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Purpose: Safe and effective analgesia sub partu is one of the central issues in optimizing vaginal delivery birth experiences. Meptazinol is a common opiate approved for treating labor pain in the first stage of labor. According to the manufacturer, manual meptazinol can be applied intramuscularly or intravenously. The aim of this study was to compare the two application methods in terms of efficacy in pain relief, occurrence of side effects and treatment satisfaction., Methods: 132 patients with singleton term pregnancies and intended vaginal delivery, receiving meptazinol during first stage of labor were included in this prospective cohort study from 05/2020 to 01/2021. We evaluated effectiveness in pain relief and treatment satisfaction using numeric rating scales (NRS) and documented the occurrence of adverse effects. Chi-square test or Fisher exact test were used to compare categorical data and Mann-Whitney U test to compare continuous data between the two treatment groups. Statistical analysis was done by SPSS 27.0. A p value < 0.05 was considered to indicate statistical significance (two tailed)., Results: Meptazinol decreased labor pain significantly from a NRS of 8 (IQR 8-10) to 6 (IQR 4.75-8) in both treatment groups with no difference in effectiveness between the groups. Frequency of effective pain reduction of a decrease of 2 or more on the NRS did not differ between groups (39.4% vs 54.5%, p = 0.116), as the occurrence of adverse effects. 12% of the newborns were admitted to NICU, the median NApH was 7.195., Conclusion: Meptazinol significantly reduces labor pain regardless of the method of application: intramuscular or intravenous. According to our data, no preferable route could be identified. The comparably poorer perinatal outcome in our study cohort hinders us to confirm that meptazinol is safe and can be recommended without restrictions., (© 2023. The Author(s).)

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.

Background and Objective: Pethidine (meperidine) can decrease labor pain-associated mother's hyperventilation and high cortisol-induced newborn complications. However, prenatal transplacentally acquired pethidine can cause side effects in newborns. High pethidine concentrations in the newborn brain extracellular fluid (bECF) can cause a serotonin crisis. Therapeutic drug monitoring (TDM) in newborns' blood distresses them and increases infection incidence, which can be overcome by using salivary TDM. Physiologically based pharmacokinetic (PBPK) modeling can predict drug concentrations in newborn plasma, saliva, and bECF after intrauterine pethidine exposure., Methods: A healthy adult PBPK model was constructed, verified, and scaled to newborn and pregnant populations after intravenous and intramuscular pethidine administration. The pregnancy PBPK model was used to predict the newborn dose received transplacentally at birth, which was used as input to the newborn PBPK model to predict newborn plasma, saliva, and bECF pethidine concentrations and set correlation equations between them., Results: Pethidine can be classified as a Salivary Excretion Classification System class II drug. The developed PBPK model predicted that, after maternal pethidine intramuscular doses of 100 mg and 150 mg, the newborn plasma and bECF concentrations were below the toxicity thresholds. Moreover, it was estimated that newborn saliva concentrations of 4.7 µM, 11.4 µM, and 57.7 µM can be used as salivary threshold concentrations for pethidine analgesic effects, side effects, and the risk for serotonin crisis, respectively, in newborns., Conclusion: It was shown that saliva can be used for pethidine TDM in newborns during the first few days after delivery to mothers receiving pethidine., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To compare the efficacy and adverse effects of intravenous meperidine and inhaled nitrous oxide for intrapartum analgesia in multiparous patients., Methods: This randomized controlled trial was conducted in the delivery ward of a university teaching medical center in Afula, Israel. Multiparous patients with term, singleton pregnancies who were in labor were randomized in a 1:1 ratio to 50 mg intravenous meperidine or inhaled nitrous oxide. The primary outcome was pain intensity 20-30 minutes after analgesic administration, measured on a visual analog scale (VAS) from 0 to 10 cm. Secondary outcomes included the need for additional analgesia, labor length, delivery mode, patient satisfaction, and maternal and neonatal adverse effects. To detect a 1-cm (±2.6) difference in VAS score between the groups, 214 total participants were needed to achieve 80% power with an alpha of 0.05., Results: From August 2016 through May 2019, 214 participants were enrolled. Fourteen were excluded after randomization. Of the 200 analyzed, 102 received nitrous oxide, and 98 received intravenous meperidine. Demographic and obstetric variables were comparable between the two groups. The VAS score 20-30 minutes after analgesic administration did not differ between the groups (7.7±2.3 cm and 7.6±2.7 cm in the nitrous oxide and meperidine groups, respectively, P=.89). There were no significant differences between the groups in the rate of additional analgesic use, labor length, delivery mode, Apgar scores, rate of breastfeeding, patient satisfaction, or maternal and neonatal adverse effects., Conclusion: Pain intensity was comparable in multiparous patients 20-30 minutes after administration of meperidine and nitrous oxide. Adverse effects were also comparable., Clinical Trial Registration: ClinicalTrials.gov, NCT02783508., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Molar incisor hypomineralization (MIH) affects the first permanent molars and permanent incisors whose formative embryological process develops around birth and the first year of life. This study's main objective is to assess the relationship between MIH, on the one hand, with the administration during childbirth of epidural bupivacaine, intramuscular meperidine with haloperidol, synthetic intravenous oxytocin, and prostaglandins such as dinoprostone vaginally, and on the other hand, with suffered pathologies during the first year of life. Cross-sectional retrospective study was carried out on 111 children who attended dental check-ups. Oral examination was carried out to determine MIH involvement. Data on the administration of medications during delivery and the illnesses suffered by the children in the first year of life were taken from the hospital records. Significant relationship with Pearson's chi-square was found between the presence of MIH and the administration of meperidine with haloperidol intramuscularly and the vaginal administration of dinoprostone during labour. Also in children who have suffered serious infections and those who have received antibiotics in early childhood. In recent years there has been a growing trend in many countries to medicalize childbirth even above what the World Health Organization recommends. Some of the drugs used in these protocols could be involved in the appearance of dental mineralization alterations of the MIH type and this would help to explain the increase in its prevalence., (© 2022. The Author(s).)

Aim: The number of therapeutic endoscopic procedures in elderly individuals keeps increasing and this population has a high risk of adverse events related to sedation and general anesthesia. However, there is a paucity on data about the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in this population., Methods: In total, 417 consecutive ERCP procedures were performed in 362 patients between September 2018 and January 2020. Of these, 59 patients (74 sessions) were aged ≥80 years (Group A) and 173 patients (193 procedures) were aged ≤65 years (Group B). We analyzed the prospectively collected data of patient- and procedure-related variables., Results: The procedure time was significantly longer in Group A (P < 0.05). The prevalence of comorbidities, use of anticoagulants and American Society of Anesthesiologists (ASA) physical status classification levels were significantly higher in Group A (P < 0.05). The incidence of periampullary diverticula, malignancy, rate of difficult cannulation, mean number of stones, use of biliary stents and stent dysfunction was also significantly higher in Group A (P < 0.05). The medication doses used were significantly higher and emergence symptoms were significantly more frequent in Group B (P < 0.05). The rates of bleeding, pancreatitis, perforation, cholangitis, hypoxia, hypotension and the length of hospital stay did not significantly differ between the two groups. The overall success rate of the procedure was comparable in the two groups (P = 0.874)., Conclusions: ERCP can be safely performed in elderly patients using a combination of midazolam and ketamine without propofol. The incidence of complications is comparable with that observed in younger patients. Geriatr Gerontol Int 2021; 21: 887-892., (© 2021 Japan Geriatrics Society.)

