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CLINICAL SYNTHESIS   |    
Ask the Expert: Psychosomatic Medicine/Delirium
José R. Maldonado, M.D.
FOCUS 2009;7:336-342.
View Author and Article Information

CME Disclosure

José R. Maldonado, M.D., Associate Professor of Psychiatry and Medicine; Chief, Medical and Forensic Psychiatry Section; and Medical Director, Psychosomatic Medicine Program, Stanford University School of Medicine, Stanford, CA.

No conflict of interest to report.

I have been asked to consult on a patient who suffers from delirium. What are the pertinent risk factors and are there any good treatment algorithms?

Delirium is a challenging neuropsychiatric problem affecting medically ill patients. It is also the most common psychiatric syndrome found in the general hospital setting. Its prevalence surpasses that of the most commonly known and identified psychiatric syndromes and varies depending on the medical setting (1). By definition, delirium is an acute or subacute organic mental syndrome characterized by disturbance of consciousness, global cognitive impairment, disorientation, the development of perceptual disturbance, attention deficits, disordered sleep-wake cycle, fluctuation in presentation (e.g., waxing and waning), and changes in psychomotor activity (depending on the type of delirium) (1).

Seldom are we able to identify a single clear cause for the development of delirium in any one patient. Therefore, the syndrome of delirium is better understood as having a multifactorial etiology. These multiple etiological entities may give rise to transient disruption of normal neuronal activity, which in turn cause the various manifestations of delirium. Details of the pathogenesis of delirium have been discussed extensively elsewhere (2).

Of the many risk factors identified as causative of delirium (1), the following are the most common: It is impossible to cover all possible risk factors and mechanisms of delirium production in this commentary, but these have been thoroughly discussed in two recent review papers (1, 2). Table 1 also has a useful mnemonic for insults that may lead to delirium: "I watch death."

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Table 1.

Insults That May Lead to Delirium

Another important aspect to consider is the differential diagnosis. The symptoms of delirium vary from patient to patient and sometimes within a single patient over time. Some have suggested that there are motor variations (i.e., hyperactive, hypoactive, and mixed states) regarding their presentation (47). But what a clinician needs to keep in mind is that symptoms of delirium may present like mania, psychosis, catatonia, and even depression. In fact, data suggests that nearly 40% of the times when psychosomatic medicine consultants are asked to assist in the management of depression of hospitalized medically ill patients, these subjects were, in fact, experiencing hypoactive delirium and not major depression (48, 49). Substance intoxication/abuse (particularly CNS stimulant agent intoxication [e.g., cocaine and amphetamines]) and withdrawal states (particularly from CNS depressant agents [e.g., alcohol, benzodiazepines, and barbiturates]) may all lead to various forms of delirium (usually the hyperactive type). Conversely, acute intoxication with a CNS depressant or withdrawal from a CNS stimulant may lead to hypoactive forms of delirium.

Understanding delirium is important because of its high prevalence and the increased morbidity and mortality rates associated with its development. The incidence of delirium in the ICU has been reported to be as high as 81.3% (50). Several studies have found that patients who developed delirium fared much worse than their counterparts without delirium when controlling for all other factors. One study (51) showed that the mortality rate was higher among patients with delirium (as high as 8% compared with 1% in patients without delirium). In another study, patients in the ICU who developed delirium had higher 6-month mortality rates (34% versus 15%, p=0.03) (52). Similarly, another study showed that the 90-day mortality was as high as 11% among patients with delirium, compared with only 3% among elderly patients without delirium (53). Not only is delirium associated with increased mortality, but the rate of morbidity is also increased. Multiple studies have demonstrated that patients with delirium have prolonged hospital stays (i.e., average 5—10 days longer), compared with patients with the same medical problem who do not develop delirium as a complication (5052, 54).

