In Reply

We thank Dr. Tusman et al. for their interest in our review on intraoperative protective ventilation.¹  They claim that our recommendations neglected experimental and clinical evidence that disagree with the results of the recently published High versus Low Positive End-expiratory Pressure during General Anaesthesia for Open Abdominal Surgery (PROVHILO) study.²  Although inappropriate for drawing clinical recommendations, experimental studies provide the physiologic pillars of interventions. Therefore, our review article included a thorough appraisal of the mechanisms of ventilator-induced lung injury and possible strategies to prevent injury. Clinical recommendations must rely on clinical investigations, especially randomized controlled trials. Accordingly, we conducted a literature search and identified a few randomized controlled trials, which were ultimately meta-analyzed. Different from what Dr. Tusman et al. assert, selection was objective and unbiased. With 900 patients included in the study, the international, multicenter PROVHILO study²  is the largest randomized controlled trial in this field, and the meta-analysis was obviously influenced by this study’s results.

When criticizing the recruitment maneuver used in PROVHILO study,²  Dr. Tusman et al. overlooked some basic mechanisms of recruitment and misunderstood the type of maneuver we applied. In the lungs, reopening of atelectatic tissue mimics avalanches, with different regions opening at distinct pressures and times.³  Furthermore, histologic analysis shows that approximately 5 s is enough to obtain recruitment once a particular opening pressure is exceeded.⁴  In PROVHILO study,²  the recruitment maneuver was based on a stepwise increase of tidal volumes at a positive end-expiratory pressure (PEEP) of 12 cm H₂O. The time spent at different inspiratory pressures, including levels above 30 cm H₂O, was approximately 15 s at each pressure. Thus, comparison with a maneuver based on the sustained inflation with PEEP of 0 cm H₂O⁵  is misleading. In addition, the comparative increase in compliance was 33% on average, which in noninjured lungs ventilated with low tidal volume is more than modest and hardly explained by redistribution of ventilation without opening of atelectatic areas. We decisively disagree that the occurrence of postoperative atelectasis in PROVHILO study²  indicates inappropriate intraoperative lung recruitment. Pain, partial immobilization, and limited ability to cough, among many other postoperative factors, likely explain that finding and are obviously not related to intraoperative recruitment maneuvers.

We are aware that intraoperative fluid loading could be harmful in patients undergoing surgery. Accordingly, the PROVHILO protocol recommended “to avoid fluid overload (according to the discretion of the attending anesthetist).” When judging this aspect, one must take the whole picture into account and consider that patients in the study underwent major open abdominal surgery, with significant blood loss and intravascular volume shifts.²  Therefore, and in contrast to the statement of Dr. Tusman et al., the incidence of postoperative pulmonary complications was as high as predicted in the risk category,⁶  whereas the risk of nonpulmonary complications was not assessed.

Dr. Tusman et al. also overlooked the fact that our recommendations targeted nonobese patients undergoing open abdominal surgery only.¹  In the publication that questioned our recommendations, other types of patients and surgical procedures were included.⁷  Furthermore, despite its impressive number of records, that single-center, retrospective study⁷  did not directly evaluate the role of PEEP on mortality.

Future randomized controlled trials will show whether high PEEP level, individually titrated or not, with or without recruitment maneuvers, is superior to low PEEP level in terms of clinical outcome in other types of patients and surgical procedures. The current discussion reminds us of the debate about the studies that failed to demonstrate the usefulness of recruitment maneuvers in patients suffering from acute respiratory distress syndrome. For many years, “inappropriate maneuvers,” “nonindividualized PEEP levels,” “unsuitable therapy windows,” “meaningless endpoints,” and “inappropriate patient selection” were believed to be responsible for the lack of effect of recruitment maneuvers on clinically relevant endpoints. Enchanted by aseptic lung injury models that reproduced some but not all relevant aspects of the complex clinical scenario, passionate researchers have insisted on their own beliefs, denied clinical evidence, and put patients at risk.

For our group, stating that future studies might lead to adjustments in recommendations is not paradoxical but rather reflects our principle of being open to evidence from ever evolving experimental and clinical research. This is how we understand science targeted at improving patient care.