Nephrology Hypertension

Medical Management of the Dialysis Patient: Cognitive Function, Depression and Psychosocial Adaptation

Does this dialysis patient have delirium, dementia or depression?

  • Delirium is an acute confusional state characterized by a recent onset of fluctuating awareness, impairment of memory and attention, and disorganized thinking that can be attributable to a medical condition, an intoxication, or medication side effects (Table I). In dialysis patients, delirium may also be caused by retention of uremic solutes (uremic encephalopathy) or by brain edema during dialysis (dialysis dysequilibrium).

  • Dementia is a chronic confusional state characterized by impairment in memory and at least one other cognitive domain, such as language, orientation, reasoning or executive functioning. The impairment in cognitive function must represent a decline from the patient's baseline level of cognitive function and must be severe enough to interfere with daily activities and independence. Mild cognitive impairment is the most common terminology used to describe chronic cognitive impairment beyond that associated with normal aging but not crossing the threshold for dementia diagnosis.

  • Major Depression is a syndrome of depressed mood or anhedonia, often accompanied by disturbances in ideation or neurovegetative or somatic symptoms that are present daily for at least two weeks. Dysthymia is a chronic but milder depressive disorder.

Table I.

Differentiating features of delirium, dementia and depression

What tests to perform?

What instruments can be used to diagnose delirium, dementia and depression in dialysis patients?

  • Delirium: The Confusion Assessment Method has a sensitivity and specificity for delirium detection >90% in hospitalized patients. Its accuracy has not been evaluated in dialysis patients

  • Dementia:A wide range of screening tests are available with a range of administration times. Most have not been validated in dialysis patients. For example, a score of 4 or less on the Six-item Screener has >90% sensitivity and >70% specificity for a dementia diagnosis in the general population. The Mini-Cog combining the Six-item Screener and the Clock Drawing Task, has similarly high sensitivity and specificity. Both tests can be administered in less than 3 minutes. Screening tests should be followed by clinical evaluation to establish diagnosis.

  • Depression: Several questionnaires to screen for depressive symptoms have been validated for use in patients on dialysis, including the Beck Depression Inventory, the Centers for Epidemiologic Studies Depression Scale and the Patient Health Questionnaire [insert link here]. Due to the overlap of somatic symptoms associated with end-stage renal disease (ESRD) and somatic symptoms of depression, the cut-off required for a positive screen is more stringent (i.e. higher) in patients with ESRD.

Screening tests should be followed by clinical evaluation to establish diagnosis.

Should there be routine screening for dementia and depression in dialysis patients?

The US Preventive Services Task Force (USPSTF) recommends screening for depression in practices that have available support systems to assure accurate diagnosis and effective treatment and follow-up. Based on the high prevalence of depression in dialysis patients and the availability of social support services within most dialysis clinics, it seems reasonable to screen dialysis patients for depression with one of the above tools. In contrast, the USPSTF has said there is insufficient evidence to recommend for or against dementia screening in older adults.

These recommendations are based on intermediate specificity of most screening instruments, the unknown potential harms of incorrectly labeling patients as cognitively impaired, and modest efficacy of drug treatments for dementia. However, there may also be useful information gained from dementia screening, particularly in dialysis patients, since the prevalence of cognitive impairment is substantially higher than the general population. Dementia screening in this population may be useful for modality selection, enhancing compliance, and for advance care planning.

What tests should be performed to identify the underlying cause(s) of delirium in a dialysis patient?

Causes of delirium

  • Electrolyte disorders – hyponatremia, hypoglycemia, hypercalcemia

  • Infections – catheter-related bacteremia, urosepsis, pneumonia, meningitis

  • Drug intoxication – illicit drugs, opioids, benzodiazepines, antihistamines, antipsychotics, anticonvulsants, antiemetics, others

  • Alcohol or drug withdrawal

  • Cerebrovascular disorder – stroke, hypertensive encephalopathy

  • Subdural hematoma

  • Advanced heart or liver failure

  • Uremic encephalopathy

  • Dialysis dysequilibrium

Delirium evaluation

1. History and physical examination. These are essential to establish acuity of change in mental status and provide clues about the underlying etiology.

2. Laboratory tests. Electrolytes, complete blood count, liver function, drug screen.

3. Comprehensive medication review. Medications are a common cause or contributing factor for delirium. All prescription and over the counter medications should be reviewed.

4. Neuroimaging. If an obvious cause for delirium is identified and there is no history of trauma or focal neurologic signs, routine neuroimaging may not be indicated for the initial evaluation but may be reconsidered if there is no improvement with appropriate medical treatment.

