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.

Effects of medication on dopamine transporter imaging using [123I]I-FP-CIT SPECT in routine practice.

PURPOSE: Dopamine transporter (DAT) imaging is used to support the diagnosis of neurodegenerative parkinsonian disorders. Specific medications have been reported to confound the interpretation of [123I]I-FP-CIT SPECT scans, but there is limited data. The aim of the current study is to identify potential medication effects on the interpretation of [123I]I-FP-CIT SPECT scans in routine practice. MATERIALS AND METHODS: Consecutive patients undergoing a [123I]I-FP-CIT SPECT/CT scan on a 360° CZT camera between September 2019 and December 2022 were included. An exhaustive review of patient medications (antidepressants, antipsychotics, anti-epileptics, anti-parkinsonians, benzodiazepines, lithium, opioids, and stimulants) was performed. Two experienced nuclear physicians, blinded to the medication reports, interpreted the [123I]I-FP-CIT SPECT scans visually and a semi-quantitative analysis was performed using a local normal database. RESULTS: The study included 305 patients (71.0 ± 10.4, 135 women) and 145 (47.5%) visually interpreted normal scans. In normal scans, the striatum/occiput radioligand uptake ratio was decreased by noradrenergic and specific serotonergic antidepressants (NASSAs) (n = 15, z-score of - 0.93) and opioid medication (tramadol, n = 6, z-score of - 0.85) and was associated with a younger age in the multivariate analysis. In the overall population, the striatum/occiput ratio was influenced by NASSAs and associated with consensual visual analysis, age, sex, and anti-parkinsonian medications related to the status of the disease. CONCLUSION: Our study confirms the potential impact of antidepressant (NASSA) and opioid (tramadol) medications on the semi-quantitative analysis of [123I]I-FP-CIT SPECT scans. However, when performing a visual analysis, only NASSAs significantly impacted the interpretation of [123I]I-FP-CIT SPECT scans.

Comprehensive overview of analytical and bioanalytical methodologies for the opioid analgesics - Tramadol and combinations.

Synthetic opioids like Tramadol are used to treat mild to moderate pain. Its ability to relieve pain is about a tenth that of morphine. Furthermore, Tramadol shares similar effects on serotonin and norepinephrine to several antidepressants known as serotonin-norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine and duloxetine. The present review paper discusses the recent developments in analytical methods for identifying drugs in pharmaceutical preparations and toxicological materials, such as blood, saliva, urine, and hair. In recent years, a wide variety of analytical instruments, including capillary electrophoresis, NMR, UV-visible spectroscopy, HPTLC, HPLC, LC-MS, GC, GC-MS, and electrochemical sensors, have been used for drug identification in pharmaceutical preparations and toxicological samples. The primary quantification techniques currently employed for its quantification in various matrices are highlighted in this research.

Structural elucidation of tramadol, its derivatives, and metabolites using chemical derivatization and liquid chromatography-high-resolution tandem mass spectrometry.

RATIONALE: Tramadol (T) is a strong painkiller drug that belongs to the opioid analgesic group. Several accidental intoxication cases after oral administration of T have been reported in the past decade. Tramadol, its derivatives, and metabolites present information-limited mass spectra with one prominent peak representing the amine-containing residue; therefore, their structural determination based on both electron impact mass spectrometry (EI-MS) and ESI-MS/MS spectra could be misleading. METHODS: A novel analytical method for the structural elucidation of tramadol, its four homologs, and its two main phase I metabolites (N-desmethyltramadol and O-desmethyltramadol) was developed using chemical modification and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS) with Orbitrap technology. RESULTS: After chemical derivatization, each of the investigated T series exhibited informative mass spectra that enabled better exposition of their structures. The developed method was successfully implemented to explicitly identify the structures of tramadol and its N-desmethyltramadol metabolite in urine samples at low ng/mL levels. CONCLUSIONS: An efficient derivatization-aided strategy was developed for rapidly elucidating the structure of tramadol-like compounds. The method is intended to assist forensic chemists in better diagnosing T and its analogs and metabolites in clinical or forensic toxicology laboratories.

