Regional pulmonary perfusion, blood volume, and their relationship change in experimental early ARDS.

Regional pulmonary perfusion (Q) has been investigated using blood volume (Fb) imaging as an easier-to-measure surrogate. However, it is unclear if changing pulmonary conditions could affect their relationship. We hypothesized that vascular changes in early acute respiratory distress syndrome (ARDS) affect Q and Fb differently. Five sheep were anesthetized and received lung protective mechanical ventilation for 20 h while endotoxin was continuously infused. Using dynamic 18F-FDG and 13NN Positron Emission Tomography (PET), regional Fb and Q were analysed in 30 regions of interest (ROIs) and normalized by tissue content (Fbn and Qn, respectively). After 20 h, the lung injury showed characteristics of early ARDS, including gas exchange and lung mechanics. PET images of Fbn and Qn showed substantial differences between baseline and lung injury. Lung injury caused a significant change in the Fbn-Qn relationship compared to baseline (p < 0.001). The best models at baseline and lung injury were Fbn = 0.32 + 0.690Qn and Fbn = 1.684Qn-0.538Qn2, respectively. Endotoxine-associated early ARDS changed the relationship between Fb and Q, shifting from linear to curvilinear. Effects of endotoxin exposure on the vasoactive blood flow regulation were most likely the key factor for this change limiting the quantitative accuracy of Fb imaging as a surrogate for regional Q.

Dynamic lung aeration and strain with positive end-expiratory pressure individualized to maximal compliance versus ARDSNet low-stretch strategy: a study in a surfactant depletion model of lung injury.

BACKGROUND: Positive end-expiratory pressure (PEEP) individualized to a maximal respiratory system compliance directly implies minimal driving pressures with potential outcome benefits, yet, raises concerns on static and dynamic overinflation, strain and cyclic recruitment. Detailed accurate assessment and understanding of these has been hampered by methodological limitations. We aimed to investigate the effects of a maximal compliance-guided PEEP strategy on dynamic lung aeration, strain and tidal recruitment using current four-dimensional computed tomography (CT) techniques and analytical methods of tissue deformation in a surfactant depletion experimental model of acute respiratory distress syndrome (ARDS). METHODS: ARDS was induced by saline lung lavage in anesthetized and mechanically ventilated healthy sheep (n = 6). Animals were ventilated in a random sequence with: (1) ARDSNet low-stretch protocol; (2) maximal compliance PEEP strategy. Lung aeration, strain and tidal recruitment were acquired with whole-lung respiratory-gated high-resolution CT and quantified using registration-based techniques. RESULTS: Relative to the ARDSNet low-stretch protocol, the maximal compliance PEEP strategy resulted in: (1) improved dynamic whole-lung aeration at end-expiration (0.456 ± 0.064 vs. 0.377 ± 0.101, P = 0.019) and end-inspiration (0.514 ± 0.079 vs. 0.446 ± 0.083, P = 0.012) with reduced non-aerated and increased normally-aerated lung mass without associated hyperinflation; (2) decreased aeration heterogeneity at end-expiration (coefficient of variation: 0.498 ± 0.078 vs. 0.711 ± 0.207, P = 0.025) and end-inspiration (0.419 ± 0.135 vs. 0.580 ± 0.108, P = 0.014) with higher aeration in dorsal regions; (3) tidal aeration with larger inspiratory increases in normally-aerated and decreases in poorly-aerated areas, and negligible in hyperinflated lung (Aeration × Strategy: P = 0.026); (4) reduced tidal strains in lung regions with normal-aeration (Aeration × Strategy: P = 0.047) and improved regional distributions with lower tidal strains in middle and ventral lung (Region-of-interest [ROI] × Strategy: P < 0.001); and (5) less tidal recruitment in middle and dorsal lung (ROI × Strategy: P = 0.044) directly related to whole-lung tidal strain (r = 0.751, P = 0.007). CONCLUSIONS: In well-recruitable ARDS models, a maximal compliance PEEP strategy improved end-expiratory/inspiratory whole-lung aeration and its homogeneity without overinflation. It further reduced dynamic strain in middle-ventral regions and tidal recruitment in middle-dorsal areas. These findings suggest the maximal compliance strategy minimizing whole-lung dynamically quantified mechanisms of ventilator-induced lung injury with less cyclic recruitment and no additional overinflation in large heterogeneously expanded and recruitable lungs.

