Species-specific effects of positive end-expiratory pressure (PEEP) on diaphragm and chest wall geometry in mice, rats and humans

Acute Renal Failure and Mechanical Ventilation: Reality or Myth?

To examine the circulatory and respiratory effects of extrinsic positive end-expiratory pressure (PEEPe) in patients with chronic obstructive pulmonary disease (COPD) and dynamic hyperinflation during controlled mechanical ventilation. Different levels of PEEPe were applied randomly in mechanically ventilated patients with COPD and dynamic hyperinflation. Respiratory Intensive Care Unit of a University Hospital. 9 patients with acute respiratory failure and dynamic hyperinflation due to acute exacerbation of COPD. PEEPe 35%, 58% and 86% of intrinsic PEEP (PEEPi) were applied. Using flow-directed pulmonary artery catheters hemodynamic measurements were obtained, while simultaneously lung volumes, airflows and airway pressures were recorded. In order to estimate alveolar pressures (Palv), rapid airway occlusions during passive expiration were also performed. At no level of PEEPe were significant changes in cardiac output, gas exchange variables, dead space, airways inflation resistances and respiratory system static end-inspiratory compliance observed. At high level of PEEPe central venous, mean pulmonary arterial and pulmonary capillary wedge pressures were increased significantly. All but one patient were flow-limited during passive expiration. PEEPe 86% of PEEPi caused a significant increase in end-expiratory lung volume and total PEEP. Iso-volume pressure-flow curves showed volume-dependence expiratory flow limitation in 2 patients, while in 8 patients volume-dependence of critical driving pressure (Palv-mouth pressure) that decreased flows was also observed. The effects of PEEPe on iso-volume flow and hence on lung mechanics and hemodynamics, depend on many factors, such as airways resistances, lung volumes and airway characteristics, making the patient response to PEEPe unpredictable.

BackgroundSurgery for severe scoliosis (SS) is usually performed in the prone position. Changes in respiratory mechanics related to position and positive end expiratory pressure (PEEP) titration during anesthesia of SS are understudied.We aimed to investigate the effect of prone position and PEEP on the respiratory mechanics of scoliotic children undergoing spine surgery.MethodsProspective, crossover study performed in two pediatric hospitals (Montevideo, Uruguay-Centro Hospitalario Pereira Rossell- and Milano, Italy-Vittore Buzzi Children’s Hospital). Shortly after intubation, pulmonary mechanics measurements were performed using inspiratory and expiratory breath holds during volume-controlled ventilation with a set tidal volume (TV) of 8 ml/kg and a respiratory rate adjusted to maintain normocapnia. Measurements of peak (PIP), plateau (PPLAT) and total PEEP (tPEEP) were obtained at three levels of applied PEEP: 0 (ZEEP), 5, and 10 cmH2O both in supine (baseline) and prone positions. Driving pressure (∆P: PPLAT–tPEEP) was calculated to obtain static respiratory system compliance (Crs: TV/∆P). Crs and pressures were analyzed using a mixed linear regression model with a random subject effect in their relationship with position and PEEP.ResultsSixty-nine patients were enrolled. Crs was negatively associated with Cobb angle in all the cohorts. Only in secondary scoliosis, it was positively associated with body mass index. Crs was also negatively correlated with the prone position and positively correlated with increasing PEEP levels. The interaction between PEEP and position was studied and showed no significance.ConclusionsCrs is influenced by the severity of scoliosis and the nutritional status during spine surgery. The addition of PEEP improves Crs and reduces ∆P in the supine position, but both worsen in the prone position. These changes can be related to the effects of position on chest wall compliance.

Objective To investigate the effect of positive end expiratory pressure (PEEP) on intra-abdominal pressure (IAP) in critical patients with different pulmonary diseases. Methods 72 critical patients undergoing mechanical ventilation (MV) were enrolled in this study in Intensive Care Unit from January 2012 to December 2016. According to their lung lesions, the patients was divided into three groups: chronic obstructive pulmonary disease (COPD) group, acute respiratory distress syndrome (ARDS) group, and normal group, 24 cases in each group. IAP, lung compliance (CL), total compliance (CT), and thoracic compliance (CTH) were obtained with a horizontal position under different PEEP conditions of 0, 3 ,6, 9,12, and 15 cmH2O (1 cmH2O = 0.098 kPa). The relationship between IAP and PEEP, CL, CT, and CTH were analyzed. Results The effect of PEEP on IAP in critical patients with different pulmonary diseases: ARDS group < normal group < COPD group (P<0.05). Lung compliance in each group: ARDS group < normal group < COPD group (P<0.05). Positive correlation was found between IAP and PEEP (r=0.92, P<0.01). There were closed correlation between IAP and CL, CT, CTH (r=0.83, 0.64, -0.56; P<0.05). Conclusion There are major differences in the effect of PEEP on IAP among the patients with different pulmonary diseases. The effect is related to the lung compliance. Key words: Intra-abdominal pressure; Positive end expiratory pressure; Lung compliance

