Assessing & Managing ICU Delirium: What is the Evidence? Dale Needham, MD, PhD Professor Pulmonary & Critical Care Medicine, and Physical Medicine & Rehabilitation Medical Director, Critical Care Physical Med & Rehab Program Johns Hopkins University Overview of Presentation Guidelines: Delirium assessment in ICU Definition: What is delirium? Epidemiology: Delirium in ICU Prognosis: ICU delirium and patient outcomes Evaluation: CAM-ICU; validation Management: What is the evidence? Quality Improvement: Johns Hopkins MICU project dale.needham@jhmi.edu @DrDaleNeedham www.hopkinsmedicine.org/oacis 2013 SCCM 6 yrs; 19,000 ref; GRADE evaluation Pts s/b awake & follow commands Regular Assessment of Pain Sedation Delirium Self-report; BPS, CPOT * Crit Care Med 2013; volume 41: pg 263 onward RASS, SAS Use light sedation or DSI Protocol Analgesia first CAM-ICU, ICDSC Mobilize early May use -Dexmed. infusion -Atypical antipsychotic Avoid Benzodiazepine; Sleep promotion; Inter-Disciplinary team Delirium Definition Abrupt onset (devlp over hrs/days) with fluctuation during day Inattention inability to direct, sustain & shift attention Decreased awareness of environment disoriented Change in cognition &/or perception Short-term memory, language/speech abnormalities Hallucinations: auditory or tactile [not a requirement] Adapted from DSM -5 American Psychiatric Association. 2013 Epidemiology of ICU Delirium 20-80% of ICU patients have delirium during ICU Frequently unrecognized or misdiagnosed by clinicians Subtypes: Hyperactive (agitated, increased motor activity) 1% Hypoactive (sleepy, inattentive, decreased motor activity) 44% Mixed 55% Onset: ICU Day 2 (+/- 2) Duration: 4 (+/- 2) days 50% & 10% of ARDS pts delirious at ICU & hospital discharge Ely, EW, et al. JAMA 2001; 286, 2703-2710 Ely, EW, et al. CCM 2001; 9:1370-1379 Peterson, et al JAGS 2006: 54:479-484 McNicoll L, JAGS 2003;51:591-98; Fan, et al CCM 2008:94-99. Routine Assessment of ICU Patients for Delirium How many routinely assess ICU pts for delirium? Difficult due to non-verbal ventilated patients Why do it? Associated with worse outcomes - prognostic value A measure of brain failure to be considered with signs of other organ impairments (hypoxemia, hypotension, etc) What is the effect on patient outcomes? 1
Delirium and Patient Outcomes - Independently associated with increased risk of death - - Increased Mechanical Ventilation duration - Increased Length of Stay - Higher ICU costs -?Maybe associated with PTSD after ICU? Ely. ICM 2001; 27, 1892-1900 Ely, JAMA 2004; 291: 1753-1762 Lin, SM CCM 2004; 32: 2254-2259 Girard CCM 38(7):1513-1520 Milbrandt E.,CCM 2004; 32:955-962. Jackson. Neuropsychology Review 2004; 14: 87-98. Oimet ICM 2007; 33:1007-1013; Davydow Gen. Hosp. Psych 2008;30:421-434 821 ICU pts with respiratory failure or shock 74% delirious during hospital stay ~1/3 & 1/4 had cognitive scores at 1 year follow-up c/w moderate TBI & mild Alzheimer's, respectively Affected both older and younger pts Delirium duration associated with impairment 12 Delirium Assessment in ICU: CAM-ICU Based on the CAM Most widely used Diagnostic tool by non-psychiatrists Advantages: ease, speed, reliability, validity Validated against expert opinion & DSM Required adaptation for non-verbal ICU patient ICU version based on validated assessment methods, expert opinion & pilot testing Two Step Approach to Assessing Consciousness Step 1. Level of consciousness: Arousal/Sedation Assessment (RASS, SAS) (If pt opens eyes or moves