Exploring alveolar recruitability using positive end-expiratory pressure in mice overexpressing TGF-ß1: a structure-function analysis.

Pre-injured lungs are prone to injury progression in response to mechanical ventilation. Heterogeneous ventilation due to (micro)atelectases imparts injurious strains on open alveoli (known as volutrauma). Hence, recruitment of (micro)atelectases by positive end-expiratory pressure (PEEP) is necessary to interrupt this vicious circle of injury but needs to be balanced against acinar overdistension. In this study, the lung-protective potential of alveolar recruitment was investigated and balanced against overdistension in pre-injured lungs. Mice, treated with empty vector (AdCl) or adenoviral active TGF-ß1 (AdTGF-ß1) were subjected to lung mechanical measurements during descending PEEP ventilation from 12 to 0 cmH2O. At each PEEP level, recruitability tests consisting of two recruitment maneuvers followed by repetitive forced oscillation perturbations to determine tissue elastance (H) and damping (G) were performed. Finally, lungs were fixed by vascular perfusion at end-expiratory airway opening pressures (Pao) of 20, 10, 5 and 2 cmH2O after a recruitment maneuver, and processed for design-based stereology to quantify derecruitment and distension. H and G were significantly elevated in AdTGF-ß1 compared to AdCl across PEEP levels. H was minimized at PEEP = 5-8 cmH2O and increased at lower and higher PEEP in both groups. These findings correlated with increasing septal wall folding (= derecruitment) and reduced density of alveolar number and surface area (= distension), respectively. In AdTGF-ß1 exposed mice, 27% of alveoli remained derecruited at Pao = 20 cmH2O. A further decrease in Pao down to 2 cmH2O showed derecruitment of an additional 1.1 million alveoli (48%), which was linked with an increase in alveolar size heterogeneity at Pao = 2-5 cmH2O. In AdCl, decreased Pao resulted in septal folding with virtually no alveolar collapse. In essence, in healthy mice alveoli do not derecruit at low PEEP ventilation. The potential of alveolar recruitability in AdTGF-ß1 exposed mice is high. H is optimized at PEEP 5-8 cmH2O. Lower PEEP folds and larger PEEP stretches septa which results in higher H and is more pronounced in AdTGF-ß1 than in AdCl. The increased alveolar size heterogeneity at Pao = 5 cmH2O argues for the use of PEEP = 8 cmH2O for lung protective mechanical ventilation in this animal model.

Contribution of electrical impedance tomography to personalize positive end-expiratory pressure under ECCO2R.

Extracorporeal Carbon Dioxide Removal (ECCO2R) is used in acute respiratory distress syndrome (ARDS) patients to facilitate lung-protective ventilatory strategies. Electrical Impedance Tomography (EIT) allows individual, non-invasive, real-time, bedside, radiation-free imaging of the lungs, providing global and regional dynamic lung analyses. To provide new insights for future ECCO2R research in ARDS, we propose a potential application of EIT to personalize End-Expiratory Pressure (PEEP) following each reduction in tidal volume (VT), as demonstrated in an illustrative case. A 72-year-old male with COVID-19 was admitted to the ICU for moderate ARDS. Monitoring with EIT was started to determine the optimal PEEP value (PEEPEIT), defined as the intersection of the collapse and overdistention curves, after each reduction in VT during ECCO2R. The identified PEEPEIT values were notably low (< 10 cmH2O). The decrease in VT associated with PEEPEIT levels resulted in improved lung compliance, reduced driving pressure and a more uniform ventilation pattern. Despite current Randomized Controlled Trials showing that ultra-protective ventilation with ECCO2R does not improve survival, the applicability of universal ultra-protective ventilation settings for all patients remains a subject of debate. Inappropriately set PEEP levels can lead to alveolar collapse or overdistension, potentially negating the benefits of VT reduction. EIT facilitates real-time monitoring of derecruitment associated with VT reduction, guiding physicians in determining the optimal PEEP value after each decrease in tidal volume. This original description of using EIT under ECCO2R to adjust PEEP at a level compromising between recruitability and overdistention could be a crucial element for future research on ECCO2R.

Obesity and anesthesia.

PURPOSE OF REVIEW: Surgical procedures on obese patients are dramatically increasing worldwide over the past few years. In this review, we discuss the physiopathology of predominantly respiratory system in obese patients, the importance of preoperative evaluation, preoxygenation and intraoperative positive end expiratory pressure (PEEP) titration to prevent pulmonary complications and the optimization of airway management and oxygenation to reduce or prevent postoperative respiratory complications. RECENT FINDINGS: Many patients are coming to preoperative clinic with medication history of glucagon-like-peptide 1 agonists ( GLP-1) agonists and it has raised many questions regarding Nil Per Os (NPO)/perioperative fasting guidelines due to delayed gastric emptying caused by these medications. American Society of Anesthesiologists (ASA) has come up with guiding document to help with such situations. Ambulatory surgery centers are doing more obesity cases in a safe manner which were deemed unsafe at one point . Quantitative train of four (TOF) monitoring, better neuromuscular reversal agents and gastric ultrasounds seemed to have made a significant impact in the care of obese patients in the perioperative period. SUMMARY: Obese patients are at higher risk of perioperative complications, mainly associated with those related to the respiratory function. An appropriate preoperative evaluation, intraoperative management, and postoperative support and monitoring is essential to improve outcome and increase the safety of the surgical procedure.

