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Some reviews of clomid noted that the drug can also cause weight gain, hair loss and vision impairment clomid cost Before using the product you should consult with a specialist and to get acquainted with the instructions approved by the manufacturer.Cialis ne doit pas être prise à tous. Il est important que cialis en ligne est prescrit par un médecin, bien se familiariser avec les antécédents médicaux du patient. Ich habe Probleme mit schnellen Montage. Lesen Sie Testberichte Nahm wie cialis rezeptfrei 30 Minuten vor dem Sex, ohne Erfolg. Beginn der Arbeiten nach 4 Stunden, links ein Freund ein trauriges Ja, und Schwanz in sich selbst nicht ausstehen, wenn es keinen Wunsch ist.
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Symptom Management and Supportive Care
The Assessment and Management of Delirium in Cancer Patients HIRLEY H. BUSH,a,b,c,d EDUARDO BRUERA
aDepartment of Palliative Care & Rehabilitation Medicine, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA; bMcCulloch House, Southern Health Care Network, Melbourne, Victoria, Australia; cFaculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia; dDivision of Palliative Care, University of Ottawa, Ottawa, Ontario, Canada Key Words. Delirium • Neoplasms • Palliative care • Diagnostic techniques and procedures • Antipsychotic agents
Shirley H. Bush: None; Eduardo Bruera: None.
Section editor Russell Portenoy has disclosed no financial relationships relevant to the content of this article.
The paper discusses s.c. administration of the parenteral preparation of olanzapine.
The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and freefrom commercial bias.
After completing this course, the reader will be able to: 1. Summarize the current evidence regarding strategies for the assessment and management of delirium in advanced 2. Outline the medications most commonly implicated for drug-induced delirium.
3. Compare the various pharmacological agents available for use in managing cancer-related delirium.
This article is available for continuing medical education credit at CME.TheOncologist.com.
Delirium remains the most common and distressing neu-
lirium, and the diagnosis and management of opioid-in-
ropsychiatric complication in patients with advanced can-
duced neurotoxicity. The early symptoms and signs of
cer. Delirium causes significant distress to patients and
delirium and the use of delirium-specific assessment tools
their families, and continues to be underdiagnosed and un-
for routine delirium screening and monitoring in clinical
dertreated. The most frequent, consistent, and, at the same
practice are summarized. Finally, management options
time, reversible etiology is drug-induced delirium result-
are reviewed, including pharmacological symptomatic
ing from opioids and other psychoactive medications. The
management and also the provision of counseling support
objective of this narrative review is to outline the causes of
to both patients and their families to minimize distress. The
delirium in advanced cancer, especially drug-induced de-
Correspondence: Shirley Bush, M.B.B.S., M.R.C.G.P., Division of Palliative Care, Bruyère Continuing Care, 43 Bruyère Street, Ottawa,Ontario, K1N 5C8, Canada. Telephone: 613-562-6262; Fax: 613-562-6371; e-mail: email@example.com Received June 18, 2009; ac- cepted for publication September 14, 2009; first published online in The Oncologist Express on October 6, 2009. AlphaMed Press
1083-7159/2009/$30.00/0 doi: 10.1634/theoncologist.2009-0122
The Oncologist 2009;14:1039 –1049 www.TheOncologist.com
Assessment and Management of Delirium in Cancer Patients lirium are more likely to receive psychotropic medications "Most delirious patients are considered either dull, stupid, and may have a better prognosis than patients with hypoac- ignorant, or uncooperative. It is only when their behaviour tive delirium . Hypoactive delirium may be more resis- and content of thought are grossly deviant that an abnormal tant to pharmacological treatment . The majority of mental state is recognised, although ids [sic] not always delirium episodes are either of the hypoactive or mixed sub- correctly identified as delirium" .
type [22, 23]. Lawlor et al. , in a prospective study, Despite the passage of time since Engel and Romano's de- found that delirium was mixed in 48 of 71 (68%) patients.
scription of delirium caused by global brain dysfunction in The hyperactive and mixed subtypes are highly associated their classic paper in 1959, delirium continues to be frequently with drug-induced delirium, whereas predominantly hypo- underdiagnosed or misdiagnosed by health care professionals active delirium is associated with dehydration and enceph- [2– 4] and continues to be inadequately treated .
