Application Of Positive End-expiratory Pressure Research Articles

Adjustment of positive end-expiratory pressure to body mass index during mechanical ventilation in general anesthesia: BodyVent, a randomized controlled trial

BackgroundIn patients requiring general anesthesia, lung-protective ventilation can prevent postoperative pulmonary complications, which are associated with higher morbidity, mortality, and prolonged hospital stay. Application of positive end-expiratory pressure (PEEP) is one component of lung-protective ventilation. The correct strategy for setting adequate PEEP, however, remains controversial. PEEP settings that lead to a lower pressure difference between end-inspiratory plateau pressure and end-expiratory pressure (“driving pressure,” ΔP) may reduce the risk of postoperative pulmonary complications. Preliminary data suggests that the PEEP required to prevent both end-inspiratory overdistension and end-expiratory alveolar collapse, thereby reducing ΔP, correlates positively with the body mass index (BMI) of patients, with PEEP values corresponding to approximately 1/3 of patient’s respective BMI. Thus, we hypothesize that adjusting PEEP according to patient BMI reduces ΔP and may result in less postoperative pulmonary complications.MethodsPatients undergoing general anesthesia and endotracheal intubation with volume-controlled ventilation with a tidal volume of 7 ml per kg predicted body weight will be randomized and assigned to either an intervention group with PEEP adjusted according to BMI or a control group with a standardized PEEP of 5 mbar. Pre- and postoperatively, lung ultrasound will be performed to determine the lung aeration score, and hemodynamic and respiratory vital signs will be recorded for subsequent evaluation. The primary outcome is the difference in ΔP as a surrogate parameter for lung-protective ventilation. Secondary outcomes include change in lung aeration score, intraoperative occurrence of hemodynamic and respiratory events, oxygen requirements and postoperative pulmonary complications.DiscussionThe study results will show whether an intraoperative ventilation strategy with PEEP adjustment based on BMI has the potential of reducing the risk for postoperative pulmonary complications as an easy-to-implement intervention that does not require lengthy ventilator maneuvers nor additional equipment.Trial registrationGerman Clinical Trials Register (DRKS), DRKS00031336. Registered 21st February 2023.Trial statusThe study protocol was approved by the ethics committee of the Christian-Albrechts-Universität Kiel, Germany, on 1st February 2023. Recruitment began in March 2023 and is expected to end in September 2023.

Use of positive end‐expiratory pressure (20 cmH2O) for 60 s during elective heart surgery: A randomized clinical trial

AbstractBackgroundAlthough lung expansion therapy with positive end‐expiratory pressure (PEEP) following heart surgery is associated with positive clinical outcomes, whether such therapy can improve oxygenation and diminish the occurrence of lung complications when performed during heart surgery with extracorporeal circulation (ECC) is not yet clear.ObjectiveAnalyze the impact of lung expansion therapy with PEEP at 20 cmH2O for 60 s during elective heart surgery.MethodsA randomized clinical trial was conducted. The experimental group (EG) (n = 27) received PEEP at 20 cmH2O for 60 s during heart surgery at the moment in which ECC was ended. No intraoperative maneuver was performed in the control group (CG) (n = 15).ResultsThe incidence of atelectasis upon hospitalization and the pre‐maneuver oxygenation index (PaO2/FiO2) were similar between the groups. A lower incidence of atelectasis in the immediate postoperative period (7.4%, p = 0.03) and shorter time on noninvasive mechanical ventilation (TNIMV) (5.78 ± 2.54, p = 0.01) were found in the EG compared with the CG.ConclusionsThe application of PEEP at 20 cmH2O for 60 s during heart surgery reduces the incidence of atelectasis in the immediate postoperative period and shortens the TNIMV. This maneuver proved to be safe, with no adverse events.

Effects of positive end-expiratory pressure on intracranial pressure, cerebral perfusion pressure, and brain oxygenation in acute brain injury: Friend or foe? A scoping review

BackgroundPatients with acute brain injury (ABI) are a peculiar population because ABI does not only affect the brain but also other organs such as the lungs, as theorized in brain–lung crosstalk models. ABI patients often require mechanical ventilation (MV) to avoid the complications of impaired respiratory function that can follow ABI; MV should be settled with meticulousness owing to its effects on the intracranial compartment, especially regarding positive end-expiratory pressure (PEEP). This scoping review aimed to (1) describe the physiological basis and mechanisms related to the effects of PEEP in ABI; (2) examine how clinical research is conducted on this topic; (3) identify methods for setting PEEP in ABI; and (4) investigate the impact of the application of PEEP in ABI on the outcome. MethodsThe five-stage paradigm devised by Peters et al. and expanded by Arksey and O'Malley, Levac et al., and the Joanna Briggs Institute was used for methodology. We also adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension criteria. Inclusion criteria: we compiled all scientific data from peer-reviewed journals and studies that discussed the application of PEEP and its impact on intracranial pressure, cerebral perfusion pressure, and brain oxygenation in adult patients with ABI. Exclusion criteria: studies that only examined a pediatric patient group (those under the age of 18), experiments conducted solely on animals; studies without intracranial pressure and/or cerebral perfusion pressure determinations, and studies with incomplete information. Two authors searched and screened for inclusion in papers published up to July 2023 using the PubMed-indexed online database. Data were presented in narrative and tubular form. ResultsThe initial search yielded 330 references on the application of PEEP in ABI, of which 36 met our inclusion criteria. PEEP has recognized beneficial effects on gas exchange, but it produces hemodynamic changes that should be predicted to avoid undesired consequences on cerebral blood flow and intracranial pressure. Moreover, the elastic properties of the lungs influence the transmission of the forces applied by MV over the brain so they should be taken into consideration. Currently, there are no specific tools that can predict the effect of PEEP on the brain, but there is an established need for a comprehensive monitoring approach for these patients, acknowledging the etiology of ABI and the measurable variables to personalize MV. ConclusionPEEP can be safely used in patients with ABI to improve gas exchange keeping in mind its potentially harmful effects, which can be predicted with adequate monitoring supported by bedside non-invasive neuromonitoring tools.

