Negative Polysomnogram ih Patients with Obstructive Sleep Apnea Syndrome* R. Jonathan Dean, M.D.;t aml Bashir A. Chaudhary, M.D., F.C.C.P.t

We evaluated the possibility that in some patients with obstructive sleep apnea, the initial polysomnogram may be negative. We ~ewed polysomnograms performed at the Medical College of Georgia from 1984 to 1990 and bmd nine patients whose initial polysomnogram was negative but whose repeat polysomnogram con6rmed obstructive sleep apnea. All nine patients (&ve women and. four men; average age, 44.2 years) had an apnea index of less than 5 (fewer than &ve apneic episodes per hour) and had a total of fewer than 20 apneic episodes during the initial overnight polysomnogram. The change in average weight was not signi&cant. Three patients had received short-term oxygen therapy, and two of these three received nasal continuous positive airway pressure prior to the initial study. The time that patients spent supine increased from 101 min in the

Q vernight polysomnography is a sensitive diagnos-

tic tool for evaluating sleep-related disorders. 1 Generally, a single satisfactory overnight polysomnogram is considered acceptable. indeed, the American Thoracic Society Consensus Conference on Cardiopulmonary Sleep Studies in 1988 concluded that "a single overnight polysomnogram is sufficient to exclude clinically .important sleep apnea:'2 We reviewed all polysomnograms performed at the Medical College of Georgia during a six-year period to investigate the possibility that a subset of patients with severe obstructive sleep apnea might have an initial satisfactory negative overnight polysomnogram. We found nine patients with obstructive sleep apnea whose initial polysomnogram was negative and reviewed these studies. PATIENTS AND METHODS

\\\l reviewed all overnight polysomnograms performed in the sleep laboratory of the Medical College of Georgia from April 1984 to March 1990. There were 241 patients who had more than one polysomnogram. The repeat polysomnograms had been done to evaluate the efficacy of surgical or medical therapy in 187 cases and to supplement inadequate studies In 26 cases. Twenty-eight patients were studied again because of persistence of symptoms suggestive of sleep apnea. Patients with 30 or more apneic episodes and an *From the Section of Pulmonary Diseases, Department of Medicine, Medical College of Georgia, Augusta. tSenior Pulmonary Fellow. tProfessor of Medicine and Director, Sleep Disorders Center. This study was presented in part at the Annual Meeting, Southern Chapter, American College of Chest Physicians, Nashville, October 14-17, 1990. Manuscript received December 6; revision accepted April 29. Dr. Choudhary, Pulmonary Section (AF .2030), Ifevrint re~ds: Medical College of Georgia, Augusta 30912

initial study to 180 min in the second, but this was not significant (p = 0.12). Comparison of the initial and diagnostic polysomnograms showed significantly reduced total sleep time (from 3.75± 1.84 h to 5.32± l.ll h; p=0.04) and reduced rapid eye movement (REM) sleep time (from 0.27 ± 0.27 h to O. 75 ± 0.58 h; p = 0.037) in the initial study. We conclude that in a small subset of patients with obstructive sleep apnea, the initial polysomnogram may be falseiy negative, which could be due to previous therapy, a reduction in total sleep time and REM sleep, or other unidenti&ed factors. (Chest 199!; 101:105-08)


CPAP =continuous positive airway pressure; REM= rapid eye movement.


apnea index (number of apneic episodes per hour) of 5 or more were considered to have sleep apnea syndrome. •.3 Actual recording time ranged from 4.25 to 8 h (average, 6.65 h) and from 7 to 8 h (average, 7.9 h) during the initial and second polysomnograms, respectively. Electrocardiographic, electroencephalographic, electrooculographic, and electromyographic recordings were monitored during all tests, as were chest wall and abdominal movements (Respitnice Corp, Ardsley, NY) and oxygen saturation and oronasal airflow (thermistors). An apneic episode was defined as cessation of air.flow for at lelst 10 s. A hypopneic episode was defined as reduction in airflow associated with at least 4 percent reduction in oxygen saturation. All studies were performed by the same methods and were reviewed by the same physician. Of the 241 i>atients with multiple polysomnograms, nine had an initial negative polysomnogram followed by a positive i>olysoinnogram. Each of the nine patients had an apnea index of less than 5 and fewer than 20 total apneic episOdes during the initial study. We reviewed all patient data concerning weight, age, body position, sleep stages, total sleep time, sleep efficiency, total apneic episodes, apnea index, total hypopneic episodes, hypopnea index, and previous oxygen or continuous positive airway pressure (CPAP) therapy related to the initial and diagnostic polysomnogram. RESULTS

