A Meta-Analysis Showing the Quantitative Evidence Base of Preemptive Pregabalin for Postoperative Pain from Cancer-Related Surgery.

Background and Objectives: As an adjunct to postoperative multimodal analgesic regimens, pregabalin has been reported in reducing postoperative acute pain and opioid consumption. However, there is only a small amount of evidence for preemptive pregabalin in patients undergoing cancer-related surgery. This systematic review was conducted to integrate high-quality evidence to evaluate the preemptive analgesic effects of pregabalin in cancer-related surgery. Materials and Methods: Seven electronic databases were searched in a combination of subject terms and free words. Efficacy and safety of preemptive pregabalin on postoperative pain for cancer-related surgery were evaluated by assessing resting and dynamic pain scores postoperatively, cumulative morphine equivalent consumption, time to first analgesic request, hemodynamic parameters, and the safety indicators. Results: Thirteen trials were incorporated for quantitative synthesis. The pooled results showed administration of pregabalin preoperatively is clinically significant for improving resting (weighted mean difference (WMD), -1.53 cm; 95% CI, -2.30 to -0.77) and dynamic (WMD, -1.16 cm; 95% CI, -2.22 to -0.11) pain severity scores at 2 h postoperatively and prolonging time to first analgesic request (WMD, 2.28 h; 95% CI, 0.79 to 3.77) in cancer-related surgery. Preemptive pregabalin was also statistically effective in some other pain indicators but would increase the risk of pregabalin-related side effects after surgery. Conclusions: Our findings do not support the administration of pregabalin in doses larger than 300 mg when put in cancer-related surgery. Taken together, more high-quality research particularly focused on the optimal dosages and timing of pregabalin in cancer-related surgery is needed in the future to establish stronger evidence for therapeutic effects.

[Visualized analysis of knowledge map for traditional Chinese medicine prevention and treatment of pulmonary nodules based on CiteSpace].

This study aims to analyze the current status and development trend of the prevention and treatment of pulmonary nodules(PN) with traditional Chinese medicine(TCM) based on knowledge map and to provide both references and suggestions for future research directions. CNKI, Wanfang, VIP, and SinoMed were searched for relevant papers from the inception to December 31, 2021. Eligible articles were included according to the inclusion and exclusion criteria. The line chart was drawn based on the annual publication volume of articles, and the research interests of this field were learned. The knowledge maps of prevention and treatment of PN with TCM were drawn in CiteSpace 5.8.R1, and the authors, institutions, contents, and hotspots were analyzed. A total of 122 articles were included and the line chart demonstrated that the annual publication volume has been rising since 2018. According to the knowledge maps, the most prolific author was ZHANG Xiao-mei and there were four main research teams. Beijing University of Chinese Medicine and its affiliated hospitals were in a leading position in this field. The main research contents were disease, pathogenesis, and treatment, and the hotspots were data mining and TCM syndrome. The research on prevention and treatment of PN with TCM has become an increasing field of interest in recent years. In the future, the cross-regional cooperation and communication between research teams and institutions should be strengthened for more real-world studies and basic studies about the prevention and treatment of PN with TCM, so that the high-level evidence can be obtained and the underlying mechanisms of TCM formulae in the treatment of PN be clarified.

Effects of transcutaneous electrical acupoint stimulation on early postoperative pain and recovery: a comprehensive systematic review and meta-analysis of randomized controlled trials.

Background: Previous studies have indicated beneficial outcomes of transcutaneous electrical acupoint stimulation (TEAS), but high-quality and comprehensive meta-analyses are lacking. The aim was to quantitatively analyze the efficacy and safety of perioperative TEAS on postoperative pain and recovery. Methods: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched through July 2022. Randomized controlled trials (RCTs) that examined the perioperative application of TEAS in adults compared with sham-TEAS and/or non-TEAS were eligible. Cumulative analgesic consumption within 24 h and rest pain scores at 2, 6, 12, and 24 h postoperatively were the two co-primary outcomes. Results: Seventy-six RCTs (n = 9,665 patients) were included. Patients treated with TEAS experienced a reduction in clinical importance in cumulative analgesic (morphine equivalent) consumption (WMD: -14.60 mg, 97.5% CI: -23.60 to -5.60; p < 0.001) and a reduction in statistical importance in rest pain scores at multiple time points within the first 24 postoperative hours. The secondary outcome analysis also identified clinically significant recovery benefits to TEAS during the first 24 h after surgery. Furthermore, TEAS could effectively reduce opioid-related side effects and did not increase serious side effects. Conclusion: This article describes current evidence about TEAS intervention on early postoperative pain and recovery. The results support the effectiveness of TEAS, but more high-quality evidence of clinical applicability is also needed. Systematic review registration: PROSPERO (CRD42021249814).

