Lung Protective Ventilation Research Articles

ANESTHETIC CONSIDERATIONS FOR CRITICALLY ILL PATIENTS WITH SEPSIS

Objective: Sepsis is a life-threatening condition characterized by organ dysfunction due to a dysregulated host response to infection. Critically ill patients with sepsis often require surgical interventions, presenting significant anesthetic challenges due to profound physiological alterations and multiple organ dysfunctions. Methods: This systematic review aims to synthesize current evidence on anesthetic management strategies for critically ill patients with sepsis. A comprehensive literature search was conducted in PubMed, Embase, and Cochrane Library databases for studies published up to October 2023. Inclusion criteria encompassed clinical trials, observational studies, reviews, and guidelines focusing on anesthetic considerations in septic patients. Results: Key findings indicate that thorough preoperative assessment, vigilant hemodynamic monitoring, careful selection of anesthetic agents, and tailored ventilatory strategies are crucial for improving perioperative outcomes. Hemodynamic instability necessitates the use of invasive monitoring and vasoactive medications like norepinephrine. Etomidate and ketamine are preferred induction agents due to their hemodynamic stability, with considerations for their side effects. Maintenance anesthesia often favors total intravenous techniques to minimize cardiovascular depression. Protective lung ventilation strategies are essential due to the high risk of acute respiratory distress syndrome (ARDS). Postoperative care requires multidisciplinary collaboration to manage ongoing sepsis and prevent complications. Conclusion: This review highlights the importance of individualized anesthetic plans and suggests that adherence to evidence-based practices can enhance patient outcomes in this high-risk group.

Clinical practice of one-lung ventilation in mainland China: a nationwide questionnaire survey

BackgroundLimited information is available regarding the application of lung-protective ventilation strategies during one-lung ventilation (OLV) across mainland China. A nationwide questionnaire survey was conducted to investigate this issue in current clinical practice.MethodsThe survey covered various aspects, including respondent demographics, the establishment and maintenance of OLV, intraoperative monitoring standards, and complications associated with OLV.ResultsFive hundred forty-three valid responses were collected from all provinces in mainland China. Volume control ventilation mode, 4 to 6 mL per kilogram of predictive body weight, pure oxygen inspiration, and a low-level positive end-expiratory pressure ≤ 5 cm H2O were the most popular ventilation parameters. The most common thresholds of intraoperative respiration monitoring were peripheral oxygen saturation (SpO2) of 90–94%, end-tidal CO2 of 45 to 55 mm Hg, and an airway pressure of 30 to 34 cm H2O. Recruitment maneuvers were traditionally performed by 94% of the respondents. Intraoperative hypoxemia and laryngeal injury were experienced by 75% and 51% of the respondents, respectively. The proportions of anesthesiologists who frequently experienced hypoxemia during OLV were 19%, 24%, and 7% for lung, cardiovascular, and esophageal surgeries, respectively. Up to 32% of respondents were reluctant to perform lung-protective ventilation strategies during OLV. Multiple regression analysis revealed that the volume-control ventilation mode and an SpO2 intervention threshold of < 85% were independent risk factors for hypoxemia during OLV in lung and cardiovascular surgeries. In esophageal surgery, working in a tier 2 hospital and using traditional ventilation strategies were independent risk factors for hypoxemia during OLV. Subgroup analysis revealed no significant difference in intraoperative hypoxemia during OLV between respondents who performed lung-protective ventilation strategies and those who did not.ConclusionsLung-protective ventilation strategies during OLV have been widely accepted in mainland China and are strongly recommended for esophageal surgery, particularly in tier 2 hospitals. Implementing volume control ventilation mode and early management of oxygen desaturation might prevent hypoxemia during OLV.

Adherence to Lung Protective Ventilation in ARDS: A Mixed Methods Study Using Real-Time Continuously Monitored Ventilation Data

Adherence to Lung Protective Ventilation in ARDS: A Mixed Methods Study Using Real-Time Continuously Monitored Ventilation Data

Bronchoscopic lung lavage and exogenous surfactant successfully reverse respiratory failure after severe chlorine exposure: A pediatric case report.