An initial negative study followed by a diagnostic

study was found in 9 of 28 patients who had been studied again because of a strong clinical impression of sleep apnea. The comparison of the polysomnographic data from the first and the second .studies is shown in Tuble 1. The second polysomnogratil showed mild obstructive sleep apnea in two patients and severe obstructive sleep apnea (apnea index, >20) in seven. The average time between the first and second studies was 18. 7 months (range, 3 to 50 months). There were four men and five women in the sb.idy group. The average patient age at the time of the first CHEST I 101 I 1 I JANUARY, 1992


Table 1-Compariaon of Polyaomnographic Data from the First and Second Studiea*

Patient l 2 3 4 5 6 7 8 9 Mean

Age, yr 31 44 21 41 47 60 51 62

41 44.2


Weight, kg


112.7/107.7 107. 7/106.4 169.Vl91.8 144.51122. 7 152.31177.3 85181.8 106.8/106.8 104.51106.4 157.7/150.5 125.51126.6 126.7/127.9

Interval between Tests, mo

Total Sleep 1ime, h

50 3 47 3 5 7 14 18 21 18.7

5.514.2 1.4113.9 1.3815.82 3.9316.6 6.17/6.02 4.2514.42 5.8816.88 2.7/4.43 2.615.65 3.7515.32

Total 1ime REM Sleep, h 00

00 Oil.OS 0.55/0.50 0.47/0.80 0.6311.83 0.48/0.83 0.30/0.57 0/1.16 0.27/0.75

Apnea Index

Hypopnea Index

Lowest Oxygen,%

0.3618.6 &22.6 0/8.8 3.0SIJ6 1.62156.2 4.24145.9 0/47.52 3.7/41.8 1.65138.8

Q.f20.24 6.14/14.9 0/13.23 2.3111.52 6.32131

9V49 44148 82/47 40/39 38148 9.5192 79142 38175 36131 60.3152.3


0/18.02 30.4/16.25 31.15132. 74 8.48117.54

*In most columns, values are expressed as value from first study/value from second study. REM =rapid eye movement.

study was 44.2 years (range, 21 to 62 years). The overall change in average weight (from 126.7 to 127.9 kg) was not significant; however, two patients gained more than 4.5 kg between tests. One of these two patients had mild obstructive sleep apnea, and one had severe obstructive sleep apnea. .lmJious 1herapy Three of the nine patients (patients 4, 5, and 7) had received previous oxygen therapy. In addition, two of these three (patients 4 and 5) had received CPAP therapy prior to their initial study. These three patients had been acutely ill withiri one week prior to the initial polysomnogram; in fact, two patients (patients 4, and 5) had been mechanically ventilated because of respiratory failure. One patient with a previous diagnosis of hypothyroidism was euthyroid on a regimen of replacement levothyroxine at the time of both studies (patient 7). Two patients were receiving alprazolam at the time of both the first and the second studies (patients 1 and 5). Three patients were receiving theophylline during both the first and the second studies (patients 1, 5, and 7). Five patients (patients 2, 4, 5, 7, and 8) were receiving diuretic therapy during both studies. One patient (patient 9) was taking furosemide during the second study. One patient (patient 9) was taking protriptyline during both studies. Seven patients did not drink alcohol and the two remaining patients denied taking alcohol before either study. No patient was taking progesterone during either study. Table 2-Apnea lbluea during First and Second Polyaomnograma*

First study Second study Probability value

Total Apneic Episodes

Apnea Index

Apnea-Sleep Ratio

6.33±6.48 214.22 ± 143.84 0.000515

1.65±1.71 38.8±23.4 0.00021

0.86±0.76 21.83± 13.l 0.00019

*Values are expressed as mean± SD for the nine patients.


