2023 American Heart Association and American Academy of Pediatrics Focused Update on Neonatal Resuscitation: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

This 2023 focused update to the neonatal resuscitation guidelines is based on 4 systematic reviews recently completed under the direction of the International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Systematic reviewers and content experts from this task force performed comprehensive reviews of the scientific literature on umbilical cord management in preterm, late preterm, and term newborn infants, and the optimal devices and interfaces used for administering positive-pressure ventilation during resuscitation of newborn infants. These recommendations provide new guidance on the use of intact umbilical cord milking, device selection for administering positive-pressure ventilation, and an additional primary interface for administering positive-pressure ventilation.

Chronic Neuromuscular Respiratory Failure and Home Assisted Ventilation.

Chronic respiratory failure is a common, important complication of many types of neuromuscular and chest wall disorders. While the pathophysiology of each disease may be different, these disorders can variably affect all muscles involved in breathing, including inspiratory, expiratory, and bulbar muscles, ultimately leading to chronic respiratory failure and hypoventilation. The use of home assisted ventilation through noninvasive interfaces aims to improve the symptoms of hypoventilation, improve sleep quality, and, when possible, improve mortality. An increasing variety of interfaces has allowed for improved comfort and compliance. In a minority of scenarios, noninvasive ventilation is either not appropriate or no longer effective due to disease progression, and a transition to tracheal ventilation should be considered.

Extracorporeal Carbon Dioxide Removal to Avoid Invasive Ventilation During Exacerbations of Chronic Obstructive Pulmonary Disease: VENT-AVOID Trial - A Randomized Clinical Trial.

Rationale: It is unclear whether extracorporeal CO2 removal (ECCO2R) can reduce the rate of intubation or the total time on invasive mechanical ventilation (IMV) in adults experiencing an exacerbation of chronic obstructive pulmonary disease (COPD). Objectives: To determine whether ECCO2R increases the number of ventilator-free days within the first 5 days postrandomization (VFD-5) in exacerbation of COPD in patients who are either failing noninvasive ventilation (NIV) or who are failing to wean from IMV. Methods: This randomized clinical trial was conducted in 41 U.S. institutions (2018-2022) (ClinicalTrials.gov ID: NCT03255057). Subjects were randomized to receive either standard care with venovenous ECCO2R (NIV stratum: n = 26; IMV stratum: n = 32) or standard care alone (NIV stratum: n = 22; IMV stratum: n = 33). Measurements and Main Results: The trial was stopped early because of slow enrollment and enrolled 113 subjects of the planned sample size of 180. There was no significant difference in the median VFD-5 between the arms controlled by strata (P = 0.36). In the NIV stratum, the median VFD-5 for both arms was 5 days (median shift = 0.0; 95% confidence interval [CI]: 0.0-0.0). In the IMV stratum, the median VFD-5 in the standard care and ECCO2R arms were 0.25 and 2 days, respectively; median shift = 0.00 (95% confidence interval: 0.00-1.25). In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO2R arm (22% vs. 0%, P = 0.02) with no difference in the IMV stratum (17% vs. 15%, P = 0.73). Conclusions: In subjects with exacerbation of COPD, the use of ECCO2R compared with standard care did not improve VFD-5. Clinical trial registered with www.clinicaltrials.gov (NCT03255057).

Impact of High Dose Early Mobilization on Outcomes for Patients with Diabetes: A Secondary Analysis of the TEAM Trial.