Contrasting Effects of Music Therapy and Aromatherapy on Perioperative Anxiety: A Systematic Review and Meta-Analysis.

INTRODUCTION: Music therapy and aromatherapy have been demonstrated effective for perioperative anxiety. However, the available studies have indicated discordant results about which adjunct treatment is better for perioperative anxiety. Therefore, we conducted this meta-analysis to explore the contrasting effects between them. METHODS: Six electronic databases were searched for clinical trials evaluating the efficacy of music therapy compared with aromatherapy in alleviating perioperative anxiety. The primary outcome was the postintervention anxiety level. Secondary outcomes included differences in blood pressure and heart rate before and after the intervention as well as pain scores at intraoperative and postoperative time points. The study protocol was registered on PROSPERO (CRD42021249737). RESULTS: Twelve studies (894 patients) were included. The anxiety level showed no statistically significant difference (SMD, 0.28; 95% CI: -0.12, 0.68; p = 0.17). The analysis of blood pressure and heart rate also did not identify statistically significant differences. Notably, the pain scores at the intraoperative time point suggested that aromatherapy was superior to music therapy (WMD, 0.29 cm; 95% CI: 0.05, 0.52; p = 0.02), while those at 4 h after surgery indicated the opposite results (WMD, -0.48 cm; 95% CI: -0.60, -0.36; p < 0.001). CONCLUSION: Low-to-moderate quality evidence suggests that music therapy and aromatherapy have similar potential to relieve perioperative anxiety. The potential data indicate that the two therapies have different benefits in intervention duration and age distribution. More direct high-quality comparisons are encouraged in the future to verify this point.Musik- und Aromatherapie haben sich bei perioperativen Angstzuständen als wirksam erwiesen. Die verfügbaren Studien zeigten jedoch widersprüchliche Ergebnisse zur Frage, welche adjuvante Therapie bei perioperativen Angstzuständen besser ist. Daher führten wir die vorliegende Metaanalyse durch, um die unterschiedlichen Effekte der beiden Therapien zu untersuchen.Sechs (6) elektronische Datenbanken wurden nach klinischen Studien zur Wirksamkeit von Musiktherapie im Vergleich zur Aromatherapie bei der Linderung perioperativer Angstzustände durchsucht. Primäres Zielkriterium war das Angstniveau nach der Intervention. Die sekundären Zielkriterien umfassten die Unterschiede bei Blutdruck und Herzfrequenz vor und nach der Intervention sowie die Schmerz-Scores zu intra- und postoperativen Zeitpunkten. Das Studienprotokoll wurde auf PROSPERO (CRD42021249737) registriert.Zwölf (12) Studien (894 Patienten) wurden eingeschlossen. Das Angstniveau zeigte keinen statistisch signifikanten Unterschied (SMD, 0,28; 95%-KI: −0,12, 0,68, p = 0,17) und auch die Analyse von Blutdruck und Herzfrequenz ergab keine statistisch signifikanten Unterschiede. Insbesondere die Schmerz-Scores zum intraoperativen Zeitpunkt sprachen dafür, dass die Aromatherapie gegenüber der Musiktherapie überlegen war (WMD, 0,29 cm; 95%-KI: 0,05, 0,52; p = 0,02), während die Werte 4 Stunden nach der Operation gegenteilige Ergebnisse zeigten (WMD, −0,48 cm; 95%-KI: −0,60, −0,36, p < 0,001).Evidenzen von geringer bis mässiger Qualität deuten darauf hin, dass Musik- und Aromatherapie ein vergleichbares Potenzial bei der Linderung perioperativer Ängste besitzen. Die potenziellen Daten zeigen, dass die beiden Therapien unterschiedliche Vorteile hinsichtlich Interventionsdauer und Altersverteilung haben. Künftig sollten mehr direkte und qualitativ hochwertige Vergleiche durchgeführt werden, um diesen Aspekt zu überprüfen.