Methods for determination of optimal positive end-expiratory pressure: a protocol for a scoping review

IntroductionTitrated application of positive end-expiratory pressure (PEEP) is an important part of any mechanical ventilation strategy. However, the method by which the optimal PEEP is determined and titrated varies widely....

Lack of Association between Diaphragm Thickening Fraction and Transdiaphragmatic Pressure Swing in COVID-19 Pneumonia during Helmet Continuous Positive Airway Pressure: Research Letter.

Recently, evaluation of the diaphragm by means of ultrasound has become popular.1 The increase in diaphragm thickness during inspiration (thickening fraction) has been proposed as a noninvasive bedside measure of diaphragm function,2,3 although previous studies have reported wide variability between thickening, inspiratory effort, and transdiaphragmatic pressure.4–6 We hypothesized that the force-length and force-generating relationship in the diaphragm is altered by different positive end-expiratory pressure (PEEP) levels in patients with SARS-CoV-2.7We investigated the relationship between diaphragm thickening fraction and transdiaphragmatic pressure swing during noninvasive helmet continuous positive airway pressure. From March to December 2021, a total of 26 consecutive patients with laboratory-confirmed SARS-CoV-2 infection admitted to the intensive care unit of Santa Chiara Hospital (Trento, Italy) were prospectively enrolled. The study was approved by the ethics committee (Rep. Int. 282/2022), and written informed consent was obtained. At intensive care unit admission, according to the local protocol, noninvasive respiratory assistance with helmet continuous positive airway pressure was started, and a nasogastric tube provided with two balloons for registering the esophageal and gastric pressures was inserted.8 Intragastric positioning of the tube was checked with standard methods; both balloons were inflated with manufacturer- recommended volume. Intragastric position of the lower balloon was confirmed by positive pressure deflections during gentle abdominal compressions; the mid-lower third esophageal position of the proximal balloon was confirmed by inspiratory negative deflections and the presence of cardiac artifacts. In vivo calibration of the filling volume was performed. Patients underwent a trial with three increasing levels of PEEP, lasting 30 min each. The first level was set at 0 cm H2O. PEEP was then increased to 5 and 10 cm H2O; fractional expired oxygen tension was left unchanged. An average of three measurements was made, with careful attention to select the same breaths for the diaphragm ultrasound and for esophageal/gastric pressure measurements. During the last 5 min of each step, esophageal and transdiaphragmatic pressure swing and diaphragmatic ultrasound were recorded. The right hemidiaphragm was identified in the zone of apposition as a three-layered structure by B-mode ultrasonography, with the probe at the mid-axillary line at the 10th intercostal space.1 Thickness was measured from frozen M-mode images as the distance from the pleural to the peritoneal line. All the examinations were performed by the same expert physician and recorded for a subsequent offline analysis.The study population had a median age of 67.5 [62.3–72.5 interquartile range] yr, 16 (61.5%) were male, body mass index was 27 [24–33 interquartile range] kg/m2, and Pao2/fractional expired oxygen tension ratio and Paco2 at admission were 122 [103–139 interquartile range] and 39 [37–44 interquartile range] mmHg, respectively. No association was found between diaphragm thickening fraction and transdiaphragmatic pressure swings or esophageal pressure swings, at 0 cm H2O, 5 cm H2O, and 10 cm H2O (fig. 1).In a previous investigation, Steinberg et al.9 found that neither thickening fraction nor diaphragmatic excursion was able to estimate esophageal pressure swings in patients with SARS-CoV-2. We sought to extend these findings by investigating the relationship between diaphragm ultrasound and the transdiaphragmatic pressure swing, which should be more representative of the contribution of the diaphragm to the total inspiratory effort. Similar to other authors,4 we confirm the lack of association between diaphragm thickening and the transdiaphragmatic pressure. Despite that it may lie on the nonlinear pressure–volume relationship of the diaphragm, during a single breath, the diaphragm inspiratory thickening and the transdiaphragmatic pressure generated depend on the specific pattern of thoracoabdominal motion (i.e., a descent of the diaphragm rather than expansion of the rib cage). The application of PEEP also causes changes in the diaphragm geometry also modifying the force generated by the diaphragm that may not be uniform across the muscle.The different position of the diaphragm muscle over its force or length relationship is likely explained by changes in end-expiratory lung volume during the PEEP trial. Although not directly measured, diaphragm dysfunction can also be a contributing factor; COVID-19 is associated with a viral myositis,10 which might have affected diaphragm force-generating capacity.However, the impact of the small sample size on any statistical inference must be considered, and the lack of Gilbert index and pressure-time product of diaphragmatic pressure calculation reduces the interpretation of our results.In summary, despite being promising for its feasibility and noninvasive characteristics, the assessment of diaphragm thickening should not be used as a surrogate for inspiratory effort. In SARS-CoV-2 patients during helmet continuous positive airway pressure in the acute setting, an increase in inspiratory effort, as measured by transdiaphragmatic pressure swings, is not related to diaphragm thickening fraction. We suggest caution against using this tool to inform clinical choices about respiratory support, at least until more robust data will be available.Support was provided solely from institutional and/or departmental sources.The authors declare no competing interests.

