Effects of sodium bicarbonate administration on the exercise tolerance of normal subjects breathing through dead space.

STUDY OBJECTIVE: The purpose of this study was to determine whether the administration of sodium bicarbonate to normal individuals would increase their PaCO2 and thereby decrease the ventilatory requirements at a given workload. DESIGN: In this double-blind crossover study, six normal men ingested either 3 mEq/kg NaHCO3 or 1 mEq/kg NaCl once a day for 5 days, in addition to 40 mg of furosemide and 40 mEq KCl. After each 5-day treatment, the subjects underwent a symptom-limited maximal bicycle ergometer exercise test while breathing through external dead space (with a volume of approximately 50% of their FEV1), a second exercise test without any external dead space, and an assessment of their respiratory response to hypercapnia. RESULTS: The administration of the NaHCO3 resulted in a significant increase in the arterial HCO3- from 20.8 to 24.0 mEq/L and a significant increase in the PaCO2 from 31.7 to 36.9 mm Hg at rest that persisted during exercise. During exercise periods with the added dead space, the Borg scores were significantly lower at each workload after the subjects received bicarbonate, but the maximal exercise level did not increase. The mean (+/-SD) slope of the mouth occlusion pressure response to hypercapnia was significantly lower after the administration of NaHCO3 than after NaCl, respectively: 0.73+/-0.41 vs 1.27+/-0.97 cm H2O/mm Hg. CONCLUSION: From this study we conclude that the administration of NaHCO3 results in a significant increase in the PaCO2, decreases the ventilation and the Borg score at equivalent workloads, and decreases the hypercapnic response in normal individuals.

Comparison of mitoxantrone and tetracycline as pleural sclerosing agents in rabbits.

Bleomycin is the antineoplastic agent used most commonly for the treatment of malignant pleural effusion. It is absorbed rapidly from the pleural space and does not elicit pleurodesis in the normal rabbit pleura. Mitoxantrone is a new antineoplastic that differs from bleomycin in that it binds to membranes. Accordingly it might remain in the pleural space for a longer period and produce a pleurodesis. The objective of this project was to determine whether mitoxantrone is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anesthetized male rabbits: 35 mg/kg tetracycline or 0.5, 1.0, or 2.0 mg/kg mitoxantrone. The animals were killed at 28 days and the pleural spaces assessed grossly for pleurodesis and microscopically for fibrosis and inflammation. The mean degree of gross pleurodesis did not differ significantly in the rabbits that received tetracycline (3.8 +/- 0.4) and in the rabbits that received 2 mg/kg mitoxantrone (3.2 +/- 1.3). The degree of pleural and lung inflammation was significantly greater after mitoxantrone than after tetracycline, both ipsilaterally and contralaterally. The mortality after the highest dose of mitoxantrone was 50%. From this study we conclude that the intrapleural administration of mitoxantrone in rabbits can produce a pleurodesis. The histologic picture after mitoxantrone administration differs markedly from that after tetracycline injection. After mitoxantrone injection there are many more inflammatory cells present on the side that received the injection, and there is much more fibrosis and inflammation in the contralateral pleura and lung. The model of pleural fibrosis following intrapleural mitoxantrone may be useful for the study of pleural fibrosis.

Significance of iatrogenic pneumothoraces.

The purpose of this study was to review the cases of iatrogenic pneumothorax that occurred between October 1983 and December 1988 at the Veterans Administration Medical Center, Long Beach, Calif, to determine the treatment and complications. During this time period, 106 patients were identified with iatrogenic pneumothorax, and the charts of 98 were available for review. There were 90 cases of spontaneous pneumothorax at this institution during the same time period. The most common cause of iatrogenic pneumothorax was transthoracic needle aspiration (35), followed by thoracentesis (30), subclavian venipuncture (23), and positive pressure ventilation (7). In 11 cases, the cause was due to miscellaneous triggers. The majority of the patients (65 of 98) were treated with chest tubes. The chest tubes were in place 4.7 +/- 3.9 days. Nine of the patients required a second chest tube. Aspiration of the pneumothorax only was attempted in five patients, and all patients subsequently received a chest tube. Two patients died from iatrogenic pneumothorax. One patient receiving positive pressure ventilation developed an unrecognized tension pneumothorax. The other patient developed a pneumothorax after thoracentesis and was treated with a chest tube, which led to a staphylococcal empyema and death. From this study, we conclude that the incidence of iatrogenic pneumothorax exceeds that of spontaneous pneumothorax and that there is substantial morbidity and some mortality from iatrogenic pneumothorax.

Reanalysis of the 12-minute walk in patients with chronic obstructive pulmonary disease.

The purpose of this study was to determine the correlation between different intervals in the 12-min walk test, to determine which of the intervals best correlated with maximal oxygen intake (VO2max) and maximal CO2 expelled (VCO2max) and to determine the degree of correlation between changes in the VO2max and changes in the walk test and spirometry. Nine elderly (age, 67 +/- 4 years) patients with moderate COPD (FEV1, 1.32 +/- 0.28 L) who were ventilatory limited were seen 6 times over a 14-week period. At each visit they performed spirometry, a 12-min walk, and a symptom-limited maximal exercise test. During the 12-min walk the distances traversed in each 2-min interval were recorded. A Borg score was obtained at the end of each 2 min. The distances that the patients walked in each 2-min interval were very similar, but the mean Borg score became higher the longer the patient walked. The Borg score after 2 min was 1.64 +/- 1.15, while the Borg score after 12 min was 5.70 +/- 3.59. The correlation coefficients between the distance walked at various intervals and the oxygen consumption (VO2)/kg (approximately 0.65) and the VCO2/kg (approximately 0.52) were very similar. However, changes in the VO2/kg were more closely correlated with changes in the 12-min walk (r = 0.72), than with changes in the 6-min walk (r = 0.64), the 4-min walk (r = 0.59), or the 2-min walk (r = 0.53). This latter observation suggests that the 12-min walk may be preferable to tests in which the patient walks 4 or 6 min for documenting changes in the exercise capabilities.

