Obstructive Sleep Apnea following Topical Oropharyngeal Anesthesia in Loud Snorers1,2
GEOFFREY A. CHADWICK, PAUL CROWLEY, MUIRIS X. FITZGERALD, RONAN G. O'REGAN, and WALTER T. McNICHOLAS
Introduction
T he patency of the upper airway is dependent on a balance between the negative intrapharyngeal pressure during inspiration, which promotes closure, and the counteracting effect of the upper airway dilating muscles (1). Obstructive sleep apnea (OSA) occurs when the upper airway dilating muscles are unable to balance the effects of this negative inspiratory pressure. Factors that narrow the upper airway, such as enlarged tonsils, increasethe negativeintrapharyngeal pressure during inspiration and thus predispose to obstructive apnea (2, 3). It has also been proposed that patients with clinically significant OSA have an added neurologic deficit that contributes to the development of the syndrome (4, 5). The precise nature of this deficit, however, has not been identified. Several recent reports indicate a role for upper airway reflex mechanisms in the maintenance of upper airway patency (6-9). Animal studies (10)have shown that interference with such reflex mechanisms by oropharyngeal anesthesia results in upper airwayocclusion and thus supports the possibility that defects in such reflex mechanisms contribute to the development of OSA. Recently, MeNicholas and colleagues (11) showed that topical oropharyngeal anesthesia in normal human subjects results in a statistically but not clinicallysignificant increase in the frequency of obstructive apneas during sleep. However, the conditions pertaining in the upper airway during sleep in patients with clinically significant OSA differ from those in normal subjects, with considerable mechanical vibration and fluctuating pressures related to the effects of snoring and repetitive obstructive apneas. Under these circumstances the effect of upper airway reflexes may be lost. Wetherefore sought to investigate the effects of oropharyngeal anesthesia in a group of otherwise asymptomatic snorers, a group recog810
SUMMARY Previous studies support the presence of an upper airway reflex mechanism that eontributes to the maintenance of upper airway patency during sleep. We Investigated the possibility that Interference with this reflex mechanism contributes to the development of obstructive sleep apnea. Eight otherwise asymptomatic snorers (seven male and one female), age 39 ± 5.3 yr (mean ± SEM), underwent overnight sleep studies on three successive nights. An acclimatization night was followed by two study nights randomly assigned to control (C) and oropharyngeal anesthesia (OPA).On the OPAnight topical anesthesia was Induced using 10% lidocaine spray and 0.25% buplvocaine gargle. A saline placebo was used on night C. All subjects slept well on both study nights (mean sleep duration was 6.2 h on both study nights), and sleep stage distribution was similar on both nights. Obstructive apneas and hypopneas (OAH) rose from 114 ± 43 during C to 170 ± 49 during OPA (p < 0.02). Central apneas and hypopneas (CAH)were unchanged between the two nights (8 ± 4.9 versus 7 ± 3). The duration of OAH was similar on both study nights (20 ± 1.9 s during C versus 20 ± 1.5 s during OPA). The frequency of movement arousals terminating OAH tended to be higher during OPA(7 ± 2.9/h) than during C (3 ± 0.7); P NS. The frequency of oxyhemoglobin desaturatlons was also higher during OPA (5 ± 2.1/h) than during C (3 ± 1.4), P < 0.07.These data Indicate that OPA Increases the frequency of OAH during sleep but not their duration, suggesting that defective upper airway reflexes may Influence the Initiation of obstructive respiratory events but not their termination. Weconclude that upper airway reflexes are Important In the pathophyslol. ogy of OSA. AM REV R~PlR DIS 1991; 143:810-813
=
nized to be intermediate between normal and clinically significant OSA (12). Methods Eight otherwise asymptomatic loud snorers (seven male and one female) aged 39 ± 5 yr (mean ± standard error of the mean, SEM) were studied. None had any symptoms of respiratory disease, and none was on any medication. All had normal spirometry and blood pressure. None spontaneously complained of significant daytime sleepiness, although one patient admitted to mild daytime sleepiness on direct questioning. Subjects were studied on three successivenights in a respiratory sleep laboratory using standard polysomnographic techniques (13),which consist of continuous recordings of electroencephalogram (EEG), eye movements, and submental electromyogram (EM G), all from surface electrodes. Respiration was recorded continuously and noninvasively using a respiratory inductance plethysmograph (Respitraces; Ambulatory Monitoring, Inc., Ardsley, NY), which was calibrated using the isovolume technique (14). When calibrated against a spirometer this device has been shown by many investigators to provide a relatively accurate means of noninvasively quantifying respiration (15, 16) and thus is well suited to studying respiration
during sleep. The Respitrace can also distinguish obstructive from central apneas by showing the presence or absence of equal and opposite rib cage and abdominal movement, respectively, where the net tidal volume is zero, indicating apnea (17). In the present report apnea is defined as an absence of movement in the sum channel of the Respitrace lasting at least 10 sand hypopnea as a period of 10 s or more when the tidal volume abruptly falls to less than 50070 ofthe average tidal volume for the preceding 30 s. Hypopneas were usually terminated by an arousal pattern on the EEG. The variables were recorded continuously on a polygraph recorder (Model 78D; Grass Instruments, Quincy, MA), and oxygen saturation was also recorded continuously using an ear oximeter (Biox'" IIa; Biox
(Received inoriginalform July 2, 1990andin revised form October 15, 1990) 1 From the Departments of Respiratory Medicine and Physiology and the Respiratory Sleep Laboratory, University College and St. Vincent's Hospital, Dublin, Ireland. 2 Correspondence and requests for reprints should be addressed to Dr. Walter McNicholas, Department of Respiratory Medicine, St. Vincent's Hospital, Elm Park, Dublin 4, Ireland.
