Prevention of pulmonary morbidity for patients with neuromuscular disease.

STUDY OBJECTIVE: To evaluate the effects of a respiratory muscle aid protocol on hospitalization rates for respiratory complications of neuromuscular disease. DESIGN: A retrospective cohort study. METHODS: A home protocol was developed in which oxyhemoglobin desaturation was prevented or reversed by the use of noninvasive intermittent positive-pressure ventilation and manually and mechanically assisted coughing as needed. The patients who had more than one episode of respiratory failure before having access to the protocol were considered to have had preprotocol periods (group 1). Other patients were given access to the protocol when their assisted peak cough flows decreased to < 270 L/min before any episodes of respiratory distress (group 2). The number of hospitalizations and days hospitalized were compared longitudinally for preprotocol and protocol access periods (group 1). In addition, avoided hospitalizations were identified as "episodes" of need for continuous ventilatory support and desaturations reversed by assisted coughing that were managed at home. Data were segregated by access to protocol and by extent of baseline ventilator use. RESULTS: Of the 47 group 1 patients with preprotocol periods who have subsequently had episodes, 10 had episodes before requiring ongoing ventilator use. They had 1.06 +/- 0.84 preprotocol hospitalizations per year per patient and 20.76 +/- 36.01 hospitalization days per year per patient over 3.42 +/- 3.36 years per patient vs 0.03 +/- 0.11 hospitalizations per year per patient and 0.06 +/- 0.20 hospitalization days per year per patient with protocol use over 1.94 +/- 0.74 years per patient. Of these 47 group 1 patients, 33 eventually required part-time ventilatory aid and, using the protocol as needed, had 0.08 +/- 0.17 hospitalizations per year per patient and 1.43 +/- 3.71 hospitalization days per year per patient over 3.91 +/- 3.50 years per patient, as opposed to 1.40 +/- 1.96 hospitalizations per year per patient and 20.14 +/- 41.15 hospitalization days per year per patient preprotocol and preventilator use over 5.89 +/- 6.89 years per patient. Twelve patients in group 1 eventually required continuous noninvasive ventilation and, using the protocol as needed, had 0.07 +/- 0.14 hospitalizations per year per patient and 0.39 +/- 0.73 hospitalization days per year per patient over 5.35 +/- 5.10 years per patient by comparison with 0.97 +/- 0.74 hospitalizations per year per patient and 10.39 +/- 8.66 hospitalization days per year per patient over 2.18 +/- 1.91 years per patient preprotocol and preventilator use. For the 94 patients overall when having access to the protocol, 1.02 +/- 0.99 hospitalizations per year per patient were avoided by 14 patients before requiring ongoing ventilator use over 4.82 +/- 1.61 years, 0.99 +/- 1.12 hospitalizations per year per patient were avoided by 73 part-time ventilator users over 3.21 +/- 3.15 years, and 0.80 +/- 0.85 hospitalizations per year per patient were avoided by 31 full-time ventilator users over 4.78 +/- 4.88 years. All preprotocol and protocol rate comparisons were statistically significant at p < 0.004. CONCLUSION: Patients have significantly fewer hospitalizations per year and days per year when using the protocol as needed than without the protocol. The use of inspiratory and expiratory aids can significantly decrease hospitalization rates for respiratory complications of neuromuscular disease.

Kinematic analysis of patients with spinal muscular atrophy during spontaneous breathing and mechanical ventilation.

Patients with infantile spinal muscular atrophy develop pectus excavatum along with a severe restrictive syndrome as a result of failure to expand the upper chest wall and lungs because of intercostal muscle weakness. By using an automatic motion analyzer to provide three-dimensional computer analyses of images sampled at 25 Hz, 9 spinal muscular atrophy Type II patients and 13 controls underwent kinematic analysis of thoracoabdominal movements partitioned into the upper thorax, lower thorax, and abdominal volume compartments. The analyses were performed during spontaneous breathing for the controls and during spontaneous breathing and while using mechanically assisted ventilation for the patients. Vital capacity, maximum inspiratory pressures, and nocturnal oxyhemoglobin saturation and transcutaneous carbon dioxide tensions were also measured for the patients. The kinematic data demonstrated a paradoxical ventilatory pattern for the spontaneously breathing SMA patients with the following inspiratory volume changes: upper thorax, -6.4+/-9.6%; lower thorax, 7.3+/-15.8%; abdominal, 99.1+/-21.3%. During mechanical ventilation, the compartmental volume changes were as follows: upper thorax, 13.5+/-6%; lower thorax, 13.7+/-7.9%; abdominal, 72.7+/-9.3%. This kinematic pattern is comparable with that seen in spontaneously breathing normal subjects. We conclude that mechanical ventilation can normalize kinematic volume changes during alveolar ventilation and that this might help deter loss of thoracic compliance caused by the chronic hypoventilation of the upper thoracic compartments. Kinematic analysis may be helpful for choosing the ventilation parameters to optimize therapeutic benefits.