Although the symptoms of accidental chlorine inhalation are typically mild, severe exposure can result in acute respiratory distress syndrome (ARDS). We present a case of pediatric ARDS due to chlorine exposure in which lung lavage and exogenous surfactant were successful in avoiding more invasive and costly treatments. Chlorine inhalation as a result of swimming pool chlorination accidents is relatively common. Because symptoms are typically mild (cough and bronchospasm), complications such as severe acute respiratory distress syndrome (ARDS) are identified at a late stage, which places the patient's life at risk and necessitates highly invasive interventions. We present a case of severe ARDS in a 14-year-old boy following accidental exposure to chlorine powder. Upon arrival in the pediatric emergency department, the patient received oxygen administration, nebulized salbutamol, and intravenous steroids because of dyspnea and cyanosis. Despite this treatment, the patient's respiratory condition deteriorated. Early intubation and lung-protective ventilation transitorily improved hypoxemia. Given the underlying pathophysiology of chlorine lung injury characterized by surfactant dysfunction, the boy was treated with repeated bronchoscopic lung lavages followed by exogenous surfactant (Curosurf 30 mg/kg total), 1 h after intubation and subsequently after 6 and 12 h, when he achieved a significant and stable reduction in ventilatory requirements. This case study illustrates the beneficial effects of target therapy with bronchoscopic lung lavage followed by exogenous surfactant in chlorine related ARDS to prevent more invasive and costly treatments.

Recent Advances and Future Directions in Extracorporeal Carbon Dioxide Removal.

Extracorporeal carbon dioxide removal (ECCO2R) is an emerging technique designed to reduce carbon dioxide (CO2) levels in venous blood while enabling lung-protective ventilation or alleviating the work of breathing. Unlike high-flow extracorporeal membrane oxygenation (ECMO), ECCO2R operates at lower blood flows (0.4-1.5 L/min), making it less invasive, with smaller cannulas and simpler devices. Despite encouraging results in controlling respiratory acidosis, its broader adoption is hindered by complications, including haemolysis, thrombosis, and bleeding. Technological advances, including enhanced membrane design, gas exchange efficiency, and anticoagulation strategies, are essential to improving safety and efficacy. Innovations such as wearable prototypes that adapt CO2 removal to patient activity and catheter-based systems for lower blood flow are expanding the potential applications of ECCO2R, including as a bridge-to-lung transplantation and in outpatient settings. Promising experimental approaches include respiratory dialysis, carbonic anhydrase-coated membranes, and electrodialysis to maximise CO2 removal. Further research is needed to optimise device performance, develop cost-effective systems, and establish standardised protocols for safe clinical implementation. As the technology matures, integration with artificial intelligence (AI) and machine learning may personalise therapy, improving outcomes. Ongoing clinical trials will be pivotal in addressing these challenges, ultimately enhancing the role of ECCO2R in critical care and its accessibility across healthcare settings.

ECMO for Adult Respiratory Failure: A Rapid Review of Clinical and Service Delivery Evidence to Guide Policy in Wales.

While several studies have summarised the clinical effectiveness evidence for extracorporeal membrane oxygenation (ECMO), there are no evidence syntheses of the impact of centres' ECMO patient volume on patient outcomes or the impact of bedside ECMO care being delivered by either a perfusionist or a nurse. There is also limited information on the cost-effectiveness of ECMO. This review was carried out to evaluate the clinical effectiveness and cost of different service delivery models of pulmonary ECMO to inform NHS Wales commissioning policy. The study utilised rapid review methodology, consisting of a systematic literature search and the inclusion of the highest quality of evidence available. Out of 1997 records identified via literature searches, 12 studies fell within the scope. The 2 meta-analyses comparing ECMO with lung-protective ventilation favoured ECMO. Five studies looking at the clinical impact of centre patient volume had large heterogeneity. Three studies estimated that with sufficient patient volume, nurse-delivered ECMO was cost-saving, with thresholds varying between 92 and 155 patient days per year. Three studies looked at the cost impact of ECMO delivery, with ECMO being cost incurring, but potentially cost-effective, with costs per patient being lower at higher volume centres. The available evidence supports the use of ECMO in adult respiratory failure patients, despite it being cost-incurring. ECMO can be nurse-delivered without a significant negative impact on patient care. Yet decision-makers need to consider their local circumstances when making commissioning decisions.

