Dyssynchronous diaphragm contractions impair diaphragm function in mechanically ventilated patients.

BACKGROUND: Pre-clinical studies suggest that dyssynchronous diaphragm contractions during mechanical ventilation may cause acute diaphragm dysfunction. We aimed to describe the variability in diaphragm contractile loading conditions during mechanical ventilation and to establish whether dyssynchronous diaphragm contractions are associated with the development of impaired diaphragm dysfunction. METHODS: In patients receiving invasive mechanical ventilation for pneumonia, septic shock, acute respiratory distress syndrome, or acute brain injury, airway flow and pressure and diaphragm electrical activity (Edi) were recorded hourly around the clock for up to 7 days. Dyssynchronous post-inspiratory diaphragm loading was defined based on the duration of neural inspiration after expiratory cycling of the ventilator. Diaphragm function was assessed on a daily basis by neuromuscular coupling (NMC, the ratio of transdiaphragmatic pressure to diaphragm electrical activity). RESULTS: A total of 4508 hourly recordings were collected in 45 patients. Edi was low or absent (≤ 5 µV) in 51% of study hours (median 71 h per patient, interquartile range 39-101 h). Dyssynchronous post-inspiratory loading was present in 13% of study hours (median 7 h per patient, interquartile range 2-22 h). The probability of dyssynchronous post-inspiratory loading was increased with reverse triggering (odds ratio 15, 95% CI 8-35) and premature cycling (odds ratio 8, 95% CI 6-10). The duration and magnitude of dyssynchronous post-inspiratory loading were associated with a progressive decline in diaphragm NMC (p < 0.01 for interaction with time). CONCLUSIONS: Dyssynchronous diaphragm contractions may impair diaphragm function during mechanical ventilation. TRIAL REGISTRATION: MYOTRAUMA, ClinicalTrials.gov NCT03108118. Registered 04 April 2017 (retrospectively registered).

Effect of Nasal Continuous Positive Airway Pressure on Retinopathy of Prematurity in Preterm Newborns: A Comparative Analysis with Mechanical Ventilation and High-Flow Nasal Cannula Therapy.

BACKGROUND Retinopathy of prematurity (ROP), originally described as retrolental fibroplasia, represents an abnormal growth of blood vessels in the premature retina that can occur in response to oxygen therapy. The association between ROP and invasive mechanical ventilation has been widely studied in the literature; however, the relationships between different types of ventilation and ROP have not been as well documented. This study aimed to compare the association of ROP incidence with mechanical ventilation (MV), nasal continuous positive airway pressure (nCPAP), and high-flow nasal cannula (HFNC) therapies in 130 pre-term infants with gestational ages <32 weeks. MATERIAL AND METHODS The study includes 130 premature newborns, out of which 54 underwent MV therapy, either alone or in combination with nCPAP or HFNC therapy, 63 underwent nCPAP therapy, either alone or in combination with MV or HFNC therapy, and 23 underwent HFNC therapy, either alone or in combination with MV or nCPAP therapy. The relationships between ROP and the 3 types of ventilation were analyzed by univariate followed by multivariate logistic regression. RESULTS When adjusting for covariates, only nCPAP and birth weight were significantly associated with ROP, the former being a strong risk factor, with an adjusted odds ratio (AOR) of 7.264 (95% CI, 2.622-20.120; P<0.001), and the latter being a weak protective factor, with an AOR of 0.998 (95% CI, 0.996-0.999; P<0.05). CONCLUSIONS The results showed nCPAP was a strong ROP risk factor, birth weight was a weak ROP protective factor, and MV and HFNC were not significantly associated with increased ROP risk.

Efficacy of melatonin in decreasing the incidence of delirium in critically ill adults: a randomized controlled trial.

