High Positive End-expiratory Pressure Group Research Articles

Meta-Analysis of Higher PEEP Strategies' Effects on Mortality Rates and Inflammatory Mediators in Patients with ARDS: A Perspective Review on Patients with Severe COVID-19-Associated ARDS

<strong>Background: </strong>Different strategies of positive end-expiratory pressure (PEEP) in mechanical ventilation are crucial for patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS). PEEP acts as a “double-edged sword” for ARDS patients. PEEP could recover pulmonary atelectasis but can induce alveolar hyperinflation.<p><strong>Objective: </strong>This review aimed to evaluate the effect of higher PEEP in patients with severe COVID-19-associated ARDS.</p><p><strong>Method: </strong>This meta-analysis included randomized controlled trial (RCT) studies to assess the mortality rates, barotrauma events, and inflammatory mediators modulation due to higher PEEP strategies. The pooled effect of the mortality rates and barotrauma events were presented as risk ratios (RR) with 95% confidence of interval (CI) using random-effects model (REM) or fixed-effects model (FEM).</p><p><strong>Results: </strong>We identified twelve RCTs comparing higher versus lower PEEP in ARDS patients. There was unsignificant result in overall mortality rates group [RR=0.94,95%CI(85,1.03),p=0.21] but not in mortality after positive response of oxygenation group [RR=0.88,95%CI(0.81,0.95),p=0.002] in higher PEEP group. In terms of patients without positive response of oxygenation, higher PEEP group had significantly higher mortality rates [RR=1.07,95%CI(1.00,1.15),p=0.06]. Higher PEEP significantly reduced the mortality rates in ARDS patients with PaO<sub>2</sub>/FiO<sub>2</sub><150 mmHg [RR=0.867,95%CI(0.74,1.00),p=0.04] instead of patients with moderate ARDS (PaO<sub>2</sub>/FiO<sub>2 </sub>≥150 mmHg) [RR=1.12, 95%CI(0.85,1.47), p=0.44]. There were no differences in overall barotrauma events [RR=1.03,95%CI(0.78,1.36),p=0.85] between higher and lower PEEP group. The use of higher and lower PEEP also contribute to the modulation of inflammatory mediators including TNF-α, IL-6, IL-1RA, and IL-8.</p><p><strong>Conclusion: </strong>Higher PEEP could reduce the mortality of patients with ARDS who responded to the oxygenation. Higher PEEP does not increase the risk of overall barotrauma events. Higher PEEP can modulate the inflammatory mediators.</p>

High versus low positive end-expiratory pressure setting in patients receiving veno-venous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome: study protocol for the multicentre, randomised ExPress SAVER Trial

IntroductionWhile limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted,...

Lung Ultrasound to Determine the Effect of Lower vs. Higher PEEP on Lung Aeration in Patients without ARDS—A Substudy of a Randomized Clinical Trial

Background: Ventilation with lower positive end–expiratory pressure (PEEP) may cause loss of lung aeration in critically ill invasively ventilated patients. This study investigated whether a systematic lung ultrasound (LUS) scoring system can detect such changes in lung aeration in a study comparing lower versus higher PEEP in invasively ventilated patients without acute respiratory distress syndrome (ARDS). Methods: Single center substudy of a national, multicenter, randomized clinical trial comparing lower versus higher PEEP ventilation strategy. Fifty–seven patients underwent a systematic 12–region LUS examination within 12 h and between 24 to 48 h after start of invasive ventilation, according to randomization. The primary endpoint was a change in the global LUS aeration score, where a higher value indicates a greater impairment in lung aeration. Results: Thirty–three and twenty–four patients received ventilation with lower PEEP (median PEEP 1 (0–5) cm H2O) or higher PEEP (median PEEP 8 (8–8) cm H2O), respectively. Median global LUS aeration scores within 12 h and between 24 and 48 h were 8 (4 to 14) and 9 (4 to 12) (difference 1 (–2 to 3)) in the lower PEEP group, and 7 (2–11) and 6 (1–12) (difference 0 (–2 to 3)) in the higher PEEP group. Neither differences in changes over time nor differences in absolute scores reached statistical significance. Conclusions: In this substudy of a randomized clinical trial comparing lower PEEP versus higher PEEP in patients without ARDS, LUS was unable to detect changes in lung aeration.

