CPAP Titration for Sleep Apnea Using a Split-Night Protocol

CPAP Titration for Sleep Apnea Using a Split-Night Protocol* Yoshihiro Yamashiro, MD, and Meir H. Kryger, MD, FCCP We studied 107 patients with sleep-disordered breathing to confirm the effectiveness of continuous positive airway pressure (CPAP) titration using a split-night protocol. Patients spent two consecutive nights in our laboratory with complete polysomnography. On the first night, we applied a split-night protocol; the first half of the night was used as a baseline (B), and after a diagnosis was made, CPAP was applied during the second half of the night (SN). On the second night (2N), patients spent the entire night on CPAP to confirm the effectiveness of CPAP treatment. The SN and 2N both revealed a significant reduction in arousal index (37 .8 ± 27.9 on B, 13.2 ± 12.1 on SN, 11.4± 8.0on 2N, values are mean± SD, p<0.001), apnea hypopnea index (AHI) (23.6 ± 26.3/h on B, 3.0 ± 3.7/ h on SN, 2.4 ± 2.6/h on 2N, p<0.001), percent total sleep time below 90% Sa02 (21.0±27.2% on B, 8.2 ± 13.8% on SN, 4.9 ± 10.2% on 2N, p<0.001), and percent total sleep time below 80% Sa02 (1.1 ± 3.8% on B, 0.0±0.1 % on SN, 0.1 ±0.5% on 2N, p<0.001). There were no significant differences between the SN and the

2N for these measurements. Final CPAP pressure was significantly lower at the end of the SN when compared with the 2N (8.8±2.7 em HzO on SN, vs 10.3±2.8 em H 20 on 2N, p<0.001). When patients were divided into three groups (AHI<20, n=69; 2040, n=20), the final CPAP pressure was different only in the group with AHI <20 (8.1 ± 2.3 em H 20 on SN, 9.6±2.3 em H 20 on 2N, p<0.001). We conclude that a split-night protocol may be sufficient to determine the effective CPAP pressure, especially in patients with an (Chest 1995; 107:62-66) AHI>20.

most laboratories, patients with sleep apnea are I nevaluated for an entire diagnostic night followed

evaluated in our clinical laboratory. The patients were 90 men and 17 women (aged 52.3±12.1 [mean±SD] years; body mass index, 34.4±8.2 kg/ m2). All of them were referred to our laboratory because of excessive daytime sleepiness or snoring. Patients were not screened and had not had polysomnography prior to being in this study, and were newly diagnosed as having OSA or UARS. Twenty-three patients who had periodic limb movements in sleep in addition to sleep-disordered breathing were included in the study. None of the patients had other diseases that affect sleep-disordered breathing or sleep quality. All of the patients spen t two consecutive nights in our laboratory. On the first night, patients underwent a split-night protocol. Patients were in bed for 7 to 8 h and were instrumented for complete polysomnography. All of the patients had been instructed that CP AP might be applied during the night, and had seen a short film explaining CP AP. No other instruction or training for adaptation to CP AP was done. On the split night, after 3 to 4 hof baseline sleep for diagnostic purposes, we applied CP AP to the patients for the remainder of the night. The assessment was made by technicians during the study based on breathing abnormalities (apnea and hypopnea), oxygen desaturation, and disordered breathing-related arousals. Diagnosis was confirmed by physicians analyzing the entire polysomnographic record on the following day. Patients with severe apnea confirmed by repetitive oxygen desaturations below 80% or with cardiac arrhythmias had CPAP applied earlier. In some patients, apnea may not have been confirmed until later in the night, and accordingly, CPAP was applied later. The CPAP pressure was started at 3 em H20 and was increased gradually by l or 2 em H20 until apneas, hypopneas, and disordered breathing-related arousals were abolished. On the second night, patients were studied on CP AP for the entire night to confirm the effectiveness of treatment. Again, CP AP pressure was started at 3 em H20 and the pressure increased more rapidly than during the split night. When the final pressure of the

