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.

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.

Eighteen patients (nine asthmatic patients and nine with poorly reversible airflow obstruction) with stable, severe chronic airflow obstruction, completed a four-week randomized, doubled-blind, placebo-control, crossover trial comparing the acute and chronic effects of terbutaline administered by metered-dose inhaler (MDI) and nebulizer (NEB). Equipotent doses of terbutaline were selected from the comparison of separate cumulative dose-response curves for MDI and NEB. The MDI and NEB given acutely produced similar bronchodilatation and improvement in exercise performance. Spirometric indices, 6 min walking distance, symptom scores and extra beta-agonist use were no different between MDI and NEB treatment fortnights in the outpatient study. We conclude that the degree of bronchodilatation achieved in these patients is a reflection of the dose of bronchodilator administered and not the mode of administration. There is no justification for the preferred outpatient use of nebulized bronchodilators in patients with stable chronic airflow obstruction who can use adequate doses of bronchodilators via a metered-dose inhaler.

We investigated the hypothesis that prior airway muscarinic receptor stimulation (with aerosolized methacholine) would modify the bronchoconstrictor response to histamine, which is, in part, vagally mediated. On four different experiment days, the following combinations of methacholine and histamine inhalation challenges were performed in 15 subjects (nine normal and six asthmatic) in a random fashion: methacholine-histamine, histamine-methacholine; methacholine-methacholine and histamine-histamine. Cumulative provocative dose of each agonist which caused a 50 percent decrease in SGaw was estimated (PD50). The second challenge was performed approximately 1 hour after the first challenge, when SGaw had returned to baseline. In normal subjects, prior muscarinic stimulation with methacholine suppressed the subsequent bronchoconstrictor response to histamine (mean +/- SE PD50 histamine increased from 13.7 +/- 3.1 to 28.4 +/- 7.2 breath units), without modifying the bronchoconstrictor response to methacholine. In asthmatic subjects, prior methacholine exposure failed to modify the bronchoconstrictor responses to histamine and methacholine. In contrast, prior challenge with histamine did not modify the subsequent bronchoconstrictor responses to histamine and methacholine in both normal and asthmatic subjects. Pretreatment with ipratropium bromide attenuated the histamine-induced bronchoconstriction, suggesting that airway effects of histamine, in part, are vagally mediated. These data suggest that prior muscarinic stimulation has a protective effect on histamine-induced bronchoconstriction in normal subjects and the absence of this inhibitory effect in asthmatic patients may represent loss of a protective muscarinic receptor mechanism.

Twelve healthy men were studied to determine the effect of ventilatory stimulation with chlormadinone acetate (CMA), a potent synthetic progesterone, in small doses (5 mg/day), on arterial blood gas levels. Using a randomized, double-blind, crossover trial, one week of CMA administration caused a significant reduction in arterial CO2 tension (PaCO2) by 4.1 +/- 2.9 (SD) mm Hg. The magnitude of the fall in PaCO2 was about the same as that obtained with dose of 50 mg per day in our previous study. The results indicate that the dosages of progestin and the effect of the drug on ventilation were not in parallel, and it may provide the idea that larger doses of progestin would not necessarily be required to stimulate ventilation.

Patients with established adult respiratory distress syndrome (ARDS) have a mortality rate that exceeds 50 percent. We analyzed the magnitude of hypoxemia as manifest by the PaO2/FIO2 ratio and its early response to conventional therapy including positive end-expiratory pressure (PEEP) in the placebo group of a large multicenter study. The PaO2/FIO2 ratio was not different at the time of diagnosis of ARDS in those patients who lived compared to those who subsequently died. After one day of conventional therapy including PEEP, those patients who survived increased their PaO2/FIO2 ratio. The nonsurvivors did not improve over a seven-day course. The difference in the PaO2/FIO2 ratio was significant throughout the seven-day observation period. We conclude that the early response to conventional therapy picks a patient population with a good prognosis and can be used as a test of likely survival from ARDS.

Elevated endorphin levels in patients with COPD may act to diminish the sensation of dyspnea. Exogenous opioids decrease exertional dyspnea and increase exercise capacity in COPD patients. The purpose of this study was to determine the effects of endogenous opioids on the exercise capacity and control of breathing in patients with COPD. We hypothesized that naloxone, an opioid antagonist, would block the endogenous endorphins and decrease the exercise capacity of our patients. Six patients (mean age, 58.8 +/- 3.2 years) with COPD (mean FEV1, 1.28 +/- 0.46 L) underwent identical incremental cycle ergometer tests to exhaustion (Emax) and assessment of their hypercapnic and hypoxic ventilatory responses and mouth occlusion pressure responses following the IV administration of naloxone (0.4 mg/kg) (N) or placebo (P) in a randomized, double-blind fashion. Perceived dyspnea (modified Borg scale), breathing patterns, and expired gas levels were compared at rest and at maximal workload (WL). There was no significant difference after N compared with after P in the WL or the duration of work. At Emax there were no significant differences after N compared with after P in ventilation, the level of dyspnea, P0.1, VO2, or VCO2. The ventilatory response to CO2 production during exercise (delta VE/delta VCO2) and the ventilatory and mouth occlusion pressure responses to hypoxia and hypercapnia did not differ significantly after N compared with after P. This study does not support the hypothesis that endogenous opioids play a significant role in dampening dyspnea and facilitating exercise in patients with COPD.

