To maintain healthy circadian rhythm of sleep and waking is an important element of life cycle. It is very common to complaint sleep problems from ESRD patients. In clinical setting, a lot of burdens were borne by sleep disturbance in ESRD patients. There is a battery of reports about sleep disturbances in HD patients.
A very high prevalence of subjective sleep complaints has been reported by over 50-80% of patients surveyed [12, 13, 14, 15, 16, 17, 19]. ESRD directly affected QOS, and therefore impacted the QOL [15]. Performing a more complete comprehending the sleep problems occurred by HD patients is important if developing better health outcomes is the object.
1. Sleep Disturbances in Dialysis Patients
Sleep problems are always existence from general population to ESRD patients.
Daly and Hassall reported one of the earliest studies about sleep problem in 34 HD patients in 1970 [36]. It was noted that patients slept less on nights following dialysis. Total sleep time is apparently deceased and poor recovery of physical energy. Strub et al in their analysis illustrated that 63% of a sample of 22 HD patients reported subjective sleep disturbance represented by diminished sleep efficiency, portioned sleep, and more time lying awake in bed [37]. This was one of the earliest studies reported the prevalence of sleep complaints in HD patients. They
found that there was no difference in age, personality, or medications between subjects with sleep symptoms and those without. The limits of this study were small sample size and without controlling variables that affect sleep quality.
In 1992, Holly et al. assessed the prevalence of 48 HD patients, 22 peritoneal dialysis (PD) patients, and 41 control subjects [12]. Fifty-two percent of HD, 50%
of PD and 12% of control subjects reported sleeping problems. Caffeine intake and worry were associated with sleep disturbance. The same authors reported that jerking legs (28%), trouble falling asleep (67%), early morning waking (72%), nighttime waking (80%), and restless legs (83%) were the major complaints by HD patients [38]. The prevalence of self-reported sleep complaints was equal in HD and PD patients in this study. Walker et al. [14] described the extent, severity, and types of subjective sleep disturbance with a sleep questionnaire in a 64 HD patients units.
Fifty-four patients completed the survey and 83% of subjects had sleep-wake complaints. The most common complaints included daytime sleepiness (66.7%), daily naps (59.2%), restless leg syndrome (RLS) (57.4%), disturbed sleep (51.8%), and use of sleeping medication (46.3%). Twenty-eight patients reported disturbed sleep characterized by delayed sleep onset, frequent awakening, RLS causing disturbed sleep, or generalized restlessness during the night. Their data revealed that RLS had an association with levels of urea and creatinine. Another complaint was often claimed to clinical team by HD patients. Which was daily sleepiness. In 1994, a study reported trouble sleeping and daily sleepiness were highly ranked in the KDQOL bothersome symptoms in HD patients from 9 different outpatient dialysis center located in California [34].
Winkelman et al. [39] designed a study to investigate the incidence of RLS in HD patients and to identify associated factors in 1996. They studied 204 HD patients with questionnaire about symptoms of RLS, sleep habits, pruritus, and
adherence to dialysis therapy. The study used 129 patients with heart disease as control group. ESRD patients received laboratory tests and sensory nerve amplitudes recorded. Twenty percent of the HD patients and 6 % of the control subjects reported moderate to severe RLS. Sleep onset with delay and reduction of total sleep time in HD patients compared to control group. RLS were correlated with sleep measures and pruritus. Sleep complaints included nocturnal awakening, sleep onset latency, total sleep time diminished, use of sleep medications, and nocturnal leg movement. They found increased mortality in patients with RLS at a 2.5-year follow-up.
Benz et al. conducted a study to investigate predictors of mortality with reviewed the medical record in twenty-nine ESRD patients who had previously undergone polysomnography (PSG) between 1990 and 1993 [16]. They examine the associated between periodic limb movements (PLMS) in sleep and mortality in ESRD. Post 48 months follow-up, the patients with a PLMS index less than 20 had high mortality than patients with a PLMS index of 20 or greater. After controlling for the other risk factors, such as, urea reduction rate, albumin level, and hematocrit, comparing patients having greater PLMS index with patients having less PLMS index in survival rate still reached statistical significance. This study reported the potentially new predictors of mortality in ESRD patients with sleep disorders.
