12RC4 Postoperative delirium Claudia Spies Department of Anaesthesiology and Surgical Intensive Care Medicine, Charité-Universitaetsmedizin Berlin, Berlin, Germany
Tuesday, 14 June 2011
9:30 - 10:15
Room: G105
Definition Delirium is one of the most frequent diagnoses after surgery and in the intensive care unit (ICU) [1-3]. Delirium is an acute decline in attention and cognition. To make a diagnosis, there are two classification systems: the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) [4] and the International Classification of Diseases (ICD-10) [5]. According to the DSM-IV, delirium is defined as an acute or fluctuating course of mental status change, combined with inattention, and either an altered level of consciousness or disorganized thinking. While the core criteria are similar in both systems, ICD-10 requires three additional criteria to make a diagnosis, i.e. disturbances in psychomotor behaviour, the sleep-wake-cycle and emotionality. Typically, delirium is characterised by an acute onset and fluctuating course in contrast to other psychiatric disorders such as dementia, psychosis, or anxiety/depressive disorders.
Clinical presentation In the clinical practice, postoperative delirium is categorised into three major subtypes: • Hyperactive delirium, which usually attracts the clinician’s attention due to the exaggerated response to external stimuli and psychomotor hyperactivity. This subtype accounts for about 5 % of all cases [3]. • Hypoactive delirium associated with reduced attention and psychomotor retardation and is present in about 30 % of delirious patients. • About 55 % of delirious patients exhibit a mixed type that shows both hyperactive and hypoactive symptoms [6]. Subsyndromal delirium exhibits some, but not all the characteristics of delirium to a full extent [7]. Emergence delirium is defined as a self-limiting episode of short duration immediately following emergence from general anaesthesia [8, 20].
Incidence and outcome Delirium has been shown to be present in approximately 14 % of patients before discharge from the recovery room to the normal ward after surgery [2], in 35 - 65% in patients older than 60 years [9, 10] and in up to 82% of intensive care unit patients [11]. Although described as a transient state, it is recognised that delirium is associated with serious adverse outcomes such as sustained functional and cognitive deficit, need for home care and long-term institutionalisation, as well as increased long-term mortality [11-13]. Increased duration of intensive care unit and hospital stay [14] and increased incidence of complications in delirious patients contribute to significantly increased healthcare costs [15].
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Pathophysiology The current hypotheses concerning the development of postoperative delirium focus on the imbalance of neurotransmitter systems, inflammatory processes and chronic stress as the most important mechanisms identified so far. On the neurotransmitter level, predominantly anticholinergic activity and an enhanced dopaminergic and glutamatergic activity contribute to a delirious state [16]. Inflammatory processes activate cytokine production (interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor α (TNF-α), and interferon) that can influence the permeability of the blood-brain barrier, initiate leucocyte migration and activation of microglia and affect neurotransmission itself [17, 18]. Stress leads to activation of the sympathetic nervous system and hypothalamic–pituitary–adrenocortical axis contributing to the increase in cytokine levels but also resulting in hypercortisolism, which contributes to delirium by an acting on hippocampal serotonin (5-hydroxytryptamine [5-HT]) 5-HT1A receptors [16].
Risk factors Numerous risk factors have been identified and described in the past, contributing to the concept of a multifactorial process of delirium as described by Inouye et al [9]. In this model, predisposing factors are individual factors that determine a patient’s vulnerability, whereas precipitating factors are related to external noxious stimuli or insults (see Table 1A and 1B, respectively).
