Download Adaptive Servo-Ventilation in Patients With Idiopathic Cheyne

SCIENTIFIC INVESTIGATION
Adaptive Servo-Ventilation in Patients With Idiopathic Cheyne-Stokes Breathing
Katsuhisa Banno, M.D.; Kuniyuki Okamura, M.D.; Meir H. Kryger, M.D.
Sleep Disorders Center, St. Boniface General Hospital, Section of Respiratory Diseases, University of Manitoba, Winnipeg, Manitoba, Canada
from 35.2 to 3.5 per hour of sleep on ASV. There was a significant reduction in the mean number of arousals caused by abnormal breathing
events: from 18.5 to 1.1 per hour of sleep. After six to twelve months
of using ASV, the patients had maintained significant improvement in
subjective daytime alertness and mood.
Conclusion: A trial of ASV for patients with idiopathic CSB is recommended if they do not have improvement in sleep respiration or daytime
performance on CPAP and/or oxygen.
Keywords: Adaptive servo-ventilation, central sleep apnea, CheyneStokes respiration, daytime sleepiness, periodic breathing, sleep
Citation: Banno K; Okamura K; Kryger MH. Adaptive servo-ventilation
in patients with idiopathic cheyne-stokes breathing. J Clin Sleep Med
2006;2(2):181-186.
Background: Cheyne Stokes Breathing (CSB), a form of central sleep
apnea is often found in medical illnesses such as heart failure, stroke
or renal failure. Adaptive servo-ventilation (ASV) has been reported to
be an effective treatment of CSB in heart failure. However, there are no
reports about using ASV for idiopathic CSB, which is not associated with
heart failure or other serious medical problems.
Case summary: We evaluated three patients with idiopathic CSB and
examined the feasibility of using ASV to treat them. The patients had a
periodic breathing pattern resembling Cheyne-Stokes Breathing. During
polysomnography, the abnormal breathing pattern was present while patients were both awake and asleep. The patients were first tested on continuous positive airway pressure (CPAP) and/or oxygen; however they
did not respond well to either of these treatments. They were then assessed on ASV. The mean abnormal breathing events index decreased
C
and Cheyne-Stokes breathing. These treatments may improve
sleep respiration.4 In heart failure, it has been hypothesized that
CPAP stabilizes the respiratory pattern by increasing PaCO2 and
increasing intrathoracic pressure, which decreases left ventricular
afterload. Adaptive servo-ventilation (ASV), a new noninvasive
ventilation modality, recently has been reported to be effective in
patients with heart failure and Cheyne-Stokes breathing.5-9 However, we are not aware of reports about using ASV for CheyneStokes breathing in the absence of heart failure or any other serious medical problem.
We evaluated the efficacy of respiratory interventions, including CPAP, oxygen, and ASV, for the treatment of idiopathic
Cheyne-Stokes breathing in 3 patients. The patients were assessed
with comprehensive polysomnography, including synchronized
digital video recording, the monitoring of neurophysiologic measures (electroencephalogram, chin electromyogram, electrooculogram, anterior tibialis electromyogram) and cardiorespiratory
variables: chest-wall motion, abdominal motion, nasal pressure,
oronasal PCO2 , SpO2 (by ear oximeter), and electrocardiogram.
Nasal pressure, oronasal CO2, chest wall, and abdominal motion
were used to assess respiratory events. Video records were used
for additional assessment of abnormal breathing. The sleep record was analyzed manually for sleep staging using a 30-second
epoch.10 Abnormal breathing patterns were defined using conventional criteria.1 After a definitive diagnosis was made, the patients
were tested with following treatments: CPAP, nasal oxygen, and
CPAP and nasal oxygen. The patients were then assessed while
on the ASV at the default settings (AutoSet CS; ResMed, Sydney,
Australia), described in detail elsewhere.6 We report our experience in using ASV for the treatment of idiopathic Cheyne-Stokes
breathing.
