Demoule, Alexandre

Heunks, Leo

Piquilloud, Lise

English

EUR Research Repository

EUR Research Information PortalHow we approach titrating PEEP in patients with acute hypoxemic failurePublished in:Critical CarePublication status and date:Published: 31/10/2023DOI (link to publisher):10.1186/s13054-023-04694-1Document VersionPublisher's PDF, also known as Version of recordDocument License/Available under:CC BYCitation for the published version (APA):Heunks, L., Piquilloud, L., & Demoule, A. (2023). How we approach titrating PEEP in patients with acute hypoxemic failure.Critical Care, 27(1), Article 415. https://doi.org/10.1186/s13054-023-04694-1Link to publication on the EUR Research Information PortalTerms and Conditions of UseExcept as permitted by the applicable copyright law, you may not reproduce or make this material available to any third partywithout the prior written permission from the copyright holder(s). 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Critical Care          (2023) 27:415  https://doi.org/10.1186/s13054-023-04694-1PERSPECTIVEHow we approach titrating PEEP in patients with acute hypoxemic failureLeo Heunks1,2*, Lise Piquilloud3 and Alexandre Demoule4,5 IntroductionIn the recent ESICM guidelines on Acute Respiratory Distress Syndrome [1], the group of experts was “unable to make a recommendation for or against routine PEEP titration with higher PEEP/FiO2 strategy versus a lower PEEP/FiO2 strategy.” Also, the committee was “unable to make a recommendation for or against PEEP titra-tion guided by respiratory mechanics, compared to PEEP titration principally on PEEP/FiO2 strategy.” These rec-ommendations are undoubtedly sound from a methodo-logical perspective but leave the clinicians at the bedside in dire straits. At the bedside, we need to decide regard-ing the best PEEP for a specific patient at a specific point in time. In this short comment, we share our approach on titrating PEEP at the bedside in patients with acute res-piratory distress syndrome (ARDS).What are we aiming for with PEEP?In the original ARDS description by Ashbaugh [2], it was already reported that applying PEEP improves oxy-genation (N = 5). For a long time, the primary reason to apply PEEP was to improve arterial oxygenation. How-ever, when it became clear that inhomogeneous lung tis-sue may play an important role in the pathophysiology of VILI, the major aim for PEEP titration was to get a more homogeneous lung tissue or, in other terms, to find an optimal balance between lung recruitment and overdis-tension. Also, clinicians should be aware of the detrimen-tal effects of (high) PEEP on hemodynamics, especially right ventricular function. Therefore, at the bedside we need to find the right balance between lung recruitment and hyperinflation, while closely monitoring the hemo-dynamic response.What do the RCTs tell us?Today, three large RCTs have from slightly different perspective compared the effect of lower versus higher PEEP on clinical outcome. These studies are summa-rized in Table 1. These studies did not show a clear ben-efit from one approach versus the other. It is important to understand why these trails did not demonstrate an effect of one PEEP approach against the other. This can be understood if we look at the two CT scans in Fig. 1. Both patients present with acute hypoxemic failure, requiring endotracheal intubation. The CT scan in the left panel shows limited consolidations, while consolida-tions are extensive in the CT scan at the right panel. It is easy to understand that higher PEEP may be beneficial in the patient in the right panel (potentially recruitable lung), while it will only facilitate pulmonary hyperinfla-tion in the other patient. Recently, a multicenter trial showed that aggressive lung recruitment maneuvers associated with PEEP titration according to respiratory system compliance increased mortality of patients with moderate to severe ARDS [3]. Application of high PEEP Open Access© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecom‑mons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Critical