AJHP RESIDENTS EDITION Hospital delirium treatment
AJHP RESIDENTS EDITION
Hospital delirium treatment: Continuation of antipsychotic therapy from the intensive care unit to discharge Rachel W. Flurie, Jeffrey P. Gonzales, Asha L. Tata, Leah S. Millstein, and Mangla Gulati
D
elirium occurs in up to 80% of intensive care unit (ICU) patients.1 The classic definition of delirium includes an acute onset and fluctuating course, inattention, disorganized thinking, and altered consciousness. Delirium is associated with increased mortality, longer hospital and ICU stays, and longterm cognitive impairment.1,2 These adverse outcomes have been reported not only in ICU patients but also in patients who experience delirium on medical wards.3,4 The most common medications used to treat delirium are antipsychotics; yet, professional societies do not recommend their routine use due to a lack of proven efficacy.2 In clinical practice, antipsychotics are used to manage the symptoms of delirium, with one survey finding that 39% of ICU practitioners prescribed atypical antipsychotics and 89% prescribed haloperidol for symptom management. 5 Controversy exists regarding the appropriate duration
Purpose. The rate of continuation of antipsychotics for the management of delirium during hospital transitions of care in a tertiary care medical center was investigated. Methods. A retrospective chart review was conducted for adult patients admitted to the medical intensive care unit (MICU) between June 1, 2011, and May 31, 2012, who were initiated on antipsychotic therapy at least 24 hours before transfer out of the MICU. The primary outcome evaluated was the percentage of patients initiated on an antipsychotic in the MICU who were continued on therapy after transfer to a medical ward. Secondary outcomes included the appropriateness of continuing antipsychotic therapy during transitions of care and the percentage of patients continued on an antipsychotic after hospital discharge. Results. Of the 87 patients who met the study inclusion criteria, 23 (26%) were continued on antipsychotic therapy after their transfer from the MICU to the medical
of treatment with antipsychotics for this indication. Clinical trials assess-
Rachel W. Flurie, Pharm.D., BCPS, is Assistant Professor, Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond; at the time of writing she was Postgraduate Year 1–2 Pharmacotherapy Resident, University of Maryland School of Pharmacy, Baltimore. J effrey P. G onzales, P harm.D., BCPS, FCCM, is Associate Professor, Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy. Asha L. Tata, Pharm.D., BCPS, is Clinical Pharmacist, Department of Pharmacy, University of Maryland Medical Center, Baltimore. Leah S. Millstein, M.D., is Assistant Professor, Divisions of General
ward. Of the 23 patients continued on antipsychotic therapy, 9 (39%) were discharged from the hospital with an antipsychotic. Fourteen of the 23 patients were eligible for assessment of inappropriate antipsychotic continuation upon transfer from the MICU. Of these 14 patients, 9 (64%) were inappropriately continued on an antipsychotic. Patients continued on antipsychotic therapy at hospital discharge were more likely to be discharged to a facility (rehabilitation, skilled nursing facility, or healthcare institution) (p = 0.049). Conclusion. The continuation of antipsychotics for the management of delirium during transitions of care was a common practice at a tertiary care medical center. Patients receiving antipsychotics for treatment of delirium in the MICU were inappropriately continued on these agents when transferred from the MICU to the medical floor or discharged from the hospital. Am J Health-Syst Pharm. 2015; 72(suppl 3):S133-9
ing the efficacy of antipsychotics for hospital delirium have limited
Internal Medicine and Pediatrics, University of Maryland School of Medicine, Baltimore. Mangla Gulati, M.D., FACP, FSHM, is Assistant Professor, Department of Medicine, University of Maryland School of Medicine. Address correspondence to Dr. Gonzales ([email protected]. edu). The authors have declared no potential conflicts of interest. Copyright © 2015, American Society of Health-System Pharmacists, Inc. All rights reserved. 1079-2082/15/1201-S133. DOI 10.2146/ajhp150474
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
S133
AJHP RESIDENTS EDITION Hospital delirium treatment
Rachel W. Flurie, Pharm.D., BCPS, is Assistant Professor, Department of Pharmacotherapy and Outcomes Science, at Virginia Commonwealth University School of Pharmacy. She received her Bachelor of Arts degree in Chemistry from St. Mary’s College of Maryland. She received her Doctor of Pharmacy degree from the University of Maryland in 2012 and completed a 24-month ASHPaccredited pharmacotherapy residency in 2014. She is board certified in pharmacotherapy. Dr. Flurie practices as a clinical pharmacy specialist on inpatient internal medicine and digestive health services at a tertiary care, academic medical center. She is a member of the respective education committees for the Virginia Society of Health-System Pharmacists and the clinical pharmacy and pharmacology group of the Society of Critical Care Medicine.
