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Respiratory Disorders and Quality of Sleep in Patients on the Waiting List for Lung Transplantation
Respiratory Disorders and Quality of Sleep in Patients on the Waiting List for Lung Transplantation N. Pascual, B. Jurado, J.M. Rubio, F. Santos, R. Lama, and A. Cosano ABSTRACT Background. The purpose of this study was to assess the quality of sleep and extent of respiratory disorders in patients awaiting lung transplantation as compared with a control group. Methods. From September 2003 to November 2003, 17 clinically stable patients on the waiting list for lung transplantation and 14 healthy controls (with similar age, gender, and body mass index) were studied. Diagnostic polysomnography (PSG) was carried out for all subjects. Results. Seventeen patients were included, 15 men and 2 women, aged 51 ⫾ 14 years. The indication for lung transplantation was emphysema in 7 cases, pulmonary fibrosis in 6, and “other” in 4. Patients awaiting lung transplantation had the following respiratory values: mean FEV1, 1105 mL (34% of predicted); PaO2, 54 mm Hg; and PaCO2, 44 mm Hg. Significant differences were found among the waiting-list patients in terms of predominance of light sleep, wakeful periods, and phase changes per sleep-hour, as compared with the control group. The recording of the respiratory events showed an apnea– hypopnea index of 6.13, sleeping time with SaO2 ⬍90% of 1.80%, and a mean number of significant desaturations (⬍4%) of 6.38. There were no statistically significant differences with respect to the control group. Conclusions. Poor quality of sleep was observed in patients awaiting lung transplantation as compared with a healthy control group. There was no evidence of more respiratory events or significant desaturations in these patients, probably due to the provision of supplementary oxygen therapy during the PSG.
V
ARIOUS sleep disorders have been described in subjects with respiratory conditions1,2 in addition to alterations in gas exchange parameters,3–5 such as the onset of hypoxemia attributed to nocturnal hypoventilation.6,7 However, nocturnal polysomnography (PSG) has not been used routinely to confirm these alterations. Therefore, a study aimed at analyzing the alterations in sleep patterns and the possible reduction in oxygen levels, despite optimum treatment, might be useful to identify those patients who could benefit from PSG to improve the management of their disease. This study was designed to assess the sleep quality and the extent of respiratory disorders during sleep in a population of patients awaiting lung transplantation for various pulmonary diseases, and also to determine possible differences when compared with a healthy control group.
PATIENTS AND METHODS From September 2003 to November 2003, 17 patients on the waiting list for lung transplantation were reviewed in the Department of Respiratory Sleep Disorders at our institution. Patients ⬍20 years or ⬎70 years, those clinically unstable at the time of the PSG, and those unable to complete the PSG were excluded from the study. Fourteen healthy volunteers were included as controls.
Study Material In both patients and controls, a polysomnographic study lasting 1 night was completed, with a monitoring time of at least 360 From the Department of Respiratory Diseases, University Hospital Reina Sofia, Cordoba, Spain. Address reprint requests to Dr Natalia Pascual Martı´nez, C/Isla Graciosa 10, Portal 2-4-2, 14011 Co´rdoba, Spain. E-mail: [email protected].
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.02.043
Transplantation Proceedings, 37, 1537–1539 (2005)
1537
1538 minutes. The PSG was carried out with a Compumedic Sleep VS Polysomnograph (Australia). Monitoring was carried out of two electroencephalographic channels (C4/A1 and C3/A2), electrooculogram, and submental and anterior tibial electromyogram. Oronasal airflow was monitored by a thermistor. The signal from a thoracic microphone was recorded. Thoracic and abdominal efforts were monitored by inductance plethysmography (Abbotsford, Australia). Electrocardiogram (EEG) and oxygen saturation (SaO2) data were recorded by digital pulse oximeter (Pulsox-7, Minolta). The recordings were read manually in accordance with recommendations by Rechtschaffen and Kales.8 Apnea was defined as the cessation of oronasal airflow for ⱖ10 seconds. Hypopnea was defined when a reduction of airflow of ⱖ50% was observed, accompanied by oxygen desaturation of ⱖ4%, with or without accompanying arousal. Presence of an arousal was established as the abrupt change in EEG frequency, including theta and alpha waves and/or frequencies ⬎16 Hz, excluding sleep spindles, and lasting ⬎3 seconds, assuming that the patient was asleep before and after the arousal. The apnea– hypopnea index (AHI) for each subject was defined as the number of apneas and hypopneas per hour of sleep. An AHI of ⱖ10 was considered abnormal. A diagnosis of upper airway resistance syndrome was established in those patients presenting daytime hypersomnia and a PSG respiratory arousals index of ⬎10 per hour of sleep. Hypoventilation was defined as the confirmation of nocturnal desaturations without associated obstructive apneas or hypopneas, accompanied by hypoxemia and daytime hypercapnia.
