Pilot Randomized Controlled Trial of Spinal Versus General Anesthesia for Hip Fracture Surgery

To the Editor: Each year, more than 250,000 older U.S. adults experience hip fractures.1 Few randomized studies are available regarding the effect of anesthesia on outcomes after hip fracture surgery,2 and the feasibility of randomized studies in this context has been questioned.3 A pilot study (ClinicalTrials.gov identifier NCT02190903) was conducted at one urban academic health system to explore the feasibility of a prospective, randomized trial to compare outcomes of hip fracture surgery with spinal versus general anesthesia. After institutional review board approval was received, 12 participants were randomized to receive spinal anesthesia with intravenous sedation or general anesthesia for hip fracture surgery. Inclusion criteria were aged 18 and older, femoral neck or pertrochanteric hip fracture requiring surgery, and ability to speak English and provide written informed consent. Exclusion criteria were pathological or periprosthetic fracture, concurrent conditions requiring surgery (e.g., multitrauma, acute cholecystitis), Montreal Cognitive Assessment4 score less than 16, delirium at time of screening, known contraindications to spinal anesthesia or volatile general anesthetics, and pregnancy. All enrolled individuals provided written informed consent and underwent an interview with a trained research coordinator to assess eligibility and to complete a brief medical history interview, the Montreal Cognitive Assessment, and a delirium screen using the Confusion Assessment Method (CAM).5 Blinded research coordinators assessed outcomes daily on Postoperative Days (PODs) 1 through 5 or through discharge for participants discharged before POD 5. The primary outcome was new diagnosis of delirium as determined according to a positive CAM screen at any point during POD 1 through 5 or between randomization and discharge for participants discharged before POD 5. Because the primary goal was to assess study feasibility, rather than to make efficacy comparisons, a formal power calculation was not conducted; instead a sample size of 12 participants was chose as sufficient to yield information for future study planning. Data were analyzed according to intention to treat using Fisher exact tests and the Wilcoxon rank-sum test. The study CONSORT diagram appears in Figure 1. Eighty individuals with hip fracture were assessed for eligibility between July 2014 and March 2015; 15 completed informed consent, and 12 were randomized, six of whom were assigned to general anesthesia and six to spinal anesthesia. Five (83%) in the general anesthesia arm and four in the spinal anesthesia arm (67%) were male (P > .99). The median age of participants randomized to receive general anesthesia was 62.5 (range 57–88) and of those randomized to spinal anesthesia was 80.5 (range 62–92) (P = .17). Three (50%) participants in the general anesthesia arm and two (33%) in the spinal anesthesia arm had one or more major comorbidities (P > .99). Three (50%) participants in the general anesthesia arm and four in the spinal anesthesia arm had femoral neck fractures; three (50%) in the general anesthesia arm and two (33%) in the spinal anesthesia arm had pertrochanteric fractures (P > .99). All six participants in the general anesthesia arm received general anesthesia; in the spinal anesthesia arm, four (67%) participants received spinal anesthesia and two (33%) received general anesthesia because of inability to place the spinal block. Postoperative delirium occurred in two (33%) participants randomized to receive general anesthesia and none randomized to receive spinal anesthesia (P = .45). There were no in-hospital deaths; one participant in the general anesthesia arm experienced a nonfatal postoperative myocardial infarction. This pilot study provides several insights into the feasibility of randomized controlled trials to compare outcomes of individuals receiving spinal with outcomes of those receiving general anesthesia for hip fracture surgery. These insights have informed the implementation of the Regional vs. General Anesthesia for Promoting Independence after Hip Fracture Surgery trial, a multicenter pragmatic study funded by the Patient Centered Outcomes Research Institute to compare short- and long-term outcomes of 1,600 individuals with hip fracture randomized to spinal or general anesthesia (ClinicalTrials.gov identifier NCT02507505). First, 12 of 36 individuals initially assessed as meeting study inclusion criteria (33%) were successfully randomized, a relatively high rate given the context of an acute traumatic injury in a frail elderly population. Second, because there was a 33% rate of crossover from spinal to general anesthesia, this pilot study highlights the importance of rigorous participant selection and proper spinal technique for limiting crossover in future studies. Finally, there was a high degree of acceptance among the clinical staff for the study treatment regimens, further supporting the feasibility of further large-scale randomized comparisons of spinal and general anesthesia for hip fracture surgery. Conflict of Interest: The authors have no conflicts to report. Funded by National Institute on Aging Grant K08AG043548–04 to MDN. Author Contributions: Neuman M.D.: obtaining funding; study concept and design; acquisition, analysis, and interpretation of data; writing first draft of manuscript; critical revision of manuscript; final approval of submitted manuscript. Mehta S.: study concept and design, analysis and interpretation of data, critical revision of manuscript, final approval of submitted manuscript. Bannister E.R.: acquisition, analysis, and interpretation of data; critical revision of manuscript; final approval of submitted manuscript. Hesketh P.J.: acquisition and analysis of data, critical revision of manuscript, final approval of submitted manuscript. Horan A.D. and Elkassabany N.M.: study concept and design, interpretation of data, critical revision of manuscript, final approval of submitted manuscript. Sponsor's Role: The study sponsor had no role in the design, methods, subject recruitment, data collections, analysis, or preparation of the paper.