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Biomedical subjects

K R Chapman

Publications and source records attributed to K R Chapman.

At least 19 recordsLinked to original sources

Respiratory interaction after spinal anesthesia and sedation with midazolam.

The combined use of midazolam and spinal anesthesia is common in clinical practice. Despite the known potential for each to alter ventilation, the effect of their interaction has not been examined. Nineteen healthy volunteers were studied to assess the impact of intravenous midazolam (0.05 or 0.075 mg/kg), spinal anesthesia (T3-T8; mean level, T6), and their combination on resting ventilation and ventilatory responses to progressive hyperoxic hypercapnia. Resting ventilatory pattern was altered significantly by each condition. Midazolam caused a 29% decrease in resting tidal volume and a 24% decrease in mean inspiratory flow rate, while respiratory frequency increased by 14% and minute ventilation remained unchanged. By contrast, spinal anesthesia alone caused a 32% increase in tidal volume, a 24% increase in mean inspiratory flow rate, and a 13% increase in minute ventilation accompanied by a 14% decrease in respiratory frequency. The combination of midazolam and spinal anesthesia caused a significant decrease in minute ventilation (19%), tidal volume (28%), and mean inspiratory flow rate (27%), all of which were significantly more than the predicted sum of the individual interventions. Midazolam and spinal anesthesia each produced a significant decrease in hypercapnic ventilatory response slope, whereas their combination provoked no net change in hypercapnic ventilatory response slope. Interpretation of the hypercapnic ventilatory response data was complicated by shifts in the position of the ventilatory response curve, particularly under the spinal anesthesia condition. It is concluded that intravenous midazolam depresses resting ventilation, spinal anesthesia stimulates resting ventilation, and their combination has a modest synergistic effect of depressing resting ventilation.

Adult

Heterogeneous airway tone in asthmatic subjects.

We examined the effect of volume history on the dynamic relationship between airways and lung parenchyma (relative hysteresis) in 20 asthmatic subjects. The acoustic reflection technique was employed to evaluate changes in airway cross-sectional areas during a slow continuous expiration from total lung capacity to residual volume and inspiration back to total lung capacity. Lung volume was measured continuously during this quasi-static maneuver. We studied three anatomic airway segments: extra- and intrathoracic tracheal and main bronchial segments. Plots of airway area vs. lung volume were obtained for each segment to assess the relative magnitude and direction of the airway and parenchymal hysteresis. We also performed maximal expiratory flow-volume and partial expiratory flow-volume curves and calculated the ratio of maximal to partial flow rates (M/P) at 30% of the vital capacity. We found that 10 subjects (group I) showed a significant predominance of airway over parenchymal hysteresis (P < 0.005) at the extra- and intrathoracic tracheal and main bronchial segments; these subjects had high M/P ratios [1.53 +/- 0.27 (SD)]. The other 10 subjects (group II) showed similar airway and parenchymal hysteresis for all three segments and significantly lower M/P ratios (1.16 +/- 0.20, P < 0.01). We conclude that the effect of volume history on the relative hysteresis of airway and lung parenchyma and M/P ratio at 30% of vital capacity in nonprovoked asthmatic subjects is variable. We suggest that our findings may result from heterogeneous airway tone in asthmatic subjects.

Adolescent

Physiologic and nonphysiologic determinants of aerobic fitness in mild to moderate asthma.