Effects of positive end-expiratory pressure on cerebral hemodynamics in acute brain injury patients.

Background: Cerebral autoregulation is the mechanism that allows to maintain the stability of cerebral blood flow despite changes in cerebral perfusion pressure. Maneuvers which increase intrathoracic pressure, such as the application of positive end-expiratory pressure (PEEP), have been always challenged in brain injured patients for the risk of increasing intracranial pressure (ICP) and altering autoregulation. The primary aim of this study is to assess the effect of PEEP increase (from 5 to 15cmH2O) on cerebral autoregulation. Secondary aims include the effect of PEEP increase on ICP and cerebral oxygenation. Material and Methods: Prospective, observational study including adult mechanically ventilated patients with acute brain injury requiring invasive ICP monitoring and undergoing multimodal neuromonitoring including ICP, cerebral perfusion pressure (CPP) and cerebral oxygenation parameters obtained with near-infrared spectroscopy (NIRS), and an index which expresses cerebral autoregulation (PRx). Additionally, values of arterial blood gases were analyzed at PEEP of 5 and 15cmH2O. Results are expressed as median (interquartile range). Results: Twenty-five patients were included in this study. The median age was 65years (46-73). PEEP increase from 5 to 15cmH2O did not lead to worsened autoregulation (PRx, from 0.17 (-0.003-0.28) to 0.18 (0.01-0.24), p = 0.83). Although ICP and CPP changed significantly (ICP: 11.11 (6.73-15.63) to 13.43 (6.8-16.87) mm Hg, p = 0.003, and CPP: 72.94 (59.19-84) to 66.22 (58.91-78.41) mm Hg, p = 0.004), these parameters did not reach clinically relevant levels. No significant changes in relevant cerebral oxygenation parameters were observed. Conclusion: Slow and gradual increases of PEEP did not alter cerebral autoregulation, ICP, CPP and cerebral oxygenation to levels triggering clinical interventions in acute brain injury patients.

One-Lung Ventilation and Postoperative Pulmonary Complications After Major Lung Resection Surgery. A Multicenter Randomized Controlled Trial

The effect of one-lung ventilation (OLV) strategy based on low tidal volume (TV), application of positive end-expiratory pressure (PEEP), and alveolar recruitment maneuvers (ARM) to reduce postoperative acute respiratory distress syndrome (ARDS) and pulmonary complications (PPCs) compared with higher TV without PEEP and ARM strategy in adult patients undergoing lobectomy or pneumonectomy has not been well established. Multicenter, randomized, single-blind, controlled trial. Sixteen Italian hospitals. A total of 880 patients undergoing elective major lung resection. Patients were randomized to receive lower tidal volume (LTV group: 4 mL/kg predicted body weight, PEEP of 5 cmH2O, and ARMs) or higher tidal volume (HTL group: 6 mL/kg predicted body weight, no PEEP, and no ARMs). After OLV, until extubation, both groups were ventilated using a tidal volume of 8 mL/kg and a PEEP value of 5 cmH2O. The primary outcome was the incidence of in-hospital ARDS. Secondary outcomes were the in-hospital rate of PPCs, major cardiovascular events, unplanned intensive care unit (ICU) admission, in-hospital mortality, ICU length of stay, and in-hospital length of stay. ARDS occurred in 3 of 438 patients (0.7%, 95% CI 0.1-2.0) and in 1 of 442 patients (0.2%, 95% CI 0-1.4) in the LTV and HTV group, respectively (Risk ratio: 3.03 95% CI 0.32-29, p=0.372). Pulmonary complications occurred in 125 of 438 patients (28.5%, 95% CI 24.5-32.9) and in 136 of 442 patients (30.8%, 95% CI 26.6-35.2) in the LTV and HTV group, respectively (risk ratio: 0.93, 95% CI 0.76-1.14, p=0.507). The incidence of major complications, in-hospital mortality, and unplanned ICU admission, ICU and in-hospital length of stay were comparable in both groups. In conclusion, among adult patients undergoing elective lung resection, an OLV with lower tidal volume, PEEP 5 cmH2O, and ARMs and a higher tidal volume strategy resulted in low ARDS incidence and comparable postoperative complications, in-hospital length of stay, and mortality.

The Effects of Positive End Expiratory Pressure and Lung Volume on Diaphragm Thickness and Thickening

