14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans.

Obstructive sleep apnoea syndrome (OSAS) causes nocturnal chronic intermittent hypoxia (IH) that contributes to excess cardiovascular morbidity. To explore the consequences of IH, we used our recently developed model of nocturnal IH in healthy humans to characterise the profile of this blood pressure increase, to determine if it is sustained and to explore potential physiological mechanisms. We performed 24-h ambulatory monitoring of blood pressure in 12 healthy subjects before and after 2 weeks of IH exposure. We also assessed systemic haemodynamics, muscle sympathetic nerve activity (MSNA), ischaemic calf blood flow responses and baroreflex gain. We obtained blood samples for inflammatory markers before, during and after exposure. IH significantly increased daytime ambulatory blood pressure after a single night of exposure (3 mmHg for mean and diastolic) and further increased daytime pressures after 2 weeks of exposure (8 mmHg systolic and 5 mmHg diastolic). Mean ± sd MSNA increased across the exposure (17.2 ± 5.1 versus 21.7 ± 7.3 bursts·min⁻¹; p < 0.01) and baroreflex control of sympathetic outflow declined from -965.3 ± 375.1 to -598.4 ± 162.6 AIU·min⁻¹ ·mmHg⁻¹ (p < 0.01). There were no evident changes in either vascular reactivity or systemic inflammatory markers. These data are the first to show that the arterial pressure rise is sustained throughout the waking hours beyond the acute phase immediately after exposure. Moreover, they may suggest that sympathoactivation induced by IH likely contributes to blood pressure elevation and may derive from reduced baroreflex inhibition. These mechanisms may reflect those underlying the blood pressure elevation associated with OSAS.

Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity.

Chronic intermittent hypoxia (CIH) is thought to be responsible for the cardiovascular disease associated with obstructive sleep apnea (OSA). Increased sympathetic activation, altered vascular function, and inflammation are all putative mechanisms. We recently reported (Tamisier R, Gilmartin GS, Launois SH, Pepin JL, Nespoulet H, Thomas RJ, Levy P, Weiss JW. J Appl Physiol 107: 17-24, 2009) a new model of CIH in healthy humans that is associated with both increases in blood pressure and augmented peripheral chemosensitivity. We tested the hypothesis that exposure to CIH would also result in augmented muscle sympathetic nerve activity (MSNA) and altered vascular reactivity contributing to blood pressure elevation. We therefore exposed healthy subjects between the ages of 20 and 34 yr (n = 7) to 9 h of nocturnal intermittent hypoxia for 28 consecutive nights. Cardiovascular and hemodynamic variables were recorded at three time points; MSNA was collected before and after exposure. Diastolic blood pressure (71 +/- 1.3 vs. 74 +/- 1.7 mmHg, P < 0.01), MSNA [9.94 +/- 2.0 to 14.63 +/- 1.5 bursts/min (P < 0.05); 16.89 +/- 3.2 to 26.97 +/- 3.3 bursts/100 heartbeats (hb) (P = 0.01)], and forearm vascular resistance (FVR) (35.3 +/- 5.8 vs. 55.3 +/- 6.5 mmHg x ml(-1) x min x 100 g tissue, P = 0.01) all increased significantly after 4 wk of exposure. Forearm blood flow response following ischemia of 15 min (reactive hyperemia) fell below baseline values after 4 wk, following an initial increase after 2 wk of exposure. From these results we conclude that the increased blood pressure following prolonged exposure to CIH in healthy humans is associated with sympathetic activation and augmented FVR.

A new model of chronic intermittent hypoxia in humans: effect on ventilation, sleep, and blood pressure.

