Low Positive End-expiratory Pressure Research Articles

Exaggerated Ventilator-Induced Lung Injury in an Animal Model of Type 2 Diabetes Mellitus: A Randomized Experimental Study.

Although ventilator-induced lung injury (VILI) often develops after prolonged mechanical ventilation in normal lungs, pulmonary disorders may aggravate the development of adverse symptoms. VILI exaggeration can be anticipated in type 2 diabetes mellitus (T2DM) due to its adverse pulmonary consequences. Therefore, we determined whether T2DM modulates VILI and evaluated how T2DM therapy affects adverse pulmonary changes. Rats were randomly assigned into the untreated T2DM group receiving low-dose streptozotocin with high-fat diet (T2DM, n = 8), T2DM group supplemented with metformin therapy (MET, n = 8), and control group (CTRL, n = 8). In each animal, VILI was induced by mechanical ventilation for 4 h with high tidal volume (23 ml/kg) and low positive end-expiratory pressure (0 cmH2O). Arterial and venous blood samples were analyzed to measure the arterial partial pressure of oxygen (PaO2), oxygen saturation (SaO2), and the intrapulmonary shunt fraction (Qs/Qt). Airway and respiratory tissue mechanics were evaluated by forced oscillations. Lung histology samples were analyzed to determine injury level. Significant worsening of VILI, in terms of PaO2, SaO2, and Qs/Qt, was observed in the T2DM group, without differences in the respiratory mechanics. These functional changes were also reflected in lung injury score. The MET group showed no difference compared with the CTRL group. Gas exchange impairment without significant mechanical changes suggests that untreated diabetes exaggerates VILI by augmenting the damage of the alveolar–capillary barrier. Controlled hyperglycemia with metformin may reduce the manifestations of respiratory defects during prolonged mechanical ventilation.

Intraoperative protective mechanical ventilation in patients requiring emergency abdominal surgery: the multicentre prospective randomised IMPROVE-2 study protocol

IntroductionEmergency abdominal surgery is associated with a high risk of postoperative complications. One of the most serious is postoperative respiratory failure (PRF), with reported rates up to 20%–30% and attributable...

Myocardial Function during Ventilation with Lower versus Higher Positive End-Expiratory Pressure in Patients without ARDS.

The aim of this study was to investigate whether lower PEEP (positive end-expiratory pressure) had beneficial effects on myocardial function among intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) compared to higher PEEP. In this pre-planned substudy of a randomized controlled trial (RELAx), comparing lower to higher PEEP, 44 patients underwent transthoracic echocardiography. The exclusion criteria were known poor left ventricular function and severe shock requiring high dosages of norepinephrine. To create contrast, we also excluded patients who received PEEP between 2 cmH2O and 7 cmH2O in the two randomization arms of the study. The primary outcome was the right ventricular myocardial performance index (MPI), a measure of systolic and diastolic function. The secondary outcomes included systolic and diastolic function parameters. A total of 20 patients were ventilated with lower PEEP (mean ± SD, 0 ± 1 cmH2O), and 24 patients, with higher PEEP (8 ± 1 cmH2O) (mean difference, −8 cmH2O; 95% CI: −8.1 to −7.9 cmH2O; p = 0.01). The tidal volume size was low in both groups (median (IQR), 7.2 (6.3 to 8.1) versus 7.0 (5.3 to 9.1) ml/kg PBW; p = 0.97). The median right ventricular MPI was 0.32 (IQR, 0.26 to 0.39) in the lower-PEEP group versus 0.38 (0.32 to 0.41) in the higher-PEEP group; the median difference was –0.03; 95% CI: −0.11 to 0.03; p = 0.33. The other systolic and diastolic parameters were similar. In patients without ARDS ventilated with a low tidal volume, a lower PEEP had no beneficial effects on the right ventricular MPI.