Care*Correspondence:Leo HeunksL.Heunks@erasmusmc.nl1 Department of Intensive Care Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015GD Rotterdam, The Netherlands2 Department of Intensive Care, Radboudumc, Nijmegen, The Netherlands3 Adult Intensive Care Unit, University Hospital and University of Lausanne, Lausanne, Switzerland4 INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale Et Clinique, Sorbonne Université, Paris, France5 Service de Médecine Intensive ‑ Réanimation (Département R3S), AP‑HP, Groupe Hospitalier Universitaire APHP‑Sorbonne Université, Site Pitié‑Salpêtrière, Paris, FrancePage 2 of 5Heunks et al. Critical Care          (2023) 27:415 levels in patients with little potential for lung recruitment may have contributed to poor outcomes in this study. Thus, the discussion whether PEEP in patients with acute hypoxemic failure should be set “low” or “high” does not make much sense from a physiological perspective.A higher PEEP may only be beneficial in patients with potential for lung recruitment, but none of the three RCT’s evaluated the potential for lung recruitment prior to PEEP selection. Although not specifically evaluating higher versus lower PEEP, Constantin and colleagues [4] compared personalized mechanical ventilation (based on lung morphology assessed by chest X-ray or chest CT scan) versus standard of care. In the control group, PEEP was set according to low PEEP/  FiO2 table and TV was set at 6ml/Kg predicted bodyweight (PBW). In the per-sonalized group, patients with focal ARDS received TV of 8ml/Kg PBW and PEEP between 5 and  9cmH2O. In the non-focal ARDS group, TV was set at 6ml/Kg PBW and PEEP titrated to reach an inspiratory plateau pressure of  30cmH2O. Of note, recruitability with PEEP was not evaluated. No significant difference was found in 90-day mortality between control group or personalized venti-lation group. However, it appeared that 21% of patients in the personalized group were misclassified (focal ver-sus non-focal ARDS) and that misclassified patients had higher mortality as comparted to control group and to correctly classified patients. This study could be inter-preted that a personalized approach to ventilator settings may have a beneficial effect on clinical outcome. Though, this remains to be established.A practical approach (Fig. 2)In patients with moderate and severe acute hypoxemic failure, we set PEEP immediately after endotracheal intubation according to the low PEEP/FiO2 table [5], which means in clinical practice a PEEP between 8 and  12cmH2O (with  Fio2 between 0.5 and 0.7). Of course, in patients with low chest wall compliance (e.g. obesity, ascites), higher PEEP levels may be selected. Although selecting the high PEEP/Fio2 table may seem justified by a meta-analysis demonstrating that higher PEEP/FiO2 may present benefit on clinical outcome in these patients Table 1  Summary of the three clinical trials evaluating “lower or higher PEEP” setting*Estimated sample size was 750 patients, but this trial was stopped after 549 patients on the basis of the specified futility stopping ruleTrial N Patients Lower PEEP Higher PEEP Primary outcomeAlveoli [5] 549* Early ARDS,  Pao2/FiO2 < 300mmHg, inclusion within 36 h of meeting eligibility criteriaLow PEEP/Fi,O2 table High PEEP/Fi,O2 table Proportion of patients who died before they were discharged home while breathing without assistance was not different between groups (25% vs 28%)LOV [13] 983 Early ARDS, Pa,O2/Fi,O2 < 250mmHg, inclusion within 48 h of meeting eligibility criteriaLower PEEP/Fio2 table High PEEP/Fi,O2 table. Protocol modifica‑tions during trialAll‑cause hospital mortality was not different between groups (40% vs 35%)Express [8] 767 Early ARDS, Pa,O2/Fi,O2 < 300mmHg, inclusion within 48 h of meeting eligibility criteriaPEEP between 5 and 9  cmH2O As high as possible while maintaining Pplat <  30cmH2O28‑day motility was not different between groups (31% vs 28%)Fig. 1 CT scan of two ARDS patients with different potential for lung recruitment. This figure shows images of two different patients, both fulfilling the criteria