Sakami et al examined insomnia and the affecting effect on immune functions in 578 Japanese men without any toxic exposure [40]. The study found the prevalence of insomnia in 9.2% Japanese men. The insomniac men without any medical disorders had significantly lower interferon-gamma and ratio of interferon-gamma to interleukin –4 than non-insomniac men. A significantly lower interferon-gamma to interleukin-4 ratio was detected in men with insufficient sleep or difficulty initiating sleep. They conclude that the immune system could be negatively affected
by sleep quality in insomnia. In 2005, Erten et al. reported the similar finding that lower interleukin-6 and tumor necrosis factor-alpha was got in obstructive sleep apnea patients in maintenance HD with sleep complaints [41]
Olson et al. reported a study with questionnaire in 441 subjects age 34 to 69 years old from a community to measure the association between sleep-disordered breathing (SDB) in 1995 [42]. The hypertension, coronary artery disease, and occlusive vascular disease diagnosed by physician. They found that the prevalence of hypertension, coronary artery disease, and occlusive vascular disease were significantly increased in the subjects with SDB. Hanly and Pierratos found the mean serum creatinine was lower and higher mean serum bicarbonate in patients with nocturnal HD 8 hours during six or seven nights a week than same patients on conventional HD for 4 hours on each of three days per week [43]. There was significantly reduction in sleep apnea-hypopnea index from polysomnography study compared nocturnal HD with conventional HD. In 2001, the Framingham Heart Study matched the age, sex, and body mass index from subjects with polysomnography survey. Ninety subjects with SDB defined as a respiratory disturbance index (RDI) score > 90 percentile were compared with 90 low-RDI subjects [44]. Right ventricular wall thickness was significantly increased in subjects with SDB. Zoccali et al. [45] found sleep apnea inducing nocturnal hypoxemia, after that they recorded cardiovascular events during follow-up. They excluded patients on regular HD with primary sleep apnea, pulmonary diseases, and illness causing sleep apnea. The study found that the risk of cardiovascular increased 33 % in 1 % decrease in average nocturnal oxygen saturation.
In Italy, Sabbatini et al. organized a study that aimed to investigate sleep disturbances in 694 HD patients in 21 different HD units in Naples and its neighborhood with a specific questionnaire in 2002 [46]. In this study, the
prevalence of the HD patients with sleep disturbances was 86%. There was a significantly higher sleep disturbance in HD patients on dialysis greater than 12 months than patients on dialysis less than 12 months. The patients dialyzed in the morning were in higher risk of insomnia than patients dialyzed in the afternoon.
There was a significant difference in parathyroid hormone, pre-dialysis plasma values of creatinine and urea in the insomnia group compared with control group.
Mucsi et al. designed a cross-sectional study to assess the prevalence of sleep problems and examined their effect on quality of life in Hungary [47]. Their data revealed that 65% of the patients had at least one sleep disorder. The first sleep complaint was insomnia in 49% of patients. The prevalence of patients with sleep apnea syndrome was 32%. The prevalence of patients with RLS was 15 %. They concluded that sleep disorders was correlated to illness intrusiveness, a significant factor of health-related quality of life. Another cross-sectional study reported by Mucsi et al. in 2005 [17], the aim of the study was to investigate the relationship of RLS, insomnia and specific insomnia symptoms with health-related QOL in 333 HD patients. The prevalence of RLS was 14%. There were higher co-morbidity in patients with than without RLS. RLS was associated with impaired overall QOS and poorer QOL. Parker et al. designed a study with objective polysomnography measures to compare chronic kidney disease (CKD) patients with estimated GFR of 14.5 ml/min and HD patients with Kt/V > 1.2 (equivalent to GFR of 10-15 ml/min) [48]. They reported that the total sleep time and sleep efficiency were both reduced in chronic kidney disease patients without dialysis and HD patients in 2005. More wake after sleep onset, much periodic limb movement, longer sleep latency, lower efficiency in sleep, and less sleep time were also found in comparing HD group to CKD group. After matching the metabolic data in both groups, they suggested that the sleep problems of both groups might have different etiologies. The etiologies of
sleep disturbances in CKD patients might be due to functional and psychological factors. The sleep disturbances in HD patients might be due to intrinsic sleep disruption (arousals, apnoeas and limb movements).
Merlino et al. conducted a study to assess the prevalence of sleep disorders using a self-administered questionnaire in 883 ESRD patients in Italy [49]. The record included the demographic, lifestyle, clinical and laboratory data. The percentage of insomnia, RLS, sleep apnea syndrome, nightmares and excessive daytime sleepiness were 69.1%, 18.4%, 23.6%, 13.3% and 11.8%. The data revealed 80% of patients with at least one sleep disorder. The risk factors were older age, excessive alcohol intake, smoking, polyneuropathy and dialysis in the morning.
