Literature Review - February 2022

Feb 7, 2022, 00:04 AM by Anthony Machi, MD

Cite as: Machi A. Literature review - February 2022. ASRA Pain Medicine News 2022;47.


Editor’s note: “Literature Review” is a feature designed to provide you with brief summaries of recent articles of interest, particularly from sources that our readers might not normally consume. 

Spinal Anesthesia or General Anesthesia for Hip Surgery in Older Adults

Neuman MD, Feng R, Carson JL, et al. N Engl J Med. 2021 Nov 25; 385(22):2025-35.

Introduction: Observational studies suggest benefits such as lower risk of death, delirium, and major medical complications to performing spinal anesthesia for hip fracture surgery rather than general anesthesia. Large, randomized trials assessing functional recovery and longer-term patient-centered outcomes after hip fracture surgery following spinal anesthesia versus general anesthesia are lacking. The authors hypothesized that patients receiving spinal anesthesia would have a lower mortality rate and higher likelihood of walking independently at 60 days than those receiving general anesthesia.

Methods: The authors conducted a multicenter, pragmatic, randomized superiority trial (Regional versus General Anesthesia for Promoting Independence after Hip Fracture—REGAIN). In all, 46 hospitals in the United States and Canada participated, and researchers enrolled adults 50 years or older having surgical fixation for femoral neck, intertrochanteric, or subtrochanteric hip fracture. Subjects were randomized to receive spinal or general anesthesia. The primary outcome was a composite of death or inability to walk 10 feet independently at 60 days after surgery.

Results: 1,600 patients were enrolled. The composite primary outcome of death or inability to walk occurred in 132/712 (18.5%) of patients who received spinal anesthesia and 132/733 (18%) of patients who received general anesthesia. Secondary outcomes including death during hospitalization, risk of acute kidney injury and ICU admission favored spinal anesthesia. The incidence of delirium and hospital length of stay were similar.

Key point: Spinal anesthesia was not superior to general anesthesia for the composite outcome of survivability and independent ambulation at 60 days after hip fracture surgery.


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

Li T, Li J, Yuan L, et al. JAMA. 2022 Jan 4;327(1):50-8.

Introduction: Postoperative delirium is a common problem after hip fracture surgery associated with worse outcomes. Observational studies support a lower risk of postoperative delirium when regional anesthesia is utilized relative to general anesthesia. Previous randomized trials are limited by size and methodology. The authors hypothesized that patients receiving regional (neuraxial) anesthesia would have a lower incidence of postoperative delirium in the first 7 days after surgery than patients receiving general anesthesia.

Methods: The authors conducted a pragmatic, randomized multicenter superiority trial (Regional Anesthesia vs General Anesthesia—RAGA). Nine hospitals in China participated, and researchers enrolled patients 65 years or older who had femoral neck, femoral head, intertrochanteric, or subtrochanteric hip fracture. Randomization was stratified to center, age, and presence or absence of preoperative delirium or dementia. Delirium was assessed with the Confusion Assessment Method (CAM). Dementia was assessed with the 30-point Mini Mental State Exam. Patients receiving regional had neuraxial anesthesia without sedation. Peripheral nerve blocks were encouraged in both groups. The primary outcome was assessed with the CAM once daily for the first 7 postoperative days and by chart review of the preceding 24 hours.

Results: 950 patients were enrolled, and 941 were analyzed for the primary outcome. Postoperative delirium occurred in 29/471 (6.2%) in the regional anesthesia group and 24/470 (5.1%) in the general anesthesia group. The severity of delirium, type of delirium and adverse events were similar in both groups.

Key point: The risk of postoperative delirium was not reduced by the use of regional anesthesia without sedation rather than general anesthesia in patients aged 65 or older who underwent surgery for hip fracture.


A Repeat Dose of Perioperative Dexamethasone Can Effectively Reduce Pain, Opioid Requirement, Time to Ambulation, and In-Hospital Stay After Total Hip Arthroplasty: A Prospective Randomized Controlled Trial

Lucero C, Garcia-Mansilla A, Zanotti G, et al. J Arthroplasty. 2021 Dec;36(12): 3938-44.

Introduction: Total hip arthroplasty (THA) is a common surgical procedure associated with moderate-to-severe acute postoperative pain. Dexamethasone is a potent glucocorticoid with analgesic efficacy in this patient population. The optimal dose and frequency for analgesia for this surgery are unknown. The authors hypothesized that patients receiving two doses of dexamethasone would have less pain than those receiving one dose.