for ARDS. The CT scan in the left panel is characterized by extensive ground glass appearances, but limited consolidations, whereas the patient in the right panel has extensive gravity dependent consolidations. Obviously, the potential for lung recruitment with PEEP is much higher in the patients in the right panelPage 3 of 5Heunks et al. Critical Care          (2023) 27:415  [6], none of these studies evaluated the potential for lung recruitment. Moreover, it seems that in clinical practice, few clinicians are willing to select PEEP based on high PEEP/Fi,o2 table [7].Shortly after endotracheal intubation, we identify whether the patient we are managing has potential for lung recruitment. To this aim, we perform a PEEP-responsiveness test, which consists in increasing PEEP from 5 to  15cmH2O in a single step. Response is evalu-ated after 10 min. If compliance and oxygenation do not decrease (arbitrarily 10% and 2% of  Spo2, respec-tively) and if  PaCO2 does not increase (arbitrarily 10%), this patient has probably potential for lung recruitment and hence may benefit from higher PEEP level. We thus increase PEEP level (with maintaining TV ± 6ml/Kg PBW and driving pressure <  15cmH2O) until respiratory system Fig. 2 Practical algorithm for PEEP titration in patients with acute hypoxemic failurePage 4 of 5Heunks et al. Critical Care          (2023) 27:415 static plateau pressure reaches 28-30cmH2O, according to the ExPress trial approach [8]. If the patient does not have potential for lung recruitment, we set a moderate PEEP level, e.g.,  8cmH2O. Potential for lung recruitment is evaluated daily and after transition to prone position (vice versa).However, in some patients, identifying the optimal PEEP may be more challenging, for instance, in patients with obesity because they could have low chest wall compliance, increased intraabdominal pressure, or very severe hypoxemic failure. In such patients, we use advanced respiratory monitoring to evaluate the impact of PEEP at the bedside. Measurement of esophageal pres-sure provides an estimation of global pleural pressure that allows calculating global transpulmonary pressure. Physi-ologically, it may be attractive to titrate PEEP to obtain end-expiratory transpulmonary pressure around zero, limiting alveolar collapse. This approach has been evalu-ated in the Epvent-2 trial, although PEEP was adjusted to achieve an end-expiratory transpulmonary pressure between 0 and 6  cmH2O. In the control group, PEEP was titrated using the high PEEP/FiO2 table. The primary outcome, a composition score incorporating death and ventilator free days through day 28, was not different between the two groups. In a reanalysis of this study [9], it was demonstrated that titrating PEEP to transpulmo-nary end-expiratory pressure close to zero (±  2cmH2O) was associated with greater survival as compared to more positive or negative values. It should, however, be noted that application of esophageal pressure measurement as an estimation of pleural pressure may be complex and requires expertise. Practicalities for esophageal pressure manometry have been extensively discussed previously [10].PEEP and the right ventriclePEEP may increase pulmonary vascular resistance and such right ventricle afterload further deteriorating right ventricle function [11]. In patients with high driving pressure (≥ 18  cmH2O), severe hypoxemia or hypercap-nia (≥ 48  cmH2O), routine echocardiography should be performed to search for acute cor pulmonale [12]. If cor pulmonale develops or deteriorates with higher PEEP, it may be advisable to decrease PEEP and prioritize hemo-dynamics. Respiratory rate may also be increased in par-allel in the absence of dynamic airtrapping, to the aim of reducing  PaCO2, which contributes to pulmonary hypertension.Other techniques to quantify PEEP‑induced lung recruitmentOther techniques have been used to quantify lung recruitment by PEEP, including CT scan, stress index, ultrasound, electrical impedance tomography (EIT) and recruitment-to-inflation ratio (assessment of de-recruit-ment with decreasing PEEP). However, these