How we approach titrating PEEP in patients with acute hypoxemic failure
Critical Care volume 27, Article number: 415 (2023)
In the recent ESICM guidelines on Acute Respiratory Distress Syndrome , 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 titration guided by respiratory mechanics, compared to PEEP titration principally on PEEP/FiO2 strategy.” These recommendations are undoubtedly sound from a methodological perspective but leave the clinicians at the bedside in dire straits. At the bedside, we need to decide regarding 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 respiratory distress syndrome (ARDS).
What are we aiming for with PEEP?
In the original ARDS description by Ashbaugh , it was already reported that applying PEEP improves oxygenation (N = 5). For a long time, the primary reason to apply PEEP was to improve arterial oxygenation. However, when it became clear that inhomogeneous lung tissue 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 overdistension. Also, clinicians should be aware of the detrimental 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 hemodynamic 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 summarized in Table 1. These studies did not show a clear benefit 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 consolidations 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 hyperinflation 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 . Application of high PEEP 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  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 personalized 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 ventilation group. However, it appeared that 21% of patients in the personalized group were misclassified (focal versus non-focal ARDS) and that misclassified patients had higher mortality as comparted to control group and to correctly classified patients. This study could be interpreted 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 , 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 , 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 .
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 evaluated after 10 min. If compliance and oxygenation do not decrease (arbitrarily 10% and 2% of Spo2, respectively) 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 static plateau pressure reaches 28-30cmH2O, according to the ExPress trial approach . 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 pressure provides an estimation of global pleural pressure that allows calculating global transpulmonary pressure. Physiologically, it may be attractive to titrate PEEP to obtain end-expiratory transpulmonary pressure around zero, limiting alveolar collapse. This approach has been evaluated 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 , it was demonstrated that titrating PEEP to transpulmonary 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 .
PEEP and the right ventricle
PEEP may increase pulmonary vascular resistance and such right ventricle afterload further deteriorating right ventricle function . In patients with high driving pressure (≥ 18 cmH2O), severe hypoxemia or hypercapnia (≥ 48 cmH2O), routine echocardiography should be performed to search for acute cor pulmonale . If cor pulmonale develops or deteriorates with higher PEEP, it may be advisable to decrease PEEP and prioritize hemodynamics. Respiratory rate may also be increased in parallel in the absence of dynamic airtrapping, to the aim of reducing PaCO2, which contributes to pulmonary hypertension.
Other techniques to quantify PEEP-induced lung recruitment
Other 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-recruitment with decreasing PEEP). However, these techniques are not feasible bedside (CT scan) or require further validation in clinical practice (other techniques).
The decision to titrate PEEP at the bedside may be complex and without clear guidelines. In this manuscript, we outline an approach based on physiology and clinical experience.
Availability of data and materials
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 respiratory support strategies. Intensive Care Med. 2023;49(7):727–59.
Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet. 1967;2(7511):319–23.
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.
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.
Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT, National Heart L, Blood Institute 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.
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.
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.
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.
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.
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 esophageal pressure measurement in patients with respiratory failure. Am J Respir Crit Care Med. 2014;189(5):520–31.
MekontsoDessap A, Charron C, Devaquet J, Aboab J, Jardin F, Brochard L, Vieillard-Baron A. Impact of acute hypercapnia and augmented positive end-expiratory pressure on right ventricle function in severe acute respiratory distress syndrome. Intensive Care Med. 2009;35(11):1850–8.
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.
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.
The authors declare no competing interests.
Ethics approval and consent to participate
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Heunks, L., Piquilloud, L. & Demoule, A. How we approach titrating PEEP in patients with acute hypoxemic failure. Crit Care 27, 415 (2023). https://doi.org/10.1186/s13054-023-04694-1