Tramadol use and incident dementia in older adults with musculoskeletal pain: a population-based retrospective cohort study.

We aimed to assess the association of tramadol use with the risk of dementia. This population-based retrospective cohort study using the Korean National Health Insurance Service database included a total of 1,865,827 older adult patients aged 60 years or older with common musculoskeletal pain between January 1, 2003, and December 31, 2007. Individuals who were newly dispensed tramadol (N = 41,963) were identified and propensity score-matched with those who were not (N = 41,963). Over a maximum of 14-year follow-up, the incidence rates (events per 1000 person-years) of all-cause dementia were 6.1 for nonusers, 6.2 for those with cumulative tramadol use of 1-14 days, 7.7 for those with 15-90 days of use, and 8.0 for those with > 90 days of use. Longer cumulative duration of tramadol use was associated with an increased risk of all-cause dementia compared with nonuse (1 to 14 days: aHR 1.06, 95% CI 0.96-1.17; 15 to 90 days: aHR 1.14, 95% CI 1.10-1.35; and more than 90 days: aHR 1.18, 95% CI 1.00-1.39; test for trend: P < 0.001). The results showed a similar pattern for Alzheimer's disease and were robust across subgroup and sensitivity analyses, but not for vascular dementia. This study found that exposure to tramadol was associated with an increased risk of dementia. Taking this potential risk into consideration, clinicians should carefully weigh potential benefits and risks when prescribing tramadol to older adults with musculoskeletal pain.

Real-world usage pattern, effectiveness and safety of oral tramadol/dexketoprofen trometamol fixed-dose combination in moderate-to-severe acute pain in Asia: a prospective, multicentre, observational study.

OBJECTIVES: This study aims to determine the usage pattern, effectiveness and safety of oral tramadol 75 mg and dexketoprofen trometamol 25 mg fixed-dose combination (TRAM/DKP FDC) in the short-term treatment of moderate-to-severe acute pain in real-world clinical practice in Asia. DESIGN: Real-world, prospective, multicentre, observational, phase IV study. SETTING: 13 tertiary-care hospital sites across the Philippines, Thailand, Malaysia and Singapore. PARTICIPANTS: Adult patients aged 18-80 years prescribed TRAM/DKP FDC for the short-term (up to 5 days) treatment of moderate-to-severe acute pain. MAIN OUTCOME MEASURES: Primary endpoints were the proportion of patients prescribed TRAM/DKP FDC with different types of postsurgical and non-surgical treatments, and the average dosing frequency and duration of TRAM/DKP FDC treatment. Secondary endpoints were the proportion of patients achieving ≥30% pain reduction at 8 hours post the first dose (pain severity was assessed using the 11-point Numeric Pain Rating Scale); patient satisfaction at the end of treatment (based on a 5-point Patient Global Evaluation Scale (PGE)) and safety including the incidence of adverse drug reactions (ADRs). RESULTS: Among 599 patients (median age 44 years, 61.3% female) enrolled in this study, 68.61% (n=411) were postsurgical and 31.39% (n=188) were non-surgical patients. TRAM/DKP FDC was prescribed in a diverse group of postsurgical patients (eg, orthopaedic, general and cancer surgery) as well as in non-surgical conditions (eg, lower back pain and musculoskeletal pain). In the majority of patients, TRAM/DKP FDC was prescribed every 8 hours (65.94%) and for 5 days (78.80%). There was a significant reduction in pain intensity throughout the study and 65% of patients achieved ≥30% pain reduction from baseline at 8 hours post the first dose of TRAM/DKP FDC on day 1. 95.69% of patients were satisfied with the treatment (rated good, very good and excellent on the PGE scale). Overall, 13.9% of patients reported ADRs; most were mild to moderate in severity. The most common ADRs were nausea, vomiting and dizziness. CONCLUSION: This study showed that TRAM/DKP FDC was used in diverse types of postsurgical and non-surgical patients in the real-world setting in Asia. It effectively reduced pain and was well tolerated with a high level of patient satisfaction.

Association of Tramadol Versus Codeine Prescriptions with all-cause mortality and cardiovascular diseases among patients with osteoarthritis: a systematic review and meta-analysis of propensity score-matched population-based cohort studies.