5. Other tests. The electroencephalogram (EEG) can rule out seizure activity. Beyond the identification of seizures, the specificity of EEG for differentiating uremic encephalopathy from other causes of delirium has not been extensively studied. Biomarkers including levels of blood urea nitrogen (BUN) correlate poorly with uremic symptoms including encephalopathy. The diagnosis of uremic encephalopathy is usually established retrospectively. It should be considered in dialysis patients with known suboptimal delivery of dialysis or other uremic symptoms.

What tests should be performed to identify the underlying cause of dementia in a dialysis patient?

1. Neuropsychological testing. For patients who screen positive, more extensive neuropsychological testing can confirm the diagnosis, indicate the severity, and in some cases provide clues about the etiology. Screening tests may be less sensitive in highly-educated patients; thus in cases where dementia may be suggested by the clinical history but screening tests are negative more extensive neuropsychological testing may be useful.

2. Neuroimaging. For the general population, the American Academy of Neurology recommends routine structural neuroimaging with either noncontrast computed tomography or magnetic resonance imaging in the initial evaluation of dementia.

3. Laboratory testing. The American Academy of Neurology recommends testing for vitamin B12 deficiency and hypothyroidism. In contemporary dialysis patients, aluminum intoxication is a rare cause of dementia. Testing for HIV or neurosyphyllis may be considered in a patient with risk factors.

4. Other tests. Lumbar puncture and brain biopsy are not routine but may be indicated in certain clinical settings. Sleep disorders, including sleep apnea, restless legs syndrome, and periodic limb movements of sleep may be a reversible cause of cognitive impairment in dialysis patients. Sleep studies may be useful in selected patients with suggestive symptoms.

What tests should be performed in dialysis patients who screen positive for depression?

1. Structured clinical interview to confirm diagnosis.

2. Determine whether co-existing psychiatric disorders are present, especially substance abuse and cognitive impairment.

3. Determine whether suicidal ideation is present.

How should patients with delirium, dementia, or depression be managed?

Delirium

1. Treat precipitating factors.

2. Manage behavioral symptoms. Pharmacologic therapy for behavioral symptoms is indicated only when delirium threatens patient safety or interrupts essential therapy. Haloperidol is the agent of choice, with a usual starting dose of 0.25 to 0.5 mg twice daily. Atypical antipsychotic medications, such as risperidone, olanzapine, and quietapine, have also been used for this purpose. Because of a possible risk of increased mortality when used in patients with dementia, short-term use is recommended. Benzodiazepines, atypical antipsychotics, and some antidepressants have also been used for treatment of delirium, but these agents have side effects that make them less desirable as first-line agents except in the case of benzodiazepines for alcohol withdrawal.

3. Prevent complications of delirium. Supportive care to prevent aspiration, deep venous thrombosis, and pressure sores should be provided in all patients.

4. Special considerations for patients with uremic encephalopathy. An increase in the intensity or frequency of dialysis may be considered in dialysis patients who have delirium and no other obvious cause.

5. Special considerations for patients with dialysis dysequilibrium. Preventative measures should be considered in high-risk patients, such as the elderly, those with severe azotemia, and those undergoing the initial dialysis treatment. These measures include performance of reduced efficiency dialysis, such as with reduced blood and/or dialysate flow rates, use of concurrent dialysate flow, or continuous renal replacement therapies. The administration of mannitol or an increase in the dialysate sodium concentration may also help to prevent or attenuate symptoms.

Dementia

1. Pharmacologic therapy. Two classes of medications are now available for treatment of both Alzheimer’s and vascular dementia, cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist (NMDA), memantine. The clinical benefit of both classes of medications appears to be modest. There is no data on safety or efficacy in patients with ESRD. For this reason, treatment decisions should be individualized. Of the available cholinesterase inhibitors, galantamine requires dose adjustment in patients with reduced kidney function and is not recommended in patients with ESRD. The other agents in this class do not appear to require dose adjustment in the setting of ESRD. Memantine, an NMDA receptor antagonist, has a maximum dose of 5mg twice a day in patients with ESRD.

2. Behavioral symptoms. Behavioral symptoms should be managed by first removing precipitating factors (e.g. pain), and then by providing psychosocial interventions (e.g. caregiver education). Pharmacologic therapy may be provided if other approaches are unsuccessful. See also section on managing behavioral symptoms in delirium.

3. Assessment of patient safety and caregiving needs. Involvement of other dialysis team members, such as the dialysis nurse, social worker and dietician, and the primary care provider may be helpful to address medication compliance, the patient's ability to perform self-care functions, and patient safety in the current living environment while maximizing functional ability.

