We designed a randomized controlled study to evaluate the benefit of upper-limb exercise training, alone and in combination with walking training, in patients with severe CAO. In an outpatient department supervised by a physiotherapist, we evaluated 28 patients with severe stable CAO (FEV1, 32 percent of predicted). Patients were randomly allocated to either a control (eight), upper-limb (six), lower-limb (seven), or combined (seven) exercise group. The upper-limb group trained with a circuit of upper-limb exercises, the lower-limb group by walking, and the combined group with both. Exercise was for one hour three times per week for eight weeks. Assessment before and after training included pulmonary function, mouth pressures, respiratory muscle endurance, maximal bicycle exercise test, maximal and submaximal arm ergometer, six-minute walking distance, and a scale of well-being (Bandura scale). Twenty-six patients completed the program. There was a significant improvement (Wilcoxon rank sum test) in the following: six-minute walking distance in the lower-limb (p less than 0.005) and combined (p less than 0.003) groups; arm ergometer in the upper-limb (p less than 0.005) and combined (p less than 0.04) groups; and the scale of well-being in the combined (p less than 0.005) group. There was no significant change in any other parameter measured. We conclude that exercise training improves exercise performance in severe CAO, that the training is specific for the muscle group trained, and that upper-limb exercises should be included in training programs for these patients.

This prospective study was done to determine whether immediate echocardiography, to implicate or exclude a cardiac basis for breathlessness, can improve the management of acute dyspnea. One hundred ninety-six consecutive patients admitted to the hospital with a chief complaint of dyspnea were randomized to receive or not receive an echocardiogram within 24 hours of admission. Most patients randomized to echo and control groups had cardiac or pulmonary disease and were comparable in their other clinical characteristics. Predefined study end points included the following: change in diagnosis or treatment; performance of additional diagnostic cardiopulmonary studies; and duration of hospitalization (the principal end point). Changes in diagnosis or treatment during hospitalization were as infrequent among patients randomized to echo as among control patients. Echocardiography independently confirmed the clinical diagnosis in 72 percent of echo-randomized patients. Even when echo findings conflicted with the clinical diagnosis, the diagnosis and management plan rarely changed. Additional cardiac or pulmonary studies were ordered as frequently among patients randomized to echocardiography as among those randomized to control. The mean duration of hospital stay also did not differ between the two groups, and no clinical parameter served to predict which subgroup of patients might benefit from echocardiography. Although echocardiography can be expeditiously obtained during respiratory exacerbations of cardiopulmonary disease, indiscriminate echo does not necessarily hasten or alter the treatment of such patients.

We studied the treatment of multiple rib fractures in NIC, comparing ventilatory with nonventilatory methods in 69 patients who were randomly allocated to one of the following two treatments: (1) a CPAP mask combined with regional analgesia (n = 36); or (2) endotracheal intubation and mechanical ventilation with PEEP (n = 33). Clinical outcome was as follows: mean duration of treatment, 4.5 +/- 2.3 days for the group with CPAP and 7.3 +/- 3.7 days for the intubated group (p = 0.0003); mean number of days spent in intensive care, 5.3 +/- 2.9 days and 9.5 +/- 4.4 days, respectively (p = less than 0.0001); mean period of hospitalization, 8.4 +/- 7.1 days and 14.6 +/- 8.6 days, respectively (p = 0.0019); and patients developing complications: 28 percent (10/36) and 73 percent (24/33), respectively. Infections caused the difference in complications, primarily pneumonias, which occurred in 14 percent (5/36) of the group with CPAP but in 48 percent (16/33) of the intubated group. We conclude that treatment with a CPAP mask combined with regional analgesia can shorten and simplify treatment in these patients, mainly through a decreased infection rate, when compared with intubation and mechanical ventilation, and we recommend this treatment in patients similar to our sample.

In a double-blind, crossover study, nebulized ketanserin, a 5-HT2 receptor antagonist, and a placebo were given to eight patients with moderate to severe nonasthmatic COPD. Intravenous ketanserin had rapid onset of action and induced a longer lasting bronchial response than inhaled ketanserin. These results confirm that ketanserin acts as a mild bronchodilator in patients with COPD and demonstrate that the inhaled route has no advantage over the intravenous route in terms of effectiveness. Thus, 5-HT may play a role in bronchomotor tone, at least in patients with chronic airway obstruction.