Effect of decreasing PEEP on hyperinflation and collapse in COVID-19: A computed tomography study.

BACKGROUND: High positive end-expiratory pressure (PEEP>10 cmH2O) is commonly used in mechanically ventilated hypoxemic patients with COVID-19. However, some epidemiological and physiological studies indirectly suggest that using a lower PEEP may primarily and beneficially decrease lung hyperinflation in this population. Herein we directly quantified the effect of decreasing PEEP from 15 to 10 cmH2O on lung hyperinflation and collapse in mechanically ventilated patients with COVID-19. METHODS: Twenty mechanically ventilated patients with COVID-19 underwent a lung computed tomography (CT) at PEEP of 15 and 10 cmH2O. The effect of decreasing PEEP on lung hyperinflation and collapse was directly quantified as the change in the over-aerated (density below -900 HU) and non-aerated (density above -100 HU) lung volumes. The net response to decreasing PEEP was computed as the sum of the change in those two compartments and expressed as the change in the "pathologic" lung volume. If the pathologic lung volume decreased (i.e., hyperinflation decreased more than collapse increased) when PEEP was decreased, the net response was considered positive; otherwise, it was considered negative. RESULTS: On average, the ratio of arterial tension to inspiratory fraction of oxygen (PaO2:FiO2) in the overall study population was 137 (119-162) mmHg. In 11 (55%) patients, the net response to decreasing PEEP was positive. Their over-aerated lung volume decreased by 159 (98-186) mL, while the non-aerated lung volume increased by only 58 (31-91) mL. In nine (45%) patients, the net response was negative. Their over-aerated lung volume decreased by 46 (18-72) mL, but their non-aerated lung volume increased by 107 (44-121) mL. CONCLUSION: In 20 patients with COVID-19 the net response to decreasing PEEP, as assessed with lung CT, was variable. In approximately half of them it was positive (and possibly beneficial), with a decrease in hyperinflation larger than the increase in collapse.

Outcomes of Acute Respiratory Failure in Patients With Cancer in the United States.

OBJECTIVE: To determine the epidemiological effect-magnitude and outcomes of patients with cancer vs those without cancer who are hospitalized with acute respiratory failure (ARF). PATIENTS AND METHODS: We reviewed hospitalizations within the National Inpatient Sample (NIS) database between January 1, 2016, and December 31, 2018. Patients were classified based on a diagnosis of solid-organ cancer, hematologic cancer, or no cancer. Noninvasive positive pressure ventilation (NIPPV) failure was defined as patients who initially received NIPPV and had progression to invasive mechanical ventilation. Weighted samples were used to derive population estimates. RESULTS: During the study period, there were an estimated 8,837,209 admissions with ARF in the United States, 8.9% (783,625) of which had solid-organ cancer and 2.0% (176,095) had hematologic cancers. Annually, 319,907 patients with cancer are admitted with ARF, with 27.3% (87,302) requiring invasive mechanical ventilation and 10.0% (31,998) requiring NIPPV. In-hospital mortality was higher in patients with cancer vs those without cancer (24.0% [76,813] vs 12.3% [322,465]; P<.001), and this proprotion persisted when stratified by the highest method of oxygen delivery. Patients with cancer had longer hospital length of stay (7.0 days [3.0 to 12.0 days] vs 5.0 days [3.0 to 10.0 days]; P<.001) and were more likely to have NIPPV failure (14.9% [3,992] vs 12.8% [41,875]). Compared with those with solid-organ cancer, patients with hematologic cancers experienced worse outcomes. The association between underlying cancer diagnosis and outcomes remained consistent when adjusted for age, sex, and comorbidities. CONCLUSION: In the United States, patients with cancer account for over 10% of ARF hospital admissions (959,720 of 8,837,209). They experience an approximately 2-fold higher mortality versus those without cancer. Those with hematologic cancers appear to experience worse outcomes than patients with solid-organ cancers.

Maintaining moderate versus lower PEEP after cardiac surgery: a propensity-scored matched analysis.

