Efficacy of epinephrine in local infiltration analgesia on pain relief and opioid consumption following total knee arthroplasty: a randomized controlled trial.

BACKGROUND AND PURPOSE: Local infiltration analgesia (LIA) is one of the effective regimens to reduce pain after total knee arthroplasty (TKA). Epinephrine is a commonly used sympathetic adjunct in LIA. It is expected to enhance the intensity and extend the duration of LIA. The primary aim of the study was to evaluate the efficacy of epinephrine on postoperative pain control after primary TKA. PATIENTS AND METHODS: A total of 80 patients who underwent primary TKA were randomized into an epinephrine (EN) and a control (C) group. Postoperative visual analogue pain score (VAPS) and morphine consumption were recorded every 6 hours until 48 hours after operation. The VAPS 6-48 hours were compared using repeated measure statistics. The range of motion (ROM) on discharge and complications were also compared between these 2 groups. RESULTS: The study showed that although VAPS differed statistically between the 2 groups at 12 hours (C higher) and 48 hours (C lower) postoperatively (p = 0.04 and 0.02, respectively), repeated measures analysis revealed that there were no significant differences in 6-48 hours VAPS (p = 0.6). Total morphine consumption in the EN and C groups was 3.4 (SD 3.7) and 4.2 (SD 4.4) mg, respectively (p = 0.4). ROM on discharge was also similar between the groups. No complications were detected in this study. CONCLUSION: Our study showed that additional epinephrine in LIA had a statistically significant reduction in VAPS at 12 hours and morphine usage during 6-12 hours when compared with the control group. However, the magnitude of difference did not reach minimal clinically importance difference (MCID) value for TKA.

[Pathogenesis and staging treatment for non-specific low back pain based on the meridian sinew theory].

Based on the physiological and pathological characteristics of meridian sinew theory, the staging treatment of non-specific low back pain (NLBP) is explored to provide the reference of clinical practice. The twelve meridian sinews of the human body communicate with the bones and joints of the whole body, which governs the movement, body protection and defense, and meridian regulation. Physiologically, the meridian sinew maintains the functions of the lumbar region. In pathology, the meridian sinew may encounter stasis and pain, contraction and spasm or "transverse collateral" formation. According to the pathological staging of meridian sinew disorders, the progress of NLBP is divided into 3 phases and the corresponding treatments are provided. Mild stimulation and rapid analgesia is suggested to promote tissue repair at the early phase; muscle spasm is relieved to adjust muscular status at the middle phase; and the "cord-like" muscle foci is removed at the later phase of the disease.

A buprenorphine depot formulation provides effective sustained post-surgical analgesia for 72 h in mouse femoral fracture models.

Adequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are only available in the USA and have limited duration of action. Recently, a new microparticulate Buprenorphine formulation (BUP-Depot) for sustained release has been developed as a potential future alternative to standard formulations available in Europe. Pharmacokinetics indicate a possible effectiveness for about 72 h. Here, we investigated whether the administration of the BUP-Depot ensures continuous and sufficient analgesia in two mouse fracture models (femoral osteotomy) and could, therefore, serve as a potent alternative to the application of Tramadol via the drinking water. Both protocols were examined for analgesic effectiveness, side effects on experimental readout, and effects on fracture healing outcomes in male and female C57BL/6N mice. The BUP-Depot provided effective analgesia for 72 h, comparable to the effectiveness of Tramadol in the drinking water. Fracture healing outcome was not different between analgesic regimes. The availability of a Buprenorphine depot formulation for rodents in Europe would be a beneficial addition for extended pain relief in mice, thereby increasing animal welfare.

Efficacy of a Modified Cocktail for Periarticular Local Infiltration Analgesia in Total Knee Arthroplasty: A Prospective, Double-Blinded, Randomized Controlled Trial.