Prone Position Minimizes the Exacerbation of Effort-dependent Lung Injury: Exploring the Mechanism in Pigs and Evaluating Injury in Rabbits

Vigorous spontaneous effort can potentially worsen lung injury. This study hypothesized that the prone position would diminish a maldistribution of lung stress and inflation after diaphragmatic contraction and reduce spontaneous effort, resulting in less lung injury. A severe acute respiratory distress syndrome model was established by depleting surfactant and injurious mechanical ventilation in 6 male pigs ("mechanism" protocol) and 12 male rabbits ("lung injury" protocol). In the mechanism protocol, regional inspiratory negative pleural pressure swing (intrabronchial balloon manometry) and the corresponding lung inflation (electrical impedance tomography) were measured with a combination of position (supine or prone) and positive end-expiratory pressure (high or low) matching the intensity of spontaneous effort. In the lung injury protocol, the intensities of spontaneous effort (esophageal manometry) and regional lung injury were compared in the supine position versus prone position. The mechanism protocol (pigs) found that in the prone position, there was no ventral-to-dorsal gradient in negative pleural pressure swing after diaphragmatic contraction, irrespective of the positive end-expiratory pressure level (-10.3 ± 3.3 cm H2O vs. -11.7 ± 2.4 cm H2O at low positive end-expiratory pressure, P = 0.115; -10.4 ± 3.4 cm H2O vs. -10.8 ± 2.3 cm H2O at high positive end-expiratory pressure, P = 0.715), achieving homogeneous inflation. In the supine position, however, spontaneous effort during low positive end-expiratory pressure had the largest ventral-to-dorsal gradient in negative pleural pressure swing (-9.8 ± 2.9 cm H2O vs. -18.1 ± 4.0 cm H2O, P < 0.001), causing dorsal overdistension. Higher positive end-expiratory pressure in the supine position reduced a ventral-to-dorsal gradient in negative pleural pressure swing, but it remained (-9.9 ± 2.8 cm H2O vs. -13.3 ± 2.3 cm H2O, P < 0.001). The lung injury protocol (rabbits) found that in the prone position, spontaneous effort was milder and lung injury was less without regional difference (lung myeloperoxidase activity in ventral vs. dorsal lung, 74.0 ± 30.9 μm · min-1 · mg-1 protein vs. 61.0 ± 23.0 μm · min-1 · mg-1 protein, P = 0.951). In the supine position, stronger spontaneous effort increased dorsal lung injury (lung myeloperoxidase activity in ventral vs. dorsal lung, 67.5 ± 38.1 μm · min-1 · mg-1 protein vs. 167.7 ± 65.5 μm · min-1 · mg-1 protein, P = 0.003). Prone position, independent of positive end-expiratory pressure levels, diminishes a maldistribution of lung stress and inflation imposed by spontaneous effort and mitigates spontaneous effort, resulting in less effort-dependent lung injury.