BACKGROUND: Setting positive end-expiratory pressure (PEEP) at around 5 cm H2O in the early postoperative period seems a common practice for most patients. It remains unclear if the routine application of higher levels of PEEP confers any meaningful clinical benefit for cardiac surgical patients. The aim of this study was to compare moderate versus conventional lower PEEP on patient-centered outcomes in the intensive care unit (ICU). METHODS: This is a single-center retrospective study involving patients receiving cardiac surgery from June 2022 to May 2023. Propensity-score matching (PSM) was used to balance the baseline differences. Primary outcomes were the duration of mechanical ventilation and ICU length of stay. Secondary outcomes included PaO2/FiO2 ratio at 24 h and the need for prone positioning during ICU stay. RESULTS: A total of 334 patients were included in the study, 102 (31%) of them received moderate PEEP (≥ 7 cm H2O) for the major time in the early postoperative period (12 h). After PSM, 79 pairs of patients were matched with balanced baseline data. The results showed that there was marginal difference in the distribution of mechanical ventilation duration (p = 0.05) and the Moderate PEEP group had a higher extubation rate at the day of T-piece trial (65 [82.3%] vs 52 [65.8%], p = 0.029). Applying moderate PEEP was also associated with better oxygenation. No differences were found regarding ICU length of stay and patients requiring prone positioning between groups. CONCLUSION: In selective cardiac surgical patients, using moderate PEEP compared with conventional lower PEEP in the early postoperative period correlated to better oxygenation, which may have potential for earlier liberation of mechanical ventilation.

[Clinical research progress in non-invasive positive pressure ventilation in 2023].

Non-invasive positive pressure ventilation (NPPV) is a widely used method of providing respiratory support in a variety of clinical settings, including emergency departments, general wards, and intensive care units. The relevant research articles on NPPV published between 1st October 2022 and 30th September 2023 were retrieved from Medline and reviewed. In the management of acute respiratory failure (ARF) associated with COVID-19, studies have highlighted the significant influence of regional economic status on the choice of respiratory support strategies. It has been observed that NPPV is more suitable for patients with mild to moderate acute respiratory distress syndrome (ARDS) than for those with severe ARDS, as the latter group has an increased risk of delayed intubation. In addition, patients with severe dyspnea tended to benefit more from NPPV compared with high flow nasal cannula (HFNC) and conventional oxygen therapy, with a reduced risk of self-induced lung injury. For non-COVID-19-related ARF, research shows no significant differences in mortality and intubation rates between HFNC and NPPV in patients with hypercapnic ARF. The updated HACOR score and ROX score have been validated to have a high predictive value for clinical outcomes in patients receiving NPPV for hypoxemic ARF. With regard to weaning from invasive mechanical ventilation, immediate application of NPPV after extubation showed a lower mortality rate compared to continued invasive weaning. Moreover, NPPV with active humidification significantly decreased the reintubation rate within 7 days after extubation compared with HFNC. The choice between using NPPV and HFNC should be based on the specific etiology of the patient's condition. The potential effect of noninvasive high-frequency oscillatory ventilation on CO2 clearance was also investigated.

Mechanical Ventilation, Past, Present, and Future.

Mechanical ventilation (MV) has played a crucial role in the medical field, particularly in anesthesia and in critical care medicine (CCM) settings. MV has evolved significantly since its inception over 70 years ago and the future promises even more advanced technology. In the past, ventilation was provided manually, intermittently, and it was primarily used for resuscitation or as a last resort for patients with severe respiratory or cardiovascular failure. The earliest MV machines for prolonged ventilatory support and oxygenation were large and cumbersome. They required a significant amount of skills and expertise to operate. These early devices had limited capabilities, battery, power, safety features, alarms, and therefore these often caused harm to patients. Moreover, the physiology of MV was modified when mechanical ventilators moved from negative pressure to positive pressure mechanisms. Monitoring systems were also very limited and therefore the risks related to MV support were difficult to quantify, predict and timely detect for individual patients who were necessarily young with few comorbidities. Technology and devices designed to use tracheostomies versus endotracheal intubation evolved in the last century too and these are currently much more reliable. In the present, positive pressure MV is more sophisticated and widely used for extensive period of time. Modern ventilators use mostly positive pressure systems and are much smaller, more portable than their predecessors, and they are much easier to operate. They can also be programmed to provide different levels of support based on evolving physiological concepts allowing lung-protective ventilation. Monitoring systems are more sophisticated and knowledge related to the physiology of MV is improved. Patients are also more complex and elderly compared to the past. MV experts are informed about risks related to prolonged or aggressive ventilation modalities and settings. One of the most significant advances in MV has been protective lung ventilation, diaphragm protective ventilation including noninvasive ventilation (NIV). Health care professionals are familiar with the use of MV and in many countries, respiratory therapists have been trained for the exclusive purpose of providing safe and professional respiratory support to critically ill patients. Analgo-sedation drugs and techniques are improved, and more sedative drugs are available and this has an impact on recovery, weaning, and overall patients' outcome. Looking toward the future, MV is likely to continue to evolve and improve alongside monitoring techniques and sedatives. There is increasing precision in monitoring global "patient-ventilator" interactions: structure and analysis (asynchrony, desynchrony, etc). One area of development is the use of artificial intelligence (AI) in ventilator technology. AI can be used to monitor patients in real-time, and it can predict when a patient is likely to experience respiratory distress. This allows medical professionals to intervene before a crisis occurs, improving patient outcomes and reducing the need for emergency intervention. This specific area of development is intended as "personalized ventilation." It involves tailoring the ventilator settings to the individual patient, based on their physiology and the specific condition they are being treated for. This approach has the potential to improve patient outcomes by optimizing ventilation and reducing the risk of harm. In conclusion, MV has come a long way since its inception, and it continues to play a critical role in anesthesia and in CCM settings. Advances in technology have made MV safer, more effective, affordable, and more widely available. As technology continues to improve, more advanced and personalized MV will become available, leading to better patients' outcomes and quality of life for those in need.