Drive Pressure-Guided Individualized Positive End-Expiratory Pressure in Traumatic Brain Injury Surgery: A Randomized Controlled Trial.

Intraoperative lung-protective ventilation strategies (LPVS) have been shown to improve lung oxygenation and prevent postoperative pulmonary problems in surgical patients. However, the application of positive end-expiratory pressure (PEEP)-based LPVS in emergency traumatic brain injury (TBI) has not been thoroughly explored. The purpose of this study is to evaluate the effects of drive pressure-guided individualized PEEP on perioperative pulmonary oxygenation, postoperative pulmonary complications, and recovery from neurological injury in patients with TBI. A total of 111 TBI patients who met the inclusion criteria at Northern Jiangsu People's Hospital were randomized into three groups: group A (0 PEEP, 50% inhaled oxygen concentration, and 6 mL/kg tidal volume), group B (5 cmH2O PEEP, 50% inhaled oxygen concentration, and 6 mL/kg tidal volume), and group C (individualized PEEP guided by driving pressure, 50% inhaled oxygen concentration, and 6 mL/kg tidal volume). The primary endpoints were lung ultrasound score (LUS), optic nerve sheath diameter (ONSD), and serum levels of neuron-specific enolase (NSE) and High mobility group box 1 protein (HMGB1). Secondary endpoints included intraoperative hemodynamic and respiratory mechanics parameters, postoperative pulmonary complications, and clinical lung infection scores. Eighty-nine patients completed the final analysis. LUS was significantly lower in group C compared to group A at T4 (least square mean [95% confidence interval (CI)]: 2.50 [1.35, 3.65] vs. 5.25 [4.10, 6.40], p < 0.05). Although ONSD increased gradually in group C, it did not differ substantially from group A postoperatively (least square mean [95% CI]: 5.09 [4.90, 5.27] vs 5.16 [4.97, 5.34] mm, p > 0.05). Serum NSE levels in group C were significantly lower on postoperative days 1 (4.40 [3.89, 4.41] vs. 10.95 [10.44, 11.46], p < 0.05) and 3 (2.79 [2.28, 3.30] vs. 10.95 [10.44, 11.46], p < 0.05). Additionally, serum HMGB1 levels in group C were significantly reduced on postoperative days 1 (229 [200, 258] vs. 662 [633, 691], p < 0.05) and 3 (166 [137, 195] vs. 662 [633, 691], p < 0.05). Individualized PEEP guided by driving pressure can improve perioperative pulmonary oxygenation and reduce the incidence of postoperative pulmonary complications. Furthermore, this strategy did not significantly elevate intraoperative intracranial pressure (ICP) and promoted recovery from postoperative neurological injury, likely by reducing the inflammatory response. https://www.chictr.org.cn/ (clinical trial no. ChiCTR2200066795).

Safety of flow-controlled ventilation with positive and negative end-expiratory pressure in a swine model of intracranial hypertension

