Bidirectional pressure: a mini review of ventilator-lung-kidney interactions.

Acute kidney injury and respiratory failure that requires mechanical ventilation are both common complications of critical illnesses. Failure of either of these organ systems also increases the risk of failure to the other. As a result, there is a high incidence of patients with concomitant acute kidney injury and the need for mechanical ventilation, which has a devasting impact on intensive care unit outcomes, including mortality. Despite decades of research into the mechanisms of ventilator-lung-kidney interactions, several gaps in knowledge remain and current treatment strategies are primarily supportive. In this review, we outline our current understanding of the mechanisms of acute kidney injury due to mechanical ventilation including a discussion of; 1) The impact of mechanical ventilation on renal perfusion, 2) activation of neurohormonal pathways by positive pressure ventilation, and 3) the role of inflammatory mediators released during ventilator induced lung injury. We also provide a review of the mechanisms by which acute kidney injury increases the risk of respiratory failure. Next, we outline a summary of the current therapeutic approach to preventing lung and kidney injury in the critically ill, including fluid and vasopressor management, ventilator strategies, and treatment of acute kidney injury. Finally, we conclude with a discussion outlining opportunities for novel investigations that may provide a rationale for new treatment approaches.

Unmasking Negative Pressure Pulmonary Edema Following Hanging: A Case Series.

Pulmonary edema is a rare mechanism of death that develops after partial hanging, a potential complication that physicians should consider early in the management of these patients. This case series discusses the presentation, evaluation, and treatment course of three patients who had attempted suicide by hanging and were admitted to the hospital. These patients were admitted to the intensive care unit after being stabilized and supportive treatment was provided. In all the cases, a radiological scan of the chest revealed diffuse infiltrates consistent with pulmonary edema on both sides, features of which were also noted during a diagnostic bronchoscopy. After providing the best intensive care in the hospital, two patients clinically improved, and one patient succumbed to cardiac arrest. As most patients will be brought dead to the hospital following hanging, negative pressure pulmonary edema remains underdiagnosed. Thus, this case series enumerates the possible etiologies of negative pressure pulmonary edema and its contribution to death following suicidal hanging.

Outpatient versus inpatient management of preterm prelabor rupture of membranes: A systematic review and meta-analysis.

INTRODUCTION: To compare neonatal, obstetrical, and maternal outcomes associated with outpatient versus inpatient management of pregnancies with preterm prelabor rupture of membranes (PPROM). MATERIAL AND METHODS: A search of MEDLINE, EMBASE, the Cochrane Database and Central Register from January 1, 1990 to July 31, 2023 identified randomized controlled trials (RCTs) and cohort studies comparing outpatient with inpatient management for pregnant persons diagnosed with PPROM before 37 weeks' gestation. No language restriction was applied. We applied a random effects model for meta-analysis. Trustworthiness was assessed using recently published guidance and Risk of bias using the RoB 2.0 tool for RCTs and ROBINS-I tool for cohort studies. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to assess the certainty of evidence (COE). Outcomes of interest included perinatal mortality, neonatal morbidities, latency and gestational age at delivery, and maternal morbidities. RCTs and cohort studies were analyzed separately. This study was registered in the International Prospective Register of Systematic Reviewsr: CRD42022295275. RESULTS: From 2825 records, two RCTs and 10 cohort studies involving 1876 patients were included in the review and meta-analysis. Outpatient management protocols varied but generally included brief initial hospitalization, strict eligibility criteria, and surveillance with laboratory and ultrasound investigations. Outpatient management showed lower rates of neonatal respiratory distress syndrome (cohort: RR 0.63 [0.52-0.77, very low COE]), longer latency to delivery (RCT: MD 7.43 days [1.14-13.72 days, moderate COE], cohort: MD 8.78 days [2.29-15.26 days, low COE]), higher gestational age at birth (cohort: MD 7.70 days [2.02-13.38 days, low COE]), lower rates of Apgar scores <7 at 5 min of life (cohort: RR 0.66 [0.50-0.89, very low COE]), and lower rates of histological chorioamnionitis (cohort: RR 0.74 [0.62-0.89, low COE]) without increased risks of adverse neonatal, obstetrical, or maternal outcomes. CONCLUSIONS: Meta-analysis of data from RCTs and cohort studies with very low-to-moderate certainty of evidence indicates that further high-quality research is needed to evaluate the safety and potential benefits of outpatient management for selected PPROM cases, given the moderate-to-high risk of bias in the included studies.

