A prospective randomized study was conducted in 200 patients undergoing coronary artery bypass surgery. All patients received intravenous (IV) cephalothin prophylaxis for 48 hours beginning with anesthetic induction. Group A (99 eligible patients) received cephalexin 500 mg po, qid for three extra days. Group B (94 eligible patients) received no oral therapy. The overall infection rate was 9.3 percent (18 patients). Six patients had multiple sites of involvement. There was no difference between group A (9.0 percent, nine patients) vs B (9.5 percent, nine patients) (p greater than 0.5). The median sternotomy infection rate, superficial or deep, was 2.6% (five patients). The surgical wound infection rate was 4.7 percent (nine patients). The overall infection rate compares favorably with that of high risk groups for clean surgical procedures defined in SENIC study. There was no advantage to prolonged oral cephalexin prophylaxis following coronary artery bypass (CAB) surgery.

A controlled double-blind crossover study of ocular complications associated with nebulized ipratropium bromide and salbutamol therapy for respiratory distress was undertaken in 46 chronic bronchitis patients. There was no significant rise in intraocular pressure or change in anterior chamber angle in patients with open-angle glaucoma, narrow-angle glaucoma or control subjects following treatment with either drug. However, when the two drugs were used in combination, intraocular pressure rose in patients with narrow-angle glaucoma but not in patients with open-angle glaucoma or in control subjects. Transient angle closure was seen in five of these patients. Intraocular pressures did not rise when swimming goggles were used to protect the eyes or when antiglaucoma treatment was continued. Nebulized bronchodilator therapy is safe in nonglaucomatous patients and those with open-angle glaucoma. Ocular complications can follow combined ipratropium bromide and salbutamol nebulization in patients with narrow-angle glaucoma, but can be prevented by using the drugs separately, protecting the eyes and ensuring continued antiglaucoma measures.

To assess the safety of combined intervention in acute myocardial infarction, a pilot study of thrombolysis and beta-adrenergic blockade was performed. Twenty-five subjects were randomized to therapy with intravenous (IV) metoprolol and IV streptokinase (group 1) or to IV metoprolol (group 2) alone. Two-dimensional echocardiography was performed before intervention and five days later. The mean time from onset of symptoms to intervention was 1.92 hours. No major adverse reactions related to the intervention were observed in either group. Significant improvement from baseline was observed with combined therapy on both the biplane mean ejection fraction (p less than .02) and a calculated wall motion index of regional wall motion abnormalities (p less than .002). The presumed reperfusion rate was significantly higher in group 1 (p less than .03). Intravenous metoprolol and IV streptokinase in combination was found to be safe in the acute phase of acute myocardial infarction when administered to appropriate patients without contra-indications and deserves further study.

Esmolol, an intravenous, ultrashort-acting beta-blocker, was studied for its ability to safely control supraventricular arrhythmias up to 24 hours in 15 postoperative cardiothoracic surgery patients with atrial fibrillation or flutter and rapid ventricular response. Esmolol obtained an initial therapeutic response in nine (60 percent) patients. Mean heart rate for the 15 patients was reduced from 139 +/- 12 beats/min before therapy to 106 +/- 21 beats/min during esmolol infusion (p less than 0.01). The mean time to a therapeutic response after initiation of therapy, using a multistep titration regimen (500 micrograms/kg/min loading infusions over one minute, prior to incremental titration steps from 50 to 300 micrograms/kg/min over 4 to 14 minutes), was 22 +/- 9 minutes, and therapy was continued for 17 +/- 9 hours in responders. Esmolol significantly lowered blood pressure in the group studied and resulted in mild supine or orthostatic hypotension in ten (67 percent) patients. Side effects, including hypotension (10/15 patients), gastrointestinal disturbances (2/15), and weakness or somnolence (6/15), were transient and were not associated with serious clinical sequelae. We conclude that esmolol is effective for rate control in a majority of postoperative cardiothoracic surgery patients with atrial fibrillation or flutter. Side effects, although mild, occur relatively frequently, limiting prolonged infusions and warranting close surveillance of patients.

