Delirium is defined as an acute

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1 Marisa Wan, MD, FRCPC, Jocelyn M. Chase, MD, FRCPC Delirium in older adults: Diagnosis, prevention, and treatment Recognizing delirium promptly and treating the underlying cause can prevent the significant consequences of an acute disturbance in cognition, which include cognitive and functional decline, falls, and admission to long-term care. ABSTRACT: Delirium is common in hospitalized older adults and is known to increase the risk for subsequent functional decline and mortality. The pathophysiology is not fully understood, but delirium may be due to inflammatory mechanisms and a cholinergic neurotransmitter deficiency in the brain. During acute illness, older patients are at risk of delirium due to a decreased cognitive reserve. A high index of suspicion can allow clinicians to recognize delirium promptly and search for the underlying cause. Workup includes a thorough history, physical examination, and investigations to identify acute illness or destabilized chronic conditions. Therapy focuses on treating the triggering cause as well as addressing patient-specific and environmental risk factors that may contribute to the development or worsening of delirium. Ideally, nonpharmacological strategies should be used to address six risk factors that contribute to delirium: cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration. While antipsychotics can be used off-label to manage symptoms of delirium, they do not treat the underlying cause and are associated with side effects. Delirium is defined as an acute decline in cognitive functioning and should be considered a medical emergency as it is often the result of a noxious disruption to equilibrium. Delirium is common in the hospitalized older adult, with some studies reporting incidence rates of 29% to 64%. 1 The consequences of delirium are significant and include associations with increased mortality, cognitive and functional decline, falls, and admission to long-term care. 1 When delirium does occur, the medical team and patient s family should be aware that further support on discharge may be needed given the risk of cognitive and functional decline associated with delirium. Delirium is considered a quality indicator in the care of hospitalized older patients. 2 A better understanding of the pathophysiology of delirium and some effective strategies for This article has been peer reviewed. Dr Wan is a staff geriatrician at Providence Health Care. Dr Chase is a clinical instructor in the Division of Geriatric Medicine at the University of British Columbia and a staff geriatrician at St. Paul s Hospital. bc medical journal vol. 59 no. 3, april 2017 bcmj.org 165

2 diagnosis, prevention, and management can help clinicians ensure that patients affected by delirium receive the care they need. Risk factors and pathophysiology Delirium can arise following one single destabilizing medical event, but more often multiple factors contribute to its initiation and development. In addition, some patients are more vulnerable than others. In one study, Inouye and colleagues identified the most important preadmission risk factors for delirium to be visual impairment, severe illness, cognitive impairment, and volume depletion. 3 The greatest in-hospital risk factors found in another study were the use of physical restraints, malnutrition, polypharmacy, the use of a urinary catheter, and any iatrogenic event. 4 With each additional predisposing factor, the likelihood of delirium grows and should prompt a clinician to consider prevention strategies. The pathogenesis behind delirium is not fully understood, but several mechanisms have been postulated. Systemic inflammatory cytokine response and neurotransmitter disruption are the two main mechanisms thought to link multifactorial medical conditions and delirium. 5 During a systemic inflammatory response such as sepsis, proinflammatory cytokines released in the peripheral circulation enter the central nervous system, altering endothelial function, diminishing perfusion, activating microglia, and causing neuronal apoptosis and neurotoxicity. This process is selfpropelling and can last for months after the initial event. 5 Anticholinergic medications are known to induce or worsen delirium by binding to nicotinic and muscarinic receptors in the brain, modulating cognition and arousal, and lending support to the concept of cholinergic deficiency in delirium. 