Inhaled topical lidocaine, used to produce anesthesia of the respiratory tract prior to bronchoscopy, may cause bronchoconstriction in asthmatic patients. We investigated whether the degree of histamine airway responsiveness would predict the development and extent of lidocaine-induced bronchoconstriction in 20 asthmatic patients. The provocation concentration of histamine producing a 20 percent fall in FEV1 (PC20) was measured. On a separate day, challenge with 6 ml 4 percent lidocaine (Xylocaine 4 percent topical) was performed. There was no correlation between the response to lidocaine and the histamine PC20. Five patients (25 percent) showed a fall in FEV1 of greater than 15 percent (max 42.1 percent). Three responders were rechallenged double-blind with the commercial 4 percent lidocaine preparation and with a 4 percent preservative-free lidocaine solution. There was no difference in the response to these two solutions. These results demonstrate that inhaled topical lidocaine induces bronchoconstriction in a significant proportion of patients with asthma. This response is not related to airway histamine responsiveness or to the preservative in the lidocaine preparation.

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.

We studied the effects of salbutamol, ipratropium bromide and cromolyn sodium on PGF2 alpha-induced bronchospasm in ten patients with asthma. Initially, the bronchial reactivity to IC-PGF2 alpha and the DP20-PGF2 alpha were determined. Recalculations were made two days later and again 1 h after administration of various drugs given on different days. Salbutamol and ipratropium bromide induced significant bronchodilation and of similar magnitude 1 h after administration. On the day salbutamol was given, surface area under the dose-response curve to PGF2 alpha was significantly higher and the final drop of FEV1 significantly lower than those observed on days when placebo, ipratropium bromide and cromolyn sodium were given. No differences among these values were found for placebo, ipratropium bromide and cromolyn sodium. Thus, beta 2 stimulants attenuate significantly PGF2 alpha-induced bronchospasm, while ipratropium bromide and cromolyn sodium do not have protective effect.

The efficacy and safety of sequential intravenous/oral ciprofloxacin in moderate to severe respiratory tract infections (RTI) were compared with those of ceftazidime in a prospective clinical trial. Sixty-six patients received IV ciprofloxacin (200 to 300 mg twice daily), followed by oral ciprofloxacin (500 mg twice daily). Fifty-six patients received intravenous ceftazidime (1 to 2 g two to three times daily). Ciprofloxacin was as effective as ceftazidime and produced a 91 percent clinical cure rate. Significantly more pretreatment bacterial isolates were susceptible to ciprofloxacin, and ciprofloxacin had a significantly higher rate of sputum bacterial eradication than did ceftazidime. Ciprofloxacin showed broad in vitro antibacterial activity with particularly low minimal inhibitory concentrations for Gram-negative organisms. Ciprofloxacin was well tolerated; there were few adverse effects. Ciprofloxacin was an effective and well-tolerated treatment for severe RTI that had the advantages of broad in vitro antibacterial activity, twice-daily dosing, and sequential availability in an intravenous and oral formulation.

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.

The efficacy of nedocromil sodium (4 mg twice daily by inhalation) in treating bronchial asthma was assessed by double-blind, placebo-controlled group comparison in 69 adults from three centers. The patients (34 active, 35 placebo) had a history of bronchial asthma with at least 15 percent reversibility. Inhaled corticosteroids, used by 22 and 24 subjects in the active and placebo groups respectively, were discontinued before the study, in which a two-week baseline was followed by six weeks of treatment. Two-weekly clinic assessments of lung function, symptoms and final opinions of treatment were significantly (p less than 0.05 p less than 0.001) in favor of nedocromil sodium. Daily diary cards showed a similar trend with significant drug effects seen after the third week. Blood and urine samples showed no abnormalities and the majority of patient withdrawals (five from nedocromil sodium and six from placebo treatment) were due to worsening asthma. Overall, we found nedocromil sodium to be well tolerated and effective in the management of bronchial asthma.

We examined airway responsiveness to allergen inhalation using a novel technique by which dynamic compliance (Cdyn) and pulmonary resistance (Rl) are simultaneously calculated by Fourier-series analysis of flow and transpulmonary pressure during tidal breathing. C0 and C0.5 (Cdyn at the frequency of zero and 0.5 Hz, respectively) were computed using the regression line of Cdyn versus frequency measured at the fundamental and first three harmonics in each breathing cycle. First, the validity of this system was tested by comparing Rl, C0 and C0.5 during five consecutive breaths with those obtained by the conventional method. A good correlation was seen in Rl, C0 and C0.5 between the two methods. Second, we studied airway response to allergen inhalation before and after oral administration of a long-acting beta 2-stimulant (procaterol, 50 micrograms or 100 micrograms) or placebo in a double-blind crossover trial in six atopic asthmatic subjects. In control allergen inhalation tests by administration of placebo, Rl increased progressively, and C0.5, expressed as percentage of control compliance at zero frequency (C0.5/COcont), decreased progressively. After 100 micrograms procaterol, Rl response to allergen was almost completely inhibited. However, a decrease in C0.5/C0cont was still observed. These findings suggest that pretreatment of asthmatic patients with procaterol can release allergen-induced bronchoconstriction of the central airways, but cannot release that of the peripheral airways.

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.

To determine the effects of prophylactic treatment with EACA for blood loss after cardipulmonary bypass surgery, 350 consecutive patients undergoing open-heart surgery were studied. One hundred seventy patients received an initial dose of 5 g of EACA prior to skin incision, followed by intravenous administration of 1 g/h for the next 6 to 8 h. The control group received saline solution in the same fashion. The EACA-treated group had decreased chest tube blood loss 24 h postoperatively. In addition, EACA-treated patients had fewer myocardial infarctions, cerebrovascular accidents or reoperations for bleeding. Treated patients needed fewer units of blood transfusions than the nontreated group. There was no incidence of hyperthrombotic state or other side effects in the EACA-treated group. We concluded that prophylactic treatment with EACA for open-heart surgery requiring extracorporeal circulation may reduce the total blood loss and the number of blood transfusions in a safe and tolerable manner.

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.

A double-blind crossover study of the effects of real and placebo acupuncture on bronchial reactivity to histamine was carried out on 16 patients with moderately severe asthma. Treatment with real or placebo acupuncture failed to modulate the bronchial hyperreactivity to histamine. These results suggest that a single treatment with acupuncture is unlikely to provide improvement in the management of acute bronchial asthma.

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).