Cite as: Nanda M, Meng H. Literature review - February 2025. ASRA Pain Medicine News 2025;50. https://doi.org/10.52211/asra020125.014.

Literature Review

Acute Pain

By James C. Krakowski, MD, FASA, Monika Nanda, MBBS, MPH, FASA, Breethaa Janani Selvamani, MBBS, MD

Effect of Low-Dose Dexmedetomidine to Prolong Spinal Anesthesia in Elderly Patients: A Prospective Randomized Controlled Study

Sangkum L et al. BMC Anesthesiol 2024;24(1):427. https://doi.org/10.1186/s12871-024-02815-z

Summary by James C. Krakowski, MD, FASA

Introduction: Dexmedetomidine, an α-2 adrenoreceptor agonist, has been studied for its sedative and analgesic properties, which may prolong block duration. This study evaluates the effect of low-dose intravenous dexmedetomidine on spinal block duration, postoperative analgesia, and hemodynamic stability in elderly patients undergoing transurethral resection of the prostate (TURP).

Methods: This double-blind, randomized controlled trial included 38 patients aged 60–80 years scheduled for elective TURP under spinal anesthesia. Patients were randomized to receive 0.4 µg/kg of intravenous dexmedetomidine (Group D) or normal saline (Group C) following spinal anesthesia with 0.5% bupivacaine. The primary outcome measured was 2-dermatome regression time. Secondary outcomes included sensory block levels, hemodynamic changes, and postoperative pain scores at 0, 6, 12, and 24 hours. Patients and providers were blinded, and the analysis followed an intention-to-treat principle.

Results: Group D exhibited significantly prolonged 2-dermatome regression time as compared to Group C (104.44 ± 16.97 min vs. 80.63 ± 15.59 min; p < 0.05). The peak sensory block level was higher in Group D (median T7) than in Group C (median T10, p = 0.017). No significant difference in postoperative pain score or time to first analgesic use was observed. Both groups demonstrated similar incidences of hypotension and bradycardia with no complications reported.

Key Point: Low-dose intravenous dexmedetomidine significantly prolongs spinal anesthesia in elderly patients undergoing TURP, providing hemodynamic stability without increasing side effects, though postoperative analgesia outcomes remained unchanged.

Oral Ketamine for Acute Postoperative Analgesia (OKAPA) Trial: A Randomized Controlled, Single Center Pilot Study

Dinsmore M et al. J Clin Anesth 2025;100:111690. https://doi.org/10.1016/j.jclinane.2024.111690

Summary by Monika Nanda, MBBS, MPH, FASA

Introduction: Postoperative pain management after major spine surgeries remains a significant clinical challenge. While the use of intravenous ketamine is well-established for postoperative pain management, its oral form remains underexplored. This pilot study examined the feasibility, safety, and analgesic potential of low dose oral ketamine in postoperative pain management after multilevel spine surgery.

Methods: This prospective, double-blinded, placebo-controlled, randomized feasibility trial was conducted at Toronto Western Hospital. Forty adults undergoing multi-level lumbar spine surgery were randomized to receive either oral ketamine (30 mg liquid mixed in apple juice) or placebo every 8 hours for 3 days. Patients using up to 90 mg morphine equivalents per day were eligible for inclusion. The primary outcome was the Quality of Recovery-15 (QoR-15) score. Secondary outcomes included median opioid consumption as morphine equivalents, pain intensity, and pain interference measured by the Patient-Reported Outcomes Measurement Information System questionnaire. Data was collected preoperatively and on postoperative days 1,7 and 30.

Results: Data from 35 patients (18 ketamine, 17 placebo) was analyzed. There were no significant differences in QoR-15 scores or pain intensity. However, the ketamine group used significantly fewer oral opioids on postoperative days 3 and 7 and had fewer days on opioids overall. Adverse effects were minimal and comparable between groups.

Key Point: In this pilot study, low-dose oral ketamine was found to be a safe, novel, opioid-sparing adjunct for reducing opioid use after major spine surgery without increasing side effects. Future larger studies should address efficacy and dose-finding given the poor oral availability of ketamine.