by a continuous positive airway pressure (CPAP) titration night. A single, split-night study for diagnosis and treatment has been reported to be adequate in 78% of patients.l If confirmed, this type of protocol would be convenient and may be cost-effective. However, this report used data from a single night and selected patients with an apnea hypopnea index (AHI) >20. A recent study by Sanders et al, 2 comparing the results of split-night CPAP and secondnight CPAP, also concluded that determining adequate CPAP pressure can be determined in a single night for most patients with obstructive sleep apnea (OSA) .2 The 50 patients evaluated by Sanders et al 2 had severe OSA (AHI; 76.7 ±30.6). Therefore we studied 107 consecutive patients with sleep-disordered breathing (OSA and upper airway resistance syndrome[UARS]3 ) using a split-night protocol on the first night, and compared the results with a second night with CPAP. MATERIALS AND METHODS

Subjects We selected 107 patients who had sleep-disordered breathing *From the Department of Respiratory Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. Manuscript received January 28, 1994; revision accepted June 2. Reprint requests: Dr. Kryger, Sleep Disorders Center, 351 Tache Avenue, Winnipeg, Manitoba R2H 2A6

62

AHI=apnea hypopnea index; Ar-I=arousal index; CPAP= continuous positive airway pressure; OSA=obstructive sleep apnea; Sa02=arterial oxygen saturation; SEI=sleep efficiency index; TRT=total recording time; TST=total sleep time; UARS=upper airway resistance syndrome

Key words: CP AP, sleep apnea syndrome, split-night protocol

CPAP Titration for Sleep Apnea Using Split-Night Protocol (Yamashiro, Kryger)

Table !-Results in 107 Patients*

TRT, min TST, min SEI,% S1, % S2,% S3+4,% SREM, % Ar-I, h AHI, h %TST below 90% SaOz %TST below 80% Sa0 2 CPAP, em HzO

l. Baseline

2. Split-Night CPAP

3. Second-Night CPAP

p Value

232.6±64.8 176.3±59.8 75.8±14.8 7.4±6.4 70.9±15.3 10.5±11.6 11.2 ±9.5 37.8±27.9 23.6±26.3 21.0±27.2 1.1±3.8

228.4±69.9 160.7±66.0 68.9±17.8 7.4±7.2 59.5±15.9 7.8±9.9 25.3± 14.4 13.2± 12.1 3.0± 3.7 8.2±13.8 0.0±0.1 8.8±2.7

467.6±30.9 366.0±59.9 78.5±10.7 5.1±2.7 62.1 ± 12.5 12.4±8.6 20.4±7.8 11.4±8.0 2.4±2.6 4.9±10.2 0.1 ±0.5 10.3±2.8

<0.001 3>1&2 <0.0013>1&2 <0.001 1 &3>2 <0.01 1&2>3 <0.001 1>2&3 <0.01 3>2 <0.001 2>3> 1 <0.001 1>2&3 <0.001 1>2&3 <0.001 1>2&3 <0.001 1>2&3 <0.001

*Values are mean±SD. SEI=sleep efficiency index; S1, %=percent of TST in stage 1; S2, %=percent of TST in stage 2; S3+4, %=percent of TST in stages 3 and 4 sleep; SREM, %=percent of TST in stage REM. split-night study was reached, effectiveness was evaluated and the CP AP pressure optimized. We recorded the electroencephalogram (C4/ A1 , 01 / A2), electro-oculogram, and mental electromyogram from surface electrodes. Arterial oxygen saturation (SaOz) was recorded continuously with a pulse oximeter (BIOX 3700, Ohmeda, Boulder, Colo) using an ear probe. Respiratory excursions of the chest wall and abdomen were monitored by using respiratory inductive plethysmography (SARA Unit, Vitalog Inc, Redwood, Calif). The electrocardiogram was recorded and heart rate was determined beat by beat using a tachometer. Airflow was detected by monitoring expired C02 at the nose and mouth through a nasal can.nula attached to a C02 analyzer (Normocap 200, Datex Medical Instruments, Tewksbury, Mass). The electromyogram of the anterior tibialis was recorded from surface electrodes on both legs. All variables were recorded at a speed of 10 mm / s onto paper using a polygraph (Grass model 78E, Grass Instruments, Quincy, Mass). All respiratory excursions, SaOz, airflow, and heart rate were sampled by a microcomputer system (IBM AT compatible).4

