BACKGROUND: Post-cardiac arrest syndrome (PCAS) presents a multifaceted challenge in clinical practice, characterized by severe neurological injury and high mortality rates despite advancements in management strategies. One of the important critical aspects of PCAS is post-arrest lung injury (PALI), which significantly contributes to poor outcomes. PALI arises from a complex interplay of pathophysiological mechanisms, including trauma from chest compressions, pulmonary ischemia-reperfusion (IR) injury, aspiration, and systemic inflammation. Despite its clinical significance, the pathophysiology of PALI remains incompletely understood, necessitating further investigation to optimize therapeutic approaches.
METHODS: This review comprehensively examines the existing literature to elucidate the epidemiology, pathophysiology, and therapeutic strategies for PALI. A comprehensive literature search was conducted to identify preclinical and clinical studies investigating PALI. Data from these studies were synthesized to provide a comprehensive overview of PALI and its management.
RESULTS: Epidemiological studies have highlighted the substantial prevalence of PALI in post-cardiac arrest patients, with up to 50% of survivors experiencing acute lung injury. Diagnostic imaging modalities, including chest X-rays, computed tomography, and lung ultrasound, play a crucial role in identifying PALI and assessing its severity. Pathophysiologically, PALI encompasses a spectrum of factors, including chest compression-related trauma, pulmonary IR injury, aspiration, and systemic inflammation, which collectively contribute to lung dysfunction and poor outcomes. Therapeutically, lung-protective ventilation strategies, such as low tidal volume ventilation and optimization of positive end-expiratory pressure, have emerged as cornerstone approaches in the management of PALI. Additionally, therapeutic hypothermia and emerging therapies targeting mitochondrial dysfunction hold promise in mitigating PALI-related morbidity and mortality.
CONCLUSIONS: PALI represents a significant clinical challenge in post-cardiac arrest care, necessitating prompt diagnosis and targeted interventions to improve outcomes. Mitochondrial-related therapies are among the novel therapeutic strategies for PALI. Further clinical research is warranted to optimize PALI management and enhance post-cardiac arrest care paradigms.

OBJECTIVE: A low dynamic driving pressure during mechanical ventilation for general anesthesia has been associated with a lower risk of postoperative respiratory complications (PRC), a key driver of healthcare costs. It is, however, unclear whether maintaining low driving pressure is clinically relevant to measure and contain costs. We hypothesized that a lower dynamic driving pressure is associated with lower costs.
METHODS: Multicenter retrospective cohort study.
METHODS: Two academic healthcare networks in New York and Massachusetts, USA.
METHODS: 46,715 adult surgical patients undergoing general anesthesia for non-ambulatory (inpatient and same-day admission) surgery between 2016 and 2021.
METHODS: The primary exposure was the median intraoperative dynamic driving pressure.
METHODS: The primary outcome was direct perioperative healthcare-associated costs, which were matched with data from the Healthcare Cost and Utilization Project-National Inpatient Sample (HCUP-NIS) to report absolute differences in total costs in United States Dollars (US$). We assessed effect modification by patients\' baseline risk of PRC (score for prediction of postoperative respiratory complications [SPORC] ≥ 7) and effect mediation by rates of PRC (including post-extubation saturation < 90%, re-intubation or non-invasive ventilation within 7 days) and other major complications.
RESULTS: The median intraoperative dynamic driving pressure was 17.2cmH2O (IQR 14.0-21.3cmH2O). In adjusted analyses, every 5cmH2O reduction in dynamic driving pressure was associated with a decrease of -0.7% in direct perioperative healthcare-associated costs (95%CI -1.3 to -0.1%; p = 0.020). When a dynamic driving pressure below 15cmH2O was maintained, -US$340 lower total perioperative healthcare-associated costs were observed (95%CI -US$546 to -US$132; p = 0.001). This association was limited to patients at high baseline risk of PRC (n = 4059; -US$1755;97.5%CI -US$2495 to -US$986; p < 0.001), where lower risks of PRC and other major complications mediated 10.7% and 7.2% of this association (p < 0.001 and p = 0.015, respectively).
CONCLUSIONS: Intraoperative mechanical ventilation targeting low dynamic driving pressures could be a relevant measure to reduce perioperative healthcare-associated costs in high-risk patients.

