Electrical impedance tomography: Usefulness for respiratory physiotherapy in critical illnesses.

Respiratory physiotherapy, including the management of invasive mechanical ventilation (MV) and noninvasive mechanical ventilation (NIV), is a key supportive intervention for critically ill patients. MV has potential for inducing ventilator-induced lung injury (VILI) as well as long-term complications related to prolonged bed rest, such as post-intensive care syndrome and intensive care unit acquired weakness. Physical and respiratory therapy, developed by the critical care team, in a timely manner, has been shown to prevent these complications. In this pathway, real-time bedside monitoring of changes in pulmonary aeration and alveolar gas distribution associated with postural positioning, respiratory physiotherapy techniques and changes in MV strategies can be crucial in guiding these procedures, providing safe therapy and prevention of potential harm to the patient. Along this path, electrical impedance tomography (EIT) has emerged as a new key non-invasive bedside strategy free of radiation, to allow visualization of lung recruitment. This review article presents the main and potential applications of EIT in relation to physiotherapy techniques in the ICU setting.

Energy dissipation during expiration and ventilator-induced lung injury: an experimental animal study.

The amount of energy delivered to the respiratory system is recognized as a cause of ventilator-induced lung injury (VILI). How energy dissipation within the lung parenchyma causes damage is still a matter of debate. Expiratory flow control has been proposed as a strategy to reduce the energy dissipated into the respiratory system during expiration and, possibly, VILI. We studied 22 healthy pigs (29 ± 2 kg), which were randomized into a control (n = 11) and a valve group (n = 11), where the expiratory flow was controlled through a variable resistor. Both groups were ventilated with the same tidal volume, positive end-expiratory pressure (PEEP), and inspiratory flow. Electric impedance tomography was continuously acquired. At completion, lung weight, wet-to-dry ratios, and histology were evaluated. The total mechanical power was similar in the control and valve groups (8.54 ± 0.83 J·min-1 and 8.42 ± 0.54 J·min-1, respectively, P = 0.552). The total energy dissipated within the whole system (circuit + respiratory system) was remarkably different (4.34 ± 0.66 vs. 2.62 ± 0.31 J/min, P < 0.001). However, most of this energy was dissipated across the endotracheal tube (2.87 ± 0.3 vs. 1.88 ± 0.2 J/min, P < 0.001). The amount dissipated into the respiratory system averaged 1.45 ± 0.5 in controls versus 0.73 ± 0.16 J·min-1 in the valve group, P < 0.001. Although respiratory mechanics, gas exchange, hemodynamics, wet-to-dry ratios, and histology were similar in the two groups, the decrease of end-expiratory lung impedance was significantly greater in the control group (P = 0.02). We conclude that with our experimental conditions, the reduction of energy dissipated in the respiratory system did not lead to appreciable differences in VILI.NEW & NOTEWORTHY Energy dissipation within the respiratory system is a factor promoting ventilator-induced lung injury (VILI). In this animal study, we modulated the expiratory flow, reducing the energy dissipated in the system. However, this reduction happened mostly across the endotracheal tube, and only partly in the respiratory system. Therefore, in healthy lungs, the advantage in energy dissipation does not reduce VILI, but the advantages might be more relevant in diseased lungs under injurious ventilation.

Physiological and Pathophysiological Consequences of Mechanical Ventilation.

Mechanical ventilation is a life-support system used to ensure blood gas exchange and to assist the respiratory muscles in ventilating the lung during the acute phase of lung disease or following surgery. Positive-pressure mechanical ventilation differs considerably from normal physiologic breathing. This may lead to several negative physiological consequences, both on the lungs and on peripheral organs. First, hemodynamic changes can affect cardiovascular performance, cerebral perfusion pressure (CPP), and drainage of renal veins. Second, the negative effect of mechanical ventilation (compression stress) on the alveolar-capillary membrane and extracellular matrix may cause local and systemic inflammation, promoting lung and peripheral-organ injury. Third, intra-abdominal hypertension may further impair lung and peripheral-organ function during controlled and assisted ventilation. Mechanical ventilation should be optimized and personalized in each patient according to individual clinical needs. Multiple parameters must be adjusted appropriately to minimize ventilator-induced lung injury (VILI), including: inspiratory stress (the respiratory system inspiratory plateau pressure); dynamic strain (the ratio between tidal volume and the end-expiratory lung volume, or inspiratory capacity); static strain (the end-expiratory lung volume determined by positive end-expiratory pressure [PEEP]); driving pressure (the difference between the respiratory system inspiratory plateau pressure and PEEP); and mechanical power (the amount of mechanical energy imparted as a function of respiratory rate). More recently, patient self-inflicted lung injury (P-SILI) has been proposed as a potential mechanism promoting VILI. In the present chapter, we will discuss the physiological and pathophysiological consequences of mechanical ventilation and how to personalize mechanical ventilation parameters.