BACKGROUND: Periarticular local infiltration analgesia (LIA) is largely utilized for controlling pain after total knee arthroplasty (TKA). The present work aimed to assess the efficacy of a modified LIA cocktail for patients undergoing TKA. METHODS: Magnesium sulfate (MgSO4) and sodium bicarbonate (NaHCO3) were added to a conventional LIA cocktail comprising ropivacaine, epinephrine, and dexamethasone. After the safety of this modified cocktail was tested in rats, its efficacy and safety were evaluated in a prospective, double-blinded study including 100 individuals randomized to receive periarticular infiltration of the modified cocktail or a conventional cocktail. The primary outcome was postsurgical use of morphine hydrochloride for rescue analgesia. Secondary outcomes were the time until the first rescue analgesia, postsurgical pain (on a visual analog scale [VAS]), functional recovery (assessed by range of knee motion and ambulation distance), time to discharge, and complication rates. RESULTS: Adding NaHCO3 to the local anesthetics caused some instantaneous precipitation in all cases. Administering the modified cocktail to rats did not obviously damage the injected area of the nerve or surrounding tissues. Administration of the modified cocktail to patients was associated with markedly reduced postsurgical morphine use in the initial 24 hours (4.2 ± 5.0 versus 14.6 ± 8.9 mg, p < 0.001), reduced total morphine use (9.8 ± 8.4 versus 19.6 ± 11.4 mg, p < 0.001), prolonged time to the first rescue analgesia, lower VAS pain scores at rest and during motion at 12 and 24 hours following the operation, better functional recovery on postoperative days 1 and 2, and a shorter hospital stay. The modified and conventional cocktail groups had similar rates of complications. CONCLUSIONS: The present modification of a conventional cocktail significantly prolonged analgesia and reduced opioid consumption, which may substantially improve pain control in arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Real-time evaluation of the independent analgesic efficacy of dexmedetomidine.

BACKGROUND: Dexmedetomidine has analgesic properties, but the intraoperative analgesic effect of dexmedetomidine is often masked by the effects of other general anaesthetics. Therefore, the degree to which it reduces intraoperative pain intensity remains unclear. The objective of this double-blind, randomised controlled trial was to evaluate the independent intraoperative analgesic efficacy of dexmedetomidine in real-time. METHODS: This single-centre study enrolled 181 patients who were hospitalised for below-knee orthopaedic surgeries between 19 January 2021 to 3 August 2021 were eligible for this is single-centre study. Peripheral neural block was performed on patients scheduled for below-knee orthopaedic surgeries. Patients were randomly assigned to the dexmedetomidine or midazolam group and were intravenously administered with 1.5 µg kg-1 h-1 dexmedetomidine or 50 µg kg-1 h-1 midazolam, respectively. The analgesic efficacy was evaluated using the real-time non-invasive nociception monitoring. The primary endpoint was the attainment rate of the nociception index target. The secondary endpoints included the occurrence of intraoperative hypoxemia, haemodynamic parameters, the consciousness index, electromyography and patient outcomes. RESULTS: On Kaplan-Meier survival analysis, the defined nociception index target was attained in 95.45% and 40.91% of patients receiving dexmedetomidine and midazolam, respectively. Log-rank analysis revealed that the dexmedetomidine group attained the nociception index target significantly faster and the median attainment time of the nociception index target in the dexmedetomidine group was 15 min. Dexmedetomidine group was associated with a significantly lower incidence of hypoxemia. There was no significant difference in blood pressure between the dexmedetomidine and midazolam groups. Further, the dexmedetomidine group had a lower maximum visual analogue scale score and lower analgesic consumption postoperatively. CONCLUSIONS: Dexmedetomidine has independent analgesia and systemically administered as an adjuvant agent has better analgesic efficacy than midazolam without severe side effects. TRIAL REGISTRATION: clinicaltrial.gov Registry Identifier: NCT-04675372.Registered on 19/12 /2020.

Effect of oral pre-emptive analgesia on pain management after total knee arthroplasty: a protocol for systematic review and meta-analysis.

