Does spinal anaesthesia interact with sedation to alter ventilatory responses?
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Adult↗
Biomedical subjects
K R Chapman
Publications and source records attributed to K R Chapman.
Effects of atenolol vs diltiazem on the haemodynamic effects of an inhaled beta 2-adrenoceptor agonist.
To determine the effects of concurrent beta 1-adrenoceptor blocker or calcium channel antagonist administration on the haemodynamic sequelae of an inhaled beta 2-selective adrenoceptor agonist bronchodilator, we examined echocardiographically the effects of fenoterol (400 micrograms) by metered dose inhaler following oral pre-treatment with (a) placebo, (b) atenolol or (c) diltiazem. Following placebo, fenoterol produced significant decreases in diastolic blood pressure (14% +/- 6%), total peripheral vascular resistance (TPR) (31% +/- 9%) and end-systolic stress (ESS) (15% +/- 21%). Cardiac output rose significantly (42% +/- 23%) as did heart rate (25% +/- 13%). After atenolol, responses to fenoterol were significantly blunted. Post-fenoterol heart rate, systolic blood pressure, % fractional shortening, stroke volume, ejection fraction, cardiac output and pressure/volume ratio increased significantly less after atenolol pre-treatment as compared to placebo pretreatment. TPR decreased significantly less. After diltiazem pre-treatment, the response to inhaled fenoterol was not different from that following placebo pre-treatment. We conclude that atenolol blunts the haemodynamic changes induced by fenoterol inhalation whereas diltiazem has little effect.
Adult↗
A placebo-controlled dose-response study of enprofylline in the maintenance therapy of asthma.
We assessed the efficacy and side effects of oral enprofylline in the maintenance therapy of 206 asthmatics 19 to 71 yr of age. After a 1-wk placebo run-in, patients were randomized to receive in double-blind fashion one of three doses of slow-release enprofylline tablets (150 mg, 300 mg, or 450 mg twice daily) or matching placebo for 4 wk. At baseline, mean (SD) peak expiratory flow rate (PEFR) was 62 (19)% of predicted normal values. The mean increase in morning PEFR 12 h after dosing was: for 450 mg, 14(17)%; for 300 mg, 8(23)%; for 150 mg, 2(11)%, for placebo 0(10)%. The increases over baseline for 450 mg and 300 mg compared with 150 mg and placebo were statistically significant. The mean asthma symptoms score (scale zero to 3) exhibited a dose-related reduction. Significantly less beta 2-receptor agonist inhalations were used in the 450-mg group than in the placebo group. There was a statistically significant increase in headache and nausea with the doses 450 mg and 300 mg given twice daily during the first treatment week compared with 150 mg and placebo. Subsequent to the first week, there were no differences between the active treatments and placebo with respect to the incidence of these and other side effects. We conclude that oral enprofylline, in a dosage of 300 to 450 mg twice daily is an effective and well-tolerated drug that may be useful in the maintenance therapy of asthma.
Adult↗
Cardiovascular response to acute airway obstruction and hypoxia.
We wished to evaluate the role of hypoxia in the production of cardiovascular manifestations of acute airway obstruction. We monitored blood pressure, electrocardiogram, and radionuclide ejection fraction in 14 healthy volunteers on exposure to four experimental conditions: expiratory resistive loading while breathing room air (RAL), expiratory resistive loading while hypoxic (HL), hypoxia alone (H), and expiratory resistive loading while voluntarily hyperventilating in a pattern similar to HL trials (VL). Mean respiratory-related oscillation in systolic blood pressure (pulsus paradoxus) increased significantly under each experimental condition compared with those at baseline (2 +/- 2.3 mm Hg): for RAL, 21 +/- 8.4 mm Hg; for HL, 34 +/- 16.3 mm Hg; for H, 10 +/- 5.4 mm Hg; for VL 26 +/- 13.4 mm Hg. Pulsus paradoxus was significantly greater under conditions of moderate hypoxia (saturation, 80%) than of mild hypoxia (saturation, 90%). Electrocardiographic changes were more marked under HL and H conditions than under RAL and VL conditions. HL induced changes in blood pressure and frontal QRS axis that were qualitatively similar to those seen in naturally occurring asthma. Radionuclide ejection fraction showed no dramatic change with any experimental condition. We conclude that hypoxia magnifies the cardiovascular changes induced by acute expiratory resistive loads and may contribute to the degree of pulsus paradoxus seen in severe asthma.
Acute Disease↗
Possible mechanisms of periodic breathing during sleep.
