1. You are asked to review Mr X, a 78year old gentleman in ICU, who is in the process of being weaned off the ventilator. The nurse calls you because Mr X is trying to jump out of bed. Assess and manage Mr X. Alex Yartsev, 15/4/2011 Delirium in the ICU

2. Oh’s Intensive Care manual, 6 th edition, ch. 42 Why is Mr X doing that? - Inability to communicate something - Pain – he is lying on top of a forgotten 10ml syringe - Dementia – this is what he is normally like at the nursing home - Psychosis – we accidentally stopped his risperidone and started an MAOI - Intoxication – APS team started ketamine - Withdrawal – he drinks - Delirium Tremens – he REALLY drinks - ENCEPHALOPATHY: An alteration in the level or content of consciousness due to a process extrinsic to the brain. metabolic vs structural

3. Oh’s Intensive Care manual, 6 th edition, ch. 42 A moment for Encephalopathy -SEPSIS -ICU DELIRIUM …also… -Hepatic failure -Renal Failure -Hypoxia or hypercapnea -Hyper or hyponatremia -Hyper or hypoglycaemia -Hyper or hypothyroidism -Acidosis -Addisonian crisis…………………..many others

4. Oh’s Intensive Care manual, 6 th edition, ch. 42 Septic Encephalopathy -A flavour almost exclusive to the ICU - according to Ohs, 8-80% of septic patients are affected - Defined as encephalopathy in the presence of extracranial infection, without any other good reason to explain it. - Lots of theories regarding pathogenesis: -Cerebral oedema due to leaky capillaries -Damaged BBB -Endotoxin-induced decrease in O2 consumption in the brain -No lateralizing signs -Rarely is there flap or myoclonus -Treatment ought to focus on the infectious cause

5. Oh’s Intensive Care manual, 6 th edition, ch. 42 “ICU Encephalopathy” - so, it’s the 5 th -7 th day of your admission. Or you are the night reg and its your 5 th - 7 th night shift - You havent slept - Your circadian rhythm is disturbed - You are full of mind-altering drugs - You are constantly uncomfortable - Your environment is noisy and monotonous -Diagnosis of exclusion

6. Why is this a problem? -Irritates the nurse -Staff may get attacked -Tubes and lines get dislodged - damage to the patient and to the budget -Total tissue oxygen consumption increases -Quality of monitoring is compromised -Duration of stay is increased -Extubation is delayed (bolusbolusbolus) - Higher incidence of nosocomial pneumonia (aspiration or otherwise) Delirium is an independent predictor of -increased mortality -length of stay -cost of care Equivalent to organ failure ! Weirdly, aggressive delirium has a better prognosis than “quiet” delirium ;GL Fraser, RR Riker The frequency and cost of patient-initiated device removal in the ICU, - Pharmacotherapy, 2001 vol 21 issue 1The frequency and cost of patient-initiated device removal in the ICU Pun BT, et al The importance of diagnosing and managing ICU delirium Chest. 2007 Aug;132(2):624-36. Pandharipande PPandharipande P, Delirium: acute cognitive dysfunction in the critically ill Curr Opin Crit Care. 2005 Aug;11(4):360-8. Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult.Crit Care Med 2002;30:119–141

7. Risk factors for ICU delirium - Prolonged sedation / mechanical ventilation - Severity of illness - Use of sedatives and analgesics (benzos > opiates) - Age - Most studies don’t seem to differentiate between causes of delirium. -Their list of risk factors includes history of smoking, alcoholism, liver dysfunction, sepsis, and other causes of metabolic or toxic encephalopathy. Lin SMLin SM et al, Risk factors for the development of early-onset delirium and the subsequent clinical outcome in mechanically ventilated patients. J Crit Care. 2008 Sep;23(3):372-9. Epub 2007 Jan 31. Ouimet SOuimet S et. al. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med. 2007 Jan;33(1):66-73. Epub 2006 Nov 11.

8. Assessment of delirium in the ICU -Is Mr X actually delirious? -Jacobi et.al. (2002) recommends the use of the Confusion Assessment Method in the ICU (CAM-ICU) -Apparently, 2 minutes to complete. -Requires some degree of cooperation. -According to a 2008 survey, only 9% of all Australian units use any sort of scale like this. Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult.Crit Care Med 2002;30:119–141 Shehabi Y, Sedation and delirium in the intensive care unit: an Australian and New Zealand perspective. Botha JA, Boyle MS, Ernest D, Freebairn RC, Jenkins IR, Roberts BL, Seppelt IM. Anaesth Intensive Care. 2008 Jul;36(4):570-8.Sedation and delirium in the intensive care unit: an Australian and New Zealand perspective.

9. Alex Yartsev, 15/4/2011 Diagnosis of ICU delirium - Diagnosis of exclusion - Imaging excludes structural causes of encephalopathy - Bloods exclude many of the metabolic causes - What remains is excluded with history - Easier said than done -Address the cause? -“Multifactorial” is a safe guess.

