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The Efficacy of Erector Spinae Plane Block Versus Subcostal Transversus Abdominis Plane Block in Laparoscopic Nephrectomy: A Randomized Clinical Trial.

OBJECTIVES: This study compared the efficacy and safety of erector spinae plane block (ESPB) versus subcostal transversus abdominis plane (TAP) block in reducing postoperative pain among patients undergoing laparoscopic nephrectomy. METHODS: This randomized clinical trial enrolled 70 adult patients, ASA physical status I or II, who underwent total (radical) laparoscopic nephrectomy under general anesthesia. Patients were randomly assigned to 2 groups. Group ESPB received an ultrasound-guided ESPB at the T7 transverse process level, while group TAP received an ultrasound-guided subcostal TAP block. The primary outcome was the total amount of morphine consumed at 6 and 24 hours postoperatively. Secondary outcomes included the incidence of patients requiring opioid analgesia, time to rescue analgesia, visual analog scale of pain intensity, time to postoperative ambulation, intraoperative and postoperative hemodynamics, arterial partial pressure of oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 or P /F) ratio, and incidence of complications. RESULTS: Compared with the TAP group, the ESPB group exhibited significantly lower median morphine consumption at 24 hours ( P =0.032), prolonged time to first analgesic rescue ( P =0.049), and lower incidence of rescue morphine requirement (OR=0.23; 95% CI=0.06-0.94; P =0.031), with lower visual analog scale pain scores at 12, 18, and 24 hours postoperatively ( P <0.001). The mean arterial blood pressure and heart rates were comparable between groups. No significant adverse effects from either approach. DISCUSSION: In laparoscopic nephrectomy, ultrasound-guided ESPB may safely and effectively be used to improve pain management and reduce pain intensity, with stable hemodynamics and a comparable risk of postoperative complications to the ultrasound-guided subcostal TAP block.

Humans

Clinical effectiveness of transversus abdominis plane block versus local anaesthesia wound infiltration for postoperative pain relief after laparoscopic appendicectomy in children: A multicentre, double-blind, randomised, controlled phase III trial.

BACKGROUND: Postoperative pain relief after laparoscopic appendicectomy in children provided by transversus abdominis plane (TAP) block and local anaesthesia wound infiltration (LAWI) of trocar insertion sites has never been compared. OBJECTIVE: To investigate whether TAP block could decrease postoperative opioid requirements after laparoscopic appendicectomy in children compared with LAWI. DESIGN: Multicentre, double-blind, phase III randomised trial. SETTING: Two tertiary paediatric surgery centres. PATIENTS: Children aged 3 to 15&#x200a;years admitted for laparoscopic appendicectomy. MAIN OUTCOME MEASURES: The primary outcome was the total dose of nalbuphine delivered within 24&#x200a;h after surgery. Secondary outcomes were the Face Legs Activity Cry Consolability (FLACC) scale values at 1, 2, 6, 12 and 24&#x200a;h, the time from levobupivacaine injection to the first dose of nalbuphine, and the time from the end of surgery to the first mobilisation. Patients received either ultrasound-guided TAP block (TAP group) or LAWI of trocar insertion sites (infiltration group) with 0.6&#x200a;ml&#x200a;kg -1 of levobupivacaine 2.5&#x200a;mg&#x200a;ml -1 , combined with standardised systemic multimodal analgesia including paracetamol, ketoprofen, phloroglucinol and nalbuphine. RESULTS: Forty-six and 50 patients were analysed in the TAP and infiltration groups, respectively [age: 10 [7 to 12] versus 10 [8 to 12] years; females: 16 (35%) versus 25 (50%); duration of surgery: 71 [64 to 90] versus 69 [56 to 89] min]. The primary outcome (total nalbuphine dose) was 0.2 [0.0 to 0.2] and 0.2 [0.0 to 0.2] mg&#x200a;kg -1 in the TAP and infiltration groups, respectively ( P &#x200a;=&#x200a;0.95). FLACC scale values did not significantly differ between the two groups ( P &#x200a;=&#x200a;0.78). Time to the first dose of nalbuphine or to first mobilisation was not significantly different between groups ( P value for log-rank test&#x200a;=&#x200a;0.095 and 0.18, respectively). CONCLUSION: TAP block does not appear to provide a greater opioid-sparing effect than LAWI of trocar insertion sites after laparoscopic appendicectomy in children, when combined with systemic multimodal analgesia including nonsteroidal anti-inflammatory drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04969133.