treatment durations (6–10 days).6,7 However, symptoms of delirium can persist long after the acute condition has resolved and as patients transition to lower levels of care. Currently, data are lacking to suggest that the continuation of antipsychotics during transitions of care is beneficial to patients. In addition, long-term use of antipsychotics creates the potential for inappropriate medication continuation and increased adverse effects (i.e., extrapyramidal symptoms, sedation, glucose intolerance, lipid abnormalities, orthostatic S134
hypotension, anticholinergic effects, and death).8-11 The National Partnership to Improve Dementia Care has joined with the Centers for Medicare and Medicaid Services and other organizations to establish a national goal of reducing the use of antipsychotic medications in long-term nursing home residents by 25% by the end of 2015.12 The American Geriatrics Society, as part of the Choosing Wisely campaign initiated by the American Board of Internal Medicine Foundation, is discouraging physicians from using antipsychotics as first-line therapies to treat the behavioral and psychological symptoms of dementia.13 Because patients with dementia are at risk for delirium and symptoms of both disorders overlap, antipsychotics initiated for the management of acute delirium may be inappropriately continued when symptoms do not improve due to worsening dementia. The purpose of this study was to determine the percentage of critically ill patients who were continued on antipsychotics after being transferred from the ICU. Methods This study was conducted at a 750-bed, tertiary care center in Baltimore, Maryland, and approved by an institutional review board. A retrospective chart review was conducted for adult patients admitted to the medical ICU (MICU) between June 1, 2011, and May 31, 2012, who were initiated on antipsychotic therapy (haloperidol, quetiapine, risperidone, olanzapine, or ziprasidone) at least 24 hours before transfer out of the MICU. Patients were excluded if they were on antipsychotic therapy before MICU admission or if they were transferred from the MICU to a nonmedical ward. The primary outcome was the percentage of patients initiated on an antipsychotic in the MICU who were continued on
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
therapy after transfer to a medical ward. Secondary outcomes were the appropriateness of continuing antipsychotic therapy during transitions of care and the percentage of patients continued on an antipsychotic after hospital discharge. Inappropriate antipsychotic continuation was defined as a negative score on the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) within 24 hours before MICU transfer. The CAM-ICU is an assessment tool that has been validated in ICU patients and designed for use by healthcare professionals not trained in psychiatry.14 It incorporates criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for the diagnosis of delirium and was derived from the Confusion Assessment Method, which was validated in a general medicine and outpatient geriatric population.15 The CAM-ICU assesses the four features of delirium: (1) acute onset and fluctuating course, (2) inattention, (3) altered consciousness, and (4) disorganized thinking. Patients are scored as positive, negative, or unable to assess. A positive score is given when a patient exhibits both features 1 and 2 and either feature 3 or 4. A negative score is given when criteria for a positive score are not met; when all four features cannot be assessed, a patient is scored as “unable to assess.” The CAM-ICU is included in the bedside charting and performed by trained nurses every 4 hours. Currently, there is no structured delirium assessment tool that is used for nonICU patients at our institutiton. Patient demographics were recorded on study day 1. Risk factors for delirium were collected, which included comorbidities (dementia, Parkinson’s disease, depression, bipolar disorder, schizophrenia, hypertension, and cerebrovascular accident), history of substance use (alcohol, tobacco, illicit drugs, and prescription drugs), illness severity, mechanical ventilation, immobility, insertion of a bladder
AJHP RESIDENTS EDITION Hospital delirium treatment
catheter, use of physical restraints, and concomitant opioid or benzodiazepine use.2,16,17 Illness severity was assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE II).18 Data on the patient’s hospitalization included the antipsychotic medication regimen, admitting MICU diagnosis, duration of MICU and hospital stays, and hospital discharge location. Information collected on the antipsychotic regimen included the daily dose, number of doses, and duration of therapy. Antipsychotic doses were evaluated comprehensively and included one-time, scheduled, and as-needed doses. CAM-ICU scores were collected within 24 hours before patient transfer out of the MICU to determine if the patient was still experiencing delirium. Two patient groups were analyzed: patients transferred from the MICU to the medical ward (transition group 1) and patients discharged from the medical ward to home or another facility (transition group 2). The rate of antipsychotic continuation was determined for the primary and secondary outcomes for patients in each group. Within each group, prespecified variables were tested to detect differences between patients who were continued and those who were not continued on antipsychotic therapy. For transition group 1, prespecified variables included age, sex, race, comorbidities (e.g., neurologic or psychiatric disorder, hypertension, cerebrovascular accident), length of MICU stay, length of hospital stay, APACHE II score, concurrent opioid or benzodiazepine use, history of substance use, immobility, mechanical ventilation, insertion of a bladder catheter, and use of physical restraints. For transition group 2, prespecified variables included comorbidities, concurrent opioid or benzodiazepine use, history of substance use, and place of discharge (home, rehabilitation facility, skilled nursing facility, or other healthcare institution). Patient and hospital char-
acteristics were compared between groups using the unpaired t test for continuous variables and chi-square test for dichotomous variables. The a priori level of significance was 0.05 with a two-tailed test. All data were analyzed using PRISM, version 4.0 (GraphPad, San Diego, CA). Results Between June 1, 2011, and May 31, 2012, 1276 individual patients were admitted to the MICU. Of those patients, 87 met the inclusion criteria. Patient demographic data and delirium risk factors are listed in Table 1. All 87 patients had CAM-ICU scores documented, and 61 (70%) had a positive score at least once while in the MICU. A total of 46 patients (53%) had a positive score within 24 hours of receiving the first dose of an antipsychotic. Seventeen patients (20%) had a negative CAM-ICU score, and 22 patients (25%) could not be assessed when the first dose of antipsychotic was administered. For 2 patients, CAM-ICU scores were not recorded when the first dose of antipsychotic was administered. Haloperidol was the most common antipsychotic administered in the MICU and medical ward (Table 2). In the MICU, quetiapine was the antipsychotic continued the longest, with an average duration of therapy of 9.5 ± 8.7 days (Table 2). There was a significant decrease in the average number of haloperidol doses administered to patients when they were transferred from the MICU to the medical ward (7.7 ± 9.1 doses versus 2.8 ± 1.7 doses, p = 0.01). There were no significant differences in the number of doses administered to patients while in the MICU versus the medical ward. There were no differences in the duration of therapy for haloperidol, quetiapine, and olanzapine (Table 2). Of the 87 patients included in the study, 23 (26%) were continued on antipsychotic therapy after their transfer from the MICU to the medical ward. There were no significant
differences in baseline characteristics or risk factors between patients who were continued and those who were not continued on antipsychotic therapy (Table 1). Of the 23 patients continued on antipsychotic therapy, 9 (39%) were discharged from the hospital with an antipsychotic. Patients’ comorbidities and risk factors are presented in Table 3. A total of 14 patients had a positive or negative CAM-ICU score within 24 hours of MICU transfer and were eligible for assessment of inappropriate continuation. Of those patients, 9 (64%) were inappropriately continued on an antipsychotic (i.e., had a negative CAM-ICU score within 24 hours of MICU transfer). Discussion This study found that the continuation of antipsychotics for the management of delirium during transitions of care was common. Importantly, 39% of patients who were continued on antipsychotic therapy from the MICU to the medical ward were also continued on antipsychotic therapy at hospital discharge. Without compelling evidence to show that patients incur more than symptomatic relief with the use of antipsychotics, the continuation of these potentially inappropriate medications during transitions of care may contribute to long-term polypharmacy and unnecessary adverse effects.9 Efforts to decrease the off-label use of antipsychotics for patients in long-term care facilities are important among national health organizations, and this study opens up the possibility of expanding those efforts to hospitalized patients.12,13 In this study, haloperidol was the most frequently used antipsychotic for delirium, followed by several second-generation antipsychotics, which is consistent with previous studies.5,7 There was variability in the mean total daily doses and the number of doses administered,
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
S135
AJHP RESIDENTS EDITION Hospital delirium treatment
Table 1.
