Matthew S Duprey1, John W Devlin2,3,4, John L Griffith5, Thomas G Travison4,6, Becky A Briesacher2, Richard Jones6,7, Jane S Saczynski2, Eva M Schmitt6, Yun Gou6, Edward R Marcantonio4,6,8, Sharon K Inouye4,6,8. 1. From the School of Public Health, Brown University, Providence, Rhode Island. 2. Department of Pharmacy and Health Systems Sciences, Bouve College of Health Sciences, Northeastern University, Boston, Massachusetts. 3. Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 4. Harvard Medical School, Boston, Massachusetts. 5. Department of Health Sciences, Bouve College of Health Sciences, Northeastern University, Boston, Massachusetts. 6. Aging Brain Center, Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts. 7. Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, Rhode Island. 8. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Abstract
BACKGROUND: Postoperative delirium is frequent in older adults and is associated with postoperative neurocognitive disorder (PND). Studies evaluating perioperative medication use and delirium have generally evaluated medications in aggregate and been poorly controlled; the association between perioperative medication use and PND remains unclear. We sought to evaluate the association between medication use and postoperative delirium and PND in older adults undergoing major elective surgery. METHODS: This is a secondary analysis of a prospective cohort study of adults ≥70 years without dementia undergoing major elective surgery. Patients were interviewed preoperatively to determine home medication use. Postoperatively, daily hospital use of 7 different medication classes listed in guidelines as risk factors for delirium was collected; administration before delirium was verified. While hospitalized, patients were assessed daily for delirium using the Confusion Assessment Method and a validated chart review method. Cognition was evaluated preoperatively and 1 month after surgery using a neurocognitive battery. The association between prehospital medication use and postoperative delirium was assessed using a generalized linear model with a log link function, controlling for age, sex, type of surgery, Charlson comorbidity index, and baseline cognition. The association between daily postoperative medication use (when class exposure ≥5%) and time to delirium was assessed using time-varying Cox models adjusted for age, sex, surgery type, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation (APACHE)-II score, and baseline cognition. Mediation analysis was utilized to evaluate the association between medication use, delirium, and cognitive change from baseline to 1 month. RESULTS: Among 560 patients enrolled, 134 (24%) developed delirium during hospitalization. The multivariable analyses revealed no significant association between prehospital benzodiazepine (relative risk [RR], 1.44; 95% confidence interval [CI], 0.85-2.44), beta-blocker (RR, 1.38; 95% CI, 0.94-2.05), NSAID (RR, 1.12; 95% CI, 0.77-1.62), opioid (RR, 1.22; 95% CI, 0.82-1.82), or statin (RR, 1.34; 95% CI, 0.92-1.95) exposure and delirium. Postoperative hospital benzodiazepine use (adjusted hazard ratio [aHR], 3.23; 95% CI, 2.10-4.99) was associated with greater delirium. Neither postoperative hospital antipsychotic (aHR, 1.48; 95% CI, 0.74-2.94) nor opioid (aHR, 0.82; 95% CI, 0.62-1.11) use before delirium was associated with delirium. Antipsychotic use (either presurgery or postsurgery) was associated with a 0.34 point (standard error, 0.16) decrease in general cognitive performance at 1 month through its effect on delirium (P = .03), despite no total effect being observed. CONCLUSIONS: Administration of benzodiazepines to older adults hospitalized after major surgery is associated with increased postoperative delirium. Association between inhospital, postoperative medication use and cognition at 1 month, independent of delirium, was not detected.
BACKGROUND: Postoperative delirium is frequent in older adults and is associated with postoperative neurocognitive disorder (PND). Studies evaluating perioperative medication use and delirium have generally evaluated medications in aggregate and been poorly controlled; the association between perioperative medication use and PND remains unclear. We sought to evaluate the association between medication use and postoperative delirium and PND in older adults undergoing major elective surgery. METHODS: This is a secondary analysis of a prospective cohort study of adults ≥70 years without dementia undergoing major elective surgery. Patients were interviewed preoperatively to determine home medication use. Postoperatively, daily hospital use of 7 different medication classes listed in guidelines as risk factors for delirium was collected; administration before delirium was verified. While hospitalized, patients were assessed daily for delirium using the Confusion Assessment Method and a validated chart review method. Cognition was evaluated preoperatively and 1 month after surgery using a neurocognitive battery. The association between prehospital medication use and postoperative delirium was assessed using a generalized linear model with a log link function, controlling for age, sex, type of surgery, Charlson comorbidity index, and baseline cognition. The association between daily postoperative medication use (when class exposure ≥5%) and time to delirium was assessed using time-varying Cox models adjusted for age, sex, surgery type, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation (APACHE)-II score, and baseline cognition. Mediation analysis was utilized to evaluate the association between medication use, delirium, and cognitive change from baseline to 1 month. RESULTS: Among 560 patients enrolled, 134 (24%) developed delirium during hospitalization. The multivariable analyses revealed no significant association between prehospital benzodiazepine (relative risk [RR], 1.44; 95% confidence interval [CI], 0.85-2.44), beta-blocker (RR, 1.38; 95% CI, 0.94-2.05), NSAID (RR, 1.12; 95% CI, 0.77-1.62), opioid (RR, 1.22; 95% CI, 0.82-1.82), or statin (RR, 1.34; 95% CI, 0.92-1.95) exposure and delirium. Postoperative hospital benzodiazepine use (adjusted hazard ratio [aHR], 3.23; 95% CI, 2.10-4.99) was associated with greater delirium. Neither postoperative hospital antipsychotic (aHR, 1.48; 95% CI, 0.74-2.94) nor opioid (aHR, 0.82; 95% CI, 0.62-1.11) use before delirium was associated with delirium. Antipsychotic use (either presurgery or postsurgery) was associated with a 0.34 point (standard error, 0.16) decrease in general cognitive performance at 1 month through its effect on delirium (P = .03), despite no total effect being observed. CONCLUSIONS: Administration of benzodiazepines to older adults hospitalized after major surgery is associated with increased postoperative delirium. Association between inhospital, postoperative medication use and cognition at 1 month, independent of delirium, was not detected.
Authors: Tammy T Hshieh; Jirong Yue; Esther Oh; Margaret Puelle; Sarah Dowal; Thomas Travison; Sharon K Inouye Journal: JAMA Intern Med Date: 2015-04 Impact factor: 21.873
Authors: Eva M Schmitt; Edward R Marcantonio; David C Alsop; Richard N Jones; Selwyn O Rogers; Tamara G Fong; Eran Metzger; Sharon K Inouye Journal: J Am Med Dir Assoc Date: 2012-09-19 Impact factor: 4.669
Authors: Eva M Schmitt; Jane S Saczynski; Cyrus M Kosar; Edward R Marcantonio; Thomas Travison; Sharon K Inouye; Richard N Jones; David C Alsop; Tamara G Fong; Eran Metzger; Zara Cooper Journal: J Am Geriatr Soc Date: 2015-12-14 Impact factor: 5.562