There have been increasing concerns about adverse effects and drug interactions with meperidine. The goal of this study was to characterize meperidine use in the United States. Meperidine distribution data were obtained from the Drug Enforcement Administration's Automated of Reports and Consolidated Orders System. The Medicare Part D Prescriber Public Use File was utilized to capture overall trends in national prescriptions in this observational report. Nationally, meperidine distribution decreased by 94.6% from 2001 to 2019. In 2019, Arkansas, Alabama, Oklahoma, and Mississippi saw significantly greater distribution when compared with the US state average of 9.27 mg per 10 persons (SD = 6.82). Meperidine distribution showed an 18-fold difference between the highest state (Arkansas = 36.8 mg) and lowest state (Minnesota = 2.1 mg). Five of the six states with the lowest distribution were in the Northeast. Meperidine distribution per state was correlated with the prevalence of adult obesity (r(48) = +0.48, p < .001). Family medicine and internal medicine physicians accounted for 28.9% and 20.5%, respectively, of meperidine total daily supply (TDS) in 2017. Interventional pain management (5.66) and pain management (3.48) physicians accounted for the longest TDS per provider. The use of meperidine declined over the last two decades. Meperidine varied by geographic region with south-central states, and those with more obesity, showing greater distribution. Primary care doctors continue to account for the majority of meperidine daily supply. Increasing knowledge of meperidine's undesirable adverse effects like seizures and serious drug-drug interactions is likely responsible for these pronounced reductions., (© 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

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.

Background: Meperidine, a synthetic opioid, has a rapid onset and short duration of action. Mounting evidence has challenged meperidine's analgesic benefits, and concerns have been raised about its safety profile. Despite recommendations to restrict the prescription of meperidine, the drug remains frequently used., Objectives: The aim of this study was to evaluate the evidence regarding the efficacy and safety of meperidine for acute postoperative and labor pain., Study Design: This was a narrative review of the analgesic efficacy and side effects of meperidine compared to other analgesic drugs for acute postoperative and labor pain in adults., Setting: Randomized controlled trials that compared the analgesic efficacy and side effect profile of meperidine versus another analgesic drug in adult patients were evaluated., Methods: A systemized search of randomized controlled trials studying meperidine for acute postoperative or labor pain in the adult patient population from PubMed, Medline, and EMBASE was performed. Included studies reported on different routes of meperidine administration including intramuscular, intravenous, and patient-controlled analgesia in various surgical procedures such as abdominal surgery, Cesarean section, gynecological surgery, orthopedic surgery, cardiothoracic surgery, as well as for labor analgesia. Meperidine's analgesic efficacy and safety profile were compared to other opioids (morphine, tramadol, fentanyl, buprenorphine, nalbuphine, and pentazocine), nonsteroidal anti-inflammatory drugs (ketorolac, diclofenac, and indomethacin), dipyrone, ketamine, and bupivacaine., Results: A total of 62 randomized controlled trials published between 1972 and 2018 were reviewed. Meperidine had a similar or inferior analgesic efficacy compared to other analgesics for acute postoperative or labor pain. Meperidine was associated with more sedation and respiratory depression., Limitations: The sample sizes of many clinical studies were small, and therefore probably insufficiently powered to detect differences in uncommon side effects, such as central nervous system toxicity. In addition, some of the included clinical studies were old., Conclusion: Considering the availability of other effective analgesics with potentially fewer side effects, the use of meperidine for acute postoperative or labor pain should not be recommended., Key Words: Acute postoperative pain, adverse effects, labor analgesia, meperidine, pethidine.

Background and Aims: The administration of intravenous conscious sedation to patients undergoing GI endoscopy carries a risk of cardiopulmonary adverse events. Our study aim was to create a score that stratifies the risk of occurrence of either high-dose conscious sedation requirements or a failed procedure., Methods: Patients receiving endoscopy via endoscopist-directed conscious sedation were included. The primary outcome was occurrence of sedation failure, which was defined as one of the following: (1) high-dose sedation, (2) the need for benzodiazepine/narcotic reversal agents, (3) nurse-documented poor patient tolerance to the procedure, or (4) aborted procedure. High-dose sedation was defined as >10 mg of midazolam and/or >200 μg of fentanyl or the meperidine equivalent. Patients with sedation failure (n = 488) were matched to controls (n = 976) without a sedation failure by endoscopist and endoscopy date., Results: Significant associations with sedation failure were identified for age, sex, nonclonazepam benzodiazepine use, opioid use, and procedure type (EGD, colonoscopy, or both). Based on these 5 variables, we created the high conscious sedation requirements (HCSR) score, which predicted the risk of sedation failure with an area under the curve of 0.70. Compared with the patients with a risk score of 0, risk of a sedation failure was highest for patients with a score ≥3.5 (odds ratio, 17.31; P = 2 × 10 -14 ). Estimated area under the curve of the HCSR score was 0.68 (95% confidence interval, 0.63-0.72) in a validation series of 250 cases and 250 controls., Conclusions: The HCSR risk score, based on 5 key patient and procedure characteristics, can function as a useful tool for physicians when discussing sedation options with patients before endoscopy., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: To explore women's experiences of remifentanil or pethidine for labour pain and infant feeding behaviours at 6weeks post partum., Design: Qualitative postnatal sub-study to the randomised controlled trial of remifentanil intravenous patient controlled analgesia (PCA) versus intramuscular pethidine for pain relief in labour (RESPITE). Semistructured telephone interviews were conducted at 6 weeks post partum, and thematic analysis was undertaken., Setting: Women recruited to the RESPITE trial from seven UK hospitals., Participants: Eighty women consented and 49 (30 remifentanil group and 19 pethidine group) completed the interview., Results: Eight themes emerged which encompassed women's antenatal plans for pain management ( Birth Expectations ) through to their future preferences for pain relief ( Reflections for Future Choices ). Many women who used remifentanil felt it provided effective pain relief ( Effectiveness of Pain Relief ), whereas women in the pethidine group expressed more mixed views. Both groups described side effects, with women using pethidine frequently reporting nausea ( Negative Physiological Responses ) and women using remifentanil describing more cognitive effects ( Cognitive Effects ). Some women who used remifentanil reported restricted movements due to technical aspects of drug administration and fear of analgesia running out ( Issues with Drug Administration ). Women described how remifentanil enabled them to maintain their ability to stay focused during the birth ( Enabling a Sense of Control ). There was little difference in reported breastfeeding initiation and continuation between pethidine and remifentanil groups ( Impact on Infant Behaviour and Breastfeeding )., Conclusions: Qualitative insights from a follow-up study to a trial which explored experiences of intravenous remifentanil PCA with intramuscular pethidine injection found that remifentanil appeared to provide effective pain relief while allowing women to remain alert and focused during labour, although as with pethidine, some side effects were noted. Overall, there was little difference in reported breastfeeding initiation and duration between the two groups., Trial Registration Number: ISRCTN29654603., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2018 Japan Society of Obstetrics and Gynecology.)