Kyphoscoliosis ventilatory insufficiency: noninvasive management outcomes.

OBJECTIVE: To determine the effects on symptoms, pulmonary function, sleep, and other clinical variables of treating kyphoscoliosis-associated chronic alveolar hypoventilation with nocturnal nasal ventilation. DESIGN: Sixteen patients with kyphoscoliosis were treated with nocturnal nasal ventilation delivered by volume-cycled (seven patients) and pressure-cycled (nine patients) ventilators. Dyspnea, morning headaches, fatigue, hypersomnolence, and perceived sleep quality were assessed. RESULTS: All pretreatment symptoms improved significantly with nasal ventilation. Likewise, PaO2 (mm Hg), PaO2/FlO2, PaCO2 (mm Hg), pH, and forced vital capacity (in milliliters and as a percentage of predicted normal) significantly improved with treatment. Maximum inspiratory pressures and maximum expiratory pressures also significantly increased. Tidal volumes increased significantly and breathing frequency decreased (not significant). Although perceived sleep quality improved, as well as sleep oxyhemoglobin saturation, there was no significant change in sleep architecture. Hospitalization days for respiratory difficulties also decreased from 10.9 +/- 13.3 days in the 6 mo before intermittent positive-pressure ventilation to 0 days during the first 6 mo of treatment. CONCLUSIONS: Although not apparently affecting sleep architecture, nocturnal nasal ventilation can significantly improve nocturnal and daytime blood gases, pulmonary function, and symptoms of hypoventilation for patients with severe kyphoscoliosis.

Neuromuscular ventilatory insufficiency: effect of home mechanical ventilator use v oxygen therapy on pneumonia and hospitalization rates.

The purpose of this study was to determine rates of pneumonia and hospitalization for patients receiving oxygen therapy, patients having indwelling tracheostomy tubes, and those using tracheostomy or noninvasive methods of home mechanical ventilation. Six hundred eighty-four users of assisted ventilation for 13,751 patient-years or 19.8 years per patient were surveyed by mail and twice by telephone over a span of four years. Pneumonia and hospitalization rates were significantly higher for ventilator users with chronic obstructive pulmonary disease or with neuromuscular ventilatory insufficiency and gastrostomy tubes than for ventilator users with neuromuscular ventilatory insufficiency without gastrostomy tubes. Of the latter group, more than 90% of the pneumonias and hospitalizations were triggered by otherwise benign intercurrent upper respiratory tract infections. Oxygen therapy was associated with a significantly (P < 0.001) higher rate of pneumonias and hospitalizations than that seen for untreated patients after initial episodes of respiratory distress or during the use of either tracheostomy intermittent positive pressure ventilation or noninvasive ventilatory assistance methods. The lowest pneumonia and hospitalization rates (P < 0.001) were by full-time, noninvasive intermittent positive pressure ventilation users. We conclude that oxygen therapy is not an effective substitute for assisted ventilation for patients with primarily ventilatory insufficiency. Noninvasive ventilatory aids can be used effectively for up to full-time ventilatory support for patients with neuromuscular conditions whose bulbar muscle function is adequate to avert the need for gastrostomy tube placement.

A study of thyrotropin-releasing hormone for the treatment of spinal muscular atrophy: a preliminary report.

OBJECTIVE: To determine whether thyrotropin-releasing hormone (TRH) can increase muscle strength in children with spinal muscular atrophy types 2 and 3. DESIGN: A randomized, double-blinded, controlled, 5-wk drug trial of six subjects and three controls. Subjects and controls ranged from 4 to 8 yr of age and were randomly assigned to treatment and placebo groups in a ratio of 2:1. TRH (protirelin) or placebo was delivered intravenously through percutaneous intravenous catheters at a dose of 0.1 mg/kg (in 50 ml of normal saline) for a total of 29 days. Patients were evaluated using electromyography and handheld dynamometry of the deltoids, biceps, triceps, wrist extensors, hip flexors, quadriceps, hamstrings, and grip strength before and immediately after 5 wk of treatment. A unidirectional t test was used to compare mean values. RESULTS: Dynamometry improved significantly only for the six treated subjects (P < 0.02). Peroneal nerve conduction velocities were significantly faster in the treatment group (paired t test, P = 0.036). The parents of the treated children also provided anecdotal evidence of improvements in function. Improvements lasted 6-12 mo. CONCLUSIONS: TRH may be a useful treatment for spinal muscular atrophy. A larger, crossover design group comparison study is warranted.