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Therapeutic Hypothermia and Temperature... Dec 2015Meperidine is used for pain control and treatment of shivering. Concerns about neurotoxicity, particularly seizures, have led to efforts limiting meperidine use. We... (Review)
Review
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.
Topics: Analgesics, Opioid; Humans; Meperidine; Pain Threshold; Risk Assessment; Risk Factors; Seizures; Shivering
PubMed: 26087278
DOI: 10.1089/ther.2015.0013 -
Pain Physician Mar 2020Meperidine, a synthetic opioid, has a rapid onset and short duration of action. Mounting evidence has challenged meperidine's analgesic benefits, and concerns have been... (Review)
Review
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.
Topics: Adult; Analgesia, Patient-Controlled; Analgesics, Opioid; Cesarean Section; Female; Humans; Labor Pain; Meperidine; Morphine; Pain, Postoperative; Postoperative Nausea and Vomiting; Pregnancy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32214301
DOI: No ID Found -
BMC Veterinary Research Oct 2020Meperidine 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...
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.
Topics: Administration, Intravenous; Analgesics, Opioid; Animals; Central Nervous System; Female; Heart Rate; Horses; Hot Temperature; Male; Meperidine; Nociception; Urticaria
PubMed: 32998730
DOI: 10.1186/s12917-020-02564-4 -
Anaesthesiology Intensive Therapy 2015Labour 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%... (Review)
Review
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.
Topics: Analgesia, Obstetrical; Analgesics, Opioid; Female; Humans; Labor Pain; Meperidine; Pain Measurement; Piperidines; Poland; Practice Guidelines as Topic; Pregnancy; Remifentanil
PubMed: 25751295
DOI: 10.5603/AIT.2015.0008 -
Pharmacology Research & Perspectives Aug 2021There 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...
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.
Topics: Analgesics, Opioid; Drug Utilization; Humans; Meperidine; Obesity; Pain; Practice Patterns, Physicians'; United States
PubMed: 34128348
DOI: 10.1002/prp2.809 -
BMJ Open Feb 2022Shivering is a common complication in the postoperative period. The incidence of shivering has been reported to range from 5% to 65% under general anaesthesia and as 33%...
INTRODUCTION
Shivering is a common complication in the postoperative period. The incidence of shivering has been reported to range from 5% to 65% under general anaesthesia and as 33% during epidural anaesthesia. Shivering can increase perioperative risk in patients. Both dexmedetomidine and meperidine are effective agents for the prevention of postanaesthetic shivering. However, few studies have compared the anti-shivering effects of different agents following coronary artery bypass graft (CABG). This study aims to compare the effects of dexmedetomidine and meperidine on the incidence of shivering in patients undergoing CABG.
METHODS AND ANALYSIS
A total of 180 patients aged 18-75 years, with an American Society of Anesthesiologists (ASA) grade of II-IV, undergoing elective CABG will be enrolled and randomly assigned to the dexmedetomidine, meperidine and control groups (placebo) in an intended 1:1:1 allocation ratio. The patients will be followed up for 7 days after surgery. The primary outcome is the incidence of shivering within 24 hours postoperatively. The secondary outcomes are the number of remedial drugs used after surgery, the incidence of postoperative hypotension and bradycardia, sedation scores, endotracheal extubation time, intensive care unit length of stay, incidence of postoperative delirium within 7 days after surgery, incidence of postoperative arrhythmias, incidence of postoperative nausea and vomiting, average hospital length of stay and mortality rate 30 days after surgery.
ETHICS AND DISSEMINATION
The study protocol was approved by the ethics committee of The First Affiliated Hospital of Shandong First Medical University on 20 January 2021 (YXLL-KY-2021(002)) and registered at ClinicalTrials.gov. The results of this study will be presented at national and international scientific meetings and conferences. We plan to publish the data in peer-reviewed international scientific journals.
TRIAL REGISTRATION NUMBER
NCT04735965.
Topics: Coronary Artery Bypass; Dexmedetomidine; Double-Blind Method; Humans; Meperidine; Randomized Controlled Trials as Topic; Shivering
PubMed: 35149565
DOI: 10.1136/bmjopen-2021-053865 -
The Journal of Clinical Pediatric... Mar 2022This retrospective study compares the efficacy and safety of variable dosing of Midazolam (Mid) with and without Meperidine (Mep) combinations for managing varying...
Retrospective Comparisons of the Efficacy and Safety of Variable dosing of Midazolam with and without Meperidine for Management of Varying Levels of Anxiety of Pediatric Dental Patients: 35 years of Sedation Experience.
PURPOSE
This retrospective study compares the efficacy and safety of variable dosing of Midazolam (Mid) with and without Meperidine (Mep) combinations for managing varying levels of anxiety and uncooperative behavior of young pediatric dental patients over a thirty-five-year period.