OBJECTIVE: To determine whether enteral melatonin decreases the incidence of delirium in critically ill adults. METHODS: In this randomized controlled trial, adults were admitted to the intensive care unit and received either usual standard care alone (Control Group) or in combination with 3mg of enteral melatonin once a day at 9 PM (Melatonin Group). Concealment of allocation was done by serially numbered opaque sealed envelopes. The intensivist assessing delirium and the investigator performing the data analysis were blinded to the group allocation. The primary outcome was the incidence of delirium within 24 hours of the intensive care unit stay. The secondary outcomes were the incidence of delirium on Days 3 and 7, intensive care unit mortality, length of intensive care unit stay, duration of mechanical ventilation and Glasgow outcome score (at discharge). RESULTS: We included 108 patients in the final analysis, with 54 patients in each group. At 24 hours of intensive care unit stay, there was no difference in the incidence of delirium between Melatonin and Control Groups (29.6 versus 46.2%; RR = 0.6; 95%CI 0.38 - 1.05; p = 0.11). No secondary outcome showed a statistically significant difference. CONCLUSION: Enteral melatonin 3mg is not more effective at decreasing the incidence of delirium than standard care is in critically ill adults.

Frequency, complications, and mortality of inhalation injury in burn patients: A systematic review and meta-analysis protocol.

INTRODUCTION: Burns are tissue traumas caused by energy transfer and occur with a variable inflammatory response. The consequences of burns represent a public health problem worldwide. Inhalation injury (II) is a severity factor when associated with burn, leading to a worse prognosis. Its treatment is complex and often involves invasive mechanical ventilation (IMV). The primary purpose of this study will be to assess the evidence regarding the frequency and mortality of II in burn patients. The secondary purposes will be to assess the evidence regarding the association between IIs and respiratory complications (pneumonia, airway obstruction, acute respiratory failure, acute respiratory distress syndrome), need for IMV and complications in other organ systems, and highlight factors associated with IIs in burn patients and prognostic factors associated with acute respiratory failure, need for IMV and mortality of II in burn patients. METHODS: This is a systematic literature review and meta-analysis, according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). PubMed/MEDLINE, Embase, LILACS/VHL, Scopus, Web of Science, and CINAHL databases will be consulted without language restrictions and publication date. Studies presenting incomplete data and patients under 19 years of age will be excluded. Data will be synthesized through continuous (mean and standard deviation) and dichotomous (relative risk) variables and the total number of participants. The means, sample sizes, standard deviations from the mean, and relative risks will be entered into the Review Manager web analysis software (The Cochrane Collaboration). DISCUSSION: Despite the extensive experience managing IIs in burn patients, they still represent an important cause of morbidity and mortality. Diagnosis and accurate measurement of its damage are complex, and therapies are essentially based on supportive measures. Considering the challenge, their impact, and their potential severity, IIs represent a promising area for research, needing further studies to understand and contribute to its better evolution. The protocol of this review is registered on the International prospective register of systematic reviews platform of the Center for Revisions and Disclosure of the University of York, United Kingdom (https://www.crd.york.ac.uk/prospero), under number RD42022343944.

Multicentre, randomised controlled trial of physiological-based cord clamping versus immediate cord clamping in infants with a congenital diaphragmatic hernia (PinC): statistical analysis plan.

BACKGROUND: Infants born with congenital diaphragmatic hernia (CDH) are at high risk of respiratory insufficiency and pulmonary hypertension. Routine practice includes immediate clamping of the umbilical cord and endotracheal intubation. Experimental animal studies suggest that clamping the umbilical cord guided by physiological changes and after the lungs have been aerated, named physiological-based cord clamping (PBCC), could enhance the fetal-to-neonatal transition in CDH. We describe the statistical analysis plan for the clinical trial evaluating the effects of PBCC versus immediate cord clamping on pulmonary hypertension in infants with CDH (PinC trial). DESIGN: The PinC trial is a multicentre, randomised controlled trial in infants with isolated left-sided CDH, born ≥ 35.0 weeks of gestation. The primary outcome is the incidence of pulmonary hypertension in the first 24 h after birth. Maternal outcomes include estimated maternal blood loss. Neonatal secondary outcomes include mortality before discharge, extracorporeal membrane oxygenation therapy, and number of days of mechanical ventilation. Infants are 1:1 randomised to either PBCC or immediate cord clamping using variable random permutated block sizes (4-8), stratified by treatment centre and estimated severity of pulmonary hypoplasia (i.e. mild/moderate/severe). At least 140 infants are needed to detect a relative reduction in pulmonary hypertension by one third, with 80% power and 0.05 significance level. A chi-square test will be used to evaluate the hypothesis that PBCC decreases the occurrence of pulmonary hypertension. This plan is written and submitted without knowledge of the collected data. The trial has been ethically approved. TRIAL REGISTRATION: ClinicalTrials.gov NCT04373902 (registered April 2020).

