Managing Delirium: The best way to achieve clarity (of mind) Tim Walsh. Professor of Critical Care, Edinburgh University

Transcription

1 Managing Delirium: The best way to achieve clarity (of mind) Tim Walsh Professor of Critical Care, Edinburgh University

2 Lecture Plan: a route to clarity What is delirium? Why is delirium important? Step 1: minimise deep sedation Step 2: consider delirium risk Step 3: diagnose delirium systematically Step 4: distinguish agitation from non-agitated delirium Step 5: Optimise drug therapy Prevention Manage agitation Step 6: Use non-pharmacologic measures

3 Delirium definition Key features Acute onset Altered consciousness Sensory inattention Disordered thinking Fluctuating state over time High prevalence among critically ill (20-80%) Case mix dependent Method of diagnoses

4 Clinical manifestations Sub-syndromal classification Agitated 10% Hypoactive 40-60% Mixed 20-40% Spectrum of severity Interaction with sedation Hallucinations and delusions common not necessary for diagnosis Frightening memories associated with increased Posttraumatic stress

5 Lecture Plan: a route to clarity What is delirium? Why is delirium important? Step 1: minimise deep sedation Step 2: consider delirium risk Step 3: diagnose delirium systematically Step 4: distinguish agitation from non-agitated delirium Step 5: Optimise drug therapy Prevention Manage agitation Step 6: Use non-pharmacologic measures

6 42 studies Delirium occurred (as dichotomous variable) in 32% of patients Delirium associated with: Mortality during admission (risk ratio 2.19 (CI 1.78 to 2.70; P<0.001) Longer durations of mechanical ventilation, ICU stay, hospital stay Higher incidence of cognitive dysfunction among survivors

7 Duration of delirium and survival Ely et al. JAMA 2004;291:1753

8 Cognitive impairment Pandharipande, et al NEJM 2013; 369: months: 25% scores similar to mild Alzheimers disease Multiple cognitive domains Not strongly associated with comorbidity Association with delirium duration

9 Delirium and cognitive impairment RBANS global cognition scores at 12 months Pandharipande et al. NEJM 2013;369:1306

10 Importance of delirium Clinical Associated with major adverse clinical outcomes Economic Associated with greater illness cost and loss of Quality Adjusted Life Years (QALYs) Patient centred Frightening memories Sleep disturbance Possibly psychological outcomes (via frightening/delusional memories) Research shows clear association but does not prove causal relationship

11 Lecture Plan: a route to clarity What is delirium? Why is delirium important? Step 1: minimise deep sedation Step 2: consider delirium risk Step 3: diagnose delirium systematically Step 4: distinguish agitation from non-agitated delirium Step 5: Optimise drug therapy Prevention Manage agitation Step 6: Use non-pharmacologic measures

12 Daily Interruption of Sedative Infusions in Critically Ill Patients Undergoing Mechanical Ventilation John P. Kress, M.D., et al NEJM 2000 Volume 342:

13 Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial Girard TD et al. Lancet 2008; 371: 126

14 Trend to lower mortality Lower ventilation days Higher nursing resource use Higher rates of agitation in non-sedated group

15 ANZICS observational study Am J Respir Crit Care Med. 2012;186: Early deep sedation associated with higher mortality (in adjusted analyses)

16 Implications of minimising sedation Admission Old New Avoidance of unnecessary or unintended prolongation Dealing with prolonged periods of wakefulness Discharge

17 Implications of minimising sedation Tolerance of intubation and invasive ventilation Analgesia Antinociception Airway reflexes Minimising risk of delirium Pharmacological management of delirium syndrome Non-pharmacological management of delirium syndrome Dealing with agitation

18 Lecture Plan: a route to clarity What is delirium? Why is delirium important? Step 1: minimise deep sedation Step 2: consider delirium risk Step 3: diagnose delirium systematically Step 4: distinguish agitation from non-agitated delirium Step 5: Optimise drug therapy Prevention Manage agitation Step 6: Use non-pharmacologic measures

19 Patient characteristics associated with higher risk delirium Older Age (about 2% increased risk per year older) Dementia/cognitive impairment Alcohol and drug misuse Impaired vision/hearing Acute illness related factors Drugs (dopaminergic; anticholinergic; benzodiazepines) Almost always multiple factors are present in the ICU patients

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21 Lecture Plan: a route to clarity What is delirium? Why is delirium important? Step 1: minimise deep sedation Step 2: consider delirium risk Step 3: diagnose delirium systematically Step 4: distinguish agitation from non-agitated delirium Step 5: Optimise drug therapy Prevention Manage agitation Step 6: Use non-pharmacologic measures

