David Meagher Professor of Psychiatry University of Limerick Medical School

Transcription

1 Treatment of delirium in different clinical conditions: can we offer evidence-based guidelines? David Meagher Professor of Psychiatry University of Limerick Medical School

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3 Yes!...BUT HOW? Is all delirium the same? What are we actually treating? And What prescription for future work to allow for more rational and targeted management with EM guidelines

4 What is delirium?

5 Delirium : Unitary concept All acute disturbances of global cognition AKA Acute confusion ICU psychosis Post-operative psychosis Terminal cognitive failure Acute Brain Failure Terminal restlessness Circa 30 synonyms

6 DSM IV (-TR) Disturbed consciousness with inattention Altered cognition (memory / language /orientation / perception) Acute onset / fluctuating course Evidence of etiology Accurate cognitive assessment is cornerstone of identification

7 BUT : Is all delirium the same? Comorbid dementia Delirium Clinical (Motor) Subtypes Etiology

8 Motor variants of delirium

9 Single etiology delirium is exceptional

10 Elderly cognitively impaired adult Delirium Symptom severity Young previously healthy adult Syndromal threshold Etiology severity TBI With brief LOC Benzodiazepine withdrawal Pneumonia Hypoxia Medication adverse effects Seizure Time

11 Patient needs DO differ Vulnerability to adverse effects (cerebrovascular / extrapyramidal xs sedation) Outcome concerns : Pall care vs Persistent cognitive problems (LTCI)

12 Persistent Cognitive Deficits Following Delirium Episode: Possible Mechanisms Neurotoxicity of underlying etiologies Neurotoxicity of medications Unresolved, prolonged, or recurrent delirium Neurotoxic effects of delirium complications Progression or acceleration of preexisting cognitive decline Direct toxic effect of delirious state Trzepacz PT, Meagher DJ. APA Textbook of Neuropsychiatry, chapter 11, 5th edition, 2007

13 How does treatment work? Individual Symptoms Syndromal? Symptoms follow same trajectory Clinical subtypes

14 What about phenomenological profile? Is delirium really a unitary syndrome?

15 Delirium is a complex neuropsychiatric syndrome Present Score 2 or more Inattention 97% 1 73% Sleep disturbance 97% 2 73% LTM 89% 64% STM 88% 53% Visuospatial 87% 64% Disorientation 76% 42% Agitation 62% 27% Retardation 62% 37% Language abn 57% 25% Thought disorder 54% 22% Affective changes 53% 18% Perceptual abn 50% 26% Disturbed thought content 31% 9% Meagher et al, British J Psychiatry 2007

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18 Delirium : Heterogeneity Etiology Comorbidities Phenomenology Prognosis? Treatment needs

19 Perceived MOA of antipsychotics in delirium treatment % sedation antipsychotic anti-delirium Other 0 1 Haloperidol preferred AP for sedation as MOA and EPS as most conerning side effect! Meagher, Int Psychogeriatrics, 2009

20 Delirium Rating Scale (DRS) and MMSE in Double-Blind Delirium Study Baseline Day 2 End of Treatment Breitbart et al. Am J Psychiatry 1996; 153:2:

21 Symptom vs syndrome? 50% reduction in DRS-R98 severity scores (5 cog + 8 non-cognitive symptoms) MANDATES substantial change in both cognitive and noncognitive elements of the syndrome i.e. response NOT just sedative or antipsychotic effect

22 Therapeutic caution / impulsivity ICU CL Psych Geriatric Med Syndromal MOA Pall Care Old age Psych Paediatrics Symptomatic MOA

23 Doctors differ? APA Guidelines (1999) Haloperidol up to 2mg four hourly Meagher & Leonard (2008) 20 prospective studies 10 randomised comparisons Mostly low-dose treatment Total N= 582 patients Response rate 70% (64-82%) Typically in 2-6 days Royal College of Physicians (BGS) 2006 Keep drug sedation to a minimum Use when agitation or psychosis mandates Inouye (2006: NEJM) Pharmacologic management should be reserved for patients whose symptoms of delirium would threaten their own safety, or the safety of others, or would result in the interruption of essential therapy

24 NICE The review ultimately focuses on three studies Hu 2006 : 180 Geriatric med Lee 2005 : 40 CL psych Skrobik 2004 : 77 ICU If non-pharmacological approaches are ineffective, consider giving short term (for 1 week or less) haloperidol or olanzapine if people with delirium are distressed or a risk to themselves or others.

25 A Prescription for treatment studies in delirium Jury still not absolutely convinced as to efficacy Secondary issues include impact: Across populations Across clinical subtypes In different etiological types Vs individual symptoms of delirium both cog and non-cognitive In comorbid dementia patients Safety across populations Optimal dosing ; why low doses only reported?

26 Overview (1) Although delirium is considered as a unitary syndrome, it is highly heterogenous in causation, comorbidity, phenomenological profile, prognosis AND INEVITABLY TREATMENT NEEDS (2) In real world practice, there is a remarkable inconsistency in treatment practices which is mirrored by inconsistencies in evidence-based (?!?) guidelines (3) Urgent need for studies that explore (a) Benefits and risks across populations / treatment settings (b) Individual symptom response (4) Seems unlikely that evidence-based guidelines CAN EVER fully account for the complexity of delirium; ultimately treatment MUST BE highly individualised BUT can be informed by best use of available evidence

27 European Delirium Association 5 th Annual Meeting, Amsterdam Medical Center, November david.meagher@ul.ie