Delirium and acute confusional states: Prevention, treatment, and prognosis

INTRODUCTION — Delirium is an acute confusional state characterized by an alteration of consciousness with reduced ability to focus, sustain, or shift attention. This results in a cognitive or perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia. Delirium develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. Delirium is typically caused by a medical condition, substance intoxication, or medication side effect.

Delirium is considered by some to be a specific type of confusional state that is characterized by increased vigilance along with psychomotor and autonomic overactivity and manifested as agitation, tremulousness, and hallucinations. In this discussion, however, the term "delirium" will be used synonymously with "acute confusional state" and will include states characterized by somnolence and decreased arousal, so-called "hypoactive delirium."

The management of delirium is based primarily upon expert consensus and observational studies, and only a small number of controlled clinical trials, which are difficult to perform in patients with cognitive impairment. The preponderance of evidence is most compelling for primary prevention of delirium using nonpharmacologic, multicomponent approaches targeted broadly at high-risk patients [1-3]. Prevention and therapy of delirium are based on the following principles:

●Avoiding factors known to cause or aggravate delirium, such as multiple medications, dehydration, immobilization, sensory impairment, and disruption of the sleep-wake cycle

●Identifying and treating the underlying acute illness

●Providing supportive and restorative care to prevent further physical and cognitive decline

●Where appropriate, controlling dangerous and severely disruptive behaviors using low-dose, short-acting pharmacologic agents so the first three steps can be accomplished

The prevention, treatment, and prognosis of delirium will be reviewed here. The definition, epidemiology, pathogenesis, clinical features, and diagnosis of delirium are discussed separately. (See "Diagnosis of delirium and confusional states".)

PREVENTION — No intervention or group of interventions reliably prevents delirium; however, multicomponent, nonpharmacologic interventions that manage many of the modifiable risk factors appear to reduce the incidence of delirium [3,4].

Modifying risk factors — A number of factors have been identified as causing or contributing to delirium in at-risk patients.

Examples of interventions designed to mitigate risk factors for delirium include:

●Orientation protocols – Provision of clocks, calendars, windows with outside views, and verbally reorienting patients may mitigate confusion that results from disorientation in unfamiliar environments.

●Cognitive stimulation – Patients with cognitive impairment, in particular, may benefit from activity such as regular visits from family and friends. At the same time, sensory overstimulation should be avoided, particularly at night.

●Facilitation of physiologic sleep – Nursing and medical procedures, including the administration of medications, should be avoided during sleeping hours when possible. Night-time noise should be reduced. One randomized trial found that the use of earplugs at night was associated with a lower incidence of confusion in intensive care unit (ICU) patients [5].

●Early mobilization and minimized use of physical restraints for patients with limited mobility – One study in mechanically ventilated, critically ill patients found that early institution of physical and occupational therapy along with consequent interruption in use of sedatives was associated with a lower number of hospital days with delirium [6].

●Visual and hearing aids for patients with these impairments

●Avoiding and/or monitoring the use of problematic medications – Medications are often implicated in precipitating delirium, particularly in those already at risk (table 1).

Benzodiazepines, in particular, are often implicated. In one systematic review, the authors concluded that benzodiazepines should be avoided in high-risk patients, while caution should be used in prescribing opioids, dihydropyridines, and antihistamines [7].

In one large cluster-randomized control study based in nursing homes, implementation of a computerized system to identify the use of problematic medications and trigger a medication review was associated with a lower incidence of delirium (HR = 0.42) [8].

●Avoiding and treating medical complications – A number of medical conditions are known to cause or aggravate delirium; these should be managed aggressively and prevented where possible.

Some studies have focused specifically on early volume repletion for patients with delirium. While one small study failed to show a benefit for hydration management on the incidence of delirium in a long-term care setting, the small number of patients (98) and short time period of intervention (four weeks) limited the ability of this study to demonstrate efficacy [9].

Hypoxemia and infections are other common complications in high-risk settings and patients. These may contribute to delirium and should be actively monitored for and treated when identified. An interventional program administered via a geriatric consultant team that emphasized avoiding medical complications achieved a one-third reduction in the incidence of delirium among 126 older adult patients undergoing hip surgery [10].