Efficacy and Safety of Lidocaine Patch in the Management of Acute Postoperative Wound Pain: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: This study sought to quantify the pooled effects of lidocaine patch (LP) on postoperative pain and side effects through a comprehensive review and meta-analysis. Approach: The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), AMSTAR, and the Cochrane Collaboration. Randomized controlled trials comparing LP with placebo were retrieved from five electronic databases. Primary outcome in the study was cumulative intravenous morphine equivalent consumption (mg) within 24 h postoperatively. Results: Twelve trials comprising 617 patients were included in the final analysis. Primary result indicated that the analgesic effects LP were only statistical but not clinically significant of postoperative intravenous morphine consumption within 24 h (mean difference, -4.61 mg; 95% confidence interval, -8.09 to -1.14). Interestingly, the results of subgroup and meta-regression analysis indicated that preoperative administration of LP had potential advantages in postoperative wound pain management. It is also worthwhile to mention that LP provided a clinically important benefit in rest pain scores within 24-h postoperatively. Apart from these, other secondary outcome analysis did not uncover any particularly significant analgesic or safety advantages to LP. Finally, LP also does not increase the risk of any local anesthetic-related side effects. Innovation: This systematic review and meta-analysis provides moderate-to-high quality evidence undermining the role of LP for management of acute postoperative wound pain after surgical procedures and the justification for the associated extra costs. Conclusion: Taken together, the current evidence does not support LP as part of a routine multimodal analgesia strategy to alleviate early postoperative acute pain. However, further studies should explore the clinical value of preoperative administration and the long-term effect of LP.

Efficacy and Safety of Methylprednisolone for Lung Surgery: a Systematic Review and Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The administration of methylprednisolone (MP) is a component of perioperative multimodal analgesia that mitigates the potentially deleterious effects of postoperative pain and opioid consumption. However, a systematic evaluation of the efficacy and safety of MP is lacking. The present systematic review and meta-analysis was performed to quantify the potential clinical benefits and risks of perioperative MP in lung surgery. METHODS: We searched seven electronic databases for randomized controlled trials (RCTs) comparing MP with placebo. Coprimary outcomes were rest pain scores, dynamic pain scores, and cumulative morphine equivalent consumption within 24 h postoperatively. RESULTS: A total of 11 trials including 643 participants were selected for our meta-analysis. The results demonstrated that the MP group had a significant difference in coprimary outcomes (rest pain scores, dynamic pain scores, and cumulative morphine equivalent consumption) compared with the placebo group; nevertheless, the improvement was not clinically meaningful based on minimum clinically important differences (MCID). Notably, MP administration reduced serum levels of interleukin (IL)-6 at 6 h (weighted mean difference -20.49 pg/mL; 95% CI -29.94 to -11.04), and decreased the incidence rate of acute lung injury (rate ratio 0.18; 95% CI 0.03-0.98) and cognitive dysfunction (rate ratio 0.43; 95% CI 0.21-0.88) compared with the placebo group. CONCLUSIONS: Our findings suggest that the administration of MP contributed to an insignificant relief in acute postoperative pain for lung surgery in a clinical setting. Future studies should focus on exploring the role of MP in reducing pulmonary and surgical-related complications after lung surgery. CLINICAL TRIAL NUMBER: PROSPERO registration number CRD42022314224.

Patient-derived organoids of lung cancer based on organoids-on-a-chip: enhancing clinical and translational applications.

Lung cancer is one of the most common malignant tumors worldwide, with high morbidity and mortality due to significant individual characteristics and genetic heterogeneity. Personalized treatment is necessary to improve the overall survival rate of the patients. In recent years, the development of patient-derived organoids (PDOs) enables lung cancer diseases to be simulated in the real world, and closely reflects the pathophysiological characteristics of natural tumor occurrence and metastasis, highlighting their great potential in biomedical applications, translational medicine, and personalized treatment. However, the inherent defects of traditional organoids, such as poor stability, the tumor microenvironment with simple components and low throughput, limit their further clinical transformation and applications. In this review, we summarized the developments and applications of lung cancer PDOs and discussed the limitations of traditional PDOs in clinical transformation. Herein, we looked into the future and proposed that organoids-on-a-chip based on microfluidic technology are advantageous for personalized drug screening. In addition, combined with recent advances in lung cancer research, we explored the translational value and future development direction of organoids-on-a-chip in the precision treatment of lung cancer.

