Identifying Daytime Hypercapnia Using Transcutaneous Carbon Dioxide Monitoring in Patients With Amyotrophic Lateral Sclerosis.

Introduction/aims: Respiratory failure from hypoventilation is the most common cause of death in amyotrophic lateral sclerosis (ALS). However, ALS care rarely assesses hypercapnia, a physiologic measure of hypoventilation. We investigated the prevalence and clinical significance of daytime hypercapnia measured by transcutaneous carbon dioxide (tcCO₂) monitoring in patients with ALS.

Methods: This retrospective study included patients seen at two ALS clinics in the United States between 2012 and 2024 who had tcCO₂ measured concurrently with pulmonary function tests (PFTs), which included forced vital capacity (FVC) and, at one site, maximum inspiratory pressure (MIP). We assessed the prevalence of hypercapnia (tcCO₂ > 45 mmHg), the sensitivity and specificity of patient symptoms and PFTs for hypercapnia, and the relationship between hypercapnia and survival.

Results: Daytime hypercapnia was present in 33/328 (10%) patients at baseline. Hypercapnia was associated with an increased rate of death (aHR 2.1, 95% CI 1.4-3.3). Orthopnea or dyspnea was 70% sensitive for hypercapnia (95% CI 51%-84%). Absolute value of MIP (|MIP|) < 60 cmH₂O was 95% sensitive (95% CI 74%-100%) and 22% specific (95% CI 16%-30%), FVC < 50% predicted was 33% sensitive (95% CI 18%-52%) and 82% specific (95% CI 78%-87%), and FVC < 80% predicted was 85% sensitive (95% CI 68%-95%) and 31% specific (95% CI 26%-36%) for hypercapnia.

Discussion: TcCO₂ monitoring identified strengths and weaknesses of PFTs in identifying hypercapnia in ALS. We found high sensitivity of |MIP| < 60 cmH₂O and FVC < 80% predicted and high specificity of FVC < 50% predicted. Prospective studies should investigate the optimal clinical role for tcCO₂.