Humans

The analgesic efficacy of intrathecal morphine compared to peripheral regional analgesia in total hip arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Following elective total hip arthroplasty, pain continues to be a significant problem. Intrathecal morphine or peripheral regional analgesia, that is local infiltration analgesia or peripheral nerve block, are common analgesic modalities, but it is still not known which is superior. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: The following electronic databases were searched from inception to 24 March 2026: CENTRAL; Ovid Embase; Ovid MEDLINE; Scopus; and Web of Science. ELIGIBILITY CRITERIA: Randomised controlled trials that compared intrathecal morphine to peripheral regional analgesia in patients scheduled for elective total hip arthroplasty under general or spinal anaesthesia. RESULTS: Eight trials and 471 patients were included. The peripheral regional analgesia was peripheral nerve block in six trials and local infiltration analgesia in two trials. No difference was demonstrated between intrathecal morphine and peripheral regional analgesia in regard to the first coprimary outcome, the pain score at rest at 24&#x200a;h. The quality of evidence was moderate. Intrathecal morphine was found to be superior to peripheral regional analgesia with respect to the second coprimary outcome, the cumulative intravenous morphine equivalent consumption at 24&#x200a;h. Mean difference (95% CI) was 11.38&#x200a;mg (4.31-18.45; P &#x200a;=&#x200a;0.002, I2 &#x200a;=&#x200a;81%). The quality of evidence was low. Intrathecal morphine was revealed to be superior to peripheral regional analgesia at 8-12&#x200a;h for the pain score at rest, 1.24 (0.60-1.88); P &#x200a;=&#x200a;0.0001, I2 &#x200a;=&#x200a;68%; pain score on movement, 1.15 (0.12-2.17), P &#x200a;=&#x200a;0.03, I2 &#x200a;=&#x200a;65%; but the rate of in hospital pruritus was reduced with peripheral regional analgesia, 0.31 (0.17-0.58), P &#x200a;=&#x200a;0.0002, I2 &#x200a;=&#x200a;0%. No differences in functional status were shown. CONCLUSIONS: We found no difference between intrathecal morphine and peripheral regional analgesia in regard to pain score at rest at 24 h. Intrathecal morphine may lead to a favourable effect on some but not all analgesic indices compared to peripheral regional analgesia in elective total hip arthroplasty. The quality of evidence for these positive effects was low. Intrathecal morphine reduced the systemic opioid consumption, but is not in itself an opioid free strategy. This notion is supported by the increased incidence of in hospital pruritus with intrathecal morphine. The quality of evidence for this was high. In view of the quality of evidence, high quality randomised controlled trials are required to substantiate these results.

Humans

Comparison of analgesic efficacy of pericapsular group of nerve block versus anterior quadratus lumborum block in adult patients undergoing unilateral hip arthroplasty: A comparative randomized controlled trial.

BACKGROUND: Total hip arthroplasty is a painful surgical procedure; therefore, it is a challenge to manage effective pain control during the perioperative period. STUDY OBJECTIVES: We compared the analgesic efficacy of the pericapsular nerve group block and the anterior quadratus lumborum block in patients undergoing unilateral hip arthroplasty. DESIGN: Randomized controlled trial. SETTINGS: Operating room of a tertiary care center. PATIENTS: 92 adult patients of >18&#xa0;years who underwent elective, unilateral total hip arthroplasty under spinal anesthesia were randomized to either Group P (USG guided PENG block with 30&#xa0;ml 0.25% ropivacaine +4&#xa0;mg dexamethasone) or Group Q (USG guided QL block with 30&#xa0;ml 0.25% ropivacaine +4&#xa0;mg dexamethasone) 20&#xa0;min before surgery. MEASUREMENTS: We compared the total perioperative fentanyl consumption between the two groups in the first 24&#xa0;h as the primary outcome. Other outcomes included time to first rescue analgesia in the postoperative period, NRS scores at rest and on movement at 0, 2, 4, 6, 12, and 24&#xa0;h, incidence of intraoperative hemodynamic changes, and incidence of postoperative PONV. MAIN RESULTS: There was no significant difference in the total fentanyl consumption between the two groups: 237.5 (150-450) &#x3bc;g in the P group and 250 (125-400) &#x3bc;g in the Q group; p&#xa0;=&#xa0;0.617. The time to first rescue analgesia was similar in both groups: the P group (198 [123-268] minutes) and the Q group (241 [180-318] minutes); p&#xa0;=&#xa0;0.120. There was also no difference in pain scores, intraoperative hemodynamic changes, or PONV. CONCLUSION: There was no difference in the perioperative opioid consumption, pain scores, and adverse event rates between the pericapsular nerve group block and anterior quadratus lumborum block in adult patients undergoing unilateral hip arthroplasty. TRIAL REGISTRATION: Clinical Trials Registry of India (CTRI number: CTRI/2023/08/057157).