Transition Group 1 Patient Demographics and Delirium Risk Factorsa Antipsychotic Continued From MICU to Medical Ward? Characteristic Mean ± S.D. age, yr Sex, no. (%) pts Male Female Race, no. (%) pts White African American Other Comorbidities, no. (%) pts Hypertension Neurologic or psychiatric disorderb Cerebrovascular accident Mean ± S.D. MICU LOS, days Mean ± S.D. hospital LOS, days Risk factors Mean ± S.D. APACHE II score Administration of opioid(s) in MICU, no. (%) pts Administration of benzodiazepine(s) in MICU, no. (%) pts Administration of opioid(s) and benzodiazepine(s) in MICU, no. (%) pts Administration of opioid(s) or benzodiazepine(s) in MICU, no. (%) pts History of substance use, no. (%) pts Immobility, no. (%) pts Mechanical ventilation, no. (%) pts Mean ± S.D. no. days of mechanical ventilation Bladder catheter, no. (%) pts Use of physical restraints, no. (%) pts
Yes (n = 23)
No (n = 64)
p
57.1 ± 15.9
55.0 ± 16.4
0.59
15 (65) 8 (35)
30 (46) 34 (53)
0.15 0.13
12 (52) 11 (49) 0
31 (48) 32 (49) 1 (2)
0.76 0.76 0.71
13 (57) 6 (26) 1 (4) 14.1 ± 11.4 34.1 ± 31.0
32 (50) 10 (15) 4 (6) 12.6 ± 11.5 26.5 ± 20.0
0.59 0.27 0.74 0.60 0.19
26.5 ± 5.1 22 (96)
25.4 ± 6.4 52 (81)
0.38 0.10
20 (87)
49 (77)
0.29
19 (83)
42 (66)
0.13
23 (100) 13 (57) 5 (22) 22 (97)
59 (92) 33 (51) 15 (23) 51 (80)
0.17 0.68 0.87 0.07
9.1 ± 10.3 22 (96) 21 (91)
9.0 ± 10.5 60 (94) 54 (84)
0.96 0.74 0.41
MICU = medical intensive care unit, LOS = length of stay, APACHE II = Acute Physiology and Chronic Health Evaluation II. Bipolar disorder, dementia, depression, Parkinson’s disease, or schizophrenia.
a
b
which is reflective of the disparity in real-world practice. Duration of therapy was shortest for haloperidol and longest for quetiapine, which is reasonable as haloperidol may be used for acute episodes of hyperactivity and quetiapine can be used for mixed-type delirium or sleep–wake cycle disturbances. The optimal dosing and duration of antipsychotic therapy for delirium symptom management are unclear. In addition, there are no recommendations or validated assessment tools that can be used to signify appropriate treatment discontinuation in the S136
non-ICU setting.19,20 In a recent, singlecenter retrospective study including 156 patients from multiple ICUs, 27% of patients transferred from an ICU to another unit were discharged from the hospital on an atypical antipsychotic.21 The authors reported that only 32.5% of those patients had evidence warranting continuation of the medication or weaning instructions for the medication. The methods for evaluation of appropriate continuation were not explicitly stated, though the authors mentioned that many of the patients had evidence of delirium resolution or no reported indication
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
for continuation of the antipsychotic at discharge. Jasiak et al.22 conducted a retrospective review of 80 patients and showed that 48% of patients started on atypical antipsychotics for ICU delirium continued their therapy after ICU transfer. Of those patients, 71% were continued on therapy as an outpatient. The percentage of patients who had documentation of ICU delirium was low, with only half of the patients having an initial or final CAM-ICU score recorded. In addition, the authors assumed that all patients were receiving antipsychotics
AJHP RESIDENTS EDITION Hospital delirium treatment
Table 2.
Antipsychotic Medication Administration for MICU and Medical Warda Characteristic Antipsychotic administered, no. (%) pts Haloperidol Quetiapine Olanzapine Ziprasidoneb Median no. (range) antipsychotics administered per patient Mean ± S.D. antipsychotic daily dose, mg/day Haloperidol Quetiapine Olanzapine Ziprasidone Mean ± S.D. no. antipsychotic doses administered Haloperidol Quetiapine Olanzapine Ziprasidone Mean ± S.D. duration of antipsychotic therapy, days Haloperidol Quetiapine Olanzapine Ziprasidone
MICU (n = 87)
Medical Ward (n = 23)
85 (98) 14 (16) 4 (5) 1 (1)
18 (78) 6 (26) 2 (9) 0
1 (1–4)
1.5 (1–2)
9.4 ± 7.7 71.7 ± 34.6 8.4 ± 4.3 60
4.3 ± 2.4 64.8 ± 32.2 9.2 ± 4.7 0
0.007 0.68 0.86
7.7 ± 9.1 17.6 ± 17.9 9.8 ± 13.7 10
2.8 ± 1.7 7.7 ± 8.3 19.0 ± 19.8 0
0.01 0.22 0.53
3.6 ± 3.4 9.5 ± 8.7 4.8 ± 6.2 5
2.4 ± 1.4 4.5 ± 3.9 12.0 ± 14.1 0
0.13 0.20 0.40
p 0.0007 0.27 0.44
MICU = medical intensive care unit. Ziprasidone results for one patient.
a
b
for treatment of delirium, even those without diagnostic documentation. Our study confirmed the diagnosis of delirium using the CAM-ICU score (70% of our patients had at least one positive score). The current study also differs from the previous studies by including the most commonly used antipsychotic, haloperidol.5,21,22 The exclusion of haloperidol eliminates a large patient population and may impact the generalizability of the results of previous studies. The results of this study highlight the importance of routine reassessment of patients to provide a clear indication of high-risk medications during transitions of care. Patients are assessed for delirium in the ICU, but routine assessment may not be performed once patients are transferred to the medical ward. Physicians or pharmacists may be hesi-
tant to discontinue an antipsychotic without a clear initial indication or symptom resolution, allowing the patient to continue a potentially inappropriate medication. Several assessment tools have been validated for use in acute care medical patients.15,23 Our study had several limitations. First, while the CAM-ICU provides an objective assessment, its ability to detect delirium in a real-world setting has come into question. A study found that when the assessment, administered by ICU nurses, was compared to the gold standard of a multidisciplinary team of delirium experts, the sensitivity of the CAM-ICU was 47%.24 However, the CAM-ICU is recommended by the latest guidelines for the assessment of ICU delirium.2 In addition, there is the potential that the medical team made a diagnosis of delirium regardless of
the CAM-ICU score. Given the retrospective design of this study, any such discrepancy could not be verified for the study participants. Secondly, inappropriate continuation was defined as a negative CAM-ICU score within 24 hours of transfer from the MICU. As there is no delirium assessment on the medical wards at our institution, we could not assess for recurrence of delirium once patients were transferred out of the MICU. Further, patients who had a CAM-ICU score of “unable to assess” or did not have a score within 24 hours of transfer from the MICU were excluded from analysis. While antipsychotics are used for multiple off-label indications in the ICU such as sedation, agitation, and delirium prevention,5,25 many of the off-label indications could be symp-
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
S137
AJHP RESIDENTS EDITION Hospital delirium treatment
Table 3.
