METHODS: An iterative airway pressure reconstruction (IPR) method is used to reconstruct asynchronous airway pressure waveforms to better match passive breathing airway waveforms using a single compartment model. The reconstructed pressure enables estimation of respiratory mechanics of airway pressure waveform essentially free from asynchrony. Reconstruction enables real-time breath-to-breath monitoring and quantification of the magnitude of the asynchrony (MAsyn).
RESULTS AND DISCUSSION: Over 100,000 breathing cycles from MV patients with known asynchronous breathing were analyzed. The IPR was able to reconstruct different types of asynchronous breathing. The resulting respiratory mechanics estimated using pressure reconstruction were more consistent with smaller interquartile range (IQR) compared to respiratory mechanics estimated using asynchronous pressure. Comparing reconstructed pressure with asynchronous pressure waveforms quantifies the magnitude of asynchronous breathing, which has a median value MAsyn for the entire dataset of 3.8%.
CONCLUSION: The iterative pressure reconstruction method is capable of identifying asynchronous breaths and improving respiratory mechanics estimation consistency compared to conventional model-based methods. It provides an opportunity to automate real-time quantification of asynchronous breathing frequency and magnitude that was previously limited to invasively method only.
METHODS: Data from 275 breaths aggregated from all mechanically ventilated patients at Christchurch Hospital were used in this study. The breath specific respiratory elastance is calculated using a time-varying elastance model. A pressure reconstruction method is proposed to reconstruct pressure waves identified as being affected by SB effort. The area under the curve of the time-varying respiratory elastance (AUC Edrs) are calculated and compared, where unreconstructed waves yield lower AUC Edrs. The difference between the reconstructed and unreconstructed pressure is denoted as a surrogate measure of SB effort.
RESULTS: The pressure reconstruction method yielded a median AUC Edrs of 19.21 [IQR: 16.30-22.47]cmH2Os/l. In contrast, the median AUC Edrs for unreconstructed M-wave data was 20.41 [IQR: 16.68-22.81]cmH2Os/l. The pressure reconstruction method had the least variability in AUC Edrs assessed by the robust coefficient of variation (RCV)=0.04 versus 0.05 for unreconstructed data. Each patient exhibited different levels of SB effort, independent from MV setting, indicating the need for non-invasive, real time assessment of SB effort.
CONCLUSION: A simple reconstruction method enables more consistent real-time estimation of the true, underlying respiratory system mechanics of a SB patient and provides the surrogate of SB effort, which may be clinically useful for clinicians in determining optimal ventilator settings to improve patient care.
OBJECTIVE: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.
DATA SOURCES: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.
STUDY SELECTION: Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.
DATA EXTRACTION AND SYNTHESIS: In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.
MAIN OUTCOMES AND MEASURES: The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.
RESULTS: A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P
METHODS: This single-center prospective observational study was conducted in a general ICU. Mechanically ventilated critically ill adult patients (age ≥18 years) without pre-existing systemic neuromuscular diseases and expected to stay for ≥96 h in the ICU were included. US measurements were performed within 48 h of ICU admission (baseline), at day 7, day 14 of ICU stay and at ICU discharge (if stay >14 days). Quadriceps muscle layer thickness (QMLT), rectus femoris cross sectional area (RFCSA), vastus intermedius pennation angle (PA) and fascicle length (FL), and rectus femoris echogenicity (mean and standard deviation [SD]) were measured. Patients' next-of-kin were interviewed by using established questionnaires for their pre-hospitalization nutritional risk (nutrition risk screening-2002) and functional status (SARC-F, clinical frailty scale [CFS], Katz activities of daily living [ADL] and Lawton Instrumental ADL).
RESULTS: Ninety patients were recruited. A total of 86, 53, 24 and 10 US measures were analyzed, which were performed at a median of 1, 7, 14 and 22 days from ICU admission, respectively. QMLT, RFCSA and PA reduced significantly over time. The overall trend of change of FL was not significant. The only independent predictor of 60-day mortality was the change of QMLT from baseline to day 7 (adjusted odds ratio 0.95 for every 1% less QMLT loss, 95% confidence interval 0.91-0.99; p = 0.02). Baseline measures of high nutrition risk (modified nutrition risk in critically ill ≥5), sarcopenia (SARC-F ≥4) and frailty (CFS ≥5) were associated with lower baseline QMLT, RFCSA and PA and higher 60-day mortality.
CONCLUSIONS: Every 1% loss of QMLT over the first week of critical illness was associated with 5% higher odds of 60-day mortality. SARC-F, CFS and mNUTRIC are associated with quadriceps muscle status and 60-day mortality and may serve as a potential simple and indirect measures of premorbid muscle status at ICU admission.
