There are numerous factors that may contribute to disturbed sleep in hospitalized patients, including primary sleep disorders, medical illnesses, psychiatric illness, drugs, and the hospital environment. Additionally, the manifestations of sleep disruption and/or sleep deprivation will vary depending on the individual.
By far, insomnia is the most common sleep complaint among patients in both ambulatory and hospital settings. The prevalence of chronic insomnia is high, with approximately 20–30% of the general population reporting ongoing symptoms. Chronic insomnia is associated with decreased quality of life, daytime functional limitations, chronic pain, increased risk of medical and psychiatric illnesses, substance abuse, increased utilization of health services, and increased risk of death.
Insomnia can manifest in several ways. The International Classification of Sleep Disorders (ICSD-2) published by the American Academy of Sleep Medicine (AASM) defines insomnia as difficulty initiating or maintaining sleep, waking up too early, or sleep that is chronically nonrestorative or perceived to be poor in quality. To meet diagnostic criteria for insomnia, these symptoms must be associated with daytime mental or physical sequelae that impair the functional status of the individual. Insomnia may be a primary disorder or may be comorbid with another physical or mental illness.
In the landmark Sleep Heart Health Study, population subgroups were identified who were at increased risk for poor sleep. Older individuals (> 60 years old) were shown to have a lower arousal threshold associated with increased awakenings at night, decreased sleep efficiency, and decreased REM quantity. Each of these changes contributes to poor sleep quality and can result in poor daytime functioning, excessive sleepiness, or cognitive changes, which are commonly noted in the elderly. Although women demonstrated increased SWS compared to men, they had more complaints of poor sleep quality associated with worsening daytime functioning. The precise reason for this is unknown but is speculated to involve hormonal influence as well as greater prevalence of comorbid conditions associated with insomnia, such as depression.
Other common primary sleep disorders that frequently coexist with medical illnesses include obstructive sleep apnea (OSA), restless leg syndrome (RLS), and periodic limb movement disorder (PLMD). Table 94-1 describes these common sleep disorders and provides differential diagnoses to consider. These disorders may present with a variety of symptoms.
Table 94-1 Clinical Features and Differential Diagnoses of Common Primary Sleep Disorders ||Download (.pdf)
Table 94-1 Clinical Features and Differential Diagnoses of Common Primary Sleep Disorders
|Sleep Disorder||Clinical Features||Differential Diagnosis|
|Obstructive sleep apnea (OSA)||Repetitive episodes of upper airway obstruction that occur during sleep, usually associated with oxygen desaturation. Episodes include loud snoring or gasps lasting 20–30 seconds. Associated with morning headaches and dry mouth.||Sleep-related laryngospasm, nocturnal gastroesophageal reflux, narcolepsy, hypersomnia, PLMD, central alveolar hypoventilation, paroxysmal nocturnal dyspnea, primary snoring, Cheyne-Stokes ventilation, nocturnal asthma.|
|Periodic limb movement disorder (PLMD)||Periodic episodes of repetitive and stereotyped limb movements: extension of the big toe with partial flexion of the ankles, knees, or hips. Muscle contractions last 0.5 to 5 seconds, with 20- to 40-second intervals between them.||Sleep starts (occurs just prior to, not during, sleep, and does not have a regular periodicity like PLMD), nocturnal epileptic seizures, myoclonic epilepsy.|
|Restless leg syndrome (RLS)||Uncomfortable leg sensations that occur prior to sleep onset that leads to an irresistible urge to move the legs. Described as “achy,” “crawling,” “pulling,” “prickling,” or “tingling,” and disrupts sleep onset.||Chronic myelopathy, peripheral neuropathy, akathisia, fasciculation syndromes. RLS may be triggred by iron deficiency anemia, so consider iron studies.|
|Sleep starts||Sudden, brief contraction of the legs that occurs at sleep onset. Usually benign, but may worsen during hospitalization, and interfere with sleep.||PLMD, RLS, hyperexplexia syndrome in which generalized myoclonus is readily elicited by stimuli.|
OSA affects approximately 24% of men and 9% of women in the United States and is associated with substantial mental and physical morbidity. Untreated OSA likely contributes to a significant proportion of acute hospital admissions, particularly for heart or respiratory failure. OSA may go unrecognized until a patient is incidentally hospitalized and observed to have difficulty breathing, paradoxical breathing, or oxygen desaturation. Risk factors for OSA include obesity, hypothyroidism, male gender, family history, African American race, and certain craniofacial characteristics: acromegaly, micrognathia or retrognathia, large tongue, or Mallampati class 3–4. OSA is characterized by episodes of complete or partial pharyngeal obstruction during sleep that cause snoring, apneic episodes, choking, dyspnea, and restlessness. These episodes are associated with intermittent nocturnal sympathetic activation leading to nocturnal awakenings and cortical arousals, all of which lead to daytime symptoms of fatigue, sleepiness, and cognitive impairment. Chronic sympathetic activation and intermittent hypoxemia are associated with increased vascular injury and inflammation that are known to occur in cardiovascular disease. Treatment of OSA with positive airway pressure (PAP) is shown to improve control of hypertension, diabetes, pulmonary hypertension, atrial fibrillation, and mortality.