811
OBSTRUCTIVE SLEEP APNEA AFTER TOPICAL OROPHARYNGEAL ANESTHESIA IN LOUD SNORERS
Inc., Boulder. CO). Significant oxygen desaturation was taken as greater than 4010 (18). Wealso considered making additional more direct measurements of the presence or absence of respiratory effort during apnea. such as recordings of esophageal pressure or diaphragmatic EMG. Werejected both these additional recordings. however. since both would have required a catheter to be passed through the upper airway. which may have altered the frequency of abnormal respiratory events during sleep. The first of the three study nights was an acclimatization night during which the various monitoring devices were attached but no recordings made. This night was intended to minimize the first night effect (19). The second and third nights were randomly designated control (C) or oropharyngeal anesthesia (OPA). Subjects wereinstructed to abstain from alcohol for 24 h before each study. On the OPA night the oropharynx was sprayed repeatedly with a 4% lidocaine solution until the gag reflex was abolished (maximum total dose required was 180mg in any patient). Subjects were instructed to spit out any saliva formed during this procedure to minimize systemic absorption of anesthetic. Each subject then gargled 10 ml of a 0.25070 solution of bupivocaine for 1 min. This solution was then spit out and none swallowed. The additional use of bupivocaine was because of its longer duration of action than lidocaine [4 to 6 h as opposed to 1.5to 2 h (20)]. The oropharynx was again sprayed with lidocaine after 4 h of sleep. Additional bupivocaine was not administered at this stage because we believed that sustained gargling for 1 min would be technically difficult in a recently wakened subject. On the control night each subject had the oropharynx sprayed with saline before sleep. and again after 4 h. to mimic the anesthesia night as closely as possible. All polygraph and oximetry records were coded such that the reader was unaware of which type of study (C or OPA) was being analyzed. and all studies were analyzed by the same person. Statistical analysis was by paired t testing.
TABLE 1 SLEEP STAGE DISTRIBUTION (MIN) DURING STUDY NIGHTS*
Awake Stage 1 Stage 2 SWS REM Total sleep Sleep latency Sleep efficiency, %
Control
OPA
23 ± 5 22 ± 8.9 229 ± 18 44 ± 9.4 82 ± 9.6 377 ± 12 8 ± 1.7 94 ± 1
47 ± 16 25 ± 6.6 231 ± 17 47 ± 9.3 70 ± 12.2
Definition of abbreviations: OPA = oropharyngeal anestheslow-wave sleep; REM rapid-eye-movement sia; SWS sleep; sleep efficiency = time asleep as a percentage of time in bed. * Data are given as mean ± SEM.
=
=
differences in OAR between nights was during stages 1 and 2 sleep. All subjects showed an increase in numbers of OAR during OPA (figure 2). Furthermore, several subjects had sufficient OAR on the control night (C) to qualify for a diagnosis of obstructive sleep apnea syndrome as conventionally defined. There was no significant difference in the frequency of OAR between the early and late parts of the night during OPA. This lack of difference may in part be because
70 Fig. 1. Frequency of obstructive apneas and hypopneas during different sleep stages on both control and anesthesia nights. Data are presented as mean ± SEM. Definitionof abbreviations: OAH = obstructive apneas and hypopneas; OPA = oropharyngeal anesthesia; n.s. = not significant; SWS = slow-wave sleep; REM = rapid-eye-movement sleep. Closed bars = control; hatched bars = OPA.
Discussion
The main finding of this study is that obstructive respiratory events during sleep
OAH per hour
p=n.s.
60
50 40 30 20 10
Stage 1/2
Results
Sleep stage distribution for the eight subjects is given in table 1. All subjects slept wellon both study nights, achieving both rapid-eye-movement (REM) and slowwave sleep. There was no significant difference in the distribution of sleep stages between the two nights, and sleep efficiency (time asleep as a proportion of total study time) was also similar. Data on obstructive respiratory events are given in figures 1 and 2. Obstructive apneas and hypopneas (OAH) were significantly more frequent during OPA and were most frequent during REM sleep (figure 1). However, the most significant
373 ± 15 17 ± 4.8 89 ± 3.7
REM sleep tended to predominate in the latter part of each study. The numbers of central apneas and hypopneas were small and did not differ between the two study nights (1.4 ± 0.8/h during C compared to 1.2 ± O.4/h during OPA, mean ± SEM). The frequency of movement arousals (defined as a period of gross artifact on all polysomnographic channels) terminating abnormal respiratory events was proportional to the frequency of OAH and showed a trend to be greater during the OPA night (figure 3). Approximately 15070 of OAH wereassociated with falls in Sao, of 4070 or more (figure 4). The frequency of desaturations was significantly greater during stages 1 and 2 sleep on the OPA night compared to C and was of borderline significance overall. The duration of abnormal respiratory events was similar on both nights. CAH lasted 13 ± 2.4 s during C versus 12 ± 2.4 during OPA. OAR lasted 20 ± 1.9 s during C verus 20 ± 1.5 during OPA.
