Adult Acute Respiratory Distress Syndrome Research Articles

Endotyping in ARDS: one step forward in precision medicine

BackgroundThe Berlin definition of acute respiratory distress syndrome (ARDS) includes only clinical characteristics. Understanding unique patient pathobiology may allow personalized treatment. We aimed to define and describe ARDS phenotypes/endotypes combining clinical and pathophysiologic parameters from a Canadian ARDS cohort.MethodsA cohort of adult ARDS patients from multiple sites in Calgary, Canada, had plasma cytokine levels and clinical parameters measured in the first 24 h of ICU admission. We used a latent class model (LCM) to group the patients into several ARDS subgroups and identified the features differentiating those subgroups. We then discuss the subgroup effect on 30 day mortality.ResultsThe LCM suggested three subgroups (n1 = 64, n2 = 86, and n3 = 30), and 23 out of 69 features made these subgroups distinct. The top five discriminating features were IL-8, IL-6, IL-10, TNF-a, and serum lactate. Mortality distinctively varied between subgroups. Individual clinical characteristics within the subgroup associated with mortality included mean PaO2/FiO2 ratio, pneumonia, platelet count, and bicarbonate negatively associated with mortality, while lactate, creatinine, shock, chronic kidney disease, vasopressor/ionotropic use, low GCS at admission, and sepsis were positively associated. IL-8 and Apache II were individual markers strongly associated with mortality (Area Under the Curve = 0.84).PerspectiveARDS subgrouping using biomarkers and clinical characteristics is useful for categorizing a heterogeneous condition into several homogenous patient groups. This study found three ARDS subgroups using LCM; each subgroup has a different level of mortality. This model may also apply to developing further trial design, prognostication, and treatment selection.

Plasma renin as a novel prognostic biomarker of sepsis-associated acute respiratory distress syndrome

Sepsis-associated acute respiratory distress syndrome (ARDS) is a life-threatening condition in critical care medicine for which there is a substantial need for early prognostic biomarkers of outcome. The present study seeks to link plasma renin levels and 30-day mortality in sepsis-associated ARDS patients treated at our institution. The Registry of Critical Illness (RoCI) prospectively enrolled patients from the intensive care units (ICU) within a single academic medical center, and a convenience sample of patients with sepsis-associated ARDS was analyzed from this cohort. This study was approved by the Mass General Brigham Institutional Review Boards (IRB) as part of the RoCI, and all procedures performed were in accordance with the ethical standards of the institutional board. From April 2012 to February 2019, a cohort of 32 adult sepsis-associated ARDS patients with 500 µL of plasma samples available on Day 0 and Day 3 of their ICU stay were enrolled. Renin levels were measured twice, on Day 0 and Day 3 via the direct renin enzyme-linked immunosorbent assay (ELISA EIA-525) by DRG diagnostics. Day 0 and Day 3 renin were statistically evaluated via logistic regression to predict 30-day mortality. Direct renin levels of 64 samples were assayed from 32 sepsis-associated ARDS patients (50% male; mean ± SD, 55 ± 13.8 years old). The 30-day hospital mortality rate was 59.4%. Patients who died within 30 days of admission were more likely to have an elevated Day 3 Renin (Odds ratio [OR] = 6, 95% CI 1.25–28.84) and have received vasopressors (OR = 13.33, 95% CI 1.43–123.95). Adjusting for vasopressor use as a proxy for septic shock status, patients with an Elevated Day 3 Renin had a 6.85 (95% CI 1.07–43.75) greater odds of death than those with Low-Normal Day 3 Renin. Patients with sustained Elevated Renin levels from Day 0 to Day 3 had the highest risk of death in a 30-day window. In this study, we found that renin may be a novel biomarker that has prognostic value for patients with sepsis-associated ARDS. Future studies evaluating renin levels in patients with sepsis-associated ARDS are needed to validate these findings.

Prone position in the mechanical ventilation of acute respiratory distress syndrome children: a systematic review and meta-analysis.