INTRODUCTION: Total knee arthroplasty (TKA) is currently regarded as an effective treatment for knee osteoarthritis, relieving patients' pain and significantly enhancing their quality of life and activity levels, allowing them to return to work and daily life after surgery. However, some TKA patients suffer from varying degrees of postoperative residual pain and opioid abuse, which negatively impacts their recovery and quality of life. It has been reported that preoperative treatment with multimodal analgesics improves postoperative pain and reduces opioid consumption. However, there is no conclusive evidence that pre-emptive analgesia provides the same benefits in TKA. In order to inform future research, this protocol focuses on the efficacy and safety of oral analgesics used in TKA pre-emptive analgesia. METHODS AND ANALYSIS: We will search the literature on the involvement of pre-emptive analgesia in the management of pain in TKA from the PubMed, EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews, from their inception to 1 February 2023. Additionally, clinical registry platforms will be investigated to collect data for ongoing studies. Using the Cochrane Risk of Bias Tool, the quality assessment will be conducted. RevMan V.5.4 will be used for the meta-analysis. The statistic I 2 will be used to measure the percentage of total variability due to heterogeneity between studies. Where appropriate, subgroup and sensitivity analyses, assessment of evidence quality and publication bias will be conducted. ETHICS AND DISSEMINATION: No ethical approval and consent is required for this systematic review. Moreover, the results of this systematic review will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022380782.

Ultrasound-Guided Rhomboid Block versus Paravertebral Block in Postoperative Analgesia for Video-Assisted Thoracoscopic Surgery: A Prospective Randomized Controlled Clinical Trial.

Introduction: The anesthetic efficacy of the ultrasound-guided rhomboid intercostal block (RIB) in alleviating postoperative pain has been well concerned. This study aims to compare the effectiveness between ultrasound-guided RIB and paravertebral block (PVB) in alleviating acute pain following video-assisted thoracic surgery. Methods: It was a prospective, randomized, double-blinded clinical trial involving 132 patients with video-assisted thoracic surgery divided into three groups: the general anesthesia (GA) group, RIB group, and PVB group on T5 vertebra, using 0.4% ropivacaine at 3 mg/kg, registered in the Chinese Clinical Trial Registry (ChiCTR2100054057, "https://www.chictr.org.cn"). The visual analogue scale (VAS) scores at rest and cough during 48 h postoperatively and the postoperative consumption of pain rescue were the primary outcomes, and the QoR15 score 48 h postoperatively, the usage of opioids during and after operation, and nerve block-related complications were the secondary outcomes. Demographic characteristics, surgery characteristics, and primary outcomes between the groups were compared. Results: A total of 120 eligible patients were recruited, including 40 in each group. Baseline and surgery characteristics between the groups were comparable (all p > 0.05). The PVB and RIB groups were better than the GA group in the primary and secondary outcomes (p < 0.05). The static VAS score, QoR15 score, and block-related complications within 48 hours after surgery were better in the RIB group than in the PVB group (p < 0.001). Conclusion: Both PVB and RIB can provide adequate analgesia and accelerate the recovery of patients. Compared with PVB, RIB has a better analgesic effect, especially to avoid paravertebral pain caused by block, and the operation of RIB is more straightforward and the safety is higher.

Neuraxial analgesia during labor and postpartum depression: Systematic review and meta-analysis.

BACKGROUND: Severe pain has been linked to depression, which raises the question of whether neuraxial analgesia during childbirth is associated with a reduced risk of postpartum depression. This association has been explored, but previous studies did not control or analyze relevant confounders. We conducted a systematic review and meta-analysis to determine the association between neuraxial analgesia and postpartum depression. METHODS: A systematic review was conducted using PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Studies that tested the effect of neuraxial analgesia during labor on depression or depressive symptoms in the first year postpartum were included. Relevant articles were extracted independently by 2 authors. RESULTS: In total, 14 studies (86,231 women) were included. The association between neuraxial analgesia and the long-term incidence of postpartum depression after childbirth was the risk ratio = 0.75, 95% confidence interval (CI): 0.56-1.00, P = .05; I2 = 79%, P < .00001. There was a significant association (pooled risk ratio = 0.55, 95% CI: 0.34-0.90, P = .02; I2 = 55%, P = .06) between neuraxial analgesia and the incidence of postpartum depression in the first week after delivery. The subgroup analysis showed a trend suggesting that in Asian populations, those who received neuraxial analgesia had lower postpartum depression rates than those who received non-neuraxial analgesia (risk ratio = 0.57, 95% CI: 0.38-0.86; P = .008; I2 = 82%) at ≥4 weeks after delivery. CONCLUSION: Neuraxial analgesia may be beneficial for the short-term and long-term mental effects of parturient women, especially for short term after delivery. High-quality studies addressing the role of neuraxial analgesia during labor and its impact on postpartum depression remain necessary.