Randomized Trial of Protective Lung Ventilation in Organ Donors

<h3>Purpose</h3> A protective ventilation strategy that targeted lower tidal volume (TV) and higher positive end expiratory pressure (PEEP) improved lung utilization in European donors but has not been tested in a US donor population. We conducted a randomized trial of an open lung protective ventilator (OLPV) strategy with lower TV, higher PEEP and protocolized recruitment maneuvers (RM) compared to a conventional ventilator (CV) strategy with higher TV and lower PEEP in deceased donors in Northern California. The primary outcome was donor lung utilization for transplantation. <h3>Methods</h3> Donors were eligible for inclusion if greater than 13 years of age and PaO₂/FiO₂ was between 150 and 400. Eligible donors were randomized to volume control ventilation with OLPV [TV 6 ml/kg predicted body weight (PBW), PEEP 10, protocolized RM] or CV [TV 10ml/kg PBW, PEEP 5, RM only after vent disconnect] for the duration of donor management. Lungs were evaluated for transplant potential on standard ventilator settings in both arms [TV 10ml/kg PBW, PEEP 5, FiO₂ 1.0]. <h3>Results</h3> Between July 2018 and December 2019, 153 donors were randomized (74 to OLPV, 79 to CV) and included in the final analysis. The trial stopped early due to changes in donor management at the participating OPO. Donor demographics were similar by treatment arm and compliance with the ventilator protocols was excellent. Median duration of treatment was 49.5 hours and did not differ by arm. Among 153 donors, 33 became lung donors, 16/74 (21.6%) in the OLPV arm and 17/79 (21.5%) in the CV arm, P = 0.99. Change in donor oxygenation as measured by PaO₂/FiO₂ from enrollment to procurement did not differ by treatment arm; median change (IQR) in OLPV versus CV was 53 (-5 to 139) vs 46 (-77 to 117), P = 0.14. Change in static compliance of the respiratory system also did not differ by treatment arm. There was no difference in need for vasopressors between arms. One serious adverse event that was possibly related to the study intervention occurred in the CV arm with expansion of a pneumothorax requiring chest tube placement. Among 29 lung recipients in whom detailed data were available, duration of mechanical ventilation, ICU stay and hospital stay did not differ by donor treatment arm. <h3>Conclusion</h3> An open lung protective ventilator strategy was safe but did not improve donor lung utilization or oxygenation compared to a conventional ventilator strategy in a population of US organ donors. Funding: NIH HL126176

Effects of different positive end-expiratory pressure titration strategies during prone positioning in patients with acute respiratory distress syndrome: a prospective interventional study

BackgroundProne positioning in combination with the application of low tidal volume and adequate positive end-expiratory pressure (PEEP) improves survival in patients with moderate to severe acute respiratory distress syndrome (ARDS). However, the effects of PEEP on end-expiratory transpulmonary pressure (Ptpexp) during prone positioning require clarification. For this purpose, the effects of three different PEEP titration strategies on Ptpexp, respiratory mechanics, mechanical power, gas exchange, and hemodynamics were evaluated comparing supine and prone positioning.MethodsIn forty consecutive patients with moderate to severe ARDS protective ventilation with PEEP titrated according to three different titration strategies was evaluated during supine and prone positioning: (A) ARDS Network recommendations (PEEPARDSNetwork), (B) the lowest static elastance of the respiratory system (PEEPEstat,RS), and (C) targeting a positive Ptpexp (PEEPPtpexp). The primary endpoint was to analyze whether Ptpexp differed significantly according to PEEP titration strategy during supine and prone positioning.ResultsPtpexp increased progressively with prone positioning compared with supine positioning as well as with PEEPEstat,RS and PEEPPtpexp compared with PEEPARDSNetwork (positioning effect p < 0.001, PEEP strategy effect p < 0.001). PEEP was lower during prone positioning with PEEPEstat,RS and PEEPPtpexp (positioning effect p < 0.001, PEEP strategy effect p < 0.001). During supine positioning, mechanical power increased progressively with PEEPEstat,RS and PEEPPtpexp compared with PEEPARDSNetwork, and prone positioning attenuated this effect (positioning effect p < 0.001, PEEP strategy effect p < 0.001). Prone compared with supine positioning significantly improved oxygenation (positioning effect p < 0.001, PEEP strategy effect p < 0.001) while hemodynamics remained stable in both positions.ConclusionsProne positioning increased transpulmonary pressures while improving oxygenation and hemodynamics in patients with moderate to severe ARDS when PEEP was titrated according to the ARDS Network lower PEEP table. This PEEP titration strategy minimized parameters associated with ventilator-induced lung injury induction, such as transpulmonary driving pressure and mechanical power. We propose that a lower PEEP strategy (PEEPARDSNetwork) in combination with prone positioning may be part of a lung protective ventilation strategy in patients with moderate to severe ARDS.Trial registrationGerman Clinical Trials Register (DRKS00017449). Registered June 27, 2019. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017449

Differential Prognostic Analysis of Higher and Lower PEEP in ARDS Patients: Systematic Review and Meta-Analysis.

