---------------------------SLEEP DISORDERS: OVERVIEW---------------------------
                                   STATEMENT
Sleep disturbances occur in about 12 to 25% of the general population in
industrialized countries,[1] often associated with situational stress, illness,
aging, and drug treatment.[2]  Approximately 45% of people with cancer have
been found to have a higher incidence of sleep disturbances than that of either
a general population or persons with nonmalignant medical conditions.[3]
Physical illness, pain, hospitalization, and the psychological impact of a
malignant disease may disrupt the sleeping patterns of persons with cancer.
Poor sleep adversely affects daytime mood and performance.  In the general
population, persistent insomnia has been associated with a higher risk of
developing clinical anxiety or depression.  Adequate sleep may increase the
cancer patient's pain tolerance.

Sleep consists of two phases: rapid eye movement (REM) and non-REM (NREM)
sleep.[4]  REM sleep, also known as "dream sleep", is the active or paradoxic
phase of sleep, in which the brain is active while the body is essentially
paralyzed.  NREM is the quiet or restful phase of sleep.  NREM, also referred
to as slow wave sleep, is divided into four stages of progressively deepening
sleep based on EEG findings.[2,5]

The stages of sleep occur in a repeated pattern or cycle of NREM followed by
REM, with each cycle lasting approximately 90 minutes.  The sleep cycle is
repeated 4 to 6 times during a 7 to 8 hour sleep period.[5]  Each cycle
consists of most or all of the stages of NREM followed by REM.  The sleep-wake
cycle is dictated by an inherent biological clock or circadian rhythm.
Disruptions in individual sleep patterns can disrupt the circadian rhythm and
impair the sleep cycle.[6]

Four major categories of sleep disorders have been defined by the Sleep
Disorders Classification Committee:
  1) disorders of initiating and maintaining sleep (insomnias)
  2) disorders of the sleep-wake cycle
  3) dysfunctions associated with sleep, sleep stages, or partial arousals
     (parasomnias)
  4) disorders of excessive somnolence.
References:
  1. Walsleben J: Sleep disorders.  American Journal of Nursing 82(6):
     936-940, 1982.
  2. Kaempfer SH:  Comfort: Sleep.  In: Johnson BL, Gross J, Eds.: Handbook of
     Oncology Nursing. New York: John Wiley & Sons, 1985, pp 167-184.
  3. Beszterczey A, Lipowski ZJ: Insomnia in cancer patients (letter).
     Canadian Medical Association Journal 116(4): 355, 1977.
  4. Guyton AC.:  Textbook of Medical Physiology. Philadelphia: WB Saunders,
     7th ed., 1986.
  5. Feirerman JR: Disordered sleep.  Emergency Medicine 2: 160-171, 1985.
  6. Taub JM, Berger RJ: The effects of changing the phase and duration of
     sleep.  Journal of Experimental Psychology: Human Perception and
     Performance 2(1): 30-41, 1976.


SLEEP DISORDERS: SLEEP DISTURBANCE IN CANCER PATIENTS

Cancer patients are at great risk for developing insomnias and disorders of the
sleep-wake cycle.  Insomnia is the most common sleep disturbance in this
population, and is most often secondary to physical and/or psychological
factors related to cancer and/or cancer treatment.  Anxiety and depression,
common psychological responses to the diagnosis of cancer, cancer treatment,
and hospitalization, are highly correlated with insomnia.[1-3]  Psychological
stress of having cancer is the most common psychological cause of insomnia.

Physical factors related to cancer include paraneoplastic syndromes associated
with steroid production, symptoms associated with tumor invasion (draining
lesions, GI and GU alterations, pain, obstruction, fever, cough, dyspnea),
pruritus, and fatigue.  Treatment-related factors include surgical pain,
administration of corticosteroids as chemotherapeutic agents, and symptoms
associated with treatment such as nausea, vomiting, frequent elimination, and
fatigue.[4]

Side effects of treatment that may affect the sleep-wake cycle include:[5]

  -pain
  -tension
  -anxiety
  -night sweats
  -GI disturbances (i.e., incontinence, diarrhea, constipation)
  -GU disturbances (i.e., incontinence, retention, GU irritation)
  -respiratory disturbances

