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Delirium in Critical Care

Symposium organised and funded by Orion Pharma. Daniel Conway Consultant in Anaesthesia & ICM Manchester Royal Infirmary. Delirium in Critical Care. ICS SoA 2013. Prescribing information for Dexdor ( dexmedotomidine ) is on the last slide. Item Date: Dec 13 DEX4260g.

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Delirium in Critical Care

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  1. Symposium organised and funded by Orion Pharma Daniel Conway Consultant in Anaesthesia & ICM Manchester Royal Infirmary Delirium in Critical Care ICS SoA 2013 www.drdconway.com Prescribing information for Dexdor (dexmedotomidine) is on the last slide Item Date: Dec 13 DEX4260g

  2. Disclosure Honoraria Glaxo-Smith Kline Orion Pharma www.drdconway.com

  3. David AaronovitchTimes columnist & ICU patient they brought me round in the intensive care unit and that’s when the madness began... www.drdconway.com

  4. DSM5 2013 Definition Delirium An acute or subacute disturbance of alertness, awareness, and attention. Associated with change in cognition usually with a fluctuating course. Hyperactive, hypoactive & mixed Short term vs. persistent duration www.drdconway.com

  5. Delirium in Critical Care 10% of hospital patients NICE CG103 20-30% non ventilated critical care patients 50% of ventilated ICU patients Ely JAMA 2004 Consequences for ICU Patients Associated with ICU & long term mortality DECCA Crit Care 2010 Post-traumatic Stress Disorder Jones ICM 2007 Cognitive Dysfunction Girard CCM 2010 Increased costMilbrandt CCM 2004 www.drdconway.com

  6. Long Term Consequences Pandharipande P BRAIN-ICU NEJM 2013 Duration of delirium but NOT sedative / analgesic use was associated with cognitive impairment

  7. A man who is "of sound mind" is one who keeps the inner madman under lock and key. Paul Valéry Risk Factors for Delirium www.drdconway.com

  8. Increasing Age Severity of Illness Coma Morphine & sedatives Trauma / Head Injury Sepsis Metabolic Acidosis Urea Delirium Risk Factors Skrobik CCM 2013 IL-6 PGP-inhibitors Not fentanyl or midazolam www.drdconway.com

  9. Tackling Delirium: Inspiration www.mc.vanderbilt.edu/icudelirium www.icudelirium.co.uk www.drdconway.com

  10. Screening for Delirium CAM-ICU Confusion assessment method ICDSC Int. Care Delirium Screening Checklist 8 features  consciousness Psychomotor slowing / agitation Sleep/wake disturbance Inattention Disorientation Delusions Inappropriate speech Fluctuation • 4 features •  consciousness • Fluctuating mental state • Inattention • Disordered thinking  consciousness / residual sedation may confound delirium screening ‘True’ delirium associated with poor long term outcomeKress ‘13

  11. Initial 10 week audit 2007 • 55 patients ICU & HDU • RASS>-1 then CAM-ICU • 32% incidence delirium • Association • Mechanical Ventilation • Opioids • Benzodiazepines • Previous mental health conditions www.drdconway.com

  12. ABCDE Minimise long-acting opioid & BDZ may reduce oversedation Visual & hearing aids Day – night lighting Early Mobilisation Haloperidol 2.5mg but not as prophylaxis Olanzapine 5mg od Skrobik Y, AnesAlg 2010 Alpha 2 Agonists Benzodiazepines +/- dexmedetomidine for alcohol withdrawal Tolonen J, Eur J Em Med 2012 Preventing & Managing Delirium 07- CAM-ICU monitoring www.drdconway.com

  13. Sedation in Critical Care:The Changing Landscape Kress, Hall JAMA 2012 SEDATION PROTOCOL Sedation Score Daily Wake Up ~2000 Length of MV LOS in ICU & Hosp Delirium DEEP SEDATION Reduce stress & work of breathing >10 years ago ICU Survival Excessive Sedation? ANALGO -SEDATION Analgesia First ABCDE Approach ~2010 Delirium Long Term Outcomes QUALITY time www.drdconway.com

  14. Earplugs, Music & Sleep on ICU Van Rompaey B,Crit Care 2012 • Chlan L,JAMA 2013 • RCT 373 ICU patients • Music or Noise Cancelling headphones reduce anxiety and sedative use RCT 137 patients Earplugs at night Reduced confusion Improved sleep www.drdconway.com

  15. Re-Audit 2012 with CAM-ICU • >600 CAM-ICU on 107 ICU patients • 69% 2007 to 43% in 2012 www.drdconway.com

  16. Number of positive episodes Error bars 95% CI 2007 2012 spring 2012fall Pisani, KongAmJRCCM ’09 Delirium in elderly ICU Duration associated with 6 & 12-month mortality 10%  risk of death per day with delirium BRAIN-ICU NEJM 2013 Duration associated with impaired cognition www.drdconway.com

  17. Haloperidol and ICU Delirium • 45 patients >65 yr non-cardiac surgery • Haloperidol 0.5mg bolus + 0.1mg/hr • Delirium 7 days 15.3% haloperidol v 23.2% placebo (p=.031) Wang CCM 2012 HOPE-ICU Paige Lancet 2013 • 140 patients with and w/o delirium RCT • Haloperidol 2.5mg tds had same LoS free of delirium as standard care (6d) www.drdconway.com

