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[JAMA发表述评]:接受手术的患者PEEP的设置
2019年06月22日 研究点评, 进展交流 暂无评论

Editorial June 3, 2019

Setting Positive End-Expiratory Pressure in Mechanically Ventilated Patients Undergoing Surgery

Thomas Godet, Emmanuel Futier

JAMA. 2019;321(23):2285-2287. doi:10.1001/jama.2019.7540

What is the optimal level of positive end-expiratory pressure (PEEP) for patients receiving mechanical ventilation? Despite decades of investigations, this question continues to be discussed among researchers and clinicians with no clear answer, leaving bedside management uncertain. The concept of protecting the lung during mechanical ventilation is considered a fundamental approach for patients in the intensive care unit with acute respiratory distress syndrome (ARDS),1 and is now attracting increasing interest for patients without injured lungs both in the intensive care unit and in the operating room.2-4

There is agreement that all patients receiving mechanical ventilation should benefit from low rather than high tidal volume to limit overdistension. However, ventilation at too low lung volumes can also cause injury through multiple mechanisms. The recent Protective Ventilation in Patients Without ARDS trial5showed that there does not seem to be additional benefit with extremely low tidal volumes (ie, <6 mL/kg of predicted body weight) in patients without ARDS. There is also clear evidence for benefit when using PEEP to prevent injury from atelectrauma. However, there are no guidelines for level of PEEP based on the results from randomized clinical trials (RCTs), with most evidence arising from RCTs that compared ventilation with a low vs a high level of PEEP.4,6 Thus, determining the optimal level of PEEP for the individual patient remains an important clinical issue.

One of the greatest challenges in caring for patients with obesity is optimization of mechanical ventilation. The pathophysiological changes induced by obesity, especially in respiratory mechanics, make these patients prone to difficult intubation, pulmonary complications, and prolonged duration of ventilation. Even though some evidence suggests that alveolar recruitment maneuvers along with a higher level of PEEP (the so-called open-lung strategy) improve oxygenation and lung mechanics in obese patients, most of the evidence to guide this strategy was based on small, single-center RCTs,7 and data on patient outcomes are lacking.

In an article in JAMA, the Protective Intraoperative Ventilation With Higher Versus Lower Levels of Positive End-Expiratory Pressure in Obese Patients (PROBESE) trial investigators8 report the results of a large RCT that was conducted at 77 sites in 23 countries and involved 2013 obese adults (body mass index [calculated as weight in kilograms divided by height in meters squared] ≥35) with an intermediate to high risk of developing postoperative pulmonary complications, who were undergoing laparoscopic or nonlaparoscopic surgery lasting 2 hours or longer. Patients were randomized to receive low tidal volume ventilation (7 mL/kg of predicted body weight) and either a high or low level of PEEP. Patients in the high level of PEEP group received a fixed PEEP level of 12 cm H2O added to alveolar recruitment maneuvers until an airway plateau pressure between 40 and 50 cm H2O was reached (alveolar recruitment maneuvers were performed after intubation and repeated every hour after any disconnection from the ventilator and before the end of surgery). Patients in the low level of PEEP group received a fixed PEEP level of 4 cm H2O without alveolar recruitment maneuvers, a strategy that was chosen to reflect best current practice.9 In both groups, the lowest fraction of inspired oxygen (but not <0.4) was targeted while maintaining greater than 92% oxygen saturation as measured by pulse oximetry. Other aspects of care were managed according to local expertise and routine clinical practice.

The primary outcome was a composite of postoperative pulmonary complications within the first 5 days following surgery, consisting of mild, moderate, and severe respiratory failure; ARDS; bronchospasm; new pulmonary infiltrates; pulmonary infection; aspiration pneumonitis; pleural effusion; atelectasis; cardiopulmonary edema; and pneumothorax. In the intention-to-treat analysis, patients randomized to receive a higher level of PEEP and repeated alveolar recruitment maneuvers (n = 989) did not experience a significant decrease in the primary outcome compared with patients randomized to receive a lower level of PEEP (n = 987), with rates for the composite outcome of 21.3% vs 23.6%, respectively (absolute difference, −2.3% [95% CI, −5.9% to 1.4%]). The results were similar in the per-protocol and sensitivity analyses. There were also no significant differences in the components of the primary outcome, or in the rates for most of the secondary outcomes, with the exception of hypoxemia that was more frequent in the low level of PEEP group, whereas hypotension and bradycardia were more common in the high level of PEEP group. As the authors acknowledge, given that no adjustment was made for multiple comparisons, these outcomes should be considered exploratory.