Hypnotic drugs can also cause insomnia in cancer patients.  Insomnia is
produced by tolerance to or withdrawal from a wide variety of hypnotic agents
and other central nervous system depressants.  Sustained use of central nervous
system stimulants (e.g., amphetamines, caffeine, diet pills), hypnotics (e.g.,
glutethimide, pentobarbital, chloral hydrate, secobarbital sodium, amobarbital
sodium), cancer chemotherapeutic agents (especially antimetabolites),
anticonvulsants (e.g., phenytoin), adrenocorticotropin, oral contraceptives,
monoamine oxidase inhibitors, alpha-methyldopa, propranolol, atenolol, alcohol,
and thyroid preparations can cause insomnia.  In addition, withdrawal from
central nervous system depressants (barbiturates, glutethimide, chloral
hydrate, methaqualone, ethchlorvynol, alcohol, over-the-counter and
prescription antihistamine sedatives, and bromides), benzodiazepines, major
tranquilizers, tricyclic and monamine oxidase inhibitor antidepressants,
illicit drugs (e.g., marijuana, cocaine, phencyclidine, opiates), and agents
containing aspirin may cause insomnia.  The most commonly prescribed hypnotics
interfere with REM sleep resulting in increased irritability, apathy, and
diminished mental alertness.  Abrupt withdrawal of hypnotics may lead to many
symptoms including nervousness, jitteriness, and REM rebound.  Berlin defined
REM rebound as a "marked increase in REM sleep with increased frequency and
intensity of dreaming, including nightmares."[6]  The increased physiologic
arousal that occurs during REM rebound may be dangerous for patients with
peptic ulcers or a history of cardiovascular problems.

Hospitalized patients are likely to experience frequent interruptions of sleep
due to treatment schedules, hospital routines, and roommates, which singularly
or collectively alter the sleep-wake schedule.  Other factors influencing
sleep-wake schedules in the hospital setting include age, noise, temperature,
comfort, pain, and anxiety.[7]

Consequences of sleep disturbances can influence outcomes of medical and
supportive care measures.  The patient with mild to moderate sleep disturbances
might experience irritability and inability to concentrate, which may in turn
affect the patient's compliance with treatment protocols, ability to make
decisions, and relationships with significant others.  Depression and anxiety
can also be end-results of sleep disturbances.  Supportive care measures are
directed toward quality of life issues and promote adequate rest.
References:
  1. Coursey RD: Personality measures and evoked responses in chronic
     insomniacs.  Journal of Abnormal Psychology 84(3): 239-249, 1975.
  2. Freemon FR:  Sleep Research: A Critical Review. Springfield, IL: Thomas
     Publishing, 1972.
  3. Johns MW, Bruce DW, Masterton JP: Psychological correlates of sleep
     habits reported by healthy young adults.  British Journal of Medical
     Psychology 47(2): 181-187, 1974.
  4. Clark J, Landis L, McGee R:  Nursing management of outcomes of disease,
     psychological response, treatment, and complications.  In: Ziegfeld CR,
     Ed.: Core Curriculum for Oncology Nursing. Philadelphia: W.B. Saunders,
     1987, pp 271-319.
  5. Page M:  Sleep pattern disturbance.  In: McNally JC, Stair JC, Somerville
     ET, Eds.: Guidelines for Cancer Nursing Practice. Orlando, FL: Grune and
     Stratton, Inc., 1985, pp 89-95.
  6. Berlin RM: Management of insomnia in hospitalized patients.  Annals of
     Internal Medicine 100(3): 398-404, 1984.
  7. Webster RA, Thompson DR: Sleep in hospital.  Journal of Advanced Nursing
     11(4): 447-457, 1986.


MANAGEMENT OF SLEEP DISTURBANCES: ASSESSMENT

Assessment is the initial step in management strategies.  Assessment data will
include predisposing factors, sleep patterns, emotional status, exercise and
activity level, diet, symptoms, medications, and caregiver routines.[1]  The
sections below outline recommendations for a sleep history and physical
examination.  Data can be retrieved from multiple sources including the
patient's subjective report of sleep difficulty, objective observations of
behavioral and physiologic manifestations of sleep disturbances, and reports
from the patient's significant others regarding the patient's quality of
sleep.[2]

--Sleep history assessment--

Risk factors
The following factors may increase risk for sleep disorders:

  -disease factors including paraneoplastic syndromes with increased steroid
     production; symptoms associated with tumor invasion (e.g., obstruction,
     pain, fever, shortness of breath, pruritus, fatigue);
  -treatment factors including symptoms related to surgery (e.g., pain,
     frequent monitoring, narcotics); chemotherapy (e.g., exogenous
     corticosteroids); symptoms related to chemotherapy
  -medications such as narcotics, sedatives/hypnotics, steroids,
     caffeine/nicotine
  -environment
  -physical and/or psychological stress
  -depression
  -anxiety

Characterization of sleep
The following should be assessed in taking a sleep history:

  -usual patterns of sleep, including usual bedtime, routine prior to retiring
     (e.g., food, bath, medications), length of time before onset of sleep, and
     duration of sleep (awaking episodes during night, ability to resume sleep,
     and usual time to awaken)
  -characteristics of disturbed sleep (changes following diagnosis, treatment,
     and/or hospitalization)
  -perception of significant others on quantity and quality of patient's sleep
  -family history of sleep disorders
References:
  1. Kaempfer SH:  Insomnia.  In: Baird SB, Ed.: Decision Making in Oncology
     Nursing. Philadelphia: B.C. Decker, Inc., 1988, pp 78-79.
  2. Kaempfer SH:  Comfort: Sleep.  In: Johnson BL, Gross J, Eds.: Handbook of
     Oncology Nursing. New York: John Wiley & Sons, 1985, pp 167-184.


MANAGEMENT OF SLEEP DISTURBANCES: MANAGEMENT STRATEGIES

Management of sleep disturbances should focus on treatment of the underlying
malignancy and the identification and management of environmental and
psychological factors.  Management of sleep disturbances combines
non-pharmacologic and pharmacologic approaches individualized for the patient.

Treatment of the malignancy may resolve the sleep disturbance.  When sleep
disturbances are caused by symptoms of cancer or treatment, measures that
control or alleviate symptoms are often the key to resolving sleep
disturbances.

Non-pharmacologic strategies
The environment can be modified to decrease sleep disruption.  Minimizing
noise, dimming or turning off lights, adjusting room temperature, and
consolidating patient care tasks to decrease interruptions can increase the
amount of uninterrupted sleep.

Other actions or interventions that may promote rest include: [1,2]

  -keeping the patient's skin clean and dry
  -giving backrubs and/or massaging areas of the body the patient might find
     comforting (e.g., bony prominences, head and scalp, shoulders, hands,
     feet)
  -keeping bedding and/or surfaces of support devices (chairs, pillows) clean,
     dry, and wrinkle-free
  -ensuring adequate bedcovers for warmth
  -regulating fluid intake to avoid nocturia
  -encouraging bowel and bladder elimination before sleep
  -promoting optimal bowel function (increased fluids, fiber in diet, use of
     stool softeners and laxatives)
  -using condom catheter for nocturnal incontinence
  -providing high protein bedtime snack
  -avoiding beverages with caffeine
  -encouraging patient to dress in loose, soft clothing
  -facilitating comfort through repositioning and support with pillows as
     needed
  -encouraging exercise or activity no less than 2 hours before bedtime
  -providing a light snack
  -keeping regular bedtime and awakening hours

Psychological interventions are directed toward facilitating the patient's
coping processes through education, support, and reassurance.  As the patient
learns to cope with the stresses of illness and hospitalization, sleep may
improve.[3]  Communication and verbalization of concerns, and openness between
the patient, family, and health care team should be encouraged.

Pharmacologic management of sleep disturbances
When sleep disturbances are not resolved with other supportive care measures,
the use of sleep medications on a short-term or intermittent basis may be
necessary.  However, prolonged use of sleep medications for persistent insomnia
can impair natural sleep patterns (i.e., REM deprivation) and alter physiologic
functions.  Prolonged use (>1 to 2 weeks) may result in tolerance,
psychological and physical dependence, drug intoxication, and drug hangover.[4]
Agents used in the management of sleep disturbances are included in Table 1.

Benzodiazepines are currently the drug of choice in the management of sleep
disturbances.  Used as an adjunct to other treatment for short periods of time,
these agents are safer and more effective in producing natural sleep because
they are less disruptive of REM sleep than other hypnotic agents.
Benzodiazepines have an anti-anxiety effect in low doses and a hypnotic effect
in high doses.