OBJECTIVE: This study aimed to assess the impact of a lung-protective ventilation strategy utilizing transpulmonary driving pressure titrated positive end-expiratory pressure (PEEP) on the prognosis [mechanical ventilation duration, hospital stay, 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP), survival outcome] of patients with Acute Respiratory Distress Syndrome (ARDS).
METHODS: A total of 105 ARDS patients were randomly assigned to either the control group (n = 51) or the study group (n = 53). The control group received PEEP titration based on tidal volume [A tidal volume of 6 mL/kg, flow rate of 30-60 L/min, frequency of 16-20 breaths/min, constant flow rate, inspiratory-to-expiratory ratio of 1:1 to 1:1.5, and a plateau pressure ≤ 30-35 cmH2O. PEEP was adjusted to maintain oxygen saturation (SaO2) at or above 90%, taking into account blood pressure], while the study group received PEEP titration based on transpulmonary driving pressure (Esophageal pressure was measured as a surrogate for pleural pressure using an esophageal pressure measurement catheter connected to the ventilator. Tidal volume and PEEP were adjusted based on the observed end-inspiratory and end-expiratory transpulmonary pressures, aiming to maintain a transpulmonary driving pressure below 15 cmH2O during mechanical ventilation. Adjustments were made 2-4 times per day). Statistical analysis and comparison were conducted on lung function indicators [oxygenation index (OI), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2)] as well as other measures such as heart rate, mean arterial pressure, and central venous pressure in two groups of patients after 48 h of mechanical ventilation. The 28-day mortality rate, duration of mechanical ventilation, length of hospital stay, and ventilator-associated pneumonia (VAP) incidence were compared between the two groups. A 60-day follow-up was performed to record the survival status of the patients.
RESULTS: In the control group, the mean age was (55.55 ± 10.51) years, with 33 females and 18 males. The pre-ICU hospital stay was (32.56 ± 9.89) hours. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was (19.08 ± 4.67), and the mean Murray Acute Lung Injury score was (4.31 ± 0.94). In the study group, the mean age was (57.33 ± 12.21) years, with 29 females and 25 males. The pre-ICU hospital stay was (33.42 ± 10.75) hours. The mean APACHE II score was (20.23 ± 5.00), and the mean Murray Acute Lung Injury score was (4.45 ± 0.88). They presented a homogeneous profile (all P > 0.05). Following intervention, significant improvements were observed in PaO2 and OI compared to pre-intervention values. The study group exhibited significantly higher PaO2 and OI compared to the control group, with statistically significant differences (all P < 0.05). After intervention, the study group exhibited a significant increase in PaCO2 (43.69 ± 6.71 mmHg) compared to pre-intervention levels (34.19 ± 5.39 mmHg). The study group\'s PaCO2 was higher than the control group (42.15 ± 7.25 mmHg), but the difference was not statistically significant (P > 0.05). There were no significant differences in hemodynamic indicators between the two groups post-intervention (all P > 0.05). The study group demonstrated significantly shorter mechanical ventilation duration and hospital stay, while 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP) showed no significant differences. Kaplan-Meier survival analysis revealed a significantly better survival outcome in the study group at the 60-day follow-up (HR = 0.565, 95% CI: 0.320-0.999).
CONCLUSIONS: Lung-protective mechanical ventilation using transpulmonary driving pressure titrated PEEP effectively improves lung function, reduces mechanical ventilation duration and hospital stay, and enhances survival outcomes in patients with ARDS. However, further study is needed to facilitate the wider adoption of this approach.

