A Comparison of Reported Sleep Disorders in Patients on Chronic Hemodialysis and Continuous Peritoneal Dialysis

A Comparison of Reported Sleep Disorders in Patients on Chronic Hemodialysis and Continuous Peritoneal Dialysis Jean L. Holley, MD, Sheryl Nespor, CRNP, and Raymond Rault, MD • There are few data about the prevalence and characteristics of reported sleep disorders in chronic dialysis patients and, although insomnia is often used as a marker of uremia, there are few data relating complaints of sleep to adequacy of dialysis. We therefore surveyed 48 hemodialysis (HD) patients, 22 continuous peritoneal dialysis (PO) patients, and 41 healthy control subjects about disordered sleep. The questionnaire included demographic data, questions characterizing the reported sleep problems, and linear analogue scales quantitating the severity of the sleep disturbance and feelings of anxiety, worry, and sadness. Kt/V determinations were also made for each dialysis patient. Fifty-two percent of the HD, 50% of the PO, and 12% of the control subjects reported problems sleeping (P < 0.001, all dialysis patients v controls). No differences between HD and PO in characteristics of sleep problems were seen. Sleep severity scale results confirmed sleep disorders (7.2 in those with v 0.95 in those without sleep disorders, where 0 = sleep a little problem and 10 = a big problem, P < 0.001). Caffeine intake (P < 0.05) and worry (P < 0.004) were the only factors associated with reported sleep disturbances. Kt/V values (1.4 ± 0.3) did not predict reported sleep problems. Mean reported hours of sleep per night (5.5 ± 2 v 5.8 ± 1.4) and desired hours of sleep per night (8.3 ± 2 v 7.6 ± 1.3) were similar among dialysis patients and controls reporting sleep problems. Dialysis patients and controls without self-reported sleep disorders slept a mean of 7.1 ± 2.4 and 7 ± 1.1 h/night, respectively. These reported hours of sleep per night were not statistically different between those with and without self-perceived sleep disorders. More dialysis patients reported restless legs (30/36 v 1/7 controls, P < 0.009). Nighttime waking (80% of dialysis patients and 71% of controls), early moming waking (72% of dialysis patients and 57% of controls), and trouble falling asleep (67% of dialysis patients and 86% of controls) were similar in the control subjects and the dialysis patients. Further study of sleep disorders in dialysis patients is needed. © 1992 by the Natio,!al Kidney Foundation, Inc. INDEX WORDS: Dialysis; insomnia; hemodialysis; peritoneal dialysis.

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ETWEEN 14% to 42% of the general population report problems sleeping. 1 Although insomnia is often included in studies of somatic complaints of dialysis patients2 and may be a criterion for adequacy of dialysis, 3 little is known about the prevalence and characteristics of sleep disorders among patients on chronic dialysis. Medical conditions that cause pain, anxiety, and depression, 4 caffeinated beverages, 5 and cigarette smoking6 have been associated with problems sleeping. Sleep apnea, 7 periodic leg movements of sleep, 8 and restless legs syndrome9 are common in dialysis patients and may cause sleep disturbance, but other factors contributing to sleep disorders in dialysis patients have not been reported. Some have suggested that sleep disorders may be more common in hemodialysis (HD) than peritoneal dialysis (PD) patients,2 but few comparFrom the Renal-Electrolyte Division, University of Pittsburgh and Presbyterian University Hospital, Pittsburgh, PA. Portions of the data have been previously reported in the ASAIO Transactions, 1991 and the Journal of the American Society of Nephrology, September 1991. Address reprint requests to Jean L. Holley, MD, RenalElectrolyte Division, University of Pittsburgh, F 1159 Presbyterian University Hospital, Pittsburgh, PA 15213. © 1992 by the National Kidney Foundation, Inc. 0272-6386/92/1902-0008$3.00/0 156

ative studies have been performed. We therefore surveyed chronic HD and PD patients to investigate the prevalence of sleep disorders and to characterize the reported sleep disorders in these patients. METHODS

