[Skip to Content]
[Skip to Content Landing]

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

Educational Objective To determine to what extent lighter vs higher sedation levels during spinal anesthesia reduces incident delirium in patients who are undergoing hip fracture repair.
1 Credit CME
Key Points

Question  Does limiting sedation levels during hip fracture repair under spinal anesthesia reduce postoperative delirium overall or when stratified by baseline comorbidity?

Findings  In this randomized clinical trial that included 200 older patients randomized to receive lighter vs heavier sedation, limiting levels of sedation provided no significant overall benefit in reducing incident delirium. However, in a prespecified subgroup analysis, heavier vs lighter sedation levels doubled the risk of postoperative delirium in patients with low baseline comorbidities as defined by a Charlson comorbidity index score of 0.

Meaning  Limiting intraoperative sedation levels may reduce delirium in older patients with low baseline comorbidity.

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

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Accepted for Publication: May 13, 2018.

Corresponding Author: Frederick E. Sieber, MD, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Bayview Medical Center, 4940 Eastern Ave, Baltimore, MD 21224 (fsieber1@jhmi.edu).

Published Online: August 8, 2018. doi:10.1001/jamasurg.2018.2602

Author Contributions: Drs Sieber and Wang had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Sieber, Neufeld, Gottschalk, Rosenberg, Mears, Stewart, Li, Wang.

Acquisition, analysis, or interpretation of data: Sieber, Neufeld, Gottschalk, Bigelow, Oh, Rosenberg, Mears, Stewart, Ouanes, Jaberi, Hasenboehler, Wang.

Drafting of the manuscript: Sieber, Gottschalk, Bigelow, Oh, Rosenberg, Wang.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Sieber, Wang.

Obtained funding: Sieber, Gottschalk, Wang.

Administrative, technical, or material support: Sieber, Neufeld, Gottschalk, Bigelow, Oh, Mears, Stewart, Ouanes.

Supervision: Sieber, Neufeld, Bigelow.

Other - classification interpretation of all included hip fractures: Hasenboehler.

Other - data management: Stewart.

Conflict of Interest Disclosures: None reported.

Funding/Support: This research was supported by National Institute on Aging grant R01 AG033615.

Role of the Funder/Sponsor: The National Institute of Aging had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Reducible Research Statement: Individual participant data that underlie the results reported in this article, study protocol, statistical analysis plan, and analytic code will be available for analysis after deidentification (text, tables, figures, and appendices) beginning 9 months and ending 36 months after article publication to researchers who provide a methodologically sound proposal to achieve the aims in the approved proposal. Proposals should be directed to fsieber1@jhmi.edu. To gain access, data requestors will need to sign a data access agreement.

Additional Contributions: We thank the assessment team (Kori Kindbom, MA, Rachel Burns, BS, and Michael Sklar, MA, Johns Hopkins University School of Medicine) for their follow-up of patients. These individuals were part of the study assessment and follow-up team and were compensated for their services through the study’s National Institutes of Health grant. We also thank the data safety and monitoring board members (Jeffery Carson, MD, Rutgers University, Lee Fleisher, MD, University of Pennsylvania, Steve Epstein, MD, Georgetown University, Jay Magaziner, PhD, University of Maryland, Anne Lindblad, PhD, the Emmes Corporation, and Sarang Kim, MD, Rutgers University) for their time, effort, and oversight (see protocol) and Linda Sevier, Johns Hopkins Bayview Medical Center, for her preparation of the manuscript.