Delirium remains the most common and devastating The differential diagnosis of delirium includes dementia neuropsychiatric complication in patients with advanced and depression, and other psychiatric disorders. In demen- cancer [2, 6], although a delirium episode is reversible in up tia, in contrast to delirium, there is little or no clouding of to 50% of cases [7, 8]. Delirium causes significant distress consciousness, and the onset is insidious. However, the to patients and their families [9, 10]. In a recent study of 99 symptoms of Lewy Body dementia (comprising cognitive patients with advanced cancer who had recovered from de- impairment, visual hallucinations, delusions, and parkin- lirium, 74% remembered their delirium episode . Pa- sonism) do fluctuate. Patients with dementia may also com- tients who recalled their delirium episode reported a monly present with a superimposed delirium. Hypoactive higher level of distress than patients with no recall .
delirium, with somnolence and withdrawal, may be mis- Delirium impairs patient communication, thus challeng- diagnosed as depression. Hyperactive delirium may be ing the assessment of pain and other symptoms . De- mistaken for manic and psychotic episodes, anxiety, or lirium also causes significant morbidity, increasing the akathisia. Increased expression of pain in an agitated pa- length of hospital stay and also increasing the risk for tient may be misinterpreted and inappropriately treated falls and associated sustained injuries [12, 13]. The de- as a pain syndrome, with the resulting increased opioid velopment of delirium prognosticates a greater likeli- administration exacerbating the delirium severity , hood of death .
rather than correctly identified as disinhibition because The purpose of this review is to update oncologists on of delirium.
the clinical assessment and management of this syndrome, with a focus on drug-induced delirium.
PATHOPHYSIOLOGY AND CAUSES
The cholinergic hypothesis describes a deficiency of ace-
DEFINITION AND PREVALENCE
tylcholine and an excess of dopamine as mediators for de- Delirium is defined as a disturbance of consciousness with lirium . Other neurotransmitter hypotheses postulate reduced ability to focus, sustain, or shift attention, with the role of glutamate, serotonin, cortisol, and endogenous changes in cognition or perceptual disturbances that occur opioid [3, 28, 29]. The role of cytokines is attracting recent over a short period of time and tend to fluctuate over the interest, especially interleukin (IL)-1, IL-6, and IL-8, and course of the day, with an organic etiology .
also interferon and tumor necrosis factor [30, 31]. It has Delirium is present in 26%– 44% of advanced cancer been suggested that IL-6 has a role in hyperactive delirium patients at the time of admission to an acute care hospital or . Transient thalamic dysfunction has been postulated as palliative care unit, and ⬎80% of patients with advanced a mechanism for drug-induced delirium . Future re- cancer develop delirium in the last hours and days before search may identify pathophysiological mechanisms spe- death [8, 16, 17].
cific for other delirium subtypes.
According to the level of psychomotor activity, three The organic etiology of delirium is usually multifacto- clinical delirium subtypes have been described: hyperac- rial, with a median of three (range, one to six) precipitants tive, hypoactive, and mixed (with alternating features of per delirium episode  (Fig. 1).
both hyperactive and hypoactive delirium) [18, 19]. How- On multivariate analysis, one small prospective study in ever, in many studies to date, the true nature of the psy- 145 oncology admissions found the following five risk fac- chomotor abnormality has been difficult to determine tors for the development of delirium: advanced age, cogni- because of its fluctuation (observed more in longitudinal tive impairment, low albumin, bone metastases, and studies) and also the potentially confounding effect of med- hematological malignancy . However, often a specific ications used to treat delirium. Patients with hyperactive de- cause remains unidentified. Predisposing factors increase a CANCER BYPRODUCTS,
anticholinergics, e.g., primary and corticosteroids, metastatic brain tumor, antidepressants, leptomeningeal disease, benzodiazepines, Electrolyte imbalance
Side effects of
Other medical conditions
e.g., withdrawal syndromes Organ failure
(alcohol, medication, nicotine), nutritional deficiencies, coagulopathy, anemia Infection
e.g., pneumonia, e.g., hypoglycemia, Figure 1. Factors contributing to delirium in cancer patients.
patient's baseline susceptibility for developing delirium.
