RAGA Trial: Effect of Regional vs General Anesthesia on Incidence of Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery

Summary by Natasha Samanich MD, 3.13.23
https://jamanetwork.com/journals/jama/fullarticle/2787494


Clinical Hypothesis: in older patients undergoing surgical repair for hip fracture, regional anesthesia compared with general anesthesia would reduce the incidence of postoperative delirium.

Take Home Message:

  • Regional anesthesia without sedation compared to GA did not significantly reduce the incidence of postoperative delirium during the first 7 days postop in patients aged 65 years and older undergoing hip fracture surgery.

    • 6.2% in the regional anesthesia group compared with 5.1% in the general anesthesia group.

  • Similar incidence in the number of postop delirium episodes, the incidence of hyperactive delirium, and the incidence of hypoactive delirium between the RA and GA groups.

  • No difference in 3-day worst pain scores, length of hospital stay, and all-cause 30-day mortality  

 

 Summary

Background: Predisposing factors to postoperative delirium include: age, cognitive impairment, frailty, and complex comorbidities, with emergency surgery, pain, and psychotropic medications as associated important precipitating factors. The association of GA with postoperative delirium has had mixed results in previous studies and reviews. This trial seeks to answer the question: In older adults undergoing surgical repair for hip fracture, does regional anesthesia reduce the incidence of postoperative delirium compared with general anesthesia?

 

Study Design: Multicenter randomized controlled trial 


Methods: 

Inclusion criteria:

  • Age 65 and older  

  • Fragility hip fracture (femoral neck, femoral head, intertrochanteric, or subtrochanteric)

  • ASA status I through IV

  • Scheduled for surgical repair

 

Exclusion criteria: 

  • Age < 65

  • Multiple trauma or fractures

  • Contraindications for regional or general anesthesia

  • Malignant hyperthermia

  • Enrolled in another randomized clinical trial 

 

After being screened and consented, eligible patients were randomized and then stratified by center, patient age (65-80, >80), presence/absence of preoperative delirium, and presence/absence of preexisting dementia to ensure equal distribution between groups. Delirium was diagnosed using the Confusion Assessment Method (CAM). Cognitive function was measured using 30-point MMSE. 

Regional anesthesia included: spinal, epidural, or CSE and was provided without sedation. Type, dose, and use of nerve block were at the discretion of the consultant anesthesiologist. GA was induced with IV agents and maintained using IV and inhalational anesthetic agents. Consultant anesthesiologist independently determined airway management and ventilation mode. Both groups were highly recommended to use single injection or continuous infusion of LA for peripheral nerve block techniques. Medications known to impair cognitive function (BZDs, ketamine) were prohibited. Postoperative analgesia was prescribed per location practice. 

 

Primary outcome: incidence of delirium during first 7 postoperative days, using CAM assessed daily by blinded trained consultant psychiatrist trial collaborators

 

Secondary outcome: episodes, severity and subtypes of delirium; worst pain score over first 7 POD; length of hospitalization; 30-day all-cause mortality; predefined criteria for adverse events; 6-month and 1-year follow up for delirium incidence, type, and severity; cognitive function, quality of life, and mortality; hospitalization cost

- post hoc outcomes included subsyndromal delirium (presence of any CAM features with absence of full syndromal delirium) and delirium symptoms (subsyndromal delirium plus syndromal delirium)

 

Results: 950 participants were consented and randomly assigned to receive regional anesthesia (n=476) or general anesthesia (n=474); in each group 471 patients underwent surgery. The number of participants experiencing delirium on 1 or more occasions during first 7 POD were 29 in regional group (6.2%) and 24 in GA group (5.1%) (unadjusted risk difference [RD], 1.1%; 95% CI, –1.7% to 3.8%; P = .48; unadjusted relative risk [RR], 1.2 [95% CI, 0.7 to 2.0]; P = .57]). The severity, and frequency of episodes or subtypes of 7-day postoperative delirium were also not significantly different. No difference was found between groups for median worst pain scores or length of hospitalization. Adverse events were reported in 106 episodes in the regional anesthesia group (17.6%) and 102 in the general anesthesia group (16.8%), with the most frequently reported adverse events being nausea and vomiting (47 [44.3%] vs 34 [33.3%]) and postoperative hypotension (13 [12.3%] vs 10 [9.8%]). 

 

Discussion: In this trial, regional anesthesia without sedation compared to GA did not significantly reduce the incidence of postoperative delirium in patients aged 65 years and older undergoing hip fracture surgery. This trial is notably the largest study involving regional anesthesia without sedation for hip fracture surgery with postoperative delirium as an outcome. Limitations include that sample size was calculated based on a conservative estimate of CAM diagnosed postoperative delirium (26%), however in this trial the incidence was much lower than expected (5.1-6.2%) which would make it unlikely for it to be able to achieve statistical significance. Majority of participants were also recruited from a single hospital which may influence outcomes. Compared to cohorts from trials from other countries, these trials' mean age was substantially younger (77), compared to REGAIN trial (84). REGAIN reported a much higher incidence of delirium, similar between spinal and GA groups, however almost all patients in their regional group received sedation.