Transition Group 2 Patient Characteristics and Delirium Risk Factors No. (%) Patients
Characteristic
Antipsychotic Continued From Medical Ward to Discharge (n = 9)
Antipsychotic Not Continued From Medical Ward to Discharge (n = 14)
5 (56) 2 (22) 1 (11)
7 (50) 4 (29) 0
0.79 0.74 0.20
7 (78)
7 (50)
0.18
0
1 (7)
0.41
0
1 (7)
0.41
7 (78) 6 (67)
7 (50) 6 (43)
0.18 0.26
1 (11) 7 (78)
5 (36) 5 (36)
0.19 0.049
Comorbidities Hypertension Neurologic or psychiatric disordera Cerebrovascular accident Risk factors Administration of opioid(s) in medical ward Administration of benzodiazepine(s) in medical ward Administration of opioid(s) and benzodiazepine(s) in medical ward Administration of opioid(s) or benzodiazepine(s) in medical ward History of substance use Place of discharge Discharge to home Discharge to facilityb
p
Bipolar disorder, dementia, depression, Parkinson’s disease, or schizophrenia. Rehabilitation facility, skilled nursing facility, or other healthcare institution.
a
b
toms of unrecognized delirium, and reassessment of antipsychotic continuation during transitions of care is still important in these patients. Future areas for study should include (1) prospective analysis to understand the clinical decisionmaking of providers when treating delirium, (2) evaluation of the longterm impact of continuing antipsychotic therapy for delirium, and (3) ways to improve communication of medication regimens during transitions of care. Plans to reduce antipsychotic continuation could involve reassessing patients on the medical wards, improving documentation of the indication for use in the medical record, or developing protocols to taper off antipsychotics before patients are discharged from the hospital. Conclusion The continuation of antipsychotics for the management of delirium during transitions of care was a common practice at a tertiary care mediS138
cal center. Patients receiving antipsychotics for treatment of delirium in the ICU were inappropriately continued on these agents when transferred from the MICU to the medical floor or discharged from the hospital. References 1. Pun BT, Ely EW. The importance of diagnosing and managing ICU delirium. Chest. 2007; 132:624-36. 2. Barr J, Fraser GL, Puntillo K et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013; 41:263-306. 3. Leslie DL, Zhang Y, Holford TR et al. Premature death associated with delirium at 1-year follow-up. Arch Intern Med. 2005; 165:1657-62. 4. Edlund A, Lundstrom M, Karlsson S et al. Delirium in older patients admitted to general internal medicine. J Geriatr Psychiatry Neurol. 2006; 19:83-90. 5. Patel RP, Gambrell M, Speroff T et al. Delirium and sedation in the intensive care unit (ICU): survey of behaviors and attitudes of 1,384 healthcare professionals. Crit Care Med. 2009; 37:825-32. 6. Tahir TA, Eeles E, Karapareddy V et al. A randomized controlled trial of quetiapine versus placebo in the treatment of delirium. J Psychosom Res. 2010; 69:485-90.
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
7. Devlin JW, Roberts RJ, Fong JJ et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med. 2010; 38:419-27. 8. Abidi S, Bhaskara SM. From chlorpromazine to clozapine—antipsychotic adverse effects and the clinician’s dilemma. Can J Psychiatry. 2003; 48:749-55. 9. Gill SS, Bronskill SE, Normand SL et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007; 146:775-86. 10. Strawn JR, Keck PE, Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry. 2007; 164:870-6. 11. Buckley NA, Sanders P. Cardiovascular adverse effects of antipsychotic drugs. Drug Saf. 2000; 23:215-28. 12. Centers for Medicare and Medicaid Services. National Partnership to Improve Dementia Care exceeds goal to reduce use of antipsychotic medications in nursing homes: CMS announces new goal (September 2014). www.cms.gov/Newsroom/MediaRelease Database/Press-releases/2014-Pressreleases-items/2014-09-19.html (accessed 2014 Dec 4). 13. Choosing Wisely. American Geriatrics Society: ten things physicians and patients should question (February 2013). www.choosingwisely.org/wp-content/ uploads/2015/02/AGS-Choosing-WiselyList.pdf (accessed 2014 Dec 4).
AJHP RESIDENTS EDITION Hospital delirium treatment
14. Ely EW, Margolin R, Francis J et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001; 29:1370-9. 15. Inouye SK, van Dyck CH, Alessi CA et al. Clarifying confusion: the Confusion Assessment Method. Ann Intern Med. 1990; 113:941-8. 16. Van Rompae y B, Elsev iers MM, Schuurmans MJ et al. Risk factors for delirium in intensive care patients: a prospective cohort study. Crit Care. 2009; 13:R77. 17. Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors, and consequences of ICU delirium. Intensive Care Med. 2007; 33:66-73. 18. Kanus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985; 13:818-29. 19. McCusker J, Cole M, Dendukuri N et al. The course of delirium in older medical inpatients: a prospective study. J Gen Intern Med. 2003; 18:696-704. 20. Pandharipande PP, Girard TD, Jackson JC et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013; 369:1306-16. 21. Kram BL, Kram SJ, Brooks KR. Implications of atypical antipsychotic prescribing in the intensive care unit. J Crit Care. 2015; 30:814-8. 22. Jasiak KD, Middleton EA, Camamo JM et al. Evaluation of discontinuation of atypical antipsychotics prescribed for ICU delirium. J Pharm Pract. 2012; 26:253-6. 23. Trzepacz PT, Mittal D, Torres R et al. Validation of the Delirium Rating ScaleRevised-98: comparison with the Delirium Rating Scale and the Cognitive Test for Delirium. J Neuropsychiatry Clin Neurosci. 2001; 13:229-42. 24. Van Eijk MM, van den Boogaard M, van Marum RJ et al. Routine use of the Confusion Assessment Method for the Intensive Care Unit: a multicenter study. Am J Respir Crit Care Med. 2011; 184:340-4. 25. Girard TD, Pandharipande PP, Carson SS et al. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebocontrolled trial. Crit Care Med. 2010; 38:428-37.