Background Positive end-expiratory pressure (PEEP) refers to the positive pressure in the respiratory tract at the end of the exhalation when we use a ventilator. The differences of higher PEEP and lower PEEP on clinical outcomes in acute respiratory distress syndrome (ARDS) patients are less well known. Methods A comprehensive literature search of all randomized control trials (RCTs) was conducted using PubMed, Embase, World Health Organization (WHO) Global Index Medicus, WHO clinical trial registry, and Clinicaltrials.gov. Inclusion criteria included RCTs comparing the clinical outcomes of higher and lower PEEP in ARDS patients. Results Eleven studies were included in the final analysis. In the higher PEEP group, the hospital mortality, 28-day mortality, and ICU mortality showed no significantly lower risk compared to the lower PEEP group (RR = 0.92, 95% CI 0.80–1.05, p = 0.22; RR = 0.88, 95% CI 0.73–1.05, p = 0.15; RR = 0.84, 95% CI 0.67–1.05, p = 0.12; respectively). High certainty could be obtained that there is no significant difference between the clinical outcomes of higher PEEP and lower PEEP in ARDS patients. Conclusions There is no significant difference of the hospital mortality, 28-day mortality, and ICU mortality between higher and lower PEEP in ARDS patients.

Lung and chest wall mechanical properties in metformin-treated and untreated models of type 2 diabetes

The adverse respiratory consequences of type 2 diabetes mellitus (T2DM) may reflect compromised lung function and/or alterations of the chest wall because of skeletal muscle stiffening. We assessed the separate contributions of these compartments to respiratory complications in diabetes and explored the effects of metformin on respiratory abnormalities. Experiments were performed in untreated rats (control, n = 7), high-fat diet-fed rats receiving streptozotocin (T2DM, n = 7), and metformin-treated diabetic rats (MET, n = 6). Newtonian resistance, tissue damping, and elastance were separately assessed for lung and chest wall components by measuring the esophageal pressure during forced oscillations at low (0 cmH2O), medium (3 cmH2O), and high positive end-expiratory pressure (PEEP) (6 cmH2O). Tissue hysteresivity was calculated as damping/elastance. Blood gas parameters were used to assess gas exchange, and lung histology was performed to characterize collagen expression. T2DM at low PEEP compromised airway and lung tissue mechanics in association with gas-exchange defects and collagen overexpression. Abnormal chest wall mechanics in T2DM was indicated only by decreased tissue hysteresivity. No difference in lung or chest wall mechanics, gas exchange, or lung histology was observed between the MET and control groups. These findings suggest the primary involvement of the pulmonary system in the respiratory consequences of T2DM, with chest wall properties only disturbed by a shift toward the dominance of elastic forces at low PEEP. The adequacy of metformin to treat the adverse respiratory consequences of diabetes was also revealed, in addition to its well-established beneficial effects on other organs.NEW & NOTEWORTHY The present study examined the contributions of the lungs and chest wall to respiratory complications in a rat model of diabetes and clarified the effects of metformin on these changes. At low positive end-expiratory pressure, type 2 diabetes was linked to dysfunctional airway and lung tissue mechanics in relation with gas-exchange defects and collagen overexpression, whereas decreased tissue hysteresivity was manifested in the chest wall abnormalities. Metformin treated all adverse respiratory consequences of diabetes.

Innovations in Emergency Airway Management: Lessons-Learned from Early Cross-Cultural Management of Covid-19

The Texas Tech University Center for Emerging Energy Sciences Research Group implemented rapid translation and analytics of Chinese COVID-19 medical literature in February 2020, which enabled emerging innovations in patient care. Specifically, techniques to optimize patient care through improved ventilation and oxygenation recognizing newly discovered pathophysiology were designed and prototyped in this invention. COVID-19 respiratory distress distinguishes itself from acute respiratory distress syndrome (ARDS) and pathophysiology of SARS-COV-2 by requiring higher O2 and lower pressure requirements for adequate oxygenation. Specifically, low positive end-expiratory pressure ventilator parameters are necessary to optimize patient care. Paradoxically, COVID-19 patients display severe "silent" hypoxemia often associated with near normal respiratory compliance. This clinical presentation is considered unusual for severe ARDS patients and implies non-uniformity in disease management of acute respiratory and pre-hospital patients. A clinical need for new innovative approaches to management that may also benefit decompression sickness, high altitude pulmonary edema and other chronic respiratory disease patients.&lt;br/&gt; We present these observations as an example of the need for closely-collaborating, interdisciplinary teams to facilitate rapid innovation when sudden, severe health threats first emerge. This approach is invaluable to medical innovations needed to counter threats due natural to man-made conditions.