entral sleep apnea syndrome, a disorder characterized by
recurrent apneic episodes in the absence of upper-airway
obstruction during sleep, causes nocturnal oxygen desaturations,
recurrent arousals, and subjective daytime sleepiness.1,2 Central
sleep apnea syndrome has been reported to be present in alveolar
hypoventilation disorders, heart failure, and neurologic disorders,
and some cases are idiopathic.1,2 Cyclic breathing with regularly
repeating periods of central apneas or hypopneas alternating with
periods of hyperpnea in a gradual crescendo and decrescendo pattern is termed Cheyne-Stokes breathing, which is often associated
with heart failure or neurologic disorders.1 Cheyne-stokes breathing is defined as “Other Central Sleep Apnea, including Cheyne
Stokes Breathing Pattern” in the International Classification of
Sleep Disorders-2.3 Association with a serious medical illness,
such as heart failure, stroke, or renal failure, is usually necessary to document this diagnosis by International Classification of
Sleep Disorders-2.
Various respiratory interventions, including continuous positive airway pressure (CPAP), bilevel positive airway pressure, or
nasal oxygen have been evaluated in patients with heart failure
Disclosure Statement
This was not an industry supported study. Drs. Okamura, Banno, and
Kryger have indicated no financial conflicts of interest.
Submitted for publication July 29, 2005
Accepted for publication November 24, 2005
Address correspondence to: Meir Kryger M.D., Sleep Disorders Center, St.
Boniface General Hospital, Room R2034, 351 Tache Avenue, Winnipeg, Manitoba, R2H 2A6, Canada; Tel: (204) 235-3406; Fax: (204) 235-0021; E-mail:
[email protected]
Journal of Clinical Sleep Medicine, Vol. 2, No. 2, 2006
181
K Banno, K Okamura, and MH Kryger
Table 1—Results of Polysomnographic Findings in 3 Cases
Case 1
Baseline CPAPa Oxygen ASV
Sleep stage, % of total sleep time
1
1.4
7.0
4.4
2
47.2
51.6
50.5
3
17.0
4.1
8.8
4
7.4
1.7
0
REM
27.0
35.7
36.3
Apnea index, no./h
Total
30.4
26.5
5.7
Obstructive
1.4
0.6
0.2
Mixed
0
0
0
Central
29.0
25.9
5.5
Average SpO2
94.8
95.6
94
SpO2 < 90%, % of time
0.7
0
0
Mean heart rate, bpm
56
54
53
Arousal index, no./h
Total
22.2
23.3
9.7
Spontaneous
4.1
2.0
4.0
Respiratory
12.3
13.8
1.6
PLM
5.8
7.5
4.0
Baseline
Case 2
CPAP Oxygen
ASV
Baseline
Case 3
CPAPb Oxygen
ASV
11.1
53.1
8.6
19.2
8.0
14.0
46.0
5.6
19.3
14.7
17.8
69.2
0
0
13.0
4.5
40.2
37.1
0
18.2
6.9
80.1
2.0
11.0
0
22.4
47.1
0
0
30.6
11.8
57.7
1.3
10.9
18.3
35.6
13.6
2.9
19.1
92
4.3
45
21.0
2.5
0
18.5
95
0
46
13.5
1.2
4.5
7.8
95.9
0.1
43
3.6
0
0
3.6
95.2
0
43
39.5
0
0
39.5
90.9
10.9
42
16.9
0
0
16.9
97.3
0
41
1.3
0.5
0.4
0.4
95.1
0.2
41
48.6
7.7
20.2
20.7
25.7
9.3
8.8
7.6
34.5
8.2
7.2
18.9
29.1
29.1
0
0
32.2
5.4
22.9
3.9
16.9
5.6
9.2
2.1
13.2
6.8
1.8
4.6
ASV refers to adaptive-servo ventilation; REM, rapid eye movement; PLM: periodic limb movement.
a
The continuous positive airway pressure (CPAP) was terminated shortly because of the worsening of apneic episodes.
b
The patient could not tolerate CPAP.