Individualized PEEP guided by EIT in patients undergoing general anesthesia: A systematic review and meta-analysis.

BACKGROUND: The determination of optimal positive end-expiratory pressure (PEEP) values in patients undergoing general anesthesia remains controversial. Electrical impedance tomography (EIT) directed individualized PEEP has emerged as a novel approach to PEEP setting and has garnered increasing attention. This meta-analysis aims to systematically assess the effect of EIT-guided PEEP setting compared to traditional fixed PEEP values or other PEEP titration strategies in patients undergoing general anesthesia. METHODS: A comprehensive search of electronic databases, including PubMed, Web of Science, EMBASE, and the Cochrane Library, was conducted from inception to January 2023, with no language restrictions. The search terms used were "EIT"and "PEEP" with their corresponding free words. Two researchers independently conducted literature screening, data extraction, and quality evaluation. The primary outcomes of interest were oxygenation index (OI), lung compliance, and number of postoperative pulmonary complications (PPCs). The secondary outcomes included mean arterial blood pressure (MAP) and number of vasoactive drug injections. RevMan 5.3 software was used to analyze the data and draw the forest plot, and Stata 14.2 software was used to conduct sensitivity analysis to assess the stability of the results. RESULTS: 5 studies involving 272 participants were included in this meta-analysis. Our findings suggest that EIT-guided individualized PEEP setting is superior to traditional fixed PEEP values and other individualized PEEP titration methods in terms of intraoperative OI(OR = 95.73, 95%CI: (49.10, 142.37); P < 0.0001) and lung compliance(OR = 7.69, 95%CI: (5.55, 9.83); P < 0.00001), without affecting intraoperative hemodynamic parameters such as MAP(OR = 2.07, 95%CI: (-1.00, 5.13); P = 0.19) and the number of intravenous vasoactive drugs(OR = 1.22, 95%CI: (0.68, 2.21); P = 0.51) or increasing the incidence of postoperative PPCs(OR = 0.87, 95%CI: (0.41, 1.82); P = 0.71). CONCLUSIONS: Our meta-analysis suggests potential benefits of EIT-guided individualized PEEP setting in improving intraoperative oxygenation and lung compliance in patients undergoing general anesthesia. However, further research is needed to establish conclusive evidence, and caution should be exercised in interpreting these findings as the current literature remains inconclusive regarding the impact on intraoperative hemodynamics and postoperative complications.

Expiratory Muscle Activity Counteracts Positive End-Expiratory Pressure and Is Associated with Fentanyl Dose in Patients with Acute Respiratory Distress Syndrome.

Rationale: Hypoxemia during mechanical ventilation might be worsened by expiratory muscle activity, which reduces end-expiratory lung volume through lung collapse. A proposed mechanism of benefit of neuromuscular blockade in acute respiratory distress syndrome (ARDS) is the abolition of expiratory efforts. This may contribute to the restoration of lung volumes. The prevalence of this phenomenon, however, is unknown. Objectives: To investigate the incidence and amount of end-expiratory lung impedance (EELI) increase after the administration of neuromuscular blocking agents (NMBAs), clinical factors associated with this phenomenon, its impact on regional lung ventilation, and any association with changes in pleural pressure. Methods: We included mechanically ventilated patients with ARDS monitored with electrical impedance tomography (EIT) who received NMBAs in one of two centers. We measured changes in EELI, a surrogate for end-expiratory lung volume, before and after NMBA administration. In an additional 10 patients, we investigated the characteristic signatures of expiratory muscle activity depicted by EIT and esophageal catheters simultaneously. Clinical factors associated with EELI changes were assessed. Measurements and Main Results: We included 46 patients, half of whom showed an increase in EELI of >10% of the corresponding Vt (46.2%; IQR, 23.9-60.9%). The degree of EELI increase correlated positively with fentanyl dosage and negatively with changes in end-expiratory pleural pressures. This suggests that expiratory muscle activity might exert strong counter-effects against positive end-expiratory pressure that are possibly aggravated by fentanyl. Conclusions: Administration of NMBAs during EIT monitoring revealed activity of expiratory muscles in half of patients with ARDS. The resultant increase in EELI had a dose-response relationship with fentanyl dosage. This suggests a potential side effect of fentanyl during protective ventilation.