Approximately 20% of patients with OSA will have concomitant RLS or PLMS/D, which are distinct problems and need to be differentiated from peripheral neuropathy and positional or nocturnal leg cramps. RLS is thought to affect as much as 40% of the population and is characterized by an unpleasant crampy, “creeping” or “crawling” sensation in the lower extremities that is relieved by persistently moving the legs. RLS frequently starts in the late evening or before bedtime, and often is a major cause of sleep-onset insomnia. The requisite bed rest during hospitalization can worsen RLS, further exacerbating sleep problems. It is also associated with many metabolic disorders, particularly renal disease, iron deficiency, and diabetes. Other conditions associated with RLS include pregnancy, rheumatoid arthritis, fibromyalgia, multiple sclerosis, and Parkinson disease. The etiology of RLS is not completely understood, but it may relate to inadequate generation or transport of dopamine due to iron deficiency or other metabolic disturbances. Serum iron and ferritin levels should be evaluated and treated if ferritin levels are < 75 μg. Aggressive treatment of other underlying diseases should be considered as first-line therapy. Selective serotonin uptake inhibitors (SSRIs) and alcohol may exacerbate RLS and should be avoided. Additional treatment includes the use of a dopaminergic agent at bedtime, such as ropinirole (Requip). Other agents that are effective, particularly in individuals with neuropathy, are gabapentin, narcotics, and benzodiazepines.
PLMD occurs in about 80% of those with RLS and is characterized by stereotyped involuntary limb movements that occur every 20 to 40 seconds during sleep. These can result in frequent cortical arousals, daytime somnolence, and fatigue. PLMS are found at higher frequency in several medical conditions, including hypertension, renal disease, and alcohol dependence. PLMS can be treated with longer-acting benzodiazepines such as clonazepam, and with dopaminergic agents.
General Medical Disorders
Numerous medical illnesses can directly impair sleep physiology, leading to a cyclical interaction in which impaired sleep impedes recovery (Figure 94-1). Table 94-2 lists selected medical and neurologic conditions, their associated sleep-related problems, and suggestions on how to alleviate these problems.
Factors related to sleep deprivation and illness.