Statistical Analysis The quality of sleep and the existence of respiratory disorders in patients on the waiting list for lung transplantation were compared with a control group. Differences between both groups were analyzed using the unpaired Student’s t test. Differences were considered significant at P ⬍ .05.
RESULTS
Seventeen patients were included, 15 men and 2 women, with a mean age of 51 ⫾ 14 years and a body mass index (BMI) of 24.2 ⫾ 4.9. Fourteen healthy controls were also included, 8 men and 6 women, with a mean age of 52 ⫾ 16 years and a BMI of 26.2 ⫾ 5. The indication for lung transplantation was emphysema in 7 patients, pulmonary fibrosis in 6, cystic fibrosis in 3, and primary pulmonary hypertension in 1. The patient group presented a mean FEV1 of 1105 mL (34% of predicted), mean PaO2 of 54 mm Hg, and mean PCO2 of 44 mm Hg (on room air). The results of the PSG in relation to sleep architecture are shown in Table 1. We observed a significantly poorer quality of sleep in those patients awaiting lung transplantation compared with the control group, as documented by the greater predominance of light sleep, more fragmented sleep patterns with more phase changes per hour, and greater average time of wakefulness between sleep periods. Table 2 shows information regarding the respiratory events detected after analysis of the sleep studies. In the group of patients awaiting lung transplantation, the mean AHI and mean number of episodes of hypopnea per hour were greater than in the control group, but without a significant difference. In two patients, the AHI was ⬎15. A comparison
PASCUAL, JURADO, RUBIO ET AL Table 1. Parameters of Sleep Architecture in Both Study Groups Patients
Cycles/night Phase changes per sleep-hour Wakeful periods (%) Arousals/hour Total sleep time (TST) (min) Phase 1 ⫹ 2 (%) Phase 3 ⫹ 4 (%) REM (%)
Controls
P
2.82 ⫾ 1.13 9.65 ⫾ 2.61
3.21 ⫾ 0.9 9.11 ⫾ 7
NS .001
25.51 ⫾ 15 22.13 ⫾ 7.29 257.52 ⫾ 57
8.52 ⫾ 8 14.09 ⫾ 9 316.25 ⫾ 52
.013 NS NS
64 ⫾ 6 21.55 ⫾ 8.2 14.67 ⫾ 4
.043 NS NS
68.93 ⫾ 15 20.26 ⫾ 11 13.17 ⫾ 14
Data are expressed as mean ⫾ SD. NS, differences not significant. REM, rapid eye movement.
of the percentage of the whole sleep time when the SaO2 was ⬍90% (T90) showed no differences and only one patient was at ⬎5%. The mean number of major desaturations detected was small in both groups and differences were not significant. DISCUSSION
Despite numerous sleep studies carried out in different respiratory units, no studies, to our knowledge, have been directed at a population on the waiting list for lung transplantation. In this study we observed a poor quality of sleep in patients on the transplant waiting list compared with a healthy control group, as demonstrated by increased light phases, fragmented sleep, and frequent wakeful periods. However, unlike previous reports,1,3 we did not detect a larger number of respiratory events in our patients. This may be explained by the small sample size and, at least in part, by the administration of oxygen during the PSG, which is a determinant factor in the reduction of SaO2 and, therefore, influences the number of hypopneic episodes recorded during the PSG. The same applies to the gaseous changes described in subjects with sleep-related respiratory diseases,1,5 mainly hypoxemia, attributed to a nocturnal hypoventilation process.9 However, this was not observed in our patients. We found a small number of significant reductions in SaO2, probably due, as stated previously, to the need for supplementary oxygen therapy during the PSG. Patients with chronic obstructive pulmonary disease predominated in our study. These patients suffer from poor quality sleep.1,2 Their hypoxemia worsens significantly durTable 2. Records of Respiratory Events in Both Study Groups
Episodes of hypopnea/hour AHI CT90% ID4%
Patients
Controls
P
5.82 ⫾ 7.53 6.13 ⫾ 6 1.80 ⫾ 5 6.38 ⫾ 9
2.90 ⫾ 3.47 4.34 ⫾ 4.22 1.80 ⫾ 3.9 6.37 ⫾ 5.77
NS NS NS NS
Data are expressed as mean ⫾ SD. NS, differences not significant; AHI, apnea/hypopnea index. CT90%, sleeping time with SaO2 ⬍90%; ID4%, number of significant desaturations ⬍4%.