techniques are not feasible bedside (CT scan) or require further vali-dation in clinical practice (other techniques).ConclusionThe decision to titrate PEEP at the bedside may be com-plex and without clear guidelines. In this manuscript, we outline an approach based on physiology and clinical experience.Author contributionsLH, LP and AD designed, wrote and approved the manuscript.FundingNot applicable.Availability of data and materialsNot applicable.DeclarationsCompeting interestsThe authors declare no competing interests.Ethics approval and consent to participateNot applicable.Received: 2 August 2023   Accepted: 18 October 2023References 1. Grasselli G, Calfee CS, Camporota L, Poole D, Amato MBP, Antonelli M, Arabi YM, Baroncelli F, Beitler JR, Bellani G, et al. ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respira‑tory support strategies. Intensive Care Med. 2023;49(7):727–59. 2. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet. 1967;2(7511):319–23. 3. Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial I, Cavalcanti AB, Suzumura EA, Laranjeira LN, Paisani DM, Damiani LP, Guimaraes HP, Romano ER, Regenga MM, Taniguchi LNT, et al. Effect of lung recruitment and titrated positive end‑expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA. 2017;318(14):1335–45. 4. Constantin JM, Jabaudon M, Lefrant JY, Jaber S, Quenot JP, Langeron O, Ferrandiere M, Grelon F, Seguin P, Ichai C, et al. Personalised mechanical ventilation tailored to lung morphology versus low positive end‑expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single‑blind, randomised controlled trial. Lancet Respir Med. 2019;7(10):870–80. 5. Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukie‑wicz M, Schoenfeld D, Thompson BT, National Heart L, Blood Insti‑tute ACTN. Higher versus lower positive end‑expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004;351(4):327–36. 6. Dianti J, Tisminetzky M, Ferreyro BL, Englesakis M, Del Sorbo L, Sud S, Talmor D, Ball L, Meade M, Hodgson C, et al. Association of positive end‑expiratory pressure and lung recruitment selection strategies with mortality in acute respiratory distress syndrome: a systematic review and network meta‑analysis. Am J Respir Crit Care Med. 2022;205(11):1300–10.Page 5 of 5Heunks et al. Critical Care          (2023) 27:415   7. Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, 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(8):788–800. 8. Mercat A, Richard JC, Vielle B, Jaber S, Osman D, Diehl JL, Lefrant JY, Prat G, Richecoeur J, Nieszkowska A, et al. Positive end‑expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008;299(6):646–55. 9. Sarge T, Baedorf‑Kassis E, Banner‑Goodspeed V, Novack V, Loring SH, Gong MN, Cook D, Talmor D, Beitler JR. Group EP‑S: effect of esophageal pressure‑guided positive end‑expiratory pressure on survival from acute respiratory distress syndrome: a risk‑based and mechanistic reanalysis of the epvent‑2 trial. Am J Respir Crit Care Med. 2021;204(10):1153–63. 10. Akoumianaki E, Maggiore SM, Valenza F, Bellani G, Jubran A, Loring SH, Pelosi P, Talmor D, Grasso S, Chiumello D, et al. The application of esopha‑geal pressure measurement in patients with respiratory failure. Am J Respir Crit Care Med. 2014;189(5):520–31. 11. MekontsoDessap A, Charron C, Devaquet J, Aboab J, Jardin F, Brochard L, Vieillard‑Baron A. Impact of acute hypercapnia and augmented posi‑tive end‑expiratory pressure on right ventricle function in severe acute respiratory distress syndrome. Intensive Care Med. 2009;35(11):1850–8. 12. MekontsoDessap A, Boissier F, Charron C, Begot E, Repesse X, Legras A, Brun‑Buisson C, Vignon P, Vieillard‑Baron A. Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact. Intensive Care Med. 2016;42(5):862–70. 13. Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, Davies AR, Hand LE, Zhou Q, Thabane L, et al. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end‑expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008;299(6):637–45.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in pub‑lished maps and institutional affiliations.