BACKGROUND: Today, the prescription of tramadol in patients with osteoarthritis (OA) has increased significantly, which can be associated with serious consequences. Contradictory results have been reported regarding the association of tramadol versus codeine with the risk of all-cause mortality (ACM) and cardiovascular diseases (CVD). METHODS: This systematic review and meta-analysis aimed to evaluate, for the first time, the association of tramadol versus codeine with the risk of ACM and CVD in OA patients for the first time. We searched PubMed, Scopus, Embase, Web of sciences, and Google Scholar with specific keywords and mesh terms to find relevant studies until January 2024. Two independent researchers did the process of searching and screening articles. Cochran's Q and I2 tests evaluated the heterogeneity of the studies. Egger's test was used to evaluate the existence of publication bias. RESULTS: Seven population-based cohort studies, matched by the propensity score method, including 1,939,293 participants, were reviewed. The study pooled results did not show a significant association between the prescriptions of tramadol versus codeine with increasing the risk of ACM in OA patients. (Hazard ratio (HR): 1.084, 95% confidence interval (95%) CI: 0.883, 1.286, P: 0.56) In addition, the prescription of tramadol versus codeine was not associated with an increased risk of CVD in OA. (HR: 1.025, 95% CI: 0.89, 1.16, P: 0.68, I2 = 37.8%) CONCLUSION: Our systematic review showed that tramadol prescription compared to codeine in OA patients was not associated with an increased risk of ACM and CVD.

Morphine-induced fever: a case report and review of the literature.

BACKGROUND: Morphine is widely used to treat moderate-to-severe cancer pain. However, it causes various adverse effects, with morphine-induced fever being an extremely rare and poorly understood symptom. CASE PRESENTATION: We report the case of a 58-year-old Chinese woman with advanced lung cancer. Due to the ineffectiveness of tramadol for pain relief, her treatment regimen was switched to morphine. Following the change, she developed nausea, vomiting, dizziness, and elevated body temperature. A similar episode occurred subsequently. After a drug review, the pharmacist speculated that morphine was the most likely causative agent. Upon discontinuation of morphine, her body temperature returned to baseline levels. CONCLUSIONS: This case highlights the need for healthcare providers to consider morphine as a potential cause of unexplained fever in patients. The fever may be caused by a hypersensitive response, as there was a significant increase in eosinophils during the fever episodes.

[Pain relief after abdominal oncologic surgery. Evaluation of the effectiveness and safety of a fixed combination of diclofenac and orphenadrine]. / Obezbolivanie posle abdominal'nykh onkokhirurgicheskikh vmeshatel'stv. Otsenka effektivnosti i perenosimosti fiksirovannoi kombinatsii diklofenaka i orfenadrina.

OBJECTIVE: Evaluation of the analgesic, opioid-sparing, anti-inflammatory and adverse effects of the diclofenac and orphenadrine (Neodolpasse) fixed combination for analgesia in the postoperative period of surgical cancer patients. MATERIAL AND METHODS: A randomized, single-center, prospective, comparative study evaluated two analgesic regimens in 40 cancer patients undergoing various open cavity surgeries, including extensive combined interventions associated with the resection of 3 or more organs. The study was conducted following the transfer from the ICU to the surgical department during the early activation period, within the first two postoperative days. In the first group N (n=20), "Neodolpasse" (a fixed combination of 75 mg Diclofenac and 30 mg Orphenadrine) was administered as an infusion, twice daily. In the second group K (n=20) analgesia was performed with ketoprofen as an intravenous infusion at a daily dose of 200 mg. Patients in both groups received scheduled prolonged epidural analgesia with 0.2% ropivacaine, and when the severity of pain in a visual analogue scale (VAS) increased to more than 40 mm, so an additional dose of 100 mg tramadol was administered intramuscularly. Daily measurments of blood creatinine level and C-reactive protein were taken, postoperative blood loss was accounted for, as well as postoperative complications according to the Clavien-Dindo classification. RESULTS: The comparative analysis of the indicators of pain syndrome severity showed that the patients in group N exhibited a more pronounced analgesic effect, so on the second postoperative day 30% of patients reported moderate pain (from 50 to 60 mm on the pain scale), on the third day - 15%, and by the fourth day - all 100% of patients experienced pain of low intensity. The additional analgesia with tramadol in group N was required twice less than in the comparison group, and such adverse effects as nausea, drowsiness, and weakness were significantly more common in the ketoprofen group. In both groups, the average blood creatinine level did not exceed permissible values, and the C-reactive protein was elevated at all stages of the study but tended to decrease by the fourth day. The analysis of postoperative complications according to the Clavien-Dindo scale at the time of discharge did not reveal a direct correlation between the occurred complications and the use of NSAIDs. Adverse effects such as anastomotic failure, gastrointestinal complications, or other hemorrhagic manifestations were not recorded. CONCLUSION: The inclusion of Neodolpasse into multimodal analgesic regimens resulted in the most pronounced analgesic and opioid-sparing effects in surgical cancer patients using laparotomy access. Additionally, the application of short courses of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a favorable safety profile.

