Diagnosis and Management of ICU Delirium June 24, 2010 - July 1, 2010 Dave Miller, MD and Becky Logiudice, MS, RN

Talk Outline Why is this important? What is delirium? Using CAM-ICU to diagnose ICU delirium How do I treat delirium? Goal-oriented sedation

Why is this important? Perspective from SB   Perspective from SB About my delirium memories from the ICU, I have had few. The time I spent seems like it was in a huge, empty gray space, sort of like a monstrous underground parking garage with no cars, only me, floating or seeming to float, on something. Every once in a while I would get to an edge of something horrible and once I remember I thought, "if I just let go, then this horror will be over…” When I try to write about that time (and I have tried over and over), words just won't come and in my line of writing, personal essays, if it doesn't just come gushing out, I have to stop. And that's where I am now http://www.icudelirium.org/outcomes.html#reports

Why is this important? 183 ÷ (183+41) = 0.82 Pun B T , Ely E W Chest 2007;132:624-636

Why is this important? Common Increased mortality Increased LOS Increased complications Increased costs May be associated with increased dementia and long-term cognitive impairment

Girard DT et al. Crit Care Med 2010;38(7):epub ahead of print

Pun BT and Ely EW. Chest 2007;132:624-636

What is Delirium? Answer # 1 You’ll Know it when you see it. . .

What is delirium? Pun B T , Ely E W Chest 2007;132:624-636

What is delirium? Answer # 2 Disturbance of consciousness Inattention Change in cognition or perceptual disturbance Develops over hours to days Fluctuates over time

How do I diagnose delirium? Case 1 Mr. D, a 70-year old with severe COPD, is in the MICU on a ventilator for respiratory failure. Initially he needed high levels of sedation, but now Propofol has been decreased and Mr. D is awake but agitated, grimacing, thrashing and trying to sit up in bed. He makes eye contact, but won’t follow commands Is Mr. D delirious? How do you know?

Assessment of ICU patients Patient Comfort Pain Sedation Delirium 0 -10 scale FRACC Subjective/ physiologic factors Sedation assessment scale (RASS, SAS, MAAS) CAM-ICU

Assessment tool: CAM-ICU

Assessment tool: CAM-ICU Richmond Agitation-Sedation Scale (RASS)

RASS +4 Combative Combative, violent, immediate danger to staff +3 Very agitated Pulls or removes tubes or catheters; aggressive +2 Agitated Frequent non-purposeful movement, fights ventilator +1 Restless Anxious and apprehensive, but movements not aggressive or vigorous Alert and calm -1 Drowsy Not fully alert but has eye opening to voice and sustained eye contact (> 10 s) -2 Light sedation Briefly awakens to voice with eye opening and eye contact (< 10 s) -3 Moderate sedation Movement or eye opening to voice but no eye contact -4 Deep sedation No response to voice, but movement or eye opening to physical stimulation -5 Not arousable No response to voice or physical stimulation

Assessment tool: CAM-ICU Attention Screening Examination

Attention Screening Examination Auditory Squeeze my hand each time I say the letter “A” SAVEAHAART More than 2 wrong responses = POSTIVE Visual (cannot hear or squeeze hands) Show 5 pictures, then show 5 repeat and 5 new in random order More than 2 wrong responses = POSITIVE

Assessment tool: CAM-ICU Assessing for Disorganized Thinking: Answer 4 simple yes/no questions and follow a 2-step command: E.g.,“Will a stone float on water?” “Hold up 2 fingers on one hand, then on the other hand.”

How do I diagnose delirium? Case 1 revisited Mr. D, a 70-year old with severe COPD, is in the MICU on a ventilator for respiratory failure. Initially he needed high levels of sedation, but now Propofol has been decreased and Mr. D is awake but agitated, grimacing, thrashing and trying to sit up in bed. He makes eye contact, but won’t follow commands Is Mr. D delirious? How do you know?

Case 1 revisited STEP 1: Mr. D is assessed to be a RASS +2, which is an acute change from his baseline STEP 2: He squeezes hands on “A” once out of 5 times (4 errors) so is inattentive STEP 4: Because his level of consciousness is altered (RASS +2), STEP 3 does not need to be assessed. Mr. D is delirious!

Case 2 The next day, Mr. D is awake and calm (RASS 0). He was given several doses of lorazepam overnight for “agitation.” He remains intubated, but is following commands appropriately. Is Mr. D delirious now?

How should we manage Mr. D? STEP 1: He is awake and calm (RASS 0) now, but fluctuated within the last 24 hours STEP 2: He scores 6/10 on the Attention Screening Examination (POSITIVE) STEP 3: Because his level of consciousness is not currently altered, he is tested for disorganized thinking. He scores 3 out of 5 because when asked “Are there elephants in the sea?” and “Can you use a hammer to cut wood?” he answers “YES!” (POSITIVE) How should we manage Mr. D?