To determine the effect of respiratory control system loop gain on periodic breathing during sleep, 10 volunteers were studied during stage 1-2 non-rapid-eye-movement (NREM) sleep while breathing room air (room air control), while hypoxic (hypoxia control), and while wearing a tight-fitting mask that augmented control system gain by mechanically increasing the effect of ventilation on arterial O2 saturation (SaO2) (hypoxia increased gain). Ventilatory responses to progressive hypoxia at two steady-state end-tidal PCO2 levels and to progressive hypercapnia at two levels of oxygenation were measured during wakefulness as indexes of controller gain. Under increased gain conditions, five male subjects developed periodic breathing with recurrent cycles of hyperventilation and apnea; the remaining subjects had nonperiodic patterns of hyperventilation. Periodic breathers had greater ventilatory response slopes to hypercapnia under either hyperoxic or hypoxic conditions than nonperiodic breathers (2.98 +/- 0.72 vs. 1.50 +/- 0.39 l.min-1.Torr-1; 4.39 +/- 2.05 vs. 1.72 +/- 0.86 l.min-1.Torr-1; for both, P less than 0.04) and greater ventilatory responsiveness to hypoxia at a PCO2 of 46.5 Torr (2.07 +/- 0.91 vs. 0.87 +/- 0.38 l.min-1.% fall in SaO2(-1); P less than 0.04). To assess whether spontaneous oscillations in ventilation contributed to periodic breathing, power spectrum analysis was used to detect significant cyclic patterns in ventilation during NREM sleep. Oscillations occurred more frequently in periodic breathers, and hypercapnic responses were higher in subjects with oscillations than those without. The results suggest that spontaneous oscillations in ventilation are common during sleep and can be converted to periodic breathing with apnea when loop gain is increased.
Adult↗
The P90 as a clinically relevant landmark on the oxyhemoglobin dissociation curve.
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Animals↗
Controversies in pulmonary medicine. Patients with COPD should be started initially on anticholinergic bronchodilators.
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Adrenergic beta-Agonists↗
Asthma: 2. Trends in pharmacologic therapy.
The most reasonable first therapy for ambulatory asthmatic patients is regular use of a selective beta 2-adrenoreceptor agonist administered with a metered-dose inhaler. When asthma is of more than mild severity, a second agent that acts through a different pharmacologic pathway is added. Although theophylline has traditionally been this second agent, recent concerns about its safety have prompted increasing use of inhalational agents such as corticosteroids, anticholinergics and mast cell stabilizers as appropriate second-line therapy. The use of such combination regimens and newer strategies such as high-dose inhaled corticosteroid therapy will reduce the proportion of patients who require systemic corticosteroid therapy for adequate control of asthma. The use of combination inhalational therapy also has a role in the management of asthma in the emergency department, the combination of a nebulized adrenoreceptor agonist and a nebulized anticholinergic being more effective than either agent alone in acute, severe asthma. The role of newer xanthine derivatives, antihistamines, calcium channel blockers and selective anti-inflammatory agents remains investigational.
Adrenal Cortex Hormones↗
Asthma: 1. Pathophysiologic features and evaluation of severity.
The response of asthmatic airways to irritant stimuli is twofold: bronchoconstriction and airway inflammation. The inevitable mechanical consequence of bronchoconstriction is hyperinflation of the lungs, a phenomenon that produces characteristic clinical and radiologic signs. Hyperinflation helps to maintain airway patency at the expense of increased respiratory muscle work. Airway inflammation accounts in large part for the increased ventilatory drive of asthmatic patients, which results in alveolar hyperventilation and dyspnea. The resultant respiratory alkalosis further compromises tissue oxygen delivery both by cerebral vasoconstriction and by the leftward shift of the oxyhemoglobin dissociation curve. Optimal correction of hypoxia in the hyperventilating asthmatic patient requires delivery of oxygen at a high flow rate. Failure of patients with asthma to respond to simple bronchodilator therapy indicates the presence of continuing inflammatory activity and hence the need for anti-inflammatory therapy and frequency monitoring.
Airway Obstruction↗
Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room.
The effectiveness of nebulized anticholinergic and sympathomimetic regimens was evaluated in a double-blind study of 199 patients with acute airways obstruction. Patients were assigned to one of three treatment regimens according to a randomized schedule: 0.5 mg of ipratropium bromide, 1.25 mg of fenoterol hydrobromide, and 0.5 mg of ipratropium plus 1.25 mg of fenoterol. In 148 patients with acute exacerbations of asthma (mean one-second forced expiratory volume, 1.18 +/- 0.64 liters), all three regimens produced significant improvement in one-second forced expiratory volume (p less than 0.001). The greatest improvement followed treatment with the ipratropium-fenoterol combination (0.53 +/- 0.40 liters at 45 minutes; 0.57 +/- 0.51 liters at 90 minutes) and was significantly greater than that following either ipratropium alone (p less than 0.001) or fenoterol alone (p less than 0.05). In 51 patients with acute exacerbations of chronic obstructive pulmonary disease (mean one-second forced expiratory volume, 0.67 +/- 0.29 liter), each regimen produced significant improvement in one-second forced expiratory volume at both 45 and 90 minutes (for all, p less than 0.05), but there was no significant difference among the three treatment regimens. It is concluded that, in patients with acute asthma, combination therapy with sympathomimetic and anticholinergic agents is more efficacious than either one alone. In patients with acute exacerbations of chronic obstructive pulmonary disease, although either sympathomimetic or anticholinergic therapy provides bronchodilatation, no further benefit could be demonstrated from combination therapy.
