Respiratory parameters on diagnostic sleep studies predict survival in patients with amyotrophic lateral sclerosis.

OBJECTIVE: In amyotrophic lateral sclerosis (ALS), respiratory muscle involvement and sleep-disordered breathing relate to worse prognosis. The present study investigated whether respiratory outcomes on first-ever sleep studies predict survival in patients with ALS, specifically taking into account subsequent initiation of non-invasive ventilation (NIV). METHODS: From patients with ALS, baseline sleep study records, transcutaneous capnometry, early morning blood gas analysis, survival data and clinical disease characteristics were retrospectively analyzed. Patients were stratified according to whether enduring NIV was consecutively established ("NIV(+)") or not ("NIV(-)"). RESULTS: Among the study cohort (n = 158, 72 female, 51 with bulbar onset ALS, 105 deceased) sleep-disordered breathing was present at baseline evaluation in 97 patients. Early morning base excess (EMBE) > 2 mmol/l predicted nocturnal hypercapnia. Ninety-five patients were NIV(+) and 63 were NIV(-). Survival from baseline sleep studies was significantly reduced in NIV(-) but not in NIV(+) patients with nocturnal CO2 tension ≥ 50 mmHg, apnea hypopnea index ≥ 5/h, and EMBE > 2 mmol/l. Hazard ratio for EMBE > 2 mmol/l was increased in NIV(-) patients only, and EMBE independently predicted survival in both NIV(-) and NIV(+) patients. Furthermore, EMBE on baseline sleep studies was the only predictor for survival from symptom onset, and hazard ratio for shorter survival was markedly higher in the NIV(-) than the NIV(+) group (2.85, p = 0.005, vs. 1.71, p = 0.042). INTERPRETATION: In patients with ALS, EMBE > 2 mmol/l predicts nocturnal hypercapnia and shorter survival. Negative effects of sleep-disordered breathing on survival are statistically abolished by sustained NIV.

Prevalence of sleep apnoea and capnographic detection of nocturnal hypoventilation in amyotrophic lateral sclerosis.

OBJECTIVE: This retrospective study aimed to investigate whether overnight oxymetry and early morning blood gas analysis predict nocturnal hypoventilation (NH) as reflected by night-time hypercapnia in patients with amyotrophic lateral sclerosis (ALS). In addition, prevalence and clinical determinants of sleep apnoea in ALS were evaluated. METHODS: In 250 patients with non-ventilated ALS, transcutaneous capnometry was performed along with polysomnography or polygraphy and early morning blood gases. RESULTS: 123 patients were female, and 84 patients had bulbar-onset ALS. 40.0% showed NH, and an apnoea-hypopnoea index (AHI) >5/hour was found in 45.6%. In 22.3%, sleep apnoea and NH coincided. The obstructive apnoea index was significantly higher than the central apnoea index (p<0.0001). Both NH and sleep apnoea were significantly more common in male than in female patients. Sleep apnoea and AHI were associated with better bulbar function. Desaturation time (t<90%) and transcutaneous CO2 were negatively correlated with upright vital capacity. Early morning base excess (EMBE), bicarbonate and t<90% were independent predictors of NH. However, among 100 patients with NH, 31 were missed by t<90% >5 min and 17 were not identified when EMBE >3 mmol/L and t<90% >5 min were combined. CONCLUSION: In ALS, sleep apnoea is common and often accompanies NH. It is mainly obstructive, and central apnoea appears to be clinically irrelevant. Polygraphy or oxymetry alone are not sufficient to uncover NH. Combination of EMBE and t<90% may increase sensitivity, but transcutaneous capnography is strongly recommended for reliable detection of NH in patients with ALS.