Delirium
Introduction
Delirium, or encephalopathy, is an acute neuropsychiatric disorder characterized by a fluctuating confusional state with inattention. Delirium can be caused and perpetuated by cancer itself, related medical issues, and many treatment modalities used in cancer treatment. It is linked to a number of negative healthcare outcomes, impacting the patient, family, and healthcare system overall. Although studies show a wide range in prevalence depending on individual factors, it is clear that patients with cancer are at an increased risk of delirium. In fact, studies show that as many as 90% of hospitalized patients with cancer experience delirium at some time.
| Box 1. Selected Negative Outcomes of Delirium During Hospitalization |
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Difficulty toileting (constipation, urinary tract infections) Limited mobility (decubitus ulcers, muscle atrophy) Accidental self-harm (falls risk, manipulation of lines or equipment) Physical harm to care providers Caregiver burnout impacting medical providers and family Long-term care needs (physical rehabilitation, nursing facility placement) Persistent cognitive impairments High hospital readmission rates Increased healthcare utilization and costs Increased risk of mortality
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| Box 2. Selected Risk Factors for Delirium in Cancer |
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Older age History of cognitive impairment Vision or hearing impairments Impaired mobility Malnutrition Use of opioids, benzodiazepines, and/or anticholinergic agents Cancer with intracranial or bone involvement Hypercalcemia Elevated blood urea nitrogen (BUN)
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Evaluation and Diagnosis
The Diagnostic and Statistical Manual of Mental Disorders (DSM-V) defines delirium as a disturbance in attention and awareness with a change in at least one additional domain of cognition that develops over a short period of time, is a change from the patient’s baseline, and fluctuates in severity. Delirium can be further classified by the etiology, course, and impact on psychomotor function. Although delirium is often identified by the presence of paranoia, hallucinations, or illusions, these disturbances are not required for the diagnosis but often present.
| Box 3. Common Features of Delirium |
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Subacute or acute onset (hours to days) Waxing and waning mental status Inattention Disorganization of thought Disorientation Perceptual disturbances such as hallucinations or illusions Delusional beliefs, particularly paranoia Disruption in sleep-wake cycle Psychomotor agitation or retardation
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Screening tools for delirium are available. The Confusion Assessment Method (CAM) is often used by nursing staff, particularly in an adapted version for the intensive care setting.
| Table 1. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) | ||
| No | Yes | |
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Feature 1: Acute onset or fluctuating course A. Is there evidence of an acute change in mental status from baseline? B. Or, did the behavior fluctuate during the past 24 hours? |
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Feature 2: Inattention Ask the patient to squeeze the provider’s hand when the provider says the letter A in a sequence of letters. Did the patient have difficulty focusing attention? |
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Feature 3: Disorganized thinking A. Did they answer 3 or more of the following 4 questions incorrectly? 1. Will a stone float on water? 2. Are there fish in the sea? 3. Does 1 pound weigh more than 2 pounds? 4. Can you use a hammer to pound a nail? B. Or, did they demonstrate unclear thinking when asked to follow a command? Hold up 2 fingers and ask the patient to hold up the same number of fingers. Then ask them to do the same with the other hand without demonstrating it. |
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Feature 4: Altered level of consciousness Is the patient’s level of consciousness anything other than alert? |
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| Are Features 1 and 2 and either 3 or 4 present? | ||
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Adapted from: Ely EW, Inouye SK, Bernard GR, et al. Delirium in Mechanically Ventilated Patients: Validity and Reliability of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). JAMA. Dec 5 2001;286(21):2703-2710.
The evaluation of a cancer patient with suspected delirium includes a history often reliant on collateral information from family and other providers, comprehensive review of the patient’s medical course, and a complete physical exam. It is important to closely review the medication list and screen for the use of other herbs, supplements, over-the-counter medications, or illicit substances. Particular attention should be paid to medications that can cause or exacerbate delirium, such as opioids, benzodiazepines, anticholinergic agents, steroids, or cephalosporin antibiotics. Necessary medical tests should be obtained as appropriate based on the individual medical circumstances. This might include blood work, urinalysis, pertinent drug screening, cerebrospinal fluid studies, imaging, electroencephalogram (EEG), or electrocardiogram (EKG).
| Box 4. Selected Etiology of Delirium in Patients with Cancer |
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Opportunistic infections Dehydration Electrolyte disturbance Thiamine deficiency Coagulopathies Bleeding risk with thrombocytopenia Pain Paraneoplastic syndromes Intracranial cancer involvement (primary brain tumor, metastases, leptomeningeal disease) Seizures Brain irradiation Opioid toxicity Corticosteroids Cephalosporin antibiotics (such as cefepime)
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Treatment
The management of delirium centers on identifying and addressing the underlying cause(s). Modifications to the patient’s environment and the use of behavioral strategies can be helpful in both prevention and treatment of delirium. The tables below outline helpful non-pharmacological and pharmacological strategies.