RATIONALE: Patients with diabetes represent almost 20% of all ICU admissions and might respond differently to high dose early active mobilization. OBJECTIVES: To assess whether diabetes modified the relationship between the dose of early mobilization on clinical outcomes in the TEAM trial. METHODS: All TEAM trial patients were included. The primary outcome was days alive and out of hospital at day 180. Secondary outcomes included 180-day mortality and long-term functional outcomes at day 180. Logistic and median regression models were used to explore the effect of high dose early mobilization on outcomes by diabetes status. MEASUREMENTS AND MAIN RESULTS: All 741 patients from the original trial were included. Of these, 159 patients (21.4%) had diabetes. Patients with diabetes had a lower number of days alive and out of hospital at day 180 (124 [0-153] vs. 147 [82-164], p = 0.013), and higher 180-day mortality (30% vs. 18%, p = 0.044). In patients receiving high dose early mobilization, days alive and out of hospital at day 180 was 73.0 (0.0 - 144.5) in patients with diabetes and 146.5 (95.8 - 163.0) in patients without diabetes (p for interaction = 0.108). However, in patients with diabetes, high dose early mobilization increased the odds of mortality at 180 days (adjusted odds ratio 3.47; 95% confidence interval [CI], 1.67-7.61, p value for interaction, 0.001). CONCLUSIONS: In this secondary analysis of the TEAM trial, in patients with diabetes, a high dose early mobilization strategy did not significantly decrease the number of days alive and out of hospital at day 180 but it increased 180-day mortality.

Expiratory Muscle Activity Counteracts Positive End-Expiratory Pressure and Is Associated with Fentanyl Dose in Patients with Acute Respiratory Distress Syndrome.

Rationale: Hypoxemia during mechanical ventilation might be worsened by expiratory muscle activity, which reduces end-expiratory lung volume through lung collapse. A proposed mechanism of benefit of neuromuscular blockade in acute respiratory distress syndrome (ARDS) is the abolition of expiratory efforts. This may contribute to the restoration of lung volumes. The prevalence of this phenomenon, however, is unknown. Objectives: To investigate the incidence and amount of end-expiratory lung impedance (EELI) increase after the administration of neuromuscular blocking agents (NMBAs), clinical factors associated with this phenomenon, its impact on regional lung ventilation, and any association with changes in pleural pressure. Methods: We included mechanically ventilated patients with ARDS monitored with electrical impedance tomography (EIT) who received NMBAs in one of two centers. We measured changes in EELI, a surrogate for end-expiratory lung volume, before and after NMBA administration. In an additional 10 patients, we investigated the characteristic signatures of expiratory muscle activity depicted by EIT and esophageal catheters simultaneously. Clinical factors associated with EELI changes were assessed. Measurements and Main Results: We included 46 patients, half of whom showed an increase in EELI of >10% of the corresponding Vt (46.2%; IQR, 23.9-60.9%). The degree of EELI increase correlated positively with fentanyl dosage and negatively with changes in end-expiratory pleural pressures. This suggests that expiratory muscle activity might exert strong counter-effects against positive end-expiratory pressure that are possibly aggravated by fentanyl. Conclusions: Administration of NMBAs during EIT monitoring revealed activity of expiratory muscles in half of patients with ARDS. The resultant increase in EELI had a dose-response relationship with fentanyl dosage. This suggests a potential side effect of fentanyl during protective ventilation.

High Airway Occlusion Pressure Is Associated with Dyspnea and Increased Mortality in Critically Ill Mechanically Ventilated Patients.

Rationale: Airway occlusion pressure at 100 ms (P0.1) reflects central respiratory drive. Objectives: We aimed to assess factors associated with P0.1 and whether an abnormally low or high P0.1 value is associated with higher mortality and longer duration of mechanical ventilation (MV). Methods: We performed a secondary analysis of a prospective cohort study conducted in 10 ICUs in France to evaluate dyspnea in communicative MV patients. In patients intubated for more than 24 hours, P0.1 was measured with dyspnea as soon as patients could communicate and the next day. Measurements and Main Results: Among 260 patients assessed after a median time of ventilation of 4 days, P0.1 was 1.9 (1-3.5) cm H2O at enrollment, 24% had P0.1 values >3.5 cm H2O, 37% had P0.1 values between 1.5 and 3.5 cm H2O, and 39% had P0.1 values <1.5 cm H2O. In multivariable linear regression, independent factors associated with P0.1 were the presence of dyspnea (P = 0.037), respiratory rate (P < 0.001), and PaO2 (P = 0.008). Ninety-day mortality was 33% in patients with P0.1 > 3.5 cm H2O versus 19% in those with P0.1 between 1.5 and 3.5 cm H2O and 17% in those with P0.1 < 1.5 cm H2O (P = 0.046). After adjustment for the main risk factors, P0.1 was associated with 90-day mortality (hazard ratio per 1 cm H2O, 1.19 [95% confidence interval, 1.04-1.37]; P = 0.011). P0.1 was also independently associated with a longer duration of MV (hazard ratio per 1 cm H2O, 1.10 [95% confidence interval, 1.02-1.19]; P = 0.016). Conclusions: In patients receiving invasive MV, abnormally high P0.1 values may suggest dyspnea and are associated with higher mortality and prolonged duration of MV.