Prone position has been well recognized for the treatment of adult acute respiratory distress syndrome (ARDS). We aimed to evaluate the role of prone position in the mechanical ventilation in children with ARDS, to provide evidence to the treatment and care of children with ARDS. We searched the Pubmed et al. databases by computer until January 23, 2024 for randomized controlled trials (RCTs) on the role of prone position in the mechanical ventilation in children with ARDS. We evaluated the quality of included studies according to the quality evaluation criteria recommended by the Cochrane library. RevMan 5.3 software was used for meta-analysis. 7 RCTs involving 433 children with ARDS were included. Meta-analysis indicated that prone position is beneficial to improve the arterial oxygenation pressure [MD = 4.27 mmHg, 95% CI (3.49, 5.06)], PaO2/FiO2 [MD = 26.97, 95% CI (19.17, 34.77)], reduced the oxygenation index [MD = -3.52, 95% CI (-5.41, -1.64)], mean airway pressure [MD = -1.91 cmH2O, 95% CI (-2.27, -1.55)] and mortality [OR = 0.33, 95% CI (0.15, 0.73), all P < 0.05]. There were no statistical differences in the duration of mechanical ventilation between the prone position group and control group [MD = -17.01, 97.27, 95% CI (-38.28, 4.26), P = 0.12]. Egger test results showed that no significant publication bias was found (all P > 0.05). Prone position ventilation has obvious advantages in improving oxygenation, but there is no significant improvement in the time of mechanical ventilation in the treatment of children with ARDS. In the future, more large-sample, high-quality RCTs are still needed to further analyze the role of prone position in the mechanical ventilation in children with ARDS.

Lung Ultrasound Evaluation of Aeration Changes in Response to Prone Positioning in Acute Respiratory Distress Syndrome (ARDS) Patients Requiring Venovenous Extracorporeal Membrane Oxygenation: An Observational Study.

Prone positioning (PP) has been proven to be a beneficial approach in enhancing survival outcomes for patients with severe acute respiratory distress syndrome (ARDS) who need venovenous extracorporeal membrane oxygenation (V-V ECMO) support. The study utilized bedside lung ultrasound (LUS) to evaluate changes in lung aeration caused by PP in ARDS patients receiving V-V ECMO. This retrospective single-center study involved adult ARDS patients requiring V-V ECMO. The assessment of LUS involved examining specific dorsal lung regions, encompassing 16 areas, during three pre-defined time points: baseline (10 minutes prior), three-hour PP positioning, and 10-minute post-supine repositioning, all within the initial three days. Based on the oxygenation response to PP, patients were categorized into responder and non-responder groups. The primary outcome was LUS score changes during the initial three-day period. Secondary outcomes examined the impact of PP on the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) (P/F) ratio, V-V ECMO weaning success, length of ICU stay, and hospital survival. Among the enrolled patients (27 in total), 16 were responders and 11 were non-responders. In the responder group, the global LUS score underwent a significant reduction from 26.38 ± 4.965 at baseline to 20.75 ± 3.337 (p < 0.001) after the first PP session, which further decreased to 15.94 ± 2.816 (p< 0.001) after three days. However, no significant differences were observed among PP non-responders. The oxygenation reaction yielded comparable results. There was a significant correlation between the duration of daily PP and the reduction in global LUS score among PP responders (r = -0.855, p < 0.001). In cases where the global LUS score decreased by > 7.5 after three days of PP, the area under the receiver operating characteristic curve (AUROC) for predicting ECMO weaning success was 0.815, while it was 0.761 for predicting hospital survival. LUS has the potential to predict the response to PP and evaluate the prognosis of ARDS patients with V-V ECMO, althoughmore studies are demanded in the future.

Novel Oxygenation and Saturation Indices for Mortality Prediction in COVID-19 ARDS Patients: The Impact of Driving Pressure and Mechanical Power.

