Tramadol-paracetamol for postoperative pain after spine surgery - A randomized, double-blind, placebo-controlled study.

OBJECTIVES: Multimodal pain management is one component in enhanced recovery after surgery protocol. Here we evaluate the efficacy of tramadol-paracetamol in acute postoperative pain and pain outcome at 12 months after spine surgery in randomized, double-blind, placebo-controlled trial. METHODS: We randomized 120 patients undergoing spine surgery to receive, for add-on pain management, two tramadol-paracetamol 37.5 mg/325 mg (n = 61) or placebo tablets (n = 59) twice a day for 5 postoperative days. In the hospital, multimodal pain management consisted of dexketoprofen and oxycodone. After discharge, patients were prescribed ibuprofen 200 mg, maximum 1,200 mg/day. Pain, analgesic use, and satisfaction with pain medication were followed up with the Brief Pain Inventory questionnaire before surgery and at 1 and 52 weeks after surgery. The primary outcome was patients' satisfaction with pain medication 1 week after surgery. RESULTS: At 1 week after surgery, patients' satisfaction with pain medication was similarly high in the two groups, 75% [interquartile range, 30%] in the placebo group and 70% [40%] in the tramadol-paracetamol group (p = 0.949) on a scale: 0% = not satisfied, 100% = totally satisfied. At 1 week, ibuprofen dose was lower in the placebo group 200 mg [1,000] compared to the tramadol-paracetamol group, 800 mg [1,600] (p = 0.016). There was no difference in the need for rescue oxycodone. Patients in the tramadol-paracetamol group had more adverse events associated with analgesics during the first postoperative week (relative risk = 1.8, 95% confidence interval, 1.2-2.6). CONCLUSION: Add-on pain treatment with tramadol-paracetamol did not enhance patients' satisfaction with early pain management after back surgery.

Simultaneous determination of methadone and tramadol in serum samples by ultrasonic-assisted micro solid phase extraction and gas chromatography-mass spectrometry.

Ultrasonic-assisted dispersive micro solid phase extraction (UA-DMSPE) is proposed as a fast and easy technique for the extraction and preconcentration of methadone and tramadol from serum samples. Different sorbents including carbon nanotubes, oxidized carbon nanotubes, and TiO2 nanoparticles were compared to extract methadone and tramadol. The best performance was obtained using oxidized carbon nanotubes due to the strong affinity between the drugs and carbon nanotube adsorbents. Final analysis of drugs performed by using gas chromatography-mass spectrometric detection. Different parameters affecting the extraction efficiency, such as the sample volume, amount of adsorbent, desorption solvent type and volume, centrifugation time, and speed were investigated and optimized. The striking features of this technique are correlated to its speed and the small volumes of sample (about 1 mL), desorption solvent (about 50 µL), and adsorbent (about 0.001 g) for analysis of drugs, and finally, milder centrifugation conditions relative to the previously reported adsorbent. The optimal parameters were achieved as follows: pH value was set at 9, the sample volume was adjusted to 1200 µL, the amount of adsorbent used was 1 mg, the extraction time was set at 5 min, and the volume of the desorption solvent was adjusted to 50 µL. The limits of detections (0.5 and 0.8 ng mL-1) and quantifications (1.5 and 2.5 ng mL-1) were obtained for methadone and tramadol, respectively. The developed method also showed good repeatability, relative standard deviation (RSD) of 9.49 % and 7.47 % (n = 5), for the spiked aqueous solution at the concentration level of 10, 50, and 100 ng mL-1 for analytes, and linearity, R ≥ 0.9809. The results showed that UA-DMSPE is a quick, relatively inexpensive, and environmentally friendly alternative technique for the extraction of opiate drugs from serum samples.

A novel comparison of erector spinae plane block and paravertebral block in laparoscopic cholecystectomy.

OBJECTIVE: Erector spinae plane block is an updated method than paravertebral block, possessing a lower risk of complications. This study aimed to compare erector spinae plane and paravertebral blocks to safely reach the most efficacious analgesia procedure in laparoscopic cholecystectomy cases. METHODS: The study included 90 cases, aged 18-70 years, classified as American Society of Anesthesiologists I-II, who underwent an laparoscopic cholecystectomy procedure. They were randomly separated into three groups, namely, Control, erector spinae plane, and paravertebral block. No block procedure was applied to Control, and a patient-controlled analgesia device was prepared containing tramadol at a 10 mg bolus dose and a 10-min locked period. The pain scores were recorded with a visual analog scale for 24 h postoperatively. RESULTS: The visual analog scale values at 1, 5, 10, 20, and 60 min at rest and 60 min coughing were found to be significantly higher in Control than in paravertebral block. A significant difference was revealed between Control vs. paravertebral block and paravertebral block vs. erector spinae plane in terms of total tramadol consumption (p=0.006). Total tramadol consumption in the first postoperative 24 h was significantly reduced in the paravertebral block compared with the Control and erector spinae plane groups. CONCLUSION: Sonography-guided-paravertebral block provides sufficient postoperative analgesia in laparoscopic cholecystectomy surgery. Erector spinae plane seems to attenuate total tramadol consumption.