Introduction: Diaphragm dysfunction is common in patients undergoing mechanical ventilation. The application of positive end-expiratory pressure (PEEP) and the varying end-expiratory lung volume cause changes in diaphragm geometry. We aimed to assess the impact of the level of PEEP and lung inflation on diaphragm thickness, thickening fraction and displacement. Methods: An observational study in a mixed medical and surgical ICU was conducted. The patients underwent a PEEP-titration trial with the application of three random levels of PEEP: 0 cmH2O (PEEP0), 8 cmH2O (PEEP8) and 15 cmH2O (PEEP15). At each step, the indices of respiratory effort were assessed, together with arterial blood and diaphragm ultrasound; end-expiratory lung volume was measured. Results: 14 patients were enrolled. The tidal volume, diaphragm displacement and thickening fraction were significantly lower with higher levels of PEEP, while both the expiratory and inspiratory thickness increased with higher PEEP levels. The inspiratory effort, as evaluated by the esophageal pressure swing, was unchanged. Both the diaphragm thickening fraction and displacement were significantly correlated with inspiratory effort in the whole dataset. For both measurements, the correlation was stronger at lower levels of PEEP. The difference in the diaphragm thickening fraction during tidal breathing between PEEP 15 and PEEP 0 was negatively related to the change in the functional residual capacity and the change in alveolar dead space. Conclusions: Different levels of PEEP significantly modified the diaphragmatic thickness and thickening fraction, showing a PEEP-induced decrease in the diaphragm contractile efficiency. When using ultrasound to assess diaphragm size and function, the potential effect of lung inflation should be taken into account.

Effects of positive end-expiratory pressure and oxygen concentration on non-hypoxemic apnea time during face mask ventilation of anesthesia induction: A randomized controlled trial.

Background: The optimal ventilatory strategy for the face mask ventilation during anesthesia induction is still unknow. Methods: We evaluated the effect of two positive end-expiratory pressure (PEEP) levels (0cmH2O and 6cmH2O) and two oxygen concentration levels (1.0 and .6) on non-hypoxemic apnea time during face mask ventilation of anesthesia induction. Sixty adult patients scheduled for elective surgery were enrolled in this study. The patients were randomized to receive anesthesia induction with four different ventilation strategy under volume-controlled ventilation. Patients assigned to the LOZP group received low fraction of inspiration O2 (FiO2 = .6) and 0 PEEP. Patients assigned to the LOHP group received low fraction of inspiration O2 (FiO2 = .6) and 6cmH2O PEEP. Patients assigned to the HOZP group received high fraction of inspiration O2 (FiO2 = 1.0) and 0 PEEP. Patients assigned to the HOHP group received high fraction of inspiration O2 (FiO2 = 1.0) and 6cmH2O PEEP. After 3min of ventilation, the patient was intubated but disconnected from the breathing circuit. Ventilation was not initiated until the pulse oximetry dropped to 90%. The primary outcome was non-hypoxemic apnea time defined as the time from cessation of ventilation to a pulse oximeter reading of 90%. The secondary outcome was the PaO2/FiO2 ratio immediately after ventilation. Results: The non-hypoxemic apnea time was significantly longer in the group of HOHP when compared to the other three groups (192s ± 70s, 221s ± 74s, 284s ± 101s, and 353s ± 85s in the LOZP, LOHP, HOZP, and HOHP group, respectively). The PaO2/FiO2 ratio immediately after ventilation was significantly higher in the group of LOHP when compared to the other three groups (LOZP 393 ± 130, LOHP 496 ± 97, HOZP 335 ± 58, HOHP 391 ± 50). When compared the PaO2/FiO2 ratio immediately after ventilation to its value before administration of anesthesia, the PaO2/FiO2 ratio in the group of LOHP was improved, the group LOZP and HOHP remained the same, while the group HOZP significantly decreased. Conclusion: Application of PEEP and 100% of oxygen during face mask ventilation of induction could maximize the non-hypoxemic apnea time. However, the use of PEEP and 60% of oxygen during preoxygenation resulted in improved PaO2/FiO2 ratio.

Individualized positive end-expiratory pressure guided by respiratory mechanics during anesthesia for the prevention of postoperative pulmonary complications: a systematic review and meta-analysis.

The optimization of positive end-expiratory pressure (PEEP) according to respiratory mechanics [driving pressure or respiratory system compliance (Crs)] is a simple and straightforward strategy. However, its validity to prevent postoperative pulmonary complications (PPCs) remains unclear. Here, we performed a meta-analysis to assess such efficacy. We searched PubMed, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) that compared personalized PEEP based on respiratory mechanics and constant PEEP to prevent PPCs in adults. The primary outcome was PPCs. Fourteen studies with 1105 patients were included. Compared with those who received constant PEEP, patients who received optimized PEEP exhibited a significant reduction in the incidence of PPCs (RR = 0.54, 95% CI 0.42 to 0.69). The results of commonly happened PPCs (pulmonary infections, hypoxemia, and atelectasis but not pleural effusion) also supported individualized PEEP group. Moreover, the application of PEEP based on respiratory mechanics improved intraoperative respiratory mechanics (driving pressure and Crs) and oxygenation. The PEEP titration method based on respiratory mechanics seems to work positively for lung protection in surgical patients undergoing general anesthesia.

The effect of positive end-expiratory pressure on intracranial pressure in obese and non-obese severe brain injury patients: a retrospective observational study

BackgroundThe effect of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) had never been studied in obese patients with severe brain injury (SBI). The main aim was to evaluate the effect of PEEP on ICP in SBI patients with mechanical ventilation according to obesity status.MethodsSBI patients admitted to the ICU with mechanical ventilation between 2014 and 2015 were included. Demographic, hemodynamic, arterial blood gas, and ventilator data at the time of the paired PEEP and ICP observations were recorded and compared between obese (body mass index ≥ 30 kg/m2) and non-obese SBI patients. Generalized estimating equation (GEE) model was used to assess the relationship between PEEP and ICP in obese and non-obese SBI patients, respectively.ResultsSix hundred twenty-seven SBI patients were included, 407 (65%) non-obese and 220 (35%) obese patients. A total of 30,415 paired PEEP and ICP observations were recorded in these patients, 19,566 (64.3%) for non-obese and 10,849 (35.7%) for obese. In the multivariable analysis, a statistically significant relationship between PEEP and ICP was found in obese SBI patients, but not in non-obese ones. For every cmH2O increase in PEEP, there was a 0.19 mmHg increase in ICP (95% CI [0.05, 0.33], P = 0.007) and a 0.15 mmHg decrease in CPP (95% CI [-0.29, -0.01], P = 0.036) in obese SBI patients after adjusting for confounders.ConclusionsThe results suggested that, contrary to non-obese SBI patients, the application of PEEP may produce an increase in ICP in obese SBI patients. However, the effect was modest and may be clinically inconsequential.

