SPAM-sub partual analgesia with meptazinol: a prospective cohort study comparing intramuscular with intravenous administration.

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.

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

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

The Analysis of Pethidine Pharmacokinetics in Newborn Saliva, Plasma, and Brain Extracellular Fluid After Prenatal Intrauterine Exposure from Pregnant Mothers Receiving Intramuscular Dose Using PBPK Modeling.

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.

Meperidine Compared With Nitrous Oxide for Intrapartum Pain Relief in Multiparous Patients: A Randomized Controlled Trial.

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.

Relationship between molar incisor hypomineralization, intrapartium medication and illnesses in the first year of life.

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.

Efficacy and safety of endoscopic retrograde cholangiopancreatography in the very elderly by using a combination of intravenous midazolam, ketamine and pethidine.

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.

Declines and pronounced regional disparities in meperidine use in the United States.

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.

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.

Analgesic Efficacy and Adverse Effects of Meperidine in Managing Postoperative or Labor Pain: A Narrative Review of Randomized Controlled Trials.

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.

Creation of a score to predict risk of high conscious sedation requirements in patients undergoing endoscopy.

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.

Qualitative exploration of women's experiences of intramuscular pethidine or remifentanil patient-controlled analgesia for labour pain.

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.

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.

Efficacy of parecoxib sodium on postoperative shivering: meta-analysis of clinical trials.

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.

Is pethidine safe during labor? Systematic review / A petidina é segura durante o trabalho de parto? Revisão sistemática

Abstract 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.

Resumo Objetivo Verificar se a petidina é segura para o concepto quando utilizada durante o trabalho de parto. Método Revisão sistemática nas bases de dados dos Periódicos Capes/PubMed e MEDLINE/Biblioteca Virtual em Saúde (BVS). Resultados Um total de 17 estudos, publicados de 1° de janeiro de 2000 a 2 de setembro de 2016, totalizando 1.688 participantes envolvidos, foram incluídos nesta revisão. Não houve registro de depressão na vitalidade dos conceptos comdoses baixas de petidina administradas às mães durante o trabalho de parto. Conclusão Petidina intramuscular (IM) ou intravenosa (IV) em baixas doses, de até 50 mg, é segura durante o trabalho de parto.

Simultaneous quantitation of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene in human plasma using solid-phase extraction and gas chromatography/mass spectrometry: Method validation and application to cardiovascular safety of therapeutic doses.

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.

Is Pethidine Safe during Labor? Systematic Review.

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.

Objetivo Verificar se a petidina é segura para o concepto quando utilizada durante o trabalho de parto. Método Revisão sistemática nas bases de dados dos Periódicos Capes/PubMed e MEDLINE/Biblioteca Virtual em Saúde (BVS). Resultados Um total de 17 estudos, publicados de 1° de janeiro de 2000 a 2 de setembro de 2016, totalizando 1.688 participantes envolvidos, foram incluídos nesta revisão. Não houve registro de depressão na vitalidade dos conceptos com doses baixas de petidina administradas às mães durante o trabalho de parto. Conclusão Petidina intramuscular (IM) ou intravenosa (IV) em baixas doses, de até 50 mg, é segura durante o trabalho de parto.

Prospective Analysis of Minor Adverse Events After Colon Polypectomy.

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.

The Comparative Risk of Delirium with Different Opioids: A Systematic Review.

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.

Risk Factors for Intrapartum Fever in Term Gestations and Associated Maternal and Neonatal Sequelae.

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.