We studied 27 patients (seven male, 20 female) with stable mild-to-moderate asthma to measure their level of physical fitness and to determine if a relationship existed between aerobic fitness and the degree of airway reactivity, expiratory flow rates, or the amount of habitual leisure-time physical activity. Nonspecific bronchial hyperreactivity (NSBHR) was quantified by methacholine inhalation challenge. On a separate day, exercise capacity was evaluated with incremental exercise testing to exhaustion after bronchodilator pretreatment. The level of physical activity was assessed with a validated written questionnaire. FEV, was 78 +/- 13% predicted prebronchodilator and 92 +/- 14% predicted postbronchodilator. The mean provoking concentration of methacholine that caused a 20% decrease in FEV1 (PC20) was 1.14 +/- 1.38 mg/ml and ranged from 0.019 to 5.71 mg/ml. There was no correlation between PC20 and prebronchodilator FEV1 r = 0.37, p greater than 0.05). Mean maximal oxygen uptake (VO2max) was not significantly different from predicted normal values (36.9 +/- 10.8 versus 38.5 +/- 5.3, p = 0.32). Mean maximal O2pulse (maximal heart rate/VO2max), anaerobic threshold, and dyspnea index were within normal limits. There was no relationship between VO2max and FEV1 when expressed as percentages of predicted values (r = 0.08, p = 0.71) or between VO2max and PC20 (r = 0.23, p = 0.25). There was, however, a significant relationship between VO2max and the level of habitual leisure-time activity (F = 3.64, p less than 0.05). Results from the exercise questionnaire suggested that asthmatics perceive their disease as a limiting factor to improved aerobic fitness and that they lack adequate knowledge about asthma and exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Erythropoietin response to acute hypoxemia in patients with chronic pulmonary disease.

Chronic hypoxemia is associated with development of secondary polycythemia. To evaluate effects of transient hypoxemia on serum EPO activity in patients with chronic lung disease, we studied six oxygen-dependent patients who underwent either a 4-h oxygen withdrawal or their routine therapy, in a randomized, blinded fashion, on two separate days. Serum EPO did not differ at baseline between study days. Erythropoietin levels did not change significantly over time during normoxic conditions. Under hypoxic conditions, serum EPO levels rose over 4 h with the change from baseline first becoming significant at 2 h. The log of serum EPO response showed an inverse correlation with the level of arterial oxygen saturation. We conclude that patients with chronic lung disease are able to produce EPO in response to acute hypoxemic stress. Transient episodes of hypoxemia, such as occur during sleep or exercise, may result in increased red blood cell production stimulated by this EPO response.

Acute Disease

Sustained improvement in asthma with long-term use of formoterol fumarate.

Inhaled formoterol fumarate, a long acting beta 2 agonist, produces bronchodilatation that is sustained for approximately 12 hours. To determine whether such bronchodilator effects are maintained and asthma control sustained during chronic administration, we monitored airflow indices and clinical control in 112 asthmatic patients who self administered formoterol twice daily for periods ranging from 9 to 12 months. Subjects were recruited immediately following completion of a 3-month double-blind comparison of formoterol, 12 micrograms, bid versus salbutamol, 200 micrograms, qid. Assessments were conducted at baseline, 3, 6, and 9 months, where baseline represents the final visit of the 3-month comparative study. Patients were asked to complete diary cards and twice daily PEFR for a 2-week period before each assessment. Throughout the follow-up study, there was no indication of worsening of asthma control or deteriorating lung function. For the patients who continued to receive formoterol, the previous improvement in asthma control and lung function was maintained at the level reached in the 3-month study. There was an improvement in flow rates and asthma symptoms in the group switched from salbutamol to formoterol by the first clinic visit. This improvement in asthma control and lung function was maintained over the subsequent 6 months. Formoterol was well tolerated during the study period. We conclude that prolonged use of formoterol fumarate twice daily results in sustained improvement in symptoms and flow rates in asthma with no evidence of tachyphylaxis.

Adolescent

Anticholinergic bronchodilators for adult obstructive airways disease.

Quaternary anticholinergic bronchodilators offer gradual and sustained bronchodilation to patients who have asthma or chronic obstructive pulmonary disease. For asthma, the anticholinergic compounds are less potent than the beta-adrenergic agents but have useful additive bronchodilator properties when combined with beta-adrenergic agents or theophylline. They may be particularly useful in combination regimens for patients who have severe asthma and for older asthmatics. The rationale for such a combination is most compelling in the treatment of acute exacerbations of asthma. For chronic obstructive pulmonary disease, anticholinergic compounds offer greater bronchodilation than beta-adrenergic agents for most patients and are thus considered useful initial therapy in maintenance regimens.

Adult

Therapeutic algorithm for chronic obstructive pulmonary disease.

