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• W2891399019 abstract "Knowledge on lung physiology and lung injury mechanisms related to positive pressure ventilation has evolved from animal models advancing the concepts of volutrauma, barotrauma, atelectrauma, and biotrauma1Dreyfuss D. Saumon G. Ventilator-induced lung injury: lessons from experimental studies.Am J Respir Crit Care Med. 1998; 157: 294-323Crossref PubMed Scopus (1901) Google Scholar, 2Dos Santos C.C. Slutsky A.S. Invited review: mechanisms of ventilator-induced lung injury: a perspective.J Appl Physiol. 2000; 89: 1645-1655Crossref PubMed Scopus (421) Google Scholar to applications in mechanically ventilated patients in the ICU and, more recently, in the operating room to reduce pulmonary complications.3Miskovic A. Lumb A.B. Postoperative pulmonary complications.Br J Anaesth. 2017; 118: 317-334Abstract Full Text Full Text PDF PubMed Scopus (391) Google Scholar A defining point in the field was the demonstration that, in patients with acute respiratory distress syndrome (ARDS), protecting the lungs by using lower tidal volumes VT (i.e. VT scaled to lung size as 6 ml kg−1 of predicted body weight) had a substantial impact on patient outcomes in the ICU.4Acute Respiratory Distress Syndrome Network Brower R.G. Matthay M.A. et al.Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med. 2000; 342: 1301-1308Crossref PubMed Scopus (10374) Google Scholar The benefit was presumably derived from limitation of lung stretch, and the practice of lower VT has been adopted in ICUs and operating rooms,5Wanderer J.P. Ehrenfeld J.M. Epstein R.H. et al.Temporal trends and current practice patterns for intraoperative ventilation at U.S. academic medical centers: a retrospective study.BMC Anesthesiol. 2015; 15: 40Crossref PubMed Scopus (35) Google Scholar although still not universally implemented.6Bellani G. Laffey J.G. Pham T. et al.Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries.JAMA. 2016; 315: 788-800Crossref PubMed Scopus (2869) Google Scholar The use of lower plateau pressures and higher PEEP was an additional principle that accompanied lower VT composing the so-called protective ventilatory strategies. Yet, knowledge of the interplay between these variables is still incomplete, and a large registry-based study suggested that lower VT combined with insufficient PEEP may worsen outcomes.7Levin M.A. McCormick P.J. Lin H.M. Hosseinian L. Fischer G.W. Low intraoperative tidal volume ventilation with minimal PEEP is associated with increased mortality.Br J Anaesth. 2014; 113: 97-108Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar Attempts to understand how injurious conditions during mechanical ventilation produce lung injury led investigators to apply engineering concepts. Volumetric strain, the change in lung volume divided by the initial reference volume, is one of those concepts.8Fung Y.C. Stress, deformation, and atelectasis of the lung.Circ Res. 1975; 37: 481-496Crossref PubMed Scopus (57) Google Scholar Such a concept is expected to be relevant clinically, as, even if the total lung size were similar for different patients, the presence of atelectasis in some patients results in only a fraction of the lung receiving the total VT, likely producing a more injurious condition than when VT is distributed to the whole lung. For instance, it is intuitive that VT=500 ml would be more injurious in a patient with a very small functional residual capacity (FRC) of 500 ml as in ARDS (volumetric strain=500/500=100%) than in a patient with a normal FRC of 2000 ml (volumetric strain=500/2000=25%). Lung strain is composed of both a static and a dynamic component. The FRC can be understood as the resting lung volume in the absence of any additional external interventions (i.e. at PEEP of 0 cm H2O). Considering the initial lung volume to calculate strain as FRC, static lung strain derives from the presence of an end-expiratory lung volume (EELV) different from FRC as a result of the additional lung volume resulting from the application of PEEP.9Protti A. Cressoni M. Santini A. et al.Lung stress and strain during mechanical ventilation: any safe threshold?.Am J Respir Crit Care Med. 2011; 183: 1354-1362Crossref PubMed Scopus (258) Google Scholar, 10Paula L.F. Wellman T.J. Winkler T. et al.Regional tidal lung strain in mechanically ventilated normal lungs.J Appl Physiol. 