This well-conducted study is important because it represents the first large RCT providing data on patients who were excluded from earlier lung-protective ventilation studies and from the existing evidence. The results may be disappointing for clinicians and somewhat unexpected from what would have been predicted from previous small RCTs. Clinicians who prefer to see the glass half full may interpret the PROBESE results as suggesting an empirical strategy with a higher level of PEEP is equally as ineffective as a lower level of PEEP in preventing postoperative pulmonary complications. Other clinicians may suggest that the risk of hemodynamic compromise, as evidenced by a higher incidence of hypotension and bradycardia in the higher level of PEEP group, should prompt the adoption of a strategy with a lower level of PEEP. Because the study protocol did not provide a standard hemodynamic algorithm to titrate fluids and vasoactive drugs, caution in the interpretation is warranted.

The results from the PROBESE trial are analogous to that of an earlier RCT by the same study group that involved healthy weight patients4 and used similar methods as those used in the current report. Do these predominantly neutral results mean higher levels of PEEP and recruitment maneuvers should not be applied in mechanically ventilated patients? Perhaps. Alternatively, it may be possible that the optimal level of PEEP may lie between these extreme PEEP values. There is wide variability among patients in response to PEEP and recruitment maneuvers,10 and a single, uniformly applied level of PEEP cannot reflect individual patient differences. Some may intuitively suggest that an individualized strategy to titrate PEEP tailored to individual patient physiology would have been more informative.11 The results from the PROBESE trial were consistent across predefined subgroup analyses. Nonetheless, the possibility remains that there were different effects of PEEP among patients in both groups.

As the investigators report, the higher level of PEEP and alveolar recruitment maneuver strategy was associated with lower levels of driving pressure than in the lower level of PEEP group, which is expected from a strategy aimed at achieving higher volumes of aerated lung. Although the intervention effect may appear similar at the group level, it does not rule out the possibility of significant heterogeneity at the patient level. For example, a higher level of PEEP may result in low driving pressure for a given patient but with opposite effects in others. Such heterogeneity can lead to significant differences in outcomes.12 In other words, a higher level of PEEP may have been beneficial in some patients, but may have been harmful and not necessary in other patients.

Several other potential explanations should be considered when interpreting the results from the PROBESE trial, one of which is the patient population. Of the patients included in the intention-to-treat analysis, only 15.9% had high risk of postoperative pulmonary complications, those that theoretically (and intuitively) are expected to benefit the most from protective ventilation, and were exposed to relatively short durations of mechanical ventilation (median duration of 3 hours in both groups). Thus, it is reassuring that rates of individual pulmonary complications were low in both treatment groups, with the most common complication being mild respiratory failure (defined as hypoxemia responding to supplemental oxygen of ≤2 L/min).

What are the implications of the results from the PROBESE trial and where do clinicians go from here? First, it is reasonable to assume that a higher level of PEEP should not routinely be used in all mechanically ventilated patients. Should clinicians embrace the concept of permissive atelectasis and consider applying lower levels of PEEP for all patients? There is no evidence from this study to support such a hypothesis. Second, from a physiological perspective, there is a rationale to consider personalized adjustments in PEEP levels rather than fixed low or high PEEP levels uniformly applied to all patients. However, it is clear that efforts at reducing postoperative pulmonary complications are not just about providing protective ventilation and that a multimodal approach of care, including the early postoperative period, is certainly needed. Hopefully, additional treatment strategies will continue to be evaluated prospectively with the goal to promote more personalized approaches in caring for patients.

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