An Extracorporeal Membrane Oxygenation First Strategy in COVID-19 Acute Respiratory Distress Syndrome.

COVID-19 can be associated with acute respiratory distress syndrome, which increases the likelihood of morbidity and mortality. Ventilator-induced lung injury is a known complication of mechanical ventilation (MV) and can further compound lung injury and recovery. Escalation to extracorporeal membrane oxygenation can be required in patients who deteriorate on MV. We report our experience with complete avoidance of MV using an ECMO First strategy deployed in an awake nonintubated COVID-19 patient with severe pneumonia.

TLR4/TRAF6/NOX2 signaling pathway is involved in ventilation-induced lung injury via endoplasmic reticulum stress in murine model.

In ventilation-induced lung injury (VILI), prolonged nonpathogen-mediated inflammation is triggered as a result of alveolar hyperinflation. In our previous study, we suggested that endoplasmic reticulum (ER) stress-mediated inflammation was involved in VILI, but how ER stress is triggered remains unknown. Toll-like receptor 4 (TLR4) activation plays an important role in mechanical ventilation (MV)-induced lung inflammation, however, it is unknown whether ER stress is activated by TLR4 to participate in VILI. In this study, C57BL/6 mice were exposed to MV with high tidal volumes (HTV 20 ml/kg). Mice were pretreated with TAK-242 the TLR4 inhibitor, C25-140, the TRAF6 inhibitor, or GSK2795039, the NOX2 inhibitor. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected to measure lung injury, inflammatory responses and mRNA/protein expression associated with ER stress and the TLR4/TRAF6/NOX2 signaling pathway. Our results indicate that MV with HTV caused the TLR4/TRAF6/NOX2 signaling pathway activation and production of large amounts of ROS, which led to ER stress and NF-κB mediated inflammation in VILI. Furthermore, TLR4/TRAF6/NOX2 signaling pathway inhibition attenuated ER stress response and alleviate lung injury in mice.

Review of the Mechanisms of Ventilator Induced Lung Injury and the Principles of Intraoperative Lung Protective Ventilation.

Intraoperative ventilator induced lung injury is associated with development of postoperative pulmonary complications. Despite advances in modes and methods of mechanical ventilation, postoperative pulmonary complications remain as one of the leading causes of adverse outcomes following surgery and anesthesia. In an attempt to reduce the incidence of postoperative pulmonary complications, the use of an intraoperative ventilatory technique to minimize lung injury has been introduced. Lung protective ventilation typically entails the use of a physiologic tidal volume, positive end expiratory pressure, extended inspiratory time, and an alveolar recruitment maneuver. The goal of intraoperative lung protective ventilation is to prevent or at least minimize development of ventilator induced lung injury by maintaining a homogeneous lung and alveolar stability during and after a surgical procedure. To appreciate the value of the application of an intraoperative lung protective ventilation strategy, the pathophysiology and developmental processes of ventilator induced lung injury must first be understood. The primary purpose of this paper is to provide a basic understanding of the relationship between conventional intraoperative mechanical ventilation, pulmonary derangement and lung injury as well as a rationale for the use of individualized lung protective ventilation to optimize surgical patient pulmonary outcomes.

Impact of positive biphasic pressure during low and high inspiratory efforts in Pseudomonas aeruginosa-induced pneumonia.