●Managing pain – Pain may be a significant risk factor for delirium. The use of nonopioid medications should be used where possible, as these are less likely to aggravate delirium. Clinicians must balance the benefits of using opioids to treat significant pain with the potential for an opioid-related delirium. Nonpharmacologic interventions are appealing in this setting. In one study, fascia iliaca compartment block after hip surgery was associated with a reduced incidence of postoperative delirium in intermediate-risk, but not in high-risk, patients [11].

Studies in patients undergoing surgery suggest that pre-emptive pain treatment may reduce the incidence of delirium. In one study of 58 older patients, administration of ketamine (given as a single dose during induction of anesthesia for cardiac surgery) was associated with a lower rate of postoperative delirium (3 versus 31 percent) [12]. However, making generalized recommendations from such studies is difficult because of the small sample size, inconsistent use of nonpharmacologic interventions, and lack of information regarding long-term outcomes [13]. Ketamine does not appear to be more generally useful in the prevention of postoperative delirium, as discussed in the following section.

Certain classes of opioids are probably best avoided in older patients and others prone to delirium. Meperidine, in particular, has been shown in multiple prospective studies to increase the risk for delirium [14-16].

Cancer patients with terminal delirium and pain may benefit from switching from shorter-acting opioids to long-acting agents such as methadone [17]. Clinicians should also consider the possibility that opioid-induced hyperalgesia may cause breakthrough pain and should consider using nonopioid analgesia for pain control. (See "Prevention and management of side effects in patients receiving opioids for chronic pain", section on 'Opioid-induced hyperalgesia'.)

Use of nursing protocols to better manage pain has been demonstrated to reduce the severity and duration, but not the incidence, of delirium [18].

In one study, a multicomponent intervention used standardized protocols to screen and control for six risk factors for delirium in 852 hospitalized patients aged 70 or older: cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration [19]. Interventions such as those listed above were targeted to the identified risk factors. This program resulted in a significant reduction in the number of delirium episodes compared with usual care (62 versus 90) and in the total number of days with delirium (105 versus 161); there was no effect upon delirium severity or the rate of recurrence. The investigators have since reported that community hospitals were able to successfully implement this program when there was a commitment of resources by hospital leadership and appropriate adaptation of protocols to local needs [20]. Subsequent randomized studies have confirmed that such multicomponent interventions can reduce the incidence of delirium and/or related complications [3,21-23].

Medications to prevent delirium — The available evidence does not support the use of medications to prevent delirium in high-risk settings such as acute care, intensive care, cardiac surgery, or other postoperative care [24-27]. Investigators continue to study the potential benefit of cholinesterase inhibitors, antipsychotic agents, and others:

●Cholinesterase inhibitors (eg, rivastigmine, donepezil) have been proposed as a means to prevent delirium in selected patients and high-risk settings (eg, older patients with or without dementia, postoperative and poststroke settings) [28,29]. However, clinical trials have not demonstrated a reduction in the prevalence or incidence of delirium, and side effects have been greater in patients receiving these medications [29-33].

●Antipsychotic agents, given prophylactically and in low dose, have been studied in the postoperative and critical care setting, and have been associated with inconsistent and, at best, modest benefits in the incidence, severity, and duration of delirium [34-40]. In one of these studies, treatment was associated with increased severity and longer duration of delirium [39]. A 2013 systematic review and meta-analysis of six studies concluded that such treatment reduced the incidence of delirium, but not the severity or duration; nor was the incidence of associated adverse events reduced [37]. In this analysis, second-generation antipsychotics appeared to be more beneficial compared with haloperidol.

●Dexmedetomidine administration has been studied in the treatment and prevention of delirium in the postoperative and critical care setting, with mixed results. In one randomized trial, low-dose dexmedetomidine (0.1 mcg/kg per hour, administered for the first 32 hours postoperatively) was associated with a lower incidence of postoperative delirium (9 versus 23 percent; OR 0.35, 95% CI 0.22-0.54). Some, but not all, studies have found similar results [41-43]. Adverse effects of dexmedetomidine include dose-dependent bradycardia and hypotension [44-46].

●Gabapentin, in pilot study, reduced the incidence of postoperative delirium, perhaps by reducing pain and opioid administration [47].