How we approach titrating PEEP in patients with acute hypoxemic failure

Heunks, L.

Piquilloud, L.

Demoule, A.

Serveur académique lausannois

Heunks et al. Critical Care          (2023) 27:415  https://doi.org/10.1186/s13054-023-04694-1PERSPECTIVEHow we approach titrating PEEP in patients with acute hypoxemic failureLeo Heunks1,2*, Lise Piquilloud3 and Alexandre Demoule4,5 IntroductionIn the recent ESICM guidelines on Acute Respiratory Distress Syndrome [1], the group of experts was “unable to make a recommendation for or against routine PEEP titration with higher PEEP/FiO2 strategy versus a lower PEEP/FiO2 strategy.” Also, the committee was “unable to make a recommendation for or against PEEP titra-tion guided by respiratory mechanics, compared to PEEP titration principally on PEEP/FiO2 strategy.” These rec-ommendations are undoubtedly sound from a methodo-logical perspective but leave the clinicians at the bedside in dire straits. At the bedside, we need to decide regard-ing the best PEEP for a specific patient at a specific point in time. In this short comment, we share our approach on titrating PEEP at the bedside in patients with acute res-piratory distress syndrome (ARDS).What are we aiming for with PEEP?In the original ARDS description by Ashbaugh [2], it was already reported that applying PEEP improves oxy-genation (N = 5). For a long time, the primary reason to apply PEEP was to improve arterial oxygenation. How-ever, when it became clear that inhomogeneous lung tis-sue may play an important role in the pathophysiology of VILI, the major aim for PEEP titration was to get a more homogeneous lung tissue or, in other terms, to find an optimal balance between lung recruitment and overdis-tension. Also, clinicians should be aware of the detrimen-tal effects of (high) PEEP on hemodynamics, especially right ventricular function. Therefore, at the bedside we need to find the right balance between lung recruitment and hyperinflation, while closely monitoring the hemo-dynamic response.What do the RCTs tell us?Today, three large RCTs have from slightly different perspective compared the effect of lower versus higher PEEP on clinical outcome. These studies are summa-rized in Table 1. These studies did not show a clear ben-efit from one approach versus the other. It is important to understand why these trails did not demonstrate an effect of one PEEP approach against the other. This can be understood if we look at the two CT scans in Fig. 1. Both patients present with acute hypoxemic failure, requiring endotracheal intubation. The CT scan in the left panel shows limited consolidations, while consolida-tions are extensive in the CT scan at the right panel. It is easy to understand that higher PEEP may be beneficial in the patient in the right panel (potentially recruitable lung), while it will only facilitate pulmonary hyperinfla-tion in the other patient. Recently, a multicenter trial showed that aggressive lung recruitment maneuvers associated with PEEP titration according to respiratory system compliance increased mortality of patients with moderate to severe ARDS [3]. Application of high PEEP Open Access© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecom‑mons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Critical Care*Correspondence:Leo HeunksL.Heunks@erasmusmc.nl1 Department of Intensive Care Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015GD Rotterdam, The Netherlands2 Department of Intensive Care, Radboudumc, Nijmegen, The Netherlands3 Adult Intensive Care Unit, University Hospital and University of Lausanne, Lausanne, Switzerland4 INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale Et Clinique, Sorbonne Université, Paris, France5 Service de Médecine Intensive ‑ Réanimation (Département R3S), AP‑HP, Groupe Hospitalier Universitaire APHP‑Sorbonne Université, Site Pitié‑Salpêtrière, Paris, FrancePage 2 of 5Heunks et al. Critical Care          (2023) 27:415 levels in patients with little potential for lung recruitment may have contributed to poor outcomes in this study. Thus, the discussion whether PEEP in patients with acute hypoxemic failure should be set “low” or “high” does not make much sense from a physiological perspective.A higher PEEP may only be beneficial in patients with potential for lung recruitment, but none of the three RCT’s evaluated the potential for lung recruitment prior to PEEP selection. Although not specifically evaluating higher versus lower PEEP, Constantin and colleagues [4] compared personalized