Benzodiazepines differ from each other in duration of action and
pharmacokinetics.  Long-acting benzodiazepines are characterized by:
  1) half-lives > 24 hours
  2) pharmacologically active metabolites
  3) accumulation with multiple dosages, and
  4) impaired clearance in the elderly and those with liver disease.

Intermediate- and short-acting benzodiazepines have half-lives from 4 to 24
hours.  Active metabolites are uncommon in short-acting benzodiazepines,
accumulation with multiple doses is rare, and age and liver disease have a
minimal effect on drug clearance.  While long-acting agents may produce daytime
hangover, short-acting agents are more often associated with dependence,
rebound insomnia, early morning insomnia, daytime anxiety, and serious
withdrawal effects such as seizures.[3]

In general, non-benzodiazepines should be reserved for patients who cannot
tolerate benzodiazepines.  Antihistamines have become popular drugs for the
management of sleep disturbances among cancer patients.  The anticholinergic
properties of antihistamines relieve nausea and vomiting as well as insomnia.
These agents must be used with caution since daytime sedation and delirium can
occur.  Tricyclic antidepressants, such as amitriptyline or doxepin, may be
effective in patients who are depressed.  When given at bedtime, they can
eliminate the need for an additional hypnotic.  The hypnotic effects of
marijuana (tetrahydrocannabinol or THC) are similar to conventional hypnotics
in reducing REM sleep.  Side effects prior to sleep induction and hangover make
the THC less acceptable than benzodiazepines.[5]

Alcohol used in moderation may decrease tension and promote sleep in some
patients.  Aspirin is believed to promote sleep onset through increasing
serotonin action, which is thought to enhance the onset of sleep without
disrupting the normal sleep cycle.[4]

Barbiturates are generally not recommended for the management of sleep
disturbances in cancer patients.  Barbiturates have a number of adverse
effects, including the development of tolerance, and they also have a narrow
margin of safety.

Most hypnotics are effective initially, but lose efficacy when used regularly.
Patients can become dependent upon a hypnotic after only one week of regular
use.  Sleep medications can become a primary cause of sleep disturbances.[6]

                   TABLE 1: MEDICATIONS USED TO PROMOTE SLEEP

drug category      medication        hypnotic dose          onset (duration
                                     (route)                of action)
-------------      ----------        -------------          ---------------

benzodiazepines    diazepam          5-10 mg (capsule,      30-60 min
                   (Valium)          tablet)                (6-8 hours)

                   flurazepam        15-30 mg               1 hr
                   (Dalmane)         (capsule)              (24 hrs)

                   lorazepam         2-4 mg                 highly
                   (Ativan)          (capsule)              individual

                   oxazepam          10-30 mg               shorter than
                   (Serax)           (capsule,              diazepam
                                      tablet)

                   temazepam         15-30 mg               30 min
                   (Restoril)        (capsule)              (6-8 hrs)

                   triazolam         0.125-0.5 mg           shorter than
                   (Halcion)         (tablet)               flurazepam
                                                            (peaks 1-1.5
                                                             hours)

chloral            chloral hydrate   0.5-1.0 g              30-60 min
derivatives                          (capsule, syrup,       (4-8 hrs)
                                      suppository)

acetylinic         ethchlorvynol     0.5-1.0 g              15-30 min
alcohol            (Placidyl)        (capsule)              (4-5 hrs)

piperidinedione    glutethimide      250-500 mg             30 min
derivatives        (Doriden)         (capsule,              (4-8 hrs)
                                      tablet)

antihistamines     diphenhydramine   50-100 mg              10-30 min
                   (Benadryl)        (tablet, capsule,      (4-6 hrs)
                                      syrup)

                   hydroxyzine       25-100 mg              15-30 min
                   (Vistaril,        (tablet, capsule,      (4-6 hrs)
                    Atarax)           syrup)