Respiratory entrainment related reverse triggering in mechanically ventilated children.

BACKGROUND: The underlying pathophysiological pathways how reverse triggering is being caused are not fully understood. Respiratory entrainment may be one of these mechanisms, but both terms are used interchangeably. We sought to characterize reverse triggering and the relationship with respiratory entrainment among mechanically ventilated children with and without acute lung injury. METHODS: We performed a secondary phyiology analysis of two previously published data sets of invasively mechanically ventilated children < 18 years with and without lung injury mechanically ventilated in a continuous or intermittent mandatory ventilation mode. Ventilator waveforms, electrical activity of the diaphragm measured with surface electromyography and oesophageal tracings were analyzed for entrained and non-entrained reverse triggered breaths. RESULTS: In total 102 measurements (3110 min) from 67 patients (median age 4.9 [1.8 ; 19,1] months) were analyzed. Entrained RT was identified in 12 (12%) and non-entrained RT in 39 (38%) recordings. Breathing variability for entrained RT breaths was lower compared to non-entrained RT breaths. We did not observe breath stacking during entrained RT. Double triggering often occurred during non-entrained RT and led to an increased tidal volume. Patients with respiratory entrainment related RT had a shorter duration of MV and length of PICU stay. CONCLUSIONS: Reverse triggering is not one entity but a clinical spectrum with different mechanisms and consequences. TRIAL REGISTRATION: Not applicable.

Respiratory Support After Extubation in Children With Pediatric ARDS.

BACKGROUND: Postextubation respiratory support in pediatric ARDS may be used to support the recovering respiratory system and promote timely, successful liberation from mechanical ventilation. This study's aims were to (1) describe the use of postextubation respiratory support in pediatric ARDS from the time of extubation to hospital discharge, (2) identify potential risk factors for postextubation respiratory support, and (3) provide preliminary data for future larger studies. METHODS: This pilot single-center prospective cohort study recruited subjects with pediatric ARDS. Subjects' respiratory status up to hospital discharge, the use of postextubation respiratory support, and how it changed over time were recorded. Analysis was performed comparing subjects who received postextubation respiratory support versus those who did not and compared its use among pediatric ARDS severity categories. Multivariable logistic regression was used to determine variables associated with the use of postextubation respiratory support and included oxygenation index (OI), ventilator duration, and weight. RESULTS: Seventy-three subjects with pediatric ARDS, with median age and OI of 4 (0.6-10.5) y and 7.3 (4.9-12.7), respectively, were analyzed. Postextubation respiratory support was provided to 54/73 (74%) subjects: 28/45 (62.2%), 19/21 (90.5%), and 7/7 (100%) for mild, moderate, and severe pediatric ARDS, respectively, (P = .01). OI and mechanical ventilation duration were higher in subjects who received postextubation respiratory support (8.7 [5.4-14] vs 4.6 [3.7-7], P < .001 and 10 [7-17] d vs 4 [2-7] d, P < .001) compared to those who did not. At hospital discharge, 12/67 (18.2%) survivors received home respiratory support (6 subjects died prior to hospital discharge). In the multivariable model, ventilator duration (adjusted odds ratio 1.3 [95% CI 1.0-1.7], P = .050) and weight (adjusted odds ratio 0.95 [95% CI 0.91-0.99], P = .02) were associated with the use of postextubation respiratory support. CONCLUSIONS: The majority of intubated subjects with pediatric ARDS received respiratory support postextubation, and a substantial proportion continued to require it up to hospital discharge.

