inspiration occlusion (Pmusc,index) and the least square fitting (Pmusc,lsf) against the reference method based on Pes; (2) to test the accuracy of Pmusc,lsf and of Pmusc,index to detect overassistance, defined as Pmusc ≤ 1 cmH2O. We studied 18 patients at three different PSV levels. At each PSV level, Pmusc, Pmusc,lsf, Pmusc,index were calculated on the same breaths. Differences among Pmusc, Pmusc,lsf, Pmusc,index were analyzed with linear mixed effects models. Bias and agreement were assessed by Bland-Altman analysis for repeated measures. The ability of Pmusc,lsf and Pmusc,index to detect overassistance was assessed by the area under the receiver operating characteristics curve. Positive and negative predictive values were calculated using cutoff values that maximized the sum of sensitivity and specificity. At each PSV level, Pmusc,lsf was not different from Pmusc (p = 0.96), whereas Pmusc,index was significantly lower than Pmusc. The bias between Pmusc and Pmusc,lsf was zero, whereas Pmusc,index systematically underestimated Pmusc of 6 cmH2O. The limits of agreement between Pmusc and Pmusc,lsf and between Pmusc and Pmusc,index were ± 12 cmH2O across bias. Both Pmusc,lsf ≤ 4 cmH2O and Pmusc,index ≤ 1 cmH2O had excellent negative predictive value [0.98 (95% CI 0.94-1) and 0.96 (95% CI 0.91-0.99), respectively)] to identify over-assistance. The inspiratory effort during PSV could not be accurately estimated by the least square fitting or end-inspiratory occlusion method because the limits of agreement were far above the signal size. These non-invasive approaches, however, could be used to screen patients at risk for absent or minimal respiratory muscles activation to prevent the ventilator-induced diaphragmatic dysfunction.

Effects of Positive End-Expiratory Pressure in "High Compliance" Severe Acute Respiratory Syndrome Coronavirus 2 Acute Respiratory Distress Syndrome.

OBJECTIVES: Clinical observation suggests that early acute respiratory distress syndrome induced by the severe acute respiratory syndrome coronavirus 2 may be "atypical" due to a discrepancy between a relatively unaffected static respiratory system compliance and a significant hypoxemia. This would imply an "atypical" response to the positive end-expiratory pressure. DESIGN: Single-center, unblinded, crossover study. SETTING: ICU of Bari Policlinico Academic Hospital (Italy), dedicated to care patients with confirmed diagnosis of novel coronavirus disease 2019. PATIENTS: Eight patients with early severe acute respiratory syndrome coronavirus 2 acute respiratory distress syndrome and static respiratory compliance higher than or equal to 50 mL/cm H2O. INTERVENTIONS: We compared a "lower" and a "higher" positive end-expiratory pressure approach, respectively, according to the intervention arms of the acute respiratory distress syndrome network and the positive end-expiratory pressure setting in adults with acute respiratory distress syndrome studies. MEASUREMENTS AND MAIN RESULTS: Patients were ventilated with the acute respiratory distress syndrome network and, subsequently, with the ExPress protocol. After 1 hour of ventilation, for each protocol, we recorded arterial blood gas, respiratory mechanics, alveolar recruitment, and hemodynamic variables. Comparisons were performed with analysis of variance for repeated measures or Friedman test as appropriate. Positive end-expiratory pressure was increased from 9 ± 3.5 to 17.7 ± 1.7 cm H2O (p < 0.01). Alveolar recruitment was 450 ± 111 mL. Static respiratory system compliance decreased from 58.3 ± 7.6 mL/cm H2O to 47.4 ± 14.5 mL/cm H2O (p = 0.018) and the "stress index" increased from 0.97 ± 0.03 to 1.22 ± 0.07 (p < 0.001). The PaO2/FIO2 ratio increased from 131 ± 22 to 207 ± 41 (p < 0.001), and the PaCO2 increased from 45.9 ± 12.7 to 49.8 ± 13.2 mm Hg (p < 0.001). The cardiac index went from 3.6 ± 0.4 to 2.9 ± 0.6 L/min/m (p = 0.01). CONCLUSIONS: Our data suggest that the "higher" positive end-expiratory pressure approach in patients with severe acute respiratory syndrome coronavirus 2 acute respiratory distress syndrome and high compliance improves oxygenation and lung aeration but may result in alveolar hyperinflation and hemodynamic alterations.

Continuous assessment of neuro-ventilatory drive during 12 h of pressure support ventilation in critically ill patients.

