[Subtrochanteric femur fractures-epidemiology, surgical procedures, influence of time to surgery and comorbidities on complications : A risk-adjusted regression analysis of routine data from 2124 cases]. / Subtrochantäre Femurfrakturen ­ Epidemiologie, Operationsverfahren sowie Einfluss der präoperativen Verweildauer und von Nebendiagnosen auf Komplikationen : Eine risikoadjustierte Regressionsanalyse mittels Routinedaten anhand von 2124 Fällen.

BACKGROUND: There are approximately 12,000 subtrochanteric femur fractures in Germany per year with a rising trend but studies about the epidemiology and the surgical outcome are rare. Furthermore, there are no guidelines from expert societies and there is no adequate quality assurance. OBJECTIVE: Presentation of the epidemiology and the current treatment situation with respect to the patient collective, comorbidities, time to surgery and surgical procedures used as well as the identification of modifiable risk factors with respect to complications. MATERIAL AND METHODS: Analysis of routine data based on an established data model in 2124 cases. The descriptive statistics contain data on basic patient characteristics, such as age, comorbidities, surgical procedure, time to surgery and mortality. In the analytical statistics the impact of risk factors (surgical procedure, time to surgery etc.) on the endpoints mortality, complications and decubitus was investigated by logistical regression analyses. RESULTS: Of the patients 55% were operated on within the first 24h. Intramedullary osteosynthesis (89%) is the most frequently used surgical method (prostheses 2%, extramedullary procedures 5%). Within the first postoperative year 37% of the patients received a higher level of care, where the care was moved from outpatient to inpatient treatment. The mortality in the first postoperative year was 26%, while early complications were observed in 6%. A delay in surgical treatment was associated with an increased mortality and intrinsic factors, which were difficult to influence. Intramedullary osteosynthesis had the lowest mortality and revision rates. CONCLUSION: Concerning the epidemiological data, the patient collectives of subtrochanteric fractures and femoral neck or pertrochanteric fractures were very similar. Major delays in the time to surgery of subtrochanteric fractures can be associated with increased complication rates and mortality. Therefore, programs to prevent older patients from falling have a high priority.

Effects of hypermetabolism on ventilation and chemosensitivity.

Muscular exercise is associated with hypermetabolism and increased hypoxic ventilatory response (HVR). In order to dissociate mechanical and metabolic factors, the effect of hypermetabolism on hypoxic ventilatory response was evaluated at rest. Carbohydrate and protein feeding increases metabolic rate, and their effects on chemosensitivity, ventilation, and blood pH were evaluated in six normal subjects 2 h and 3 h after calorically equal test meals (1,000 cal). After carbohydrate, base-line oxygen consumption (Vo(2)) increased from 237+/-11.3 ml/min (SEM) to 302+/-19.4 (P < 0.001) and 303+/-18.5 (P < 0.001) at 2 h and 3 h, respectively. Hypoxic ventilatory response, measured as shape parameter A, increased from a control of 144+/-11.8 to 330+/-61.0 (P < 0.01) at 2 h and 286+/-57.0 (P < 0.05) at 3 h. These changes were associated with a mild metabolic acidosis as pH decreased from a control of 7.402+/-0.004 to 7.371+/-0.009 (P < 0.005) at 2 h and 7.377+/-0.008 (P < 0.005) at 3 h. After protein, Vo(2) increased from 241+/-6.7 to 265+/-6.2 (P < 0.02) and 270+/-5.4 (P < 0.001), an overall increase less than that which occurred after carbohydrate (P < 0.01). Hypoxic ventilatory response increased from 105+/-14.5 to 198+/-24.3 (P < 0.02) at 2 h and 219+/-17.3 (P < 0.01) at 3 h, which was not different from the increase with carbohydrate. After protein, no acidosis occurred. Thus, after protein, HVR increased despite the absence of a systemic acidosis. We conclude that both carbohydrate and protein feedings are associated with resting hypermetabolism and increased HVR compared with the fasting state. For both meals, increased metabolic rate was correlated with increased hypoxic response.

Hereditary aspects of decreased hypoxic response.

