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American Journal of Obstetrics and... Feb 1985Normeperidine, the active meperidine metabolite, has been implicated in adverse neonatal effects that may occur following administration of meperidine to parturients....
Normeperidine, the active meperidine metabolite, has been implicated in adverse neonatal effects that may occur following administration of meperidine to parturients. However, recent studies have suggested that normeperidine levels are not high enough to have adverse effects following single low doses of meperidine. It is not clear what occurs following multiple injections. Therefore the purpose of this study was to quantitate plasma levels of meperidine and normeperidine in the mother following multiple doses of meperidine over long time periods and to determine the half-life of normeperidine. Twelve mothers who received multiple intravenous doses of meperidine were studied. The results show that both meperidine and normeperidine accumulate in maternal plasma following multiple injections and that the half-life of normeperidine averages 20.6 hours. The data suggest that maximum exposure of the fetus to both meperidine and normeperidine would result from multiple doses to the mother because of a continued diffusion gradient from mother to fetus.
Topics: Adolescent; Adult; Female; Half-Life; Humans; Labor, Obstetric; Meperidine; Postpartum Period; Pregnancy
PubMed: 3970109
DOI: 10.1016/0002-9378(85)90313-8 -
Archives of Internal Medicine Apr 1980Meperidine hydrochloride was evaluated in a prospectively randomized double-blind study for its effectiveness in stopping shaking chills occurring with amphotericin B... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Meperidine hydrochloride was evaluated in a prospectively randomized double-blind study for its effectiveness in stopping shaking chills occurring with amphotericin B infusions. Seven patients were randomized on multiple occasions for a total of 19 reactions. In the meperidine group, nine of nine reactions stopped within 30 minutes of the administration of meperidine, with a mean cessation time of 10.8 minutes. The placebo group had a mean time of 37.4 minutes to cessation of reactions with three of ten reactions subsiding spontaneously. The mean dose of meperidine hydrochloride for cessation of reaction was 45 mg. The comparisons between meperidine and placebo for cessation of reaction within 30 minutes and the mean time to cessation of reaction were significantly different. Side effects with meperidine were minimal and less severe than the shaking chills and fever seen with amphotericin B infusions. Meperidine can eliminate these reactions more effectively and more rapidly than simply discontinuing the amphotericin B.
Topics: Adult; Aged; Amphotericin B; Double-Blind Method; Female; Fever; Humans; Male; Meperidine; Middle Aged; Placebos; Tremor
PubMed: 7362377
DOI: No ID Found -
Journal of Ayub Medical College,... 2023Shivering is one of the most common adverse outcomes associated with the administration of spinal anaesthesia, which, when clinically relevant, leads to numerous...
BACKGROUND
Shivering is one of the most common adverse outcomes associated with the administration of spinal anaesthesia, which, when clinically relevant, leads to numerous detrimental effects on the human body. Hence, its management becomes imperative. Meperidine, an opioid analgesic, is the drug of choice for this condition. However, the use of meperidine is controversial, as it carries the devastating adverse effect of respiratory depression. We explored the role of granisetron, a 5HT3 antagonist and a commonly used antiemetic premedication, in minimising the incidence of post-spinal shivering and decreasing the use of meperidine as a rescue drug.
METHODS
Overall, 160 parturient patients, between the ages 18-50, undergoing uncomplicated, elective caesarean section, were enrolled in the study, and randomized into two groups with 80 participants each: Group A received 3ml of normal saline, and Group B was administered 3 mg granisetron,15 minutes before spinal anaesthesia institution. Incidence of clinically relevant shivering (score of 3 or more) was noted, and it was recorded whether meperidine was used or not.
RESULTS
67.5% of participants in Group A, and 32.5% of patients in Group B, experienced clinically relevant shivering, with 62.5% of patients in Group A and 28.75% in Group B warranting the use of meperidine. There was a statistically significant difference between the two groups in terms of incidence of clinically relevant shivering, and meperidine consumption (p-value <0.001).
CONCLUSIONS
Premedication with 3 mg granisetron effectively attenuates the occurrence of post-spinal shivering and, hence, lowers the requirement of meperidine as rescue medication.
Topics: Humans; Pregnancy; Female; Adolescent; Young Adult; Adult; Middle Aged; Meperidine; Granisetron; Shivering; Pharmaceutical Preparations; Cesarean Section; Anesthesia, Spinal
PubMed: 38406929
DOI: 10.55519/JAMC-04-11651 -
Archives of Surgery (Chicago, Ill. :... Jan 2002Intravenous patient-controlled analgesia (IV PCA) meperidine hydrochloride can be used with a reasonable margin of safety.
HYPOTHESIS
Intravenous patient-controlled analgesia (IV PCA) meperidine hydrochloride can be used with a reasonable margin of safety.
DESIGN
A retrospective review was performed of 355 medical records of patients receiving IV PCA meperidine treatment. Four groups of patients were defined, based on daily meperidine dose and the presence or absence of central nervous system excitation adverse effects. Use of more than 600 mg/d of meperidine hydrochloride was considered a high dose.
