Data on patients with amyotrophic lateral sclerosis (ALS) admitted to the intensive care unit (ICU) for acute respiratory failure are scarce, and early prognostic markers are lacking.

We conducted a retrospective cohort study of consecutive patients with ALS admitted for acute respiratory failure to two ICUs of a tertiary referral center between 2016 and 2022. The primary outcome was 3-month mortality. Factors associated with 3-month mortality were assessed using multivariable Cox proportional hazards regression. Survival and functional outcomes were evaluated up to 12 months.

Among 139 patients [median age 66 (IQR 57–73) years, 61.2% being men], 109 (78.4%) patients presented with hypercapnia and 82 (59.0%) with hypoxemia (defined as PaO₂/FiO₂ ratio < 300) at ICU admission, with frequent overlap between both conditions. Non-invasive ventilation was used in 79.9% of patients, while 13.7% were intubated, and 2.2% underwent tracheostomy. Three-month mortality was 48.2%, increasing to 61.2% and 74.1% at 6 and 12 months respectively. In multivariable analysis, hypoxemia at ICU admission was independently associated with increased 3-month mortality (HR = 2.27, 95% CI: 1.28–4.01; P  = 0.005), along with older age (HR=1.03 per year, 95% CI: 1.00–1.06; P  = 0.035). Among patients alive at 3 months, a majority (79.2%) were living at home.

ICU admission for acute respiratory failure in ALS is associated with substantial short-term mortality, consistent with the poor prognosis inherent to the natural history of the disease. Hypoxemia at admission identifies a subgroup at particularly high risk of death and may help inform early prognostic assessment and shared decision-making. However, patients who survive the acute ICU phase frequently achieve favorable short-term outcomes, with most living at home at 3 months.