Decreased ventilatory responses to hypoxia and hypercapnia have been demonstrated in a variety of disorders; however, the etiology of these decreased drives remains virtually unknown. Recent observations have suggested a familial influence on hypoxic and hypercapnic ventilatory response, but it is unclear whether this influence is the result of hereditary or environmental influences. Therefore we measured the ventilatory response to isocapnic hypoxia (HVR) and hyperoxic hypercapnia in 12 pairs of identical and 12 pairs of nonidentical twins. Significant correlation (P less than 0.01) was found for HVR within identical twin pairs but not within nonidentical twin pairs. Identical twins resembled each other more closely with respect to HVR than was the case for nonidentical twins (P less than 0.0125). This was independent of body size, blood PCO2, or pH. No such correlation could be found for ventilatory response to hyperoxic hypercapnia. It is concluded that hereditary influences affect HVR and it is speculated that such influences may play a role in clinical conditions characterized by decreased hypoxic ventilatory responses.

Bradycardia during sleep apnea. Characteristics and mechanism.

To determine the characteristics of and mechanisms causing the bradycardia during sleep apnea (SA), both patients with SA and normals were studied. Evaluation of six consecutive SA patients demonstrated that bradycardia occurred during 95% of all apneas (central, obstructive, and mixed) and became marked with increased apnea length (P less than 0.01) and increased oxyhemoglobin desaturation (P less than 0.01). Heart rate slowed 9.5 beats per minute (bpm) during apneas of 10-19 s in duration, 11.4 bpm during 20-39s apneas, and 16.6 bpm during 40-59-s apneas. Sleep stage had no effect unexplained by apnea length or degree of desaturation. Oxygen administration to four SA patients completely prevented the bradycardia although apneas lengthened (P less than 0.05) in three. Sleeping normal subjects did not develop bradycardia during hypoxic hyperpnea but, instead, HR increased with hypoxia in all sleep stages, although the increase in HR was not as great as that which occurred while awake. Breath holding in awake normals did not result in bradycardia during hyperoxia (SaO2 = 99%), but was consistently (P less than 0.01) associated with heart rate slowing during room air breath-holds (-6 bpm) at SaO2 = 93%, with more striking slowing (-20 bpm) during hypoxic breath-holds (P less than 0.01) at SaO2 = 78%. Breath holding during hyperoxic hypercapnia had no significant effect on rate. Breath holding in awake SA subjects demonstrated similar findings. We conclude that the bradycardia of SA is a consistent feature of apnea and results from the combined effect of cessation of breathing plus hypoxemia.

Transient oxygen desaturation following radiographic contrast medium administration.

To determine if angiography results in arterial oxygen desaturation, we prospectively studied 40 clinically stable patients undergoing arterial angiography. Arterial oxygen saturation (Sao2) was monitored before, during, and for at least three minutes after contrast medium injection. The mean (+/- SEM) Sao2 was 94.2% +/- 0.39% before injection and fell to 92.6% +/- 0.66% following injection. Eleven patients (28%) demonstrated a decrease in Sao2 of more than 3%, with six (15%) having a postinjection Sao2 of less than 90%. To determine if the vascular route of injected contrast medium influenced the subsequent level of oxygenation, we similarly evaluated the Sao2 of 20 consecutive patients undergoing venous angiography. The Sao2 was 94.2% +/- 0.33% before contrast medium injection and fell to 92.5% +/- 0.78% following injection. Six patients (30%) experienced a fall in Sao2 of more than 3%, with four (20%) having a postinjection Sao2 of less than 90%. We conclude that arterial oxygen desaturation occurs frequently in patients undergoing angiography.

Central sleep apnea. Improvement with acetazolamide therapy.

Respiratory rhythm during sleep may be dependent on blood pH with apneas being associated with alkalosis. Acidification may therefore have therapeutic value in some forms of sleep apnea. We administered acetazolamide to six patients with symptomatic central sleep apnea, a disorder of respiratory rhythm with little or no upper airway obstruction. Sleep studies were carried out before and after one week of drug therapy, during which time the mean arterial pH decreased from 7.42 to 7.34. All six patients had significant improvement, demonstrating a 69% reduction in total apneas. Five of the six patients reported better-quality sleep and decreased daytime hypersomnolence. Subsequent studies in normal subjects showed that acetazolamide, like other agents known to produce a metabolic acidosis, shifted the hypercapnic ventilatory response to the left 5 +/- 0.54 mm Hg. This may be important in mediating the observed decrease in apneas.

Thyrotoxicosis: comparison of effects of thyroid ablation and beta-adrenergic blockade on metabolic rate and ventilatory control.