●Melatonin has shown inconsistent efficacy in the prevention of delirium. In two small trials in older inpatients (67,145 patients) with medical illness, the melatonin agonists, ramelteon and melatonin, appeared to be associated with a lower incidence of delirium [48,49]. Preoperative administration of melatonin was found to reduce the incidence of postoperative delirium in a randomized trial of 222 patients undergoing hip surgery [50]. By contrast, in a larger trial in 452 patients with acute hip fracture, there was no benefit from melatonin administration [51].

●Analgesics to control pain may reduce the incidence or severity of delirium, as discussed in the section above. However, they should not be used unselectively. While prophylactic use of ketamine to prevent pain has been associated with reduced incidence of postoperative delirium as discussed in the section above, a randomized trial including a broad patient group undergoing a variety of surgeries found no difference in delirium incidence between the ketamine and placebo groups [52]. Negative experiences such as hallucinations and nightmares were higher in patients receiving ketamine.

MANAGEMENT — The principles underlying the management of delirium are summarized in the algorithm (algorithm 1). The algorithm includes two pathways that are followed simultaneously: one to manage the behavior disturbance, and another to find and treat the underlying medical disorder. An important caveat is that the symptoms of delirium can have a prolonged duration, extending many weeks into the postacute period after the underlying causes and risk factors have been corrected.

Treatment of underlying conditions — Virtually any medical condition can precipitate delirium in a susceptible patient; multiple underlying conditions are often found [53]. When the underlying acute illness responsible for delirium is identified, specific therapy is directed toward the medical condition. (See "Acute toxic-metabolic encephalopathy in adults", section on 'Specific etiologies'.)

The conditions noted most commonly in prospective studies of delirium include:

●Metabolic encephalopathy – These include the following, which are discussed in detail separately. (See "Acute toxic-metabolic encephalopathy in adults".)

•Fluid and electrolyte disturbances (dehydration, hyponatremia/hypernatremia, hypo/hypercalcemia)

•Infections (sepsis, urinary tract, respiratory tract, skin and soft-tissue)

•Organ failure (uremia, liver failure, hypoxemia/hypercarbia)

•Hypoglycemia

●Drug toxicity – Drug toxicity causes or contributes to approximately 30 percent of all cases of delirium (table 1) [54]. Clinicians must be aware that delirium can occur even with "therapeutic" levels of such agents as digoxin or lithium, particularly in at-risk patients.

Certain acute drug-poisoning syndromes can be rapidly treated with the appropriate antidote. (See "General approach to drug poisoning in adults".)

●Withdrawal from alcohol and sedatives – The treatment of alcohol withdrawal is discussed separately. (See "Management of moderate and severe alcohol withdrawal syndromes", section on 'Management'.)

While Wernicke encephalopathy is not common, many older hospitalized patients have biochemical evidence of thiamine deficiency [55]. In addition, chronic alcoholism is often difficult to detect in this population, and symptoms of persistent alcoholic delirium may be difficult to distinguish from those of Wernicke encephalopathy [56]. Thiamine supplementation is inexpensive and virtually risk free; it should be provided to all hospitalized patients with evidence of nutritional deficiency. (See "Wernicke encephalopathy".)

Supportive medical care — The delirious patient is at risk for complications of immobility and confusion, leading to a high prevalence of irreversible functional decline.

It has long been assumed that the outcome of delirium could be improved by earlier identification of the disorder and comprehensive intervention to treat underlying causes and prevent subsequent complications such as immobility, aspiration, and skin breakdown. Unfortunately, there are few controlled studies. One study found that early identification and comprehensive geriatric consultation for patients with established delirium had little impact on length of stay, functional outcome, or survival [57]; another found that multicomponent interventions shortened the duration of delirium but had no impact on mortality or nursing home use [58]. Stronger evidence supports the use of these interdisciplinary efforts for prevention of delirium. (See 'Modifying risk factors' above.)

Nonetheless, an interdisciplinary approach to delirium should focus upon maintaining adequate hydration and nutrition, enhancing mobility and range of motion, treating pain and discomfort, preventing skin breakdown, ameliorating incontinence (seen in over half of delirious patients), and minimizing the risk of aspiration pneumonitis.

