Delirium Unarousable to Ashley Thompson, Pharm D., BCPS voice - PDF document

5/9/2015 Acute ICU Delirium Controversies mental Sedation status change & Updates Fluctuating Disorganized COMA mental thinking status Delirium Unarousable to Ashley Thompson, Pharm D., BCPS voice Critical Care Pharmacist Arousable to UCSF Medical Center Analgesia voice May 2015 Altered level Inattention of consciousness Pun, et al. Chest 2007; 132; 624-636 Ely, et al. JAMA . 2001; 286:2703-2710 Diagnostic and Statistical Manual of Mental Disorders (4th ed.) The Bedside Assessment Scope of the Problem  Independent predictor of mortality  ↑ Long term cognitive dysfunction RN = 35%  ↑ duration of mechanical ventilation, reintubation rates Attending = 28%  ↑ hospital/ICU length of stay  ↑ healthcare costs  Reduced functional status at discharge Pun, et al. Chest 2007; 132; 624-636 Ely EW, et al. JAMA . 2004; 291(14):1753-1762 Pandharipande PP. NEJM 2013;369:1306-16. AJRCCM 2009 12. 1; 180(11): 1092 – 1097 Girard, et al. Crit Care Med 2012; 38:1513-1520 Milbrandt et al. Crit Care Med. 2004;32 (4): 955-962 Intensive Care Med (2009) 35: 1276-1280 Delirium is unrecognized in up to 84% of Does level of sedation influence CAM- hospitalized adults ICU positivity? …But what I see these days are paralyzed, sedated patients, lying without motion, appearing to be dead, except for the monitors +1B that tell me otherwise… Validated Screening tool - Tomas Petty, 1998 Crit Care Med 2013; 41:263 – 306. JAMA 1990;263(8):1097 – 101. Am J Med 1994;97(3):278 – 88. 1

5/9/2015 Rapidly Reversible, Sedation-related No Sedation versus Persistent Delirium No sedation vs Prop/Midaz (+ SWU) + open label morphine  Prospective observational blinded study, Single centered  Results: (N=102) o No sedation is feasible; 18% didn’t tolerate  Results: o  vent days (4 days, P=0.019)* o Patients 10x more likely to be CAM-ICU + before sedation o  ICU (9 days)/Hospital LOS (24 days) interruption vs after (P < 0.001) o  mortality (22% vs 38%, P=0.06) o Not all “types” of delirium are the same o No difference in PTSD (follow-up study) Mechanically o Post-hoc analysis DSI Outcome ventilated, •  hyperactive delirium sedated MICU pts – hypoactive, i.e sedation induced, not measured •  Acute renal failure If CAM-ICU + (followed by (-) after If CAM-ICU + = DSI) = rapidly reversible sedation- persistent delirium related delirium Patel SB, et al. Am J Respir Crit Care Med 2014; 189: 658-665 Strom T, et al. Lancet 2010;375:475-80. Rapidly Reversible, Sedation-related versus Rapidly Reversible, Sedation-related Persistent Delirium versus Persistent Delirium Mortality Each day of persistent delirium was associated with a 14% ↑ risk of death by 1 year (P<0.001) Patel SB, et al. Am J Respir Crit Care Med 2014; 189: 658-665 Patel SB, et al. Am J Respir Crit Care Med 2014; 189: 658-665 Benzodiazepines & Delirium Do Benzodiazepines increase a patients risk of developing delirium? Lorazepam was an independent risk factor for daily transition to delirium (OR 1.2 95% CI 1.1-1.4, p=0.003) Pandharipande, et al. Anesthesiology 2006; 104:21 – 6. 2

5/9/2015 SEDCOM Trial: Daily prevalence of Factors Predisposing to Coma & Delirium delirium COMA associated with duration, NOT daily dose of drug exposure Riker R, et al. JAMA . 2009; 301 (5):489-499. Skrobik Y, et al. Crit Care Med 2013; 41: 999-1008 Factors Predisposing to Coma & Delirium Factors Predisposing to Coma & Delirium Inflammation & Delirium Midazolam & delirium  LOWER levels in patients with delirium vs no delirium (p=0.001)  Time to first occurrence of delirium: o Unrelated to dose or presence of (p=0.4 p=0.3 respectively , cox analysis)  Duration of first episode of delirium, not associated with: o Concomitant administration (p=0.26) o Cumulative midazolam administration (p=0.96)  Days in delirium/days in ICU o Not associated with midazolam doses on delirium days (p=0.25) o Not associated with cumulative doses (p=0.96) Skrobik Y, et al. Crit Care Med 2013; 41: 999-1008 Skrobik Y, et al. Crit Care Med 2013; 41: 999-1008 Does delirium respond to RCTs for Antipsychotic use in ICU pharmacological treatment? delirium? 1. Devlin, et al. (n=36); treatment o Quetiapine vs haloperidol PRN o ↓time to first delirium resolution (1 vs 4.5 days) o ↓ duration of delirium (36 vs 120 hours) o ↓agitation (6 vs 36 hours) o ↓PRN haloperidol vs placebo 2. MIND (n=101), prophylaxis, no difference “Doctor, she’s not all there. The wit, the comprehension, o Prophylactic ziprasidone vs haloperidol vs placebo the concentration…The best way to describe it is mental disorganization, like there is a connection 3. HOPE-ICU (n=142), prophylaxis; no difference missing or a synapse not firing. It has been 10 o Prophylactic haloperidol IV ATC vs placebo months, and I just keep waiting for it to straighten itself out. Is this it ?” Devlin, et al. Crit Care Med 2010; 38 Girad, et al . Crit Care Med; 2010; 38:428-437 - Family testimonial (icudelirium.org) Page VJ et al . Lancet Resp Med 2013;1(7):515-23. 3