The effectiveness and safety of once-daily administration of drugs in the treatment of moderate to severe hypertension was studied. Forty men taking diuretics were randomized to atenolol (A, n = 18), 50 mg/day, or betaxolol (B, n = 22), a new B1-blocker, 20 mg/day, if their SDAP was 105 to 125 mm Hg at baseline (weeks 2 to 4). At week 6, if SDAP was greater than 95 mm Hg, minoxidil (M), 5.5 mg/day, was added. The patients were seen every two weeks to week 16 (end of drug titration) and then every four weeks to week 32. The dosages were increased to 200 mg/day for A, 80 mg/day for B, and 20 mg/day for M as needed. Physical examinations, chest x-ray films, ECGs, echocardiograms, spirometric studies, 24-h ambulatory arterial pressures (AAP), and blood chemistry analyses were done at baseline and during treatment. A and B combined with a diuretic (furosemide, F) and M decreased the arterial pressures and heart rates equally well by both clinical and AAP measurements (p less than .001). The IVS was decreased (p less than .05), whereas LVIDd, RVIDd, and cardiothoracic ratios were increased by both A and B (p less than .05, p less than .01). No changes were noted in LVPW, LVM, EF, FS, spirometric values, or blood chemistry analyses. Common side effects were weight gain, edema, and hypertrichosis. Once-daily administration of A or B in combination with F and M were effective in the treatment of moderate to severe hypertension. Although effective, prolonged use of M may lead to volume overload and cardiomegaly. The significance of these latter findings is not yet known.

Two hundred (200) consecutive medical and surgical patients requiring mechanical ventilation were entered into a prospective randomized trial of weaning by either intermittent mandatory ventilation (IMV) or T-piece. Patients in these groups were of similar age and sex and had the same total ventilation time (TVT). The study design provided equal time for each weaning mode after specific criteria for oxygenation and ventilation were satisfied (PaO2 greater than 55 mm Hg on FIO2 less than 0.5; VE less than 12 L/min and two of the following four parameters: MVV greater than 2 VE, VT greater than 5 ml/kg, FVC greater than 10 ml/kg, NIF less than or equal to -20 cm H2O). Of the original 200 patients 165 were entered into the weaning phase; 35 patients were withdrawn prior to weaning due to the discretion of the attending physician or protocol error. Weaning time was not different between the IMV (5.3 +/- 1.2 h, mean +/- SEM) and T-piece groups (5.9 +/- 1.4 h, p = NS). Of the 165 patients, 155 (93 percent) were weaned successfully by protocol, 79 in the IMV and 76 in the T-piece group. Of 155 patients, 136 (88 percent) were weaned on the first attempt by protocol. Of the 19 who were not weaned, 11 were weaned successfully on the second and five on the third trial; three patients required three-day weans. We conclude that clinically stable patients who require short-term mechanical ventilation and meet standard bedside weaning criteria can be weaned efficiently by protocol using either IMV or T-piece techniques.

Medroxyprogesterone acetate (MPA) could change the frequency and/or duration of disordered breathing events (DBEs) in patients with the obstructive sleep apnea (OSA) syndrome by altering pharyngeal muscle function relative to diaphragm and external intercostal function. Ten male patients with OSA syndrome underwent an initial polysomnogram with monitoring of EEG, EOG, myohyoid EMG, oral and nasal airflow, abdominal and thoracic movement, and SaO2. The patients were then entered into a randomized, double-blind crossover study using MPA, 150 mg/day, and MPA placebo. Each patient took tablets for one week and then had a second polysomnogram. After a three week washout, the patient again took tablets for a week prior to the third and final sleep study. There was no significant difference between drug and placebo for DBE time (expressed as a percentage of sleep time), DBE frequency, DBE mean duration or mean fall in O2 saturation during DBEs. We conclude that treatment with MPA does not alter indices of severity of the OSA syndrome.