Effects of Individualised High Positive End-Expiratory Pressure and Crystalloid Administration on Postoperative Pulmonary Function in Patients Undergoing Robotic-Assisted Radical Prostatectomy: A Prospective Randomised Single-Blinded Pilot Study

Robotic-assisted laparoscopic prostatectomy (RALP) is typically conducted in steep Trendelenburg position (STP). The aim of the study was to evaluate whether crystalloid administration and individual management of positive end-expiratory pressure (PEEP) improve peri- and post-operative pulmonary function in patients undergoing RALP. Prospective randomised single-centre single-blinded explorative study. Patients were either allocated to a standard PEEP (5 cmH2O) group or an individualised high PEEP group. Furthermore, each group was divided into a liberal and a restrictive crystalloid group (8 vs. 4 mL/kg/h predicted body weight). Individualised PEEP levels were determined by means of preoperative recruitment manoeuvre and PEEP titration in STP. Informed consent was obtained from 98 patients scheduled for elective RALP. The following intraoperative parameters were analysed in each of the four study groups: ventilation setting (peak inspiratory pressure [PIP], plateau pressure, driving pressure [Pdriv], lung compliance [LC] and mechanical power [MP]) and postoperative pulmonary function (bed-side spirometry). The spirometric parameters Tiffeneau index (FEV1/FVC ratio) and mean forced expiratory flow (FEF25-75) were measured pre- and post-operatively. Data are shown as mean ± standard deviation (SD), and groups were compared with ANOVA. A p-value of <0.05 was considered significant. The two individualised high PEEP groups (mean PEEP 15.5 [±1.71 cmH2O]) showed intraoperative significantly higher PIP, plateau pressure and MP levels but significantly decreased Pdriv and increased LC. On the first and second postoperative day, patients with individualised high PEEP levels had a significantly higher mean Tiffeneau index and FEF25-75. Perioperative oxygenation and ventilation and postoperative spirometric parameters were not influenced by restrictive or liberal crystalloid infusion in either of the two respective PEEP groups. Individualised high PEEP levels (≥14 cmH2O) during RALP improved intraoperative blood oxygenation and resulted in more lung-protective ventilation. Furthermore, postoperative pulmonary function was improved for up to 48 h after surgery in the sum of the two individualised high PEEP groups. Restrictive crystalloid infusion during RALP seemed to have no effect on peri- and post-operative oxygenation and pulmonary function.

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.

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.

Optimal Positive End Expiratory Pressure Levels in Ventilated Patients Without Acute Respiratory Distress Syndrome: A Bayesian Network Meta-Analysis and Systematic Review of Randomized Controlled Trials

Background: To find the optimal positive end expiratory pressure (PEEP) in mechanical ventilated patients without Acute Respiratory Distress Syndrome (ARDS), we conducted a Bayesian network meta-analysis and systematic review of randomized controlled trials (RCTs) comparing different level of PEEP based on a novel classification of PEEP level: ZEEP group (PEEP = 0 cm H2O); lower PEEP group (PEEP = 1–6 cm H2O); intermediate PEEP group (PEEP = 7–10 cm H2O); higher PEEP group (PEEP > 10 cm H2O).Result: Twenty eight eligible studies with 2,712 patients were included. There were no significant differences in the duration of mechanical ventilation between higher and intermediate PEEP (MD: 0.020, 95% CI: −0.14, 0.28), higher and lower PEEP (MD: −0.010, 95% CI: −0.23, 0.22), higher PEEP and ZEEP (MD: 0.010, 95% CI: −0.40, 0.22), intermediate and lower PEEP (MD: −0.040, 95% CI: −0.18, 0.040), intermediate PEEP and ZEEP (MD: −0.010, 95% CI: −0.42, 0.10), lower PEEP and ZEEP (MD: 0.020, 95% CI: −0.32, 0.13), respectively. Higher PEEP was associated with significantly higher PaO2/FiO2 ratio(PFR) when compared to ZEEP (MD: 73.24, 95% CI: 11.03, 130.7), and higher incidence of pneumothorax when compared to intermediate PEEP, lower PEEP and ZEEP (OR: 2.91e + 12, 95% CI: 40.3, 1.76e + 39; OR: 1.85e + 12, 95% CI: 29.2, 1.18e + 39; and OR: 1.44e + 12, 95% CI: 16.9, 8.70e + 38, respectively). There was no association between PEEP levels and other secondary outcomes.Conclusion: We identified higher PEEP was associated with significantly higher PFR and higher incidence of pneumothorax. Nonetheless, in terms of other outcomes, no significant differences were detected among four levels of PEEP.Systematic Review Registration: The study had registered on an international prospective register of systematic reviews, PROSPERO, on 09 April 2021, identifier: [CRD42021241745].

