The hormonal mechanism of the effects of meperidine, sertraline, tianeptine, and their combinations on reproductive functions in female rats.

BACKGROUND: Infertility caused by drugs that inhibit serotonin reuptake has been attributed to serotonin toxicity. Serotonin has been linked to cause a rise in prolactin and cortisol. This study examined the effects of meperidine, sertraline, tianeptine and combinations on female rat reproductive function. METHODS: Female rats were split into 8 groups (n=7): healthy control (HG), meperidine (MG), sertraline (SG), tianeptine (TG), meperidine+sertraline (MSG), meperidine+tianeptine (MTG), sertraline+tianeptine (STG), meperidine+sertraline+tianeptine (MSTG). Meperidine (20 mg/kg, 2×1) was injected intramuscularly. Sertraline (30 mg/kg, 1×1) and tianeptine (5 mg/kg, 1×1) were given orally. The HG received distilled water as solvent. Treatments continued for 20 days. Then, adult males were added to the rat groups and drug treatment continued for another five days. Blood samples were collected on day 26 for biochemical tests. RESULTS: Total oxidant status (TOS) and total antioxidant status (TAS) were not statistically significant between groups (p>0.05). Meperidine (p<0.001) and sertraline (p<0.001) alone increased prolactin levels in comparison to HG and tianeptine inhibited the increase (p<0.001). While meperidine increased corticosterone levels versus HG (p<0.001), sertraline and tianeptine were close to HG (p>0.05). Number of infertile animals was 6 for meperidine, 3 for sertraline, and none for tianeptine. While the duration of pregnancy in MG (15 days) and SG (15 days) was longer compared to HG (2.86 days), no change was observed in TG (2.5 days). CONCLUSION: Tianeptine and other serotonin re-uptake stimulants may be useful in the treatment of reproductive dysfunction and infertility due to serotonin re-uptake inhibitor treatment.

Meperidine compared to morphine for rigors associated with monoclonal antibody-related infusion reactions.

INTRODUCTION: Infusion reactions, characterized by symptoms such as rigors, fever, and hypotension, are common adverse events that occur during monoclonal antibody (MAB) therapy. The treatment of rigors often involves opioids, most commonly meperidine, despite limited evidence supporting use in the setting of MAB infusions. This study aims to compare the efficacy and safety of intravenous (IV) meperidine and morphine is treatment of MAB-related rigors, filling a significant gap in the literature. METHODS: This was a single-center, retrospective cohort study which reviewed patients either inpatient or within outpatient infusion centers from January 2015 to January 2024. Patients receiving IV 2 mg morphine or 25 mg meperidine for MAB-related rigors were included. The primary outcome was defined as the number of opioid doses required for rigors ablation. Secondary outcomes included rates of naloxone administration and documented sedation. RESULTS: A total of 1251 administration events were screened, of which 127 and 26 rigor events were in the meperidine and morphine cohorts, respectively, were included. A majority of both cohorts required only one dose of either agent for rigors ablation with <20% of either cohort requiring 2 or more doses (p = 0.539). Low rates of sedation were observed in both groups. CONCLUSION: Both meperidine and morphine effectively manage MAB-related rigors within minimal safety concerns. These findings suggest that morphine is a suitable alternative to meperidine for this indication, which may influence future formulary decision, provide alternatives for drug shortage, and optimize supportive care for patients undergoing MAB therapy.

The Effect of Granisetron, Ondansetron, and Meperidine in Preventing Postoperative Shivering: Controlled Clinical Trial.