Background: The oxygenation index (OI) and oxygen saturation index (OSI) are proven mortality predictors in pediatric and adult patients, traditionally using mean airway pressure (Pmean). We introduce novel indices, replacing Pmean with DP (ΔPinsp), MPdyn, and MPtot, assessing their potential for predicting COVID-19 acute respiratory distress syndrome (ARDS) mortality, comparing them to traditional indices. Methods: We studied 361 adult COVID-19 ARDS patients for 7 days, collecting ΔPinsp, MPdyn, and MPtot, OI-ΔPinsp, OI-MPdyn, OI-MPtot, OSI-ΔPinsp, OSI-MPdyn, and OSI-MPtot. We compared these in surviving and non-surviving patients over the first 7 intensive care unit (ICU) days using Mann-Whitney U test. Logistic regression receiver operating characteristic (ROC) analysis assessed AUC and CI values for ICU mortality on day three. We determined cut-off values using Youden's method and conducted multivariate Cox regression on parameter limits. Results: All indices showed significant differences between surviving and non-surviving patients on the third day of ICU care. The AUC values of OI-ΔPinsp were significantly higher than those of P/F and OI-Pmean (P values .0002 and <.0001, respectively). Similarly, AUC and CI values of OSI-ΔPinsp and OSI-MPdyn were significantly higher than those of SpO2/FiO2 and OSI-Pmean values (OSI-ΔPinsp: P < .0001, OSI-MPdyn: P values .047 and .028, respectively). OI-ΔPinsp, OSI-ΔPinsp, OI-MPdyn, OSI-MPdyn, OI-MPtot, and OSI-MPtot had AUC values of 0.72, 0.71, 0.69, 0.68, 0.66, and 0.64, respectively, with cut-off values associated with hazard ratios and P values of 7.06 (HR = 1.84, P = .002), 8.04 (HR = 2.00, P ≤ .0001), 7.12 (HR = 1.68, P = .001), 5.76 (HR = 1.70, P ≤ .0001), 10.43 (HR = 1.52, P = .006), and 10.68 (HR = 1.66, P = .001), respectively. Conclusions: Critical values of all indices were associated to higher ICU mortality rates and extended mechanical ventilation durations. The OI-ΔPinsp, OSI-ΔPinsp, and OSI-MPdyn indices displayed the strongest predictive capabilities for ICU mortality. These novel indices offer valuable insights for intensivists in the clinical management and decision-making process for ARDS patients.

Categorizing Acute Respiratory Distress Syndrome with Different Severities by Oxygen Saturation Index.

The oxygen saturation index (OSI), defined by FIO2/SpO2 multiplied by the mean airway pressure, has been reported to exceed the Berlin definition in predicting the mortality of acute respiratory distress syndrome (ARDS). The OSI has served as an alternative to the Berlin definition in categorizing pediatric ARDS. However, the use of the OSI for the stratification of adult ARDS has not been reported. A total of 379 invasively ventilated adult ARDS patients were retrospectively studied. The ARDS patients were classified into three groups by their incidence rate of mortality: mild (OSI < 14.69), moderate (14.69 < OSI < 23.08) and severe (OSI > 23.08). OSI-based categorization was highly correlated with the Berlin definition by a Kendall's tau of 0.578 (p < 0.001). The Kaplan-Meier curves of the three OSI-based groups were significantly different (p < 0.001). By the Berlin definition, the hazard ratio for 28-day mortality was 0.58 (0.33-1.05) and 0.95 (0.55-1.67) for the moderate and severe groups, respectively (compared to the mild group). In contrast, the corresponding hazard ratio was 1.01 (0.69-1.47) and 2.39 (1.71-3.35) for the moderate and severe groups defined by the OSI. By multivariate analysis, OSI-based severe ARDS was independently associated with 28-D or 90-D mortality. In conclusion, we report the first OSI-based stratification for adult ARDS and find that it serves well as an alternative to the Berlin definition.

Prognostic value of time-varying dead space estimates in mechanically ventilated patients with acute respiratory distress syndrome

BackgroundThe dead space fraction (VD/VT) has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome (ARDS). However, its measurement relies on expired carbon dioxide, limiting its widespread application in clinical practice. Several estimates employing routine variables have been found to be reliable substitutes for direct measurement of VD/VT. In this study, we evaluated the prognostic value of these dead space estimates obtained in the first 7 days following the initiation of ventilation. MethodsThis retrospective observational study was conducted using data from the Chinese database in intensive care (CDIC). Eligible participants were adult ARDS patients receiving invasive mechanical ventilation while in the intensive care unit between 1st January 2014 and 31st March 2021. We collected data during the first 7 days of ventilation to calculate various dead space estimates, including ventilatory ratio (VR), corrected minute ventilation (V˙Ecorr), VD/VT (Harris–Benedict), VD/VT (Siddiki estimate), and VD/VT (Penn State estimate) longitudinally. A time-dependent Cox model was used to handle these time-varying estimates. ResultsA total of 392 patients (median age 66 [interquartile range: 55–77] years, median SOFA score 9 [interquartile range: 7–12]) were finally included in our analysis, among whom 132 (33.7%) patients died within 28 days of admission. VR (hazard ratio [HR]=1.04 per 0.1 increase, 95% confidence interval [CI]: 1.01 to 1.06; P=0.013), V˙Ecorr (HR=1.08 per 1 increase, 95% CI: 1.04 to 1.12; P < 0.001), VD/VT (Harris–Benedict) (HR=1.25 per 0.1 increase, 95% CI: 1.06 to 1.47; P=0.006), and VD/VT (Penn State estimate) (HR=1.22 per 0.1 increase, 95% CI: 1.04 to 1.44; P=0.017) remained significant after adjustment, while VD/VT (Siddiki estimate) (HR=1.10 per 0.1 increase, 95% CI: 1.00 to 1.20; P=0.058) did not. Given a large number of negative values, VD/VT (Siddiki estimate) and VD/VT (Penn State estimate) were not recommended as reliable substitutes. Long-term exposure to VR >1.3, V˙Ecorr >7.53, and VD/VT (Harris–Benedict) >0.59 was independently associated with an increased risk of mortality in ARDS patients. These findings were validated in the fluid and catheter treatment trial (FACTT) database. ConclusionsIn cases where VD/VT cannot be measured directly, early time-varying estimates of VD/VT such as VR, V˙Ecorr, and VD/VT (Harris–Benedict) can be considered for predicting mortality in ARDS patients, offering a rapid bedside application.