Geo-economic Influence on the Effect of Fluid Volume for Sepsis Resuscitation: A Meta-Analysis.

Rationale: Sepsis management relies on fluid resuscitation avoiding fluid overload and its related organ congestion. Objectives: To explore the influence of country income group on risk-benefit balance of fluid management strategies in sepsis. Methods: We searched e-databases for all randomized controlled trials on fluid resuscitation in patients with sepsis or septic shock up to January 2023, excluding studies on hypertonic fluids, colloids, and depletion-based interventions. The effect of fluid strategies (higher versus lower volumes) on mortality was analyzed per income group (i.e., low- and middle-income countries [LMICs] or high-income countries [HICs]). Measurements and Main Results: Twenty-nine studies (11,798 patients) were included in the meta-analysis. There was a numerically higher mortality in studies of LMICs as compared with those of HICs: median, 37% (interquartile range [IQR]: 26-41) versus 29% (IQR: 17-38; P = 0.06). Income group significantly interacted with the effect of fluid volume on mortality: Higher fluid volume was associated with higher mortality in LMICs but not in HICs: odds ratio (OR), 1.47; 95% confidence interval (95% CI): 1.14-1.90 versus 1.00 (95% CI: 0.87-1.16), P = 0.01 for subgroup differences. Higher fluid volume was associated with increased need for mechanical ventilation in LMICs (OR, 1.24 [95% CI: 1.08-1.43]) but not in HICs (OR, 1.02 [95% CI: 0.80-1.29]). Self-reported access to mechanical ventilation also significantly influenced the effect of fluid volume on mortality, which increased with higher volumes only in settings with limited access to mechanical ventilation (OR: 1.45 [95% CI: 1.09-1.93] vs. 1.09 [95% CI: 0.93-1.28], P = 0.02 for subgroup differences). Conclusions: In sepsis trials, the effect of fluid resuscitation approach differed by setting, with higher volume of fluid resuscitation associated with increased mortality in LMICs and in settings with restricted access to mechanical ventilation. The precise reason for these differences is unclear and may be attributable in part to resource constraints, participant variation between trials, or other unmeasured factors.

Shift-Level Team Familiarity Is Associated with Improved Outcomes in Mechanically Ventilated Adults.

RATIONALE: Organizing intensive care unit (ICU) interprofessional teams is a high priority due to workforce needs, but the role of interprofessional familiarity remains unexplored. OBJECTIVE: Determine if mechanically ventilated patients cared for by teams with greater familiarity have improved outcomes, such as lower mortality, shorter duration of mechanical ventilation (MV), and greater spontaneous breathing trial (SBT) implementation. METHODS: We used electronic health records data of 5 ICUs in an academic medical center to map interprofessional teams and their ICU networks, measuring team familiarity as network coreness and mean team value. We used patient-level regression models to link team familiarity with patient outcomes, accounting for patient/unit factors. We also performed a split-sample analysis by using 2018 team familiarity data to predict 2019 outcomes. MEASUREMENTS: Team familiarity was measured as the average number of patients shared by each clinician with all other clinicians in the ICU (i.e., coreness) and the average number of patients shared by any two members of the team (i.e., mean team value). MAIN RESULTS: Among 4,485 encounters, unadjusted mortality was 12.9%, average duration of MV was 2.32 days and SBT implementation was 89%; average team coreness was 467.2 (SD = 96.15) and average mean team value was 87.02 (SD=42.42). A standard-deviation increase in team coreness was significantly associated with a 4.5% greater probability of SBT implementation, 23% shorter MV duration, and 3.8% lower probability of dying; mean team value was significantly associated with lower mortality. Split-sample results were attenuated but congruent in direction and interpretation. CONCLUSIONS: Interprofessional familiarity was associated with improved outcomes; assignment models that prioritize familiarity might be a novel solution.

