Influence of ventilatory settings on pendelluft and expiratory muscle activity in hypoxemic patients resuming spontaneous breathing.

Harmful effects of spontaneous breathing have been shown in experimental severe acute respiratory distress syndrome (ARDS). However, in the clinical setting, spontaneous respiration has been indicated only in mild ARDS. To date, no study has compared the effects of spontaneous assisted breathing with those of fully controlled mechanical ventilation at different levels of positive end-expiratory pressure (PEEP) on lung injury in ARDS. To compare the effects of assisted pressure support ventilation (PSV) with pressure-controlled ventilation (PCV) on lung function, histology and biological markers at two different PEEP levels in mild ARDS in rats. Randomised controlled experimental study. Basic science laboratory. Thirty-five Wistar rats (weight ± SD, 310 ± 19) g received Escherichia coli lipopolysaccharide (LPS) intratracheally. After 24 h, the animals were anaesthetised and randomly allocated to either PCV (n=14) or PSV (n=14) groups. Each group was further assigned to PEEP = 2 cmH2O or PEEP = 5 cmH2O. Tidal volume was kept constant (≈6 ml kg). Additional nonventilated animals (n=7) were used as a control for postmortem analysis. Ventilatory and mechanical parameters, arterial blood gases, diffuse alveolar damage score, epithelial integrity measured by E-cadherin tissue expression, and biological markers associated with inflammation (IL-6 and cytokine-induced neutrophil chemoattractant, CINC-1) and type II epithelial cell damage (surfactant protein-B) were evaluated. In both PCV and PSV, peak transpulmonary pressure was lower, whereas E-cadherin tissue expression, which is related to epithelial integrity, was higher at PEEP = 5 cmH2O than at PEEP = 2 cmH2O. In PSV, PEEP = 5 cmH2O compared with PEEP = 2 cmH2O was associated with significantly reduced diffuse alveolar damage score [median (interquartile range), 11 (8.5 to 13.5) vs. 23 (19 to 26), P = 0.005] and expressions of IL-6 and CINC-1 (P = 0.02 for both), whereas surfactant protein-B mRNA expression increased (P = 0.03). These changes suggested less type II epithelial cell damage at a PEEP of 5 cmH2O. Peak transpulmonary pressure correlated positively with IL-6 [Spearman's rho (ρ) = 0.62, P = 0.0007] and CINC-1 expressions (ρ = 0.50, P = 0.01) and negatively with E-cadherin expression (ρ = -0.67, P = 0.0002). During PSV, PEEP of 5 cmH2O, but not a PEEP of 2 cmH2O, reduced lung damage and inflammatory markers while maintaining epithelial cell integrity.

Electrical Impedance Tomography to Set Positive End Expiratory Pressure During Pediatric Extracorporeal Membrane Oxygenation for Respiratory Failure... Is it Feasible?

Acute respiratory distress syndrome is characterized by collapse of gravitationally dependent lung regions that usually diverts tidal ventilation toward nondependent regions. We hypothesized that higher positive end-expiratory pressure and enhanced spontaneous breathing may increase the proportion of tidal ventilation reaching dependent lung regions in patients with acute respiratory distress syndrome undergoing pressure support ventilation. Prospective, randomized, cross-over study. General and neurosurgical ICUs of a single university-affiliated hospital. We enrolled ten intubated patients recovering from acute respiratory distress syndrome, after clinical switch from controlled ventilation to pressure support ventilation. We compared, at the same pressure support ventilation level, a lower positive end-expiratory pressure (i.e., clinical positive end-expiratory pressure = 7 ± 2 cm H2O) with a higher one, obtained by adding 5 cm H2O (12 ± 2 cm H2O). Furthermore, a pressure support ventilation level associated with increased respiratory drive (3 ± 2 cm H2O) was tested against resting pressure support ventilation (12 ± 3 cm H2O), at clinical positive end-expiratory pressure. During all study phases, we measured, by electrical impedance tomography, the proportion of tidal ventilation reaching dependent and nondependent lung regions (Vt%dep and Vt%(nondep)), regional tidal volumes (Vt(dep) and Vt(nondep)), and antero-posterior ventilation homogeneity (Vt%nondep/Vt%dep). We also collected ventilation variables and arterial blood gases. Application of higher positive end-expiratory pressure levels increased Vt%dep and Vtdep values and decreased Vt%nondep/Vt%dep ratio, as compared with lower positive end-expiratory pressure (p < 0.01). Similarly, during lower pressure support ventilation, Vt%dep increased, Vtnondep decreased, and Vtdep did not change, likely indicating a higher efficiency of posterior diaphragm that led to decreased Vt%nondep/Vt%dep (p < 0.01). Finally, PaO2/FIO2 ratios correlated with Vt%dep during all study phases (p < 0.05). In patients with acute respiratory distress syndrome undergoing pressure support ventilation, higher positive end-expiratory pressure and lower support levels increase the fraction of tidal ventilation reaching dependent lung regions, yielding more homogeneous ventilation and, possibly, better ventilation/perfusion coupling.