This team approach should also include family or other caregivers who may feel frightened or exhausted; delirium can be the "last straw" for those who have been caring for the demented. Caregiver resources must be realistically assessed.

Because delirium may require weeks or months to fully resolve, management often extends into subacute settings [59,60]. Transfers of care to new settings are periods of particular vulnerability for older patients, and it is important to effectively communicate information about mental status to the accepting treatment team [61].

Managing agitation — Managing disruptive behavior, particularly agitation and combative behavior, is a challenging aspect of delirium therapy. This hyperactive delirium is less common in older patients and, when it occurs, alternates with periods of hypoactive delirium, which may be less obvious to the clinical staff [62]. Periods of disruptive and hyperactive behavior place the patient at risk for falls, wandering off, or inadvertently removing intravenous lines and feeding tubes.

When delirium is manifest by agitation, symptom control is occasionally necessary to prevent harm or to allow evaluation and treatment. While nonpharmacologic interventions should be the mainstay of treatment, a cautious trial of psychotropic medication may be warranted in these circumstances. Unfortunately, there are limited data to guide treatment as the available studies have significant methodologic limitations [25,26]. It has also been observed that use of psychotropic medication to manage delirium appears to correlate more strongly with caregiver distress than with the actual severity of delirium symptoms [63].

Nonpharmacologic interventions — Mild confusion and agitation may respond to interpersonal and environmental manipulations. The hospital environment, characterized by high ambient noise, poor lighting, lack of windows, frequent room changes, and restraint use, often contributes to worsening confusion. Special units that address these concerns have improved the functional outcomes of hospitalization in such frail patients [64]. Frequent reassurance, touch, and verbal orientation can lessen disruptive behaviors; family members or other familiar persons are preferred, but professional sitters can also be used to effect. Delusions and hallucinations should be neither endorsed nor challenged. Other specific interventions are discussed above. (See 'Modifying risk factors' above.)

Physical restraints should be used only as a last resort, if at all, as they frequently increase agitation and create additional problems, such as loss of mobility, pressure ulcers, aspiration, and prolonged delirium. In one study, restraint use among patients in a medical inpatient unit was associated with a threefold increased odds of persistent delirium at time of hospital discharge [65]. Alternatives to restraint use, such as constant observation (preferably by someone familiar to the patient such as a family member), may be more effective.

Antipsychotic medications — When indicated, antipsychotic agents are generally used to treat severe agitation in the patient with delirium, because these symptoms are associated with self-harm and effective alternatives are not available. No medication is currently approved by the US Food and Drug Administration (FDA) for the management of delirium, so the use of these agents for such an indication is off-label.

Based on limited evidence, we suggest low-dose haloperidol (0.5 to 1 mg) be used as needed to control moderate to severe agitation or psychotic symptoms, up to a maximum dose of 5 mg per day. Continuous or prophylactic dosing is not recommended. Higher doses may be used in closely monitored settings (intensive care unit [ICU]) where the goals and sedation needs are different (see "Sedative-analgesic medications in critically ill adults: Properties, dose regimens, and adverse effects", section on 'Antipsychotics'). Haloperidol can be administered orally, intramuscularly (IM), or intravenously. The onset of action may be as soon as 5 to 20 minutes after intravenous administration or longer with the IM or oral route. An immediate response is not expected. Intravenous haloperidol has been associated with clinically significant QT prolongation requiring additional precautions with its use. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".)

We recommend only short-term use of antipsychotic agents, as these agents have been associated with a higher risk of mortality and possibly stroke when used in patients with dementia [66]. (See "Management of neuropsychiatric symptoms of dementia".)

Data supporting the use of antipsychotic agents for managing delirium are limited [25,67,68]. In one of the largest randomized trials, 1183 patients with delirium in the intensive care unit were treated with twice-daily haloperidol, ziprasidone, or placebo; doses were adjusted based on resolution of symptoms or the development of side effects [69]. Outcomes (median days alive without delirium or coma) were similar between patient groups. Limitations of this study include that both hypoactive and hyperactive delirium was included, and that the primary endpoint was duration of delirium rather than control of agitation, which is the usual indication for these agents. In addition, all patients were treated with a multicomponent nonpharmacologic intervention, which may have contributed to the overall lower rate of delirium and the ability to detect differences related to medical treatment. Other smaller trials have suggested that these agents may reduce the severity of delirium episodes [34,70,71], but overall, the evidence supporting the use of pharmacologic agents is inconclusive [27].