Background and Aims: Positive end-expiratory pressure (PEEP) is routinely applied in mechanically ventilated patients to improve gas exchange and respiratory mechanics by increasing end-expiratory lung volume. In a recent study in rats, we demonstrated that PEEP causes diaphragm remodeling, especially longitudinal muscle atrophy. The effects of PEEP on the human diaphragm are unknown. Our aim was to investigate the acute in vivo effects of PEEP on human diaphragm geometry and function, as this is a prerequisite for diaphragm remodeling. Methods: Healthy volunteers (n=19) were non-invasively ventilated with PEEP 2, 5, 10 and 15 cmH2O. MRI was performed to investigate PEEP-induced changes in diaphragm geometry. Subjects were instrumented with nasogastric catheters to measure diaphragm neuromechanical efficiency at different PEEP levels. To confirm findings of healthy subjects, dynamic diaphragm MRI was performed in an invasively ventilated patient. Results: Increasing PEEP from 2 to 15 cmH2O resulted in a caudal diaphragm displacement (19 [14-26] mm, P Conclusion: PEEP leads to a caudal displacement of the diaphragm with concomitant muscle shortening and thickening in the zones of apposition, leading to a reduction in diaphragm contractile function. These findings suggest that conditions required to develop longitudinal atrophy in the human diaphragm are present with the application of PEEP.

BackgroundIn acute respiratory distress syndrome (ARDS) patients, it has recently been proposed to set positive end-expiratory pressure (PEEP) by targeting end-expiratory transpulmonary pressure. This approach, which relies on the measurement of absolute esophageal pressure (Pes), has been used in supine position (SP) and has not been investigated in prone position (PP). Our purposes were to assess Pes-guided strategy to set PEEP in SP and in PP as compared with a PEEP/FIO2 table and to explore the early (1 h) and late (16 h) effects of PP on lung and chest wall mechanics.ResultsWe performed a prospective, physiologic study in two ICUs in university hospitals on ARDS patients with PaO2/FIO2 < 150 mmHg. End-expiratory Pes (Pes,ee) was measured in static (zero flow) condition. Patients received PEEP set according to a PEEP/FIO2 table then according to the Pes-guided strategy targeting a positive (3 ± 2 cmH2O) static end-expiratory transpulmonary pressure in SP. Then, patients were turned to PP and received same amount of PEEP from PEEP/FIO2 table then Pes-guided strategy. Respiratory mechanics, oxygenation and end-expiratory lung volume (EELV) were measured after 1 h of each PEEP in each position. For the rest of the 16-h PP session, patients were randomly allocated to either PEEP strategy with measurements done at the end. Thirty-eight ARDS patients (27 male), mean ± SD age 63 ± 13 years, were included. There were 33 primary ARDS and 26 moderate ARDS. PaO2/FIO2 ratio was 120 ± 23 mmHg. At same PEEP/FIO2 table-related PEEP, Pes,ee averaged 9 ± 4 cmH2O in both SP and PP (P = 0.88). With PEEP/FIO2 table and Pes-guided strategy, PEEP was 10 ± 2 versus 12 ± 4 cmH2O in SP and 10 ± 2 versus 12 ± 5 cmH2O in PP (PEEP strategy effect P = 0.05, position effect P = 0.96, interaction P = 0.96). With the Pes-guided strategy, chest wall elastance increased regardless of position. Lung elastance and transpulmonary driving pressure decreased in PP, with no effect of PEEP strategy. Both PP and Pes-guided strategy improved oxygenation without interaction. EELV did not change with PEEP strategy. At the end of PP session, respiratory mechanics did not vary but EELV and PaO2/FIO2 increased while PaCO2 decreased.ConclusionsThere was no impact of PP on Pes measurements. PP had an immediate improvement effect on lung mechanics and a late lung recruitment effect independent of PEEP strategy.