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
S139
AJHP RESIDENTS EDITION
Hospital delirium treatment: Continuation of antipsychotic therapy from the intensive care unit to discharge Rachel W. Flurie, Jeffrey P. Gonzales, Asha L. Tata, Leah S. Millstein, and Mangla Gulati
D
elirium occurs in up to 80% of intensive care unit (ICU) patients.1 The classic definition of delirium includes an acute onset and fluctuating course, inattention, disorganized thinking, and altered consciousness. Delirium is associated with increased mortality, longer hospital and ICU stays, and longterm cognitive impairment.1,2 These adverse outcomes have been reported not only in ICU patients but also in patients who experience delirium on medical wards.3,4 The most common medications used to treat delirium are antipsychotics; yet, professional societies do not recommend their routine use due to a lack of proven efficacy.2 In clinical practice, antipsychotics are used to manage the symptoms of delirium, with one survey finding that 39% of ICU practitioners prescribed atypical antipsychotics and 89% prescribed haloperidol for symptom management. 5 Controversy exists regarding the appropriate duration
Purpose. The rate of continuation of antipsychotics for the management of delirium during hospital transitions of care in a tertiary care medical center was investigated. Methods. A retrospective chart review was conducted for adult patients admitted to the medical intensive care unit (MICU) between June 1, 2011, and May 31, 2012, who were initiated on antipsychotic therapy at least 24 hours before transfer out of the MICU. The primary outcome evaluated was the percentage of patients initiated on an antipsychotic in the MICU who were continued on therapy after transfer to a medical ward. Secondary outcomes included the appropriateness of continuing antipsychotic therapy during transitions of care and the percentage of patients continued on an antipsychotic after hospital discharge. Results. Of the 87 patients who met the study inclusion criteria, 23 (26%) were continued on antipsychotic therapy after their transfer from the MICU to the medical
of treatment with antipsychotics for this indication. Clinical trials assess-
Rachel W. Flurie, Pharm.D., BCPS, is Assistant Professor, Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond; at the time of writing she was Postgraduate Year 1–2 Pharmacotherapy Resident, University of Maryland School of Pharmacy, Baltimore. J effrey P. G onzales, P harm.D., BCPS, FCCM, is Associate Professor, Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy. Asha L. Tata, Pharm.D., BCPS, is Clinical Pharmacist, Department of Pharmacy, University of Maryland Medical Center, Baltimore. Leah S. Millstein, M.D., is Assistant Professor, Divisions of General
ward. Of the 23 patients continued on antipsychotic therapy, 9 (39%) were discharged from the hospital with an antipsychotic. Fourteen of the 23 patients were eligible for assessment of inappropriate antipsychotic continuation upon transfer from the MICU. Of these 14 patients, 9 (64%) were inappropriately continued on an antipsychotic. Patients continued on antipsychotic therapy at hospital discharge were more likely to be discharged to a facility (rehabilitation, skilled nursing facility, or healthcare institution) (p = 0.049). Conclusion. The continuation of antipsychotics for the management of delirium during transitions of care was a common practice at a tertiary care medical center. Patients receiving antipsychotics for treatment of delirium in the MICU were inappropriately continued on these agents when transferred from the MICU to the medical floor or discharged from the hospital. Am J Health-Syst Pharm. 2015; 72(suppl 3):S133-9
ing the efficacy of antipsychotics for hospital delirium have limited
Internal Medicine and Pediatrics, University of Maryland School of Medicine, Baltimore. Mangla Gulati, M.D., FACP, FSHM, is Assistant Professor, Department of Medicine, University of Maryland School of Medicine. Address correspondence to Dr. Gonzales ([email protected]. edu). The authors have declared no potential conflicts of interest. Copyright © 2015, American Society of Health-System Pharmacists, Inc. All rights reserved. 1079-2082/15/1201-S133. DOI 10.2146/ajhp150474
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
S133
AJHP RESIDENTS EDITION Hospital delirium treatment
Rachel W. Flurie, Pharm.D., BCPS, is Assistant Professor, Department of Pharmacotherapy and Outcomes Science, at Virginia Commonwealth University School of Pharmacy. She received her Bachelor of Arts degree in Chemistry from St. Mary’s College of Maryland. She received her Doctor of Pharmacy degree from the University of Maryland in 2012 and completed a 24-month ASHPaccredited pharmacotherapy residency in 2014. She is board certified in pharmacotherapy. Dr. Flurie practices as a clinical pharmacy specialist on inpatient internal medicine and digestive health services at a tertiary care, academic medical center. She is a member of the respective education committees for the Virginia Society of Health-System Pharmacists and the clinical pharmacy and pharmacology group of the Society of Critical Care Medicine.