Ultrasound-Guided Serratus Anterior Plane Block Versus Paravertebral Block for Postoperative Analgesia in Children Undergoing Video-Assisted Thoracoscopic Surgery: A Randomized, Comparative Study

Elemam E et al. J Cardiothorac Vasc Anesth 2024; S1053-0770(24)00761-4. https://doi.org/10.2147/JPR.S471813

Summary by Breethaa Janani Selvamani, MBBS, MD

Introduction: Postoperative pain control following pediatric surgeries is challenging. This study compared the analgesic efficacy of serratus anterior plane block (SAPB) and thoracic paravertebral block (PVB) in children undergoing video-assisted thoracoscopic surgeries (VATS).

Methods: This randomized trial enrolled 70 pediatric patients aged 2-10 years that underwent VATS. Patients were randomized into two groups, SAPB versus PVB. Following induction of general anesthesia, both groups received 0.4 ml/kg of 0.25% bupivacaine in the deep serratus anterior plane versus the paravertebral space under ultrasound guidance. The primary outcome was morphine consumption within the first 24 hours after surgery. The secondary outcomes included Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) score, intraoperative fentanyl consumption, and the time required to perform the block.

Results: Fifty-seven patients were analyzed. The morphine consumption in the first 24 hours postoperatively was similar between the SAPB and PVB groups (p=0.678). Similarly, intraoperative fentanyl consumption and postoperative CHEOPS scores were comparable between both the groups. The time needed to perform the block (minutes) was significantly (p<0.001) shorter in the SAPB group than in the PVB group.

Key Point: SAPB provides effective postoperative pain control that is comparable to thoracic PVB in pediatric VATS.

Chronic Pain

By Mohammad R. Rasouli, MD, Harsha Shanthanna. MD. PhD. FRCPC, and Vinita Singh, MD, MSCR

Post-Amputation Pain: Combined Analyses of Randomized Controlled Trials Evaluating Opioids and Gabapentinoids versus Placebo

Arthur A et al. J Pain Res 2024; 17:3449-53. https://doi.org/10.2147/JPR.S486220

Summary by  Mohammad R. Rasouli, MD

Introduction: Each year, approximately 185,000 patients in the United States undergo extremity amputation, often experiencing chronic post-amputation pain and reliance on chronic use of opioids. Efforts to maintain or improve the quality of life for patients suffering from post-amputation pain have primarily focused on pharmacologic treatments, including opioids and anticonvulsants; however, there is evidence of insufficient response to these medications. This study aims to analyze randomized controlled trials (RCTs) that evaluate the effectiveness of opioids and gabapentinoids, two commonly used pharmacologic treatments for post-amputation pain.

Methods: The authors used key words including “post-amputation pain,” “phantom pain,” and “residual limb pain” as well as additional keys words on PubMed to identify RCTs of pharmacological interventions. Studies that demonstrated significant post-amputation pain reduction (≥ 50%) with opioids or gabapentinoids were included.

Results: Four trials assessing post-amputation pain over 4 to 6 weeks were included, two involving morphine and two involving gabapentin. The combined analysis of morphine trials revealed that morphine significantly alleviated post-amputation pain compared to placebo (P=0.02) with a number needed to treat (NNT) of 3.9 (95% CI: 2.5 to 9.3). Similarly, gabapentin also showed efficacy compared to placebo (p=0.004) with an estimated NNT of 8.9 (95% CI: 5.3 to 27.8).

Key Point: Both opioids and gabapentin are effective in treatment of post-amputation pain; however, only a limited number of trials achieved ≥ 50% pain reduction, highlighting an unmet need for more effective pain management in this population. Future research should focus on larger RCTs with extended follow-up to address this gap.

