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* From the Sleep Disorders Center (Dr. Krachman and Mr. Berger), Division of Pulmonary and Critical Care Medicine (Dr. D’Alonzo), and Division of Cardiology (Dr. Eisen), Temple University School of Medicine, Philadelphia, PA.
Correspondence to: Samuel L. Krachman, DO, FCCP; Division of Pulmonary and Critical Care, Temple University School of Medicine, 767 Parkinson Pavilion, Broad and Tioga Streets, Philadelphia, PA 19140
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Abstract |
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Design: Prospective, randomized, controlled trial.
Setting: University hospital.
Patients: Twenty-five stable patients (mean [± SD] age, 56 ± 9) with CHF and a mean left ventricular ejection fraction (LVEF) of 17 ± 0.8%.
Interventions and measurements: All patients had a right heart catheterization prior to the study and an echocardiogram performed to measure LVEF. In addition, all patients had an initial sleep study to identify the presence of CSR. Sleep studies included continuous recordings of breathing pattern, pulse oximetry, and EEG. Those patients identified as having CSR were randomized to a night on oxygen therapy (2 L/min by nasal cannula) and another night on nasal CPAP therapy (9 ± 0.3 cm H2O).
Results: Fourteen of the 25 patients (56%) studied had CSR (apnea hypopnea index [AHI], 36 ± 7 events per hour) during their initial sleep study. Nine of the 14 patients with CSR completed the study. When compared with baseline measurements, both oxygen therapy and nasal CPAP therapy significantly decreased the AHI (from 44 ± 9 to 18 ± 5 and 15 ± 8 events per hour, respectively; p < 0.05), with no significant difference between the two modalities. The mean oxygen saturation increased significantly and to a similar extent with oxygen therapy and nasal CPAP therapy (from 93 ± 0.7% to 96 ± 0.8% and 95 ± 0.7%, respectively; p < 0.05), as did the lowest oxygen saturation during the night (from 80 ± 2% to 85 ± 3% and 88 ± 2%, respectively; p < 0.05). In addition, the mean percent time the oxygen saturation was < 90% also improved with both interventions (from a baseline of 17 ± 5 to 6 ± 3% with oxygen therapy and 5 ± 2% with nasal CPAP therapy; p < 0.05). When compared with baseline measurements, the apnea-hypopnea length, cycle length, circulation time, and heart rate did not significantly change with either oxygen therapy or nasal CPAP therapy. Total sleep time and sleep efficiency decreased only with nasal CPAP therapy (from 324 ± 20 to 257 ± 14 min, and from 82 ± 3 to 72 ± 2%, respectively; p < 0.05). The arousal index, when compared with baseline, remained unchanged with both oxygen therapy and nasal CPAP therapy.
Conclusion: CSR occurs frequently in stable patients with severe CHF. In addition, oxygen therapy and nasal CPAP therapy are equally effective in decreasing the AHI in those CHF patients with CSR.
Key Words: apnea-hypopnea index • Cheyne-Stokes respiration • congestive heart failure • nasal continuous positive airway pressure • oxygen therapy
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Introduction |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Oxygen therapy and nasal continuous positive airway pressure (CPAP) have both independently been shown to be effective in the treatment of CSR during sleep in patients with CHF.11 12 13 14 15 16 In addition, the long-term use of nasal CPAP has been shown to improve left ventricular function.13 14 15 Yet, no study has prospectively compared oxygen therapy and nasal CPAP therapy in regard to their effectiveness in treating CSR during sleep in patients with CHF. We prospectively studied a group of CHF patients (New York Heart Association [NYHA] class IV) with an LVEF of < 40% to examine (1) the prevalence of CSR during sleep in these patients, and (2) in those patients found to have CSR during sleep, to directly compare in a randomized manner, the effects of oxygen therapy and nasal CPAP therapy on this form of sleep-disordered breathing.