Effects of buspirone on anxiety levels and exercise tolerance in patients with chronic airflow obstruction and mild anxiety.

The objective of this study was to determine if buspirone would alleviate anxiety and improve exercise tolerance of anxious patients with chronic airflow obstruction (CAO). Eleven male patients with mild to moderate anxiety and CAO completed this study comparing buspirone, 10 to 20 mg given three times a day, with placebo. Patients were evaluated with State Trait Anxiety Inventory, spirometry, 12-min walk, incremental exercise on a cycle ergometer to symptom limitation and measurement of dyspnea with a modified Borg scale at exercise levels and the end of each 2 min on 12-min walk. There were no significant differences in anxiety scores, work load, maximum oxygen consumption per minute, maximum expired volume per minute, PETCO2, PETO2, 12-min walking distance or dyspnea scores after 6 weeks of buspirone or placebo therapy. We conclude that administration of buspirone has no significant effect on anxiety levels, exercise capabilities or PETO2 or PETCO2 in patients with CAO and mild anxiety.

Conversion of COPD patients from multiple to single dose theophylline. Serum levels and symptom comparison.

The objective of the present study was to determine if patients with COPD who were taking Theo-Dur bid or tid (total dose 400 to 900 mg per day) could be safely switched to Uni-Dur, 800 mg given qd at bedtime. Twenty-eight patients were enrolled in the study, and 23 completed the study. The mean daily dose of theophylline prior to the study was 828 mg, while the mean dose after three weeks of Uni-Dur therapy was 783 mg. The mean serum theophylline level 10.5 +/- 3.6h after the last Theo-Dur dose was 10.5 mg/L. After three weeks of Uni-Dur therapy, the mean theophylline level at 8:00 AM was 14.6 mg/L, while the mean theophylline level at 8:00 PM was 9.9 mg/L. This latter level did not differ significantly from that obtained at the start of the study 10.5 +/- 3.6 h after the last dose of Theo-Dur. After three weeks of Uni-Dur therapy, the peak expiratory flow rate, the FEV1, and the FVC were not significantly changed from those at the initial evaluation. Twenty-one of the 23 patients ended up receiving 800 mg Uni-Dur qd. From this study, we conclude that once daily theophylline dosing with Uni-Dur compared with bid or tid dosing with Theo-Dur produces similar theophylline levels and pulmonary function, and most COPD patients who are taking 400 to 900 mg Theo-Dur daily can be managed with 800 mg Uni-Dur once daily at bedtime.

Nebulizer vs spacer for bronchodilator delivery in patients hospitalized for acute exacerbations of COPD.

This double-blind crossover study compared the efficacy of two methods of delivery (MDI-spacer and nebulizer) of inhaled albuterol to patients hospitalized for an acute exacerbation of COPD. Within 24 h of admission, 20 subjects (mean age, 69 years) with severe airflow obstruction (mean FEV, 0.69 L) were subjected to a treatment with an MDI-spacer (0.36 mg of albuterol or placebo) followed by treatment with a nebulizer (2.5 mg of albuterol or placebo). Active drug was given by only one device (randomly assigned in a double-blind manner), and the entire sequence was repeated in 4 h, with active drug given in the alternate device. Spirometric data and the Borg dyspnea score were obtained before and 1 h after each sequence of treatments. Treatment resulted in significant improvements in the FEV1, FVC, and Borg score. The percent improvement in the FEV1 was slightly larger after treatment with the nebulizer (16.7 percent vs 13.4 percent). Improvements in the Borg score were slightly larger after treatment with the MDI-spacer (-1.08 vs -0.73). However, these differences were not statistically significant. This study suggests that the MDI-spacer system is an effective method of sympathomimetic delivery in this setting, provided patients are able to master the technique.

Prevalence of depression and anxiety in patients with COPD. Relationship to functional capacity.

The objective of this study was twofold: (1) to document the prevalence of depression and anxiety in patients with moderate or severe chronic obstructive pulmonary disease; and (2) to determine whether the presence of depression or anxiety adversely affected the functional capabilities of the patient as reflected by the distance he could walk in 12 minutes. Forty-five patients with an FEV1 less than 1,250 ml underwent pulmonary function testing including spirometry, single breath diffusing capacity, and arterial blood gas determinations. The degree of depression was assessed by the Beck depression inventory, while the degree of anxiety was assessed by the State-Trait anxiety inventory. Forty-two percent of the patients had significant depression, while only 2 percent of the patients had significant anxiety. There was a highly significant correlation between the depression scores and the anxiety scores (r = 0.81, p less than 0.001). There was no significant correlation between the level of depression or anxiety and the distance that the patient could walk in 12 minutes. From this study, we conclude that the prevalence of depression in patients with moderate or severe COPD approaches 50 percent while the incidence of anxiety is much lower (2 percent).