Table 94-2 Common Chronic Diseases, Potential Effect on Sleep, and Suggested Interventions to Optimize Sleep ||Download (.pdf)
Table 94-2 Common Chronic Diseases, Potential Effect on Sleep, and Suggested Interventions to Optimize Sleep
|Disease||Effect on Sleep||Interventions to Improve Sleep|
|CHF||Orthopnea, paroxysmal nocturnal dyspnea, sleep-disordered breathing, increased sympathetic tone, nighttime diuresis, Cheyne-Stokes respiration.||Keep the head of bed elevated ≥ 30 degrees. Nocturnal O2 to keep O2 saturation > 88%. Daytime diuresis. Optimize cardiac function to treat Cheyne-Stokes respiration. Consider CPAP for CHF.|
|COPD||Persistent nocturnal hypoxemia with complications (eg, cor pulmonale, polycythemia).||O2 for COPD and persistent hypoxemia (PaO2 55–60 mm Hg).|
|Sporadic nighttime desaturations.||PaO2 ≤ 55 mm Hg → monitor O2 saturation by pulse oximetry. If patient desaturates to ≤ 88% at night consistently, start nocturnal O2. For hypercapnea, adjust O2 to maintain O2 saturation at 88–90%.|
|Increased risk of airflow obstruction during REM.||Consider bedtime tiotropium and inhaled long-acting beta-adrenergic agonist agents.|
|Inhibition of respiratory muscles in REM.||Avoid sedative-hypnotics that cause respiratory depression.|
|Decreased functional residual capacity from recumbent position during sleep.||Keep the head of bed elevated > 30 degrees.|
|ESRD||Pruritus, nausea; increased risk of RLS and PLMD in patients with ESRD.||Consider ropinirole and pramipexole if RLS; if medications contraindicated, massage or walking will relieve discomfort. Correct hyperphosphatemia and uremia. Consider antipruritic and antiemetic agents.|
|Thyroid Disorders||Hypothyroidism—daytime hypersomnolence.||Treat underlying thyroid dysfunction. Discourage naps during the day, keep lights on during the day, and off during the night.|
|Hyperthyroidism—hyperarousal symptoms (restlessness, tachycardia, diaphoresis, anxiety).||Treat underlying thyroid dysfunction. Low-dose beta-blocker (eg, propranolol, atenolol) for symptomatic relief.|
|Diabetes||Bedtime hyperglycemia → polydipsia, polyuria → frequent awakenings; or unnecessary nighttime monitoring of glucose levels. Inadequate scheduled or as needed insulin doses? High carbohydrate intake at bedtime?||Optimize blood glucose control. Increase scheduled or as needed insulin doses; consider consulting a dietitian to assess actual carbohydrate intake in the evening. Once bedtime glucose levels consistently ≤ 200 mg/dL, and no overnight hypoglycemic episodes, consider decreasing frequency of glucose monitoring at night.|
|Early morning (eg, 0200–0400) hypoglycemic episodes → symptoms awaken patient, or lead to frequent routine glucose monitoring overnight.||Optimize blood glucose control. Once bedtime glucose levels consistently ≤ 200 mg/dL, and no overnight hypoglycemic episodes, consider decreasing frequency of glucose monitoring at night (eg, if currently checking every 2 h → every 4 h or more appropriate?)|
|Stroke||Focal neurologic deficits (eg, dysphagia, weakness or paralysis).||Keep head of bed > 30 degrees. Regularly suction secretions. Poststroke patients have an increased risk of hypersomnia, insomnia, and/or OSA.|
A recent study examined risk factors for sleep disturbance during hospitalization and found that the severity of comorbid conditions and poor performance of activities of daily living (ADL) predicted sleep complaints during admission. Physician awareness of the impact of sleep disturbance in hospitalized patients is vital since about half of patients admitted on general medical wards will complain of sleep disruption.
Patients with pulmonary disorders and OSA can be profoundly affected by the normal physiologic changes that occur during sleep, particularly in REM sleep. REM sleep is associated with increased upper airway collapsibility and accessory muscle atonia (causing decreased muscle strength), which can result in episodes of marked oxygen desaturation. Patients with chronic obstructive pulmonary disease (COPD) demonstrate decreased total sleep time (TST), SWS, and REM sleep due to shortness of breath, nocturnal cough, and wheezing that impair sleep quality and duration. Sleep deprivation then further negatively impacts the work of breathing, creating a vicious cycle. Noninvasive positive pressure ventilation (NPPV) improves sleep efficiency, total sleep time, and quality of life in patients with hypercapnic COPD without significantly improving gas exchange and should be considered as an adjunctive therapy for improving sleep and quality of life in these patients.
Endocrine and metabolic disorders have also been associated with sleep disruption. Patients with diabetes mellitus have decreased total sleep time and impaired sleep quality due to nocturia and neuropathic pain. Inadequate sleep may also affect glucose control. Inadequate quality or quantity of sleep has been shown to be a risk factor for developing type 2 diabetes mellitus in large prospective studies and is associated with increased levels of glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus. Both hypo- and hyperthyroidism have been associated with sleep disruption. Hypothyroidism is associated with daytime somnolence, fatigue due to reduced SWS and often coexists with OSA. Hyperthyroid patients often complain of insomnia, which has been attributed to a hypermetabolic state.