Objective To evaluate the effect of parecoxib on preventing postoperative shivering. Methods Main outcomes were the relative risk (odds ratio, OR) and 95% confidence interval (CI) relative to the incidence of shivering. Results Fourteen trials with 1,175 patients were analyzed. The pooled evidence suggested that parecoxib sodium, given before anesthesia or postoperatively (only 4 cases), had the potential to prevent postoperative shivering (OR = 0.21, 95% CI, 0.16, 0.29). Compared with the placebo, parecoxib sodium significantly lowered the incidence of postoperative shivering as follows: mild shivering [OR = 0.51, 95% CI (0.35, 0.74)]; moderate shivering [OR = 0.28, 95% CI (0.18, 0.45)]; severe shivering [OR = 0.18, 95% CI (0.10, 0.33)]. Compared with placebo, there was no significant association of parecoxib sodium with restlessness [OR = 0.95, 95% CI (0.59, 1.52)] or nausea/vomiting [OR = 0.24, 95% CI (0.09, 0.66)]. In addition, pethidine rescue was used significantly more often in the control group than in the parecoxib sodium group [OR = 0.22, 95% CI (0.09, 0.53)]. Conclusions Parecoxib sodium may be an effective strategy for preventing postoperative shivering.

Purpose  To verify if pethidine is safe for the conceptus when used during labor. Methods  Systematic review in the Capes Periodicals/PubMed and MEDLINE/Virtual Health Library (BVS, in the Portuguese acronym) databases. Results  A total of 17 studies published from January 1st, 2000, to September 2nd, 2016, with a total of 1,688 participants involved were included in the present review. There was no record of conceptus vitality decrease associated with low doses of pethidine being administered to mothers during labor. Conclusions  Intramuscular (IM) or intravenous (IV) pethidine at low doses, of up to 50 mg, is safe to administer during labor., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Rationale: Several opioid analgesics have been related to the prolongation of cardiac repolarization, a condition which can be fatal. In order to establish a correct estimation of the risk/benefit balance of therapeutic doses of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene, it was necessary to develop an analytical method to determinate plasma concentrations of these opioids., Methods: Here we describe a method which incorporates strong alkaline treatment to obtain norpropoxyphene amide followed by a one-elution step solid-phase extraction, and without further derivatization. Separation and quantification were achieved by gas chromatography/electron ionization mass spectrometry (GC/EI-MS) in selected-ion monitoring mode. Quantification was performed with 500 μL of plasma by the addition of deuterated analogues as internal standards., Results: The proposed method has been validated in the linearity range of 25-1000 ng/mL for all the analytes, with correlation coefficients higher than 0.990. The lower limit of quantification was 25 ng/mL. The intra- and inter-day precision, calculated in terms of relative standard deviation, were 2.0-12.0% and 6.0-15.0%, respectively. The accuracy, in terms of relative error, was within a ± 10% interval. The absolute recovery and extraction efficiency ranged from 81.0 to 111.0% and 81.0 to 105.0%, respectively., Conclusions: A GC/MS method for the rapid and simultaneous determination of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene in human plasma was developed, optimized and validated. This procedure was shown to be sensitive and specific using small specimen amounts, suitable for application in routine analysis for forensic purposes and therapeutic monitoring. To our knowledge, this is the first full validation of the simultaneous determination of these opioids and their metabolites in plasma samples., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: The risks of minor adverse events (MAEs) such as abdominal pain and bloating after colon polypectomy (CP) are less clearly documented than major adverse events. However, these complications may cause significant discomfort during the performance of normal activities. We aimed to estimate the incidence of MAE, associated risk factors, and healthcare resource utilization after CP., Methods: Patients who underwent CP were prospectively enrolled in this study. Trained nurses contacted patients by telephone at 7 and 30 days after the CP and administered a standardized questionnaire to obtain information regarding the development of complications. MAEs were defined as any discomfort the patient experienced after CP excluding major bleeding, perforation, and post-polypectomy coagulation syndrome., Results: Among a total of 2716 patients, 2253 patients completed the interview at 7 and 30 days. MAEs occurred in 263 patients (11.7%) before day 7, among which the most common were abdominal pain (4.5%), rectal bleeding (2.8%), and bloating (2.6%). Cumulative incidence of MAEs was in 267 patients (11.9%) at 30 days. On multivariate analysis, female sex (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.58-3.18) and use of meperidine (OR 1.54, 95% CI 1.04-2.27) were risk factors for the occurrence of MAEs. Two patients (0.7%) required hospital admission, 117 patients (43.8%) were treated medically in the outpatient clinic, and the majority at 148 patients (55.4%) experienced resolution of symptoms after observation., Conclusions: The post-CP MAE rate was as low as 11.8%. The MAEs occurred mainly in the first seven postoperative days and resulted in little use of healthcare resources.

Objective: There is substantial evidence that the use of opioids increases the risk of adverse outcomes such as delirium, but whether this risk differs between the various opioids remains controversial. In this systematic review, we evaluate and discuss possible differences in the risk of delirium from the use of various types of opioids in older patients., Methods: We performed a search in MEDLINE by combining search terms on delirium and opioids. A specific search filter for use in geriatric medicine was used. Quality was scored according to the quality assessment for cohort studies of the Dutch Cochrane Institute., Results: Six studies were included, all performed in surgical departments and all observational. No study was rated high quality, one was rated moderate quality, and five were rated low quality. Information about dose, route, and timing of administration of the opioid was frequently missing. Pain and other important risk factors of delirium were often not taken into account. Use of tramadol or meperidine was associated with an increased risk of delirium, whereas the use of morphine, fentanyl, oxycodone, and codeine were not, when compared with no opioid. Meperidine was also associated with an increased risk of delirium compared with other opioids, whereas tramadol was not. The risk of delirium appeared to be lower with hydromorphone or fentanyl, compared with other opioids. Numbers used for comparisons were small., Conclusion: Some data suggest that meperidine may lead to a higher perioperative risk for delirium; however, high-quality studies that compare different opioids are lacking. Further comparative research is needed.

The effect of pethidine as patient-controlled epidural analgesia (PCEA) on specific biochemical components in breast milk in relation to the timing of secretory activation is not well investigated. The aim of this study was to compare biochemical timing of secretory activation between women who had a vaginal (V) or Caesarean birth with pethidine-PCEA (CBP). Several milk samples were collected daily from 36 mothers (17 V, 19 CBP) for the first 265 h post-partum. Protein and lactose concentrations and Na + and K + ion levels were measured. Samples were assigned to three time periods: 0-72, >72-165 and >165-265 h post-partum for statistical analyses. Data were analyzed using linear mixed effect models. In the first 72 h post-partum, the mean difference in lactose concentration was 5 gL -1 higher in group V (P < 0.05). From >72-165 h post-partum, protein and Na + concentrations were lower in group V (P = 0.05, P = 0.02), and K + levels were higher in group V (P < 0.001). From >165-265 h post-partum, there were no significant differences between the groups. Biochemically, secretory activation had occurred by 72 h post-partum in both groups. There were greater variations in measured biochemical components observed within group CBP initially. However, by 165 h post-partum, there were no differences in the biochemical components between the groups. This suggests that effects of pethidine-PCEA are diminished by 72 h post-partum and undetected by 165 h., (© 2016 John Wiley & Sons Ltd.)

