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.

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.

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.

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.

Different interventions for preventing postoperative catheter-related bladder discomfort: a systematic review and meta-analysis.

OBJECTIVE: Catheter-related bladder discomfort (CRBD) is a common complication of intraoperative urinary catheterization. Various studies have evaluated the efficacy of different interventions in postoperative CRBD. The present review was performed to assess the efficacy of these interventions. METHODS: PubMed, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) databases were systematically searched to identify randomized controlled trials (RCTs) investigating the efficacy of different drugs for the prevention of postoperative CRBD. This review evaluated the incidence and severity of CRBD after different interventions at 0, 1, 2, and 6 h postoperatively. RESULTS: Forty-five studies including 31 different drugs were analyzed. Eleven drugs were investigated in more than two RCTs, of which dexmedetomidine, gabapentin, tolterodine, tramadol, ketamine, nefopam, oxybutynin, pregabalin, and pudendal nerve block (PNB) generally showed significantly higher efficacy than controls postoperatively. Solifenacin only showed significant efficacy compared with the control at 0 h, and intravenous lidocaine only showed significant efficacy compared with the control at 6 h. There were insufficient trials to draw conclusions regarding atropine, butylscopolamine, chlorpheniramine, clonidine, darifenacin, diphenhydramine, glycopyrrolate, intravesical bupivacaine, ketamine-haloperidol, pethidine-haloperidol, ketorolac, lidocaine-prilocaine cream, magnesium, hyoscine n-butyl bromide, oxycodone, paracetamol, parecoxib, trospium, resiniferatoxin, or amikacin. However, all but pethidine-haloperidol and chlorpheniramine showed some efficacy at various time points compared with controls. CONCLUSION: This review suggests that dexmedetomidine, gabapentin, tolterodine, tramadol, ketamine, nefopam, oxybutynin, pregabalin, and PNB are effective in preventing postoperative CRBD. Considering the efficacy and adverse effects of all drugs, dexmedetomidine and gabapentin were ranked best.

Comparison of Intravenous Ketamine with Intrathecal Meperidine in Prevention of Post-anesthetic Shivering after Spinal Anesthesia for Lower Limb Orthopedic Surgeries: A Double-blind Randomized Clinical Trial.

Background: Post-anesthetic shivering is one of the most common complications after anesthesia. Ketamine has been considered to be an effective treatment for post-anesthetic shivering, but the evidence for its therapeutic benefit after spinal anesthesia is limited. The aim of this study was to compare the effects of intravenous ketamine with intrathecal meperidine in the prevention of post-anesthetic shivering after spinal anesthesia for lower limb orthopedic surgeries. Methods: In a double-blind randomized parallel-group clinical trial, a total of 150 patients scheduled for lower limb orthopedic surgeries under spinal anesthesia were selected and randomly divided into three equally sized groups of intravenous ketamine (0.5 mg/kg), intrathecal meperidine (0.2mg/kg) or intravenous normal saline (as placebo). The intensity of shivering in patients were evaluated during surgery and after transfer into the post anesthesia care unit. Also, changes in patients' drowsiness, nausea, vomiting, pruritus, mean arterial pressure, heart rate, and arterial oxygen saturation (SPO2) during surgery and until the end of anesthesia were evaluated. Results: In all times of evaluation (20, 60, 80, 100 and 120 minutes after onset of spinal anesthesia) patients in control group showed a greater intensity of shivering compared to other groups. However, patients who received intrathecal meperidine experienced significantly lower intensity of post anesthetic shivering (p<0.05). The results showed a significant mean arterial pressure and heart rates differences between the three groups, only on 20 and 60 minutes after initiation of spinal anesthesia. The incidence of nausea, vomiting, and pruritus was not significantly different in all three groups, although all patients who received ketamine experienced drowsiness after surgery (p<0.001). Conclusion: The results of the present study showed that, although both intrathecal meperidine and intravenous ketamine could effectively prevent postoperative shivering after spinal anesthesia in lower limb orthopedic surgeries, intrathecal meperidine was associated with more efficacy benefits and a lower frequency of side effects such as post-anesthesia drowsiness.

Pharmacokinetics and pharmacodynamics of meperidine after intramuscular and subcutaneous administration in horses.