To elucidate the role of the beta-sympathetic system in thyrotoxicosis (THY), we examined cardiac sensitivity to infused beta-agonist and compared the effect of beta-blockade with that of resolution of the hyperthyroid state. Beta-sympathetic (beta-SYM) sensitivity was measured as the heart rate response to isoproterenol in THY patients and in normal subjects. The patients with THY showed both lower threshold (P less than 0.05) and increased slope (P less than 0.05) of the heart rate-isoproterenol response, suggesting beta-SYM hypersensitivity. The beta-SYM like features of THY were measured in 7 patients before and 7 days after beta-SYM blockade with propranolol (mean dose 411 +/- 32 mg/day [SEM]) which was shown to block the heart rate response to isoproterenol. These results were compared with those in a similar group of thyrotoxic patients rendered euthyroid with 131I. During beta-SYM blockade, heart rate decreased from 101 +/- 6.3 to 78 +/- 4.6 (P less than 0.01), but the elevated metabolic rate (V02), resting ventilation (VE), and increased hypoxic and hypercapnic ventilatory responses were not significantly affected. In the group rendered euthyroid with 131I, heart rate decreased from 110 +/- 3.5 to 76 +/- 7.8 (P less than 0.02), but in contrast to the result of beta-SYM blockade, a 28% decrease in VO2 (P less than 0.01), 41% decrease in VE (P less than 0.05), a 38% decrease in hypercapnic ventilatory response (P less than 0.05), and a 66% decrease in hypoxic response (P less than 0.03) occurred. During THY, beta-SYM mechanisms are responsible for part of the tachycardia, but the metabolic and ventilatory abnormalities are not beta-SYM mediated.

Relative selective action of propranolol on cardiovascular and respiratory responses to isoproterenol.

Organ selectivity of beta sympathetic blockade with propranolol was studied in 6 normal men by comparing the cardiovascular and respiration responses during isoproterenol infusions before and after propranolol. Beta sympathetic blockade was achieved with propranolol and was considered present when there was no heart rate (HR) response to isoproterenol during an infusion tenfold greater than that which raised HR 25% during a control period. During blockade there was no change in HR or systolic or diastolic blood pressure during isoproterenol infusions. There was a consistent (p less than 0.05) rise in resting ventilation (+17%), oxygen consumption (+9%), and carbon dioxide production (+15%) with low-dose (raised HR 10% before blockade) isoproterenol infusion during blockade. These respiratory effects of low-dose isoproterenol during cardiovascular blockade were quantitatively similar to that before blockade. With infusion that raised HR 25%, there was a further increase in VE, VO2, and VCO2 before blockade but no further increase during beta blockade. Changes in acid-base status did not explain the increase in VE during blockade. We conclude that there are differences between effectiveness of propranolol blockade of the cardiovascular system and of the respiratory system.

Depressed ventilatory response in oculocraniosomatic neuromuscular disease.

Four patients with ptosis, external ophthalmoplegia, and ragged-red fibers on muscle biopsy were found to have decreased ventilatory responses to hypoxia and hypercapnia. Respiratory muscle weakness was not responsible for these findings since these responses were normal in muscle disease control patients. An altered metabolic state also can cause diminished ventilatory response, but overall oxygen consumption data in the ragged-red fiber patients were normal. The decreased ventilatory responses may be clinically significant because two of the ragged-red fiber patients had episodes suspicious of hypoventilation with poor response to hypoxia.

Ventilatory response in myotonic dystrophy.

Patients with myotonic dystrophy often develop respiratory failure caused by alveolar hypoventilation. Abnormalities in the ventilatory response to hypoxia and hypercapnia may explain this phenomenon. Accordingly, hypoxic and hypercapnic responses were measured in seven patients with myotonic dystrophy who had only mild respiratory muscle weakness. Hypoxic response was significantly reduced, while hypercapnic response was affected more irregularly. It is possible that the high incidence of respiratory failure in such patients is related to decreased hypoxic ventilatory response, occurring because of an underlying neurogenic deficit.

Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome.