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Materials and Methods |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Patients were admitted to an inpatient heart failure unit. This unit is designed to evaluate and list cardiomyopathy patients for possible heart transplantation. All of the patients in the study were listed for transplant and resided in the unit awaiting surgery. Following admission, all patients had right heart catheterizations performed to optimize their medical regimen, including the initiation and titration of inotropic infusions. The patients’ right heart catheters then were exchanged for surgically placed indwelling central venous catheters, and the patients remained on continuous inotropic infusions at their previously determined dose. All patients were ambulatory and active in physical therapy conditioning programs at the time of the study. Although the above sequence by which patients are evaluated and listed for transplant is routinely performed at our institution, it does not necessarily reflect a standard that is practiced at other transplant centers.
Echocardiogram and Right Heart Catheterization
All patients had echocardiograms and right heart catheterization
measurements obtained within 1 month of the study. As stated above, at
the time of the right heart catheterization the patient’s medical
therapy was optimized and measurements were recorded just before the
catheter was removed. The measurements obtained included right atrial
pressure, pulmonary artery pressure, and pulmonary capillary wedge
pressure (PCWP). All measurements were obtained with the transducer
zeroed at the level of the right atrium and at the end of expiration.
Cardiac output was measured as the mean of three recordings using the
thermodilution technique with normal saline at room temperature. The
patients’ inotropic infusion dose remained unchanged after the
catheter was discontinued and replaced with a surgically placed
indwelling central venous catheter. Echocardiograms were obtained
following right heart catheterization, with the measurement of the LVEF
recorded.
Nasal CPAP Technique
Patients were allowed to acclimate themselves to the nasal CPAP
equipment (REMstar; Respironics Inc; Murrysville, PA) prior to
the CPAP study night. This involved the use of the equipment during the
daytime while the patients were awake, starting at a low pressure of 5
cm H2O. Patients were instructed to use the nasal
CPAP 1 to 2 h twice daily. Over a 5- to 7-day period, the level of
CPAP was gradually increased toward a goal level of 10 to 12 cm
H2O, as tolerated. These levels are similar to
those previously shown to be effective in the treatment of CSR in CHF
patients.13
14
16
Oxygen Therapy
During the oxygen study night, oxygen was administered at 2
L/min by nasal cannula. All patients were allowed to acclimate
themselves to the nasal cannula during the day, while they were awake,
prior to the study night.
Sleep Studies
The polysomnogram recording consisted of breathing pattern
(abdominal and rib cage motion), pulse oximetry (model N-100;
Nellcor Puritan Bennett; Pleasanton, CA), oral and nasal thermistors,
ECG, electrooculogram, digastric electromyogram, and
electroencephalograph. All variables were recorded continuously and
were stored on a computerized system (Alice 3; Healthdyne Information
Enterprises, Inc; Marietta, GA). Sleep stage was classified by the
standard criteria of Rechtschaffen and Kales.17
Central
apneas were defined by the lack of airflow for > 10 s, associated
with the absence of rib cage and abdominal movement. Central hypopneas
were defined by a 50% decrease in airflow for > 10 s, associated
with a decrease in rib cage and abdominal excursion. The central
apnea-hypopnea index (AHI) was expressed as the number of apneas and
hypopneas per hour of sleep. CSR was determined to be present when the
central AHI was 
10/h.18
The cycle length was defined
as the sum of the hyperpnea length and apnea length. The circulation
time was calculated as the time from the end of a central apnea to the
nadir in oxygen saturation. For each study, the cycle length, apnea
length, and circulation time were determined by calculating the mean of
10 consecutive measurements obtained during stage-2 sleep. Other sleep
parameters that were determined included the following: (1) total sleep
time; (2) sleep efficiency, defined as the total sleep time divided by
the time in bed; (3) arousals, defined as the appearance of alpha waves
on EEG that were 3 to 15 s in duration19
; and (4) the
percentage of time during the night that the oxygen saturation was
< 90%.
Protocol
All patients had a baseline study to determine whether CSR was
present during sleep. Those patients that demonstrated CSR during their
baseline study then were entered into the second part of the study,
which consisted of 2 additional nights.