A prolongation of the QTc-interval has been described for several opioids, including pethidine (meperidine)., Objective: To evaluate in the clinical setting the frequency and risk factors associated with the QT-interval prolongation induced by meperidine., Research Design and Methods: We recruited patients requiring meperidine administration and recorded their medical history and comorbidities predisposing to QT-interval prolongation. Ionograms and electrocardiograms (ECGs) were performed at baseline and during treatment; QT was corrected using the Bazzet, Fridericia, Framinghan, and Hogdes formulas. We measured meperidine and normeperidine by gas chromatography. Values are expressed as mean ± SD (range)., Results: 58 patients were studied (43.1% males). All patients received meperidine at a dose of 304 ± 133 (120 - 480) mg/day. Meperidine and normeperidine concentrations were 369 ± 60 (265 - 519) and 49 ± 17 (15 - 78) ng/mL, respectively. Intratreatment control found QTcB 370 ± 30 (305 - 433), QTcFri 353 ± 35 (281 - 429), QTcFra 360 ± 30 (299 - 429), QTcH 359 ± 27 (304 - 427), ΔQTcB +9 ± 42 (-90 to +136), ΔQTcFri +4 ± 45 (-86 to +137), ΔQTcFra +5 ± 40 (-77 to +129), and ΔQTcH +7 ± 40 (-76 to +129) ms. Meperidine concentration correlated with QTc-interval (R > 0.36) and ΔQTc (R > 0.69) but the correlation was even better for normeperidine concentration, QTc (R > 0.52) and ΔQTc (R > 0.81). Depending on the QTc correction formula used, 13 - 15 patients (22.41 - 25.86%) presented ΔQTc values > 30 ms, and 7 - 8 patients (12.07- 13.79%) showed ΔQTc values > 60 ms. Renal failure was associated with risk for ΔQTc > 30 ms of 3.74 (IC95% 1.73 - 8.10) and for ΔQTc > 60 ms of 4.27 (IC 95% 1.26 - 14.48). No patient developed arrhythmias during the study., Conclusions: Meperidine treatment causes ECG changes (QTc-interval prolongation) in high correlation with normeperidine plasma concentration. Renal failure increases the risk.
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Aim: To determine factors associated with intrapartum fever and to examine associated maternal and neonatal outcomes., Methods: Retrospective study of patients between 360/7 and 420/7 gestational weeks who entered spontaneous or induced active labor and developed temperature ≥38°C; a similar group that did not develop fever were controls. Univariate and multivariate analyses were performed with p < 0.05 as significant., Results: Fifty-four febrile patients and 306 nonfebrile controls met inclusion criteria. Nulligravidity (45.8 vs. 77.8%, p < 0.001), length of first stage ≥720 min (OR 3.59, 95% CI 1.97-6.55, p < 0.001), length of second stage ≥120 min (OR 4.76, 95% CI 2.29-9.89, p < 0.001), membrane rupture ≥240 min (46.4 vs. 79.6%, p < 0.001), increasing number of vaginal exams (4 vs. 6, p < 0.001), oxytocin (44.8 vs. 63.0%, p = 0.014), and meperidine (14.7 vs. 35.2%, p < 0.001) were all associated with intrapartum fever. Associated morbidity included cesarean delivery (22.5 vs. 44.4%, p = 0.001), Apgar score <7 at 5 min (0.7 vs. 5.6%, p = 0.011), and neonatal intensive care unit admission (9.5 vs. 51.9%, p < 0.001)., Conclusion: We have identified several noninfectious factors that are associated with intrapartum fever. Modification of risk factors may improve both maternal and neonatal outcomes., (© 2017 S. Karger AG, Basel.)

Background: The commonest opioid used for pain relief in labour is pethidine (meperidine); however, its effectiveness has long been challenged and the drug has known side effects including maternal sedation, nausea and potential transfer across the placenta to the foetus. Over a third of women receiving pethidine require an epidural due to inadequate pain relief. Epidural analgesia increases the risk of an instrumental vaginal delivery and its associated effects. Therefore, there is a clear need for a safe, effective, alternative analgesic to pethidine. Evidence suggests that remifentanil patient-controlled analgesia (PCA) reduces epidural conversion rates compared to pethidine; however, no trial has yet investigated this as a primary endpoint. We are, therefore, comparing pethidine intramuscular injection to remifentanil PCA in a randomised controlled trial., Methods/design: Women in established labour, requesting systemic opioid pain relief, will be randomised to either intravenously administered remifentanil PCA (intervention) or pethidine intramuscular injection (control) in an unblinded, 1:1 individual randomised trial. Following informed consent, 400 women in established labour, who request systemic opioid pain relief, from NHS Trusts across England will undergo a minimised randomisation by a computer or automated telephone system to either pethidine or remifentanil. In order to balance the groups this minimisation is based on four parameters; parity (nulliparous versus multiparous), maternal age (<20, 20 < 30, 30 < 40, 40+ years), ethnicity (South Asian (Pakistani/Indian/Bangladeshi) versus Other) and induced versus spontaneous labour. The effectiveness of pain relief provided by each technique will be recorded every 30 min after time zero, until epidural placement, delivery or transfer to theatre, quantified by Visual Analogue Scale. Incidence of maternal side effects including sedation, delivery mode, foetal distress requiring delivery, neonatal status at delivery and rate of initiation of breastfeeding within the first hour of birth will also be recorded. Maternal satisfaction with her childbirth experience will be determined by a postpartum questionnaire prior to discharge from the delivery ward., Discussion: The RESPITE trial's primary outcome is the proportion of women who have an epidural placed for pain relief in labour in each arm., Trial Registration: Current Controlled Trials registration number: ISRCTN29654603 . Registered on 23 July 2013.

Purpose: To compare the efficacy and remifentanil with midazolam for conscious sedation during endoscopic retrograde cholangiopancreatography (ERCP)., Methods: 99 patients scheduled for ERCP were randomly allocated to be treated with either meperidine/midazolam (group C, n = 33), remifentanil (group R, n = 33), or the remifentanil plus midazolam (group RM, n = 33). In group C, intermittent intravenous meperidine and midazolam were administrated during the procedure; in group R, remifentanil was infused continuously at a rate of 0.2 μg/kg/min for 5 minutes preoperatively, and decreased to 0.15 μg/kg/min when the procedure began; in group RM, midazolam 0.02 mg/kg was administered preoperatively, and remifentanil was administered in the same manner as in group R. Blood pressure, heart rate, respiratory rate, O 2 -saturation, and bispectral index (BIS) of the patients were recorded. The modified Aldrete scores, operator satisfaction scores, and side effects of the patients were noted as were the operative duration and anesthesia duration., Results: The blood pressure of the patients were significantly increased in group R and group C compared to baseline, and no significant changes were noted in group RM. Group RM experienced the least variability in heart rate. BIS was decreased the most in groups C and RM. Hypoxemia was observed most frequently in group RM. Nausea and pain was highest in group C. Amnesia was most often reported in groups C and RM. Operator satisfaction and modified Aldrete of the patients was increased in group R., Conclusion: Both continuous remifentanil infusion alone and remifentanil plus midazolam provided satisfactory analgesia when used for sedation for ERCP, however, continuous remifentanil infusion alone resulted in increased operator satisfaction scores and expedited recoveryroom discharge.

