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At least 19 recordsLinked to original sources

Meperidine is alive and well in the new millennium: evaluation of meperidine usage patterns and frequency of adverse drug reactions.

STUDY OBJECTIVES: To report a classic case of normeperidine toxicity, and to present institution-specific data on meperidine usage patterns and the frequency of adverse drug reactions (ADRs). METHODS: A chart review was conducted of patients at high risk for ADRs. High-risk patients were identified through the pharmacy computer system as those with renal insufficiency (creatinine clearance < or = 50 ml/min), those receiving meperidine with patient-controlled analgesia (PCA), or those receiving more than 200 mg/day of intravenous meperidine for multiple days. RESULTS: Twenty-five percent of patients who received meperidine had some degree of renal insufficiency. The average daily dose of meperidine was 230 mg; cumulative doses ranged from 10-7200 mg. Adverse drug reactions documented in 20 (14%) of 141 patients were confusion, anxiety, nervousness, hallucinations, twitching, and seizure. Sixteen of the 20 patients received meperidine by PCA pump or a combination of PCA and intravenous administration. Patients with ADRs to meperidine were older (58.5 vs 46.4 yrs, p = 0.004), received more concomitant benzodiazepines (65.0% vs 4.1%, p < 0.0001), and had a longer hospital stay (median 9.5 vs 4.6 days, p < 0.001) than those who did not experience an ADR. A significant difference was found in cumulative PCA doses between patients with and without documented ADRs (median meperidine dose 863 and 455 mg, respectively, p = 0.0157). Doses were directly correlated with both renal function (p < 0.05) and length of stay (p < 0.008). Dosing, duration, and frequency of ADRs for patients using PCA differed significantly between prescribing services (p < 0.01). CONCLUSION: Patients using PCA meperidine are at particularly high risk of experiencing ADRs based on cumulative doses and duration of treatment. Adverse drug reactions were documented in approximately 14% of patients. Our results warrant restriction of PCA meperidine and evaluation of meperidine usage policies to improve pain management services and decrease the frequency of ADRs.

Adult↗

Meperidine and lidocaine block of recombinant voltage-dependent Na+ channels: evidence that meperidine is a local anesthetic.

BACKGROUND: The opioid meperidine induces spinal anesthesia and blocks nerve action potentials, suggesting it is a local anesthetic. However, whether it produces effective clinical local anesthesia in peripheral nerves remains unclear. Classification as a local anesthetic requires clinical local anesthesia but also blockade of voltage-dependent Na+ channels with characteristic features (tonic and phasic blockade and a negative shift in the voltage-dependence of steady-state inactivation) involving an intrapore receptor. The authors tested for these molecular pharmacologic features to explore whether meperidine is a local anesthetic. METHODS: The authors studied rat skeletal muscle mu1 (RSkM1) voltage-dependent Na+ channels or a mutant form heterologously coexpressed with rat brain Na+ channel accessory beta1, subunit in Xenopus oocytes. Polymerase chain reaction was used for mutagenesis, and mutations were confirmed by sequencing. Na+ currents were measured using a two-microelectrode voltage clamp. Meperidine and the commonly used local anesthetic lidocaine were applied to oocytes in saline solution at room temperature. RESULTS: Meperidine and lidocaine produced tonic current inhibition with comparable concentration dependence. Meperidine caused phasic current inhibition in which the concentration-response relationship was shifted to fivefold greater concentration relative to lidocaine. Meperidine and lidocaine negatively shifted the voltage dependence of steady-state inactivation. Mutation of a putative local anesthetic receptor reduced phasic inhibition by meperidine and lidocaine and tonic inhibition by lidocaine, but not meperidine tonic inhibition. CONCLUSIONS: Meperidine blocks Na+ channels with molecular pharmacologic features of a local anesthetic. The findings support classification of meperidine as a local anesthetic but with less overall potency than lidocaine.

Algorithms↗

A comparison of the haemodynamic effects of intrathecal meperidine, meperidine-bupivacaine mixture and hyperbaric bupivacaine.

PURPOSE: To study the haemodynamic effects of intrathecal meperidine, administered either alone or mixed with bupivacaine. METHODS: We studied 42 Chinese patients, aged 59-87 yr, scheduled for transurethral bladder or prostate surgery, randomized into three equals groups, that received either meperidine 0.8 mg.kg-1, meperidine 0.4 mg.kg-1 plus 1.5 ml of 0.5% heavy bupivacaine or 3 ml of heavy bupivacaine 0.5%. Non-invasive systolic (SAP) and mean (MAP) arterial pressures, central venous pressure and cardiac index, stroke index and heart rate (HR) measured by the BoMed NCCOM3-R7S bioimpedance device, were recorded over the first 25 min. Systemic vascular resistance index (SVRI) was derived. Onset of sensory and motor block was also measured. Decreases in MAP of 25% were treated with colloid and metaraminol. RESULTS: The onset of block was slower in the meperidine group (P < 0.05). Decreases in SAP, MAP and SVRI (all; P < 0.001) occurred within five minutes in all three groups. The HR was increased in the bupivacaine group (P = 0.03), but bradycardias treated with atropine occurred in six patients receiving meperidine and four patients receiving the mixture. Six patients receiving meperidine and two patients receiving the mixture required general anaesthesia for inadequate block. The incidence of nausea and vomiting was higher in the patients receiving meperidine (P < 0.05). No other complications were encountered. CONCLUSIONS: Intrathecal meperidine used alone or mixed with bupivacaine has no intra-operative advantage over heavy bupivacaine 0.5%.