References
1.
Gleason  LJ, Schmitt  EM, Kosar  CM,  et al.  Effect of delirium and other major complications on outcomes after elective surgery in older adults.  JAMA Surg. 2015;150(12):1134-1140. doi:10.1001/jamasurg.2015.2606PubMedGoogle ScholarCrossref
2.
Leslie  DL, Marcantonio  ER, Zhang  Y, Leo-Summers  L, Inouye  SK.  One-year health care costs associated with delirium in the elderly population.  Arch Intern Med. 2008;168(1):27-32. doi:10.1001/archinternmed.2007.4PubMedGoogle ScholarCrossref
3.
Pandharipande  P, Ely  EW.  Sedative and analgesic medications: risk factors for delirium and sleep disturbances in the critically ill.  Crit Care Clin. 2006;22(2):313-327, vii. doi:10.1016/j.ccc.2006.02.010PubMedGoogle ScholarCrossref
4.
Pandharipande  P, Shintani  A, Peterson  J,  et al.  Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients.  Anesthesiology. 2006;104(1):21-26. doi:10.1097/00000542-200601000-00005PubMedGoogle ScholarCrossref
5.
Dubois  MJ, Bergeron  N, Dumont  M, Dial  S, Skrobik  Y.  Delirium in an intensive care unit: a study of risk factors.  Intensive Care Med. 2001;27(8):1297-1304. doi:10.1007/s001340101017PubMedGoogle ScholarCrossref
6.
Marcantonio  ER, Goldman  L, Mangione  CM,  et al.  A clinical prediction rule for delirium after elective noncardiac surgery.  JAMA. 1994;271(2):134-139. doi:10.1001/jama.1994.03510260066030PubMedGoogle ScholarCrossref
7.
Sieber  FE, Gottshalk  A, Zakriya  KJ, Mears  SC, Lee  H.  General anesthesia occurs frequently in elderly patients during propofol-based sedation and spinal anesthesia.  J Clin Anesth. 2010;22(3):179-183. doi:10.1016/j.jclinane.2009.06.005PubMedGoogle ScholarCrossref
8.
Li  T, Wieland  LS, Oh  E,  et al.  Design considerations of a randomized controlled trial of sedation level during hip fracture repair surgery: a strategy to reduce the incidence of postoperative delirium in elderly patients.  Clin Trials. 2017;14(3):299-307. doi:10.1177/1740774516687253PubMedGoogle ScholarCrossref
9.
Glass  PS, Bloom  M, Kearse  L, Rosow  C, Sebel  P, Manberg  P.  Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers.  Anesthesiology. 1997;86(4):836-847. doi:10.1097/00000542-199704000-00014PubMedGoogle ScholarCrossref
10.
Folstein  MFFS, Folstein  SE, McHugh  PR.  “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician.  J Psychiatr Res. 1975;12(3):189-198. doi:10.1016/0022-3956(75)90026-6PubMedGoogle ScholarCrossref
11.
Inouye  SK, van Dyck  CH, Alessi  CA, Balkin  S, Siegal  AP, Horwitz  RI.  Clarifying confusion: the confusion assessment method. A new method for detection of delirium.  Ann Intern Med. 1990;113(12):941-948. doi:10.7326/0003-4819-113-12-941PubMedGoogle ScholarCrossref
12.
Trzepacz  PT, Mittal  D, Torres  R, Kanary  K, Norton  J, Jimerson  N.  Validation of the delirium rating scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium.  J Neuropsychiatry Clin Neurosci. 2001;13(2):229-242. doi:10.1176/jnp.13.2.229PubMedGoogle ScholarCrossref
13.
Sieber  FE, Zakriya  KJ, Gottschalk  A,  et al.  Sedation depth during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip fracture repair.  Mayo Clin Proc. 2010;85(1):18-26. doi:10.4065/mcp.2009.0469PubMedGoogle ScholarCrossref
14.
Charlson  ME, Pompei  P, Ales  KL, MacKenzie  CR.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.  J Chronic Dis. 1987;40(5):373-383. doi:10.1016/0021-9681(87)90171-8PubMedGoogle ScholarCrossref
15.
Lawton  MP, Brody  EM.  Assessment of older people: self-maintaining and instrumental activities of daily living.  Gerontologist. 1969;9(3):179-186. doi:10.1093/geront/9.3_Part_1.179PubMedGoogle ScholarCrossref
16.
Ewing  JA.  Detecting alcoholism. The CAGE questionnaire.  JAMA. 1984;252(14):1905-1907. doi:10.1001/jama.1984.03350140051025PubMedGoogle ScholarCrossref
17.
Yesavage  JA, Sheikh  JI.  9/Geriatric Depression Scale (GDS).  Clin Gerontol. 1986;5(1-2):165-173. doi:10.1300/J018v05n01_09Google ScholarCrossref
18.
Morris  JC.  The Clinical Dementia Rating (CDR): current version and scoring rules.  Neurology. 1993;43(11):2412-2414. doi:10.1212/WNL.43.11.2412-aPubMedGoogle ScholarCrossref
19.
Smith  PJ, Attix  DK, Weldon  BC, Monk  TG.  Depressive symptoms and risk of postoperative delirium.  Am J Geriatr Psychiatry. 2016;24(3):232-238. doi:10.1016/j.jagp.2015.12.004PubMedGoogle ScholarCrossref
20.
Gruber-Baldini  AL, Zimmerman  S, Morrison  RS,  et al.  Cognitive impairment in hip fracture patients: timing of detection and longitudinal follow-up.  J Am Geriatr Soc. 2003;51(9):1227-1236. doi:10.1046/j.1532-5415.2003.51406.xPubMedGoogle ScholarCrossref
