Background: Chronic hypercapnic respiratory failure is associated with high mortality.While prior work has demonstrated a mortality improvement with high intensity noninvasive 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 Methods: 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 timevarying covariate to test the association between PCO2 and all-cause mortality adjusting for known cofounders
Results: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).
Conclusion: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.