Electrical Impedance Tomography-based Ventilation Patterns in Patients after Major Surgery.

Rationale: General anesthesia and mechanical ventilation have negative impacts on the respiratory system, causing heterogeneous distribution of lung aeration, but little is known about the ventilation patterns of postoperative patients and their association with clinical outcomes. Objectives: To clarify the phenotypes of ventilation patterns along a gravitational direction after surgery by using electrical impedance tomography (EIT) and to evaluate their association with postoperative pulmonary complications (PPCs) and other relevant clinical outcomes. Methods: Adult postoperative patients at high risk for PPCs, receiving mechanical ventilation on ICU admission (N = 128), were prospectively enrolled between November 18, 2021 and July 18, 2022. PPCs were prospectively scored until hospital discharge, and their association with phenotypes of ventilation patterns was studied. The secondary outcomes were the times to wean from mechanical ventilation and oxygen use and the length of ICU stay. Measurements and Main Results: Three phenotypes of ventilation patterns were revealed by EIT: phenotype 1 (32% [n = 41], a predominance of ventral ventilation), phenotype 2 (41% [n = 52], homogeneous ventilation), and phenotype 3 (27% [n = 35], a predominance of dorsal ventilation). The median PPC score was higher in phenotype 1 and phenotype 3 than in phenotype 2. The median time to wean from mechanical ventilation was longer in phenotype 1 versus phenotype 2. The median duration of ICU stay was longer in phenotype 1 versus phenotype 2. The median time to wean from oxygen use was longer in phenotype 1 and phenotype 3 than in phenotype 2. Conclusions: Inhomogeneous ventilation patterns revealed by EIT on ICU admission were associated with PPCs, delayed weaning from mechanical ventilation and oxygen use, and a longer ICU stay.

Oxygen-Saturation Targets and Cognitive and Functional Outcomes in Mechanically Ventilated Adults.

Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown.Objectives: To compare the effects of lower (90% [range, 88-92%]), intermediate (94% [range, 92-96%]), and higher (98% [range, 96-100%]) oxygen-saturation targets on long-term outcomes.Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction.Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91-96%), 95% (93-97%), and 97% (95-99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92-2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62-1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83-1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life.Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes.

Electrical Impedance Tomography to Monitor Hypoxemic Respiratory Failure.

Hypoxemic respiratory failure is one of the leading causes of mortality in intensive care. Frequent assessment of individual physiological characteristics and delivery of personalized mechanical ventilation (MV) settings is a constant challenge for clinicians caring for these patients. Electrical impedance tomography (EIT) is a radiation-free bedside monitoring device that is able to assess regional lung ventilation and changes in aeration. With real-time tomographic functional images of the lungs obtained through a thoracic belt, clinicians can visualize and estimate the distribution of ventilation at different ventilation settings or following procedures such as prone positioning. Several studies have evaluated the performance of EIT to monitor the effects of different MV settings in patients with acute respiratory distress syndrome, allowing more personalized MV. For instance, EIT could help clinicians find the positive end-expiratory pressure that represents a compromise between recruitment and overdistension and assess the effect of prone positioning on ventilation distribution. The clinical impact of the personalization of MV remains to be explored. Despite inherent limitations such as limited spatial resolution, EIT also offers a unique noninvasive bedside assessment of regional ventilation changes in the ICU. This technology offers the possibility of a continuous, operator-free diagnosis and real-time detection of common problems during MV. This review provides an overview of the functioning of EIT, its main indices, and its performance in monitoring patients with acute respiratory failure. Future perspectives for use in intensive care are also addressed.