Efficacy of periarticular local infiltrative anaesthesia (modified Ranawat cocktail regimen) for postoperative pain control and reducing morbidity in total knee arthroplasty: a tertiary centre retrospective study.

INTRODUCTION: surgical pain is managed with multi-modal anesthesia in total knee arthroplasty (TKA). It is dubious whether including local infiltrative anaesthesia (LIA) before wound closure provides adequate pain control and decreases morbidity. MATERIAL AND METHODS: this was a retrospective conducted to assess postoperative pain control, morbidity index, and opioid consumption in 116 patients who underwent TKA and were divided into two groups based on LIA (Modified Ranawat Regimen) or normal saline infiltration in the wound. RESULTS: the mean NRS score was significantly lower in LIA group (3.2) as compared to the control group (3.9) in the first 24 hours. Functional milestones were relatively achieved earlier in LIA group but the values were not significant. Tramadol consumption was remarkably higher in the control group as compared to LIA group on day 1 and 2. As per the morbidity index the mean score on day one was 16.18 and 23.40 which decreased to 6.37 and 9.21 by day three in LIA and control group respectively indicating morbidity has decreased but more so in LIA group. CONCLUSION: our study concludes that use of modified cocktail regimen in the knee effectively decreased morbidity with excellent to good results, declining NRS score, minimal rescue analgesia requirement, early ambulation with better safety.

INTRODUCCIÓN: el dolor quirúrgico se trata con anestesia multimodal en la artroplastia total de rodilla (ATR). Es dudoso que incluir anestesia local infiltrativa (LIA) antes del cierre de la herida proporcione un control adecuado del dolor y disminuya la morbilidad. MATERIAL Y MÉTODOS: se realizó una retrospectiva para evaluar el control del dolor posoperatorio, el índice de morbilidad y el consumo de opioides en 116 pacientes sometidos a ATR y se dividieron en dos grupos según el LIA (régimen de Ranawat modificado) o la infiltración de solución salina normal en la herida. RESULTADOS: la puntuación media NRS fue significativamente menor en el grupo LIA (3.2) en comparación con el grupo control (3.9) en las primeras 24 horas. Los hitos funcionales se alcanzaron relativamente antes en el grupo LIA, pero los valores no fueron significativos. El consumo de tramadol fue notablemente mayor en el grupo de control en comparación con el grupo de LIA los días 1 y 2. Según el índice de morbilidad, la puntuación media el día uno fue 16.18 y 23.40, que disminuyó a 6.37 y 9.21 en el día tres en el grupo de LIA y control, respectivamente, lo que indica que la morbilidad ha disminuido, pero más en el grupo LIA. CONCLUSIÓN: nuestro estudio concluye que el uso de un régimen de cóctel modificado en la rodilla disminuyó efectivamente la morbilidad con resultados excelentes a buenos, una disminución de la puntuación NRS, un requisito mínimo de analgesia de rescate y una deambulación temprana con mayor seguridad.

Efficacy of adductor canal and popliteal plexus block combined with local anesthetic injection in the interspace between the popliteal artery and posterior capsule of the knee and local infiltrative analgesia for postoperative pain and functional outcome after total knee arthroplasty: A randomized controlled study.