                   promethazine      25-50 mg               20 min
                   (Phenergan)       (capsule,              (4-6 hrs)
                                      tablet, syrup,
                                      suppository)
References:
  1. Page M:  Sleep pattern disturbance.  In: McNally JC, Stair JC, Somerville
     ET, Eds.: Guidelines for Cancer Nursing Practice. Orlando, FL: Grune and
     Stratton, Inc., 1985, pp 89-95.
  2. Kaempfer SH:  Insomnia.  In: Baird SB, Ed.: Decision Making in Oncology
     Nursing. Philadelphia: B.C. Decker, Inc., 1988, pp 78-79.
  3. Berlin RM: Management of insomnia in hospitalized patients.  Annals of
     Internal Medicine 100(3): 398-404, 1984.
  4. Kaempfer SH:  Comfort: Sleep.  In: Johnson BL, Gross J, Eds.: Handbook of
     Oncology Nursing. New York: John Wiley & Sons, 1985, pp 167-184.
  5. Hollister LE: Health aspects of cannabis.  Pharmacological Reviews 38(1):
     1-20, 1986.
  6. Hayter J:  Advances in sleep research: implications for nursing practice.
      In: Tierney AJ, Ed.: Recent Advances in Nursing: Clinical Nursing
     Practice. Edinburgh, Scotland: Churchill Livingstone, 1986, pp 21-43.


SLEEP DISORDERS: SPECIAL CONSIDERATIONS

The patient with pain
The experience of pain may be heightened by the use of sleep medications.
Analgesics or non-pharmacologic pain management should be administered before
sleep medications.

The elderly
Elderly patients frequently have insomnia due to age-related changes in sleep.
The sleep cycle in this population is characterized by lighter sleep, more
frequent awakenings, and less total sleep time.  Anxiety, depression, loss of
social support, and a diagnosis of cancer are contributory factors in sleep
disturbances in the elderly.[1]

Providing a regular schedule of meals, discouraging daytime naps, and
encouraging physical activity may improve sleep.  Hypnotic prescriptions for
elderly patients must be adjusted for variations in metabolism and increased
sensitivity.  Dosages should be reduced by 30 to 50% (e.g., flurazepam 15 mg,
temazepam 15 mg, and triazolam 0.125 mg).  Problems associated with drug
accumulation (especially flurazepam) must be weighed against the risks of more
severe withdrawal or rebound effects associated with short-acting
benzodiazepines.  An alternate drug for elderly patients is chloral hydrate.[1]

Somnolence syndrome
Cranial irradiation and intrathecal methotrexate are used to prevent the
development of central nervous system (CNS) leukemia in children with acute
lymphocytic leukemia (ALL).  Somnolence syndrome (SS) is a complication of
cranial irradiation occurring in 30 to 50% of patients who receive over 2400
cGy at daily dose fractions of 150 to 200 cGy.  The syndrome may appear 4 to 6
weeks following completion of therapy.  SS is characterized by mild drowsiness
to moderate lethargy and, occasionally, low-grade fever.  The pathophysiology
is unknown, but electroencephalogram (EEG) and cerebral spinal fluid
abnormalities are detectable in affected children.  Whether the occurrence of
SS correlates with permanent CNS dysfunction and whether reduced daily
fractions affect the incidence or severity of late CNS dysfunction are subjects
of current research.[2]  While supportive care measures cannot prevent the
occurrence of SS, acknowledgement of the existence of this problem may prevent
or minimize anxieties for children and parents when symptoms of SS appear."

Sleep apnea following mandibulectomy
Anterior mandibulectomy can result in the development of sleep apnea.  All
patients with head and neck tumors who have had extensive anterior oral cavity
resection should be evaluated prior to decannulation of the tracheostomy tube.
Subsequent flap and/or reconstruction of the lower jaw seems to prevent the
development of sleep apnea.  In contrast, facial sling suspension of the lower
lip does not prevent the development of sleep apnea.[3]  Assessment for
symptoms and preparation for the appearance of symptoms in this population
provide indications for interventions related to sleep apnea.
References:
  1. Berlin RM: Management of insomnia in hospitalized patients.  Annals of
     Internal Medicine 100(3): 398-404, 1984.
  2. Littman P, Rosenstock J, Gale S, et al.: The somnolence syndrome in
     leukemic children following reduced daily dose fractions of cranial
     radiation.  International Journal of Radiation Oncology, Biology,
     Physics 10(10): 1851-1853, 1984.
  3. Panje WR, Holmes DK: Mandibulectomy without reconstruction can cause
     sleep apnea.  Laryngoscope 94(12, Part 1): 1591-1594, 1984.
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