Humans

Evaluation of the intraoperative analgesic effects of perioperative electroacupuncture: a randomised, blinded clinical trial in dogs.

OBJECTIVE: To evaluate the effect of perioperative electroacupuncture (EA) on intraoperative analgesic requirements in dogs undergoing tibial tuberosity advancement (TTA) surgery. STUDY DESIGN: Prospective, randomised, blinded, controlled clinical study. ANIMALS: A group of 29 client-owned dogs diagnosed with cranial cruciate ligament rupture that underwent TTA surgery. METHODS: Dogs were treated with EA at predefined acupuncture points (LI-4, ST-36, LIV-3, SP-6 and GB-34) perioperatively as additional analgesia (group EA, n = 14) or were allocated to the control group (group C, n = 15). All dogs were anaesthetised with a standardised protocol including methadone, dexmedetomidine, propofol and ketamine. The intraoperative delivery of sevoflurane and fentanyl was guided in response to signs of nociception by a purpose-designed flowchart, by the same anaesthetist who was blinded to treatment group. A Wilcoxon rank sum test was applied for the fentanyl consumption analysis. Heart rate, mean arterial blood pressure and end-tidal sevoflurane were descriptively analysed between groups for specific time points. A p value < 0.05 was considered significant. RESULTS: The EA group needed significantly less fentanyl with 0.7 (0-2.7) &#x3bc;g kg-1 hour-1 administered versus 2.0 (1.2-5.5) &#x3bc;g kg-1 hour-1 in group C (p = 0.031). Fifty percent of the EA group was not administered a fentanyl bolus, whereas all dogs in group C required at least one bolus. CONCLUSIONS AND CLINICAL RELEVANCE: Perioperative EA reduced mean fentanyl consumption by more than 60% in dogs undergoing TTA surgery.

Animals

Application of SPI-guided analgesia in laparoscopic gynecologic surgery: a randomized controlled trial evaluating the remifentanil-sparing effect and predictive value of time-weighted SPI.

This study aimed to achieve two primary objectives: (1) to evaluate the opioid-sparing effect of Surgical Pleth Index (SPI)-directed analgesia during surgery via a randomized controlled trial (RCT), and (2) to propose and preliminarily assess a novel dynamic metric, Threshold-based Time-Weighted SPI (Tb-TW-SPI), which integrates stimulus intensity and duration, for its predictive efficacy regarding postoperative moderate-to-severe pain. Employing an RCT combined with exploratory analysis, 61 patients undergoing elective laparoscopic gynecologic surgery were randomized into an SPI-directed analgesia group or a conventional analgesia group. The primary outcome was total intraoperative remifentanil consumption. Postoperatively, an exploratory analysis of the control group data evaluated the correlation between Tb-TW-SPI and Numeric Rating Scale (NRS) pain scores in the post-anesthesia care unit (PACU), calculating its predictive value for moderate-to-severe pain (NRS&#x2009;&#x2265;&#x2009;4). Results: The SPI-directed group required significantly less intraoperative remifentanil than the conventional group [median (IQR): 5.84(5.02,6.62)vs. 6.96(5.81,8.19)&#xb5;g/kg/h; P&#x2009;=&#x2009;0.016]. Postoperative pain scores did not differ significantly between groups (P&#x2009;>&#x2009;0.05). Exploratory analysis of the conventional analgesia group revealed that Tb-TW-SPI values were significantly higher in patients with moderate-to-severe postoperative pain (NRS&#x2009;&#x2265;&#x2009;4) compared to those without (P&#x2009;=&#x2009;0.0417).The area under the ROC curve for Tb-TW-SPI predicting this pain was 0.74 (95% CI: 0.52-0.96), with 67% sensitivity and 76% specificity at an optimal cutoff of 1210. This RCT suggests that SPI-directed analgesia can safely and moderately reduce intraoperative remifentanil consumption. Furthermore, the proposed Tb-TW-SPI metric, in this exploratory analysis, suggests potential for predicting postoperative pain, though this finding requires validation in larger cohorts with higher-frequency SPI sampling, offering a new direction for SPI interpretation. Large-scale, multicenter trials are warranted to validate the predictive utility of Tb-TW-SPI. Clinical Trial Registration, China Clinical Trial Registry: ChiCTR2400088444.