The effects of vitamin C supplementation in the critically ill patients outcomes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin C has significant anti-inflammatory effects and is particularly important for critically ill patients. However due to inconsistent research findings in critically ill patients in meta-analysis. Therefore, the primary objective of this meta-analysis is to investigate the effects of isolated intravenous supplementation of vitamin C in adults with critical illness by comprehensively incorporating articles from randomized controlled trials. METHODS: Articles included searching through PubMed, Embase, Medline, Cochrane Library, and Web of Science up to April 28, 2023, for articles on vitamin C and the critically ill. We calculated pooled standard relative risk (RR), mean difference (MD), and 95% confidence intervals (CIs). And the protocol for the review has been registered on PROSPERO (CRD42023425193). RESULTS: There are 2047 critically ill included in 19 articles. Compared with placebo, patients who underwent intravenous vitamin C (IVVC) have reduced duration of vasopressor used (SMD 0.26; CI 0.01-0.51; I2 = 87.0%, P = .044), mechanical ventilation (SMD -0.29; CI -0.55 to -0.03; I2 = 36.8%, P = .031). However, the administration of IVVC had no statistical difference in 28-d mortality (RR 0.95; CI 0.80-1.11; I2 = 12.2%, P = .337), mortality (RR 0.79; CI 0.55-1.12; I2 = 0%, P = .188), fluid intake (SMD -0.02; CI -0.25 to 0.20; I2 = 0%, P = .838), urine output (SMD 0.23; CI -0.03 to 0.49; I2 = 0%, P = .084), ICU days (SMD 0.10; CI -0.03 to 0.22; I2 = 0%, P = .127), hospital stay (SMD 0.10; CI -0.12 to 0.32; I2 = 0%, P = .375), and pneumonia (RR 0.85; CI 0.50-1.44; I2 = 0%, P = .552). CONCLUSION: This study comprehensively and systematically evaluated IVVC supplementation in the critically ill through a meta-analysis of RCT. There is no difference except for patients who had reduced duration of vasopressor use and mechanical ventilation by the administration of IVVC. Of course. More scientific and rigorous conclusions can be drawn from multi-center RCT research in the future.

Nation-wide survey of oral care practice in Japanese intensive care units: A descriptive study.

Oral care for critically ill patients helps provide comfort and prevent ventilator-associated pneumonia. However, a standardized protocol for oral care in intensive care units is currently unavailable. Thus, this study aimed to determine the overall oral care practices, including those for intubated patients, in Japanese intensive care units. We also discuss the differences in oral care methods between Japanese ICUs and ICUs in other countries. This study included all Japanese intensive care units meeting the authorities' standard set criteria, with a minimum of 0.5 nurses per patient at all times and admission of adult patients requiring mechanical ventilation. An online survey was used to collect data. Survey responses were obtained from one representative nurse per intensive care unit. Frequency analysis was performed, and the percentage of each response was calculated. A total of 609 hospitals and 717 intensive care units nationwide participated; among these, responses were collected from 247 intensive care units (34.4%). Of these, 215 (87.0%) and 32 (13.0%) reported standardized and non-standardized oral care, respectively. Subsequently, the data from 215 intensive care units that provided standardized oral care were analyzed in detail. The most common frequency of practicing oral care was three times a day (68.8%). Moreover, many intensive care units provided care at unequal intervals (79.5%), mainly in the morning, daytime, and evening. Regarding oral care methods, 96 (44.7%) respondents used only a toothbrush, while 116 (54.0%) used both a toothbrush and a non-brushing method. The findings of our study reveal current oral care practices in ICUs in Japan. In particular, most ICUs provide oral care three times a day at unequal intervals, and almost all use toothbrushes as a common tool for oral care. The results suggest that some oral care practices in Japanese ICUs differ from those in ICUs in other countries.

Airway stenting for liberation from positive pressure ventilation in patients with central airway obstruction presenting with acute respiratory failure.

BACKGROUND: Central airway obstruction (CAO) can lead to acute respiratory failure (RF) necessitating positive pressure ventilation (PPV). The efficacy of airway stenting to aid liberation from PPV in patients with severe acute RF has been scarcely published. We present a systematic review and our recent experience. METHODS: A systematic review of PubMed was performed, and a retrospective review of cases performed at our two institutions from 2018 to 2022 in adult patients who needed stent insertion for extrinsic or mixed CAO complicated by RF necessitating PPV. RESULTS: Fifteen studies were identified with a total of 156 patients. The weighted mean of successful liberation from PPV post-stenting was 84.5% and the median survival was 127.9 days. Our retrospective series included a total of 24 patients. The most common etiology was malignant CAO (83%). The types of PPV used included high-flow nasal cannula (HFNC) (21%), non-invasive ventilation (NIV) (17%) and Invasive Mechanical Ventilation (62%). The overall rate of successful liberation from PPV was 79%, with 55% of HFNC and NIV cases being liberated immediately post-procedure. The median survival of the patients with MCAO that were successfully liberated from PPV was 74 days (n = 16, range 3-893 days), and for those with that failed to be liberated from PPV, it was 22 days (n = 4, range 9-26 days). CONCLUSION: In patients presenting with acute RF from extrinsic or mixed morphology CAO requiring PPV, airway stenting can successfully liberate most from the PPV. This may allow patients to receive pathology-directed treatment and better end-of-life care.