500
SWS
REM
Overall
Total Number of OAH
400
Fig. 2. Total number of obstructive apneas and hypopneas (OAH) in each of the eight subjects on both control and anesthesia (OPA) nights.
300
200
100
ol-----~==-----------
Control
OPA
CHADWICK, CROWLEY, FITZGERALD, O'REGAN, AND McNICHOLAS
812 Arousals per hour
12 1
Fig. 3. Frequency of movement arousals terminating abnormal respiratory events during different sleep stages on both control and anesthesia nights. Data are presented as mean ± SEM. Definition of abbreviations: OPA :: oropharyngeal anesthesia; SWS = slow-wave sleep; REM :: rapid-eye-movement sleep. None of the differences achieved statistical significance. Closed bars :: control; hatched bars = OPA.
10
8
6
4
2 0'---Stage 1/2
SWS
REM
Overall
20 Desaturations per hour p=n.s.
Fig. 4. Frequency of desaturations greater than 4% during different sleep stages on both control and anesthesia nights. Data are presented as mean ± SEM. Definition of abbreviations: OPA :: oropharyngeal anesthesia; n.s. :: not significant, SWS :: slow-wave sleep; REM :: rapid-eye-movement sleep. Closed bars » control; hatched bars :: OPA.
15
10
5
0'---Stage 1/2
sws
REM
in loud snorers occur more frequently after topical oropharyngeal anesthesia. These findings complement our previous study in normal subjects (11) and support the hypothesis that interference with upper airway reflex mechanisms compromises upper airway patency during sleep and thus contributes to the development of obstructive sleep apnea (OSA). The present findings also complement previous animal studies that have reported upper airway obstruction after upper airway anesthesia under certain experimental conditions, sometimes to the point of death of the animal (10). The precise nature of this postulated reflex mechanism cannot be identified from the present study, but previous animal studies favor a pressure-sensitive reflex mechanism as most likely (7-9). Support for a similar reflex mechanism in humans is the finding that pharyngeal airflow resistance increases during sleep following topical upper airway anesthesia (21). The presence of such a reflex mechanism based in the upper airway would fit well with current concepts of the pathogenesis of upper airway occlusion during sleep in patients with OSA in that an imbalance between intrapharyngeal pressure and the contraction of upper airway dilating muscles ap-
Overall
pears to be of critical importance to the development of obstructive apnea in such patients (1). Thus in light of this evidence it seems not unreasonable to suggest that a defect in such a pressure-sensitive reflex mechanism could contribute to the development of OSA. Support for the presence of such a defect is the finding of impaired detection of added inspiratory resistance in patients with OSA (5). It could be postulated that a subtle upper airway neuromuscular reflex that played a role in the maintenance of upper airway patency in normal subjects might not be detectable in patients with OSA for at least two reasons. First, a defect in such a reflex mechanism may play a primary role in the pathogenesis of OSA by contributing to the development of upper airway occlusion during sleep. Second, the mechanical vibration of the upper airway associated with loud snoring may blunt the afferent receptor for the reflex, which is presumed to lie in the oropharyngeal wall. Our data do not support the second possibility, since our subjects with loud snoring would also be expected to have a mechanical vibration in the upper airway similar to that in patients with OSA. The present findings also provide some evidence against the first possibility in that most subjects
showed a substantial increase in OAH after OPA that would not be expected if the upper airway reflexes were defective. Our results also show that OPA affects the frequency of obstructive events but not their duration. These findings suggest that OPA influences the initiation of obstructive events but not their termination. Thus other mechanisms that do not involve upper airway reflexes, such as hypoxemia and hypercapnia, are likely to be more important in the termination of apnea. In our study only a minority of obstructive events were associated with a desaturation of greater than 4070. This finding likely reflects the fact that all subjects had awake Sa02greater than 95% and were thus on the flat upper part of the oxyhemoglobin dissociation curve. They would therefore have required a substantial fall in arterial P0 2, of the order of 25 to 30 mm Hg, to produce a 4070 fall in Sa0 2. Thus a significant degree of hypoxemia may have contributed to the termination of obstructive events during sleep without being reflected in a large change in Sa02. Loud snorers are regarded as an intermediate stage between normality and clinical OSA (12). Our data support this contention in that there was a relatively high frequency of OAH during the control night, much higher than has been previously documented in normal control subjects (11, 18). In fact, several of our subjects had apnea and hypopnea frequencies that fell within the range of OSA as conventionally defined (22). Potential confounding effects of the topical anesthetic, for example by systemic absorption or local direct effects on the patency of the oropharyngeal lumen, can be discounted for the following reasons. The total dose of topical anesthetic used was quite small, and wetook considerable precautions during administration to prevent the systemic absorption of anesthetic by asking each subject to spit out saliva formed during administration. Furthermore, local anesthetics, when absorbed in significant amounts, tend to produce stimulation rather than depression of the central nervous system (20). In a previous study (11) we found that such effects are only seen when twice or three times the amount of anesthetic as used in the present study were administered using the techniques described previously. There are no data on any direct effect of topical anesthetic on oropharyngeal patency. However, a recent study by Cole and Haight (23) showed that intranasal lidocaine has no effect on
OBSTRUCTIVE SLEEP APNEA AFTER TOPICAL OROPHARYNGEAL ANESTHESIA IN LOUD SNORERS
nasal airway resistance, which suggests that the anesthetic has no direct effect on upper airway patency. Further studies are required to establish the presence or absence of protective upper airway reflexesin patients with established OSA. Should such reflexesbe present in established OSA, this may have implications for the role of uvulopalatopharyngoplasty in the management of the condition, since it could be argued that the surgical techniques involved in this procedure may in some patients interfere with the afferent limb of upper airway-based protective reflexes, as described previously. Such effects may at least partly outweigh the beneficial effects of UPPP related to enlargement of the upper airway lumen. Our data do not offer specific evidence in this regard, however. References 1. RemmersJE, deGroot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 1978; 44:931-8. 2. Orr WC, Martin RJ. Obstructive sleep apnea associated with tonsillar hypertrophy in adults. Arch Intern Med 1981; 141:990-2. 3. McNicholas WT, 'Iarlo S, Cole P, et al. Obstructive apneas during sleep in patients with seasonal allergicrhinitis. Am RevRespirDis 1982; 126:625-8. 4. Onal E, Lopata M, O'Connor T. Pathogenesis of apneas in hypersomnia-sleep apnea syndrome.