We performed a randomized trial comparing two dosing regimens of recombinant tissue plasminogen activator (rt-PA) plus heparin vs heparin alone in the treatment of acute proximal deep vein thrombosis in 83 patients. Of 12 patients who received 0.5 mg/kg rt-PA plus heparin over 4 h, seven (58 percent) had greater than 50 percent lysis of the thrombus, compared with none of 12 who received placebo plus heparin (p = 0.002). Of 28 patients who received 0.5 mg/kg rt-PA over 8 h, repeated in 24 h, six (21 percent) had greater than 50 percent lysis, compared with two (7 percent) of 30 patients who received placebo plus heparin (p = 0.11). The 4-h infusion of rt-PA produced a 40 percent reduction and the 8-h infusion an 11 percent reduction in plasma fibrinogen concentration. At long-term follow-up, three (25 percent) of 12 patients in whom greater than 50 percent lysis was achieved had symptoms of the postphlebitic syndrome, compared with 19 (56 percent) of 34 patients in whom lysis was less than 50 percent (p = 0.07).

Thrombolytic therapy has been shown to limit infarct size, improve ventricular function, and decrease mortality in suspected evolving myocardial infarction (MI). Aspirin therapy also decreases mortality as well as stroke and reinfarction in suspected evolving MI. The combined ability of both agents to lyse as well as to prevent clots yields a greater benefit than either alone. The use of aspirin with thrombolysis also protects against the increase in reinfarction observed when thrombolytic therapy is given alone. While ongoing research is evaluating the optimal thrombolytic agent as well as the possible role of heparin, it is already clear that the use of aspirin with thrombolytic therapy will significantly decrease reinfarction, stroke, and vascular mortality in suspected evolving MI.

We studied the safety and efficacy of albuterol (salbutamol) delivered by continuous nebulization (CN) in the initial emergency department treatment of asthma. In a randomized fashion 21 patients received 5 mg of albuterol by bolus nebulization (BN) at time 0 and again 60 minutes later. Twenty-one others received albuterol (0.2 mg/ml) by CN using a calibrated nebulizer with a known output of 25 ml/h. Thus, each patient had received 10 mg of albuterol over two hours. FEV1, blood pressure (BP), heart rate (HR), respiratory rate (RR), and hand tremor were recorded at 30-minute intervals. The FEV1 was 1.48 +/- 0.64 L prior to BN and increased to a maximum of 2.20 +/- 0.94 L (p less than 0.05) 90 minutes later. The FEV1 prior to CN was 1.13 +/- 0.51 L and improved to 2.20 +/- 1.02 L (p less than 0.05) at 120 minutes. The FEV1 did not differ significantly between regimens over the 2-hour period. Both modes of therapy were well tolerated. There was a slight but significant increase in HR at 30 and 90 minutes in the BN group when compared with CN. There was no significant difference in BP, RR, or tremor between the groups. Thus, albuterol by CN was found to be equally effective as the same medication by BN in the early treatment of asthma in patients seen in the emergency department.

Pentoxifylline is a xanthine derivative with hemorrheologic and vascular properties that may improve gas exchange in patients with chronic obstructive pulmonary disease (COPD). We tested this hypothesis in 12 patients with COPD (mean FEV1 = 40 percent predicted; mean DCO, 8.6 ml/min/mm Hg) randomly divided into a treatment and control group and six healthy volunteers. Following establishment of baseline DCO and maximum expiratory flow volume (MEFV) curve values, each subject in the treatment and healthy groups took 400 mg of pentoxifylline three times a day for 12 weeks. Weekly DCO and MEFV curves were measured before treadmill exercise in both COPD groups and before and after exercise in the healthy group. The MEFV curve parameters from the final three weeks of therapy did not differ significantly from baseline values. During this time, however, the treatment COPD group's resting DCO rose by 8.2 +/- 2.4 percent over baseline level (p less than 0.01). Treadmill walk time increased from 17.7 +/- 2.9 minutes to 23.2 +/- 2.9 minutes (p less than 0.02). This was accompanied by improved exercise oxygen saturation measured by oximetry (SoxiO2). Premedication SoxiO2 fell from 92.8 +/- 1.2 percent to 88.6 +/- 2.5 percent during exercise, and from 94.4 +/- 1.1 percent to only 91.8 +/- 1.0 percent after 12 weeks of medication (p less than 0.05). No such improvement was noted in the control COPD group. Although the healthy group's resting SoxiO2 and DCO did not change during treatment, their exercise DCO increased significantly from 36.3 +/- 3.1 ml/min/mm Hg to 41.8 +/- 3.5 ml/min/mm Hg (p less than 0.001). These data demonstrate that pentoxifylline improves gas exchange, possibly by increasing cardiac output, and/or by raising mixed venous PO2, and/or by improving blood flow to underperfused alveoli.