Effect of coolant spray on rib fracture pain of geriatric blunt thoracic trauma patients: a randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the effectiveness of cryotherapy in elderly patients with rib fractures due to blunt thoracic trauma. METHODS: In this prospective randomized controlled study, geriatric patients were assigned to groups to receive either coolant spray (n=51) or placebo spray (n=50). The visual analog scale scores of all patients were recorded before starting spray application (V0), as well as at 10th (V1), 20th (V2), 30th (V3), 60th (V4), 120th (V5), and 360th (V6) minute. The mean decreases in the visual analog scale scores were calculated. RESULTS: The differences between V0 and V1, V0 and V2, V0 and V3, and V0 and V4 mean visual analog scale scores measured in the coolant spray group were found to be significantly higher (p<0.001). In V1, V2, V3, and V4 measurements, the incidence of "clinical effectiveness" in the coolant spray group was significantly higher than in the placebo group (p=0.001). CONCLUSIONS: Coolant spray therapy can be used as a component of multimodal therapy to provide adequate analgesia due to rib fractures in geriatric patients.

Prolonged Dystocic Labor in Neuraxial Analgesia and the Role of Enkephalin Neurotransmitters: An Experimental Study.

The investigation studied the enkephalinergic neuro fibers (En) contained in the Lower Uterine Segment (LUS) during the prolonged dystocic labor (PDL) with Labor Neuraxial Analgesia (LNA). PDL is generally caused by fetal head malpositions in the Occiput Posterior Position (OPP), Persistent Occiput Posterior Position (POPP), in a transverse position (OTP), and asynclitism (A), and it is detected by Intrapartum Ultrasonography (IU). The En were detected in the LUS samples picked up during cesarean section (CS) of 38 patients undergoing urgent CS in PDL, compared to 37 patients submitted to elective CS. Results were statistically evaluated to understand the differences in En morphological analysis by scanning electron microscopy (SEM) and by fluorescence microscopy (FM). The LUS samples analysis showed an important reduction in En in LUS of CS for the PDL group, in comparison with the elective CS group. The LUS overdistension, by fetal head malpositions (OPP, OTP, A) and malrotations, lead to dystocia, modification of vascularization, and En reduction. The En reduction in PDL suggests that drugs used during the LNA, usually local anesthetics and opioids, cannot control the "dystocic pain", that differs from normal labor pain. The IU administration in labor and the consequent diagnosis of dystocia suggest stopping the numerous and ineffective top-up drug administration during LNA, and to shift the labor to operative vaginal delivery or CS.

"Procedural sedation and analgesia in Italian pediatric emergency departments: a subgroup analysis in italian hospitals".

To date, pain and anxiety are the most common symptoms reported by children who refer to pediatric emergency department. Despite it is well known that the undertreatment of this condition has some negative consequences in a short term and long term of time, gaps in the management of pain in this setting still persist. This subgroup analysis aims to describe the current state of art of pediatric sedation and analgesia in Italian emergency departments and to identify existing gaps to solve. This is a subgroup analysis of a cross-sectional European survey of pediatric emergency departments sedation and analgesia practice undertaken between November 2019 and March 2020. The survey proposed a case vignette and questions addressing several domains, like the management of pain, availability of medications, protocols and safety aspects, staff training and availability of human resources around procedural sedation and analgesia. Italian sites responding to the survey were identified and their data were isolated and checked for completeness. Eighteen Italian sites participated to the study, the 66% of which was represented University Hospitals and/or Tertiary Care Centers. The most concerning results were an inadequate sedation to 27% of patients, lack of availability of certain medications like nitrous oxide, the lack of use of intranasal fentanyl and topical anesthetics at the triage, the rare use of safety protocols and preprocedural checklists, lack of staff training and lack of space. Furthermore, the unavailability of Child Life Specialists and hypnosis emerged. Despite procedural sedation and analgesia in Italian pediatric emergency departments is progressively more used than previously, several aspects still require an implementation. Our subgroup analysis could be a starter point for further studies and to improve and make the current Italian recommendations more homogeneous.