BACKGROUND: In patients requiring general anesthesia, lung-protective ventilation can prevent postoperative pulmonary complications, which are associated with higher morbidity, mortality, and prolonged hospital stay. Application of positive end-expiratory pressure (PEEP) is one component of lung-protective ventilation. The correct strategy for setting adequate PEEP, however, remains controversial. PEEP settings that lead to a lower pressure difference between end-inspiratory plateau pressure and end-expiratory pressure (\"driving pressure,\" ΔP) may reduce the risk of postoperative pulmonary complications. Preliminary data suggests that the PEEP required to prevent both end-inspiratory overdistension and end-expiratory alveolar collapse, thereby reducing ΔP, correlates positively with the body mass index (BMI) of patients, with PEEP values corresponding to approximately 1/3 of patient\'s respective BMI. Thus, we hypothesize that adjusting PEEP according to patient BMI reduces ΔP and may result in less postoperative pulmonary complications.
METHODS: Patients undergoing general anesthesia and endotracheal intubation with volume-controlled ventilation with a tidal volume of 7 ml per kg predicted body weight will be randomized and assigned to either an intervention group with PEEP adjusted according to BMI or a control group with a standardized PEEP of 5 mbar. Pre- and postoperatively, lung ultrasound will be performed to determine the lung aeration score, and hemodynamic and respiratory vital signs will be recorded for subsequent evaluation. The primary outcome is the difference in ΔP as a surrogate parameter for lung-protective ventilation. Secondary outcomes include change in lung aeration score, intraoperative occurrence of hemodynamic and respiratory events, oxygen requirements and postoperative pulmonary complications.
CONCLUSIONS: The study results will show whether an intraoperative ventilation strategy with PEEP adjustment based on BMI has the potential of reducing the risk for postoperative pulmonary complications as an easy-to-implement intervention that does not require lengthy ventilator maneuvers nor additional equipment.
BACKGROUND: German Clinical Trials Register (DRKS), DRKS00031336. Registered 21st February 2023.
METHODS: The study protocol was approved by the ethics committee of the Christian-Albrechts-Universität Kiel, Germany, on 1st February 2023. Recruitment began in March 2023 and is expected to end in September 2023.

Despite strong evidence of important benefits of volume-targeted ventilation, many high-risk extremely preterm infants continue to receive traditional pressure-controlled ventilation in the United States and elesewhere. Reluctance to abandon one\'s comfort zone, lack of suitable equipment and a lack of understanding of the subtleties of volume-targeted ventilation appear to contribute to the relatively slow uptake of volume-targeted ventilation. This review will underscore the benefits of using tidal volume as the primary control variable, to improve clinicians\' understanding of the way volume-targeted ventilation interacts with the awake, breathing infant and to provide information about evidence-based tidal volume targets in various circmstances. Focus on underlying lung pathophysiology, individualized ventilator settings and tidal volume targets are essential to successful use of this approach thereby improving important clinical outcomes.

Background: The ability to predict a long duration of mechanical ventilation (MV) by clinicians is very limited. We assessed the value of machine learning (ML) for early prediction of the duration of MV > 14 days in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Methods: This is a development, testing, and external validation study using data from 1173 patients on MV ≥ 3 days with moderate-to-severe ARDS. We first developed and tested prediction models in 920 ARDS patients using relevant features captured at the time of moderate/severe ARDS diagnosis, at 24 h and 72 h after diagnosis with logistic regression, and Multilayer Perceptron, Support Vector Machine, and Random Forest ML techniques. For external validation, we used an independent cohort of 253 patients on MV ≥ 3 days with moderate/severe ARDS. Results: A total of 441 patients (48%) from the derivation cohort (n = 920) and 100 patients (40%) from the validation cohort (n = 253) were mechanically ventilated for >14 days [median 14 days (IQR 8-25) vs. 13 days (IQR 7-21), respectively]. The best early prediction model was obtained with data collected at 72 h after moderate/severe ARDS diagnosis. Multilayer Perceptron risk modeling identified major prognostic factors for the duration of MV > 14 days, including PaO2/FiO2, PaCO2, pH, and positive end-expiratory pressure. Predictions of the duration of MV > 14 days showed modest discrimination [AUC 0.71 (95%CI 0.65-0.76)]. Conclusions: Prolonged MV duration in moderate/severe ARDS patients remains difficult to predict early even with ML techniques such as Multilayer Perceptron and using data at 72 h of diagnosis. More research is needed to identify markers for predicting the length of MV. This study was registered on 14 August 2023 at ClinicalTrials.gov (NCT NCT05993377).