Driving pressure of respiratory system and lung stress in mechanically ventilated patients with active breathing.

BACKGROUND: During control mechanical ventilation (CMV), the driving pressure of the respiratory system (ΔPrs) serves as a surrogate of transpulmonary driving pressure (ΔPlung). Expiratory muscle activity that decreases end-expiratory lung volume may impair the validity of ΔPrs to reflect ΔPlung. This prospective observational study in patients with acute respiratory distress syndrome (ARDS) ventilated with proportional assist ventilation (PAV+), aimed to investigate: (1) the prevalence of elevated ΔPlung, (2) the ΔPrs-ΔPlung relationship, and (3) whether dynamic transpulmonary pressure (Plungsw) and effort indices (transdiaphragmatic and respiratory muscle pressure swings) remain within safe limits. METHODS: Thirty-one patients instrumented with esophageal and gastric catheters (n = 22) were switched from CMV to PAV+ and respiratory variables were recorded, over a maximum of 24 h. To decrease the contribution of random breaths with irregular characteristics, a 7-breath moving average technique was applied. In each patient, measurements were also analyzed per deciles of increasing lung elastance (Elung). Patients were divided into Group A, if end-inspiratory transpulmonary pressure (PLEI) increased as Elung increased, and Group B, which showed a decrease or no change in PLEI with Elung increase. RESULTS: In 44,836 occluded breaths, ΔPlung ≥ 12 cmH2O was infrequently observed [0.0% (0.0-16.9%) of measurements]. End-expiratory lung volume decrease, due to active expiration, was associated with underestimation of ΔPlung by ΔPrs, as suggested by a negative linear relationship between transpulmonary pressure at end-expiration (PLEE) and ΔPlung/ΔPrs. Group A included 17 and Group B 14 patients. As Elung increased, ΔPlung increased mainly due to PLEI increase in Group A, and PLEE decrease in Group B. Although ΔPrs had an area receiver operating characteristic curve (AUC) of 0.87 (95% confidence intervals 0.82-0.92, P < 0.001) for ΔPlung ≥ 12 cmH2O, this was due exclusively to Group A [0.91 (0.86-0.95), P < 0.001]. In Group B, ΔPrs showed no predictive capacity for detecting ΔPlung ≥ 12 cmH2O [0.65 (0.52-0.78), P > 0.05]. Most of the time Plungsw and effort indices remained within safe range. CONCLUSION: In patients with ARDS ventilated with PAV+, injurious tidal lung stress and effort were infrequent. In the presence of expiratory muscle activity, ΔPrs underestimated ΔPlung. This phenomenon limits the usefulness of ΔPrs as a surrogate of tidal lung stress, regardless of the mode of support.

Effects of individualized positive end-expiratory pressure on intraoperative oxygenation in thoracic surgical patients: study protocol for a prospective randomized controlled trial.

BACKGROUND: Intraoperative hypoxemia and postoperative pulmonary complications (PPCs) often occur in patients with one-lung ventilation (OLV), due to both pulmonary shunt and atelectasis. It has been demonstrated that individualized positive end-expiratory pressure (iPEEP) can effectively improve intraoperative oxygenation, increase lung compliance, and reduce driving pressure, thereby decreasing the risk of developing PPCs. However, its effect during OLV is still unknown. Therefore, we aim to investigate whether iPEEP ventilation during OLV is superior to 5 cmH2O PEEP in terms of intraoperative oxygenation and the occurrence of PPCs. METHODS: This study is a prospective, randomized controlled, single-blind, single-center trial. A total of 112 patients undergoing thoracoscopic pneumonectomy surgery and OLV will be enrolled in the study. They will be randomized into two groups: the static lung compliance guided iPEEP titration group (Cst-iPEEP Group) and the constant 5 cmH2O PEEP group (PEEP 5 Group). The primary outcome will be the oxygenation index at 30 min after OLV and titration. Secondary outcomes are oxygenation index at other operative time points, PPCs, postoperative adverse events, ventilator parameters, vital signs, pH value, inflammatory factors, and economic indicators. DISCUSSION: This trial explores the effect of iPEEP on intraoperative oxygenation during OLV and PPCs. It provides some clinical references for optimizing the lung protective ventilation strategy of OLV, improving patient prognosis, and accelerating postoperative rehabilitation. TRIAL REGISTRATION: www.Chictr.org.cn ChiCTR2300073411 . Registered on 10 July 2023.