Obstructive sleep apnea is characterized by repetitive nocturnal upper airway obstructions that are associated with sleep disruption and cyclic intermittent hypoxia (CIH) The cyclic oscillations in O(2) saturation are thought to contribute to cardiovascular and other morbidity, but animal and patient studies of the pathogenic link between CIH and these diseases have been complicated by species differences and by the effects of confounding factors such as obesity, hypertension, and impaired glucose metabolism. To minimize these limitations, we set up a model of nocturnal CIH in healthy humans. We delivered O(2) for 15 s every 2 min during sleep while subjects breathed 13% O(2) in a hypoxic tent to create 30 cycles/h of cyclic desaturation-reoxygenation [saturation of peripheral O(2) (Sp(O(2))) range: 95-85%]. We exposed subjects overnight for 8-9 h/day for 2 wk (10 subjects) and 4 wk (8 subjects). CIH exposure induced respiratory disturbances (central apnea hypopnea index: 3.0 +/- 1.9 to 31.1 +/- 9.6 events/h of sleep at 2 wk). Exposure to CIH for 14 days induced an increase in slopes of hypoxic and hypercapnic ventilatory responses (1.5 +/- 0.6 to 3.1 +/- 1.2 l.min(-1).% drop in Sp(O(2)) and 2.2 +/- 1.0 to 3.3 +/- 0.9 l.min(-1).mmHg CO(2)(-1), respectively), consistent with hypoxic acclimatization. Waking normoxic arterial pressure increased significantly at 2 wk at systolic (114 +/- 2 to 122 +/- 2 mmHg) and for diastolic at 4 wk (71 +/- 1.3 to 74 +/- 1.7 mmHg). We propose this model as a new technique to study the cardiovascular and metabolic consequences of CIH in human volunteers.

Bronchoconstrictor effects of leukotriene C in humans.

Maximum expiratory flow rate at 30 percent of vital capacity above residual volume served as an index of airway obstruction in comparing the effects of leukotriene C and histamine administered by aerosol to five normal persons. Leukotriene C was 600 to 9500 times more potent than histamine on a molar basis in producing an equivalent decrement in the residual volume. The leukotriene C response was slow in onset and prolonged, reminiscent of the effects of aerosol allergen challenge in asthmatic allergic subjects.

Mechanisms of pulsus paradoxus during resistive respiratory loading and asthma.

To determine the mechanisms of pulsus paradoxus during asthma, six subjects known to have cold air bronchial hyperreactivity were studied while in a quiescent phase of their disease. All were free of significant airway obstruction at the time of study. After placement of an esophageal balloon to estimate intrathoracic pressure, the subjects were assessed during quiet breathing, resistive airway loading and then during a stable period of airway obstruction induced by cold air. Steady state left ventricular volume and performance were measured using radionuclide ventriculography; right ventricular volume was calculated from the stroke volume ratio and right ventricular ejection fraction. Cardiac cycles were segregated according to their occurrence in inspiration or expiration using a flow signal from a pneumotachograph. Combined inspiratory and expiratory resistance produced pulsus paradoxus and changes in esophageal pressure that were similar to those during asthma and significantly greater than those during quiet breathing. These changes were accompanied by decreases in left ventricular diastolic volume and stroke volume during inspiration, and increases in these variables during expiration; right ventricular volume and stroke volume demonstrated changes reciprocal to those seen in the left ventricle. These data indicate that during periods of increase in airway resistance, abnormal pulsus paradoxus results from an exaggeration in the normal inspiratory-expiratory difference in stroke volume mediated primarily by the effects of intrathoracic pressure on ventricular preload.

Drivers with untreated sleep apnea. A cause of death and serious injury.

Three patients with untreated sleep apnea fell asleep while driving and caused serious automobile accidents. One person died, another became permanently paraplegic, and the three patients with sleep apnea were seriously injured in these crashes. This sequela of sleep apnea is not surprising, since subjects with sleep apnea may be poor drivers with a high accident rate and a high incidence of "near-miss" vehicular incidents. Because drivers with untreated sleep apnea may cause a large number of preventable automobile accidents, physicians have specific duties involving these drivers. First, physicians must try to identify impaired drivers with sleep apnea before they have an accident; routinely asking patients about loud snoring and hypersomnolence may help identify these impaired drivers. Second, physicians must consider the diagnosis of sleep apnea when examining patients who fall asleep while driving. Next, physicians must warn their patients with sleep apnea about the risks of driving with untreated sleep apnea. Finally, physicians must treat any seriously impaired driver with sleep apnea and keep these patients from driving until they can receive successful treatment.

Hemodynamic consequences of obstructive sleep apnea.