mechanical ventilation (based on lung morphology assessed by chest X-ray or chest CT scan) versus standard of care. In the control group, PEEP was set according to low PEEP/  FiO2 table and TV was set at 6ml/Kg predicted bodyweight (PBW). In the per-sonalized group, patients with focal ARDS received TV of 8ml/Kg PBW and PEEP between 5 and  9cmH2O. In the non-focal ARDS group, TV was set at 6ml/Kg PBW and PEEP titrated to reach an inspiratory plateau pressure of  30cmH2O. Of note, recruitability with PEEP was not evaluated. No significant difference was found in 90-day mortality between control group or personalized venti-lation group. However, it appeared that 21% of patients in the personalized group were misclassified (focal ver-sus non-focal ARDS) and that misclassified patients had higher mortality as comparted to control group and to correctly classified patients. This study could be inter-preted that a personalized approach to ventilator settings may have a beneficial effect on clinical outcome. Though, this remains to be established.A practical approach (Fig. 2)In patients with moderate and severe acute hypoxemic failure, we set PEEP immediately after endotracheal intubation according to the low PEEP/FiO2 table [5], which means in clinical practice a PEEP between 8 and  12cmH2O (with  Fio2 between 0.5 and 0.7). Of course, in patients with low chest wall compliance (e.g. obesity, ascites), higher PEEP levels may be selected. Although selecting the high PEEP/Fio2 table may seem justified by a meta-analysis demonstrating that higher PEEP/FiO2 may present benefit on clinical outcome in these patients Table 1  Summary of the three clinical trials evaluating “lower or higher PEEP” setting*Estimated sample size was 750 patients, but this trial was stopped after 549 patients on the basis of the specified futility stopping ruleTrial N Patients Lower PEEP Higher PEEP Primary outcomeAlveoli [5] 549* Early ARDS,  Pao2/FiO2 < 300mmHg, inclusion within 36 h of meeting eligibility criteriaLow PEEP/Fi,O2 table High PEEP/Fi,O2 table Proportion of patients who died before they were discharged home while breathing without assistance was not different between groups (25% vs 28%)LOV [13] 983 Early ARDS, Pa,O2/Fi,O2 < 250mmHg, inclusion within 48 h of meeting eligibility criteriaLower PEEP/Fio2 table High PEEP/Fi,O2 table. Protocol modifica‑tions during trialAll‑cause hospital mortality was not different between groups (40% vs 35%)Express [8] 767 Early ARDS, Pa,O2/Fi,O2 < 300mmHg, inclusion within 48 h of meeting eligibility criteriaPEEP between 5 and 9  cmH2O As high as possible while maintaining Pplat <  30cmH2O28‑day motility was not different between groups (31% vs 28%)Fig. 1 CT scan of two ARDS patients with different potential for lung recruitment. This figure shows images of two different patients, both fulfilling the criteria for ARDS. The CT scan in the left panel is characterized by extensive ground glass appearances, but limited consolidations, whereas the patient in the right panel has extensive gravity dependent consolidations. Obviously, the potential for lung recruitment with PEEP is much higher in the patients in the right panelPage 3 of 5Heunks et al. Critical Care          (2023) 27:415  [6], none of these studies evaluated the potential for lung recruitment. Moreover, it seems that in clinical practice, few clinicians are willing to select PEEP based on high PEEP/Fi,o2 table [7].Shortly after endotracheal intubation, we identify whether the patient we are managing has potential for lung recruitment. To this aim, we perform a PEEP-responsiveness test, which consists in increasing PEEP from 5 to  15cmH2O in a single step. Response is evalu-ated after 10 min. If compliance and oxygenation do not decrease (arbitrarily 10% and 2% of  Spo2, respec-tively) and if  PaCO2 does not increase (arbitrarily 10%), this patient has probably potential for lung recruitment and hence may benefit from higher PEEP level. We thus increase PEEP level (with maintaining TV ± 6ml/Kg PBW and driving pressure <  15cmH2O) until respiratory system Fig. 2 Practical algorithm for PEEP titration in patients with acute hypoxemic failurePage 4 of 5Heunks et al. Critical Care          (2023) 27:415 static plateau pressure reaches 28-30cmH2O, according to the ExPress trial approach [8]. If the patient does not have potential for lung recruitment, we set a moderate PEEP level, e.g.,  8cmH2O. Potential for lung recruitment is evaluated daily and after transition to prone position (vice