CASE REPORTS
CONTINUOUS POSITIVE AIRWAY PRESSURE
Case 1
The patient was tested on CPAP. However, his periodic breathing worsened after he was started on CPAP. Because of this negative response, the assessment on CPAP was terminated.
A 51-year-old male insurance executive (body mass index:
24.4 kg/m2) was referred because of observed apneas and excessive daytime sleepiness interfering with his ability to be productive at work. His Epworth Sleepiness Scale score11 was 20. On
average, he slept 7.5 hours every night. He denied hypnagogic
hallucinations, cataplexy, or sleep paralysis. He had symptoms of
restless legs syndrome. His medical history was noncontributory.
The family history revealed that his father died of myocardial infarction at age 52, and his brother also had a myocardial infarction at age 47 with subsequent angioplasty. Physical examination
revealed that he had a long uvula and nasal obstruction on his left
side. There were no findings suggestive of heart failure or cerebral neurologic disorders.
OXYGEN
Because nasal CPAP worsened his apnea, the patient was then
assessed on oxygen at 2 liters per minute, which decreased the
oxygen desaturation index (3%) from 16.4 to 4.0 per hour of sleep
time, although it did not eliminate the central apneas (Table 1).
There was no significant change in the arousal index or the sleep
structure. He was sent home on nocturnal oxygen.
He stated that there was improvement in his work performance
and daytime alertness; however, his sleepiness was not entirely
controlled by oxygen. Therefore, modafinil was started for his
residual sleepiness. After a few months of using modafinil, he
developed atrial fibrillation. Modafinil was discontinued.
BASELINE ASSESSMENT
ADAPTIVE SERVO-VENTILATION
The patient was assessed by overnight polysomnography,
which confirmed central sleep apneas with an apnea-hypopnea
index (AHI) of 30.4 per hour. Almost all of the respiratory events
were central apneas, and the breathing pattern had the configuration of Cheyne-Stokes breathing. He spent 0.7% of the sleep time
with an SpO2 < 90%. The arousal index was 22.2; 12.3 arousals
per hour of sleep were related to abnormal breathing events. The
cause of his subjective daytime sleepiness was considered to be
the abnormal breathing pattern. The highest recorded end-tidal
CO2 was 39.8 mmHg. There were 59.7 leg movements per hour;
however, only 5.8 arousals per hour were caused by leg movements. Blood was tested to exclude known biochemical causes
of movement disorder; no abnormalities in thyroid function, iron
stores, or vitamin B12 levels were found. The results of the baseline polysomnographic study are presented in Table 1.
Journal of Clinical Sleep Medicine, Vol. 2, No. 2, 2006
Because the other treatments did not resolve the patient’s problem, another sleep study was done to assess response to ASV. The
study showed that the patient still had periodic breathing when
he was both awake and asleep. The ASV machine compensated
by generating pressure when his ventilation decreased (Figure 1).
Although the SpO2 was oscillating at the beginning of the polysomnographic recording, ASV gradually normalized the SpO2
level (Figure 2). The arousal index was 9.7 per hour; 1.6 were
related to abnormal respiratory events. The abnormal breathing
pattern was well controlled by ASV. The AHI was 5.7 per hour
on ASV. The patient stated that there was a more significant improvement in daytime alertness with ASV than with any previous
treatments that he had tried. It was recommended that he use ASV
treatment at home.