Effect of positive end-expiratory pressure value on change in end-tidal carbon dioxide as a predictor of fluid responsiveness in Patients Undergoing Passive Leg Raising Maneuver

Abstract Identification of patients’ fluid status in the emergency room should be made before giving fluid therapy. This study aimed to determine the effect of positive end-expiratory pressure on change in end-tidal carbon dioxide during passive leg raising maneuver to predict fluid responsiveness. Thirty subjects aged 18-65 years in the resuscitation room, all on the ventilator, were divided into three groups according to their positive end-expiratory pressure value: low (0-5 cmH2O), moderate (6-10 cmH2O), and high (&gt;10 cmH2O). Every subject underwent passive leg raising to simulate fluid administration. Values of blood pressure, heart rate, cardiac output, and end-tidal carbon dioxide were recorded before and after the maneuver. Analysis of the three groups found a significant correlation between change in end-tidal carbon dioxide with a cut-off value of 5% and 1 mmHg with fluid responsiveness of subjects in the low (p = 0.028) and moderate (p = 0.013) but not in the high positive end-expiratory pressure group (p = 0.333). In conclusion, change in end-tidal carbon dioxide in mechanically ventilated patients undergoing passive leg raising maneuvers can be used as a predictor of fluid responsiveness, but this method cannot be used on patients with high positive end-expiratory pressure (&gt; 10 cmH2O) Keywords : change in end tidal carbon dioxide, fluid responsiveness, positive end-expiratory pressure, passive leg raising, cardiac output surrogateCorrespondence : lutfithe13th@gmail.com

Association of early positive end-expiratory pressure settings with ventilator-free days in patients with coronavirus disease 2019 acute respiratory distress syndrome: A secondary analysis of the Practice of VENTilation in COVID-19 study.

BACKGROUNDThere is uncertainty about how much positive end-expiratory pressure (PEEP) should be used in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19).OBJECTIVETo investigate whether a higher PEEP strategy is superior to a lower PEEP strategy regarding the number of ventilator-free days (VFDs).DESIGNMulticentre observational study conducted from 1 March to 1 June 2020.SETTING AND PATIENTSTwenty-two ICUs in The Netherlands and 933 invasively ventilated COVID-19 ARDS patients.INTERVENTIONSPatients were categorised retrospectively as having received invasive ventilation with higher (n=259) or lower PEEP (n=674), based on the high and low PEEP/FiO2 tables of the ARDS Network, and using ventilator settings and parameters in the first hour of invasive ventilation, and every 8 h thereafter at fixed time points during the first four calendar days. We also used propensity score matching to control for observed confounding factors that might influence outcomes.MAIN OUTCOMES AND MEASURESThe primary outcome was the number of VFDs. Secondary outcomes included distant organ failures including acute kidney injury (AKI) and use of renal replacement therapy (RRT), and mortality.RESULTSIn the unmatched cohort, the higher PEEP strategy had no association with the median [IQR] number of VFDs (2.0 [0.0 to 15.0] vs. 0.0 [0.0 to 16.0] days). The median (95% confidence interval) difference was 0.21 (−3.34 to 3.78) days, P = 0.905. In the matched cohort, the higher PEEP group had an association with a lower median number of VFDs (0.0 [0.0 to 14.0] vs. 6.0 [0.0 to 17.0] days) a median difference of −4.65 (−8.92 to −0.39) days, P = 0.032. The higher PEEP strategy had associations with higher incidence of AKI (in the matched cohort) and more use of RRT (in the unmatched and matched cohorts). The higher PEEP strategy had no association with mortality.CONCLUSIONIn COVID-19 ARDS, use of higher PEEP may be associated with a lower number of VFDs, and may increase the incidence of AKI and need for RRT.TRIAL REGISTRATIONPractice of VENTilation in COVID-19 is registered at ClinicalTrials.gov, NCT04346342.

Effect of different levels of PEEP on mortality in ICU patients without acute respiratory distress syndrome: systematic review and meta-analysis with trial sequential analysis.

ObjectiveTo determine whether higher positive end- expiratory pressure (PEEP) could provide a survival advantage for patients without acute respiratory distress syndrome (ARDS) compared with lower PEEP.MethodsEligible studies were identified through searches of Embase, Cochrane Library, Web of Science, Medline, and Wanfang database from inception up to 1 June 2021. Trial sequential analysis (TSA) was used in this meta-analysis.Data synthesisTwenty-seven randomized controlled trials (RCTs) were identified for further evaluation. Higher and lower PEEP arms included 1330 patients and 1650 patients, respectively. A mean level of 9.6±3.4 cmH2O was applied in the higher PEEP groups and 1.9±2.6 cmH2O was used in the lower PEEP groups. Higher PEEP, compared with lower PEEP, was not associated with reduction of all-cause mortality (RR 1.03; 95% CI 0.91–1.18; P =0.627), and 28-day mortality (RR 1.07 ; 95% CI 0.92–1.24; P =0.365). In terms of risk of ARDS (RR 0.43; 95% CI 0.24–0.78; P =0.005), duration of intensive care unit (MD -1.04; 95%CI-1.36 to −0.73; P < 0.00001), and oxygenation (MD 40.30; 95%CI 0.94 to 79.65; P = 0.045), higher PEEP was superior to lower PEEP. Besides, the pooled analysis showed no significant differences between groups both in the duration of mechanical ventilation (MD 0.00; 95%CI-0.13 to 0.13; P = 0.996) and hospital stay (MD -0.66; 95%CI-1.94 to 0.61; P = 0.309). More importantly, lower PEEP did not increase the risk of pneumonia, atelectasis, barotrauma, hypoxemia, or hypotension among patients compared with higher PEEP. The TSA analysis showed that the results of all-cause mortality and 28-day mortality might be false-negative results.ConclusionsOur results suggest that a lower PEEP ventilation strategy was non-inferior to a higher PEEP ventilation strategy in ICU patients without ARDS, with no increased risk of all-cause mortality and 28-day mortality. Further high-quality RCTs should be performed to confirm these findings.