BACKGROUND: During pneumonia, normal alveolar areas coexist adjacently with consolidated areas, and high inspiratory efforts may predispose to lung damage. To date, no study has evaluated different degrees of effort during Biphasic positive airway pressure (BIVENT) on lung and diaphragm damage in experimental pneumonia, though largely used in clinical setting. We aimed to evaluate lung damage, genes associated with ventilator-induced lung injury (VILI) and diaphragmatic injury, and blood bacteria in pressure-support ventilation (PSV), BIVENT with low and high inspiratory efforts in experimental pneumonia. MATERIAL AND METHODS: Twenty-eight male Wistar rats (mean ± SD weight, 333±78g) were submitted Pseudomonas aeruginosa-induced pneumonia. After 24-h, animals were ventilated for 1h in: 1) PSV; 2) BIVENT with low (BIVENTLow-Effort); and 3) BIVENT with high inspiratory effort (BIVENTHigh-Effort). BIVENT was set at Phigh to achieve VT = 6 ml/kg and Plow at 5 cmH2O (n = 7/group). High- and low-effort conditions were obtained through anaesthetic infusion modulation based on neuromuscular drive (P0.1). Lung mechanics, histological damage score, blood bacteria, and expression of genes related to VILI in lung tissue, and inflammation in diaphragm tissue. RESULTS: Transpulmonary peak pressure and histological damage score were higher in BIVENTHigh-Effort compared to BIVENTLow-Effort and PSV [16.1 ± 1.9cmH2O vs 12.8 ± 1.5cmH2O and 12.5 ± 1.6cmH2O, p = 0.015, and p = 0.010; median (interquartile range) 11 (9-13) vs 7 (6-9) and 7 (6-9), p = 0.021, and p = 0.029, respectively]. BIVENTHigh-Effort increased interleukin-6 expression compared to BIVENTLow-Effort (p = 0.035) as well as expressions of cytokine-induced neutrophil chemoattractant-1, amphiregulin, and type III procollagen compared to PSV (p = 0.001, p = 0.001, p = 0.004, respectively). Tumour necrosis factor-α expression in diaphragm tissue and blood bacteria were higher in BIVENTHigh-Effort than BIVENTLow-Effort (p = 0.002, p = 0.009, respectively). CONCLUSION: BIVENT requires careful control of inspiratory effort to avoid lung and diaphragm damage, as well as blood bacteria. P0.1 might be considered a helpful parameter to optimize inspiratory effort.

Imaging atelectrauma in Ventilator-Induced Lung Injury using 4D X-ray microscopy.

Mechanical ventilation can damage the lungs, a condition called Ventilator-Induced Lung Injury (VILI). However, the mechanisms leading to VILI at the microscopic scale remain poorly understood. Here we investigated the within-tidal dynamics of cyclic recruitment/derecruitment (R/D) using synchrotron radiation phase-contrast imaging (PCI), and the relation between R/D and cell infiltration, in a model of Acute Respiratory Distress Syndrome in 6 anaesthetized and mechanically ventilated New-Zealand White rabbits. Dynamic PCI was performed at 22.6 µm voxel size, under protective mechanical ventilation [tidal volume: 6 ml/kg; positive end-expiratory pressure (PEEP): 5 cmH2O]. Videos and quantitative maps of within-tidal R/D showed that injury propagated outwards from non-aerated regions towards adjacent regions where cyclic R/D was present. R/D of peripheral airspaces was both pressure and time-dependent, occurring throughout the respiratory cycle with significant scatter of opening/closing pressures. There was a significant association between R/D and regional lung cellular infiltration (p = 0.04) suggesting that tidal R/D of the lung parenchyma may contribute to regional lung inflammation or capillary-alveolar barrier dysfunction and to the progression of lung injury. PEEP may not fully mitigate this phenomenon even at high levels. Ventilation strategies utilizing the time-dependence of R/D may be helpful in reducing R/D and associated injury.

Mechanical Ventilation with Moderate Tidal Volume Exacerbates Extrapulmonary Sepsis-Induced Lung Injury via IL33-WISP1 Signaling Pathway.