STUDY DESIGN
Reviews of the sedation logs of 1,785 sedation visits are compared with emphasis on what dosing proves both safe and effective for differing levels of challenging pediatric behavior. Variable dosing of midazolam with and without meperidine which spanned low-end, mid-range, and upper-end were judged making use of a pragmatic approach which defined sedation success as optimal, adequate, inadequate, or over-dosage. Behavioral and physiologic assessment was included with attention to readily observable analysis of the extent to which need for physical restraint occurred to control interfering behavior. Assessment of arousal levels requiring stimulation along with the frequency of alterations in oxygen de-saturation and adverse reactions were included as indications of safety.
RESULTS
Where Mep was used, success rates were consistently higher; working times were significantly prolonged and greater control was provided to avoid adverse reactions by virtue of reversal capability for both agents.
CONCLUSIONS
Predictability and working time of Midazolam was enhanced by combination with narcotic for all levels of patient anxiety. Dosages of 0.7-1.0 mg/kg Mid combined with 1.0-1.5 mg/kg Mep offers the most effective and safe results to overcome need for restraint for moderate and severe levels of anxiety, respectively.
Topics: Anxiety; Child; Conscious Sedation; Humans; Hypnotics and Sedatives; Meperidine; Midazolam; Retrospective Studies
PubMed: 35533228
DOI: 10.17796/1053-4625-46.2.11 -
Anesthesiology Dec 1993Meperidine, which binds both mu and kappa opioid receptors, is reportedly more effective in treating shivering than are equianalgesic doses of morphine (a nearly pure... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Meperidine, which binds both mu and kappa opioid receptors, is reportedly more effective in treating shivering than are equianalgesic doses of morphine (a nearly pure mu-receptor agonist). Furthermore, butorphanol, a kappa-receptor agonist/antagonist, treats shivering better than does fentanyl, which mostly binds mu receptors. These data indicate that much of meperidine's special antishivering activity may be mediated by its kappa activity. Accordingly, the authors tested the hypothesis that the antishivering activity of meperidine will be minimally impaired by low-dose naloxone (blocking most mu-receptors), but largely prevented by high-dose naloxone (blocking all mu and most kappa receptors).
METHODS
Twelve volunteers each participated on 2 days. On both days, shivering was induced by central venous infusion of cold fluid. Twenty minutes later, six volunteers were given a placebo infusion of saline on one day, or an infusion of 0.5 microgram.kg-1.min-1 naloxone hydrochloride ("low-dose," designed to block mu receptors) on the other. The second group of six volunteers was given a saline bolus and infusion on one day, or a bolus of 11.5 micrograms/kg naloxone hydrochloride followed by an infusion of naloxone at 5 micrograms.kg-1.min-1 ("high-dose," designed to block both mu and kappa receptors) on the other day. The infusions were continued for the duration of the study. The order of the treatment days (saline vs. naloxone) was randomly assigned, and the study was double blinded. Fifteen minutes after the test infusion was started, all 12 volunteers were given an intravenous bolus of 1 mg/kg meperidine hydrochloride. Pupillary diameter and light reflex amplitude were used to quantify opioid-receptor agonist activity; shivering intensity was evaluated using oxygen consumption.
RESULTS
Administration of naloxone alone did not alter oxygen consumption, pupil size, or the pupillary light reflex. No pupillary constriction was detected in either group when naloxone and meperidine were combined; in contrast, meperidine alone decreased pupil size and amplitude of the light reflex 30%. The meperidine bolus decreased oxygen consumption nearly to control values when the volunteers were given saline placebo. Combined administration of meperidine and low-dose naloxone also significantly reduced oxygen consumption, but the reduction and the duration of the reduction was less than during saline. When the volunteers were given high-dose naloxone, meperidine only slightly reduced oxygen consumption, and the values rapidly returned to premeperidine levels.
CONCLUSIONS
These data indicate that the antishivering property of meperidine is not fully mediated by mu-receptors. Although meperidine has well-known nonopioid actions, stimulation of kappa receptors seems a likely alternative explanation for much of the drug's antishivering action.
Topics: Adult; Body Temperature; Double-Blind Method; Humans; Meperidine; Naloxone; Oxygen Consumption; Pupil; Receptors, Opioid, kappa; Receptors, Opioid, mu; Shivering
PubMed: 8267194
DOI: 10.1097/00000542-199312000-00009 -
British Medical Journal Apr 1947
Topics: Meperidine
PubMed: 20343513
DOI: 10.1136/bmj.1.4503.579-b -
Medicina (Kaunas, Lithuania) Oct 2023: 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...
: 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. : 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. : 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. : 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.
Topics: Rats; Animals; Meperidine; Epinephrine; Norepinephrine; Hydrocortisone; Metyrapone; Caffeine; Analgesics; Epilepsy; Seizures
PubMed: 37893510
DOI: 10.3390/medicina59101793