Managing ICU Delirium Look for it Communication between nursing and MDs Identify and treat correctable risk factors Optimize non-pharmacologic interventions Goal-oriented sedation with daily wake-ups Pharmacologic intervention

Managing ICU Delirium Modify Risk Factors Host Factor Acute Illness Iatrogenic/ Environmental Age Sepsis Metabolic disturbance Baseline comorbidity Hypoxemia Lights, noise, sleep pattern Baseline cognitive impairment Global severity of illness score Anticholinergic, sedative and analgesic meds

Severity of illness and age are independent risk factors for delirium Pandharipande et al. Anesthesiology 2006;104:21-26

Lorazepam dose is an independent risk factor for delirium Also: Other Benzos Opiates Propofol Anticholinergics H2 blockers Steroids Some antibiotics Psych meds Pandharipande et al. Anesthesiology 2006;104:21-26

Non-Pharmacologic Management Orientation Visual and hearing aids Communicate and re-orient frequently Familiar objects and people Consistent nursing staff TV, news, music during the day Environment Sleep hygiene: Lights off at night, on during day. Sleep aids? Control excess noise at night Ambulate or mobilize early and often Pun B T , Ely E W Chest 2007;132:624-636

Pharmacologic Management Antipsychotics Little controlled data, but anecdotal and case-series evidence One small recent RCT comparing Haldol vs placebo found no difference in mortality, LOS, side effects Haldol IV recommended by SCCM Long half-life (18-54 hours) Risk of: QT prolongation, NMS, akathisia Monitor QTc BID, follow K, Mg, Ca. Beware other drugs that prolong QT (MANY including anti-arrhythmics, quinolones, erythromycin, methadone) Jacobi et al. Crit Care Med 2002;30:119-141 Girard et al. Crit Care Med 2010; 38: 428-37

Pharmacologic Management Haloperidol (Haldol) Action: CNS depressant and dopamine receptor antagonist Side Effects: Prolonged QT interval, Extrapyramidal symptoms, tardive dyskinesia (long term use) IV Dosing: Starting dose: Mild agitation 2mg IV, Moderate to severe agitation 5mg IV After 20 min. of 1st dose, if still agitated increase the previous doses by 5mg every 20min until calm. Max dose 30 mg in 24 hours Once pt is calm, 25% of loading dose should be given Q 6 hours scheduled Once pt is delirium free for 24 hours taper off haldol

Atypical Antipsychotics Recent double-blind RCT of quetiapine (Seroquil) 50mg BID vs placebo Haldol PRN – study drug increased if any PRN in 24 hours 36 ICU patients with delirium Shorter time to resolution of delirium (1 vs 4.5 days) Reduced duration of delirium (36 vs 120 hours) More somnolence with quetiapine, other SEs similar Devlin JW et al. Crit Care Med 2010; 38: 419-426

Atypical Antipsychotics (Second Generation) Not typically given IV or IM Quetiapine (Seroquil) 25mg - 50mg PO Risperidone (Risperdal) 1 mg - 3 mg PO daily Olanzapine (Zyprexa) 5mg- 20 mg PO 5mg -10 mg IM

1. Analgesia 2. Sedation 3. Delirium In Pain? Fentanyl prn Morphine prn Reassess If not controlled with 2-3 doses/hour, start Fentanyl gtt 2. Sedation RASS at target (-1 to 0)? Undersedated Benzo prn Propofol gtt Benzo gtt Oversedated Hold sedatives and analgesics to achieve RASS target. Restart at 50% if needed 3. Delirium CAM-ICU positive? Underlying cause Non-pharm management Pharm management Reassess

Sedation Management What is the Daily RASS Goal? What is the patient’s RASS now? Is the patient on optimal sedation for the RASS goal? Combination of sedative and narcotic is synergistic Side effects of most agents include: Delirium Hypotension Respiratory depression Increased tolerance with withdrawal syndromes Risk of seizures if stopped abruptly Difficulty assessing neurologic status

Sedation and Analgesia: Challenges Inappropriate sedation (over and under) is a frequent problem, causing: Increased levels of agitation, delirium Sleep fragmentation Increased rates of VAP, nosocomial infections, days on mechanical ventilation, hospital stays, costs Self-extubation, reintubation, accidental line removal Sedation is rarely discussed in a uniform fashion among health care providers Sessler CN. Chest 2004;126:1727-1730 Wit M et al. Am J of Crit Care 2003; 12: 343-348. Sessler CN. Am J Resp CCM 2002; 166:1338-1334