Most patients with extreme obesity do not exhibit alveolar hypoventilation, but an intriguing minority do. The mechanism(s) of this phenomenon remain unknown. A disorder in ventilatory control has been suggested as a major factor in the pathogenesis of the obesity-hypoventilation syndrome. Accordingly, hypoxic and hypercapnic ventilatory drives were measured in 10 patients with the typical symptoms of the syndrome: obesity, hypersomnolence, hypercapnia, hypoxemia, polycythemia and cor pulmonale. Hypoxic ventilatory drive, measured as the shape parameter A, averaged 21.9 +/- 5.35, approximately one-sixth that in normal controls, A = 126 +/- 8.6 (P less than 0.01). The ventilatory response to hypercapnia also was markedly reduced, the slope of the response averaging 0.51 +/- 0.005, or about one-third the normal value of 1.83 +/- 0.13 (P less than 0.01). This decreased responsiveness in hypoxic and hypercapnic ventilatory drive was consistent throughout the group. The depression in ventilatory drive found in the obesity-hypoventilation syndrome may be causally related to the alveolar hypoventilation manifested by these patients.

The effect of positional changes on oxygenation in patients with pleural effusions.

In unilateral parenchymal pulmonary disease, arterial oxygenation decreases when the patient is positioned such that the abnormal lung is dependent; however, few studies have evaluated the effect of the body position on oxygenation in patients with unilateral or asymmetric pleural effusions. To our knowledge, no previous study has evaluated the possible transient effects of changing position on the level of arterial oxygen saturation (SaO2) in such patients. Accordingly, we studied ten normoxic patients spontaneously breathing room air, who had asymmetric pleural effusions as documented by chest x-ray film and physical examination. We monitored pulse, respiratory rate, and blood pressure every five minutes and SaO2 by ear oximetry continuously while patients were in the following positions: sitting; supine; and left and right lateral decubitus. The mean SaO2 was 95 percent and 94.3 percent in the sitting and supine positions, respectively. Mean SaO2 fell to 93.4 percent when the patients were positioned so that the side with the largest pleural effusion was dependent. When the side with the pleural effusion was down, the mean SaO2 was significantly lower than in either the sitting position or with the side with the pleural effusion up. We could find no significant relationship between the size of the pleural effusion and the amount of arterial oxygen desaturation. We conclude that there is a decrease in SaO2 in normoxic patients when the side with the larger pleural effusion is dependent; however, this decreased SaO2 does not appear to be clinically significant in patients with normal SaO2.

The control of breathing in clinical practice.

The control of breathing results from a complex interaction involving the respiratory centers, which feed signals to a central control mechanism that, in turn, provides output to the effector muscles. In this review, we describe the individual elements of this system, and what is known about their function in man. We outline clinically relevant aspects of the integration of human ventilatory control system, and describe altered function in response to special circumstances, disorders, and medications. We emphasize the clinical relevance of this topic by employing case presentations of active patients from our practice.

Pulmonary function in obstructive sleep apnea. Relationships to pharyngeal resistance and cross-sectional area.

Reduction in the size of the pharynx and increased pharyngeal airflow resistance have been demonstrated in patients with obstructive sleep apnea (OSA). We evaluated 15 men with severe OSA and 10 nonapneic control subjects matched for age and weight in order to determine if PCSA, inspiratory pharyngeal airflow resistance, and abnormal breathing events during sleep were associated with alterations in the flow-volume relationship and other awake PFTs. Pharyngeal cross-sectional area was determined by CT, and pharyngeal resistance between choanae and epiglottis was measured during quiet awake breathing. In patients with OSA, there was an inverse relationship between the mean cross-sectional area of the oropharynx and the ratio of FEF50%/FIF50% (rs = -0.54; p = 0.03). In all subjects, pharyngeal resistance was inversely related to percentage of predicted values for FEF25-75% (rs = -0.56; p = 0.01). The frequency of apneas during sleep was significantly (p less than 0.05) related to the percentage of predicted values for MVV, TLC, FVC, and PIF. Obesity appears to account for the strength of these relationships. Flow-volume loops and other PFTs did not distinguish patients with OSA from controls.

Breathing during sleep in stable asthmatic subjects. Influence of inhaled bronchodilators.

