Clinical Monograph: Delirium
An Evidence-Based Medicine (EBM) Monograph
for Psychosomatic Medicine Practice
View the entire Delirium monograph as PDF 
Delirium – EBM Summary
| On this page: | Introduction • Screening & Assessment • Treatment • Quality Indicators | |
| On other pages: | References • Appendixes: A B C D E |
INTRODUCTION
Objective and methods
This monograph summarizes current knowledge related to the diagnosis, epidemiology, etiology, and management of delirium. The monograph is based on the guideline ‘delirium’ of the National Institute of Clinical Excellence (NICE) [1], as well as on systematic reviews and pivotal trials. The quality of the evidence discussed in this monograph is graded as ‘high’, ‘moderate’, ‘low’ or ‘very low’, following the ‘Grading of Recommendations Assessment, Development and Evaluation’ (GRADE) system, which was developed by the Cochrane Center [1]. Readers are encouraged to consult the recommended readings for more detailed information (Appendix A)
Definition and symptoms
Delirium is an acute neuropsychiatric disorder characterized by a disturbed level of consciousness with reduced ability to focus, sustain, or shift attention, and accompanied by changes in cognition, such as memory deficits, disorientation, speech and language disturbances, delusions and perceptual abnormalities. These changes in cognition are not better accounted for by a pre-existing or evolving dementia. In addition, sleep-wake cycle disturbance, increased or decreased motor activity, and emotional disturbances are often present. The disturbance typically develops over a short period of time and tends to fluctuate during the course of the day [2].Clinically, a distinction between hyperactive and hypo-active delirium is often made on the basis of motor activity. Though this may be clinically useful, it has not found its way into the classification systems.
Diagnosis
The gold standard for the diagnosis of delirium are the criteria of the 4th edition of the Diagnostic and Statistical Manual (DSM IV; codes 291.0 to 293.0 and 780.09) or the 10th edition of the International Classification of Disease (ICD 10; code F05) [2, 3].
Prevalence and incidence
The occurrence of delirium depends on the setting.
- In the general population, the reported prevalence is low and ranges from <0.05 to 0.4%, with a higher prevalence in older people of 1.1% in those over 55 years [4, 5].
- For hospital inpatients, a median prevalence of 21.4%, a median incidence of 15.2%, and a median occurrence rate of 22% is reported on general medical wards. In the NICE guideline the term ‘occurrence rate’ is used when there is overlap between prevalence and incidence data, such as may occur when in incidence studies prevalent delirium upon entering the study is not excluded.
- The occurrence rate on general surgical wards is reported to be 44%; no data on prevalence and incidence rates in this setting are available [1].
- Occurrence rates are higher on Intensive Care Units, with a occurrence rates reported as high as 80%, depending on type of ICU [1].
- In long term care, low quality evidence shows a median occurrence rate of 15.9% [6].
Risk factors
Delirium is currently seen as the resultant of a complex interaction of predisposing and precipitating factors [7].
High quality evidence identifies the following risk factors for incident delirium
- Older age
- Cognitive impairment
- Visual impairment [1]
Moderate quality evidence identifies the following risk factors for incident delirium:
- lllness severity
- Comorbidity
- Infection
- Fractures
- Vascular surgery
- Presence of a bladder catheter [1].
Moderate to low quality evidence identifies the following risk factors for persistence of delirium:
- Cognitive impairment
- Medical comorbidity
- Vision impairment)
- Use of physical restraints [1].
Low level evidence identifies the following risk factors for increased severity of delirium:
- Number of room changes
- Absence of clock or watch
- Cognitive impairment
- Not wearing glasses [1].
Low level of evidence shows no, or no clinically relevant, association for incidence or severity of with a variety of variables, such as sex, mobility, hearing impairment, incontinence, dehydration and polypharmacy [1]. Clinical experience however supports close attention for polypharmacy as a contributing cause of delirium.
Prognosis
Delirium has a number of negative prognostic implications.
High quality evidence
- Increased length of hospital stay, particularly for ICU patients [1, 9]
- Increased and earlier post-discharge institutionalization [1]
Moderate to high quality evidence
- Increased mortality: the mortality of delirium patients during their hospital stay is 22 – 76%; the mortality in the first year after discharge is 35 – 40% [8].
Moderate quality evidence
- Delirium is a risk factor for cognitive decline and dementia after 3 years [1]
Low quality evidence
Costs
Several studies have demonstrated significantly increased costs of health care for patients who develop delirium [9, 10]. One study estimated these costs to be at least 2.5 times greater per day for delirious patients compared to non-delirious patients [11].
SCREENING AND ASSESSMENT
Most health care providers recognize that delirium is a serious, underdiagnosed problem, but a minority routinely screen for delirium and few use a specific tool for assessment [12]. Failure to detect delirium has been associated with poorer outcomes, including increased mortality [13], while explicit recognition of delirium has been associated with lower mortality and shorter inpatient stays [14].
Assessment consists of establishing the diagnosis, assessing severity and assessing clinical risks. Of the available diagnostic instruments, the Confusion Assessment Method (CAM) is preferred in a clinical setting, since it has the highest positive and lowest negative likelihood ratio (LR) (positive LR 9.6; 95% CI 5.8 – 16.0; negative LR 0.16; 95% CI 0.09 – 0.29) (moderate quality evidence) (http://www.healthcare.uiowa.edu/igec/tools/cognitive/CAM.pdf) [1, 15]. The MMSE score had the lowest discriminatory properties (moderate quality evidence) [15]. The MMSE should not be used alone to diagnose delirium.