High-dose Meloxicam Provides Improved Analgesia in Female CD1 Mice: A Pharmacokinetic and Efficacy Study.

Meloxicam is a nonsteroidal anti-inflammatory analgesic drug that is often used in mice. However, doses of 1 to 5 mg/kg given twice daily were recently reported to provide inadequate analgesia. Some studies suggest that doses of up to 20 mg/kg may be necessary for adequate pain management. We investigated the analgesia provided by a high-dose of meloxicam in female CD1 mice. Pharmacokinetic analyses demonstrated that a subcutaneous injection of 10 mg/kg or 20 mg/kg of meloxicam produced therapeutic plasma concentrations for at least 12 h. Ovariectomies via ventral laparotomy were performed to assess analgesic efficacy. Mice were treated immediately before surgery with a high-dose of 10 mg/kg, a low-dose of 2.5 mg/kg, or saline, followed by every 12 h for 36 h. At 3, 6, 12, 24, and 48 h after surgery, mice were assessed for pain based on the following behaviors: distance traveled, time mobile, grooming, rearing, hunched posture, orbital tightening, and von Frey. Initially, some mice received a 20-mg/kg loading dose followed by 10 mg/kg every 12 h. This regimen caused severe morbidity and mortality in 2 mice. Subsequently, this regimen was abandoned, and mice assigned to the high-dose group received 10 mg/kg every 12 h. Mice that received the 10-mg/kg dose after surgery showed less orbital tightening between 3 to 6 h and reduced frequency of hunched posture for 48 h compared with mice that received either the low-dose or saline. However, mice were significantly less mobile for 6 to 12 h after surgery regardless of treatment. These data indicate that a meloxicam dose of 10 mg/kg every 12 h provides better analgesia than a 2.5-mg/kg dose but does not completely alleviate pain.

Ultrasound-guided erector spinae plane block for postoperative analgesia in Chinese patients undergoing laparoscopic cholecystectomy: a double-blind randomized controlled trial.

PURPOSE: Pain management after laparoscopic cholecystectomy (LC) is a main concern for Chinese clinicians. This study aims to explore the effect of erector spinae plane block (ESPB) on the postoperative analgesia of patients undergoing LC in China. METHODS: In this randomized controlled trial (RCT), 220 patients were randomized into the ESPB group and control group. Patients in the ESPB group received a bilateral ESPB, and patients in the control group were injected saline. Lornoxicam (0.08 mg/mL, 100 mL) was used as routine analgesia for both groups after the surgery. Visual analog scale (VAS) score at rest state at 12 h postoperative was the primary outcome and divided into no pain, mild pain, moderate pain, and severe pain. RESULTS: Finally, 197 patients were included for analysis. At postoperative 12 h, ESPB group observed less patients with moderate pain (0% vs. 8.91%) and severe pain (0% vs. 0.99%) than the control group (P < 0.001). Moreover, ESPB group found less dose of additional sufentanil (5.55 ± 1.37 µg vs. 10.67 ± 5.05 µg), less requirement for rescue analgesia (13.54% vs. 31.68%), earlier first time to leave bed (10 h vs. 18 h), and earlier first exhaust time (17.5 h vs. 25 h), less adverse reactions (5.21% vs. 17.82%), and higher satisfaction degree (78.13% vs. 31.68%) (all P < 0.05). CONCLUSIONS: ESPB was followed by better postoperative analgesia and less opioid consumption.

Efficacy and safety of pregabalin in eye pain: A systematic review.