Leptospirosis-Associated Acute Respiratory Distress Syndrome (ARDS) in Pregnancy: A Rare Presentation.

Leptospirosis, a zoonotic disease caused by spirochetes of the genus Leptospira, poses unique challenges in pregnancy due to its varied clinical presentation and potential adverse outcomes for both mother and fetus. We present a case of a 24-year-old primigravida at 35 weeks of gestation who presented with fever, dyspnea, and abdominal pain, and was ultimately diagnosed with leptospirosis complicated by acute respiratory distress syndrome (ARDS). Prompt initiation of antibiotic therapy, supportive care, and timely delivery via emergency cesarean section led to favorable maternal and neonatal outcomes. This case report underscores the importance of considering leptospirosis in pregnant patients presenting with similar symptoms, particularly in endemic regions, and highlights the critical role of multidisciplinary management in optimizing outcomes.

Betamethasone treatment-to-delivery interval, retreatment, and severe intraventricular hemorrhage in infants <28 weeks' gestation.

BACKGROUND: Antenatal corticosteroids decrease the incidence of severe intraventricular hemorrhages (grades 3,4) in preterm infants. It is unclear whether their beneficial effects on intraventricular hemorrhage wane with time (as occurs in neonatal respiratory distress) and if repeat courses can restore this effect. Prior randomized controlled trials of betamethasone retreatment found no benefit on severe intraventricular hemorrhage rates. However, the trials may have included an insufficient number of infants at risk for intraventricular hemorrhage to be able to adequately address this question. Severe intraventricular hemorrhages occur almost exclusively in infants born <28 weeks, whereas only 7% (0%-16%) of the retreatment trials' populations were <28 weeks. OBJECTIVE: To determine if the risk of severe intraventricular hemorrhage in infants delivered <28 weeks increases when the betamethasone treatment-to-delivery interval increases beyond 9 days and to determine if betamethasone retreatment prior to delivery decreases the rate of hemorrhage. STUDY DESIGN: Observational study examining the incidence of intraventricular hemorrhage before (epoch 1) and after (epoch 2) a practice change that encouraged obstetricians to retreat pregnant women still at high risk of delivery before 28 weeks' gestation when >9 days elapsed from the first dose of betamethasone. Multivariable analyses with logistic regression using generalized estimating equations techniques were conducted to examine the rates of intraventricular hemorrhage among 410 infants <28 weeks' gestation who either delivered between 1-9 days (n=290) after the first 2-dose betamethasone course or delivered ≥10 days (and eligible for retreatment) (n=120). RESULTS: After adjusting for potential confounding variables, infants who delivered ≥10 days after a single betamethasone course had an increased risk of either severe intraventricular hemorrhage alone or the combined outcome severe intraventricular hemorrhage or death before 4 days (OR (95%CI): 2.8 (1.2, 6.6)) compared with infants who delivered between 1-9 days after betamethasone. Among the 120 infants who delivered ≥10 days after the first dose of betamethasone, 64 (53%) received a second/retreatment course of antenatal betamethasone. The severe intraventricular hemorrhage rate in infants whose mothers received a second/retreatment course of betamethasone was similar to the rate in infants who delivered within 1-9 days and significantly lower than in those who delivered ≥10 days without retreatment (OR (95%CI): 0.10 (0.02, 0.65). Following the change in guidelines, the rate of retreatment in infants who delivered ≥10 days after the first betamethasone course (and before 28 weeks) increased from epoch 1 to epoch 2 (25% to 87%, p<0.001) and the rate of severe intraventricular hemorrhage decreased from 22% to 0% (p<0.001). In contrast, the rate of severe intraventricular hemorrhage in infants who delivered 1-9 days after the initial betamethasone dose (who were not eligible for retreatment) did not change between epochs 1 and 2 (12% and 11%, respectively). CONCLUSIONS: Although betamethasone's benefits on severe intraventricular hemorrhage appear to wane after the first dose, retreatment with a second course appears to restore its beneficial effects. Encouraging earlier retreatment of women at high risk of delivery before 28 weeks was associated with a lower rate of severe intraventricular hemorrhages among infants delivering <28 weeks.