ABSTRACT: IL-33 and WNT1-inducible secreted protein (WISP1) play central roles in acute lung injury (ALI) induced by mechanical ventilation with moderate tidal volume (MTV) in the setting of sepsis. Here, we sought to determine the inter-relationship between IL-33 and WISP1 and the associated signaling pathways in this process.We used a two-hit model of cecal ligation puncture (CLP) followed by MTV ventilation (4 h 10 mL/kg) in wild-type, IL-33-/- or ST2-/- mice or wild-type mice treated with intratracheal antibodies to WISP1. Macrophages (Raw 264.7 and alveolar macrophages from wild-type or ST2-/- mice) were used to identify specific signaling components.CLP + MTV resulted in ALI that was partially sensitive to genetic ablation of IL-33 or ST2 or antibody neutralization of WISP1. Genetic ablation of IL-33 or ST2 significantly prevented ALI after CLP + MTV and reduced levels of WISP1 in the circulation and bronchoalveolar lung fluid. rIL-33 increased WISP1 in alveolar macrophages in an ST2, PI3K/AKT, and ERK dependent manner. This WISP1 upregulation and WNT ß-catenin activation were sensitive to inhibition of the ß-catenin/TCF/CBP/P300 nuclear pathway.We show that IL-33 drives WISP1 upregulation and ALI during MTV in CLP sepsis. The identification of this relationship and the associated signaling pathways reveals a number of possible therapeutic targets to prevent ALI in ventilated sepsis patients.

Mechanisms of hyperventilation-induced lung injuries in neonatal rats.

BACKGROUND: The aim of this study was to investigate the mechanism of early inflammatory injury in neonatal ventilator-induced lung injuries (VILI). METHODS: Newborn rats were randomly assigned to groups and administrated mechanical ventilation with different tidal volumes. Morphological changes in lung tissues were observed, and the levels of interleukin-6 (IL-6), cysteinyl leukotriene mRNA (CysLT1 mRNA), and nuclear factor-κB mRNA (NF-κBp65 mRNA) in lung tissues were analyzed. RESULTS: The ventilation groups exhibited different degrees of inflammatory cell infiltration, which was aggravated as the tidal volume and ventilation time increased. The IL-6 levels of the hyperventilation 5H, conventional ventilation 5H, hyperventilation 3H, control, and normal lung-tissue group were 785.33±39.06, 701.6±33.65, 686.65±46.85, 637.63±40.55, and 635.02±65.78 pg/g, respectively. Hyperventilation increased the levels of IL-6 and NF-κBp65 mRNA as the ventilation time increased, and IL-6 was positively correlated with NF-κBp65 mRNA levels (r=0.72, P<0.01). Longer hyperventilation periods upregulate the level of CysLT1 mRNA. CysLT1 mRNA/GAPDH of the hyperventilation 5H group was 2.14±1.45 (P<0.01). CONCLUSIONS: Mechanical ventilation with a large tidal volume can cause VILI, characterized at an early stage by inflammatory responses and particularly by the increased secretion and invasion of inflammatory cytokines and inflammatory cells. The activation of the NF-κB-IL-6 signaling pathway was an important mechanism for the initiation of VILI. Additionally, CysLT1 was involved in the inflammatory VILI damage, and its upregulation occurred later than that of IL-6.

Body Habitus and Dynamic Surgical Conditions Independently Impair Pulmonary Mechanics during Robotic-assisted Laparoscopic Surgery.