BACKGROUND: Recently, use of HT35 receptor antagonists to prevent postoperative shivering has attracted a great deal of attention. This study was conducted with the aim of investigating the effectiveness of granisetron as an HT35 antagonist when compared with ondansetron and meperidine in preventing postoperative shivering. MATERIAL AND METHODS: In this triple blind random clinical trial study, 90 patients 18-50 years of age with ASA Class I and II undergoing general anesthesia were randomly assigned into one of the three drug groups: O (4-mg ondansetron), G (40 µg/kg of granisetron), and P (25 mg meperidine), immediately before induction of anesthesia. After anesthesia induction, at the end of the surgery, after the entrance and after leaving the recovery state, central temperature, peripheral temperature, heart rate, systolic blood pressure, diastolic blood pressure, and shivering were measured and documented. Two-tailed P < 0.05 was considered significant. RESULTS: In the meperidine, ondansetron, and granisetron groups, 4 (13.3%), 3 (10%), and 10 (33.3%) of patients experienced shivering during recovery, where the difference between the ondansetron and granisetron groups was significant (p-value=0.02). The variations in the mean arterial pressure during the investigation stages only in the ondansetron group were not significant (p>0.05). At the beginning of recovery, the reduction of peripheral temperature significantly was lower in the ondansetron group (p<0.05), while reduction of the central temperature was significantly (p<0.05) higher in the granisetron group. By the end of the recovery, the variations in the peripheral temperature across the three groups were consistent with the changes at the beginning of recovery, but variations of the central temperature across the three groups was not significantly diverse. CONCLUSION: Granisetron was not found to be much effective in preventing postoperative shivering. Ondansetron and meperidine were equally effective in preventing postoperative shivering. Ondansetron also causes less hemodynamic changes compared to other drugs, while granisetron is more effective in terms of preventing nausea and vomiting.

Comparison of Analgesic Effects of Ketorolac Plus Apotel to Meperidine in Patients Undergoing Right Thoracotomy: A Double-Blind Randomized Clinical Trial.

Background: Postoperative pain management using nonsteroidal anti-inflammatory drugs with no narcotic-attributed adverse effects, such as respiratory depression, nausea, and vomiting, is still the subject of extensive research. However, concerns about bleeding and nephrotoxicity have limited routine use. Objectives: The present trial aimed to compare the effects of ketorolac/apotel and meperidine on postoperative pain relief in patients undergoing thoracotomy. Methods: This randomized controlled trial enrolled 122 patients who were candidates for right thoracotomy. The patients were randomly divided into two groups that received ketorolac (30 mg)/apotel (1 g) or meperidine (0.5 - 1 mg/kg) at the beginning of recovery, respectively. This study assessed the Numeric Rating Scale pain score immediately and 30 and 60 minutes after the surgery in the recovery room, blood pressure, oxygen saturation (SpO2), sweating, and pulse rate. Results: The average pain score at recovery time was significantly lower in the ketorolac/apotel group (2.06 ± 1.40) than in the meperidine group (2.76 ± 1.61) (P = 0.011). In contrast to the ketorolac/apotel group, an increasing trend was observed in pain scores in the meperidine group throughout the time sequence (P < 0.05). However, a slight non-significant increase was also observed in the ketorolac/apotel group. No statistical differences were observed in blood pressure (P = 0.826), SpO2 (P = 0.826), and pulse rate (P = 0.811) between the two study groups. Conclusions: This study provides support that the combination of ketorolac/apotel offers a slightly superior analgesic effect for patients undergoing thoracotomy, compared to meperidine. Pain management is crucial during recovery, and the current study's findings suggest that administering ketorolac/apotel provides effective analgesia during recovery after thoracic surgery.

Examining the efficacy of intravenous ibuprofen and meperidine for preventing post-operative shivering after laparoscopic cholecystectomy with general anesthesia.