Patients with obstructive sleep apnea demonstrate both acute and chronic hemodynamic changes attributable to their disease. Acutely, these patients experience repetitive nocturnal hemodynamic oscillations. Sudden increases in heart rate and arterial pressure occur in association with decreases in left ventricular stroke volume immediately following apnea termination. These hemodynamic changes are likely attributable primarily to the effects of oxygen desaturation and arousal, an abrupt change in state. These acute changes occur against a background of altered cardiovascular control. Patients with sleep apnea, even when sleeping without obstructions, fail to display the normal nocturnal decline in arterial pressure of 10-15% from the waking value. The absence of a nocturnal decline may have chronic consequences, such as development of left ventricular hypertrophy. Another chronic hemodynamic consequence of sleep apnea may be sustained diurnal hypertension. Epidemiologic studies suggest individuals with sleep disordered breathing are at greater risk of daytime hypertension, even after controlling for other risk factors. Although sleep apnea may contribute to pulmonary, as well as systemic hypertension, sleep apnea alone does not appear to be a cause of decompensated right heart failure. Although knowledge of the hemodynamic consequences of sleep apnea has grown in recent years, much remains to be learned.

Patients with obstructive sleep apnea have an abnormal peripheral vascular response to hypoxia.

Patients with obstructive sleep apnea (OSA) have been reported to have an augmented pressor response to hypoxic rebreathing. To assess the contribution of the peripheral vasculature to this hemodynamic response, we measured heart rate, mean arterial pressure (MAP), and forearm blood flow by venous occlusion plethysmography in 13 patients with OSA and in 6 nonapneic control subjects at arterial oxygen saturations (Sa(O(2))) of 90, 85, and 80% during progressive isocapnic hypoxia. Measurements were also performed during recovery from 5 min of forearm ischemia induced with cuff occlusion. MAP increased similarly in both groups during hypoxia (mean increase at 80% Sa(O(2)): OSA patients, 9 +/- 11 mmHg; controls, 12 +/- 7 mmHg). Forearm vascular resistance, calculated from forearm blood flow and MAP, decreased in controls (mean change -37 +/- 19% at Sa(O(2)) 80%) but not in patients (mean change -4 +/- 16% at 80% Sa(O(2))). Both groups decreased forearm vascular resistance similarly after forearm ischemia (maximum change from baseline -85%). We conclude that OSA patients have an abnormal peripheral vascular response to isocapnic hypoxia.

Respiratory function of velopharyngeal constrictor muscles during wakefulness in normal adults.

The levator veli palatini (LVP) and the superior pharyngeal constrictor (SPC) influence velopharyngeal patency and soft palate position, but their behavior during respiration is incompletely characterized. To further clarify their respiratory function, we recorded electromyographic activity (EMG) in the LVP and the SPC in awake normal subjects breathing orally. EMG data were obtained in six subjects for the LVP and in nine subjects for the SPC. EMG activity and timing and ventilation were measured during isocapnic hypoxia and hyperoxic hypercapnia. Phasic EMG activity was inconsistently present during unstimulated oral breathing. Timing of EMG phasic activity was variable for both muscles. Peak LVP activity was mainly or exclusively expiratory in three of six subjects. Peak SPC activity was mainly or exclusively expiratory in five of nine subjects. With chemostimulation, recruitment of phasic activity was observed in the LVP and in four of six subjects and in the SPC in five of nine subjects. Tonic activity increased in four of six subjects for the LVP and in three of nine subjects for the SPC. However, the response was alinear, and intersubject as well as breath-to-breath variability was substantial. In conclusion, LVP and SPC are characterized by the higher inter- and intrasubject variability of EMG activity, timing of activation, and response to chemostimulation.

Relationship between velopharyngeal dimensions and palatal EMG during progressive hypercapnia.

To examine the contribution of specific palatal muscles to velopharyngeal dimensions, we recorded electromyographic (EMG) activity in the levator veli palatini, the tensor veli palatini, and the palatoglossus while examining the velopharynx (VP) with videoendoscopy in eight awake normal adults. Simultaneous display of VP images and airflow provided precise timing of events. Video images and EMG signals were recorded during progressive hypercapnia. Every tenth breath was analyzed. For each selected breath, VP area, anteroposterior and lateral diameters, and EMG activity were determined at five points: beginning, middle, and end of inspiration and middle and end of expiration. VP measurements changed significantly during the respiratory cycle. Although maximum area was measured at end inspiration or middle expiration and minimum area at the beginning or end of the breath, respiratory-related changes in VP measurements and EMG activity were characterized by substantial inter- and intrasubject variability. This variability is similar to velopharyngeal behavior during nonrespiratory tasks and suggests that upper airway patency is determined by multiple factors.

Drug-induced arterial pressure elevation is associated with arousal from NREM sleep in normal volunteers.

