Effect of Depth of Sedation in Older Patients Undergoing Hip Fracture Repair on Postoperative Delirium: The STRIDE Randomized Clinical Trial

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.

Figure 1.. Consolidated Standard of Reporting Diagram for STRIDE Study

Patients were recruited between November 18, 2011, and May 19, 2016. JHBMC indicates John Hopkins Bayview Medical Center; MMSE, Mini-Mental State Examination.

Figure 2.. Kaplan-Meier Curve Showing Intention-to-Treat Analysis of Cumulative Incidence of Delirium During Postoperative Days 1 to 5 in the Lighter Sedation and Heavier Sedation Groups

Log-rank P = .46.

Figure 3.. Charlson Comorbidity Index Scores

A, The adjusted hazard ratio showed that patients with the least comorbidity (Charlson comorbidity index = 0) were 2.3 times more likely to experience postoperative delirium after receiving heavier sedation levels than after receiving lighter sedation levels. B, Risk estimates for in-hospital postoperative delirium by treatment group and the associated 95% confidence intervals. Sample sizes (incident cases/total cases) are indicated in eTable 1 in Supplement 2. B, The difference in delirium risk after heavier and lighter sedation levels was not significant in patients with greater preoperative comorbidity. The dashed horizontal line indicates a 36.5% risk of in-hospital postoperative delirium, which was the estimated overall risk from the entire STRIDE sample. C, Percentage of patients stratified by Charlson comorbidity index score.