Finally, the development of delirium has been associated with significant increases in the cost of delivering care. A study of cardiac surgery demonstrated that the calculated additional cost caused by the development of postoperative delirium after cardiac surgery was $6,150 per patient (55). Similarly, a subsequent study of the same population demonstrated that the development of postoperative delirium nearly doubled the cost of care in cardiac valve replacement (i.e., $6,763 in patients who did not develop delirium versus $12,965 in patients who developed delirium). A study of a step-down critical care unit showed that even though only 14% of patients developed delirium, they represented 22% of ALL hospital days during the index period (54). The same study showed that patients with delirium remained hospitalized an average of 9.2 days longer than their counterparts without delirium at an average cost of $28,000 per patient. A study of patients in the ICU with delirium showed that health care costs were 31% higher than for patients with similar medical problems but without delirium (i.e., $41,836 versus $27,106 per patient) (56). In addition, in a study of hospitalized elderly patients, data show that 1) delirium is common, 2) patients with delirium had significantly higher unadjusted health care costs and survived fewer days, 3) the average costs per day among patients with delirium were 2.5-fold greater than those for patients without delirium; and 4) the total cost estimates attributable to delirium ranged from $16,303 to $64,421 per patient (57).

As can be surmised from the above facts, it is imperative to treat delirium early, but it is more important to prevent it. There are several excellent studies suggesting potential interventions for the prevention of delirium. The best nonpharmacological method is the multicomponent intervention method described below (58). With this intervention strategy a 40% reduction in the odds of developing delirium has been seen. Other nonpharmacological prevention strategies, primarily consisting of the prophylactic use of neuropsychiatric consultation in "at-risk patients" have also demonstrated a lower incidence of postoperative delirium and a reduction in associated complications (e.g., decubitus ulcers, urinary tract infections, nutritional complications, sleeping problems, and falls) (59, 60). There have also been pharmacological interventions in small, but promising studies that have demonstrated significant reductions in the development of delirium. Several studies have demonstrated that antipsychotics, given preoperatively, may reduce the incidence of postoperative delirium (6164). Some studies have suggested that the long-term use of acetylcholinesterase inhibitors in at-risk populations may lower the incidence of postoperative delirium (65, 66). However, studies using short-term preoperative treatment failed to demonstrate any benefit (67, 68). A recently published article demonstrated a dramatic reduction in the incidence of postoperative delirium (3% versus 50%) in cardiac patients with the use of the novel anesthetic dexmedetomidine and avoidance of the use of more conventional GABA-ergic agents (69).

There are few conclusive studies demonstrating efficacy in treatment. Many studies using pharmacological agents have shown either conflicting findings, or the study population or data size is inadequate to allow for generalizability of the results. Thus, what follows is a basic algorithm for the prevention and management of delirium. Steps associated with robust evidence-based data are identified with an asterisk (*). The others have been developed from clinical practice or empirical data based on theoretical models. A more thorough discussion of these, along with their theoretical rationale, is beyond the scope of this commentary and can be found elsewhere (1, 2, 7072).

  • Timely diagnosis

    • Be vigilant for the possibility of delirium; remember that many symptoms may be confused with other psychiatric syndromes, particularly depression in cases of hypoactive delirium and agitation in cases of substance intoxication and withdrawal.

    • Obtain information on the patient's baseline level of cognitive functioning from all available accessory sources (e.g., spouse, family, or nursing staff).

    • Screen for the development of delirium in high-risk groups. Use objective delirium rating scales if possible [e.g., Delirium Rating Scale-98 (73) or confusion assessment method (74)].

  • Identify and treat underlying medical problems that may be causing or contributing to delirium in your particular patient (Table 1). The ultimate treatment of choice is the timely discovery and correction of the underlying medical causes of delirium. That is, aggressively treat infectious processes and electrolyte imbalances, correct vital signs and end-organ functioning, restore a more physiological sleep-wake cycle, minimize fear, anxiety, and pain, and manage extrinsic/environmental factors, such as lighting and noise control.*

  • Institute non-pharmacological treatment strategies* (based on Inouye's multicomponent intervention method for prevention of delirium in elderly patients) (58).

    • Correct malnutrition, dehydration, and electrolyte abnormalities as quickly and safely as possible.

    • Remove immobilizing lines and devices (i.e., intravenous lines, chest tubes, bladder catheters and physical restraints) as early as safely possible.

    • Correct any sensory deficits the patient may have (i.e., eyeglasses or hearing aids).