BACKGROUND: Adductor canal block and periarticular infiltration analgesia (PIA) have been shown to relieve pain in total knee arthroplasty (TKA) effectively. However, their analgesic effectiveness has some limitations. Thus, we considered a novel blocking site that could achieve analgesia without affecting the muscle strength of the lower limbs. METHODS: Seventy-two patients undergoing primary unilateral total knee arthroplasty were randomized into two groups. One group was treated with adductor canal and popliteal plexus (APB) combined with interspace between the popliteal artery and posterior capsule of the knee (iPACK) and local infiltration anesthesia (LIA) and the other was treated with PIA. The primary outcomes included postoperative pain, as assessed by the visual analog scale (VAS), and the consumption of oral tramadol. Secondary outcomes included functional recovery and daily ambulation distance. Tertiary outcomes included postoperative adverse effects. RESULTS: The APB group had lower VAS scores after surgery at rest and during motion. Compared with the PIA group, the walking distance of the APB group on the second day was greater. The muscle strength of the APB group was lower than that of the PIA group at the early stage. Patients in the APB group also consumed less tramadol than those in the PIA group. There was no difference in the incidence of adverse events between the two groups. CONCLUSIONS: APB combined with iPACK and LIA is a novel block for TKA, and it can reduce postoperative pain sooner after TKA without affecting postoperative functional recovery or increasing complications.

The influence of tramadol on bowel function: A randomised, placebo-controlled trial.

Tramadol is a weak opioid used to treat moderate pain. Stronger opioids inhibit gastrointestinal function, but little is known about the gastrointestinal effects of tramadol. Our aim was to investigate if tramadol causes opioid-induced bowel dysfunction (OIBD). Twenty healthy male participants (mean age 24 [range 20-31] years) were included. Tramadol (extended-release formulation, 200 mg/day) or placebo was administered for 10 days in two study periods separated by 3 weeks. Gastrointestinal transit times and segmental volume, motility and water content were investigated with the 3D-transit system and magnetic resonance imaging. Bowel movements and gastrointestinal symptoms were recorded daily. Tramadol prolonged colonic transit time (34 h vs. 25 h, p < 0.001) and increased small bowel motility (p < 0.01) and water content (p = 0.002) compared to placebo. Across all days of treatment, tramadol reduced the number of mean daily bowel movements (p = 0.001) and increased mean stool consistency (p = 0.006). Gastrointestinal symptom scores increased with tramadol (indigestion: +358%, p = 0.01; constipation: +475%, p = 0.01). Additionally, more participants fulfilled the diagnostic criteria for constipation after tramadol treatment compared to placebo (40% vs. 0%, p < 0.001). This study showed that tramadol treatment is associated with OIBD, and management of constipation and other bowel symptoms should, therefore, be prioritised when treating pain patients with tramadol.

Pharmacogenetic Approach to Tramadol Use in the Arab Population.

Tramdol is one of most popular opioids used for postoperative analgesia worldwide. Among Arabic countries, there are reports that its dosage is not appropriate due to cultural background. To provide theoretical background of the proper usage of tramadol, this study analyzed the association between several genetic polymorphisms (CYP2D6/OPRM1) and the effect of tramadol. A total of 39 patients who took tramadol for postoperative analgesia were recruited, samples were obtained, and their DNA was extracted for polymerase chain reaction products analysis followed by allelic variations of CYP2D6 and OPRM A118G determination. Numerical pain scales were measured before and 1 h after taking tramadol. The effect of tramadol was defined by the difference between these scales. We concluded that CYP2D6 and OPRM1 A118G single nucleotide polymorphisms may serve as crucial determinants in predicting tramadol efficacy and susceptibility to post-surgical pain. Further validation of personalized prescription practices based on these genetic polymorphisms could provide valuable insights for the development of clinical guidelines tailored to post-surgical tramadol use in the Arabic population.

The Role of NLRP1 Inflammasome and Interleukin 1ß in Experimental Neuropathic Pain Model in Rat and the Effect of Tramadol Treatment.