BACKGROUND: Body habitus, pneumoperitoneum, and Trendelenburg positioning may each independently impair lung mechanics during robotic laparoscopic surgery. This study hypothesized that increasing body mass index is associated with more mechanical strain and alveolar collapse, and these impairments are exacerbated by pneumoperitoneum and Trendelenburg positioning. METHODS: This cross-sectional study measured respiratory flow, airway pressures, and esophageal pressures in 91 subjects with body mass index ranging from 18.3 to 60.6 kg/m2. Pulmonary mechanics were quantified at four stages: (1) supine and level after intubation, (2) with pneumoperitoneum, (3) in Trendelenburg docked with the surgical robot, and (4) level without pneumoperitoneum. Subjects were stratified into five body mass index categories (less than 25, 25 to 29.9, 30 to 34.9, 35 to 39.9, and 40 or higher), and respiratory mechanics were compared over surgical stages using generalized estimating equations. The optimal positive end-expiratory pressure settings needed to achieve positive end-expiratory transpulmonary pressures were calculated. RESULTS: At baseline, transpulmonary driving pressures increased in each body mass index category (1.9 ± 0.5 cm H2O; mean difference ± SD; P < 0.006), and subjects with a body mass index of 40 or higher had decreased mean end-expiratory transpulmonary pressures compared with those with body mass index of less than 25 (-7.5 ± 6.3 vs. -1.3 ± 3.4 cm H2O; P < 0.001). Pneumoperitoneum and Trendelenburg each further elevated transpulmonary driving pressures (2.8 ± 0.7 and 4.7 ± 1.0 cm H2O, respectively; P < 0.001) and depressed end-expiratory transpulmonary pressures (-3.4 ± 1.3 and -4.5 ± 1.5 cm H2O, respectively; P < 0.001) compared with baseline. Optimal positive end-expiratory pressure was greater than set positive end-expiratory pressure in 79% of subjects at baseline, 88% with pneumoperitoneum, 95% in Trendelenburg, and ranged from 0 to 36.6 cm H2O depending on body mass index and surgical stage. CONCLUSIONS: Increasing body mass index induces significant alterations in lung mechanics during robotic laparoscopic surgery, but there is a wide range in the degree of impairment. Positive end-expiratory pressure settings may need individualization based on body mass index and surgical conditions.

NEK7 mediated assembly and activation of NLRP3 inflammasome downstream of potassium efflux in ventilator-induced lung injury.

Disordered immune regulation and persistent inflammatory damage are the key mechanisms of ventilator-induced lung injury (VILI). NLR family pyrin domain containing 3 (NLRP3) inflammasome activation causes VILI by mediating the formation of inflammatory mediators and infiltration of inflammatory cells, increasing pulmonary capillary membrane permeability, which leads to pulmonary edema and lung tissue damage. What mediates activation of NLRP3 inflammasome in VILI? In this study, we constructed an in vitro cyclic stretch (CS)-stimulated mouse lung epithelial (MLE-12) cell model that was transfected with NIMA-related kinase 7 (NEK7) small interfering RNA (siRNA) or scramble siRNA (sc siRNA) and pretreated with or without glibenclamide (glb). We also established a VILI mouse model, which was pretreated with glibenclamide or oridonin (Ori). Our goal was to investigate the regulatory effects of NEK7 on NLRP3 inflammasome activation and the anti-inflammatory effects of glibenclamide and oridonin on VILI. Mechanical stretch exaggerated the interaction between NEK7 and NLRP3, leading to assembly and activation of NLRP3 inflammasome downstream of potassium efflux. NEK7 depletion and treatment with glibenclamide or oridonin exerted anti-inflammatory effects that alleviated VILI by blocking the interaction between NEK7 and NLRP3, inhibiting NLRP3 inflammasome activation. NEK7 is a vital mediator of NLRP3 inflammasome activation, and glibenclamide or oridonin may be candidates for the development of new therapeutics against VILI driven by the interaction between NEK7 and NLRP3.

Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model.

Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in inducing both apoptotic and inflammatory processes. Low-molecular-weight heparin (LMWH) has been shown to have anti-inflammatory activities. However, the effects of HIF-1α and LMWH on sepsis-related acute lung injury (ALI) have not been fully delineated. We hypothesized that LMWH would reduce lung injury, production of free radicals and epithelial apoptosis through the HIF-1α pathway. Male C57BL/6 mice were exposed to 6-mL/kg or 30-mL/kg MV for 5 h. Enoxaparin, 4 mg/kg, was administered subcutaneously 30 min before MV. We observed that MV with endotoxemia induced microvascular permeability; interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2 and vascular endothelial growth factor protein production; neutrophil infiltration; oxidative loads; HIF-1α mRNA activation; HIF-1α expression; bronchial epithelial apoptosis; and decreased respiratory function in mice (p < 0.05). Endotoxin-induced augmentation of VILI and epithelial apoptosis were reduced in the HIF-1α-deficient mice and in the wild-type mice following enoxaparin administration (p < 0.05). Our data suggest that enoxaparin reduces endotoxin-augmented MV-induced ALI, partially by inhibiting the HIF-1α pathway.