The bronchoconstriction of asthma displays a circadian rhythm with exacerbations often occurring in the early morning hours. Gas exchange abnormalities during sleep in patients with severe asthma have been documented; however, the influence of sleep on gas exchange in the asthmatic with few or no daytime or nocturnal symptoms is poorly understood. To determine if abnormalities in oxygenation might occur during sleep, we studied 12 stable adult asthmatic patients with reversible airflow obstruction during sleep on three consecutive nights, with night 1 being for acclimatization. On test nights 2 and 3, the subjects received, in random double-blind fashion, either inhaled fenoterol or its placebo. Spirometry was performed before and after bronchodilator treatment and on the next morning. The mean FEV1 was 63 percent predicted before treatment. There was significant (p less than 0.05) improvement in FEV1 on fenoterol night after treatment which was also present the next morning. Mean prefenoterol FEV1 was 2.04 +/- .15 (SEM) and increased to 2.61 +/- .17 after the bronchodilator. The mean morning FEV1 was 2.27 +/- .20. Mean preplacebo FEV1 was 2.07 +/- .12 and did not change significantly with placebo bronchodilator. Sleep analysis demonstrated no significant differences in total sleep time or duration of oxyhemoglobin desaturation between nights. The incidence of sleep disordered breathing was very low (0.14 apneas/hour). The frequency of apneas and hypopneas did not change significantly with treatment. Two of the 12 subjects experienced an asthma attack on placebo night which did not recur following active bronchodilator administration. We conclude that stable asthmatic patients with few nocturnal complaints have a low frequency of disordered breathing and desaturation events during sleep.

Is an anticholinergic agent superior to a beta 2-agonist in improving dyspnea and exercise limitation in COPD?

STUDY OBJECTIVE: To evaluate the impact of a week-long course of inhaled albuterol compared with ipratropium on expiratory peak flow, exercise performance, and dyspnea in patients with stable COPD. DESIGN AND INTERVENTIONS: A double-blind, two-period, crossover evaluation, wherein the subjects inhaled albuterol, two puffs four times a day (qid) for 7 days, or ipratropium, two puffs quid for 7 days, in random sequence. SETTING: Outpatients of the Pennsylvania State University Hospital, Lebanon VA Medical Center, and local private office practices. PARTICIPANTS: A sample of 15 subjects with stable COPD with FEV1 < 55% predicted. MEASUREMENTS AND RESULTS: Variables measured at baseline (no inhaled bronchodilator) and/or on day 7 of each arm included FEV1 (liters), 12-min walk test distance (meters), "rescue" puffs of metaproterenol needed each week, and dyspnea scoring after walking, on the Borg Category Scale (0 to 10 = maximal). There was no significant difference in distance walked in 12 min (mean of 751.0 +/- 55.5 [+/- SE]) vs 755.7 +/- 61.3 m) or perceived dyspnea (mean 2.7 +/- 0.4 vs 3.3 +/- 0.4) during albuterol or ipratropium use. Seven patients preferred ipratropium, seven preferred albuterol, and one had no preference. CONCLUSION: We conclude that the effects of 1 week of albuterol or ipratropium have similar effects on exercise performance and subjective dyspnea in patients with stable COPD.

Effects of oral narcotics on sleep-disordered breathing in healthy adults.

Alcohol and benzodiazepines may increase sleep-disordered breathing by decreasing activity of pharyngeal dilating muscles, favoring the development of obstructive apneas and hypopneas. Narcotics cause greater depression of wakeful respiration than the previously mentioned drugs; however, the influence of narcotics on the upper airway and breathing during sleep has not been studied. We, therefore, examined, in 12 healthy adults, the effects of oral hydromorphone hydrochloride (2 and 4 mg) on breathing during sleep and on a variety of awake respiratory variables (minute ventilation, gas exchange, and chemoresponsiveness). In addition, awake pharyngeal inspiratory airflow resistance was determined before and after narcotic administration to assess the drug's influence on patency of the upper airway. Following both doses, minute ventilation decreased, and carbon dioxide pressure increased. The 4-mg dose of hydromorphone hydrochloride also produced a significant decrement in the hypoxic ventilatory response, whereas hypercapnic responsiveness and pharyngeal resistance did not change following either dose of the drug. Despite the respiratory depression during wakefulness described previously, no significant change was observed in any measure of sleep-disordered breathing after either dose of narcotic. We conclude that in healthy individuals without suspected sleep apnea, oral hydromorphone in standard dosages does not significantly increase sleep-disordered breathing. This result may be due to a lack of selective depression of upper-airway muscular function by the doses of narcotic used.

Salmeterol vs theophylline: sleep and efficacy outcomes in patients with nocturnal asthma.