AIM: To evaluate the effects of tramadol on inflammation by measuring NLRP1 and IL-1 beta (IL-1ß) levels in an experimental neuropathic pain model. MATERIAL AND METHODS: Sprague-Dawley rats were divided into three groups: control, chronic constriction injury (CCI), and CCI + tramadol. Neuropathic pain was assessed using mechanical allodynia, thermal hyperalgesia, and cold allodynia. IL-1ß and NLRP1 levels were evaluated using ELISA on sciatic nerve (SN), dorsal root ganglion (DRG), and serum either on day 3 or days 8 postsurgery. RESULTS: On day 3, paw withdrawal latency (PWL) was lower in the CCI and CCI + tramadol groups than the control group in both mechanical and cold allodynia tests. On day 8, the PWL in the CCI group was also lower than in the control group. In contrast, tramadol increased the PWL on day 8 compared to day 3 in the CCI group. During cold allodynia, PWL decreased in the CCI group, however, tramadol reversed this effect on days 3 and 8. Tramadol, therefore, ameliorated pain hypersensitivity in mechanical/cold allodynia tests. Serum IL-1ß levels were higher in the CCI + tramadol and CCI groups than the control group, although serum IL-1ß levels in the CCI and CCI + tramadol groups were comparable. Tramadol decreased the IL-1ß and NLRP1 in DRG compared with the CCI group. A similar trend was observed in the SN samples. CONCLUSION: Our experiments revealed an increase in IL-1ß and NLRP-1 levels in a neuropathic pain model and found that tramadol had an anti-inflammatory effect on the IL-1ß and NLRP1 inflammasomes.

Comparison of the efficacy and safety of transdermal buprenorphine patch to conventional analgesics after operative fixation of extra capsular fracture of proximal femur.

INTRODUCTION: Proximal femur fractures are common among older individuals and pose challenges in achieving effective post-operative analgesia. Age-related co-morbidities limit the selection of analgesics in this population. This study aimed to compare the safety and effectiveness of transdermal buprenorphine (TDB) patch with traditional analgesics after fixation of an extracapsular fracture of the proximal femur. METHODOLOGY: A prospective randomized controlled study was conducted over a 2-year period, involving 60 patients who underwent surgery for extra capsular intertrochanteric fracture fixation. The patients were randomly assigned to two groups by random envelope method. Group A received an intravenous formulation of paracetamol and tramadol for the initial 48 h, followed by an oral formulation. Group B received a transdermal buprenorphine (TDB) patch delivering 5 mcg/hour immediately after surgery, which continued for 2 weeks postoperatively. During the 14-day monitoring period, patients' pain scores were assessed using the Visual Analog Scale (VAS) at rest and during movement. The primary objective was to maintain a VAS score of 4 or lower. Rescue analgesics were administered if the VAS score reached 6. The secondary objectives included evaluating the quantity of rescue analgesics required and monitoring for any adverse effects or complications. RESULTS: Pain scores at rest and during movement were significantly lower in Group B at all-time points (p-value 0.0006 - ≤ 0.0001), and the requirement for rescue analgesia was also significantly lower in this group. The administration of the TDB patch did not result in any significant adverse effects. CONCLUSION: TDB patch is secure and offers better compliance and analgesia than other analgesics in the postoperative period whilst treating proximal femur extra capsular fracture.

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.

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.

Nickel oxide nanoparticles modified with dimethylglyoxime grafted on a cellulose surface as an efficient adsorbent for thin film microextraction of tramadol in biological fluids followed by its determination using HPLC.

In the current study, nickel oxide nanoparticles (NiO NPs) modified with dimethylglyoxime (DMG) were deposited onto the cellulose surface (Ni(DMG)2-NiO-Cell) and used as an efficient adsorbent for thin film microextraction (TFME) of tramadol (TRA). The extracted TRA was determined using a high-performance liquid chromatography-ultraviolet detector (HPLC-UV). NiO NPs were synthesized by co-precipitation method on the surface of the cellulose substrate; afterward, its surface was modified by DMG to increase the extraction capability of the thin film toward TRA. The synthesized NiO-Cell and Ni(DMG)2-NiO-Cell thin films were characterized using various techniques. The effect of modification of the NiO thin film with DMG reagent on the extraction efficiency was investigated. The crucial parameters influencing the extraction efficiency, including extraction time, desorption time, desorption solvent, pH and salt content, were investigated via a one-at-a-time approach. The figures of merit for the developed method were evaluated in urine, plasma, and deionized water under the optimized extraction and desorption condition. The limits of detection and limits of quantification were in the range of 0.1 to 1 ng mL-1 and 0.3 to 3 ng mL-1, respectively, for the studied samples. The linear dynamic ranges of the developed TFME-HPLC-UV method were 0.3-1000, 1-2500, and 3-5000 ng mL-1 for the deionized water, urine, and plasma samples, respectively. The reproducibility and repeatability of the developed method was assayed in terms of intra-day, inter-day, and inter-thin film precisions by conducting six-replicate experiments at the concentration level of 0.1 and 1 µg mL-1, which were in the range of 5.9% to 8.3%. The sufficiency and applicability of the developed TFME-HPLC-UV method was investigated by determining TRA in urine and plasma samples, and the resulting relative recoveries (RR%) were 85.9% and 91.7%, respectively.