Background: Meperidine (pethidine) is an opioid analgesic that offers little advantage relative to other opioids and several disadvantages including limited potency, short duration of action, and the production of a neurotoxic metabolite (normeperidine) with a long half-life. Older adults are more sensitive to meperidine's side effects and may have diminished renal function which leads to the accumulation of normeperidine. The Institute for Safe Medication Practices has suggested avoiding meperidine in older adults, limiting its dose (≤600 mg/day) and duration of use (≤48 h). The objective of this study was to determine the level of meperidine use in older adults and assess the dosage and duration of meperidine with reference to these safety recommendations., Methods: A longitudinal study using administrative healthcare data was conducted to examine meperidine utilization and levels of high dose and extended duration prescribing among persons ≥65 years of age between April 1, 2001, and March 31, 2014 in Manitoba, Canada. The number of meperidine prescriptions, users, duration of treatment, defined daily doses (DDD) dispensed and number of prescribers were determined over the study period., Results: In the Manitoba older adult population there was a marked decline in meperidine users and prescriptions from 2001 to 2014. There was an average use of 26.4 (95 % CI 24.0-28.8) DDDs of meperidine per user per year. While only 3.7 % of the prescriptions exceeded the 600 mg maximum daily dose, 96.7 % of prescriptions exceeded the recommended 2 days of therapy. For the remaining users of meperidine, the amount of meperidine used per person rose from 18.98 to 56.14 DDDs/user/year over the study period. The number of prescribers of meperidine declined throughout the study, but low DDD prescribers declined more quickly than high DDD prescribers., Conclusions: While meperidine use has declined, the remaining use appears to be decreasing in safety, with more meperidine prescribed per user. This seems to be driven by the continued prescribing by a small number of high DDD prescribers. Targeted educational initiatives directed at this small group of prescribers may be helpful. Alternatively removing meperidine from medication insurance schemes may provide additional incentive to avoid meperidine in older adults.

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.

Meperidine is used for pain control and treatment of shivering. Concerns about neurotoxicity, particularly seizures, have led to efforts limiting meperidine use. We reviewed the body of evidence linking meperidine to seizures. We searched PubMed for the terms meperidine, normeperidine, pethidine, and norpethidine; each was combined with the terms: seizure, epilepsy, epileptogenic, toxicity, overdose, seizure threshold, and convulsion. Articles were assessed for relevance. Semiologies were reviewed to ascertain seizure likelihood. Our search yielded 351 articles, of which 66 were relevant. Of these, 33 had primary clinical data on meperidine-associated seizures, comprising 50 patients. Twenty events were deemed likely to be seizures, 26 indeterminate, and 4 unlikely. Most studies were case reports. Confounding comorbidities were frequent. The evidence base for meperidine-associated seizures in man is scant. Seizure risk associated with meperidine appears to be overstated. The utility of meperidine should continue to be explored, especially for therapeutic hypothermia.

The study investigated patient discharge parameters and postdischarge adverse events after discharge among children who received oral conscious sedation for dental treatment. This prospective study involved 51 patients needing dental treatment under oral conscious sedation. Each patient received one of various regimens involving combinations of a narcotic (ie, morphine or meperidine), a sedative-hypnotic (ie, chloral hydrate), a benzodiazepine (ie, midazolam or diazepam), and/or an antihistamine (ie, hydroxyzine HCl). Nitrous oxide and local anesthesia were used in conjunction with all regimens. After written informed consent was obtained, each guardian was contacted by phone with specific questions in regard to adverse events following the dental appointment. Out of 51 sedation visits, 46 were utilized for analysis including 23 boys and 23 girls ranging from 2 years 2 months to 10 years old (mean 5.8 years). 60.1% of patients slept in the car on the way home, while 21.4% of that group was difficult to awaken upon reaching home. At home, 76.1% of patients slept; furthermore, 85.7% of patients who napped following the dental visit slept longer than usual. After the appointment, 19.6% exhibited nausea, 10.1% vomited, and 7.0% experienced a fever. A return to normal behavior was reported as follows: 17.4% in <2 hours, 39.1% in 2-6 hours, 28.3% in 6-10 hours, and 15.2% in >10 hours. Postdischarge excessive somnolence, nausea, and emesis were frequent complications. The time to normality ranged until the following morning demonstrating the importance of careful postdischarge adult supervision.

Saddle spinal is a reliable method for control of pain during labor. This method has rapid onset and causes complete sensory block without significant influence on motor neurons.Our goal was to compare the analgesic efficacy and side effects of pethidine and sufentanil via saddle spinal administration during labor.600 parturients requesting analgesia were randomly divided into 2 groups. First group was composed of 300 patients received 0.4 mg/kg pethidine and the second group was composed of 300 patients received 0.1 μg/kg sufentanil. Then, analgesia according to Visual Analogue Scale (VAS), itching, nausea, apnea and urinary retention were examined between 2 groups.VAS=3 was noted in both groups. Equal rate of apnea was seen in both groups. Patients received pethidine showed significantly a higher rate of nausea compared with sufentanil group (P<0.0001). Pruritus was significantly higher in patients received sufantanil (P<0.0001).Our findings suggest that saddle spinal by pethidine or sufentanil causes a considerable analgesia for labor. Proper management of the untoward effects of this method may introduce it as a safe and low-cost method for painless labor., (© Georg Thieme Verlag KG Stuttgart · New York.)

Labour is thought to be one of the most intense and painful experiences in a woman's life. Numerous studies using a Visual Analogue Scale invariably demonstrate that 20% of women in labour describe the pain as "unbearable" and 60% describe the pain as "very intense". Since the mid-1980s, continuous epidural analgesia during labour has been considered the gold standard of labour anaesthesia and is currently the most frequently used. There are situations in which this type of analgesia could not be used. An alternative pain management is administration of parenteral opioids, the most frequently used of which is pethidine. Its use is associated with adverse effects and unsatisfactory analgesia. Since the second half of the 20th century, a new generation of opioids, such as fentanyl or remifentanil, has been used. Despite their much better pharmacokinetic and pharmacodynamic parameters, obstetricians, midwives and neonatologists are most aware of pethidine, probably because it has been used for the longest period of time, despite its disadvantages and the risk that its use entails. The drug that is nearest to ideal is remifentanil. The countries in which it is widely used as an alternative type of labour anaesthesia have developed practice standards or guidelines practice. Guidelines and alternatives to pethidine protocols for effective labour analgesia in Poland might be merited.

Purpose: To investigate postdischarge events occurring in children during the 24 hours following sedation for dentistry., Methods: A convenience sample of 50 children undergoing sedation with combinations of midazolam, hydroxyzine, and meperidine were included. Parents received a standardized timesheet to record child's behavior, alertness, activity level, motor imbalance, emesis, and soft tissue trauma every two hours from discharge until bedtime. A questionnaire asked about transportation, supervision, and return to normal activity. Families were telephoned after 24 hours to collect the information., Results: Sixty-six percent of children slept in the car; of these, 30 percent were supervised by only the driver, and 12 percent were difficult to awaken. Agitation was observed in 22 percent, restlessness in 10 percent, withdrawn behavior in 16 percent, and soft tissue trauma in 18 percent. Motor imbalance was significantly associated with midazolam (P=.002), as was restlessness (P=.004). Eighty-two percent slept between discharge and bedtime, with 16 percent sleeping for greater than four hours. Return to normal activity was greater than four hours in 36 percent, and was inversely correlated with age (P=.02)., Conclusions: Postdischarge sleepiness, drug-specific motor imbalance, sleep during transit, and recovery times greater than four hours were common and warrant vigilant adult supervision.