    • Promote as normal a circadian sleep pattern as possible. It is better if this can be achieved by environmental manipulations, such as light control (i.e., lights on and curtains drawn during the day and lights off at night) and noise control (i.e., provide ear plugs, turn off TVs, and minimize night staff chatter) rather than by the use of medications.

    • Provide adequate intellectual and environmental stimulation as early as possible (e.g., orient the patient to date, time, and circumstance regularly, provide a newspaper, or set the TV to a news broadcast rather than to reruns).

    • Minimize environmental isolation.

  • Consider pharmacological treatment strategies.

    • Conduct an inventory of all pharmacological agents being administered to the patient. Any medication or agent known to cause delirium or to have high anticholinergic potential should be discontinued, if possible, or a suitable alternative should be instituted.*

    • Avoid using GABA-ergic agents to control agitation, if possible.* Exception: In patients undergoing CNS depressant withdrawal (i.e., alcohol, benzodiazepines, or barbiturates) or when more appropriate agents have failed and sedation is needed to prevent patient's harming himself or herself.

    • Adequately assess and treat pain because uncontrolled pain has been found to be a contributor to the development and exacerbation of delirium.*

    • Avoid the use of opioids for behavioral control of agitation (i.e., use only for pain management), because opioid use has been associated with delirium.*

    • For the pharmacological target management of delirium (all types) consider using the following.

      • Acetylcholinesterase inhibitor (e.g., rivastigmine, donepezil, physostigmine, or rivastigmine) for correction of central anticholinergic syndrome.

      • Serotonin antagonist (e.g., ondansetron), to control toxic elevations of serotonin usually associated with hypoactive delirium, although some studies have suggested use of a serotonin antagonist may be indicated in all types of delirium.

      • Opioid agent rotation, such as switching from morphine and meperidine to fentanyl or hydromorphone.

      • Melatonin or melatonin agonists (e.g., ramelteon) to promote a more natural sleep.

      • Dopamine antagonists to manage the theorized abnormally elevated levels of dopamine and provide restoration of putative hippocampal functions (e.g., short-term memory) and reversal of other regional brain disturbances (e.g., agitation, psychosis, or primitive reflexes), as well as to protect neurons against hypoxic stress and injury (2, 75). The dose of dopamine antagonist used may depend on the type of delirium being treated (1, 7679).

      • α2 Adrenergic agonists (e.g., dexmedetomidine or clonidine) for protection against the acute release of norepinephrine due to hypoxia or ischemia, which leads to further neuronal injury and the development or worsening of delirium. The data to date are more robust for delirium prevention (69, 80),* although data are emerging for treatment, especially delirium associated with massive norepinephrine discharges (i.e., alcohol withdrawal).

      • N-methyl-d-aspartate receptor blocking agents to minimize glutamine-induced neuronal injury (e.g., amantadine or memantine).

    • For hyperactive delirium:

      • Use low to moderate doses of haloperidol (e.g., <20 mg/24 hour), if the patient's cardiac condition allows it and there are no significant electrolyte abnormalities.*

        • Before using haloperidol, obtain a 12-lead electrocardiogram and measure the corrected Q-T interval (QTc) and electrolyte levels. Correct potassium and magnesium levels, if needed.

        • If possible, avoid the use of other medications known to increase QTc and/or inhibitors of CYP3A4.

        • Discontinue use of haloperidol if QTc increases to >25% of baseline or >500msec.

      • When the use of haloperidol is contraindicated or not desirable (i.e., prolonged QTc or history of severe extrapyramidal symptoms), atypical antipsychotics should be considered (1, 81):

        • Evidence is better for risperidone and quetiapine.*

        • Limited data are available for olanzapine, aripiprazole, and perospirone.

        • Avoid clozapine and ziprasidone. Note: antipsychotics should be used with caution and only short term for the management of delirium or agitation in patients suffering from dementia. Data suggest a twofold increase in mortality for patients with dementia after long-term treatment with antipsychotic agents (82).

    • For hypoactive delirium:

      • Evidence suggests that dopamine antagonists may still have a place, given the excess dopamine theory.