Postoperative shivering is a common complication that can lead to increased postoperative complications. This study aimed to compare the effectiveness of intravenous ibuprofen and meperidine in preventing shivering following laparoscopic cholecystectomy. A total of 120 patients, aged 20-70 and classified as ASA I-II, were enrolled in this triple-blind clinical trial. The participants were randomly assigned to one of three groups: ibuprofen (800mg IV), meperidine (30 mg), or placebo (normal saline 2 ml), administered 30 minutes before the end of surgery. The occurrence of postoperative shivering was assessed and recorded at regular intervals (0, 5, 10, 15, 30, and 60 minutes after surgery). Additionally, postoperative pain levels were measured using a visual analog scale (VAS), sedation levels were evaluated using the Ramsay Sedation Scale (RSS), and the incidence of postoperative nausea and vomiting was documented. The prevalence and severity of postoperative shivering were not statistically significant between groups. The VAS was significantly lower in the meperidine group than the ibuprofen group throughout the study (p <0.001). The VAS was significantly lower in the ibuprofen group than the placebo group at 0 and 15 minutes after surgery. Although the incidence of nausea was slightly higher in the meperidine group, the difference was not statistically significant (p=0.75). Sedation scores were consistently lower in the ibuprofen group and higher in the meperidine group compared to the other groups (p<0.0001) The meperidine group had a significantly higher sedation score indicative of deep sleepiness (score of 4) than the other groups. Intravenous ibuprofen demonstrated comparable efficacy to meperidine in controlling shivering. Additionally, the incidence of nausea, vomiting, and sleepiness was lower in the intravenous ibuprofen group, suggesting it is a potential alternative to meperidine.

The Role of Adrenaline, Noradrenaline, and Cortisol in the Pathogenesis of the Analgesic Potency, Duration, and Neurotoxic Effect of Meperidine.

Background and Objectives: The purpose of the study was to investigate the role of adrenaline (ADR), noradrenaline (NDR), and cortisol in the pathogenesis of the analgesic potency, duration, and epilepsy-like toxic effect of meperidine. Materials and Methods: The experimental animals were separated into 11 groups of six rats. In the meperidine (MPD) and metyrosine + meperidine (MMPD) groups, paw pain thresholds were measured before and after the treatment between the first and sixth hours (one hour apart). In addition, ADR and NDR analyses were performed before and after the treatment, between the first and fourth hours (one hour apart). For the epilepsy experiment, caffeine, caffeine + meperidine, and caffeine + meperidine + metyrapone groups were created, and the treatment was applied for 1 day or 7 days. Groups were created in which caffeine was used at both 150 mg/kg and 300 mg/kg. Epileptic seizures were observed in epilepsy groups, latent periods were determined, and serum cortisol levels were measured. Results: In the MPD group, pain thresholds increased only at the first and second hours compared to pre-treatment, while ADR increased at the third hour, leading to a decrease in pain thresholds. In the MMPD group, the increase in paw pain thresholds at 1 and 6 h was accompanied by a decrease in ADR and NDR. In the caffeine (150 mg/kg) + meperidine group, 1-day treatment did not cause epileptic seizures, while seizures were observed and cortisol levels increased in the group in which treatment continued for 7 days. When cortisol levels were compared between the group in which caffeine (300 mg/kg) + meperidine + metyrapone was used for 7 days and the animals receiving caffeine (300 mg/kg) + metyrapone for 7 days, it was found that cortisol levels decreased and the latent period decreased. Conclusions: The current study showed that if serum ADR and cortisol levels are kept at normal levels, a longer-lasting and stronger analgesic effect can be achieved with meperidine, and epileptic seizures can be prevented.

Adequate Anesthesia and More Effective Analgesia by Adjusted Doses of Bupivacaine during Cesarean Section: A Randomized Double-blind Clinical Trial.