Background: Several surveys over the past few years have demonstrated that postoperative pain in children is not treated appropriately. One pharmacological treatment option in a multimodal approach for postoperative pain treatment is the systemic administration of opioids. However, opioids are rarely used for postoperative pain treatment in children due to fear of adverse events. One long-standing opioid for systemic use is nalbuphine, a kappa-receptor agonist and µ-receptor antagonist. The efficacy of nalbuphine is believed to be similar to morphine. Increased dosing might result in a ceiling effect, and thus less analgesia than expected. In addition, there might be a lower risk for opioid-induced side effects (nausea, vomiting) and severe adverse events (respiratory depression) due to the antagonistic effect of the µ-receptor. Nalbuphine may be an useful opioid for postoperative use in children, but exact efficacy (e.g. compared to other commonly used opioids) has not been determined yet., Objectives: To assess the efficacy and adverse events of nalbuphine for acute postoperative pain treatment in children undergoing surgery., Search Methods: We systematically searched the following databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7), MEDLINE via Pubmed (January 1966 to July 2013) and EMBASE via Ovid (January 1947 to July 2013). We did not impose any restrictions regarding language or publication date. We checked all reference lists of retrieved articles for additional references., Selection Criteria: All randomised controlled trials (RCTs) investigating nalbuphine compared with placebo or other opioids were included., Data Collection and Analysis: Two review authors independently scanned the retrieved articles and made a decision regarding inclusion or exclusion of studies for this review. The same authors also performed the data extraction and the assessment of risk of bias., Main Results: Ten RCTs including 658 patients were finally included in this systematic review. Five trials compared nalbuphine with placebo. Data from one out of five studies for the outcome moderate/severe pain following nalbuphine compared to placebo gave a risk ratio (RR) 1 hour postoperatively (postop) of 0.1 (95% confidence interval (CI) 0.01 to 0.71; low quality evidence) and a RR 2 hours postop of 0.14 (95% CI 0.02 to 1.06; low quality evidence). The estimated RR based on data from a single study indicated that nalbuphine reduced the requirement for analgesia two hours postop (RR 0.47; 95% CI 0.27 to 0.84; low quality evidence). Two included trials compared nalbuphine with morphine and showed a nonsignificant lower or comparable RR for moderate/severe pain at 1 hour postop (RR 0.84; 95% CI 0.12 to 5.74; low quality evidence), and 2 hours postop (RR 1.09; 95% CI 0.59 to 2.01; low quality evidence) for nalbuphine versus morphine. Four trials compared nalbuphine with tramadol for postoperative pain; data from one trial (per outcome) revealed a lower but nonsignificant RR for the need of additional rescue analgesics in children receiving nalbuphine (RR 2 hours postop 0.75; 95% CI 0.39 to 1.43; low quality evidence) (RR 12 hours postop 0.33; 95% CI 0.04 to 2.77; low quality evidence). One out of three trials comparing nalbuphine with pethidine demonstrated that the RR was not significantly lower following nalbuphine administration compared to pethidine (RR 2 hours postop 1.07; 95% CI 0.52 to 2.23; low quality evidence) (RR 24 hours postop 1.13; 95% CI 0.52 to 2.44; very low quality evidence). The most common adverse event was postoperative nausea and vomiting (PONV). Only one included trial reported that the RR for PONV in the postoperative care unit (PACU) was not significantly higher following nalbuphine compared to placebo (RR 1.00; 95% CI 0.16 to 6.42; low quality evidence) nor to morphine (RR 1.33; 95% CI 0.64 to 2.77; low quality evidence)., Authors' Conclusions: Because the overall quality of available evidence was low, this systematic review could not definitively show that the analgesic efficacy of nalbuphine is superior compared to placebo. Furthermore, due to the lack of significant results the comparison with other common opioids is also unclear. The same holds true for the evidence focusing on adverse events following nalbuphine compared to placebo or other opioid administration. The evidence is limited, because studies did not report conclusively all important postoperative pain outcomes (e.g. number of patients with the need for rescue analgesia, postoperative pain scores). Thus, a quantitative analysis was not possible for many major aspects (e.g. rescue analgesia, pain scores) and heterogeneity could not be further explored.

Background and Objectives: A review of all the adjuncts for intravenous regional anaesthesia concluded that there is good evidence to recommend NonSteroidal Anti-Inflammatory agents and pethidine in the dose of 30mg dose as adjuncts to intravenous regional anaesthesia. But there are no studies to compare pethidine of 30mg dose to any of the NonSteroidal Anti-Inflammatory agents., Methods: In a prospective, randomized, double blind study, 45 patients were given intravenous regional anaesthesia with either lignocaine alone or lignocaine with pethidine 30mg or lignocaine with ketprofen 100mg. Fentanyl was used as rescue analgesic during surgery. For the first 6h of postoperative period analgesia was provided by fentanyl injection and between 6 and 24h analgesia was provided by diclofenac tablets. Visual analogue scores for pain and consumption of fentanyl and diclofenac were compared., Results: The block was inadequate for one case each in lignocaine group and pethidine group, so general anaesthesia was provided. Time for the first dose of fentanyl required for postoperative analgesia was significantly more in pethidine and ketoprofen groups compared to lignocaine group (156.7±148.8 and 153.0±106.0 vs. 52.1±52.4min respectively). Total fentanyl consumption in first 6h of postoperative period was less in pethidine and ketoprofen groups compared to lignocaine group (37.5±29.0mcg, 38.3±20.8mcg vs. 64.2±27.2mcg respectively). Consumption of diclofenac tablets was 2.4±0.7, 2.5±0.5 and 2.0±0.7 in the control, pethidine and ketoprofen group respectively, which was statistically not significant. Side effects were not significantly different between the groups., Conclusion: Both pethidine and ketoprofen are equally effective in providing postoperative analgesia up to 6h, without significant difference in the side effects and none of the adjuncts provide significant analgesia after 6h., (Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

In this study, the analgesic effects of dexketoprofen trometamol and meperidine hydrochloride were compared in patients diagnosed with renal colic. This study was a prospective, randomized, double-blind study. Fifty-two patients, between the ages of 18 and 70 years who were diagnosed with renal colic, were enrolled in the study after obtaining ethics committee approval. Before drug injection, dexketoprofen trometamol and meperidine hydrochloride were placed in closed envelopes, and the patients were randomly given a single dose of intravenous infusion for 20 minutes. Severity of pain and symptoms was evaluated with the numerical rating scale and renal colic symptom score for each patient immediately before administration of drugs and 30 minutes after the end of the application. At the same time, systolic arterial blood pressure, diastolic arterial pressure, respiratory rate, heart rate, nausea, vomiting, and reactions due to drug administration were recorded before and after drug administration. In statistical methods, t test, analysis of variance, and repeated measure analysis were used for the analysis of normally distributed continuous variables and the Mann-Whitney U, Kruskal-Wallis and Friedman tests were used for analysis of not-normally distributed continuous variables. In the analysis of discrete variables, the χ test was used. In both groups, a significant decrease was found in numerical rating scale values measured 30 minutes after drug administration, but the decline in dexketoprofen trometamol group (P = 0.02) was found to be more. Although a significant decrease was found in the renal colic symptom score (P < 0.001) values measured after drug administration in the dexketoprofen trometamol group, no significant decrease was found in the meperidine HCl (P = 0.058) group. After drug administration, a statistically significant decrease was found in the systolic arterial blood pressure, heart rate, and respiratory rate in both groups. Also, a statistically significant decrease was found in the diastolic arterial pressure in the meperidine group. But these changes in vital findings were not serious enough to disrupt patients' clinical status. With this study, we concluded that dexketoprofen trometamol, from the nonsteroidal anti-inflammatory drug group, can be within the primary treatment options for renal colic because of better analgesic efficacy, being well tolerated by patients compared with meperidine hydrochloride.