Effect of a Lower vs Higher Positive End-Expiratory Pressure Strategy on Ventilator-Free Days in ICU Patients Without ARDS

It is uncertain whether invasive ventilation can use lower positive end-expiratory pressure (PEEP) in critically ill patients without acute respiratory distress syndrome (ARDS). To determine whether a lower PEEP strategy is noninferior to a higher PEEP strategy regarding duration of mechanical ventilation at 28 days. Noninferiority randomized clinical trial conducted from October 26, 2017, through December 17, 2019, in 8 intensive care units (ICUs) in the Netherlands among 980 patients without ARDS expected not to be extubated within 24 hours after start of ventilation. Final follow-up was conducted in March 2020. Participants were randomized to receive invasive ventilation using either lower PEEP, consisting of the lowest PEEP level between 0 and 5 cm H2O (n = 476), or higher PEEP, consisting of a PEEP level of 8 cm H2O (n = 493). The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for the difference in ventilator-free days at day 28 of -10%. Secondary outcomes included ICU and hospital lengths of stay; ICU, hospital, and 28- and 90-day mortality; development of ARDS, pneumonia, pneumothorax, severe atelectasis, severe hypoxemia, or need for rescue therapies for hypoxemia; and days with use of vasopressors or sedation. Among 980 patients who were randomized, 969 (99%) completed the trial (median age, 66 [interquartile range {IQR}, 56-74] years; 246 [36%] women). At day 28, 476 patients in the lower PEEP group had a median of 18 ventilator-free days (IQR, 0-27 days) and 493 patients in the higher PEEP group had a median of 17 ventilator-free days (IQR, 0-27 days) (mean ratio, 1.04; 95% CI, 0.95-∞; P = .007 for noninferiority), and the lower boundary of the 95% CI was within the noninferiority margin. Occurrence of severe hypoxemia was 20.6% vs 17.6% (risk ratio, 1.17; 95% CI, 0.90-1.51; P = .99) and need for rescue strategy was 19.7% vs 14.6% (risk ratio, 1.35; 95% CI, 1.02-1.79; adjusted P = .54) in patients in the lower and higher PEEP groups, respectively. Mortality at 28 days was 38.4% vs 42.0% (hazard ratio, 0.89; 95% CI, 0.73-1.09; P = .99) in patients in the lower and higher PEEP groups, respectively. There were no statistically significant differences in other secondary outcomes. Among patients in the ICU without ARDS who were expected not to be extubated within 24 hours, a lower PEEP strategy was noninferior to a higher PEEP strategy with regard to the number of ventilator-free days at day 28. These findings support the use of lower PEEP in patients without ARDS. ClinicalTrials.gov Identifier: NCT03167580.

Distribution of Ventilation in Pneumoperitoneum: Comment.

We read with great interest a very informative and well-conducted study by Shono et al. titled “Positive End-expiratory Pressure and Distribution of Ventilation in Pneumoperitoneum Combined with Steep Trendelenburg Position” published in the Journal.1 The study has objectively shown that application of positive end-expiratory pressure (PEEP) of 15 cm H2O resulted in more homogeneous ventilation and favorable pulmonary physiologic effects during robot-assisted laparoscopic prostatectomy, but did not improve postoperative lung function. Whereas that authors have focused on the beneficial pulmonary effects of high PEEP values, the article would benefit readers considerably if the authors could address its potential ill effects on some other organ systems.In this regard we wish to highlight our concern regarding application of high PEEP on intracranial pressure (ICP) in patients given a steep Trendelenberg position. It is known that ICP rises rapidly with pneumoperitoneum and this increase is more pronounced due to the effects of gravity in patients assuming the head-down Trendelenburg position.2,3 Increased intraabdominal pressure displaces the diaphragm cranially, narrowing the inferior vena cava and decreasing venous return which, in turn, increases the ICP.3 The high intrathoracic pressures due to positive pressure ventilation and high intraabdominal pressure due to pneumoperitoneum cause a triple compartment syndrome because of an increase in ICP. In susceptible populations such as patients with head injuries or patients who have undiagnosed intracranial pathology, neurologic deterioration could be a concern. Clinically, even minor adverse effects of raised ICP may present in different ways.4 In a study by Cooke et al., headache and nausea were found to be significantly higher after laparoscopic abdominal surgery, possibly due to raised ICP.4Shono et al. have reported that phenylephrine requirement in the high PEEP group was significantly greater than in the normal PEEP group. For maintenance of cerebral perfusion pressure, a higher mean arterial pressure should have been targeted in view of the raised ICP. The authors have reported a raised arterial carbon dioxide of 49 ± 5 mm Hg which may also have detrimental effect on the ICP. Adjusting the respiratory rate to normalize the end tidal carbon dioxide could have been considered in the study design. In susceptible individuals, surgeries lasting 484 ± 81 min with a persistently high ICP resulting from a high PEEP of 15 cm H2O could result in a greater incidence of complications. These complications should be investigated before we can recommend universal application of a high PEEP in all patients. Prospective authors planning similar studies could consider adding incidence of adverse effects on ICP or intraocular pressure as one of their secondary objectives; otherwise, they could include these concerns as limitations of their study.The authors declare no competing interests.

