Delirium is a common neuropsychiatric condition that affects 15% to 70% of elderly medical and surgical patients. It tends
to be a transient disorder, although long-term complications are not uncommon. Medical comorbidity is the rule, and predisposing,
as well as precipitating, factors are important to consider in its management. Major risk factors for delirium include advanced
age, cognitive impairment, and chronic medical illness. Delirium is associated with several adverse outcomes including mortality,
increased length of hospital stay, increased risk of dementia, and high rates of institutional placement. Delirium is distressing
for patients, families, and staff. Nonpharmacologic-integrated intervention programs may improve outcome and may be incorporated
into the overall medical management.
Key words: delirium • encephalopathy • acute confusional state cognitive function • risk factors • prevention
Drugs discussed: haloperidol/Haldol • risperidone/Risperdal olanzapine/Zyprexa • quetiapine/Seroquel
Delirium, a condition that presents in medical and surgical settings, is known by various names, including organic brain syndrome,
intensive care unit (ICU) psychosis, encephalopathy, and acute confusional state. ICU psychosis was once considered a psychological
defense against loss of autonomy in ICU patients. Although that is no longer thought to be the case, our understanding of
this intriguing phenomenon is limited. However, advances are being made at unraveling the underlying pathophysiologic mechanisms
that lead to this disturbing condition.1
Diagnosing delirium
The Confusion Assessment Method (CAM) is a simple, valid instrument for diagnosing delirium.2 The CAM algorithm consists of four items operationalized from the DSM-III-R delirium criteria. CAM criteria are:
1. acute onset and fluctuating course of mental status change;
2. inattention;
3. disorganized thinking;
4. altered level of consciousness.
The diagnosis of delirium requires the presence of features 1 and 2, along with either 3 or 4. The CAM has a sensitivity of
94% to 100% and a specificity of 90% to 95%, compared with diagnosis by a psychiatrist. Several other instruments for diagnosing
delirium and evaluating the severity of delirium are available in the literature.3 Delirium can present as either hypoactive, hyperactive, or mixed.
Natural history of delirium
Delirium is a relatively brief, transient disorder frequently associated with medical and psychiatric co-morbidity. Major
risk factors for delirium include advanced age, cognitive impairment, and chronic medical illness.4 In such individuals, even apparently minor insults (eg, change of medication, minor infection) can trigger a delirium episode.
Those with more advanced age and pre-existing cognitive impairment tend to have a more prolonged, severe delirium.5,6
Delirium is common among elderly patients admitted to the hospital, with 15% to 70% of elderly medical and surgical inpatients
experiencing delirium at some point in their hospital stay.7,8 In a prospective study of medical inpatients age 65 and older, 15% developed delirium.9 In that study, delirium lasted one day or less in 69% of cases; the course of delirium was highly variable; prolonged episodes
of delirium were documented; and multiple recurrences of delirium were observed. Some cases of delirium can be traced to a
single cause; however, delirium is often the end result of a number of predisposing and precipitating factors. Duration of
delirium may be summarized as follows:
- 20% of delirium lasts one day;
- 50% lasts three days;
- 67% is over in four days;
- 20% lasts 5 to 10 days, and
- 15% lasts 10 days to one month.10
Implications of delirium
Delirium is associated with increased morbidity, mortality, and length of hospitalization.7,11 Persistent deficits following delirium are common, with up to 60% of individuals having persistent cognitive impairment
following such an episode.12 Delirium also poses an increased risk for the subsequent development of dementia.13 The risk of death at one-year follow-up for patients who were delirious was 62% greater than non-delirious controls in a
recent study.11
Delirium is a distressing condition for patients, family, and staff.14,15 The patient is often unable to communicate appropriately or at all, and is unable to fully participate in treatment decisions.16 This may lead to more investigations and interventions than necessary.
The family cannot appropriately communicate with their loved one, and by observing the suffering, feels helpless, which in
turn leads to severe stress and distress on the part of the family.17 Providing education about the course and causes of delirium to patients and their families is an important part of delirium
management.8
Figure 1 Implications of delirium
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For the medical and nursing staff, delirium makes assessment of other symptoms more difficult, and there is an increased risk
of conflict between members of staff regarding patient management, and between staff and family who might feel that not enough
is being done (figure 118 ).