Concomitant use of pre-emptive analgesia with local and general anesthesia in rat uterine pain surgical model.

Preemptive analgesia is used for postoperative pain management, providing pain relief with few adverse effects. In this study, the effect of a preemptive regime on rat behavior and c-fos expression in the spinal cord of the uterine surgical pain model was evaluated. It was a lab-based experimental study in which 60 female Sprague-Dawley rats; eight to 10 weeks old, weighing 150-300 gm were used. The rats were divided into two main groups: (i) superficial pain group (SG) (with skin incision only), (ii) deep pain group (with skin and uterine incisions). Each group was further divided into three subgroups based on the type of preemptive analgesia administered i.e., "tramadol, buprenorphine, and saline subgroups." Pain behavior was evaluated using the "Rat Grimace Scale" (RGS) at 2, 4, 6, 9 and 24 h post-surgery. Additionally, c-fos immunohistochemistry was performed on sections from spinal dorsal horn (T12-L2), and its expression was evaluated using optical density and mean cell count 2 hours postoperatively. Significant reduction in the RGS was noted in both the superficial and deep pain groups within the tramadol and buprenorphine subgroups when compared to the saline subgroup (p ≤ .05). There was a significant decrease in c-fos expression both in terms of number of c-fos positive cells and the optical density across the superficial laminae and lamina X of the spinal dorsal horn in both SD and DG (p ≤ .05). In contrast, the saline group exhibited c-fos expression primarily in laminae I-II and III-IV for both superficial and deep pain groups and lamina X in the deep pain group only (p ≤ .05). Hence, a preemptive regimen results in significant suppression of both superficial and deep components of pain transmission. These findings provide compelling evidence of the analgesic efficacy of preemptive treatment in alleviating pain response associated with uterine surgery.

Comparison of analgesic efficacy of tramadol, morphine and methadone in cats undergoing ovariohysterectomy.

OBJECTIVES: The aim of this study was to compare the analgesic efficacy and the effect on physiological variables and behavior of the use of tramadol, methadone and morphine as preoperative analgesia in healthy cats undergoing elective ovariohysterectomy. METHODS: Cats undergoing ovariohysterectomy were randomly assigned to receive one of the following premedication treatments intramuscularly: methadone (0.2 mg/kg; n = 10); morphine (0.2 mg/kg; n = 10); or tramadol (3 mg/kg; n = 10). Induction of anesthesia was done with propofol, and maintenance of anesthesia was done with isoflurane. Intraoperative heart rate, arterial blood pressure, respiratory rate, end-tidal isoflurane concentration and frequency of rescue analgesia (fentanyl 2.5 µg/kg) were compared between groups. Postoperative analgesia was assessed using the UNESP-Botucatu Multidimensional Composite Pain Scale, and perioperative serum glucose, cortisol concentrations and postoperative rescue analgesia were evaluated. RESULTS: Intraoperative rescue analgesia was required in 76.5% of cats at some time during surgery, and 27% of cats required postoperative rescue analgesia up to 6 h after extubation. There were no significant differences between groups with respect to intraoperative and postoperative rescue analgesia, pain scale scores and end-tidal isoflurane concentrations. In the immediate postoperative period, after extubation, most of the patients presented with hypothermia; however, 1-6 h postoperatively, hyperthermia was observed in most of the patients, and was most common in the tramadol group. CONCLUSIONS AND CLINICAL RELEVANCE: Under the conditions of this study, methadone, morphine and tramadol produced satisfactory postoperative analgesia in most of the cats undergoing ovariohysterectomy, and the effects lasted up to 6 h postoperatively. Intraoperative analgesia was not sufficient in most cases. Significant cardiovascular or respiratory effects contraindicating the use of these drugs were not found. Postanesthetic hyperthermia occurred with all opioids studied and was more frequent in the tramadol group.

Efficacy of Serratus Posterior Superior Intercostal Plane Block on Postoperative Pain and Total Analgesic Consumption in Patients Undergoing Reduction Mammoplasty Surgery: An Evidence Based Report.