For example, encouraging family and friends to be at the bedside and placing the bed near the window can be beneficial. When there is a risk of harm or significant distress as the result of delirium, psychiatric medication may be considered for acute symptom management. The goal is to limit polypharmacy, so choosing one agent and titrating the dose when appropriate is ideal. When symptoms are frequent, scheduled dosing instead of as needed (PRN) dosing is often used. If additional PRN medications are required, this can help to guide titration of the scheduled dose. There should always be a management plan for how to taper and discontinue these medications when they are no longer necessary.
| Box 4. Non-Pharmacological: Behavioral Strategies for Managing Delirium |
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· Presence of family/ friends/ known supports, encourage frequent visits from family and friends. · Ensure access to necessary tools like glasses, hearing aids, and dentures. Help patients to use these tools and have them in/ on/ working. · Maintain consistency in providers, including nursing staff. · Frequent reorientation with visual cues at each interaction. · Use clear, concise communication. · Ask permission before touching the patient; during interactions, describe what you are doing and the rationale to enhance adherence and relieve distress. · Maintain a consistent sleep/ wake cycle. · Keep blinds open and lights on during the day and blinds closed and lights off at night. · Reduce external stimuli. · Keep familiar items and/or photos at the bedside. · Limit the number of people present during staff rounds. · Consider the use of 1:1 supervision. · Serve meals with pre-wrapped foods if paranoia is predominant. · If the patient is at imminent risk of harming themselves or others, the use of physical restraints might be necessary. Use the least restrictive restraints for the shortest period of time possible.
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| Table 2. Pharmacological Strategies for Managing Agitation in Delirium | ||
| Medication Class | Reasons to Consider | Cautions |
| Typical antipsychotics | Available IV |
Level of sedation varies Risk for EPS Risk for QT prolongation |
| Atypical antipsychotics |
Available IM, dissolvable pills Lower risk for EPS Drug-specific impacts on appetite, nausea, sleep might be of benefit |
Higher risk for metabolic side effects in long-term risk Risk for QT prolongation |
| Benzodiazepines |
Class of choice for withdrawal from alcohol or benzodiazepines Class of choice for intoxication on stimulants or anticholinergic toxicity Useful in catatonia |
Can exacerbate delirium when it is from other etiologies |
| Valproic acid |
Available IV and in sprinkles Does not prolong QT Option for loading dose |
Highly protein-bound. Risk of thrombocytopenia, hepatotoxicity. |
| Alpha adrenergic agonists | Dexmedetomidine is fast acting and highly effective for severe agitation in the ICU setting | Requires close monitoring |
| Melatonin | Reinforcement of proper day-night diurnal variation |
Limited evidence for PRN use, favor scheduled use
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Extrapyramidal symptoms, EPS. Pro re nata (as needed), PRN.
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Conclusion
Delirium is prevalent in cancer care and is associated with significant morbidity and mortality. Delirium in cancer is often reversible but can also be present at the end of life. Early recognition, a thorough review of potential etiologies, and development of a management plan can help to limit risks to the patient and encourage recovery. This plan may include treatment of medical issues, addressing potential medication side effects, modifying the environment, and/or using behavioral approaches.
References
- American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th).
- Trzepacz P.T., Meagher D.J., Leonard M. (2011). Delirium. In J.L. Levenson (Ed.), Textbook of Psychosomatic Medicine (2nd, pp. 71-114).
- Breitbart W.S., Alicia Y. (2010). Delirium. In J.C. Holland, W.S. Breitbart, P.B. Jacobsen, M.S. Lederberg, M.J. Loscalzo, R. McCorkle (Eds.), Psycho-Oncology (2nd, pp. 332-339).
- Breitbart, W. S., & Alicia, Y. (Apr 10 2012). Evidence-based treatment of delirium in patients with cancer. J clin Oncol. 30(11),1206-1214.
- Roth AJ, Levenson JA. (2015). Psychiatric Emergencies. In J. C. Holland, M. Golant, D. B. Greenberg, M.K. Hughes, J.A. Levenson, M.J. Loscalzo, W.F. Pirl (Eds.), Psycho-Oncology: A Quick Reference on the Psychosocial Dimensions of Cancer Symptom Management (2nd, pp. 37-44).