Aged↗

Meperidine and normeperidine levels following meperidine administration during labor. I. Mother.

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.

Adult↗

Meperidine and normeperidine levels following meperidine administration during labor. II. Fetus and neonate.

The time interval between the administration of meperidine to laboring patients and delivery may affect neonatal status, but sophisticated analytic techniques have not been used to determine the exposure of the fetus to meperidine at various drug-delivery intervals. By means of gas chromatography and mass spectrometry, the concentrations of meperidine and normeperidine (the principle metabolite of meperidine) were quantitated in the umbilical cord venous and arterial plasma at delivery and in the urine of the neonate for three days postpartum. Following 50 mg. of meperidine administered intravenously during labor, fetal exposure to meperidine was highest two to three hours after maternal medication while fetal exposure to normeperidine was highest four hours or more after medication. We conclude from this study that there is a definite but nonlinear relationship between the drug-delivery interval and the amount of meperidine and normeperidine an infant receives; and that the drug-delivery intervals resulting in maximum fetal exposure reported here correspond with those resulting in maximum neonatal depression reported by others.

Chromatography, Gas↗

Hemodynamic effects in dogs of nitrous oxide-meperidine and meperidine, respectively, in comparison with nitrous oxide.

The aim of this investigation on dogs, was to examine the hemodynamic effects of nitrous oxide (N2O) plus meperidine and of meperidine with room air ventilation, respectively, compared with those of N2O on its own. When meperidine (bolus dose 3 mg.kg-1 and continued infusion 4 mg.kg-1.h-1) was added to 80% N2O, mean arterial blood pressure fell from about 20 to 10 kPa (150 to 75 mmHg), as a result of a decrease in peripheral vascular resistance, but no compensatory changes in cardiac output were seen. When N2O was withdrawn, during continued meperidine infusion, cardiac output and stroke volume increased, while peripheral resistance remained low. Coronary vasodilation was noted when meperidine was added to N2O, and persisted when N2O was withdrawn. In the pulmonary circulation a different response was found. Here, no effects were observed when meperidine was added to N2O, while pressure and resistance decreased when N2O was withdrawn and meperidine continued.

Animals↗

Plasma concentrations of meperidine and normeperidine following continuous intrathecal meperidine in patients with neuropathic cancer pain.

BACKGROUND: Intrathecal administration of meperidine, an opioid with local anesthetic activity, can induce analgesia in patients with intractable cancer pain. However, continuous intrathecal administration may result in the accumulation of normeperidine, responsible for central nervous system toxicity. METHODS: Ten patients with neuropathic cancer pain, not responding to conventional opioid therapy, were treated with continuous intrathecal administration of meperidine. In all patients, plasma concentrations of meperidine and normeperidine were measured the first days after the start of treatment. Visual analog scale scores were recorded to evaluate pain relief. Quality of life was assessed before and 3 weeks following the start of intrathecal treatment. RESULTS: In three patients the plasma concentrations of meperidine and normeperidine increased rapidly. In one patient the plasma normeperidine concentration was higher than the meperidine concentration. One patient demonstrated transient symptoms suggestive for central nervous system excitation. Three weeks following the start of treatment, seven patients were available for evaluation of their quality of life. Pain relief and overall quality of life improved during the intrathecal treatment. CONCLUSION: We conclude that continuous intrathecal administration of meperidine alone, or in combination with clonidine, can provide significant pain relief in patients with poor pain control despite pharmacological treatment. However, accumulation of meperidine and normeperidine resulting in central nervous system toxicity may occur during this treatment.

Aged↗

Effects of intravenous meperidine and meperidine with promethazine on uterine activity and fetal heart rate during labor.

A prospective study of the effects of the i.v. injection of 75 mg meperidine, alone or combined with 25 mg promethazine, was conducted by continuous and direct monitoring of the fetus and of intrauterine pressure. The study was carried out in 16 primiparas and 24 multiparas in active spontaneous labor with cervical dilatation of 3 to 4 cm. Administration of meperidine and of meperidine with promethazine was associated with an increase in uterine activity of 31 to 45% (Montevideo units), respectively. The most marked effects were on the amplitude of the uterine contractions. There was no significant change in uterine tone. A tetanic response was recorded in two patients who vomited after the administration of meperidine with promethazine and was followed by slowing of the fetal heart rate. In no other cases were there significant changes in fetal heart rate. Except for the latter two patients, no adverse effect of meperidine or of meperidine with promethazine on the fetal heart rate was noted. The condition of the newborns at birth was excellent in all but three cases, in two of which maternal amniotic infection and high fever were present.

