Volume-Targeted Versus Pressure-Limited in Noninvasive Ventilation in Hypercapnic Respiratory Failure. What Could Be Established in Real Practice?—Reply

In Reply:

We thank Drs Briones Claudett and Esquinas for their interest and for commenting on our work.¹ It is our immense pleasure to response to such comments.

Regarding the methodology, we recruited 58 subjects with mild-to-moderate acute hypercapnic respiratory failure that mainly included COPD, asthma, bronchiectasis, and obstructive sleep apnea syndrome. Despite the small sample size, there were similar demographic and baseline characteristics between the two groups. As noted by Drs Briones Claudett and Esquinas, we included 7 subjects (12%) who had received noninvasive ventilation (NIV) previously, suggesting that in these subjects chronic hypercapnic respiratory failure occurred in the past. However, it is difficult to retrospectively obtain the specific conditions on which the previous NIV treatment was given.

It is of great importance to precisely define the severity of illness. Herein, we defined the eligible subjects as those with arterial pH < 7.35 and ≥ 7.25 with P_aCO2 >45 mm Hg and formulated the specific exclusion criteria. Despite no specific data on the severity of mental status impairment, we excluded patients with severe metabolic acidosis and lack of cooperation, which suggests that the subjects had favorable mental status. Considering that the changes of bicarbonates and base excess were not the primary variables, we did not present them in the Results section, even if we did in fact record them and found that there were no between-group and within-group differences over the first 6 h in these two variables. Moreover, the changes of pH and P_aCO2 at 0, 2, and 6 h were provided, which indirectly indicate the metabolic compensation level. In this study, despite no report on conventional therapy concerning COPD, the decision to conduct such treatment was left to the attending physician who was blinded to the study, suggesting that there might be similar treatment processes between the two groups.

We do not agree that the NIV use was prolonged. In this study, to avert respiratory distress after NIV liberation as much as possible, we formulated a rigorous withdrawal protocol for NIV, including the gradual decrease of pressure support level and the daily use of NIV under the conditions of clinical stability, and we established the specific criteria of NIV liberation. As a result, we found that the daily use of NIV was gradually decreased during the first 5 d after randomization, and the median (IQR) duration of NIV was 6.0 d (4.0–9.5 d) in the pressure-limited NIV (PL-NIV) group and 9.0 d (4.0–13.0 d) in the volume-targeted NIV (VT-NIV) group. There was no significant difference between the two groups.

In our protocol, we adjusted the inspiratory positive airway pressure (IPAP) level to obtain a tidal volume (V_T) of 8–10 mL/kg predicted body weight for PL-NIV, while the target V_T was set at 10 mL/kg predicted body weight for VT-NIV. We found that the exhaled V_T at the beginning of NIV was 9.5 ± 2.4 mL/kg in the PL-NIV group and 10.1 ± 1.5 mL/kg in the VT-NIV group, and the exhaled V_T at 6 h was 10.3 ± 2.3 mL/kg in the PL-NIV group and 10.4 ± 1.3 mL/kg in the VT-NIV group. There were no significant difference between the groups. We agree that the IPAP level had a tendency to be increased in the PL-NIV group. However, as the target to adjust IPAP level, the actual exhaled V_T was not significantly different between the groups, and thus the decrement of P_aCO2 was not significantly different between the groups. Certainly, as suggested by Frat an Thille,² an adequate tidal volume is the cornerstone of NIV efficiency in acute hypercapnic respiratory failure, whatever mode is used. Accordingly, whether the IPAP level should be increased as much as possible deserves further investigation.

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