Comparison of low and high positive end-expiratory pressure during low tidal volume ventilation

Editor, We read with interest the article ‘Comparison of low and high positive end-expiratory pressure during low tidal volume ventilation in robotic gynaecological surgical patients using electrical impedance tomography’ by Chun et al.1 The finding that a low positive end-expiratory pressure (PEEP) level may be sufficient in the selected study group is not surprising considering that the study population was quite young and without overweight people (mean BMI 22.4 and 23.4 kg m−2 in the two groups, respectively). Thus, the study population likely consisted of individuals with high lung elasticity and little tendency for airway closure. There was no difference between the two study groups in arterial blood gases or the widely recognised oxygenation index PaO2/FiO2. However, the authors report a significant difference between groups in the obscure oxygenation index called ‘oxygenation factor’. This factor is derived from calculating PaO2/(FiO2 x MPAW), where MPAW is the mean airway pressure, and has been found to be inversely correlated to the degree of intrapulmonary shunting.2 As the authors found a significant higher oxygenation factor in the low PEEP group compared with the high PEEP group, they suggest that a ‘PEEP of 4 cmH2O might be better for ventilation strategy in consideration of intrapulmonary shunt’.1 Several objections may be raised in regard to this proposition, apart from the fact that the oxygenation factor appears to be a post hoc analysis. First, the oxygenation factor was validated treating postoperative patients with PEEP following cardiac surgery.2 In contrast, Chun et al.1 prophylactically and randomly assigned healthy patients with no preceding impact on lung physiology to two different PEEP levels. Second, we find it very unlikely that the intrapulmonary shunt would be less with PEEP of 4 cmH2O than with PEEP 8 cmH2O.3 How could that possibly be physiologically explained when the intrapulmonary shunt primarily correlates with the amount of atelectatic lung tissue? In our opinion, the effect on the oxygenation factor is simply a mathematical consequence of the different levels of PEEP. We welcome the study by Chen et al.,1 as it adds further knowledge regarding intra-operative ventilation of the healthy and normal-weight patient. However, the discussion regarding optimal PEEP during general anaesthesia is already complex and confusing. We therefore believe it is important to be careful when discussing the physiological mechanisms and possible further implications from this study, not to add further confusion. Acknowledgements relating to this article Assistance with the letter: none. Financial support and sponsorship: none. Conflicts of interest: none.

Does Iso-mechanical Power Lead to Iso-lung Damage?: An Experimental Study in a Porcine Model.

Excessive tidal volume, respiratory rate, and positive end-expiratory pressure (PEEP) are all potential causes of ventilator-induced lung injury, and all contribute to a single variable: the mechanical power. The authors aimed to determine whether high tidal volume or high respiratory rate or high PEEP at iso-mechanical power produce similar or different ventilator-induced lung injury. Three ventilatory strategies-high tidal volume (twice baseline functional residual capacity), high respiratory rate (40 bpm), and high PEEP (25 cm H2O)-were each applied at two levels of mechanical power (15 and 30 J/min) for 48 h in six groups of seven healthy female piglets (weight: 24.2 ± 2.0 kg, mean ± SD). At iso-mechanical power, the high tidal volume groups immediately and sharply increased plateau, driving pressure, stress, and strain, which all further deteriorated with time. In high respiratory rate groups, they changed minimally at the beginning, but steadily increased during the 48 h. In contrast, after a sudden huge increase, they decreased with time in the high PEEP groups. End-experiment specific lung elastance was 6.5 ± 1.7 cm H2O in high tidal volume groups, 10.1 ± 3.9 cm H2O in high respiratory rate groups, and 4.5 ± 0.9 cm H2O in high PEEP groups. Functional residual capacity decreased and extravascular lung water increased similarly in these three categories. Lung weight, wet-to-dry ratio, and histologic scores were similar, regardless of ventilatory strategies and power levels. However, the alveolar edema score was higher in the low power groups. High PEEP had the greatest impact on hemodynamics, leading to increased need for fluids. Adverse events (early mortality and pneumothorax) also occurred more frequently in the high PEEP groups. Different ventilatory strategies, delivered at iso-power, led to similar anatomical lung injury. The different systemic consequences of high PEEP underline that ventilator-induced lung injury must be evaluated in the context of the whole body.