21.
Hajat  Z, Ahmad  N, Andrzejowski  J.  The role and limitations of EEG-based depth of anaesthesia monitoring in theatres and intensive care.  Anaesthesia. 2017;72(suppl 1):38-47. doi:10.1111/anae.13739PubMedGoogle ScholarCrossref
22.
Patel  SB, Poston  JT, Pohlman  A, Hall  JB, Kress  JP.  Rapidly reversible, sedation-related delirium versus persistent delirium in the intensive care unit.  Am J Respir Crit Care Med. 2014;189(6):658-665. doi:10.1164/rccm.201310-1815OCPubMedGoogle ScholarCrossref
23.
Brown  KE, Mirrakhimov  AE, Yeddula  K, Kwatra  MM.  Propofol and the risk of delirium: exploring the anticholinergic properties of propofol.  Med Hypotheses. 2013;81(4):536-539. doi:10.1016/j.mehy.2013.06.027PubMedGoogle ScholarCrossref
24.
Balasubramaniam  B, Park  GR.  Sexual hallucinations during and after sedation and anaesthesia.  Anaesthesia. 2003;58(6):549-553. doi:10.1046/j.1365-2044.2003.03147.xPubMedGoogle ScholarCrossref
25.
Inouye  SK, Zhang  Y, Jones  RN, Kiely  DK, Yang  F, Marcantonio  ER.  Risk factors for delirium at discharge: development and validation of a predictive model.  Arch Intern Med. 2007;167(13):1406-1413. doi:10.1001/archinte.167.13.1406PubMedGoogle ScholarCrossref
26.
Lee  HB, Mears  SC, Rosenberg  PB, Leoutsakos  JM, Gottschalk  A, Sieber  FE.  Predisposing factors for postoperative delirium after hip fracture repair in individuals with and without dementia.  J Am Geriatr Soc. 2011;59(12):2306-2313. doi:10.1111/j.1532-5415.2011.03725.xPubMedGoogle ScholarCrossref
27.
Friedman  SM, Mendelson  DA.  Epidemiology of fragility fractures.  Clin Geriatr Med. 2014;30(2):175-181. doi:10.1016/j.cger.2014.01.001PubMedGoogle ScholarCrossref
28.
de Jonghe  A, van Munster  BC, Goslings  JC,  et al; Amsterdam Delirium Study Group.  Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-blind randomized controlled trial.  CMAJ. 2014;186(14):E547-E556. doi:10.1503/cmaj.140495PubMedGoogle ScholarCrossref
29.
Carson  JL, Terrin  ML, Noveck  H,  et al; FOCUS Investigators.  Liberal or restrictive transfusion in high-risk patients after hip surgery.  N Engl J Med. 2011;365(26):2453-2462. doi:10.1056/NEJMoa1012452PubMedGoogle ScholarCrossref
30.
Gruber-Baldini  AL, Marcantonio  E, Orwig  D,  et al.  Delirium outcomes in a randomized trial of blood transfusion thresholds in hospitalized older adults with hip fracture.  J Am Geriatr Soc. 2013;61(8):1286-1295. doi:10.1111/jgs.12396PubMedGoogle ScholarCrossref
31.
Duppils  GS, Wikblad  K.  Acute confusional states in patients undergoing hip surgery. a prospective observation study.  Gerontology. 2000;46(1):36-43. doi:10.1159/000022131PubMedGoogle ScholarCrossref
32.
Bellelli  G, Mazzola  P, Morandi  A,  et al.  Duration of postoperative delirium is an independent predictor of 6-month mortality in older adults after hip fracture.  J Am Geriatr Soc. 2014;62(7):1335-1340. doi:10.1111/jgs.12885PubMedGoogle ScholarCrossref
33.
Burgos  E, Gómez-Arnau  JI, Díez  R, Muñoz  L, Fernández-Guisasola  J, Garcia del Valle  S.  Predictive value of six risk scores for outcome after surgical repair of hip fracture in elderly patients.  Acta Anaesthesiol Scand. 2008;52(1):125-131. doi:10.1111/j.1399-6576.2007.01473.xPubMedGoogle ScholarCrossref
34.
Johnson  DJ, Greenberg  SE, Sathiyakumar  V,  et al.  Relationship between the Charlson Comorbidity Index and cost of treating hip fractures: implications for bundled payment.  J Orthop Traumatol. 2015;16(3):209-213. doi:10.1007/s10195-015-0337-zPubMedGoogle ScholarCrossref
35.
Yohannes  AM, Chen  W, Moga  AM, Leroi  I, Connolly  MJ.  Cognitive impairment in chronic obstructive pulmonary disease and chronic heart failure: a systematic review and meta-analysis of observational studies.  J Am Med Dir Assoc. 2017;18(5):451.e1-451.e11. doi:10.1016/j.jamda.2017.01.014PubMedGoogle ScholarCrossref
36.
Yaffe  K, Ackerson  L, Kurella Tamura  M,  et al; Chronic Renal Insufficiency Cohort Investigators.  Chronic kidney disease and cognitive function in older adults: findings from the chronic renal insufficiency cohort cognitive study.  J Am Geriatr Soc. 2010;58(2):338-345. doi:10.1111/j.1532-5415.2009.02670.xPubMedGoogle ScholarCrossref
37.
Eggermont  LH, de Boer  K, Muller  M, Jaschke  AC, Kamp  O, Scherder  EJ.  Cardiac disease and cognitive impairment: a systematic review.  Heart. 2012;98(18):1334-1340. doi:10.1136/heartjnl-2012-301682PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close