Dexamethasone Does Not Provide Additional Clinical Analgesia Effect to Local Wound Infiltration: A Comprehensive Systematic Review and Meta-Analysis.

Objective: Although the use of dexamethasone as an adjunct agent is associated with alleviating pain and prolonging analgesic duration in local wound infiltration (LWI), efficacy and safety of dexamethasone infiltration have not been fully explored. The study sought to quantify the pooled effects of dexamethasone infiltration on postoperative pain, analgesic consumption, and side effects through a review of randomized controlled trials (RCTs). Approach: RCTs comparing dexamethasone + LWI with LWI alone were retrieved from seven electronic databases. Co-primary outcomes were rest pain scores and cumulative morphine equivalent consumption within 24 h postoperatively. The study followed PRISMA, AMSTAR, and the Cochrane Collaboration. Results: Eight trials comprising 609 patients were included in the final analysis. Results indicated that dexamethasone infiltration effects were only statistical but not clinically significant at individual time points of rest pain and patient satisfaction scores. Notably, the effect of dexamethasone infiltration therapy on other pain-related parameters, including cumulative morphine consumption (mean difference, -9.05 mg; 95% CI: -22.47 to 4.37), was not significantly different compared with the control group. Analysis showed no significant differences in safety indicators between the two groups. The overall quality of evidence was high to very low. Innovation: Although statistically significant effects of dexamethasone infiltration were observed for some outcomes of postoperative wound pain, the overall benefits were below the expected minimal clinically important difference. Conclusions: In summary, the current evidence does not support routine clinical use of dexamethasone in LWI. However, further studies should explore the clinical value of preemptive analgesia and safety of a combination of dexamethasone with ropivacaine for LWI.

Does the last 20 years paradigm of clinical research using volatile organic compounds to non-invasively diagnose cancer need to change? Challenges and future direction.

PURPOSE: Volatile organic compounds (VOCs) have shown great potential as novel biomarkers for cancer detection; however, comprehensive quantitative analysis is lacking. In this study, we performed a bibliometric analysis of non-invasive cancer diagnosis using VOCs to better characterise international trends and to predict future hotspots in this field, and then we focussed on human studies to analyse clinical characteristics for presenting the current controversies and future perspectives of further clinical work. METHODS: Publications, from 2002 to 2022, were retrieved from the Web of Science Core Collection database. CiteSpace and VOSviewer were used to generate network maps and identify the annual publications, top countries, authors, institutions, journals, references, and keywords. Then, we further screened clinical trials, and the key information was extracted into Microsoft Excel for further systematical analysis. RESULTS: Six hundred and forty-one articles were identified to evaluate research trends, of which 301 clinical trials were selected for further systematical analysis. Overall, the annual publications in this area increased, with an overall upward trend, while the quality of clinical research remains remarkably uneven. CONCLUSION: The study of non-invasive cancer diagnosis using VOCs would continue to be an active field. However, without stringent clinical design criteria, most suitable acquisition and analysis devices and statistical approaches, a list of exclusive, specific, reliable and reproducible VOCs to identify a disease and these VOCs appearing in a breath at detectable levels at early stage disease, the clinical utility of VOC tests will be difficult to have any breakthroughs.

Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene.