Pulmonary Surfactant in Adult ARDS: Current Perspectives and Future Directions.

Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults, leading to the requirement for mechanical ventilation and poorer outcomes. Dysregulated surfactant metabolism and function are characteristic of ARDS. A combination of alveolar epithelial damage leading to altered surfactant synthesis, secretion, and breakdown with increased functional inhibition from overt alveolar inflammation contributes to the clinical features of poor alveolar compliance and alveolar collapse. Quantitative and qualitative alterations in the bronchoalveolar lavage and tracheal aspirate surfactant composition contribute to ARDS pathogenesis. Compared to neonatal respiratory distress syndrome (nRDS), replacement studies of exogenous surfactants in adult ARDS suggest no survival benefit. However, these studies are limited by disease heterogeneity, variations in surfactant preparations, doses, and delivery methods. More importantly, the lack of mechanistic understanding of the exact reasons for dysregulated surfactant remains a significant issue. Moreover, studies suggest an extremely short half-life of replaced surfactant, implying increased catabolism. Refining surfactant preparations and delivery methods with additional co-interventions to counteract surfactant inhibition and degradation has the potential to enhance the biophysical characteristics of surfactant in vivo.

Predictive value of plasma sICAM-1 and sP-Selectins in the risk of death in patients with acute respiratory distress syndrome.

To evaluate the predictive value of sICAM-1 and sP-Selectins in the risk of death in a prospective cohort of adult acute respiratory distress syndrome (ARDS). Adult ARDS patients were included. Plasma sICAM-1, sP-Selectins, and inflammatory cytokines (TNF-α, IL-1b, IL-6, IL-8, and IL-17A) were detected in ARDS subjects. The correlation between different factors and the potential of sICAM-1 and sP-Selectins as endothelial markers to predict the risk of deathfrom ARDS was analyzed.

A clinical case of development of Waterhouse-Friderichsen syndrome after SARS-CoV-2 infection in a patient with rheumatoid arthritis and secondary adrenal AA-amyloidosis

We present a clinical observation of a patient whose cause of death was a new coronavirus infection COVID-19 complicated by bilateral viral interstitial pneumonia and adult acute respiratory distress syndrome. The presence of background diseases-rheumatoid arthritis and secondary AA-adrenal amyloidosis-worsened the prognosis. Waterhouse-Friderichsen syndrome with hemorrhage and foci of necrosis in the adrenal cortex developed against a background of SARS-CoV-2 infection. The unique feature of this case is the long-term favorable course of the disease and its rapid progression after infection with SARS-CoV-2. The associated syndrome of disseminated intravascular coagulation further aggravated the patient's condition.

A Systematic Review of Mortality Rates Among Adult Acute Respiratory Distress Syndrome Patients Undergoing Extracorporeal Membrane Oxygenation Therapy.