Development of an automated, general-purpose prediction tool for postoperative respiratory failure using machine learning: A retrospective cohort study.

STUDY OBJECTIVE: Postoperative respiratory failure is a major surgical complication and key quality metric. Existing prediction tools underperform, are limited to specific populations, and necessitate manual calculation. This limits their implementation. We aimed to create an improved, machine learning powered prediction tool with ideal characteristics for automated calculation. DESIGN, SETTING, AND PATIENTS: We retrospectively reviewed 101,455 anesthetic procedures from 1/2018 to 6/2021. The primary outcome was the Standardized Endpoints in Perioperative Medicine consensus definition for postoperative respiratory failure. Secondary outcomes were respiratory quality metrics from the National Surgery Quality Improvement Sample, Society of Thoracic Surgeons, and CMS. We abstracted from the electronic health record 26 procedural and physiologic variables previously identified as respiratory failure risk factors. We randomly split the cohort and used the Random Forest method to predict the composite outcome in the training cohort. We coined this the RESPIRE model and measured its accuracy in the validation cohort using area under the receiver operating curve (AUROC) analysis, among other measures, and compared this with ARISCAT and SPORC-1, two leading prediction tools. We compared performance in a validation cohort using score cut-offs determined in a separate test cohort. MAIN RESULTS: The RESPIRE model exhibited superior accuracy with an AUROC of 0.93 (95% CI, 0.92-0.95) compared to 0.82 for both ARISCAT and SPORC-1 (P-for-difference < 0.0001 for both). At comparable 80-90% sensitivities, RESPIRE had higher positive predictive value (11%, 95% CI: 10-12%) and lower false positive rate (12%, 95% CI: 12-13%) compared to 4% and 37% for both ARISCAT and SPORC-1. The RESPIRE model also better predicted the established quality metrics for postoperative respiratory failure. CONCLUSIONS: We developed a general-purpose, machine learning powered prediction tool with superior performance for research and quality-based definitions of postoperative respiratory failure.

Worsening of lung perfusion to tissue density distributions during early acute lung injury.

Lung perfusion magnitude and distribution are essential for oxygenation and, potentially, lung inflammation and protection during acute respiratory distress syndrome (ARDS). Yet, perfusion patterns and their relationship to inflammation are unknown pre-ARDS. We aimed to assess perfusion/density ratios and spatial perfusion-density distributions and associate these to lung inflammation, during early lung injury in large animals at different physiological conditions caused by different systemic inflammation and positive end-expiratory pressure (PEEP) levels. Sheep were protectively ventilated (16-24 h) and imaged for lung density, pulmonary capillary perfusion (13Nitrogen-saline), and inflammation (18F-fluorodeoxyglucose) using positron emission and computed tomography. We studied four conditions: permissive atelectasis (PEEP = 0 cmH2O); and ARDSNet low-stretch PEEP-setting strategy with supine moderate or mild endotoxemia, and prone mild endotoxemia. Perfusion/density heterogeneity increased pre-ARDS in all groups. Perfusion redistribution to density depended on ventilation strategy and endotoxemia level, producing more atelectasis in mild than moderate endotoxemia (P = 0.010) with the oxygenation-based PEEP-setting strategy. The spatial distribution of 18F-fluorodeoxyglucose uptake was related to local Q/D (P < 0.001 for Q/D group interaction). Moderate endotoxemia yielded markedly low/zero perfusion in normal-low density lung, with 13Nitrogen-saline perfusion indicating nondependent capillary obliteration. Prone animals' perfusion was remarkably homogeneously distributed with density. Lung perfusion redistributes heterogeneously to density during pre-ARDS protective ventilation in animals. This is associated with increased inflammation, nondependent capillary obliteration, and lung derecruitment susceptibility depending on endotoxemia level and ventilation strategy.NEW & NOTEWORTHY Perfusion redistribution does not follow lung density redistribution in the first 16-24 h of systemic endotoxemia and protective tidal volume mechanical ventilation. The same oxygenation-based positive end-expiratory pressure (PEEP)-setting strategy can lead at different endotoxemia levels to different perfusion redistributions, PEEP values, and lung aerations, worsening lung biomechanical conditions. During early acute lung injury, regional perfusion-to-tissue density ratio is associated with increased neutrophilic inflammation, and susceptibility to nondependent capillary occlusion and lung derecruitment, potentially marking and/or driving lung injury.