Serratus posterior superior intercostal plane block (SPSIPB) is a novel technique that provides analgesia in shoulder, hemithorax and in the back of the neck. In this study, the efficacy of this block on postoperative pain and quality of recovery is reported in ten consecutive patients who had undergone reduction mammoplasty. Blocks were performed bilaterally with 30 ml 0.25 % bupivacaine for each side, at the end of surgery. Cumulative tramadol consumption and numerical rating scale (NRS) scores during rest (static) and coughing (dynamic) were assessed within the first postoperative 24 hours. Mean total tramadol consumption was 39 ±9.94 mg. NRS scores above 4 were observed in 5 patients in the dynamic NRS assessment at the postoperative 1st hour, while static and dynamic NRS scores were ≤4 at other durations. SPSIPB may play a part in postoperative multimodal analgesia following mammoplasty in the future and may reduce total analgesic consumption. Key Words: Serratus posterior superior intercostal plane block, Reduction mammoplasty, Breast surgery, Postoperative analgesia.

Analgaesic Effect of Erector Spinae Plane Block in Coronary Surgery: A Randomised Controlled Trial.

OBJECTIVE: To investigate the effect of preemptive erector spinae plane (ESP) block application on postoperative pain scores and opioid demand in off-pump coronary artery bypass graft (CABG) surgery. STUDY DESIGN: Randomised-controlled trial. Place and Duration of the Study: Department of Anaesthesiology and Reanimation, Abant Izzet Baysal University (AIBU) Medical School, Bolu, Turkiye, from November 2020 to April 2021. METHODOLOGY: Fifty patients between the ages of 50 and 75 years, received CABG surgery. These participants who were at risk of the American Society of Anesthesiologists (ASA) III were randomly divided into two groups: ESP (Group E) and Control (Group C). Intervention in Group E was performed bilaterally at the T5 level before the operation. In the study, the primary outcome was postoperative opioid demand while the secondary outcomes consisted of intraoperative opioid demand, visual analogue scale scores, and the duration of hospital stay. RESULTS: Tramadol demand was significantly decreased in Group E at 0-1, 1-12, 12-24, and 0-48 hours (p <0.05). Intraoperative fentanyl demand for Group E was also statistically significantly decreased (p= 0.001). In Group E, the visual analogue scale scores at 30 minutes, 1st, 2nd, 4th, 8th, 12th hour, and 16th hour after postoperative extubation were observed to be significantly lower than those of Group C (p <0.05). CONCLUSION: Preemptive ESP block application in CABG surgery patients reduced postoperative tramadol demand, intraoperative fentanyl demand, and postoperative pain scores. KEY WORDS: Coronary artery bypass surgery, Erector spinae plane block, Acute postoperative pain.

Opioid therapy trajectories of patients with chronic non-cancer pain over 1 year of follow-up after initiation of short-acting opioid formulations.

OBJECTIVE: This study compared opioid utilization trajectories of persons initiating tramadol, short-acting hydrocodone, or short-acting oxycodone, and it characterized opioid dose trajectories and type of opioid in persistent opioid therapy subsamples. METHODS: A retrospective cohort study of adults with chronic non-cancer pain who were initiating opioid therapy was conducted with the IQVIA PharMetrics® Plus for Academics data (2008-2018). Continuous enrollment was required for 6 months before ("baseline") and 12 months after ("follow-up") the first opioid prescription ("index date"). Opioid therapy measures were assessed every 7 days over follow-up. Group-based trajectory modeling (GBTM) was used to identify trajectories for any opioid and total morphine milligram equivalent measures, and longitudinal latent class analysis was used for opioid therapy type. RESULTS: A total of 40 276 tramadol, 141 023 hydrocodone, and 45 221 oxycodone initiators were included. GBTM on any opioid therapy identified 3 latent trajectories: early discontinuers (tramadol 39.0%, hydrocodone 54.1%, oxycodone 61.4%), late discontinuers (tramadol 37.9%, hydrocodone 39.4%, oxycodone 33.3%), and persistent therapy (tramadol 6.7%, hydrocodone 6.5%, oxycodone 5.3%). An additional fourth trajectory, intermittent therapy (tramadol 16.4%), was identified for tramadol initiators. Of those on persistent therapy, 2687 individuals were on persistent therapy with tramadol, 9169 with hydrocodone, and 2377 with oxycodone. GBTM on opioid dose resulted in 6 similar trajectory groups in each persistent therapy group. Longitudinal latent class analysis on opioid therapy type identified 6 latent classes for tramadol and oxycodone and 7 classes for hydrocodone. CONCLUSION: Opioid therapy patterns meaningfully differed by the initial opioid prescribed, notably the presence of intermittent therapy among tramadol initiators and higher morphine milligram equivalents and prescribing of long-acting opioids among oxycodone initiators.