Methods: A single-center, single-blinded, randomized trial was performed. Researchers enrolled patients aged 18 or older undergoing unilateral primary total hip replacement. Subjects were randomized in a 1:1 ratio to receive either a one-time dose of dexamethasone 8 mg at induction of anesthesia or two doses of dexamethasone 8 mg with the first dose occurring at induction of anesthesia and the second dose eight hours later. Pain was assessed with the visual analog scale at 8-, 16- and 24-hours following surgery. All patients received spinal anesthesia, local infiltration at the site of surgery, and multimodal analgesia with acetaminophen and celecoxib and tramadol for breakthrough pain. Peripheral nerve blocks were not performed.

Results: 58 patients were enrolled to the one-dose group and 66 to the two-dose group, with 54 and 61 subjects analyzed respectively. There was no difference in pain-VAS at 8 hours but a significant difference at 16 and 24 hours (2[IQR1-3] and 1[IQR0-1] vs 4[IQR3-5] and 2.5[IQR2-3], p<0.0001). Opioid requirements and postoperative nausea and vomiting were higher in the one-dose group. Other adverse events were similar in both groups.

Key point: Repeat dosing of dexamethasone is associated with improved analgesia following THA. Larger trials are recommended to examine the efficacy and safety of perioperative repeat dosing of dexamethasone for THA.


Factors Associated with Implantable Pulse Generator Site Pain: A Multicenter Cross-Sectional Study

Choi H, Gaiha R, Moeschler SM, et al. Neuromodulation. 2021 Dec;24(8):1351-6.

Introduction: Pain associated with the implantable pulse generator (IPG) is a recognized complication of neuromodulation systems causing significant morbidity that requires surgical revision in 10-20% of cases. Risk factors for IPG site pain are not well delineated. The authors sought to characterize factors related to IPG site pain.

Methods: A multicenter cross-sectional survey of patients was conducted at two medical centers in the United States. Patients who had undergone placement of a permanent neuromodulation system with IPG including spinal cord stimulator (SCS), deep brain stimulator (DBS), and sacral nerve stimulator between January 1, 2010, and December 31, 2015, were included. Patients were mailed a questionnaire inquiring about pain incidence, severity, and frequency at the IPG site; impairment of daily activity; and other factors. Demographic data and technical information regarding the IPG were obtained from the medical record.

Results: 844 patients were identified, and 424 completed surveys were analyzed for the study. The incidence of any chronic IPG site pain was 31.1% with mild, moderate, and severe pain reported by 68.2%, 24.2%, and 7.6% of patients, respectively. Patients with SCS were twice as likely to experience IPG site pain as those with DBS or sacral nerve stimulator (RR = 2.0, 95% CI = 1.45-2.89), which was similar to the increased risk of pain at an IPG site in the back/gluteal region.

Key point: The incidence of chronic IPG site pain was 31.1% in this patient population, with 7.6% of patients experiencing severe pain and with a higher incidence of IPG site pain occurring in patients receiving SCS.


Examination of the Contribution of Nav1.7 to Axonal Propagation in Nociceptors

Goodwin G, McMurray S, Stevens EB, et al. Pain. 2021 Sep 23. Published ahead of print.

Introduction: There are 9 different voltage-gated sodium channel alpha subtypes (Nav1.1-1.9), of which 5 are expressed in sensory neurons and of which 3 are important in peripheral pain transmission (Nav1.7-1.9). Of these, Nav1.7 is an important target for analgesic drugs because loss of function at this channel causes insensitivity to pain without other deficits, except anosmia. However, previous examinations have revealed discordance between analgesia produced by Nav1.7 loss-of-function and peripherally restricted Nav1.7 inhibitors, many of which failed to progress in clinical trials for lack of efficacy. The consequence of Nav1.7 inhibition at peripheral nociceptor axons is not well defined.

Methods: The authors examined the role of Nav1.7 to axonal propagation in nociceptors using sodium channel blockers in in vivo electrophysiological and calcium imaging recordings in mice. The sodium channel blockers tetrodotoxin (TTX) (1-10 µM) and PF-05198007 (300 nM-1µM) were applied to the sciatic nerves of mice between stimulating and recording sites.

Results: 10 µM TTX blocked 66.3% heat-sensitive nociceptors innervating the skin and 45% innervating muscle. A similar proportion of heat sensitive nociceptors were blocked with PF-05198007.

Key point: Approximately one-third of nociceptors do not depend on Nav1.7 or other TTX-S NavS for axonal propagation. Many muscle nociceptors also do not depend on Nav1.7 for propagation. This may explain why previous peripheral Nav1.7 inhibitors lacked efficacy for chronic pain. Pharmacologic agents that can penetrate the blood-brain barrier and engage central Nav1.7 channels remain potential effective analgesic agents.



Machi_Anthony LR


Anthony Machi, MD, is an assistant professor in the department of Anesthesiology and Pain Management at the University of Texas (UT) Southwestern Medical Center in Dallas. Dr. Machi is also the program director for the fellowship in regional anesthesiology and acute pain medicine.


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