        • If haloperidol is used, recommended doses are in the very low range (i.e., 0.25—1 mg/24 h).*

        • If an atypical antipsychotic is preferred, consider an agent with low sedation (i.e., risperidone); unless a sedative agent is needed to restore the sleep-wake cycle if there is not response to E.4 (see above).

      • In patients with extreme psychomotor retardation or catatonic features, in the absence of agitation or psychosis, consider the use of psychostimulant agents (e.g., methylphenidate, dextroamphetamine, or modafinil) or conventional dopamine agonists (e.g., bromocriptine, amantadine, or memantine).

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Trzepacz PT: The Delirium Rating Scale. its use in consultation-liaison research.  Psychosomatics 1999; 40: 193— 204
[PubMed]
 
Inouye S, van Dyck CH, Alessi, CA, Balkin S, Siegal AP, Horwitz RI: Clarifying confusion: the confusion assessment method. A new method for detection of delirium.  Ann Intern Med 1990; 113: 941— 948
[PubMed]
 
Brown T: Basic mechanisms in the pathogenesis of delirium, in  The Psychiatric Care of the Medical Patient . Edited by Stoudemire A, Fogel BS, Greenberg DB,  New York,  Oxford Press, 2000, pp 571— 580
 
Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians: Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult.  Crit Care Med 2002; 30: 119— 141
[PubMed]
[CrossRef]
 
Riker RR, Fraser GL, Cox PM: Continuous infusion of haloperidol controls agitation in critically ill patients.  Crit Care Med 1994; 22: 433— 440
[PubMed]
[CrossRef]
 
Shapiro BA, Warren J, Egol AB, Greenbaum DM, Jacobi J, Nasraway SA, Schein RM, Spevetz A, Stone JR: Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Society of Critical Care Medicine.  Crit Care Med 1995; 23: 1596— 1600
[PubMed]
[CrossRef]
 
Tune, L. The role of antipsychotics in treating delirium. Curr Psychiatry Rep 2002. Jun [cited 4 3]; 209-12]. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12003684
 
Maldonado JR, van der Starre PJ, Block T, Wysong A: Post-operative sedation and the incidence of delirium and cognitive deficits in cardiac surgery patients.  Anesthesiology 2003; 99: 465
 
Lonergan E, Britton AM, Luxenberg J, Wyller T: Antipsychotics for delirium.  Cochrane Database Syst Rev 2007: CD005594d
 
Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, Gill R, Juszczak E, Yu LM, Jacoby R, DART-AD Investigators: The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial.  Lancet Neurol 2009; 8: 151— 157
[PubMed]
[CrossRef]
 
References Container
Anchor for Jump
Table 1.

Insults That May Lead to Delirium

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References

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Maldonado JR: Pathoetiological model of delirium: a comprehensive understanding of the neurobiology of delirium and an evidence-based approach to prevention and treatment.  Crit Care Clin 2008; 24: 789— 856
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Elie M, Cole MG, Primeau FJ, Bellavance F: Delirium risk factors in elderly hospitalized patients.  J Gen Intern Med 1998; 13: 204— 12
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Inouye S, Zhang Y, Jones RN, Shi P, Cupples LA, Calderon HN, Marcantonio ER: Risk factors for delirium at discharge: development and validation of a predictive model.  Arch Intern Med 2007; 167: 1406— 1413
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Gibson GE, Peterson C: Aging decreases oxidative metabolism and the release and synthesis of acetylcholine.  J Neurochem 1981; 37: 978— 984
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Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW: Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients.  Anesthesiology 2006; 104: 21— 6
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Milstein A, Pollack A, Kleinman G, Barak Y; Confusion/delirium following cataract surgery: an incidence study of 1-year duration.  Int Psychogeriatr 2002; 14: 301— 306
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[CrossRef]
 
Bergmann K, Eastham EJ: Psychogeriatric ascertainment and assessment for treatment in an acute medical ward setting.  Age Ageing 1974; 3: 174— 188
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[CrossRef]
 