Comparative Evaluation of the Local Anesthetic Action of Tramadol Hydrochloride With Adrenaline Versus Lidocaine Hydrochloride With Adrenaline for Maxillary Exodontia: A Randomized Control Trial.

BACKGROUND: Tramadol hydrochloride (T-HCl) has demonstrated to have a local anesthetic effect similar to lidocaine hydrochloride (L-HCl) when administered locally for minor oral surgical procedures. PURPOSE: Our study aimed to compare the anesthetic effect of T-HCl versus L-HCl in maxillary premolar extraction. STUDY DESIGN, SETTING AND SAMPLE: The study is a split-mouth, double-blind randomized clinical trial at the Faculty of Dental Sciences, Ramaiah University of Applied Sciences, Bengaluru, India. The study sample was composed of patients referred for maxillary bicuspid extraction. Patients were excluded from the sample if, allergic to the study drugs, pregnant or lactating females, and smokers. EXPOSURE VARIABLE: The variable is an anesthetic drug administered for local anesthesia and it is grouped into 2 categories, T-HCl and L-HCl. A supraperiosteal infiltration of T-HCl with adrenaline on one side and L-HCl with adrenaline on the contralateral side was injected. MAIN OUTCOME VARIABLE: The primary outcome variable was profound anesthesia of T-HCl, where the patient sensed the loss of sensation of touch, temperature, and pain. Secondary outcomes were onset and duration of anesthesia, intraoperative pain, postoperative analgesia, and adverse reactions, were recorded. ANALYSES: Inferential statistics, the χ2 Test, the Mann-Whitney Test, and the Wilcoxon signed-rank test were used to compare the parameters. The level of significance was set at ≤ 0.05. RESULTS: A total of 40 patients were included, and 80 teeth were extracted. Profound anesthesia was achieved in all the cases. The mean subjective duration of anesthesia in the T-HCl and L-HCl groups was 130.80 ± 20.01 minutes and 111.40 ± 14.87 minutes, respectively, with a P value of .001. The mean Visual Analogue Scale (VAS) score for pain during the procedure in the T-HCl and L-HCl groups was 0.60 ± 0.67 and 1.10 ± 0.71, respectively, with a P value of .002. The mean Visual Analogue Scale score for pain postoperatively in the T-HCl and L-HCl groups was 0.70 ± 0.72 and 1.40 ± 0.67, respectively, with a P value of .001. Six patients in T-HCl required postoperative analgesia when compared to 18 patients in L-HCl (P value < .003). CONCLUSIONS AND RELEVANCE: T-HCl provides similar anesthetic outcomes in the extraction of maxillary bicuspids as L-HCl.

Comparison of the analgesic efficacy of the ultrasound-guided transversalis fascia plane block and erector spinae plane block in patients undergoing open inguinal hernia repair under spinal anesthesia.

BACKGROUND: Open inguinal hernia repair (OIHR) surgery is a common surgical procedure, and ultrasound guided interfascial plane blocks can also be included in current approaches to postoperative multimodal analgesia regimens. This study aimed to compare the postoperative analgesic efficacy of the erector spinae plane block (ESPB) and transversalis fascia plane block (TFPB) in patients undergoing OIHR. METHODS: This prospective, randomized, assessor-blinded comparative study was conducted in the postoperative recovery room and ward of a tertiary hospital. A total of 80 patients with American Society of Anesthesiologists physical status I-III were enrolled and allocated equally to either the ESPB or TFPB group. The patients received standard multimodal analgesia in addition to an ultrasound-guided ESPB or TFPB. During the first 24 h postoperatively, tramadol consumption was assessed and pain levels at rest and during movement were compared using numeric rating scale (NRS) scores at 1, 3, 6, 9, 12, 18, and 24 h postoperatively. RESULTS: The results showed no difference in NRS scores at any time point between the groups, except for NRS at rest in the third hour. However, tramadol consumption was lower in the TFPB group than in the ESPB group overall (88 ± 75.2 vs. 131 ± 93.7 mg, respectively; P = 0.027, mean difference: -43, 95% CI [-80.82, -5.18]). CONCLUSIONS: The TFPB leads to lower tramadol requirements in the first 24 h postoperatively than the ESPB in patients undergoing OIHR.

Co-crystal of Tramadol-Celecoxib Versus Tramadol or Placebo for Acute Moderate-to-Severe Pain After Oral Surgery: Randomized, Double-Blind, Phase 3 Trial (STARDOM1).