Background: Several adjuvants, added to local anesthetics, were suggested to induce an ideal regional block with high-quality analgesia. The purpose of this study was to evaluate the particular blocking properties of low-dose bupivacaine in combination with meperidine and fentanyl in spinal anesthesia during Cesarean sections. Methods: A randomized, double-blind clinical trial was conducted at Hafez Hospital affiliated with Shiraz University of Medical Sciences (Shiraz, Iran) from February 2015 to February 2016. A total of 120 pregnant women, who underwent spinal anesthesia during elective Cesarean section were enrolled in the study. Based on block-wise randomization, the patients were randomly assigned to three groups, namely "B" group received 2 mL bupivacaine 0.5% (10 mg), "BM" group received 8 mg bupivacaine and 10 mg meperidine, and "BF" group received 8 mg bupivacaine and 15 µg fentanyl intrathecally. The block onset, the duration of analgesia, and the time of discharge from the post-anesthesia care unit (PACU) were all assessed. Data were analyzed using SPSS software version 21, and P<0.05 were considered statistically significant. Results: The mean duration of motor blocks in the B group (150 min) were significantly higher than the BM (102 min) and BF (105 min) groups (P<0.0001). In both the BM and BF groups, the duration of sensory and motor blocks was the same. The length of stay in the PACU was significantly longer in the B group (P<0.001) than the BM and BF groups. When meperidine or fentanyl was added to bupivacaine, the duration of the analgesia lengthened (P<0.001). Conclusion: Intrathecal low-dose spinal anesthesia induced by bupivacaine (8 mg) in combination with meperidine and/or fentanyl for Cesarean section increased maternal hemodynamic stability, while ensuring effective anesthetic conditions, extending effective analgesia, and reducing the length of stay in PACU.Trial Registration Number: IRCT2015013119470N14.

Analgesic Effect of Preoperative Intravenous Administration of Paracetamol on Post-cesarean Pain: A Randomized Clinical Trial.

Background: Pain control after every surgery, especially cesarean section, is very important, and physicians strive to discover pain control methods using the least amount of opioids. Paracetamol is a non-opioid analgesic with few complications. Objectives: The present study aimed to investigate the analgesic effect of preoperative intravenous administration of paracetamol on post-cesarean pain. Methods: This randomized, double-blind clinical trial was conducted on 240 pregnant women under spinal anesthesia who were candidates for elective cesarean section. The patients' weight, height, age, and body mass index (BMI) were recorded, and patients were randomly divided into 2 equal groups (n = 120). In the first group, 10 mg/kg paracetamol in 100 mL of normal saline (paracetamol group) and, in the second group, 100 mL normal saline (control group) were administered 15 minutes before surgery intravenously. Blood pressure, pulse rate, chills, and nausea were recorded during and 1 hour after surgery; in addition, the visual analogue scale (VAS) and the need for additional analgesics were recorded 1, 2, 4, 6, 12, and 24 hours after surgery. Results: Mean pain scores were significantly lower in the paracetamol group (4.01 ± 2.22) than in the control group 6 hours (4.83 ± 2.35; P = 0.008) and 24 hours (2.26 ± 1.85 and 2.67 ± 1.80, respectably; P = 0.038) after surgery. Mean meperidine consumption was lower in the paracetamol group than in the control group, but it was not significant. No significant difference was found between the 2 groups in the frequency of chills and nausea (P > 0.05). Conclusions: Within the limitations of the current study, preoperative intravenous administration of paracetamol significantly reduced post-cesarean pain within 24 hours.

Variation in adverse drug events of opioids in the United States.

Background: The United States (US) ranks high, nationally, in opioid consumption. The ongoing increase in the misuse and mortality amid the opioid epidemic has been contributing to its rising cost. The worsening health and economic impact of opioid use disorder in the US warrants further attention. We, therefore, assessed commonly prescribed opioids to determine the opioids that were over-represented versus under-represented for adverse drug events (ADEs) to better understand their distribution patterns using the Food and Drug Administration's Adverse Event Reporting System (FAERS) while correcting for distribution using the Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (ARCOS). Comparing the ratio of the percentage of adverse drug events as reported by the FAERS relative to the percentage of distribution as reported by the ARCOS database is a novel approach to evaluate post-marketing safety surveillance and may inform healthcare policies and providers to better regulate the use of these opioids. Methods: We analyzed the adverse events for 11 prescription opioids, when correcting for distribution, and their ratios for three periods, 2006-2010, 2011-2016, and 2017-2021, in the US. The opioids include buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, and tapentadol. Oral morphine milligram equivalents (MMEs) were calculated by conversions relative to morphine. The relative ADEs of the selected opioids, opioid distributions, and ADEs relative to distribution ratios were analyzed for the 11 opioids. Results: Oxycodone, fentanyl, and morphine accounted for over half of the total number of ADEs (n = 667,969), while meperidine accounted for less than 1%. Opioid distributions were relatively constant over time, with methadone repeatedly accounting for the largest proportions. Many ADE-to-opioid distribution ratios increased over time, with meperidine (60.6), oxymorphone (11.1), tapentadol (10.3), and hydromorphone (7.9) being the most over-represented for ADEs in the most recent period. Methadone was under-represented (<0.20) in all the three periods. Conclusion: The use of the FAERS with the ARCOS provides insights into dynamic changes in ADEs of the selected opioids in the US. There is further need to monitor and address the ADEs of these drugs.