Malignant hyperthermia (MH) is an autosomal dominant genetic condition of the skeletal muscle triggered by inhaled general anesthetic agents or succinylcholine and associated with a hypermetabolic state and skeletal muscle rigidity. Tachycardia, increased carbon dioxide production, hypercarbia, hyperthermia, acidosis, hyperkalemia, cardiac arrhythmias, muscle rigidity, and rhabdomyolysis are common symptoms of MH. As the progression of the syndrome could be rapid or less evident, even experienced physicians have difficulty in diagnosing MH, which can lead to delays in treatment and increased mortality. We report a rare case of a 36-year-old man, who underwent open reduction and internal fixation of the left clavicle after inhaled anesthetics. The patient developed dyspnea, hypotension, unremitting hyperthermia, tachycardia, and elevated serum myoglobin, and finally died of pyemia and disseminated intravascular coagulation. We reviewed the process of disease development, summarized the steps of diagnosis, and improved genetic testing. Exome sequencing revealed a new mutation c.8519G>A (p.arg2840 GLN) in the RYR1 gene that could be associated with MH. The gene mutation was also found in his daughter's genetic test. This case emphasized the importance of the awareness of MH and its atypical clinical symptoms. The presence of dyspnea, hypotension, unremitting hyperthermia, tachycardia, and raised myoglobin in serum might further strengthen the clinical diagnosis of suspected MH.

Targeted Approaches to HER2-Low Breast Cancer: Current Practice and Future Directions.

HER2-low breast cancer (BC) has a poor prognosis, making the development of more suitable treatment an unmet clinical need. While chemotherapy is the main method of treatment for HER2-low BC, not all patients benefit from it. Antineoplastic therapy without chemotherapy has shown promise in clinical trials and is being explored further. As quantitative detection techniques become more advanced, they assist in better defining the expression level of HER2 and in guiding the development of targeted therapies, which include directly targeting HER2 receptors on the cell surface, targeting HER2-related intracellular signaling pathways and targeting the immune microenvironment. A new anti-HER2 antibody-drug conjugate called T-DM1 has been successfully tested and found to be highly effective in clinical trials. With this progress, it could eventually be transformed from a disease without a defined therapeutic target into a disease with a defined therapeutic molecular target. Furthermore, efforts are being made to compare the sequencing and combination of chemotherapy, endocrine therapy, and HER2-targeted therapy to improve prognosis to customize the subtype of HER2 low expression precision treatment regimens. In this review, we summarize the current and upcoming treatment strategies, to achieve accurate management of HER2-low BC.

Preoperative Oral Gabapentin in the Management of Postoperative Catheter-Related Bladder Discomfort in Adults: A Systematic Review and Meta-Analysis.

Objective: To evaluate the efficacy and safety of preoperative oral gabapentin in preventing postoperative Catheter-Related Bladder Discomfort (CRBD) in surgical patients. Methods: Randomized controlled trials in which gabapentin was used for the prevention of CRBD in surgical patients with transurethral catheterization were evaluated. The primary outcome was the incidence of moderate-to-severe CRBD at 0, 1, 2, and 6 h after surgery, and secondary outcomes included the incidence of any grade CRBD, postoperative pain, and adverse events. Pooled risk ratios (RRs) and mean difference (MD), 95% confidence intervals (CIs), and P values were estimated using fixed and random effects statistical models. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the levels of certainty for key results. Results: A total of 6 randomized controlled trials involving 679 participants were included in the meta-analysis. Gabapentin significantly reduced the risk of moderate-to-severe CRBD at 0, 1, 2, and 6 h (0 h: RR = 0.19, 95% CI: 0.11 to 0.31, p < 0.00001; 1 h: RR = 0.40, 95% CI: 0.25 to 0.66, p < 0.001; 2 h: RR = 0.38, 95% CI: 0.26 to 0.56, p < 0.00001; 6 h: RR = 0.20, 95% CI: 0.11 to 0.38, p < 0.00001). The overall incidence of CRBD at 1 h showed no statistical difference between the two groups (RR = 0.55, 95% CI: 0.30 to 1.00, p = 0.05). The risk of CRBD was significantly reduced in the gabapentin group at 0, 2, and 6 h after surgery (0 h: RR = 0.59, 95% CI: 0.46 to 0.74, p < 0.0001; 2 h: RR = 0.62, 95% CI: 0.51 to 0.75, p < 0.00001; 6 h: RR = 0.66, 95% CI: 0.52 to 0.83, p < 0.001). In addition, gabapentin was associated with low postoperative pain intensity without significant side effects. Conclusion: Preoperative oral gabapentin as an adjunct to surgery is effective in decreasing the risk and severity of CRBD over a short time after surgery, and it can decrease postoperative pain without significant side effects. Overall, the level of certainty was moderate to low. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42021228171.