Effects of Intrathoracic Pressure changes on Diaphragmatic Blood Flow during Mechanical Ventilation

IntroductionAlthough mechanical ventilation (MV) is a life‐saving intervention, prolonged MV can lead to deleterious effects on diaphragm function, such as ventilator‐induced diaphragmatic dysfunction (VIDD) and vascular incompetence. Specifically, prolonged MV elicits time‐dependent reductions in diaphragm blood flow, induces vascular dysfunction, and limits the hyperemic response to contractions associated with weaning. During MV, positive‐end expiratory pressure (PEEP) is used to maintain small airway patency and mitigate alveolar damage; yet increased intrathoracic pressure with high levels of PEEP may impair diaphragm perfusion.PurposeTo test the following hypotheses: 1) Diaphragm blood flow during MV will be less with high vs. low‐peep, and 2) ablation of intrathoracic pressures (via pneumothorax (PTX)) will not alter diaphragm blood flow during MV vs. the low‐peep condition.MethodsFemale Sprague‐Dawley rats (~5 mo) were randomly divided into low PEEP (LP; 1cmH2O, n=7) or high PEEP (HP; 9 cmH2O, n=6) groups during mechanical ventilation. Blood flow, via the fluorescent microsphere technique, was determined during spontaneous breathing (SB) and 10 minutes after intubation and the onset of MV with LP or HP. Thereafter, for a third determination of diaphragm blood flow, the LP group underwent a surgical laparotomy (LAP; to determine effects of intrabdominal pressure on perfusion) and the HP group was subjected to a pneumothorax (PTX), with microsphere infusions occurring 10 minutes after the completion of surgery. Following the final fluorescent microsphere infusion, tissues were harvested for blood flow analysis. The diaphragm was sectioned into costal (ventral, medial, and dorsal) and crural portions to determine diaphragmatic blood flow distribution.ResultsCompared to SB, both LP and HP MV significantly reduced diaphragm medial costal blood flow (LP, 61.9 ± 7.5 vs 43.8 ± 4.9; HP, 46.2 ± 7.7 vs 21.8 ± 3.7 mL/100g/min; P≤0.05). HP MV significantly reduced blood flow to the ventral and medial costal diaphragm compared to LP MV (P≤0.05). In the HP MV+PTX condition, medial and dorsal costal blood flow was significantly increased versus HP MV (P≤0.05). LP MV + LAP did not significantly increase diaphragm blood flow compared to LP MV. Diaphragm perfusion during HP MV+PTX and LP MV were not different (P&gt;0.05).ConclusionThis study demonstrates that HP MV reduces diaphragmatic blood flow to a greater extent than LP MV. Following a PTX in the HP MV condition, diaphragmatic blood flow is not different compared to the LP MV condition, suggesting that the reductions in diaphragmatic blood flow with LP MV are independent of intrathoracic pressure changes, and due likely to diaphragm quiescence.Support or Funding InformationSupported by: NIH HL137156‐01A1

Positive End-expiratory Pressure and Distribution of Ventilation in Pneumoperitoneum Combined with Steep Trendelenburg Position.

Pneumoperitoneum and a steep Trendelenburg position during robot-assisted laparoscopic prostatectomy have been demonstrated to promote a cranial shift of the diaphragm and the formation of atelectasis in the dorsal parts of the lungs. However, neither an impact of higher positive end-expiratory pressure (PEEP) on preserving the ventilation in the dorsal region nor its physiologic effects have been fully examined. The authors hypothesized that PEEP of 15 cm H2O during robot-assisted laparoscopic prostatectomy might maintain ventilation in the dorsal parts and thus improve lung mechanics. In this randomized controlled study, 48 patients undergoing robot-assisted laparoscopic prostatectomy were included in the analysis. Patients were assigned to the conventional PEEP (5 cm H2O) group or the high PEEP (15 cm H2O) group. Regional ventilation was monitored using electrical impedance tomography before and after the establishment of pneumoperitoneum and 20° Trendelenburg position during the surgery. The primary endpoint was the regional ventilation in the dorsal parts of the lungs while the secondary endpoints were lung mechanics and postoperative lung function. Compared to that in the conventional PEEP group, the fraction of regional ventilation in the most dorsal region was significantly higher in the high PEEP group during pneumoperitoneum and Trendelenburg position (mean values at 20 min after taking Trendelenburg position: conventional PEEP, 5.5 ± 3.9%; high PEEP, 9.9 ± 4.7%; difference, -4.5%; 95% CI, -7.4 to -1.6%; P = 0.004). Concurrently, lower driving pressure (conventional PEEP, 14.9 ± 2.5 cm H2O; high PEEP, 11.5 ± 2.8 cm H2O; P < 0.001), higher lung dynamic compliance, and better oxygenation were demonstrated in the high PEEP group. Postoperative lung function did not differ between the groups. Application of a PEEP of 15 cm H2O resulted in more homogeneous ventilation and favorable physiologic effects during robot-assisted laparoscopic prostatectomy but did not improve postoperative lung function.