BackgroundPatients with brain damage often require mechanical ventilation. Although lung-protective ventilation is recommended, the application of increased positive end-expiratory pressure (PEEP) has been associated with elevated intracranial pressure (ICP) due to altered cerebral venous return. This study investigates the effects of flow-controlled ventilation (FCV) using negative end-expiratory pressures (NEEP), on cerebral hemodynamics in a swine model of intracranial hypertension.MethodsA model of intracranial hypertension involving bilateral trepan bolt holes was performed in 14 pigs. Pressure-controlled volume-guaranteed ventilation (PCV-VG) with PEEP and FCV using PEEP and then NEEP were applied. Intracranial pressure and oxygenation, as well as systemic hemodynamics and gas exchange parameters, were continuously monitored. Data were collected at baseline and at varying PEEP levels for both PCV-VG and FCV ventilation modalities. Following this, FCV ventilation and NEEP levels of -3, -6 and -9 cmH2O were applied.ResultsICP remained stable with low PEEP levels, but significantly decreased with NEEP. Lower ICP following NEEP improved cerebral perfusion pressure and cerebral tissue oxygenation (p < 0.05 for all). FCV with NEEP at EEP-6 and EEP-9 significantly improved cardiac output and mean arterial pressure (MAP), compared to PCV-VG and FCV using PEEP (p < 0.05, respectively). There were no significant differences in gas exchange parameters between modalities (PCV-VG vs FCV), and between the application of PEEP or NEEP. No significant correlations were observed between ΔICP and ΔMAP.ConclusionThe application of FCV with NEEP appears to be a safe ventilation mode and offers an additional tool for controlling severe intracranial pressure episodes. These findings warrant validation in future studies and may lead to important potential applications in clinical practice.

Bedside Assessment of the Respiratory System During Invasive Mechanical Ventilation.

Assessing the respiratory system of a patient receiving mechanical ventilation is complex. We provide an overview of an approach at the bedside underpinned by physiology. We discuss the importance of distinguishing between extensive and intensive ventilatory variables. We outline methods to evaluate both passive patients and those making spontaneous respiratory efforts during assisted ventilation. We believe a comprehensive assessment can influence setting mechanical ventilatory support to achieve lung and diaphragm protective ventilation.

Improving lung protective mechanical ventilation: the individualised intraoperative open-lung approach

Improving lung protective mechanical ventilation: the individualised intraoperative open-lung approach

Dynamic driving pressure predicts ventilator-induced lung injury in mice with and without endotoxin-induced acute lung injury.

Mechanical ventilation is a necessary lifesaving intervention for patients with Acute Respiratory Distress Syndrome (ARDS) but it can cause ventilator induced lung injury (VILI), which contributes to the high ARDS mortality rate (≈40%). Bedside determination of optimally lung-protective ventilation settings is challenging because the evolution of VILI is not immediately reflected in clinically available, patient-level, data. The goal of this work was therefore to test ventilation waveform-derived parameters that represent the degree of ongoing VILI and can serve as targets for ventilator adjustments. VILI was generated at three different positive end expiratory pressures in a murine inflammation-mediated (lipopolysaccharide, LPS) acute lung injury model and in initially healthy controls. LPS injury increased expression of proinflammatory cytokines and caused widespread atelectasis, predisposing the lungs to VILI as measured in structure, mechanical function, and inflammation. Changes in lung function were used as response variables in an elastic net regression model that predicted VILI severity from tidal volume, dynamic driving pressure (PDDyn), mechanical power calculated by integration during inspiration or the entire respiratory cycle, and power calculated according to Gattinoni' s equation. Of these, PDDyn best predicted functional outcomes of injury using either data from the entire dataset or from 5-minute time windows. The windowed data shows higher predictive accuracy after a ≈1-hour 'run in' period and worse accuracy immediately following recruitment maneuvers. This analysis shows that low driving pressure is a computational biomarker associated with better experimental VILI outcomes and supports the use of driving pressure to guide ventilator adjustments to prevent VILI.

Association Between Anaesthesiologists' Sex and Anaesthesiology Quality Metrics and Postoperative Outcomes: A Retrospective Analysis.