Reversal of neuromuscular block: what are the costs?

Patients requiring neuromuscular block for anaesthesia have a higher risk of adverse postoperative outcomes. The choice of reversal drug and its corresponding dose is critical for improving clinical outcomes. Although drug costs are higher for sugammadex relative to neostigmine, additional factors need to be considered when choosing one drug over the other. New data from a recent study in the British Journal of Anaesthesia indicate cost advantages for sugammadex in low-risk and ambulatory patients, but for neostigmine in high-risk patients. These findings highlight the need to take local and temporal factors into consideration in addition to clinical effectiveness when performing cost analyses for administrative decision-making.

An anesthesia-centered bundle to reduce postoperative pulmonary complications: The PRIME-AIR study protocol.

BACKGROUND: Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality after open abdominal surgery. Optimized perioperative lung expansion may minimize the synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction. This ongoing study will assess whether an anesthesia-centered bundle focused on perioperative lung expansion results in decreased incidence and severity of PPCs after open abdominal surgery. METHODS: Prospective multicenter randomized controlled pragmatic trial in 750 adult patients with at least moderate risk for PPCs undergoing prolonged (≥2 hour) open abdominal surgery. Participants are randomized to receive either a bundle intervention focused on perioperative lung expansion or usual care. The bundle intervention includes preoperative patient education, intraoperative protective ventilation with individualized positive end-expiratory pressure to maximize respiratory system compliance, optimized neuromuscular blockade and reversal management, and postoperative incentive spirometry and early mobilization. Primary outcome is the distribution of the highest PPC severity by postoperative day 7. Secondary outcomes include the proportion of participants with: PPC grades 1-2 through POD 7; PPC grades 3-4 through POD 7, 30 and 90; intraoperative hypoxemia, rescue recruitment maneuvers, or cardiovascular events; and any major extrapulmonary postoperative complications. Additional secondary and exploratory outcomes include individual PPCs by POD 7, length of postoperative oxygen therapy or other respiratory support, hospital resource use parameters, Patient-Reported Outcomes Measurements (PROMIS®) questionnaires for dyspnea and fatigue collected before and at days 7, 30 and 90 after surgery, and plasma concentrations of lung injury biomarkers (IL6, IL-8, RAGE, CC16, Ang-2) analyzed from samples obtained before, end of, and 24 hours after surgery. DISCUSSION: Participant recruitment for this study started January 2020; results are expected in 2024. At the conclusion of this trial, we will determine if this anesthesia-centered strategy focused on perioperative lung expansion reduces lung morbidity and healthcare utilization after open abdominal surgery. TRIAL REGISTRATION: ClinicalTrial.gov NCT04108130.

Quantitative Imaging Metrics for the Assessment of Pulmonary Pathophysiology: An Official American Thoracic Society and Fleischner Society Joint Workshop Report.

Multiple thoracic imaging modalities have been developed to link structure to function in the diagnosis and monitoring of lung disease. Volumetric computed tomography (CT) renders three-dimensional maps of lung structures and may be combined with positron emission tomography (PET) to obtain dynamic physiological data. Magnetic resonance imaging (MRI) using ultrashort-echo time (UTE) sequences has improved signal detection from lung parenchyma; contrast agents are used to deduce airway function, ventilation-perfusion-diffusion, and mechanics. Proton MRI can measure regional ventilation-perfusion ratio. Quantitative imaging (QI)-derived endpoints have been developed to identify structure-function phenotypes, including air-blood-tissue volume partition, bronchovascular remodeling, emphysema, fibrosis, and textural patterns indicating architectural alteration. Coregistered landmarks on paired images obtained at different lung volumes are used to infer airway caliber, air trapping, gas and blood transport, compliance, and deformation. This document summarizes fundamental "good practice" stereological principles in QI study design and analysis; evaluates technical capabilities and limitations of common imaging modalities; and assesses major QI endpoints regarding underlying assumptions and limitations, ability to detect and stratify heterogeneous, overlapping pathophysiology, and monitor disease progression and therapeutic response, correlated with and complementary to, functional indices. The goal is to promote unbiased quantification and interpretation of in vivo imaging data, compare metrics obtained using different QI modalities to ensure accurate and reproducible metric derivation, and avoid misrepresentation of inferred physiological processes. The role of imaging-based computational modeling in advancing these goals is emphasized. Fundamental principles outlined herein are critical for all forms of QI irrespective of acquisition modality or disease entity.