Traditionally, patients with acute airflow obstruction are treated with bronchodilator aerosols delivered by continuous flow nebulizers. While bronchodilator administration with the metered dose inhaler (MDI) and reservoir or spacer attachment is as effective as administration with the nebulizer in most settings, the former has not been widely accepted for treatment of acute airway obstruction in the emergency room. We compared the efficacy of the continuous flow nebulizer to that of the MDI with InspirEase (reservoir spacer) in 75 patients (45 men and 30 women), ages 18-73 (chi 44 years) who presented to the emergency room with acute asthma and COPD. Subjects in each group (22 COPD and 53 asthma) were randomly assigned to treatment with three puffs of metaproterenol (0.65 mg/puff) via the MDI with InspirEase plus nebulizer with placebo, or placebo MDI with InspirEase plus nebulizer with 15 mg metaproterenol in double blind fashion. Either treatment was given three times at 30 min intervals. The FEV1 and dyspnea scores according to the Borg scale were measured at baseline, 30 min after the first treatment, and 30 min after the third. There was no significant outcome difference between the two treatments in either diagnostic group. There also was no significant outcome difference for patients with baseline FEV1 less than 0.9L. Serum theophylline levels, the need for concomitant therapy with corticosteroids, or additional emergency room therapy after the study, hospitalizations and treatment side effects did not differ between treatment groups. We conclude that there is no demonstrable advantage of a continuous flow nebulizer over an MDI with InspirEase for the treatment of acute airflow obstruction.

To establish a dose-response curve for the effects of isocapnic hypoxemia on cardiac output (CO), we studied 20 healthy men, aged 20 to 34 years, using a tight-fitting face mask and an isocapnic partial rebreathing system (a modified anesthesia machine). We blended oxygen and hypoxic gas to achieve arterial oxygen saturations (SaO2) of 80, 85, and 90 percent; subjects also breathed 100 percent oxygen and room air (RA). Target SaO2 and end-tidal carbon dioxide were continuously monitored using an ear oximeter and CO2 gas analyzer. Subjects experienced the five SaO2 measurements in random order. CO was measured noninvasively at approximately two-minute intervals, using continuous-wave Doppler echocardiography. Mean cardiac output increased with increasing hypoxemia from 6.84 L/min at FIo2 1.0 to 8.44 L/min at SaO2 80 percent (p less than 0.0005); the increase was entirely due to increased heart rate. We concluded that cardiac output increases significantly in a dose-response manner in response to acute isocapnic hypoxemia in normal persons.

We compared the bronchodilating effects of intravenously administered enprofylline (2 mg/kg) with nebulized terbutaline (10 mg) in patients presenting to hospital with acute asthma in a multicenter double-blind parallel study. One hundred twenty three patients were randomized into the study, and 69 of these fulfilled the inclusion criteria and a retrospective time to study entry criterion; 34 received enprofylline and 35 received terbutaline. There was no significant difference in maximum increase in forced expired volume in 1 second (FEV1) between the enprofylline group (0.24 +/- 0.33 L) and the terbutaline group (0.25 +/- 0.28 L) (p greater than 0.05), nor for the increase in FEV1 over the 1-hour study period. Tremor was reported more in the group receiving terbutaline, and nausea was reported more in the group receiving enprofylline. Two patients experienced hypotension and one patient had a vasovagal episode with enprofylline treatment. Both agents acted as bronchodilators with similar efficacy in patients with acute asthma in this study.