versa).However, in some patients, identifying the optimal PEEP may be more challenging, for instance, in patients with obesity because they could have low chest wall compliance, increased intraabdominal pressure, or very severe hypoxemic failure. In such patients, we use advanced respiratory monitoring to evaluate the impact of PEEP at the bedside. Measurement of esophageal pres-sure provides an estimation of global pleural pressure that allows calculating global transpulmonary pressure. Physi-ologically, it may be attractive to titrate PEEP to obtain end-expiratory transpulmonary pressure around zero, limiting alveolar collapse. This approach has been evalu-ated in the Epvent-2 trial, although PEEP was adjusted to achieve an end-expiratory transpulmonary pressure between 0 and 6  cmH2O. In the control group, PEEP was titrated using the high PEEP/FiO2 table. The primary outcome, a composition score incorporating death and ventilator free days through day 28, was not different between the two groups. In a reanalysis of this study [9], it was demonstrated that titrating PEEP to transpulmo-nary end-expiratory pressure close to zero (±  2cmH2O) was associated with greater survival as compared to more positive or negative values. It should, however, be noted that application of esophageal pressure measurement as an estimation of pleural pressure may be complex and requires expertise. Practicalities for esophageal pressure manometry have been extensively discussed previously [10].PEEP and the right ventriclePEEP may increase pulmonary vascular resistance and such right ventricle afterload further deteriorating right ventricle function [11]. In patients with high driving pressure (≥ 18  cmH2O), severe hypoxemia or hypercap-nia (≥ 48  cmH2O), routine echocardiography should be performed to search for acute cor pulmonale [12]. If cor pulmonale develops or deteriorates with higher PEEP, it may be advisable to decrease PEEP and prioritize hemo-dynamics. Respiratory rate may also be increased in par-allel in the absence of dynamic airtrapping, to the aim of reducing  PaCO2, which contributes to pulmonary hypertension.Other techniques to quantify PEEP‑induced lung recruitmentOther techniques have been used to quantify lung recruitment by PEEP, including CT scan, stress index, ultrasound, electrical impedance tomography (EIT) and recruitment-to-inflation ratio (assessment of de-recruit-ment with decreasing PEEP). However, these techniques are not feasible bedside (CT scan) or require further vali-dation in clinical practice (other techniques).ConclusionThe decision to titrate PEEP at the bedside may be com-plex and without clear guidelines. In this manuscript, we outline an approach based on physiology and clinical experience.Author contributionsLH, LP and AD designed, wrote and approved the manuscript.FundingNot applicable.Availability of data and materialsNot applicable.DeclarationsCompeting interestsThe authors declare no competing interests.Ethics approval and consent to participateNot applicable.Received: 2 August 2023   Accepted: 18 October 2023References 1. Grasselli G, Calfee CS, Camporota L, Poole D, Amato MBP, Antonelli M, Arabi YM, Baroncelli F, Beitler JR, Bellani G, et al. ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respira‑tory support strategies. Intensive Care Med. 2023;49(7):727–59. 2. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet. 1967;2(7511):319–23. 3. Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial I, Cavalcanti AB, Suzumura EA, Laranjeira LN, Paisani DM, Damiani LP, Guimaraes HP, Romano ER, Regenga MM, Taniguchi LNT, et al. Effect of lung recruitment and titrated positive end‑expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA. 2017;318(14):1335–45. 4. Constantin JM, Jabaudon M, Lefrant JY, Jaber S, Quenot JP, Langeron O, Ferrandiere M, Grelon F, Seguin P, Ichai C, et al. Personalised mechanical ventilation tailored to lung morphology versus low positive end‑expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single‑blind, randomised controlled trial. Lancet Respir Med. 2019;7(10):870–80. 5. Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukie‑wicz M, Schoenfeld D, Thompson BT, National Heart L, Blood Insti‑tute ACTN. 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How we approach titrating PEEP in patients with acute hypoxemic failure.

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How we approach titrating PEEP in patients with acute hypoxemic failure

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