Higher PEEP improves outcomes in ARDS patients with clinically objective positive oxygenation response to PEEP: a systematic review and meta-analysis

BackgroundMortality in patients with acute respiratory distress syndrome (ARDS) remains high. These patients require mechanical ventilation strategies that include high positive end-expiratory pressure (PEEP). It remains controversial whether high PEEP can improve outcomes for ARDS patients, especially patients who show improvement in oxygenation in response to PEEP. In this meta-analysis, we aimed to evaluate the effects of high PEEP on ARDS patients.MethodsWe electronically searched randomized controlled trials (RCTs) reported in the MEDLINE, CENTRAL, EMBASE, CINAHL and Web of Science databases from January 1990 to December 2017. Meta-analyses of the effects of PEEP on survival in adults with ARDS were conducted using the methods recommended by the Cochrane Collaboration.ResultsA total of 3612 patients from nine randomized controlled trials (RCTs) were included. There were 1794 and 1818 patients in the high and low PEEP groups, respectively. Hospital mortality showed no significant difference between the high and low PEEP groups (RR = 0.92; 95% CI, 0.79 to 1.07; P = 0.26). Similar results were found for 28-d mortality (RR = 0.88; 95% CI, 0.72 to 1.07; P = 0.19) and ICU mortality (RR = 0.83; 95% CI, 0.65 to 1.07; P = 0.15). The risk of clinically objectified barotrauma was not significantly different between the high and low PEEP groups (RR = 1.24; 95% CI, 0.74 to 2.09, P = 0.41). In the subgroup of ARDS patients who responded to increased PEEP by improved oxygenation (from 6 RCTs), high PEEP significantly reduced hospital mortality (RR = 0.83; 95% CI 0.69 to 0.98; P = 0.03), ICU mortality (RR = 0.74; 95% CI, 0.56 to 0.98; P = 0.04),but the 28-d mortality was not decreased(RR = 0.83; 95% CI, 0.67 to 1.01; P = 0.07). For ARDS patients in the low PEEP group who received a PEEP level lower than 10 cmH2O (from 6 RCTs), ICU mortality was lower in the high PEEP group than the low PEEP group (RR = 0.65; 95% CI, 0.45 to 0.94; P = 0.02).ConclusionsFor ARDS patients who responded to increased PEEP by improved oxygenation, high PEEP could reduce hospital mortality, ICU mortality and 28-d mortality. High PEEP does not increase the risk of clinically objectified barotrauma.

Respiratory effects of low versus high tidal volume with or without positive end-expiratory pressure in anesthetized dogs with healthy lungs

OBJECTIVE To evaluate the impact of 2 tidal volumes (TVs) with or without positive end-expiratory pressure (PEEP) on lung mechanics, aeration, and gas exchange in healthy anesthetized dogs. ANIMALS 40 mixed-breed dogs with healthy lungs. PROCEDURES Anesthetized dogs were randomly assigned to 4 groups (n = 10/group) with different ventilatory settings: TV of 8 mL/kg and PEEP of 0 cm H2O (low TV group), TV of 8 mL/kg and PEEP of 5 cm H2O (low TV plus PEEP group), TV of 15 mL/kg and PEEP of 0 cm H2O (high TV group), or TV of 15 mL/kg and PEEP of 5 cm H2O (high TV plus PEEP group). Expired CO2 and respiratory rate were titrated on the basis of a predetermined stepwise protocol. Gas exchange, respiratory mechanics, and pulmonary aeration were evaluated by means of CT 30 minutes after starting mechanical ventilation at the assigned setting. RESULTS Partial pressures of arterial and expired CO2 were higher in the low TV and low TV plus PEEP groups than in the high TV and high TV plus PEEP groups. Peak and plateau airway pressures were higher in the PEEP group than in the other groups. Static lung compliance was higher in the high TV plus PEEP group than in the low TV group. Relative percentages of atelectatic and poorly aerated lung were lower in the high TV plus PEEP group than in the other groups. Oxygenation was similar among groups. CONCLUSIONS AND CLINICAL RELEVANCE Differences in TV and PEEP application during mechanical ventilation may affect respiratory function in anesthetized dogs with healthy lungs. Ventilation with a TV of 15 mL/kg and PEEP of 5 cm H2O significantly improved lung compliance and reduced the amount of atelectatic and poorly aerated lung.