A novel tramadol-polycaprolactone implant could palliate heroin conditioned place preference and withdrawal in rats: behavioral and neurochemical study.

Drug dependence is a chronic brain disease characterized by craving and recurrent episodes of relapse. Tramadol HCl is a promising agent for withdrawal symptoms management, considering its relatively low abuse potential and safety. Oral administration, however, is not preferred in abstinence maintenance programs. Introducing an implantable, long-lasting formula is suggested to help outpatient abstinence programs achieve higher rates of treatment continuation. Tramadol implants (T350 and T650) were prepared on polycaprolactone polymer ribbons by the wet method. Male Wistar rats were adapted to heroin-conditioned place preference (CPP) at escalating doses (3-30 mg/kg, intraperitoneally, for 14 days). Implants were surgically implanted in the back skin of rats. After 14 days, the CPP score was recorded. Naloxone (1 mg/kg, intraperitoneally) was used to induce withdrawal on day 15, and symptoms were scored. Elevated plus maze and open field tests were performed for anxiety-related symptoms. Striata were analyzed for neurochemical changes reflected in dopamine, 3,4-dihydroxyphenyl acetic acid, gamma-aminobutyric acid, and serotonin levels. Brain oxidative changes including glutathione and lipid peroxides were assessed. The tramadol implants (T350 and T650) reduced heroin CPP and limited naloxone-induced withdrawal symptoms. The striata showed increased levels of 3,4-dihydroxyphenyl acetic acid, and serotonin and decreased levels of gamma-aminobutyric acid and dopamine after heroin withdrawal induction, which were reversed after implanting T350 and T650. Implants restore the brain oxidative state. Nonsignificant low naloxone-induced withdrawal score after the implant was used in naive subjects indicating low abuse potential of the implants. The presented tramadol implants were effective at diminishing heroin CPP and withdrawal in rats, suggesting further investigations for application in the management of opioid withdrawal.

Combined antiallodynic effects of Neurotropin®-tramadol and Neurotropin®-mirogabalin in rats with L5-spinal nerve ligation.

We aimed to examine the efficacy of combination therapies of Neurotropin® with tramadol and Neurotropin with mirogabalin for neuropathic pain management. A neuropathic pain model (L5 spinal nerve ligation model: L5-SNL) using male Wistar rats was generated through tight ligation of the left fifth lumbar nerve using silk sutures. Mechanical allodynia was assessed using the 50% paw withdrawal threshold. The combined antiallodynic effects were evaluated using isobolographic analyses. Small intestinal transit was evaluated using the charcoal meal test, and motor coordination using the rota-rod test. Neurotropin (50-200 NU/kg, p.o.), tramadol (7.5-60 mg/kg, p.o.), and mirogabalin (3-30 mg/kg, p.o.) showed a dose-dependent antiallodynic effect in L5-SNL rats. The combined antiallodynic effects of Neurotropin and tramadol were additive or synergistic, whereas those of Neurotropin and mirogabalin were additive. Neurotropin (100-400 NU/kg, p.o.) did not affect the small intestinal transit, whereas tramadol (30-100 mg/kg, p.o.) significantly inhibited it. Neurotropin (100-400 NU/kg, p.o.) did not affect the walking time, whereas mirogabalin (10-100 mg/kg, p.o.) significantly decreased it. Neurotropin dose-dependently ameliorated mechanical allodynia in rats, and combination therapy with Neurotropin-tramadol or Neurotropin-mirogabalin may alleviate neuropathic pain without aggravating the adverse effects of tramadol and mirogabalin.

The impact of tightened prescribing restrictions for PBS-subsidised opioid medicines and the introduction of half-pack sizes, Australia, 2020-21: an interrupted time series analysis.