Female↗

The bioavailability of meperidine using urine assays for meperidine and normeperidine.

The results of a two-way crossover trial of two commercial preparations of meperidine hydrochloride in 24 healthy volunteers is reported. The urinary excretion patterns resulting from dosing with the two preparations were followed for 48 hours, and the urine concentrations of meperidine and a major metabolite, normeperidine, were determined by gas liquid chromatography. Statistical analysis of the data showed no significant difference between the urine concentrations of meperidine and normeperidine produced by either preparation, and the preparations are of comparable bioavailability. The use of the urinary excretion pattern and concentrations represents a rapid, accurate, and quantitative method for determining the bioavailability of different preparations of meperidine hydrochloride.

Adult↗

Gas chromatographic analysis of meperidine and normeperidine: determination in blood after a single dose of meperidine.

A method is described for the determination of meperidine and its pharmacologically active metabolite, normeperidine, in blood, plasma, and urine using gas chromatography with nitrogen-phosphorus detection. Structural analogs of both meperidine and normeperidine were used as internal standards. Unlike previously reported assays, this procedure was sensitive and convenient enough for use in pharmacokinetic studies of both meperidine and normeperidine following single doses of meperidine. The assay was sensitive to 5 ng of meperidine/ml and 2.5 ng of normeperidine/ml extracted from a 1-ml biological sample. The between-assay coefficients of variation at these concentrations were 9.4 and 10.4%, respectively.

Adult↗

Direct stimulation of urokinase, plasmin, and collagenase by meperidine: a possible mechanism for the ability of meperidine to enhance cervical effacement and dilation.

Current hypotheses suggest that the degradation of cervical collagen and elastin leads to cervical effacement and dilation during labor. The collagenolytic activity is thought to be initiated through the conversion of latent (pro)collagenase to active collagenase by the plasmin formed from plasminogen or by other proteases similarly formed from their inactive zymogens. We presently demonstrate that meperidine stimulates the activity of several enzymes in the proteolytic cascade leading toward proteolysis of connective tissue proteins. Meperidine in its therapeutic concentration range produces a 26% stimulation of urokinase activity on substrate S-2444, a 39% stimulation of plasmin activity on substrate S-2551, and a 33% stimulation of collagenase activity on 14C-labeled globin substrate. These direct effects on the enzyme activities are noted in vitro with the purified enzymes and were confirmed with several small molecular weight chromogenic substrates and with 14C-globin protein substrate. Oxytocin at levels found during active labor fails to stimulate the in vitro activity of purified urokinase, plasmin, collagenase, trypsin, or tissue-type plasminogen activator. The effect of meperidine on the proteolytic enzymes suggests that its ability to promote cervical effacement and distention during labor may be at least partially due to a meperidine-induced stimulation of cervical proteases.

Cervix Uteri↗

Meperidine metabolites: identification of N-hydroxynormeperidine and a hydroxy-methoxy derivative of meperidine in biological fluids.

Gas chromatographic and gas chromatographic-mass spectrometric techniques were used to identify non-acidic metabolites of meperidine (N-methyl-4-phenyl-4-carbethoxypiperidine) excreted in human, rat, and guinea pig urine. Following enzymic hydrolysis N-hydroxynormeperidine was identified in the urine of all three species in addition to the expected metabolites normeperidine and meperidine N-oxide. In rat urine the p-hydroxyphenyl metabolite of meperidine was present in appreciable amounts. Also present in small quantity was a new phenolic metabolite of meperidine containing both hydroxyl and O-methoxyl substituents in the phenyl ring of the parent drug. The latter two metabolites were excreted as conjugates in the rat.

Adult↗

A prospective study of 2 sedation regimens in children: chloral hydrate, meperidine, and hydroxyzine versus midazolam, meperidine, and hydroxyzine.

The aim of this study was to compare both the behavioral and physiological effects of 2 drug regimens in children: chloral hydrate (CH), meperidine (M), and hydroxyzine (H) (regimen A) versus midazolam (MZ), M, and H (regimen B). Patients between 24 and 54 months of age were examined by crossover study design. Behavior was analyzed objectively by the North Carolina Behavior Rating System and subjectively through an operator and monitor success scale. Physiological data were recorded every 5 minutes and at critical points throughout the appointment. Sixteen patients completed this study. No significant differences in behavior were noted by the North Carolina Behavior Rating System or the operator and monitor success scale. A quiet or annoyed behavior was observed 93% and 90% of the time for regimen A and regimen B, respectively. Using the operator and monitor success scale, 63% of regimen A and 56% of regimen B sedations were successful. No statistically significant differences were noted in any of the physiological parameters between the 2 regimens. Ten episodes of hemoglobin desaturation were detected with regimen A sedations. There were no differences between the sedative drug regimens CH/M/H and MZ/M/H for behavioral outcomes or physiological parameters.

Analgesics, Opioid↗