During the second night, patients with CSR were randomized to a night spent either with oxygen therapy at 2 L/min by nasal cannula or with nasal CPAP at the highest level tolerated while awake during the previous week (see above). The third night consisted of the opposite therapy for each patient.
Statistical Analysis
Data are represented as the mean ± SE except where stated.
Unpaired Student’s t tests were used to compare variables
in patients with and without CSR. One-way repeated analysis of variance
was used to compare patient variables at baseline, on oxygen, and on
nasal CPAP. When significant, pairwise multiple comparisons were made
using the Student-Newman-Keuls method.
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Results |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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When compared with baseline, both oxygen therapy and nasal CPAP therapy significantly decreased the AHI, from 44 ± 9 to 18 ± 5 and 15 ± 8 events per hour, respectively (p < 0.001), with no significant difference between the two treatment modalities (Fig 1 ). The mean oxygen saturation during the night (Fig 2 ), when compared with baseline, significantly increased with both oxygen therapy and nasal CPAP therapy, from 93 ± 0.7 to 96 ± 0.8 and 95 ± 0.7%, respectively (p < 0.001). In addition, the lowest oxygen saturation during the night significantly improved with both treatment modalities, from a baseline of 80 ± 2% to 85 ± 3% with oxygen therapy and 88 ± 2% with nasal CPAP therapy (p = 0.01). The mean percentage of time that oxygen saturation was < 90% also improved with both interventions, from a baseline of 17 ± 5% to 6 ± 3% with oxygen therapy and 5 ± 2% with nasal CPAP therapy (p = 0.02). There was no significant difference between the two treatment modalities regarding the improvements noted in oxygenation during the night.
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When compared with baseline, total sleep time was not changed with oxygen therapy, but it was significantly less with nasal CPAP therapy, falling from a baseline of 324 ± 20 to 297 ± 13 min with oxygen therapy and 257 ± 14 min with nasal CPAP therapy (p < 0.05 as compared with both baseline and oxygen therapy) (Fig 3 , top, A). A similar decrease in sleep efficiency was seen with nasal CPAP therapy, falling from a baseline of 82 ± 3% to 81 ± 1% with oxygen therapy and 72 ± 2% with nasal CPAP therapy (p < 0.05 as compared with both baseline and oxygen therapy) (Fig 3 , bottom, B). The number of arousals per hour was not significantly different with either treatment, changing from a baseline of 14 ± 5 arousals per hour to 9 ± 3 and 15 ± 5 arousals per hour, respectively, with oxygen therapy and nasal CPAP therapy (p = 0.28). In addition, the sleep architecture (Table 3 ), expressed as a percentage of total sleep time including the percentage of stage 1 and stage 2 sleep, was not different as compared with baseline for either oxygen therapy or nasal CPAP therapy.
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Discussion |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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In the present study, the prevalence of CSR was slightly higher than
previously reported.1
2
3
4
Findley et al2
studied 15 patients with CHF who had a mean LVEF of 32%. They noted
CSR during sleep in 6 of their patients (40%). There were no
differences in left ventricular function in these patients when
compared with those without CSR. Lofaso et al3
found a
similar prevalence of CSR (45%) in a group of 20 stable patients with
CHF who were on the list for heart transplantation. Again, there was no
difference in left ventricular function in patients with and without
CSR, with all patients having an LVEF of < 15%. In a larger study,
Hoffman et al4
noted CSR to be present in 42 of 95
patients (44%) shortly after medical treatment for acute pulmonary
edema that required mechanical ventilation. Left ventricular function
again did not predict which patients would have CSR. More recently,
Javaheri et al1
reported a prevalence of 45% in 42 stable
outpatients with CHF (LVEF, 
45%). They noted that left ventricular
function was significantly more impaired in the group with CSR (LVEF,
22%) compared with those without CSR (LVEF, 30%) and that it was the
single most important risk factor for the development of
sleep-disordered breathing.