Humans

Naltrexone Is Superior to Placebo for Abstinence and Craving Reduction in Alcohol-Associated Cirrhosis: NAL-CI Trial.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) coexisting with cirrhosis carries high morbidity and mortality, with no approved pharmacotherapy for AUD. We evaluated the safety and efficacy of naltrexone, an opioid receptor antagonist, in patients with compensated alcohol-associated cirrhosis (AaC) and AUD. METHODS: One hundred patients with compensated AaC and DSM-5 AUD were randomised 1:1 to naltrexone (50&#x2009;mg/day) or placebo for 12&#x2009;weeks. The primary endpoint was point-prevalence abstinence at 12&#x2009;weeks, defined as no alcohol use in the four preceding weeks. Secondary endpoints included craving (Obsessive Compulsive Drinking Scale [OCDS]-Obsessive and Compulsive subscales), lapses, relapses, and hepatic safety. Standardised psychosocial support was provided to both arms. RESULTS: Baseline characteristics were well matched between groups (mean MELD 12.6 vs. 12.7; CTP score 5.9 vs. 6.2; age 42.9 vs. 44.3&#x2009;years). AUDIT and OCDS scores were comparable between groups. Abstinence at 12&#x2009;weeks was significantly higher with naltrexone: 64% (32/50) versus 22% (11/50), p&#x2009;<&#x2009;0.001; OR 10.86 (95% CI: 1.89-62.2). Naltrexone significantly reduced lapses at 3&#x2009;months (28% vs. 54%, p&#x2009;=&#x2009;0.008) and showed a trend toward fewer heavy-drinking relapses (12% vs. 28%, p&#x2009;=&#x2009;0.07). Maintenance of abstinence at 6&#x2009;months favoured naltrexone (22% vs. 8%, p&#x2009;=&#x2009;0.09). No patient developed hepatic decompensation attributable to study medication, and no AST/ALT elevation exceeding 5&#xd7; ULN was observed in either group. Mean craving scores were lower with naltrexone by week 12 than with placebo: OCDS-O score (6.63&#x2009;&#xb1;&#x2009;1.16 vs. 9.29&#x2009;&#xb1;&#x2009;1.78, p&#x2009;<&#x2009;0.01) and OCDS-C score (6.35&#x2009;&#xb1;&#x2009;1.23 vs. 9.02&#x2009;&#xb1;&#x2009;1.86, p&#x2009;<&#x2009;0.01). Adverse events were comparable between the groups. CONCLUSION: Naltrexone is safe and effective in patients with compensated alcohol-associated cirrhosis, achieving a threefold higher abstinence rate and significantly reducing craving compared with placebo. These findings support the use of naltrexone as a pharmacological option in patients with compensated AaC and AUD. TRIAL REGISTRATION: NCT04391764.