Background: Evidence suggests differences in medical practice and patient outcomes between male and female physicians and surgeons. To date, no such relationships were investigated in anaesthesiologists. This study aimed to investigate an association between anaesthesiologists' sex and anaesthesia quality metrics as well as outcomes. Methods: We performed a population-based, single-centre, retrospective cohort study. Data were gathered from all patients undergoing anaesthesia between 1 January 2014 and 31 March 2022 at a large tertiary centre in Vienna, Austria. We examined 30-day mortality in relation to the sex of the anaesthesiologist after adjusting for various patient, physician, and hospital factors. Additionally, we assessed anaesthesiologists' sex and several anaesthesia quality benchmarks. Results: The final dataset included 94,254 cases. The study showed a very small but statistically significant correlation between male anaesthesia providers and an elevated risk for all-cause mortality within 30 days (adjusted odds ratio [aOR]: 1.0026; 95% confidence interval [CI], 1.0003-1.0048). Both male and female anaesthesiologists demonstrated similar proficiency in managing hemodynamic stability, blood glucose levels, preventing postoperative acute kidney injury (AKI) and lung-protective ventilation. However, male anaesthesiologists showed slightly higher adherence to guidelines for PONV prophylaxis. Conclusions: In a dataset of nearly 95,000 cases, there was a clinically marginal but statistically significant association between male provider sex and 30-day mortality.

How to protect the diaphragm and the lung with diaphragm neurostimulation.

In the current review, we aim to highlight the evolving evidence on using diaphragm neurostimulation to develop lung and diaphragm protective mechanical ventilation. Positive-pressure ventilation (PPV) causes stress and strain to the lungs which leads to ventilator-induced lung injury (VILI). In addition, PPV is frequently associated with sedatives that induce excessive diaphragm unloading which contributes to ventilator-induced diaphragmatic dysfunction (VIDD). The nonvolitional diaphragmatic contractions entrained by diaphragm neurostimulation generate negative pressure ventilation, which may be a beneficial alternative or complement to PPV. Although well established as a permanent treatment of central apnea syndromes, temporary diaphragm neurostimulation rapidly evolves to prevent and treat VILI and VIDD. Experimental and small clinical studies report comprehensive data showing that diaphragm neurostimulation has the potential to mitigate VIDD and to decrease the stress and strain applied to the lungs. Scientific interest in temporary diaphragm neurostimulation has dramatically evolved in the last few years. Despite a solid physiological rationale and promising preliminary findings confirming a beneficial effect on the diaphragm and lungs, more studies and further technological advances will be needed to establish optimal standardized settings and lead to clinical implementation and improved outcomes.

Metabolic Effects of Sodium Thiosulfate During Resuscitation from Trauma and Hemorrhage in Cigarette-Smoke-Exposed Cystathionine-γ-Lyase Knockout Mice.

Acute and chronic pre-traumatic cigarette smoke exposure increases morbidity and mortality after trauma and hemorrhage. In mice with a genetic deletion of the H2S-producing enzyme cystathione-γ-lyase (CSE-/-), providing exogenous H2S using sodium thiosulfate (Na2S2O3) improved organ function after chest trauma and hemorrhagic shock. Therefore, we evaluated the effect of Na2S2O3 during resuscitation from blunt chest trauma and hemorrhagic shock on CSE-/- mice with pre-traumatic cigarette smoke (CS) exposure. Since H2S is well established as being able to modify energy metabolism, a specific focus was placed on whole-body metabolic pathways and mitochondrial respiratory activity. Following CS exposure, the CSE-/- mice underwent anesthesia, surgical instrumentation, blunt chest trauma, hemorrhagic shock for over 1 h (target mean arterial pressure (MAP) ≈ 35 ± 5 mmHg), and resuscitation for up to 8 h comprising lung-protective mechanical ventilation, the re-transfusion of shed blood, fluid resuscitation, and continuous i.v. noradrenaline (NoA) to maintain an MAP ≥ 55 mmHg. At the start of the resuscitation, the mice randomly received either i.v. Na2S2O3 (0.45 mg/gbodyweight; n = 14) or the vehicle (NaCl 0.9%; n = 11). In addition to the hemodynamics, lung mechanics, gas exchange, acid-base status, and organ function, we quantified the parameters of carbohydrate, lipid, and protein metabolism using a primed continuous infusion of stable, non-radioactive, isotope-labeled substrates (gas chromatography/mass spectrometry) and the post-mortem tissue mitochondrial respiratory activity ("high-resolution respirometry"). While the hemodynamics and NoA infusion rates did not differ, Na2S2O3 was associated with a trend towards lower static lung compliance (p = 0.071) and arterial PO2 (p = 0.089) at the end of the experiment. The direct, aerobic glucose oxidation rate was higher (p = 0.041) in the Na2S2O3-treated mice, which resulted in lower glycemia levels (p = 0.050) and a higher whole-body CO2 production rate (p = 0.065). The mitochondrial respiration in the heart, kidney, and liver tissue did not differ. While the kidney function was comparable, the Na2S2O3-treated mice showed a trend towards a shorter survival time (p = 0.068). During resuscitation from blunt chest trauma and hemorrhagic shock in CSE-/- mice with pre-traumatic CS exposure, Na2S2O3 was associated with increased direct, aerobic glucose oxidation, suggesting a switch in energy metabolism towards preferential carbohydrate utilization. Nevertheless, treatment with Na2S2O3 coincided with a trend towards worsened lung mechanics and gas exchange, and, ultimately, shorter survival.