to voice, go to Step 2 Otherwise, stop pt is comatose unable to assess for Step 2) Step 2. Content of consciousness: Delirium Assessment (CAM-ICU) Step 2: CAM-ICU Assessment: 4 Features 1. Acute onset of mental status changes or a fluctuating course and 2. Inattention and 3. Disorganized Thinking or 4. Altered level of consciousness Ely et al, Crit Care Med 2001;29:1370-79 Ely, E.W., et al. JAMA2001; 286, 2703-2710 Validation of CAM-ICU 2 example studies (Vanderbilt & Taiwan) ~100 mechically ventilated patients in MICU & CCU Gold standard: >30 min assessment by delirium experts/psych using DSM-IV Sensitivity: 91 100%; Specificity: 98 100% Inter-rater reliability: kappa = 0.91-0.96 Mean time to complete = 2 minutes 2 meta-analyses w/ 9-12 validation studies showed pooled: Sens: 74 80%; Spec 96%; AUC ROC: 0.96 0.97 Ely JAMA 2001; Lin CCM 2004; Neto CCM 2012 2
Educational Website www.icudelirium.org What about Management of Delirium? Management of ICU Delirium Identify and Modify Risk Factors 1. Multi-faceted delirium protocol (no ICU evidence) Inouye NEJM 1999: primary prevention in >800 in elderly medical in-pts: delirium incidence: 10 vs. 15%, p = 0.02 2. Early mobilization of patients 3. Sedation/medications 1. minimize excess benzodiazepine, narcotic & corticosteroid 2. novel GABA-sparing agents (e.g., alpha-2 agonist dexmedetomidine) 4. Improve sleep (no RCT) Lancet May 2009 Identical sedation in intervention and control group Primary Outcome of RCT Pandharipande P et al. (Lorazepam) Anesthesiology 2006;104:21 26; Oimet ICM 2007; 33:1007-1013; Pandharipande P et al. (Midazolam) J Trauma 2008 Dubois MJ et al., (Morphine) Intensive Care Med 2001; 27:1297 1304. Corticosteroids & Transition to Delirium in ARDS ICAP study Baltimore 13 ICUs in 4 hospitals 330 ALI pts with 2,286 ICU days of observeration Probability of transition to delirium increased with lorazepam dose given in prior 24 hr Risk of delirium increased dramatically for each year of life after 65 year old Pandharipande P et al., Anesthesiology 2006;104:21 26. Factors independently associated with delirium (OR, 95%CI): Older age (compared to <40 years old): 40-60 years (1.8, 1.3 to 2.6) >60 years (2.5, 1.7 to 3.9) Any systemic corticosteroid in prior 24 hr (1.5, 1.1 to 2.2) No dose-response, but majority of doses were high: Prednisone-equivalent doses during days of transition 44 (13, 75) mg 3
Dexmedetomidine (Precedex) MENDS RCT JAMA 2007: 106 mech vent pts dexmedetomidine vs. lorazepam for <5 days % of days within 1 point of RASS goal: 80% vs. 67%, p=0.04 Median days alive without coma: 7.0 vs. 3.0, p=0.01 SEDCOM RCT JAMA 2008: 68 centers in 5 countries; 375 MV pt dex v. versed til extubation (goal light sedn RASS -2 to +1) Primary outcome: % of time at RASS target range, 77% vs. 75%, NS Delirium prevalence (CAM-ICU): 54% vs. 77%, p<0.001 MV duration: 3.7 vs. 5.6 days (p=0.01); ICU stay: 5.9 vs. 7.6 d, NS Bradycardia: 42 vs. 19%, p<0.001; Brady Treatment: 5% vs. 1%, p=0.07 Pandharipande P et al. JAMA 2007; Riker et al JAMA 2009 Dexmedetomidine MIDEX & PRODEX JAMA 2012: >30 center in >6 countries (EU) 2 RCTs of Dex. vs. Midazolam or Propofol ~250 MV patient RCT (goal of light to moderate sedation ) Primary outcomes: % of time at target sedation: No significant difference Duration of MV: for midazolam: 5.1 vs. 6.8 days (p=0.03); for propofol: no significant difference Secondary outcomes: Improved interaction (VAS) Delirium prevalence: no data No difference in mortality/length of stay More hypotension