Posttraumatic pneumonectomy and management of severely contaminated pleural space.

Posttraumatic pneumonectomy and management of severely contaminated pleural space.

Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis.

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.

Influence of the end inspiratory pause on respiratory mechanics and tidal gas distribution of surgical patients ventilated under a tailored open lung approach strategy: A randomised, crossover trial

BackgroundThe effect of modifying the end inspiratory pause (EIP) on respiratory mechanics and gas distribution of surgical patients ventilated with an open lung approach (OLA) has not been addressed before. MethodsProspective, randomised, crossover study carried out in a tertiary hospital. Subjects were assigned to receive an initial EIP of 10% or 30% of the total inspiratory time. We compared standard ventilation [time 0: tidal volume (VT) 7 mL × kg−1, respiratory rate (RR) 13, inspiratory:expiratory (I:E) rate 1:2, positive end-expiratory pressure (PEEP) 5 cm H2O and EIP 10% and 30% for groups 1 and 2, respectively) with tailored OLA (similar parameters except for a tailored PEEP after a stepwise recruitment manoeuvre), followed by a crossover assignment sequence between groups (times 2–4). ResultsWe included 32 adult subjects undergoing major surgery. Tailored OLA strategy was associated with a significant increase in PEEP, plateau pressure (Pplat), PaO2, and compliance of the respiratory system (CRS) with a significant decrease in driving pressure (Pdriv) and PaCO2, and a more homogeneous gas distribution in both groups. A significantly lower PEEP (p < 0.001), Pdriv (5 [5–6] versus 6.5 [6–8] cmH2O; p < 0.001) and mean airway pressure (Pmean; p < 0.001) together with a higher CRS (77 [67−87] versus 58 [52−70] ml*cmH2O−1; p < 0.001) were observed when an EIP of 30% was applied as compared to an EIP of 10%. ConclusionThe use of a tailored OLA strategy combined with a longer EIP is associated with a higher CRS, and a lower Pdriv, Pmean and PEEP. Additional studies are necessary to assess if the improved ventilatory conditions observed with a longer EIP are associated with better patients’ outcomes.Trial registration at clinicaltrials.gov with identifier: NCT03568786.

Pulmonary complications and respiratory management in neurocritical care: a narrative review.

Neurocritical care (NCC) is not only generally guided by principles of general intensive care, but also directed by specific goals and methods. This review summarizes the common pulmonary diseases and pathophysiology affecting NCC patients and the progress made in strategies of respiratory support in NCC. This review highlights the possible interactions and pathways that have been revealed between neurological injuries and respiratory diseases, including the catecholamine pathway, systemic inflammatory reactions, adrenergic hypersensitivity, and dopaminergic signaling. Pulmonary complications of neurocritical patients include pneumonia, neurological pulmonary edema, and respiratory distress. Specific aspects of respiratory management include prioritizing the protection of the brain, and the goal of respiratory management is to avoid inappropriate blood gas composition levels and intracranial hypertension. Compared with the traditional mode of protective mechanical ventilation with low tidal volume (Vt), high positive end-expiratory pressure (PEEP), and recruitment maneuvers, low PEEP might yield a potential benefit in closing and protecting the lung tissue. Multimodal neuromonitoring can ensure the safety of respiratory maneuvers in clinical and scientific practice. Future studies are required to develop guidelines for respiratory management in NCC.