Patients and Controls All patients receiving chronic HD at the University of Pittsburgh outpatient dialysis center were asked to complete the questionnaire. Five patients refused; 48 patients participated. The questionnaire was explained to each patient and informed consent (under the guidelines of the University of Pittsburgh Institutional Review Board for Biomedical Research) was obtained by one of us (S.N.) during a routine HD treatment. Twenty-two patients undergoing continuous PD (either continuous ambulatory peritoneal dialysis [CAPD] or continuous cycling peritoneal dialysis [CCPD]) at the same dialysis center completed the questionnaire during a routine clinic visit. No PD patient refused to participate in the study. Forty-one control subjects also completed the questionnaire. These individuals were healthy adults working at either the outpatient dialysis facility or a local manufacturing plant.

Questionnaire The questionnaire consisted of three parts: demographic data, yes/no responses to questions about sleep problems, and a linear analogue scale lO,ll quantitating the severity of the reported sleep disorder and characterizing three personality traits. The demographic data obtained on each dialysis patient and control subject included age, gender, use of sleeping medi-

American Journal of Kidney Diseases, Vol XIX, No 2 (February), 1992: pp 156-161

SLEEP DISORDERS IN HD AND PO PATIENTS Table 1. Demographic Data

(n

Age (yr) Men/women No. with sleep problems (%) Time on dialysis ,.;1 yr 1-3 yr >3 yr

HD = 48)

(n

PB = 22)

Controls (n = 41)

51 ± 18 18/30

43 ± 13 11/11

43 ± 11 12/29

25 (52)

11 (50)

7 (12)*

7 8 33

10 4 8t

, P < 0.001, controls versus all dialysis patients. t P < 0.02. cation, presence of bone pain, arthritis, asthma, pruritus, use of cigarettes, and caffeine intake (cups of coffee and cans of caffeinated soft drinks consumed per day). Additionally, dialysis patients designated the time they had been on maintenance dialysis, whether they were receiving recombinant human erythropoietin, and whether they had problems sleeping before they started dialysis. Patients and control subjects who responded yes to the question, "Is trouble sleeping a problem for you now?" answered eight additional questions characterizing the reported sleep disorder (Appendix). All patients and control subjects completed questions scored by a linear analogue scale quantitating the sleep disorder and characterizing the respondent's degree of anxiety, worry, and sadness (Appendix). Data were obtained from patient and subject reports only; no objective timing of hours sleeping was performed. Bed partners of patients and subjects were not surveyed about nocturnal arousals or sleep times. KtjV was determined for each dialysis patient. Predialysis and postdialysis blood urea nitrogen levels, blood flow rate, dialysis treatment time, and patient weight were used to calculate KtjV values in the hemodialysis patients. Kt/V determinations for peritoneal dialysis patients were calculated using the formula: (DIP urea X 24 hour drain volume X 7 days)/ patient weight X 0.6, where D/P urea is assumed to be 1, and 0.6 is the estimated urea distribution for men; 0.55 was used as the estimated urea distribution for women. 12 All patients were dialyzed with cuprophane dialyzers, which were not reused.

Statistical Analysis Chi-square analysis and Fisher's exact test, where appropriate, were used to compare proportions among groups. Unpaired and paired Student's t tests were used to compare nominal data. Data obtained from the linear analogue scales followed a non parametric distribution and were analyzed by the Mann-Whitney test; median values for these determinations are reported. All other data are given as mean values ± SD. Significance was accepted as a P value less than or equal to 0.05.