Abrupt changes in arterial pressure produce arousal in sleeping animals. To determine whether arterial pressure elevations can cause arousal from sleep in humans, we studied five healthy individuals without sleep complaints or cardiac abnormalities. Monitoring included electroencephalogram, electrooculogram, and electromyogram to determine stage sleep; finger cuff to measure arterial pressure; and electrocardiogram to measure heart rate. We administered intravenous bolus doses of either phenylephrine or saline after performing a dose-response curve to establish the amount of phenylephrine that produced a 20-mmHg increase in mean arterial pressure. Ten boluses of phenylephrine and ten boluses of saline were then administered in random order during stable non-rapid-eye-movement sleep. An observer blinded to the order of drug administration identified arousals using a standard definition. Arousals were five times more likely to occur after phenylephrine than after saline (58 vs. 12%; P = 0.0071). Phenylephrine administration produced heart rate slowing, indicative of baroreflex stimulation. We conclude that pharmacologically induced arterial pressure elevation is associated with arousal from sleep in normal volunteers.

Peripheral vascular resistance increases after termination of obstructive apneas.

The mechanisms by which obstructive apneas produce intermittent surges in arterial pressure remain poorly defined. To determine whether termination of obstructive apneas produce peripheral vasoconstriction, we assessed forearm blood flow during and after obstructive events in sleeping patients experiencing spontaneous upper airway obstructions. In all subjects, heart rate was monitored with an electrocardiogram and blood pressure was monitored continuously with digital plethysmography. In 10 patients (protocol 1), we used forearm plethysmography to assess forearm blood flow, from which we calculated forearm vascular resistance by performing venous occlusions during and after obstructive episodes. In an additional four subjects, we used simultaneous Doppler and B-mode images of the brachial artery to measure blood velocity and arterial diameter, from which we calculated brachial flow continuously during spontaneous apneas (protocol 2). In protocol 1, forearm vascular resistance increased 71% after apnea termination (29.3 +/- 15.4 to 49.8 +/- 26.5 resistance units, P < 0.05) with all patients showing an increase in resistance. In protocol 2, brachial resistance increased at apnea termination in all subjects (219.8 +/- 22.2 to 358.3 +/- 46.1 mmHg x l(-1) x min; P = 0.01). We conclude that termination of obstructive apneas is associated with peripheral vasoconstriction.

Hemodynamic changes associated with obstructive sleep apnea followed by arousal in a porcine model.

To study the effects of airway obstruction (AWO) and arousal on coronary blood flow, mean arterial pressure (MAP), and heart rate, pigs were chronically instrumented with arterial catheters, Doppler flow probes on the left circumflex coronary artery, and electrodes for determination of sleep stages. A modified tracheostomy tube was placed in the trachea to obstruct the upper airway during sleep sessions. In control studies, during non-rapid-eye-movement (NREM) sleep, MAP was 84 +/- 2 mmHg before AWO and increased by 5 +/- 2 mmHg on arousal. MAP was lower during rapid-eye-movement (REM) sleep (62 +/- 2 mmHg), and the increase on arousal was fourfold greater (22 +/- 2 mmHg). Heart rate was similar in both sleep stages (NREM: 120 +/- 4 beats/min; REM: 124 +/- 5 beats/min) and increased significantly on arousal (NREM: 12 +/- 2 beats/min; REM: 18 +/- 1 beats/min). Coronary blood flow was similar during both stages (NREM: 43 +/- 4 ml/min; REM: 46 +/- 8 ml/min) and increased by 12-15% on arousal. Coronary vascular resistance index increased significantly by 24% on arousal from AWO during REM sleep. All increases and decreases were significant at P < 0.05. Receptor blockade studies were performed to assess alpha-adrenergic receptor involvement.

Patterned cardiovascular responses to sleep and nonrespiratory arousals in a porcine model.