2016; 121: 1335-1347Crossref PubMed Scopus (33) Google Scholar The dynamic component, dynamic lung strain, is a consequence of tidal ventilation. Not only large whole-lung dynamic strains are associated with lung injury, but also regional dynamic strains are related to local inflammation.11Wellman T.J. Winkler T. Costa E.L. et al.Effect of local tidal lung strain on inflammation in normal and lipopolysaccharide-exposed sheep*.Crit Care Med. 2014; 42: e491-500Crossref PubMed Scopus (72) Google Scholar Minimisation of dynamic lung strain is, consequently, a result of the implementation of lower VT strategies, and consistent with preclinical data relating lung inflammation and injury with dynamic volumetric strain, either combined with lung blood volume12Motta-Ribeiro G.C. Hashimoto S. Winkler T. et al.Deterioration of regional lung strain and inflammation during early lung injury.Am J Respir Crit Care Med. 2018 May 22; ([Epub ahead of print] PMID: 29787304)https://doi.org/10.1164/rccm.201710-2038OCCrossref PubMed Scopus (47) Google Scholar or in isolation.11Wellman T.J. Winkler T. Costa E.L. et al.Effect of local tidal lung strain on inflammation in normal and lipopolysaccharide-exposed sheep*.Crit Care Med. 2014; 42: e491-500Crossref PubMed Scopus (72) Google Scholar A recent advance in the field is evidence that VT normalised to respiratory system compliance (VT/CRS) represents the ventilation variable that best stratifies for survival in ARDS patients.13Amato M.B. Meade M.O. Slutsky A.S. et al.Driving pressure and survival in the acute respiratory distress syndrome.N Engl J Med. 2015; 372: 747-755Crossref PubMed Scopus (1510) Google Scholar The ratio VT/CRS defines the driving pressure (ΔP), which can be estimated from the difference between plateau pressure and PEEP in the absence of respiratory effort, as in fully paralysed patients. In ARDS patients, changes in VT and PEEP were not by themselves predictive of survival, except when they resulted in ΔP changes.13Amato M.B. Meade M.O. Slutsky A.S. et al.Driving pressure and survival in the acute respiratory distress syndrome.N Engl J Med. 2015; 372: 747-755Crossref PubMed Scopus (1510) Google Scholar Such results appear to challenge initial findings on the role of reduced VT to improve survival. A registry-based study on a large population of surgical patients undergoing general anaesthesia with mechanical ventilation also proposed driving pressure as an important correlate for major postoperative pulmonary complications,14Ladha K. Vidal Melo M.F. McLean D.J. et al.Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study.BMJ. 2015; 351: h3646Crossref PubMed Scopus (205) Google Scholar which are still prevalent in the protective ventilation era.15Fernandez-Bustamante A. Frendl G. Sprung J. et al.Postoperative pulmonary complications, early mortality, and hospital stay following noncardiothoracic surgery: a multicenter study by the Perioperative Research Network investigators.JAMA Surg. 2017; 152: 157-166Crossref PubMed Scopus (283) Google Scholar The predictive value of driving pressure for major postoperative pulmonary complications was also superior to VT by itself.14Ladha K. Vidal Melo M.F. McLean D.J. et al.Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study.BMJ. 2015; 351: h3646Crossref PubMed Scopus (205) Google Scholar The relevance of driving pressure as a predictor of postoperative pulmonary complications was further emphasised in a meta-analysis of randomised clinical trial data of studies on intraoperative mechanical ventilation.16Neto A.S. Hemmes S.N. Barbas C.S. et al.Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data.Lancet Respir Med. 2016; 4: 272-280Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar In all these studies, the reason why VT/CRS would be such a relevant variable was its interpretation as a measure of whole lung strain easily obtained with clinical measurements. This is based on the presumption that CRS is a measure of aerated lung volume.13Amato M.B. Meade M.O. Slutsky A.S. et al.Driving pressure and survival in the acute respiratory distress syndrome.N Engl J Med. 2015; 372: 747-755Crossref PubMed Scopus (1510) Google Scholar, 14Ladha K. Vidal Melo M.F. McLean D.J. et al.Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study.BMJ. 2015; 351: h3646Crossref PubMed Scopus (205) Google Scholar, 17Gattinoni L. Pesenti A. Avalli L. Rossi F. Bombino M. Pressure-volume curve of total respiratory system in acute respiratory failure. Computed tomographic scan study.Am Rev Respir Dis. 1987; 136: 730-736Crossref PubMed Scopus (707) Google Scholar Whilst regional strain can occur even in the presence of acceptable global strain,10Paula L.F. Wellman T.J. Winkler T. et al.Regional tidal lung strain in mechanically ventilated normal lungs.J Appl Physiol. 