Because of the longer clinical experience with haloperidol, it remains the standard therapy in this setting [72]. The newer atypical antipsychotic agents, quetiapine, risperidone, ziprasidone, and olanzapine, have fewer side effects in other clinical settings, and in small studies they appear to have similar efficacy to haloperidol [73-75]. A meta-analysis of three small studies that compared haloperidol with risperidone and olanzapine found that the three agents were similarly effective in treating delirium [76]. A small clinical trial compared escalating doses of quetiapine with placebo as add-on treatment to as-needed haloperidol in 36 patients in the ICU with delirium [77]. Quetiapine was associated with a shorter duration of delirium, reduced agitation, and higher rates of discharge to home after hospitalization. By contrast, a randomized trial comparing haloperidol, ziprasidone, and placebo in ICU patients found that active treatment did not improve outcomes when measured by number of days alive without altered mental status or the incidence of adverse events [68].

Extrapyramidal side effects are higher in patients treated with high-dose haloperidol (>4.5 mg per day), but were similar among patients treated with low-dose haloperidol, olanzapine, and risperidone in one study [76,78]; in general, haloperidol should be avoided in favor of atypical antipsychotics in patients with parkinsonism. Sedation and hypotension can also occur as a side effect of these medications [77]. (See "Prognosis and treatment of dementia with Lewy bodies" and "Management of nonmotor symptoms in Parkinson disease".)

Benzodiazepines — Benzodiazepines have a limited role in the treatment of delirium; they are primarily indicated in cases of sedative drug and alcohol withdrawal or when antipsychotic drugs are contraindicated. Surveys of practicing clinicians suggest that benzodiazepines are overprescribed for patients with delirium [79]. (See "Sedative-analgesic medications in critically ill adults: Selection, initiation, maintenance, and withdrawal".)

Benzodiazepines (eg, lorazepam 0.5 to 1 mg) have a more rapid onset of action (five minutes after parenteral administration) than the antipsychotics, but they can worsen confusion and sedation [70]. In a prospective study of ICU patients, lorazepam was an independent risk factor for incident delirium, increasing the risk by approximately 20 percent [80]. A systematic review of benzodiazepine use in delirium found two studies comparing benzodiazepine versus antipsychotic agents; one study found no advantage, the other found decreased effectiveness of benzodiazepines compared with antipsychotics [81]. In two randomized trials of sedative treatment in mechanically ventilated ICU patients, the benzodiazepine midazolam was associated with significantly more delirium compared with dexmedetomidine treatment (77 versus 54 percent) [82], while similar outcomes were observed with lorazepam and dexmedetomidine [83].

Cholinesterase inhibitors — Cholinesterase inhibitors do not have a role in the treatment or symptom management of delirium.

A randomized clinical trial compared rivastigmine with placebo in 104 hospitalized intensive care patients with delirium who were also prescribed haloperidol. The trial was stopped early because of higher mortality in the rivastigmine group (22 versus 8 percent) [84]. Median duration of delirium was also longer in the rivastigmine group (5 versus 3 days, p = 0.06). Cholinesterase inhibitors are also not helpful in the prevention of delirium. (See 'Prevention' above.)

Other sedative agents — Other sedative agents (eg, dexmedetomidine, propofol, as well as benzodiazepines and antipsychotics) are often used in the critical care setting to manage anxiety and pain, as well as delirium, and are believed at times to contribute to delirium as well as to manage agitation. The selection and management of these agents are discussed separately. (See "Sedative-analgesic medications in critically ill adults: Selection, initiation, maintenance, and withdrawal" and "Sedative-analgesic medications in critically ill adults: Properties, dose regimens, and adverse effects".)

Managing pain — In the appropriate setting (postoperative, post-trauma), the role of pain as a contributor to delirium and agitation should be considered, and analgesia provided. As discussed above, therapies to reduce pain should be administered with some caution as they also have the potential to contribute to delirium. (See 'Modifying risk factors' above.)

In one randomized study of 53 patients after cardiac surgery, those who received morphine (5 mg IM) had more rapid improvement of agitation and were less likely to require additional sedatives than those who were administered haloperidol (5 mg IM) [85]. Other outcomes were not assessed.

