Evaluation of multifaceted, interdisciplinary efforts to improve the management of delirium in the intensive care unit Jenny Park, Pharm.D. PGY-1 Pharmacy Practice Resident St. Joseph’s Regional Medical Center NJSHP Residency Research Forum

St. Joseph’s Healthcare System 651 bed Magnet TM designated private non-profit teaching facility Level II Trauma Center Critical Care Unit –Surgical ICU (SICU): 12 beds –Medical ICU (MICU): 28 beds –Cardiac Care Unit (CCU): 16 beds Decentralized Pharmacy Model –Critical Care –Pediatrics –Open 24 hours/day, 7 days/week –Over 120 full-time employees Pharmacy Practice Residency Program 2

Background Acute disorder of attention and cognition Variable prevalence: 20 to 83% Risk Factors –Medical condition –Immobilization –Toxin –Medications: benzodiazepines, opiates, steroids, anticholinergics Consequences –Mortality –Time on ventilator –Length of stay –Cognitive impairment Treatment: Nonpharmacological 3 Ely EW, et al. JAMA 2001, 286(21): Inouye SK, et al. Lancet 2014; 383: Van Rompaey B, et al. Crit Care 2008;12(1):R16.

Background: CAM-ICU Diagnostic tool for delirium 4 Feature 1 - Acute change mental status Feature 2 – Inattention “Squeeze my hand when I say letter A” C A S A B L A N C A Feature 3 – Altered level of consciousness RASS score other than 0 Feature 4 – Disorganized thinking 4 Questions 1 Command AND OR Van Rompaey B, et al. Crit Care 2008;12(1):R16.

St. Joseph’s Regional Medical Center Introduced CAM-ICU in January 2015 Became mandatory in June 2015 Major barriers encountered –Low rates of detection of delirium (+) CAM-ICU: 1% –Non-compliance –Incomplete education 5

Study Objective Assess the impact of a multifaceted intervention in improving the perception and management of delirium in the ICU 6 Primary Outcomes Correct response rates of survey Reduction of deliriogenic medications Secondary Outcomes Duration of mechanical ventilation Mortality Restarting home medication Addition of atypical antipsychotics Addition of typical antipsychotics Average comfort score (survey) Barriers to assessment of delirium (survey)

Method Retrospective study Inclusion Criteria –Positive CAM-ICU –MICU or SICU 7 Pre-Intervention 50 patients January 2015 – January 2016 Survey: October 2015 Post- Intervention 50 patients February 2016 – April 2016 Survey: April 2016 Statistics: Student’s t-test, Fischer’s exact test IRB approval

Survey 1.Incidence of delirium A.<5% B.5-15% 8 3. Not used for treatment for delirium A.Non-pharmacological B.2 nd generation antipsychotics C.Dexmedetomidine D.Benzodiazepines C.>15% D.Uncertain 2. Type of delirium with greatest mortality A.Hypoactive B.Hyperactive C.Alzheimer’s D.Mixed 4. Hallmark sign of delirium A.Agitation B.Hallucination C.Inattention D.Personality change 5. Patient case RASS -2 (yesterday +2) 3 errors when asked to squeeze his hand when letter A is read after C A S A B L A N C A Patient responded as follows. –Will a stone float on water? No –Are there fish in the sea? Yes –Does one pound weigh more than two pounds? Yes –Can you use a hammer to pound a nail? Yes When asked patient to hold up 2 fingers, then the same for the other hand (with demonstration), patient lifted his index finger only. Patient has delirium A.Patient has delirium B.Patient does not have delirium C.Uncertain

Survey 6. Comfort score using CAM-ICU Uncomfortable Comfortable 7. Barriers that you encounter in assessment of delirium (Choose all that apply) A.Insufficient time B.Complexity of the assessment tool C.Difficult to assess in patients on ventilators D.Difficult to assess in sedated patients E.Other medical staff already assessed the patient F.Not sure how to assess delirium in the ICU 8. How many years have you been in practice? A.< 1 year B.1 – 5 years 9. Provider Status A.Nurse B.APN C.6 – 10 years D.> 10 years C.Medical resident D.Fellow E.Attending

Method: Intervention 1 hour in-services to ICU nurses (8 sessions) 20 minute in-services to ICU residents (7 sessions) Provided Education Distributed to ICU nurses and residents Adapted from Vanderbilt University with permission Created Treatment Guideline Identified patients with (+) CAM-ICU within past 24 hours Reviewed medication regimen if (+) CAM-ICU (5days/wk) Made Pharmacy Intervention 10

SJHMC Treatment Guideline 11 Non-delirious (Negative CAM-ICU) Reassess CAM-ICU at least every shift Delirious (Positive CAM-ICU) Consider differential diagnosis (THINK)  Toxic Situations: CHF, shock, dehydration  Hypoxemia  Infection, Immobilization (recent surgery)  Nonpharmacological  K+ or electrolyte imbalance Non pharmacological protocol  Orientation  Environment  EPM (Early Progressive Mobility) Identify deliriogenic drugs Too sedated (RASS -4 or -5) Does patient need deep sedation? Consider non-benzodiazepine sedation strategies (propofol or dexmedetomidine) RASS +4 to 0 Optimize pain control Reassess target sedation goal SAT  SBT Consider atypical antipsychotics (example: quetiapine) Adapted from Vanderbilt University with permission RASS -1 to -3

