Frederick E Sieber1, Karin J Neufeld2, Allan Gottschalk3,4, George E Bigelow5, Esther S Oh6, Paul B Rosenberg2, Simon C Mears7, Kerry J Stewart8, Jean-Pierre P Ouanes3, Mahmood Jaberi1, Erik A Hasenboehler9, Tianjing Li10, Nae-Yuh Wang11. 1. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland. 2. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. 3. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland. 4. Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland. 5. Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, J. V. Brady Behavioral Biology Research Center, Johns Hopkins Bayview Campus, Baltimore, Maryland. 6. Division of Geriatric Medicine and Gerontology, Psychiatry and Behavioral Sciences & Neuropathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 7. Department of Orthopedic Surgery, University of Arkansas for Medical Sciences. Little Rock. 8. Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland. 9. Adult and Trauma Surgery, Department of Orthopaedic Surgery, Johns Hopkins Bayview Medical Center, Baltimore, Maryland. 10. Center for Clinical Trials and Evidence Synthesis, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 11. Departments of Medicine (General Internal Medicine), Biostatistics, and Epidemiology, and Welch Center for Prevention, Epidemiology, and Clinical Research, The Johns Hopkins University, Baltimore, Maryland.
Abstract
Importance: Postoperative delirium is the most common complication following major surgery in older patients. Intraoperative sedation levels are a possible modifiable risk factor for postoperative delirium. Objective: To determine whether limiting sedation levels during spinal anesthesia reduces incident delirium overall. Design, Setting, and Participants: This double-blind randomized clinical trial (A Strategy to Reduce the Incidence of Postoperative Delirum in Elderly Patients [STRIDE]) was conducted from November 18, 2011, to May 19, 2016, at a single academic medical center and included a consecutive sample of older patients (≥65 years) who were undergoing nonelective hip fracture repair with spinal anesthesia and propofol sedation. Patients were excluded for preoperative delirium or severe dementia. Of 538 hip fractures screened, 225 patients (41.8%) were eligible, 10 (1.9%) declined participation, 15 (2.8%) became ineligible between the time of consent and surgery, and 200 (37.2%) were randomized. The follow-up included postoperative days 1 to 5 or until hospital discharge. Interventions: Heavier (modified observer's assessment of sedation score of 0-2) or lighter (observer's assessment of sedation score of 3-5) propofol sedation levels intraoperatively. Main Outcomes and Measures: Delirium on postoperative days 1 to 5 or until hospital discharge determined via consensus panel using Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria. The incidence of delirium was compared between intervention groups with and without stratification by the Charlson comorbidity index (CCI). Results: Of 200 participants, the mean (SD) age was 82 (8) years, 146 (73%) were women, 194 (97%) were white, and the mean (SD) CCI was 1.5 (1.8). One hundred participants each were randomized to receive lighter sedation levels or heavier sedation levels. A good separation of intraoperative sedation levels was confirmed by multiple indices. The overall incident delirium risk was 36.5% (n = 73) and 39% (n = 39) vs 34% (n = 34) in heavier and lighter sedation groups, respectively (P = .46). Intention-to-treat analyses indicated no statistically significant difference between groups in the risk of incident delirium (log-rank test χ2, 0.46; P = .46). However, in a prespecified subgroup analysis, when stratified by CCI, sedation levels did effect the delirium risk (P for interaction = .04); in low comorbid states (CCI = 0), heavier vs lighter sedation levels doubled the risk of delirium (hazard ratio, 2.3; 95% CI, 1.1- 4.9). The level of sedation did not affect delirium risk with a CCI of more than 0. Conclusions and Relevance: In the primary analysis, limiting the level of sedation provided no significant benefit in reducing incident delirium. However, in a prespecified subgroup analysis, lighter sedation levels benefitted reducing postoperative delirium for persons with a CCI of 0. Trial Registration: clinicaltrials.gov Identifier: NCT00590707.
RCT Entities:
Importance: Postoperative delirium is the most common complication following major surgery in older patients. Intraoperative sedation levels are a possible modifiable risk factor for postoperative delirium. Objective: To determine whether limiting sedation levels during spinal anesthesia reduces incident delirium overall. Design, Setting, and Participants: This double-blind randomized clinical trial (A Strategy to Reduce the Incidence of Postoperative Delirum in Elderly Patients [STRIDE]) was conducted from November 18, 2011, to May 19, 2016, at a single academic medical center and included a consecutive sample of older patients (≥65 years) who were undergoing nonelective hip fracture repair with spinal anesthesia and propofol sedation. Patients were excluded for preoperative delirium or severe dementia. Of 538 hip fractures screened, 225 patients (41.8%) were eligible, 10 (1.9%) declined participation, 15 (2.8%) became ineligible between the time of consent and surgery, and 200 (37.2%) were randomized. The follow-up included postoperative days 1 to 5 or until hospital discharge. Interventions: Heavier (modified observer's assessment of sedation score of 0-2) or lighter (observer's assessment of sedation score of 3-5) propofol sedation levels intraoperatively. Main Outcomes and Measures: Delirium on postoperative days 1 to 5 or until hospital discharge determined via consensus panel using Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria. The incidence of delirium was compared between intervention groups with and without stratification by the Charlson comorbidity index (CCI). Results: Of 200 participants, the mean (SD) age was 82 (8) years, 146 (73%) were women, 194 (97%) were white, and the mean (SD) CCI was 1.5 (1.8). One hundred participants each were randomized to receive lighter sedation levels or heavier sedation levels. A good separation of intraoperative sedation levels was confirmed by multiple indices. The overall incident delirium risk was 36.5% (n = 73) and 39% (n = 39) vs 34% (n = 34) in heavier and lighter sedation groups, respectively (P = .46). Intention-to-treat analyses indicated no statistically significant difference between groups in the risk of incident delirium (log-rank test χ2, 0.46; P = .46). However, in a prespecified subgroup analysis, when stratified by CCI, sedation levels did effect the delirium risk (P for interaction = .04); in low comorbid states (CCI = 0), heavier vs lighter sedation levels doubled the risk of delirium (hazard ratio, 2.3; 95% CI, 1.1- 4.9). The level of sedation did not affect delirium risk with a CCI of more than 0. Conclusions and Relevance: In the primary analysis, limiting the level of sedation provided no significant benefit in reducing incident delirium. However, in a prespecified subgroup analysis, lighter sedation levels benefitted reducing postoperative delirium for persons with a CCI of 0. Trial Registration: clinicaltrials.gov Identifier: NCT00590707.
Authors: Christopher G Hughes; Christina S Boncyk; Deborah J Culley; Lee A Fleisher; Jacqueline M Leung; David L McDonagh; Tong J Gan; Matthew D McEvoy; Timothy E Miller Journal: Anesth Analg Date: 2020-06 Impact factor: 5.108
Authors: Hugh C Hemmings; Paul M Riegelhaupt; Max B Kelz; Ken Solt; Roderic G Eckenhoff; Beverley A Orser; Peter A Goldstein Journal: Trends Pharmacol Sci Date: 2019-05-27 Impact factor: 14.819
Authors: Elizabeth Mahanna-Gabrielli; Katie J Schenning; Lars I Eriksson; Jeffrey N Browndyke; Clinton B Wright; Deborah J Culley; Lis Evered; David A Scott; Nae Yah Wang; Charles H Brown; Esther Oh; Patrick Purdon; Sharon Inouye; Miles Berger; Robert A Whittington; Catherine C Price; Stacie Deiner Journal: Br J Anaesth Date: 2019-08-19 Impact factor: 9.166