Sedation (short term) Propofol Dexmedetomidine (Precedex) Sedative hypnotic with mild amnestic properties, NO analgesia, Rapid induction, rapid recovery Not recommended > 3 days Side Effects: Hypotension 1/3 of all patients, respiratory depression, bradycardia, arrhythmia, Lipemia, hypertriglycerdemia, Pancreatitis, Infection Risk Propofol Infusion Syndrome: acute refractory bradycardia and metabolic acidosis, rhabdomyolysis, hyperlipidemia or an enlarged fatty liver Dexmedetomidine (Precedex) Alpha-2 agonist Anxiolytic, analgesia, amnesia No respiratory depression, patient sedate but arousable Bradycardia, hypo/hypertension Use < 24h

Sedation Benzodiazepines Onset Duration Elimination midazolam<diazepam<lorazepam Start with IV push before starting an infusion Duration diazepam>lorazepam>midazolam> propofol (NB midazolam and diazepam highly lipophilic) Elimination renal failure: active metabolites accumulate for midazolam and diazepam cirrhosis: prolongation of metabolism to active metabolites for midazolam & diazepam

Pain Management Opiates Consider non-opiate analgesics Little amnestic effect Active metabolites, lipid deposition (Fentanyl) Side effects: Respiratory depression Hypotension (Morphine > Fentanyl) GI (constipation, ileus, gastroparesis, nausea) Delirium Tolerance followed by withdrawal syndromes

Goal-oriented Management Multidisciplinary process that incorporates expertise from physicians, nurses, pharmacy, and others Uses appropriate quantitative scales to assess and set treatment goals Provides etiology-driven treatment (treat pain with analgesics, anxiety with anxiolytics, etc) Avoids over-sedation & under-sedation Minimizes the use of sedatives, which can lead to delirium, further agitation, withdrawal syndromes Monitors response to therapeutic interventions Kress JP, Hall JB. CCM 2006;2541-2546 Sessler CN. Chest 2004; 1727-1730 Weinert et al. Am J Crti Care 2001; 156-167.

Managing ICU Delirium Look for it Communication between nursing and MDs Identify and treat correctable risk factors Optimize non-pharmacologic interventions Goal-oriented sedation with daily wake-ups Pharmacologic intervention

Daily Wake-Ups Kress et al, NEJM 2000: 128 vented MICU patients randomized to daily awakening vs usual care AND midazolam vs propofol (all patients received morphine) Infusions off until following commands or agitated Shorter time on vent (4.9 vs 7.3 days) Shorter time in ICU (6.4 vs 9.9 days) Fewer diagnostic tests for mental status No difference in complications or PTSD No difference between propofol and midazolam Kress JP. NEJM 2000. 342:1471-1477 Sessler CN. Crit Care Clin 2009. 25: 489-513

Wake-Up and Breathe Multi-center RCT 336 vented ICU patients randomized to spontaneous awakening followed by spontaneous breathing trial vs usual sedation with daily SBT Safety screens for both SAT and SBT SAT passed if patient opened eyes to verbal stimuli or tolerated being off sedation for > 4 hours Girard TD et al. Lancet 2008. 371:126-34

Hooper MH. Crit Care Clin 2009. 25:515-525

Wake-Up and Breathe Increased ventilator-free days (14.7 vs 11.6 days) Shorter ICU and hospital LOS (9.1 and 12.9 days; 14.9 and 19.2 days) 14% absolute reduction in risk of death at 1 year Girard TD et al. Lancet 2008. 371:126-34

Expectations for Our ICU (as of July 1, 2010) Documentation of RASS Q4 h (all patients) Documentation of CAM-ICU Q8 h (all patients) Discussion of RASS and CAM-ICU by team on daily work rounds Use MAH Sedation Guideline for sedation and delirium management Consideration of daily wake-up and daily SBT if appropriate Inclusion of sedation goals on daily goal sheets

Case 3: 57F intubated for ARDS -- Day 10 Feature 1. RASS is 0. Last shift, RASS was +2. 2. SAVEAHAART: 50% 3. Disorganized thinking: Will a leaf float on water? Yes Are elephants in the sea? Yes Do 2 pounds weigh more than 1? Yes Can you use a hammer to cut wood? Yes Fails to hold up 2 fingers Score: 2 of possible 5 points 4. Altered Level of Consciousness: RASS 0 How should we manage her? + + + -

Summary Delirium is common and has serious negative consequences May be missed without assessment Management is multidisciplinary Risk factor modification Non-pharmacologic intervention Pharmacologic intervention Optimize goal-directed sedation and analgesia WWW.ICUDELIRIUM.ORG