Apnea Inder and Total Apneic Episodes

The mean values for apneic episodes, apnea index, and total apneic sleep time (percentage) are presented in Table 2. The mean number of apneic episodes and the mean apnea index were 6.33 and 1.65, respectively, on the first polysomnogram and 214.22 and 38.8, respectively, on the second polysomnogram. Hypopnea Index and Total Hypopneic Episodes

The mean number of hypopneic episodes and the mean hypopnea index were 24.2 and 8.48, respectively, on the first polysomnogram and 59.8 and 17.54, respectively, on the second polysomnogram (Table 1). Only two patients had more than 15 apneic and hypopneic episodes per hour of sleep. Sleep and Sleep Stages

Tables 3 and 4 show mean and percentage of sleep time in the various sleep stages for the nine patients. Mean total sleep time during the first study was 3. 75 ± 1.84 h and increased significantly during the second study to 5.32± 1.11 h. Sleep efficiency also increased from 55.2 percent to 68.0 percent, but this was not statistically significant. lime spent in each sleep stage increased during the second study, but only the increase in REM sleep (from 0.27 ± 0.27 h to 0.75±0.58 h) was significant. Five of the six patients who demonstrated severe obstructive sleep apnea on the second polysomnogram showed an increase in REM sleep; one patient with severe obstructive sleep apnea showed a slight decrease (from 0.55 h to 0.5 h). Two patients with obstructive sleep apnea did not enter REM sleep in either study. Supine vs Lateral Decubitus

In the first study, the patients slept in the supine position an average of 96. 7 min (36 percent of total sleep time) and in the lateral decubitus position an average of 171.1 min (64 percent of total sleep time). During the sleep study, the patients slept an average Negative Polysomnogram in OSAS (Deen, Chaudhary}

Table 3-Tune in \brious Sleep Stagea During the First and Second Polysonanograma• Sleep Tune, h

First study Second study Probability value


Stage I

Stage II

3.75::!:1.84 5.32±1.11 0.04

0.90±0.65 1.03±0.59 NS

1.23±0.99 1.80±0.68 NS


. 'Stage III

0.54±0.62 0.78±0.29 NS

Stage IV

REM Sleep

0.80±1.08 0.97±1.52 NS

0.27±0.27 0.75±0.58 0.037

*Values are expressed as mean± SD for the nine patients. NS= not significant.

of 180 min (56 percent of total sleep time) in the supine position and an average of 139.8 min (44 percent of total sleep time) in the lateral decubitus position. Although sleep time in the supine position increased during the second polysomnogram, this difference was not significant (p = 0.12). Four of nine patients spent more total sleep time in the supine position during the first study. DISCUSSION

The frequency of patients with obstructive sleep apnea who initially have a negative polysomnogram cannot be determined from this retrospective review since only a small number of the total patients with an initial negative polysomnogram were studied again. Our findings indicate that false-negative overnight polysomnograms do indeed occur and are associated with a reduction in REM sleep and total sleep time. A reduction in total REM sleep was a major finding in all but one of the initial studies in patients with severe obstructive sleep apnea. This could be the major factor accounting for an initial negative study. Two patients with mild obstructive sleep apnea failed to enter REM sleep in either test. The initial test on all nine patients showed a reduction in total time spent in all stages of non-REM sleep, the percentage of REM sleep, and sleep efficiency, although these changes were not statistically significant. Some of the factors contributing to a false-negative polysomnogram include previous therapy (ie, oxygen, nasal CPAP, mechanical ventilation), weight, the severity of the illness, the effect of sleep posture, and the quantity and quality of sleep. The initial polysomnograms were considered satisfactory considering the average recording time of 6.615 h (minimum, 4.25 h). All of the patients with severe obstructive sleep apnea slept a minimum of 2.6 h during the initial negative polysomnogram. It is possible that some patients with a long interval

between studies simply had an initial true-negative polysomnogram, and that obstructive sleep apnea developed prior to the second study. However, this seems rather unlikely since all of these patients initially presented with symptoms strongly suggestive of obstructive sleep apnea. Every patient had a history of snoring, disturbed sleep, and evidence of marked daytime somnolence. The sleep studies were repeated because of continuation of the same symptoms. The effect of previous oxygen therapy has been shown to cause an unpredictable response in the number ofapneic episodes in patients with obstructive sleep apnea. 4 Oxygen therapy has been shown to reduce the rate of disordered breathing episodes and to improve the sleep structure, with an increase in total sleep time and a decrease in number of awakenings. 5 Previous use of nasal CPAP may decrease the number of apneic episodes for a prolonged period following discontinuation. 8 Wittig et al, 7 comparing night-to-night tests, found that patients with infrequent apneic episodes had a highly variable number of such episodes. The same study also showed that patients with frequent apneic episodes (> 100 per night) had a consistent number of such episodes during two overnight studies. Our findings are to the contrary, with a significant difference in total apneic episodes in a subset of patients with severe obstructive sleep apnea. Two patients had severe obstructive sleep apnea on the second polysomnogram with the initial polysomnograms showing many hypopneas. These two patients can be classified as having sleep hypopnea syndrome, which has been defined by the presence of more than 15 apneic episodes plus hypopneic episodes per hour of sleep.8 Syndromes of sleep anpea and sleep hypopnea are probably interrelated, but as yet no uniformity of opinion exists as to whether these two should be combined.a