Changes induced by nifedipine (10 mg sublingually) in the residual luminal diameter of significant (greater than 50 percent) coronary lesions were assessed angiographically in 69 patients with effort-induced angina (group 1), in 22 patients with mixed angina (group 2), and in 14 patients with Prinzmetal's angina (group 3). These changes were related to the clinical response to treatment with the same drug, as evaluated through diary records and Holter monitoring in the mixed (spontaneous component) and Prinzmetal forms and through exercise testing in effort-induced and mixed (effort-associated component) angina. In groups 1 and 2, segments of stenotic vessels showed either an increase or decrease or no change in diameter with the calcium antagonist; in group 3, the majority of the lesions had compliant portions which invariably responded with dilatation. Nifedipine failed to improve cases with exertional (20 percent [14/69] unchanged; 19 percent [13/69] worsened) and mixed (41 percent [9/22] exacerbated) forms; 100 percent of the 14 patients with the Prinzmetal form had relief of the anginal episodes. In group 1, the response to exercise tests was dissociated from the short-term vasomotor pattern, and the pressure-rate product failed to explain the clinical results. Forty-five percent (ten) of the patients in group 2 showed significant short-term widening of critical stenoses, as well as obvious improvement; patients who did worse with treatment in this group had reacted to nifedipine with narrowing of critical stenoses. These data suggest that the response to nifedipine of classic effort-induced angina is probably the net result of an interaction of changes in myocardial oxygen consumption and supply; coronary vasomotion has a role in mixed angina, and influences of nifedipine may be either favorable or unfavorable; stenotic lesions in the Prinzmetal form are quite sensitive to the relaxant action of calcium blockade, and this probably represents a background to the highly positive clinical response to treatment.

Adenosine has been found to contract human bronchial smooth muscle in vitro and to induce bronchoconstriction in asthmatic patients when administered by inhalation. The aim of the present study was to investigate if elevation of circulating levels of adenosine influence bronchial tone or bronchial reactivity. Seven patients with bronchial asthma in whom bronchial hyperreactivity had been confirmed in a pretrial bronchial histamine challenge (PC20 FEV1 0.064 to 2.45 mg/ml) received intravenous infusions of adenosine in increasing doses (10, 30 and 50 micrograms/kg/min, 6 min on each dose step) or placebo (saline solution) on two different days in a randomized, single-blind manner. Heart rate, blood pressure and lung function (lung volumes, flow-volume loops and airway conductance) were measured on each dose step. Infusion rate was held constant (at 50 micrograms/kg/min) throughout the trial and a bronchial methacholine challenge was performed during the infusion of adenosine or placebo. Infusions of adenosine and placebo did not influence heart rate, blood pressure or bronchial tone on either day and bronchial reactivity was similar on both days. We conclude that bronchial tone and bronchial reactivity in asthmatic patients are not increased by intravenously administered adenosine at a dose level which, in other studies, has been shown to induce regional effects in the systemic arterial circulation.

Patients with nocturnal asthma have their lowest pulmonary function and lowest serum epinephrine level at 4 to 6 AM. We studied a new long-acting beta-adrenergic agonist, procaterol, in ten patients with nocturnal asthma. The patients received 0.1 mg of procaterol one night and a placebo the other night in random order. Pulmonary function tests were performed every two hours from 10 PM to 8 AM. Pulmonary sounds were recorded using a modified stethoscope and were subsequently analyzed to estimate the proportion of time occupied by wheezing (est Tw/Ttot). The forced expiratory volume in one second (FEV1) while receiving the placebo and procaterol were similar at 10 PM (placebo, 1.35 +/- 0.18 L [mean +/- SE]; procaterol, 1.48 +/- 0.20 L); however, by 4 AM, the FEV1 had dropped significantly lower on the night with the placebo (1.01 +/- 0.14 L) than the night with procaterol (1.30 +/- 0.19 L; p less than 0.05). The est Tw/Ttot was similar at 12 AM for both nights, but at 4 AM, there was a significant increase in the est Tw/Ttot for the group with placebo but not the group with procaterol. The use of a long-acting beta-adrenergic sympathomimetic agent reversed the obstruction of the airways seen with nocturnal asthma.

The cardiovascular effects of smoking, including the occurrence of ventricular arrhythmias, were examined in 52 patients with ischemic heart disease. The study was a randomized, crossover comparison between smoking six cigarettes and nonsmoking with observer-blinded primary outcome measurements. Continuous Holter ECG recording for four hours showed no significant differences in the proportion of patients experiencing ventricular ectopy or the total number and complexity of ventricular premature beats during smoking vs nonsmoking. Aside from the first cigarette, smoking did not significantly alter blood pressure or heart rate. Mean (+/- SEM) plasma epinephrine (pg/ml) increased (p = 0.02) from baseline (52 +/- 4) to a maximum of 64 +/- 6 at 240 minutes with younger subjects exhibiting a more marked rise (p = 0.02) than subjects over 55 years of age. Plasma norepinephrine was unchanged by smoking. A power calculation confirmed the conclusion that the resumption of smoking after overnight abstention does not acutely increase the occurrence of ventricular ectopic activity in patients with ischemic heart disease.