Higher PEEP versus Lower PEEP Strategies for Patients with Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis.

Higher positive end-expiratory pressure (PEEP) levels may reduce atelectrauma, but increase over-distention lung injury. Whether higher PEEP improves clinical outcomes among patients with acute respiratory distress syndrome (ARDS) is unclear. To compare clinical outcomes of mechanical ventilation strategies using higher PEEP levels versus lower PEEP strategies in patients with ARDS. We performed a systematic review and meta-analysis of clinical trials investigating mechanical ventilation strategies using higher versus lower PEEP levels. We used random effects models to evaluate the effect of higher PEEP on 28-day mortality, organ failure, ventilator-free days, barotrauma, oxygenation, and ventilation. We identified eight randomized trials comparing higher versus lower PEEP strategies, enrolling 2,728 patients with ARDS. Patients were 55 (±16) (mean ± SD) years old and 61% were men. Mean PEEP in the higher PEEP groups was 15.1 (±3.6) cm H2O as compared with 9.1 (±2.7) cm H2O in the lower PEEP groups. Primary analysis excluding two trials that did not use lower Vt ventilation in the lower PEEP control groups did not demonstrate significantly reduced mortality for patients receiving higher PEEP as compared with a lower PEEP (six trials; 2,580 patients; relative risk, 0.91; 95% confidence interval [CI] = 0.80-1.03). A higher PEEP strategy also did not significantly decrease barotrauma, new organ failure, or ventilator-free days when compared with a lower PEEP strategy (moderate-level evidence). Quality of evidence for primary analyses was downgraded for precision, as CIs of outcomes included estimates that would result in divergent recommendations for use of higher PEEP. Secondary analysis, including trials that did not use low Vt in low-PEEP control groups, showed significant mortality reduction for high-PEEP strategies (eight trials; 2,728 patients; relative risk, 0.84; 95% CI = 0.71-0.99), with greater mortality benefit observed for high PEEP in trials that did not use lower Vts in the low-PEEP control group (P = 0.02). Analyses stratifying by use of recruitment maneuvers (P for interaction = 0.69), or use of physiological targets to set PEEP versus PEEP/FiO2 tables (P for interaction = 0.13), did not show significant effect modification. Use of higher PEEP is unlikely to improve clinical outcomes among unselected patients with ARDS.

Lung Rest During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure-Practice Variations and Outcomes.

Describe practice variations in ventilator strategies used for lung rest during extracorporeal membrane oxygenation for respiratory failure in neonates, and assess the potential impact of various lung rest strategies on the duration of extracorporeal membrane oxygenation and the duration of mechanical ventilation after decannulation. Retrospective cohort analysis from the Extracorporeal Life Support Organization registry database during the years 2008-2013. All extracorporeal membrane oxygenation runs for infants less than or equal to 30 days of life for pulmonary reasons were included. Ventilator type and ventilator settings used for lung rest at 24 hours after extracorporeal membrane oxygenation initiation were obtained. A total of 3,040 cases met inclusion criteria. Conventional mechanical ventilation was used for lung rest in 88% of cases and high frequency ventilation was used in 12%. In the conventional mechanical ventilation group, 32% used positive end-expiratory pressure strategy of 4-6 cm H2O (low), 22% used 7-9 cm H2O (mid), and 43% used 10-12 cm H2O (high). High frequency ventilation was associated with an increased mean (SEM) hours of extracorporeal membrane oxygenation (150.2 [0.05] vs 125 [0.02]; p < 0.001) and an increased mean (SEM) hours of mechanical ventilation after decannulation (135 [0.09] vs 100.2 [0.03]; p = 0.002), compared with conventional mechanical ventilation among survivors. Within the conventional mechanical ventilation group, use of higher positive end-expiratory pressure was associated with a decreased mean (SEM) hours of extracorporeal membrane oxygenation (high vs low: 136 [1.06] vs 156 [1.06], p = 0.001; mid vs low: 141 [1.06] vs 156 [1.06]; p = 0.04) but increased duration of mechanical ventilation after decannulation in the high positive end-expiratory pressure group compared with low positive end-expiratory pressure (p = 0.04) among survivors. Wide practice variation exists with regard to ventilator settings used for lung rest during neonatal respiratory extracorporeal membrane oxygenation. Use of high frequency ventilation when compared with conventional mechanical ventilation and use of low positive end-expiratory pressure strategy when compared with mid positive end-expiratory pressure and high positive end-expiratory pressure strategy is associated with longer duration of extracorporeal membrane oxygenation. Further research to provide evidence to drive optimization of pulmonary management during neonatal respiratory extracorporeal membrane oxygenation is warranted.