OBJECTIVES: To evaluate the impact of the tightened Pharmaceutical Benefits Scheme (PBS) prescribing rules for immediate release (IR) and controlled release (CR) opioid medicines (1 June 2020), which also eliminated repeat dispensing without authorisation for codeine/paracetamol and tramadol IR and introduced half-pack size item codes for IR formulations. DESIGN, SETTING: Population-based interrupted time series analysis of PBS dispensing data claims for a 10% sample of PBS-eligible residents and IQVIA national opioid medicine sales data (PBS-subsidised and private prescriptions), 28 May 2018 - 6 June 2021. MAIN OUTCOME MEASURES: Mean amount of PBS-subsidised opioid medicines dispensed per day and mean overall amount sold per day - each expressed as oral morphine equivalent milligrams (OME) - overall, by formulation type (IR, CR), and by specific formulation. RESULTS: During the twelve months following the PBS changes, daily PBS-subsidised opioid medicine dispensing was 81 565 OME lower (95% CI, -106 146 to -56 984 OME) than the mean daily level for 2018-20, a decline of 3.8% after adjusting for the pre-intervention trend; the relative reduction was greater for IR (8.4%) than CR formulations (2.6%). Total daily sales of all, IR formulation, and CR formulation opioid medicines did not change significantly after the PBS changes. Repeat dispensing of prescriptions comprised 7.4% of PBS-subsidised opioid dispensing before 1 June 2020, and 1.3% after the changes. Half-pack sizes comprised 8.4% of PBS-subsidised IR opioid medicine dispensing and 2.8% of all opioid medicines sold in the twelve months after the PBS changes. CONCLUSIONS: The introduction of new PBS rules for subsidised opioid medicines was followed by a decline in PBS-subsidised dispensing. Some people may have bypassed the new restrictions by switching to private prescriptions, but our findings suggest that opioid medicine use in Australia declined as a result of the new restrictions.

Bioenergetics disruption, oxidative stress, and inflammation as underlying mechanisms of tramadol-induced nephrotoxicity.

Tramadol (TR), a commonly prescribed pain reliever for moderate to severe pain, has been associated with kidney damage. This study investigates TR-induced nephrotoxicity mechanisms, focusing on its effects on renal proximal tubular cells (PTCs). The study findings demonstrate that TR disrupts PTC bioenergetic processes, leading to oxidative stress and inflammation. Significant toxicity to PTCs was observed with estimated effective concentration 50 values of 9.8 and 11.5 µM based on 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays, respectively. TR also interferes with the function of PTC transporters, including organic cation uptake transporter 1, organic cation transporter 2, P-glycoprotein, and multidrug resistance protein 2. Furthermore, bioenergetics assays showed that TR reduced the activities of mitochondrial complexes I and III, adenosine triphosphate production, mitochondrial membrane potential, and oxygen consumption rate while increasing lactate release. TR also increased the production of reactive oxygen species, lipid peroxidation thiobarbituric acid reactive substances end products, and the expression of the NRf2 gene while decreasing reduced glutathione (GSH-R) stores and catalase and superoxide dismutase antioxidant activities. Additionally, TR increased the production of inflammatory cytokines (TNF-α and IL-6) and their coding genes expression. Interestingly, the study found that antioxidants like GSH-R, inhibitors of IL-6 and TNF-α, and mitochondrial activating Co-Q10 could protect cells against TR-induced cytotoxicity. The study suggests that TR causes nephrotoxicity by disrupting bioenergetic processes, causing oxidative stress and inflammation, but antioxidants and agents targeting mitochondria may have protective and curative potential.

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.

Opioid analgesics prescribing trends 2010-2019 in Slovenia: National database study.

OBJECTIVE: Significant increases in global opioid use have been reported in recent decades. This study analyzed opioid utilization in outpatient care in Slovenia between 2010 and 2019. METHODS: This retrospective cross-sectional study performed a nationwide database analysis of all outpatient opioid analgesic prescriptions based on Slovenian health insurance claims data. Prevalence was defined as the number of recipients prescribed at least one opioid per 1000 inhabitants. Opioid consumption was presented as the total number of dispensed prescriptions per 1000 inhabitants and dispensed defined daily doses (DDD) per 1000 inhabitants for each year analyzed. RESULTS: The age-standardized prevalence of opioid recipients decreased by 21.5% during the study period. Total opioid consumption decreased both in the number of prescriptions (-9.2%) and DDD (-5.4%). Tramadol consumption decreased in terms of the number of prescriptions (-12.2%) and DDD (-2.7%), whereas prescriptions for strong opioids increased (10.2%) and DDDs decreased (-16.2%). The results suggest less intensive prescribing of strong opioids and more intensive prescribing for tramadol. The most frequently used strong opioids were fentanyl and oxycodone/naloxone. CONCLUSIONS: The prevalence of opioid recipients and opioid consumption is decreasing in Slovenia. Further research is needed to understand whether this finding reflects safe use or underuse of these important analgesics.