DISCUSSION: This review presents the significant clinical aspects and variables of ventilation management, the potential risks associated with suboptimal ventilation management, and a review of the major recent attempts to improve ventilation in the context of these variables. The unique aspect of this review is a focus on these key elements relevant to engineering new approaches. In particular, the need for ventilation strategies which consider, and directly account for, the significant differences in patient condition, disease etiology, and progression within patients is demonstrated with the subsequent requirement for optimal ventilation strategies to titrate for patient- and time-specific conditions.
CONCLUSION: Engineered, protective lung strategies that can directly account for and manage inter- and intra-patient variability thus offer great potential to improve both individual care, as well as cohort clinical outcomes.
RESEARCH QUESTION: The differential impact of frequently used CSs and their regimens on long-term (> 5 years) cardiorespiratory progression in children with DMD is unknown.
STUDY DESIGN AND METHODS: This was a retrospective longitudinal study including children with DMD followed at Dubowitz Neuromuscular Centre, Great Ormond Street Hospital London, England, from May 2000 to June 2017. Patients enrolled in any interventional clinical trials were excluded. We collected patients' anthropometrics and respiratory (FVC, FVC % predicted and absolute FVC, and noninvasive ventilation requirement [NIV]) and cardiac (left ventricular shortening function [LVFS%]) function. CSs-naïve patients had never received CSs. Patients who were treated with CSs took either deflazacort or prednisolone, daily or intermittently (10 days on/10 days off) for > 1 month. Average longitudinal models were fitted for yearly respiratory (FVC % predicted) and cardiac (LVFS%) progression. A time-to-event analysis to FVC % predicted < 50%, NIV start, and cardiomyopathy (LVFS% < 28%) was performed in CS-treated (daily and intermittent) vs CS-naïve patients.
RESULTS: There were 270 patients, with a mean age at baseline of 6.2 ± 2.3 years. The median follow-up time was 5.6 ± 3.5 years. At baseline, 263 patients were ambulant. Sixty-six patients were treated with CSs daily, 182 patients underwent CSs intermittent > 60% treatment, and 22 were CS-naïve patients. Yearly FVC % predicted declined similarly from 9 years (5.9% and 6.9% per year, respectively; P = .27) in the CSs-daily and CSs-intermittent groups. The CSs-daily group declined from a higher FVC % predicted than the CSs-intermittent group (P < .05), and both reached FVC % predicted < 50% and NIV requirement at a similar age, > 2 years later than the CS-naïve group. LVFS% declined by 0.53% per year in the CSs-treated group irrespective of the CSs regimen, significantly slower (P < .01) than the CSs-naïve group progressing by 1.17% per year. The age at cardiomyopathy was 16.6 years in the CSs-treated group (P < .05) irrespective of regimen and 13.9 years in the CSs-naïve group.
INTERPRETATION: CSs irrespective of the regimen significantly improved respiratory function and delayed NIV requirement and cardiomyopathy.
METHODS: This prospective study over November 2017-October 2019 was conducted in a single-center multidisciplinary pediatric intensive care unit (PICU) and included patients <21years of age with PARDS. Clinical history of those requiring mechanical ventilation for <3 days was interrogated and cases in which the diagnosis of PARDS were unlikely, identified. The impact of chronic comorbidities on clinical outcomes, in particular, pulmonary disease and immunosuppression, were analyzed.
RESULTS: Eighty-five of 1272 PICU admissions (6.7%) met the criteria for PARDS and were included. Median age and oxygenation indexes were 2.8 (0.6, 8.3) years and 10.6 (7.6, 15.4), respectively. Overall mortality was 12 out of 85 (14.1%). Despite fulfilling criteria in 6/85 (7.1%), hypoxemia contributed by bronchospasm, mucus plugging, fluid overload, and atelectasis was quickly reversible and PARDS was unlikely in these patients. Comorbidities (57/85 [67.1%]) were not associated with worsened outcomes. However, pre-existing pulmonary disease and immunosuppression were associated with severe PARDS (12/20 [60.0%] vs 19/65 [29.2%]; P = .017), extracorporeal membrane oxygenation use (5/20 [25.0%] vs 3/65 [4.6%]; P = .016) and reduced ventilator free days (VFD) (15 [0, 19] vs 21 [6, 23]; P = .039), compared with those without them.
CONCLUSION: A small percentage of children fulfilling the PALICC definition had quickly reversible hypoxemia with likely alternate pathophysiology to PARDS. Patients with pulmonary comorbidities and immunosuppression had a more severe course of PARDS compared with others.