“The question that immediately arises from the current post hoc analysis is whether longer exposure times to low mechanical power may also promote ventilator-induced lung injury or whether there is a safety threshold below which no harm is caused to the lung irrespective of the duration of mechanical ventilation.”
In this issue of Anesthesiology, Yoon et al. present the results of a post hoc analysis of data from a multicenter randomized controlled trial of driving pressure–guided ventilation in lung resection surgery in 1,170 patients between 2020 and 2021. They computed the total mechanical energy and the time-weighted average mechanical power in a subset of 1,055 patients of that study, of whom 41% (431 of 1,055) developed pulmonary complications. Mechanical energy was independently associated with postoperative pulmonary complications in that subpopulation, while an association between mechanical power and adverse pulmonary events was detected in cases requiring at least 210 min of one-lung ventilation. Importantly, the authors included variables in the regression models based on consensus among the investigators, as well as evidence from the literature, and performed adjustments for a number of risk predictors that might interfere with the results, enhancing the predictive value of the models. Notably, in subgroup analyses, the associations between mechanical energy, but not the time-weighted average mechanical power, and postoperative pulmonary complications were consistent in different ranges of commonly monitored respiratory variables, including VT, RR, peak and plateau pressures, PEEP, and driving pressure. The authors confirmed the findings of other groups that only the elastic-dynamic component of mechanical power seems to carry significant information in models preadjusted to severity of lung disease. They also found that the linear formula 4 × driving pressure + RR, which is associated with the elastic-dynamic component, was associated with postoperative pulmonary complications, while mechanical power was not. Last, but not least, normalization of mechanical energy and mechanical power to predicted body weight or respiratory system compliance, that is, surrogates of lung mass and volume, did not change the effect size but strengthened their association with postoperative pulmonary complications. The effect size might also have been higher if normalization had considered the lung mass or volume of the ventilated lung only.
To better interpret these results, it is important to address the original study conducted by the authors, the calculation of mechanical energy and mechanical power, and the pathophysiology of lung injury. The data used in this post hoc analysis were derived from an investigation in which patients were randomly assigned to one-lung ventilation with either a fixed level of PEEP of 5 cm H2O or PEEP set to minimize the driving pressure, whereby a lung recruitment maneuver preceded the setting of PEEP in both groups. Also, during one-lung ventilation, all patients were ventilated with VT of 5 ml/kg of the predicted body weight and inspiratory oxygen fraction of 0.80, and RR was set in the range of 10 to 18/min to maintain end-tidal carbon dioxide between 33 and 45 mmHg. Importantly, peripheral oxygen saturation values as low as 90% were allowed during one-lung ventilation before rescue maneuvers were performed, which is in line with common clinical practice. In spite of a relatively high dispersion of PEEP values in the group with titrated PEEP, the absolute difference in driving pressure between groups during one-lung ventilation was mostly in the range of 1 to 2 cm H2O, which is statistically significant but clinically irrelevant. In fact, individualized PEEP did not reduce the incidence of postoperative pulmonary complications compared to the fixed PEEP of 5 cm H2O. It is worth noting, however, that in a post hoc unadjusted analysis, the incidence of postoperative pulmonary complications increased nonlinearly with the driving pressure. In our opinion, the most likely explanation is that the comorbidities of the patients determined that association.
The equations used by the authors to calculate mechanical energy and mechanical power, although simplified, include all potential variables related to lung injury obtainable directly from the mechanical ventilator during volume-controlled mechanical ventilation. However, more recently, the value of the elastic-static and resistive components has been questioned. From a technical perspective, both mechanical power and its elastic-dynamic component might be easily displayed by modern ventilators. However, simplified mechanical energy and mechanical power equations suffer from important limitations that apply also to expanded equations. First, they do not estimate the amount of energy that is effectively dissipated by the lungs during mechanical ventilation but rather the amount that is transferred to the respiratory system during inspiration. Second, the driving pressure includes the pressure that is needed to move not only the lungs but also the chest wall. Even though the calculations might prove useful to track mechanical energy and mechanical power in a single patient, the dispersion that may arise as a result of different chest wall properties might become prohibitive in terms of setting safety thresholds across patient populations. It is worth noting that mechanical power values reported in the postoperative pulmonary complication post hoc analysis, which are in the range of 5.5 of 8.7 J/min in the group that developed postoperative pulmonary complications and 5.2 to 8.5 J/min in the group without postoperative pulmonary complications, are substantially lower than the threshold of 12 J/min suggested as likely safe. In addition, safety thresholds for cumulative mechanical energy have not been explored yet.
From a pathophysiological perspective, the finding that mechanical energy, but not mechanical power, was associated with postoperative pulmonary complications is intriguing and offers new insight into the mechanisms of ventilator-induced lung injury. While mechanical power seems to merge all potential factors leading to ventilator-induced lung injury, the time of exposure to increased mechanical power has been frequently neglected in most analyses. The question that immediately arises from the current post hoc analysis is whether longer exposure times to low mechanical power may also promote ventilator-induced lung injury or whether there is a safety threshold below which no harm is caused to the lung irrespective of the duration of mechanical ventilation. Another important aspect to consider is whether safety thresholds are dependent on the underlying lung conditions, with previously normal lungs being less prone to injury than diseased lungs. Although those questions might sound trivial, they challenge the concept of mechanical power as the unifying mechanism of ventilator-induced lung injury. Taken together with experimental findings that not only mechanical power must be reduced to avoid ventilator-induced lung injury but also the key variables that determine mechanical power, most notably VT and driving pressure, must be situated within their respective protective ranges exposure time to MV seems to play a key role as well. Thus, we might postulate that ventilator-induced lung injury might result not only when mechanical power exceeds the regenerative capabilities of the lung tissue but also when mechanical energy accumulated in the lungs exceeds those capabilities. Figure 1 illustrates this concept by means of an analogy with filling a bowl with water, where the inflow rate represents mechanical power, the volume of water in the bowl is the accumulated mechanical energy, the escape or outflow rate represents the regenerative capability of the lungs, and overflow represents the occurrence of ventilator-induced lung injury. If the flow rate is high and the escape rate is moderate, but the exposure time is short, the bowl will not overflow (fig. 1A). When the exposure time increases, the same filling rate leads to overflow at the same escape rate (fig. 1B). Theoretically, a moderate filling rate might lead the bowl to overflow if the exposure time is long enough and the escape rate is low (fig. 1C). It remains unclear, however, if the energy that accumulates in the lungs due to PEEP would also result in lung injury, given that it does not result in tidal movement of lung units. Further, it is conceivable that the balance between energy dissipated by the lungs and the regeneration mechanisms are modulated by multiple independent factors, including fluid accumulation, presence of oxygen radicals, exposure to random-modulative agents, and genetic susceptibility, among others, which might be particularly relevant during one-lung ventilation.
A final aspect that deserves consideration when interpretating this post hoc analysis is that while the multivariable logistic regression models used by the authors included confounders that are relevant from a clinical perspective, they are not immune to missing confounders. For this reason, association analyses do not build evidence for decision-making, which requires well powered interventional trials. The anesthesiology community should be thankful to Yoon et al. for the efforts they put into this well performed post hoc analysis and the important information conveyed, which further advanced our knowledge about ventilator-induced lung injury. In our view, however, the body of evidence accumulated so far is not sufficient yet to support the use of mechanical energy and mechanical power as aids to guide protective mechanical ventilation settings during one-lung ventilation, nor during two-lung ventilation, in the operating room and intensive care unit.
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