OBJECTIVE: To describe the pharmacokinetics and pharmacodynamics of meperidine after IM and subcutaneous administration in horses. STUDY DESIGN: prospective, randomized, blinded, crossover trial. ANIMALS: Six adult horses weighing 494 ± 33 kg. METHODS: Treatments included meperidine 1 mg/kg IM with saline 6 mL subcutaneously, meperidine 1 mg/kg subcutaneously with saline 6 mL IM, and saline 6 mL subcutaneously and 6 mL IM, with a 7-day washout between treatments. Plasma meperidine concentrations and pharmacodynamic values (thermal and mechanical thresholds, physiological variables, fecal production) were collected at various time points for 24 hours. Accelerometry data were obtained for 8 hours to measure locomotor activity. Data were analyzed with a mixed effects model, and α was set at .05. RESULTS: Meperidine terminal half-life (T1/2 ), maximal plasma concentrations, and time to maximal concentration were 186 ± 59 and 164 ± 56 minutes, 265.7 ± 47.2 and 243.1 ± 80.1 ng/mL at 17 ± 6, and 24 ± 13 minutes for IM at subcutaneous administration, respectively. No effect of treatment or time was observed on thermal or mechanical thresholds, heart rate, respiratory rate, locomotor activity, frequency of defecations, or fecal weight (P > .2 for all). CONCLUSION: Maximum meperidine concentrations were achieved quickly with a short T1/2 in both treatment groups. Neither IM nor subcutaneous meperidine influenced thermal or mechanical threshold or physiological variables. CLINICAL SIGNIFICANCE: The short half-life and lack of detectable antinociceptive effect do not support IM or subcutaneous administration meperidine at 1 mg/kg for analgesia in horses.

Meperidine pharmacokinetics and effects on physiologic parameters and thermal threshold following intravenous administration of three doses to horses.

BACKGROUND: Meperidine is a synthetic opioid that belongs to the phenylpiperidine class and is a weak mu receptor agonist. In horses there are a limited number of published studies describing the analgesic effects of systemically administered meperidine in horses. The objective of this study was to describe the pharmacokinetics, behavioral and physiologic effects and effect on thermal threshold of three doses of intravenously administered meperidine to horses. Eight University owned horses (four mares and four geldings, aged 3-8 years were studied using a randomized balanced 4-way cross-over design. Horses received a single intravenous dose of saline, 0.25, 0.5 and 1.0 mg/kg meperidine. Blood was collected before administration and at various time points until 96 hours post administration. Plasma and urine samples were analyzed for meperidine and normeperidine by liquid chromatography-mass spectrometry and plasma pharmacokinetics determined. Behavioral and physiologic data (continuous heart rate, step counts, packed cell volume, total plasma protein and gastrointestinal sounds) were collected at baseline through 6 hours post administration. The effect of meperidine administration on thermal nociception was determined and thermal excursion calculated. RESULTS: Meperidine was rapidly converted to the metabolite normeperidine. The volume of distribution at steady state and systemic clearance (mean ± SD) ranged from 0.829 ± 0.138-1.58 ± 0.280 L/kg and 18.0 ± 1.4-22.8 ± 3.60 mL/min/kg, respectively for 0.5-1.0 mg/kg doses. Adverse effects included increased dose-dependent central nervous excitation, heart rate and cutaneous reactions. Significant effects on thermal nociception were short lived (up to 45 minutes at 0.5 mg/kg and 15 minutes at 1.0 mg/kg). CONCLUSIONS: Results of the current study do not support routine clinical use of IV meperidine at a dose of 1 mg/kg to horses. Administration of 0.5 mg/kg may provide short-term analgesia, however, the associated inconsistent and/or short-term adverse effects suggest that its use as a sole agent at this dose, at best, must be cautiously considered.

Endogenous pore-forming protein complex targets acidic glycosphingolipids in lipid rafts to initiate endolysosome regulation.

Bacterial pore-forming toxin aerolysin-like proteins (ALPs) are widely distributed in animals and plants. However, functional studies on these ALPs remain in their infancy. ßγ-CAT is the first example of a secreted pore-forming protein that functions to modulate the endolysosome pathway via endocytosis and pore formation on endolysosomes. However, the specific cell surface molecules mediating the action of ßγ-CAT remain elusive. Here, the actions of ßγ-CAT were largely attenuated by either addition or elimination of acidic glycosphingolipids (AGSLs). Further study revealed that the ALP and trefoil factor (TFF) subunits of ßγ-CAT bind to gangliosides and sulfatides, respectively. Additionally, disruption of lipid rafts largely impaired the actions of ßγ-CAT. Finally, the ability of ßγ-CAT to clear pathogens was attenuated in AGSL-eliminated frogs. These findings revealed a previously unknown double binding pattern of an animal-secreted ALP in complex with TFF that initiates ALP-induced endolysosomal pathway regulation, ultimately leading to effective antimicrobial responses.