Humans

Evaluating the utility of melatonin in spine surgery: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Spine surgery is increasingly performed worldwide, and acute postoperative stressors such as pain and anxiety remain highly prevalent despite historical management with opioids and other pharmacological agents. Recently, interest has emerged in melatonin administration given its endogenous physiological roles, low cost, favorable adverse event profile, and documented benefits throughout surgical literature. PURPOSE: This study aims to consolidate the existing evidence on melatonin's utility specifically in spine surgery, an area not yet comprehensively evaluated, to inform clinical practice and enhance spine surgeon comprehension. STUDY DESIGN/SETTING: Preregistered on PROSPERO, this systematic review queried PubMed/MEDLINE, CINAHL, SPORTDiscus, and Web of Science on November 21st, 2025, for studies reporting outcomes following melatonin administration in patients undergoing spine surgery. METHODS: Study quality was assessed using the Cochrane Risk-of-Bias 2 tool. Extracted variables included demographics, comparator medications, dosages, and other relevant details. Statistical analyses included frequency-weighted means (FWMs), associated standard deviations, narrative syntheses, and limited meta-analyses, where appropriate. RESULTS: A total of 6 moderate-quality randomized trials were included from 749 screened. Melatonin (3-10 mg) was administered to 227 patients (FWM age=43.3&#xb1;8.6 years; 46.2% male; BMI=26.6&#xb1;3.2 kg/m2), placebo to 125 patients (age=43.2&#xb1;10.1 years; 60% male; BMI=28.5&#xb1;4.3 kg/m2), and active pharmacologic comparators (fentanyl, gabapentin, dexmedetomidine, zolpidem) to 151 patients (age=46.6&#xb1;8.9 years; 40.5% male; BMI=26.3&#xb1;3.5 kg/m2). Procedures primarily involved uncomplicated lumbar laminectomies (1-4 levels), with outcomes assessed up to 24 hours postoperatively. Melatonin was associated with significant improvements in early postoperative VAS-pain scores, blood-pressure-related, analgesic-related, and anxiety-related outcomes versus placebo across most reporting studies. Compared with active pharmacologic agents, significant benefits were observed only in select nausea- and anxiety-related instances. Limited meta-analysis (n=2) demonstrated higher 24-hour VAS-pain for melatonin versus gabapentin, though mean difference was near-negligible and harbored extensive statistical constraints. CONCLUSION: Melatonin demonstrates variable utility following spine surgery, with generally consistent anxiolysis and frequent benefit versus placebo but less consistent and comparatively weaker efficacy relative to active pharmacologic comparators. Future outcome-homogenous studies incorporating more granular, expansive comparator arms and more robust quantitative analyses are needed to further elucidate melatonin's role in advancing spine care. LEVEL OF EVIDENCE: Level II.

Humans

Impact on analgesia, diaphragmatic function, and recovery between erector spinae plane block versus superior trunk block in arthroscopic shoulder surgery: a randomized controlled trial.

BACKGROUND: Effective analgesia and preservation of diaphragmatic function are key considerations in analgesia for shoulder surgery. The superior trunk block provides analgesia with reduced phrenic nerve involvement, while the erector spinae plane block offers minimal impact on diaphragm motion. This randomized controlled trial compared the analgesic efficacy, impact on diaphragmatic motion, and postoperative recovery between the two blocks. METHODS: Sixty patients undergoing arthroscopic shoulder surgery were randomized to receive either erector spinae plane block or superior trunk block. Primary outcomes were postoperative VAS and changes in diaphragmatic excursion. Secondary outcomes included Quality of Recovery-15 (QoR-15) scores, morphine-equivalent consumption, and the handgrip strength motor blockade. RESULTS: The superior trunk block resulted in significantly lower dynamic VAS at 1-h postoperatively (0.1 [0.0, 0.2] vs. 5.7 [4.0, 7.6]; p&#x2009;<&#x2009;0.001) and reduced 24-h morphine consumption (7.8 [2.5, 15.0] mg vs. 12.7 [7.5, 17.3] mg; p&#x2009;=&#x2009;0.038) compared to the erector spinae plane block. However, diaphragmatic excursion was better preserved in the erector spinae plane block group (8.37% &#xb1; 20.7% vs. -20.09% &#xb1; 22.2%; p&#x2009;<&#x2009;0.001), with a lower incidence of partial hemidiaphragm paresis (3.3% vs. 46.7%; p&#x2009;<&#x2009;0.001). At 24&#x2009;h postoperatively, QoR-15 scores were higher in the superior trunk block group (p&#x2009;=&#x2009;0.047), and no patient in either group developed handgrip motor blockade. CONCLUSIONS: Superior trunk block offers superior early postoperative analgesia and better overall recovery, while erector spinae plane block minimizes diaphragmatic impairment. However, the erector spinae plane block may represent an option only in carefully selected patients at high respiratory risk, acknowledging its significantly poorer early analgesic profile.

Humans

Safety Profile of the Non-steroidal Anti-inflammatory Drug Celecoxib in the Short-Term Management of Acute Non-cancer Pain: A Systematic Review with Meta-analysis of Randomised Controlled Trials.