6 In addition, metabolic abnormalities may lead to decreased acetylcholine synthesis and synaptic transmission. Dopamine, norepinephrine, and serotonin can also play a role in arousal, and their levels are affected The presence of delirium may indicate underlying brain vulnerability and should therefore increase suspicion for an underlying cognitive impairment or dementia, especially if the precipitating insult appears disproportionately minor. by the cholinergic pathway. 6 The function of other neurotransmitters in delirium, such as glutamate, melatonin, and gamma-aminobutyric acid, is less well understood. 6 The presence of delirium may indicate underlying brain vulnerability and should therefore increase suspicion for an underlying cognitive impairment or dementia, especially if the precipitating insult appears disproportionately minor. 7 The pathophysiological changes described here also suggest that delirium itself can cause permanent neuronal damage, thereby contributing to the risk of cognitive decline. 8 Clinically, it can take up to 12 months for patients to return to their cognitive baseline after an episode of delirium, and some never regain their previous cognitive function. 9 Diagnosis One commonly used diagnostic definition of delirium is based on DSM-5 criteria and requires a new acute dis turbance in cognition, fluctuating attention, and alteration of the sleep-wake cycle with changes that are primarily related to an underlying medical cause and not better explained by an evolving dementia. 10 Patients may present with hyperactive delirium, which is associated with agitation and hypervigilance, or they may present with hypoactive delirium, which is associated with drowsiness and apathy. It is not uncommon for patients to have both forms at various times during the course of the same illness. It is particularly easy to miss a patient with hypoactive delirium as they do not call attention to themselves, perhaps explaining why the hypoactive form is associated with a poorer prognosis. 1 The diagnosis of delirium requires a patient interview, a physical examination, cognitive testing, and a review of the medical chart and any collateral information. Screening tools are an attractive adjunct to clinical assessment, especially if time is limited. One of the most widely used is the confusion assessment method (CAM), validated in various settings, including intensive care units, emergency departments, and nursing 166 bc medical journal vol. 59 no. 3, april 2017 bcmj.org

3 Table 1. Nonpharmacological strategies for addressing delirium risk factors, based on the Hospital Elder Life Program (HELP). 14,16 Risk factors Cognitive impairment Sleep deprivation Immobility Vision impairment Hearing impairment Dehydration Other Strategies homes, and proven to have high interobserver reliability. 11,12 The abbreviated 3-minute 3D-CAM, consisting of clinical observation and a onepage patient questionnaire, can be used at the bedside. 13 Any assessment should focus on the main features of delirium. A diagnosis is suggested by acute-onset confusion and inattention plus disordered thinking or altered level of consciousness. Many hospitals now include a version of the CAM on nursing assessment flowsheets, helping physicians to quickly scan the chart for signs of delirium. Because a multitude of underlying causes may be involved, a broad diagnostic approach is needed and clinicians should keep an open mind about the possibility of more than one contributing medical problem. The workup should include a detailed assessment to search for the precipitant, whether it is an acute medical illness, a change in therapy, or the destabilization of a chronic condition. Causes of physical discomfort such as constipation and urinary retention are common precipitants but are often overlooked. During the physical examination, the clinician should look for evidence of occult infection, volume depletion, abdominal pathology, deep vein thrombosis, and a neurological cause. 1 The investigations ordered will depend on the assessment, but generally include an electrocardiogram, a complete blood count with differential, and testing for electrolytes (including calcium, phosphate, and magnesium), liver enzymes, thyroid function, troponin, and vitamin B12. A chest X-ray or urinalysis and culture should be considered if symptoms suggest infection, keeping in mind that elderly patients can fail to manifest typical signs of infection (elevated white blood cell count, fever, or focal symptoms). Neuroimaging is indicated for patients with focal neurological deficits, unexplained confusion, or suspected head trauma. 1 Worsening severity or a prolonged course should prompt a repeat workup for ongoing medical instability, new precipitants, or less common causes of delirium such as encephalitis, rapidly progressive dementia, or seizure. 