Statistical Analysis Sleep stages were scored manually according to standard criterias The AHI was calculated by a computer system 6 Arousals were defined as alpha activity or increased EEG frequency last-

ing for 3 to 15 s. The AHI, total recording time (TRT; minutes), total sleep time (TST; minutes), sleep efficiency index (SEI; %TST / TRT), percentage of each sleep stage, arousal index (Ar-I; number of arousals per hour of sleep), percentage of TST spent below 90% SaOz, and percentage of TST spent below 80% SaOz were determined for each condition: baseline (until CPAP was applied); split-night CPAP (after CP AP was applied); and second night CPAP. Final pressure of CPAP (em HzO) at the end of each night was also determined. We also divided the patients into three groups (AHI<20 n=69, 2040 n=20) and calculated the same parameters. One-way analysis of variance and Tukey's post hoc comparison were employed for statistical analysis. For the sleep stages we compared the percent of the night of each stage with itself for the three conditions. RESULTS

Results in the 107 patients are shown in Table l. The differences in TRT and TST simply reflect the split-night and second-night protocol. The SEI was significantly lower during the split-night CPAP period than during baseline and second-night CP AP. There were also significant differences between

Table 2-Results in 69 Patients With AH1<20*

TRT, min TST, min SEI, % S1,% S2,% S3+4, % SREM,% Ar-I, h AHI, h %TST below 90% SaOz %TST below 80% SaOz CPAP, em HzO

l. Baseline

2. Split- Night CPAP

3. Second-Night CPAP

250.1 ±60.7 185.6±59.2 74.1 ± 14.3 7.5±7.0 66.5± 14.8 12.8± 11.8 13.2±9.6 25.7±18.2 8.6±5.6 17.6±28.6 0.4±1.2

211 .2±67.6 145.7 ± 62.4 67.0± 17.6 8.4±8.3 62.0± 15.3 5.4±8.5 24.3± 15.2 13.5± 12.6 2.0±2.4 7.0±17.2 0.0±0.1 8.1 ± 2 .3

470.5±27.6 367.8±58.6 78.7±10.9 5. 1± 2.5 62.3±12.4 12.3±8.7 20.3±7.7 10.9±7.8 1.9±2.0 4.8±10.9 0.0±0.0 9.6±2.3

p Value <0.001 <0.001 <0.001 <0.01 NS <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001

3>1>2 3> 1>2 1&3>2 2>3 1&3>2 2&3> 1 1>2&3 1>2&3 1>2&3 1>2&3

*Values are mean±SD. NS =not significant. SEI=sleep efficiency index; S1, %=percent of TST in stage 1; S2, %=percent of TST in stage 2; S3+4, %=percent of TST in stages 3 and 4 sleep; SREM, %=percent of TST in stage REM. CHEST / 107 / 1 I JANUARY, 1995

63

Table 3-Results in 18 Patients With 20
TRT, min TST, min SEI,% 51,% 52,% S3+4,% SREM,% Ar-1, h AHI, h %TST below 90% Sa02 %TST below 80% Sa02 CPAP, em H20

l. Baseline

2. Split-Night CPAP

3. Second-Night CPAP

p Value

217.1 ±64.5 171.5±59.5 79.5±18.0 6.7±4.5 75.5±12.9 6.7±8.1 11.1±8.7 46.2±23.6 29.0±6.2 21.7 ±24.1 1.3±2.9

246.5±68.2 178.7±70.4 71.9 ± 19.0 5.1 ±3.4 53.7 ± 18.1 11.5± 13.4 29.7±13.2 11.5±11.9 3.0±2.8 4.8± 11.3 0.0±0.1 9.6±2.8

457.9±42.6 365.8±57.4 79.7±8.7 4.3± 1.9 61.8 ± 11.2 13.4±8.6 20.5±6.1 9.9±4.4 2.9±2.8 3.2±8.2 0.0±0.1 11.7±3.6