INTRODUCTION: Co-crystal of tramadol-celecoxib (CTC) is the first analgesic co-crystal for acute pain. This completed phase 3 multicenter, double-blind trial assessed the efficacy and safety/tolerability of CTC in comparison with that of tramadol in the setting of moderate-to-severe pain up to 72 h after elective third molar extraction requiring bone removal. METHODS: Adults (n = 726) were assigned randomly to five groups (2:2:2:2:1): orally administered twice-daily CTC 100 mg (44 mg rac-tramadol hydrochloride/56 mg celecoxib; n = 164), 150 mg (66/84 mg; n = 160) or 200 mg (88/112 mg; n = 160); tramadol 100 mg four times daily (n = 159); or placebo four times daily (n = 83). Participants in CTC groups also received twice-daily placebo. The full analysis set included all participants who underwent randomization. The primary endpoint was the sum of pain intensity differences over 0 to 4 h (SPID0-4; visual analog scale). Key secondary endpoints included 4-h 50% responder and rescue medication use rates. Safety endpoints included adverse events (AEs), laboratory measures, and Opioid-Related Symptom Distress Scale (OR-SDS) score. RESULTS: All CTC doses were superior to placebo (P < 0.001) for primary and key secondary endpoints. All were superior to tramadol for SPID0-4 (analysis of covariance least squares mean differences [95% confidence interval]: - 37.1 [- 56.5, - 17.6], - 40.2 [- 59.7, - 20.6], and - 41.7 [- 61.2, - 22.2] for 100, 150, and 200 mg CTC, respectively; P < 0.001) and 4-h 50% responder rate. Four-hour 50% responder rates were 32.9% (CTC 100 mg), 33.8% (CTC 150 mg), 40.6% (CTC 200 mg), 20.1% (tramadol), and 7.2% (placebo). Rescue medication use was lower in the 100-mg (P = 0.013) and 200-mg (P = 0.003) CTC groups versus tramadol group. AE incidence and OR-SDS scores were highest for tramadol alone. CONCLUSIONS: CTC demonstrated superior pain relief compared with tramadol or placebo, as well as an improved benefit/risk profile versus tramadol. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02982161; EudraCT number, 2016-000592-24.

Effects of Modified Thoracoabdominal Nerve Block Through Perichondrial Approach on Postoperative Pain and Analgaesic Consumption in Patients Undergoing Laparoscopic Cholecystectomy.

OBJECTIVE: To investigate postoperative analgaesic efficacy of modified thoracoabdominal nerve block through perichondrial approach (M-TAPA) and its effect on opioid consumption in patients undergoing laparoscopic cholecystectomy (LC) surgery. STUDY DESIGN: Randomised, controlled trial. Place and Duration of the Study: Department of Anaesthesiology and Reanimation, Sivas Cumhuriyet University, Sivas, Turkiye, from April to May 2023. METHODOLOGY: The study was conducted in two randomised groups: M-TAPA (n = 21) and control group (CG) (no block) (n = 21). All patients had standard general anaesthesia. M-TAPA patients had bilateral M-TAPA block with 0.25% bupivacaine (total volume, 40 ml) at the end of the surgery. In contrast, CG patients had only tramadol for postoperative pain. A numerical rating scale (NRS) and visual analogue scale (VAS) were used for postoperative pain assessment. Total tramadol consumption was calculated. RESULTS: M-TAPA's NRS and VAS scores were lower in postoperative 24 hours (p<0.05). Total tramadol consumption was 116.67 ± 32.91 mg in CG and 35.71 ± 39.19 mg in M-TAPA (p<0.001). CONCLUSION: Bilateral M-TAPA block for postoperative pain control after LC surgery provided effective analgaesia for up to 24 hours and reduced total opioid consumption. Although the M-TAPA block is a novel approach, it will be a part of multimodal analgaesia for routine postoperative pain management in abdominal surgeries. However, more studies with higher numbers of patients will be needed. KEY WORDS: Analgaesia, Bupivacaine, Laparoscopic cholecystectomy, Nerve block, Pain management.

Risk Factors for Opioid Misuse, Abuse, and Dependence Among Pain Clinic Patients: A Cross-Sectional Study at King Khalid University Hospital during 2020.

BACKGROUND Physicians are faced with the risk of patients developing opioid use disorders (OUDs) when prescribing patients opioids for long periods of time. Therefore, it is highly recommended to continuously monitor and evaluate long-term non-cancer pain patients who are prescribed opioids. This study aims to estimate the prevalence of OUDs in 103 patients with active opioid prescriptions attending the Pain Clinic at King Khalid University Hospital. MATERIAL AND METHODS A cross-sectional study was conducted at King Khalid University Hospital's pain clinic from 2020 to 2022. A list of all patients attending the Pain Clinic with an opioid prescription was provided by the hospital. Through telephone interviews, consent was secured followed by the collection of demographic variables and prescription-related variables. Additionally, patients were asked to complete the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST 3.1) opioid questionnaire. RESULTS Most of the 103 patients were at moderate risk for abuse (91.3%), while a smaller percentage were at high risk (dependence) (5.8%) and low risk (misuse) (2.9%). Tramadol was the most-prescribed opioid (43.7%). Young age (<50) (Z=2.534; P=0.011), opioid use for more than 90 days (Z=2.788; P=0.005), and the prescription of tramadol (Z=4.124; P<0.001) were associated with higher risk of OCDs. CONCLUSIONS Younger patients, opioid use >90 days, and tramadol are associated with a higher risk of opioid misuse. However, further studies on a larger scale and in various settings are needed to provide evidence accurately reflecting the general population, as this study focused on the population of pain clinic attendees.

