title: Association between sedating medications and delirium in older inpatients.
abstract: OBJECTIVE
  To examine the association between Beers criteria sedative medications and delirium in a large cohort of hospitalized elderly adults with common medical conditions.
  
  
  METHODS
  Retrospective cohort and nested case-control studies.
  
  
  METHODS
  374 U.S. hospitals.
  
  
  METHODS
  All individuals aged 65 and older admitted to the hospital between September 2003 and June 2005 with one of six principal diagnoses (acute myocardial infarction, chronic obstructive pulmonary disease, community-acquired pneumonia, congestive heart failure, ischemic stroke, urinary tract infection).
  
  
  METHODS
  Primary outcome was presumed hospital-acquired delirium, defined as initiation of an antipsychotic medication or restraints on hospital Day 3 or later. Logistic and proportional hazards regression were used to model the associations between sedative exposure and delirium.
  
  
  RESULTS
  The dataset contained 225,028 participants (median age 82; 58% female). Four percent fit the definition of hospital-acquired delirium (median onset Day 5). In all, 38,883 (17%) participants received one or more sedative medications. In the cohort study, diphenhydramine (adjusted odds ratio (AOR) = 1.22, 95% confidence interval (CI) = 1.09-1.36) and short-acting benzodiazepines (AOR = 1.18, 95% CI = 1.03-1.34) were associated with greater risk of subsequent delirium. In the nested case-control study, diphenhydramine, short- and long-acting benzodiazepines and promethazine were associated with delirium. Amitriptyline and muscle relaxants were not associated with delirium in either study. Confounding by indication could not be excluded for drugs that are sometimes used improperly to treat delirium.
  