Kalisvaart K, Vreeswijk R, de Jonghe JF, van der Ploeg T, van Gool WA, Eikelenboom P: Risk factors and prediction of postoperative delirium in elderly hip-surgery patients: implementation and validation of a medical risk factor model.  J Am Geriatr Soc 2006; 54: 817— 822
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Wahlund L, Bjorlin GA: Delirium in clinical practice: experiences from a specialized delirium ward.  Dement Geriatr Cogn Disord 1999; 10: 389— 392
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Wacker P, Nunes PV, Cabrita H, Forlenza OV: Post-operative delirium is associated with poor cognitive outcome and dementia.  Dement Geriatr Cogn Disord 2006; 21: 221— 227
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Lowery DP, Wesnes K, Ballard CG: Subtle attentional deficits in the absence of dementia are associated with an increased risk of post-operative delirium.  Dement Geriatr Cogn Disord 2007; 23: 390— 394
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Aldemir M, Ozen S, Kara IH, Sir A, Bac B: Predisposing factors for delirium in the surgical intensive care unit.  Crit Care 2001; 5: 265— 270
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Cacchione PZ, Culp K, Dyck MJ, Laing J: Risk for acute confusion in sensory-impaired, rural, long-term-care elders.  Clin Nurs Res 2003; 12: 340— 355
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Francis J: Three millennia of delirium research: moving beyond echoes of the past.  J Am Geriatr Soc 1999; 47: 1382
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Tuma R, DeAngelis LM: Altered mental status in patients with cancer.  Arch Neurol 2000; 57: 1727— 1731
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Breitbart W, Gibson C, Tremblay A: The delirium experience: delirium recall and delirium-related distress in hospitalized patients with cancer, their spouses/caregivers, and their nurses.  Psychosomatics 2002; 43: 183— 194
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Lawlor PG, Gagnon B, Mancini IL, Pereira JL, Hanson J, Suarez-Almazor ME, Bruera ED: Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study.  Arch Intern Med 2000; 160: 786— 794
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Girard TD, Pandharipande PP, Ely EW: Delirium in the intensive care unit.  Crit Care 2008; 12( suppl 3): S3
 
Plaschke K, Thomas C, Engelhardt R, Teschendorf P, Hestermann U, Weigand MA, Martin E, Kopitz J: Significant correlation between plasma and CSF anticholinergic activity in presurgical patients.  Neurosci Lett 2007; 417: 16— 20
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Tune L, Carr S, Hoag E, Cooper T: Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium.  Am J Psychiatry 1992; 149: 1393— 1394
[PubMed]
 
Flacker JM, Wei JY: Endogenous anticholinergic substances may exist during acute illness in elderly medical patients.  J Gerontol A Biol Sci Med Sci 2001; 56: M353— M355
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Mach JR Jr, Dysken MW, Kuskowski M, Richelson E, Holden L, Jilk KM: Serum anticholinergic activity in hospitalized older persons with delirium: a preliminary study.  J Am Geriatr Soc 1995; 43: 491— 495
[PubMed]
 
Mulsant BH, Pollock BG, Kirshner M, Shen C, Dodge H, Ganguli M: Serum anticholinergic activity in a community-based sample of older adults: relationship with cognitive performance.  Arch Gen Psychiatry 2003; 60: 198— 203
[PubMed]
[CrossRef]
 
McCusker J, Verdon J, Caplan GA, Meldon SW, Jacobs P: Older persons in the emergency medical care system.  J Am Geriatr Soc 2002; 50: 2103— 2105
[PubMed]
[CrossRef]
 
Berger M, Vollmann J, Hohagen F, Konig A, Lohner H, Voderholzer U, Riemann D: Sleep deprivation combined with consecutive sleep phase advance as a fast-acting therapy in depression: an open pilot trial in medicated and unmedicated patients.  Am J Psychiatry 1997; 154: 870— 872
[PubMed]
 
Evans JI, Lewis SA: Sleep studies in early delirium and during drug withdrawal in normal subjects and the effect of phenothiazines on such states.  Electroencephalogr Clin Neurophysiol 1968; 25: 508— 509
 
Johns M, Large AA, Masterton JP, Dudley HA: Sleep and delirium after open heart surgery.  Br J Surg 1974; 61: 377— 381
[PubMed]
[CrossRef]
 
Lipowski ZJ: Delirium (acute confusional states).  JAMA 1987; 258: 1789— 1792
[PubMed]
[CrossRef]
 