and bradycardia Jakob JAMA 2012 Antipsychotics and Delirium Quetiapine v. Placebo Safety & Efficacy (Devlin, CCM 2010): Phase II RCT 36 ICU pt w/ delirium (ISDSC score >4) IV haldol prn plus either Quetiapine vs. Placebo Dose incr d incrementally to 200 mg bid if 1 haldol dose w/in 24 hrs Drug Tx stopped when delirium resolve, Tx >10 days, or ICU d/c Results (Quetiapine vs. Placebo) Time to 1 st resolution of delirium 1.0 v. 4.5 day (p =.001) Delirium duration 36 v. 120 hours (p =.006) Agitation: 6 vs. 36 hrs (p = 0.02) Days of use of prn IV haldol: 3 v. 4 days (p =.05) Discharge home or rehab: 89 vs. 56% (p=0.06) In-hospital mortality: 11 vs. 17% (p=ns) Similar frequency of increased QTc; No EPS in either group Haloperidol in ICU RCT (Hope-ICU trial) Page et al, The Lancet Respiratory Medicine, 2013 Blinded RCT prevention/resolution of delirium/coma: IV Haloperidol vs Placebo (n=141) Mech vent medical-surgical adult ICU pts (APACHE II 20 vs 20) Enrolled irrespective of delirum/coma status Treatment started within 72 hours of ICU admission 2.5 mg IV haloperidol q8h vs placebo Given until: Delirium/Coma free for >48h, ICU discharge, or Day 14 Goal RASS: 0 to -1 (unless MD otherwise specify), via: titration of Propofol & Fentanyl infusions; w/ decr study drug thereafter Results: Delirium/coma-free ICU days (5 vs 6, p=0.53) (1st 14 d) No serious adverse effects (over-sedation: 11% vs 7%; no dif in QTc) RASS +2 in haldol vs placebo (13% vs 20% p=0.008) (1 st 14d) Ventilator-free days (21 vs 17, p=0 88) (1st 28 d) New Sedation Protocol Crit Care Med 2013;41:1435-1442 Acute Lung Injury patients in a 16 bed Medical ICU Intervention: Prospective structured QI (20 mo.); n = 82 Control: Retrospective ALI cohort (30 mo.); n = 120 Control had goal-directed sedation & daily interruption Goal patient below Hager et al, 2013; Crit Care Med; 41: 1435-1442 - RASS goal: 0 - Fentanyl & versed (A-1) - Avoid infusions, use prn - Initially q 5 min (if needed) - Then q 1-2hr - Daily stop of prn & infusion - Anticipate agitation - Do no use benzo - Use IV haldol (check QTc) 4
Changes in Sedation of ALI Patients (see Hager... Needham, et al. Crit Care Med 2013;41:1435-1442) ARDS Severity & Early Sedation (sickest) High severity of illness, median APACHE II = 29 Before QI 10/04 4/07 (n=120) After QI 7/09 4/11 (n=82) P-value* On narcotic infusion (% days) 74 (50, 100) 33 (10, 65) <0.001 On benzodiazepine infusion (% days) 70 (46, 94) 22 (0, 50) <0.001 Median RASS Score** -4 (-5, -2) -1.5 (-3, 0) <0.001 Awake & Not delirious (% days) 0 (0, 18) 19 (0, 50) <0.001 No sig. dif btwn groups in ARDS severity Half severe ARDS Sig. decr in infusions; Only 25-31% in QI ** RASS scores: No sedation (-1, 0, +1), light sedation (-2, -3), deep sedation (-4, -5), and agitated (>+1) Hager Needham et al. Critical Care Medicine 2013;41: e241-e243 JHH MICU Sleep QI CCM 2013 Kamdar Needham et al Crit Care Med, March 2013 Conclusions: Common problem for ICU patients Associated with many negative clinical outcomes CAM-ICU is valid, reliable & quick for delirium assessment Current treatment recommendation exist more RCT needed Unanswered?: haldol, atypical antipsychotics, new agents Delirium can be markedly improved through QI Ongoing research: effects on l-t patient psych & cognition To learn more American Delirium Society (ADS) 5th Annual Meeting Baltimore, Maryland May 31 June 2, 2015 ADS: ICU Delirium Course Half Day Sun. 5/31/15 Baltimore, Maryland Check us out at: http://www.americandeliriumsociety.org/ 5