This Invited Commentary accompanies the following original article:
Marret E, Cinotti R, Berard L, et al. Protective ventilation during anaesthesia reduces major postoperative complications after lung cancer surgery. A double-blind randomised controlled trial. Eur J Anaesthesiol 2018; 35:727–735.
Postoperative pulmonary complications have been shown to have a negative impact on patients’ outcome, increasing postoperative mortality and hospital length of stay, especially in thoracic surgical procedures.1 In recent decades, research has focused on preventing postoperative pulmonary complications using protective ventilation strategies. Widely accepted recommendations include the use of low tidal volumes, ideally targeted to 6 to 8 ml kg−1 of predicted body weight, and the lowest possible driving and plateau pressures.2 Although there is a compelling rationale for applying ‘protective’ ventilatory strategies in all mechanically ventilated patients, there is still limited evidence in certain clinical scenarios including thoracic surgery, in which the role of the distinct ventilator settings remains to be clarified,3,4 and the application of low tidal volume ventilation is still suboptimal.5 In earlier trials in nonthoracic surgery, the combination of lower tidal volume and higher positive end-expiratory pressure (PEEP) levels improved respiratory function6 and decreased the incidence of postoperative pulmonary complications.7 However, when different PEEP levels were compared at the same protective tidal volume in a large randomised controlled trial (RCT), the incidence of postoperative pulmonary complications was unchanged and higher PEEP was associated with adverse haemodynamic effects.8 Nonetheless, in thoracic surgery the exclusion of one lung and one-lung ventilation are almost always required: this peculiar approach modifies profoundly the respiratory mechanics and physiology including reduced end-expiratory lung volume, changes in perfusion–ventilation matching in the ventilated lung, with additional potential sources of alveolar damage compared with nonthoracic surgery. Therefore, the translation of the findings of trials conducted in abdominal surgery to this setting is challenging, and questions remain about the ideal ventilation strategy to be used to minimise the risk of postoperative pulmonary complications.
The findings presented in this issue of the European Journal of Anaesthesiology by Marret et al.9 comparing lung-protective ventilation with conventional ventilation in patients undergoing general anaesthesia and one-lung ventilation for thoracic surgery contribute importantly to this debate. The authors have conducted a multicentre RCT evaluating the effects of low tidal volume and PEEP on the incidence of a composite outcome of major postoperative complications, including pneumonia, acute respiratory distress syndrome (ARDS), pulmonary embolism, shock, myocardial infarction or death. Patients in the control group received no PEEP and a tidal volume of 10 ml kg−1 of ideal body weight, whereas in the intervention group a tidal volume of 5 ml kg−1 and PEEP between 5 and 8 cmH2O were applied. In neither group was the tidal volume changed after lung isolation and application of one-lung ventilation. Despite the interruption of the trial due to a low inclusion rate, the incidence of major postoperative complications was significantly and markedly reduced in the ‘protective’ group receiving lower tidal volume and higher PEEP, with most of the observed events being postoperative pulmonary complications. Whether these findings can be considered definitive remains questionable, as the study was underpowered for the primary endpoint. Nevertheless, even if the results were fortuitous, the study may still be seen as hypothesis-generating, and the data used for planning of appropriately powered trials in this field.
The trial started including patients in 2008, when research was beginning to focus on the translation to the operating room of the achievements obtained in the ventilatory management of patients with ARDS.6–8,10 Although there are few descriptive reports on the intra-operative management of patients receiving one-lung ventilation, it is common practice in many specialised centres to reduce tidal volume after lung exclusion, and both animal11 and clinical12 studies in thoracic surgery suggested this approach starting from the early 2000s. The reduction of tidal volume when switching from two-lung to one-lung ventilation appears to have a robust pathophysiological rationale: the damage caused by high tidal volume ventilation is mediated by an increase in alveolar dynamic strain, that is the ratio of tidal volume to end-expiratory lung volume.13 This is also linked to the rationale of titrating tidal volume on the predicted rather than total body weight, as lung size, and thus end-expiratory lung volume, is related to patients’ height and sex rather that to weight, as also confirmed in computed tomography studies.14 Exclusion of one lung from ventilation abruptly reduces the end-expiratory lung volume on which tidal volume exerts its action, resulting in an increased dynamic strain of the ventilated lung. Therefore, the application of a tidal volume of 10 ml kg−1 predicted body weight during one-lung ventilation might be equivalent to the application of 20 ml kg−1 predicted body weight during two-lung ventilation, with major increase in stress and strain. Moreover, the extent of this increase might differ in left-lung vs. right-lung exclusion, due to the different sizes of the lungs.
PEEP could reduce the dynamic strain by increasing the end-expiratory lung volume but introduces an injurious static strain component. Although these concepts related to strain were almost exclusively investigated in ARDS patients, it seems reasonable to assume that the same high tidal volume can be more injurious when delivered to a single lung also in noninjured lungs. Therefore, the control group of the study by Marret et al.9 might have received a tidal volume higher than is currently used during one-lung ventilation. Moreover, in this study, tidal volume reduction and PEEP increase were combined as a bundle of interventions; therefore, it is difficult to discriminate whether the clinical improvement was due to the former or to the latter.
The setting of PEEP is the most debated aspect of protective mechanical ventilation, both in the ICU and in the operating room.3,4 In addition to the previously mentioned PROVHILO trial,8 a recent study in abdominal surgery found no advantages of individualised PEEP titration on the lowest driving pressure vs. a fixed low PEEP level.15 Although higher PEEP seems protective when combined with a tidal volume size reduction,11,12 the role of PEEP alone during thoracic surgery is poorly investigated. In a recent meta-analysis, Liu et al.16 concluded that protective ventilation with low tidal volume reduces the incidence of postoperative pulmonary complications in patients receiving one-lung ventilation, but in most studies PEEP increase was a co-intervention.
In conclusion, although the study of Marret et al.9 reinforces the relevance of using protective ventilatory strategies in surgical patients, further studies are warranted to confirm this claim and clarify several aspects of mechanical ventilation during one-lung ventilation. Of note, a large multicentre international RCT (NCT02963025, www.provenet.eu) is currently investigating the effects of higher vs. lower PEEP in thoracic surgery, while maintaining low tidal volume in both groups and reducing tidal volume when switching to one-lung ventilation. We believe that further research should provide insights on less understood points such as the effects of PEEP or recruitment manoeuvres on postoperative pulmonary complications, which are still fields of debate and discussion.
Acknowledgements relating to this article
Assistance with the commentary: none.
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Conflicts of interest: none.
Comment from the Editor: this Invited Commentary was checked by the editors but was not sent for external peer review.
This article was checked and accepted by the Editors, but was not sent for external peer-review.
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