Intra-articular remifentanil on postoperative pain in knee arthroscopic surgery; a double blind randomized clinical trial.

BACKGROUND: We aimed to assess the efficacy of intra-articular remifentanil in relieving postoperative pain after knee arthroscopy. METHODS: We conducted a double-blind randomized clinical trial study on 60 patients. Patients were divided into two equal groups. The control group received 25 ml of intra-articular normal saline, and the intervention group received 200 µg of remifentanil dissolved in 25 ml of saline. We evaluated at rest postoperative pain at 1, 3, 6, 12, 18, and 24 h after the surgery using the Visual Analog Scale (VAS). Patients with VAS scores of 4 or more received meperidine (pethidine). The first time meperidine was requested and the total amount of meperidine consumed was recorded. RESULTS: Out of 60 patients, 49 were male (81.6%), and the mean age of participants was 32.71 (7.02) years. An hour after the surgery, the control group showed a mean VAS score of 8.66 (1.26), and decreased to 2.53 (1.67) at the end of 24 h. The intervention group started with a mean VAS score of 2.23 (1.81) and ended at 0.10 (0.305). All patients in the control group and 11 (36.7%) patients in the intervention group asked for analgesics during follow-up. The mean total meperidine dose in the control and intervention groups was 108.33 (23.97) mg and 13.33 (19.40) mg, respectively (P < 0.001; 95% confidence interval of the difference 83.72 to 106.27). CONCLUSIONS: Intra-articular remifentanil may decrease postoperative pain and analgesic requirements in patients undergoing knee arthroscopy.

The Assessment of Marcaine Versus Meperidine for Spinal Anesthesia in Anorectal Surgery: A Randomized Clinical Trial.

Background: Spinal anesthesia (SA) for the surgical management of chronic anal fissures is favored by surgeons as it provides an early return to daily activities; however, the agents applied for SA to achieve the best outcomes with minimized adverse effects are a matter of debate. Objectives: This study aimed to assess the utility of Marcaine versus meperidine for SA induction of anoderm surgery. Methods: This randomized clinical trial (RCT) was conducted on 138 patients with chronic anal fissures who were candidates for surgical management in 2020. The patients were randomly assigned to two groups of SA using 2.5 mL of hyperbaric Marcaine 0.5% (n = 69) or 1 mg/kg of meperidine (n = 69). Pain severity (measured via Numerical Rating Scale (NRS)), anal sphincter tone manometry (measured at baseline and the end of the sphincterotomy), and drug-related adverse effects were compared between the groups. Results: Both agents led to significant pain relief within 24 hours after SA (P < 0.05); nevertheless, pain severity was remarkably lower in meperidine-treated patients in different measurements performed during the first 24 hours after SA (P < 0.05). The sphincteric tone significantly decreased in both groups (P < 0.001), while the postoperative tone was significantly less in the Marcaine-treated patients (65.22 ± 3.02 versus 46.04 ± 1.97, P < 0.001). The two groups did not differ regarding the adverse effects (P > 0.05). Conclusions: Meperidine for SA in anal fissure surgical management was relatively superior to Marcaine, as postoperative pain control was remarkably better achieved with meperidine. However, anal sphincter tone reached a normal range in Marcaine-treated cases, and the average tone in those anesthetized with meperidine was slightly above the normal limits.