Analysis of Two Treatment Modalities for Post-surgical Pain after Hemorrhoidectomy.

Background: This non-randomized study aimed to compare the efficacy of two pharmacological treatments, "around-the-clock" analgesic treatment (ACAT) and "on-demand" analgesic treatment (ODAT), for managing postoperative pain following hemorrhoidectomy. Material and Methods: The study, conducted from July 2016 to December 2020, included 5335 hemorrhoidectomy patients. Participants were divided into ACAT (3767) and ODAT (1568) groups. The study was registered at clinicaltrials.gov (NCT04953182). Results: Patients had a mean age of 47.47 years, with 59.98% males. Postoperatively, 14.13% reported severe pain, 36.49% moderate, 34.28% mild, and 15.09% no pain. ACAT group's maximum pain was 3.04 (VAS), ODAT 4.95 (p; average pain was 0.79 (ACAT) and 1.45 (ODAT). Discharge pain was 0.42 (ACAT) and 0.63 (ODAT) VAS. The ACAT group consistently reported lower levels of pain across all measured instances. Higher BMI and younger age were pain risk factors (p=.049, p .001 respectively). ACAT administration resulted in reduced opioid usage, with meperidine showing a 68.38% decrease, morphine 43.57% less, tramadol 46.82% less, oxycodone reduced by 38.74%, and codeine by 53.40%. Additionally, the use of non-opioid analgesics was notably lower in the ACAT group, ranging from 16% to 59% less compared to the ODAT group. Conclusion: Hemorrhoidectomy induces moderate postoperative pain, with only 14% experiencing severe pain. A fixed schedule multimodal pain regimen, regardless of procedure and anesthesia type, reduces pain from moderate to mild post-hemorrhoidectomy. This approach also decreases opioid and non-opioid analgesic requirements. Higher BMI and younger age are identified as risk factors for elevated postoperative pain.

Association of the OPRM1 variant rs1799971 (A118G) and clinical manifestations in tramadol poisoned patients: a cross-sectional study.

INTRODUCTION: The opioid receptor mu1 is a protein coding gene that can have different codes for a protein and may have variations (polymorphisms) affecting how opioids work. The aim of this study was to investigate the prevalence of the most common opioid receptor mu1 polymorphism (A118G) and any relationship between this polymorphism and features following tramadol overdose. MATERIALS AND METHODS: This was a cross-sectional study of patients admitted with tramadol poisoning to an Iranian hospital. These patients were not taking any other drugs or medications and had no history of seizures. RESULTS: The results showed that among the 83 patients included in the study, 57 (69 per cent) had the AA genotype, 25 (30 per cent) had the AG genotype, and one (1 per cent) had the GG genotype for the opioid receptor mu1 A118G polymorphism. Nausea and/or vomiting occurred in nine (11 per cent) patients and dizziness in 38 (46 per cent) patients. Serious adverse events included seizures in 51 (60 per cent) patients and respiratory failure requiring mechanical ventilation in 21 (25 per cent) patients. However, there was no significant association between the opioid receptor mu1 A118G polymorphism and these adverse events. DISCUSSION: In our study, the frequency of the A allele was greater than the G allele, and the AA genotype was more prevalent than AG. The GG genotype was the least common among the polymorphisms of opioid receptor mu1 rs1799971. There was no significant association between the opioid receptor mu1 A118G polymorphism and symptoms in tramadol-poisoned patients. Although these allele proportions are similar to the results reported in other Caucasian populations, they are dissimilar to the findings in Chinese and Singaporean populations. In these Asian studies, the predominant allele was the G allele. It has been suggested that a mutated G allele will decrease the production of opioid receptor mu1-related messenger ribonucleic acid and related proteins, leading to fewer mu-opioid receptors in the brain. CONCLUSIONS: This study found no significant association between the opioid receptor mu1 A118G polymorphism and adverse outcomes in tramadol-poisoned patients. However, more research is needed to draw more definitive conclusions due to the limited evidence and variability of opioid receptor mu1 polymorphisms in different populations.