The Impact of Protective Ventilation Strategy, Applied in Patients During Prolonged Gynecological Surgery, on Postoperative Oxygenation

&#x0D; &#x0D; &#x0D; Atelectasis occurs in nearly 90% of patients operated under general anaesthesia and persists for about 24 hours after laparoscopic surgery and 3 days after open surgery. According to some randomized studies, intraoperative application of mechanical protective ventilation with a low tidal volume (VT), positive end-expiratory pressure (PEEP) and recruitment maneuvers (RMs) decreases left to right shunting and improves postoperative oxygenation. During these trials statistically significantly higher values of oxygen partial pressure (PaO2) in arterial blood gas analysis and PaO2/FiO2 ratio (FiO2 – fraction of inspired oxygen; FiO2 = 0.21) were observed in patients ventilated with PEEP and RMs.&#x0D; Our purpose is to prove that the application of PEEP in patients during prolonged gynecological surgery can improve postoperative oxygenation and decrease the incidence of postoperative atelectasis.&#x0D; In this observational cohort study we included women, who underwent conventional gynecological surgery with a duration of more than 2 hours. Pa- tients were divided into 2 groups – control group A (35 patients) and exposed group B (35 patients). The ones in the control group were ventilated with a tidal volume (VT) of 8–10 ml/kg, without PEEP and RMs, whereas those in group B were ventilated with VT = 6−8 ml/kg (based on ideal body weight), PEEP = 6 cm H2O and RMs performed after intubation, at every disconnection from the ventilator and at extubation.&#x0D; We proved that the patients in group B had statistically significantly higher values of PaO2 and PaO2/FiO2 on the first postoperative day, therefore intraoperative protective mechanical ventilation improves postoperative oxygenation. We also observed a significantly reduced incidence of newly developed postoperative atelectasis in this patient group. Patients in group A had a significantly longer stay in intensive care unit (ICU) than those in group B. The use of protective ventilation strategy (low VT, PEEP and RMs) in patients during prolonged gynecological surgery can decrease the incidence of postoperative atelectasis and improves oxygenation on the first postoperative day.&#x0D; &#x0D; &#x0D;

Change of Anesthetic Management From Open to Laparoscopic Living Donor Right Hepatectomy After Learning Curve

In our hospital, open living donor hepatectomy (OLDH) began in 1996 and laparoscopic living donor hepatectomy (LLDH) began in 2013. In this study, we focus on the change of anesthetic management from OLDH to LLDH. Under the approval of the Institutional Review Board of our hospital, medical records of the last 2 years (2011 and 2012 vs 2019 and 2020) of each OLDH and LLDH era were collected. Left hepatectomy in any period and OLDH during the LLDH era were excluded. There were 175 OLDHs and 213 LLDHs. We performed 836 cases of OLDH before 2011 and 206 cases of LLDH before 2019. Laryngeal mask airway replaced intubation in half of LLDH cases. Erector spinae plane block was performed in a quarter of LLDH cases. Lung-protective ventilation with low tidal volume and positive end-expiratory pressure were applied for LLDH. Additional peripheral venous line was decreased, and there was no central venous catheterization. Anesthesia duration time was reduced and crystalloid infusion per hour was also decreased. There was no intraoperative transfusion and there was no difference in postoperative transfusion incidence. Reoperation rate was not different. Only 1 donor in OLDH transferred to the intensive care unit after the operation because of uncontrolled hypertension. Length of hospital stay was decreased. As the surgical tactics for living liver donors become less invasive, the anesthetic strategy also becomes less invasive. In addition, new types of airway management, ventilation method, and analgesic technique have been introduced.