Macrophage ferroportin serves as a therapeutic target against bacteria-induced acute lung injury by promoting barrier restoration.

Acute respiratory distress syndrome (ARDS) is a common lung disorder that involves severe inflammatory damage in the pulmonary barrier, but the underlying mechanisms remain elusive. Here, we demonstrated that pulmonary macrophages originating from ARDS patients and mice caused by bacteria were characterized by increased expression of ferroportin (FPN). Specifically deleting FPN in myeloid cells conferred significant resistance to bacterial infection with improved survival by decreasing extracellular bacterial growth and preserving pulmonary barrier integrity in mice. Mechanistically, macrophage FPN deficiency not only limited the availability of iron to bacteria, but also promoted tissue restoration via growth factor amphiregulin, which is regulated by cellular iron-activated Yes-associated protein signaling. Furthermore, pharmacological treatment with C-Hep, the self-assembled N-terminally cholesterylated minihepcidin that functions in the degradation of macrophage FPN, protected against bacteria-induced lung injury. Therefore, therapeutic strategies targeting the hepcidin-FPN axis in macrophages may be promising for the clinical treatment of acute lung injury.

Alternative adenosine Receptor activation: The netrin-Adora2b link.

During hypoxia or inflammation, extracellular adenosine levels are elevated. Studies using pharmacologic approaches or genetic animal models pertinent to extracellular adenosine signaling implicate this pathway in attenuating hypoxia-associated inflammation. There are four distinct adenosine receptors. Of these, it is not surprising that the Adora2b adenosine receptor functions as an endogenous feedback loop to control hypoxia-associated inflammation. First, Adora2b activation requires higher adenosine concentrations compared to other adenosine receptors, similar to those achieved during hypoxic inflammation. Second, Adora2b is transcriptionally induced during hypoxia or inflammation by hypoxia-inducible transcription factor HIF1A. Studies seeking an alternative adenosine receptor activation mechanism have linked netrin-1 with Adora2b. Netrin-1 was originally discovered as a neuronal guidance molecule but also functions as an immune-modulatory signaling molecule. Similar to Adora2b, netrin-1 is induced by HIF1A, and has been shown to enhance Adora2b signaling. Studies of acute respiratory distress syndrome (ARDS), intestinal inflammation, myocardial or hepatic ischemia and reperfusion implicate the netrin-Adora2b link in tissue protection. In this review, we will discuss the potential molecular linkage between netrin-1 and Adora2b, and explore studies demonstrating interactions between netrin-1 and Adora2b in attenuating tissue inflammation.

Reintubation After Lung Cancer Resection: Development and External Validation of a Predictive Score.