Safety and efficacy of a combination of pethidine and levallorphan for pain relief during labor: An observational study.

AIM: To evaluate the safety, effect on breastfeeding and efficacy of a combination of pethidine and levallorphan (Pethilorfan) for pain relief during labor. METHODS: We compared maternal or neonatal morbidities, suckling difficulties in newborns and breastfeeding rates between 177 women who received 50-200 mg (as pethidine) of Pethilorfan during labor (Pethilorfan group) and 354 women who delivered their infants without analgesic drugs immediately before or after each woman in the Pethilorfan group (control group) from January 1, 2005 to December 31, 2016. We performed univariate and multivariate analyses for comparison between the two groups. We also evaluated the efficacy of Pethilorfan retrospectively. RESULTS: The Pethilorfan group included more women with prolonged and/or operative deliveries than the control group. Nevertheless, no significant differences were seen between the two groups in the rates of Apgar scores less than 7 at 1 or 5 min, composite neonatal morbidities, hyperbilirubinemia or respiratory disturbances. The incidence of suckling difficulties lasting over 24 h and the breastfeeding rates at discharge or after 1 month were also similar. Maternal adverse effects of Pethilorfan were generally mild and transient. The efficacy ratio of Pethilorfan was 83.6%, although its analgesic effect was usually incomplete. CONCLUSION: Pethilorfan can be used safely for labor pain relief without increasing maternal or neonatal morbidities, or impeding breastfeeding, if it is administered at a prudent dosage. Parenteral opioids including Pethilorfan should remain as an option for treating women in labor pain, particularly when epidural analgesia is not readily available or contraindicated.

Intravenous remifentanil patient-controlled analgesia versus intramuscular pethidine for pain relief in labour (RESPITE): an open-label, multicentre, randomised controlled trial.

BACKGROUND: About a third of women receiving pethidine for labour pain subsequently require an epidural, which provides effective pain relief but increases the risk of instrumental vaginal delivery. Remifentanil patient-controlled analgesia (PCA) in labour is an alternative to pethidine, but is not widely used. We aimed to evaluate epidural analgesia progression among women using remifentanil PCA compared with pethidine. METHODS: We did an open-label, multicentre, randomised controlled trial in 14 UK maternity units. We included women aged 16 years or older, beyond 37 weeks' gestation, in labour with a singleton cephalic presentation, and who requested opioid pain relief. We randomly assigned eligible participants (1:1) to either the intravenous remifentanil PCA group (40 µg bolus on demand with a 2 min lockout) or the intramuscular pethidine group (100 mg every 4 h, up to 400 mg in 24 h), using a web-based or telephone randomisation service with a minimisation algorithm for parity, maternal age, ethnicity, and mode of labour onset. Because of the differences in routes of drug administration, study participants and health-care providers were not masked to the group allocation. The primary outcome was the proportion of women who received epidural analgesia after enrolment for pain relief in labour. Primary analyses were unadjusted and analysed by the intention-to-treat principle. This study is registered with the ISRCTN registry, number ISRCTN29654603. FINDINGS: Between May 13, 2014, and Sept 2, 2016, 201 women were randomly assigned to the remifentanil PCA group and 200 to the pethidine group. One participant in the pethidine group withdrew consent, leaving 199 for analyses. The proportions of epidural conversion were 19% (39 of 201) in the remifentanil PCA group and 41% (81 of 199) in the pethidine group (risk ratio 0·48, 95% CI 0·34-0·66; p<0·0001). There were no serious adverse events or drug reactions directly attributable to either analgesic during the study. INTERPRETATION: Intravenous remifentanil PCA halved the proportion of epidural conversions compared with intramuscular pethidine. This finding challenges routine pethidine use as standard of care in labour. FUNDING: National Institute for Health Research Clinician Scientist Award.

Analysis of factors associated with extended recovery time after colonoscopy.