Long-term treatment of chronic bronchitis with chest physiotherapy with or without positive expiratory pressure (PEP) by mask was studied in 43 patients randomly allocated to PEP treatment (PEP group, 20 patients) and conventional chest physiotherapy (control group, 23 patients). After instruction, the treatments were self-administered twice daily for 12 months (34 patients) and 5 months (9 patients). Twice weekly, patients filled in a diary concerning symptoms. The PEP group had significantly less cough and less mucus production. The number of acute exacerbations were calculated from the diaries and were lower in the PEP group compared to the control group, and 85 percent of the patients in the PEP group were free from acute exacerbations versus 48 percent in the control group. The PEP group also used less antibiotics and mucolytics. The PEP group had a small increase in FEV1 of mean 62 ml compared to a small decrease of 43 ml for the control group. Treatment with a simple PEP device can reduce morbidity in patients with chronic bronchitis and may preserve lung function from a more rapid decline.

Thirteen patients with acute pulmonary embolism were treated in a randomized double-blind fashion either with recombinant tissue plasminogen activator (rt-PA) 40 to 80 mg, usually in combination with heparin, or with placebo plus heparin. The drug was administered intravenously over 40 to 90 minutes. Nine patients received rt-PA, and four received placebo. A lytic effect was observed 1.5 and three hours after the onset of therapy with rt-PA based upon elevated levels of fragment-D dimers. Among the patients who received rt-PA, there was a modest improvement of the total pulmonary resistance 1.5 hours after the start of therapy, but the angiograms showed no significant changes in two hours. After 24 hours, the lung scans showed a trend toward greater improvement with rt-PA, but the rate of improvement in comparison to control subjects was not statistically significant. Massive bleeding occurred in one patient. The observations in this study suggest that rt-PA has little effect in two hours on angiographic clot burden, but may produce some improvement in hemodynamics. The treatment, however, is not without risk.

The bronchodilator effects were compared in 16 stable asthma patients for 12 hours after either 12 micrograms formoterol or 200 micrograms salbutamol from a metered-dose aerosol in a randomized, double-blind, crossover study. The FEV1 measured before 1, 2, 4, 6, 8, 10 and 12 hours after administration was used as the parameter. From 2 hours onwards after dosage, the bronchodilator effect of formoterol was statistically significantly greater than that of salbutamol. The effect of formoterol lasted longer, and even after 12 hours, the FEV1 was still 20 percent above the baseline value. This is clinically significant and offers new possibilities for treatment of the so-called "morning dip." Both agents were well tolerated.

High airway pressure may be injurious to lung parenchyma, but lowering airway pressure using conventional mechanical ventilation necessitates lowering tidal volume (VT). Intubated patients in the surgical intensive care unit (SICU) were randomly assigned to group 1 (VT = 12 ml/kg, n = 56) or group 2 (VT = 6 ml/kg, n = 47). Variables recorded included acute physiology and chronic health evaluation (APACHE II) score, mean peak airway pressure (MPAP), mean PaO2/FIO2, incidence of pulmonary infectious complications (PIC), duration of intubation (DOI), and duration of SICU stay (DOS). Results in the table are means +/- SE. (table; see text) The incidence of pulmonary infection tended to be lower and DOI and DOS tended to be shorter for nonneurosurgical and noncardiac surgical patients randomized to low VT, suggesting that morbidity may be decreased. The use of low VT was associated with a statistically significant but clinically irrelevant decrease in oxygenation. The routine use of low VT appeared to be safe in a selected population of patients in the SICU.