Role Of Granisetron In Minimising Use Of Meperidine As A Rescue Drug For Post Spinal Shivering.

BACKGROUND: Shivering is one of the most common adverse outcomes associated with the administration of spinal anaesthesia, which, when clinically relevant, leads to numerous detrimental effects on the human body. Hence, its management becomes imperative. Meperidine, an opioid analgesic, is the drug of choice for this condition. However, the use of meperidine is controversial, as it carries the devastating adverse effect of respiratory depression. We explored the role of granisetron, a 5HT3 antagonist and a commonly used antiemetic premedication, in minimising the incidence of post-spinal shivering and decreasing the use of meperidine as a rescue drug. METHODS: Overall, 160 parturient patients, between the ages 18-50, undergoing uncomplicated, elective caesarean section, were enrolled in the study, and randomized into two groups with 80 participants each: Group A received 3ml of normal saline, and Group B was administered 3 mg granisetron,15 minutes before spinal anaesthesia institution. Incidence of clinically relevant shivering (score of 3 or more) was noted, and it was recorded whether meperidine was used or not. RESULTS: 67.5% of participants in Group A, and 32.5% of patients in Group B, experienced clinically relevant shivering, with 62.5% of patients in Group A and 28.75% in Group B warranting the use of meperidine. There was a statistically significant difference between the two groups in terms of incidence of clinically relevant shivering, and meperidine consumption (p-value <0.001). CONCLUSIONS: Premedication with 3 mg granisetron effectively attenuates the occurrence of post-spinal shivering and, hence, lowers the requirement of meperidine as rescue medication.

Comparisons of Varying Dosages of Chloral Hydrate-Hydroxyzine with and without Meperidine for Managing Challenging Pediatric Dental Behavior: A Retrospective study of 35 years of Sedation Experiences.

PURPOSE: This retrospective study compares the efficacy and safety of variable dosing of Chloral Hydrate - Hydroxyzine with and without Meperidine (Mep)for managing varying levels of anxiety and uncooperative behavior of young pediatric dental patients over a 35-year period. STUDY DESIGN: Reviews of the sedation logs of 2,610 children, 3-7 years were compared in search of what dosing proves safe and effective for differing levels of challenging behavior. Variable dosing of CH with and without Mep were judged using a pragmatic approach which defined sedation success as optimal, adequate, inadequate, or over-dosage using oneway analysis of variance. Descriptive analyses of behavior and physiologic assessment was included with regard to the extent to which physical restraint occurred to control interfering behavior. Arousal levels requiring stimulation, oxygen desaturation, and adverse reactions were included as indications of safety. RESULTS: Where Mep was used, success rates were consistently higher; need for higher-end dosing of CH was not found beneficial when Mep was included. Significantly less need for physical restraint accompanied the addition of Mep. CONCLUSIONS: There appears to be strong basis for the safety and efficacy of the use of CH-H-Mep in combination at lower dosing than historically used. Addition of Mep was observed to enhance sedations, permit lower CH dosing, lessen or eliminate the need for physical restraint and adverse reactions.

Retrospective Comparisons of the Efficacy and Safety of Variable dosing of Midazolam with and without Meperidine for Management of Varying Levels of Anxiety of Pediatric Dental Patients: 35 years of Sedation Experience.