Table 1A Predisposing factors for postoperative delirium (adapted from Inouye [16]) Age of 65 years or older Male sex Dementia Cognitive impairment History of delirium Depression Functional dependence Immobility Low level of activity History of falls Visual impairment Hearing impairment Dehydration Malnutrition Treatment with multiple psychoactive drugs Treatment with many drugs Alcohol abuse Severe illness Multiple coexisting conditions Chronic renal or hepatic disease History of stroke Neurologic disease Metabolic derangements Fracture or trauma Terminal illness Infection with human immunodeficiency virus
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Table 1B Precipitating factors for postoperative delirium (adapted from Inouye [16]) Sedative hypnotics Narcotics Anticholinergic drugs Treatment with multiple drugs Alcohol or drug withdrawal Stroke, particularly non-dominant hemispheric Intracranial bleeding Meningitis or encephalitis Infections Iatrogenic complications Severe acute illness Hypoxia Shock Fever or hypothermia Anaemia Dehydration Poor nutritional status Low serum albumin level Metabolic derangements (e.g. electrolyte, glucose, acid–base) Orthopaedic surgery Cardiac surgery Prolonged cardiopulmonary bypass Non-cardiac surgery Admission to an intensive care unit Use of physical restraints Use of bladder catheter Use of multiple procedures Pain Emotional stress Prolonged sleep deprivation
Delirium and age distribution Postoperative delirium is more likely to occur in elderly patients, i.e. patients aged 60-70 years. Nevertheless, emergence delirium is a form of postoperative delirium predominantly observed in preschool children aged 2–5 years [19]. In a recently published work, it was also present in adult patients under 40 years [20]. Emergence delirium (ED, also interchangeably termed emergence ‘agitation’, ‘excitement’ or ‘confusion’) is self-limiting by definition with a mean duration of 15 min [8], but can suddenly become dangerous and has serious consequences for the patient such as injury, increased pain, haemorrhage, self-extubation and removal of catheters requiring physical or chemical restraint.
Association with postoperative cognitive deficit (POCD) POCD describes a disturbance of cognitive functions that occurs after surgery. To be properly diagnosed, pre-operative neuropsychological testing is required in order to define a baseline function and detect a subsequent decline [17]. The profile of risk factors is similar to postoperative delirium, which has lead to the assumption of a common aetiology. In a recent study by Rudolph et al, patients with postoperative delirium had a greater incidence of early POCD, but no definitive conclusions about long-term POCD could be drawn because of limited power and missing data [21].
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Assessment of delirium In order to detect and appropriately treat postoperative delirium, patients should be assessed using a standardised and validated tool or score. Besides the criteria defined by the ICD-10 or DSM-IV, a number of tools have been developed that can be applied in clinical practice. For the purpose of screening in the recovery room or regular ward, the Nu-DESC developed by Gaudreau [22] has been introduced as a tool that can be applied by nursing staff (Table 2). This method appears to be advantageous because it accounts for the fact that in most hospitals patients can be observed continuously by nursing staff (rather than by physicians), both in the recovery room as well as on the ward [23]. Therefore, an easy-to-use screening tool that is based on assessment by nursing staff may be used to detect a large proportion of delirious patients who may be otherwise unrecognised. In particular it may detect patients with hypoactive delirium who represent approximately one-third of all cases of postoperative delirium [3].
Prevention and treatment 11
Due to the multifactorial cause of delirium, prevention and treatment should be based on multicomponent approaches [16]. This
Seeing or hearing things that are not there; distortions of visual
includes non-pharmacological as well as pharmacological treatment and treatment of any potential underlying causes, i.e. medical conobjects
ditions that promote delirium. Prevention strategies and non-pharmacological treatment imply a set of anti-delirant measures such as 0
V. Psychomotor retardation
1
2
orientation and therapeutic activities for cognitive impairment, early mobilisation, reduction of psycho-active drugs, prevention of sleep Delayed responsiveness, few or no spontaneous actions/words; deprivation, cient oxygenreaction delivery to the brain, fluid and electrolyte balance, pain management, bowel and bladder function, nutrition, e.g. when thesuffi patient is prodded, is deferred, the patient prevention of postoperative complications and appropriate environmental stimuli [24]. These strategies should be optimised during the is unarousable, or both Total score entire peri-operative period and routinely performed using a checklist adapted to local needs (Figure 1). Delirium
≥2 yes
<2 no
Figure 1 Figure 1 to detect and manage postoperative delirium; monitoring performed in the recovery room and every 8 hr Checklist Checklist to detect and manage postoperative delirium; monitoring performed in the recovery on theand ward room every 8 hr on the ward Date Time Delirium monitoring
NuDesc performed
Yes :____________points No: Why not -not applicable Why not
Delirium checklist If delirium is positive start check for: Analgesia
Dehydratation
NRS / VRS / NAS
______________points
BPS- NI
______________points
Analgesics given?
Who ? When?
Signs: Skin? Jugular vein? Urine output last 4 hours?
