Noninvasive ventilation for acute respiratory distress syndrome: the importance of ventilator settings

Noninvasive ventilation (NIV) is a well-established treatment for acute respiratory failure (1), especially in patients with hypercapnia (2) and cardiogenic pulmonary edema (3). Conversely, the use of NIV for hypoxemic respiratory failure, including the acute respiratory distress syndrome (ARDS), is still controversial (4-12). Avoidance of NIV in these patients is often justified by the association between a failed NIV attempt with worse prognosis (8,11-13). In these studies, however, it is unclear whether NIV failure was responsible for the worse prognosis (a causal association, likely by delaying intubation) or if it was merely a marker of the underlying disease severity, such as severe sepsis, higher SAPS-II score, and lower arterial partial pressure of oxygen to inspired fraction ratio (PF-ratio) (8,14,15). A recent study showed similar adjusted outcomes in patients who failed a trial of NIV as compared to patients primarily intubated, supporting the non-causal association hypothesis (14).

Despite the debatable recommendation, NIV is regularly used for hypoxemic respiratory failure (13). Specifically for ARDS patients, a recent study (16) showed that NIV was used in 14.4% of patients (436 of 3,022), with 69% of them (300 of 436) being exclusively managed with NIV. These numbers highlight the importance of the topic, on which there is scarce literature.

In a recent study, Patel et al. (17) brought to attention the importance of the NIV interface in the outcome of ARDS patients. In this single-center trial, interrupted early for efficacy, 83 ARDS patients requiring NIV by face mask for at least 8 hours were randomized to NIV by helmet or to continue with the face mask. In the helmet group, intubation rate (the primary endpoint) was less than a third that in the face-mask group (18.2% vs. 61.5%). The lower intubation rate was associated with more ventilator-free days and lower mortality.

Can we attribute all of this expressive difference in outcome solely to the interface? To be able to address this question, it can be useful to examine the results more closely. The most common reason for intubation was tachypnea and hypoxemia (83.3% for the face mask vs. 37.5% for the helmet). Positive end-expiratory pressure (PEEP), a ventilatory setting used to avert hypoxemia, was set 3 cmH₂O higher in the helmet group [median of 8.0 (5.0–10.0) vs. 5.1 (5.0–8.0) cmH₂O]. This could explain at least in part the significant reduction in the intubation rate in the helmet group. In their discussion, the authors argued that, in the face-mask group, patient intolerance and excess air leaks limited the titration of PEEP to higher levels. Curiously, pressure support levels were 3 cmH₂O higher in the face-mask group leading to comparable total inspiratory pressures (~16 cmH₂O) between groups. It is true that the helmet interface has been associated with better tolerance in some studies (18). On the other hand, other authors (19,20) have been able to deliver even higher inspiratory pressures (≥20 cmH₂O) through face masks with good tolerance (19). Of note, one study showed that the amount of leak was related to the total inspiratory pressure, not the PEEP (19). In that study, either a low PEEP (5 cmH₂O) and high pressure support (15 cmH₂O) or a high PEEP (10 cmH₂O) and low pressure support (10 cmH₂O) were both well tolerated and associated with similar measured leaks (~36%). In Patel’s study, subjective decisions regarding patient comfort and excess leaks might have influenced the results. More stringent criteria for the definition of patient tolerance and acceptable leaks would have been welcome.

Several studies (21-23) have shown that using the helmet interface predisposes to CO₂ rebreathing due to its increased internal volume. In fact, the helmet works as a semi-closed system, and the degree of CO₂ rebreathing depends basically on the amount of fresh gas (on top of the patient minute ventilation) and the CO₂ production by the patient (21). For example, in a study by Taccone et al. (21) in normal volunteers with high flow rates of fresh gas (60 L/min), the inspired pressure of CO₂ (PiCO₂) was on average 2.5 mmHg; with a flow rate of fresh gas of 10 L/min, the average PiCO₂ was 13.7 mmHg, an amount of rebreathing similar to that obtained with a critical care ventilator (average PiCO₂ of 12.4 mmHg) such as the one used in the Patel’s study (17). Bear in mind that the flow rate of fresh gas has to be on top of the patients’ minute volume. This quantity is also known as bias flow and is settable in some mechanical ventilators within a prespecified range. In the mechanical ventilator used in Patel’s study, this quantity is limited to 10 L/min and is unrelated with the peak inspiratory flow displayed by the ventilator. It is the bias flow and not the inspiratory flow the quantity that matters for the rebreathing of CO₂, what suggests that there was considerable rebreathing in Patel’s study.