Acute respiratory distress syndrome (ARDS) is a severe lung disease associated with a high mortality rate. Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for severe ARDS patients who do not respond to conventional treatments. Nevertheless, the optimal management of ARDS patients undergoing ECMO and their mortality rates remain subjects of controversy. Thus, this systematic review aims to assess mortality rates in ARDS patients on ECMO and identify associated factors. The review adhered to the Preferred Reporting Items for Systemic Review and Meta-Analysis (PRISMA) 2020 guidelines. A comprehensive literature search was conducted on PubMed, PubMed Central (PMC), Medline, and Embase. In accordance with our inclusion and exclusion criteria, filters, and key terms, we proceeded to screen the articles. After assessing the relevance of each article to our topic, further screening was carried out. Quality assessment of the articles was conducted, resulting in the inclusion of a total of 12 articles for the review. The primary outcome focused on mortality rates among ARDS patients undergoing ECMO. Secondary outcomes explored potential contributors to mortality, including patient age, underlying cause of ARDS, and Sequential Organ Failure Assessment (SOFA) scores at the initiation of ECMO. Mortality rates exhibited significant variation, ranging from 22% to 62.6%. Several factors emerged as potential predictors of mortality, encompassing patient age, comorbidities, complications during ECMO therapy, and treatment-related variables. This systematic review offers valuable insights into the intricate factors influencing mortality rates among ARDS patients on ECMO. A comprehension of these factors is essential to steer clinical practice and enhance patient outcomes. While ECMO serves as a restorative avenue for ARDS patients, future research is warranted to further elucidate these complex interactions and refine ECMO therapy protocols.

Synthetic surfactant with a combined SP-B and SP-C analogue is efficient in rabbit models of adult and neonatal respiratory distress syndrome

Respiratory distress syndrome (RDS) in premature infants is caused by insufficient amounts of endogenous lung surfactant and is efficiently treated with replacement therapy using animal-derived surfactant preparations. On the other hand, adult/acute RDS (ARDS) occurs secondary to for example, sepsis, aspiration of gastric contents, and multitrauma and is caused by alveolar endothelial damage, leakage of plasma components into the airspaces and inhibition of surfactant activity. Instillation of surfactant preparations in ARDS has so far resulted in very limited treatment effects, partly due to inactivation of the delivered surfactants in the airspace. Here, we develop a combined surfactant protein B (SP-B) and SP-C peptide analogue (Combo) that can be efficiently expressed and purified from Escherichia coli without any solubility or purification tag. NMR spectroscopy shows that Combo peptide forms α-helices both in organic solvents and in lipid micelles, which coincide with the helical regions described for the isolated SP-B and SP-C parts. Artificial Combo surfactant composed of synthetic dipalmitoylphosphatidylcholine:palmitoyloleoylphosphatidylglycerol, 1:1, mixed with 3 weights % relative to total phospholipids of Combo peptide efficiently improves tidal volumes and lung gas volumes at end-expiration in a premature rabbit fetus model of RDS. Combo surfactant also improves oxygenation and respiratory parameters and lowers cytokine release in an acid instillation-induced ARDS adult rabbit model. Combo surfactant is markedly more resistant to inhibition by albumin and fibrinogen than a natural-derived surfactant in clinical use for the treatment of RDS. These features of Combo surfactant make it attractive for the development of novel therapies against human ARDS.

Retracted: Meta-Analysis of the Effect of Glucocorticoids on Adult Acute Respiratory Distress Syndrome.

[This retracts the article DOI: 10.1155/2022/4020489.].

Role of virtual reality distraction technique to improve chest burns with acute respiratory distress syndrome (ARDS) following smoke inhalation in middle-aged adults – A randomized controlled study

BackgroundBurns of the chest region constitute a common burn and develops skin contractures around the thorax region. Inhalation of toxic gases and chemical irritants during the fire leads to Acute Respiratory Distress Syndrome (ARDS). Breathing exercises are painful but are needed to help counteract contractures and increase lung capacity. These patients are usually in pain and extremely anxious about chest physiotherapy. Virtual reality distraction is one such technique that is gaining immense popularity when compared to other pain distraction techniques. However, studies examining the efficacy of the virtual reality distraction technique in this population are lacking. ObjectivesTo find and compare the effects of the virtual reality distraction technique as a pain alleviation tool for reducing pain during chest physiotherapy in chest burns patients with ARDS in middle-aged adults. MethodsA randomized controlled study was conducted at the physiotherapy department between 1st Sep 2020 and 30th Dec 2022. The eligible sixty subjects were randomized into two groups: The virtual reality distraction group (n = 30) received virtual reality distraction technique and the control group (n = 30) received progressive relaxation technique before chest physiotherapy as a pain distraction technique. All the participants received chest physiotherapy as a common treatment (treatment as usual). Primary (Visual Analogue Scale – VAS) and secondary (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, peak expiratory flow (PEF), residual volume (RV), functional residual capacity (FRC), total lung capacity (TLC), RV/TLC, and diffusing capacity for carbon monoxide of the lungs (DLCO) outcome measures were measured at baseline, after four weeks, eight weeks and at six months follow up. The effects between the two groups were analyzed using the independent t-test and chi-square test. The intra-group effect was analyzed with a repeated measure ANOVA test. ResultsBaseline demographic characters and study variables show homogenous distribution between the groups (p > 0.05). Four weeks following two different training protocols virtual reality distraction group shows more significant changes in pain intensity, FVC, FEV1, FEV1/FVC, PEF, RV, FRC, TLC, RV/TLC, and DLCO (p = 0.001) but not in RV (p = 0.541). The similar improvements were noted in the 8 weeks and 6 months follow up. ConclusionThe reports of the study concluded that virtual reality distraction is an effective and useful technique in reducing pain and increasing lung capacity in chest burn patient with ARDS following smoke inhalation in community-dwelling middle-aged adults. In the virtual reality distraction group, the patients reported significantly less pain and clinically meaningful changes in pulmonary functions as compared to the control group (physiotherapy + relaxation).