Am Rev Respir Dis 1982; 125:167-74. 5. McNicholas WT, BowesG, Zamel N, Phillipson EA. Impaired detection of added inspiratory resistance in patients with obstructive sleep apnea. Am Rev Respir Dis 1984; 129:45-8. 6. Mathew OP, Remmers JE. Respiratory function of the upper airway. In: Saunders NA, Sullivan CE, eds. Sleep and breathing: lung biology in health and disease. Vol. 21. New York: Marcel Dekker, 1984; 163-200. 7. Mathew OP, Abu-Osba YK, Thach BT. Influence of upper airway pressure changes on genioglossus muscle respiratory activity. J Appl Physiol 1982; 52:438-44. 8. Mathew OP, Abu-Osba YK, Thach BT.Genioglossus muscle responses to upper airway pressure changes: afferent pathways. J Appl Physioll982; 52:445-50. 9. Hwang JC, St John WM, Bartlett D. Afferent pathways for hypoglossal and phenic responses to changes in upper airway pressure. Respir Physiol 1983; 49:341-55. 10. Abu-Osba YK, Mathew OP, Thach BT. An animal model for sensory deprivation producing obstructive apnea with postmortem findings of sudden infant death syndrome. Pediatrics 1981; 68: 796-801. 11. McNicholas WT, Coffey M, McDonnell T, O'Regan R, Fitzgerald MX. Upper airway obstruction during sleep in normal subjects after selective topical oropharyngeal anesthesia. Am Rev Respir Dis 1987; 135:1316-9. 12. Issa FG, Sullivan CEo Upper airway closing pressure in snorers. J Appl Physiol1984; 57:528-35. 13. Rechtschaffen A, Kales A. A manual of standardised terminology, techniques and scoring system for sleep stages in human subjects. Washington, DC: National Institutes of Health, 1968;publication 204. 14. Konno K, Mead J. Measurement of the sepa-
813 rate volume changes of ribcage and abdomen during breathing. J Appl Physiol 1967; 22:407-22. 15. Zimmerman PV, Connellan SJ, Middleton HC, Tabona MV, Goldman MD, Pride N. Postural changes in ribcage and abdominal volumemotion coefficients and their effect on the calibration of a respiratory inductance plethysmography. Am Rev Respir Dis 1983; 127:209-14. 16. Hudgel DW, Capehart M, Johnson B, Hill P, Robertson D. Accuracy of tidal volume, lung volume and flow measurements by inductance vest in COPD patients. J Appl Physiol1984; 56:1659-65. 17. Cohn MA, Watson H, Weisshaut R, Stott F, Sackner MA. A transducer for noninvasive monitoring of respiration. In: Stott FD, Raftery EB, Sleight P, Goulding L, eds, ISAM 1977:proceedings of the second international symposium on ambulatory monitoring. London: Academic Press, 1978; 119-28. 18. Block AJ, Boysen PG, Wynne JW, Hunt LA. Sleep apnea, hypopnea and oxygen desaturation in normal subjects. N Engl J Med 1979;300:513-7. 19. Agnew HW, WebbWB, WilliamsRL. The first night effect: an EEG study of sleep. Psychophysiology 1966; 2:263-6. 20. Ritchie JM, Cohen PJ. Local anesthetics. In: Goodman LS, Gilman A, eds. The Pharmacological basis of therapeutics. 5th ed. New York: MacMillan, 1975; 379-403. 21. DeWeese EL, Sullivan TY. Effects of upper airway anesthesia on pharyngeal patency during sleep. J Appl Physiol 1988; 64:1346-53. 22. Guilleminault C, Tilkian A, Dement WC. The sleep apnea syndromes. Annu Rev Med 1976; 27:465-84. 23. Cole P, Haight JS. Nasal mucosal anaesthesia and airflow resistance. Rhinology 1985; 23: 209-12.