OBJECTIVE: To summarise the literature regarding the safety of short-term use of the non-steroidal anti-inflammatory drug&#xa0;(NSAID) celecoxib. STUDY DESIGN: Systematic review with meta-analysis of randomised trials. Participants comprised individuals of all ages with acute non-cancer pain. Interventions included celecoxib at 200-400 mg/day for up to 10 days. The comparators were placebo, other NSAIDs (including cyclooxygenase-2 [COX-2] inhibitors and non-selective NSAIDS [nsNSAIDS]), or opioids. DATA SOURCES: Five databases were searched from inception to April 2025: Embase, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus. Additionally, a registry was searched: ClinicalTrials.gov. DATA SYNTHESIS: Meta-analyses using Mantel-Haenszel and random-effects model were used to calculate risk ratios (RRs) and 95% confidence intervals (CIs) for severe cardiovascular, respiratory, and gastrointestinal adverse events and secondary outcomes. The Cochrane Risk of Bias Tool for randomised trials (RoB-2) was used to assess bias risk. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) was conducted to assess the certainty of evidence of each reported outcome. RESULTS: Title/abstract and full text screening comprised 3976 and 273 studies, respectively. Fifty studies were included with 10,693 participants. The RRs for adverse events were no different between celecoxib and placebo for severe events (3 studies) (RR 0.44 [95% CI 0.10-2.03]), cardiovascular (3 studies) (RR 0.84 [95% CI 0.24-2.92]), respiratory (4 studies) (RR 1.23 [95% CI 0.29-5.26]), and gastrointestinal events (33 studies) (RR 0.96 [95% CI 0.64-1.43]). There was no difference between celecoxib and NSAIDS for gastrointestinal adverse events, RR 0.89 (95% CI 0.68-1.17). Celecoxib had a lower risk compared to opioids for gastrointestinal events, RR 0.34 (95% CI 0.14-0.86), and showed a lower risk of nausea compared with placebo, RR 0.75 (95% CI 0.60-0.93), and nsNSAIDS, RR 0.80 (95% CI 0.64-0.99). Most studies had some risk of bias concerns, and the overall certainty of evidence for most outcomes was very low. Celecoxib appears to be safe for acute non-cancer pain when compared to placebo, NSAIDS, and opioids. It had a lower risk compared to opioids for gastrointestinal adverse events in general, nausea and vomiting, as well as a lower risk for nausea adverse events when compared to placebo and nsNSAIDS. REGISTRATION: PROSPERO-CRD42025642152.

Journal Article

Impact of PerioperAtive LidocAine Infusions on Enhanced Recovery After Noncardiac Surgery (IMPALA-ERAS) in an inpatient setting: rationale, design and protocol for a sequential, repeated crossover trial.

INTRODUCTION: Multimodal analgesic strategies designed to minimise perioperative opioid exposure are fundamental components of enhanced recovery after surgery (ERAS) pathways. Despite widespread implementation of ERAS protocols, the optimal analgesic regimen remains undefined, as the individual contributions of specific agents to overall analgesic efficacy and opioid-sparing effects are not fully elucidated. Intravenous lidocaine, a widely utilised local anaesthetic, possesses both analgesic and anti-inflammatory properties and has been associated with improved gastrointestinal recovery. This study seeks to pragmatically evaluate the impact of incorporating perioperative intravenous lidocaine infusion into established ERAS pathways on postoperative functional recovery. METHODS AND ANALYSIS: The Impact of PerioperAtive LidocAine Infusions (IMPALA) on ERAS trial is a single-centre, pragmatic, cluster-randomised, double-blinded, placebo-controlled study. A total of 2290 patients undergoing elective colorectal surgery, emergency general surgery, urology, ventral hernia repair, surgical oncology or spine surgery will be randomly assigned to receive either intraoperative and postoperative intravenous lidocaine infusions (administered for up to 48 hours) or placebo as part of a standardised multimodal analgesic regimen integrated into established ERAS pathways. The primary outcome is case mix index-adjusted resource length of stay, defined as the time interval from surgical initiation to hospital discharge adjusted for case mix index. The primary outcome is total inpatient opioid consumption within the first 72 hours, reported in oral morphine milligram equivalents. Secondary outcomes include various in-hospital clinical endpoints derived from the electronic health record. ETHICS AND DISSEMINATION: This protocol and accompanying statistical analysis plan outline the study design, primary and secondary endpoints and analytic methodology. The IMPALA-ERAS trial has received ethical approval from the Vanderbilt University Institutional Review Board (IRB: 250617). The findings will be disseminated via peer-reviewed publications and presentations at national conferences. Results from this trial are expected to inform evidence-based practices regarding perioperative lidocaine infusion and its potential contributions to enhanced postoperative recovery in surgical patients. TRIAL REGISTRATION NUMBER: NCT07224711.

Humans

Continuous Intravenous Lidocaine for Refractory Cancer Pain in Palliative Care: A Multicenter Feasibility Study.