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Adaptive Servo-Ventilation for Idiopathic CSB
CHIN
C3-A2
C4-A1
O1-A2
O2-A1
ROC-A1
LOC-A2
ECG
LEG(L)
LEG(R)
100
SpO2 (%)
80
C
A
Thoracic
movement
30 sec
Abdominal
movement
Pulse (bpm)
100
End tidal PCO2
(mmHg)
40
50
0
Pressure (ASV)15
(cmH2O)
0
D
B
Figure 1—Polysomnographic recording shows repetitive episodes of central sleep apnea in rapid eye movement (REM) sleep with significant oscillations in the oxygen saturation level (Case 1). These episodes varied from 20 to 30 seconds in duration. When the patient stopped breathing (black
arrow A), the adaptive servo-ventilator increased pressure (black arrow B), and when the patient started breathing actively (black arrow C), the
pressure output decreased (black arrow D). CHIN refers to chin electromyogram; C3-A2, C4-A1, O1-A2, O2-A1, electroencephalogram; ROC-A1,
LOC-A2, electrooculogram; LEG(L), LEG(R): electromyogram in lower limbs; ASV, adaptive servo ventilation.
of 35.6 per hour; 53.7% of the abnormal respiratory events were
central apneas (Table 1). These had the configuration of CheyneStokes breathing. The arousal index was 48.6 per hour; 20.2 were
related to abnormal breathing events. There were 60.5 leg movements per hour of sleep, which were also observed on synchronized digital video.
FOLLOW-UP
After the patient had been using ASV at home every night for
1 month, he stated that subjective daytime sleepiness was completely diminished. In addition, his subjective mood and cognitive
function were dramatically improved, which made him feel like a
new person. The improvement was still noted after 6 months.
CONTINUOUS POSITIVE AIRWAY PRESSURE
Case 2
We tested the patient on CPAP, which did not eliminate his abnormal breathing events (AHI=21.0 per hour). He had 25.7 arousals and 22.7 leg movements per hour of sleep.
A 58-year-old male lawyer (body mass index=26.6 kg/m2) was
referred because of snoring, observed sleep apneas, and daytime
sleepiness (Epworth Sleepiness Scale score = 11). He napped
daily because of sleepiness, which substantially interfered with
his work performance. He denied hypnagogic hallucinations,
cataplexy, sleep paralysis, and symptoms of restless legs. There
was no other major medical history except for hypertension and
occasional palpitations. His father died of a heart attack at age
64. Physical examination revealed that there were no remarkable
findings. He had mild retrognathia. There were no findings of
heart failure or neurologic disorders. Biochemical evaluations for
thyroid disease were negative.
OXYGEN
The patient was then tested with nasal oxygen at 2 liters per
minute. The AHI decreased from 35.6 to 13.5 per hour. The percentage of time with an SpO2 < 90% decreased from 4.3% to
0.1%. The arousal index decreased from 48.6 to 34.5 per hour;
18.9 were related to abnormal leg movements. The patient continued to have leg movements at 41.5 per hour. He was started on
oxygen at 2 liters per minute at home. However, his subjective
daytime sleepiness continued, and impaired concentration in the
work place was still problematic.
BASELINE
CPAP AND OXYGEN
The patient was assessed by overnight polysomnography, which
confirmed sleep apneas of primarily the central type with an AHI
Journal of Clinical Sleep Medicine, Vol. 2, No. 2, 2006
Because his apneas did not resolve with the use of CPAP or
183
K Banno, K Okamura, and MH Kryger
10 min
100
SpO2 (%)
90
Thoracic
movement
Abdominal
movement
End tidal PCO2
(mmHg)
50
0
Pressure (ASV) 15
(cmH2O)
0
Figure 2—The tracing adapted from a polysomnographic recording shows 30 minutes of data on the adaptive servo-ventilator (ASV), which
starts with episodes of periodic breathing with oscillations in oxygen saturation. The oscillations decrease with time so that by the right side of the
record, about 30 minutes later, the patient’s breathing pattern is ultimately normalized, as is the oxygen saturation, and the output from the ASV is
constant.
oxygen, the patient was also tested on a combination of CPAP and
oxygen, which improved his abnormal breathing events (AHI=
13.6 per hour). He spent no time below an SpO2 of 90%. However, he continued to have 52.1 movements per hour and 54.3
arousals per hour; 6.8 were related to abnormal breathing, 27.2
were related to leg movements.
