In Reply:

We thank Qu et al. and Dr. Gil for their letters1,2  and interest in our publication.3  Both letters examine the components of our lung protective ventilation bundle (tidal volume less than 8 ml/kg ideal body weight, positive end-expiratory pressure [PEEP] greater than or equal to 5 cm H2O, and modified driving pressure [peak inspiratory pressure − PEEP] less than 16 cm H2O).

We selected a pragmatic definition that would be amenable to testing via future prospective interventional studies. Analogous bundles have shown effectiveness for improving outcomes in other domains such as prevention of ventilator associated pneumonia4  and central line–associated bloodstream infections.5  This bundle was defined a priori and reflects the multiple simultaneous considerations anesthesiologists make when seeking to reduce postoperative cardiac surgical pulmonary complications. Thresholds were based upon approximately 75% historic compliance rates (Supplemental Digital Content 1A to C, http://links.lww.com/ALN/C26), such that each component remains achievable if tested in an interventional study. Our tidal volume threshold of 8 ml/kg ideal body weight is a commonly accepted goal for protective ventilation6 ; the PEEP threshold of 5 cm H2O reflects the default setting of on many institutions’ ventilators; and the threshold of 16 cm H2O for driving pressure falls within the range of previously cited thresholds.7,8  As noted by Qu et al., although our chosen thresholds are consistent with previous literature, an exploratory study investigating combinations of thresholds for lung protective ventilation bundle components may best identify an optimal target. Furthermore, although the interpretability of our study findings benefited from a pragmatic, universal definition of a bundled lung protective ventilation strategy, we agree with Qu et al. and Dr. Gil that an individualized approach to lung-protective ventilation—specific to patient and case characteristics—may be the ideal strategy to mitigate postoperative pulmonary complications. While such methods are described in recent studies,9,10  they may be challenging to implement in a real-world setting across a broad patient population.

Regarding the point that a U-shaped distribution may exist between body mass index and postoperative pulmonary complications, and that lower driving pressures are harder to achieve in obese patients, we agree this issue should be addressed in any study of lung protective ventilation strategies. We categorized body mass index rather than modeling it continuously, such that multivariable models could appropriately adjust for both extremes. While patients with elevated body mass indices are less likely to receive a bundled lung protective ventilation strategy (Supplemental Digital Content 2, http://links.lww.com/ALN/C27), most commonly due to modified driving pressures greater than 16 cm H2O, we observed no independent association between body mass index and postoperative pulmonary complications (Supplemental Digital Content 3, http://links.lww.com/ALN/C28), and the relationship between bundles and postoperative pulmonary complications were robust when evaluated across prespecified body mass index ranges (Supplemental Digital Content 10, http://links.lww.com/ALN/C35). One potential explanation is that a high airway driving pressure in obese individuals is more likely to reflect to reflect chest wall elastance rather than lung elastance (i.e., higher airway driving pressure without a higher transpulmonary driving pressure).

To Dr. Gil’s concern that higher levels of PEEP may be harmful to patients, we agree this may be the case at high levels; however, we disagree that our study provides evidence to support a threshold of 5 cm H2O as independently protective or harmful. Specifically, our study demonstrated no independent association between PEEP greater than 5 cm H2O and postoperative pulmonary complications (adjusted odds ratio, 1.18; 95% CI, 0.91 to 1.53; fig. 4).

To Qu et al.’s point that consensus definitions of postoperative pulmonary complications exist—acknowledged by our study11,12 —we agree that such definitions are useful for improving comparisons across studies. We carefully selected a composite pulmonary complication comprised from consensus definitions, but strategically omitted several components (atelectasis, aspiration, pleural effusion, bronchospasm, and pneumothorax) due to either limitations in our observational data quality or lack of an underlying mechanism amenable to treatment via lung-protective ventilation. Heterogeneous definitions may lead to varied outcome incidences and associations. We emphasize these incidences (table 2) and explore associations via sensitivity analyses (Supplemental Digital Content 6, http://links.lww.com/ALN/C31). We observed that a lung-protective ventilation bundle remained protective against each pulmonary complication outcome component except for prolonged ventilation. As Qu et al. suggest, the lack of independent association between a lung-protective ventilation bundle and prolonged ventilation may have existed, as other mechanisms (e.g., neurologic and hemodynamic derangements precluding safe early extubation) may better explain this finding.

We thank Qu et al. and Dr. Gil for their comments regarding our study. Although the optimal target for intraoperative lung protective ventilation in the cardiac surgical patient is yet to be fully elucidated, our study supports the importance of further studies of intraoperative ventilator management.

Research Support

All work and partial funding attributed to the Department of Anesthesiology, University of Michigan Medical School (Ann Arbor, Michigan). The project was supported in part by the National Heart, Lung, and Blood Institute (grant no. 1K01HL141701-02; Bethesda, Maryland) and the National Institute of General Medicine Sciences (grant no. 5T32GM103730-05; Bethesda, Maryland). Dr. Likosky received support (R01-HS-022535) from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or Agency for Healthcare Research and Quality.

Competing Interests

Dr. Kheterpal declares financial relationships with entities outside the scope of this project, including support from Merck (Kenilworth, New Jersey; utilization patterns and outcomes of sugammadex administration); Apple (Cupertino, California; health trajectories as observed via wearable technologies); and Blue Cross Blue Shield Michigan (Detroit, Michigan; anesthesiology quality improvement). The other authors declare no competing interests beyond those described in the funding statement.

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