[Efficacy and safety of different nerve block methods for the treatment of pudendal neuralgia].

Objective: To identify efficacy and safety of pudendal nerve block in tubing through the third posterior sacral foramen for the treatment of pudendal neuralgia (PN). Methods: A retrospective study with 222 PN patients was conducted in the Department of Pain Management of Beijing Tsinghua Changgung Hospital from January 2020 to April 2023. These patients were divided into two groups based on their treatment methods: pudendal nerve block in tubing through the third posterior sacral foramen (observation group, n=101) and ultrasound-guided pudendal nerve block (control group, n=121). Primary outcome measure was the 90-day postoperative pain relief rate. Secondary outcome measures included visual analog scale (VAS) at 1, 7, 14, 30 and 90 d after surgery, the incidence of tramadol uses after surgery, postoperative self-rating anxiety scale (SAS) scores and the incidence of adverse events. Factors that influenced pain relief within 90 days after surgery were analyzed by using binary logistic regression analysis. Results: Observation group included 34 males and 67 females, aged (49.8±16.0) years old. Control group included 38 males and 83 females, aged (43.7±14.0) years old. The 90-day postoperative pain relief rate of the observation group patients was 38.6% (39/101), which was higher than the 24.0% (29/121) of the control group patients (P=0.018). Both the observation group and the control group showed an interaction effect of time and group after treatment for VAS scores (both P<0.05). In intra-group comparison, the VAS scores at 1, 7, 14, 30 and 90 d after treatment in both groups were lower than those before treatment (all P<0.05). In inter-group comparison, the differences of the VAS scores were not statistically significant in the observation group compared with those in the control group at 1, 7, 14, 30 and 90 d after surgery (all P>0.05). The SAS score of the observation group at 90 d after surgery was 51.5±6.2, which was lower than the 53.4±5.8 of the control group (P=0.022). There was no statistically significant difference in the incidence of postoperative tramadol uses and adverse events between the two groups (both P>0.05). Pudendal nerve block in tubing through the third posterior sacral foramen was a protective factor for pain postoperative relief in PN patients at 90 d after surgery (OR=1.92, 95%CI: 1.05-3.48, P=0.033). Conclusion: Pudendal nerve block in tubing through the third posterior sacral foramen is a safe and effective minimally invasive treatment. It has a higher postoperative pain relief rate within 90 d after surgery, without increasing the uses of postoperative rescue analgesics and the incidence of adverse events.

Effects of tramadol via a µ-opioid receptor on pancreatic ductal adenocarcinoma in vitro and in vivo.

INTRODUCTION: Tramadol, a weak opioid anesthetic, is used for pain management in patients with cancer, but the effects of tramadol on cancer via µ-opioid receptor are still unknown. We assessed the effects of tramadol on pancreatic ductal adenocarcinoma using transgenic mice (LSL-KrasG12D/+; Trp53flox/flox; Pdx-1cre/+ ). METHODS: Six-week-old transgenic mice were orally administered 10 mg/kg/day tramadol (n=12), 10 mg/kg/day tramadol and 1 mg/kg/day naltrexone (n=9), or vehicle water (n=14) until the humane endpoint. Cancer-related pain and plasma cytokine levels were assessed by the mouse grimace scale and cytokine array, respectively. Tumor status was determined histopathologically. Tramadol's effects on proliferation and invasion in pancreatic ductal adenocarcinoma cell lines were studied in vitro. RESULTS: Tramadol with/without naltrexone improved mouse grimace scale scores while decreasing inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. Proliferative Ki-67 and cyclins decreased by tramadol, while local M1-like tumor-associated macrophages increased by tramadol, which was blocked by naltrexone. Meanwhile, tramadol with/without naltrexone reduced juxta-tumoral cancer-associated fibroblasts and M2-like tumor-associated macrophages. Tumor-associated neutrophils, natural killers, and cytotoxic T cells were not altered. Tramadol decreased the proliferative and invasive potentials of pancreatic ductal adenocarcinoma cell lines via decreasing cyclins/cyclin-dependent kinases, which was partially reversed by naltrexone. CONCLUSIONS: These findings imply that tramadol might be a useful anesthetic for pancreatic ductal adenocarcinoma: inhibiting the proliferation and invasion along with increasing antitumor M1-like tumor-associated macrophages via the µ-opioid receptor, while improving cancer-associated pain possibly through the antitumor effects with the decrease of inflammatory cytokines.