Background: Induction of therapeutic hypothermia is often complicated by shivering. Nefopam, a nonsedative benzoxazocine analgesic, reduces the shivering threshold (triggering core temperature) with minimal side effects. Consequently, nefopam is an attractive drug for inducing therapeutic hypothermia. However, nefopam alone is insufficient and thus needs to be combined with another drug. Meperidine also reduces the shivering threshold. We therefore determined whether the combination of nefopam and meperidine is additive, infra-additive, or synergistic on the shivering threshold., Methods: Ten volunteers were each studied on 4 randomly assigned days. In random order, they were given the following treatments: (1) control, no drug; (2) nefopam to a target concentration of 0.1 μg/mL; (3) meperidine to a target concentration of 0.1 μg/mL; and (4) both nefopam and meperidine at target concentrations of 0.1 μg/mL each. Lactated Ringer's solution at 4°C was infused to decrease core temperature while mean skin temperature was kept near 30.5°C. The core temperature that increased oxygen consumption >25% defined the shivering threshold., Results: Nefopam reduced the shivering thresholds by 0.7°C ± 0.3°C compared with no drug. Meperidine reduced the shivering thresholds by 0.4°C ± 0.3°C compared with no drug. When combined, the shivering threshold decreased by only 0.6°C ± 0.4°C, which was about half what would have been expected based on the individual effects of each drug (P < 0.001). The effect of combined nefopam and meperidine on the shivering threshold was thus infra-additive., Conclusions: The combination of nefopam and meperidine should be avoided for induction of therapeutic hypothermia. Better options would be combinations of drugs that are at least additive or even synergistic.

Purpose: This study compared the incidence of adverse sedation-related events occurring with two different multiagent oral sedation regimens in pediatric dental patients., Methods: Forty healthy patients (three to six years old), received either a sedation regimen of chloral hydrate, meperidine, and hydroxyzine with nitrous oxide (CH/M/H/N2O; N=19) or a regimen of midazolam, meperidine, and hydroxyzine with nitrous oxide (MZ/M/H/N2O; N=21). The two treating dentists answered a questionnaire regarding the perioperative period. Parents received two phone interviews at eight and 24 hours after sedation. Statistical analysis included chi-square, Pearson correlation coefficient, and t-test (P<.05)., Results: Children sedated with MZ/M/H/N2O showed a significant increase in hyperactivity during dental treatment, slurring/difficulty speaking, and difficulty walking postoperatively within eight hours after discharge. Children sedated with CH/M/H/N2O showed a significant increase in frequency of sleeping, talking less than normal after arriving home, and an increased need for postoperative pain medication., Conclusions: Different oral sedation regimens produce different adverse sedation-related events. The provider of pediatric oral sedation should select a sedative regimen with an adverse sedation-related profile that he/she believes is optimal for the patient being treated. Parents should be counseled as to possible postsedation effects anticipated based on the sedative regimen administered.

Background and Study Aim: The combination of midazolam and opioid has been widely used as a standard sedative regimen for endoscopic retrograde cholangiopancreatography (ERCP). Following recent evidence that dexmedetomidine may exert a synergistic effect in combination with midazolam, this study compared the sedative effect and adverse events of midazolam - meperidine - dexmedetomidine (MMD) and midazolam - meperidine during ERCP., Patients and Methods: A total of 110 patients who were scheduled for ERCP were prospectively enrolled and randomly assigned, in a double-blind manner, to the MMD (n = 53) or midazolam - meperidine (n = 57) groups. Each patient received an intravenous (IV) bolus dose of midazolam and meperidine (0.06 mg/kg and 50 mg, 30 % reduction and 25 mg for patients aged ≥ 65 years, respectively). To this dose, a continuous IV infusion of dexmedetomidine (1 μg/kg/h; MMD group) or the same volume of normal saline (midazolam - meperidine group) was added. The sedation level (Ramsay Sedation Scale [RSS]) as well as hemodynamic and respiratory changes were assessed., Results: Adequate sedation (RSS ≥ 3) was maintained during ERCP in 75.5 % and 36.8 % of the MMD and midazolam - meperidine group, respectively (P < 0.001). RSS scores were significantly higher in the MMD group (P < 0.001). Intraoperative bispectral index scores were significantly lower in the MMD group (P < 0.001) than in the midazolam - meperidine group. Lower additional (P = 0.001) and total (P = 0.003) doses of midazolam were required in the MMD group. Patients in the MMD group showed lower pain scores (P < 0.001) and higher satisfaction scores (P < 0.001). Desaturation occurred more frequently in the midazolam - meperidine group (11 vs. 1; P = 0.003)., Conclusions: The addition of dexmedetomidine to the midazolam - meperidine regimen provided better sedative efficacy and a superior safety profile during ERCP compared with a midazolam - meperidine regimen.This trial was registered at ClinicalTrials.gov Identifier (NCT01404689)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Pethidine is an opioid that gains its popularity for the effective pain control through acting on the opioid-receptors. However, rapid pain relief sometimes brings about unfavourable side effects that largely limit its clinical utility. Common side effects include nausea, vomiting and hypotension. In patients with impaired renal and liver function, and those who need long-term pain control, pethidine may cause excitatory central nervous system (CNS) effects through its neurotoxic metabolite, norpethidine, resulting in irritability and seizure attack. On the contrary, though not clinically apparent, pethidine potentially causes inhibitory impacts on the CNS and impairs normal cerebellar and oculomotor function in the short term. In this case report, we highlight opioid's inhibitory side effects on the cerebellar structure that causes dysmetria, dysarthria, reduced smooth pursuit gain and decreased saccadic velocity.

Introduction: Recent guidelines recommend routine pulse oximetric monitoring during endoscopy, however, this has not been the common practice yet in the majority of the local endoscopic units., Aims: To draw attention to the importance of the routine use of pulse oximetric recording during endoscopy., Method: A prospective multicenter study was performed with the participation of 11 gastrointestinal endoscopic units. Data of pulse oximetric monitoring of 1249 endoscopic investigations were evaluated, of which 1183 were carried out with and 66 without sedation., Results: Oxygen saturation less than 90% was observed in 239 cases corresponding to 19.1% of all cases. It occurred most often during endoscopic retrograde cholangiopancreatography (31.2%) and proximal enteroscopy (20%). Procedure-related risk factors proved to be the long duration of the investigation, premedication with pethidine (31.3%), and combined sedoanalgesia with pethidine and midazolam (34.38%). The age over 60 years, obesity, consumption of hypnotics or sedatives, severe cardiopulmonary state, and risk factor scores III and IV of the American Society of Anestwere found as patient-related risk factors., Conclusion: To increase the safety of patients undergoing endoscopic investigation, pulse oximeter and oxygen supplementation should be the standard requirement in all of the endoscopic investigation rooms. Pulse oximetric monitoring is advised routinely during endoscopy with special regard to the risk factors of hypoxemia.