Table 1. Medications that contribute to delirium [7, 25,
Examples are pre-existing cognitive impairment, such as dementia, and reduced sensory input because of poor vision or deafness.
antidepressants, selective serotonin The most commonly implicated medications are opioids reuptake inhibitors, neuroleptics,nonbenzodiazepine hypnotics (see section below on opioid-induced neurotoxicity), corti- costeroids, benzodiazepines, and anticholinergics [7, 25, Corticosteroids, antihistamines, H 35, 36] (Table 1). In addition to delirium, other features of blockers, antibiotics (quinolones), anticholinergic drug toxicity are mydriasis, hyperthermia, fever with no sweating, flushed appearance, dry skin, and certain antivirals urinary retention.
In a prospective cohort study in 261 cancer hospital in- patients, Gaudreau et al.  found that the risk for delir-ium doubled if the daily dose equivalent (DDE) of s.c.
agement of cancer pain, produces a high rate of neurotox- morphine was ⬎90 mg/day or if the DDE of lorazepam icity because approximately 60% of it is metabolized to was ⬎2 mg/day. A DDE ⬎15 mg/day of oral dexameth- normeperidine. Leipzig et al.  found that 77% of cancer asone led to a 2.7 higher risk for the development of de- patients receiving opioids had an impaired mental status.
lirium, but no association with anticholinergics was The features of OIN are severe sedation, hallucinations, found in that study .
cognitive impairment, delirium, myoclonus, seizures, hy- Opioid-induced neurotoxicity (OIN) is a syndrome of peralgesia, and allodynia. These symptoms can develop as a neuropsychiatric side effects seen with opioid therapy. Ta- single feature or in any combination and order. Hallucina- ble 2 outlines the risk factors for this syndrome. OIN can tions tend to be visual or tactile, with visual hallucinations occur with all known opioid agonists that are used in cancer occurring in almost half of hospice inpatients . Patients pain management, including morphine, hydromorphone, with a history of seizures, cerebral metastases, or metabolic oxycodone, fentanyl, and methadone [37, 38]. Meperidine, abnormalities may have a predisposition to developing an opioid analgesic that is not recommended for the man- tonic-clonic OIN-associated seizures. The oncologist must
Assessment and Management of Delirium in Cancer Patients (Small intestine mucosa) (Proximal renal tubule) NO binding to opioid • morphine ethereal ACTIVE metabolite (? ANTIANALGESIC) Cognitive impairment/ Neurotoxic properties (especially if high-dose morphine or prolonged RENAL EXCRETION – related to Creatinine Clearance Figure 2. Morphine metabolism [37, 41, 44]. aThe percentage breakdown of metabolites remains the same for all routes of ad-
Abbreviations: M-3-G, morphine-3-glucuronide; M-6-G, morphine-6-glucuronide.
remain vigilant because any patient prescribed opioids is at patients receiving high-dose or prolonged treatment with potential risk for developing OIN.
morphine. It is unknown to what extent morphine-6-gluc- Opioid-induced central nervous system (CNS) adverse uronide (M-6-G) contributes to OIN.
effects are related to the anticholinergic actions of opioids, Opioid neurotoxicity is also thought to involve endocy- with inhibition of central cholinergic activity in multiple tosis of opioid receptors and also activation of N-methyl- cortical and subcortical regions of the brain, in addition to D-aspartate receptors, where the neurotransmitter is an imbalance in CNS cholinergic and dopaminergic sys- glutamate . It has been suggested that inhibition of gly- tems . The accumulation of toxic opioid metabolites cine in dorsal horn neurons leads to myoclonus and hyper- has also been implicated (Fig. 2). Using the example of algesia . It has also been proposed that the neurotoxic morphine as the "gold standard" opioid, the major metabo- effect of opioids may occur via a nonopioid receptor–me- lite (44%–55%), morphine-3-glucuronide (M-3-G), has no diated mechanism .
-opioid binding and consequently no analgesic properties[37, 41]. M-3-G is thought to be responsible for the cluster of OIN symptoms described above. However, the evidence For didactic purposes, we separately discuss the clinical for this is conflicting. Gong et al. , in 1992, reported that features and assessment of delirium and the evaluation of M-3-G did not produce excitatory and antianalgesic effects contributory factors. However, in daily clinical practice, in rats, and Penson et al.  more recently, in 2001, did not this process takes place in a fully integrated fashion.
induce neurotoxicity when small i.v. doses of M-3-G wereinjected into healthy volunteers. Normorphine, another Clinical Features of Delirium
nonopioid-binding neurotoxic metabolite, accounts for Early diagnosis is important, because this enables not only only approximately 5% of morphine metabolism .
earlier treatment but also provision of education and sup- However, this mediator may play a more prominent role in port to the patient and family.