Administration, Intranasal↗
Aging effects on the interaction of hypercapnia and hypoxia as ventilatory stimuli.
We measured ventilatory responses to progressive hypercapnia at two steady-state levels of oxygenation and to progressive hypoxia at two steady-state levels of CO2 in 10 elderly and 10 young individuals. Under hyperoxic conditions, the ventilatory response to progressive hypercapnia was not significantly different between age groups but, under hypoxic conditions, the response to hypercapnia was lower in the elderly group. The interaction of hypercapnic and hypoxic stimuli was greater among young persons as indicated by a higher ratio of the hypercapnic response slopes (hypoxic/hyperoxic); 1.48 +/- 0.19 versus 0.98 +/- 0.11, p less than .05. The ventilatory response to hypoxia at the lower CO2 level was significantly greater among elderly than among young adults but not significantly different between age groups at the higher CO2 level. The ratio of hypoxic response slopes (high PCO2/lower PCO2) was 1.56 +/- 0.17 among elderly participants and 3.14 +/- 0.63 among young participants (p less than .05). These results suggest that aging diminishes the multiplicative effect of hypercapnia and hypoxia as ventilatory stimuli.
Adult↗
Effect of inspiratory resistive loading on control of ventilation during progressive exercise.
Eight healthy volunteers performed gradational tests to exhaustion on a mechanically braked cycle ergometer, with and without the addition of an inspiratory resistive load. Mean slopes for linear ventilatory responses during loaded and unloaded exercise [change in minute ventilation per change in CO2 output (delta VE/delta VCO2)] measured below the anaerobic threshold were 24.1 +/- 1.3 (SE) = l/l of CO2 and 26.2 +/- 1.0 l/l of CO2, respectively (P greater than 0.10). During loaded exercise, decrements in VE, tidal volume, respiratory frequency, arterial O2 saturation, and increases in end-tidal CO2 tension were observed only when work loads exceeded 65% of the unloaded maximum. There was a significant correlation between the resting ventilatory response to hypercapnia delta VE/delta PCO2 and the ventilatory response to VCO2 during exercise (delta VE/delta VCO2; r = 0.88; P less than 0.05). The maximal inspiratory pressure generated during loading correlated with CO2 sensitivity at rest (r = 0.91; P less than 0.05) and with exercise ventilation (delta VE/delta VCO2; r = 0.83; P less than 0.05). Although resistive loading did not alter O2 uptake (VO2) or heart rate (HR) as a function of work load, maximal VO2, HR, and exercise tolerance were decreased to 90% of control values. We conclude that a modest inspiratory resistive load reduces maximum exercise capacity and that CO2 responsiveness may play a role in the control of breathing during exercise when airway resistance is artificially increased.
Adult↗
Changes in inspiratory muscle electrical activity and upper airway resistance during periodic breathing induced by hypoxia during sleep.
We hypothesized that: the balance of electrical activities between the upper airway and chest wall inspiratory muscles affects upper airway inspiratory caliber, and at low levels of central respiratory neural efferent activity, an imbalance between the electrical activities of these 2 inspiratory muscle groups exists that results in a decreased upper airway caliber. These hypotheses were tested during periodic breathing induced by mild hypoxemia in NREM sleep in 9 healthy male subjects. In 6 subjects during periodic breathing as central respiratory neural activity decreased, the tonic and phasic EMG activity of the upper airway inspiratory muscles decreased at a rate greater than that of the chest wall EMG activity. When the ratio of upper airway to chest wall EMG activity decreased below a critical level, which was reproducible across subjects, upper airway inspiratory resistance increased hyperbolically. Resistance at peak inspiratory flow increased from 4.10 +/- 0.97 (mean +/- SEM) to 48.70 +/- 21.00 cmH2O/L/s as tidal volume decreased from 0.79 +/- 0.12 to 0.20 +/- 0.02 L during periodic breathing in these subjects. In the 3 remaining subjects, the ratio of the upper airway to chest wall EMG activity did not decrease below the critical level as the activity of both muscle groups decreased during periodic breathing, and upper airway resistance did not increase. We conclude that within the confines of this study the nonlinear activation of upper airway and chest wall inspiratory muscles contributed to fluctuations in upper airway resistance observed during periodic breathing in sleep.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Segmental pulmonary consolidation due to amiodarone.
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Amiodarone↗
Conjunctival oxygen tension and its relationship to arterial oxygen tension.