PURPOSE: This retrospective study compares the efficacy and safety of variable dosing of Midazolam (Mid) with and without Meperidine (Mep) combinations for managing varying levels of anxiety and uncooperative behavior of young pediatric dental patients over a thirty-five-year period. STUDY DESIGN: Reviews of the sedation logs of 1,785 sedation visits are compared with emphasis on what dosing proves both safe and effective for differing levels of challenging pediatric behavior. Variable dosing of midazolam with and without meperidine which spanned low-end, mid-range, and upper-end were judged making use of a pragmatic approach which defined sedation success as optimal, adequate, inadequate, or over-dosage. Behavioral and physiologic assessment was included with attention to readily observable analysis of the extent to which need for physical restraint occurred to control interfering behavior. Assessment of arousal levels requiring stimulation along with the frequency of alterations in oxygen de-saturation and adverse reactions were included as indications of safety. RESULTS: Where Mep was used, success rates were consistently higher; working times were significantly prolonged and greater control was provided to avoid adverse reactions by virtue of reversal capability for both agents. CONCLUSIONS: Predictability and working time of Midazolam was enhanced by combination with narcotic for all levels of patient anxiety. Dosages of 0.7-1.0 mg/kg Mid combined with 1.0-1.5 mg/kg Mep offers the most effective and safe results to overcome need for restraint for moderate and severe levels of anxiety, respectively.

A hypothetical proposal to employ meperidine and tamoxifen in treatment of glioblastoma. Role of P-glycoprotein, ceramide and metabolic pathways.

Meperidine (pethidine) is a µ-opioid receptor (MOR) agonist widely used in the treatment of cancer pain. While MOR agonists in experimental models have demonstrated both pro- and antitumorigenic properties, meperidine has unique features which may be predominantly anticancer in nature. Meperidine both inhibits NMDA (N-methyl-D-Aspartate) receptors, which are involved in the progression of glioblastoma, and blocks NADH:Ubiquinone Oxidoreductase, which may hinder mitochondrial respiration. In the developing embryonic neural tissue, meperidine reduces cell proliferation around the neural tube and lowers the expression of the B RE (brain and reproductive organ-expressed). This is notable given that the B RE gene is implicated in cancer chemoresistance and gliomagenesis. Further, meperidine inhibits P-glycoprotein, which is involved in cancer multidrug resistance and the degradation of the sphingolipid backbone, ceramide. By enhancing the pro-autophagic and pro-apoptotic ceramide levels in cancer cells, meperidine stimulates cell death and reverses multidrug resistance. Tamoxifen, a safe medication employed in the treatment of breast cancer, directly blocks P-glycoprotein and boosts levels of ceramide both via inhibition of glycosylceramide synthase and ceramidase. Further, tamoxifen blocks NMDA-neurotoxicity and therefore it may act synergistically with meperidine in reducing glioblastoma progression associated with NMDA-activation. Finally, tamoxifen blocks glycolysis which may enhance the mitochondrial-blocking activity of meperidine to shut down energy metabolism of glioblastoma cells. Because of these properties, we believe that the combination of meperidine and tamoxifen merits study in cell culture and animal models to investigate a potential synergistic relationship in the treatment of glioblastoma.

Efficacy and safety of EBUS-TBNA under conscious sedation with meperidine and midazolam.

BACKGROUND: According to the guidelines, endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is the technique of choice for the diagnosis of mediastinal involvement in lung cancer; it is also useful for other mediastinal malignancies and benign pathology. Nevertheless, there is still discussion about whether to perform it under general anesthesia or under conscious sedation. METHODS: We retrospectively analyzed the data of all patients who underwent EBUS-TBNA under conscious sedation with up to 1 mg/kg of meperidine and up to 0.15 mg/kg of midazolam in the Interventional Pulmonology Unit of the Azienda USL-IRCCS Santa Maria Nuova of Reggio Emilia during 2 consecutive years. Demographic data, indication for the procedure, duration, number of lymph node sampled, number of passes per station, diagnostic yield, drugs dosage, questionnaire score, and complications were collected. RESULTS: A total of 302 patients underwent EBUS-TBNA, and 68% of the patients were males and the mean age was 65 ± 13 years old. The average duration of procedures was 24.4 minutes and the mean dosage of drugs was 4.32 ± 1.52 mg for midazolam and 50.86 ± 13.71 mg for meperidine. The mean number of lymph nodes sampled per patient was 1.75 ± 0.82, and each patient received an average of 4.71 ± 1.78 passes. A total of 90.7% of patients completed the procedures, 85% had adequate samples, and 94.4% of patients declared with Likert's questionnaire that they strongly agree to repeat the test if necessary. CONCLUSION: EBUS-TBNA performed under conscious sedation with meperidine and midazolam is feasible and well-tolerated and has a similar diagnostic yield of that reported in literature.