From November 1, 1982 through December 31, 1985, there were 19 centers and 382 patients that evaluated the effect of methylprednisolone sodium succinate (MPSS) on the septic syndrome. Seventeen of these centers enrolled 304 patients in a prospective, randomized, double-blind, placebo-controlled study to determine if early treatment with MPSS would decrease the incidence of severity of the adult respiratory distress syndrome (ARDS) in patients at risk of ARDS from sepsis. To ensure early institution of the MPSS or placebo therapy (PLA), patients with the presumptive diagnosis of sepsis were identified. That diagnosis was based on the presence of fever or hypothermia (temperature greater than 38.3 degrees C or less than 35.5 degrees C, rectal), tachypnea (greater than 20 bpm), tachycardia (greater than 90 bpm) and the presence of one of the following indices of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels or oliguria. The treatment, either MPSS 30 mg/kg or PLA, was given in four 20-minute infusions six hours apart and was initiated within two hours of the presumptive diagnosis of sepsis. The development and reversal of the adult respiratory distress syndrome (ARDS) was followed and resulted in data on 304 of the 382 randomized patients. A trend toward increased incidence of ARDS was seen in the MPSS group 50/152 (32 percent) compared to the placebo group 38/152(25 percent) p = 0.10. Significantly fewer MPSS patients reversed their ARDS 15/50 (31 percent) compared to placebo 23/38 (61 percent) p = 0.005. The 14-day mortality in patients with ARDS treated with MPSS was 26/50 (52 percent) compared to placebo 8/22 (22 percent) p = 0.004. We conclude that early treatment of septic syndrome with MPSS does not prevent the development of ARDS. Additionally, MPSS treatment impedes the reversal of ARDS and increases the mortality rate in patients with ARDS.

The role played by serotonin (5-HT) in the regulation of bronchomotor tone has up to now been a much debated question, although there is good evidence that it induces intense bronchoconstriction after inhalation in asthmatic patients. Serotonin has been found to contract the tracheobronchial smooth muscle of different animals. Some data suggest that tracheobronchial contraction due to serotonin is mediated by its interaction with the S2-receptor. The blockade of this receptor by ketanserin, a serotoninergic antagonist which primarily binds to S2-serotoninergic receptors, produces bronchodilation. The respiratory effects of intravenously administered ketanserin (10 mg) or placebo were compared in a double-blind crossover study in 14 patients with chronic obstruction of the airways. The forced expiratory volume in one second (FEV1) and the instantaneous forced expiratory flow after 50 percent of the forced vital capacity has been exhaled (FEF50%) did not change after placebo, but they increased significantly after administration of ketanserin. The results suggest that in patients with chronic obstructive pulmonary disease, serotonin may play a role in the development of obstruction of the airways, even if the mechanism remains undefined.

In a randomized study, we determined the clinical and financial effects of replacing arterial blood gas measurements with finger pulse oximeter readings during the process of tapering supplemental oxygen in hospitalized patients. The 16 patients in the control group, whose management followed conventional practice in our hospital, received a total of 57 arterial blood gas measurements during the 6.6 (mean) days it took for them to taper to their discharge supplemental oxygen level (usually room air). The 13 patients randomized to the oximeter study group had their arterial oxygen saturation monitored by pulse oximetry. The physicians of patients in the oximeter group were at liberty to obtain arterial blood gas determinations during the study if they desired. The oximeter study group had fewer (p less than 0.005) arterial punctures for blood gas measurements (total of 16 for the group) and fewer (p less than 0.001) days on supplemental oxygen (mean of 2.7 days per patient). We conclude that substituting noninvasive pulse oximetry for arterial blood gas measurements during reductions of supplemental oxygen shortened the days of oxygen use and decreased the number of arterial blood gas determinations in our patients. In addition to reducing the discomfort to patients, the use of oximetry was of financial benefit in that it reduced medical personnel time, blood gas analyzer use, and duration of oxygen administration.