Uncovering eco-friendly design in the ancient bronze goose-and-fish lamp: an unnoticeable gap boosts ventilation.

The bronze goose-and-fish lamp exhibited in the national museum of China is a 2,000-y-old artifact once used for indoor lighting by nobility in the Western Han dynasty (206 BCE TO 25 CE). The beauty of this national treasure arises from its elegant shape vividly showing a goose catching fish with beautiful colors painted over the whole body. Beyond the artistic and historical value, what enchants people most is the eco-design concept of this oil-burning lamp. It is widely believed that the smoke generated by burning animal oil can flow into the goose belly through its long neck, then be absorbed by prefilled water in the belly, hence mitigating indoor air pollution. Although different mechanistic hypotheses such as natural convection and even the siphon effect have been proposed to qualitatively rationalize the above-claimed pollution mitigation function, due to the absence of a true scientific analysis, the definitive mechanism remains a mystery. By rigorous modeling of the nonisothermal fluid flow coupled with convection-diffusion of pollutant within and out of the lamp, we discover that it is the unnoticeable gap between goose body and lamp tray (i.e., an intrinsic feature of the multicompartmental design) that can offer definitive ventilation in the lamp. The ventilation is facilitated by natural convection due to oil burning. Adequate ventilation plays a key role in enabling pollution mitigation, as it allows pollutant to reach the goose belly, travel over and be absorbed by the water.

Ventilator-induced Lung Injury Promotes Inflammation within the Pleural Cavity.

Mechanical ventilation contributes to the morbidity and mortality of patients in intensive care, likely through the exacerbation and dissemination of inflammation. Despite the proximity of the pleural cavity to the lungs and exposure to physical forces, little attention has been paid to its potential as an inflammatory source during ventilation. Here, we investigate the pleural cavity as a novel site of inflammation during ventilator-induced lung injury. Mice were subjected to low or high tidal volume ventilation strategies for up to 3 hours. Ventilation with a high tidal volume significantly increased cytokine and total protein levels in BAL and pleural lavage fluid. In contrast, acid aspiration, explored as an alternative model of injury, only promoted intraalveolar inflammation, with no effect on the pleural space. Resident pleural macrophages demonstrated enhanced activation after injurious ventilation, including upregulated ICAM-1 and IL-1ß expression, and the release of extracellular vesicles. In vivo ventilation and in vitro stretch of pleural mesothelial cells promoted ATP secretion, whereas purinergic receptor inhibition substantially attenuated extracellular vesicles and cytokine levels in the pleural space. Finally, labeled protein rapidly translocated from the pleural cavity into the circulation during high tidal volume ventilation, to a significantly greater extent than that of protein translocation from the alveolar space. Overall, we conclude that injurious ventilation induces pleural cavity inflammation mediated through purinergic pathway signaling and likely enhances the dissemination of mediators into the vasculature. This previously unidentified consequence of mechanical ventilation potentially implicates the pleural space as a focus of research and novel avenue for intervention in critical care.

Breath Markers of Oxidative Stress in Children with Severe Viral Lower Respiratory Tract Infection.

Severe viral lower respiratory tract infection (LRTI), resulting in both acute and long-term pulmonary disease, constitutes a substantial burden among young children. Viral LRTI triggers local oxidative stress pathways by infection and inflammation, and supportive care in the pediatric intensive care unit may further aggravate oxidative injury. The main goal of this exploratory study was to identify and monitor breath markers linked to oxidative stress in children over the disease course of severe viral LRTI. Exhaled breath was sampled during invasive ventilation, and volatile organic compounds (VOCs) were analyzed using gas chromatography and mass spectrometry. VOCs were selected in an untargeted principal component analysis and assessed for change over time. In addition, identified VOCs were correlated with clinical parameters. Seventy breath samples from 21 patients were analyzed. A total of 15 VOCs were identified that contributed the most to the explained variance of breath markers. Of these 15 VOCs, 10 were previously linked to pathways of oxidative stress. Eight VOCs, including seven alkanes and methyl alkanes, significantly decreased from the initial phase of ventilation to the day of extubation. No correlation was observed with the administered oxygen dose, whereas six VOCs showed a poor to strong positive correlation with driving pressure. In this prospective study of children with severe viral LRTI, the majority of VOCs that were most important for the explained variance mirrored clinical improvement. These breath markers could potentially help monitor the pulmonary oxidative status in these patients, but further research with other objective measures of pulmonary injury is required.