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.

Comparative safety of tramadol and other opioids following total hip and knee arthroplasty.

BACKGROUND: Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex pharmacology and may be no safer than full opioid agonists. We compared the safety of tramadol, oxycodone, and hydrocodone among opioid-naïve older adults following elective THA/TKA. METHODS: This retrospective cohort included Medicare Fee-for-Service beneficiaries ≥ 65 years with elective THA/TKA between January 1, 2010 and September 30, 2015, 12 months of continuous Parts A and B enrollment, 6 months of continuous Part D enrollment, and no opioid use in the 6 months prior to THA/TKA. Participants initiated single-opioid therapy with tramadol, oxycodone, or hydrocodone within 7 days of discharge from THA/TKA hospitalization, regardless of concurrently administered nonopioid analgesics. Outcomes of interest included all-cause hospitalizations or emergency department visits (serious adverse events (SAEs)) and a composite of 10 surgical- and opioid-related SAEs within 90-days of THA/TKA. The intention-to-treat (ITT) and per-protocol (PP) hazard ratios (HRs) for tramadol versus other opioids were estimated using inverse-probability-of-treatment-weighted pooled logistic regression models. RESULTS: The study population included 2,697 tramadol, 11,407 oxycodone, and 14,665 hydrocodone initiators. Compared to oxycodone, tramadol increased the rate of all-cause SAEs in ITT analyses only (ITT HR 1.19, 95%CLs, 1.02, 1.41; PP HR 1.05, 95%CLs, 0.86, 1.29). Rates of composite SAEs were not significant across comparisons. Compared to hydrocodone, tramadol increased the rate of all-cause SAEs in the ITT and PP analyses (ITT HR 1.40, 95%CLs, 1.10, 1.76; PP HR 1.34, 95%CLs, 1.03, 1.75), but rates of composite SAEs were not significant across comparisons. CONCLUSIONS: Postoperative tramadol was associated with increased rates of all-cause SAEs, but not composite SAEs, compared to oxycodone and hydrocodone. Tramadol does not appear to have a superior safety profile and should not be preferentially prescribed to opioid-naïve older adults following THA/TKA.

Adverse childhood experiences, individual-level risk and protective factors, and recent drug use in a community sample of Nigerian women.

Adverse childhood experiences (ACEs) are associated with a wide range of health problems and health-compromising behaviors, including drug use, but are understudied in sub-Saharan Africa. Further, some data suggest that some types of ACEs are more strongly associated with outcomes than others. We investigated associations between different types of ACEs and recent drug use among 2,011 women living in Katsina State, Nigeria. This community-based survey included questions on ACE exposure, modifiable individual-level risk and promotive factors, and past-year drug use. Tobacco, cannabis, and the nonmedical use of cough syrup with codeine and tramadol were the most frequently used drugs. Logistic regressions revealed that across most drugs, ACEs reflecting abuse, neglect, and household dysfunction, but not community violence, increased the likelihood of drug use, odds ratios (ORs) = 1.30-3.10. Ease of access to drugs, ORs = 1.33-2.98, and personal religiosity, ORs = 1.19-2.27, also enhanced the risk of drug use, and higher depressive affect was associated with codeine, OR = 1.27, and tramadol use, ORs = 2.42. Practicing religious rites, ORs = 0.38-0.70; disapproval of drug use, ORs = 0.36-0.57; and perceived harm from drug use, ORs = 0.54-0.71, reduced the likelihood of drug use. Efforts to prevent abuse, neglect, and household dysfunction; reduce access to drugs; treat depression; and increase disapproval and harm associated with drug use may reduce drug use in the context of ACE exposure.