Several microprocessor exercise physiology systems have been introduced recently. Comparison of the data output between these systems and more traditional nonautomated systems has not been reported extensively. Twelve normal adult men were exercised in random sequence on different days on a Sensormedics MMC Horizon system, the Medical Graphics Corporation System 2000, and a nonautomated system. heart rate, minute ventilation, tidal volume, respiratory frequency, oxygen consumption, and carbon dioxide production were compared at each level of work during a maximal incremental test and during a constant work load test. The overall data output between the three systems was comparable. However, minute ventilation was consistently higher on the Medical Graphics system, oxygen consumption was consistently lower on the Horizon system, and a technical error was discovered in the Medical Graphics system which resulted in a systematic overestimation of carbon dioxide production. Different methods of analyzing the data from the same test (60-s average, 15-s average, breath-by-breath, and 8-breath average) resulted in differences of up to 20 percent in the maximal values. This was greater than the differences between the three systems. Despite the comparability of the data output, important differences did exist which can be potentially significant when data output from one system are compared to predicted normal values obtained under different conditions.

Patients with chronic lung disease productive of sputum are generally encouraged to drink a large amount of fluid to facilitate sputum production. This clinical practice has not been tested systematically. Twelve outpatients with chronic obstructive pulmonary disease in clinically stable condition who had daily sputum production were asked in random sequence: 1) to drink one glass of fluid every waking hour after supper and upon waking the next morning (hydration), 2) to drink no fluid after supper and upon waking the next morning (dry), and 3) to drink fluid ad lib (ad lib). Each morning sputum collection was started upon waking and continued for four hours. The differences in volume, elasticity of sputum, respiratory symptoms, and ease of expectoration were not significant. We conclude that moderate hydration and dehydration have no effect on volume expectorated, the elasticity of sputum, respiratory symptoms or forced expiratory volume in one second.

Ambroxol is a mucolytic agent which is widely used in chronic bronchitis in Europe. We conducted a double-blind randomized controlled trial of ambroxol vs matched placebo in 90 patients with chronic bronchitis and difficulty clearing secretions. It was concluded that there was no advantage to taking ambroxol.

A prospective, double blind study was conducted to determine the degree of concordance of pen and palpation methods of measuring skin induration to Mantoux tuberculin tests. One hundred thirty-five skin tests were performed in patients with previously bacteriologically proved tuberculous disease. An experienced reader who was only able to see the forearm of the patient measured the induration by the palpation technique. The measurement was then repeated by the pen method under the same conditions, on the same day. Results of the study indicated that the pen method yielded statistically the same frequency distribution of indurations as the palpation method and the pen method appeared to be more sensitive.

We assessed the importance of Streptococcus pneumoniae and immunologic response to 14-valent pneumococcal vaccine in a randomized (saline placebo or vaccine) double-blind pilot study involving 103 patients with chronic obstructive pulmonary disease (COPD). Antibody titers, the flora of the sputum, respiratory infections or pneumonias, and deaths were monitored. The patients' antibody titers before immunization were higher than healthy control subjects. Titers rose normally in those vaccinated but declined more rapidly. Differences between the group receiving placebo and vaccine were not significant at 12 and 24 months. The incidence of pneumonia was high before and after vaccine (47/1,000 vs 41/1,000 patient-years). Nonpneumococcal causes predominated (73 percent of pneumonias; 83.4 percent of lethal pneumonias). Isolates from sputum were predominantly nonvaccine types (50 to 62.5 percent). Twenty-seven patients died; pneumonia occurred in six (one pneumococcal in a vaccinated patient) as a terminal complication of other diseases. Thus, although pneumonia occurred frequently in these patients with COPD and contributed to mortality in 22 percent (six) of the 27 deaths, the predominance of nonpneumococcal causes and the data on antibodies and sputum suggest that pneumococcal vaccine may not be as beneficial for patients with COPD as was hoped. More observations are needed.