RESULTS

The demographic data for the hemodialysis and peritoneal dialysis patients and the control

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subjects are shown in Table 1. More dialysis patients reported problems sleeping (P < 0.001). Sleep disorders affected HO and PO patients equally (52% and 50% of patients, respectively). HO and PO patients differed only by the time on maintenance dialysis; HO patients had been on dialysis significantly longer than PO patients. Thirty-three of the 48 HO patients (69%) and eight of22 (36%) PO patients had been on dialysis for 3 or more years. Because time on dialysis was not associated with reported sleep disturbances (P = 0.10) and characteristics of reported sleep problems and personality traits were not different between the HO and PO patients, they were combined as dialysis patients for all subsequent data evaluations. Table 2 compares dialysis patients and control subjects by somatic complaints, the use of cigarettes and caffeine, and self-reported scores for sadness, anxiety, and worry. The characteristics of the 36 dialysis patients with and the 34 patients without sleep disorders are illustrated in Table 3. The severity of the reported sleep disorder scored by the linear analogue scale confirmed the yesj no responses to the question, "Is trouble sleeping a problem for you now?" (median score, 7.2 in patients reporting sleep disorders v 0.95 in those without problems sleeping, P < 0.001 by MannWhitney test). No differences between patients with and without reported sleep disturbances were seen in reported weekly alcohol intake or the use of recombinant human erythropoietin

Table 2. Characteristics of Dialysis Patients and Controls Dialysis Patients (n = 70)

Sleep disorder Arthritis Bone Pain Pruritus Cigarette use Caffeine intake> 1 cup or can/d Sadness' Anxiety' Worry'

Controls (n = 41)

p

36 (51%) 26 (37%) 23(33%) 40(57%) 24(34%)

7(12%) 7(17%) 5(12%) 1 (2%) 7(17%)

0.001 0.09 0.04 0.001 0.07

35(50%) 2.8 5.0 3.9

34(83%) 1.8 4.5 6.0

0.005 0.02 0.86 0.08

, Median values for linear analogue scales. Significance was assessed by the Mann-Whitney test. 0 = rarely sad, rarely worry, calm; 10 = often sad, often worry, anxious.

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HOLLEY, NESPOR, AND RAULT

Table 3. Characteristics of Dialysis Patients With and Without Sleep Disorders With Sleep Disorder (n = 36)

Sleep severity (range)* Sleeping medicine Cigarette use Caffeine intaket Pruritus Bone pain Sadness' Anxiety' Worry' KT/V

Without Sleep Disorder (n = 34)

Dialysis Patients (n = 36)

0.95 (0.95-6.2)

0.001

8 14 (39%) 10 = 0,9 17"" 1.1 23(64%) 15 (42%) 3.3 5.3 5.1 1.4 ± 0.3

0 10 (29%) 15 = 0, 1 18",,1.1 17 (50%) 8 (24%) 2.7 4.4 2.8 1.4 ± 0.3

0.003 0.40 0.05

1

:s;

1

Controls (n = 7)

p

p

7.2 (0.2-10)

:s;

Table 4. Characteristics of Sleep Disorder

0.24 0.10 0.27 0.12 0.004 NS

, By linear analogue scales, median values given: sleep severity where 0 = a little problem, 10 = a big problem; 0 = rarely sad, calm, rarely worry; 10 = often sad, anxious, often worry. t By cups of coffee or cans of caffeinated soft drinks consumed per day. .

the use of recombinant human erythropoietin (22/36 patients with and 14/34 patients without sleep disorders were receiving erythropoietin). Table 4 shows the reported hours of nighttime sleep and daytime napping for the seven control subjects and the 36 dialysis patients reporting problems sleeping. The reported hours of sleep per night in the dialysis patients and controls without sleep problems (7.1 ± 2.4 and 7 ± 1.1 hours, respectively) were not significantly different from the patients and controls with perceived sleep disorders. Significantly more dialysis patients napped (20/36 v 1/7 controls, P < 0.0001 by Fisher's exact test). When the time of daytime napping and the hours of nighttime sleep were combined and compared with the desired hours of sleep, a significant difference was found (6.2 v 8.3 hours, P < 0.001 by paired t test). The mean reported duration of the sleep disorder was 6.8 years, with a range of 2.7 to 10.8 years. Sleep disorders occurring before the initiation of dialysis were not associated with current sleep disorders in dialysis patients (11/34 v 12/35, X2 = 0.3, P = 0.86). The characteristics of the sleep disturbances experienced by the dialysis patients are listed in Table 5. Most patients reported multiple distur-