Precision of CT-derived alveolar recruitment assessed by human observers and a machine learning algorithm in moderate and severe ARDS

BackgroundAssessing measurement error in alveolar recruitment on computed tomography (CT) is of paramount importance to select a reliable threshold identifying patients with high potential for alveolar recruitment and to rationalize positive end-expiratory pressure (PEEP) setting in acute respiratory distress syndrome (ARDS). The aim of this study was to assess both intra- and inter-observer smallest real difference (SRD) exceeding measurement error of recruitment using both human and machine learning-made lung segmentation (i.e., delineation) on CT. This single-center observational study was performed on adult ARDS patients. CT were acquired at end-expiration and end-inspiration at the PEEP level selected by clinicians, and at end-expiration at PEEP 5 and 15 cmH2O. Two human observers and a machine learning algorithm performed lung segmentation. Recruitment was computed as the weight change of the non-aerated compartment on CT between PEEP 5 and 15 cmH2O.ResultsThirteen patients were included, of whom 11 (85%) presented a severe ARDS. Intra- and inter-observer measurements of recruitment were virtually unbiased, with 95% confidence intervals (CI95%) encompassing zero. The intra-observer SRD of recruitment amounted to 3.5 [CI95% 2.4–5.2]% of lung weight. The human–human inter-observer SRD of recruitment was slightly higher amounting to 5.7 [CI95% 4.0–8.0]% of lung weight, as was the human–machine SRD (5.9 [CI95% 4.3–7.8]% of lung weight). Regarding other CT measurements, both intra-observer and inter-observer SRD were close to zero for the CT-measurements focusing on aerated lung (end-expiratory lung volume, hyperinflation), and higher for the CT-measurements relying on accurate segmentation of the non-aerated lung (lung weight, tidal recruitment…). The average symmetric surface distance between lung segmentation masks was significatively lower in intra-observer comparisons (0.8 mm [interquartile range (IQR) 0.6–0.9]) as compared to human–human (1.0 mm [IQR 0.8–1.3] and human–machine inter-observer comparisons (1.1 mm [IQR 0.9–1.3]).ConclusionsThe SRD exceeding intra-observer experimental error in the measurement of alveolar recruitment may be conservatively set to 5% (i.e., the upper value of the CI95%). Human–machine and human–human inter-observer measurement errors with CT are of similar magnitude, suggesting that machine learning segmentation algorithms are credible alternative to humans for quantifying alveolar recruitment on CT.

Invasive Ventilatory Support in Patients With Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

To provide evidence for the Second Pediatric Acute Lung Injury Consensus Conference updated recommendations and consensus statements for clinical practice and future research on invasive mechanical ventilation support of patients with pediatric acute respiratory distress syndrome (PARDS). MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). We included clinical studies of critically ill patients undergoing invasive mechanical ventilation for PARDS, January 2013 to April 2022. In addition, meta-analyses and systematic reviews focused on the adult acute respiratory distress syndrome population were included to explore new relevant concepts (e.g., mechanical power, driving pressure, etc.) still underrepresented in the contemporary pediatric literature. Title/abstract review, full text review, and data extraction using a standardized data collection form. The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize relevant evidence and develop recommendations, good practice statements and research statements. We identified 26 pediatric studies for inclusion and 36 meta-analyses or systematic reviews in adults. We generated 12 recommendations, two research statements, and five good practice statements related to modes of ventilation, tidal volume, ventilation pressures, lung-protective ventilation bundles, driving pressure, mechanical power, recruitment maneuvers, prone positioning, and high-frequency ventilation. Only one recommendation, related to use of positive end-expiratory pressure, is classified as strong, with moderate certainty of evidence. Limited pediatric data exist to make definitive recommendations for the management of invasive mechanical ventilation for patients with PARDS. Ongoing research is needed to better understand how to guide best practices and improve outcomes for patients with PARDS requiring invasive mechanical ventilation.