INTRODUCTION: Pressure support ventilation (PSV) should allow spontaneous breathing with a "normal" neuro-ventilatory drive. Low neuro-ventilatory drive puts the patient at risk of diaphragmatic atrophy while high neuro-ventilatory drive may causes dyspnea and patient self-inflicted lung injury. We continuously assessed for 12 h the electrical activity of the diaphragm (EAdi), a close surrogate of neuro-ventilatory drive, during PSV. Our aim was to document the EAdi trend and the occurrence of periods of "Low" and/or "High" neuro-ventilatory drive during clinical application of PSV. METHOD: In 16 critically ill patients ventilated in the PSV mode for clinical reasons, inspiratory peak EAdi peak (EAdiPEAK), pressure time product of the trans-diaphragmatic pressure per breath and per minute (PTPDI/b and PTPDI/min, respectively), breathing pattern and major asynchronies were continuously monitored for 12 h (from 8 a.m. to 8 p.m.). We identified breaths with "Normal" (EAdiPEAK 5-15 µV), "Low" (EAdiPEAK < 5 µV) and "High" (EAdiPEAK > 15 µV) neuro-ventilatory drive. RESULTS: Within all the analyzed breaths (177.117), the neuro-ventilatory drive, as expressed by the EAdiPEAK, was "Low" in 50.116 breath (28%), "Normal" in 88.419 breaths (50%) and "High" in 38.582 breaths (22%). The average times spent in "Low", "Normal" and "High" class were 1.37, 3.67 and 0.55 h, respectively (p < 0.0001), with wide variations among patients. Eleven patients remained in the "Low" neuro-ventilatory drive class for more than 1 h, median 6.1 [3.9-8.5] h and 6 in the "High" neuro-ventilatory drive class, median 3.4 [2.2-7.8] h. The asynchrony index was significantly higher in the "Low" neuro-ventilatory class, mainly because of a higher number of missed efforts. CONCLUSIONS: We observed wide variations in EAdi amplitude and unevenly distributed "Low" and "High" neuro ventilatory drive periods during 12 h of PSV in critically ill patients. Further studies are needed to assess the possible clinical implications of our physiological findings.

Effect of a Lower vs Higher Positive End-Expiratory Pressure Strategy on Ventilator-Free Days in ICU Patients Without ARDS: A Randomized Clinical Trial.

Importance: It is uncertain whether invasive ventilation can use lower positive end-expiratory pressure (PEEP) in critically ill patients without acute respiratory distress syndrome (ARDS). Objective: To determine whether a lower PEEP strategy is noninferior to a higher PEEP strategy regarding duration of mechanical ventilation at 28 days. Design, Setting, and Participants: Noninferiority randomized clinical trial conducted from October 26, 2017, through December 17, 2019, in 8 intensive care units (ICUs) in the Netherlands among 980 patients without ARDS expected not to be extubated within 24 hours after start of ventilation. Final follow-up was conducted in March 2020. Interventions: Participants were randomized to receive invasive ventilation using either lower PEEP, consisting of the lowest PEEP level between 0 and 5 cm H2O (n = 476), or higher PEEP, consisting of a PEEP level of 8 cm H2O (n = 493). Main Outcomes and Measures: The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for the difference in ventilator-free days at day 28 of -10%. Secondary outcomes included ICU and hospital lengths of stay; ICU, hospital, and 28- and 90-day mortality; development of ARDS, pneumonia, pneumothorax, severe atelectasis, severe hypoxemia, or need for rescue therapies for hypoxemia; and days with use of vasopressors or sedation. Results: Among 980 patients who were randomized, 969 (99%) completed the trial (median age, 66 [interquartile range {IQR}, 56-74] years; 246 [36%] women). At day 28, 476 patients in the lower PEEP group had a median of 18 ventilator-free days (IQR, 0-27 days) and 493 patients in the higher PEEP group had a median of 17 ventilator-free days (IQR, 0-27 days) (mean ratio, 1.04; 95% CI, 0.95-∞; P = .007 for noninferiority), and the lower boundary of the 95% CI was within the noninferiority margin. Occurrence of severe hypoxemia was 20.6% vs 17.6% (risk ratio, 1.17; 95% CI, 0.90-1.51; P = .99) and need for rescue strategy was 19.7% vs 14.6% (risk ratio, 1.35; 95% CI, 1.02-1.79; adjusted P = .54) in patients in the lower and higher PEEP groups, respectively. Mortality at 28 days was 38.4% vs 42.0% (hazard ratio, 0.89; 95% CI, 0.73-1.09; P = .99) in patients in the lower and higher PEEP groups, respectively. There were no statistically significant differences in other secondary outcomes. Conclusions and Relevance: Among patients in the ICU without ARDS who were expected not to be extubated within 24 hours, a lower PEEP strategy was noninferior to a higher PEEP strategy with regard to the number of ventilator-free days at day 28. These findings support the use of lower PEEP in patients without ARDS. Trial Registration: ClinicalTrials.gov Identifier: NCT03167580.