Lung Protective Mechanical Ventilation in Severe Acute Brain Injured Patients.

Lung Protective Mechanical Ventilation in Severe Acute Brain Injured Patients.

Optimizing perioperative lung protection strategies for reducing postoperative respiratory complications in pediatric patients: a narrative review.

Despite significant advancements in the safe delivery of anesthesia and improvements in surgical techniques, postoperative respiratory complications (PRCs) remain a serious concern. PRCs can lead to increased length of hospital stay, worsened patient outcomes, and higher hospital and postoperative costs. Perioperative lung injury and PRCs are more common in children than in adults owing to children's unique physiology and anatomical characteristics. Studies have shown that lung-protective ventilation (LPV) strategies can improve lung function and minimize the risk of PRCs in adults. However, individualized LPV in children remains underexplored. This narrative review provides an overview of the various perioperative pulmonary protection strategies and their effect on pediatric PRCs. We searched PubMed for articles published from 2000 to 2024, setting our inclusion criteria to include studies that involved pediatric patients, addressed LPV strategies, and reported data on PRCs. Non-English language studies, case reports, editorials, conference abstracts, and non-full text published literatures were excluded. We utilized the following keyword strategy: (((lung protective ventilation) OR (PEEP)) OR (recruitment maneuver)) OR (low tidal volume) AND (2000:2024[pdat])) AND (pediatric) filters. In total, 1,106 articles were retrieved, with only 23 being deemed relevant to the review. Data extraction and analysis were conducted by two independent researchers to ensure accuracy and consistency. We conducted descriptive statistical analysis for quantitative data and thematic analysis for qualitative data. The key content are an overview of risk factors for PRCs in children including the patients themselves, anesthesia, and surgery, as well as the effectiveness of LPV strategies in pediatric surgery, including low tidal volume (TV), positive end-expiratory pressure (PEEP), ultrasound-guided pulmonary recruitment maneuver (RM), low fraction of inspired oxygen (FiO2), pressure-controlled ventilation (PCV), as well as fluids, pain, and high-flow nasal cannula (HFNC). We found that age, mechanical ventilation with general anesthesia, and thoracic surgery increased the risk of PRCs in children. The application of LPV strategies in pediatric surgery had positive effect, including low TV combined with titrated PEEP, age- and physiologically appropriate FiO2, ultrasound-guided RM, target directed fluid infusion, adequate analgesia, and the use of HFNC in special circumstances. However, we also found that the application of LPV has certain potential risks and therefore needs to be implemented according to the patient's actual age and physical condition. Perioperative LPV strategies show potential benefits in reducing lung injury and PRCs in pediatric patients. These strategies, including low TV, appropriate individualized PEEP, lung RM, and avoidance of high FiO2, appear to be effective methods for protecting lung function in pediatric patients. Additionally, perioperative fluid management and effective pain control are crucial for lung protection. The emerging use of HFNC therapy shows promise, but further research is needed to fully understand its benefits.

Transvenous phrenic nerve stimulation reduces diaphragm injury during controlled mechanical ventilation in a preclinical model of ARDS.