<0.001 3> 1&2 <0.0013>1&2 NS NS <0.001 1>2&3 NS <0.001 2>3> 1 <0.001 1>2&3 <0.001 1>2&3 <0.01 1>2&3 <0.05 1>2&3 NS

*Values are mean± SD. NS=not significant. SEI=sleep efficiency index; 51 , %=percent of TST in stage 1; 52, %=percent of TST in stage 2; 53+4, %=percent of TST in stages 3 and 4 sleep; SREM, %=percent of TST in stage REM.

baseline and the split -night CP AP, and between baseline and the second night CP AP for percent stage 2, percent stage REM , Ar-1, AHI, percent TST below 90% Sa02, and percent TST below 80% Sa02. However, there was no significant difference between the split-night CPAP and second-night CPAP for Ar-I, AHI, percent TST below 90% Sa02, and percent TST below 80% Sa02. Differences between the split-night CPAP and second-night CPAP were found only in SEI, percent S1, percent S3+4, and the final pressure of CPAP . When the patients were divided into three groups (AHI<20, 2040; Tables 2 through 4), there were significant improvements in Ar-1, AHI, and percent TST below 90% Sa02 during both CP AP conditions in all three groups. A significant rebound in REM sleep was also found in all groups. In the group with AHI <20, SEI and percent S3+4 were significantly lower during the split-night CPAP than during baseline and the second-night CPAP, and

percent S1 during the split-night CPAP was lower than during the second-night CPAP. Differences in the final CP AP pressure were only significant in the patients with AHI <20. The distribution of CP AP pressure differences in the three groups is shown in Table 5. Eight patients who were changed to bilevel positive airway pressure (ventilatory support system [BiP AP®]) were excluded from the calculation of CP AP pressure differences. Figure 1 shows a significant negative correlation between TRT at baseline and AHI in 107 patients (r=-0.41, p<0.001), confirming that patients with more severe apnea were started on a regimen of CP AP earlier in the night. When the patients were divided into two subgroups, (1) those with CPAP time in the split-night exceeding 3 h, and (2) and those with CP AP time less than 3 h, the final CP AP pressure difference (~CP AP) between the split night and second night was significantly greater in second group (~CPAP: mean=l.7 ± 1.7 em H20 [n=75] vs

Table 4-Results in 20 Patients With AHI>40*

TRT, min TST, min SEI,% 51,% S2,% 53+4,% SREM, % Ar-1, h AHI , h %TST below 90% Sa02 %TST below 80% Sa02 CPAP, em H20

l. Baseline

2. Split-Night CPAP

3. Second-Night CPAP

p Value

186.0±54.1 148.6±55.6 78.6±13.0 7.8±5.6 81.7 ± 12.7 6.2± 12.3 4.4±6.2 71.8±29.1 70.5±23.3 32.2±22.6 3.1±7.7

271.8±57.9 196.1 ±59.2 72.8±17.2 5.8±4.2 56.4±14.6 13.0± 11.9 25.1 ± 12.3 13.7±10.9 6.3±5.9 15.6±22.9 0.0±0.1 11.2±3.2

466.2±29.4 360.2±68.8 76.8±12.2 5.5±4.0 62.0± 14.4 11.8±8.3 20.7±9.7 14.6±10.4 3.7±3.6 6.8±9.8 0.3± 1.2 11.6±3.0

<0.001 3>2> 1 <0.001 3>2> 1 NS NS <0.001 1>2&3 NS <0.001 2&3> 1 <0.001 1>2&3 <0.001 1>2&3 <0.001 1>2&3 NS NS

*Values are mean± SD. NS=not significant. SEI=sleep efficiency index; 51, %=percent of TST in stage 1; 52, %=percent of TST in stage 2; 53+4, %=percent of TST in stages 3 and 4 sleep; SREM %=percent of TST in stage REM.