Pulmonary response prediction through personalized basis functions in a virtual patient model.

BACKGROUND AND OBJECTIVE: Recruitment maneuvers with subsequent positive-end-expiratory-pressure (PEEP) have proven effective in recruiting lung volume and preventing alveoli collapse. However, determining a safe, effective, and patient-specific PEEP is not standardized, and this more optimal PEEP level evolves with patient condition, requiring personalised monitoring and care approaches to maintain optimal ventilation settings. METHODS: This research examines 3 physiologically relevant basis function sets (exponential, parabolic, cumulative) to enable better prediction of elastance evolution for a virtual patient or digital twin model of MV lung mechanics, including novel elements to model and predict distension elastance. Prediction accuracy and robustness are validated against recruitment maneuver data from 18 volume-controlled ventilation (VCV) patients at 7 different baseline PEEP levels (0 to 12 cmH2O) and 14 pressure-controlled ventilation (PCV) patients at 4 different baseline PEEP levels (6 to 12 cmH2O), yielding 623 and 294 prediction cases, respectively. Predictions were made up to 12 cmH2O of added PEEP ahead, covering 6 × 2 cmH2O PEEP steps. RESULTS: The 3 basis function sets yield median absolute peak inspiratory pressure (PIP) prediction error of 1.63 cmH2O for VCV patients, and median peak inspiratory volume (PIV) prediction error of 0.028 L for PCV patients. The exponential basis function set yields a better trade-off of overall performance across VCV and PCV prediction than parabolic and cumulative basis function sets from other studies. Comparing predicted and clinically measured distension prediction in VCV demonstrated consistent, robust high accuracy with R2 = 0.90-0.95. CONCLUSIONS: The results demonstrate recruitment mechanics are best captured by an exponential basis function across different mechanical ventilation modes, matching physiological expectations, and accurately capture, for the first time, distension mechanics to within 5-10 % accuracy. Enabling the risk of lung injury to be predicted before changing ventilator settings. The overall outcomes significantly extend and more fully validate this digital twin or virtual mechanical ventilation patient model.

Intraoperative individualization of positive-end-expiratory pressure through electrical impedance tomography or esophageal pressure assessment: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review of randomized-controlled trials (RCTs) with meta-analyses aimed to compare the effects on intraoperative arterial oxygen tension to inspired oxygen fraction ratio (PaO2/FiO2), exerted by positive end-expiratory pressure (PEEP) individualized trough electrical impedance tomography (EIT) or esophageal pressure (Pes) assessment (intervention) vs. PEEP not tailored on EIT or Pes (control), in patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach. METHODS: PUBMED®, EMBASE®, and Cochrane Controlled Clinical trials register were searched for observational studies and RCTs from inception to the end of August 2022. Inclusion criteria were: RCTs comparing PEEP titrated on EIT/Pes assessment vs. PEEP not individualized on EIT/Pes and reporting intraoperative PaO2/FiO2. Two authors independently extracted data from the enrolled investigations. Data are reported as mean difference and 95% confidence interval (CI). RESULTS: Six RCTs were included for a total of 240 patients undergoing general anesthesia for surgery, of whom 117 subjects in the intervention group and 123 subjects in the control group. The intraoperative mean PaO2/FiO2 was 69.6 (95%CI 32.-106.4 ) mmHg higher in the intervention group as compared with the control group with 81.4% between-study heterogeneity (p < 0.01). However, at meta-regression, the between-study heterogeneity diminished to 44.96% when data were moderated for body mass index (estimate 3.45, 95%CI 0.78-6.11, p = 0.011). CONCLUSIONS: In patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach, PEEP personalized by EIT or Pes allowed the achievement of a better intraoperative oxygenation compared to PEEP not individualized through EIT or Pes. PROSPERO REGISTRATION NUMBER: CRD 42021218306, 30/01/2023.

Effects of THE PEEP-ZEEP Maneuver in Adults Receiving Mechanical Ventilation: A Systematic Review with Meta-Analysis.

INTRODUCTION: It is important to clarify the secretion clearance and lung-related effects of the PEEP-ZEEP maneuver in adults undergoing mechanical ventilation (MV). There is no published comprehensive meta-analysis of the effects of PEEP-ZEEP in adults receiving MV. OBJECTIVES: The aim of this study was to analyze published randomized controlled trials, investigating the effects of the PEEP-ZEEP maneuver in adults undergoing mechanical ventilation. METHODS: We searched Embase, PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from the date of inception of the databases until 6 May 2023. Quality assessment was using the Cochrane Systematic Assessment Handbook. The GRADE system was used to grade the quality of the evidence. RESULTS: A total of 12 trials were included, and the results of the meta-analysis showed that PEEP-ZEEP was not superior to bag squeezing for the removal of bronchial secretions. One study showed a significant increase in the amount of secretion retrieved with the PEEP-ZEEP when compared with tracheal suctioning. Additionally, PEEP-ZEEP was more effective than bag squeezing at improving oxygen saturation. However, one trial showed that bag squeezing was better at improving dynamic compliance. No other differences were found between PEEP-ZEEP and other techniques, except for one study showing more frequent changes in diastolic blood pressure with PEEP-ZEEP compared with ventilator hyperinflation. CONCLUSION: PEEP-ZEEP was not superior to bag squeezing in removing bronchial secretions. However, it improves oxygen saturation when compared to bag squeezing, and no adverse effects on patients' respiratory systems have yet been observed.