GEOFFREY A. CHADWICK, PAUL CROWLEY, MUIRIS X. FITZGERALD, RONAN G. O'REGAN, and WALTER T. McNICHOLAS
Introduction
T he patency of the upper airway is dependent on a balance between the negative intrapharyngeal pressure during inspiration, which promotes closure, and the counteracting effect of the upper airway dilating muscles (1). Obstructive sleep apnea (OSA) occurs when the upper airway dilating muscles are unable to balance the effects of this negative inspiratory pressure. Factors that narrow the upper airway, such as enlarged tonsils, increasethe negativeintrapharyngeal pressure during inspiration and thus predispose to obstructive apnea (2, 3). It has also been proposed that patients with clinically significant OSA have an added neurologic deficit that contributes to the development of the syndrome (4, 5). The precise nature of this deficit, however, has not been identified. Several recent reports indicate a role for upper airway reflex mechanisms in the maintenance of upper airway patency (6-9). Animal studies (10)have shown that interference with such reflex mechanisms by oropharyngeal anesthesia results in upper airwayocclusion and thus supports the possibility that defects in such reflex mechanisms contribute to the development of OSA. Recently, MeNicholas and colleagues (11) showed that topical oropharyngeal anesthesia in normal human subjects results in a statistically but not clinicallysignificant increase in the frequency of obstructive apneas during sleep. However, the conditions pertaining in the upper airway during sleep in patients with clinically significant OSA differ from those in normal subjects, with considerable mechanical vibration and fluctuating pressures related to the effects of snoring and repetitive obstructive apneas. Under these circumstances the effect of upper airway reflexes may be lost. Wetherefore sought to investigate the effects of oropharyngeal anesthesia in a group of otherwise asymptomatic snorers, a group recog810
SUMMARY Previous studies support the presence of an upper airway reflex mechanism that eontributes to the maintenance of upper airway patency during sleep. We Investigated the possibility that Interference with this reflex mechanism contributes to the development of obstructive sleep apnea. Eight otherwise asymptomatic snorers (seven male and one female), age 39 ± 5.3 yr (mean ± SEM), underwent overnight sleep studies on three successive nights. An acclimatization night was followed by two study nights randomly assigned to control (C) and oropharyngeal anesthesia (OPA).On the OPAnight topical anesthesia was Induced using 10% lidocaine spray and 0.25% buplvocaine gargle. A saline placebo was used on night C. All subjects slept well on both study nights (mean sleep duration was 6.2 h on both study nights), and sleep stage distribution was similar on both nights. Obstructive apneas and hypopneas (OAH) rose from 114 ± 43 during C to 170 ± 49 during OPA (p < 0.02). Central apneas and hypopneas (CAH)were unchanged between the two nights (8 ± 4.9 versus 7 ± 3). The duration of OAH was similar on both study nights (20 ± 1.9 s during C versus 20 ± 1.5 s during OPA). The frequency of movement arousals terminating OAH tended to be higher during OPA(7 ± 2.9/h) than during C (3 ± 0.7); P NS. The frequency of oxyhemoglobin desaturatlons was also higher during OPA (5 ± 2.1/h) than during C (3 ± 1.4), P < 0.07.These data Indicate that OPA Increases the frequency of OAH during sleep but not their duration, suggesting that defective upper airway reflexes may Influence the Initiation of obstructive respiratory events but not their termination. Weconclude that upper airway reflexes are Important In the pathophyslol. ogy of OSA. AM REV R~PlR DIS 1991; 143:810-813
=
nized to be intermediate between normal and clinically significant OSA (12). Methods Eight otherwise asymptomatic loud snorers (seven male and one female) aged 39 ± 5 yr (mean ± standard error of the mean, SEM) were studied. None had any symptoms of respiratory disease, and none was on any medication. All had normal spirometry and blood pressure. None spontaneously complained of significant daytime sleepiness, although one patient admitted to mild daytime sleepiness on direct questioning. Subjects were studied on three successivenights in a respiratory sleep laboratory using standard polysomnographic techniques (13),which consist of continuous recordings of electroencephalogram (EEG), eye movements, and submental electromyogram (EM G), all from surface electrodes. Respiration was recorded continuously and noninvasively using a respiratory inductance plethysmograph (Respitraces; Ambulatory Monitoring, Inc., Ardsley, NY), which was calibrated using the isovolume technique (14). When calibrated against a spirometer this device has been shown by many investigators to provide a relatively accurate means of noninvasively quantifying respiration (15, 16) and thus is well suited to studying respiration
during sleep. The Respitrace can also distinguish obstructive from central apneas by showing the presence or absence of equal and opposite rib cage and abdominal movement, respectively, where the net tidal volume is zero, indicating apnea (17). In the present report apnea is defined as an absence of movement in the sum channel of the Respitrace lasting at least 10 sand hypopnea as a period of 10 s or more when the tidal volume abruptly falls to less than 50070 ofthe average tidal volume for the preceding 30 s. Hypopneas were usually terminated by an arousal pattern on the EEG. The variables were recorded continuously on a polygraph recorder (Model 78D; Grass Instruments, Quincy, MA), and oxygen saturation was also recorded continuously using an ear oximeter (Biox'" IIa; Biox
(Received inoriginalform July 2, 1990andin revised form October 15, 1990) 1 From the Departments of Respiratory Medicine and Physiology and the Respiratory Sleep Laboratory, University College and St. Vincent's Hospital, Dublin, Ireland. 2 Correspondence and requests for reprints should be addressed to Dr. Walter McNicholas, Department of Respiratory Medicine, St. Vincent's Hospital, Elm Park, Dublin 4, Ireland.