Risk Factors for Mortality in Children Admitted for Suspected Malaria to a Pediatric Emergency Ward in a Low-Resource Setting: A Case-Control Study.

OBJECTIVES: To identify the risk factors for mortality after admission for suspected malaria in a pediatric emergency ward in Sierra Leone. DESIGN: Retrospective case-control. SETTING: Pujehun Hospital Pediatric Ward in Pujehun, Sierra Leone. PATIENTS: All cases were pediatric deaths after admission for suspected malaria at the Pujehun Hospital Pediatric Ward between January 1, 2015, and May 31, 2016. The case-control ratio was 1:1. The controls were infants admitted at Pujehun Hospital Pediatric Ward for malaria and discharged alive during the same period. Controls were selected as the next noncase infant admitted for malaria and discharged alive, as recorded in local medical records. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children characteristics, vital variables on hospital access, comorbidity status at admission, antibiotic and antimalarial therapy at admission; presence of hematemesis, respiratory arrest or bradypnea, abrupt worsening, and emergency interventions during hospital stay; final diagnosis before discharge or death. In total, 320 subjects (160 cases and 160 controls) were included in the study. Multivariable analysis identified being referred from peripheral health units (odds ratio, 4.00; 95% CI, 1.98-8.43), cerebral malaria (odds ratio, 6.28; 95% CI, 2.19-21.47), malnutrition (odds ratio, 3.14; 95% CI, 1.45-7.15), dehydration (odds ratio, 3.94; 95% CI, 1.50-11.35), being unresponsive or responsive to pain (odds ratio, 2.17; 95% CI, 1.15-4.13), and hepatosplenomegaly (odds ratio, 3.20; 95% CI, 1.74-6.03) as independent risk factors for mortality. CONCLUSIONS: Risk factors for mortality in children with suspected malaria include cerebral malaria and severe clinical conditions at admission. Being referred from peripheral health units, as proxy of logistics issue, was also associated with increased risk of mortality. These findings suggest that appropriate interventions should focus on training and resources, including the increase of dedicated personnel and available equipment.

ICU registries: From tracking to fostering better outcomes.

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Recruitment-to-inflation ratio reflects the impact of peep on dynamic lung strain in a highly recruitable model of ARDS.

BACKGROUND: The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan. METHODS: Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH2O) and high PEEP (i.e., PEEP generating a plateau pressure of 28-30 cmH2O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively). RESULTS: Between high (median [interquartile range] 20 cmH2O [18-21]) and low PEEP, median R/I was 1.08 [0.88-1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182-288] and 385 ml [318-668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29-0.44] at high PEEP and 0.59 [0.46-0.80] at low PEEP (p < 0.001). R/I was significantly related to PEEP-induced reduction in dynamic (r = - 0.93; [95% CI - 0.78 to - 0.98]) and global lung strain (r = - 0.57; [95% CI - 0.05 to - 0.84]). No correlation was found between R/I and and PEEP-induced changes in static lung strain (r = 0.34; [95% CI - 0.23 to 0.74]). CONCLUSIONS: In a highly recruitable ARDS model, R/I reflects the potential for lung recruitment and well estimates the extent of PEEP-induced reduction in dynamic lung strain.

Lung ultrasound and supine chest X-ray use in modern adult intensive care: mapping 30 years of advancement (1993-2023).

In critically ill patients with acute respiratory failure, thoracic images are essential for evaluating the nature, extent and progression of the disease, and for clinical management decisions. For this purpose, computed tomography (CT) is the gold standard. However, transporting patients to the radiology suite and exposure to ionized radiation limit its use. Furthermore, a CT scan is a static diagnostic exam for the thorax, not allowing, for example, appreciation of "lung sliding". Its use is also unsuitable when it is necessary to adapt or decide to modify mechanical ventilation parameters at the bedside in real-time. Therefore, chest X-ray and lung ultrasound are today's contenders for shared second place on the podium to acquire a thoracic image, with their specific strengths and limitations. Finally, electrical impedance tomography (EIT) could soon have a role, however, its assessment is outside the scope of this review. Thus, we aim to carry out the following points: (1) analyze the advancement in knowledge of lung ultrasound use and the related main protocols adopted in intensive care units (ICUs) over the latest 30 years, reporting the principal publications along the way, (2) discuss how and when lung ultrasound should be used in a modern ICU and (3) illustrate the possible future development of LUS.