Hemodynamic response to positive end-expiratory pressure and prone position in COVID-19 ARDS

BackgroundUse of high positive end-expiratory pressure (PEEP) and prone positioning is common in patients with COVID-19-induced acute respiratory failure. Few data clarify the hemodynamic effects of these interventions in this specific condition. We performed a physiologic study to assess the hemodynamic effects of PEEP and prone position during COVID-19 respiratory failure. MethodsNine adult patients mechanically ventilated due to COVID-19 infection and fulfilling moderate-to-severe ARDS criteria were studied. Respiratory mechanics, gas exchange, cardiac output, oxygen consumption, systemic and pulmonary pressures were recorded through pulmonary arterial catheterization at PEEP of 15 and 5 cmH2O, and after prone positioning. Recruitability was assessed through the recruitment-to-inflation ratio. ResultsHigh PEEP improved PaO2/FiO2 ratio in all patients (p = 0.004), and significantly decreased pulmonary shunt fraction (p = 0.012), regardless of lung recruitability. PEEP-induced increases in PaO2/FiO2 changes were strictly correlated with shunt fraction reduction (rho=-0.82, p = 0.01). From low to high PEEP, cardiac output decreased by 18 % (p = 0.05) and central venous pressure increased by 17 % (p = 0.015).As compared to supine position with low PEEP, prone positioning significantly decreased pulmonary shunt fraction (p = 0.03), increased PaO2/FiO2 (p = 0.03) and mixed venous oxygen saturation (p = 0.016), without affecting cardiac output. PaO2/FiO2 was improved by prone position also when compared to high PEEP (p = 0.03). ConclusionsIn patients with moderate-to-severe ARDS due to COVID-19, PEEP and prone position improve arterial oxygenation. Changes in cardiac output contribute to the effects of PEEP but not of prone position, which appears the most effective intervention to improve oxygenation with no hemodynamic side effects.

Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis

Two acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS. In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable. The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90-0·95) in EARLI and 0·88 (0·84-0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81-0·94] vs 0·92 [0·88-0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p<0·0001). There was a significant treatment interaction with PEEP strategy and ARDS subphenotype (p=0·041), with lower 90-day mortality in the high PEEP group of patients with the hyperinflammatory subphenotype (hyperinflammatory subphenotype: 169 [54%] of 313 patients in the high PEEP group vs 127 [62%] of 205 patients in the low PEEP group; hypoinflammatory subphenotype: 231 [34%] of 675 patients in the high PEEP group vs 233 [32%] of 734 patients in the low PEEP group). Classifier models using clinical variables alone can accurately assign ARDS subphenotypes in observational cohorts. Application of these models can provide valuable prognostic information and could inform management strategies for personalised treatment, including application of PEEP, once prospectively validated. US National Institutes of Health and European Society of Intensive Care Medicine.

Hyaluronic acid plasma levels during high versus low tidal volume ventilation in a porcine sepsis model.

BackgroundShedding of the endothelial glycocalyx can be observed regularly during sepsis. Moreover, sepsis may be associated with acute respiratory distress syndrome (ARDS), which requires lung protective ventilation with the two cornerstones of application of low tidal volume and positive end-expiratory pressure. This study investigated the effect of a lung protective ventilation on the integrity of the endothelial glycocalyx in comparison to a high tidal volume ventilation mode in a porcine model of sepsis-induced ARDS.MethodsAfter approval by the State and Institutional Animal Care Committee, 20 male pigs were anesthetized and received a continuous infusion of lipopolysaccharide to induce septic shock. The animals were randomly assigned to either low tidal volume ventilation, high tidal volume ventilation, or no-LPS-group groups and observed for 6 h. In addition to the gas exchange parameters and hematologic analyses, the serum hyaluronic acid concentrations were determined from central venous blood and from pre- and postpulmonary and pre- and postcerebral circulation. Post-mortem analysis included histopathological evaluation and determination of the pulmonary and cerebral wet-to-dry ratios.ResultsBoth sepsis groups developed ARDS within 6 h of the experiment and showed significantly increased serum levels of hyaluronic acid in comparison to the no-LPS-group. No significant differences in the hyaluronic acid concentrations were detected before and after pulmonary and cerebral circulation. There was also no significant difference in the serum hyaluronic acid concentrations between the two sepsis groups. Post-mortem analysis showed no significant difference between the two sepsis groups.ConclusionIn a porcine model of septic shock and ARDS, the serum hyaluronic acid levels were significantly elevated in both sepsis groups in comparison to the no-LPS-group. Intergroup comparison between lung protective ventilated and high tidal ventilated animals revealed no significant differences in the serum hyaluronic acid levels.