The increased prevalence of CSR in the present study may be secondary to a greater impairment in left ventricular function than noted in previous studies (Table 1) , although it should be noted that there was no significant difference in left ventricular function in those patients with and without CSR (Table 2) . In addition, all of our patients were medically optimized prior to the study, which by itself is often effective in the treatment of CSR.12 20 21 Furthermore, the use of inotropic agents has been shown to be effective in eliminating CSR induced during exercise in patients with CHF.22 Therefore, we do not believe that the severity of left ventricular dysfunction by itself explains the increased prevalence of CSR seen in our patients.
Oxygen therapy and nasal CPAP therapy were found to be equally effective in decreasing the severity of CSR during sleep in our patients with CHF. Both forms of therapy have been shown independently to be effective in the treatment of CSR in CHF patients, yet no previous study has compared these two treatment modalities. Takasaki et al13 studied the effects of nasal CPAP therapy on five patients with CHF and CSR (AHI, 69 ± 9 events per hour). They demonstrated a significant decrease in the AHI (to 15 ± 7 events per hour) when patients were restudied from 10 days to 4 weeks later. Naughton et al16 noted a similar decrease in the AHI (from 59 ± 5 to 23 ± 6 per hour) with use of nasal CPAP therapy after 1 month. More recently, Naughton et al14 examined the effects of nasal CPAP on CSR after 1 month in a randomized controlled trial. Compared with the control group, those patients treated with nasal CPAP showed a significant decrease in the AHI (from 43 ± 5 to 15 ± 5 events per hour). Our patients showed a similar decrease in the AHI (from 44 ± 9 to 15 ± 8 events per hour) with a level of nasal CPAP (9 ± 0.3 cm H2O) similar to that used in previous studies.13 14 16
One proposed mechanism to explain the benefits of nasal CPAP on CSR in patients with CHF is the effect that nasal CPAP has on left ventricular function. By increasing intrathoracic pressure and decreasing the transmural pressure across the left ventricle, nasal CPAP can decrease left ventricular afterload.23 24 An increase in LVEF reduces interstitial edema and decreases stimulation of pulmonary vagal afferents, which are thought to cause the observed hyperventilation and hypocapnia noted in these patients.18 25 A decrease in tidal volume and an increase in PaCO2 with nasal CPAP15 maintains the sleeping PaCO2 well above the apneic threshold. Previous studies that have shown a decrease in the AHI with nasal CPAP also have demonstrated a significant increase in LVEF.13 14 15
Oxygen therapy also has been shown independently to significantly decrease the AHI in patients with CSR.11 12 Hanly et al11 studied the effects of low-flow oxygen (2 to 3 L/min) on CSR during sleep in nine patients with CHF. They noted a significant decrease in the AHI (from 30 ± 8 to 14 ± 2 events per hour) when oxygen was administered during the study night. Walsh et al12 noted a similar decrease in the AHI (from 35 ± 7 to 20 ± 5 events per hour) when oxygen was administered for one night to seven patients with mild-to-moderate CHF. It is theorized that the supplemental oxygen increases the oxygen stores in the body, which have become depleted in the presence of interstitial edema. The increased oxygen stores allow for better buffering and prevent instability in arterial blood gas tensions during transient changes in ventilation. Thus, the respiratory control system is dampened and more stable. In addition, by removing the hypoxic stimulus to hyperpnea with supplemental oxygen, the PaCO2 is able to increase well above the sleep-related apneic threshold. Our patients demonstrated a similar decrease in the AHI (from 44 ± 9 to 18 ± 5 events per hour) with supplemental oxygen, as previously has been reported.11 12 Although oxygen therapy has been shown to significantly decrease the AHI, it is unknown whether long-term use will lead to an improvement in left ventricular function similar to that seen with nasal CPAP use.