Optimization of protective lung ventilation in thoracic surgery

Background: Today protective ventilation is the predominant ventilation methodology. It includes the use of low tidal volume, inspiratory pressure limitation, and the application of positive end-expiratory pressure. However, several retrospective studies have shown that tidal volume, inspiratory pressure, and Positive End-Expiratory Pressure (PEEP) are not associated with patients’ treatment outcomes, but could be associated only when they influence driving pressure.Objective: Optimization of the strategy of protective one-lung ventilation under the control of driving pressure, to reduce early postoperative respiratory complications in patients operated for lung cancer.Material and methods: A prospective controlled study was conducted on 110 patients undergoing extended anatomical lung resections with subsequent comparison of clinical results depending on the level of driving pressure during one-lung ventilation. Postoperative pulmonary complications based on the Melbourne scale that appeared within 3 days after surgery became the endpoint.Results: A correlation was established between the level of driving pressure and the level of PaO2 in the intraoperative period – high inverse (r = – 0.901). The greatest value in the development of postoperative respiratory failure is driving pressure, exceeding 15 cm of water (Odds ratio = 18.25). In the first 3 days, postoperative pulmonary complications, determined by the Melbourne group scale, occurred in 9 (8.2%) patients in whom the driving pressure exceeded 15 cm of water, and in 3 patients (2.7%) with a driving pressure level less than 15 cm of water (p = 0.016).Conclusion: Driving pressure excess with values of more than 15 cm of water significantly increases the incidence of postoperative pulmonary complications. Fixed PEEP will be inappropriate both high and low, and individualized PEEP titrated by CStat may reduce driving pressure and become the next step in protective one-lung ventilation.

Electrical impedance tomography for titration of positive end-expiratory pressure in acute respiratory distress syndrome patients with chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) is one of most common comorbidities in acute respiratory distress syndrome (ARDS). There are few specific studies on the appropriate ventilation strategy for patients with ARDS comorbid with COPD, especially regarding on positive end-expiratory pressure (PEEP) titration.MethodsTo compare the respiratory mechanics in mechanical ventilated ARDS patients with or without COPD and to determine whether titration of PEEP based on electrical impedance tomography (EIT) is superior to the ARDSnet protocol. This is a single center, perspective, repeated measure study. ARDS patients requiring mechanical ventilation who were admitted to the intensive care unit between August 2017 and December 2020 were included. ARDS patients were divided according to whether they had COPD into a COPD group and a non-COPD group. Respiratory mechanics, gas exchange, and hemodynamics during ventilation were compared between the groups according to whether the PEEP level was titrated by EIT or the ARDSnet protocol.ResultsA total of twenty-seven ARDS patients including 14 comorbid with and 13 without COPD who met the study eligibility criteria were recruited. The PEEP levels titrated by EIT and the ARDSnet protocol were lower in the COPD group than in the non-COPD group (6.93 ± 1.69 cm H2O vs. 12.15 ± 2.40 cm H2O, P < 0.001 and 10.43 ± 1.20 cm H2O vs. 14.0 ± 3.0 cm H2O, P < 0.001, respectively). In the COPD group, the PEEP level titrated by EIT was lower than that titrated by the ARDSnet protocol (6.93 ± 1.69 cm H2O vs. 10.43 ± 1.20 cm H2O, P < 0.001), as was the global inhomogeneity (GI) index (0.397 ± 0.040 vs. 0.446 ± 0.052, P = 0.001), plateau airway pressure (16.50 ± 4.35 cm H2O vs. 20.93 ± 5.37 cm H2O, P = 0.001), dead space ventilation ratio (48.29 ± 6.78% vs. 55.14 ± 8.85%, P < 0.001), ventilation ratio (1.63 ± 0.33 vs. 1.87 ± 0.33, P < 0.001), and mechanical power (13.92 ± 2.18 J/min vs. 15.87 ± 2.53 J/min, P < 0.001). The cardiac index was higher when PEEP was treated by EIT than when it was titrated by the ARDSnet protocol (3.41 ± 0.50 L/min/m2 vs. 3.02 ± 0.43 L/min/m2, P < 0.001), as was oxygen delivery (466.40 ± 71.08 mL/min/m2 vs. 411.10 ± 69.71 mL/min/m2, P = 0.001).ConclusionTitrated PEEP levels were lower in patients with ARDS with COPD than in ARDS patients without COPD. In ARDS patient comorbid with COPD, application of PEEP titrated by EIT was lower than those titrated by the ARDSnet protocol, which contributed to improvements in the ventilation ratio, mechanical energy, cardiac index, and oxygen delivery with less of an adverse impact on hemodynamics.

Biological impact of restrictive and liberal fluid strategies at low and high PEEP levels on lung and distal organs in experimental acute respiratory distress syndrome.