  18. HOPE for Haloperidol ? • 73 yo man, ETOH and periph. vascular disease • 16 hr limb salvage surgery ICU  BKA • Extubated 18h, 2L O2 , no vasopressors • Mildly confused, CAM+ve, oramorph Sat, 8pm-would you prescribe haloperidol? In the night, agitated+++ given 15mg haloperidol + clonidine + benzo & spent the next day asleep… HOPE-ICU showed haloperidol reduces agitation (I would consider a pre-emptive strike!) www.drdconway.com

  19. Thanks for listening • Delirium is Common • Associated with worse long term outcomes • Prevention & Management includes Non-pharmacology • HOPE for haloperidol Many Thanks To… Adam Jones Sanchia Pickering Tony Dunne Hannah Lees Richard Clark www.drdconway.com Item Date Nov 13 DEX4260g

  20. Dexdor 100 micrograms per ml concentrate for solution for infusion (dexmedetomidine) Prescribing Information • Indication: Sedation of adult ICU patients requiring sedation level not deeper than arousal in response to verbal stimulation (RASS 0 to -3). Dosage and administration: Hospital use only, by healthcare professionals skilled in management of patients requiring intensive care. Administer only as diluted intravenous infusion using controlled infusion device. Dexmedetomidine is very potent and the infusion rate is given per hour. Switch patients already intubated and sedated to dexmedetomidine with initial infusion rate of 0.7 micrograms/kg/h and adjust stepwise within range 0.2 to 1.4 micrograms/kg/h to achieve desired sedation level. Consider lower starting infusion rate for frail patients. After dose adjustment, new steady state sedation level may not be reached for up to one hour. Do not exceed maximum dose of 1.4 micrograms/kg/h. Switch patients failing to achieve an adequate level of sedation with maximum dose to an alternative sedative agent. Loading dose not recommended. Administer propofol or midazolam if needed until clinical effects of Dexdor established. No experience in use of Dexdor for more than 14 days. Use for longer than this period should be regularly reassessed. Elderly: No dosage adjustment required. Renal impairment: No dosage adjustment required. Hepatic impairment: Caution advised; consider reduced dose. Paediatric population: No recommendation can be made. Contraindications: Hypersensitivity. Advanced heart block (grade 2 or 3) unless paced. Uncontrolled hypotension. Acute cerebrovascular conditions. Warnings and precautions: Intended for use in intensive care setting, use in other environments not recommended. Continuous cardiac monitoring required. Monitor respiration in non-intubated patients. Do not use as induction agent for intubation or to provide sedation during muscle relaxant use. Dexdor reduces heart rate and blood pressure but at higher concentrations causes peripheral vasoconstriction and hypertension. Not suitable in patients who will not tolerate lack of deep sedation and easy rousability. Users should be ready to use alternative sedative for acute control of agitation or during procedures, especially during the first few hours of treatment. Caution with: pre-existing bradycardia; high physical fitness and slow resting heart rate; pre-existing hypotension, hypovolaemia, chronic hypotension or reduced functional reserve; severe ventricular dysfunction; the elderly; impaired peripheral autonomic activity (e.g. due to spinal cord injury); ischaemic heart disease or severe cerebrovascular disease; severe hepatic impairment; severe neurological disorders such as head injury and after neurosurgery. Reduce dose or discontinue if signs of myocardial or cerebral ischaemia. Additive effects may occur with other substances with sedative or cardiovascular actions. Some patients receiving Dexdor have been observed to be arousable and alert when stimulated; this alone should not be considered as evidence of lack of efficacy. Do not use as sole treatment in status epilepticus. Consider possibility of withdrawal reaction if patient develops agitation and hypertension shortly after stopping dexmedetomidine. Not recommended in malignant hyperthermia-sensitive individuals. Discontinue treatment in event of sustained unexplained fever. Undesirable effects: Very common (>1/10): Bradycardia, hypotension, hypertension. Common (1>100 to <1/10): Hyperglycaemia, hypoglycaemia, agitation, myocardial ischaemia or infarction, tachycardia, nausea, vomiting, dry mouth, withdrawal syndrome, hyperthermia. Uncommon (1>1,000 to <1/100): Metabolic acidosis, hypoalbuminaemia, hallucination, atrioventricular block first degree, cardiac output decreased, dyspnoea, abdominal distension, drug ineffective, thirst. See SPC for further details. Legal category: POM. Presentations, basic NHS costs and marketing authorization numbers: Dexdor 2 ml ampoule x 5, £78.30, EU/1/11/718/001; Dexdor 2 ml ampoule x 25, £391.50, EU/1/11/718/002; Dexdor 4 ml vial x 4, £125.28, EU/1/11/718/004; Dexdor 10ml vial x 4, £313.20, EU/1/11/718/006. Distributed by: Orion Pharma (UK) Ltd. Oaklea Court, 22 Park Street, Newbury, Berkshire, RG14 1EA, UK. Full prescribing information is available on request. Dexdor is a registered trademark. Date of Prescribing Information: Feb 2013. • Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Orion Pharma (UK) Ltd on 01635 520300.

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