Unlabelled: BACKGROUND AND STUDY: Combined use of opiates and benzodiazepines often results in delayed discharge after colonoscopy., Aims: To compare sedation quality of two dosages of patient controlled analgesia remifentanil with one another and with that of a midazolam-meperidine association during colonoscopy., Methods: Ninety patients undergoing colonoscopy were randomly assigned to three groups. Group M received a meperidine bolus (0.7 mg/kg) and sham patient controlled analgesia. Group R1 received remifentanil 0.5 μg/kg and group R2 remifentanil 0.8 μg/kg together with a patient-controlled analgesia pump injecting further boluses (2-min lock-out). Technical difficulties of the examination, gastroenterologist's and patient's satisfaction with sedoanalgesia were evaluated after colonoscopy on a 100 mm Visual Analogue Scale. Patient's satisfaction was assessed 24 h later., Results: Group M had more adverse events (p = 0.044), required more rescue boluses (p = 0.0010), had lower Observer's Assessment of Alertness and Sedation Scale score at the end of the procedure (p = 0.0016) and longer discharge time (p = 0.0001). Groups R1 and R2 did not differ with respect to these variables. Patient's degree of pain and satisfaction with sedo-analgesia, endoscopist's technical difficulty and satisfaction were not different among groups., Conclusions: Remifentanil patient controlled analgesia is a safe approach to sedation for colonoscopy., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Analgesia and coping with labor pain can prevent suffering during childbirth. Nonpharmacologic methods help women manage labor pain. Strong evidence is available for the efficacy of continuous one-to-one support from a woman trained to provide nonmedical care during labor, immersion in warm water during first-stage labor, and sterile water injected intracutaneously or subcutaneously at locations near a woman's lumbosacral spine to reduce back-labor pain. Sterile water injections also reduce the incidence of cesarean deliveries. Nitrous oxide labor analgesia is not potent, but helps women relax, gives them a sense of control, and reduces and distracts their perception of pain. It is inexpensive; can be administered and discontinued safely, simply, and quickly; has no adverse effects on the normal physiology and progress of labor; and does not require intensive monitoring or co-interventions. Parenteral opioids provide mild-to-moderate labor pain relief, but cause side effects. Although observational studies have found associations between maternal use of opioids and neonatal complications, little higher level evidence is available except that meperidine is associated with low Apgar scores. Patient-controlled intravenous administration of remifentanil provides better analgesia and satisfaction than other opioids, but can cause severe side effects; continuous monitoring of arterial oxygen saturation, anesthesia supervision, one-to-one nursing, and availability of oxygen are recommended. The demand for inexpensive, simple, safe but effective labor pain management for women will undoubtedly increase in places that lack wide access to it now., (© 2012, Copyright the Author Journal compilation © 2012, Wiley Periodicals, Inc.)

Objective: To observe the effect of electroacupuncture on supplementary analgesia and improvement of adverse reactions induced by dolantin in oocyte retrieval, and to provide scientific and effective evidence for application of electroacupuncture in oocyte retrieval., Methods: One hundred and thirty-four patients undergoing in vitro fertilization and embryo transfer (IVF-ET) were randomly divied into an observation group and a a control group, 67 cases in each group. They were all received intramuscular injection of 50 mg dolantin at 30 mn before the operation, and then the observation group was treated with acupuncture at Baihui (GV 20), pain point (Extra, right), Sanyangluo (TE 8, right), Zusanli (ST 36, right) and ear uterus point (right ear). Pain point and Sanyangluo (TE 8) were received electroacupuncture stimulation after Deqi until the oocyte retrieval operation was finished, and the oocyte retrieval operation was performed in the control group after 30 min of injection of dolantin. The pain grade and score were observed and the adverse reactions during operation or 1 h and 2 h after the operation were recorded., Results: The excellent analgesia rate was 97.0% (65/ 67) in the observation group and 92.5% (62/67) in the control group, with significant difference in the analgesia effect (P < 0.05). The pain grade and pain score in the observation group were both superior to those in the control group (both P < 0.05). There were fewer cases with the adverse reactions i.e. vertigo, sweating, nausea in the observation group than that in the control group during operation or 1 h and 2 h after the operation (all P < 0.05)., Conclusion: In the oocyte retrieval operation, under the guidance of vaginal B ultrasound, electroacupuncture has a good intraoperative supplementary analgesia effect without intraoperative and postoperative adverse reactions induced by dolantin.

Objective: To evaluate the efficacy and adverse effects of an intravenous infusion of 1000 mg of paracetamol as compared with an intravenous injection of 50mg of pethidine hydrochloride for intrapartum analgesia., Methods: In a randomized prospective study at Ain Shams University, Cairo, Egypt, between April and August 2010, 102 low-risk primiparous women in active labor were allocated to received either paracetamol (n=52) or pethidine hydrochloride (n=50). The primary outcome was the efficacy of the drug to supply adequate analgesia as measured by a change in the visual analog scale (VAS) pain intensity score at various times after drug administration. The secondary outcomes included the need for additional rescue analgesia and the presence of adverse maternal or fetal events., Results: As recorded by the VAS score, there was significant pain reduction at 15 minutes, and at 1 and 2 hours in both groups (P<0.001). The reduction in pain was significantly greater in the pethidine group only at 15 minutes (P=0.004). None of the women in the paracetamol group had adverse effects, as compared with 64% of the women receiving pethidine., Conclusion: The effectiveness of intravenous paracetamol was comparable to that of intravenous pethidine, but paracetamol had fewer maternal adverse effects., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Purpose: To evaluate the impact of a prescriber focused individual educational and audit-feedback intervention undertaken by the Nova Scotia Prescription Monitoring Program (NSPMP) in March/April 2007 to reduce meperidine use., Method: The NSPMP records all prescriptions for controlled substances dispensed in community pharmacies in Nova Scotia, Canada. Oral meperidine use from 1 July 2005 to 31 December 2009 was examined using NSPMP data. Monthly totals for the following were obtained: number of individual patients who filled at least one meperidine prescription, number of prescriptions, and number of tablets dispensed. Data were analyzed graphically to observe overall trends. The intervention effect was estimated on the logarithmic scale with autocorrelations over time modeled by an integrated autoregressive moving average model for each outcome measure., Results: An overall trend toward decreasing use from July 2005 to December 2009 was apparent for all three outcome measures. The intervention was associated with a statistically significant reduction in meperidine use, after adjusting for the overall long-term trend. Compared with the pre-intervention period, the monthly number of patients declined by 12% (p < 0.001; 95% confidence interval [CI] = 5%-18%), prescriptions by 10% (p < 0.001; 95%CI = 3%-17%), and tablets by 13.5% (p < 0.001, 95%CI = 6%-29%) in the post-intervention period., Conclusion: Given the risks associated with meperidine, determining that this intervention successfully reduced meperidine use is encouraging. This study highlights the potential for using population data such as the NSPMP to evaluate the effectiveness of population-level interventions to improve medication use, including professional, organizational, financial, and regulatory initiatives., (Copyright © 2011 John Wiley & Sons, Ltd.)

Meperidine is an opiod analgesic used in a variety of clinical situations. The active metabolite, normeperidine, is a central nervous system excitatory agent and has the ability to cause irritability, hyperreflexia, tremor, myoclonus and seizures. Previously identified risk factors for the development of meperidine-related seizures include renal failure, high meperidine dosages, and co-adminestration of hepatic enzyme inducing medications or phenothiazines which decreases seizure treshold. Patients with normal renal function rarely manifest seizure activity when given meperidine. Here we report a 10 year old boy with a femur fraction who had normal renal function. We used low dose meperidine due to post operative pains.