Blood tests were done to exclude known biochemical causes
of movement disorders that may also contribute to his daytime
sleepiness. Therefore, pramipexole was started to treat the abnormal leg movements that caused arousals. The patient was ultimately started on a combination of CPAP and oxygen at home.
Residual sleepiness remained.
his wife stated that he was very irritable. He denied hypnagogic
hallucinations, cataplexy, sleep paralysis, or symptoms of restless
legs. He did not awaken with an acid taste in his mouth, a feeling
of choking, palpitations, or headaches. There was no peripheral
edema in the lower limbs. His pharyngeal airway was within normal limits. He had retrognathia. There was no history of cardiovascular diseases or stroke.
BASELINE
The sleep study showed central sleep apneas with periodic
breathing, which were observed during sleep and wakefulness.
These had the configuration of Cheyne-Stokes breathing. These
apneic episodes were in the range of about 50 seconds in duration, during which time his oxygen saturation decreased from the
high 90s to the low 80s. Once he fell asleep, he continued to have
periodic breathing, with episodes at a rate of 39.5 per hour of
sleep. He spent 10.9% of time below an SpO2 of 90%. Synchronized digital video revealed that there were times during the night
when he had periodic breathing with ventilation increasing and
decreasing with no evidence of obstruction. At other times, the
patient had some evidence of obstruction, with loud snorts occurring before the resumption of ventilation. The sleep structure
was abnormal, with 32.2 arousals per hour of sleep; 22.9 episodes
were related to abnormal respiratory events. There was no rapid
eye movement sleep. There were 48.3 leg movements during
sleep; 3.9 episodes per hour of sleep were related to arousals.
The sleep efficiency was 74.1%. The baseline polysomnographic
findings are presented in Table 1. It was concluded that he had
combination of periodic breathing and upper-airway obstruction.
ADAPTIVE SERVO-VENTILATION
We tested the patient on ASV treatment because, although he
was on CPAP and oxygen, the residual sleepiness was impacting
his work performance. On an ASV device, his abnormal breathing
pattern was completely eliminated. His AHI was 3.6. He spent no
time with an SpO2 < 90%. His arousal index was 29.1 per hour;
all arousals were spontaneous. Periodic leg movements per hour
of sleep were now 0. The patient stated that his energy level and
concentration were far better on ASV than other treatments that he
had tried. We recommended he use ASV at home.
FOLLOW-UP
The patient had been using ASV at home every night. One
month after he started to use ASV, he stated that he felt much better on ASV than any treatments that he had tried before. His sleepiness was completely controlled on ASV, which resulted in substantial improvement in concentration at work. At the 12-month
follow-up visit, he stated that the improvement of his symptoms
on ASV was still maintained.
CONTINUOUS POSITIVE AIRWAY PRESSURE
Although he was assessed on CPAP, he could not tolerate
CPAP at all. Thus oxygen was tried on him as part of a split-night
study.
Case 3
A 69-year-old male farmer (body mass index = 27.1 kg/m2) was
referred for assessment of sleep-related breathing disorder due to
observed apneas. The patient had a history of snoring for 60 years.
Although he did not complain of pathologic daytime sleepiness,
Journal of Clinical Sleep Medicine, Vol. 2, No. 2, 2006
OXYGEN
The patient was then tested on oxygen at 1 liter per minute.
The percentage time of with an SpO2 < 90% was decreased from
184
Adaptive Servo-Ventilation for Idiopathic CSB
breathing. When tidal volume decreased, the computerized system increased ventilatory support; when ventilation was normal
or increased, the ventilatory support decreased (see Figure 1).
The compensation of ventilation improved sleep respiration and,
thus, reduced nocturnal arousals. In this study, the reason why
ASV was more effective than the other treatments in resolving
abnormal breathing and sleep structure was unclear.