RESPIRATORY DISORDER AND SLEEP
ing sleep, especially during the REM phase and when severe hypoxemia already exists while the patient is awake.9 However, on the basis of our results, the addition of oxygen therapy adequately corrects the possible nocturnal desaturations described in these patients. Accepting the limitations of the small sample size in this study, unless there is a clinical suspicion of obstructive sleep apnea syndrome, our results do not support the indication for generalized PSG in patients awaiting lung transplantation.
REFERENCES 1. Fleetham J, West P, Mezon B, et al: Sleep, arousals and oxygen desaturation in chronic obstructive pulmonary disease. Am Rev Respir Dis 126:429, 1982 2. Calverley PMA, Brezinova V, Douglas NJ, et al: The effect of oxygenation on sleep quality in chronic bronchitis and emphysema. Am Rev Respir Dis 126:206, 1982
1539 3. Wynne JW, Block AJ, Hemenway J, et al: Disordered breathing and oxygen desaturation during sleep in patients with chronic obstructive lung disease (COLD). Am J Med 66:573, 1979 4. Perez-Padilla R, West P, Lertzman M, et al: Breathing during sleep in patients with interstitial lung disease. Am Rev Respir Dis 132:224, 1985 5. Tepper RS, Skatrud JB, Dempsey JA: Ventilation and oxygenation changes during sleep in cystic fibrosis. Chest 84:388, 1983 6. Ballard RD, Clover CW, Suh BY: Influence of sleep on respiratory function in emphysema. Am J Respir Crit Care Med 151:945, 1995 7. Gould GA, Gugger M, Molloy J: Breathing pattern and eye movement density during REM sleep in man. Am Rev Respir Dis 138:874, 1988 8. Rechtschaffen A, Kales A: A Manual of Standardized Terminology, Techniques and Scoring Systems for Sleep Stages of Human Subjects. Los Angeles, Calif: Brain Information Service– Brain Research Institute, University of California; 1968 9. Connaughton JJ, Catterall JR, Elton RA, et al: Do sleep studies contribute to the management of patients with severe chronic obstructive pulmonary disease? Am Rev Respir Dis 138: 341, 1988
V
ARIOUS sleep disorders have been described in subjects with respiratory conditions1,2 in addition to alterations in gas exchange parameters,3–5 such as the onset of hypoxemia attributed to nocturnal hypoventilation.6,7 However, nocturnal polysomnography (PSG) has not been used routinely to confirm these alterations. Therefore, a study aimed at analyzing the alterations in sleep patterns and the possible reduction in oxygen levels, despite optimum treatment, might be useful to identify those patients who could benefit from PSG to improve the management of their disease. This study was designed to assess the sleep quality and the extent of respiratory disorders during sleep in a population of patients awaiting lung transplantation for various pulmonary diseases, and also to determine possible differences when compared with a healthy control group.
PATIENTS AND METHODS From September 2003 to November 2003, 17 patients on the waiting list for lung transplantation were reviewed in the Department of Respiratory Sleep Disorders at our institution. Patients ⬍20 years or ⬎70 years, those clinically unstable at the time of the PSG, and those unable to complete the PSG were excluded from the study. Fourteen healthy volunteers were included as controls.
Study Material In both patients and controls, a polysomnographic study lasting 1 night was completed, with a monitoring time of at least 360 From the Department of Respiratory Diseases, University Hospital Reina Sofia, Cordoba, Spain. Address reprint requests to Dr Natalia Pascual Martı´nez, C/Isla Graciosa 10, Portal 2-4-2, 14011 Co´rdoba, Spain. E-mail: [email protected].