Using a miniaturized Clark electrode embedded in a polymethylmethacrylate eyepiece, we measured transconjunctival oxygen tension (PcjO2) in 5 healthy volunteer subjects at multiple levels of steady-state isocapnic hypoxia, normoxia, and hyperoxia. PcjO2 was linearly related to arterial oxygen tension (PaO2) as PaO2 ranged from 28 to 205 mm Hg (PcjO2 = 0.59 PaO2 + 0.36 mm Hg; r = 0.94; standard error of the estimate = 7.09 mm Hg). However, the relationships between PcjO2 and PaO2 varied significantly among subjects. Whereas the overall mean ratio of PcjO2 to PaO2 was 0.59, the mean ratio for subjects ranged from 0.47 to 0.79 and was significantly different among subjects (P less than 0.0001). The time response of the electrode to a step change in oxygen tension in vitro was exponential, with a 90% response time of 38 seconds after a lag of 3.7 seconds. The time responses to in vivo changes in oxygen tension were also exponential. From hypoxia to normoxia, 90% response time was 45.0 seconds after a lag of 5.1 seconds; from room air to hypoxia, 90% response time was 72.4 seconds after a lag of 30.3 seconds; from room air to hyperoxia, 90% response time was 87.2 seconds after a lag of 6.8 seconds. We conclude that, although PcjO2 measured by a miniaturized Clark electrode is linearly related to PaO2 in healthy subjects, variation in the relationship of PcjO2 to PaO2 among individuals will prevent precise estimation of PaO2 for any individual unless subject-specific calibration is performed.
Adult↗
Range of accuracy of two wavelength oximetry.
Earlier reports of a two wavelength oximeter suggested a tendency toward overestimation of arterial oxygen saturation (SaO2) at the lowest values examined. To investigate this possible inaccuracy, we compared oximeter readings to SaO2 over a wider range of laboratory-induced steady-state hypoxia than has previously been reported. For values of SaO2 greater than 75 percent, oximeter readings were linearly related to SaO2 such that y = 0.94 SaO2 + 8.7 (r = 0.96) and the mean difference between oximeter reading and SaO2 was 0.09 percent. However, when SaO2 was less than 75 percent, the instrument readings were progressively higher than the SaO2 so that when SaO2 was approximately 50 percent, the oximeter reading was approximately 65 percent. These data show that the two wavelength oximeter displays falsely elevated readings when the arterial saturation falls below 75 percent.
Adult↗
Circulating immune complexes in rheumatoid arthritis: a prospective study using five immunoassays.
We evaluated 257 patients with rheumatoid arthritis (RA) to determine the frequency of circulating immune complexes (CIC) in the serum, relationships between the presence of CIC, clinical indices of disease activity and other laboratory features, and relationships between changes in CIC levels and changes in disease activity. CIC were detected by fluid phase Clq binding activity, conglutinin binding activity, anti-C3 assay, staphylococci protein A binding assay and the precipitation of cryoglobulins. CIC in the serum were found to correlate with indices of disease activity, extraarticular features and the presence of rheumatoid factor. A change in Clq binding activity correlated with a parallel change in the joint count.
Antibodies, Antinuclear↗
Ventilatory patterns during hypoxia, hypercapnia, and exercise in adolescents with mild scoliosis.
Adolescents with mild, asymptomatic scoliosis (thoracic curvature less than 35 degrees) may have little or no impairment of resting lung volumes. Progression to more severe disease may, however, be accompanied by lung restriction, impaired exercise tolerance, and respiratory failure with CO2 retention. We wished to see whether adolescents with mild scoliosis and minimally abnormal resting pulmonary mechanics had impairment of their responses to hypercapnia, hypoxia, and progressive cycle exercise. Forty-four adolescents with idiopathic scoliosis were studied. The mean forced vital capacity (FVC), expressed as a percentage of the predicted value, was 94.3 +/- 2.2 (SE). The mean ventilatory response to hypercapnia (2.57 +/- 0.24 L/min/mm Hg) was within the normal range but was achieved with a tidal volume response (1.87 +/- .17% vital capacity [VC]/mm Hg) that was significantly lower than that previously reported in healthy young adults. Ventilatory responses to exercise were also within the normal range, the mean dyspnea index (VE-max/maximal voluntary ventilation) = 0.92 +/- 0.04. However, at a ventilation of 30 L/min, the tidal volume was 0.38 +/- 0.01% FVC, which was considerably lower than predicted. The tidal volume response to hypoxia was also abnormally low, the mean response being 0.52 +/- 0.059% VC/% decrease in arterial O2 saturation. These findings indicated that, even when scoliosis is asymptomatic and associated with minimal impairment of resting pulmonary function, abnormal patterns of ventilation occur during exercise or in response to chemical stimuli.
Adolescent↗