Respiratory support with standard low-flow oxygen therapy, high-flow oxygen therapy or continuous positive airway pressure in adults with acute hypoxaemic respiratory failure in a resource-limited setting: protocol for a randomised, open-label, clinical trial - the Acute Respiratory Intervention StudiEs in Africa (ARISE-AFRICA) study.

RATIONALE: Acute hypoxaemic respiratory failure (AHRF) is associated with high mortality in sub-Saharan Africa. This is at least in part due to critical care-related resource constraints including limited access to invasive mechanical ventilation and/or highly skilled acute care workers. Continuous positive airway pressure (CPAP) and high-flow oxygen by nasal cannula (HFNC) may prove useful to reduce intubation, and therefore, improve survival outcomes among critically ill patients, particularly in resource-limited settings, but data in such settings are lacking. The aim of this study is to determine whether CPAP or HFNC as compared with standard oxygen therapy, could reduce mortality among adults presenting with AHRF in a resource-limited setting. METHODS: This is a prospective, multicentre, randomised, controlled, stepped wedge trial, in which patients presenting with AHRF in Uganda will be randomly assigned to standard oxygen therapy delivered through a face mask, HFNC oxygen or CPAP. The primary outcome is all-cause mortality at 28 days. Secondary outcomes include the number of patients with criteria for intubation at day 7, the number of patients intubated at day 28, ventilator-free days at day 28 and tolerance of each respiratory support. ETHICS AND DISSEMINATION: The study has obtained ethical approval from the Research and Ethics Committee, School of Biomedical Sciences, College of Health Sciences, Makerere University as well as the Uganda National Council for Science and Technology. Patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04693403. PROTOCOL VERSION: 8 September 2023; version 5.

Accidental Intravenous Administration of Simethicone in a 4-Year-Old Patient: A Case Report.

Simethicone is an antiflatulent medication exclusively administered orally, thus its systemic effects remain unknown. We present a case of an inadvertent intravenous administration of simethicone to a 4-year-old patient, precipitating respiratory difficulty, cyanosis, and altered mental status. The patient's condition improved rapidly with appropriate interventions, leading to discharge in a fully recovered state. To date, only one documented instance of intravenous simethicone administration exists in medical literature.

Physiological and clinical effects of trunk inclination adjustment in patients with respiratory failure: a scoping review and narrative synthesis.

BACKGROUND: Adjusting trunk inclination from a semi-recumbent position to a supine-flat position or vice versa in patients with respiratory failure significantly affects numerous aspects of respiratory physiology including respiratory mechanics, oxygenation, end-expiratory lung volume, and ventilatory efficiency. Despite these observed effects, the current clinical evidence regarding this positioning manoeuvre is limited. This study undertakes a scoping review of patients with respiratory failure undergoing mechanical ventilation to assess the effect of trunk inclination on physiological lung parameters. METHODS: The PubMed, Cochrane, and Scopus databases were systematically searched from 2003 to 2023. INTERVENTIONS: Changes in trunk inclination. MEASUREMENTS: Four domains were evaluated in this study: 1) respiratory mechanics, 2) ventilation distribution, 3) oxygenation, and 4) ventilatory efficiency. RESULTS: After searching the three databases and removing duplicates, 220 studies were screened. Of these, 37 were assessed in detail, and 13 were included in the final analysis, comprising 274 patients. All selected studies were experimental, and assessed respiratory mechanics, ventilation distribution, oxygenation, and ventilatory efficiency, primarily within 60 min post postural change. CONCLUSION: In patients with acute respiratory failure, transitioning from a supine to a semi-recumbent position leads to decreased respiratory system compliance and increased airway driving pressure. Additionally, C-ARDS patients experienced an improvement in ventilatory efficiency, which resulted in lower PaCO2 levels. Improvements in oxygenation were observed in a few patients and only in those who exhibited an increase in EELV upon moving to a semi-recumbent position. Therefore, the trunk inclination angle must be accurately reported in patients with respiratory failure under mechanical ventilation.