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.02.043
Transplantation Proceedings, 37, 1537–1539 (2005)
1537
1538 minutes. The PSG was carried out with a Compumedic Sleep VS Polysomnograph (Australia). Monitoring was carried out of two electroencephalographic channels (C4/A1 and C3/A2), electrooculogram, and submental and anterior tibial electromyogram. Oronasal airflow was monitored by a thermistor. The signal from a thoracic microphone was recorded. Thoracic and abdominal efforts were monitored by inductance plethysmography (Abbotsford, Australia). Electrocardiogram (EEG) and oxygen saturation (SaO2) data were recorded by digital pulse oximeter (Pulsox-7, Minolta). The recordings were read manually in accordance with recommendations by Rechtschaffen and Kales.8 Apnea was defined as the cessation of oronasal airflow for ⱖ10 seconds. Hypopnea was defined when a reduction of airflow of ⱖ50% was observed, accompanied by oxygen desaturation of ⱖ4%, with or without accompanying arousal. Presence of an arousal was established as the abrupt change in EEG frequency, including theta and alpha waves and/or frequencies ⬎16 Hz, excluding sleep spindles, and lasting ⬎3 seconds, assuming that the patient was asleep before and after the arousal. The apnea– hypopnea index (AHI) for each subject was defined as the number of apneas and hypopneas per hour of sleep. An AHI of ⱖ10 was considered abnormal. A diagnosis of upper airway resistance syndrome was established in those patients presenting daytime hypersomnia and a PSG respiratory arousals index of ⬎10 per hour of sleep. Hypoventilation was defined as the confirmation of nocturnal desaturations without associated obstructive apneas or hypopneas, accompanied by hypoxemia and daytime hypercapnia.
Statistical Analysis The quality of sleep and the existence of respiratory disorders in patients on the waiting list for lung transplantation were compared with a control group. Differences between both groups were analyzed using the unpaired Student’s t test. Differences were considered significant at P ⬍ .05.
RESULTS
Seventeen patients were included, 15 men and 2 women, with a mean age of 51 ⫾ 14 years and a body mass index (BMI) of 24.2 ⫾ 4.9. Fourteen healthy controls were also included, 8 men and 6 women, with a mean age of 52 ⫾ 16 years and a BMI of 26.2 ⫾ 5. The indication for lung transplantation was emphysema in 7 patients, pulmonary fibrosis in 6, cystic fibrosis in 3, and primary pulmonary hypertension in 1. The patient group presented a mean FEV1 of 1105 mL (34% of predicted), mean PaO2 of 54 mm Hg, and mean PCO2 of 44 mm Hg (on room air). The results of the PSG in relation to sleep architecture are shown in Table 1. We observed a significantly poorer quality of sleep in those patients awaiting lung transplantation compared with the control group, as documented by the greater predominance of light sleep, more fragmented sleep patterns with more phase changes per hour, and greater average time of wakefulness between sleep periods. Table 2 shows information regarding the respiratory events detected after analysis of the sleep studies. In the group of patients awaiting lung transplantation, the mean AHI and mean number of episodes of hypopnea per hour were greater than in the control group, but without a significant difference. In two patients, the AHI was ⬎15. A comparison
PASCUAL, JURADO, RUBIO ET AL Table 1. Parameters of Sleep Architecture in Both Study Groups Patients
Cycles/night Phase changes per sleep-hour Wakeful periods (%) Arousals/hour Total sleep time (TST) (min) Phase 1 ⫹ 2 (%) Phase 3 ⫹ 4 (%) REM (%)
Controls
P
2.82 ⫾ 1.13 9.65 ⫾ 2.61
3.21 ⫾ 0.9 9.11 ⫾ 7
NS .001
25.51 ⫾ 15 22.13 ⫾ 7.29 257.52 ⫾ 57
8.52 ⫾ 8 14.09 ⫾ 9 316.25 ⫾ 52
.013 NS NS
64 ⫾ 6 21.55 ⫾ 8.2 14.67 ⫾ 4
.043 NS NS
68.93 ⫾ 15 20.26 ⫾ 11 13.17 ⫾ 14
Data are expressed as mean ⫾ SD. NS, differences not significant. REM, rapid eye movement.