Neurologic and Psychiatric Conditions
Since the brain and its various neurotransmitter systems are critical in regulating sleep and wakefulness, patients with neurologic disorders have an increased risk of developing sleep disorders. Common problems include increased sleep fragmentation and wakefulness, with increases of stage 1 sleep and reductions of SWS and REM. Patients with neurodegenerative disorders have an increased risk of REM sleep behavior disorder characterized by vivid and unusual dreams with physically vigorous, violent-type behaviors that may appear as acute delirium and result in patient injury. About half of hospitalized patients with traumatic brain injury report insomnia and may develop circadian rhythm disturbances. Poststroke patients can develop insomnia or hypersomnia and are at higher risk for developing OSA in the first several months.
Fifty-seven percent of patients with chronic pain also complain of impaired sleep. Sleep disruption is so common in fibromyalgia (75%) that it is considered to be a key diagnostic symptom. Poor nighttime sleep is associated with decreased pain tolerance and greater pain intensity the following day. Pain causes sleep fragmentation by increasing cortical arousals; in turn, sleep deprivation may increase pain sensitivity by inhibiting opioid protein synthesis or reducing opioid receptor affinity.
- It is important to note that sleep is a biological necessity and will occur, albeit poorly, even among patients with intense pain; physicians must avoid the cognitive trap of assuming that a patient must not be having severe pain if he or she is able to sleep.
Sleep disturbance is a diagnostic criterion for mood, anxiety, substance abuse, and psychotic disorders. Thus, comorbid psychiatric disorders must be considered in hospitalized patients with sleep complaints, even if not previously diagnosed. Major depression is particularly common in hospitalized patients with early morning insomnia. Longitudinal studies have found that prior insomnia was associated with two- to fivefold increase in the odds of mood and anxiety disorders and suicide. Often, sleep disorders precede the onset of clinical depression, supporting the importance of assessing patient sleep quality during hospitalization.
Substance abuse disorders are also associated with sleep problems. Over half of patients undergoing alcohol rehabilitation exhibit symptoms of insomnia, such as increased sleep latency during the six months prior to entering treatment, and many report using alcohol for the purpose of initiating sleep. Indeed, untreated insomnia and other sleep problems may increase the risk of developing substance abuse problems due to “self-medicating” with alcohol and other substances to help with sleep. While alcohol and illicit substance intoxication and withdrawal are known to disrupt sleep directly, sleep disturbances may persist long after withdrawal symptoms have abated, sometimes years later.
Many drugs used during hospitalization, such as antidepressants, anxiolytics, and narcotics, are well known to affect sleep. Table 94-3 depicts commonly used drugs and their effect on sleep architecture.
Table 94-3 Selected Drugs, Their Effects on Sleep Architecture, and Clinical Implications ||Download (.pdf)
Table 94-3 Selected Drugs, Their Effects on Sleep Architecture, and Clinical Implications
|Drug Class||Examples of Drugs||Sleep Architecture||Clinical Implications|
|TCAs||Amoxapine, amitriptyline, imipramine, nortriptyline, desipramine, doxepin, clomipramine||Suppresses REM sleep, ↑ TST, ↑ stage 2 sleep||Very sedating. Can cause restlessness, psychomotor agitation during sleep, subjectively poorer sleep quality, and daytime sedation.|
|SSRIs||Fluoxetine, sertraline, citalopram, escitalopram, paroxetine||SSRIs ↑ TST, are less sedating than TCAs and MAOIs. May ↓ REM, ↑ TWT, ↑ TST, ↓ SE||Some patients experience activation rather than sedation.|
|SNRI||Venlafaxine, duloxetine||Varies. ↓ TST.||Activating in some patients; sedating in 12–31%. If keeps patient awake, switch to am dosing. If sedating, switch to pm dosing. May cause vivid dreams or nightmares, and exacerbate underlying anxiety disorders such as posttraumatic stress disorder.|
|Stimulants||Ephedrine, pseudoephedrine, modafinil||↓ TST, ↓ SWS, ↑ sleep latency.||Activating. Avoid after 6 pm.|