Comparison of clinical effects of meperidine and sufentanil added to 0.5% hyperbaric bupivacaine for spinal anesthesia in patients undergoing cesarean delivery: a randomized controlled trial.

PURPOSE: The objective of this study was to compare the effect of adding meperidine or sufentanil to hyperbaric bupivacaine in patients undergoing elective cesarean delivery (CD) under spinal anesthesia. The primary outcome was the first analgesic request time, and secondary outcomes included an analgesic requirement in the first 24 h and intraoperative and postoperative side effects. METHODS: This was a randomized, double-blind clinical trial in which patients were allocated into two groups. One group received preservative-free meperidine 12.5 mg (1 mL) in addition to 0.5% 10 mg (2 mL) of hyperbaric bupivacaine for spinal anesthesia. The other group received sufentanil 5 µg (1 mL) added to 0.5% 10 mg (2 mL) of hyperbaric bupivacaine. RESULTS: A total of 60 parturients were included in the study, 30 patients in each group. Time to first analgesic request was significantly longer in the meperidine group (400.0 ± 142.1 min) compared to (274.0 ± 104.1 min) in the sufentanil group (P < 0.0001). Around 73% of the parturients in the sufentanil group required analgesics at 4 h compared to 13% in the meperidine group (P < 0.0001). There were no significant differences in postoperative pruritus, nausea and vomiting, in addition to shivering. As for surgeon satisfaction, 56.7% reported excellent abdominal muscle relaxation during the surgery in the meperidine group compared to 10% in the sufentanil group (P < 0.0001). CONCLUSION: Meperidine was superior to sufentanil in terms of improved analgesia, intraoperative postoperative pruritus, and shivering, as well as increased surgeon satisfaction in women undergoing spinal anesthesia for elective cesarean delivery. CLINICAL TRIAL NUMBER AND REGISTRY: ClinicalTrials.gov (NCT04446715).

Comparing the Effect of Intrathecal Injection of Meperidine, Meperidine-Bupivacaine, and Bupivacaine Alone on Pain Severity and Hemodynamic Parameters after Elective Cesarean Section.

Background: This study aimed to evaluate the effect of meperidine and bupivacaine on maternal hemodynamic changes prior to anesthesia and compare it with post-intervention. Methods: In this clinical trial, the rate of postoperative analgesia on 90 healthy women candidates for elective cesarean section with spinal anesthesia was evaluated by meperidine, bupivacaine, and a combination of these two drugs. The study was conducted on 90 patients, including 30 patients receiving injection of meperidine, 30 patients receiving injection of bupivacaine, and 30 patients receiving injection of meperidine plus bupivacaine. Nausea, vomiting, headache, itching, and shortness of breath were also recorded. Results: The mean systolic and diastolic blood pressure as well as heart rate and mean arterial blood pressure in the meperidine group were significantly lower than those detected before the intervention (P < 0.05). The mean SpO2 index was significantly decreased in meperidine and meperidine+bupivacaine groups (P < 0.05). The prevalence of nausea, vomiting and itching was higher in meperidine group compared to those in the other two groups (P = 0.032). Conclusions: In sum, the prevalence of nausea, vomiting, and itching in the meperidine group was higher than those in the other two groups. Due to almost equal performance of meperidine and meperidine plus bupivacaine in analgesia, the stabilization of other hemodynamic indices in the meperidine plus bupivacaine group, and the decline in the prevalence of nausea, vomiting, and itching, this combination may have been a good alternative to meperidine.