The efficacy of ipratropium and salbutamol was determined in 117 patients with acute asthma who presented to an emergency department to determine whether the order of administration of the two agents affects the improvement in peak flow rates. Patients were given two nebulized treatments at an interval of one hour in a randomized, double-blind design. They received either 5 mg nebulized salbutamol followed by 0.5 mg ipratropium, ipratropium followed by salbutamol, or both drugs administered together followed by nebulized saline. Ipratropium was an effective bronchodilator when given as the first agent. Simultaneous administration with salbutamol was as effective as sequential administration. At one hour after treatment, there was no difference in peak flow between the combination of drugs and either drug given alone. Ipratropium given after salbutamol was not superior to saline solution given after the combination of drugs. Our data do not suggest a substantial therapeutic effect from addition of ipratropium to salbutamol in the immediate treatment of acute asthma.

Seventy-four pulmonologists and one allergist were recruited to assess the efficacy and safety of iodinated glycerol (Organidin), 60 mg qid, vs placebo in patients with stable chronic obstructive bronchitis in a randomized, double-blind, placebo-controlled, parallel design. A total of 361 patients (180 to iodinated glycerol and 181 to placebo) who complained of cough and difficulty bringing up sputum entered the eight-week study. Evaluations were based upon eight primary symptom efficacy parameters (cough frequency, cough severity, chest discomfort, dyspnea, ease in bringing up sputum, patient and physician global assessments, and a derived patients' global assessment), and six secondary parameters (frequency of aerosol bronchodilator use, incidence and duration of acute exacerbations, frequency of concomitant medication use, incidences of adverse experiences and dropouts). Cough frequency, cough severity, chest discomfort, patients' ease in bringing up sputum, patients' overall condition, and a derived subject global assessment were significantly (p less than 0.05) improved by iodinated glycerol as compared with placebo within eight weeks of treatment. Dyspnea showed a trend toward improvement and the physicians' global evaluation showed no significant difference between groups. Similar findings were noted in a subgroup analysis of moderately-to-severely affected patients. The mean duration (days) of acute exacerbations and number of dropouts attributable to adverse experiences were significantly less (p less than 0.05) in the iodinated glycerol group.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine a change in theophylline pharmacokinetics during concomitant thiabendazole or mebendazole therapy, we studied six normal, healthy male volunteers. Aminophylline was administered intravenously, followed by a 30-h blood sampling period. Subjects were randomized to receive thiabendazole or mebendazole, then crossed over to receive the other therapy. Theophylline concentrations were measured utilizing an HPLC technique and a one-compartment model was fit to the data. Theophylline pharmacokinetic parameters were significantly different during thiabendazole therapy. Mean theophylline half-life increased, clearance decreased and elimination rate constant decreased. Two subjects experienced severe nausea and vomiting during thiabendazole therapy. There were no significant differences in theophylline pharmacokinetic parameters during mebendazole therapy. Thiabendazole administration results in a significant decrease in theophylline clearance and beta elimination rate constant. The theophylline half-life increased significantly. Concomitant administration of theophylline and thiabendazole resulted in severe nausea and vomiting. Mebendazole administration did not seem to alter theophylline pharmacokinetics.

A prospective, randomized, controlled study was undertaken to compare the Pall Ultipor breathing circuit filter (PUBCF), a heat-and-moisture exchanger, and heated hot water systems (HHWSs) in ICU patients submitted to controlled mechanical ventilation. Humidification of inspired gas and bacterial contamination of breathing circuits were evaluated. During the study, there were six episodes of tracheostomy tube (TT) occlusion in six patients included in the PUBCF group. No patient out of 42 included in the HHWS group experienced this complication (p less than 0.01). There were 4 percent of days with thick and tenacious bronchial secretions in the PUBCF group and no case in the HHWS group (p less than 0.02). In the PUBCF group, 23 percent of days with hypothermia were noted as opposed to 12 percent in the HHWS group (p less than 0.01). Fewer breathing circuits were found to be contaminated in the PUBCF group (11 percent) than in the HHWS group (54 percent, p less than 0.01). In patients with an organism growing in bronchial specimens, the same organism was found to contaminate the breathing circuit in 10 percent of cases in the PUBCF group and 77 percent of cases in the HHWS (p less than 0.01). We conclude that, in the conditions of this study, the PUBCF did not provide sufficient humidification of inspired gas in ICU patients. Protection against contamination of breathing circuits was effective, but 10 percent of patients remained at risk for this complication.