Prevention strategies
Attempts to prevent delirium through various methods have met with mixed results.19 A large multi-component delirium prevention study, focusing on delirium risk factors amenable to practical intervention
strategies, targeting cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairments, and dehydration,
showed a reduction in delirium incidence from 15% to 9.9% in the treatment group (NNT=20).20
A geriatric consultation model intervention trial showed beneficial results: In the model, a geriatrician assessed at-risk
patients pre-operatively or shortly after surgery and continued with daily visits for the duration of the hospitalization,
making targeted recommendations based on a structured protocol. The intervention included advising on:
- adequate CNS oxygen delivery,
- pain management,
- elimination of unnecessary medications,
- regulation of bowel/bladder function,
- nutrition,
- early mobilization,
- monitoring for post-operative complications,
- assuring appropriate environmental stimuli (eg, hearing aids, eyeglasses, clock, calendar), and
- managing agitated delirium if it were to develop.21
This intervention was associated with decreased incidence of delirium (32% versus 50%, p=0.04) with an even greater reduction in incidence of severe delirium. Other non-medication prevention trials have had more
modest effects.22
Recently, medication-based trials for preventing delirium have shown mixed results. One study using haloperidol23 found that delirium incidence did not differ in the group that received haloperidol prophylaxis prior to hip surgery, although
other secondary outcomes (eg, delirium severity, duration) were favorably affected by the intervention. A second study examining
use of the cholinesterase inhibitor donepezil for prevention of post-operative delirium did not find significant differences
in favor of this treatment.24 Other authors have proposed use of benzodiazepines incorporated into possible delirium prevention strategies, but the value
of this type of intervention is not clear.25
Treatment strategies
The mainstay of delirium management is to prevent it from occurring when possible, and to promptly identify and treat underlying
medical conditions when delirium does occur.8,26 Several reviews have discussed the nonpharmacologic and pharmacologic treatment strategies for delirium.19,27,28
Nonpharmacologic interventions. Recent publications have examined multi-factorial, integrated intervention programs, focusing on nonpharmacologic intercessions.29-31 These programs center on changing the organization of providing care by reorganizing from a task-allocation care system
to that of a patient-allocation care system. In a patient-allocation system, one allocated caregiver has personal responsibility
for a particular patient, allowing such a patient to become familiar with at least one person per shift. Daytime shifts are
arranged to provide as few different personnel as possible.
These programs are based on intensive education of nursing staff and multidisciplinary team members in respect to delirium
and human interaction.29,30 Simple interventions for delirium, such as frequent orientation of patients, accommodations for visual and hearing impairments,
implementation of nonpharmacologic sleep promotion, careful attention to fluid and nutrition status, and promotion of mobility,
may have an ameliorating effect on delirium.8,20,21,26
Pharmacologic interventions. Although more is being learned about the pathophysiology of the condition,32 little new information is available regarding its pharmacologic management. The American Psychiatric Association guidelines
state that haloperidol is the drug of choice in the treatment of delirium, and that benzodiazepines may be used in specific
withdrawal states.8 However, atypical antipsychotics are being used more frequently,33 but not without concerns for potential side effects, including extrapyramidal symptoms, sedation, cardiac arrhythmias,34 cerebrovascular events,35 and death.36,37
Table 1 Recommended doses of antipsychotics for treatment of delirium in elderlya
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Delirium most commonly affects the frail elderly and any medication initiated in this population needs to be monitored with
great care to minimize possible adverse events.38 Treatment with antipsychotics needs to be undertaken cautiously in the elderly with a careful evaluation for particular
vulnerability to medication side-effects. Antipsychotic treatment should be time-limited, initiated at low-doses and titrated
carefully to minimize potential adverse effects. Typical doses of antipsychotics used in treating delirium are listed in table
1.21,39Delirium is thought to reflect neurotransmitter dysfunction, and there is some evidence that antipsychotics may "treat" delirium
by restoring the acetylcholine/dopamine balance by reducing dopaminergic neurotransmission. Antipsychotics reduce agitation
in hyperactive delirium, thereby reducing delirium severity and facilitating medical interventions and investigations, although
studies have found that individuals with hypoactive delirium also have reductions in delirium severity following treatment
with antipsychotics.38,40 Other novel treatment strategies are being assessed, such as anticonvulsants and cholinesterase inhibitors.41,42
Conclusion
Research on the pathophysiology of delirium is progressing, but still has to translate into new pharmacotherapeutic applications.
Many cases of delirium may be prevented through multidisciplinary interventions and possibly pharmacological methods. Antipsychotic
medications are currently the mainstay of pharmacotherapy for delirium. Non-pharmacologic integrated intervention programs
may improve outcome and should be incorporated into the overall medical management. Delirium remains a poorly understood condition
with potentially significant negative consequences.
Dr. van Zyl is director of consultation-liaison psychiatry, and immediate past program director, psychiatry residency training program,
Queen's University, Canada.
Dr. Seitz is a third-year psychiatry resident at Queen's University, Canada.
Disclosures: The authors have no real or apparent conflicts of interest relating to the content presented in this publication.
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