It would be foolhardy to offer an inflexible step-care protocol for the management of chronic obstructive pulmonary disease, given its heterogeneity and our uncertainty about its pathogenesis. Instead, the following outline might be regarded as a statement of principles to guide individual treatment plans. Smoking cessation is an essential, if difficult, first step, which is necessary to slow the accelerated rate of decline in pulmonary function that is characteristic of this disease. There is a compelling rationale for the use of influenza and pneumococcal vaccination, although proof of efficacy is lacking. If airways obstruction is present, inhaled quaternary anticholinergic bronchodilators seem to offer the greatest benefit with fewest side effects, making them the obvious first choice in bronchodilator therapy. In some patients, the addition of beta-agonists, theophylline, or both may augment bronchodilation. If significant airways obstruction persists despite the foregoing, an oral steroid trial is required. Some carefully selected patients whose exercise capacity has been limited despite optimal medical therapy may respond to a supervised exercise rehabilitation program. If hypoxemia is present, supplemental oxygen improves survival. Additional therapeutic modalities, ranging from preventive antioxidant administration to lung transplantation, remain investigational.

Bronchodilator Agents

Effect of a short course of prednisone in the prevention of early relapse after the emergency room treatment of acute asthma.

BACKGROUND: Relapse after the treatment of acute asthma in the emergency room is common (occurring in 25 to 30 percent of cases) and is not accurately predicted by any available measurements. We studied the usefulness of prednisone in reducing this high rate of relapse. METHODS: One hundred twenty-two patients treated in the emergency room for acute exacerbations of asthma were assigned in a randomized, double-blind fashion to receive at discharge either prednisone for eight days (the dose being tapered from 40 to 0 mg per day) or matching placebo. Ninety-three were subsequently discharged from the emergency room and participated in the trial. On days 1, 7, and 14 after discharge, the patients were assessed during home visits with spirometry and diary-card review; they were contacted by telephone on day 21. Relapse was defined as an unscheduled medical visit occasioned by the patient's perceived need for further asthma treatment. RESULTS: The overall risk of relapse was significantly lower in the prednisone group (P less than 0.05), with a significantly reduced rate of relapse during the first 10 days of follow-up (3 of 48, as compared with 11 of 45 in the placebo group; P less than 0.05). Thereafter (days 11 through 21), there was no further significant difference in relapse rates between treatment groups (five in the prednisone group and six in the placebo group). During the first week after discharge, patients receiving prednisone reported significantly lower mean (+/- SD) daily symptom scores for shortness of breath (1.4 +/- 0.4 vs. 2.5 +/- 0.4, P less than 0.01) and less frequent use of an inhaled bronchodilator (5.2 +/- 0.5 vs. 6.9 +/- 0.2 puffs per day, P less than 0.05) than patients receiving placebo. Subsequently, symptom scores and bronchodilator use were similar in the two groups. CONCLUSIONS: A short course of prednisone reduced early relapse rates after the treatment of acute asthma in the emergency room, an effect limited to the period of steroid administration.

Acute Disease

Bulbo-pontine paralysis with deafness: the Vialetto-Van Laere syndrome.

A Caucasian girl developed slowly progressive sensory neural deafness and bulbar and spinal muscle weakness typical of the Vialetto-Van Laere syndrome. As the condition progressed the major disabilities became dysphagia, respiratory muscle weakness and postural hypotension. Treatment with gastrostomy feedings, oxygen and fludrocortisone acetate produced worthwhile functional improvement.

Adolescent

A three-month comparison of twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma.

