Mechanism of CO2 retention in patients with neuromuscular disease

Background: In many studies of patients with muscle weakness, chronic hyper capnia has appeared to be out of proportion to the severity of muscle disea se, indicating that factors other than muscle weakness are involved in CO2 retention. In patients with CORD, the unbalanced inspiratory muscle loading -to-strength ratio is thought to trigger the signal for the integrated resp onse that leads to rapid and shallow breathing and eventually to chronic hy percapnia. This mechanism, although postulated, has not yet been assessed i n patients with muscular dystrophy. Subjects: Twenty consecutive patients (mean age, 47.6 years; range, 23 to 6 7 pears) were studied: 11 patients with limb-girdle dystrophy, 3 with Duche nne muscular dystrophy, with Charcot-Marie-Tooth syndrome, 1 with Becker mu scular dystrophy, 1 with myotonic dystrophy, 1 with facioscapulohumeral dys trophy, and 2 with amyotrophic lateral sclerosis, without any respiratory c omplaints. Seventeen normal subjects matched for age and sex were studied a s a control group. Methods: Routine spirometry and arterial blood gases, maximal inspiratory a nd expiratory muscle pressures (MIP and MEP, I espectively), and pleural pr essure during maximal sniff test (Pplsn), were measured. Mechanical charact eristics of the lung were assessed by evaluating lung resistance (RL) and d ynamic elastance (Eldyn). Eldyn was assessed as absolute value and as perce nt of Pplsn; Eldyn (%Pplsn) indicates the elastic load per unit of inspirat ory muscle force. Breathing pattern was assessed in terms of time (inspirat ory time [TI]; respiratory frequency [Rf]) and volume (tidal volume [VT]) c omponents of the respiratory cycle. Results: A rapid shallow breathing pattern, as indicated by a greater Rf/VT ratio and a lower TI, was found in study patients compared to control subj ects. Eldyn was greater in study patients, while MIP, MEP, and Pplsn were l on er. PaCO2 inversely related to VT, Tr, and Pplsn (p = 0.012, p = 0.019, and p = 0.002, respectively), whereas it was directly related to Rf, Rf/VT, Eldyn, and Eldyn (%Pplsn) (p < 0.004 to p < 0.0001). Also Eldyn (%Pplsn) i nversely related to TI, and the latter positively related to VT. In other w ords, increase in Eldyn (%Pplsn) was associated with decrease in TI, and th e latter was associated with lower VT and greater PaCO2. Mechanical and bre athing pattern variables were introduced in a stepwise multiple regression that selected Eldyn (%Pplsn) (p < 0.0001; r(2) = 0.62) as a unique independ ent predictor of PaCO2. Conclusions: The present study shows that in patients with neuromuscular di sease, elastic load and respiratory muscle weakness are responsible for a r apid and shallow breathing pattern leading to chronic CO2 retention.