The present study also demonstrated a significant improvement in gas exchange during sleep with both oxygen therapy and nasal CPAP therapy. Both the mean and lowest oxygen saturation during the night improved, as did the percentage of time the oxygen saturation was < 90%, with no significant difference between the two treatment modalities. Similar findings have been reported independently concerning the use of both nasal CPAP13 and oxygen.11 12
The cycle length has been shown to directly correlate with the circulation time18 26 and to be inversely proportional to cardiac output and stroke volume.26 In the present study, the cycle length, apnea length, and circulation time did not significantly change with either oxygen therapy or nasal CPAP therapy. Yet, similar findings have been reported with more prolonged use of nasal CPAP therapy, despite a significant increase in LVEF.16 Increased cardiac chamber size and end-systolic blood volume may delay transmission as well as buffer any changes in pulmonary venous blood gas tensions. This is one mechanism that has been proposed to explain how improved cardiac function may not be associated with a decrease in circulation time and cycle length.26 Hanly et al11 demonstrated that oxygen therapy increased the cycle length, yet no direct measurements of cardiac function were obtained. Whether improved cardiac function contributed to the decrease in AHI seen with both oxygen therapy and nasal CPAP therapy in the present study cannot be determined.
Total sleep time and sleep efficiency were both significantly decreased with nasal CPAP therapy when compared with measurements for both at baseline and with oxygen therapy. We believe this probably represents the patient still being unfamiliar with the nasal CPAP device, despite the fact that patients were able to practice with the system for 5 to 7 days prior to their nasal CPAP night study. This seems supported by the fact that all nine patients reported that they felt more rested following the oxygen therapy night compared with the nasal CPAP night. Buckle et al27 noted a similar lack of improvement in sleep quality in CHF patients treated in the short term with nasal CPAP. Other studies have demonstrated that more long-term use of nasal CPAP is associated with an improvement in the amount of slow-wave sleep during the night,13 as well as with a decrease in the arousal index,13 14 with no significant decrease in the total sleep time or sleep efficiency. Oxygen therapy has been shown to increase total sleep time and decrease the arousal index, even when used for just 1 night.11 12
Limitations in our methodology should be discussed. First, regarding the prevalence of CSR, all of our patients were studied without an initial acquaintance night, which would have allowed for a first-night effect of sleeping in an unfamiliar environment. It should be noted though, that our patients slept well during this initial study night, with a mean total sleep time of 314 ± 9 min and a mean sleep efficiency of 82 ± 2%. Thus, we do not feel that the prevalence of CSR was substantially underestimated. Second, our patients did not have a subsequent CPAP titration study once CSR was found to be present on their initial study night. This might have more adequately identified the appropriate level of CPAP needed to treat their CSR. Yet, our patients were titrated over a 5- to 7-day period with increasing levels of nasal CPAP, toward a goal of 10 to 12 cm H2O. Most patients were not able to tolerate these higher levels, with the mean CPAP level being 9 ± 0.3 cm H2O, which is a level shown to be effective in previous studies.13 14 16 Third, all of our patients were studied while receiving a continuous IV infusion of an inotropic medication, which by itself may improve cardiac function and CSR. Yet, all of our patients had remained on the same dose of inotropic support for a 2-week period (17 ± 4 days) prior to the control night study. Additionally, the dose remained the same throughout the study period. Finally, quality-of-life questionnaires were not obtained from our patients. Although these questionnaires may have more fully characterized the baseline function of our patients, we investigated the acute 1-night effect of both oxygen therapy and nasal CPAP therapy, and these questionnaires would not have been of value in this setting.
In conclusion, sleep-disordered breathing of the Cheyne-Stokes variety occurs frequently in stable patients with severe CHF. Oxygen therapy and nasal CPAP therapy are equally effective in decreasing the AHI and improving nocturnal oxygenation in these patients. Different mechanisms may be responsible for the improvements in sleep-disordered breathing found with these two treatment modalities. Future investigation should focus on comparing the effects of oxygen therapy and nasal CPAP therapy on left ventricular function, as well as on determining whether either therapy alters the mortality rate.
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Footnotes |
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Received for publication March 4, 1999. Accepted for publication July 23, 1999.
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