Outcomes of combined mitochondria and mesenchymal stem cells-derived exosome therapy in rat acute respiratory distress syndrome and sepsis.

BACKGROUND: The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging. AIM: To investigate whether combined adipose-derived mesenchymal-stem-cells (ADMSCs)-derived exosome (EXAD) and exogenous mitochondria (mitoEx) protect the lung from ARDS complicated by SS. METHODS: In vitro study, including L2 cells treated with lipopolysaccharide (LPS) and in vivo study including male-adult-SD rats categorized into groups 1 (sham-operated-control), 2 (ARDS-SS), 3 (ARDS-SS + EXAD), 4 (ARDS-SS + mitoEx), and 5 (ARDS-SS + EXAD + mitoEx), were included in the present study. RESULTS: In vitro study showed an abundance of mitoEx found in recipient-L2 cells, resulting in significantly higher mitochondrial-cytochrome-C, adenosine triphosphate and relative mitochondrial DNA levels (P < 0.001). The protein levels of inflammation [interleukin (IL)-1ß/tumor necrosis factor (TNF)-α/nuclear factor-κB/toll-like receptor (TLR)-4/matrix-metalloproteinase (MMP)-9/oxidative-stress (NOX-1/NOX-2)/apoptosis (cleaved-caspase3/cleaved-poly (ADP-ribose) polymerase)] were significantly attenuated in lipopolysaccharide (LPS)-treated L2 cells with EXAD treatment than without EXAD treatment, whereas the protein expressions of cellular junctions [occluding/ß-catenin/zonula occludens (ZO)-1/E-cadherin] exhibited an opposite pattern of inflammation (all P < 0.001). Animals were euthanized by 72 h post-48 h-ARDS induction, and lung tissues were harvested. By 72 h, flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflammatory cells (Ly6G+/CD14+/CD68+/CD11b/c+/myeloperoxidase+) and albumin were lowest in group 1, highest in group 2, and significantly higher in groups 3 and 4 than in group 5 (all P < 0.0001), whereas arterial oxygen-saturation (SaO2%) displayed an opposite pattern of albumin among the groups. Histopathological findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers (CD68+/γ-H2AX) displayed an identical pattern of SaO2% among the groups (all P < 0.0001). The protein expressions of inflammatory (TLR-4/MMP-9/IL-1ß/TNF-α)/oxidative stress (NOX-1/NOX-2/p22phox/oxidized protein)/mitochondrial-damaged (cytosolic-cytochrome-C/dynamin-related protein 1)/autophagic (beclin-1/Atg-5/ratio of LC3B-II/LC3B-I) biomarkers exhibited a similar manner, whereas antioxidants [nuclear respiratory factor (Nrf)-1/Nrf-2]/cellular junctions (ZO-1/E-cadherin)/mitochondrial electron transport chain (complex I-V) exhibited an opposite manner of albumin among the groups (all P < 0.0001). CONCLUSION: Combined EXAD-mitoEx therapy was better than merely one for protecting the lung against ARDS-SS induced injury.

Changing clinical practice and prognosis for severe respiratory failure over time: A nationwide inpatient database study.