64

CPAP Titration for Sleep Apnea Using Split-Night Protocol (Yamashiro, Kryger)

Table 5-Distribution of CPAP Pressure Differences in Three Groups CPAP Pressure Difference, em H20 -4 to -3 -2 to 0 0 0 to 2 3 to 4 >4 Changed to ventilatory support system

AHI>40 (n=20)

AHI<20 (n=69)

20
0 7 12 27 15 3 5

0

1

5 5

2 8 6 0

2

2

3 2

2.7 ± 1.9 em H 20 [n=24], p<0.04). This suggests that if the split-night CPAP time is less than 3 h, a greater error would occur in split-night CPAP pressure. There was no significant correlation between AHI and CP AP pressure difference. DISCUSSION

Our results show that there is a significant reduction in Ar-1, AHI, percent TST below 90% Sa02, and percent TST below 80% Sa02 during both the splitnight CPAP and the second-night CPAP compared with baseline; however, there were no significant differences between the split-night CPAP and the second-night CPAP. These results suggest that a split-night protocol is as effective as a second night in reducing apnea and hypopnea, improving oxygenation, and reducing arousals. The improvements during the split-night CPAP are significant even though this time period includes the gradual increase of CPAP pressure. This initially slow CPAP increase may explain the persistence of percent TST below 90% Sa02=4.9%, and may explain part of the persistently abnormal Ar-1. The Ar-1 is also likely to be affected by periodic limb movements in sleep. We did not analyze the period after reaching final CP AP pressure on the first night because it was too short to 140

•

120 100

:f <(

80 60

••

•

r=-0.41 y=-0 .16x+62.6 p<0.001

• •• •• • ••

• •

•

40 20 100

150

200

250

Baseline TRT

300

350

400

min

FIGURE l. A significant correlation between baseline total recording time and apnea hypopnea index.

compare with the baseline values of the split-night ' study. In terms of sleep quality, SEI was lowest during the split-night CPAP segment. We believe that this is caused by the procedure to fit a nasal mask, and that patients then had to adapt to CP AP and fall asleep again . Rebound was confirmed by a rise in percent stage REM during both the split-night and secondnight CP AP conditions, and by an increase in percent stages 3+4 during the second-night CPAP. CPAP may not have been applied for long enough on the split-night to document percent stages 3+4 increase. In addition, percent stages 3+4 may have been confounded by the propensity for slow-wave sleep in the first third and REM sleep in the last third of the night. However, the large reduction in arousals may indicate an improvement in sleep quality. Final CP AP pressure was significantly higher in the second-night CPAP. This difference, however, was small, and when the patients were divided into three groups, significant differences were found only in the group with AHI <20. This difference may be due to the relatively small number of patients in the groups with 2040. However, the distribution of final CP AP pressure shows that final CP AP pressure on the second night was higher than on the split-night in 70% of the group with AHI<20 (Table 5). There was a significant correlation between TRT and AHI during the baseline study. This indicates that if patients had a greater AHI, CP AP was applied earlier. If the AHI was low, the baseline recording time needed to confirm a diagnosis was longer. There was a significant difference in ~CP AP pressure between the subgroups (1) CPAP time more than 3 h and (2) CP AP time less than 3 h on the split night, suggesting that if split-night CPAP time was less than 3 h, a greater error might occur in split-night CPAP pressure titration. There may not be sufficient time, therefore, to confirm the effectiveness of CPAP in patients with AHI <20. Since both the technician and the patients knew that there would be another study on the next night, it is possible that the technicians may have waited for the second night for definitive titration in some patients. Most laboratories are using a protocol for patients with sleep apnea that includes an entire diagnostic night followed by a CP AP titration night. There is night-to-night variability in apnea 7-lO and this variability may lead to a false-negative study if patients have a low AHI. In most reports, night-to-night variability in AHI was found mainly in patients with AHI <20. We also found significant differences in the final pressure of CP AP in patients with AHI <20; this may be due to variability in AHI. In patients with AHI<20 (including UARS), the diagnosis and severCHEST 110711 I JANUARY, 1995