811
OBSTRUCTIVE SLEEP APNEA AFTER TOPICAL OROPHARYNGEAL ANESTHESIA IN LOUD SNORERS
Inc., Boulder. CO). Significant oxygen desaturation was taken as greater than 4010 (18). Wealso considered making additional more direct measurements of the presence or absence of respiratory effort during apnea. such as recordings of esophageal pressure or diaphragmatic EMG. Werejected both these additional recordings. however. since both would have required a catheter to be passed through the upper airway. which may have altered the frequency of abnormal respiratory events during sleep. The first of the three study nights was an acclimatization night during which the various monitoring devices were attached but no recordings made. This night was intended to minimize the first night effect (19). The second and third nights were randomly designated control (C) or oropharyngeal anesthesia (OPA). Subjects wereinstructed to abstain from alcohol for 24 h before each study. On the OPA night the oropharynx was sprayed repeatedly with a 4% lidocaine solution until the gag reflex was abolished (maximum total dose required was 180mg in any patient). Subjects were instructed to spit out any saliva formed during this procedure to minimize systemic absorption of anesthetic. Each subject then gargled 10 ml of a 0.25070 solution of bupivocaine for 1 min. This solution was then spit out and none swallowed. The additional use of bupivocaine was because of its longer duration of action than lidocaine [4 to 6 h as opposed to 1.5to 2 h (20)]. The oropharynx was again sprayed with lidocaine after 4 h of sleep. Additional bupivocaine was not administered at this stage because we believed that sustained gargling for 1 min would be technically difficult in a recently wakened subject. On the control night each subject had the oropharynx sprayed with saline before sleep. and again after 4 h. to mimic the anesthesia night as closely as possible. All polygraph and oximetry records were coded such that the reader was unaware of which type of study (C or OPA) was being analyzed. and all studies were analyzed by the same person. Statistical analysis was by paired t testing.
TABLE 1 SLEEP STAGE DISTRIBUTION (MIN) DURING STUDY NIGHTS*
Awake Stage 1 Stage 2 SWS REM Total sleep Sleep latency Sleep efficiency, %
Control
OPA
23 ± 5 22 ± 8.9 229 ± 18 44 ± 9.4 82 ± 9.6 377 ± 12 8 ± 1.7 94 ± 1
47 ± 16 25 ± 6.6 231 ± 17 47 ± 9.3 70 ± 12.2
Definition of abbreviations: OPA = oropharyngeal anestheslow-wave sleep; REM rapid-eye-movement sia; SWS sleep; sleep efficiency = time asleep as a percentage of time in bed. * Data are given as mean ± SEM.
=
=
differences in OAR between nights was during stages 1 and 2 sleep. All subjects showed an increase in numbers of OAR during OPA (figure 2). Furthermore, several subjects had sufficient OAR on the control night (C) to qualify for a diagnosis of obstructive sleep apnea syndrome as conventionally defined. There was no significant difference in the frequency of OAR between the early and late parts of the night during OPA. This lack of difference may in part be because
70 Fig. 1. Frequency of obstructive apneas and hypopneas during different sleep stages on both control and anesthesia nights. Data are presented as mean ± SEM. Definitionof abbreviations: OAH = obstructive apneas and hypopneas; OPA = oropharyngeal anesthesia; n.s. = not significant; SWS = slow-wave sleep; REM = rapid-eye-movement sleep. Closed bars = control; hatched bars = OPA.
Discussion
The main finding of this study is that obstructive respiratory events during sleep
OAH per hour
p=n.s.
60
50 40 30 20 10
Stage 1/2
Results
Sleep stage distribution for the eight subjects is given in table 1. All subjects slept wellon both study nights, achieving both rapid-eye-movement (REM) and slowwave sleep. There was no significant difference in the distribution of sleep stages between the two nights, and sleep efficiency (time asleep as a proportion of total study time) was also similar. Data on obstructive respiratory events are given in figures 1 and 2. Obstructive apneas and hypopneas (OAH) were significantly more frequent during OPA and were most frequent during REM sleep (figure 1). However, the most significant
373 ± 15 17 ± 4.8 89 ± 3.7
REM sleep tended to predominate in the latter part of each study. The numbers of central apneas and hypopneas were small and did not differ between the two study nights (1.4 ± 0.8/h during C compared to 1.2 ± O.4/h during OPA, mean ± SEM). The frequency of movement arousals (defined as a period of gross artifact on all polysomnographic channels) terminating abnormal respiratory events was proportional to the frequency of OAH and showed a trend to be greater during the OPA night (figure 3). Approximately 15070 of OAH wereassociated with falls in Sao, of 4070 or more (figure 4). The frequency of desaturations was significantly greater during stages 1 and 2 sleep on the OPA night compared to C and was of borderline significance overall. The duration of abnormal respiratory events was similar on both nights. CAH lasted 13 ± 2.4 s during C versus 12 ± 2.4 during OPA. OAR lasted 20 ± 1.9 s during C verus 20 ± 1.5 during OPA.