BACKGROUND: Severe respiratory failure requires numerous interventions and its clinical implementation changes over time. We aimed to clarify the clinical practice and prognosis of severe respiratory failure and its changes over time. METHODS: In a nationwide Japanese administrative database from 2016 to 2019, we identified nonoperative patients with severe respiratory failure without congestive heart failure as the main diagnosis who received mechanical ventilation (MV) for more than four days. We examined trends in patient characteristics, adjunctive interventions, and prognosis. RESULTS: Among 66,905 patients included in this study, patients received antibiotics (90%), high-dose corticosteroids (14%), low-dose corticosteroids (18%), and 51% were admitted to the critical care unit. Hospital mortality was 35%. Median mechanical ventilation lasted 10 days. Tracheostomy occurred in 23% of cases. Median critical care and hospital stays were 10 and 25 days, respectively. Among survivors, 23% had mechanical ventilation dependency at hospital discharge. Large relative changes in adjunctive therapies included fentanyl (30%-38%), rocuronium (4.4%-6.7%), vasopressin (3.8%-6.0%), early rehabilitation (27%-38%), extracorporeal membrane oxygenation (0.7%-1.2%), dopamine (15%-10%), and sivelestat (8.6%-3.5%). No notable changes were seen in mechanical ventilation duration, tracheostomy, critical care unit stay, hospital stay, or ventilator dependency at discharge, except for a slight reduction in hospital mortality (36%-34%). CONCLUSIONS: Several adjunctive therapies for severe respiratory failure changed from 2016 to 2019, with an increase in evidence-based practices and a slight decrease in hospital mortality.

Association of Red Blood Cell Transfusion Thresholds and Outcomes in Medical Patients with Acute Respiratory Failure Supported with Extra Corporeal Membrane Oxygenation: A Single-Center Retrospective Cohort Study.

BACKGROUND: The hemoglobin value to trigger red blood cell (RBC) transfusion for patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) is controversial. Previous guidelines recommended transfusing to a normal hemoglobin, but recent studies suggest more RBC transfusions are associated with increased adverse outcomes. RESEARCH QUESTION: Is implementation of different institutional RBC transfusion thresholds for patients receiving VV-ECMO associated with changes in RBC utilization and patient outcomes? STUDY DESIGN AND METHODS: Single-center retrospective study of patients receiving VV-ECMO using segmented regression to test associations between implementation of institutional transfusion thresholds and trends in RBC utilization. Associations with secondary outcomes, including in-hospital survival, were also assessed. RESULTS: The study included 229 patients: 91 in the "no threshold (NT)" cohort, 48 in the "hemoglobin <8 g/dL (<8 g/dL)" cohort and 90 in the "hemoglobin <7 g/dL (<7 g/dL)" cohort. Despite a decrease in RBC/ECMO day following implementation of different thresholds, (mean +/- SD; 0.6 +/- 1.0 in the NT cohort, 0.3 +/- 0.8 in the <8 g/dL cohort, and 0.3 +/- 1.1 in the <7 g/dL cohort, p < 0.001), segmented regression showed no association between implementation of transfusion thresholds and changes in trends in RBC/ECMO day. We observed an increased hazard of death in the NT cohort compared to the <8 g/dL cohort (aHR: 2.08, 95% CI: 1.12-3.88), and in the <7 g/dL cohort compared to the <8g/dL cohort (aHR: 1.93, 95% CI: 1.02-3.62). There was no difference in the hazard of death between the NT and <7 g/dL cohorts (aHR: 1.08, 95% CI: 0.69-1.69). INTERPRETATION: We observed a decrease in RBC/ECMO day over time, but changes were not associated temporally with implementation of transfusion thresholds. A transfusion threshold of hemoglobin <8 g/dL was associated with a lower hazard of death, but these findings are limited by study methodology. Further research is needed investigating optimal RBC transfusion practices for patients supported with VV-ECMO.

An infant with acral peeling of skin: A curious case of congenital syphilis.

Congenital syphilis (CS) is a vertically transmitted infection caused by the spirochete Treponema pallidum. It is seen rarely due to proper antenatal screening. Signs and symptoms appear within the first 2 years of life in early CS and after 2 years in late CS. Failure to diagnose and treat CS in its early stages can result in higher morbidity and mortality. Skin manifestations can guide toward the diagnosis of CS at an early stage. Here, we report a 2-day-old neonate who presented with acral peeling of skin along with respiratory distress and hepatosplenomegaly. Clinical suspicion of CS was made and subsequently confirmed by a positive venereal disease research laboratory test in both mother and child. The child was treated with aqueous crystalline penicillin G as per the CDC guidelines.

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.

Hypoxaemic respiratory failure and awake prone ventilation (HYPER-AP) - Protocol for randomized, controlled clinical trial.

