Lowering PCO2 with Non-invasive Ventilation is Associated with Improved Survival in Chronic Hypercapnic Respiratory Failure.

Chronic hypercapnic respiratory failure is associated with high mortality. While prior work has demonstrated a mortality improvement with high intensity non-invasive ventilation in chronic obstructive pulmonary disease, it is unclear whether a partial pressure carbon dioxide (PCO2) reduction strategy is associated with improved outcomes in other populations of chronic hypercapnia. The objective of this study was to investigate the association between PCO2 reduction (using transcutaneous partial pressure of carbon dioxide as an estimate for arterial PCO2) and survival in a broad population of individuals treated with NIV for chronic hypercapnia. We hypothesized that reductions in PCO2, would be associated with improved survival. Therefore, we performed a cohort study of all subjects evaluated from February 2012 to January 2021 for NIV initiation/optimization due to chronic hypercapnia at a home ventilation clinic in an academic center. We used multivariable Cox proportional hazard models with time-varying coefficients and PCO2 as a time-varying covariate to test the association between PCO2 and all-cause mortality adjusting for known cofounders. The mean age of 337 subjects was 57 ± 16 years; 37% female and 85% white. In univariate analysis, survival probability increased with reductions in PCO2 to <50 mm Hg after 90 days, and these remained significant after adjusting for age, sex, race, body mass index, diagnosis, Charlson comorbidity index, and baseline PCO2. In the multivariable analysis, patients who had a < 50 mm Hg had a reduced mortality risk of 94% between 90-179 days (HR=0.06; 95% CI: 0.01 - 0.50), 69% between 180 - 364 days (HR=0.31; 95% CI: 0.12 - 0.79), and 73% for 365 -730 days (HR = 0.27; 95% CI: 0.13 - 0.56). Reduction in PCO2 from baseline for subjects with chronic hypercapnia on NIV is associated with improved survival. Management strategies should target the greatest attainable reductions in PCO2.