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.

First derivative synchronous spectrofluorimetric method for the simultaneous determination of tramadol and celecoxib in their dosage forms and human plasma.

One of the most common features of many different clinical conditions is pain; hence, there is a crucial need for eliminating or reducing it to a tolerable level to retrieve physical, psychological and social functioning. A first derivative synchronous spectrofluorimetry technique is proposed for the simultaneous determination of celecoxib and tramadol HCl, a recent coformulation authorized for treating acute pain in adults. The method includes using synchronous spectrofluorimetry at ∆λ = 80 nm where tramadol HCl was determined using first derivative technique at λ = 230.2 nm, while celecoxib was determined at λ = 288.24 nm. The proposed method was successfully applied to their co-formulated dosage forms in addition to spiked human plasma and validated in agreement with the guidelines of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). The linear ranges were found to be 0.50-5.0 and 0.15-0.50, the limits of detection to be 0.088 and 0.011 and the limits of quantification to be 0.266 and 0.032 µg/ml for celecoxib and tramadol, respectively. Statistical analysis revealed no significant difference when compared with previously reported methods as evidenced by the values of the variance ratio F-test and Student t-test. The proposed method was successfully applied to commercial dosage forms and spiked human samples. Moreover, the greenness of the proposed method was investigated based on the analytical eco-scale approach, with the results showing an excellent green scale with a score of 95.

Intradermal Sterile Water Injection: Safe and Effective Alternative for Relief of Acute Renal Colic in the Emergency Department.

BACKGROUND: The optimal pain relief method for acute renal colic in the emergency department remains controversial. OBJECTIVE: We compared the safety and efficacy of intradermal sterile water injection (ISWI) to treatment with intramuscular (IM) diclofenac, intravenous (IV) opioids, and IV paracetamol in patients with acute renal colic. METHODS: This randomized, single-blind study included 320 patients with renal colic to one of four treatment groups. The first group received ISWI at four different points around the most painful flank area. Patients in the DI, PARA, and TRAM groups received 75 mg IM diclofenac, 1 g IV paracetamol, and 100 mg IV tramadol, respectively. Pain intensity was measured using a visual analog scale (VAS) before treatment and 15, 30, and 60 min after treatment. RESULTS: VAS scores 15 and 30 min after treatment were significantly lower in group ISWI than in groups DI, PARA, and TRAM. However, there were no significant differences in the decrease in the pain score at baseline and at 60 min after treatment. In addition, fewer patients required rescue analgesia in group ISWI than in group TRAM. However, no significant differences were observed between group ISWI and group DI or PARA in terms of the need for rescue analgesia. Finally, there were significantly fewer adverse events in group ISWI than in groups DI and TRAM. CONCLUSIONS: ISWI had similar efficacy, faster pain relief, and lower need for rescue analgesia compared with diclofenac, paracetamol, and tramadol for the management of acute renal colic. In addition, ISWI was well-tolerated and had no adverse effects.

Effects of Intravenous Lipid Emulsion Administration in Acute Tramadol Poisoning: A Randomized Controlled Trial.

BACKGROUND: As the prevalence of tramadol toxicity is increasing, managing these patients with the aim of treatment and complete recovery has become a major challenge for health care professionals. OBJECTIVE: This study evaluated the short-term effects of IV lipid emulsion (ILE) administration in cases of tramadol poisoning. METHODS: In this double-blind, randomized controlled trial, 120 patients with pure tramadol poisoning and a Glasgow Coma (GCS) score ≤ 12 referred to a poisoning center in Tehran, Iran were selected and randomly assigned 1:1 to receive ILE 20% (intervention) or 0.9% saline (control) after admission and primary stabilization. The patient's vital signs, GCS score, hospitalization duration, and rate of seizure occurrence were recorded and compared between the two groups. RESULTS: Mean (SD) age of participants was 25.3 (5.4) years and 84 (70%) were male. Mean (SD) ingested dose of tramadol was 3118 (244) mg, which was not different between the groups. Compared with controls, the ILE group had a higher level of consciousness after treatment (median [interquartile range] GCS score 12 [10-13] vs. 10 [8-12]; p = 0.03). In addition, length of hospitalization (median [interquartile range] (2 [1-3] days vs. 4 [4-6] days; p < 0.01) and rate of seizure occurrence were lower in the intervention group (16/60 vs. 30/60; p < 0.01). CONCLUSIONS: In the setting of tramadol poisoning with a decreased level of consciousness and based on our study's findings, administration of ILE is suggested to help manage patients in hospital emergency departments. However, larger trials might be needed to confirm these findings before entering the guidelines.