BACKGROUND: Reintubation after lung cancer resection is an important quality metric because of increased disability, mortality and cost. However, no validated predictive instrument is in use to reduce reintubation after lung resection. This study aimed to create and validate the PRediction Of REintubation After Lung cancer resection (PROREAL) score. METHODS: The study analyzed lung resection cases from 2 university hospitals. The primary end point was reintubation within 7 days after surgery. Predictors were selected through backward stepwise logistic regression and bootstrap resampling. The investigators used reclassification and receiver-operating characteristic (ROC) curve analyses to assess score performance and compare it with an established score for all surgical patients (Score for Prediction of Postoperative Respiratory Complications [SPORC]). RESULTS: The study included 2672 patients who underwent resection for lung cancer (1754, development cohort; 918, validation cohort) between 2008 and 2020, of whom 71 (2.7%) were reintubated within 7 days after surgery. Identified score variables were surgical extent and approach, American Society of Anesthesiologists physical status, heart failure, renal disease, and diffusing capacity of the lung for carbon monoxide. The score achieved excellent discrimination in the development cohort (ROC AUC, 0.90; 95% CI, 0.87-0.94) and good discrimination in the validation cohort (ROC AUC, 0.74, 95% CI; 0.66-0.82), thus outperforming the SPORC in both cohorts (P < .001 and P = .018, respectively; validation cohort net reclassification improvement, 0.39; 95% CI, 0.18-0.60; P = .001). The score cutoff of ≥5 yielded a sensitivity of 88% (95% CI, 72-95) and a specificity of 81% (95% CI,79-83) in the development cohort. CONCLUSIONS: A simple score (PROREAL) specific to lung cancer predicts postoperative reintubation more accurately than the nonspecific SPORC score. Operative candidates at risk may be identified for preventive intervention or alternative oncologic therapy.

Association between intraoperative tidal volume and postoperative respiratory complications is dependent on respiratory elastance: a retrospective, multicentre cohort study.

BACKGROUND: The impact of high vs low intraoperative tidal volumes on postoperative respiratory complications remains unclear. We hypothesised that the effect of intraoperative tidal volume on postoperative respiratory complications is dependent on respiratory system elastance. METHODS: We retrospectively recorded tidal volume (Vt; ml kg-1 ideal body weight [IBW]) in patients undergoing elective, non-cardiothoracic surgery from hospital registry data. The primary outcome was respiratory failure (requiring reintubation within 7 days of surgery, desaturation after extubation, or both). The primary exposure was defined as the interaction between Vt and standardised respiratory system elastance (driving pressure divided by Vt; cm H2O/[ml kg-1]). Multivariable logistic regression models, with and without interaction terms (which categorised Vt as low [Vt ≤8 ml kg-1] or high [Vt >8 ml kg-1]), were adjusted for potential confounders. Additional analyses included path mediation analysis and fractional polynomial modelling. RESULTS: Overall, 10 821/197 474 (5.5%) patients sustained postoperative respiratory complications. Higher Vt was associated with greater risk of postoperative respiratory complications (adjusted odds ratio=1.42 per ml kg-1; 95% confidence interval [CI], 1.35-1.50]; P<0.001). This association was modified by respiratory system elastance (P<0.001); in patients with low compliance (<42.4 ml cm H2O-1), higher Vt was associated with greater risk of postoperative respiratory complications (adjusted risk difference=0.3% [95% CI, 0.0-0.5] at 41.2 ml cm H2O-1 compliance, compared with 5.8% [95% CI, 3.8-7.8] at 14 ml cm H2O-1 compliance). This association was absent when compliance exceeded 41.2 ml cm H2O-1. Adverse effects associated with high Vt were entirely mediated by driving pressures (P<0.001). CONCLUSIONS: The association of harm with higher tidal volumes during intraoperative mechanical ventilation is modified by respiratory system elastance. These data suggest that respiratory elastance should inform the design of perioperative trials testing intraoperative ventilatory strategies.

Proteomics of lung tissue reveals differences in inflammation and alveolar-capillary barrier response between atelectasis and aerated regions.

Atelectasis is a frequent clinical condition, yet knowledge is limited and controversial on its biological contribution towards lung injury. We assessed the regional proteomics of atelectatic versus normally-aerated lung tissue to test the hypothesis that immune and alveolar-capillary barrier functions are compromised by purely atelectasis and dysregulated by additional systemic inflammation (lipopolysaccharide, LPS). Without LPS, 130 proteins were differentially abundant in atelectasis versus aerated lung, mostly (n = 126) with less abundance together with negatively enriched processes in immune, endothelial and epithelial function, and Hippo signaling pathway. Instead, LPS-exposed atelectasis produced 174 differentially abundant proteins, mostly (n = 108) increased including acute lung injury marker RAGE and chemokine CCL5. Functional analysis indicated enhanced leukocyte processes and negatively enriched cell-matrix adhesion and cell junction assembly with LPS. Additionally, extracellular matrix organization and TGF-ß signaling were negatively enriched in atelectasis with decreased adhesive glycoprotein THBS1 regardless of LPS. Concordance of a subset of transcriptomics and proteomics revealed overlap of leukocyte-related gene-protein pairs and processes. Together, proteomics of exclusively atelectasis indicates decreased immune response, which converts into an increased response with LPS. Alveolar-capillary barrier function-related proteomics response is down-regulated in atelectasis irrespective of LPS. Specific proteomics signatures suggest biological mechanistic and therapeutic targets for atelectasis-associated lung injury.