55]. Some instruments, such as the Confusion Assessment Table 2. Factors predisposing to opioid-induced
Method (CAM) , are diagnostic only and used mainly neurotoxicity (OIN) for screening. Such tools cannot be used to monitor patients Opioid factors—large dose, extended treatment time, because they do not give a severity rating. Instruments that rapid dose escalation, reduced nociceptive input measure delirium severity, in addition to being diagnostic tools, include the Memorial Delirium Assessment Scale (MDAS) [57, 58] and the brief observational Nursing De- lirium Screening Scale (NuDESC) , derived from the Borderline cognitive impairment/delirium Confusion Rating Scale (CRS) .
Use of other psychoactive drugs, e.g., benzodiazepine A brief description of three delirium assessment tools and nonbenzodiazepine hypnotics, tricyclicantidepressants used in clinical practice follows.
Previous episode of OIN CAM
The CAM  is based on the DSM-III-R criteria. Al-
though it is a brief, four-item diagnostic algorithm that
takes ⬍5 minutes to administer, it does require training in
An essential feature for the clinical diagnosis of delir- its use. It has recently been validated in the palliative care ium of the Diagnostic and Statistical Manual of Mental setting .
Disorders IV-TR (DSM-IV-TR) criteria is a disturbance ofconsciousness . Noncore clinical features of delirium include sleep–wake cycle disturbance, altered psychomotor The MDAS  is a 10-item, four-point, clinician-rated in- activity, and emotional lability. Patients may exhibit pro- strument (possible range, 0 –30). It was originally designed dromal features including anxiety, restlessness, irritability, to measure severity but can be used as a diagnostic tool us- disorientation, and sleep disturbances . Patients may ing a cutoff total MDAS score ⱖ7 of 30 . This is a val- have disorganized thinking and disjointed unintelligible idated instrument . The objective cognitive testing speech. The altered perceptions that may occur include mis- items (items 2, 3, and 4) should be completed first because perceptions, illusions, delusions, and hallucinations .
this achieves a higher rate of completion and allows as- Clinical features include neurological motor abnormalities: sessment time for the more observational or subjective tremor, asterixis, myoclonus, and tone and reflex changes . Dysgraphia may also occur . Other neurologicalabnormalities that may be present include constructional apraxia, dysnomia, and aphasia . Generalized slowing The NuDESC  is an observational five-item scale (pos- of the electroencephalogram is a classic finding .
sible range, 0 –10) that includes the four items of the CRS and an additional assessment of psychomotor retar- Delirium Assessment Tools
dation. Each symptom (disorientation, inappropriate be- Delirium is frequently underdiagnosed in the clinical set- havior, inappropriate communication, illusions, or ting, even by experienced physicians and nurses . One hallucinations, as well as psychomotor retardation) is rated study reported that physicians and nurses missed the diag- 0 –2 according to its presence and severity. It is a low bur- nosis 23% and 20% of the time, respectively . A similar den tool that takes ⬍2 minutes to complete, and can be used underdiagnosis may occur in patients admitted to clinical for screening and monitoring delirium severity. The Nu- trials .
DESC has been validated and is reported to have a sensitiv- Historically, the Mini-Mental State Examination ity of 85.7% and a specificity of 86.8% .
(MMSE)  was used in multiple studies on cognitivefailure in cancer patients with delirium [2, 8, 51–53]. How- Further Clinical Assessment
ever, the MMSE only assesses cognitive function. For ex- The assessment of delirium also includes the investigation ample, two delirious patients with an MMSE score of 14 of of all potential precipitating factors for the delirium episode 30 can range from being completely lethargic to completely (as shown in Fig. 1) in order to identify reversible causes.
agitated and unmanageable. Better tools are needed to as- Medication history for both new and continuing drugs sess perceptual abnormalities, psychomotor changes, delu- should be reviewed. Predisposing factors that increase the sions, and other delirium features. Multiple validated patient's baseline susceptibility for developing delirium delirium-specific assessment tools are now available [54, may also be identified, such as pre-existing cognitive im-
Assessment and Management of Delirium in Cancer Patients fects of OIN resolve within 3–5 days of introduction of opi- Table 3. Management of opioid-induced neurotoxicity
oid rotation and hydration. There have been some case reports examining the effect of treatment of opioid-induced Initial opioid selection (e.g., avoid opioids with active delirium with acetylcholinesterase inhibitors , but cur- metabolites in patients with known renal failure) rently there is no supporting evidence for their effectiveness Hydration (oral/parenteral: i.v. or s.c.) from controlled trials .