1 Neuroimaging, lumbar puncture, and electroencephalogram should be considered in these situations. Nonpharmacological strategies for prevention Primary prevention is the cornerstone of delirium management and has the best evidence for success of any intervention. Some institutions have adopted the Hospital Elder Life Program (HELP) to address six risk factors in older patients that commonly contribute to delirium: cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration ( Table 1 ). 14 Addressing these risk factors results in fewer days of delirium and fewer episodes of delirium, but does not reduce delirium severity and Reorient patient, encourage cognitively stimulating activities Reduce sleep interruptions with scheduling of care, promote relaxation (e.g., offer warm milk, music), institute unit-wide noise reduction Ensure early mobilization, encourage range-of-motion exercise, provide appropriate gait aids, minimize use of restraints Provide visual aids Provide hearing amplification devices, use adaptive communication techniques Recognize and treat dehydration, offer feeding assistance Reposition patient to prevent aspiration, review medications, discontinue catheter use if possible recurrence rates, 14 suggesting that once delirium develops, it is difficult to intervene. A recent meta-analysis has shown that nonpharmacological interventions not only reduce the incidence of delirium but also prevent falls. 15 Other important strategies include managing pain, maintaining nutrition, and performing a thorough medication review. 16 Discontinuation of urinary catheters whenever possible is encouraged given the association of catheters with urinary tract infections. Involving the patient s family, primary bedside nurse, and clinical nurse leader in the creation of a nursing care plan can also be instrumental in the success of these nonpharmacological delirium prevention strategies. Other important aspects of the care plan include assisted feeding and positioning in bed to prevent aspiration, frequent turning to prevent skin breakdown, and minimizing the use of restraints given the association of restraints with injury and worsened delirium. 17 If restraints must be used, the patient should be supervised vigilantly and the restraints discontinued as soon as possible. bc medical journal vol. 59 no. 3, april 2017 bcmj.org 167

4 Given the complex nature of caring for older adults, a comprehensive geriatric assessment (CGA) by a geriatrician or a physician with expertise in geriatric care can help identify treatment goals and coordinate care. A number of studies in the orthotrauma population have shown that a proactive perioperative CGA can reduce the incidence of delirium. 18,19 Treatment Sometimes a patient s behaviors continue to be concerning despite management of the underlying cause of the delirium. Treatment with medication can be an option if nonpharmacological strategies such as one-on-one reorientation from a family member or trained care aide cannot prevent aggression or severe agitation and patient or staff safety is threatened. Medication is also an option if there is sleep-wake disturbance or psychosis. However, it is important to remember that not all behaviors need to be controlled by medication, nor do medications address the underlying cause of the behavior. Table 2. Medications for management of delirium symptoms in older adults. Medication Typical antipsychotics (oral, intramuscular, and subcutaneous forms; all use is off-label) Loxapine Methotrimeprazine Dose (every 6 8 hours)* mg mg Haloperidol mg Atypical antipsychotics (oral form; all use is off-label) Quetiapine Risperidone Olanzapine (also available in intramuscular form) mg mg mg * Usual starting dose is at the lower end of the range. Robust individuals may require higher doses than listed. An additional regular afternoon and/or evening dose may be considered for patients who predictably exhibit an escalation of symptoms later in the day. Maximal dose of haloperidol is 4.50 mg per day, beyond which extrapyramidal symptoms can be significant. 23 Typical and atypical antipsychotics may be considered for management of delirium even though there is inconclusive evidence that antipsychotic use reduces delirium severity or duration. 20 Studies of antipsychotics in delirium have largely been small and of varying quality. The types and doses of antipsychotics, as well as the populations studied, have been heterogeneous, making it difficult to generalize from the findings. Potential side effects include extrapyramidal symptoms (EPS), including parkinsonism, akathisia, and dystonia, and prolongation of the QTc interval, particularly with use of haloperidol and quetiapine. 