SETTING
University tertiary care hospital.
PARTICIPANTS
Postoperative patients from general, orthopedic, neurosurgical, gynecological, and urologic procedures receiving IV PCA.
INTERVENTIONS
If patients were judged to have consumed significant amounts of meperidine, the analgesic regimen was modified to (1) discontinue meperidine therapy, (2) substitute hydromorphone hydrochloride, or (3) decrease the use of meperidine by adding oral methadone hydrochloride or transdermal fentanyl citrate to the regimen.
MAIN OUTCOME MEASURES
Patients who received less than 10 mg/kg per day of IV PCA meperidine hydrochloride therapy were unlikely to experience central nervous system excitatory adverse effects and maintain adequate analgesia.
RESULTS
The mean meperidine hydrochloride consumption for those patients classified as high dose, asymptomatic was 13.3 mg/kg per day (95% confidence interval, 12.1-14.4 mg/kg per day). This differed statistically significantly (P<.05) from the mean meperidine hydrochloride dose in patients classified as high dose, symptomatic, which was 16.9 mg/kg per day (95% confidence interval, 14.7-19.2 mg/kg per day). The duration of meperidine use did not differ among the 4 patient groups. The incidence of a central nervous system toxic reaction associated with IV PCA meperidine therapy was 2%.
CONCLUSIONS
We recommend 10 mg/kg per day as a maximum safe meperidine hydrochloride dose by an IV PCA device for no longer than 3 days. Daily patient evaluation is mandatory. Care must also be taken when using this dose to ensure the absence of renal dysfunction or enhanced hepatic metabolism of meperidine.
Topics: Adult; Analgesia, Patient-Controlled; Analgesics, Opioid; Case-Control Studies; Central Nervous System Diseases; Dose-Response Relationship, Drug; Female; Humans; Male; Meperidine; Middle Aged; Pain, Postoperative; Retrospective Studies; Time Factors
PubMed: 11772223
DOI: 10.1001/archsurg.137.1.84 -
DICP : the Annals of Pharmacotherapy 1991We examined the relationship between serum concentrations of meperidine hydrochloride and analgesic response in postsurgical patients allowed to use patient-controlled... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
We examined the relationship between serum concentrations of meperidine hydrochloride and analgesic response in postsurgical patients allowed to use patient-controlled analgesia (PCA) and compared these findings with those of patients receiving conventional intramuscular (IM) dosing. Six patients who had undergone abdominal surgery were randomly assigned to receive postoperative analgesia with either PCA or IM therapy. A sequence of five-point pain and sedation scores and serum meperidine concentrations were obtained in all patients the day after surgery. Minimum effective concentration (MEC) was defined as that concentration of meperidine at which patients felt pain relief as indicated by a decrease in pain rankings. The mean MEC for patients using PCA, 296 +/- 112 ng/mL, was significantly lower than the mean MEC in patients receiving IM dosing (551 +/- 164 ng/mL, p less than 0.05). The mean maximum change in meperidine concentrations in the PCA group, 177 +/- 88 ng/mL, was significantly lower than that of the IM group (484 +/- 125 ng/mL, p less than 0.05). Mean maximum changes in pain and sedation scores for patients in the PCA group were not significantly different from those of the IM group. During this investigation patients using PCA experienced smaller swings in meperidine concentrations than did patients receiving IM injections. MEC analysis suggests that PCA patients may experience pain relief at lower meperidine concentrations than those needed by IM patients.
Topics: Abdomen; Adult; Aged; Analgesia, Patient-Controlled; Female; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Male; Meperidine; Middle Aged; Pain, Postoperative
PubMed: 1949926
DOI: 10.1177/106002809102500703 -
Clinical Pharmacology and Therapeutics Nov 1981The effects of route of administration and altered urinary pH on the disposition of meperidine and its metabolite normeperidine were investigated in six normal,...
The effects of route of administration and altered urinary pH on the disposition of meperidine and its metabolite normeperidine were investigated in six normal, nonsmoking young men from 23 to 31 yr old. Meperidine (21.75 mg) was injected intravenously simultaneous with the same dose of deuterated (2H5) drug given orally in solution or by injection into the deltoid muscle. After intravenous administration with no control of urinary pH, meperidine blood levels declined triexponentially over 24 hr with a terminal half-life (t1/2) of 4.9 to 9.4 hr and a clearance of 472 to 686 ml/min. The 48-hr urinary recoveries of meperidine and normeperidine were about 7% and 12%. Urinary acidification with ammonium chloride reduced these amounts to less than 1% and about 7%, whereas urinary alkalinization increased them to about 20% and 24%. These pronounced changes had negligible effects on the blood concentration/time profiles. Plasma levels were proportional to the blood concentrations with a ratio of about unity for meperidine and a value 25% greater for normeperidine. Absorption after intramuscular injection was complete and followed a first-order process with t1/2 ranging from 7 to 13 min. Accordingly, maximum blood levels were achieved within 5 to 15 min and the concentration was essentially the same as after intravenous dosing. In contrast, oral bioavailability was incomplete, ranging from 47% to 73%, and at a much slower rate, with peak concentrations being observed after about 1 hr. Absorption was biphasic and was preceded by a 5- to 10-min lag period. Normeperidine blood concentration after intravenous dosing reached a maximum within 2 to 4 hr and remained at this value through 12 hr before modestly declining by 24 hr. After oral dosing the peak level was achieved more rapidly and sharply. Thus, presystemic elimination occurs after oral dosing within meperidine consistent in value with the measured blood clearance which, therefore, probably reflects only hepatic metabolism.