ObjectivesTo assess the feasibility and tolerability of continuous low-dose intravenous lidocaine infusion in patients with opioid-refractory cancer pain receiving palliative care, and to explore its potential impact on pain outcomes in real-world clinical conditions.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled feasibility study in palliative care units to evaluate continuous intravenous lidocaine infusion in patients with opioid-refractory cancer pain. Patients were randomized to receive lidocaine (5&#x2005;mg/kg/day, increased to 8&#x2005;mg/kg/day if pain reduction was <30% after 24&#x2005;h) or placebo for 48&#x2005;h. Pain intensity was assessed using the Numeric Pain Intensity Scale, with a clinically meaningful response defined as a&#x2009;&#x2265;30% reduction from baseline at 40&#x2005;min. Secondary outcomes included pain evolution over time, neuropathic pain, symptom burden, and tolerability.ResultsThirty-five patients were included in the final analysis (18 lidocaine, 17 placebo). No significant difference was observed between lidocaine and placebo for the primary endpoint or for secondary pain outcomes. Reductions in pain intensity were observed in both groups. In the lidocaine group, 61% of patients required dose escalation to 8&#x2005;mg/kg/day. Continuous intravenous lidocaine infusion was generally well tolerated, with mostly mild adverse events and no unexpected toxicity.ConclusionIn this multicenter feasibility study, continuous low-dose intravenous lidocaine did not demonstrate a clinically meaningful analgesic benefit over placebo. As the planned sample size was not reached, the study was underpowered. These findings highlight the challenges of randomized trials in palliative care and may inform future feasibility-oriented designs.

Humans

Thoracic paravertebral block with different doses of liposomal bupivacaine versus ropivacaine for postoperative analgesia in single-port thoracoscopic lung surgery: a randomized clinical trial.

OBJECTIVE: To evaluate the analgesic efficacy of thoracic paravertebral block (TPVB) with different doses of liposomal bupivacaine (LB) or ropivacaine in patients undergoing single-port thoracoscopic lung surgery. METHODS: A total of 105 patients scheduled for video-assisted single-port thoracoscopic lung surgery were randomized in a 1:1:1 ratio into three groups: low-dose LB group (group LL), high-dose LB group (group HL), or ropivacaine group (group R). All received ultrasound-guided TPVB at the T5/6 level preoperatively. The primary outcome was the area under the curve (AUC) of NRS of pain at activity (AUC-aNRS) from 1 to 72&#x2009;h postoperatively. Secondary outcomes included the AUC of NRS of pain at rest (AUC-rNRS) from 1 to 72&#x2009;h postoperatively, NRS of pain at rest and at activity at 1, 6, 24, 48, and 72&#x2009;h postoperatively, and the cumulative opioid consumption at 24, 48, and 72&#x2009;h postoperatively. Additionally, postoperative recovery and adverse events were assessed. RESULTS: AUC-aNRS differed significantly among groups (p = 0.0092), with high-dose LB lower than low-dose LB (p = 0.0071), but not versus ropivacaine. No significant difference was found in AUC-rNRS (p&#x2009;>&#x2009;0.05). The group-by-time interactions for NRS of pain at rest and at activity were not significant (p&#x2009;>&#x2009;0.05). Cumulative opioid consumption at 24, 48, and 72&#x202f;h was lower in group HL versus group LL (all p < 0.017), but not versus ropivacaine. Postoperative recovery and adverse events showed no differences (p&#x2009;>&#x2009;0.05). CONCLUSION: LB combined with TPVB is not superior to ropivacaine for postoperative analgesia in single-port thoracoscopic lung resection.

Humans

Memantine Augmentation for Obsessive-Compulsive Symptoms in Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Obsessive-compulsive symptoms are frequently observed in patients with bipolar disorder and present a significant therapeutic challenge. This study evaluated the efficacy and safety of memantine as an adjunctive therapy for obsessive-compulsive disorder in patients with bipolar disorder. METHODS: In this randomized, double-blind, placebo-controlled trial, 46 patients with bipolar disorder and obsessive-compulsive disorder, stabilized on quetiapine and lithium, were randomly assigned to receive either memantine (n = 23) or placebo (n = 23) for 6 weeks. RESULTS: The memantine group showed a significant reduction in Yale-Brown Obsessive-Compulsive Scale scores compared with the placebo group (Cohen d = 1.57 vs 0.42, P < 0.001). Nausea was the most common side effect, but overall adverse effects were minimal. CONCLUSION: Memantine appears to be a safe and effective adjunctive treatment for obsessive-compulsive disorder in patients with bipolar disorder, warranting further investigation.