Irisin attenuates ventilator-induced diaphragmatic dysfunction by inhibiting endoplasmic reticulum stress through activation of AMPK.

Mechanical ventilation (MV) is an essential life-saving technique, but prolonged MV can cause significant diaphragmatic dysfunction due to atrophy and decreased contractility of the diaphragm fibres, called ventilator-induced diaphragmatic dysfunction (VIDD). It is not clear about the mechanism of occurrence and prevention measures of VIDD. Irisin is a newly discovered muscle factor that regulates energy metabolism. Studies have shown that irisin can exhibit protective effects by downregulating endoplasmic reticulum (ER) stress in a variety of diseases; whether irisin plays a protective role in VIDD has not been reported. Sprague-Dawley rats were mechanically ventilated to construct a VIDD model, and intervention was performed by intravenous administration of irisin. Diaphragm contractility, degree of atrophy, cross-sectional areas (CSAs), ER stress markers, AMPK protein expression, oxidative stress indicators and apoptotic cell levels were measured at the end of the experiment.Our findings showed that as the duration of ventilation increased, the more severe the VIDD was, the degree of ER stress increased, and the expression of irisin decreased.ER stress may be one of the causes of VIDD. Intervention with irisin ameliorated VIDD by reducing the degree of ER stress, attenuating oxidative stress, and decreasing the apoptotic index. MV decreases the expression of phosphorylated AMPK in the diaphragm, whereas the use of irisin increases the expression of phosphorylated AMPK. Irisin may exert its protective effect by activating the phosphorylated AMPK pathway.

Bag-Valve-Mask Ventilation and Survival From Out-of-Hospital Cardiac Arrest: A Multicenter Study.

BACKGROUND: Few studies have measured ventilation during early cardiopulmonary resuscitation (CPR) before advanced airway placement. Resuscitation guidelines recommend pauses after every 30 chest compressions to deliver ventilations. The effectiveness of bag-valve-mask ventilation delivered during the pause in chest compressions is unknown. We sought to determine: (1) the incidence of lung inflation with bag-valve-mask ventilation during 30:2 CPR; and (2) the association of ventilation with outcomes after out-of-hospital cardiac arrest. METHODS: We studied patients with out-of-hospital cardiac arrest from 6 sites of the Resuscitation Outcomes Consortium CCC study (Trial of Continuous Compressions versus Standard CPR in Patients with Out-of-Hospital Cardiac Arrest). We analyzed patients assigned to the 30:2 CPR arm with ≥2 minutes of thoracic bioimpedance signal recorded with a cardiac defibrillator/monitor. Detectable ventilation waveforms were defined as having a bioimpedance amplitude ≥0.5 Ω (corresponding to ≥250 mL VT) and a duration ≥1 s. We defined a chest compression pause as a 3- to 15-s break in chest compressions. We compared the incidence of ventilation and outcomes in 2 groups: patients with ventilation waveforms in <50% of pauses (group 1) versus those with waveforms in ≥50% of pauses (group 2). RESULTS: Among 1976 patients, the mean age was 65 years; 66% were male. From the start of chest compressions until advanced airway placement, mean±SD duration of 30:2 CPR was 9.8±4.9 minutes. During this period, we identified 26 861 pauses in chest compressions; 60% of patients had ventilation waveforms in <50% of pauses (group 1, n=1177), and 40% had waveforms in ≥50% of pauses (group 2, n=799). Group 1 had a median of 12 pauses and 2 ventilations per patient versus group 2, which had 12 pauses and 12 ventilations per patient. Group 2 had higher rates of prehospital return of spontaneous circulation (40.7% versus 25.2%; P<0.0001), survival to hospital discharge (13.5% versus 4.1%; P<0.0001), and survival with favorable neurological outcome (10.6% versus 2.4%; P<0.0001). These associations persisted after adjustment for confounders. CONCLUSIONS: In this study, lung inflation occurred infrequently with bag-valve-mask ventilation during 30:2 CPR. Lung inflation in ≥50% of pauses was associated with improved return of spontaneous circulation, survival, and survival with favorable neurological outcome.