|Lipophilic beta-blockers||Propranolol, pindolol, metoprolol, timolol||↑ Awakenings, ↑ TWT, ↓ REM,||Activating. Lipophilic beta-blockers → ↑ daytime sleep when dosed in morning. Induce nightmares.|
|CNS Agents||Norepinephrine, epinephrine||Activating. ↓ REM, ↓ SWS.||Minimize use at night.|
|Dopamine||Activating. ↓ REM, ↓ SWS.||Minimize use at night.|
|Ca++ channel blockers||Amlodipine, verapamil, nifedipine||Exacerbate underlying medical condition.||↓ Lower esophageal sphincter tone → nocturnal gastroesophageal reflux → sleep disturbance.|
|Diuretics||HCTZ, furosemide||Nighttime diuresis → frequent awakenings → ↓ sleep.|
|Opioids||Codeine, morphine.||Sedating. ↓ SWS, ↓ REM.||Minimize use at night.|
|NSAIDs||Ibuprofen, indomethacin, celecoxib||↓ TST, ↓ SE.||Minimize use at night.|
|Methyl-xanthine||Theophylline||Activating. ↑ stage 1, ↓ REM.||Causes less restful sleep.|
|Antihistamines||Diphenhydramine, promethazine||Sedating||Can disrupt sleep if associated with delirium.|
|Corticosteroids||Dexamethasone, prednisone||Activating. ↓ REM, ↓ SWS, nightmares.||Can disrupt sleep, ↑ anxiety, induce mania or psychosis.|
|Quinolone||Ciprofloxacin, sparfloxacin, ofloxacin, grepafloxacin, levofloxacin||Activating.||Consider sleep agent after maximizing sleep hygiene. Linezolid rarely causes sleep disturbances.|
A common misperception is that sedatives promote quality sleep. Sedatives may initially help with sleep onset, but they actually diminish SWS and enhance stage 2 sleep, causing nonrestorative sleep. This may manifest as next day “hangover,” fatigue, irritability, and poor function. Additionally, routine medications used to treat medical illnesses also disrupt sleep. The most common agents that impair sleep include antiepileptic drugs (AEDs), tricyclic antidepressants (TCAs), antihypertensives, antihistamines, and corticosteroids. Lipophilic beta-antagonists such as propranolol and timolol can increase total wake time, decrease REM sleep, and increase the incidence of nightmares and insomnia. Hydrophilic beta-antagonists such as atenolol and sotalol do not have these effects. Anabolic steroids and beta-agonist bronchodilator therapy can cause severe anxiety, sleeplessness, and even psychosis. Vasopressor agents such as dopamine can cause cortical activation, leading to increased arousal and reduced SWS.
- Sedation with hypnotics results in nonrestorative sleep.
Medication dosing regimens used in the hospital can also impact sleep. For example, giving diuretics in the evening will result in nighttime polyuria, and dosing activating antidepressants in the late afternoon or evening can result in sleep-onset insomnia. Withdrawal from narcotics or alcohol or use of venlafaxine may cause severe REM intrusion associated with vivid dreams, nightmares, and exacerbation of underlying stress disorders. Careful evaluation and selection of all medications, interactions between agents, and paradoxical reactions to medications in the elderly must be considered if the patient is experiencing increased sleep disturbance and sleep disruption during hospitalization since these patients are especially vulnerable to drug-drug interactions, and paradoxical drug effects.
Sleeping in an unfamiliar environment is likely to negatively impact sleep, but the hospital environment has many additional disruptions, particularly in high-acuity settings. Environmental noise and patient care activities account for about 30% of patient awakenings in intensive care unit (ICU) patients. Peak noise levels in the ICU have average sound peaks of over 150 dB and often exceed 80 dB between midnight and 6 am. By comparison, a lawn mower or truck traffic has a sound level of 90 dB. The high noise level in hospitals has long been implicated as the major sleep disruptor, but studies in the past decade have found that patient care activities also cause a substantial disruption in sleep. This is in part due to routine activities, such as bathing, vital sign monitoring, radiologic studies, and phlebotomy that are conducted at night or early morning due to scheduling constraints.
Understanding that numerous factors may impair sleep during hospitalization allows clinicians to systemically evaluate and treat sleep problems. More than just prescribing sedative/hypnotic agents, the treatment for sleep disruption includes addressing multiple medical, behavioral, and environmental factors.