Positive end-expiratory pressure and recruitment maneuvers during one-lung ventilation: A systematic review and meta-analysis.

BACKGROUND: It is unclear how positive end-expiratory pressure (PEEP) and recruitment maneuvers impact patients during one-lung ventilation (OLV). We conducted a systematic review and meta-analysis of the effect of lung recruitment and PEEP on ventilation and oxygenation during OLV. METHODS: A systematic review and random-effects meta-analysis were performed. Mean difference with standard deviation was calculated. Included studies were evaluated for quality and risk of bias using the Cochrane Risk of Bias tool and the modified Newcastle-Ottawa Score where appropriate. RESULTS: In total, 926 articles were identified, of which 16 were included in meta-analysis. Recruitment maneuvers increased arterial oxygen tension (PaO2) by 82 mm Hg [20, 144 mm Hg] and reduced dead-space by 5.9% [3.8, 8.0%]. PEEP increased PaO2 by 30.3 mm Hg [11.9, 48.6 mm Hg]. Subgroup analysis showed a significant increase in PaO2 (P = .0003; +35.4 mm Hg [16.2, 54.5 mm Hg]) with PEEP compared with no PEEP but no such difference in comparisons with PEEP-treated controls. No significant difference in PaO2 was observed between "high" and "low" PEEP-treated subgroups (P = .29). No significant improvement in PaO2 was observed for subgroups coadministered PEEP, lung recruitment, and low tidal volumes. PEEP was associated with a modest but statistically significant increase in compliance (P = .03; 4.33 mL/cmH2O [0.33, 8.32]). High risk of bias was identified in the majority of studies. Considerable heterogeneity was observed. CONCLUSIONS: Recruitment maneuvers and PEEP have physiologic advantages during OLV. The optimal use of PEEP is yet to be determined. The evidence is limited by heavy use of surrogate outcomes. Future studies with clinical outcomes are necessary to determine the impact of recruitment maneuvers and PEEP during OLV.

Is Umbilical Cord Blood Therapy an Effective Treatment for Early Lung Injury in Growth Restriction?

Fetal growth restriction (FGR) and prematurity are often co-morbidities, and both are risk factors for lung disease. Despite advances in early delivery combined with supportive ventilation, rates of ventilation-induced lung injury (VILI) remain high. There are currently no protective treatments or interventions available that target lung morbidities associated with FGR preterm infants. Stem cell therapy, such as umbilical cord blood (UCB) cell administration, demonstrates an ability to attenuate inflammation and injury associated with VILI in preterm appropriately grown animals. However, no studies have looked at the effects of stem cell therapy in growth restricted newborns. We aimed to determine if UCB treatment could attenuate acute inflammation in the first 24 h of ventilation, comparing effects in lambs born preterm following FGR with those born preterm but appropriately grown (AG). Placental insufficiency (FGR) was induced by single umbilical artery ligation in twin-bearing ewes at 88 days gestation, with twins used as control (appropriately grown, AG). Lambs were delivered preterm at ~126 days gestation (term is 150 days) and randomized to either immediate euthanasia (unventilated controls, AGUVC and FGRUVC) or commenced on 24 h of gentle supportive ventilation (AGV and FGRV) with additional cohorts receiving UCB treatment at 1 h (AGCELLS, FGRCELLS). Lungs were collected at post-mortem for histological and biochemical examination. Ventilation caused lung injury in AG lambs, as indicated by decreased septal crests and elastin density, as well as increased inflammation. Lung injury in AG lambs was attenuated with UCB therapy. Ventilated FGR lambs also sustained lung injury, albeit with different indices compared to AG lambs; in FGR, ventilation reduced septal crest density, reduced alpha smooth muscle actin density and reduced cell proliferation. UCB treatment in ventilated FGR lambs further decreased septal crest density and increased collagen deposition, however, it increased angiogenesis as evidenced by increased vascular endothelial growth factor (VEGF) expression and vessel density. This is the first time that a cell therapy has been investigated in the lungs of growth restricted animals. We show that the uterine environment can alter the response to both secondary stress (ventilation) and therapy (UCB). This study highlights the need for further research on the potential impact of novel therapies on a growth restricted offspring.