STUDY OBJECTIVES: To compare the efficacy, safety, and effects on sleep quality of salmeterol and extended-release theophylline in patients with nocturnal asthma. DESIGN: Randomized, double-blind, double-dummy, three-period crossover. SETTING: Outpatients at a single center. Patients spent 1 night during screening and 2 nights during each study period in a sleep laboratory for completion of sleep studies. PATIENTS: Male and female patients who were at least 18 years old with nocturnal asthma (baseline FEV1, 50 to 90% of predicted) and who required regular bronchodilator therapy. Patients on inhaled corticosteroids, cromolyn, and nedocromil were allowed into the study if their dosing remained constant throughout the study. INTERVENTIONS: Inhaled salmeterol (42 microg per actuation), extended-release oral theophylline (titrated to serum levels of 10 to 20 microg/mL), and placebo taken twice daily. MEASUREMENTS AND RESULTS: Efficacy measurements included nocturnal spirometry, nocturnal polysomnography, sleep questionnaires, and daily measurements of lung function and symptoms. Salmeterol was superior to theophylline (p < or = 0.05) in maintaining nocturnal FEV1 levels and was superior to placebo (p < or = 0.05) in improving morning and evening peak expiratory flow (PEF) and in decreasing nighttime albuterol use. The use of salmeterol significantly increased the percentage of days and nights with no albuterol use and decreased daytime albuterol use compared with theophylline and placebo (p < or = 0.05). Sleep quality global scores significantly improved with salmeterol and placebo (p < 0.001) but not with theophylline. The effects on sleep architecture were similar across treatment groups. CONCLUSIONS: Salmeterol (but not theophylline) was associated with sustained improvements in morning PEF, protection from nighttime lung function deterioration, reductions in albuterol use, and improvements in patient perceptions of sleep. No differences were seen in polysomnographic measures of sleep quality.

Lack of effects of beta sympathetic blockade on the metabolic and respiratory responses to carbohydrate feeding.

Increases in metabolic rate, heart rate and ventilation occur following carbohydrate feeding or during beta sympathetic stimulation. Furthermore, insulin secretion and hypokalemia are features common to both which raises the question as to whether these effects of carbohydrate depend upon an intact sympathetic nervous system. Accordingly, in the present study, we measured the effects of carbohydrate feeding (250 gram meal) before and after chronic beta sympathetic blockade in sex normal men. Before blockade metabolic rate (O2 consumption) rose (P less than 0.05) from a fasting mean of 248 +/- 19.7 (SEM) ML O2/min to 292 +/- 15.2 at 1 hr. 269 +/- 13.7 at 2, and 262 +/- 18.0 at 3 hr following the meal. During blockade (oral propranolol 80 mg p.o. Q 6 h for 3 days) the post-prandial increase in O2 consumption was also significant (P less than 0.05) and almost identical to that found before blockade. A similar pattern was found for ventilation, heart rate, insulin secretion and hypokalemia, where the significant postprandial changes were not altered by blockade. A transient increase in serum triiodothyronine from a mean of 92 +/- 8.4 microgram/ML to 109 +/- 9.4 occurred at 1 hr (P less than 0.05) only during blockade. No other changes in thyroid hormonal concentrations occurred as a result of the meal. We conclude that although similarities exist between beta sympathetic stimulation and carbohydrate feeding, the post-prandial effects studied do not depend on intact beta sympathetic receptors.

Adenosine infusion and periodic breathing during sleep.

Intravenously administered adenosine may increase ventilation (VI) and the ventilatory response to CO2 (HCVR). Inasmuch as we have previously hypothesized that those with higher HCVR may be more prone to periodic breathing during sleep, we measured VI and HCVR and monitored ventilatory pattern in seven healthy subjects before and during an infusion of adenosine (80 micrograms.kg-1.min-1) during uninterrupted sleep. Adenosine increased the mean sleeping VI (7.6 +/- 0.4 vs. 6.5 +/- 0.4 l/min, P less than 0.05) and decreased mean end-tidal CO2 values (42.4 +/- 1.2 vs. 43.7 +/- 1.0 Torr, P = 0.06, paired t test) during stable breathing. In six of seven subjects, periodic breathing occurred during this infusion. The amplitude (maximum VI--mean VI) and period length of this periodic breathing was variable among subjects and not predicted by baseline HCVR [correlation coefficients (r) = 0.64, P = 0.17 and r = -0.1, P = 0.9, respectively]. Attempts to measure HCVR during adenosine infusion were unsuccessful because of frequent arousals and continued periodic breathing despite hyperoxic hypercapnia. We conclude that adenosine infusion increases VI and produces periodic breathing during sleep in most normal subjects studied.