Opioid dose reduction with or without Pharmacological Treatment of
Opioid switch/rotation The equianalgesic dose of the new opioid should bereduced by 30%–50%, e.g., morphine 3 There is limited research evidence from clinical trials, so hydromorphone, oxycodone, methadone, or fentanyl this review reports current best practice. Neuroleptics are Stop contributing drugs, e.g., hypnotics considered to be first-line agents [20, 70]. They are usually 75%–80% of episodes of drug-induced delirium resolve used as a short-term measure to relieve perceptual distur- by action of opioid rotation and discontinuation of other bance or agitation while reversible causes are investigated and treated, and include haloperidol and atypical antipsy- Psychostimulants chotics (Table 4) [20, 68 – 80]. There is no research evi- Symptomatic treatment with neuroleptics, e.g., dence to date to support particular dosing schedules and Consider benzodiazepine for myoclonus, e.g., practice. Clinical trials are needed to better inform current Reassurance and explanation Haloperidol is the most commonly used and the most studied neuroleptic [70, 81]. It is a potent dopamine D re- ceptor antagonist with few anticholinergic side effects.
However, there is limited randomized controlled trial evi- pairment or reduced sensory input with poor vision or deaf- dence for its use in the management of delirium . In the ness. Urinary retention and constipation may aggravate 2004 Cochrane review on drug therapy for delirium in ter- agitation, especially in the elderly.
minally ill patients, only one study met the review criteria In addition to the use of a delirium-specific tool, a mul- . This was the seminal double-blind, randomized com- tidimensional assessment of the patient's symptom burden, parison trial by Breitbart et al.  of haloperidol, chlor- using a validated instrument such as the Edmonton Symp- promazine, and lorazepam in the treatment of delirium in 30 tom Assessment System  enables the identification and hospitalized AIDS patients. Chlorpromazine and haloperi- quantification of other significant symptoms that are im- dol were found to be equally effective. There was a small pacting the delirium episode.
but significant decline in cognitive function over time withchlorpromazine. This study highlighted the importance of not treating delirium with a benzodiazepine as a single The multimodal management of delirium includes nonphar- agent, unless delirium is secondary to sedative or alcohol macological and environment management strategies, in addi- withdrawal, because the lorazepam arm was stopped early because of side effects (excessive sedation, increased con- simultaneously identifying and treating underlying causes fusion, disinhibition, and ataxia).
when appropriate. Comprehensive management should in- By 2007, there were three studies eligible for the Cochrane volve a multidisciplinary team. The patient's delirium severity review examining antipsychotics in delirium , comparing and response to treatment need to be monitored regularly.
haloperidol with risperidone, olanzapine, and placebo. The re-view concluded that haloperidol at a dose of ⬍3.5 mg/day, ris- Treatment of Underlying Causes
peridone, and olanzapine were equally effective.
Because 50% of delirium episodes in advanced cancer are Haloperidol has the advantage of versatile routes of ad- reversible, possible contributors to delirium (as shown in ministration: oral, s.c., i.m., and i.v. It is rarely sedating. Be- Fig. 1) should be appropriately treated. For drug-induced cause the average oral bioavailability of haloperidol is delirium, all implicated medications should be discontin- approximately 60% , parenteral doses are about twice ued or undergo a dose reduction if cessation of the impli- as potent as oral doses. High concentrations of haloperidol cated medication is not possible. Opioid rotation should be and reduced-haloperidol, the active metabolite of haloperi- instigated if opioid discontinuation is not possible [64 – 66].