BACKGROUND: Awake prone positioning is studied extensively during Covid-19 pandemic, but there is very limited evidence on its utility in acute hypoxic respiratory failure caused by bacterial infections or other causes. The aim of our research is to evaluate the impact of awake prone positioning on outcomes in non-intubated adult patients with acute non-Covid19 hypoxemic respiratory failure. METHODS: This is a multi-center randomized controlled trial (RCT) with a parallel-group design and a 1:1 allocation ratio. Adult patients, admitted to ICU and diagnosed with hypoxemic respiratory failure will be randomly allocated into intervention (awake prone position (APP)) or control group. Our hypothesis is that addition of awake prone positioning to standard oxygen, high flow oxygen therapy and non-invasive ventilation may reduce the need for mechanical ventilation in adult patients diagnosed with acute hypoxemic respiratory failure. Primary outcome is rate of endotracheal intubation; secondary outcomes include intensive care and hospital mortality, duration of mechanical ventilation, length of intensive care and hospital stay and health related quality of life post hospital discharge. Primary and secondary outcomes will be assessed at hospital discharge, 30, 90 days and 1 year following randomisation. CONCLUSION: The Hyper-AP study will assess the superiority of awake prone positioning versus standard treatment in spontaneously breathing ICU patients diagnosed with hypoxaemic respiratory failure.

Impact of intensive prone position therapy on outcomes in intubated patients with ARDS related to COVID-19.

BACKGROUND: Previous retrospective research has shown that maintaining prone positioning (PP) for an average of 40 h is associated with an increase of survival rates in intubated patients with COVID-19-related acute respiratory distress syndrome (ARDS). This study aims to determine whether a cumulative PP duration of more than 32 h during the first 2 days of intensive care unit (ICU) admission is associated with increased survival compared to a cumulative PP duration of 32 h or less. METHODS: This study is an ancillary analysis from a previous large international observational study involving intubated patients placed in PP in the first 48 h of ICU admission in 149 ICUs across France, Belgium and Switzerland. Given that PP is recommended for a 16-h daily duration, intensive PP was defined as a cumulated duration of more than 32 h during the first 48 h, whereas standard PP was defined as a duration equal to or less than 32 h. Patients were followed-up for 90 days. The primary outcome was mortality at day 60. An Inverse Probability Censoring Weighting (IPCW) Cox model including a target emulation trial method was used to analyze the data. RESULTS: Out of 2137 intubated patients, 753 were placed in PP during the first 48 h of ICU admission. The intensive PP group (n = 79) had a median PP duration of 36 h, while standard PP group (n = 674) had a median of 16 h during the first 48 h. Sixty-day mortality rate in the intensive PP group was 39.2% compared to 38.7% in the standard PP group (p = 0.93). Twenty-eight-day and 90-day mortality as well as the ventilator-free days until day 28 were similar in both groups. After IPCW, there was no significant difference in mortality at day 60 between the two-study groups (HR 0.95 [0.52-1.74], p = 0.87 and HR 1.1 [0.77-1.57], p = 0.61 in complete case analysis or in multiple imputation analysis, respectively). CONCLUSIONS: This secondary analysis of a large multicenter European cohort of intubated patients with ARDS due to COVID-19 found that intensive PP during the first 48 h did not provide a survival benefit compared to standard PP.

Hypoxemia and its clinical predictors among children with respiratory distress admitted to the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.