BACKGROUND: The pregabalin is approved for the management of persistent pain. The aim of this study is to assess the advantages and disadvantages of the use of pregabalin in eye pain management. METHODS: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched until January 2022 for randomized controlled trials. Randomized, double-blinded trials comparing pregabalin with placebo in eye pain management were included. The primary outcome was visual analog scale or numerical rating scale at acute (24 hours) and chronic (≥7 days after surgery) timepoints. The secondary outcomes were analgesic medication requirements and pregabalin-related complications (nausea, vomiting, dizziness, and headache). We also compared the effect of pregabalin on dry-eye syndrome. MAIN RESULTS: Six relevant articles were identified that studied the use of pregabalin as pain relief for photorefractive keratectomy (n = 2), laser epithelial keratomileusis (n = 1), laser-assisted in situ keratomileusis (n = 1), eyelid surgery (n = 1), and dacryocystorhinostomy (n = 1). Pregabalin was associated with a significant reduction in pain scores (95% confidence interval = -0.41 [-0.76--0.06]) 24 hours after surgical procedures. The data were insufficient to draw conclusions regarding dry eye symptoms. Because of the high heterogeneity of outcomes regarding adverse effects, there is no conclusion regarding the safety of pregabalin in eye pain. CONCLUSIONS: Pregabalin reduced acute eye pain but had no significant effect on long-term analgesia after ophthalmological surgery in adults. It had no effect on dry-eye symptoms after ocular surgery. Further studies on the safety of pregabalin in eye pain management are required to draw solid conclusions.

[Emergency medicine: what's new in 2022]. / Médecine d'urgence : ce qui a changé en 2022.

Emergency medicine is facing many challenges, particularly related to the consequences of the pandemic on the pressure of patient flows and the lack of human resources. More than ever, our discipline seeks to offer our patients quality care based on several recent studies, of which the following is a section: a) Gender effect in the administration of tranexamic acid; b) External validation of the Canadian Syncope Risk Score; c) Role of neuro-imaging in psychiatric decompensation; d) Choice of analgesia in renal colic; e) Use of carotid ultrasound for pulse control in cardiac arrest and f) The safetyness of performing simple sutures in non-sterile conditions.

La médecine d'urgence est confrontée à de nombreux défis, notamment liés aux conséquences de la pandémie sur la pression des flux patients et du manque de ressources médico-soignantes. Plus que jamais, notre discipline cherche à offrir à nos patients des soins de qualité en s'appuyant sur plusieurs études récentes dont voici une sélection : a) effet de genre dans l'administration d'acide tranexamique ; b) validation externe du Canadian Syncope Risk Score ; c) rôle de l'imagerie cérébrale dans les décompensations psychiatriques ; d) choix de l'antalgie dans la colique néphrétique ; e) utilisation de l'US carotidien dans le contrôle du pouls lors d'ACR et f) possibilité de réaliser des sutures simples sans conditions stériles.

Novel GluN2B-Selective NMDA Receptor Negative Allosteric Modulator Possesses Intrinsic Analgesic Properties and Enhances Analgesia of Morphine in a Rodent Tail Flick Pain Model.

Many cases of accidental death associated with drug overdose are due to chronic opioid use, tolerance, and addiction. Analgesic tolerance is characterized by a decreased response to the analgesic effects of opioids, requiring increasingly higher doses to maintain the desired level of pain relief. Overactivation of GluN2B-containing N-methyl-d-Aspartate receptors is thought to play a key role in mechanisms underlying cellular adaptation that takes place in the development of analgesic tolerance. Herein, we describe a novel GluN2B-selective negative allosteric modulator, EU93-108, that shows high potency and brain penetrance. We describe the structural basis for binding at atomic resolution. This compound possesses intrinsic analgesic properties in the rodent tail immersion test. EU93-108 has an acute and significant anodyne effect, whereby morphine when combined with EU93-108 produces a higher tail flick latency compared to that of morphine alone. These data suggest that engagement of GluN2B as a target has utility in the treatment of pain, and EU93-108 could serve as an appropriate tool compound to interrogate this hypothesis. Future structure-activity relationship work around this scaffold could give rise to compounds that can be co-administered with opioids to diminish the onset of tolerance due to chronic opioid use, thereby modifying their utility.