Key Points 1.Removing risk factors 2.Nonpharmacological interventions 3.Target level of sedation 4.Optimize pain management 5.Last line = medication Atypical antipsychotics 12

Results: Baseline Characteristics Pre- (n=50)Post- (n=50)P value Age, mean (SD)71 (12.59)70 (14.33)0.57 Men42%54%0.32 APACHE II score, mean (SD)*20.7 (8.06)22.63 (6.64)0.202 Hypertension or alcoholism88%96%0.27 Previously on high dose opioids † 4% 1 Mechanical ventilation at (+) CAM-ICU60%66% * APACHE II scores were not available for 4 patients in each arm due to missing data † High dose opioid = morphine po > 200mg/day 13 Deliriogenic medications < 48hr (+) CAM-ICU80%70%0.36 Benzodiazepines Average dose (lorazepam eq.) 42% 14.3 mg 38% 21.8 mg Opiates Average dose (morphine IV eq.) 68% 161 mg 54% 237 mg Steroids Average dose (hydrocortisone eq.) 14% 1210 mg 14% 379 mg Anticholinergics4%8%0.68

Results: Primary Outcome Correct Response Rates (CRRs) of Survey 14 5 multiple choice questions o Prevalence o Clinical presentation (2) o Treatment of delirium o CAM-ICU patient case P= < 0.01 n = 100 n = 89

Results: CRRs of Survey ResponsePre- (n = 100) Post- (n = 89) P value Incidence of delirium in ICU (>15%)21%30%0.18 Type of delirium with greatest mortality (hypoactive) 31%35%0.64 Agent that is not used for treatment (benzodiazepines) 38%70%<0.01 Hallmark sign (inattention)28%45%0.02 Patient case49%80%< 0.01 Response Rates49.4%73.6% 15

Results: Primary Outcome Reduction of Deliriogenic Medication 16 Deliriogenic medications o Benzodiazepines o Opiates o Anticholinergics o Steroids P = 0.22 = Pharmacist’s interventions (9%) = Other interventions (56.7%) = Baseline

Results: Secondary Outcome Pre- (n=42)Post- (n=35)p-value Duration of mechanical ventilation, hours Pre- (N=50)Post (N=50)p-value Duration of ICU stay, hours Mortality in ICU, % Restarted home medication* Addition of atypical antipsychotics*¶, % QTc prolongation Addition of typical antipsychotics*†, % Addition of dexmedetomidine*, % Pharmacist intervention7 * Within 24 hours of (+) CAM-ICU ¶ All of atypical antipsychotics were quetiapine, except for 1 patient in pre-intervention (ziprasidone) † All of typical antipsychotics were haloperidol

Results: Secondary Outcome Barriers to Assessment of Delirium 18 % of Responders Survey: Average Comfort Score Using CAM-ICU Pre intervention: 4.53 Post intervention: 5.85 p = <0.01; 30% ↑ p = p = 0.01

Pharmacist’s Intervention Reduction of benzodiazepines/opiates (n=2) –RASS -4 to -5 Optimize pain management (n=2) –Add or increase dose for inadequate pain control Medication reconciliation (n=3) –Recommend to add abruptly discontinued home medications Antidepressants Antipsychotics 19

Conclusion The multifaceted intervention improved clinicians’ understanding and assessment of delirium utilizing the CAM-ICU. 20

Strengths and Limitations Strengths Multidisciplinary effort Provided thorough education Survey was distributed 2 months after the education in order to assure that the information was retained Limitations Did not assess the impact of nonpharmacological intervention Only evaluated one component of deliriogenic risk factors Pharmacist notification of CAM-ICU was not real time Education only included nurses and medical residents 21

Future Directions Continue education in order to increase detection of delirium –Lower rates of delirium compared to reported incidence in literature 4% vs 26-80% –Different approach to education Implement a real-time pharmacy intervention 22

Learning Assessment Which of following is/are potential methods to improve clinician’s knowledge and management of delirium in the ICU? A.Education B.Implement treatment guideline C.Perform medication review to identify high risk medication D.All of the above 23

Acknowledgements Kimberly Brandt, Pharm.D. Tapan Pandya, M.D. Radhika Pisupati, Pharm.D., BCPS Margaret Ojelade, MSN, CCRN, APN Noelle Schuster, RN, MSN, CCRN-CMC Alan Sori, M.D. Mourad M. Ismail, M.D. 24

References Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU) JAMA 2001, 286(21): Inouye SK, Westendorp RG, and Saczynski JS. Delirium in elderly people. Lancet 2014; 383: Van Rompaey B, Schuurmans MJ, Shortridge-Baggett LM, et al. A comparison of the CAM-ICU and the NEECHAM confusion scale in the intensive care delirium assessment: an observation study in non- intubated patients. Crit Care 2008;12(1):R16. 25

Evaluation of multifaceted, interdisciplinary efforts to improve the management of delirium in the intensive care unit Jenny Park, Pharm.D. PGY-1 Pharmacy Practice Resident St. Joseph’s Regional Medical Center NJSHP Residency Research Forum