Mean hours sleep/night Desired hours/night Hours daytime napping

5.5 ± 2.0 8.3 ± 2.0 1.1 ± 1.3

5.8 ± 1.4 0.14 7.6 ± 1.3 0.12 0.0001

o

bances. Only one patient reported leg jerking without restless legs. The distribution of sleep disturbance characteristics among the seven control subjects reporting problems sleeping were similar to those noted by the dialysis patients with the exception of restless legs (1/7 controls v 30/ 36 dialysis patients, P < 0.009 by Fisher's exact t test). The reported frequencies of insomnia (6/ 7, 86%), nighttime waking (5/7, 71 %), early morning waking (4/7,57%), and jerking legs (0/ 7) in control subjects were not different from those reported by dialysis patients. DISCUSSION

Complaints related to sleep were reported by half of the dialysis patients and equally among patients on HD and continuous PD. Few (12%) of our control subjects reported problems sleeping. Age, gender distribution, cigarette use, arthritis, asthma, anxiety, and worry were not different among the control and dialysis patients. Bone pain, pruritus, and sadness were reported significantly more often by dialysis patients and thus could contribute to the higher prevalence of sleep complaints in dialysis patients. More control subjects noted insomnia as the primary disorder of sleep, consistent with previous reports, 13 but the characteristics of the sleep disorders recorded by the dialysis and control groups were not significantly different. Significantly more HD patients complained of bone pain (20/48 v 3/22, X2 = 5.37, P = 0.02) and were receiving erythropoietin (30/48 v 6/22, Table 5. Dialysis Patients' Reported Symptoms of Sleep Disorder (n = 36) Trouble falling asleep Nighttime waking Early AM waking Restless legs Jerking legs

24(67%) 29(80%) 26(72%) 30(83%) 10 (28%)

SLEEP DISORDERS IN HD AND PO PATIENTS

x2 =

7.5, P = 0.006), but these factors were not associated with reported sleep problems. HD patients had been on chronic dialysis therapy longer than PD patients and thus could be expected to have more severe anemia and osteodystrophy. Little data about the prevalence of sleep disorders in HD versus PD patients exist. Barrett et al, in a report about somatic symptoms experienced by dialysis patients, noted that sleep disturbance affected HD patients more than CAPD patients (40% v 22%, respectively).2 Differences in the survey tools may explain the fact that more of our PD patients (and in numbers equal to HD patients) reported sleep disturbances. Because the biochemical and humoral factors involved in normal and abnormal sleep are poorly understood, the contribution of uremic factors to sleep disorders is speculative. Sleep promoting substances such as factor Sand interleukin-1 (IL7)7,13 have been found in the dialysate effluent of CAPD patients, raising the possibility of altered metabolism and/or a loss of sleep-promoting substances contributing to the chronic insomnia reported by these patients. 14 However, only four CAPD patients were included in Moldofsky's study, and the levels of IL-1 and factor S in the effluent of control patients (those without complaints of sleep) were not provided. 14 More study of the humoral and biochemical controls of sleep, particularly related to dialysis patients, is needed. There are few formal studies of the influence of adequacy of dialysis on sleep disturbance in dialysis patients. Two available polysomnographic studies of patients with chronic renal failure suggest a correlation between sleep disturbance and blood urea nitrogen levels. IS ,16 Unfortunately, the biochemical data were not provided in these abstracts. Available data about sleep apnea in dialysis patients include biochemical measures of dialysis efficacy. In most of these studies, no relationship between serum creatinine or blood urea nitrogen levels and sleep apnea was noted. s Similarly, periodic leg movements, reported commonly in polysomnographic studies of dialysis patients, S,17 have not been associated with levels of blood urea nitrogen and creatinine. In our study, reported sleep disturbances were not associated with low KtjV determinations. Moreover, our patients have acceptable Kt/V values, yet half of them reported problems sleeping. Thus, the data from this study support pre-