We tested the hypothesis that the incidence of LRTI in critically ill blunt trauma victims can be reduced by employing continuous postural oscillation. Within 24 h of admission to the SICU, 106 patients were prospectively randomized to either a conventional bed or a RRKTT. Seven patients who were discharged from the SICU in less than 24 h were excluded from the data analyses. Until discharge from the SICU, patients were monitored daily for development of LRTI or pneumonia. Among 48 patients in the control group, 28 met criteria for LRTI and 19 met criteria for pneumonia. Among 51 patients in the RRKTT group, 13 developed LRTI and 7 developed pneumonia. The differences between groups for all LRTI and pneumonia were both significant. We conclude that continuous postural oscillation decreases the risk of pulmonary sepsis in victims of major blunt trauma.

Excessive daytime sleepiness is the most common symptom in OSAS. Administering CPAP improves breathing during sleep. We evaluated the time course of the recovery of alertness following CPAP therapy in OSAS patients. Thirty-nine patients with OSAS were treated with CPAP and evaluated after one, 14, or 42 nights of treatment, 13 patients being randomly assigned to each group. All received a diagnostic polysomnogram and MSLT before treatment. The three groups had similar baseline values for nocturnal respiratory disturbance, oxygenation during sleep, fragmentation of sleep, and level of EDS. CPAP treatment was associated with a significant improvement in sleep-related respiration, oxygenation, and sleep fragmentation. The EDS showed significant improvement after one night, and further significant improvement after 14 nights, but no further significant improvement after 42 nights. The differential rate of improvement in nocturnal parameters compared with that of primary complaint of EDS suggests that OSAS patients experience a chronic functional sleep loss. As with sleep deprivation, recovery of alertness in OSAS requires several nights of normal sleep.

Ceftriaxone is a new, third-generation cephalosporin that, because of its long half-life, offers potential advantages of cost and convenience over similar agents such as cefotaxime. We compared the two drugs in a prospective, randomized study of the treatment of chest infections in seriously ill patients. Fifty-one patients (90 percent of whom were mechanically ventilated) received either ceftriaxone, 2g IV once daily, or cefotaxime, 2 g IV thrice daily, for five days. The two groups of patients appeared demographically comparable. Ceftriaxone in a single daily dose of 2 g once daily may not be satisfactory for the treatment of serious chest infections.

Ventilatory data, including timing and partitioning of ventilation, were obtained from six subjects with advanced Duchenne muscular dystrophy, aged 16 to 22 years, during polysomnography on two consecutive nights; the subjects were randomized to breathing air or oxygen. Five of the six patients developed oxygen desaturation exceeding 5 percent during rapid eye movement (REM) sleep while breathing air. Minute ventilation on air (the mean of at least six consecutive minutes) was 6.9 +/- 0.7 (SEM) L min-1 but fell, owing to decreases in both tidal volume and frequency, to 4.9 +/- 0.3 L min-1 (p less than 0.05) in slow wave sleep and to 4.5 +/- 0.6 L min-1 (p less than 0.05) in REM sleep. Similar falls were seen on oxygen. The variability of all ventilatory data was significantly greater in REM than non-REM (NREM) sleep. The mean abdominal contribution to breathing was lower than predicted for wakefulness and all sleep stages, and two subjects showed paradoxical abdominal movement in NREM sleep; a correlation (p less than 0.05) existed between the NREM abdominal (diaphragmatic) contribution and the extent of oxygen desaturation subsequently seen in REM. We conclude that although awake minute ventilation is normal in Duchenne muscular dystrophy, hypoventilation occurs in all sleep stages, and those with diaphragmatic dysfunction are especially vulnerable to oxygen desaturation during REM sleep.