The Analgesic Benefits of Ketorolac to Local Anesthetic Wound Infiltration Is Statistically Significant But Clinically Unimportant: A Comprehensive Systematic Review and Meta-Analysis.

Objective: Even though ketorolac-infiltration is said to provide superior postoperative analgesic benefits in different surgical procedures, its safety and efficacy remain to be validated because of the lack of high-quality evidence. We aimed to summarize the efficacy and safety of ketorolac-infiltration based on published randomized-controlled trials (RCTs). Approach: This work followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, assessing the methodological quality of systematic reviews and the Cochrane Collaboration recommendations. We searched for RCTs evaluating the efficacy of ketorolac-infiltration in adults in the PubMed, Web of Science, Embase, Cochrane Library, Chinese databases, and Google Scholar. The two co-primary outcomes of this meta-analysis were rescue analgesic consumption in the 24-h postoperative period and rest pain scores. Results: Twelve trials (761 patients) were analyzed. Ketorolac-infiltration provided a clinically unimportant benefit in morphine consumption (mean difference, -2.81 mg; 95% confidence interval [CI], -5.11 to -0.50; p = 0.02; moderate-quality evidence). Low-to-moderate quality evidence supported a brief (2-6 h), clinically subtle, but statistically consistent effect of surgical site ketorolac-infiltration in reducing wound pain at rest. High-quality evidence supported shorter hospital stays for surgical patients receiving local ketorolac-infiltration when compared to controls (mean difference, -0.12 days; 95% CI, -0.17 to -0.08; p < 0.00001). Further, ketorolac-infiltration does not improve any opioid-related side effects. Innovation: Ketorolac-infiltration provides statistically significant but clinically unimportant benefits for improving postoperative wound pain. Conclusion: Overall, despite the fact that current moderate-to-high quality of evidence does not support routine using of ketorolac as an adjuvant to local anesthetic for wound infiltration, these findings underscore the importance of optimizing agents and sustained delivery parameters in postoperative local anesthetic practice. Clinical Trials.gov ID: CRD42021229095.

Gabapentin has Longer-Term Efficacy for the Treatment of Chronic Pelvic Pain in Women: A Systematic Review and Pilot Meta-analysis.

INTRODUCTION: Gabapentin has potential analgesic benefits in patients with neuropathic pain, such as post-herpetic neuralgia and diabetic peripheral neuropathy neuropathic pain. However, its efficacy in women with chronic pelvic pain (CPP) remains contradictory. In the present study, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to ascertain the efficacy of this treatment. METHODS: We systematically reviewed RCTs published in PubMed, Embase, the Cochrane Library, Web of Science, and Google Scholar databases, up to July 2021. These articles compared gabapentin with placebo or any other active treatment for CPP in women, with 'the change in pain scores from the baseline during the first 3 and 6 months of treatment' taken as the primary outcome. We considered reductions equivalent to 1.0 cm for primary outcomes to be clinically important. RESULTS: Four studies, comprising 469 participants, were included in our meta-analysis. Results revealed that the gabapentin group had significantly higher change in pain intensity scores from baseline to 3 months [weighted mean difference (WMD) - 0.61 cm; 95% confidence interval (CI) - 0.97 to - 0.25; I2 = 0%; p = 0.0009] and 6 months (WMD - 1.38 cm; 95% CI - 1.89 to - 0.88; I2 = 0%; p < 0.00001), relative to the control group. The difference of 6-month pooled result was more clinically important. Results from analysis of secondary outcomes showed that gabapentin had no beneficial efficacy during the first 3 months of treatment. Although gabapentin treatment was associated with a higher risk of dizziness and somnolence, no statistically significant differences were observed with regards to the total incidence of adverse events. CONCLUSIONS: Overall, gabapentin could be a potential treatment option for CPP in women. However, as a pilot study, further studies are needed to explore the longer-term benefits and definite safety of this therapy in the future. REGISTRATION NUMBER: PROSPERO registration number CRD42021249421.

Nalbuphine Versus Ketorolac as an Adjuvant to Local Wound Infiltration Anesthesia in Open Colorectal Surgery: A Prospective Randomized Controlled Study.