Another noteworthy finding was a significant reduction in leg
movements and arousals related to leg movements with ASV. The
leg movements were significantly decreased in Case 3 without
medications to suppress leg movements. The mechanism of improvement in the abnormal movements on ASV is not clear.
On the surface, ASV seems to an efficacious treatment for idiopathic Cheyne-Stokes breathing when breathing periodicity is
present. However, due to the methodologic issues (small sample,
no control group, no randomization), another study comparing
the outcome of ASV and other treatments is warranted to see
which approach is the most appropriate in cases with idiopathic
Cheyne-Stokes breathing.
10.9% to 0% on oxygen; however, he still had 16.9 episodes of
periodic breathing per hour of sleep.
ADAPTIVE SERVO-VENTILATION
We repeated another sleep study because neither CPAP, oxygen,
or a combination of CPAP and oxygen were sufficiently effective
to improve his abnormal breathing and symptoms. He still had
problems with mood and daytime alertness; therefore, he wanted
to pursue another treatment for his abnormal breathing. His wife
mentioned that his irritability continued, and this has been causing
a problem for them.
We tested the patient while using an ASV machine. The number of abnormal breathing events decreased to 1.3 per hour of
sleep. He had a sleep efficiency of 81.3%. There were now normal
amounts of slow-wave sleep and rapid eye movement sleep. The
patient had an improvement in his overall sleep, and he fell asleep
in 11 minutes. Leg movements per hour of sleep decreased from
48.3 (baseline) to 28.1. The following morning, he stated that he
felt much improved having been on the ASV device for an entire
night. Since the most appropriate treatment for him was ASV at
this point, he was recommended to start ASV at home.
CONCLUSIONS
Short-term treatment by using ASV improved sleep structure, sleep respiration, subjective daytime sleepiness, and mood
problems in patients with idiopathic Cheyne-Stokes breathing
(Cheyne-Stokes breathing without heart failure or other serious
medical problem). Clinicians should consider the use of ASV in
patients with idiopathic Cheyne-Stokes breathing who do not respond well or fail to tolerate CPAP, oxygen, or both CPAP and
oxygen.
FOLLOW-UP
The patient had been using ASV at home every night for 6
month since ASV was prescribed. At the 1-month and 6-month
follow-up visits, he stated that he felt much better on ASV than on
CPAP and oxygen, and his sleep quality substantially improved
on ASV. His wife also mentioned that his mood significantly improved.
REFERENCES
DISCUSSION
1.
To our knowledge, this is the first report of patients with idiopathic Cheyne-Stokes breathing who were successfully treated
with ASV. The mean abnormal breathing events decreased from
35.2 to 3.5 per hour of sleep on ASV. In addition, the mean number
of arousals related to abnormal breathing was also reduced: 18.5
to 1.1 per hour of sleep. The 3 cases all had had disturbed work
performance or mood problems caused by idiopathic CheyneStokes breathing, which were most improved by using ASV. The
elimination of abnormal breathing causing nocturnal arousals or
sleep disruption may be a key issue for improved daytime cognitive function in patients with idiopathic Cheyne-Stokes breathing.
Topfer et al7 reported that ASV improved quality of life in patients with Cheyne-Stokes breathing and heart failure. Abnormal
breathing or arousals have been reported to be reduced more by
ASV than by CPAP or oxygen.6 It has been recently reported that
ASV is a more efficacious treatment for Cheyne-Stokes breathing
caused by heart failure than is CPAP, in that ASV corrects more
abnormal breathing events than does CPAP, and patients on ASV
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our 3 cases did not have heart failure or cerebral neurologic disorders, they demonstrated repetitive central apneas that are best
characterized as Cheyne-Stokes breathing. Also, their mean heart
rate was in the low 40s to the high 50s. The abnormal breathing was found while they were both awake and asleep. Thus, the
patients may have had abnormal control of ventilation. The ASV
device did the opposite of what the patients did with respect to
Journal of Clinical Sleep Medicine, Vol. 2, No. 2, 2006
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5.
6.
7.
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