Patients with obstructive sleep apnea experience marked cardiovascular changes with apnea termination. Based on this observation, we hypothesized that sudden sleep disruption is accompanied by a specific, patterned hemodynamic response, similar to the cardiovascular defense reaction. To test this hypothesis, we recorded mean arterial blood pressure, heart rate, iliac blood flow and vascular resistance, and renal blood flow and vascular resistance in five pigs instrumented with chronic sleep electrodes. Cardiovascular parameters were recorded during quiet wakefulness, during non-rapid-eye-movement and rapid-eye-movement sleep, and during spontaneous and induced arousals. Iliac vasodilation (iliac vascular resistance decreased by -29.6 +/- 4.1% of baseline) associated with renal vasoconstriction (renal vascular resistance increased by 10.3 +/- 4.0%), tachycardia (heart rate increase: +23.8 +/- 3.1%), and minimal changes in mean arterial blood pressure were the most common pattern of arousal response, but other hemodynamic patterns were observed. Similar findings were obtained in rapid-eye-movement sleep and for acoustic and tactile arousals. In conclusion, spontaneous and induced arousals from sleep may be associated with simultaneous visceral vasoconstriction and hindlimb vasodilation, but the response is variable.

Cardiovascular responses to nonrespiratory and respiratory arousals in a porcine model.

Spontaneous and provoked nonrespiratory arousals can be accompanied by a patterned hemodynamic response. To investigate whether a patterned response is also elicited by respiratory arousals, we compared nonrespiratory arousals (NRA) to respiratory arousals (RA) induced by airway occlusion during non-rapid eye movement sleep. We monitored mean arterial blood pressure (MAP), heart rate, iliac and renal blood flow, and sleep stage in 7 pigs during natural sleep. Iliac and renal vascular resistance were calculated. Airway occlusions were obtained by manually inflating a chronically implanted tracheal balloon during sleep. The balloon was quickly deflated as soon as electroencephalogram arousal occurred. As previously reported, NRA generally elicited iliac vasodilation, renal vasoconstriction, little change in MAP, and tachycardia. In contrast, RA generally elicited iliac and renal vasoconstriction, an increase in MAP and tachycardia. The frequent occurrence of iliac vasoconstriction and arterial pressure elevation following RA but not NRA suggests that sleep state change alone does not account for the hemodynamic response to airway occlusion during sleep.

Breathing route influences upper airway muscle activity in awake normal adults.

Both nasal obstruction and nasal anesthesia result in disordered breathing during sleep in humans, and bypassing the nasal route during tidal breathing in experimental animals produces decreased electromyographic activity of upper airway (UA) dilating muscles. To investigate UA responses to breathing route in normal awake humans, we studied eight healthy males (ages 21-38 yr) during successive trials of voluntary nose breathing (N), voluntary mouth breathing (M), and mouth breathing with nose occluded (MO). We measured genioglossus electromyographic activity (EMGgg) with perorally inserted bipolar electrodes, alae nasi (EMGan) and diaphragm EMG activity (EMGdi) with surface electrodes, and minute ventilation (VE) with a pneumotachograph. Mean phasic inspiratory EMG activity of both UA muscles was significantly greater during N than during M or MO, even when a 2.5-cmH2O.l-1.s inspiratory resistance was added to MO (P less than 0.01). In contrast, neither EMGdi nor VE was consistently affected by breathing route. EMGgg during N was significantly decreased after selective topical nasal anesthesia (P less than 0.002); a decrease in EMGan did not achieve statistical significance. These data suggest that peak UA dilating muscle activity may be modulated by superficial receptors in the nasal mucosa sensitive to airflow.

Decrease in ventricular stroke volume at apnea termination is independent of oxygen desaturation.

Patients with obstructive sleep apnea experience nocturnal hemodynamic oscillations in association with repetitive respiratory events. Apnea termination (recovery) is accompanied by the nadir of arterial O2 saturation (SaO2), changes in intrathoracic pressure, and arousal from sleep. To investigate separately the contributions of hypoxemia and of arousal from sleep to changes in cardiac function, we continuously measured left ventricular stroke volume (LVSV) and mean arterial pressure (MAP) in eight subjects with severe obstructive sleep apnea (apnea-hypopnea index > 30 events/h associated with SaO2 < or = 82%) during two experimental conditions: 1) subjects slept without intervention for 1-2 h and then supplemental O2 was administered to maintain SaO2 > or = 90% (mean SaO2 nadir 92.7%) throughout the apnea-recovery cycle and 2) upper airway obstructions were abolished using nasal continuous positive airway pressure and subjects were aroused from sleep by an auditory signal. Recovery was associated with an increase in MAP and a decrease in LVSV both with and without supplemental O2. Arousal from sleep on nasal continuous positive airway pressure reproduced the postapneic elevation of MAP but not a decrease in cardiac function of the magnitude that occurred at apnea termination. We conclude that elevation of blood pressure and reduction of LVSV that occurred at apnea termination may be due to different physiological mechanisms.