Having said this, how can we reconcile the likely relevant dead space ventilation in the helmet group with the decreased respiratory rate (24.5 vs. 29.1 bpm in the face mask group) together with lower pressure support levels (8 vs. 11 cmH₂O in the face mask group)? Once more, we believe that the higher PEEP values in the helmet group might have been the key. Higher PEEP levels can promote recruitment of alveolar units leading to both decreased shunt and decreased shunt dead space ventilation. In other words, it is possible that the higher PEEP levels were responsible not only for better oxygenation (and thus lower intubation rate), but also for improved CO₂ elimination.

Perhaps one the most important contributions of Patel’s study was to emphasize that protective ventilation is as important during NIV as it is during invasive mechanical ventilation (24,25) in patients with hypoxemic respiratory failure. Lung-protective strategies were an important development in the treatment of patients with ARDS. Such strategies improve survival combining the use of low tidal volumes, low plateau pressures, and high PEEP values (24,25). Unlike patients under invasive mechanical ventilation, for whom there are established protective ventilation protocols, NIV currently lacks ventilation protocols directed to avoid the mechanisms of ventilator-induced lung injury. This is perhaps one of the major difficulties of the use of NIV in patients with ARDS. As a result, non-protective settings are commonly used. For example, tidal volumes greater than 10 mL per kilogram of predicted body weight were used in over half the patients included in a recent European cohort of acutely hypoxemic patients (26). In that study, tidal volume was a strong predictor of NIV failure, suggesting that close monitoring of tidal volume is important. In patients with persistently high tidal volumes, early invasive ventilation might be a reasonable option to avoiding ventilator induced lung injury.

In Patel’s study, besides higher PEEP levels in the helmet group, driving pressure was also lower, settings again consistent with a lung-protective strategy. Amato et al. (27), analyzing data from previously published trials of protective ventilatory strategies in ARDS, recently demonstrated that driving pressure (plateau pressure minus PEEP) was the variable most closely related to survival. This finding was later confirmed in a large prospective study in patients with ARDS (16) and also in patients (28) undergoing mechanical ventilation for general anesthesia, in whom lower driving pressures during the intraoperative period were associated with less postoperative pulmonary complications. A word of caution, though, in actively breathing patients, driving pressure is usually underestimated because of the unmeasured force exerted by the respiratory muscles.

The findings of Patel’s study highlight the importance to devise an NIV protocol specific for patients with hypoxemic respiratory failure. In hypercapnic respiratory failure, the protocol usually consists of the application of enough pressure support to improve alveolar hypoventilation and to unload the respiratory muscles, usually in combination with low values of PEEP until the underlying condition resolves (29). In hypoxemic respiratory failure, the main goals are to improve oxygenation, to unload the respiratory muscles, and to relieve dyspnea (19). The first goal a ventilatory setting by using higher PEEP levels to recruit and stabilize previously collapsed lung tissue. Therefore, PEEP is the main factor to improve oxygenation and we believe that its setting should take precedence as it could reduce the need for high inspiratory pressures. Moreover, optimization of PEEP can result in reduced tidal recruitment, improved dead space, and decreased inspiratory effort leading to lower tidal volumes (30-34). Tidal volumes need to be monitored, and pressure support levels, adjusted accordingly to avoid tidal volumes over 8 mL per kilogram of predicted body weight. Driving pressures should be kept low (note that—in the presence of respiratory muscle effort—driving pressures are underestimated). In the inability to follow these basic protective principles, intubation should be considered.

An additional and potentially valuable resource to improve oxygenation is lung recruitment, a maneuver seldom used during NIV (31,35). For example, Cammarota et al. (35) used the helmet to deliver a CPAP of 10 cmH₂O, which was transiently increased to 25 cmH₂O for 8 s to recruit the lungs. This recruitment was associated with a 37% improvement in oxygenation (from a PF-ratio of 225 to 308 mmHg).

In conclusion, the findings of Patel’s study suggest that, in patients with ARDS, NIV settings consistent with the principles of a protective ventilatory strategy produced better, clinically relevant outcomes. Use of NIV interfaces less prone to leakage may facilitate the application of lung-protective ventilation protocols for hypoxemic respiratory failure.

Acknowledgements

MA Nakamura is supported by a grant from FAPESP; CC Morais and MR Tucci are supported by a grant from CAPES (Coordination for the Improvement of Higher Level Personnel).

Footnote

Provenance: This is an invited Perspective commissioned by the Section Editor Zhongheng Zhang (Department of Critical Care Medicine, Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua, China).

Conflicts of Interest: The authors have no conflicts of interest to declare.

Comment on: Patel BK, Wolfe KS, Pohlman AS, et al. Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA 2016;315:2435-41.

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