treatment durations (6–10 days).6,7 However, symptoms of delirium can persist long after the acute condition has resolved and as patients transition to lower levels of care. Currently, data are lacking to suggest that the continuation of antipsychotics during transitions of care is beneficial to patients. In addition, long-term use of antipsychotics creates the potential for inappropriate medication continuation and increased adverse effects (i.e., extrapyramidal symptoms, sedation, glucose intolerance, lipid abnormalities, orthostatic S134
hypotension, anticholinergic effects, and death).8-11 The National Partnership to Improve Dementia Care has joined with the Centers for Medicare and Medicaid Services and other organizations to establish a national goal of reducing the use of antipsychotic medications in long-term nursing home residents by 25% by the end of 2015.12 The American Geriatrics Society, as part of the Choosing Wisely campaign initiated by the American Board of Internal Medicine Foundation, is discouraging physicians from using antipsychotics as first-line therapies to treat the behavioral and psychological symptoms of dementia.13 Because patients with dementia are at risk for delirium and symptoms of both disorders overlap, antipsychotics initiated for the management of acute delirium may be inappropriately continued when symptoms do not improve due to worsening dementia. The purpose of this study was to determine the percentage of critically ill patients who were continued on antipsychotics after being transferred from the ICU. Methods This study was conducted at a 750-bed, tertiary care center in Baltimore, Maryland, and approved by an institutional review board. A retrospective chart review was conducted for adult patients admitted to the medical ICU (MICU) between June 1, 2011, and May 31, 2012, who were initiated on antipsychotic therapy (haloperidol, quetiapine, risperidone, olanzapine, or ziprasidone) at least 24 hours before transfer out of the MICU. Patients were excluded if they were on antipsychotic therapy before MICU admission or if they were transferred from the MICU to a nonmedical ward. The primary outcome was the percentage of patients initiated on an antipsychotic in the MICU who were continued on
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
therapy after transfer to a medical ward. Secondary outcomes were the appropriateness of continuing antipsychotic therapy during transitions of care and the percentage of patients continued on an antipsychotic after hospital discharge. Inappropriate antipsychotic continuation was defined as a negative score on the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) within 24 hours before MICU transfer. The CAM-ICU is an assessment tool that has been validated in ICU patients and designed for use by healthcare professionals not trained in psychiatry.14 It incorporates criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for the diagnosis of delirium and was derived from the Confusion Assessment Method, which was validated in a general medicine and outpatient geriatric population.15 The CAM-ICU assesses the four features of delirium: (1) acute onset and fluctuating course, (2) inattention, (3) altered consciousness, and (4) disorganized thinking. Patients are scored as positive, negative, or unable to assess. A positive score is given when a patient exhibits both features 1 and 2 and either feature 3 or 4. A negative score is given when criteria for a positive score are not met; when all four features cannot be assessed, a patient is scored as “unable to assess.” The CAM-ICU is included in the bedside charting and performed by trained nurses every 4 hours. Currently, there is no structured delirium assessment tool that is used for nonICU patients at our institutiton. Patient demographics were recorded on study day 1. Risk factors for delirium were collected, which included comorbidities (dementia, Parkinson’s disease, depression, bipolar disorder, schizophrenia, hypertension, and cerebrovascular accident), history of substance use (alcohol, tobacco, illicit drugs, and prescription drugs), illness severity, mechanical ventilation, immobility, insertion of a bladder
AJHP RESIDENTS EDITION Hospital delirium treatment
catheter, use of physical restraints, and concomitant opioid or benzodiazepine use.2,16,17 Illness severity was assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE II).18 Data on the patient’s hospitalization included the antipsychotic medication regimen, admitting MICU diagnosis, duration of MICU and hospital stays, and hospital discharge location. Information collected on the antipsychotic regimen included the daily dose, number of doses, and duration of therapy. Antipsychotic doses were evaluated comprehensively and included one-time, scheduled, and as-needed doses. CAM-ICU scores were collected within 24 hours before patient transfer out of the MICU to determine if the patient was still experiencing delirium. Two patient groups were analyzed: patients transferred from the MICU to the medical ward (transition group 1) and patients discharged from the medical ward to home or another facility (transition group 2). The rate of antipsychotic continuation was determined for the primary and secondary outcomes for patients in each group. Within each group, prespecified variables were tested to detect differences between patients who were continued and those who were not continued on antipsychotic therapy. For transition group 1, prespecified variables included age, sex, race, comorbidities (e.g., neurologic or psychiatric disorder, hypertension, cerebrovascular accident), length of MICU stay, length of hospital stay, APACHE II score, concurrent opioid or benzodiazepine use, history of substance use, immobility, mechanical ventilation, insertion of a bladder catheter, and use of physical restraints. For transition group 2, prespecified variables included comorbidities, concurrent opioid or benzodiazepine use, history of substance use, and place of discharge (home, rehabilitation facility, skilled nursing facility, or other healthcare institution). Patient and hospital char-
acteristics were compared between groups using the unpaired t test for continuous variables and chi-square test for dichotomous variables. The a priori level of significance was 0.05 with a two-tailed test. All data were analyzed using PRISM, version 4.0 (GraphPad, San Diego, CA). Results Between June 1, 2011, and May 31, 2012, 1276 individual patients were admitted to the MICU. Of those patients, 87 met the inclusion criteria. Patient demographic data and delirium risk factors are listed in Table 1. All 87 patients had CAM-ICU scores documented, and 61 (70%) had a positive score at least once while in the MICU. A total of 46 patients (53%) had a positive score within 24 hours of receiving the first dose of an antipsychotic. Seventeen patients (20%) had a negative CAM-ICU score, and 22 patients (25%) could not be assessed when the first dose of antipsychotic was administered. For 2 patients, CAM-ICU scores were not recorded when the first dose of antipsychotic was administered. Haloperidol was the most common antipsychotic administered in the MICU and medical ward (Table 2). In the MICU, quetiapine was the antipsychotic continued the longest, with an average duration of therapy of 9.5 ± 8.7 days (Table 2). There was a significant decrease in the average number of haloperidol doses administered to patients when they were transferred from the MICU to the medical ward (7.7 ± 9.1 doses versus 2.8 ± 1.7 doses, p = 0.01). There were no significant differences in the number of doses administered to patients while in the MICU versus the medical ward. There were no differences in the duration of therapy for haloperidol, quetiapine, and olanzapine (Table 2). Of the 87 patients included in the study, 23 (26%) were continued on antipsychotic therapy after their transfer from the MICU to the medical ward. There were no significant
differences in baseline characteristics or risk factors between patients who were continued and those who were not continued on antipsychotic therapy (Table 1). Of the 23 patients continued on antipsychotic therapy, 9 (39%) were discharged from the hospital with an antipsychotic. Patients’ comorbidities and risk factors are presented in Table 3. A total of 14 patients had a positive or negative CAM-ICU score within 24 hours of MICU transfer and were eligible for assessment of inappropriate continuation. Of those patients, 9 (64%) were inappropriately continued on an antipsychotic (i.e., had a negative CAM-ICU score within 24 hours of MICU transfer). Discussion This study found that the continuation of antipsychotics for the management of delirium during transitions of care was common. Importantly, 39% of patients who were continued on antipsychotic therapy from the MICU to the medical ward were also continued on antipsychotic therapy at hospital discharge. Without compelling evidence to show that patients incur more than symptomatic relief with the use of antipsychotics, the continuation of these potentially inappropriate medications during transitions of care may contribute to long-term polypharmacy and unnecessary adverse effects.9 Efforts to decrease the off-label use of antipsychotics for patients in long-term care facilities are important among national health organizations, and this study opens up the possibility of expanding those efforts to hospitalized patients.12,13 In this study, haloperidol was the most frequently used antipsychotic for delirium, followed by several second-generation antipsychotics, which is consistent with previous studies.5,7 There was variability in the mean total daily doses and the number of doses administered,
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
S135
AJHP RESIDENTS EDITION Hospital delirium treatment
Table 1.