Topics: Administration, Oral; Adult; Biological Availability; Humans; Hydrogen-Ion Concentration; Injections, Intramuscular; Liver; Liver Circulation; Male; Meperidine; Urine
PubMed: 7297021
DOI: 10.1038/clpt.1981.213 -
Journal of Clinical Pharmacology Oct 1978Phenobarbital has been observed clinically to alter the metabolism of meperidine, with resultant enhanced toxicity. In order to determine if this effect occurs... (Clinical Trial)
Clinical Trial
Phenobarbital has been observed clinically to alter the metabolism of meperidine, with resultant enhanced toxicity. In order to determine if this effect occurs consistently, 12 health volunteers were entered into a two-way, crossover study comparing the pharmacokinetics and metabolism of meperidine after pretreatment with both phenobarbital and placebo. Phenobarbital pretreatment had no significant effect on serum levels or the half-life of meperidine. However, phenobarbital pretreatment resulted in a decrease in the cumulative excretion of meperidine and an increase in the cumulative excretion of the N-demethylated metabolite normeperidine. Similarly, phenobarbital pretreatment resulted in a decrease in meperidinic acid and increase in normeperidinic acid. In addition, phenobarbital pretreatment also significantly altered the hepatic clearance of meperidine, indicating an increase in the hepatic N-demethylation of meperidine. Since normeperidine has been reported to be less efficacious and more toxic than meperidine, this reported interaction may be important clinically, especially with repeated doses.
Topics: Adult; Drug Interactions; Half-Life; Humans; Meperidine; Phenobarbital; Placebos; Time Factors
PubMed: 711931
DOI: 10.1002/j.1552-4604.1978.tb01576.x -
American Journal of Obstetrics and... Apr 1979Because of the unavailability of sensitive analytic techniques, the pharmacokinetics of meperidine have not been clearly delineated in obstetric patients during labor....
Because of the unavailability of sensitive analytic techniques, the pharmacokinetics of meperidine have not been clearly delineated in obstetric patients during labor. Moreover, the production of the active meperidine metabolite--normeperidine--has not been investigated. By means of gas chromatographic and mass spectrometric techniques, these characteristics of meperidine metabolism were evaluated in 23 pregnant patients in the present study. The data show that the disappearance curve and pharmacokinetic constants for meperidine are similar to those previously reported for nonpregnant subjects. In regard to normeperidine, the data indicate that it is produced within ten minutes after meperidine injection, increases rapidly for the next 20 minutes, and then slowly increases throughout labor. The results enumerate the pharmacokinetic constants of meperidine in obstetric patients and describe the appearance of normeperidine, the active meperidine metabolite, following meperidine administration during labor.
Topics: Adult; Chromatography, Gas; Female; Humans; Kinetics; Labor, Obstetric; Mass Spectrometry; Meperidine; Pregnancy
PubMed: 434034
DOI: 10.1016/0002-9378(79)90310-7 -
International Journal of Gynaecology... Oct 1984Meperidine and its principle metabolite, normeperidine, were given intravenously to four non-human primates prior to cesarean delivery in an equivalent dose for human... (Comparative Study)
Comparative Study
Meperidine and its principle metabolite, normeperidine, were given intravenously to four non-human primates prior to cesarean delivery in an equivalent dose for human parturients. The status of the infants regarding neonatal depression was assessed at delivery. Repeated blood samples from both the mother and the neonate were obtained over a period of 4 days. The levels of meperidine and normeperidine were analyzed. The results showed that the metabolism of meperidine and normeperidine in the non-human primate was essentially the same as that observed in the human parturient. In addition, normeperidine appeared to be more toxic than meperidine to the neonate. Finally, there does not appear to be an evidence for neonatal metabolism of meperidine to normeperidine.
Topics: Animals; Animals, Newborn; Apgar Score; Female; Fetus; Humans; Macaca; Macaca mulatta; Maternal-Fetal Exchange; Meperidine; Models, Biological; Pregnancy; Pregnancy, Animal; Time Factors
PubMed: 6151917
DOI: 10.1016/0020-7292(84)90064-x -
Canadian Anaesthetists' Society Journal Nov 1982
Topics: Humans; Infusions, Parenteral; Kinetics; Meperidine; Obesity
PubMed: 7139406
DOI: 10.1007/BF03007758