dol, increase the frequency and severity of extrapyramidal See Table 3 for further management of OIN . Most ef- side effects (EPSs) . Parenteral administration of halo- Olanzapine has a common side effect of sedation, which Table 4. Guide to medications used for symptomatic
may be potentially beneficial in a hyperalert, hyperaroused treatment of delirium in advanced cancer patients patient with delirium. In addition, metabolic syndrome can Conventional neuroleptics [22, 72] occur with olanzapine , but the significance of this is unclear when used short term, as in the management of de- lirium. In an open, prospective trial of oral olanzapine for the treatment of delirium in 79 hospitalized cancer patients, Breitbart et al.  found that patients ⬎70 years of age, Atypical antipsychotics [22, 73] with hypoactive delirium, delirium of "severe" intensity (defined in their study as an MDAS score ⬎23 of 30), and a history of dementia, cerebral metastatic disease, and hyp- oxia had a poorer response to treatment. The parenteral olanzapine preparation for i.m. injection has been well tol- erated, with no injection site toxicity when administered by Methylphenidate hydrochloride  the s.c. route in some units .
A higher risk for cerebrovascular events in elderly de- mentia patients has been reported with atypical antipsy- Cholinesterase inhibitors [68, 69] chotics, especially risperidone . In a 2006 meta- Cholinomimetics  analysis assessing the adverse events associated with the use of atypical antipsychotics in the management of behav- Dexmedetomidine  ioral disturbances in patients with Alzheimer disease or other dementia , the duration of the 15 identified randomized, placebo-controlled trials was in the range of 6 –26 weeks. This None of these medications are currently recommended for the routine management of delirium. At present, they is as opposed to the usual short-term use of antipsychotics in are being investigated in the clinical setting.
the management of delirium. The use of atypical and typicalantipsychotics in the elderly has also been associated with ahigher risk for mortality [97, 98]. U.S. Food and Drug Admin- peridol reduces the risk for EPSs. However, there is marked istration (FDA) alerts have been issued for both classes of neu- variation in patient sensitivity to EPS development. In com- roleptics [99, 100].
parison with parkinsonism, neuroleptic-induced parkinson- In addition to EPSs, other adverse effects have been re- ism consists of the triad of bradykinesia, tremor, and ported with neuroleptics. QTc interval prolongation can occur, rigidity, with a predilection for the upper limbs, and with with the risk for sudden cardiac death, including with atypical gait change being mild .
antipsychotics [84, 101]. If the QTc interval is ⬎450 msec, or Clinical guidelines recommend starting haloperidol doses increases ⬎25% from baseline, then the dose of haloperidol of 0.5–2 mg, with varying frequency and routes of administra- and any other contributory medications should be re- tion [86, 87]. Most studies to date report dose ranges of 2–10 duced or ceased . In 2007, the FDA recommended mg/day [52, 88, 89]. Some authors also suggest using regular electrocardiogram monitoring when i.v. haloperidol is low-dose haloperidol for the management of hypoactive delir- given . Most reported cases of neuroleptic malig- ium [47, 90]. However, further research in the form of ran- nant syndrome have occurred in patients receiving par- domized, double-blind, placebo-controlled trials is needed in enteral haloperidol, although it may also occur with other the advanced cancer population to determine appropriate dos- neuroleptics, including atypical antipsychotics .
ing schedules for all delirium subtypes.
More recently, atypical antipsychotics, such as olanza- pine, risperidone, quetiapine, and aripiprazole, have been Simple environmental measures may help in the manage- used in the management of delirium in patients with cancer ment of patients with delirium . Education should be [20, 21, 91–93]. The reduced frequency of EPSs with this provided to the family and bedside nurse on the nature and class of antipsychotics is a result of 5-HT prognosis of delirium, and on measures required to mini- onism and muscarinic M receptor antagonism mitigating mize patient stimulation (Table 5).
D2 receptor blockade . EPSs can still occur with atyp- Up to 75% of patients recall their own symptoms after ical antipsychotics at higher doses, especially risperidone at delirium resolution . Patients require reassurance to doses ⬎6 mg/day .
help reduce their significant associated distress, with hypo-
Assessment and Management of Delirium in Cancer Patients not hastening death. Medications that have been used for PS Table 5. Summary of nonpharmacological management
include midazolam, lorazepam, phenobarbitol (phenobar- bitone), propofol, and methotrimeprazine (levomeproma- Physically safe for patient, and also for staff and family zine) (not available in the U.S.) [109 –112]. Consultation Minimize noise, excessive light, and excessive with a palliative care specialist is strongly recommended before initiating PS .