Mechanical power in pediatric acute respiratory distress syndrome: a PARDIE study

BackgroundMechanical power is a composite variable for energy transmitted to the respiratory system over time that may better capture risk for ventilator-induced lung injury than individual ventilator management components. We sought to evaluate if mechanical ventilation management with a high mechanical power is associated with fewer ventilator-free days (VFD) in children with pediatric acute respiratory distress syndrome (PARDS).MethodsRetrospective analysis of a prospective observational international cohort study.ResultsThere were 306 children from 55 pediatric intensive care units included. High mechanical power was associated with younger age, higher oxygenation index, a comorbid condition of bronchopulmonary dysplasia, higher tidal volume, higher delta pressure (peak inspiratory pressure—positive end-expiratory pressure), and higher respiratory rate. Higher mechanical power was associated with fewer 28-day VFD after controlling for confounding variables (per 0.1 J·min−1·Kg−1 Subdistribution Hazard Ratio (SHR) 0.93 (0.87, 0.98), p = 0.013). Higher mechanical power was not associated with higher intensive care unit mortality in multivariable analysis in the entire cohort (per 0.1 J·min−1·Kg−1 OR 1.12 [0.94, 1.32], p = 0.20). But was associated with higher mortality when excluding children who died due to neurologic reasons (per 0.1 J·min−1·Kg−1 OR 1.22 [1.01, 1.46], p = 0.036). In subgroup analyses by age, the association between higher mechanical power and fewer 28-day VFD remained only in children < 2-years-old (per 0.1 J·min−1·Kg−1 SHR 0.89 (0.82, 0.96), p = 0.005). Younger children were managed with lower tidal volume, higher delta pressure, higher respiratory rate, lower positive end-expiratory pressure, and higher PCO2 than older children. No individual ventilator management component mediated the effect of mechanical power on 28-day VFD.ConclusionsHigher mechanical power is associated with fewer 28-day VFDs in children with PARDS. This association is strongest in children < 2-years-old in whom there are notable differences in mechanical ventilation management. While further validation is needed, these data highlight that ventilator management is associated with outcome in children with PARDS, and there may be subgroups of children with higher potential benefit from strategies to improve lung-protective ventilation.Take Home Message: Higher mechanical power is associated with fewer 28-day ventilator-free days in children with pediatric acute respiratory distress syndrome. This association is strongest in children <2-years-old in whom there are notable differences in mechanical ventilation management.

International clinical research of critical care medicine in 2021

The progress of critical care medicine in 2021 is still encouraging. The new international guideline for management of sepsis and septic shock came out after 4 years. Besides, a couple of preferable clinical evidences were released including restrictive blood transfusion strategy for patients with acute myocardial infarction, prevention of peripheral venous catheter infection, heparin inhalation and driving pressure setting in patients with acute respiratory distress syndrome (ARDS), lower oxygenation target for acute hypoxemic respiratory failure, low level positive end-expiratory pressure in non-ARDS patients with respiratory failure, light sedation or non-sedation strategy, biological phenotypes, as well machine learning in sepsis and ARDS. However, we also encounter negative results such as balanced solution during fluid resuscitation, hypothermia therapy after out-of-hospital cardiac arrest or traumatic brain injury, adrenomedullin-specific antibody adrecizumab therapy and coupled plasma filtration-adsorption (CPFA) therapy for patients with septic shock, extracorporeal carbon dioxide removal (ECCO2R) implementation in acute hypoxic respiratory failure, continuous infusion of hypertonic saline in patients with traumatic brain injury. Collectively, in the future, individualized diagnosis and management based on the principle of "wise choice" will become the daily practice scene for all intensivists.