2016; 121: 1335-1347Crossref PubMed Scopus (33) Google Scholar and values of regional lung strain below global thresholds are still associated with regional lung inflammation,12Motta-Ribeiro G.C. Hashimoto S. Winkler T. et al.Deterioration of regional lung strain and inflammation during early lung injury.Am J Respir Crit Care Med. 2018 May 22; ([Epub ahead of print] PMID: 29787304)https://doi.org/10.1164/rccm.201710-2038OCCrossref PubMed Scopus (47) Google Scholar global estimates are certainly a valuable measure compared with the assessment of VT by itself or normalised to lung size.13Amato M.B. Meade M.O. Slutsky A.S. et al.Driving pressure and survival in the acute respiratory distress syndrome.N Engl J Med. 2015; 372: 747-755Crossref PubMed Scopus (1510) Google Scholar, 14Ladha K. Vidal Melo M.F. McLean D.J. et al.Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study.BMJ. 2015; 351: h3646Crossref PubMed Scopus (205) Google Scholar In the current issue of the British Journal of Anaesthesia, Grieco and colleagues18Grieco D.L. Russo A. Romanò B. et al.Lung volumes, respiratory mechanics and dynamic strain during general anaesthesia.Br J Anaesth. 2018; 121: 1156-1165Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar present a clinical physiology study in non-obese ASA physical status 1 and 2 patients undergoing lower or upper abdominal surgery ‘to determine whether CRS and ΔP reflect lung aerated volume and dynamic strain during general anaesthesia’. Patients (n=20) received PEEP of 2, 7, or 12 cm H2O randomly for 40 min during abdominal surgery, with CRS, driving pressure, and estimates of EELV evaluated using a modified nitrogen wash-out and wash-in technique. From this and estimates of FRC based on demographjc data, the authors derived static and dynamic strains. Consequently, the authors tested some of the previous results and assumptions used in the interpretation of those large outcome studies. Direct measurements of advanced respiratory variables during intraoperative conditions are relatively limited, and report of such data is consequently welcome. Grieco and colleagues18Grieco D.L. Russo A. Romanò B. et al.Lung volumes, respiratory mechanics and dynamic strain during general anaesthesia.Br J Anaesth. 2018; 121: 1156-1165Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar report that aerated EELV was less than the predicted awake spontaneously breathing supine FRC in 65% of patients at PEEP of 2 cm H2O and in 45% of patients at PEEP of 5 cm H2O. Thus, the recent recommendation for PEEP of ≤2 cm H2O during open abdominal surgery in non-obese surgical patients19Guldner A. Kiss T. Serpa Neto A. et al.Intraoperative protective mechanical ventilation for prevention of postoperative pulmonary complications: a comprehensive review of the role of tidal volume, positive end-expiratory pressure, and lung recruitment maneuvers.Anesthesiology. 2015; 123: 692-713Crossref PubMed Scopus (265) Google Scholar, 20Hemmes S.N. Gama de Abreu M. Pelosi P. Schultz M.J. Prove Network Investigators for the Clinical Trial Network of the European Society of AnaesthesiologyHigh versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial.Lancet. 2014; 384: 495-503Abstract Full Text Full Text PDF PubMed Scopus (466) Google Scholar would be expected to produce lung de-recruitment in a significant proportion of patients. This could contribute to the observed increase in 30-day postoperative mortality in patients ventilated with low VT and low PEEP.7Levin M.A. McCormick P.J. Lin H.M. Hosseinian L. Fischer G.W. Low intraoperative tidal volume ventilation with minimal PEEP is associated with increased mortality.Br J Anaesth. 2014; 113: 97-108Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar It is also remarkable that a median lung recruitment of 445 ml was obtained at PEEP of 7 cm H2O compared with PEEP of 2 cm H2O. This is comparable with the 15–20% reduction in FRC after the induction of general anaesthesia,21Hedenstierna G. Strandberg A. Brismar B. Lundquist H. Svensson L. Tokics L. Functional residual capacity, thoracoabdominal dimensions, and central blood volume during general anesthesia with muscle paralysis and mechanical ventilation.Anesthesiology. 