Positive for:
Fluids given
Who? What? Oral Enteral
______________ml
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12 I.V. When? In case of I.V. For how long? Hearing aids / eye glasses
Given to the patient ?
yes/no
Noise levels reduced?
Noise measurement performed ?
Yes/no
Orientation
facilitated by clock / newspaper/ relatives ?
Call physician
Performed
Measured: ______dBSPL (dBSPL = decibel sound pressure level); > 80 dBSPL: noise reduction required
Yes Who ? When ? No Not applicable
Anti-delirant treatment
Started?
Who? What? When? For how long?
Reason for delirium
Clear
What diagnosis?
Unclear?
What diagnostics was induced ? What differential diagnoses are considered?
A variety of drugs have been shown to exhibit anticholinergic side-effects or other actions that may promote delirium. Among these are agents commonly administered either as long-term medication or as newly prescribed medication in hospitalised patients such as antihistamines, diuretics, anti-arrhythmics, antibiotics, opioids, antidepressants and glucocorticoids. These should be taken into consideration when physicians think about eliminating a patient’s risk factors for delirium, although some may be unavoidable, for example in acutely ill patients in ICU. In the pharmacological treatment of delirium, haloperidol is still the drug of first choice [25]. Haloperidol has been suggested for prevention in high-risk patients [1, 26]. Alternatively, newer antipsychotics such as risperidone and olanzapine can be used [25], but no other drug appears to have significant advantages over haloperidol (according to the Cochrane recommendation) in peri-operative settings. In ICU quetiapine and ziprasidone have also been used, with different results, but the study design was not comparable [1, 25, 27, 28]. When patients exhibit anxiety or hyperactivity, benzodiazepines can be added, but they should be used with care as benzodiazepines can also act as a precipitating factor for delirium, especially in elderly patients. Lorazepam should be avoided except for alcohol withdrawal syndrome [1, 29]. For the treatment of autonomic symptoms, α2-agonists such as clonidine or dexmedetomidine may be used, but there are currently no studies of preventive (prophylactic) use after surgery [1]. Anticholinergic activity is known to play an important role in the development of delirium and inhibition of cholinesterase is regarded as one therapeutic approach. Nevertheless, the administration of rivastigmine, a cholinesterase inhibitor, cannot be recommended at the moment. In a randomised controlled trial investigating the efficacy of peri-operative rivastigmine, no difference was seen in rates of delirium, Mini-Mental State Examination and clock drawing test [30]. In a study in an ICU setting, an increased number of deaths were observed in the rivastigmine group, and lead to the abandonment of the trial [31].
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In the peri-operative period, additional preventive strategies may be successful in reducing the incidence or severity of postoperative delirium in certain high-risk patients (Figure 1). Use of ketamine at the induction of general anaesthesia may be one promising preventative therapy as this has recently been shown to be effective in cardiac surgery patients [32].
Key learning points • Postoperative delirium is associated with an increased risk of adverse outcomes including long-term cognitive dysfunction and increased mortality. • In up to one-third of delirious patients, predominantly those with hypoactive delirium, the diagnosis is missed. • Systematic screening of patients should be started in the recovery room and continued regularly on the ward to detect postoperative delirium • Preventive treatment of delirium in high-risk patients should be considered by non-pharmacological means and pharmacological means (for example, ketamine 0.5 mg/kg at induction of anaesthesia, haloperidol in elderly patients started pre-operatively and continued until day 3 after surgery 0.5-1 mg three times a day). • Management of postoperative delirium should comprise treatment of any underlying medical conditions, non-pharmacological therapy and symptomatic control, i.e. pharmacological anti-delirant therapy.