159

vious studies that noted no relationship of sleep disorders to biochemical parameters of dialysis efficacy. s, 17 Dialysis patients scored higher than the control subjects on the sadness scale, but the scores for anxiety and worry were not different between dialysis and control subjects (Table 2). However, high sadness scores were not associated with reported sleep disorders. Depression in chronic dialysis patients has long been recognized. IS Likewise, people suffering from chronic insomnia often have depressive features. 19 However, in this study, although dialysis patients scored significantly higher on the sadness scale, there was no difference in feelings of sadness between dialysis patients with and without reported sleep disorders. In contrast to sadness and anxiety, dialysis patients with sleep complaints scored significantly higher on the worry scale (5.1 v 2.8, P < 0.004). Previous studies of patients with chronic insomnia have noted the tendency of such patients to worry.13 Formal personality testing was not performed in this study, but the data obtained from the linear analogue scales are consistent with those previously reported. 4,13 The consumption of caffeinated beverages was associated with the presence of sleep complaints in dialysis patients (Table 3). Control subjects drank significantly more caffeinated beverages than did the dialysis patients (34/41 controls v 35/70 dialysis patients drank> 1 cup or can of caffeinated beverage/d, X2 = 11.9, P < 0.005). The fluid-restricted diet prescribed for chronic dialysis patients explains this difference. Caffeine and coffee intake can contribute to complaints of sleep disorder. s Our study validates this finding and extends it to chronic dialysis patients. Cigarette use can also contribute to sleep disorders. 6 When only HD patients were studied, the use of cigarettes was associated with reported sleep disorders. 20 However, with the inclusion of the PD patients, cigarette use was no longer associated with reported sleep disturbance (Table 3). Cigarette use by control subjects was not associated with reported sleep disorders. The small numbers of patients and subjects who smoked cigarettes could have contributed to the results noted. The use of recombinant human erythropoietin has significantly reduced anemia in dialysis pa-

160

tients and promoted concomitant improvements in dialysis patients' quality of life. Some have reported an improvement in insomnia in dialysis patients treated with erythropoietin. 21 However, in our study, the use of erythropoietin did not affect sleep complaints. Long-term studies of reported sleep disturbances and polysomnographic recordings before and after erythropoietin may help elucidate the role of anemia in the sleep disorders experienced by dialysis patients. Patients complaining of insomnia often underestimate their hours of sleep. 22 Because formal sleep studies were not performed on our patients, it is likely that patients and controls underestimated their actual hours of sleep. Although both the patients and controls reporting sleep disorders reported sleeping fewer hours than their counterparts without perceived sleep disorders, the difference in mean reported hours of sleep per night was not significant for either group. However, both controls and dialysis patients reporting sleep disorders desired significantly more hours of sleep. Only one control subject reported daytime napping. This finding was not unexpected because, unlike the dialysis patients, all of the controls were employed. Dialysis patients may experience sleep apnea 7 and periodic leg movements 8 , 17 during sleep. Restless legs syndrome is also well recognized in this population,9 yet there are little data about the prevalence of this syndrome in dialysis patients. More than 80% of the dialysis patients reporting problems sleeping complained of restless legs (Table 5). Only one control subject reported restless legs (1/7 v 30/36, P < 0.0009 by Fisher's t test). An assessment of restless legs in dialysis patients without sleep disturbance is needed. Formal sleep studies of chronic dialysis patients have consistently noted periodic movements of sleep, but not always in the range required for a diagnosis of nocturnal myoclonus. 8, 17 We did not interview bed partners or perform formal sleep studies of the dialysis patients reporting sleep disorders, so the occurrence of periodic movements of sleep may be underestimated. Recent therapeutic options for restless legs syndrome and periodic movements of sleep23,24 may provide the impetus for further investigation of these problems in dialysis patients.