Background: Fluid regimens in acute respiratory distress syndrome (ARDS) are conflicting. The amount of fluid and positive end-expiratory pressure (PEEP) level may interact leading to ventilator-induced lung injury (VILI). We therefore evaluated restrictive and liberal fluid strategies associated with low and high PEEP levels with regard to lung and kidney damage, as well as cardiorespiratory function in endotoxin-induced ARDS. Methods: Thirty male Wistar rats received an intratracheal instillation of Escherichia coli lipopolysaccharide. After 24h, the animals were anesthetized, protectively ventilated (VT = 6ml/kg), and randomized to restrictive (5ml/kg/h) or liberal (40ml/kg/h) fluid strategies (Ringer lactate). Both groups were then ventilated with PEEP = 3 cmH2O (PEEP3) and PEEP = 9 cmH2O (PEEP9) for 1h (n = 6/group). Echocardiography, arterial blood gases, and lung mechanics were evaluated throughout the experiments. Histologic analyses were done on the lungs, and molecular biology was assessed in lungs and kidneys using six non-ventilated animals with no fluid therapy. Results: In lungs, the liberal group showed increased transpulmonary plateau pressure compared with the restrictive group (liberal, 23.5 ± 2.9 cmH2O; restrictive, 18.8 ± 2.3cmH2O, p = 0.046) under PEEP = 9 cmH2O. Gene expression associated with inflammation (interleukin [IL]-6) was higher in the liberal-PEEP9 group than the liberal-PEEP3 group (p = 0.006) and restrictive-PEEP9 (p = 0.012), Regardless of the fluid strategy, lung mechanical power and the heterogeneity index were higher, whereas birefringence for claudin-4 and zonula-ocludens-1 gene expression were lower in the PEEP9 groups. Perivascular edema was higher in liberal groups, regardless of PEEP levels. Markers related to damage to epithelial cells [club cell secreted protein (CC16)] and the extracellular matrix (syndecan) were higher in the liberal-PEEP9 group than the liberal-PEEP3 group (p = 0.010 and p = 0.024, respectively). In kidneys, the expression of IL-6 and neutrophil gelatinase-associated lipocalin was higher in PEEP9 groups, regardless of the fluid strategy. For the liberal strategy, PEEP = 9 cmH2O compared with PEEP = 3 cmH2O reduced the right ventricle systolic volume (37%) and inferior vena cava collapsibility index (45%). Conclusion: The combination of a liberal fluid strategy and high PEEP led to more lung damage. The application of high PEEP, regardless of the fluid strategy, may also be deleterious to kidneys.

High PEEP Levels during CPR Improve Ventilation without Deleterious Haemodynamic Effects in Pigs.

Background: Invasive ventilation during cardiopulmonary resuscitation (CPR) is very complex due to unique thoracic pressure conditions. Current guidelines do not provide specific recommendations for ventilation during ongoing chest compressions regarding positive end-expiratory pressure (PEEP). This trial examines the cardiopulmonary effects of PEEP application during CPR. Methods: Forty-two German landrace pigs were anaesthetised, instrumented, and randomised into six intervention groups. Three PEEP levels (0, 8, and 16 mbar) were compared in high standard and ultralow tidal volume ventilation. After the induction of ventricular fibrillation, mechanical chest compressions and ventilation were initiated and maintained for thirty minutes. Blood gases, ventilation/perfusion ratio, and electrical impedance tomography loops were taken repeatedly. Ventilation pressures and haemodynamic parameters were measured continuously. Postmortem lung tissue damage was assessed using the diffuse alveolar damage (DAD) score. Statistical analyses were performed using SPSS, and p values <0.05 were considered significant. Results: The driving pressure (Pdrive) showed significantly lower values when using PEEP 16 mbar than when using PEEP 8 mbar (p = 0.045) or PEEP 0 mbar (p < 0.001) when adjusted for the ventilation mode. Substantially increased overall lung damage was detected in the PEEP 0 mbar group (vs. PEEP 8 mbar, p = 0.038; vs. PEEP 16 mbar, p = 0.009). No significant differences in mean arterial pressure could be detected. Conclusion: The use of PEEP during CPR seems beneficial because it optimises ventilation pressures and reduces lung damage without significantly compromising blood pressure. Further studies are needed to examine long-term effects in resuscitated animals.

Effect of positive end-expiratory pressure on central venous pressure in the closed and open thorax

Objective. The magnitude and mechanism of the rise of central venous pressure (CVP) after positive end-expiratory pressure (PEEP) among patients with cardiac disease is poorly understood. Therefore, the study aimed to compare the magnitude of change in CVP after PEEP in patients with TR (tricuspid regurgitation), high CVP, and high PCWP (pulmonary capillary wedge pressure) and in those with no TR, low CVP, and low PCWP. Additionally, we hypothesized that PEEP in the open thorax would also lead to a rise in CVP. Approach. This prospective, quasi-experimental study was conducted in patients undergoing cardiac surgery. Three consecutive readings of variables were obtained at 1 min intervals after PEEP (5 and 10 cm H2O) application in the closed and open thorax. Patients were stratified a priori into low CVP (<10 cm H2O) and high CVP (≥10 cm H2O), no TR and TR, and low PCWP (<15 mm Hg) and high PCWP (≥15 mm Hg) in the closed and open thorax. Main Results. Sixty-two patients were eligible for final analysis. The mean difference (MD) in ΔCVP (CVP10 cm H2O of PEEP—CVP zero end-expiratory pressure) was 2.33 ± 1.13 (95% CI, 2.04–2.62, P = 0.000) and 1.02 ± 0.77 (95% CI, 0.82–1.22, P = 0.000) in the closed and open thorax, respectively. The increase in CVP was higher among patients who had a lower CVP (2.64 ± 0.9 mm Hg versus 1.45 ± 1.17 mm Hg; p=0.000), in patients without TR (2.64 ± 0.97 mm Hg versus 2.14 ± 1.2 mm Hg, p=0.09) and in patients with a lower PCWP (2.4 ± 0.9 mm Hg versus 2.3 ± 1.4 mm Hg, p=0.67) at 10 cm H2O PEEP in the closed thorax. Significance. The rise in CVP was higher among patients without TR, low CVP, and low PCWP. Zero intrathoracic pressure in the open thorax did not abolish the effect of PEEP on CVP rise altogether.