Ruxolitinib: A new hope for ventilator-induced diaphragm dysfunction.

AIM: Mechanical ventilation (MV) results in diminished diaphragm size and strength, termed ventilator-induced diaphragm dysfunction (VIDD). VID increases dependence, prolongs weaning, and increases discharge mortality rates. The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is implicated in VIDD, upregulated following MV. JAK/STAT inhibition alleviates chronic muscle wasting conditions. This study aimed to explore the therapeutic potential of Ruxolitinib, an FDA approved JAK1/2 inhibitor (JI) for the treatment of VIDD. METHODS: Rats were subjected to 5 days controlled MV (CMV) with and without daily Ruxolitinib gavage. Muscle fiber size and function were assessed. RNAseq, mitochondrial morphology, respirometry, and mass spectrometry were determined. RESULTS: CMV significantly reduced diaphragm size and specific force by 45% (p < 0.01), associated with a two-fold P-STAT3 upregulation (p < 0.001). CMV disrupted mitochondrial content and reduced the oxygen consumption rate (p < 0.01). Expression of the motor protein myosin was unaffected, however CMV alters myosin function via post-translational modifications (PTMs). Daily administration of JI increased animal survival (40% vs. 87%; p < 0.05), restricted P-STAT3 (p < 0.001), and preserved diaphragm size and specific force. JI was associated with preserved mitochondrial content and respiratory function (p < 0.01), and the reversal or augmentation of myosin deamidation PTMs of the rod and head region. CONCLUSION: JI preserved diaphragm function, leading to increased survival in an experimental model of VIDD. Functional enhancement was associated with maintenance of mitochondrial content and respiration and the reversal of ventilator-induced PTMs of myosin. These results demonstrate the potential of repurposing Ruxolitinib for treatment of VIDD.

A meta-analysis and trial sequential analysis of randomised controlled trials comparing nonoperative and operative management of chest trauma with multiple rib fractures.

BACKGROUND: Operative treatment of traumatic rib fractures for better outcomes remains under debate. Surgical stabilization of rib fractures has dramatically increased in the last decade. This study aimed to perform a systematic review and meta-analysis of randomised controlled trials (RCTs) to assess the effectiveness and safety of operative treatment compared to conservative treatment in adult patients with traumatic multiple rib fractures. METHODS: A systematic literature review was performed according to the preferred reporting items for systematic reviews and meta-analyses guidelines. We searched MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials and used the Cochrane Risk-of-Bias 2 tool to evaluate methodological quality. Relative risks with 95% confidence interval (CI) were calculated for outcomes: all-cause mortality, pneumonia incidence, and number of mechanical ventilation days. Overall certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, with trial sequential analysis performed to establish implications for further research. RESULTS: From 719 records, we included nine RCTs, which recruited 862 patients. Patients were assigned to the operative group (received surgical stabilization of chest wall injury, n = 423) or control group (n = 439). All-cause mortality was not significantly different (RR = 0.53; 95% CI 0.21 to 1.38, P = 0.35, I2 = 11%) between the two groups. However, in the operative group, duration of mechanical ventilation (mean difference -4.62; 95% CI -7.64 to -1.60, P < 0.00001, I2 = 94%) and length of intensive care unit stay (mean difference -3.05; 95% CI -5.87 to -0.22; P < 0.00001, I2 = 96%) were significantly shorter, and pneumonia incidence (RR = 0.57; 95% CI 0.35 to 0.92; P = 0.02, I2 = 57%) was significantly lower. Trial sequential analysis for mortality indicated insufficient sample size for a definitive judgment. GRADE showed this meta-analysis to have very low to low confidence. CONCLUSION: Meta-analysis of large-scale trials showed that surgical stabilization of multiple rib fractures shortened the duration of mechanical ventilation and reduced the incidence of pneumonia but lacked clear evidence for improvement of mortality compared to conservative treatment. Trial sequential analysis suggested the need for more cases, and GRADE highlighted low certainty, emphasizing the necessity for further targeted RCTs, especially in mechanically ventilated patients. SYSTEMATIC REVIEW REGISTRATION: UMIN Clinical Trials Registry UMIN000049365.