Long-Term Use of Muscle Relaxant Medications for Chronic Pain, A Systematic Review

Oldfield BJ et al. JAMA Netw Open 2024;7(9):e2434835. https://doi.org/10.1001/jamanetworkopen.2024.34835

Summary by Harsha Shanthanna, MD, PhD, FRCPC

Introduction: There has been a significant increase in the use of skeletal muscle relaxants (SMRs) to avoid opioids for chronic pain. Prescription rates of SMRs doubled between 2005 and 2015 with physician visits tripling during the same period, indicating prolonged treatment with SMRs. This systematic review evaluates the effectiveness or efficacy of long-term SMR use for chronic pain.

Methods: Literature search was carried out in MEDLINE, Embase, Web of Science, CINAHL, and Cochrane registries for RCTs and cohort studies using SMRs for at least 1-month duration for chronic pain. Outcomes were pain severity, interference and quality of life. Quality assessment of RCTs was performed using the Cochrane Risk of Bias Tool for and the Newcastle-Ottawa Scales for cohort studies. The authors used a qualitative synthesis and a realist synthesis analytic approach that considers the interaction between context, mechanism, and outcome in evaluating an intervention.

Results: A total of 30 RCTs with 1,314 participants and 14 cohort studies with 1,168 participants were included. Common pain conditions were (n=10) headaches (including trigeminal neuralgia) and painful spasticity or cramps (n=10). The most common SMRs were baclofen (11 studies) and tizanidine (8 studies). Evidence of benefit was noted for

trigeminal neuralgia, neck pain, and painful cramps, while no benefit as compared to placebo were noted for other conditions, including low back pain and fibromyalgia.

Key Point: Patients prescribed SMRs for chronic pain must be assessed for effectiveness and adverse effects. Physicians should consider deprescribing if there are no improvements in pain or related goals.

Spinal Cord Stimulation vs Medical Management for Chronic Back and Leg Pain: A Systematic Review and Network Meta-Analysis

Huygen FJPM et al. JAMA Netw Open 2024;7(11):e2444608. https://doi.org/10.1001/jamanetworkopen.2024.44608

Summary by Vinita Singh, MD, MSCR

Introduction: Spinal cord stimulation (SCS) is a recognized therapy for chronic back and leg pain. In the past decade, novel forms of SCS (eg, burst, high frequency, differential target multiplexed, and closed-loop stimulation) have been introduced, promising enhanced efficacy over conventional SCS (tonic stimulation). Prior meta-analyses often excluded these novel therapies, necessitating an updated review of their effectiveness.

Methods: This systematic review and Network Meta-Analysis (NMA) evaluated RCTs comparing conventional and novel SCS therapies with conventional medical management (CMM). Studies published between January 1946 and September 2, 2022, were analyzed focusing on pain intensity, responder rates (≥50% pain reduction), quality of life, and disability indices. The Bayesian NMA framework enabled the inclusion of both direct and indirect evidence to synthesize results across treatments.

Results: A connected network of evidence was established for 13 RCTs (n=1561) from 31 eligible studies. Both conventional and novel SCS therapies were superior to CMM for responder rates in back pain (conventional SCS: OR, 3.00; 95% Crl [credible interval], 1.49 to 6.72; novel SCS: OR, 8.76; 95% Crl, 3.84 to 22.31), pain intensity in back (conventional SCS: MD, -1.17; 95% Crl, -1.64 to -0.70; novel SCS: MD, -2.34; 95% Crl, -2.96 to -1.73), pain intensity in leg (conventional SCS: MD, -2.89; 95% Crl, -4.03 to -1.81); novel SCS: MD, -4.01; 95% Crl, -5.31 to -2.75), and EQ-5D index score (conventional SCS: MD, 0.15; 95% Crl, 0.09 to 0.21; novel SCS: MD, 0.17; 95% Crl, 0.13 to 0.21). Conventional SCS was superior to CMM for functional disability (MD, -7.10; 95% Crl, -10.91 to -3.36). No statistically significant differences were observed for other comparisons.

Key Point: Both conventional and novel SCS therapies offer superior efficacy over CMM with novel SCS providing the greatest improvements in pain and quality of life outcomes.