We compared the efficacy of inhaled formoterol, a long-acting beta 2-agonist, with inhaled albuterol in 145 stable adult asthmatics in a 12-wk multicenter trial. Patients were allocated in randomized double-blind fashion to maintenance therapy with either formoterol 12 micrograms twice a day or albuterol 200 micrograms four times a day in addition to their other asthma medications. Patients were allowed to use "rescue" 100-micrograms albuterol puffs on an as-needed basis. Mean baseline FEV, in the morning before bronchodilator was 2.14 +/- 0.76 L and 1.98 +/- 0.71 L for the formoterol and albuterol groups, respectively, these values being used as baseline covariates in subsequent analysis of predrug and postdrug FEV1. Measured at each clinic visit, morning predrug FEV1 rose significantly with formoterol treatment and was significantly greater at all visits than in the albuterol group, the greatest difference being in Week 8 (2.40 +/- 0.77 versus 1.92 +/- 0.66 L, p less than 0.001). Morning FEV1 30 min postdrug was significantly higher in the formoterol group at Weeks 2 and 8, the trend not reaching statistical significance at other times. Diurnal variation in prebronchodilator peak flow rates was significantly reduced in the formoterol group throughout the trial (17 versus 42 L/min at Week 12, p less than 0.0001). The number of asthma episodes per week was significantly less in the formoterol group during Weeks 4, 8, and 12 as were the number of sleep disruptions during Weeks 2, 4, 6, 8, and 12. Significantly more rescue albuterol was required in the albuterol group by Week 2 and throughout the remainder of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation

Dysphagia as a manifestation of occult hypoxemia. The role of oximetry during meal times.

A 25-year-old woman with severe kyphoscoliosis reported a six-month history of increasing dysphagia to both liquids and solids. A barium swallow and esophageal motility studies showed no significant gastrointestinal abnormalities. Trials of antispasmodic agents were unsuccessful in relieving her symptoms. Pulmonary function tests showed a severe restrictive ventilatory defect (vital capacity = 0.67 L) with adequate oxygenation and alveolar ventilation as reflected by arterial blood gas testing during quiet wakefulness. However, continuous noninvasive oximetry demonstrated desaturation to 85 percent while eating. These transient episodes of desaturation were abolished by the administration of supplemental oxygen delivered by nasal prongs. Following the prescription of supplemental oxygen, dysphagia resolved immediately, with weight gain following over several weeks. We conclude that dysphagia may be a presenting feature of hypoxemia. This case report draws attention to the usefulness of continuous noninvasive monitoring of oxygenation and the clinical importance of at least some transient hypoxemic events.

Adult

Response characteristics of a dual transcutaneous oxygen/carbon dioxide monitoring system.

We tested the response characteristics of a dual transcutaneous (tc) PO2/PCO2 monitoring system in healthy subjects who breathed various gas mixtures, and we compared steady-state tc readings to simultaneous arterial blood gas analysis in 20 stable respiratory outpatients. The electrodes were simple to apply, required very little skin preparation, and had trivial signal drift. In healthy subjects, tcPCO2 lag time during CO2 rebreathing was 16.8 seconds, with a 90 percent response time of 77.9 seconds after CO2 breathing was discontinued. The 90 percent response times of the O2 electrode when subjects breathed a hypoxic mixture was 257 seconds after a lag of 31 seconds. When inhaled gas mixtures were changed from hypoxia to room air, the lag time was shorter (12.5 seconds), but 90 percent response time exceeded 5 minutes. In stable patients with respiratory disease, tcPCO2 and tcPO2 were linearly related to PaCO2 (range, 19 to 53 mm Hg) and PaO2 (range, 45 to 99 mm Hg), respectively (tcPCO2 = 1.4 PaCO2-9.44, with r = 0.90 and SEE = 5.35 mm Hg; tcPO2 = 0.56 PaO2 + 20.4, with r = 0.53 and SEE = 11.7 mm Hg). We conclude that the response of the dual transcutaneous monitoring system is more rapid for the CO2 than the O2 electrode and may be rapid enough to be useful in some clinical settings; however, the O2 system fails to offer the response characteristics and accuracy that would allow it to be substituted for arterial gas tensions in unstable clinical situations.

Blood Gas Monitoring, Transcutaneous

Emergency room care of asthmatics: a comparison between Auckland and Toronto.