Respiratory effects of pressure support ventilation in spontaneously breathing patients under anaesthesia: Randomised controlled trial.

BACKGROUND: Lung volume loss is a major risk factor for postoperative respiratory complications after general anaesthesia and mechanical ventilation. We hypothesise that spontaneous breathing without pressure support may enhance the risk for atelectasis development. Therefore, we aimed at characterising whether pressure support prevents changes in lung function in patients breathing spontaneously through laryngeal mask airway. METHODS: In this randomised controlled trial, adult female patients scheduled for elective gynaecological surgery in lithotomy position were randomly assigned to the continuous spontaneous breathing group (CSB, n = 20) or to the pressure support ventilation group (PSV, n = 20) in a tertiary university hospital. Lung function measurements were carried out before anaesthesia and 1 h postoperatively by a researcher blinded to the group allocation. Lung clearance index calculated from end-expiratory lung volume turnovers as primary outcome variable was assessed by the multiple-breath nitrogen washout technique (MBW). Respiratory mechanics were measured by forced oscillations to assess parameters reflecting the small airway function and respiratory tissue stiffness. RESULTS: MBW was successfully completed in 18 patients in both CSB and PSV groups. The decrease in end-expiratory lung volume was more pronounced in the CSB than that in the PSV group (16.6 ± 6.6 [95% CI] % vs. 7.6 ± 11.1%, p = .0259), with no significant difference in the relative changes of the lung clearance index (-0.035 ± 7.1% vs. -0.18 ± 6.6%, p = .963). The postoperative changes in small airway function and respiratory tissue stiffness were significantly lower in the PSV than in the CSB group (p < .05 for both). CONCLUSIONS: These results suggest that pressure support ventilation protects against postoperative lung-volume loss without affecting ventilation inhomogeneity in spontaneously breathing patients with increased risk for atelectasis development. TRIAL REGISTRATION: NCT02986269.

High positive end-expiratory pressure ventilation mitigates the progression from unilateral pulmonary contusion to ARDS: An animal study.

BACKGROUND: Pulmonary contusion (PC) is common in severely traumatized patients and can lead to respiratory failure requiring mechanical ventilation (MV). Ventilator-induced lung injury (VILI) might aggravate lung damage. Despite underrepresentation of trauma patients in trials on lung-protective MV, results are extrapolated to these patients, potentially disregarding important pathophysiological differences. METHODS: Three MV protocols with different positive end-expiratory pressure (PEEP) levels: ARDSnetwork lower PEEP (ARDSnet-low), ARDSnetwork higher PEEP (ARDSnet-high), and open lung concept (OLC) were applied in swine for 24 hours following PC. Gas exchange, lung mechanics, quantitative computed tomography, and diffuse alveolar damage (DAD) score were analyzed. Results are given as median (interquartile range) at 24 hours. Statistical testing was performed using general linear models (group effect) over all measurement points and pairwise Mann-Whitney U tests for DAD. RESULTS: There were significant differences between groups: PEEP ( p < 0.0001) ARDSnet-low (8 [8-10] cmH 2 O), ARDSnet-high (12 [12-12] cmH 2 O), OLC (21 [20-22] cmH 2 O). The fraction of arterial partial pressure of oxygen and inspired oxygen fraction ( p = 0.0016) was lowest in ARDSnet-low (78 (73-111) mm Hg) compared with ARDSnet-high (375 (365-423) mm Hg) and OLC (499 (430-523) mm Hg). The end-expiratory lung volume (EELV) differed significantly ( p < 0.0001), with highest values in OLC (64% [60-70%]) and lowest in ARDSnet-low (34% [24-37%]). Costa's surrogate for mechanical power differed significantly ( p < 0.0001), with lowest values for ARDSnet-high (73 [58-76]) compared with OLC (105 [108-116]). Diffuse alveolar damage was lower in ARDSnet-high compared with ARDSnet-low (0.0007). CONCLUSION: Progression to ARDS, 24 hours after PC, was mitigated by OLC and ARDSnet-high. Both concepts restored EELV. ARDSnet-high had the lowest mechanical power surrogate and DAD. Our data suggest, that ARDSnet-high restored oxygenation and functional lung volume and reduced physiological and histological surrogates for VILI. ARDSnet-low generated unfavorable outcomes, such as loss of EELV, increased mechanical power and DAD after PC in swine. The high respiratory rate in the OLC may blunt favorable effects of lung recruitment.

