1. Sedation & Delirium in ITU Dr James F Peerless September 2015

2. Disclaimer

3. Sedation

4. Sedation is commonly used in ICU Sedation protocols are in widespread use targeting light sedation Uses – allows patients to tolerate distressing procedures (e.g. intubation, invasive lines) – optimise mechanical ventilation – used to decrease O 2 consumption (e.g. sepsis) – decrease ICP in neurosurgical patients – facilitate cooling (e.g. therapeutic hypothermia) – control agitation

5. Side Effects Hypotension Respiratory depression Arrhythmias Drug specific effects Sleep disturbance Withdrawal Delirium ?Long-term effects

6. Past Historically use general anaesthetic drugs – No data on prolonged use Crude ventilators ETT tolerance Heavy sedation with paralysis

7. Past Morphine – Historically used in anaesthesia and palliation – Fentanyl now has largely replaced this Benzodiazepine – Uncertain washout profile Etomidate, 1972 Propofol, PRIS – rhabdomyolysis, hyperkalemia, met. acidosis – renal and cardiac failure – high mortality.

8. Past First guidance published 1995 – Six recommendations (13 references) Revised 2002 SCCM guidance – 28 recommendations (235 references) 2013 guidance – 18000 articles reviewed with 54 recommendations

9. Past Less than 20y ago  association between ventilator time and use of continuous sedation Led to development of – sedation protocols – sedation minimisation strategies Subsequent reduction in Ventilator days and LoS Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G: The use of continuous iv sedation is associated with prolongation of mechanical ventilation. Chest 1998, 114:541-548.

10. Sedation Holds Kress et al. (2000), showed reduction in LoS and ventilator time – allows comprehensive neurological and delirium assessment – assess for extubation readiness ? offers any advantages when sedation is managed with sedation protocols targeting light sedation Kress JP, Pohlman AS, O’Connor MF, Hall JB: Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000, 342:1471-1477.

11. Present Sedation holds Drive towards personalised light sedation Tracheostomies Triggered ventilators

12. Consequences of Sedation Over-sedation – Increased LoS – HD instability – Increased ventilator days Under-sedation – Increased stress response O 2 consumption Catecholamine release Myocardial ischaemia – Hyper-catabolism – Immunosuppression – Self-extubation

13. Monitoring Sedation Clinical scoring systems – Ramsey – Addenbrookes – Bloomsbury All include interpreter intervariability Difficult to discriminate between deeper levels of sedation EEG BIS

14. Monitoring Subjective clinical assessment Richmond Agitation-Sedation Score (RASS) is the most-validated and most widely-used tool – Sedation-Agitation Scale (SAS) is an alternative Views sedation and agitation as a continuum Not useful in patients receiving neuromuscular blocking agents

15. RASS

16. Procedure for RASS Assessment Observe patient – Patient is alert, restless, agitated or combative (score 0 to +4) If not alert, state patient’s name and say to open eyes and look at speaker – Patient awakens with sustained eye opening and eye contact (score –1) – Patient awakens with eye opening and eye contact, but not sustained (score – 2) – Patient has any movement in response to voice but no eye contact (score –3) When no response to verbal stimulation, physically stimulate patient by shaking shoulder and/or rubbing sternum – Patient has any movement to physical stimulation (score –4) – Patient has no response to any stimulation (score –5)

17. Aiding Sedation Pharmacotherapy Communication Explanation of events Physiotherapy Feeding and hydration Analgesia

18. Methods of Sedation Anaesthetic agents Benzodiazepines Opioids Neuroleptic agents Alpha-agonists

19. Dexmedetomidine Selective alpha-2 receptor agonist sedative, analgesic-sparing, and sympatholytic properties More easily rousable and interactive, with minimal respiratory depression cf. opioids The onset of sedation occurs within 15 mins and peak sedation occurs within 1hr of starting an IV infusion. Rapidly redistributed into peripheral tissues; metabolized by the liver Side effects: hypotension and bradycardia

20. Sleep on ITU a “natural periodic state of rest for the mind and body, in which the eyes usually close and consciousness is completely or partially lost, so that there is a decrease in bodily movement and responsiveness to external stimuli. Important component in the recovery from critical illness – tissue repair – cellular immune function However, sleep (quantity and quality) difficult to achieve in ITU

21. Aiding Sleep Non-pharmacological Modification of patient’s local environment Noise reduction – Sleep occurs best below 35 dB – Noise level > 80 dB will cause awakening Day/night lighting mimicry Music therapy