We compared emergency room visits for the treatment of asthma in two large downtown teaching hospitals: one in Auckland, New Zealand and one in Toronto, Canada. We wished to determine whether the differences in asthma mortality between New Zealand and Canada were reflected in different patterns of emergency room use or physician management. Emergency room use during the past decade was enumerated in both hospitals, and charts containing the sole diagnosis of asthma were reviewed in detail for a defined study period in 1986. In both Toronto and Auckland, the number of emergency visits for asthma had increased significantly in the past decade (P less than .015 but the rate of rise was significantly higher in Auckland (P less than .05). In Auckland, 27% of asthmatics were admitted whereas in Toronto significantly fewer (16%) were admitted (P less than .0005). Objective measures of pulmonary function were documented more frequently by emergency room physicians in New Zealand than in Canada (90% versus 48%; P less than .0005). Pulmonary function measurement was primarily by peak flow meter in Auckland and most commonly by spirometer in Toronto so that pulmonary function measurements could not be compared directly between centers. In both centers, however, admitted patients had significantly lower pulmonary function indices than discharged patients. In New Zealand, mean peak flow was 38% of the predicted value among all asthmatics assessed; in Toronto, mean FEV1 was 47% of predicted. In Toronto, pulmonary function measurements were most likely to be missing among presumably healthier discharged patients. Pulse rate, respiratory rate, and pulsus paradoxus were documented more consistently in Auckland than in Toronto.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Pulmonary function in normal subjects following exercise at cold ambient temperatures.

We measured pulmonary function in 12 healthy volunteers before and at 5-min intervals for 30 min following treadmill exercise of 30 min duration performed under control (20 degrees C) and cold (-11 degrees C) ambient temperatures. Post-run changes in forced vital capacity (FVC), residual volume (RV) and peak expiratory flow rate were similar between the two temperature conditions. FVC decreased slightly but significantly 5 min post-run (-0.25 +/- 0.20 l and -0.21 +/- 0.20 l, for control and cold conditions respectively) and returned to baseline by 30 min. RV increased significantly post-exercise (+0.07 +/- 0.09 l and +0.14 +/- 0.1 l, control and cold respectively) and remained elevated for 30 min. Forced expired volume in 1 s was not significantly different following either run. Post-exercise, maximum mid-expiratory flow rate and flows at 50% and 25% of vital capacity were not significantly different between warm and cold conditions. These data suggest that changes in lung volumes following exercise under cold ambient conditions are similar to changes seen following warm exercise of similar duration. In non-asthmatics, moderate exertion under cold ambient conditions does not appear to cause clinically significant decreases in expiratory flow rates as compared to similar exertion under warm conditions.

Adult

The role of anticholinergic bronchodilators in adult asthma and chronic obstructive pulmonary disease.

Our renewed interest in anticholinergic bronchodilator therapy has been sparked by the development of safe yet effective quaternary anticholinergic compounds including ipratropium bromide, oxitropium and atropine methonitrate. These agents offer gradual and sustained bronchodilation to patients with asthma and to patients with COPD. However, their role in the maintenance treatment of these two diseases differs significantly. In asthma, the anticholinergic drugs have useful additive properties when used with adrenergic drugs or theophylline. They may be a particularly useful component of combination regimens in patients with disease of more than mild severity and in older patients. The combination of inhaled adrenergic and anticholinergic drugs is also useful in the acute setting for acute exacerbations of asthma. In chronic obstructive lung disease, the anticholinergic compounds offer greater bronchodilatation than adrenergic drugs for the majority of patients. Thus, the inhaled anticholinergic drugs may be considered as useful initial choices in the chronic maintenance therapy of COPD.

Adult

Low-dose sufentanil and lidocaine supplementation of general anaesthesia.