Opioid Prescribing by Emergency Physicians: Trends Study of Medicare Part D Prescriber Data 2013-2019.

BACKGROUND: Emergency physicians play a critical role in mitigating the opioid epidemic in public health. OBJECTIVES: To analyze the prescribing of emergency physicians for opioids among Medicare beneficiaries enrolled in the Part D program from 2013 to 2019. METHODS: We conducted a retrospective, cross-sectional, descriptive analysis of Medicare Part D prescriber data, focusing on opioid claims between 2013 and 2019. The primary outcome variables evaluated included proportion of opioid claims, trends of the most prescribed opioids, cost of opioid claims, and days' supply per claim. RESULTS: A total of 63,586 emergency physicians were identified over the study period. Opioid prescription by emergency physicians decreased from 14.45% to 11.55%, and the cost spent on opioid drugs declined by 50%. The use of drugs such as hydrocodone-acetaminophen and oxycodone-acetaminophen declined substantially, whereas tramadol and acetaminophen-codeine prescription increased. The opioid prescribing rate and days' supply also decreased. CONCLUSIONS: The decline in traditional opioid agents such as hydrocodone-acetaminophen was partly offset by an increase in opioids like tramadol, which carry additional potential adverse events. Opioid prescribing rate, average days' supply, and cost of opioid drugs significantly decreased from 2015 to 2019, after a spike in 2015. All regions observed a decrease in emergency physicians, but opioid prescribing rates varied across regions. These trends highlight successful opioid stewardship practices in some areas and the need for further development in others. This information can aid in designing tailored guidelines and policies for emergency physicians to promote effective opioid stewardship practices.

Opioid Usage Following Oculoplastic Procedures.

BACKGROUND: With the rising toll of the opioid crisis, oculoplastic surgeons have been looking at methods to decrease opioid prescription. OBJECTIVES: The aim of this study was to identify factors that correlate with opioid usage after oculoplastic surgery. METHODS: This was a prospective study conducted at University of Texas Southwestern. All patients who underwent an oculoplastic procedure were eligible for inclusion. Patients enrolled were provided 20 tablets of tramadol 50 mg, to take 1 tablet every 6 hours as needed for pain. At their postoperative week 1 appointment, participants had the remaining number of unused opioid tablets counted. The number of tablets taken were calculated by subtracting the remaining number of tablets from the original prescribed amount. RESULTS: A total of 310 patients were enrolled in our study. Of these, 129 patients met the inclusion criteria. There was a statistically significant difference in the number of tramadol tablets taken between procedures for upper eyelids, lower eyelids, and both eyelids (P < .01). There were no statistically significant differences in tramadol usage when comparing procedures on eyelids with orbit procedures(P = .30), cosmetic with noncosmetic procedures (P = .52), males with females (P = .87), or patients naive to oculoplastic procedures with those undergoing reoperation (P = .58). Longer procedures were correlated with greater tramadol usage (R = 0.28, P < .01). CONCLUSIONS: This is the first study in the literature that has objectively quantified opioid usage after oculoplastic surgery in a prospective manner. Procedures that involve both upper and lower eyelids simultaneously and longer procedures resulted in higher opioid use. Orbital procedures, cosmetic procedures, sex, and procedural naivety were not found to be associated with higher opioid usage.

[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.