1985; 62: 247-254Crossref PubMed Scopus (228) Google Scholar suggesting that, in this small group of patients, PEEP of 7 cm H2O allowed the recovery of a substantial amount of lung volume usually lost during the induction of anaesthesia. Lung recruitment was much smaller (107 ml) between PEEP of 7 and 12 cm H2O. Such findings match well with CT imaging studies reporting reduced EELV after the induction of general anaesthesia with mechanical ventilation, with 16–20% of lung tissue showing no or poor aeration.22Reber A. Engberg G. Sporre B. et al.Volumetric analysis of aeration in the lungs during general anaesthesia.Br J Anaesth. 1996; 76: 760-766Abstract Full Text PDF PubMed Scopus (60) Google Scholar CT imaging studies have also shown that airway pressures may need to be above 40 cm H2O for at least 7–8 s to recruit previously collapsed lung areas in at-risk patients.23Whalen F.X. Gajic O. Thompson G.B. et al.The effects of the alveolar recruitment maneuver and positive end-expiratory pressure on arterial oxygenation during laparoscopic bariatric surgery.Anesth Analg. 2006; 102: 298-305Crossref PubMed Scopus (176) Google Scholar, 24Rothen H.U. Neumann P. Berglund J.E. Valtysson J. Magnusson A. Hedenstierna G. Dynamics of re-expansion of atelectasis during general anaesthesia.Br J Anaesth. 1999; 82: 551-556Abstract Full Text PDF PubMed Scopus (196) Google Scholar Thus, the observation of lung recruitment at PEEP of 7 cm H2O in the absence of a specific recruitment manoeuvre suggests a sizeable number of alveolar units with low opening pressures in normal adult lungs. An additional interesting observation was the constant cardiac output for PEEP of 2–12 cm H2O suggesting limited haemodynamic impact of these PEEP values in this group of patients. Grieco and colleagues attempted to achieve their aim by studying correlations between CRS and aerated EELV, and between ΔP and dynamic strains overall and at each PEEP level.18Grieco D.L. Russo A. Romanò B. et al.Lung volumes, respiratory mechanics and dynamic strain during general anaesthesia.Br J Anaesth. 2018; 121: 1156-1165Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar A major point is the importance of the FRC predicted from demographic data. Better correlations were found for measured aerated lung volumes below predicted FRC than above it, but it is not clear if the multiple correlations were part of the original analysis plan or an observation achieved a posteriori. Elucidation of the dependence of these correlations on predicted FRC would appear of great relevance to understanding and potentially limiting the use of the presumptions of the correlations in the cited outcome studies.13Amato M.B. Meade M.O. Slutsky A.S. et al.Driving pressure and survival in the acute respiratory distress syndrome.N Engl J Med. 2015; 372: 747-755Crossref PubMed Scopus (1510) Google Scholar, 14Ladha K. Vidal Melo M.F. McLean D.J. et al.Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study.BMJ. 2015; 351: h3646Crossref PubMed Scopus (205) Google Scholar, 16Neto A.S. Hemmes S.N. Barbas C.S. et al.Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data.Lancet Respir Med. 2016; 4: 272-280Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar Indeed, the fractional contributions of individual lung regions at different levels of EELV would influence the correlation. This information could also be valuable in the search for the ideal management of PEEP.20Hemmes S.N. Gama de Abreu M. Pelosi P. Schultz M.J. Prove Network Investigators for the Clinical Trial Network of the European Society of AnaesthesiologyHigh versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial.Lancet. 2014; 384: 495-503Abstract Full Text Full Text PDF PubMed Scopus (466) Google Scholar, 25Ferrando C. Soro M. Unzueta C. et al.Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial.Lancet Respir Med. 2018; 6: 193-203Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar, 26de Jong M.A.C. Ladha K.S. Vidal Melo M.F. et al.Differential effects of intraoperative positive end-expiratory pressure (PEEP) on respiratory outcome in major abdominal surgery versus craniotomy.Ann Surg. 2016; 264: 362-369Crossref PubMed Scopus (44) Google Scholar The dependence of the results on FRC appears to conflict with findings in ARDS patients that ΔP reductions were significantly associated with better survival irrespective of baseline elastance (the inverse of compliance) of the respiratory system,13Amato M.B. Meade M.O. Slutsky A.S. et al.Driving pressure and survival in the acute respiratory distress syndrome.N Engl J Med. 2015; 372: 747-755Crossref PubMed Scopus (1510) Google Scholar suggesting an effect throughout all ranges of lung expansion, not only that indicated by Grieco and colleagues.18Grieco D.L. Russo A. Romanò B. et al.Lung volumes, respiratory mechanics and dynamic strain during general anaesthesia.Br J Anaesth. 