The Influence of Positive End-Expiratory Pressure on Leakage and Oxygenation Using a Laryngeal Mask Airway: A Randomized Trial.

The value of positive end-expiratory pressure (PEEP) in maintaining oxygenation during ventilation with a laryngeal mask airway (LMA) mask is unclear. To clarify the potential benefit or harm to PEEP application during positive pressure ventilation with a ProSeal LMA® mask, we compared the effect of PEEP versus zero end-expiratory pressure (ZEEP) on gas leakage and oxygenation. We hypothesized that a PEEP of 8 mbar (8.2 cm H 2 O) would be associated with an increased incidence of gas leakage compared to ZEEP. We designed a prospective, controlled, randomized, single-blinded, multicenter clinical trial. Patients >18 years of age with an American Society of Anesthesiologists (ASA) physical status I/II without increased risk of aspiration were enrolled if they were scheduled for elective surgery under general anesthesia with an LMA mask. Patients were randomized to a control group managed with ZEEP or an intervention group managed with a PEEP of 8 mbar. Both groups received positive pressure ventilation. The primary end point was the occurrence of gas leakage. The Student t test and χ 2 test were used for statistical analysis. A total of 174 patients were enrolled in the ZEEP group, and 208 were enrolled in the PEEP group. The incidence of gas leakage did not differ between the 2 groups (ZEEP: 23/174, 13.2%; PEEP: 42/208, 20.2%; P = .071; odds ratio [OR], 1.611; 95% confidence interval [CI], 0.954-2.891). However, more patients required reseating of the LMA mask in the PEEP group (ZEEP: 5/174, 2.9%; PEEP: 18/208, 8.7%; P = .018; OR, 3.202; 95% CI, 1.164-8.812). The need for endotracheal intubation did not differ between groups (ZEEP: 2/174, 1.1%; PEEP: 7/208, 3.4%; P = .190; OR, 2.995; 95% CI, 0.614-14.608). After positive pressure ventilation for 25 minutes, the mean peripheral oxygen saturation (Sp o2 ) was higher in the PEEP than in the ZEEP group (98.5 [1.9]% vs 98.0 [1.4]%; P = .01). Peak inspiratory pressure (PIP; 16 [2] vs 12 [4] mbar; P < .001) and dynamic compliance (57 [14] vs 49 [14] mL/mbar; P < .001) were both higher in the PEEP group than in the ZEEP group. Use of PEEP did not affect the overall incidence of gas leakage. However, PEEP did result in a higher incidence of attempts to reseat the LMA mask compared to ZEEP, whereas the incidence of rescue intubation did not differ between groups. We concluded that a PEEP of 8 mbar did not increase overall gas leakage during positive pressure ventilation with an LMA mask, but it did slightly improve gas exchange and compliance. Overall, our study does not provide strong arguments for using PEEP during ventilation with an LMA mask in elective surgery.

Early Restrictive Fluid Strategy Impairs the Diaphragm Force in Lambs with Acute Respiratory Distress Syndrome.

The effect of fluid management strategies in critical illness-associated diaphragm weakness are unknown. This study hypothesized that a liberal fluid strategy induces diaphragm muscle fiber edema, leading to reduction in diaphragmatic force generation in the early phase of experimental pediatric acute respiratory distress syndrome in lambs. Nineteen mechanically ventilated female lambs (2 to 6 weeks old) with experimental pediatric acute respiratory distress syndrome were randomized to either a strict restrictive fluid strategy with norepinephrine or a liberal fluid strategy. The fluid strategies were maintained throughout a 6-h period of mechanical ventilation. Transdiaphragmatic pressure was measured under different levels of positive end-expiratory pressure (between 5 and 20 cm H2O). Furthermore, diaphragmatic microcirculation, histology, inflammation, and oxidative stress were studied. Transdiaphragmatic pressures decreased more in the restrictive group (-9.6 cm H2O [95% CI, -14.4 to -4.8]) compared to the liberal group (-0.8 cm H2O [95% CI, -5.8 to 4.3]) during the application of 5 cm H2O positive end-expiratory pressure (P = 0.016) and during the application of 10 cm H2O positive end-expiratory pressure (-10.3 cm H2O [95% CI, -15.2 to -5.4] vs. -2.8 cm H2O [95% CI, -8.0 to 2.3]; P = 0.041). In addition, diaphragmatic microvessel density was decreased in the restrictive group compared to the liberal group (34.0 crossings [25th to 75th percentile, 22.0 to 42.0] vs. 46.0 [25th to 75th percentile, 43.5 to 54.0]; P = 0.015). The application of positive end-expiratory pressure itself decreased the diaphragmatic force generation in a dose-related way; increasing positive end-expiratory pressure from 5 to 20 cm H2O reduced transdiaphragmatic pressures with 27.3% (17.3 cm H2O [95% CI, 14.0 to 20.5] at positive end-expiratory pressure 5 cm H2O vs. 12.6 cm H2O [95% CI, 9.2 to 15.9] at positive end-expiratory pressure 20 cm H2O; P < 0.0001). The diaphragmatic histology, markers for inflammation, and oxidative stress were similar between the groups. Early fluid restriction decreases the force-generating capacity of the diaphragm and diaphragmatic microcirculation in the acute phase of pediatric acute respiratory distress syndrome. In addition, the application of positive end-expiratory pressure decreases the force-generating capacity of the diaphragm in a dose-related way. These observations provide new insights into the mechanisms of critical illness-associated diaphragm weakness.