This randomized double-blind study compared the effects of: (1) saline infusion (C); (2) sufentanil alone (1.0 micrograms.kg-1) (S); and (3) low-dose sufentanil (0.5 micrograms.kg-1) in combination with lidocaine (1.5 mg.kg-1) (LS): on the cardiovascular responses to tracheal intubation and on postoperative ventilation as monitored by respiratory inductive plethysmography in day-care surgical procedures of approximately 60 min duration. Thirty healthy, unpremedicated patients were studied. Thiopentone requirements were reduced by 40 and 28 per cent in the S and LS groups respectively compared with control (P less than 0.001). Both treatments suppressed HR and BP responses (P less than 0.005) to intubation. Postoperatively, PaCO2 was elevated (P less than 0.05) in group S. Dose-related respiratory depression was observed. The incidence of postoperative apnoea was significantly higher in both S and LS groups than compared with control (P less than 0.05). However, only patients in group S showed higher apnoea index and mean apnoea duration over the initial 10-20 min after surgery compared with control (P less than 0.005). In addition, group S showed slower respiratory frequency and prolonged expiratory time (P less than 0.005). In conclusion, an induction dose of sufentanil (1 microgram.kg-1) used in balanced anaesthesia of less than 70 min duration was associated with significant respiratory depression, particularly during the initial 10-20 min after surgery, whereas low-dose sufentanil (0.5 micrograms.kg-1) with lidocaine (1.5 mg.kg-1) had minimal postoperative respiratory depression and comparable attenuation of pressor responses to intubation.

Adjuvants, Anesthesia

A comparison of enprofylline and theophylline in the maintenance therapy of chronic reversible obstructive airway disease.

To compare the efficacy and side effects of two xanthine derivatives in the maintenance therapy of reversible obstructive airway disease, 242 patients were assigned in randomized, double-blind fashion to receive either oral enprofylline or theophylline for 5 weeks in addition to their usual maintenance regimens. After a week of placebo xanthine therapy, enprofylline-treated patients received 150 mg of this drug twice daily (b.i.d.) for 3 days, 300 mg b.i.d. for 2 weeks, and 450 mg b.i.d. for 2 weeks. Theophylline was administered in identical doses, except that the final dosage increase was not made if plasma theophylline was 12 mg/ml or higher. At 300 mg b.i.d., both drugs significantly increased morning peak expiratory flow rate (PEFR), the mean increase above baseline being significantly higher for theophylline-treated patients (29.9 +/- 37.2 L/min) than for enprofylline-treated patients (17.4 +/- 36.9 L/min) (p = 0.023). At 450 mg b.i.d., improvement in morning PEFR was not significantly different between theophylline-treated (31.5 +/- 44.4 L/min) and enprofylline-treated groups (23.5 +/- 48.4 L/min). Evening PEFR, FEV1, and asthma symptom scores also improved significantly, demonstrating no significant difference between groups. The incidence of side effects was also similar between groups. We conclude that both enprofylline and theophylline offer useful bronchodilatation in the maintenance therapy of asthma, enprofylline, 450 mg b.i.d., being approximately equivalent to theophylline, 300 or 450 mg b.i.d.

Adolescent

Ventilatory responses to hypercapnia and hypoxia in patients with eucapnic morbid obesity before and after weight loss.

1. To examine the relationship between eucapnic morbid obesity and ventilatory responsiveness to chemical stimuli, we measured hypercapnic and hypoxic ventilatory responses in 29 patients (26 women, three men) before and 3-6 months after gastroplasty. No subject demonstrated resting awake hypercapnia and non suffered from sleep-disordered breathing. 2. Mean weight fell significantly (122.8 +/- 21.4 vs 102.2 +/- 22.8 kg, P less than 0.0001) and functional residual capacity rose slightly but significantly (1.94 +/- 0.58 vs 2.18 +/- 0.64 litres; P less than 0.05) after weight loss. 3. The hypercapnic ventilatory response slope fell significantly after weight loss (2.88 +/- 2.27 vs 2.24 +/- 1.06 litres min-1 mmHg-1, P less than 0.05) with a significant shift of the ventilatory response curve to the right. There were no statistically significant changes in the patterns of ventilatory response. 4. In addition, isocapnic hypoxic ventilatory response slopes, measured at two levels of carbon dioxide partial pressure, fell significantly after weight loss. These changes were accompanied by significant shifts of the ventilatory response curves to the left, such that, for a given oxygen saturation, mean ventilation was significantly lower in the less obese state. Similarly to hypercapnic responses, there were no statistically significant changes in ventilatory pattern despite the changes in overall ventilatory response. 5. We conclude that ventilatory responsiveness to chemical stimuli is increased in obese subjects who maintain adequate alveolar ventilation while awake.

Adult