INTRODUCTION: Adding adjuvants to local wound infiltration (LWI) provides long analgesic duration with fewer adverse effects. We aimed to compare the clinical effects of nalbuphine and ketorolac as an adjuvant to LWI in patients undergoing open colorectal cancer surgery. METHOD: A total of 126 ASA I-III patients aged ≥ 18 years who were scheduled for open colorectal cancer surgery were included. Patients were randomly assigned to receive LWI using 10 mL 0.75% ropivacaine, with 20 mL normal saline (group R), 10 mg nalbuphine in 1 mL (group RN), or 25 mg ketorolac in 0.8 mL (group RK). Analgesia duration was the primary outcome. The total 48-h postoperative morphine-equivalent consumption and additional rescue analgesia rates were recorded as key secondary outcomes. RESULTS: Among 126 patients randomized, 124 completed the trial. The duration until the first press of the analgesia pump was significantly shorter in group R (median: 320.0 min) compared with group RN (median: 829.5 min) and group RK (median: 820.0 min) (P < 0.001). The median difference in morphine consumption was 113.0 mg for group R vs. group RN (P < 0.001), and 115.5 mg for group R vs. group RK (P < 0.001). The proportion of patients using additional morphine within the first day after surgery in group R showed a higher relative risk (RR) compared with group RN (RR, 3.89; P = 0.001) and group RK (RR, 3.17; P = 0.001). There were no apparent differences between the RN and RK groups in any outcomes, whether in adjusted or unadjusted analysis. CONCLUSIONS: Among patients undergoing open colorectal cancer surgery, both nalbuphine and ketorolac infiltration achieved equally prolonged duration of analgesia and reduced morphine consumption compared with ropivacaine alone after surgery, suggesting that the equivalent analgesic dose of nalbuphine and ketorolac as local anesthetic adjuvants in LWI could have a similar analgesic effect. TRIAL REGISTRATION: ChiCTR1800019209.

Does Inhaled Methoxyflurane Implement Fast and Efficient Pain Management in Trauma Patients? A Systematic Review and Meta-Analysis.

INTRODUCTION: Evidence on the use of inhaled methoxyflurane in the management of trauma pain is conflicting and obfuscated. This study aimed to determine the efficacy and safety of inhaled methoxyflurane for trauma pain on the basis of published randomized controlled trials (RCTs). METHODS: RCTs assessing the efficacy of methoxyflurane in adults or adolescents with acute trauma pain published in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar were searched. The control groups were those that received placebo or standard analgesic treatment (SAT). The primary outcome was the change from baseline in pain scores during the first 30 min of treatment. Secondary outcomes included time to first pain relief, the proportion of patients experiencing pain relief, rescue analgesia rate, the treatment satisfaction of patients and investigators, and the methoxyflurane-related treatment-emergent adverse events (TEAEs). RESULTS: A total of nine RCTs (1806 patients) were identified. Results revealed that methoxyflurane provided a clinically unimportant benefit by improving the mean difference of change from baseline in pain intensity (from - 0.44 to - 1.23 cm, p < 0.001) at various time points within the first 20 min compared to control treatment. Besides, methoxyflurane decreased the time of onset of pain relief (mean difference - 5.29 min; 95% CI - 6.97 to - 3.62) and the proportion of patients who needed rescue analgesic medication (risk ratio 1.41; 95% CI 1.17-1.70) despite it increasing the risk of non-severe TEAEs (risk ratio 3.09; 95% CI 1.72-5.57). Notably, the benefit of almost all secondary pain-related outcomes was rendered clinically nonsignificant between methoxyflurane and SAT strata besides the time of onset of pain relief. The quality of evidence was low or very low in all outcomes. CONCLUSIONS: In emergency situations without effective therapy, this systematic review and meta-analysis provides low-quality evidence that methoxyflurane can be used as a rapid-acting and effective treatment for acute trauma pain, although its utilization is associated a risk of non-severe TEAEs. However, the current evidence does not support the notion that inhaled methoxyflurane offered superior analgesic efficacy to SAT. CLINICAL TRIAL NUMBER: PROSPERO registration number CRD42020223000.