High-Flow Nasal Cannula Reduces Effort of Breathing But Not Consistently via Positive End-Expiratory Pressure

High-flow nasal cannula (HFNC) therapy reduces the effort of breathing in patients with bronchiolitis, but the mechanisms are not understood. Theorized mechanisms include dead space washout and positive end-expiratory pressure (PEEP) application. What are the mechanisms of action of HFNC therapy in patients with bronchiolitis? Prospective, single-center study of children 3 years of age or younger with bronchiolitis from January 2020 through March 2021. Flow was titrated between 0.5 and 2 L/kg/min. Electrical impedance tomography measured end-expiratory lung impedance (EELZ) change as an end-expiratory lung volume (EELV) change surrogate and change in tidal impedance difference (ΔZ) as a tidal volume (VT) surrogate. A subset showed manometry measuring esophageal pressure change (ΔPes; transpulmonary pressure surrogate) and pressure rate product (PRP; effort of breathing metric). We hypothesized that EELV and VT would not change and that effort would reduce via respiratory rate (not ΔPes). Measurements were reported as the difference from 0.5 L/kg/min. We studied 22 patients in total, 10 with esophageal manometry. Median EELZ increased by 0.36 arbitrary unit (AU), 2.42 AU, and 4.8 AU at 1 L/kg/min, 1.5 L/kg/min, and 2 L/kg/min (P= .01, 2 L/kg/min vs0.5 L/kg/min), which corresponded to a median increase in EELV of 1.8mL/kg between 0.5 and 2 L/kg/min. Seven patients showed an increase in EELZ of > 5 AU, 12 showed no change in EELZ (± 5 AU), and three showed a decrease in EELZ of > 5 AU. ΔZ (ie, VT) did not change from 0.5 L/kg/min to 2 L/kg/min (median change, 0.29 AU; P= .48). Median PRP decreased by 78cm H2O/min from 0.5 L/kg/min to 2 L/kg/min (P= .02), with all patients demonstrating a reduction in PRP, with a nonsignificant change in ΔPes (P= .68). Increasing HFNC in children with bronchiolitis reduces the effort of breathing, but no consistent increase occurs in end-expiratory lung volume and no significant change occurs in VT or transpulmonary pressure. This suggests that PEEP application is not the primary mechanism of action of HFNC in children with bronchiolitis.

Ultraprotective versus apneic ventilation in acute respiratory distress syndrome patients with extracorporeal membrane oxygenation: a physiological study

BackgroundEven an ultraprotective ventilation strategy in severe acute respiratory distress syndrome (ARDS) patients treated with extracorporeal membrane oxygenation (ECMO) might induce ventilator-induced lung injury and apneic ventilation with the sole application of positive end-expiratory pressure may, therefore, be an alternative ventilation strategy. We, therefore, compared the effects of ultraprotective ventilation with apneic ventilation on oxygenation, oxygen delivery, respiratory system mechanics, hemodynamics, strain, air distribution and recruitment of the lung parenchyma in ARDS patients with ECMO.MethodsIn a prospective, monocentric physiological study, 24 patients with severe ARDS managed with ECMO were ventilated using ultraprotective ventilation (tidal volume 3 ml/kg of predicted body weight) with a fraction of inspired oxygen (FiO2) of 21%, 50% and 90%. Patients were then treated with apneic ventilation with analogous FiO2. The primary endpoint was the effect of the ventilation strategy on oxygenation and oxygen delivery. The secondary endpoints were mechanical power, stress, regional air distribution, lung recruitment and the resulting strain, evaluated by chest computed tomography, associated with the application of PEEP (apneic ventilation) and/or low VT (ultraprotective ventilation).ResultsProtective ventilation, compared to apneic ventilation, improved oxygenation (arterial partial pressure of oxygen, p < 0.001 with FiO2 of 50% and 90%) and reduced cardiac output. Both ventilation strategies preserved oxygen delivery independent of the FiO2. Protective ventilation increased driving pressure, stress, strain, mechanical power, as well as induced additional recruitment in the non-dependent lung compared to apneic ventilation.ConclusionsIn patients with severe ARDS managed with ECMO, ultraprotective ventilation compared to apneic ventilation improved oxygenation, but increased stress, strain, and mechanical power. Apneic ventilation might be considered as one of the options in the initial phase of ECMO treatment in severe ARDS patients to facilitate lung rest and prevent ventilator-induced lung injury.Trial registration: German Clinical Trials Register (DRKS00013967). Registered 02/09/2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013967.