Intraoperative Positive End-expiratory Pressure for Obese Patients: A Step Forward, a Long Road Still Ahead.

Pressure support ventilation in tetraplegia

Diaphragmatic electrical activity: a new tool to assess lung hyperinflation?

A 17-year-old boy with type I diabetes mellitus, was admitted to the intensive care unit with a 7-day history of right ankle contusion that progressed to erysipela, fasciitis and acute respiratory failure (septic embolic pneumonia – blood cultures positive to Staphylococcus aureus). Chest X-ray revealed bilateral infiltrates, the PaO2/FiO2 ratio was 150 and there was no evidence of pulmonary congestion. Vancomycin and surgical intervention were initiated and a thoracic computed tomography (CT) scan was performed right after the patient was intubated. The CT revealed gravity-dependent opacities and peribronchiolar patchy infiltrates. A stepwise recruitment maneuver (SRM) with high positive end expiratory pressure (PEEP) levels (25, 30, 35, 40 and 45 cmH2O) and a fixed pressure control level of 15 cmH2O was carried out at the Radiology suite, and the PEEP was titrated in order to keep the lung open and to minimize VILI. The CT scan showed that the lung opened with 45 cmH2O PEEP+15 cmH2O PCV (60 cmH2O total), and was kept open with 25 cmH2O PEEP; the PaO2/FiO2 ratio was >350. After 24 hours the PaO2/FiO2 ratio worsened and another SRM was performed; the PEEP increased to 29 cmH2O and the PaO2/FiO2 ratio increased to >350. The FiO2 was decreased to 30%, and after 96 hours the PEEP levels were progressively decreased and pressure support ventilation was initiated. After 10 days of intubation, the patient was weaned from mechanical ventilation and started on hyperbaric oxygen. After 3 days of extubation, the patient was breathing room air with SpO2 >95%. The CT scan showed that the SRM is important before increasing PEEP levels. PEEP levels must be set in order to prevent alveolar collapse according to the CT scan or PaO2/FiO2 ratio > 350, and it is important to initiate pressure support ventilation as soon as possible in order to prevent critical illness polyneuropathy. In this case we did not observe barotrauma, circulatory failure, ventilator-associated pneumonia, and the intensive care unit length of stay was 12 days. In this severe case of acute respiratory distress syndrome, the SRM with high PEEP levels and PEEP titration according to the CT scan and according to PaO2/FiO2 ratio > 350 was effective, and related to a better prognosis.