Pre-existing Immunocompromising Conditions and Outcomes of Acute COVID-19 Patients Admitted for Pediatric Intensive Care.

BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. METHODS: 55 hospitals in 30 U.S. states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted March 12, 2020-December 30, 2021 to the pediatric intensive care unit (PICU) or high acuity unit for acute COVID-19 were included. RESULTS: Of 1,274 patients, 105 (8.2%) had an ICC including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid organ transplantation, 16 (15.2%) solid tumors and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs. 4.6%, p = 0.005) and hospitalization was longer (p = 0.01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, p = 0.40). In patients with ICC, bacterial co-infection was more common in those with life-threatening COVID-19. CONCLUSIONS: In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities.

Bioinformatics analysis identifies a key gene HLA_DPA1 in severe influenza-associated immune infiltration.

BACKGROUND: Severe influenza is a serious global health issue that leads to prolonged hospitalization and mortality on a significant scale. The pathogenesis of this infectious disease is poorly understood. Therefore, this study aimed to identify the key genes associated with severe influenza patients necessitating invasive mechanical ventilation. METHODS: The current study utilized two publicly accessible gene expression profiles (GSE111368 and GSE21802) from the Gene Expression Omnibus database. The research focused on identifying the genes exhibiting differential expression between severe and non-severe influenza patients. We employed three machine learning algorithms, namely the Least Absolute Shrinkage and Selection Operator regression model, Random Forest, and Support Vector Machine-Recursive Feature Elimination, to detect potential key genes. The key gene was further selected based on the diagnostic performance of the target genes substantiated in the dataset GSE101702. A single-sample gene set enrichment analysis algorithm was applied to evaluate the participation of immune cell infiltration and their associations with key genes. RESULTS: A total of 44 differentially expressed genes were recognized; among them, we focused on 10 common genes, namely PCOLCE2, HLA_DPA1, LOC653061, TDRD9, MPO, HLA_DQA1, MAOA, S100P, RAP1GAP, and CA1. To ensure the robustness of our findings, we employed overlapping LASSO regression, Random Forest, and SVM-RFE algorithms. By utilizing these algorithms, we were able to pinpoint the aforementioned 10 genes as potential biomarkers for distinguishing between both cases of influenza (severe and non-severe). However, the gene HLA_DPA1 has been recognized as a crucial factor in the pathological condition of severe influenza. Notably, the validation dataset revealed that this gene exhibited the highest area under the receiver operating characteristic curve, with a value of 0.891. The use of single-sample gene set enrichment analysis has provided valuable insights into the immune responses of patients afflicted with severe influenza that have further revealed a categorical correlation between the expression of HLA_DPA1 and lymphocytes. CONCLUSION: The findings indicated that the HLA_DPA1 gene may play a crucial role in the immune-pathological condition of severe influenza and could serve as a promising therapeutic target for patients infected with severe influenza.

Low-volume ventilation of preinjured lungs degrades lung function via stress concentration and progressive alveolar collapse.