Tramadol use before total shoulder arthroplasty: patients have lower risk of complications and resource utilization than those using traditional opioids.

BACKGROUND: Evidence continues to mount for the deleterious effects of preoperative opioid use in the setting of total shoulder arthroplasty (TSA). Tramadol, a synthetic opioid with concomitant neurotransmitter effects, has become a popular alternative to traditional opioids, but it has not been well studied in the preoperative setting of TSA. The purpose of this study is to evaluate postsurgical outcomes in TSA for patients with preoperative tramadol use compared with patients using traditional opioids and those who were opioid naïve. METHODS: Using the IBM Watson Health MarketScan databases, a retrospective cohort study was performed for patients who underwent TSA from 2009 to 2018. Filled pain prescriptions were collected, and prescribing trends were analyzed. Outcomes were compared between 4 patient cohorts defined by preoperative analgesia use-opioid naïve, tramadol, traditional opioids, and combination (opioids and tramadol). Multivariate analysis was used to account for small variations in cohort demographics and comorbidities. Analysis focused on resource utilization and complications. Revision rates at 1 and 3 years postoperatively were also compared. RESULTS: A total of 29,454 TSA patients were studied, with 8959 available for 3-year postoperative follow-up. Of these, 10,462 (35.5%) were prescribed traditional opioids and 2214 (7.5%) tramadol only. From 2009 to 2018, prescribing trends in the United States demonstrated a significant decrease in the number of patients prescribed preoperative narcotics, whereas the number of patients prescribed preoperative tramadol and those who were opioid naïve significantly increased. Compared with opioid-naïve patients, the traditional opioid cohort had significantly increased odds of resource utilization and complications, whereas the tramadol cohort did not. Specifically, the traditional opioid cohort had an increased risk of prosthetic joint infection compared with both opioid-naïve and tramadol cohorts. The traditional opioid cohort had higher revision rates than opioid-naïve patients at 1 and 3 years, whereas the tramadol cohort did not. CONCLUSION: Despite a decrease in opioid prescriptions over the study period, many patients in the United States remain on opioids. Although tramadol is not without its own risks, our results suggest that patients taking preoperative tramadol as an alternative to traditional opioids for glenohumeral arthritic pain had a lesser postoperative risk profile, comparable with opioid-naïve patients.

Coenzyme Q10 attenuates neurodegeneration in the cerebellum induced by chronic exposure to tramadol.

BACKGROUND: Chronic use of tramadol can cause neurotoxic effects and subsequently cause neurodegeneration in the cerebellum. The main damage mechanisms identified are oxidative stress and inflammation. Currently, we investigated the effects of coenzyme Q10 (CoQ10) in attenuates of neurodegeneration in the cerebellum induced by chronic exposure to tramadol. MATERIAL AND METHODS: Seventy-two male mature albino rats were allocated into four equal groups, including; non-treated group, CoQ10 group (which received CoQ10 at 200 mg/kg/day orally for three weeks), tramadol group (which received tramadol hydrochloride at 50 mg/kg/day orally for three weeks), and tramadol+CoQ10 group (which received tramadol and CoQ10 at the same doses as the previous groups). Tissue samples were obtained for stereological, immunohistochemical, biochemical, and molecular evaluations. Also, functional tests were performed to evaluate behavioral properties. RESULTS: We found a significant increase in stereological parameters, antioxidant factors (catalase, glutathione, and superoxide dismutase), and behavioral function scores in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). In addition, malondialdehyde levels, the density of apoptotic cells, as well as the expression of pro-inflammatory (tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6) and autophagy (lysosome-associated membrane protein 2, autophagy-related 5, beclin 1, and autophagy-related 12) genes were considerably reduced in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). CONCLUSION: We conclude that the administration of CoQ10 has neuroprotective effects in the cerebellum of rats that have chronic exposure to tramadol.

Clinical Effect of Ultrasound-Guided Adductor Block on Postoperative Analgesia After Total Knee Replacement.