Additional work of breathing and breathing patterns in spontaneously breathing patients during pressure support ventilation, automatic tube compensation and amplified spontaneous pattern breathing

In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), mortality remains high. These patients require mechanical ventilation, which has been associated with ventilator-induced lung injury. High levels of positive end-expiratory pressure (PEEP) could reduce this condition and improve patient survival. This is an updated version of the review first published in 2013. To assess the benefits and harms of high versus low levels of PEEP in adults with ALI and ARDS. For our previous review, we searched databases from inception until 2013. For this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and the Web of Science from inception until May 2020. We also searched for ongoing trials (www.trialscentral.org; www.clinicaltrial.gov; www.controlled-trials.com), and we screened the reference lists of included studies. We included randomised controlled trials that compared high versus low levels of PEEP in ALI and ARDS participants who were intubated and mechanically ventilated in intensive care for at least 24 hours. Two review authors assessed risk of bias and extracted data independently. We contacted investigators to identify additional published and unpublished studies. We used standard methodological procedures expected by Cochrane. We included four new studies (1343 participants) in this review update. In total, we included 10 studies (3851 participants). We found evidence of risk of bias in six studies, and the remaining studies fulfilled all criteria for low risk of bias. In eight studies (3703 participants), a comparison was made between high and low levels of PEEP, with the same tidal volume in both groups. In the remaining two studies (148 participants), the tidal volume was different between high- and low-level groups. In the main analysis, we assessed mortality occurring before hospital discharge only in studies that compared high versus low PEEP, with the same tidal volume in both groups. Evidence suggests that high PEEP may result in little to no difference in mortality compared to low PEEP (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.04; I² = 15%; 7 studies, 3640 participants; moderate-certainty evidence). In addition, high PEEP may result in little to no difference in barotrauma (RR 1.00, 95% CI 0.64 to 1.57; I² = 63%; 9 studies, 3791 participants; low-certainty evidence). High PEEP may improve oxygenation in patients up to the first and third days of mechanical ventilation (first day: mean difference (MD) 51.03, 95% CI 35.86 to 66.20; I² = 85%; 6 studies, 2594 participants; low-certainty evidence; third day: MD 50.32, 95% CI 34.92 to 65.72; I² = 83%; 6 studies, 2309 participants; low-certainty evidence) and probably improves oxygenation up to the seventh day (MD 28.52, 95% CI 20.82 to 36.21; I² = 0%; 5 studies, 1611 participants; moderate-certainty evidence). Evidence suggests that high PEEP results in little to no difference in the number of ventilator-free days (MD 0.45, 95% CI -2.02 to 2.92; I² = 81%; 3 studies, 1654 participants; low-certainty evidence). Available data were insufficient to pool the evidence for length of stay in the intensive care unit. Moderate-certainty evidence shows that high levels compared to low levels of PEEP do not reduce mortality before hospital discharge. Low-certainty evidence suggests that high levels of PEEP result in little to no difference in the risk of barotrauma. Low-certainty evidence also suggests that high levels of PEEP improve oxygenation up to the first and third days of mechanical ventilation, and moderate-certainty evidence indicates that high levels of PEEP improve oxygenation up to the seventh day of mechanical ventilation. As in our previous review, we found clinical heterogeneity - mainly within participant characteristics and methods of titrating PEEP - that does not allow us to draw definitive conclusions regarding the use of high levels of PEEP in patients with ALI and ARDS. Further studies should aim to determine the appropriate method of using high levels of PEEP and the advantages and disadvantages associated with high levels of PEEP in different ARDS and ALI patient populations.