References 1. Schiemann A, Hadzidiakos D, Spies C. Managing ICU delirium. Current Opinion in Critical Care 2011 (in press). 2. Radtke FM, Franck M, MacGuill M, et al. Duration of fluid fasting and choice of analgesic are modifiable factors for early postoperative delirium. European Journal of Anaesthesiology 2010; 27: 411-6. 3. Lütz A, Heymann A, Radtke FM, Spies CD. [If delirium is not monitored it will often be not detected]. Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie 2010; 45: 106-11. 4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text revision. Washington DC, USA: American Psychiatric Association, 2000. 5. International Statistical Classification of Diseases and Related Health Problems 10th Revision, Version 2007 (http://apps.who.int/ classifications/apps/icd/icd10online/) 6. Peterson JF, Pun BT, Dittus RS, et al. Delirium and its motoric subtypes: a study of 614 critically ill patients. Journal of the American Geriatrics Society 2006; 54: 479-84. 7. Ouimet S, Riker R, Bergeron N, Cossette M, Kavanagh B, Skrobik Y. Subsyndromal delirium in the ICU: evidence for a disease spectrum. Intensive Care Medicine 2007; 33: 1007-13. 8. Lepousé C, Lautner CA, Liu L, et al. Emergence delirium in adults in the postanaesthesia care unit. British Journal of Anaesthesia 2006; 96: 747-53. 9. Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. Journal of the American Medical Association 1996; 275: 852-7. 10. Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip fracture: a randomized trial. Journal of the American Geriatrics Society 2001; 49: 516-22. 11. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. Journal of the American Medical Association 2004; 291: 1753-62. 12. Edlund A, Lundström M, Karlsson S, Brännström B, Bucht G, Gustafson Y. Delirium in older patients admitted to general internal medicine. Journal of Geriatric Psychiatry and Neurology 2006; 19: 83-90. 13. Girard TD, Jackson JC, Pandharipande PP, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Critical Care Medicine 2010; 38: 1513-20. 14. Thomason JW, Shintani A, Peterson JF, Pun BT, Jackson JC, Ely EW. Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients. Critical Care 2005; 9: R375-81. 15. Milbrandt EB, Deppen S, Harrison PL, et al. Costs associated with delirium in mechanically ventilated patients. Critical Care Medicine 2004; 32: 955-62. 16. Inouye SK. Delirium in older persons. New England Journal of Medicine 2006; 354: 1157-65. 17. Deiner S, Silverstein JH. Postoperative delirium and cognitive dysfunction. British Journal of Anaesthesia 2009; 103(Suppl. 1): i41-6. 18. Rudolph JL, Ramlawi B, Kuchel GA, et al. Chemokines are associated with delirium after cardiac surgery. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2008; 63: 184-9.
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19. Voepel-Lewis T, Malviya S, Tait AR. A prospective cohort study of emergence agitation in the pediatric postanesthesia care unit. Anesthesia and Analgesia 2003; 96: 1625-30. 20. Radtke FM, Franck M, Hagemann L, Seeling M, Wernecke KD, Spies CD. Risk factors for inadequate emergence after anesthesia: emergence delirium and hypoactive emergence. Minerva Anestesiologica 2010; 76: 394-403. 21. Rudolph JL, Marcantonio ER, Culley DJ, et al. Delirium is associated with early postoperative cognitive dysfunction. Anaesthesia 2008; 63: 941-7. 22. Gaudreau JD, Gagnon P, Harel F, Tremblay A, Roy MA. Fast, systematic, and continuous delirium assessment in hospitalized patients: the nursing delirium screening scale. Journal of Pain and Symptom Management 2005; 29: 368-75. 23. Radtke FM, Franck M, Schust S, et al. A comparison of three scores to screen for delirium on the surgical ward. World Journal of Surgery 2010; 34: 487-94. 24. Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. New England Journal of Medicine 1999; 340: 669-76. 25. Lonergan E, Britton AM, Luxenberg J, Wyller T. Antipsychotics for delirium. Cochrane Database Systematic Review 2007; 2: CD005594. 26. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. Journal of the American Geriatrics Society 2005; 53: 1658-66. 27. Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebocontrolled pilot study. Critical Care Medicine 2010; 38: 419-27. 28. Girard TD, Pandharipande PP, Carson SS, et al. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Critical Care Medicine 2010; 38: 428-37. 29. Lonergan E, Luxenberg J, Areosa Sastre A. Benzodiazepines for delirium. Cochrane Database Systematic Review 2009; 4: CD006379. 30. Gamberini M, Bolliger D, Lurati Buse GA, et al. Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery--a randomized controlled trial. Critical Care Medicine 2009; 37: 1762-8. 31. 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: 1829-37. 32. Hudetz JA, Patterson KM, Iqbal Z, et al. Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. Journal of Cardiothoracic and Vascular Anesthesia 2009; 23: 651-7.
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