Effect of chest wall vibration on breathlessness in normal subjects.

This study evaluated the effect of chest wall vibration (115 Hz) on breathlessness. Breathlessness was induced in normal subjects by a combination of hypercapnia and an inspiratory resistive load; both minute ventilation and end-tidal CO2 were kept constant. Cross-modality matching was used to rate breathlessness. Ratings during intercostal vibration were expressed as a percentage of ratings during the control condition (either deltoid vibration or no vibration). To evaluate their potential contribution to any changes in breathlessness, we assessed several aspects of ventilation, including chest wall configuration, functional residual capacity (FRC), and the ventilatory response to steady-state hypercapnia. Intercostal vibration reduced breathlessness ratings by 6.5 +/- 5.7% compared with deltoid vibration (P less than 0.05) and by 7.0 +/- 8.3% compared with no vibration (P less than 0.05). The reduction in breathlessness was accompanied by either no change or negligible change in minute ventilation, tidal volume, frequency, duty cycle, compartmental ventilation, FRC, and the steady-state hypercapnic response. We conclude that chest wall vibration reduces breathlessness and speculate that it may do so through stimulation of receptors in the chest wall.

Stroke volume and cardiac output decrease at termination of obstructive apneas.

Patients with obstructive sleep apnea (OSA) experience repetitive nocturnal oscillations of systemic arterial pressure that occur in association with changes in respiration and changes in sleep state. To investigate cardiac function during the cycle of obstruction (apnea) and resumption of ventilation (recovery), we continuously measured left ventricular stroke volume (LVSV) and mean arterial blood pressure (MAP) during non-rapid-eye-movement sleep in six males with severe OSA (apnea/hypopnea index > or = 30 events/h associated with oxygen saturation < 82%). LVSV was assessed continuously using an ambulatory ventricular function monitor (VEST; Capintec). The apnea-recovery cycle was divided into three phases: 1) early apnea (EA), 2) late apnea (LA), and 3) recovery (Rec). In all subjects recovery was associated with an abrupt decrease in LVSV [54.0 +/- 14.5 (SD) ml] compared with either EA (91.4 +/- 14.7 ml; P < 0.001) or LA (77.1 +/- 15.2 ml; P < 0.005). Although heart rate increased with recovery, the increase was not sufficient to compensate for the decrease in LVSV so that cardiac output (CO) fell (EA: 6,247 +/- 739 ml/min; LA: 5,741 +/- 1,094 ml/min; Rec: 4,601 +/- 1,249 ml/min; EA vs. Rec, P < 0.01; LA vs. Rec, P < 0.025). Recovery was also associated with a significant increase in MAP. We speculate that such abrupt decreases in LVSV and CO at apnea termination, occurring coincident with the nadir of oxygen saturation, may further compromise tissue oxygen delivery.

Upper airway anesthesia delays arousal from airway occlusion induced during human NREM sleep.

Six healthy subjects (5 males and 1 female, 26-40 yr old) were studied during non-rapid-eye-movement (NREM) sleep to assess the role of upper airway (UA) afferents in the arousal response to induced airway occlusion. Subjects wore an airtight face mask attached to a low-resistance one-way valve. A valve in the inspiratory circuit allowed instantaneous inspiratory airway occlusion and release; the expiratory circuit remained unoccluded at all times. Each subject was studied during two nights. On one night, occlusions were created during stable stage 2 NREM sleep before and after application of 4% lidocaine to the oral and nasal mucosa. On the other night, the protocol was duplicated with saline ("sham anesthesia") rather than lidocaine. The order of nights was randomized. Occlusions were sustained until electroencephalographic arousal. Three to 12 occlusions were performed in each subject for each of the four parts of the protocol (pre- and post-lidocaine, pre- and post-saline). The auditory threshold for arousal (1,500-Hz tone beginning at 30 dB) was also tested before and after UA lidocaine. For the group, arousal time after UA anesthesia was prolonged compared with preanesthesia arousal time (P less than 0.001); arousal time after sham anesthesia did not significantly increase from before sham anesthesia (P = 0.9). The increase in arousal time with UA anesthesia was greater than the increase with sham anesthesia (P less than 0.001). The auditory arousal threshold did not increase after UA anesthesia. Inspiratory mask pressure, arterial O2 saturation of hemoglobin, and end-tidal PCO2 during occlusions were similar before and after UA anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)