Mechanical ventilation can cause ventilation-induced lung injury (VILI). The concept of stress concentrations suggests that surfactant dysfunction-induced microatelectases might impose injurious stresses on adjacent, open alveoli and function as germinal centers for injury propagation. The aim of the present study was to quantify the histopathological pattern of VILI progression and to test the hypothesis that injury progresses at the interface between microatelectases and ventilated lung parenchyma during low-positive end-expiratory pressure (PEEP) ventilation. Bleomycin was used to induce lung injury with microatelectases in rats. Lungs were then mechanically ventilated for up to 6 h at PEEP = 1 cmH2O and compared with bleomycin-treated group ventilated protectively with PEEP = 5 cmH2O to minimize microatelectases. Lung mechanics were measured during ventilation. Afterward, lungs were fixed at end-inspiration or end-expiration for design-based stereology. Before VILI, bleomycin challenge reduced the number of open alveoli [N(alvair,par)] by 29%. No differences between end-inspiration and end-expiration were observed. Collapsed alveoli clustered in areas with a radius of up to 56 µm. After PEEP = 5 cmH2O ventilation for 6 h, N(alvair,par) remained stable while PEEP = 1 cmH2O ventilation led to an additional loss of aerated alveoli by 26%, mainly due to collapse, with a small fraction partly edema filled. Alveolar loss strongly correlated to worsening of tissue elastance, quasistatic compliance, and inspiratory capacity. The radius of areas of collapsed alveoli increased to 94 µm, suggesting growth of the microatelectases. These data provide evidence that alveoli become unstable in neighborhood of microatelectases, which most likely occurs due to stress concentration-induced local vascular leak and surfactant dysfunction.NEW & NOTEWORTHY Low-volume mechanical ventilation in the presence of high surface tension-induced microatelectases leads to the degradation of lung mechanical function via the progressive loss of alveoli. Microatelectases grow at the interfaces of collapsed and open alveoli. Here, stress concentrations might cause injury and alveolar instability. Accumulation of small amounts of alveolar edema can be found in a fraction of partly collapsed alveoli but, in this model, alveolar flooding is not a major driver for degradation of lung mechanics.

In utero ventilation induces lung parenchymal and vascular alterations in extremely preterm fetal sheep.

Extremely preterm infants are often exposed to long durations of mechanical ventilation to facilitate gas exchange, resulting in ventilation-induced lung injury (VILI). New lung protective strategies utilizing noninvasive ventilation or low tidal volumes are now common but have not reduced rates of bronchopulmonary dysplasia. We aimed to determine the effect of 24 h of low tidal volume ventilation on the immature lung by ventilating preterm fetal sheep in utero. Preterm fetal sheep at 110 ± 1(SD) days' gestation underwent sterile surgery for instrumentation with a tracheal loop to enable in utero mechanical ventilation (IUV). At 112 ± 1 days' gestation, fetuses received either in utero mechanical ventilation (IUV, n = 10) targeting 3-5 mL/kg for 24 h, or no ventilation (CONT, n = 9). At necropsy, fetal lungs were collected to assess molecular and histological markers of lung inflammation and injury. IUV significantly increased lung mRNA expression of interleukin (IL)-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF) compared with CONT, and increased surfactant protein (SP)-A1, SP-B, and SP-C mRNA expression compared with CONT. IUV produced modest structural changes to the airways, including reduced parenchymal collagen and myofibroblast density. IUV increased pulmonary arteriole thickness compared with CONT but did not alter overall elastin or collagen content within the vasculature. In utero ventilation of an extremely preterm lung, even at low tidal volumes, induces lung inflammation and injury to the airways and vasculature. In utero ventilation may be an important model to isolate the confounding mechanisms of VILI to develop effective therapies for preterm infants requiring prolonged respiratory support.NEW & NOTEWORTHY Preterm infants often require prolonged respiratory support, but the relative contribution of ventilation to the development of lung injury is difficult to isolate. In utero mechanical ventilation allows for mechanistic investigations into ventilation-induced lung injury without confounding factors associated with sustaining extremely preterm lambs ex utero. Twenty-four hours of in utero ventilation, even at low tidal volumes, increased lung inflammation and surfactant protein expression and produced structural changes to the lung parenchyma and vasculature.