Intraoperative mechanical ventilation and incidence of pneumothorax in lymphangioleiomyomatosis.

Patients with lymphangioleiomyomatosis (LAM) are considered high risk for most surgeries and require specific anesthetic considerations mainly because of the common spontaneous pneumothorax (PTX). To explore whether intraoperative mechanical ventilation could increase the risk of PTX in those patients, we included 12 surgical patients with LAM in this study, of whom four (33.3%) experienced postoperative PTX. According to our results, patients with higher CT grade, poorer pulmonary function, and a history of preoperative PTX might be more likely to develop postoperative PTX. However, intraoperative mechanical ventilation did not show obvious influence, which might help clinicians reconsider the perioperative management of LAM patients.

Nonintubated spontaneous ventilation versus intubated mechanical ventilation anesthesia for video-assisted thoracic surgery in terms of perioperative complications and practitioners' workload assessments: a pilot randomized control study.

BACKGROUND: The use of nonintubated video-assisted thoracoscopic surgery (NI-VATS) has been increasingly reported to yield favourable outcomes. However, this technology has not been routinely used because its advantages and safety have not been fully confirmed. The aim of this study was to assess the safety and feasibility of nonintubated spontaneous ventilation (NI-SV) anesthesia compared to intubated mechanical ventilation (I-MV) anesthesia in VATS by evaluating of perioperative complications and practitioners' workloads. METHODS: Patients who underwent uniportal VATS were randomly assigned at a 1:1 ratio to receive NI-SV or I-MV anesthesia. The primary outcome was the occurrence of intraoperative airway intervention events, including transient MV, conversion to intubation and repositioning of the double-lumen tube. The secondary outcomes included perioperative complications and modified National Aeronautics and Space Administration Task Load Index (NASA-TLX) scores from anesthesiologists and surgeons. RESULTS: Thirty-five patients in each group were enrolled in the intention-to-treat analysis. The incidence of intraoperative airway intervention events was greater in the NI-SV group than in the I-MV group (12 [34.3%] vs. 3 [8.6%]; OR = 0.180; 95% CI = 0.045-0.710; p = 0.009). No significant difference was found in the postoperative pulmonary complications between the groups (p > 0.05). The median of the anesthesiologists' overall NASA-TLX score was 37.5 (29-52) when administering the NI-SV, which was greater than the 25 (19-34.5) when the I-MV was administered (p < 0.001). The surgeons' overall NASA-TLX score was comparable between the two ventilation strategies (28 [21-38.5] vs. 27 [20.5-38.5], p = 0.814). CONCLUSION: The NI-SV anesthesia was feasible for VATS in the selected patients, with a greater incidence of intraoperative airway intervention events than I-MV anesthesia, and with more surgical effort required by anesthesiologists. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055427. https://www.chictr.org.cn/showproj.html?proj=147872 was registered on January 09, 2022.

Effects of prone positioning on lung mechanical power components in patients with acute respiratory distress syndrome: a physiologic study.