BACKGROUND & AIMS: A common limiting factor in the throughput of gastrointestinal endoscopy units is the availability of space for patients to recover post-procedure. This study sought to identify predictors of abnormally long recovery time after colonoscopy performed with procedural sedation. In clinical research, this type of study would be performed using only one regression modeling approach. A goal of this study was to apply various "machine learning" techniques to see if better prediction could be achieved. METHODS: Procedural data for 31,442 colonoscopies performed on 29,905 adult patients at Massachusetts General Hospital from 2011 to 2015 were analyzed to identify potential predictors of long recovery times. These data included the identities of hospital personnel, and the initial statistical analysis focused on the impact of these personnel on recovery time via multivariate logistic regression. Secondary analyses included more information on patient vitals both to identify secondary predictors and to predict long recoveries using more complex techniques. RESULTS: In univariate analysis, the endoscopist, procedure room nurse, recovery room nurse, and surgical technician all showed a statistically significant relationship to long recovery times, with p-value below 0.0001 in all cases. In the multivariate logistic regression, the most significant predictor of a long recovery time was the identity of the recovery room nurse, with the endoscopist also showing a statistically significant relationship with a weaker effect. Complex techniques led to a negligible improvement over simple techniques in prediction of long recovery periods. CONCLUSION: The hospital personnel involved in performing a colonoscopy show a strong association with the likelihood of a patient spending an abnormally long time recovering from the procedure, with the most pronounced effect for the nurse in the recovery room. The application of more advanced approaches to improve prediction in this clinical data set only yielded modest improvements.

Risk Factor for Vital Signs Fluctuation during Colonoscopy under Conscious Sedation Consisting of Midazolam and Meperidine.

BACKGROUND: Sedatives or analgesics are widely used to relieve a patient's discomfort during colonoscopy (CS). Although cardiopulmonary adverse events are sometimes experienced during the examination, the risk factors for vital signs fluctuation (VSF) have not been fully elucidated. This study thus aimed to identify the risk factors for VSF during the examination, as well as to evaluate the frequency and the degree of VSF. SUMMARY: A total of 755 consecutive subjects who received CS under endoscopist-administrated sedation using midazolam, meperidine, or combination of both were retrospectively analyzed. We assessed the distribution of vital signs during the procedure and frequency of VSF. To identify independent risk factors, we analyzed the association between VSF and subjects' characteristics and procedure information using the multivariate logistic regression model. Consequently, VSF was observed in 17% of all; hypotension and oxygen desaturation was observed in 13 and 5%, respectively. However, we could achieve the purpose of all procedure and, no one required hospitalization or extension of hospital stay. Multivariate analysis revealed that age (OR 1.05 [95% CI 1.04-1.07]), being female (OR 1.78 [95% CI 1.19-2.70]), and use of midazolam (OR 5.06 [95% CI 3.18-8.08]) were independent risk factors for VSF.

Taking the alternative route: Women's experience of intranasal fentanyl, subcutaneous fentanyl or intramuscular pethidine for labour analgesia.

OBJECTIVE: To compare women's experience of receiving either intranasal fentanyl, subcutaneous fentanyl or intramuscular pethidine for labour analgesia. DESIGN: A content analysis was undertaken as part of the third phase of a larger randomised controlled trial, using the per-protocol dataset to examine women's experiences of treatment received. Healthy women birthing at term, who received intranasal fentanyl (n=41), subcutaneous fentanyl (n=37) and/or intramuscular pethidine (n=38) for labour analgesia, were contacted at 6 weeks postpartum to complete a phone questionnaire. SETTING: A tertiary and regional maternity unit in South Australia. FINDINGS: Over 80% of women who received intranasal or subcutaneous fentanyl reported that they would use the treatment again compared to 44.8% of women who had received pethidine (self-administered intranasal fentanyl provided more expressive responses emphasising the route provided a strong sense of control and enablement. KEY CONCLUSIONS: Route of administration influenced the women's experience, more women who self-administered intranasal fentanyl reported positive emotional responses, with women reporting increased autonomy and satisfaction. Whereas, women who relied on the midwife to administer subcutaneous fentanyl or intramuscular pethidine, were more often focused on the physical effect of the drug. Pethidine was the least preferred option due to adverse effects. IMPLICATIONS FOR PRACTICE: For women requesting parenteral analgesia, fentanyl administered by less invasive routes offers women additional options that may better meet their emotional, cognitive and physical needs than the current practice of administering intramuscular pethidine.

Modulation of the sphingolipid rheostat is involved in paclitaxel resistance of the human prostate cancer cell line PC3-PR.