of the percentage of the whole sleep time when the SaO2 was ⬍90% (T90) showed no differences and only one patient was at ⬎5%. The mean number of major desaturations detected was small in both groups and differences were not significant. DISCUSSION
Despite numerous sleep studies carried out in different respiratory units, no studies, to our knowledge, have been directed at a population on the waiting list for lung transplantation. In this study we observed a poor quality of sleep in patients on the transplant waiting list compared with a healthy control group, as demonstrated by increased light phases, fragmented sleep, and frequent wakeful periods. However, unlike previous reports,1,3 we did not detect a larger number of respiratory events in our patients. This may be explained by the small sample size and, at least in part, by the administration of oxygen during the PSG, which is a determinant factor in the reduction of SaO2 and, therefore, influences the number of hypopneic episodes recorded during the PSG. The same applies to the gaseous changes described in subjects with sleep-related respiratory diseases,1,5 mainly hypoxemia, attributed to a nocturnal hypoventilation process.9 However, this was not observed in our patients. We found a small number of significant reductions in SaO2, probably due, as stated previously, to the need for supplementary oxygen therapy during the PSG. Patients with chronic obstructive pulmonary disease predominated in our study. These patients suffer from poor quality sleep.1,2 Their hypoxemia worsens significantly durTable 2. Records of Respiratory Events in Both Study Groups
Episodes of hypopnea/hour AHI CT90% ID4%
Patients
Controls
P
5.82 ⫾ 7.53 6.13 ⫾ 6 1.80 ⫾ 5 6.38 ⫾ 9
2.90 ⫾ 3.47 4.34 ⫾ 4.22 1.80 ⫾ 3.9 6.37 ⫾ 5.77
NS NS NS NS
Data are expressed as mean ⫾ SD. NS, differences not significant; AHI, apnea/hypopnea index. CT90%, sleeping time with SaO2 ⬍90%; ID4%, number of significant desaturations ⬍4%.
RESPIRATORY DISORDER AND SLEEP
ing sleep, especially during the REM phase and when severe hypoxemia already exists while the patient is awake.9 However, on the basis of our results, the addition of oxygen therapy adequately corrects the possible nocturnal desaturations described in these patients. Accepting the limitations of the small sample size in this study, unless there is a clinical suspicion of obstructive sleep apnea syndrome, our results do not support the indication for generalized PSG in patients awaiting lung transplantation.
REFERENCES 1. Fleetham J, West P, Mezon B, et al: Sleep, arousals and oxygen desaturation in chronic obstructive pulmonary disease. Am Rev Respir Dis 126:429, 1982 2. Calverley PMA, Brezinova V, Douglas NJ, et al: The effect of oxygenation on sleep quality in chronic bronchitis and emphysema. Am Rev Respir Dis 126:206, 1982
1539 3. Wynne JW, Block AJ, Hemenway J, et al: Disordered breathing and oxygen desaturation during sleep in patients with chronic obstructive lung disease (COLD). Am J Med 66:573, 1979 4. Perez-Padilla R, West P, Lertzman M, et al: Breathing during sleep in patients with interstitial lung disease. Am Rev Respir Dis 132:224, 1985 5. Tepper RS, Skatrud JB, Dempsey JA: Ventilation and oxygenation changes during sleep in cystic fibrosis. Chest 84:388, 1983 6. Ballard RD, Clover CW, Suh BY: Influence of sleep on respiratory function in emphysema. Am J Respir Crit Care Med 151:945, 1995 7. Gould GA, Gugger M, Molloy J: Breathing pattern and eye movement density during REM sleep in man. Am Rev Respir Dis 138:874, 1988 8. Rechtschaffen A, Kales A: A Manual of Standardized Terminology, Techniques and Scoring Systems for Sleep Stages of Human Subjects. Los Angeles, Calif: Brain Information Service– Brain Research Institute, University of California; 1968 9. Connaughton JJ, Catterall JR, Elton RA, et al: Do sleep studies contribute to the management of patients with severe chronic obstructive pulmonary disease? Am Rev Respir Dis 138: 341, 1988