Mistraletti G, Carloni E, Cigada M, Zambrelli E, Taverna M, Sabbatici G, Ombrello M, Elia G, Destrebecq AL, Iapichino G: Sleep and delirium in the intensive care unit.  Minerva Anesthesiol 2008; 74: 329— 333
 
Aurell J, Elmqvist D: Sleep in the surgical intensive care unit: continuous polygraphic recording of sleep in nine patients receiving postoperative care.  Br Med J (Clin Res Ed) 1985; 290: 1029— 1032
[PubMed]
[CrossRef]
 
Heller SS, Frank KA, Malm JR, Bowman FO Jr, Harris PD, Charlton MH, Kornfeld DS: Psychiatric complications of open-heart surgery: a re-examination.  N Engl J Med 1970; 283: 1015— 1020
[PubMed]
[CrossRef]
 
Helton MC, Gordon SH, Nunnery SL: The correlation between sleep deprivation and the intensive care unit syndrome.  Heart Lung 1980; 9: 464— 468
[PubMed]
 
Ito H, Harada D, Hayashida K, Ishino H, Nakayama K: Psychiatry and sleep disorders—delirium.  Seishin Shinkeigaku Zasshi 2006; 108: 1217— 1221
[PubMed]
 
Munoz X, Marti S, Sumalla J, Bosch J, Sampol G: Acute delirium as a manifestation of obstructive sleep apnea syndrome.  Am J Respir Crit Care Med 1998; 158: 1306— 1307
[PubMed]
 
Balan S, Leibovitz A, Zila SO, Ruth M, Chana W, Yassica B, Rahel B, Richard G, Neumann E, Blagman B, Habot B: The relation between the clinical subtypes of delirium and the urinary level of 6-SMT.  J Neuropsychiatry Clin Neurosci 2003; 15: 363— 366
[PubMed]
[CrossRef]
 
Olofsson K, Alling C, Lundberg D, Malmros C: Abolished circadian rhythm of melatonin secretion in sedated and artificially ventilated intensive care patients.  Acta Anaesthesiol Scand 2004; 48: 679— 684
[PubMed]
[CrossRef]
 
Shigeta H, Yasui A, Nimura Y, Machida N, Kageyama M, Miura M, Menjo M, Ikeda K: Postoperative delirium and melatonin levels in elderly patients.  Am J Surg 2001; 182: 449— 454
[PubMed]
[CrossRef]
 
Kress JP, Pohlman AS, O'Connor MF, Hall JB: Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation.  N Engl J Med 2000; 342: 1471— 1477
[PubMed]
[CrossRef]
 
Palmstierna T: A model for predicting alcohol withdrawal delirium.  Psychiatr Serv 2001; 52: 820— 823
[PubMed]
[CrossRef]
 
Ritchie J, Steiner W, Abrahamowicz M: Incidence of and risk factors for delirium among psychiatric inpatients.  Psychiatr Serv 1996; 47: 727— 730
[PubMed]
 
Vaurio LE, Sands LP, Wang Y, Mullen EA, Leung JM: Postoperative delirium: the importance of pain and pain management.  Anesth Analg 2006; 102: 1267— 1273
[PubMed]
[CrossRef]
 
Fong HK, Sands LP, Leung JM: The role of postoperative analgesia in delirium and cognitive decline in elderly patients: a systematic review.  Anesth Analg 2006; 102: 1255— 1266
[PubMed]
[CrossRef]
 
Vella-Brincat J, Macleod AD: Adverse effects of opioids on the central nervous systems of palliative care patients.  J Pain Palliat Care Pharmacother 2007; 21: 15— 25
[PubMed]
 
Wang Y, Sands LP, Vaurio L, Mullen EA, Leung JM: The effects of postoperative pain and its management on postoperative cognitive dysfunction.  Am J Geriatr Psychiatry 2007; 15: 50— 59
[PubMed]
[CrossRef]
 
Centeno C, Sanz A, Bruera E: Delirium in advanced cancer patients.  Palliat Med 2004; 18: 184— 194
[PubMed]
[CrossRef]
 