Radiologic Assessment of Lung Edema Score as a Predictor of Clinical Outcome in Children with Acute Respiratory Distress Syndrome.

The radiographic assessment of lung edema (RALE) score enables objective quantification of lung edema and is a valuable prognostic marker of adult acute respiratory distress syndrome (ARDS). We aimed to evaluate the validity of RALE score in children with ARDS. The RALE score was measured for its reliability and correlation to other ARDS severity indices. ARDS-specific mortality was defined as death from severe pulmonary dysfunction or the need for extracorporeal membrane oxygenation therapy. The C-index of the RALE score and other ARDS severity indices were compared via survival analyses. Among 296 children with ARDS, 88 did not survive, and there were 70 ARDS-specific non-survivors. The RALE score showed good reliability with an intraclass correlation coefficient of 0.809 [95% confidence interval (CI), 0.760-0.848]. In univariable analysis, the RALE score had a hazard ratio (HR) of 1.19 (95% CI, 1.18-3.11), and the significance was maintained in multivariable analysis adjusting with age, ARDS etiology, and comorbidity, with an HR of 1.77 (95% CI, 1.05-2.91). The RALE score was a good predictor of ARDS-specific mortality, with a C-index of 0.607 (95% CI, 0.519-0.695). The RALE score is a reliable measure for ARDS severity and a useful prognostic marker of mortality in children, especially for ARDS-specific mortality. This score provides information that clinicians can use to decide the proper time of aggressive therapy targeting severe lung injury and to appropriately manage the fluid balance of children with ARDS.

The future of paediatric acute respiratory distress syndrome

Heterogeneity is a familiar concept to paediatric intensive care physicians, because patients, pathologies, and treatments vary both within the paediatric intensive care unit (PICU) and within a given disease process. Paediatric acute respiratory distress syndrome (ARDS) typifies this problem. Children with ARDS vary in terms of age (and therefore lung development), underlying cause (pneumonia, sepsis, or trauma), pre-existing comorbid conditions, and baseline immunological state. There is not one pathway by which ARDS occurs or manifests, as indicated by the identification of hyperinflammatory and hypoinflammatory subtypes in adults and children. 1 Calfee CS Delucchi KL Sinha P et al. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med. 2018; 6: 691-698 Google Scholar , 2 Dahmer MK Yang G Zhang M et al. Identification of phenotypes in paediatric patients with acute respiratory distress syndrome: a latent class analysis. Lancet Respir Med. 2022; 10: 289-297 Google Scholar Furthermore, treatments probably differ in their effectiveness, with interventions that are beneficial in some patients but harmful in others, leading to a null population average treatment effect. 3 Prescott HC Calfee CS Thompson BT Angus DC Liu VX Toward smarter lumping and smarter splitting: rethinking strategies for sepsis and acute respiratory distress syndrome clinical trial design. Am J Respir Crit Care Med. 2016; 194: 147-155 Google Scholar Thus, important questions need to be addressed to improve the management and outcomes of paediatric ARDS. In a Series paper in The Lancet Respiratory Medicine, 4 Kneyber MCJ Khemani RG Bhalla A et al. Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndrome. Lancet Respir Med. 2022; (published online Dec 22.)https://doi.org/10.1016/S2213-2600(22)00483-0 Google Scholar Martin Kneyber and colleagues—a multinational group of paediatric ARDS experts—provide a welcome summary of where we are now as a field, and what tools are available to address challenges for the next generation of paediatric ARDS trials. Two key questions need to be considered to improve the management and outcomes of paediatric ARDS. First, can we improve outcomes by identifying mechanisms or pathways to target therapeutically within specific subgroups? And second, can this be done through a nuanced approach rather than through the use of blunt, pleiotropic instruments? Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndromePaediatric acute respiratory distress syndrome (PARDS) is a heterogeneous clinical syndrome that is associated with high rates of mortality and long-term morbidity. Factors that distinguish PARDS from adult acute respiratory distress syndrome (ARDS) include changes in developmental stage and lung maturation with age, precipitating factors, and comorbidities. No specific treatment is available for PARDS and management is largely supportive, but methods to identify patients who would benefit from specific ventilation strategies or ancillary treatments, such as prone positioning, are needed. Full-Text PDF