HOLLEY, NESPOR, AND RAULT

The other reported symptoms of sleep disturbance in our dialysis patients (Table 5) are similar to those reported by the general population, except that insomnia is the most common complaint in the general populationY In our study, no significant differences in symptoms of sleep disturbance were seen among the dialysis patients and the control subjects. In summary, 50% of chronic dialysis patients reported sleep disorders. The type of dialysis and dialysis adequacy (as determined by Kt/V) did not affect the prevalence of sleep disorders. Worry and caffeine intake contributed to complaints of sleep in dialysis patients. Further study of the nature and causes of disordered sleep in dialysis patients, particularly related to restless legs syndrome, is needed. ACKNOWLEDGMENT We thank Drs Beth Piraino and R. Samuel Arthur for reviewing the manuscript.

APPENDIX Patient and Subject Questionnaire I. Is trouble sleeping a problem for you now? _yes _no 2. How big a problem is sleep, or lack of sleep, to you?

A Little Problem

2. 3. 4. 5.

A Big Problem

If answer to no. I above = no, skip to question no. 6 If answer to no. I above = yes, continue with question no. 2 How much sleep do you usually get each night? _ _ How much sleep would you like to get each night? _ _ Do you nap during the day? _ yes _ no For how long? _ Do you have: Trouble falling asleep _ yes _ no Awakening during the night _ yes _ no Early morning waking _ yes _ no _ yes _ no Restless legs Jerking of your legs at night _ yes _ no

6. Describe yourself: Calm Rarely Worry Rarely Sad

Anxious Often Worry Often Sad

SLEEP DISORDERS IN HD AND PD PATIENTS

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14. Moldofsky H, Krueger JM, Walter J, et al: Sleep-promoting material extracted from peritoneal dialysate of patients with end-stage renal disease and insomnia. Perit Dial Bull 5: 189-193, 1985 15. Reichenmi1ler HE, Reinhard V, Durr F: Sleep EEG and uremia. Electroencephalogr Clin Neurophysiol 30:263264, 1971 (abstr) 16. Passouant P, Cadilhac J, Baldy-Moulinier M, et al: Nocturnal sleep in chronic uremic patients undergoing extrarenal detoxication. Electroencephalogr CIin Neurophysiol25: 91-92, 1968 (abstr) 17. Mendelson WB, Wadhwa NK, Greenberg HE, et al: Effects of hemodialysis on sleep apnea syndrome in end-stage renal disease. Clin NephroI33:247-251, 1990 18. Sachs CR, Peterson RA, Kimmel PL: Perception of illness and depression in chronic renal disease. Am J Kidney Dis 15:31-39, 1990 19. Kales A, Caldwell AB, Preston TA, et al: Personality patterns in insomnia: Theoretical implications. Arch Gen Psychiatry 33:1128-1134, 1976 20. Holley JL, Nespor S, Rault R: Characterizing sleep disorders in chronic hemodialysis patients. ASAIO Trans 37: M456-M457, 1991 (abstr) 21. Delano BG: Improvements in quality of life following treatment with r-Hu-Epo in anemic hemodialysis patients. Am J Kidney Dis 14:14-18, 1989 (suppl1) 22. Carskadon MA, Dement WC, Mitler MM, et al: Selfreports versus sleep laboratory findings in 122 drug-free subjects with complaints of chronic insomnia. Am J Psychiatry 13: 1382-1388, 1976 23. Bernick C, Lee SM, Sandjk R, Stern LZ: The effects of L-Dopa in uremic patients with restless legs syndrome. Neurology 36:161, 1986 (suppl 1, abstr) 24. Krueger BR: Restless legs syndrome and periodic movements of sleep. Mayo CIin Proc 65:999-1006, 1990