It is well-known that positive end-expiratory pressure (PEEP) can prevent ventilator-induced lung injury (VILI) and improve pulmonary physiology in animals with injured lungs. It's uncertain whether PEEP has similar effects in animals with uninjured lungs. A systematic review of randomized controlled trials (RCTs) comparing different PEEP levels in animals with uninjured lungs was performed. Trials in animals with injured lungs were excluded, as were trials that compared ventilation strategies that also differed with respect to other ventilation settings, e.g., tidal volume size. The search identified ten eligible trials in 284 animals, including rodents and small as well as large mammals. Duration of ventilation was highly variable, from 1 to 6 hours and tidal volume size varied from 7 to 60 mL/kg. PEEP ranged from 3 to 20 cmH2O, and from 0 to 5 cmH2O, in the 'high PEEP' or 'PEEP' arms, and in the 'low PEEP' or 'no PEEP' arms, respectively. Definitions used for lung injury were quite diverse, as were other outcome measures. The effects of PEEP, at any level, on lung injury was not straightforward, with some trials showing less injury with 'high PEEP' or 'PEEP' and other trials showing no benefit. In most trials, 'high PEEP' or 'PEEP' was associated with improved respiratory system compliance, and better oxygen parameters. However, 'high PEEP' or 'PEEP' was also associated with occurrence of hypotension, a reduction in cardiac output, or development of hyperlactatemia. There were no differences in mortality. The number of trials comparing 'high PEEP' or 'PEEP' with 'low PEEP' or 'no PEEP' in animals with uninjured lungs is limited, and results are difficult to compare. Based on findings of this systematic review it's uncertain whether PEEP, at any level, truly prevents lung injury, while most trials suggest potential harmful effects on the systemic circulation.

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.

BackgroundSpontaneous breathing efforts during mechanical ventilation are a widely accepted weaning approach for acute respiratory distress syndrome (ARDS) patients. These efforts can be too vigorous, possibly inflicting lung and diaphragm damage. Higher positive end expiratory pressure (PEEP) levels can be used to lower the magnitude of vigorous breathing efforts. Nevertheless, PEEP titrating tools are lacking in spontaneous mechanical ventilation (SMV). Therefore, the aim is to develop an electrical impedance tomography (EIT) algorithm for quantifying regional lung mechanics independent from a stable plateau pressure phase based on regional peak flow (RPF) by EIT, which is hypothetically applicable in SMV and to validate this algorithm in patients on controlled mechanical ventilation (CMV).MethodsThe RPF algorithm quantifies a cumulative overdistension (ODRPF) and collapse (CLRPF) rate and is validated in a prospective cohort of mechanically ventilated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients on CMV. ODRPF and CLRPF are compared with compliance-based cumulative overdistension (ODP500) and collapse (CLP500) rates from the Pulmovista 500 EIT device at multiple PEEP levels (PEEP 10 cmH2O to PEEP 24 cmH2O) in EIT measurements from CMV patients by linear mixed models, Bland-Altman analysis and intraclass correlation coefficient (ICC).ResultsSeventy-eight patients were included. Linear mixed models revealed an association between ODRPF and ODP500 of 1.02 (0.98–1.07, P<0.001) and between CLRPF and CLP500 of 0.93 (0.80–1.05, P<0.001). ICC values ranged from 0.78 to 0.86 (P<0.001) for ODRPF and ODP500 and from 0.70 to 0.85 (P<0.001) for CLRPF and CLP500 (PEEP 10 to PEEP 24). The mean bias between ODRPF and ODP500 in these PEEP levels ranged from 0.80% to 4.19% and from −1.31% to 0.13% between CLRPF and CLP500.ConclusionsA RPF approach for quantifying regional lung mechanics showed a moderate to good agreement in coronavirus disease 2019 (COVID-19) related ARDS patients on CMV compared to the compliance-based approach. This, in addition to being independent of a plateau pressure phase, indicates that the RPF approach is a valid method to explore for quantifying regional lung mechanics in SMV.