Patients with acute respiratory distress syndrome (ARDS) require periods of deep sedation and mechanical ventilation, leading to diaphragm dysfunction. Our study seeks to determine whether the combination of temporary transvenous diaphragm neurostimulation (TTDN) and mechanical ventilation changes the degree of diaphragm injury and cytokines concentration in a preclinical ARDS model. Moderate ARDS was induced in pigs using oleic acid, followed by ventilation for 12 h post-injury with volume-control at 8 mL/kg, positive end-expiratory pressure (PEEP) 5 cmH2O, respiratory rate and [Formula: see text] set to achieve normal arterial blood gases. Two groups received TTDN: every second breath (MV + TTDN50%, n = 6) or every breath (MV + TTDN100%, n = 6). One group received ventilation only (MV, n = 6). Full-thickness diaphragm and quadricep muscle biopsies were taken at study end. Samples were fixed and stained with hematoxylin and eosin and a point-counting technique was applied to calculate abnormal muscle area fraction. Cytokine concentrations were measured in homogenized tissue using porcine-specific enzyme-linked immunosorbent assay (ELISA) and compared with serum samples. Percentage of abnormal diaphragm tissue was different between MV [8.1% (6.0-8.8)] versus MV + TTDN50% [3.4% (2.1-4.8)], P = 0.010 and MV versus MV + TTDN100% [3.1% (2.5-4.0)], P = 0.005. Percentage of abnormal quadriceps tissue was not different between groups. Cytokine concentration patterns in diaphragm samples were different between all groups (P < 0.001) and the interaction between TTDN application and resultant cytokine concentration pattern was significant (P = 0.025). TTDN, delivered in synchrony with mechanical ventilation, mitigated diaphragm injury, as evidenced by less abnormal tissue in the diaphragm samples, in pigs with oleic acid-induced ARDS and is an exciting tool for lung and diaphragm-protective ventilation.NEW & NOTEWORTHY This study adds to our understanding of applying transvenous diaphragm neurostimulation synchronously with mechanical ventilation by examining its effects on diaphragm muscle injury and cytokine concentration patterns in pigs with acute respiratory distress syndrome (ARDS). We observed that using this therapy for 12 h post lung injury mitigated ventilator-induced diaphragm injury and changed the pattern of cytokine concentration measured in diaphragm tissue. These findings suggest that transvenous diaphragm neurostimulation is an exciting tool for lung and diaphragm protective ventilation.

Nuclear factor erythroid 2-related factor 2 alleviates lung endothelial cells injury by inhibition of ferroptosis.

In recent years, the survival rate of preterm infants has significantly improved due to the application of pulmonary surfactant (PS) and advancements in lung-protective mechanical ventilation strategies. However, this has been accompanied by an increased incidence of complications, particularly lung diseases triggered by elevated reactive oxygen species (ROS) induced by hyperoxia. The primary mechanism of hyperoxic lung injury (HLI) involves the excessive production of ROS within cells and the aggregation of inflammatory cells. Currently, no effective prevention or treatment methods are available. Ferroptosis, a newly identified form of cell death, is closely linked to ROS accumulation and is likely involved in HLI. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates both HLI and ferroptosis, and targeting Nrf2 to inhibit ferroptosis may represent a key therapeutic approach for treating HLI. This study aimed to investigate the involvement of ferroptosis in HLI and to elucidate the regulatory role of Nrf2. We employed the human pulmonary microvascular endothelial cell (HPMEC) model of hyperoxia exposure and corresponding intervention groups. Mitochondrial morphological alterations within HPMECs exposed to hyperoxia and various control groups were examined using transmission electron microscopy (TEM). Cell viability was assessed via the Cell Counting Kit-8 (CCK-8) assay, whereas intracellular ROS levels were quantified using the dichlorodihydrofluorescein diacetate (DCFH-DA) probe. Furthermore, the expression levels of GPX4 and Nrf2 were analyzed through quantitative polymerase chain reaction (qPCR) and western blot techniques. Relative to the control group, the HPMECs subjected to hyperoxic conditions exhibited diminished viability, heightened ROS levels, decreased GPX4 expression, and increased Nrf2 expression. These cells also demonstrated mitochondrial morphological alterations characteristic of ferroptosis, including reduced mitochondrial cristae and shrinkage. The application of a ferroptosis inhibitor mitigated cellular damage, lipid peroxidation, and the morphological manifestations of mitochondrial ferroptosis, whereas Nrf2 inhibitor ML385 reversed this effect. Ferroptosis appears to contribute to the pathogenesis of HLI, with Nrf2 serving a protective function by mitigating ferroptosis.