INTRODUCTION: Hypoxemia is a common complication of childhood respiratory tract infections and non-respiratory infections. Hypoxemic children have a five-fold increased risk of death compared to children without hypoxemia. In addition, there is limited evidence about hypoxemia and clinical predictors in Ethiopia. Therefore, this study was conducted to assess the prevalence and clinical predictors of hypoxemia among children with respiratory distress admitted to the University of Gondar Comprehensive Specialized Hospital. METHODS: An institutional-based cross-sectional study was conducted from December 2020 to May 2021 in northwest Ethiopia. A total of 399 study participants were selected using systematic random sampling. The oxygen saturation of the child was measured using Masimo rad-5 pulse oximetry. SPSS version 21 software was used for statistical analysis. RESULT: In this study, the prevalence of hypoxemia among children with respiratory distress was 63.5%. The clinical signs and symptoms significantly associated with hypoxemia were: head-nodding (AOR: 4.1, 95% CI: 1.81-9.28) and chest indrawing (AOR: 3.08, 95% CI: 1.32-7.16) which were considered statistically the risk factors for hypoxemia while inability to feed (AOR: 0.13, 95% CI: 0.02-0.77) was the protective factor for hypoxemia. The most sensitive predictors of hypoxemia were fast breathing with sensitivity (98.4%), nasal flaring (100.0%), chest indrawing (83.6%), and intercostal retraction (93.1%). The best specific predictors of hypoxemia were breathing difficulty with specificity (79.4%), inability to feed (100.0%), wheezing (83.0%), cyanosis (98.6%), impaired consciousness (94.2%), head-nodding (88.7%), and supra-sternal retraction (96.5%). CONCLUSION AND RECOMMENDATION: The prevalence of hypoxemia among children was high. The predictors of hypoxemia were the inability to feed, head nodding, and chest indrawing. It is recommended that the health care settings provide immediate care for the children with an inability to feed, head nodding, and chest indrawing. The policymakers better to focus on preventive strategies, particularly those with the most specific clinical predictors.

The clinical effectiveness of sivelestat in treating sepsis patients with both acute respiratory distress syndrome and septic cardiomyopathy.

BACKGROUND: We aimed to assess the efficacy of the neutrophil elastase inhibitor, sivelestat, in the treatment of sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM). METHODS: Between January 2019 and December 2021, we conducted a randomized trial on patients who had been diagnosed with sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM) at Wuhan Union Hospital. The patients were divided into two groups by random envelop method, the Sivelestat group and the Control group. We measured the serum concentrations of Interleukin (IL)-6, IL-8, Tumor necrosis factor-α (TNF-α), and High-mobility group box 1 (HMGB1) at five time points, which were the baseline, 12 h, 24 h, 48 h, and 72 h after admission to the ICU. We evaluated the cardiac function by sonography and the heart rate variability (HRV) with 24-hour Holter recording between the time of admission to the intensive care unit (ICU) and 72 h after Sivelestat treatment. RESULTS: From January 2019 to December 2021, a total of 70 patients were included in this study. The levels of IL-6, IL-8, and TNF-α were significantly lower in the Sivelestat group at different time points (12 h, 24 h, 48 h, and 72 h). HMGB1 levels were significantly lower at 72 h after Sivelestat treatment (19.46 ± 2.63pg/mL vs. 21.20 ± 2.03pg/mL, P = 0.003). The stroke volume (SV), tricuspid annular plane systolic excursion (TAPSE), early to late diastolic transmitral flow velocity (E/A), early (e') and late (a') diastoles were significantly low in the Control group compared with the Sivelestat group. Tei index was high in the Control group compared with the Sivelestat group (0.60 ± 0.08 vs. 0.56 ± 0.07, P = 0.029). The result of HRV showed significant differences in standard deviation of normal-to-normal intervals (SDNN), low frequency (LF), and LF/HF (high frequency) between the two groups. CONCLUSIONS: Sivelestat can significantly reduce the levels of serum inflammatory factors, improve cardiac function, and reduce heart rate variability in patients with Sepsis-induced ARDS and SCM.

Work of Breathing: Physiology, Measurement, and Diagnostic Value in Childhood Pneumonia.

In clinical practice, increased "work of breathing" (WOB) is used to rapidly identify the acutely ill child in need of immediate clinical care, and is commonly used to support a clinical diagnosis of pneumonia. However, this key clinical sign is poorly understood and inconsistently defined. This review discusses the physiology, measurement, and clinical assessment of WOB, highlighting its utility in the recognition of pneumonia in under-resourced settings, where access to diagnostic imaging may be limited.

Differential Effects of Intra-Abdominal Hypertension and ARDS on Respiratory Mechanics in a Porcine Model.