BACKGROUND: Prone positioning (PP) homogenizes ventilation distribution and may limit ventilator-induced lung injury (VILI) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The static and dynamic components of ventilation that may cause VILI have been aggregated in mechanical power, considered a unifying driver of VILI. PP may affect mechanical power components differently due to changes in respiratory mechanics; however, the effects of PP on lung mechanical power components are unclear. This study aimed to compare the following parameters during supine positioning (SP) and PP: lung total elastic power and its components (elastic static power and elastic dynamic power) and these variables normalized to end-expiratory lung volume (EELV). METHODS: This prospective physiologic study included 55 patients with moderate to severe ARDS. Lung total elastic power and its static and dynamic components were compared during SP and PP using an esophageal pressure-guided ventilation strategy. In SP, the esophageal pressure-guided ventilation strategy was further compared with an oxygenation-guided ventilation strategy defined as baseline SP. The primary endpoint was the effect of PP on lung total elastic power non-normalized and normalized to EELV. Secondary endpoints were the effects of PP and ventilation strategies on lung elastic static and dynamic power components non-normalized and normalized to EELV, respiratory mechanics, gas exchange, and hemodynamic parameters. RESULTS: Lung total elastic power (median [interquartile range]) was lower during PP compared with SP (6.7 [4.9-10.6] versus 11.0 [6.6-14.8] J/min; P < 0.001) non-normalized and normalized to EELV (3.2 [2.1-5.0] versus 5.3 [3.3-7.5] J/min/L; P < 0.001). Comparing PP with SP, transpulmonary pressures and EELV did not significantly differ despite lower positive end-expiratory pressure and plateau airway pressure, thereby reducing non-normalized and normalized lung elastic static power in PP. PP improved gas exchange, cardiac output, and increased oxygen delivery compared with SP. CONCLUSIONS: In patients with moderate to severe ARDS, PP reduced lung total elastic and elastic static power compared with SP regardless of EELV normalization because comparable transpulmonary pressures and EELV were achieved at lower airway pressures. This resulted in improved gas exchange, hemodynamics, and oxygen delivery. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00017449). Registered June 27, 2019. https://drks.de/search/en/trial/DRKS00017449.

Tiny Guides, Big Impact: Focus on the Opportunities and Challenges of miR-Based Treatments for ARDS.

Acute Respiratory Distress Syndrome (ARDS) is characterized by lung inflammation and increased membrane permeability, which represents the leading cause of mortality in ICUs. Mechanical ventilation strategies are at the forefront of supportive approaches for ARDS. Recently, an increasing understanding of RNA biology, function, and regulation, as well as the success of RNA vaccines, has spurred enthusiasm for the emergence of novel RNA-based therapeutics. The most common types of RNA seen in development are silencing (si)RNAs, antisense oligonucleotide therapy (ASO), and messenger (m)RNAs that collectively account for 80% of the RNA therapeutics pipeline. These three RNA platforms are the most mature, with approved products and demonstrated commercial success. Most recently, miRNAs have emerged as pivotal regulators of gene expression. Their dysregulation in various clinical conditions offers insights into ARDS pathogenesis and offers the innovative possibility of using microRNAs as targeted therapy. This review synthesizes the current state of the literature to contextualize the therapeutic potential of miRNA modulation. It considers the potential for miR-based therapeutics as a nuanced approach that incorporates the complexity of ARDS pathophysiology and the multifaceted nature of miRNA interactions.

Diaphragm atrophy during invasive mechanical ventilation is related to extubation failure in preterm infants: An ultrasound study.

BACKGROUND: Diaphragm dysfunction is associated with poor outcomes in critically ill patients. Ventilator-induced diaphragmatic dysfunction (VIDD), including diaphragm atrophy (DA), is poorly studied in newborns. We aimed to assess VIDD and its associations in newborns. METHODS: Single-center prospective study. Diaphragm thickness was measured at end-inspiration (TDI) and end-expiration (TDE) on the right midaxillary line. DA was defined as decrease in TDE ≥ 10%. Daily measurements were recorded in preterm newborns on invasive mechanical ventilation (IMV) for ≥2 days. Clinical characteristics of patients and extubation failure were recorded. Univariate analysis, logistic regression, and mixed models were performed to describe VIDD and associated factors. RESULTS: We studied 17 patients (median gestational age 270/7 weeks) and 22 IMV cycles (median duration 9 days). Median TDE decreased from 0.118 cm (interquartile range [IQR] 0.094-0.165) on the first IMV day to 0.104 cm (IQR 0.083-0.120) on the last IMV day (p = .092). DA occurred in 11 IMV cycles (50%) from 10 infants early during IMV (median: second IMV day). Mean airway pressure (MAP) and lung ultrasound score (LUS) on the first IMV day were significantly higher in patients who developed DA. DA was more frequent in patients with extubation failure than in those with extubation success within 7 days (83.3 vs. 33.3%, p = .038). CONCLUSIONS: DA, significantly associated with extubation failure, occurred in 58.8% of the study infants on IMV. Higher MAP and LUS at IMV start were associated with DA. Our results suggest a potential role of diaphragm ultrasound to assess DA and predict extubation failure in clinical practice.