Effects of positive end-expiratory pressure on brain oxygenation, systemic oxygen cascade and metabolism in acute brain injured patients: a pilot physiological cross-sectional study.

Patients with acute brain injury (ABI) often require the application of positive end-expiratory pressure (PEEP) to optimize mechanical ventilation and systemic oxygenation. However, the effect of PEEP on cerebral function and metabolism is unclear. The primary aim of this study was to evaluate the effects of PEEP augmentation test (from 5 to 15 cmH2O) on brain oxygenation, systemic oxygen cascade and metabolism in ABI patients. Secondary aims include to determine whether changes in regional cerebral oxygenation are reflected by changes in oxygenation cascade and metabolism, and to assess the correlation between brain oxygenation and mechanical ventilation settings. Single center, pilot cross-sectional observational study in an Academic Hospital. Inclusion criteria were: adult (> 18 y/o) patients with ABI and stable intracranial pressure, available gas exchange and indirect calorimetry (IC) monitoring. Cerebral oxygenation was monitored with near-infrared spectroscopy (NIRS) and different derived parameters were collected: variation (Δ) in oxy (O2)-hemoglobin (Hb) (ΔO2Hbi), deoxy-Hb(ΔHHbi), total-Hb(ΔcHbi), and total regional oxygenation (ΔrSO2). Oxygen cascade and metabolism were monitored with arterial/venous blood gas analysis [arterial partial pressure of oxygen (PaO2), arterial saturation of oxygen (SaO2), oxygen delivery (DO2), and lactate], and IC [energy expenditure (REE), respiratory quotient (RQ), oxygen consumption (VO2), and carbon dioxide production (VCO2)]. Data were measured at PEEP 5 cmH2O and 15 cmH2O and expressed as delta (Δ) values. Ten patients with ABI [median age 70 (IQR 62-75) years, 6 (60%) were male, median Glasgow Coma Scale at ICU admission 5.5 (IQR 3-8)] were included. PEEP augmentation from 5 to 15 cmH2O did not affect cerebral oxygenation, systemic oxygen cascade parameters, and metabolism. The arterial component of cerebral oxygenation was significantly correlated with DO2 (ΔO2HBi, rho = 0.717, p = 0.037). ΔrSO2 (rho = 0.727, p = 0.032), ΔcHbi (rho = 0.797, p = 0.013), and ΔHHBi (rho = 0.816, p = 0.009) were significantly correlated with SaO2, but not ΔO2Hbi. ΔrSO2 was significantly correlated with VCO2 (rho = 0.681, p = 0.049). No correlation between brain oxygenation and ventilatory parameters was found. PEEP augmentation test did not affect cerebral and systemic oxygenation or metabolism. Changes in cerebral oxygenation significantly correlated with DO2, SaO2, and VCO2. Cerebral oxygen monitoring could be considered for individualization of mechanical ventilation setting in ABI patients without high or instable intracranial pressure.

Comparison of the effects of open and closed aspiration on end-expiratory lung volume in acute respiratory distress syndrome.

BACKGROUND: Alveoli tend to collapse in patients with acute respiratory distress syndrome (ARDS). Endotracheal aspiration may increase alveolar collapse due to the loss of end-expiratory lung volume (EELV). We aimed to compare the loss of EELV after open and closed suction in patients with ARDS. METHODS: This randomized crossover study included 20 patients receiving invasive mechanical ventilation for ARDS. Open and closed suction were applied in a random order. Lung impedance was measured using electric impedance tomography. The change in end-expiratory lung impedance end of suction and at 1, 10, 20, and 30 min after suction, was used to represent the change in EELV. Arterial blood gas analyses and ventilatory parameters such as the plateau pressure (Pplat), driving pressure (Pdrive), and compliance of the respiratory system (CRS) were also recorded. RESULTS: Less volume loss was noted after closed suction than after open suction (mean ΔEELI: -2661 ± 1937 vs. -4415 ± 2363; mean difference: -1753; 95% CI [-2662, -844]; P = 0.001). EELI returned to baseline 10 min after closed suction but did not return to baseline even 30 min after open suction. After closed suction, the Pplat and Pdrive decreased while the CRS increased. Conversely, the Pplat and Pdrive increased while the CRS decreased after open suction. CONCLUSIONS: Endotracheal aspiration may result in alveolar collapse due to loss of EELV. Given that closed suction is associated with less volume loss at end-expiration without worsening ventilatory parameters, it should be chosen over open suction in patients with ARDS.