BackgroundThe driving pressure of the respiratory system is a valuable indicator of global lung stress during passive mechanical ventilation. Monitoring lung stress in assisted ventilation is indispensable, but achieving passive conditions in spontaneously breathing patients to measure driving pressure is challenging. The accuracy of the morphology of airway pressure (Paw) during end-inspiratory occlusion to assure passive conditions during pressure support ventilation has not been examined.MethodsRetrospective analysis of end-inspiratory occlusions obtained from critically ill patients during pressure support ventilation. Flow, airway, esophageal, gastric, and transdiaphragmatic pressures were analyzed. The rise of gastric pressure during occlusion with a constant/decreasing transdiaphragmatic pressure was used to identify and quantify the expiratory muscle activity. The Paw during occlusion was classified in three patterns, based on the differences at three pre-defined points after occlusion (0.3, 1, and 2 s): a “passive-like” decrease followed by plateau, a pattern with “clear plateau,” and an “irregular rise” pattern, which included all cases of late or continuous increase, with or without plateau.ResultsData from 40 patients and 227 occlusions were analyzed. Expiratory muscle activity during occlusion was identified in 79% of occlusions, and at all levels of assist. After classifying occlusions according to Paw pattern, expiratory muscle activity was identified in 52%, 67%, and 100% of cases of Paw of passive-like, clear plateau, or irregular rise pattern, respectively. The driving pressure was evaluated in the 133 occlusions having a passive-like or clear plateau pattern in Paw. An increase in gastric pressure was present in 46%, 62%, and 64% of cases at 0.3, 1, and 2 s, respectively, and it was greater than 2 cmH2O, in 10%, 20%, and 15% of cases at 0.3, 1, and 2 s, respectively.ConclusionsThe pattern of Paw during an end-inspiratory occlusion in pressure support cannot assure the absence of expiratory muscle activity and accurate measurement of driving pressure. Yet, because driving pressure can only be overestimated due to expiratory muscle contraction, in everyday practice, a low driving pressure indicates an absence of global lung over-stretch. A measurement of high driving pressure should prompt further diagnostic workup, such as a measurement of esophageal pressure.

Pursuing the Importance of Postoperative Atelectasis.

Objective To assess if the work of breath in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is affected by different extrinsic positive end-expiratory pressure (PEEPe) levels during (neurally adjusted ventilatory assist, NAVA). Methods From May 2012 to May 2013, 12 AECOPD patients who were admitted to the ICU of Nanjing Zhong-da hospital with an static intrinsic positive end-expiratory pressure (PEEPi_stat more than 5 cmH2O were enrolled in this study.The EFL group was defined as no increase in total-PEEP when we elevated PEEPe from 0 PEEPi_stat to 40% of PEEPi_stat and the Re group defined as the opposite. Being titrated to a level of Ramsay 3 sedation, 12 AECOPD patients were randomized to undergo pressure support ventilation (PSV) or NAVA with four different levels of PEEPe (0, 40%, 80%, 120% of PEEPi_stat). NAVA pressure limit was used to assure the equivalence of supporting pressure between NAVA and PSV. Air flow and airway pressure, esophageal pressure, and EAdi were continuously recorded.PTPes_ins and PTPes_tri at different PEEP levels in each group were calculated offline. We opted for comparison of measured parameters in the ventilation mode and PEEPe using repetitive measure analysis of variance. In NAVA or PSV mode, multiple comparison between different PEEPe level using SNK test. Results There were 6 patients in EFL group and 6 in Re group. we found no significant difference in patients age, acute physiology and chronic health evaluation II between these two groups.①The equivalence of NAVA with PSV: no significant difference was found in pressure-time wave, respiratory rate, peak airway pressure and mean airway pressure (t=0.720, 0.817, 0.621, 1.579, P>0.05).② Effects of NAVA on work of breath: at each PEEPe level, PTPes_ins was significantly lower in NAVA patients than in PSV patients (t=3.816, 3.117, 2.758, 2.572, P 0.05). ③Effects of PEEPe on work of triggering: at each PEEPe levels, PTPes_tri was significantly lower in NAVA patients than in PSV patients (t=4.624, 4.431, 4.165, 5.082, P 0.05). There was a PTPes decrease in EFL patients using PSV when PEEP was elevated, but not in RE patients. Conclusions NAVA significantly reduced work of breath and triggering in AECOPD patients compared with PSV. The work of triggering was not impacted by PEEPe in NAVA, while increased PEEPe may decrease triggering work in EFL patients with PSV. Key words: Extrinsie positive end-expiratory pressure; positive end-expiratory pressure; Work of breathing; Neurally adjusted ventilatory assist; Pressure support ventilation