Hypoactive delirium — In general, symptomatic treatment is not used for hypoactive delirium.

One study suggested that patients with hypoactive delirium have a similar response to treatment with haloperidol as those who were agitated [86]. Other case reports and one uncontrolled case series have suggested that treatment with the stimulant drug methylphenidate may be associated with improved alertness and cognition [87-89]. However, in the absence of stronger evidence, psychostimulants such methylphenidate or modafinil cannot be recommended for treating hypoactive delirium because of the potential risk of precipitating agitation or worsening psychotic symptoms [90].

Terminal delirium — Delirium is common in palliative care settings and causes significant distress to family members [91]. Underlying causes are often multifactorial, but up to 50 percent of episodes are reversible, particularly when the underlying cause is either dehydration or medication related [92,93].

Hyperactive as well as hypoactive presentations of terminal delirium are both common; the former may require management with antipsychotic medication, usually haloperidol, as described above [94,95]. In the setting of severe preterminal patient distress, palliative sedation using short-acting, titratable benzodiazepines such as midazolam has been suggested as a potential alternative [96]. However, routine use of such agents in end-of-life delirium is not warranted. A multicenter, double-blind, randomized trial of risperidone, haloperidol, and placebo among patients receiving palliative care in hospice or hospital settings found patients in the placebo arm had fewer distressing delirium symptoms and better overall survival [97]. (See 'Antipsychotic medications' above.)

In one small case series, methadone appeared to be effective in the treatment of both refractory pain and terminal delirium when antipsychotic medication was not [17]. Midazolam sedation has also been described as a therapeutic option in this setting [98,99]. (See "Overview of managing common non-pain symptoms in palliative care", section on 'Palliative sedation'.)

Ethical considerations — The treatment of patients with delirium is complicated by the critical nature of their illness and their impaired capacity to make decisions. The doctrine of "implied consent" allows the emergency treatment of patients with delirium in order to stabilize a life-threatening process [100]. However, it is important to document the assessment of cognitive abilities and decision-making capacity. Current practice leaves considerable room for improvement. As an example, in a prospective study of 173 medical and surgical procedures performed in patients with delirium at a university hospital, investigators found no documented assessments of competency or decision-making capacity, with cognitive assessments documented in only 4 percent of cases [101]. No informed consent was documented in 19 percent of procedures, and surrogates were used in only 20 percent.

Relying upon implied consent or substituted judgment in cases of delirium introduces other difficulties since clinicians and proxies do not always make the same decisions as patients. Every effort should be made to determine what the patient's own treatment preferences are, and to not assume that decision-making capacity is "all or none." In some cases, for example, psychopharmacologic treatment of delirium may restore sufficient mental capacity to allow a discussion of treatment preferences [102]. In addition, since delirium typically fluctuates in severity, there may also be periods of lucidity in which a discussion of treatment preferences may take place.

OUTCOMES — Delirium has an enormous impact upon the health of older persons. Patients with delirium experience prolonged hospitalizations, functional and cognitive decline, higher mortality, and higher risk for institutionalization, even after adjusting for baseline differences in age, comorbid illness, or dementia [103-110].

Mortality — Mortality associated with delirium is high. A report of pooled results from several studies estimated the one- and six-month mortality to be 14 and 22 percent, respectively, approximately twice that of patients without delirium [111]. These findings were likely due in part to the presence of concomitant dementia and severe physical illness (eg, sepsis). However, prospective observational studies that adjusted for dementia and other potential confounding factors still found that delirium was an independent marker for mortality at 6 or 12 months after hospitalization [103,112-115].

Studies have also found a relationship between the duration of delirium and mortality [116,117]. In one study, protracted delirium (ie, persistent symptoms of confusion at six months) was associated with increased one-year mortality compared with those whose symptoms had resolved more quickly, regardless of whether or not patients also had underlying dementia [115].

Persistent cognitive dysfunction — Signs of delirium may persist for 12 months or longer, particularly in those with underlying dementia [118].