Sleep time, 'Ai Stage I First study Second study Probability value

Stage II

32.3±33.4 33.7±24.9 20.1±12.2 35.1±12.4 NS NS

Stage III

Stage IV


11.6±10.4 15.01±5.8 NS

15.7±16.9 16.0±21.4 NS

6.17±6.29 14.01±12.5 NS

*Values are expressed as mean::!: SD for the nine patients. NS= not significant. CHEST I 101 / 1 I JANUARY, 1892


An increase in weight is associated with an increase in apneic episodes; however, the weight increases between the two studies were not significant. Additionally, patients with mild to moderate obstructive sleep apnea and an enlarged uvula have been shown to have a dramatic decrease in apneic episodes when sleeping in the lateral position. 9 Weight and postural changes in supine sleep were not significantly different in the nine patients included in our study; therefore, other variables must have been responsible for the initial negative study. The severity of illness may have resulted in a disturbance of sleep patterns, leading to a reduction in total sleep time and REM sleep time. In addition, the three most acutely ill patients were being treated with oxygen and/or nasal CPAP prior to the initial study. Because of the complicity of these interrelated and uncontrolled variables, it is impossible to identify one of them as the primary reason for the initially negative polysomnogram. Previous studies have shown an increase in apneic episodes during REM sleep. 10 This is postulated to be related to a decrease in skeletal muscle tone. Five of the six patients with severe obstructive sleep apnea had increased REM sleep in the second study. The remaining patient showed little change in the amount of REM sleep (from 0.55 to 0.5 h), but there was a significant increase in total sleep time (from 3.93 to 6.6 h) in the second study This suggests that decreases in total sleep time and particularly in REM sleep time may have contributed to the initial false-negative polysomnogram in all of these patients. Although the nine patients included in this study


represent only a small fraction of the patients with positive polysomnograms evaluated in our sleep laboratory, seven of these patients had severe obstructive sleep apnea. We conclude that any patient with prolonged signs or symptoms strongly suggestive of obstructive sleep apnea and a negative overnight polysomnogram should undergo a repeat study. ACICNOWLEDCMENTS: \\e are thanlcful to W. A. Speir, M.D., for critical review of the manuscript; to Bushra Akhtar for technical assistance; and to Kay McCoy for Secretarial assistance. REFERENCES

1 Guilleminault D, Tilkian A, Dement WC. The sleep apnea syndromes. Ann Rev Med 1976; 27:465-84 2 Indications and standards for cardiopulmonary sleep studies. Am Bev Hespir Dis 1989; 139:559-68 3 Berry DTR, \\ebb WB, Block AJ. Sleep apnea syndrome: a critical review of the apnea index as a diagnostic criterion. Chest

1986; 86:529-31 4 Rud.gel W, Hendricks C, Dadley A. Alterations In obstructive apnea patterns induced by changes In oxygen and carbon dioDde inspired concentrations. Am Bev Respir Dis 1988; 138:16-9 5 Smith PL, Haponick EF, Bleecker ER. The elFects of oxygen in patients with sleep apnea. Am Bev Respir Dis 1984; 130:958-63 6 Sullivan CE, Berton-Jones M, Issa FG. Remission of severe obesity-hypoventilation syndrome after short-term treatment during sleep with nasal continuous positive airway pressure. Am Bev Hespir Dis 1983; 19.8:177-81 7 Wittig RM, &maker A, Zorick FJ, Roehrs TA, Conway WA, Roth T. Night to night consistency of apneas during sleep. Am Bev Hespir Dis 1984; 129-.244-46 8 Gould GA, Whyte KF, Rhind GB, Airlie MA, Catterall JR, Shapiro CM, et al. The sleep hypopnea syndrome. Am Bev Hespir Dis 1988; 137:895-98 9 Chaudhary BA, Chaudhary TIC, Kolbeck RC, Harmon JD, Speir WA. Therapeutic effect of posture In sleep apnea. Sooth Med J

1986; 79:1061-063

10 Baker TL. Med Clin North Am 1985; 69:1123-52

Negative polysomnogram in patients with obstructive sleep apnea syndrome.

We evaluated the possibility that in some patients with obstructive sleep apnea, the initial polysomnogram may be negative. We reviewed polysomnograms...
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