2018; 121: 1156-1165Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Previous imaging studies also reported significant correlations between compliance and aerated lung volume in patients with acute respiratory failure at a wide range of pressures, with correlation values similar or better than those presented by Grieco and colleagues18Grieco D.L. Russo A. Romanò B. et al.Lung volumes, respiratory mechanics and dynamic strain during general anaesthesia.Br J Anaesth. 2018; 121: 1156-1165Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar in their ‘best’ conditions (i.e. at aerated lung volumes less than the predicted FRC).17Gattinoni L. Pesenti A. Avalli L. Rossi F. Bombino M. Pressure-volume curve of total respiratory system in acute respiratory failure. Computed tomographic scan study.Am Rev Respir Dis. 1987; 136: 730-736Crossref PubMed Scopus (707) Google Scholar Whether such apparent conflicting results are attributable to physiological differences between surgical patients with initially normal lungs and ARDS patients or to other issues will require further clarification. An additional important limitation of these findings is that the applicability of the results would require knowledge of the patient's aerated EELV and FRC, but such knowledge would be unusual, and assumed expected values would be required to apply the reported results. The authors acknowledge other limitations to their study. The absence of measurements of trans-pulmonary pressure, the pressure effectively distending the lungs and likely responsible for lung injury,27Mauri T. Yoshida T. Bellani G. et al.Esophageal and transpulmonary pressure in the clinical setting: meaning, usefulness and perspectives.Intensive Care Med. 2016; 42: 1360-1373Crossref PubMed Scopus (276) Google Scholar limits insight into the effect of the utilised PEEP and meaning of the resulting EELV. Availability of regional assessments of lung expansion as obtainable with different imaging techniques would be helpful to understand better how the global changes produced on EELV by PEEP effectively redistribute lung expansion, and thus, strain.12Motta-Ribeiro G.C. Hashimoto S. Winkler T. et al.Deterioration of regional lung strain and inflammation during early lung injury.Am J Respir Crit Care Med. 2018 May 22; ([Epub ahead of print] PMID: 29787304)https://doi.org/10.1164/rccm.201710-2038OCCrossref PubMed Scopus (47) Google Scholar The goal of Grieco and colleagues18Grieco D.L. Russo A. Romanò B. et al.Lung volumes, respiratory mechanics and dynamic strain during general anaesthesia.Br J Anaesth. 2018; 121: 1156-1165Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar to identify and understand if and which measures of global lung mechanics reflect more complex physiological variables during mechanical ventilation is certainly relevant. The correlations reported by these authors agree with previous studies and current assumptions related to the interpretation of driving pressures as a measure of whole-lung global strain and of CRS as an indirect measure of aerated lung volume. The results also raise concerns that the validity of those assumptions has limits. Future investigations with physiology-based hypotheses will be required to advance the understanding of such issues, and to allow the development of tools that are meaningful and available to the clinician adjusting ventilatory settings. The search for such bedside tools to identify the optimal intraoperative PEEP management continues.28Blankman P. Shono A. Hermans B.J. Wesselius T. Hasan D. Gommers D. Detection of optimal PEEP for equal distribution of tidal volume by volumetric capnography and electrical impedance tomography during decreasing levels of PEEP in post cardiac-surgery patients.Br J Anaesth. 2016; 116: 862-869Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 29Nestler C. Simon P. Petroff D. et al.Individualized positive end-expiratory pressure in obese patients during general anaesthesia: a randomized controlled clinical trial using electrical impedance tomography.Br J Anaesth. 2017; 119: 1194-1205Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar Study conception: both authors. Writing of final manuscript: both authors. The authors declare that they have no conflicts of interest. US National Institutes of Health (R01-HL121228) to M.F.V.M." @default.
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