In this study, we examined whether (1) positive end-expiratory pressure (PEEP) has a protective effect on the risk of major postoperative respiratory complications in a cohort of patients undergoing major abdominal surgeries and craniotomies, and (2) the effect of PEEP is differed by surgery type. Protective mechanical ventilation with lower tidal volumes and PEEP reduces compounded postoperative complications after abdominal surgery. However, data regarding the use of intraoperative PEEP is conflicting. In this observational study, we included 5915 major abdominal surgery patients and 5063 craniotomy patients. Analysis was performed using multivariable logistic regression. The primary outcome was a composite of major postoperative respiratory complications (respiratory failure, reintubation, pulmonary edema, and pneumonia) within 3 days of surgery. Within the entire study population (major abdominal surgeries and craniotomies), we found an association between application of PEEP ≥5 cmH2O and a decreased risk of postoperative respiratory complications compared with PEEP <5 cmH2O. Application of PEEP >5 cmH2O was associated with a significant lower odds of respiratory complications in patients undergoing major abdominal surgery (odds ratio 0.53, 95% confidence interval 0.39 - 0.72), effects that translated to deceased hospital length of stay [median hospital length of stay : 6 days (4-9 days), incidence rate ratios for each additional day: 0.91 (0.84 - 0.98)], whereas PEEP >5 cmH2O was not significantly associated with reduced odds of respiratory complications or hospital length of stay in patients undergoing craniotomy. The protective effects of PEEP are procedure specific with meaningful effects observed in patients undergoing major abdominal surgery. Our data suggest that default mechanical ventilator settings should include PEEP of 5-10 cmH2O during major abdominal surgery.

Previous studies suggest that positive end expiratory pressure (PEEP) promotes aeration of the preterm lung. The role of tidal volume has been less clear. We aimed to study the effects of different PEEPs (0, 5, 8 and 10 cm H2O) and VTs (4, 8, and 12 mL/kg) on the establishment of functional residual capacity (FRC). 27d preterm rabbit pups (equivalent to a surfactant deficient extremely preterm infant) were anaesthetised and surgically intubated. Volume targeted intermittent positive pressure ventilation (IPPV) was provided at each permutations of the above PEEPs and VTs. The primary outcome was FRC after 160 inflations, measured by plethysmography. Secondary outcomes included static compliance and homogeneity of tidal ventilation assessed using synchrotron based techniques (Spring8, Japan). Mean (SE) FRC and static compliance after 160 inflations are shown below: Table Linear regression of both FRC and compliance was statistically significant against both VT and PEEP separately (p≤0.01). No pup developed a pneumothorax. Video imaging demonstrates more homogeneous tidal ventilation in pups with better established FRC. PEEP and VT both played a role in the establishment of FRC in fully ventilated infants. Future studies should assess which strategies promote aeration at birth whilst minimising lung injury.

Fluid Balance: Another Variable to Consider with Diaphragm Dysfunction?

Recent reports have suggested that positive end-expiratory pressure (PEEP) depresses left ventricular (LV) function or shifts LV pressure-volume (PV) relationships due to neural, humoral, or mechanical events. These studies have usually utilized pressures measured during expiration. To study the mechanical effects of PEEP in expiration and inspiration, the circulation was arrested in 12 open-chest dogs, and the coronaries were perfused with a cold cardioplegic agent. Balloons were placed in the ventricles to measure ventricular pressures. Shifts in cardiopulmonary blood volume were prevented by venting the atria to atmosphere. Having ablated neural reflexes and humoral changes, we varied ventricular volumes, chest wall compliance, tidal volume, and PEEP. We found that isovolumic ventricular pressures (relative to atmosphere) increase with PEEP (P less than 0.001), and heart-lung interaction with PEEP is significantly greater in inspiration (P less than 0.001). The effect of PEEP is modified by heart volume (P less than 0.01) and respiratory system compliance (P less than 0.01). We conclude that a mechanical compressive force can be applied to the heart by the lungs as they expand, and this may explain the previous reports of diminished LV function or LV diastolic compliance with PEEP and, in part, explain the decreased cardiac output associated with PEEP. The marked increase in mechanical compressive forces applied to the heart during inspiration with PEEP may have far greater hemodynamic consequences than events during expiration.