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).
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.
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.
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.
German Clinical Trials Register (DRKS00017449). Registered June 27, 2019. https://drks.de/search/en/trial/DRKS00017449.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) for patients with acute respiratory distress syndrome (ARDS) has increased substantially. With modern trials supporting its efficacy, ECMO has become an important tool in the management of severe ARDS.
OBJECTIVE: The objectives of this paper are to discuss ECMO physiology and configurations used for patients with ARDS, review evidence supporting the use of ECMO for ARDS, and discuss aspects of management during ECMO.
CONCLUSIONS: Current evidence supports the use of ECMO, combined with an ultra-lung-protective approach to mechanical ventilation, in patients with ARDS who have refractory hypoxemia or hypercapnia with severe respiratory acidosis. Furthermore, data suggest that center volume and experience are important factors in the care of patients receiving ECMO. The use of extracorporeal technologies in expanded patient populations and the optimal management of patients during ECMO remain areas of investigation. This article is freely available.
UNASSIGNED: HINTERGRUND: Der Einsatz der extrakorporalen Membranoxygenierung (ECMO) bei Patienten mit akutem Atemnotsyndrom (ARDS) hat sich wesentlich erhöht. Da ihre Wirksamkeit durch rezente Studien belegt ist, ist die ECMO inzwischen zu einem essenziellen Instrument in der Behandlung des schweren ARDS geworden.
UNASSIGNED: Ziel dieser Veröffentlichung ist es, die ECMO-Physiologie und die bei Patienten mit ARDS verwendeten Konfigurationen zu diskutieren, die Evidenz für den Einsatz der ECMO beim ARDS zu überprüfen und Aspekte des Managements während der ECMO zu erörtern.
UNASSIGNED: Die derzeit verfügbare Evidenz spricht für den Einsatz der ECMO in Kombination mit einem ultra-lungenprotektiven Ansatz für die mechanische Beatmung von ARDS-Patienten, die eine refraktäre Hypoxämie oder Hyperkapnie mit schwerer respiratorischer Azidose aufweisen. Außerdem deuten die Daten darauf hin, dass das Volumen und die Erfahrung des Zentrums relevante Faktoren bei der Versorgung von mit ECMO behandelten Patienten sind. Weiter zu untersuchen sind nach wie vor der Einsatz extrakorporaler Technologien bei erweiterten Patientengruppen und das optimale Management von Patienten während der ECMO. Dieser Artikel ist frei verfügbar.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury characterized by severe hypoxemic respiratory failure, bilateral opacities on chest imaging, and low lung compliance. ARDS is a heterogeneous syndrome that is the common end point of a wide variety of predisposing conditions, with complex pathophysiology and underlying mechanisms. Routine management of ARDS is centered on lung-protective ventilation strategies such as low tidal volume ventilation and targeting low airway pressures to avoid exacerbation of lung injury, as well as a conservative fluid management strategy.

OBJECTIVE: To identify tidal volume (VT) and positive end-expiratory pressure (PEEP) associated with the lowest incidence and severity of postoperative pulmonary complications (PPCs) for each phenotype based on preoperative characteristics.
METHODS: The subjects of this retrospective observational cohort study were 34,910 adults who underwent surgery, using general anesthesia with mechanical ventilation. Initially, the least absolute shrinkage and selection operator regression was employed to select relevant preoperative characteristics. Then, the classification and regression tree (CART) was built to identify phenotypes. Finally, we computed the area under the receiver operating characteristic curves from logistic regressions to identify VT and PEEP associated with the lowest incidence and severity of PPCs for each phenotype.
RESULTS: CARTs classified seven phenotypes for each outcome. A probability of the development of PPCs ranged from the lowest (3.51%) to the highest (68.57%), whereas the probability of the development of the highest level of PPC severity ranged from 3.3% to 91.0%. Across all phenotypes, the VT and PEEP associated with the most desirable outcomes were within a small range of VT 7-8 ml/kg predicted body weight with PEEP of between 6 and 8 cmH2O.
CONCLUSIONS: The ranges of optimal VT and PEEP were small, regardless of the phenotypes, which had a wide range of risk profiles.