Distribution and Magnitude of Regional Volumetric Lung Strain and Its Modification by PEEP in Healthy Anesthetized and Mechanically Ventilated Dogs.

The present study describes the magnitude and spatial distribution of lung strain in healthy anesthetized, mechanically ventilated dogs with and without positive end-expiratory pressure (PEEP). Total lung strain (LSTOTAL) has a dynamic (LSDYNAMIC) and a static (LSSTATIC) component. Due to lung heterogeneity, global lung strain may not accurately represent regional total tissue lung strain (TSTOTAL), which may also be described by a regional dynamic (TSDYNAMIC) and static (TSSTATIC) component. Six healthy anesthetized beagles (12.4 ± 1.4 kg body weight) were placed in dorsal recumbency and ventilated with a tidal volume of 15 ml/kg, respiratory rate of 15 bpm, and zero end-expiratory pressure (ZEEP). Respiratory system mechanics and full thoracic end-expiratory and end-inspiratory CT scan images were obtained at ZEEP. Thereafter, a PEEP of 5 cmH2O was set and respiratory system mechanics measurements and end-expiratory and end-inspiratory images were repeated. Computed lung volumes from CT scans were used to evaluate the global LSTOTAL, LSDYNAMIC, and LSSTATIC during PEEP. During ZEEP, LSSTATIC was assumed zero; therefore, LSTOTAL was the same as LSDYNAMIC. Image segmentation was applied to CT images to obtain maps of regional TSTOTAL, TSDYNAMIC, and TSSTATIC during PEEP, and TSDYNAMIC during ZEEP. Compliance increased (p = 0.013) and driving pressure decreased (p = 0.043) during PEEP. PEEP increased the end-expiratory lung volume (p < 0.001) and significantly reduced global LSDYNAMIC (33.4 ± 6.4% during ZEEP, 24.0 ± 4.6% during PEEP, p = 0.032). LSSTATIC by PEEP was larger than the reduction in LSDYNAMIC; therefore, LSTOTAL at PEEP was larger than LSDYNAMIC at ZEEP (p = 0.005). There was marked topographic heterogeneity of regional strains. PEEP induced a significant reduction in TSDYNAMIC in all lung regions (p < 0.05). Similar to global findings, PEEP-induced TSSTATIC was larger than the reduction in TSDYNAMIC; therefore, PEEP-induced TSTOTAL was larger than TSDYNAMIC at ZEEP. In conclusion, PEEP reduced both global and regional estimates of dynamic strain, but induced a large static strain. Given that lung injury has been mostly associated with tidal deformation, limiting dynamic strain may be an important clinical target in healthy and diseased lungs, but this requires further study.

Geo-economic variations in epidemiology, ventilation management and outcome of patients receiving intraoperative ventilation during general anesthesia- posthoc analysis of an observational study in 29 countries.