500
SWS
REM
Overall
Total Number of OAH
400
Fig. 2. Total number of obstructive apneas and hypopneas (OAH) in each of the eight subjects on both control and anesthesia (OPA) nights.
300
200
100
ol-----~==-----------
Control
OPA
CHADWICK, CROWLEY, FITZGERALD, O'REGAN, AND McNICHOLAS
812 Arousals per hour
12 1
Fig. 3. Frequency of movement arousals terminating abnormal respiratory events during different sleep stages on both control and anesthesia nights. Data are presented as mean ± SEM. Definition of abbreviations: OPA :: oropharyngeal anesthesia; SWS = slow-wave sleep; REM :: rapid-eye-movement sleep. None of the differences achieved statistical significance. Closed bars :: control; hatched bars = OPA.
10
8
6
4
2 0'---Stage 1/2
SWS
REM
Overall
20 Desaturations per hour p=n.s.
Fig. 4. Frequency of desaturations greater than 4% during different sleep stages on both control and anesthesia nights. Data are presented as mean ± SEM. Definition of abbreviations: OPA :: oropharyngeal anesthesia; n.s. :: not significant, SWS :: slow-wave sleep; REM :: rapid-eye-movement sleep. Closed bars » control; hatched bars :: OPA.
15
10
5
0'---Stage 1/2
sws
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in loud snorers occur more frequently after topical oropharyngeal anesthesia. These findings complement our previous study in normal subjects (11) and support the hypothesis that interference with upper airway reflex mechanisms compromises upper airway patency during sleep and thus contributes to the development of obstructive sleep apnea (OSA). The present findings also complement previous animal studies that have reported upper airway obstruction after upper airway anesthesia under certain experimental conditions, sometimes to the point of death of the animal (10). The precise nature of this postulated reflex mechanism cannot be identified from the present study, but previous animal studies favor a pressure-sensitive reflex mechanism as most likely (7-9). Support for a similar reflex mechanism in humans is the finding that pharyngeal airflow resistance increases during sleep following topical upper airway anesthesia (21). The presence of such a reflex mechanism based in the upper airway would fit well with current concepts of the pathogenesis of upper airway occlusion during sleep in patients with OSA in that an imbalance between intrapharyngeal pressure and the contraction of upper airway dilating muscles ap-
Overall
pears to be of critical importance to the development of obstructive apnea in such patients (1). Thus in light of this evidence it seems not unreasonable to suggest that a defect in such a pressure-sensitive reflex mechanism could contribute to the development of OSA. Support for the presence of such a defect is the finding of impaired detection of added inspiratory resistance in patients with OSA (5). It could be postulated that a subtle upper airway neuromuscular reflex that played a role in the maintenance of upper airway patency in normal subjects might not be detectable in patients with OSA for at least two reasons. First, a defect in such a reflex mechanism may play a primary role in the pathogenesis of OSA by contributing to the development of upper airway occlusion during sleep. Second, the mechanical vibration of the upper airway associated with loud snoring may blunt the afferent receptor for the reflex, which is presumed to lie in the oropharyngeal wall. Our data do not support the second possibility, since our subjects with loud snoring would also be expected to have a mechanical vibration in the upper airway similar to that in patients with OSA. The present findings also provide some evidence against the first possibility in that most subjects
showed a substantial increase in OAH after OPA that would not be expected if the upper airway reflexes were defective. Our results also show that OPA affects the frequency of obstructive events but not their duration. These findings suggest that OPA influences the initiation of obstructive events but not their termination. Thus other mechanisms that do not involve upper airway reflexes, such as hypoxemia and hypercapnia, are likely to be more important in the termination of apnea. In our study only a minority of obstructive events were associated with a desaturation of greater than 4070. This finding likely reflects the fact that all subjects had awake Sa02greater than 95% and were thus on the flat upper part of the oxyhemoglobin dissociation curve. They would therefore have required a substantial fall in arterial P0 2, of the order of 25 to 30 mm Hg, to produce a 4070 fall in Sa0 2. Thus a significant degree of hypoxemia may have contributed to the termination of obstructive events during sleep without being reflected in a large change in Sa02. Loud snorers are regarded as an intermediate stage between normality and clinical OSA (12). Our data support this contention in that there was a relatively high frequency of OAH during the control night, much higher than has been previously documented in normal control subjects (11, 18). In fact, several of our subjects had apnea and hypopnea frequencies that fell within the range of OSA as conventionally defined (22). Potential confounding effects of the topical anesthetic, for example by systemic absorption or local direct effects on the patency of the oropharyngeal lumen, can be discounted for the following reasons. The total dose of topical anesthetic used was quite small, and wetook considerable precautions during administration to prevent the systemic absorption of anesthetic by asking each subject to spit out saliva formed during administration. Furthermore, local anesthetics, when absorbed in significant amounts, tend to produce stimulation rather than depression of the central nervous system (20). In a previous study (11) we found that such effects are only seen when twice or three times the amount of anesthetic as used in the present study were administered using the techniques described previously. There are no data on any direct effect of topical anesthetic on oropharyngeal patency. However, a recent study by Cole and Haight (23) showed that intranasal lidocaine has no effect on
OBSTRUCTIVE SLEEP APNEA AFTER TOPICAL OROPHARYNGEAL ANESTHESIA IN LOUD SNORERS
nasal airway resistance, which suggests that the anesthetic has no direct effect on upper airway patency. Further studies are required to establish the presence or absence of protective upper airway reflexesin patients with established OSA. Should such reflexesbe present in established OSA, this may have implications for the role of uvulopalatopharyngoplasty in the management of the condition, since it could be argued that the surgical techniques involved in this procedure may in some patients interfere with the afferent limb of upper airway-based protective reflexes, as described previously. Such effects may at least partly outweigh the beneficial effects of UPPP related to enlargement of the upper airway lumen. Our data do not offer specific evidence in this regard, however. References 1. RemmersJE, deGroot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 1978; 44:931-8. 2. Orr WC, Martin RJ. Obstructive sleep apnea associated with tonsillar hypertrophy in adults. Arch Intern Med 1981; 141:990-2. 3. McNicholas WT, 'Iarlo S, Cole P, et al. Obstructive apneas during sleep in patients with seasonal allergicrhinitis. Am RevRespirDis 1982; 126:625-8. 4. Onal E, Lopata M, O'Connor T. Pathogenesis of apneas in hypersomnia-sleep apnea syndrome.