22. Aiding Sleep Pharmacological methods Benzodiazepines Benzodiazepine receptor agonists (zopiclone) – decrease sleep latency while increasing total sleep time, without affecting sleep architecture in stages 3 and 4 and REM sleep. morning hangover Rebound insomnia Melatonin – Efficacy questioned – Reduced hangover effects

23. Approach to Sedation Sedative medications should be titrated to maintain a light rather than a deep level of sedation in adult ICU patients, unless contraindicated Keep patients comfortable and safe using the minimum possible amount of sedation Use protocolised care with sedation score monitoring Propofol is widely used as it usually allows rapid, predictable desedation Daily sedation interruptions may not be necessary in ICUs with protocolised sedation Review infusion rates at least daily, and after any procedures Treat pain with boluses of analgesics (e.g. IV morphine or fentanyl), only make minor increases in basal infusion rates Caution in renal and liver failure Use spontaneous breathing, unless contra-indicated Dexmedetomidine is increasingly preferred in delirious patients requiring ongoing sedation

24. Delirium

25. Delirium in critically ill patients is a common occurrence (up to 80% of ventilated patients), ICS and SCCM recommend daily monitoring of sedation scores and delirium in all ITU patients. Delirium outside of the ICU has been studied in more detail, and is associated with: – a three-fold increase in mortality – increased incidence of infection – increased hospital stay – long lasting and severe cognitive impairment

26. Types of Delirium Disturbance of consciousness Change in cognition Acute onset Wide range of presentations Hyperactivity in <20% of cases Hypoactive patients commonly missed – Inattention and reduced awareness Mixed

27. Differential Diagnoses Any other psychiatric disorder Mixed Dementia Depression Drug withdrawal (Schizophrenia)

28. Differentiating the Differentials Dementia – No inattention; try to engage with clinician, maintain eye contact – Remain alert with no dips in consciousness – Retain coherence with no delusions/hallucinations – Also: pre-morbid state Depression – often misdiagnosed in place of hypoactive delirium – Disorientation and cognitive impairment not present in depression

29. Prevention Most strategies aimed at minimising risk Study of 53 patients revealed average of 11 risk factors 3+ factors gave a 60% chance of delirium Reorientation Addressing visual and hearing impairments, Early mobilization Same nursing care Reduction of noise/stimuli Non-pharmacological sleep protocols Stimulating patient activities Ely EW, Gautam S, Margolin R et al. The impact of delirium in the inten- sive care unit on hospital length of stay. Intensive Care Med 2001; 27: 1892 – 900

30. Risk Factors

31. Iatrogenic: Sedative Drugs Association exists between sedative drugs and delirium – benzodiazepines being the most strongly associated – Daily wake-up tests and sedation scoring – Dose titration on individual patient basis Good pain control reduces risk of delirium – Opioids weakly associated

32. Iatrogenic: Sleep Deprivation Sleep deprivation affects ~100% of ITU patients – Average 2h.day-1 – REM <6% Difficult to improve – Maintain day/night – Lights, not sleeping during day Withdrawal of drugs can lead to REM rebound – tachycardia, hypertension and nightmares

33. Iatrogenic: Immobilisation Movement should be encouraged wherever possible. Chemical and physical restraints should only be used when necessary Identify other causes of immobility – Lines – Monitoring – Catheters

34. Assessment The CAM-ICU test is designed to be used with patients receiving ventilator support – high sensitivity and specificity Level of consciousness/arousal is recorded using a sedation score (e.g. RASS). – Patients scoring -3 or greater can then be assessed for delirium

36. Treatment Address risk factors Multi-systematic approach – sedation holds – sleep–wake cycle correction – orientation – use of visual and hearing aids Pharmacological – haloperidol – Olanzepine, quetiapine

37. Outcome Patients with delirium: – 3x higher mortality rate – Increased rate of infection – Increased ventilator, ITU and hospital days – More failed extubations – Higher cost of care – Increased adverse events: Self-extubation Loss of lines/catheters Prolonged periods of delirium on ICU are associated with an increased risk of long-term cognitive impairment at 3 months post- discharge Unpleasant and frightening experience for patients, with persistent episodes of delusions and hallucinations after recovery

38. Summary Delirium is a common, underestimated, multi- factorial problem in ITU Requires a MDT approach for assessment, management, and treatment. Mainstays of treatment – minimizing and correction of risk factors – regular screening of patients

39. References CEACCP 8(2) CEACCP 9(5) Barr et al. 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit. Critical Care Medicine 41(1): 263-306 www.lifeinthefastlane.com