Anesthesia Choice for Cognitively Impaired Patients Undergoing Hip Fracture Surgery

Contributed by Kyra O’Brien MD and Mark Neuman MD MSc, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA


The impact of general anesthesia on postoperative outcomes in patients with cognitive impairment is often debated. Some have posited that general anesthesia may have neurotoxic effects and therefore increase the risk of postoperative delirium and worsening postoperative cognitive dysfunction in patients with preoperative cognitive impairment.1 Spinal anesthesia has been suggested to reduce the likelihood of postoperative delirium in persons with cognitive impairment, but limited studies have evaluated the impact of anesthesia type in this population.2,3

The Regional versus General Anesthesia for Promoting Independence after Hip Fracture (REGAIN) trial examined outcomes with spinal versus general anesthesia for older adults undergoing hip fracture surgery and found no association of anesthesia type with delirium.4 We performed a secondary analysis of REGAIN data to understand whether this reported association differed between persons with or without baseline cognitive impairment.5

Study Design

The REGAIN trial enrolled adults aged 50 or older scheduled to undergo surgical repair of hip fracture across 46 hospitals in the United States and Canada. Consenting patients were randomized to receive spinal or general anesthesia, stratified by hospital, sex, and fracture location. Patients were screened for the presence of cognitive impairment prior to randomization via medical record review and the Short Blessed Test (SBT), a validated six-item orientation-memory-concentration test.6 We defined cognitive impairment as being present for anyone with a history of dementia or Alzheimer’s disease, or a preoperative SBT score of 5 or more. Patients were assessed for delirium once prior to randomization and once daily on postoperative days 1-3 via the 3-Minute Diagnostic Interview for Confusion Assessment Method-Defined Delirium (3D-CAM).7 In-hospital and 60-day outcome data were collected.

In our post-hoc secondary analysis of the REGAIN data, our primary outcome was presence of new or worsened delirium, defined as either a new delirium diagnosis based on the 3D-CAM, or a worsening 3D-CAM delirium severity (3D-CAM-S) score relative to baseline.8 Secondary delirium outcomes included the presence of new onset postoperative delirium and maximum postoperative delirium severity. Select secondary and exploratory functional outcomes included worsened walking ability at 60 days, any complication(s) during hospitalization or death, and death or transition to a new institutional residence at 60 days.


In the REGAIN trial, 1600 patients underwent randomization, of which 795 were assigned to spinal anesthesia and 805 were assigned to general anesthesia. Of those assigned to spinal anesthesia, 119 (15.0%) received general anesthesia, and of those assigned to general anesthesia, 28 (3.5%) received spinal anesthesia. For this analysis, 727 patients in the spinal anesthesia arm and 728 patients in the general anesthesia arm were included; reasons for exclusion included missing 3D-CAM assessments, missing dementia history or SBT assessment, death prior to anesthesia, or withdrawal prior to surgery. Two hundred ninety-five (40.6%) patients in the spinal anesthesia arm and 283 (38.9%) patients in the general anesthesia arm had baseline cognitive impairment or dementia.

The primary outcome, new or worsened delirium, occurred in 348 (23.9%) of the 1455 patients included in the analysis – 170/727 (23.4%) in the spinal anesthesia arm and 178/728 (24.5%) in the general anesthesia arm. New or worsened delirium occurred in 207 (35.8%) of the 578 patients with preoperative cognitive impairment: 100 of 295 (33.9%) in the spinal anesthesia arm versus 107 of 283 (37.8%) in the general anesthesia arm (odds ratio [OR] 0.85; 95% confidence interval [CI] 0.60 to 1.19). In patients without cognitive impairment, 70 of 432 (16.2%) in the spinal anesthesia group and 71 of 445 (16.0%) in the general anesthesia group experienced new or worsened delirium (OR 1.02; 95% CI 0.71 to 1.47, p=0.46 for the interaction effect of cognitive impairment on anesthesia route).

There was no difference in secondary outcomes of new onset delirium or in maximum 3D-CAM-S delirium severity by anesthesia type for patients with baseline cognitive impairment versus without baseline cognitive impairment, nor were there differences in complications during hospitalization and 60-day functional outcomes, transition to institutional residence, or mortality.


In our secondary analysis using data from the REGAIN trial, anesthesia type was not associated with differences in postoperative delirium or functional recovery between individuals with or without preoperative cognitive impairment. In the absence of contraindications, both spinal and general anesthesia are likely safe choices for patients undergoing hip fracture surgery regardless of whether preoperative cognitive impairment is present.


  1. Fodale V, Tripodi VF, Penna O, et al. An update on anesthetics and impact on the brain. Expert Opinion on Drug Safety. 2017;16(9):997-1008. doi:10.1080/14740338.2017.1351539
  2. Silva AR, Regueira P, Albuquerque E, et al. Estimates of Geriatric Delirium Frequency in Noncardiac Surgeries and Its Evaluation Across the Years: A Systematic Review and Meta-Analysis. Journal of the American Medical Directors Association. 2021;22(3):613-620.e9. doi:10.1016/j.jamda.2020.08.017
  3. Luk TTH, Jia B, Pang EYT, et al. Depth of Anesthesia and Postoperative Delirium. Curr Anesthesiol Rep. 2015;5(1):1-9. doi:10.1007/s40140-014-0088-z
  4. Neuman MD, Feng R, Carson JL, et al. Spinal Anesthesia or General Anesthesia for Hip Surgery in Older Adults. N Engl J Med. Published online October 9, 2021:NEJMoa2113514. doi:10.1056/NEJMoa2113514
  5. O’Brien K, Feng R, Sieber F, et al. Outcomes with spinal versus general anesthesia for patients with and without preoperative cognitive impairment: Secondary analysis of a randomized clinical trial. Alzheimer’s & Dementia. 2023;19(9):4008-4019. doi:10.1002/alz.13132
  6. Katzman R, Brown T, Fuld P, Peck A, Schechter R, Schimmel H. Validation of a short Orientation-Memory-Concentration Test of cognitive impairment. AJP. 1983;140(6):734-739. doi:10.1176/ajp.140.6.734
  7. Marcantonio ER, Ngo LH, O’Connor M, et al. 3D-CAM: Derivation and Validation of a 3-Minute Diagnostic Interview for CAM-Defined Delirium: A Cross-sectional Diagnostic Test Study. Ann Intern Med. 2014;161(8):554-561. doi:10.7326/M14-0865
  8. Vasunilashorn SM, Devinney MJ, Acker L, et al. A New Severity Scoring Scale for the 3‐Minute Confusion Assessment Method ( 3D‐CAM ). J Am Geriatr Soc. 2020;68(8):1874-1876. doi:10.1111/jgs.16538

Suggested Citation

Kyra O’Brien MD and Mark Neuman. Anesthesia Choice for Cognitively Impaired Patients Undergoing Hip Fracture Surgery; May, 2024, Available at: (accessed today’s date)

Posted in Delirium Research.

Leave a Reply