4. Advance care planning. The process of advance care planning allows patients to understand the expected prognosis, and to make decisions about their future health care before the disease becomes advanced.

The optimal management of mild cognitive impairment is uncertain. Substantial observational evidence links vascular risk factors with risk for cognitive impairment; therefore aggressive management of vascular risk factors (i.e. blood pressure control, glycemic control, increased physical activity, smoking cessation), have been suggested but most of these strategies have not been rigorously tested in the general population or in dialysis patients. Similarly, strategies to address novel ESRD related risk factors (e.g. anemia, retention of uremic solutes, etc.) are lacking supportive data from clinical trials.

Depression

Several evidence-based treatments for depression are available, including psychotherapy, exercise therapy, pharmacologic therapy, and electroconvulsive therapy. The initial choice of therapy should be based on treatment history, coexisting medical conditions, and patient preferences.

1. Psychotherapy. Although not evaluated in patients with ESRD, a recent meta-analysis reported similar efficacy of psychotherapy and pharmacologic therapy for treatment of depressive symptoms. It should be considered in patients with contraindications to pharmacologic therapy or those who fail pharmacologic therapy.

2. Exercise therapy. Short term exercise programs have proven efficacy for treatment of depressive symptoms, and may also have other benefits for ESRD patients, for example on physical health, cardiovascular health, etc. This form of therapy should be strongly considered for patients with mild or moderate depression who are able to participate in an exercise program.

3. Pharmacologic therapy. Antidepressants are a mainstay of most clinical practice guidelines for depression treatment, and also appear efficacious in short-term clinical studies of patients with ESRD. Only 40% to 65% of patients respond to treatment, and thus combination therapy may be needed. Selective serotonin-reuptake inhibitors (SSRIs) are perhaps the best-studied antidepressants in patients with ESRD and seem to have similar safety and efficacy profiles as in the general population. Several SSRIs have prolonged half-lives or metabolites that accumulate in patients with ESRD, and therefore require dose reduction. Tricyclic antidepressants are generally not considered first-line therapy in patients with ESRD because of their side effect profile and potential for causing cardiac conduction problems and orthostatic hypotension.

In general, initial treatment should begin with low doses, and clinical response and side effects should be assessed frequently in the first several months. If response has been suboptimal, the dose may be increased after 3 to 4 weeks. If symptoms persist despite a full therapeutic trial of antidepressants (e.g., 8 to 10 wk), psychiatric referral is indicated.

4. More frequent/intensive dialysis. Nonrandomized studies suggest improvement in depressive symptoms with more frequent or longer dialysis sessions. In the Frequent Hemodialysis Network (FHN) trial, six times per week in-center hemodialysis was associated with a trend towards improvement in depressive symptoms that did not reach statistical significance. Results from the FHN Nocturnal dialysis trial have not yet been reported.

5. Other approaches. Addressing difficulties in interpersonal relationships, financial hardship, and caregiver burden, as well as symptoms of anxiety or sleep disturbance may also be useful.

What happens to patients with delirium, dementia, or depression?

Delirium

Little is known about the epidemiology and outcomes of delirium among dialysis patients. In the general population, delirium occurs in 14-24% of hospitalized patients, >70% of ICU patients, and >80% of patients at the end of life. Reported mortality rates for hospitalized patients with delirium range from 22-76%. Delirium is also associated with longer hospital stays and more costly care.

Dementia

Cognitive impairment may hinder adherence with the complex regimens often prescribed to patients with ESRD, increase the risk of adverse drug events, and impair informed decision-making surrounding issues such as preemptive vascular access placement and ESRD treatment options. Among dialysis patients, a diagnosis of dementia is associated with higher risks for disability, hospitalization, withdrawal from dialysis and death.

Depression

Dialysis patients with depression have higher rates of hospitalization, peritonitis (for peritoneal dialysis patients), early mortality, and overall mortality.

What is the evidence?

Inouye, S. " Delirium in older persons". N Engl J Med . vol. 354. 2006. pp. 1157-1165.

(This article reviews the significance, differential diagnosis, and clinical approach to delirium in hospitalized patients.)

Kurella Tamura, M, Yaffe, K. " Dementia and cognitive impairment in end-stage renal disease: diagnostic and management strategies". Kidney Int. vol. 79. 2011. pp. 14-22.

(This article describes the epidemiology of dementia and reviews the evidence for various management strategies in patients with ESRD.)

Hedayati, S, Finkelstein, FO. " Epidemiology, diagnosis and management of depression in patients with CKD". Am J Kid Dis. vol. 54. 2009. pp. 741-752.

(This article describes strategies for depression detection and treatment approaches, both pharmacologic and non-pharmacologic.)

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