Background and Objectives: Intra-abdominal hypertension (IAH) and acute respiratory distress syndrome (ARDS) are common concerns in intensive care unit patients with acute respiratory failure (ARF). Although both conditions lead to impairment of global respiratory parameters, their underlying mechanisms differ substantially. Therefore, a separate assessment of the different respiratory compartments should reveal differences in respiratory mechanics. Materials and Methods: We prospectively investigated alterations in lung and chest wall mechanics in 18 mechanically ventilated pigs exposed to varying levels of intra-abdominal pressures (IAP) and ARDS. The animals were divided into three groups: group A (IAP 10 mmHg, no ARDS), B (IAP 20 mmHg, no ARDS), and C (IAP 10 mmHg, with ARDS). Following induction of IAP (by inflating an intra-abdominal balloon) and ARDS (by saline lung lavage and injurious ventilation), respiratory mechanics were monitored for six hours. Statistical analysis was performed using one-way ANOVA to compare the alterations within each group. Results: After six hours of ventilation, end-expiratory lung volume (EELV) decreased across all groups, while airway and thoracic pressures increased. Significant differences were noted between group (B) and (C) regarding alterations in transpulmonary pressure (TPP) (2.7 ± 0.6 vs. 11.3 ± 2.1 cmH2O, p < 0.001), elastance of the lung (EL) (8.9 ± 1.9 vs. 29.9 ± 5.9 cmH2O/mL, p = 0.003), and elastance of the chest wall (ECW) (32.8 ± 3.2 vs. 4.4 ± 1.8 cmH2O/mL, p < 0.001). However, global respiratory parameters such as EELV/kg bodyweight (-6.1 ± 1.3 vs. -11.0 ± 2.5 mL/kg), driving pressure (12.5 ± 0.9 vs. 13.2 ± 2.3 cmH2O), and compliance of the respiratory system (-21.7 ± 2.8 vs. -19.5 ± 3.4 mL/cmH2O) did not show significant differences among the groups. Conclusions: Separate measurements of lung and chest wall mechanics in pigs with IAH or ARDS reveals significant differences in TPP, EL, and ECW, whereas global respiratory parameters do not differ significantly. Therefore, assessing the compartments of the respiratory system separately could aid in identifying the underlying cause of ARF.

Delivery Room Lung Ultrasound-Feasibility, Normal Patterns, and Predictive Value for Respiratory Support in Term and Near-Term Neonates: A Monocentric Study.

AIM: our study aimed to characterize the lung ultrasound (LUS) patterns noted immediately after delivery in term and near-term neonates, and to investigate whether the LUS scores or patterns observed at that point could anticipate the need for respiratory support in the sample of patients studied. MATERIALS AND METHODS: We performed two ultrasound examinations: one in the delivery room and the second at one hour of age. The anterior and lateral regions of both lungs were examined. We assessed the correlation between the LUS scores or patterns and the gestational age, umbilical arterial blood gases, the need for respiratory support (CPAP or mechanical ventilation), the presence of respiratory distress, and the need for the administration of oxygen. RESULTS: LUS scores were significantly higher in the delivery room examination (8.05 ± 1.95) than at 1 h of age (6.4 ± 1.75) (p < 0.001). There were also statistically significant differences between the LUS patterns observed in different lung regions between the delivery room exam and the exam performed at 1 h of age (p values between 0.001 and 0.017). There were also differences noted regarding the LUS patterns between different lung regions at the exam in the delivery room (the right anterior region LUS patterns were significantly worse than the right lateral LUS patterns (p < 0.004), left anterior LUS patterns (p < 0.001), and left lateral LUS patterns (p < 0.001)). A statistically significant correlation was found between LUS scores and the gestational age of the patients (r = 0.568, p < 0.001-delivery room; r = 4.0443, p < 0.001-one hour of age). There were statistically significant associations between LUS scores, patterns at delivery (p < 0.001) and 1 h of age (p < 0.001), and the need for respiratory support (CPAP or mechanical ventilation). CONCLUSIONS: LUS in the delivery room offers important information regarding lung fluid elimination and aeration of the lungs, and early LUS features are significantly associated with the risk of respiratory distress and the need for respiratory support.