10. The CAM-ICU

11. Just calm down, Sir. You are in hospital. -MANAGEMENT OF ICU DELIRIUM -Preventative vs. reactive -Non-pharmacological vs pharmacological

12. Prevention of ICU delirium - Sedation Holidays -2000 study by Kress: landmark paper; 128 pts; -length of stay reduced from 9.9 to 6.6 days -9 vs 16 pts needed delirium workup -According to a 2008 survey, only 30% of Australian units use sedation holidays - Frequent reproducible assessment for pain and delirium -Jacobi et a. (2002, multidisciplinary task force) -recommend the use of a validated agitation/sedation measurement tool, -eg. Richmond Agitation-Sedation Scale - Quiet environment, thus good sleep - Music, thus reduced anxiety / improved relaxation Kress JP, Pohlman AS, O'Conner MF, et al. Daily interruption of sedation infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342: 1471–7 Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult.Crit Care Med 2002;30:119–141 Freedman NS et al., Patient perception of sleep quality and etiology of sleep disruption in the intensive care unit. Am J Resp Crit Care Med 1999;159: 1155–1162 Shehabi Y, Sedation and delirium in the intensive care unit: an Australian and New Zealand perspective. Botha JA, Boyle MS, Ernest D, Freebairn RC, Jenkins IR, Roberts BL, Seppelt IM. Anaesth Intensive Care. 2008 Jul;36(4):570-8.Sedation and delirium in the intensive care unit: an Australian and New Zealand perspective. Chlan L: Effectiveness of a music therapy intervention on relaxation and anxiety for patients receiving ventilatory assistance. Heart Lung 1998;27:169–176.

13. Pharmacological Arsenal - Benzodiazepines - Opiates - Propofol - Classical antipsychotics - Atypical antipsychotics - Dexmedetomidine / clonidine - Magnesium (!)

14. How shall I most effectively drug Mr X? -Jacobi et al (2002) recommends Haloperidol (level C data, small studies and case report series) -Cochrane library agrees to some extent: Lonergan et.al. (2007) haloperidol is better than placebo, but… - no better then olanzapine at low doses - and with more side effects at high doses Ergo, use olanzapine where possible. Lonergan et.al. (2009) – no evidence to support benzos in delirium, unless alcohol withdrawal is the cause. -Everyone agrees: monitor QTc (level B evidence) Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult.Crit Care Med 2002;30:119–141 Lonergan et.al., Benzodiazepines for delirium. Cochrane Database of Systematic Reviews 2009, Issue 4 Lonergan E, Britton AM, Luxenberg J. Antipsychotics for delirium. Cochrane Database of Systematic Reviews 2007, Issue 2. Milbrandt et.al. Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients. Crit Care Med. 2005 Jan;33(1):226-9; discussion 263-5.

15. How shall I adjust Mr X’s sedation cocktail? Keeping in mind the goal is to wean him off the ventilator -Unless he is withdrawing from alcohol, change midazolam to propofol. -ADD DEXMEDETOMIDINE. -Dex vs propofol? Ruokonen et al (2009): 87 pts; adding Dex has no effect on length of stay, but decreases length of ventilation. -Dex vs Midazolam? Riker et al (2009): 375 pts; prevalence of delirium 54%(dex) vs 76% (midaz), also faster extubation - CORRECT MAGNESIUM. - target range 1.0-2.0, in addition to remi + midaz: 63 pts, 2009 RCT by Esen -Of the delirious pts, the magnesium group had fewer days of delirium (55% vs 89%) and consumed less sedatives. Mirski et al, Cognitive improvement during continuous sedation in critically ill, awake and responsive patients: The Acute Neurological ICU Sedation Trial (ANIST) Intensive Care Medicine 2010 vol 36 issue 9 1505-1513 Ruokonen et alDexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation. Intensive Care Medicine 2009 vol 35 issue 2 282-90Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation. Riker RR, et al Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA : the journal of the American Medical Association 2009 Feb 301 issue 5Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult.Crit Care Med 2002;30:119–141 Esen F et. al. Effect of magnesium on the incidence of delirium occurrence in the ICU Critical Care 2009 vol 13 supp 1P412

16. When is it OK to restrain Mr X -NOT IDEAL. -Increases the risk of PTSD, tissue injury, pressure areas. Inhumane. -Consensus: use the least restrictive therapy available. Goal is to minimize harm from discontinuation of life-supporting therapies. -HOWEVER: -Tominaga et.al (1995) – no restraints = significant increase in self-extubations -Carrion et al (2000) – hand restraints = significantly reduced self-extubations LY Chang, KWK Wang… Influence of physical restraint on unplanned extubation of adult intensive care patients: a case-control study - American Journal of Critical Care, 2008 – AACN 2008;17: 408-415 Influence of physical restraint on unplanned extubation of adult intensive care patients: a case-control study George J. Annas, J.D., M.P.H. The Last Resort — The Use of Physical Restraints in Medical Emergencies N Engl J Med 1999; 341:1408-141 Jones C, Backman C, Capuzzo M, Flaatten H, Rylander C, Griffiths RD. (2007) Precipitants of post-traumatic stress disorder following intensive care: a hypothesis generating study of diversity in care. Intensive Care Med;33:978-85 Macciolli et.al, Clinical practice guidelines for the maintenance of patient physical safety in the intensive care unit: Use of restraining therapies—American College of Critical Care Medicine Task Force 2001–2002 Crit Care Med 2003 Vol. 31, No. 11 Carrion MI, Ayuso D, Marcos M, et al: Accidental removal of endotracheal and nasogastric tubes and intravascular catheters. Crit Care Med 2000; 28:63– 66 Tominaga GT, Rduzwick H, Scannell G, et al: Decreasing unplanned extubations in the surgical intensive care unit. Am J Surg 1995; 170:586 –590 Girard et. al, Risk factors for post-traumatic stress disorder symptoms following critical illness requiring mechanical ventilation: a prospective cohort study Crit Care. 2007;11(1):R28.

17. No questions, please.