Streamline the patient's environment Call bell and other essential items visible and CLINICAL COURSE AND PROGNOSIS
Although approximately 50% of delirium episodes are re- Simple, clear, and concise communication versible, episodes are significantly more reversible if the Glasses, hearing aid, dentures where needed precipitating factor is opioids and other psychoactive drugs Explain each intervention prior to instituting care and hypercalcemia [7, 25]. Opioid rotation and discontinu- Orient patient frequently ation of other drugs results in resolution of approximately Provide a clock and calendar that are visible from 75%– 80% of episodes of drug-induced delirium. Delirium is less likely to improve in patients with underlying demen- Name of nurse also visible from the bed tia  or if the delirium is related to hypoxic or global met- Presence of familiar objects abolic encephalopathy, or disseminated intravascular Enlist the family to assist with reorientation coagulation [7, 25].
The presence of delirium is an independent factor in pre- dicting short-term survival of patients with advanced can- cer [14, 113]. Similarly, delirium is associated with greater Other health care providers mortality in medical inpatients [12, 86]. In 121 palliative care inpatients with delirium, Leonard et al.  found that patients with more advanced age, greater cognitive im- Patient, after delirium resolution pairment, and organ failure had significantly shorter sur-vival. In patients ⬎50 years old, persistent delirium isfrequent and associated with poorer outcomes, includinggreater mortality .
active delirium being just as distressing to patients as hy- peractive delirium [9, 11].
Family caregivers observe patient behaviors and expe- Studies are required on delirium predictors that are specific to rience distress more frequently than health care profession- patients with advanced cancer and on the efficacy of multimo- als [9, 11], and require ongoing education (especially dal preventative interventions in this patient population, as regarding patient disinhibition) and psychosocial support compared with trials that have been conducted in the elderly from the interprofessional team [10, 105]. Expressive sup- . There remains limited information from pharmacological portive therapy  is often helpful in reducing family randomized controlled trials to guide practice in evidence- member distress.
based neuroleptic administration to cancer and palliative carepatients. Further research is needed to determine efficacious REFRACTORY AGITATED DELIRIUM
and safe neuroleptic dosing schedules according to the differ- This often necessitates the use of more sedative drugs for ent delirium subtypes and etiologies, and also on the role of patient comfort and symptomatic relief . Palliative se- nonpharmacological and environment management strategies dation (PS) has been defined as the monitored use of pro- to improve the comprehensive multifaceted management of portionate sedative medication to reduce the patient's this distressing syndrome.
awareness of intractable and refractory symptoms near theend of life when other interventions have failed to control them . Refractory agitated delirium is the most com- In advanced cancer patients, the high frequency of delirium ac- mon indication for PS. Other indications for PS include se- companied by the frequent underdiagnosis of this syndrome vere dyspnea or respiratory distress, pain, hemorrhage, strongly suggests that regular screening for delirium should be severe seizures, and uncontrolled myoclonus. Appropri- conducted using validated tools in order to reach an earlier di- ately titrated PS in the dying is an ethically and legally ac- agnosis. Although delirium in this population is often associ- cepted intervention, with the aim of relieving suffering and ated with a poor prognosis, 50% of patients can improve with appropriate management of contributing etiologies, especially Eduardo Bruera is supported in part by National Insti- if opioids and other psychoactive drugs are precipitating fac- tutes of Health Grant numbers: RO1NR010162-01A1, tors, and involvement of the interprofessional team. Patients, RO1CA122292-01, and RO1CA124481-01.
family, and staff require ongoing support to reduce the impactof this potentially devastating condition.
The authors would like to thank Kathy R. King for her sec- Conception/Design: Shirley H. Bush, Eduardo Bruera
Manuscript writing: Shirley H. Bush, Eduardo Bruera
retarial assistance in the preparation of this manuscript.
Final approval of manuscript: Shirley H. Bush, Eduardo Bruera
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The Assessment and Management of Delirium in Cancer Patients
Shirley H. Bush and Eduardo Bruera The Oncologist 2009;14;1039-1049; originally published online October 6, 2009; This information is current as of July 24, 2011
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