Meagher DJ Trzepacz PT: Motoric subtypes of delirium.  Semin Clin Neuropsychiatry 2000; 5: 75— 85
[PubMed]
 
Farrell KR, Ganzini L: Misdiagnosing delirium as depression in medically ill elderly patients.  Arch Intern Med 1995; 155: 2459— 2464
[PubMed]
[CrossRef]
 
Maldonado JR, Dhami N: Recognition and management of delirium in the medical and surgical intensive care wards.  J Psychosom Res 2003; 55: 150
 
Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, Truman B, Dittus R, Bernard R, Inouye SK: The impact of delirium in the intensive care unit on hospital length of stay.  Intens Care Med 2001; 27: 1892— 1900
[CrossRef]
 
Francis J, Martin D, Kapoor WN: A prospective study of delirium in hospitalized elderly.  JAMA 1990; 263: 1097— 1101
[PubMed]
[CrossRef]
 
Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS: Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit.  JAMA 2004; 291: 1753— 1762
[PubMed]
[CrossRef]
 
Pompei P, Foreman M, Rudberg MA, Inouye SK, Braund V, Cassel CK: Delirium in hospitalized older persons: outcomes and predictors.  J Am Geriatr Soc 1994; 42: 809— 815
[PubMed]
 
Maldonado JR, Dhami N, Wise L: Clinical implications of the recognition and management of delirium in general medical and surgical wards.  Psychosomatics 2003; 44: 157— 158
 
Ebert AD, Walzer TA, Huth C, Herrmann M: Early neurobehavioral disorders after cardiac surgery: a comparative analysis of coronary artery bypass graft surgery and valve replacement.  J Cardiothorac Vasc Anesth 2001; 15: 15— 19
[PubMed]
[CrossRef]
 
Milbrandt EB, Deppen S, Harrison PL, Shintani AK, Speroff T, Stiles RA, Truman B, Bernard GR, Dittus RS, Ely EW: Costs associated with delirium in mechanically ventilated patients.  Crit Care Med 2004; 32: 955— 962
[PubMed]
[CrossRef]
 
Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK: One-year health care costs associated with delirium in the elderly population.  Arch Intern Med 2008; 168: 27— 32
[PubMed]
[CrossRef]
 
Inouye S, Bogardus ST Jr, Charpentier PA, Leo-Summers L, Acampora D, Holford TR, Cooney LM Jr: A multicomponent intervention to prevent delirium in hospitalized older patients.  N Engl J Med 1999; 340: 669— 676
[PubMed]
[CrossRef]
 
Lundström M, Olofsson B, Stenvall M, Karlsson S, Nyberg L, Englund U, Borssén B, Svensson O, Gustafson Y: Postoperative delirium in old patients with femoral neck fracture: a randomized intervention study.  Aging Clin Exp Res 2007; 19: 178— 186
[PubMed]
 
Marcantonio ER, Flacker JM, Wright RJ, Resnick NM: Reducing delirium after hip fracture: a randomized trial.  J Am Geriatr Soc 2001; 49: 516— 522
[PubMed]
[CrossRef]
 
Kalisvaart K, de Jonghe JF, Bogaards MJ, Vreeswijk R, Egberts TC, Burger BJ, Eikelenboom P, van Gool WA: Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study.  J Am Geriatr Soc 2005; 53: 1658— 1666
[PubMed]
[CrossRef]
 
Larsen KA, Kelly S, Stern TA: A double-blind, randomized, placebo-controlled study of peri-operative administration of olanzapine to prevent post-operative delirium in joint replacement patients, in  Proceedings of 54th Annual Meeting of the Academy of Psychosomatic Medicine.  Amalia Island, Fla, 2007
 
Prakanrattana U, Prapaitrakool S: Efficacy of risperidone for prevention of postoperative delirium in cardiac surgery.  Anaesth Intensive Care 2007; 35: 714— 719
[PubMed]
 
Schrader SL, Wellik KE, Demaerschalk BM, Caselli RJ, Woodruff BK, Wingerchuk DM: Adjunctive haloperidol prophylaxis reduces postoperative delirium severity and duration in at-risk elderly patients.  Neurologist 2008; 14: 134— 137
[PubMed]
[CrossRef]
 