  
  CONCLUSIONS
  An association was found between several Beers criteria sedative medications and delirium in hospitalized medical patients. Given the prevalence of these medications and the morbidity associated with delirium, further investigation into the appropriateness of such prescribing is warranted.
authors: Department of Internal Medicine, Medicine Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Michael B
authors: MB
authors: Rothberg
authors: Division of General Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors: Shoshana J
authors: SJ
authors: Herzig
authors: Center for Quality of Care Research, Baystate Medical Center, Springfield, Massachusetts.|University of Massachusetts, Amherst, Massachusetts.
authors: Penelope S
authors: PS
authors: Pekow
authors: Center for Quality of Care Research, Baystate Medical Center, Springfield, Massachusetts.
authors: Jill
authors: J
authors: Avrunin
authors: Center for Quality of Care Research, Baystate Medical Center, Springfield, Massachusetts.|School of Medicine, Tufts University, Boston, Massachusetts.
authors: Tara
authors: T
authors: Lagu
authors: Center for Quality of Care Research, Baystate Medical Center, Springfield, Massachusetts.|School of Medicine, Tufts University, Boston, Massachusetts.
authors: Peter K
authors: PK
authors: Lindenauer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003693:Delirium / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D007297:Inpatients; D008297:Male; D015995:Prevalence; D011618:Psychotic Disorders / Q000188:drug therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D014150:Antipsychotic Agents; D006993:Hypnotics and Sedatives
references: Howes JB, Ryan J, Fairbrother G et al. Benzodiazepine prescribing in a Sydney teaching hospital. Med J Aust 1996;165:305-308.
references: Lagnaoui R, Moore N, Longy-Boursier M et al. Benzodiazepine use in patients hospitalized in a department of internal medicine: Frequency and clinical correlates. Pharmacoepidemiol Drug Saf 2001;10:531-535.
references: O'Reilly R, Rusnak C. The use of sedative-hypnotic drugs in a university teaching hospital. Can Med Assoc J 1990;142:585-589.
references: Ramesh M, Roberts G. Use of night-time benzodiazepines in an elderly inpatient population. J Clin Pharm Ther 2002;27:93-97.
references: Warie H, Petrovic M, Somers A et al. The use of hypnosedative drugs in a university hospital setting. Acta Clin Belg 2003;58:225-232.
references: Elliott RA, Woodward MC, Oborne CA. Improving benzodiazepine prescribing for elderly hospital inpatients using audit and multidisciplinary feedback. Intern Med J 2001;31:529-535.
references: Enriquez SG, Andrews JD. Effect of hospitalization on hypnotic drug use. Can J Hosp Pharm 1985;38(86-9):107.
references: Frighetto L, Marra C, Bandali S et al. An assessment of quality of sleep and the use of drugs with sedating properties in hospitalized adult patients. Health Qual Life Outcomes 2004;2:17.
references: Gurwitz JH, Field TS, Harrold LR et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA 2003;289:1107-1116.
references: Leape LL, Brennan TA, Laird N et al. The nature of adverse events in hospitalized patients: Results of the Harvard Medical Practice Study II. N Engl J Med 1991;324:377-384.
references: Bates DW, Cullen DJ, Laird N et al. Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group. JAMA 1995;274:29-34.
references: Trifirò G, Spina E. Age-related changes in pharmacodynamics: Focus on drugs acting on central nervous and cardiovascular systems. Curr Drug Metab 2011;12:611-620.
references: Cepeda MS, Farrar JT, Baumgarten M et al. Side effects of opioids during short-term administration: Effect of age, gender, and race. Clin Pharmacol Ther 2003;74:102-112.
references: Kruse WH. Problems and pitfalls in the use of benzodiazepines in the elderly. Drug Saf 1990;5:328-344.
references: Krahenbuhl-Melcher A, Schlienger R, Lampert M et al. Drug-related problems in hospitals: A review of the recent literature. Drug Saf 2007;30:379-407.
references: American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2012;60:616-631.
references: Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA 1996;275:852-857.
references: Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly. JAMA 1990;263:1097-1101.
references: Schor JD, Levkoff SE, Lipsitz LA et al. Risk factors for delirium in hospitalized elderly. JAMA 1992;267:827-831.
references: Marcantonio ER, Juarez G, Goldman L et al. The relationship of postoperative delirium with psychoactive medications. JAMA 1994;272:1518-1522.
references: Dai YT, Lou MF, Yip PK et al. Risk factors and incidence of postoperative delirium in elderly Chinese patients. Gerontology 2000;46:28-35.
references: Rogers MP, Liang MH, Daltroy LH et al. Delirium after elective orthopedic surgery: Risk factors and natural history. Int J Psychiatry Med 1989;19:109-121.
references: Pisani MA, Murphy TE, Van Ness PH et al. Characteristics associated with delirium in older patients in a medical intensive care unit. Arch Intern Med 2007;167:1629-1634.
references: Duppils GS, Wikblad K. Acute confusional states in patients undergoing hip surgery: A prospective observation study. Gerontology 2000;46:36-43.
references: Galanakis P, Bickel H, Gradinger R et al. Acute confusional state in the elderly following hip surgery: Incidence, risk factors and complications. Int J Geriatr Psychiatry 2001;16:349-355.
references: Gustafson Y, Berggren D, Brannstrom B et al. Acute confusional states in elderly patients treated for femoral neck fracture. J Am Geriatr Soc 1988;36:525-530.
references: Elie M, Cole MG, Primeau FJ et al. Delirium risk factors in elderly hospitalized patients. J Gen Intern Med 1998;13:204-212.
references: Gaudreau JD, Gagnon P, Roy MA et al. Association between psychoactive medications and delirium in hospitalized patients: A critical review. Psychosomatics 2005;46:302-316.
references: Rothberg MB, Pekow PS, Liu F et al. Potentially inappropriate medication use in hospitalized elders. J Hosp Med 2008;3:91-102.
references: Elixhauser A, Steiner C, Harris DR et al. Comorbidity measures for use with administrative data. Med Care 1998;36:8-27.
references: Fick DM, Cooper JW, Wade WE et al. Updating the Beers Criteria for potentially inappropriate medication use in older adults: Results of a US consensus panel of experts. Arch Intern Med 2003;163:2716-2724.
references: Inouye SK, Leo-Summers L, Zhang Y et al. A chart-based method for identification of delirium: Validation compared with interviewer ratings using the Confusion Assessment Method. J Am Geriatr Soc 2005;53:312-318.
references: Finlayson E, Maselli J, Steinman MA et al. Inappropriate medication use in older adults undergoing surgery: A national study. J Am Geriatr Soc 2011;59:2139-2144.
references: Dedhiya SD, Hancock E, Craig BA et al. Incident use and outcomes associated with potentially inappropriate medication use in older adults. Am J Geriatr Pharmacother 2010;8:562-570.
references: Fialova D, Topinkova E, Gambassi G et al. Potentially inappropriate medication use among elderly home care patients in Europe. JAMA 2005;293:1348-1358.
references: Golden AG, Preston RA, Barnett SD et al. Inappropriate medication prescribing in homebound older adults. J Am Geriatr Soc 1999;47:948-953.
references: Hanlon JT, Schmader KE, Boult C et al. Use of inappropriate prescription drugs by older people. J Am Geriatr Soc 2002;50:26-34.
references: Passarelli MC, Jacob-Filho W, Figueras A. Adverse drug reactions in an elderly hospitalised population: Inappropriate prescription is a leading cause. Drugs Aging 2005;22:767-777.
references: Perri M 3rd, Menon AM, Deshpande AD et al. Adverse outcomes associated with inappropriate drug use in nursing homes. Ann Pharmacother 2005;39:405-411.
references: Budnitz DS, Lovegrove MC, Shehab N et al. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 2011;365:2002-2012.
references: Jano E, Aparasu RR. Healthcare outcomes associated with Beers' Criteria: A systematic review. Ann Pharmacother 2007;41:438-447.
references: Inouye SK, van Dyck CH, Alessi CA et al. Clarifying confusion: The Confusion Assessment Method. A new method for detection of delirium. Ann Intern Med 1990;113:941-948.