5/9/2015 Antipsychotics : FDA Black box warning dose ADRS associated with antipsychotic dependent  risk of death in elderly with use in ICU Delirium Treatment dementia (60-70%) No antipsychotic ADRS = (%), 38 18% Antipsychotic (%), 62 Huybrechts KF et al. BMJ 2012; 344: e977 Hale GM et al. J Pharmacy Practice 2015 Wang P et al. Neng J Med 2005;353:2335-41 ADRS associated with antipsychotic Transitioning Out of the Unit? use in ICU Delirium Treatment  Retrospective cohort study (N=59) 60  Antipsychotics initiated for ICU delirium: 50 QTc o 47% continued antipsychotic on ICU 40 drowsiness discharge % 30 tachycardia o 71.4% were continued as an outpatient 20 drug-induced fever  Long-term impact? 10 neutropenia 0 ADR Risk Factor for developing ADRs APACHE II Score (p=0.038) Jasiak KD, et al. J Pharm Pract 2013;26(3):253-6. Hale GM et al. J Pharmacy Practice 2015 Statins & Delirium during Critical Statins & Delirium during Critical Illness: ICU statin use & Delirium Illness: Prehospital statin users Septic Not Septic Statin use associated with reduced Delirium (p < 0.01) Morandi AM. Et al. Crit Care Med 2014; 42: 1899-1909 Morandi AM. Et al. Crit Care Med 2014; 42: 1899-1909 4

5/9/2015 Corticosteroids & Delirium Summary: Delirium & Drugs in Patients with Acute Lung Injury  Multisite, Prospective, cohort study (N=330 MV pts  Discontinue/minimize deliriogenic medications with ALI)  Choose appropriate sedation  Role of Antipsychotics? o Lack of compelling evidence o Risk of side effects  Consider continuing preadmission statin o Need RCT to confirm Schreiber MP et al. Crit Care Med 2014; 42: 1480-1486 Sleep, Exercise & Delirium Sleep in the ICU & Delirium  50% of ICU sleep occurs during daytime hours  Opioids, Benzodiazepines disrupt REM sleep  Nocturnal [melatonin] in ICU pts negatively correlated with illness of severity Bellapart. BJA 108 (4): 572-80 (2012) Bourne RS et al. Crit Care 2008, 12:R52 Huang et al. Trials 2014, 15:327 Preventative Effects of Ramelteon on Bundled approach to sleep & ICU Delirium Delirium  Ramelteon 8mg or placebo at 2100 + prn hydroxyzine  Multifaceted QI intervention John Hopkins MICU Placebo Ramelteon Significance Stage 2: Stage 0: Stage 1: Stage 3: Environmental Pharmacologic Non-pharm All delirium 32% 3% P=0.003, RR 0.09 (95% CT Baseline interventions guideline sleep aids 0.01-0.69) Baseline Sleep QI Significance No history 30% 0% P=0.001 delirium Delirium/Coma 43% 48% P=0.04 free Time to 5.74 days 6.94 days delirium Incident 69% 49% P=0.001 (Kaplan-Meier) delirium/Coma ND: mortality, ICU/Hospital LOS, neurocognitive tests, perceived No significant differences between the groups in any sleep differences sleep quality Hatta K, et al. JAMA Psychiatry. 2014; 71 (4): 397-403 Kamdar et al. Crit Care Med 2013; 41: 800-809 5

5/9/2015 ICU Liberation is as easy as… Early Rehabilitation & Delirium • Awake & breathing coordination (DSI,  Progressive mobility algorithm beginning ~1.5 AB +1B) days post-intubation C  Primary endpoint: • Choice of sedative (nonBZD, +2B) o Independent functional status at discharge (59% v. • Delirium monitoring & management D 35%, p=0.02) (+1B)  Results: E • Early mobility (+1B) o Shorter duration of ICU delirium (2 vs. 4 days, p=0.03) with similar sedative administration/SAT F • Family involvement Critical Care 2010, 14:157 Schweickert WD, et al. Lancet 2009;373:1874-82 Curr Opin CritCare 2011,17:43 – 49 The RCTs of the ABCs… ABCDE: Is it that easy?  ABCDE bundle Implementation: Single center, AB • A: Kress JP, et al. N Engl J Med 2000; 342: 1471-7 pre/post study (n= 296) • A&B: Girard ED et al. Lancet 2008; 371: 126-34 o  delirium • Pandharipande PP et al. JAMA 2007; 298: 2644-53 C • Prevalence (62% vs 49%, p=0.02) • Riker R. et al, JAMA 2009; 301: 489-499 • Strom T, et al. Lancet 2010; 375: 475-480 • Days (33.3% vs 50%, p=0.003) o ↑ventilator free days (21 vs 24 days, p=0.04) D • Spronk PE intensive Care Med. 2009; 35:1276-1280 o  mobilization (66% vs 48%, p=0.002) • Pun, et al. Chest 2007; 132; 624-636 E • Schweickert et al. Lancet 2009; 373: 1874-82 Balas MC et al. Crit Care Med 2014; 42:1024 – 1036 Balas MC et al. Crit Care Med 2013; 41:S116 – S127 ICU Delirium Controversies & Updates Thank you Ashley Thompson, Pharm D., BCPS Critical Care Pharmacist Ashley.Thompson@ucsf.edu UCSF Medical Center May 2015 6