Perioperative Factors and Radiographic Severity Scores for Predicting the Duration of Mechanical Ventilation After Arterial Switch Surgery.

OBJECTIVES: Cardiac surgery on cardiopulmonary bypass (CPB) during the neonatal period can cause perioperative organ injuries. The primary aim of this study was to determine the incidence and risk factors associated with postoperative mechanical ventilation duration and acute lung injury after the arterial switch operation (ASO). The secondary aim was to examine the utility of the Brixia score for characterizing postoperative acute lung injury (ALI). DESIGN: A retrospective study. SETTING: A single-center university hospital. PARTICIPANTS: A total of 93 neonates with transposition of great arteries with intact ventricular septum (dTGA IVS) underwent ASO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From January 2015 to December 2022, 93 neonates with dTGA IVS were included in the study. The cohort had a median age of 4.0 (3.0-5.0) days and a mean weight of 3.3 ± 0.5 kg. About 63% of patients had ≥48 hours of postoperative mechanical ventilation after ASO. Risk factors included prematurity, post-CPB transfusion of salvaged red cells, platelets and cryoprecipitate, and postoperative fluid balance by univariate analysis. The larger transfused platelet volume was associated with the risk of ALI by multivariate analysis. The median baseline Brixia scores were 11.0 (9.0-12.0) and increased significantly in the postoperative day 1 in patients who developed moderate ALI 24 hours after admission to the intensive care unit (15.0 [13.0-16.0] v 12.0 [10.0-14.0], p = 0.046). CONCLUSIONS: Arterial switch operation results in a high incidence of ≥48-hour postoperative mechanical ventilation. Blood component transfusion is a potentially modifiable risk factor. The Brixia scores also may be used to characterize postoperative acute lung injury.

High Stretch Associated with Mechanical Ventilation Promotes Piezo1-Mediated Migration of Airway Smooth Muscle Cells.

Ventilator-induced lung injury (VILI) during mechanical ventilation (MV) has been attributed to airway remodeling involving increased airway smooth muscle cells (ASMCs), but the underlying mechanism is not fully understood. Thus, we aimed to investigate whether MV-associated high stretch (>10% strain) could modulate mechanosensitive Piezo1 expression and thereby alter cell migration of ASMCs as a potential pathway to increased ASMCs in VILI. C57BL/6 mice and ASMCs were subjected to MV at high tidal volume (VT, 18 mL/kg, 3 h) and high stretch (13% strain, 0.5 Hz, 72 h), respectively. Subsequently, the mice or cells were evaluated for Piezo1 and integrin mRNA expression by immunohistochemical staining and quantitative PCR (qPCR), and cell migration and adhesion by transwell and cell adhesion assays. Cells were either treated or not with Piezo1 siRNA, Piezo1-eGFP, Piezo1 knockin, Y27632, or blebbistatin to regulate Piezo1 mRNA expression or inhibit Rho-associated kinase (ROCK) signaling prior to migration or adhesion assessment. We found that expression of Piezo1 in in situ lung tissue, mRNA expression of Piezo1 and integrin αVß1 and cell adhesion of ASMCs isolated from mice with MV were all reduced but the cell migration of primary ASMCs (pASMCs) isolated from mice with MV was greatly enhanced. Similarly, cell line mouse ASMCs (mASMCs) cultured in vitro with high stretch showed that mRNA expression of Piezo1 and integrin αVß1 and cell adhesion were all reduced but cell migration was greatly enhanced. Interestingly, such effects of MV or high stretch on ASMCs could be either induced or abolished/reversed by down/up-regulation of Piezo1 mRNA expression and inhibition of ROCK signaling. High stretch associated with MV appears to be a mechanical modulator of Piezo1 mRNA expression and can, thus, promote cell migration of ASMCs during therapeutic MV. This may be a novel mechanism of detrimental airway remodeling associated with MV, and, therefore, a potential intervention target to treat VILI.