In the ICU setting, moderate to high quality evidence shows that the CAM-ICU has the best data supporting its use, with positive LRs ranging from 13.42 to 36.36 [1]. Although there are a number of rating scales available for assessment of severity, no recommendation for a specific scale can be given. For most delirium rating scales, low to moderate evidence supports their use in the assessment of severity of delirium. [1, 16].
TREATMENT
Treatment of delirium consists foremost of treatment of the underlying medical condition. In addition, there is evidence that symptomatic treatment, including non-pharmacological and pharmacological treatment may be beneficial to the patient. (For a list or randomized pharmacological trials, see Appendix B).
Non-pharmacological treatment
There is moderate to very low quality evidence that suggests that enhanced treatment strategies for people with delirium are more effective than usual care. However, the various mono- and multi-component interventions vary substantially and most of the studies provide lower quality evidence, with much uncertainty around the results. For this reason, the NICE guideline development group abstained from recommending a specific strategy. There was consensus however that interventions targeting better orientation may be helpful in clinical practice [1].Pharmacological symptomatic treatment
Antipsychotics
Moderate to low quality evidence shows that antipsychotic medications are effective in the treatment of symptoms of delirium. Compared to treatment with placebo, treatment with an antipsychotic medication is associated with a higher proportion of remission in patients, and a reduced severity of delirium. In one small study, haloperidol (0.25 – 10mg/d), risperidone (0.25-4mg/day), and olanzapine (1.25 – 20mg/day) were equally effective in treating delirium, with few adverse effects [17]. There is no consistent evidence on whether haloperidol results in more or more severe extrapyramidal side effects than olanzapine or risperidone [1]. Although some studies have evaluated the differential response to pharmacological treatment in patients with various motor subtypes of delirium, the low quality of available evidence does not allow any conclusion or recommendation in this respect.Other medication
There is no evidence to support the use of benzodiazepines in the treatment of delirium not related to alcohol or benzodiazepine withdrawal [1]. There is no current evidence for the efficacy of cholinesterase inhibitors as treatment for delirium [1, 18-21]. In critically ill patients, treatment of delirium with the cholinesterase inhibitor rivastigmine is associated with increased mortality [21].
Prevention
Nonpharmacological prevention
Mono-component interventions: there is no evidence of the effect of subcutaneous versus intravenous fluids on the incidence, duration or severity of delirium, both in a hospital setting and in a long term care setting (low quality evidence) [1].
Multi-component interventions: low quality evidence shows that multi-component interventions based on targeting modifiable risk factors (such as cognitive impairment, sleep deprivation, immobility, vision impairment, hearing impairment, dehydration), reduces the incidence of delirium (RR 0.66; 95% CI 0.46 to 0.95), reduces average delirium duration, and reduces the number of patients with urinary incontinence after 6 months follow up (RR 0.80; 95% CI 0.65 to 0.99). There was no difference in mortality, delirium severity, the median length of stay in hospital, post-discharge institutionalisation, the incidence of delirium after 6 months follow up, and the MMSE score after 6 months follow up [1].Pharmacological prevention
Antipsychotics
The NICE guideline summerizes that moderate to low quality evidence suggests that prophylactic treatment with typical antipsychotics does not reduce the incidence of delirium in hospital patients. One low quality RCT (level 2 evidence) with risperidone showed a significant reduction in delirium incidence (RR 0.35; 95% CI 0.16 to 0.77) which corresponds to a number needed to treat of 5 (95% CI 3 to 14) [22]. Another study with olanzapine (level 2 evidence) showed a decreased incidence but longer duration and severity of delirium in postoperative patients after joint surgery [23]. In contrast with this conclusion, a recent RCT of 457 patients after surgery randomized to haloperidol 0.5mg IV bolus and 0.1mg/hr continuous infusion for 12 hours versus placebo showed decreased incidence of delirium and shorter duration of ICU stay [24]. Prophylactic treatment with haloperidol may reduce the severity and duration of delirium, as well as the length of hospital stay [25].Other medication
Rivastigmine and donepezil do not reduce the duration of delirium, nor the length of stay in the ICU or in the general hospital (moderate quality evidence). Prophylactic treatment with risperidone did not reduce the length of hospital stay (level 2) [1, 26].
QUALITY INDICATORS
Organization of detection and management
The available evidence does not allow for recommendation of a specific model of organization of delirium detection and management. However, the NICE guideline as well as available reviews and position papers stress the importance of a systematic and proactive approach to delirium identification and treatment. The approach to delirium should include systematic screening for patients with delirium risk factors, and then systematically following them for potential incident delirium and administer interventions known to help prevent delirium. Once delirium is established, adequate pharmacological and non-pharmacological treatment should be provided. Follow-up contacts can be provided if indicated in order to taper medication or to follow the cognitive status of the patient.
Specific quality indicators
The following indicators provide insight into the quality of the organization of detection and management of delirium:
- The presence of an institutional protocol for delirium, based on a professional guideline
- The availability of professionals with expertise in delirium (psychiatrist/geriatrician) on a 24/7 basis
- Percentage of patients over 65-years that has been screened for delirium risk factors on admission or pre-operatively
- Percentage of patients at high-risk for delirium that is screened for incident delirium during the first few days of admission or post-operatively
- When delirium is present, treatment with antipsychotic medication is considered, unless medically contraindicated and benzodiazepines are avoided unless a clear reason for using them is provided (e.g., alcohol withdrawal).
(Based on: Inspectie voor de Gezondheidszorg (IGZ), Nederlandse Vereniging van Ziekenhuizen (NVZ), Nederlandse Federatie van Universitair Medische Centra (NFU), Orde van Medisch Specialisten (OMS): Quality indicator set for general hospitals: 2010. Utrecht, Health Care Inspectorate of the Netherlands, 2009.)