Lung aeration at birth

BackgroundA large proportion of patients with a SARS-Cov-2-associated respiratory failure develop an acute respiratory distress syndrome (ARDS). It has been recently suggested that SARS-Cov-2-associated ARDS may differ from usual non-SARS-Cov-2-associated ARDS by higher respiratory system compliance (CRS), lower potential for recruitment with positive end-expiratory pressure (PEEP) contrasting with severe shunt fraction. The purpose of the study was to systematically assess respiratory mechanics and recruitability in SARS-Cov-2-associated ARDS.MethodsGas exchanges, CRS and hemodynamics were assessed at 2 levels of PEEP (15 cmH2O and 5 cmH2O) within 36 h (day1) and from 4 to 6 days (day 5) after intubation. The recruited volume was computed as the difference between the volume expired from PEEP 15 to 5 cmH2O and the volume predicted by compliance at PEEP 5 cmH2O (or above airway opening pressure). The recruitment-to-inflation (R/I) ratio (i.e. the ratio between the recruited lung compliance and CRS at PEEP 5 cmH2O) was used to assess lung recruitability. A R/I ratio value higher than or equal to 0.5 was used to define highly recruitable patients.ResultsThe R/I ratio was calculated in 25 of the 26 enrolled patients at day 1 and in 15 patients at day 5. At day 1, 16 (64%) were considered as highly recruitable (R/I ratio median [interquartile range] 0.7 [0.55–0.94]) and 9 (36%) were considered as poorly recruitable (R/I ratio 0.41 [0.31–0.48]). The PaO2/FiO2 ratio at PEEP 15 cmH2O was higher compared to PEEP 5 cmH2O only in highly recruitable patients (173 [139–236] vs 135 [89–167] mmHg; p < 0.01). Neither PaO2/FiO2 or CRS measured at PEEP 15 cmH2O or at PEEP 5 cmH2O nor changes in PaO2/FiO2 or CRS in response to PEEP changes allowed to identify highly or poorly recruitable patients.ConclusionIn this series of 25 patients with SARS-Cov-2 associated ARDS, 64% were considered as highly recruitable and only 36% as poorly recruitable based on the R/I ratio performed on the day of intubation. This observation suggests that a systematic R/I ratio assessment may help to guide initial PEEP titration to limit harmful effect of unnecessary high PEEP in the context of Covid-19 crisis.

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

Background: Videolaparoscopic procedures have gained prominence due to their low invasiveness, causing less surgical trauma and better post-surgical recovery. However, the increase in intra-abdominal pressure due to the institution of pneumoperitoneum can alter the patient's homeostasis. Therefore, volume-controlled ventilation, associated with positive end-expiratory pressure (PEEP), improves arterial oxygenation and prevents pulmonary collapse, but it can lead to important hemodynamic changes. The aim of this study was to evaluate, comparatively, the effects of positive end expiratory-pressure (PEEP) on hemodynamic variables of pigs submitted to volume-controlled ventilation, during pneumoperitoneum and maintained in head-down tilt and determine which PEEP value promotes greater stability on hemodynamic variables. Materials, Methods &amp; Results: Twenty-four pigs were used, between 55 and 65-day-old, weighing between 15 and 25 kg, randomly divided into 3 distinct groups differentiated by positive end-expiratory pressure: PEEP 0 (volume-controlled ventilation and PEEP of 0 cmH2O), PEEP 5 (volume-controlled ventilation and PEEP of 5 cmH2O) and PEEP 10 (volume-controlled ventilation and PEEP of 10 cmH2O). Volume-controlled ventilation was adjusted to 8 mL/kg of tidal volume and a respiratory rate of 25 movements per min. Anesthesia was maintained with continuous infusion of propofol (0.2 mg/kg/min) and midazolam (1 mg/kg/h). Pneumoperitoneum was performed with carbon dioxide (CO2), keeping the intra-abdominal pressure at 15 mmHg and the animals were positioned on a 30° head-down tilt. The evaluations of hemodynamic variables started 30 min after induction of anesthesia (M0), followed by measurements at 15-min intervals (from M15 to M90), completing a total of 7 evaluations. The variables of interest were collected over 90 min and submitted to analysis of variance followed by Tukey´s post-hoc test, with P &lt; 0.05. The PEEP 10 group had higher values of CVP and mCPP, while the PEEP 5 group, mPAP and PVR were higher. The PEEP 0 group, on the other hand, had higher means of CI. Regarding the moments, there were differences in HR, SAP, DAP, MAP, CO, IC and TPR.Discussion: According to the literature, important hemodynamic effects due to pneumoperitoneum are reported, which can be caused by the pressure used in abdominal insufflation, CO2 accumulation, duration of the surgical procedure, hydration status and patient positioning. Mechanical ventilation associated with PEEP can also cause an increase in intrathoracic pressure and, therefore, reduce cardiac output. Cardiovascular changes are proportional to the PEEP used. Central venous pressure (PVC) measure the patient's preload, and intrathoracic pressure can interfere with this parameter. The peak pressure values in the PEEP 10 group were higher than the other groups, demonstrating that the increase in intrathoracic pressure results in higher PVC values. Regarding PAPm and PCPm, these variables can be influenced according to the PEEP values and the patient's position. In relation to CI, the increase in PEEP may reflect on intrathoracic pressure, resulting in greater compression of the heart, with a consequent reduction in cardiac output and cardiac index. Therefore, it is concluded that the PEEP effects of 0 cmH2O and 5 cmH2O on hemodynamics are discrete, under the proposed conditions. Keywords: mechanical ventilation, PEEP, head-down tilt, VCV, swine. Descritores: ventilação mecânica, PEEP, posição de Trendelenburg, suínos.

Changes in Intrathoracic Pressures Induced by Positive End-Expiratory Pressure Ventilation after Cardiac Surgical Procedures