One long-term follow-up study found that after two years, only one-third of patients who had experienced delirium still lived independently in the community [119]. Another prospective study of 225 patients after heart surgery found that those who experienced delirium were more likely to have a persistent drop in Mini-Mental State Examination (MMSE) scores over baseline at six months compared with those who did not suffer delirium (40 versus 24 percent); at 12 months the differences were not quite statistically significant (31 versus 20 percent, p = 0.055) [120]. In a study of 821 patients admitted to medical or surgical intensive care, the duration of delirium was associated with worse cognitive function at 3 and 12 months. While only 6 percent had cognitive impairment at baseline, at 12 months, 34 percent had deficits that were similar to patients with moderate traumatic brain injury [121]. Other studies have found that patients with delirium are more likely to have long-term cognitive problems than hospitalized patients who did not suffer from delirium [122]. Thus, although delirium is considered potentially reversible, impairments may be prolonged and perhaps permanent, particularly in frail, older patients.

Episodes of delirium during hospitalization adversely affect the course of the disease in patients with Alzheimer disease (AD). Of 263 participants in the Massachusetts Alzheimer's Disease Research Center patient registry who experienced hospitalization, 56 percent developed delirium during hospitalization. Although the AD patients with and without delirium had similar rates of cognitive decline prior to hospitalization, after hospitalization, deterioration proceeded at twice the rate in the year after hospitalization compared with patients who did not develop delirium. The higher rate of cognitive decline was evident for up to five years after the hospital stay [123,124]. Patients with AD who experienced delirium also had an increased risk of death and institutionalization [109].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Delirium and confusional states in older adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Delirium (confusion) (The Basics)")

●Beyond the Basics topic (see "Patient education: Delirium (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS — Delirium is an acute confusional state characterized by an alteration of consciousness with reduced ability to focus, sustain, or shift attention.

●Effective measures to prevent delirium include avoiding, where possible, those factors known to cause or aggravate delirium; orientation protocols; environmental modification and nonpharmacologic sleep aids; early mobilization and minimizing use of physical restraints; and visual and hearing aids. (See 'Prevention' above.)

●Prophylactic medications (cholinesterase inhibitors, ketamine, antipsychotic agents) have not been conclusively demonstrated to prevent delirium. (See 'Prevention' above.)

●Thiamine supplementation should be considered in all patients with delirium. (See 'Treatment of underlying conditions' above.)

●When the underlying acute illness responsible for delirium is identified, specific therapy is directed toward that condition as the most effective means of reversing the delirium. (See 'Treatment of underlying conditions' above.)

●Physical restraints should be used only as a last resort, if at all, as they frequently increase agitation and create additional problems, such as loss of mobility, pressure ulcers, aspiration, and prolonged delirium. (See 'Nonpharmacologic interventions' above.)

●Frequent reassurance, touch, and verbal orientation from familiar persons can lessen disruptive behaviors. (See 'Nonpharmacologic interventions' above.)

●A cautious trial of psychotropic medication should be reserved for as-needed treatment of severe agitation or psychosis with the potential for harm. In this setting, we suggest using low-dose haloperidol (0.5 to 1 mg orally [PO] or intramuscularly [IM]) (Grade 2C). Other antipsychotic agents (quetiapine, risperidone, ziprasidone, olanzapine) are reasonable alternatives. (See 'Antipsychotic medications' above.)

•Haloperidol is associated with a low frequency of sedation and hypotension.

•Haloperidol should be avoided in patients with underlying parkinsonism, for whom atypical antipsychotics (eg, quetiapine) are preferred.

•Short-term use of antipsychotic agents is advised.

•Clinicians should recognize when the caregiver's distress, rather than reduction of the severity or duration of delirium, is often a motivating factor in the decision to prescribe psychotropic medication.

●Benzodiazepines should be avoided in patients with or at risk for delirium, except in cases of sedative drug and alcohol withdrawal or when antipsychotic medications are contraindicated. (See 'Benzodiazepines' above.)

●Cholinesterase inhibitors are not effective in preventing or treating the symptoms of delirium, and often create undesirable side effects. (See 'Cholinesterase inhibitors' above.)

●Delirium may require weeks or months to fully resolve. Episodes of delirium may adversely affect the course of the disease in patients with Alzheimer disease (AD). Delirium appears to be associated with increased short- and long-term mortality. (See 'Outcomes' above.)