Adherence to Lung Protective Ventilation in ARDS: A Mixed Methods Study Using Real-Time Continuously Monitored Ventilation Data.

Lung-protective ventilation is a standard intervention for mitigating ventilator-induced lung injury in patients with ARDS. Despite its efficacy, adherence to contemporary evidence-based guidelines remains suboptimal. We aimed to identify factors that affect the adherence of staff to applying lung-protective ventilation guidelines by analyzing real-time, continuously monitored ventilation data over a 5-year longitudinal period. We conducted retrospective cohort and qualitative studies. Subjects with billing code J80 who survived at least 48 h of continuous mandatory ventilation with volume control in critical care settings between January 1, 2018, and December 31, 2022, were eligible. Tidal volume was measured dynamically (1-min resolution) and averaged hourly. The lung-protective ventilation setting studied was ≤ 6 mL/kg predicted body weight. A subgroup analysis was conducted by considering COVID-19 status. Focus groups of critical-care providers were convened to investigate the possible reasons for the non-utilization of lung-protective ventilation. Among 1,055 subjects, 42.4% were on lung-protective ventilation settings at 48 h. Male sex was correlated with lung-protective ventilation (odds ratio [OR] 1.63, 95% CI 1.08-2.47), whereas age ≥ 60 y was associated with no lung-protective ventilation use (OR 0.61, 95% CI 0.39-0.94] in the subjects with non-COVID-19 etiologies. Improved staff adherence was observed in the subjects with COVID-19 early in the pandemic when COVID-19 (OR 1.48, 95% CI 1.07-2.04), male sex (OR 2.42, 95% CI 1.79-3.29), and neuromuscular blocking agent use within 48 h (OR 1.69, 95% CI 1.25-2.29) were correlated with staff placing subjects on lung-protective ventilation. However, lung-protective ventilation use occurred less frequently by staff managing subjects with cancer (OR 0.59, 95% CI 0.35-0.99) and hypertension (OR 0.62, 95% CI 0.45-0.85). Focus groups supported these findings and highlighted the need for an accurate height measurement on unit admission to determine the appropriate target tidal volume. Staff are not yet universally adherent to lung-protective ventilation best practices. Strategies, for example, continuous monitoring, with frequent feedback to clinical teams may help.

Does patient-ventilator asynchrony really matter?

Past observational studies have reported the association between patient-ventilator asynchronies and poor clinical outcomes, namely longer duration of mechanical ventilation and higher mortality. But causality has remained undetermined. During the era of lung and diaphragm protective ventilation, should we revolutionize our clinical practice to detect and treat dyssynchrony? Clinicians' ability to recognize asynchronies is typically low. Automatized softwares based on artificial intelligence have been trained to largely outperform human eyesight and are close to be implemented at the bedside. There is growing evidence that in susceptible patients, dyssynchrony may lead to ventilation-induced lung injury (or patient self-inflicted lung injury) and that clusters of such dyssynchronous events have the highest association with poor outcomes. Dyssynchrony may also be associated with harm indirectly when it reflects over-assistance or over-sedation. However, the occurrence of reverse triggering by means of low inspiratory efforts during passive ventilation may prevent diaphragm dysfunction and atrophy and be beneficial. Most recent evidence on the topic suggests that synchrony between the patient and the mechanical ventilator is a critical element for protecting lung and diaphragm during the time of invasive mechanical ventilation or may reflect inadequate settings or sedation. Therefore, it is a complex situation, and clinical trials are still needed to test the effectiveness of keeping patient-ventilator interaction synchronous on clinical outcomes.