21 While the atypical antipsychotics are generally believed to have a lower propensity to induce EPS, prolonged use in patients with dementia has been associated with increased mortality. 22 Despite these drawbacks, antipsychotics can be used in limited circumstances with the understanding that the potential for side effects and the lack of robust evidence means that use of antipsychotics for symptoms of delirium is considered offlabel. Risks and benefits of treatment should be discussed before initiating anti psychotic therapy, and families should be involved to see if alternative nonpharmacological strategies can be used instead. Treatment should be for a short time, and down-titration or discontinuation should be considered on a daily basis. Typically, we start geriatric patients on lower doses and titrate as appropriate ( Table 2 ). Consultation with geriatric medicine, care of the elderly services, or a geriatric psychiatry physician, if available, can help guide management when medications are being considered. Recent studies suggest that antipsychotics are useful in delirium prophylaxis, particularly in the postsurgical period. However, there is a large variation in the surgical patient population studied as well as in the regimens used. A recent meta-analysis showed that perioperative olanzapine and risperidone were useful in delirium prevention, while no difference was found when haloperidol was compared with a placebo. 24 Because of the heterogeneity of results and small effect size, the off-label use of prophylactic antipsychotics perioperatively has not become standard of care. Similarly, there have been several studies looking at the effects of melatonin on the prevention of delirium. Al-Aama and colleagues studied 145 elderly medical patients in a randomized double-blinded placebocontrolled trial and found that the melatonin group had a significantly lower risk of delirium incidence, 25 while de Jonghe and colleagues studied the effect of melatonin on the incidence of delirium in older patients with hip fracture but did not find melatonin efficacious. 26 Overall, there is weak evidence that melatonin is effective for the prevention of delirium. However, melatonin has a good safety profile 168 bc medical journal vol. 59 no. 3, april 2017 bcmj.org

5 and may be a reasonable choice to start in hospitalized patients at high risk for delirium, or in established delirium as a sleep aid. Doses between 0.5 and 9.0 mg have been studied in delirium and in dementia patients, with 3.0 to 6.0 mg being used commonly in clinical practice. 27 Given the cholinergic deficit theory in the pathogenesis of delirium, there have also been trials with acetylcholinesterase inhibitors, medications that increase the amount of acetylcholine in the synapse. Donepezil and rivastigmine have been studied in randomized controlled trials for both the prevention and the treatment of delirium, but the results have been disappointing. One of the largest studies of rivastigmine as an adjunct to usual care with haloperidol in intensive care unit patients was stopped early after higher mortality in the rivastigmine group was observed, even though the difference was not statistically significant. 28 Similarly, studies show that donepezil is not effective for delirium prophylaxis and treatment. 29,30 Summary Delirium during hospitalization indicates medical instability that can affect a patient s independence after discharge. While the exact pathophysiology of delirium is not completely understood, certain well-established in-hospital risk factors can be identified and addressed. These include cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration. Ideally, nonpharmalogical strategies should be used to address these risk factors. The most effective approach is prevention, followed by treatment of the underlying cause. Drug therapies can be used if the safety of the patient and staff is a concern, but caution is advised given the side effects associated with certain medications. Typical and atypical antipsychotics may be used on an off-label basis for a short time and if down-titration and discontinuation are considered on a daily basis. In some institutions, efforts have been made to systematically implement measures to prevent and treat delirium. When delirium does occur, the medical team and family should be aware that the patient may need further support on discharge given the risk of cognitive and functional decline associated with delirium. Competing interests None declared. References 1. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet 2014;383(9920): Shekelle PG, MacLean CH, Morton SC, Wenger NS. Acove quality indicators. Ann Intern Med 2001;135: Inouye SK, Viscoli CM, Horwitz RI, et al. A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. Ann Intern Med 1993;119: Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA 1996;275: van Gool WA, van de Beek D, Eikelenboom P. Systemic infection and delirium: When cytokines and acetylcholine collide. Lancet 2010;375(9716): Typical and atypical antipsychotics may be used on an off-label basis for a short time and if downtitration and discontinuation are considered on a daily basis. 6. Hshieh TT, Fong TG, Marcantonio ER, Inouye SK. Cholinergic deficiency hypothesis in delirium: A synthesis of current evidence. J Gerontol A Biol Sci Med Sci 2008;63: Inouye SK. Delirium in older persons. N Engl J Med 2006;354: Fong TG, Davis D, Growdon ME, et al. The interface between delirium and dementia in elderly adults. Lancet Neurol 2015;14: Saczynski JS, Marcantonio ER, Quach L, et al. Cognitive trajectories after postoperative delirium. N Engl J Med 2012;367: American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: APA; Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: The confusion assessment method. A new method for detection of delirium. Ann Intern Med 1990;113: bc medical journal vol. 59 no. 3, april 2017 bcmj.org 169

6 12. The Hospital Elder Life Program. CAM fracture: A randomized trial. J Am Geriatr validation studies, Accessed 9 Soc 2001;49: February Lenartowicz M, Parkovnick M, McFarlan program.org/delirium-instruments/cam A, et al. An evaluation of a proactive geriatric trauma consultation service. Ann -references. 13. Marcantonio ER, Ngo LH, O Connor M, et Surg 2012;256: al. 3D-CAM: Derivation and validation of a 20. Chan PKY. Clarifying the confusion about 3-minute diagnostic interview for CAM- confusion: Current practices in managing Primary prevention is the cornerstone of delirium management and has the best evidence for success of any intervention. defined delirium: A cross-sectional diagnostic test study. Ann Intern Med 2014; 415. geriatric delirium. BCMJ 2011;53: : Taylor DM. Antipsychotics and QT prolongation. Acta Psychiatr Scand 2003;107: 14. Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older 22. Schneider LS, Dagerman KS, Insel P. Risk patients. N Engl J Med 1999;340:669- of death with atypical antipsychotic drug 676. treatment for dementia: Meta-analysis of 15. Hshieh TT, Yue J, Oh E, et al. Effectiveness of multicomponent nonpharma- JAMA 2005;294: randomized placebo-controlled trials. cological delirium interventions: A metaanalysis. JAMA Intern Med 2015;175: Wyller T. Antipsychotics for delirium. 23. Lonergan E, Britton AM, Luxenberg J, Cochrane Database Syst Rev 2007;(2): 16. O Mahony R, Murthy L, Akunne A, Young CD J; Guideline Development Group. Synopsis of the National Institute for Health and ic use for postoperative delirium: A sys- 24. Hirota T, Kishi T. Prophylactic antipsychot- Clinical Excellence guideline for prevention of delirium. Ann Intern Med 2011; Psychiatry 2013;74:e1136-e1144. tematic review and meta-analysis. J Clin 154: Al-Aama T, Brymer C, Gutmanis I, et al. 17. Sullivan-Marx EM. Delirium and physical Melatonin decreases delirium in elderly restraint in the hospitalized elderly. Image patients: A randomized, placebo- J Nurs Sch 1994;26: controlled trial. Int J Geriatr Psychiatry 18. Marcantonio ER, Flacker JM, Wright RJ, 2011;26: Resnick NM. Reducing delirium after hip 26. de Jonghe A, van Munster BC, Goslings JC, et al. Effect of melatonin on incidence of delirium among patients with hip fracture: A multicentre, double-blind randomized controlled trial. CMAJ 2014;186: E547-E de Jonghe A, Korevaar JC, van Munster BC, de Rooij SE. Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? A systematic review. Int J Geriatr Psychiatry 2010;25: van Eijk MM, Roes KC, Honing ML, et al. Effect of rivastigmine as an adjunct to usual care with haloperidol on duration of delirium and mortality in critically ill patients: A multicentre, double-blind, placebo-controlled randomised trial. Lancet 2010;376(9755): Marcantonio ER, Palihnich K, Appleton P, Davis RB. Pilot randomized trial of donepezil hydrochloride for delirium after hip fracture. J Am Geriatr Soc 2011;59 Suppl 2:S282-S Liptzin B, Laki A, Garb JL, et al. Donepezil in the prevention and treatment of postsurgical delirium. Am J Geriatr Psychiatry 2005;13: bc medical journal vol. 59 no. 3, april 2017 bcmj.org