Dautzenberg PL, Mulder LJ, Olde Rikkert MG, Wouters CJ, Loonen AJ: Delirium in elderly hospitalised patients: protective effects of chronic rivastigmine usage.  Int J Geriatr Psychiatry 2004; 19: 641— 644
[PubMed]
[CrossRef]
 
Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G: Cholinesterase inhibition as a possible therapy for delirium in vascular dementia: a controlled, open 24-month study of 246 patients.  Am J Alzheimers Dis Other Demen 2004; 19: 333— 339
[PubMed]
[CrossRef]
 
Liptzin B, Laki A, Garb JL, Fingeroth R, Krushell R: Donepezil in the prevention and treatment of post-surgical delirium.  Am J Geriatr Psychiatry 2005; 13: 1100— 1106
[PubMed]
 
Sampson EL, Raven PR, Ndhlovu PN, Vallance A, Garlick N, Watts J, Blanchard MR, Bruce A, Blizard R, Ritchie CW: A randomized, double-blind, placebo-controlled trial of donepezil hydrochloride (Aricept) for reducing the incidence of postoperative delirium after elective total hip replacement.  Int J Geriatr Psychiatry 2007; 22: 343— 349
[PubMed]
[CrossRef]
 
Maldonado J, Wysong A, van der Starre PJA, Miller C, Reitz BA: Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery.  Psychosomatics 2009; 50: 206— 217
[PubMed]
[CrossRef]
 
APA: Practice guideline for the treatment of patients with delirium, in  American Psychiatric Association Steering Committee on Practice Guidelines . Edited by Trzepacz P.  Washington, DC,  APA, 1999
 
APA: Guideline watch: practice guideline for the treatment of patients with delirium, in  American Psychiatric Association Practice Guidelines . Edited by Cook IA.  Washington, DC,  American Psychiatric Association, 2004
 
Khan RA, Kahn D, Bourgeois JA: Delirium: sifting through the confusion.  Curr Psychiatry Rep 2009; 11: 226— 234
[PubMed]
[CrossRef]
 
Trzepacz PT: The Delirium Rating Scale. its use in consultation-liaison research.  Psychosomatics 1999; 40: 193— 204
[PubMed]
 
Inouye S, van Dyck CH, Alessi, CA, Balkin S, Siegal AP, Horwitz RI: Clarifying confusion: the confusion assessment method. A new method for detection of delirium.  Ann Intern Med 1990; 113: 941— 948
[PubMed]
 
Brown T: Basic mechanisms in the pathogenesis of delirium, in  The Psychiatric Care of the Medical Patient . Edited by Stoudemire A, Fogel BS, Greenberg DB,  New York,  Oxford Press, 2000, pp 571— 580
 
Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians: Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult.  Crit Care Med 2002; 30: 119— 141
[PubMed]
[CrossRef]
 
Riker RR, Fraser GL, Cox PM: Continuous infusion of haloperidol controls agitation in critically ill patients.  Crit Care Med 1994; 22: 433— 440
[PubMed]
[CrossRef]
 
Shapiro BA, Warren J, Egol AB, Greenbaum DM, Jacobi J, Nasraway SA, Schein RM, Spevetz A, Stone JR: Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Society of Critical Care Medicine.  Crit Care Med 1995; 23: 1596— 1600
[PubMed]
[CrossRef]
 
Tune, L. The role of antipsychotics in treating delirium. Curr Psychiatry Rep 2002. Jun [cited 4 3]; 209-12]. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12003684
 
Maldonado JR, van der Starre PJ, Block T, Wysong A: Post-operative sedation and the incidence of delirium and cognitive deficits in cardiac surgery patients.  Anesthesiology 2003; 99: 465
 
Lonergan E, Britton AM, Luxenberg J, Wyller T: Antipsychotics for delirium.  Cochrane Database Syst Rev 2007: CD005594d
 
Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, Gill R, Juszczak E, Yu LM, Jacoby R, DART-AD Investigators: The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial.  Lancet Neurol 2009; 8: 151— 157
[PubMed]
[CrossRef]
 
References Container
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+

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