Taxoids are anti-cancer drugs frequently used to treat solid tumors, but they are sometimes ineffective and tumors may become resistant to their action. Here, we examined the involvement of sphingolipid metabolic enzymes in paclitaxel (PTX) resistance using a human prostate cancer cell line, PC3, and its PTX-resistant subline, PC3-PR. PTX (20 nM) suppressed cell proliferation and increased various ceramide species in PC3, but not PC3-PR, cells. PC3-PR contained higher S1P levels than did PC3, regardless of PTX treatment. Western blotting revealed that PC3-PR cells expressed higher levels of sphingosine kinase 1 (SPHK1) and glucosylceramide synthase (GCS) but lower levels of acid sphingomyelinase (ASMase) and neutral sphingomyelinase 2 than did PC3 cells. Inhibition of SPHK1 using siRNA or a pharmacological inhibitor decreased S1P levels in PC3-PR cells and inhibited proliferation in the presence or absence of PTX, suggesting that SPHK1 is at least partially responsible for PTX resistance. Similarly, GCS inhibitors (PDMP and PPMP) increased cellular ceramides and suppressed the proliferation of PC3-PR. However, inhibition of proteasome function or histone deacetylase activity increased SMase and ceramide levels and suppressed PC3-PR proliferation. These results suggest that modulation of metabolic enzyme expression and alteration of the sphingolipid rheostat protects cancer cells against PTX.

Comparison of efficacy of meperidine and fentanyl in terms of pain management and quality of life in patients with cervical cancer receiving intracavitary brachytherapy: a double-blind, randomized controlled trial.

OBJECTIVE: The aim of this study was to compare the effectiveness of two sedative regimens, a benzodiazepine with either meperidine or fentanyl, in relieving pain in patients with cervical cancer undergoing intracavitary brachytherapy in terms of pain score and quality of life. METHODS: Forty unselected outpatients undergoing brachytherapy (160 fractions) were enrolled with informed consent and randomized to receive a benzodiazepine with either meperidine or fentanyl. The perceived pain score according to a standard 10-item numeric rating scale was collected every 15 min during the procedure, and the perceived quality of life was determined at the end of each procedure using the EuroQol five-dimension questionnaire. The patients and medical staff members directly involved with the procedure were blinded to the medication used. RESULTS: The patients' pain levels were mild in both analgesic groups. Meperidine appeared to be slightly more effective than fentanyl, although the differences in the average pain score and quality of life were not statistically significant. CONCLUSION: Both meperidine and fentanyl in combination with benzodiazepine were effective in relieving pain and discomfort in patients undergoing brachytherapy. TRIAL REGISTRATION: NCT02684942, ClinicalTrials.gov.

Pain management of trauma patients in the emergency department: a study in a public hospital in Iran.

BACKGROUND: Pain is a common problem which the patients in emergency departments (ED) face, especially trauma patients under treatment may suffer from physical, psychological and ethical issues. The purpose of this study was to evaluate traumatic pain management in the emergency department at a public hospital in Iran in 2014. METHODS: This observational prospective study was conducted on 450 trauma patients admitted to a trauma emergency department. The tool used in this study has three parts: demographic data, data of trauma, and VRS (Verbal Rating Scales) score at a 7-point scale-at the arrival time to 4h later. The statistical analysis was conducted by using Mann-Whitney and Kruskal-Wallis tests, repeated measures, survival analysis, and multiple regression analysis. RESULTS: The majority of the samples were male (83.3%) with the mean age of 35.2years. The patients mostly suffered from contusions and strains (42.4%). The majority of the patients [274 patients (60.8%)] received no intervention for pain relief and only 60 patients (13.3%) received analgesics. The mean time period of the first analgesic utilization was 41 (±20.4) minutes. Pain in admission, pain assessment, and receiving intervention could explain the 32% of pain reduction. No other variables such as age, sex, education, kind of trauma, and the shift of admission were involved in pain reduction. CONCLUSIONS: This research study demonstrated that comprehensive, adequate pain management remains an obscure goal within the emergency nursing setting. There is a need to undertake further research and develop educational programs on effective analgesic practice in pain management.

A COMPARATIVE STUDY OF THE ANALGESIC EFFECT OF INTRAVENOUS PETHIDINE VS. KETOROLAC AFTER INGUINAL HERNIA SURGERY IN CHILDREN UNDER GENERAL ANESTHESIA.