Am Rev Respir Dis 1982; 125:167-74. 5. McNicholas WT, BowesG, Zamel N, Phillipson EA. Impaired detection of added inspiratory resistance in patients with obstructive sleep apnea. Am Rev Respir Dis 1984; 129:45-8. 6. Mathew OP, Remmers JE. Respiratory function of the upper airway. In: Saunders NA, Sullivan CE, eds. Sleep and breathing: lung biology in health and disease. Vol. 21. New York: Marcel Dekker, 1984; 163-200. 7. Mathew OP, Abu-Osba YK, Thach BT. Influence of upper airway pressure changes on genioglossus muscle respiratory activity. J Appl Physiol 1982; 52:438-44. 8. Mathew OP, Abu-Osba YK, Thach BT.Genioglossus muscle responses to upper airway pressure changes: afferent pathways. J Appl Physioll982; 52:445-50. 9. Hwang JC, St John WM, Bartlett D. Afferent pathways for hypoglossal and phenic responses to changes in upper airway pressure. Respir Physiol 1983; 49:341-55. 10. Abu-Osba YK, Mathew OP, Thach BT. An animal model for sensory deprivation producing obstructive apnea with postmortem findings of sudden infant death syndrome. Pediatrics 1981; 68: 796-801. 11. McNicholas WT, Coffey M, McDonnell T, O'Regan R, Fitzgerald MX. Upper airway obstruction during sleep in normal subjects after selective topical oropharyngeal anesthesia. Am Rev Respir Dis 1987; 135:1316-9. 12. Issa FG, Sullivan CEo Upper airway closing pressure in snorers. J Appl Physiol1984; 57:528-35. 13. Rechtschaffen A, Kales A. A manual of standardised terminology, techniques and scoring system for sleep stages in human subjects. Washington, DC: National Institutes of Health, 1968;publication 204. 14. Konno K, Mead J. Measurement of the sepa-
813 rate volume changes of ribcage and abdomen during breathing. J Appl Physiol 1967; 22:407-22. 15. Zimmerman PV, Connellan SJ, Middleton HC, Tabona MV, Goldman MD, Pride N. Postural changes in ribcage and abdominal volumemotion coefficients and their effect on the calibration of a respiratory inductance plethysmography. Am Rev Respir Dis 1983; 127:209-14. 16. Hudgel DW, Capehart M, Johnson B, Hill P, Robertson D. Accuracy of tidal volume, lung volume and flow measurements by inductance vest in COPD patients. J Appl Physiol1984; 56:1659-65. 17. Cohn MA, Watson H, Weisshaut R, Stott F, Sackner MA. A transducer for noninvasive monitoring of respiration. In: Stott FD, Raftery EB, Sleight P, Goulding L, eds, ISAM 1977:proceedings of the second international symposium on ambulatory monitoring. London: Academic Press, 1978; 119-28. 18. Block AJ, Boysen PG, Wynne JW, Hunt LA. Sleep apnea, hypopnea and oxygen desaturation in normal subjects. N Engl J Med 1979;300:513-7. 19. Agnew HW, WebbWB, WilliamsRL. The first night effect: an EEG study of sleep. Psychophysiology 1966; 2:263-6. 20. Ritchie JM, Cohen PJ. Local anesthetics. In: Goodman LS, Gilman A, eds. The Pharmacological basis of therapeutics. 5th ed. New York: MacMillan, 1975; 379-403. 21. DeWeese EL, Sullivan TY. Effects of upper airway anesthesia on pharyngeal patency during sleep. J Appl Physiol 1988; 64:1346-53. 22. Guilleminault C, Tilkian A, Dement WC. The sleep apnea syndromes. Annu Rev Med 1976; 27:465-84. 23. Cole P, Haight JS. Nasal mucosal anaesthesia and airflow resistance. Rhinology 1985; 23: 209-12.