Objective: To explore the clinical effects of ultrasound-guided adductor block (UGAB) on postoperative analgesia after total knee replacement. Methods: From March 2022 to June 2022, 60 patients in the First Affiliated Hospital of Chongqing Medical University were included. They were divided into control (n = 30) and ultrasonic groups (n = 30). They all received total knee arthroplasty. Before total knee arthroplasty, patients in the control and ultrasonic groups underwent general anesthesia and UGAB, respectively. Visual Analogue Scale (VAS) was used to assess the pain. The time of the first straight leg elevation and the first landing time were recorded. Knee joint function was evaluated. Information about the dosage of tramadol intramuscular injection and the number of times patient-controlled analgesia pump pressing was collected. The serum levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) were detected. Results: Compared with the control group, UGAB increased the rate of muscle contraction and relaxation and total and relaxation after total knee replacement in the ultrasonic group (P < .05). UGAB reduced VAS scores of pain during passive activity after operation (P < .05). UGAB also facilitated the first straight leg lifting time after the operation and the time of the first landing after the operation (P < .05). Meanwhile, UGAB reduced the dose of tramadol and press times of the self-control analgesia pump after operation (P < 0.05). UGAB also suppressed postoperative IL-6 and hs-CRP levels and increased postoperative joint range of motion (P < .05). Conclusion: UGAB promotes early recovery of knee function with high safety in patients undergoing total knee replacement, with reduced postoperative pain and inflammatory reaction.

Impact of CYP2D6 and CYP2B6 phenotypes on the response to tramadol in patients with acute post-surgical pain.

Tramadol is an important minor opioid prescribed for pain management. In this study, we analyzed the well-known impact of CYP2D6 genetic variation and 60 additional variants in eight candidate genes (i.e., ABCG2, SLCO1B1, CYP2D6, CYP2B6, CYP2C19, CYP2C9, CYP3A5, and CYP3A4) on tramadol efficacy and safety. Some 108 patients with pain after surgery admitted to a post-anesthesia care unit (PACU) and prescribed tramadol were recruited. They were genotyped, and tramadol M1/M2 metabolite concentrations were determined by a newly validated HPLC-MS/MS method. CYP2D6 intermediate (IM) and poor (PM) metabolizers showed lower M1 concentrations adjusted for dose/weight at 30 and 120 min compared to ultrarapid (UM) and normal (NM) metabolizers (univariate p < 0.001 and 0.020, multivariate p < 0.001 and 0.001, unstandardized ß coefficients = 0.386 and 0.346, R2 = 0.146 and 0.120, respectively). CYP2B6 PMs (n = 10) were significantly related to a higher reduction in pain 30 min after tramadol intake (univariate p = 0.038, multivariate p = 0.016, unstandardized ß coefficient = 0.224, R2 = 0.178), to lower PACU admission time (p = 0.007), and to lower incidence of adverse drug reactions (p = 0.038) compared to the other phenotypes. CYP3A4 IMs and PMs showed a higher prevalence of drowsiness and dizziness (p = 0.028 and 0.005, respectively). Our results suggest that the interaction of CYP2B6 and CYP2D6 phenotypes may be clinically relevant, pending validation of these results in large, independent cohorts. Additional research is required to clarify the impact of CYP3A4 genetic variation on tramadol response.

Quadratus lumborum and erector spinae plane blocks are effective for analgesia in laparoscopic hysterectomy: a randomized controlled trial.

OBJECTIVE: Total laparoscopic hysterectomy is the preferred technique for hysterectomy in obstetrics and gynecology clinics. However, patients who undergo these procedures often experience acute pain that may progress to chronic pain over time. Erector spinae plane block (ESPB) and anterior quadratus lumborum block (QLB) under ultrasound guidance are reported to be effective as part of the multi-modal analgesia protocol. Therefore, this study aimed to compare the effectiveness of erector spinae plane block and anterior quadratus lumborum block in reducing postoperative opioid consumption and pain scores in patients undergoing total laparoscopic hysterectomy. PATIENTS AND METHODS: Eighty-one patients who met the inclusion criteria were divided into three groups: the erector spinae plane block, anterior quadratus lumborum block, and control groups. All patients received general anesthesia and tramadol-based patient-controlled analgesia (PCA) during the postoperative period. Tramadol consumption and pain scores during the first 24 h were evaluated by a blinded researcher. Postoperative opioid consumption was the primary outcome of the study. RESULTS: Postoperative tramadol consumption was lower in the erector spinae plane block and quadratus lumborum block groups than that in the control group, with no significant differences observed between the two interventional groups. Postoperative pain scores were lower for at least 12 h in both block groups, with no significant differences observed between both groups. CONCLUSIONS: Erector spinae plane block and quadratus lumborum block improved postoperative pain management as part of the multi-modal analgesia protocol; however, erector spinae plane block may be preferable due to its rapid procedure time. The findings suggest that incorporating erector spinae plane block and quadratus lumborum block into multi-modal analgesia protocols for laparoscopic hysterectomy would have important implications for the development and standardization of pain management protocols.