65

ity may not be determined correctly in a split-night protocol. Careful follow-up may be necessary to confirm the diagnosis and the effectiveness of treatment. It has been shown that a split-night protocol was effective in determining final CPAP pressure in 78% of patients with OSA. 1 In this study, the authors selected patients with AHI>20, and analyzed data only from a single night. Sanders et al 2 studied 50 patients with severe OSA (AHI =76. 7 ± 30.6) using a similar protocol to ours, and found that a split-night protocol was effective. The CPAP pressure was lower but not statistically significant at the end of the split-night compared with the second night (13±3.5 vs 14±2.9 em HzO) . This is similar to our results in groups with 2040. However, their recording time for baseline, split-night CPAP, and the second night was shorter (sleep period time 119.9 ± 29.3, 132.4 ± 61.9, 257 ± 128.7 min) than ours. This time difference may affect the results, because there may not be enough time to reach a true final CP AP pressure. We believe that a split-night protocol was. effective in reducing arousals, apneas, and hypopneas, and improving oxygenation even in patients with AHI <20. In three patients, CP AP was changed to a ventilatory support system on the second night. Thus, in a small number of patients, a split-night study may result in the patient not being on the appropriate pressure delivery system. Thus, a split-night protocol is effective in reducing AHI and Ar-1, improving oxygenation, and sleep quality in most patients with sleep apnea and UARS. Furthermore, this protocol is convenient and may be cost-effective. Pressure determined using the splitnight protocol may not be adequate in patients with AHI <20. Patients with persistent daytime somnolence may need to be reevaluated.

CoNCLUSION

A split-night protocol may be sufficient to obtain an effective CP AP pressure for most patients with obstructive sleep apnea, especially if AHI>20. For patients with AHI<20, if symptoms are not improving, reevaluation may be necessary to confirm the effectiveness of treatment. REFERENCES

1 Iber C, O'Brien C, Schluter J, Davis S, Leatherman J, Mahowald M. Single-night studies in obstructive sleep apnea. Sleep 1991 ; 14:383-85 2 Sanders MH, Kern NB, Costantino JP, Stiller RA, Studnicki K, Coates J, et al. Adequacy of prescribing positive airway pressure therapy by mask for sleep apnea on the basis of partialnight trial. Am Rev Respir Dis 1993; 147:1169-74 3 Guilleminault C, Stoohs R, Clerk A, Cetel M, Maistros P. A cause of excessive daytime sleepiness: the upper airway resistance syndrome. Chest 1993; 104:781-87 4 West P, Kryger MH. Continuous monitoring of respiratory variables during sleep by microcomputer. Methods Inf Med 1983; 22:198-303 5 Rechtschaffen A, Kales A, eds. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. NIH publication No. 204. Bethesda, Md: National Institute of Neurological Disease and Blindness, 1968 6 George CF, Millar TW, Kryger MH. Identification and quantification of apneas by computer-based analysis of oxygen saturation. Am Rev Respir Dis 1988; 137:1238-40 7 Lord S, Sawyer B, O'Connell D, King M, Pond D, Eyland A, et al. Night-to-night variability of disturbed breathing during sleep in elderly community sample. Sleep 1991; 14:252-58 8 Mosko SS, Dickel MJ, Ashurst J. Night-to-night variability in sleep apnea and sleep-related periodic leg movements in the elderly. Sleep 1988; 11:340-88 9 Aber WR, Block AJ, Hellard DW, Webb WB. Consistency of respiratory measurements from night to night during sleep of elderly men. Chest 1989; 96:747-51 10 Meyer TJ, Eveloff SE, Kline LR, Millman RP. One negative polysomnogram does not exclude obstructive apnea. Chest 1993; 103:756-60

The XXVI Annual National Congress of the Mexican Society of Pulmonology and Thoracic Surgery March 21-24, 1995; Zacatecas, Mexico For reservations contact: Intermeeting Travel Agency, Luz Saviiion 9-803. C.P. 03100., Mexico City, Mexico. Tel: 5-687-7698 or 5-536-8151; Fax 5-536-7309.

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CPAP Titration for Sleep Apnea Using Split-Night Protocol (Yamashiro, Kryger)