28: BIOMARKER-BASED RISK STRATIFICATION IN PEDIATRIC SEPSIS FROM A LOW-MIDDLE-INCOME COUNTRY

Introduction: Most biomarker studies of sepsis and acute respiratory distress syndrome (ARDS) originate from high-income countries per World Bank classification, whereas mortality risk is higher in low- and middle-income countries. In children, the second iteration of the Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) has been validated in multiple North American pediatric intensive care units (PICUs) for prognosis, with areas under the receiver operating characteristic (AUROC) curve of > 0.80 for discriminating 28-day mortality. Given differences in epidemiology, we assessed the performance of PERSEVERE-II in septic children from Pakistan, a low-middle income country, as well as the utility of other select biomarkers. Methods: This was a prospective cohort study of children (age < 18 years) from Aga Khan University Hospital (AKUH) meeting modified pediatric Sepsis-3 criteria (pSOFA ≥ 2 and lactate > 2) between 11/2020 and 2/2022. Plasma was collected < 24 hours of PICU admission and biomarkers measured via single- and multiplex ELISAs. The AUROC for PERSEVERE-II to discriminate 28-day mortality was determined. Additional biomarkers were compared between PERSEVERE-II risk strata (low, medium, and high mortality risk), between survivors and non-survivors, and between those with and without ARDS. Projecting 15% mortality, 73 subjects were needed to detect AUROC > 0.80 at α = 0.05 and power = 0.90. Results: We enrolled 86 subjects with 20 (23%) 28-day non-survivors. PERSEVERE-II discriminated mortality with an AUROC of 0.83 (95% CI 0.72 to 0.94). Non-survivors had higher plasma angiopoietin-2 (ANG2), soluble thrombomodulin (sTM), and plasminogen activator inhibitor 1 (PAI1; all rank-sum p < 0.05), with increasing ANG2 across worsening PERSEVERE-II risk strata. Children who met ARDS criteria within 96 hours had elevated soluble receptor for advanced glycation end-products (sRAGE) and surfactant protein D (SPD; both rank-sum p < 0.05). Conclusions: PERSEVERE-II performs well in septic children from AKUH, representing the first validation of PERSEVERE-II in a low-middle income country. ANG2, sTM, and PAI1 were elevated in non-survivors, and sRAGE and SPD elevated in subjects with ARDS, suggesting a biomarker profile comparable to that of adult and pediatric sepsis and ARDS from high income countries.

The impact of reduction in intensity of mechanical ventilation upon venovenous ECMO initiation on radiographically assessed lung edema scores: A retrospective observational study.

BackgroundPatients with severe acute respiratory distress syndrome (ARDS) typically receive ultra-protective ventilation after extracorporeal membrane oxygenation (ECMO) is initiated. While the benefit of ECMO appears to derive from supporting “lung rest”, reductions in the intensity of mechanical ventilation, principally tidal volume limitation, may manifest radiologically. This study evaluated the relative changes in radiographic assessment of lung edema (RALE) score upon venovenous ECMO initiation in patients with severe ARDS.MethodsDigital chest x-rays (CXR) performed at baseline immediately before initiation of ECMO, and at intervals post (median 1.1, 2.1, and 9.6 days) were reviewed in 39 Adult ARDS patients. One hundred fifty-six digital images were scored by two independent, blinded radiologists according to the RALE (Radiographic Assessment of Lung Edema) scoring criteria. Ventilatory data, ECMO parameters and fluid balance were recorded at corresponding time points. Multivariable analysis was performed analyzing the change in RALE score over time relative to baseline.ResultsThe RALE score demonstrated excellent inter-rater agreement in this novel application in an ECMO cohort. Mean RALE scores increased from 28 (22–37) at baseline to 35 (26–42) (p < 0.001) on D1 of ECMO; increasing RALE was associated with higher baseline APACHE III scores [ß value +0.19 (0.08, 0.30) p = 0.001], and greater reductions in tidal volume [ß value −2.08 (−3.07, −1.10) p < 0.001] after ECMO initiation. Duration of mechanical ventilation, and ECMO support did not differ between survivors and non-survivors.ConclusionsThe magnitude of reductions in delivered tidal volumes correlated with increasing RALE scores (radiographic worsening) in ARDS patients receiving ECMO. Implications for patient centered outcomes remain unclear. There is a need to define appropriate ventilator settings on venovenous ECMO, counterbalancing the risks vs. benefits of optimal “lung rest” against potential atelectrauma.