INTRODUCTION: Postoperative pain due to tissue damage caused during surgery not only causes discomfort for the patients, but can also result in prolonged hospitalization, increased morbidity and respiratory disorders, and readmission to the hospital. For postoperative pain control, numerous methods and medications have been suggested, such as non-steroidal anti-inflammatory drugs (NSAIDs) and narcotics. Pethidine, as a narcotic analgesic, and ketorolac, as an NSAID, are widely used for pain control. Thus, in this study, the effects of these two drugs were studied and compared in terms of pain control after inguinal hernia surgery in children of 1-12 years of age. MATERIALS AND METHODS: Sixty-six children undergoing inguinal herniorrhaphy were selected and randomly divided into 2 groups. The first group received 0.5 mg/kg ketorolac and the second group received 1 mg/kg pethidine during extubation. Postoperative pain (using Wong Baker pain scale) and complications were measured until 24 hours after surgery. RESULTS: Mean and standard deviations of postoperative pain 1 hour after surgery in the pethidin and ketorolac groups were 5.06 ± 1.41 and 3.88 ± 0.93, respectively. The scale was significantly lower in the ketorolac group (P < 0.001). Postoperative pain intensity 2 hours after surgery in these two groups was 4.48 ± 1.52 and 3.55 ± 1.15, respectively, and the difference between the two groups was significant (P = 0.006). The variation in postoperative pain intensity in the ketorolac group was statistically lower than the pethidin group (P = 0.020). CONCLUSION.

Safety and Efficacy of Dexmedetomidine in Treating Post Spinal Anesthesia Shivering: A Randomized Clinically Controlled Dose-Finding Trial.

BACKGROUND: The optimum dose of dexmedetomidine for shivering control with the least hemodynamic derangements is still under research. OBJECTIVE: To compare the efficacy, hemodynamic and side effects of dexmedetomidine in 3 different doses with those of meperidine for the treatment of shivering in patients undergoing spinal anesthesia for minor elective lower abdominal surgery. STUDY DESIGN: Prospective double-blind randomized clinically controlled study. SETTING: University hospital. METHODS: One hundred twenty patients who developed shivering under spinal anesthesia.On shivering, patients were randomly allocated to receive an intravenous 2 mL bolus dose of meperidine 0.4 mg/kg (meperidine group, n = 30), dexmedetomidine 0.5 µg/kg (DEX I group, n = 30), 0.3 µg/kg (DEX II group, n = 30), or 0.2µg/kg (DEX III group, n = 30). Control of shivering, time taken for cessation of shivering, response rate, recurrence, hemodynamic changes, sedation score, tympanic temperature, and side effects were noted and compared between groups. RESULTS: The groups were comparable regarding demographic profile, tympanic temperature decline, and shivering onset time (P > 0.05). Lower shivering cessation time (P < 0.001) and higher response rate (P < 0.01) were observed in DEX I and II groups compared with DEX III and meperidine groups, with a nonsignificant difference between DEX I and II groups. Recurrence of shivering activity was higher in DEX III group (36.7%, P < 0.01) compared with DEX I (10%), DEX II (6.7%) and meperidine (16.7%) groups. Lower heart rates, systolic and diastolic blood pressure mean values were recorded in DEX I group (P < 0.05). Nine patients (30%) in DEX I group were in levels 3 - 5 of sedation (P < 0.02) compared with 5 (16.66%), 2 (6.66%), and 4 (13.3) patients in DEX II, DEX III, and meperidine groups, respectively. LIMITATIONS: This study is limited by its small sample size. CONCLUSIONS: Among the 3 doses investigated, dexmedetomidine 0.3µg/kg effectively treated shivering associated with spinal anesthesia with modest hemodynamic and sedation effects. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02382432. KEY WORDS: Dexmedetomidine, hypothermia, shivering, spinal anesthesia.

PPMP, a novel tubulin-depolymerizing agent against esophageal cancer in patient-derived tumor xenografts.

Esophageal cancer is one of the least studied and deadliest cancers worldwide with a poor prognosis due to limited options for treatment. Chemotherapy agents such as the microtubule-targeting compounds are the mainstay of palliation for advanced esophageal cancer treatment. However, the toxicity and side effects of tubulin-binding agents (TBAs) have promoted the development of novel, more potent but less toxic TBAs. Herein, we identified 2-[4-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrazol-5-yl]-5-[(2-methylprop-2-en-1-yl)oxy] phenol (PPMP) as a novel TBA for esophageal cancer treatment. PPMP markedly inhibited tubulin polymerization, and decreased viability and anchorage-independent growth of esophageal cancer cell lines, effects that were accompanied by G2/M arrest and apoptosis. Importantly, we produced patient-derived esophageal cancer xenografts to evaluate the therapeutic effect of PPMP in a setting that best mimics the clinical context in patients with esophageal cancer. Overall, we identified PPMP as a novel microtubule-destabilizing compound and as a new therapeutic agent against esophageal carcinoma.