2. The factors influence sleep disturbance in HD patients
The etiologies of sleep disturbance in ESRD patients on maintaining HD are often multiple factors. Parker summarized the relevant factors to influence sleep disturbance in HD patients, such as disease-related factors, psychological factors, treatment-related factors, lifestyle factors, and demographic factors. (Figure 2-1) [50].
QOS in ESRD patients is an important issue confirmed by clinicians and researchers. QOS in ESRD patients includes the quantitative and qualitative aspects of sleep, it is rather subjective and variable between individuals. However, the QOS consists many of components. It is difficult to define and measure objectively due to complex aspects. Furthermore, QOS assessed outcome may be changing by subjective perceiving in quality. Finally, sleep quality measuring is influenced by study’s architectural design.
There are a lot of evidences link diseases and sleep disorder [12, 51, 52, 53], such as cardiovascular disease, rheumatoid arthritis, fibromyalgia, asthma, chronic obstructive pulmonary disease, hyperparathyrodism, and gastroesophageal reflux.
The hypertension, coronary artery disease, claudication, and stroke are significantly correlated sleep disturbance in HD patients [42]. Uremic patients with hyperparathyrodism or pruritus complaint sleep problem [12, 39, 46].
Figure 2-1. Factors potentially contributing to sleep disturbances in dialysis patients.
Source: Parker KP. Sleep disturbances in dialysis patients. Sleep Med Rev. 2003;
7(2):131-43.
Treatment-Related Factors
-Premature discontinuation of dialysis -Cytokine production during treatment -Rapid changes in fluid electrolyte and acid-base balance Sleep Disturbances in Dialysis Patients
-Changes in sleep architecture -Sleep apnoea syndrome -Restless legs syndrome
-Periodic limb movement disorder -Excessive daytime sleepiness
The most frequent psychological problems affecting sleep disturbances include depression, anxiety, stress, and worry in general population. Worry was found to associate reported sleep disturbances in patients under dialysis[12]. In 2002, Williams et al reported a large-population study (The Kidney Outcomes Prediction and Evaluation Study, KOPE) to identify the correlation between sleep disturbances and psychosocial problems [54]. There was significantly associated in higher levels of depressive symptom with sleep disturbance. HD patients with greater levels of anxiety had poor sleep behavior than HD patients without. Especially, the patients have been in trouble falling asleep and feeling tired in the morning. The similar relationship between anxiety, worry, and sleep disorders was reported in Hong Kong Chinese patients [55]. A study from Japan reported that the anxiety and emotion-oriented coping stress were significantly associated with restless leg syndrome in ESRD patients [56]. In 2005, Wuerth et al. reported that the estimated prevalence of depression in ESRD patients was 20-30% [57]. They surveyed 380 PD patients for depression with BDI. There was 49% of patients who had a BDI score of 11 or greater than 11. Eighteen percent of the patients received pharmacologic therapy and BDI score improved from mean 17.4 to 8.4 point.
Soldatos et al. reported that cigarette smoking contributed difficult falling asleep and increasing total time awake in 1980 [58]. The similar effect was reported in ESRD patients [12, 49]. Holley et al. and Walker et al. reported that caffeine drinking was associated with sleep problem [12, 14]. The other lifestyle factors influenced sleep disturbances was alcohol consumption [49]. The report from Hong Kong did not revealed the similar effect of alcohol and caffeine drinking in Chinese ESRD patients in continuous ambulatory peritoneal dialysis [55].
In human being, aging is a nature process and the length of sleep gradually decreased. There were reports that aging was the risk factors to sleep problems in
ESRD patients [14, 49, 59], but one report indicated no relation between age and sleep disturbances [12]. Male adult was associated with more sleep disturbances in ESRD patients [14, 60], even in pediatric dialysis patients [61]. More sleep complaints in white race had also been reported [59]. The clinical parameters influencing sleep disturbances in ESRD patients include blood urea nitrogen (BUN), creatinine [16, 46, 62], anemia [63], hypertriglyceridemia [13], hypercalcemia [64], and high serum phosphate [60]. The other independent risk factor for sleep disorders was dialysis shift in the morning [49, 65].