Hemodynamic and oxygen transport effects of dopamine and dobutamine were studied in a series of 25 critically ill postoperative general surgical patients by a prospective, randomized crossover design after maximal response to fluids had been obtained. Dopamine increased MAP, HR, CI, PvO2, DO2, and Qsp while decreasing PaO2. Dobutamine increased HR, CI, SI, stroke work, DO2, VO2, and Qsp while decreasing PAWP and SVRI and PVRI. In general, the effects of the two drugs were greater in patients in the first 72 hours after surgery. The effects of dobutamine on flow and oxygen transport were greater than those of dopamine, especially in the early postoperative period. The effects were smaller and not significant in patients more than three days after surgery, as well as in those with sepsis, respiratory failure, renal failure, age over 65 years, and hyperdynamic states, in part because of the small number of patients in each group. These data are consistent with the hypothesis that the beta 2-adrenergic action of dobutamine vasodilates the previously constricted peripheral circulation, enhances tissue perfusion by improving micro-circulatory flow distribution, and improves DO2 and VO2.

Prostaglandin E1 (PGE1) was compared to placebo in a 100-patient (50 PGE1, 50 placebo) randomized, double-blind, clinical trial to determine whether PGE1 therapy enhances survival of patients with adult respiratory distress syndrome (ARDS) when infused through a central line at 30 ng/kg/min continuously for seven days. At 30 days postinfusion, 30 PGE1 and 24 placebo patients had died. Total deaths judged to be related to the syndrome were 32 and 28 in the PGE1 and placebo groups respectively at six months. We conclude that PGE1 did not enhance survival in patients with established ARDS. PGE1 augmented the hyperdynamic circulation of these patients by reducing systemic and pulmonary vascular resistance, which resulted in a reduction of blood pressures and increased stroke volume, cardiac output, and heart rate. An improvement in oxygen availability and oxygen consumption was observed with PGE1 therapy. PGE1 was associated with an increased incidence of diarrhea (six patients in the PGE1 group vs one in the placebo group, p less than 0.05). Other adverse effects included hypotension (ten patients in the PGE1 group vs seven in the placebo group), fever (six patients in the PGE1 group vs three in the placebo group), and non-fatal dysrhythmias (ten in the PGE1 group vs five in the placebo group).

A randomized, double-blind, crossover study was conducted to assess the efficacy of five weeks' treatment with terbutaline, 15 mg daily, compared with placebo in 17 evaluable patients with moderate to severe chronic airflow limitation (CAL) with a minor reversible component. A significant improvement after terbutaline treatment compared with placebo was observed in subjective assessments of breathlessness after two of the activities of daily living, and in daily peak flow measurements recorded in patient diaries. At the clinical assessment after five weeks' terbutaline therapy, 12 of 17 patients had improved pulmonary symptom scores compared with placebo, and a slight increase in FEV1 was observed relative to placebo (0.09 L, p less than 0.05). Thus, five weeks' treatment with oral terbutaline in patients with CAL resulted in significant improvements in several subjective assessments, despite a lack of effect on the majority of the objective variables.

The bronchodilator response to metaproterenol delivered by metered-dose inhaler (MDI) with a spacer device (Aerochamber [A]) and by jet nebulizer was studied in 44 asthmatic patients who presented to the emergency department with acute severe (FEV1 less than 50 percent predicted) airflow obstruction. The delivery method was randomized, double-blinded and placebo controlled. The A group received one puff of metaproterenol every five minutes for a total of three puffs (1.95 mg). The jet nebulizer group received 15 mg of metaproterenol by continuous nebulization over ten minutes. Only about 2.75 mg of the original 15 mg delivered by jet nebulizer was calculated to be available for inhalation due to the inefficiencies of the delivery system. The mean percentage of improvement in FVC and FEV1 in the A group was 33.5 and 49.0 percent, respectively. The mean percentage of improvement in FVC and FEV1 in the jet nebulizer group was 22.8 and 33.0 percent, respectively. There was no significant difference in the mean percentage of improvement values between the two groups. We were unable to demonstrate a difference in bronchodilator response to metaproterenol delivered by MDI-A and jet nebulizer in emergency department asthmatics with acute severe airflow obstruction.

Inhaled ipratropium bromide (IPR) is effective in the management of COPD. The purpose of this study was to determine if doubling the standard dose of IPR resulted in greater bronchodilation and if the addition of an inhaled beta-agonist was superior to standard dose IPR alone. Twelve male patients with stable COPD completed a double blind, randomized trial. On each of three consecutive days, following baseline spirometry, all patients inhaled two puffs of IPR. This was followed by either two additional puffs of IPR, two puffs of metaproterenol (META), or two puffs of placebo. All inhalants were delivered by an InspirEase spacer. Spirometry was repeated at 30, 60, 120, and 180 minutes. The group mean percentage increases in the FEV1 and FVC from baseline were similar at all times tested for the three protocols. In conclusion, for the group, there was no objective benefit to doubling the standard dose of IPR or combining IPR with META. Two of 12 patients benefited from combining the two bronchodilators. A potential sequence for bronchodilator testing is suggested.