22 Diagnosis Without screening tools up to 75% delirium is missed Crit Care Med (6): Two validated tools in the ICU (designed for intubated and non-intubated patients) CAM-ICU (dichotomous: yes/no) ICDSC (includes sub-syndromal delirium according to score) CAM-ICU has high sensitivity and specificity and is most validated score for use in ventilated sedated patients (Lutz et al CCM 2010; 38: 409) Non-systematic clinician assessments low sensitivity Spronk et al. ICM 2009; 35: 1276 Sedation is a confounder to assessment due to affects on cognition Accurate diagnosis requires frequent assessment by trained staff due to fluctuating patient status

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24 Lecture Plan: a route to clarity What is delirium? Why is delirium important? Step 1: minimise deep sedation Step 2: consider delirium risk Step 3: diagnose delirium systematically Step 4: distinguish agitation from non-agitated delirium Step 5: Optimise drug therapy Prevention Manage agitation Step 6: Use non-pharmacologic measures

25 Some causes of agitation Synchrony with ventilator Analgesia Delirium is Bowels Anxiety Drug withdrawal Not all agitation is delirium Agitation may be multifactorial

26 Lecture Plan: a route to clarity What is delirium? Why is delirium important? Step 1: minimise deep sedation Step 2: consider delirium risk Step 3: diagnose delirium systematically Step 4: distinguish agitation from non-agitated delirium Step 5: Optimise drug therapy Prevention Manage agitation Step 6: Use non-pharmacologic measures

27 Minimising risk of delirium Pre-emptive antipsychotic medication Important to distinguish elective surgical populations from non-elective mixed ICU populations Some evidence for low dose prophylaxis in elective surgery: Haloperidol (cardiac surgery; Wang W, et al. Crit Care Med 2012; 40: 731-9) Risperidone (cardiac surgery; Prakanrattana U et al. Anaesth Intensive Care 2007; 35: 714-9)

28 Minimising risk of delirium Pre-emptive antipsychotic medication in mechanically ventilated ICU patients No evidence of delirium reduction with haloperidol (Page et al; Lancet Respir Med 2013; 1: ) Reduced use of sedatives and opiates Agitation reduced No evidence of delirium reduction with rosuvastatin in ARDS (Needham DM, et al. The Lancet Respiratory Medicine. 2016; 4(3): ) Evidence of harm (greater mortality) with rivastigmine (van Eijk MM, et al. Lancet 2010; 376; )

29 Minimising risk of delirium Choice of sedative agent in mechanically ventilated cases MENDS (Pandharapande et al JAMA; 2007; 298:2644) Dex (continuous) vs lorazepam (intermittient) Similar prevalence of delirium (high risk group) Shorter duration; less coma days with dex SEDCOM (Riker et al JAMA; 2009; 301:489) Dex (continuous) vs midazolam (continuous) 22% ARR in delirium; reduced delirium days PRODEX and MIDEX PRODEX less effect on ventilation days Delirium not diagnosed using CAM-ICU Role of clonidine (much cheaper) uncertain

30 Cross over trial in patients with agitation: propofol vs dexmeditomidine Primary outcome change on cognitive function Sedative choice potentially important in assessing delirium

31 Treating established delirium in the ICU patient Evidence limited to small studies Frequently agitated/non-agitated delirium not distinguished Most compare haloperidol, atypical antipsychotics (olanzapine, risperidone, quetiapine), and/or placebo Relative side effects/safety uncertain No evidence to support routine treatment of hypoactive delirium with pharmacological therapy

32 Agitated delirium Important to exclude and treat other causes of agitation Haloperidol and atypical antipsychotics useful for management from patient safety perspective Decrease need for sedative drugs May support delirium resolution Main issues are side effects (extrapyramidal; QTprolongation; interaction with other drugs) Dexmedetomidine (and clonidine)

33 Additional of dexmedetomidine to standard care associated with: Reduced time to extubation Quicker resolution of delirium Lower use of antipsychotics

34 Lecture Plan: a route to clarity What is delirium? Why is delirium important? Step 1: minimise deep sedation Step 2: consider delirium risk Step 3: diagnose delirium systematically Step 4: distinguish agitation from non-agitated delirium Step 5: Optimise drug therapy Prevention Manage agitation Step 6: Use non-pharmacologic measures

35 Non-pharmacologic measures Frequent reorientation Early mobilisation Schweickert WD, et al. Lancet 2009; 373: Noise reduction (ear plugs; single rooms; ICU noise reduction) Litton E et al. Crit Care Med 2016; 44: Challenging to implement Require system-level change

36 Summary Delirium is prevalent in the ICU, and is associated with worse clinical outcomes and higher illness costs Minimising deep sedation is a vital strategy for improving ICU outcomes Delirium risk can be anticipated using available tools All ICUs should use a validated tool to diagnose delirium systematically Distinguishing agitation from non-agitated delirium is important in terms of therapeutic approach A systematic approach to diagnosing the cause of agitation is vital Delirium prevention should currently be limited to nonpharmacologic approaches and avoidance/minimising of modifiable risk factors Early dexmedetomidine can be considered for high risk patients, but the cost-benefit balance are uncertain For patients with agitated delirium the use of dexmedetomidine and antipsychotics should be considered