Transition Group 1 Patient Demographics and Delirium Risk Factorsa Antipsychotic Continued From MICU to Medical Ward? Characteristic Mean ± S.D. age, yr Sex, no. (%) pts Male Female Race, no. (%) pts White African American Other Comorbidities, no. (%) pts Hypertension Neurologic or psychiatric disorderb Cerebrovascular accident Mean ± S.D. MICU LOS, days Mean ± S.D. hospital LOS, days Risk factors Mean ± S.D. APACHE II score Administration of opioid(s) in MICU, no. (%) pts Administration of benzodiazepine(s) in MICU, no. (%) pts Administration of opioid(s) and benzodiazepine(s) in MICU, no. (%) pts Administration of opioid(s) or benzodiazepine(s) in MICU, no. (%) pts History of substance use, no. (%) pts Immobility, no. (%) pts Mechanical ventilation, no. (%) pts Mean ± S.D. no. days of mechanical ventilation Bladder catheter, no. (%) pts Use of physical restraints, no. (%) pts
Yes (n = 23)
No (n = 64)
p
57.1 ± 15.9
55.0 ± 16.4
0.59
15 (65) 8 (35)
30 (46) 34 (53)
0.15 0.13
12 (52) 11 (49) 0
31 (48) 32 (49) 1 (2)
0.76 0.76 0.71
13 (57) 6 (26) 1 (4) 14.1 ± 11.4 34.1 ± 31.0
32 (50) 10 (15) 4 (6) 12.6 ± 11.5 26.5 ± 20.0
0.59 0.27 0.74 0.60 0.19
26.5 ± 5.1 22 (96)
25.4 ± 6.4 52 (81)
0.38 0.10
20 (87)
49 (77)
0.29
19 (83)
42 (66)
0.13
23 (100) 13 (57) 5 (22) 22 (97)
59 (92) 33 (51) 15 (23) 51 (80)
0.17 0.68 0.87 0.07
9.1 ± 10.3 22 (96) 21 (91)
9.0 ± 10.5 60 (94) 54 (84)
0.96 0.74 0.41
MICU = medical intensive care unit, LOS = length of stay, APACHE II = Acute Physiology and Chronic Health Evaluation II. Bipolar disorder, dementia, depression, Parkinson’s disease, or schizophrenia.
a
b
which is reflective of the disparity in real-world practice. Duration of therapy was shortest for haloperidol and longest for quetiapine, which is reasonable as haloperidol may be used for acute episodes of hyperactivity and quetiapine can be used for mixed-type delirium or sleep–wake cycle disturbances. The optimal dosing and duration of antipsychotic therapy for delirium symptom management are unclear. In addition, there are no recommendations or validated assessment tools that can be used to signify appropriate treatment discontinuation in the S136
non-ICU setting.19,20 In a recent, singlecenter retrospective study including 156 patients from multiple ICUs, 27% of patients transferred from an ICU to another unit were discharged from the hospital on an atypical antipsychotic.21 The authors reported that only 32.5% of those patients had evidence warranting continuation of the medication or weaning instructions for the medication. The methods for evaluation of appropriate continuation were not explicitly stated, though the authors mentioned that many of the patients had evidence of delirium resolution or no reported indication
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
for continuation of the antipsychotic at discharge. Jasiak et al.22 conducted a retrospective review of 80 patients and showed that 48% of patients started on atypical antipsychotics for ICU delirium continued their therapy after ICU transfer. Of those patients, 71% were continued on therapy as an outpatient. The percentage of patients who had documentation of ICU delirium was low, with only half of the patients having an initial or final CAM-ICU score recorded. In addition, the authors assumed that all patients were receiving antipsychotics
AJHP RESIDENTS EDITION Hospital delirium treatment
Table 2.
Antipsychotic Medication Administration for MICU and Medical Warda Characteristic Antipsychotic administered, no. (%) pts Haloperidol Quetiapine Olanzapine Ziprasidoneb Median no. (range) antipsychotics administered per patient Mean ± S.D. antipsychotic daily dose, mg/day Haloperidol Quetiapine Olanzapine Ziprasidone Mean ± S.D. no. antipsychotic doses administered Haloperidol Quetiapine Olanzapine Ziprasidone Mean ± S.D. duration of antipsychotic therapy, days Haloperidol Quetiapine Olanzapine Ziprasidone
MICU (n = 87)
Medical Ward (n = 23)
85 (98) 14 (16) 4 (5) 1 (1)
18 (78) 6 (26) 2 (9) 0
1 (1–4)
1.5 (1–2)
9.4 ± 7.7 71.7 ± 34.6 8.4 ± 4.3 60
4.3 ± 2.4 64.8 ± 32.2 9.2 ± 4.7 0
0.007 0.68 0.86
7.7 ± 9.1 17.6 ± 17.9 9.8 ± 13.7 10
2.8 ± 1.7 7.7 ± 8.3 19.0 ± 19.8 0
0.01 0.22 0.53
3.6 ± 3.4 9.5 ± 8.7 4.8 ± 6.2 5
2.4 ± 1.4 4.5 ± 3.9 12.0 ± 14.1 0
0.13 0.20 0.40
p 0.0007 0.27 0.44
MICU = medical intensive care unit. Ziprasidone results for one patient.
a
b
for treatment of delirium, even those without diagnostic documentation. Our study confirmed the diagnosis of delirium using the CAM-ICU score (70% of our patients had at least one positive score). The current study also differs from the previous studies by including the most commonly used antipsychotic, haloperidol.5,21,22 The exclusion of haloperidol eliminates a large patient population and may impact the generalizability of the results of previous studies. The results of this study highlight the importance of routine reassessment of patients to provide a clear indication of high-risk medications during transitions of care. Patients are assessed for delirium in the ICU, but routine assessment may not be performed once patients are transferred to the medical ward. Physicians or pharmacists may be hesi-
tant to discontinue an antipsychotic without a clear initial indication or symptom resolution, allowing the patient to continue a potentially inappropriate medication. Several assessment tools have been validated for use in acute care medical patients.15,23 Our study had several limitations. First, while the CAM-ICU provides an objective assessment, its ability to detect delirium in a real-world setting has come into question. A study found that when the assessment, administered by ICU nurses, was compared to the gold standard of a multidisciplinary team of delirium experts, the sensitivity of the CAM-ICU was 47%.24 However, the CAM-ICU is recommended by the latest guidelines for the assessment of ICU delirium.2 In addition, there is the potential that the medical team made a diagnosis of delirium regardless of
the CAM-ICU score. Given the retrospective design of this study, any such discrepancy could not be verified for the study participants. Secondly, inappropriate continuation was defined as a negative CAM-ICU score within 24 hours of transfer from the MICU. As there is no delirium assessment on the medical wards at our institution, we could not assess for recurrence of delirium once patients were transferred out of the MICU. Further, patients who had a CAM-ICU score of “unable to assess” or did not have a score within 24 hours of transfer from the MICU were excluded from analysis. While antipsychotics are used for multiple off-label indications in the ICU such as sedation, agitation, and delirium prevention,5,25 many of the off-label indications could be symp-
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
S137
AJHP RESIDENTS EDITION Hospital delirium treatment
Table 3.