Protective ventilation from ICU to operating room: state of art and new horizons.

The prevention of ventilator-associated lung injury (VALI) and postoperative pulmonary complications (PPC) is of paramount importance for improving outcomes both in the operating room and in the intensive care unit (ICU). Protective respiratory support includes a wide spectrum of interventions to decrease pulmonary stress-strain injuries. The motto 'low tidal volume for all' should become routine, both during major surgery and in the ICU, while application of a high positive end-expiratory pressure (PEEP) strategy and of alveolar recruitment maneuvers requires a personalized approach and requires further investigation. Patient self-inflicted lung injury is an important type of VALI, which should be diagnosed and mitigated at the early stage, during restoration of spontaneous breathing. This narrative review highlights the strategies used for protective positive pressure ventilation. The emerging concepts of damaging energy and power, as well as pathways to personalization of the respiratory settings, are discussed in detail. In the future, individualized approaches to protective ventilation may involve multiple respiratory settings extending beyond low tidal volume and PEEP, implemented in parallel with quantifying the risk of VALI and PPC.

Association of Intraoperative Ventilator Management With Postoperative Oxygenation, Pulmonary Complications, and Mortality.

BACKGROUND: "Lung-protective ventilation" describes a ventilation strategy involving low tidal volumes (VTs) and/or low driving pressure/plateau pressure and has been associated with improved outcomes after mechanical ventilation. We evaluated the association between intraoperative ventilation parameters (including positive end-expiratory pressure [PEEP], driving pressure, and VT) and 3 postoperative outcomes: (1) PaO2/fractional inspired oxygen tension (FIO2), (2) postoperative pulmonary complications, and (3) 30-day mortality. METHODS: We retrospectively analyzed adult patients who underwent major noncardiac surgery and remained intubated postoperatively from 2006 to 2015 at a single US center. Using multivariable regressions, we studied associations between intraoperative ventilator settings and lowest postoperative PaO2/FIO2 while intubated, pulmonary complications identified from discharge diagnoses, and in-hospital 30-day mortality. RESULTS: Among a cohort of 2096 cases, the median PEEP was 5 cm H2O (interquartile range = 4-6), median delivered VT was 520 mL (interquartile range = 460-580), and median driving pressure was 15 cm H2O (13-19). After multivariable adjustment, intraoperative median PEEP (linear regression estimate [B] = -6.04; 95% CI, -8.22 to -3.87; P < .001), median FIO2 (B = -0.30; 95% CI, -0.50 to -0.10; P = .003), and hours with driving pressure >16 cm H2O (B = -5.40; 95% CI, -7.2 to -4.2; P < .001) were associated with decreased postoperative PaO2/FIO2. Higher postoperative PaO2/FIO2 ratios were associated with a decreased risk of pulmonary complications (adjusted odds ratio for each 100 mm Hg = 0.495; 95% CI, 0.331-0.740; P = .001, model C-statistic of 0.852) and mortality (adjusted odds ratio = 0.495; 95% CI, 0.366-0.606; P < .001, model C-statistic of 0.820). Intraoperative time with VT >500 mL was also associated with an increased likelihood of developing a postoperative pulmonary complication (adjusted odds ratio = 1.06/hour; 95% CI, 1.00-1.20; P = .042). CONCLUSIONS: In patients requiring postoperative intubation after noncardiac surgery, increased median FIO2, increased median PEEP, and increased time duration with elevated driving pressure predict lower postoperative PaO2/FIO2. Intraoperative duration of VT >500 mL was independently associated with increased postoperative pulmonary complications. Lower postoperative PaO2/FIO2 ratios were independently associated with pulmonary complications and mortality. Our findings suggest that postoperative PaO2/FIO2 may be a potential target for future prospective trials investigating the impact of specific ventilation strategies for reducing ventilator-induced pulmonary injury.