Humans

Feasibility and effectiveness of the Bergen 4-Day Treatment for obsessive-compulsive disorder in Australia: A pilot comparison with 3-week inpatient obsessive-compulsive disorder treatment.

OBJECTIVES: Obsessive-compulsive disorder is a debilitating and chronic condition that, when untreated or unresponsive to treatment, imposes a significant health and economic burden on individuals and families. This prospective non-randomised inpatient study compared the acceptability and clinical outcomes of the Bergen 4-Day Treatment programme with those of a standard 3-week specialised treatment programme for obsessive-compulsive disorder in Australia. METHOD: Twenty-five participants diagnosed with obsessive-compulsive disorder were non-randomly assigned to Bergen 4-Day Treatment (n&#x2009;=&#x2009;12) or a 3-week standard (n&#x2009;=&#x2009;13) inpatient programme. Independent assessments were completed at pre-treatment, 10&#x2009;days post treatment and at 3-month follow-up. The Yale-Brown Obsessive-Compulsive Scale was rated to assess obsessive-compulsive disorder severity, while secondary measures of depression, anxiety, obsessive beliefs and wellbeing were self-rated by participants. RESULTS: Baseline characteristics of both groups were comparable, with obsessive-compulsive disorder symptom severity within the moderate to severe range. After treatment, obsessive-compulsive disorder symptoms as well as secondary depression and anxiety symptoms were reduced in both treatment groups. Participants receiving Bergen 4-Day Treatment had significantly lower Yale-Brown Obsessive-Compulsive Scale scores at 10&#x2009;days (M&#x2009;=&#x2009;13.46) and 3&#x2009;months (M&#x2009;=&#x2009;11.84), compared to standard treatment (M&#x2009;=&#x2009;19.04 and M&#x2009;=&#x2009;19.15, respectively). Response (91.9%) and remission (45.8%) rates for the Bergen 4-Day Treatment group were significantly higher at both post-treatment timepoints, compared to the standard treatment group. No dropouts occurred in the Bergen 4-Day Treatment group, and participant satisfaction was high. CONCLUSION: The findings of this pilot open-label study suggest that Bergen 4-Day Treatment shows promise as an acceptable, efficient and effective treatment for obsessive-compulsive disorder, warranting further investigation as a scalable alternative for improving access to specialised obsessive-compulsive disorder treatment in Australia.

Humans

Atomoxetine Versus Placebo for Cognitive Deficits in Stimulant Use Disorder: A Systematic Review.

BACKGROUND: Stimulant use disorder (StUD), particularly involving cocaine and amphetamines, is associated with significant cognitive impairments that impede recovery and increase relapse risk. Atomoxetine, a selective norepinephrine reuptake inhibitor, has been proposed as a potential treatment given its role in enhancing executive function and its established efficacy in attention-deficit/hyperactivity disorder (ADHD). This systematic review aimed to evaluate the efficacy, cognitive, and mood effects of atomoxetine compared with placebo in individuals with StUD. METHODS: A comprehensive literature search of PubMed, Cochrane CENTRAL, and Embase databases was conducted to identify randomized controlled trials (RCTs) evaluating atomoxetine for StUD. Eligible studies compared atomoxetine with placebo and assessed outcomes related to cognition (attention and response inhibition), stimulant use or abstinence, mood symptoms, and safety. Data were extracted and synthesized qualitatively due to methodological heterogeneity across studies. RESULTS: Nine RCTs met the inclusion criteria. Findings on cognitive outcomes were inconsistent: Some studies reported improvements in attentional bias and inhibitory control, while others showed no significant effects. Atomoxetine did not significantly reduce stimulant use, craving, or sustain abstinence compared with placebo. Limited mood-related benefits were observed, particularly among male participants, although results were variable. Across studies, atomoxetine was well tolerated, with most adverse events mild and transient. CONCLUSION: Despite a compelling neurobiological rationale and evidence of modest cognitive and mood benefits, atomoxetine has not demonstrated consistent efficacy as a monotherapy for StUD. Its favorable safety profile may warrant further investigation in carefully defined populations, such as individuals with comorbid ADHD or in combination with behavioral interventions.

Atomoxetine Hydrochloride