BACKGROUND: The aim of this analysis is to determine geo-economic variations in epidemiology, ventilator settings and outcome in patients receiving general anesthesia for surgery. METHODS: Posthoc analysis of a worldwide study in 29 countries. Lower and upper middle-income countries (LMIC and UMIC), and high-income countries (HIC) were compared. The coprimary endpoint was the risk for and incidence of postoperative pulmonary complications (PPC); secondary endpoints were intraoperative ventilator settings, intraoperative complications, hospital stay and mortality. RESULTS: Of 9864 patients, 4% originated from LMIC, 11% from UMIC and 85% from HIC. The ARISCAT score was 17.5 [15.0-26.0] in LMIC, 16.0 [3.0-27.0] in UMIC and 15.0 [3.0-26.0] in HIC (P = .003). The incidence of PPC was 9.0% in LMIC, 3.2% in UMIC and 2.5% in HIC (P < .001). Median tidal volume in ml kg- 1 predicted bodyweight (PBW) was 8.6 [7.7-9.7] in LMIC, 8.4 [7.6-9.5] in UMIC and 8.1 [7.2-9.1] in HIC (P < .001). Median positive end-expiratory pressure in cmH2O was 3.3 [2.0-5.0]) in LMIC, 4.0 [3.0-5.0] in UMIC and 5.0 [3.0-5.0] in HIC (P < .001). Median driving pressure in cmH2O was 14.0 [11.5-18.0] in LMIC, 13.5 [11.0-16.0] in UMIC and 12.0 [10.0-15.0] in HIC (P < .001). Median fraction of inspired oxygen in % was 75 [50-80] in LMIC, 50 [50-63] in UMIC and 53 [45-70] in HIC (P < .001). Intraoperative complications occurred in 25.9% in LMIC, in 18.7% in UMIC and in 37.1% in HIC (P < .001). Hospital mortality was 0.0% in LMIC, 1.3% in UMIC and 0.6% in HIC (P = .009). CONCLUSION: The risk for and incidence of PPC is higher in LMIC than in UMIC and HIC. Ventilation management could be improved in LMIC and UMIC. TRIAL REGISTRATION: Clinicaltrials.gov , identifier: NCT01601223.

Perioperative Pulmonary Atelectasis: Part II. Clinical Implications.

The development of pulmonary atelectasis is common in the surgical patient. Pulmonary atelectasis can cause various degrees of gas exchange and respiratory mechanics impairment during and after surgery. In its most serious presentations, lung collapse could contribute to postoperative respiratory insufficiency, pneumonia, and worse overall clinical outcomes. A specific risk assessment is critical to allow clinicians to optimally choose the anesthetic technique, prepare appropriate monitoring, adapt the perioperative plan, and ensure the patient's safety. Bedside diagnosis and management have benefited from recent imaging advancements such as lung ultrasound and electrical impedance tomography, and monitoring such as esophageal manometry. Therapeutic management includes a broad range of interventions aimed at promoting lung recruitment. During general anesthesia, these strategies have consistently demonstrated their effectiveness in improving intraoperative oxygenation and respiratory compliance. Yet these same intraoperative strategies may fail to affect additional postoperative pulmonary outcomes. Specific attention to the postoperative period may be key for such outcome impact of lung expansion. Interventions such as noninvasive positive pressure ventilatory support may be beneficial in specific patients at high risk for pulmonary atelectasis (e.g., obese) or those with clinical presentations consistent with lung collapse (e.g., postoperative hypoxemia after abdominal and cardiothoracic surgeries). Preoperative interventions may open new opportunities to minimize perioperative lung collapse and prevent pulmonary complications. Knowledge of pathophysiologic mechanisms of atelectasis and their consequences in the healthy and diseased lung should provide the basis for current practice and help to stratify and match the intensity of selected interventions to clinical conditions.

Perioperative Pulmonary Atelectasis: Part I. Biology and Mechanisms.

Pulmonary atelectasis is common in the perioperative period. Physiologically, it is produced when collapsing forces derived from positive pleural pressure and surface tension overcome expanding forces from alveolar pressure and parenchymal tethering. Atelectasis impairs blood oxygenation and reduces lung compliance. It is increasingly recognized that it can also induce local tissue biologic responses, such as inflammation, local immune dysfunction, and damage of the alveolar-capillary barrier, with potential loss of lung fluid clearance, increased lung protein permeability, and susceptibility to infection, factors that can initiate or exaggerate lung injury. Mechanical ventilation of a heterogeneously aerated lung (e.g., in the presence of atelectatic lung tissue) involves biomechanical processes that may precipitate further lung damage: concentration of mechanical forces, propagation of gas-liquid interfaces, and remote overdistension. Knowledge of such pathophysiologic mechanisms of atelectasis and their consequences in the healthy and diseased lung should guide optimal clinical management.