Rebuttal From Dr Miller et al

Application of positive end-expiratory pressure (PEEP) in ARDS is evolving. Higher PEEP may prove beneficial in some patients with ARDS.1 We propose combining PEEP and Fio2 using a table. Dr Schmidt2 has appropriately pointed out several limitations of this method and suggested alternative strategies to management of PEEP. However, we remain unconvinced that these have been tested sufficiently to prove their reliability, safety, or overall clinical effectiveness. We recognize that the ability of PEEP to recruit lung units varies from patient to patient and may3 or may not4 vary by etiology of ARDS. How should this information be used? Might paired titration of PEEP and Fio2 be acceptable in extrapulmonary ARDS but not in pulmonary ARDS? Moreover, is injury among various pulmonary etiologies uniform or might hemorrhagic alveolitis respond differently than pneumococcal pneumonia after progression to ARDS? While it is important to raise the suggestion of splitting rather than lumping treatment of ARDS, answers to these questions do not presently exist. ARDS is characterized by hypoxemia because poorly aerated lung units remain perfused, creating low ventilation/perfusion regions and absolute right-to-left shunt. This hypoxemia is usually managed with supplemental oxygen delivery and/or attempts at lung unit recruitment with positive airway pressure. Both of these strategies have the potential for harm—oxygen toxicity and lung overdistention, respectively. In our opinion, Dr Schmidt overestimates the ability of current clinical tools to assess recruitment and provide a reliable guide to PEEP application. Indeed, lung recruitment correlates poorly with oxygenation. For instance, recruitment may not improve oxygenation equally in shunt from pneumonia and from pulmonary edema. Dr Schmidt2 notes that recruitability with PEEP can be as low as 13% using chest-computed tomography in ARDS.4 Nevertheless, Dr Schmidt2 argues that those with ARDS should have PEEP titrated according to recruitability rather than oxygenation. It seems implausible to manipulate recruitment using PEEP with little consideration of Fio2 manipulation given this modest effect. Applying higher PEEP only to “subjects with the potential for meaningful recruitment” seems appropriate, but how is “potential for meaningful recruitment” defined? Dr Schmidt2 argues for the stress index as a better method of determining PEEP. Our previously stated concerns about the stress index include limited data (15 human subjects),5 demonstrated benefit only for surrogate outcomes,5 requirement for heavy sedation and/or paralysis, and potential confounding of chest wall pressure-volume relationships.6 Additionally, we find visual interpretation of concavity or convexity, frequently such as with pressure-time curves, difficult and occasionally confusing. What if the interpretation is clear once and then not the next time? How often need the interpretation be made? Dichotomizing around a stress index of one may be overly simple also. Specialized recording equipment is presently necessary, and patients must be on volume-cycled ventilation with square-wave inspiratory flow. This manner of ventilation is uncommon, as most patients on volume-cycled modes receive decelerating ramp inspiratory flow. As to whether PEEP is a relevant target at all or whether an approach like the stress index might direct treatment in some other way, we defer judgment until more data are available. Forced oscillation techniques7 suffer these same limitations and lack confirmation in humans. Focusing primarily on mechanical indices of recruitment to determine PEEP targets seems both impractical and of unproven clinical benefit. Instead, a strategy (PEEP/Fio2 table) that balances all of the issues involved in supporting oxygenation and avoiding harm in a clinically “user friendly” format would seem to make the most sense. Of note, a PEEP/Fio2 table can be followed by respiratory therapists without individual orders for every change in oxygenation and has been shown in multiple studies to be safe and easily applied.8-11 PEEP/Fio2 tables with modest oxygenation goals, plateau pressure limits, and linked PEEP and Fio2 adjustment seem to address this challenge logically and effectively. These tables can have the PEEP/Fio2 linkage adjusted for disease severity (ie, acute lung injury vs ARDS) or for recruitability, should a practical approach for determining lung recruitment be developed. Presently, a PEEP/Fio2 table makes the most sense for widespread use in managing hypoxemia in acute lung injury.