Transition Group 2 Patient Characteristics and Delirium Risk Factors No. (%) Patients
Characteristic
Antipsychotic Continued From Medical Ward to Discharge (n = 9)
Antipsychotic Not Continued From Medical Ward to Discharge (n = 14)
5 (56) 2 (22) 1 (11)
7 (50) 4 (29) 0
0.79 0.74 0.20
7 (78)
7 (50)
0.18
0
1 (7)
0.41
0
1 (7)
0.41
7 (78) 6 (67)
7 (50) 6 (43)
0.18 0.26
1 (11) 7 (78)
5 (36) 5 (36)
0.19 0.049
Comorbidities Hypertension Neurologic or psychiatric disordera Cerebrovascular accident Risk factors Administration of opioid(s) in medical ward Administration of benzodiazepine(s) in medical ward Administration of opioid(s) and benzodiazepine(s) in medical ward Administration of opioid(s) or benzodiazepine(s) in medical ward History of substance use Place of discharge Discharge to home Discharge to facilityb
p
Bipolar disorder, dementia, depression, Parkinson’s disease, or schizophrenia. Rehabilitation facility, skilled nursing facility, or other healthcare institution.
a
b
toms of unrecognized delirium, and reassessment of antipsychotic continuation during transitions of care is still important in these patients. Future areas for study should include (1) prospective analysis to understand the clinical decisionmaking of providers when treating delirium, (2) evaluation of the longterm impact of continuing antipsychotic therapy for delirium, and (3) ways to improve communication of medication regimens during transitions of care. Plans to reduce antipsychotic continuation could involve reassessing patients on the medical wards, improving documentation of the indication for use in the medical record, or developing protocols to taper off antipsychotics before patients are discharged from the hospital. Conclusion The continuation of antipsychotics for the management of delirium during transitions of care was a common practice at a tertiary care mediS138
cal center. Patients receiving antipsychotics for treatment of delirium in the ICU were inappropriately continued on these agents when transferred from the MICU to the medical floor or discharged from the hospital. References 1. Pun BT, Ely EW. The importance of diagnosing and managing ICU delirium. Chest. 2007; 132:624-36. 2. Barr J, Fraser GL, Puntillo K et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013; 41:263-306. 3. Leslie DL, Zhang Y, Holford TR et al. Premature death associated with delirium at 1-year follow-up. Arch Intern Med. 2005; 165:1657-62. 4. Edlund A, Lundstrom M, Karlsson S et al. Delirium in older patients admitted to general internal medicine. J Geriatr Psychiatry Neurol. 2006; 19:83-90. 5. Patel RP, Gambrell M, Speroff T et al. Delirium and sedation in the intensive care unit (ICU): survey of behaviors and attitudes of 1,384 healthcare professionals. Crit Care Med. 2009; 37:825-32. 6. Tahir TA, Eeles E, Karapareddy V et al. A randomized controlled trial of quetiapine versus placebo in the treatment of delirium. J Psychosom Res. 2010; 69:485-90.
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
7. Devlin JW, Roberts RJ, Fong JJ et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med. 2010; 38:419-27. 8. Abidi S, Bhaskara SM. From chlorpromazine to clozapine—antipsychotic adverse effects and the clinician’s dilemma. Can J Psychiatry. 2003; 48:749-55. 9. Gill SS, Bronskill SE, Normand SL et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007; 146:775-86. 10. Strawn JR, Keck PE, Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry. 2007; 164:870-6. 11. Buckley NA, Sanders P. Cardiovascular adverse effects of antipsychotic drugs. Drug Saf. 2000; 23:215-28. 12. Centers for Medicare and Medicaid Services. National Partnership to Improve Dementia Care exceeds goal to reduce use of antipsychotic medications in nursing homes: CMS announces new goal (September 2014). www.cms.gov/Newsroom/MediaRelease Database/Press-releases/2014-Pressreleases-items/2014-09-19.html (accessed 2014 Dec 4). 13. Choosing Wisely. American Geriatrics Society: ten things physicians and patients should question (February 2013). www.choosingwisely.org/wp-content/ uploads/2015/02/AGS-Choosing-WiselyList.pdf (accessed 2014 Dec 4).
AJHP RESIDENTS EDITION Hospital delirium treatment
14. Ely EW, Margolin R, Francis J et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001; 29:1370-9. 15. Inouye SK, van Dyck CH, Alessi CA et al. Clarifying confusion: the Confusion Assessment Method. Ann Intern Med. 1990; 113:941-8. 16. Van Rompae y B, Elsev iers MM, Schuurmans MJ et al. Risk factors for delirium in intensive care patients: a prospective cohort study. Crit Care. 2009; 13:R77. 17. Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors, and consequences of ICU delirium. Intensive Care Med. 2007; 33:66-73. 18. Kanus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985; 13:818-29. 19. McCusker J, Cole M, Dendukuri N et al. The course of delirium in older medical inpatients: a prospective study. J Gen Intern Med. 2003; 18:696-704. 20. Pandharipande PP, Girard TD, Jackson JC et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013; 369:1306-16. 21. Kram BL, Kram SJ, Brooks KR. Implications of atypical antipsychotic prescribing in the intensive care unit. J Crit Care. 2015; 30:814-8. 22. Jasiak KD, Middleton EA, Camamo JM et al. Evaluation of discontinuation of atypical antipsychotics prescribed for ICU delirium. J Pharm Pract. 2012; 26:253-6. 23. Trzepacz PT, Mittal D, Torres R et al. Validation of the Delirium Rating ScaleRevised-98: comparison with the Delirium Rating Scale and the Cognitive Test for Delirium. J Neuropsychiatry Clin Neurosci. 2001; 13:229-42. 24. Van Eijk MM, van den Boogaard M, van Marum RJ et al. Routine use of the Confusion Assessment Method for the Intensive Care Unit: a multicenter study. Am J Respir Crit Care Med. 2011; 184:340-4. 25. Girard TD, Pandharipande PP, Carson SS et al. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebocontrolled trial. Crit Care Med. 2010; 38:428-37.
Am J Health-Syst Pharm—Vol 72 Dec 1, 2015—Suppl 3
S139
