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PubMed2006

The effects of meperidine in the pulmonary vascular bed of the cat.

OBJECTIVE: The purpose of this study was to test the hypothesis that meperidine induces a dilator response in the feline pulmonary vascular bed, and to identify receptors involved in the mediation or modulation of these effects. DESIGN: Prospective vehicle controlled study. SETTING: University research laboratory. SUBJECTS: Intact chest preparation; adult mongrel cats. INTERVENTIONS: In separate experiments, the effects of diphenydramine (histamine H(1)-receptor antagonist), glibenclamide (adenosine triphosphate-sensitive K+ channel blocker), L-N(5)-(1-Iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), naloxone (opioid receptor antagonist), and nimesulide (selective cyclooxygenase-2 inhibitor) were investigated on pulmonary arterial responses to meperidine and other agonists in the feline lung bed. MEASUREMENTS AND MAIN RESULTS: The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and permanently recorded. Under elevated tone conditions in the isolated left lower lobe vascular bed of the cat, meperidine induced a dose-dependent vasodilator response that was not significantly altered after administration of glibenclamide, L-NIO, and nimesulide. Responses to meperidine were significantly attenuated after the administration of diphenydramine and naloxone. CONCLUSIONS: The results suggest that meperidine has potent vasodilator activity in the feline pulmonary vascular bed, and these responses are mediated or modulated, in part, by opioid and histamine receptor-sensitive pathways.

Analgesics, Opioid↗
PubMed2005

Combining physostigmine with meperidine for sedation and analgesia during colonoscopy.

BACKGROUND AND STUDY AIM: Opiate or benzodiazepine drugs are often used during colonoscopy, but they are associated with respiratory depression and prolonged recovery. Physostigmine, a tertiary anticholinesterase agent, is known to enhance analgesia and to reverse the central nervous system depressant effects of these drugs. This study compared the effect of giving meperidine alone with the effect of giving meperidine in combination with physostigmine in patients who were undergoing complete colonoscopy. PATIENTS AND METHODS: A total of 44 outpatients undergoing elective colonoscopy were randomly assigned to receive analgesia with either meperidine 0.5 mg/kg intravenously (group 1, n=24) or physostigmine 10 micrograms/kg intravenously, followed 5 minutes later by meperidine 0.5 mg/kg intravenously (group 2; n=20). The patients were assessed with regard to oxygen saturation, hemodynamic changes, pain perception and sedation scores, readiness to go home, and adverse effects. RESULTS: The group 1 patients' oxygen saturations consistently fell, both during the procedure and in the recovery period; in group 2, oxygen saturations remained stable throughout the procedure and recovery period (95.88%+/-0.99 vs. 98.15+/-0.99, P<0.001). Patients in group 2 reported lower pain perception scores during the procedure (measured using a visual analog scale) than patients in group 1 (1.46+/-0.31 vs. 1.75+/-0.41; F1,42=6.484, P<0.015) and were less sedated during recovery (F1,41=6.56, P<0.015). No significant differences were found between the two groups with regard to heart rate or arterial blood pressure. All patients in group 2 were ready to go home after 25 minutes in the recovery area; three patients in group 1 were not ready to leave at 25 minutes and left the facility after 60 minutes. Four patients suffered from minor side effects of physostigmine (sweating and nausea). CONCLUSIONS: Combining physostigmine with meperidine as preparatory treatment for patients undergoing colonoscopy prevents respiratory depression, improves analgesia, and shortens recovery time, with only mild side effects.

Adult↗
PubMed2002

Remifentanil by patient-controlled analgesia compared with intramuscular meperidine for pain relief in labour.

BACKGROUND: The pharmacokinetics of remifentanil suggests that it may be suitable for analgesia during labour. METHODS: In an open pilot study, 36 women requesting meperidine for analgesia were recruited early in labour and randomized to receive either meperidine i.m. or remifentanil given as patient-controlled analgesia (PCA). Pain severity, sedation and anxiety were assessed with visual analogue scales and overall effective analgesia was assessed by the woman and midwife. RESULTS: The pain scores were lower in the remifentanil group: median pain score at 60 min was 72 mm for meperidine and 48 mm for remifentanil (P=0.004) and median maximum pain score during the first 2 h was 82.5 mm for the meperidine group and 66.5 mm for the remifentanil group (P=0.009). Both the midwives' and the women's assessments of overall effective analgesia were higher in the remifentanil group [Likert scale (5 = excellent to 1 = poor): chi2=12.10, P=0.002 for mothers' assessment; chi2=12.80, P=0.002 for midwives' assessment]. CONCLUSION: In this pilot study, remifentanil by PCA gave better pain relief to mothers in labour than intramuscular meperidine. However, remifentanil is a potent respiratory depressant and adequate continuous monitoring is necessary.

Adolescent↗
PubMed2003

Procainamide and quinidine inhibition of the human hepatic degradation of meperidine in vitro.

Procainamide and quinidine inhibition of the degradation of meperidine in human liver was investigated by incubation of two concentrations of either drug with meperidine in homogenates of human liver over 24 and 36 h. Meperidine concentrations declined by 26% after incubation for 24 h and by 42% after incubation for 36 h. In the presence of procainamide, however, they decreased by only 15% to 18% at 24 h and by only 26% to 28% at 36 h. In the presence of quinidine, they declined by only 18% to 19% at 24 h and by only 27% to 28% at 36 h. Procainamide and quinidine may inhibit human hepatic carboxylesterase hCE-1, which is responsible for catalyzing the hydrolysis of meperidine. This inhibition may prolong the biological half-life of meperidine in patients receiving the drug together with either procainamide or quinidine.

Chromatography, Gas↗
PubMed1997

Morphine patient-controlled analgesia is superior to meperidine patient-controlled analgesia for postoperative pain.

The choice between morphine and meperidine for postoperative pain is usually based on the preference of the prescriber, as few objective comparative data are available. This blind, randomized study compared the efficacy and side effects of morphine and meperidine administered by patient-controlled analgesia (PCA) for postoperative pain. One hundred two consenting patients scheduled for major abdominal surgery were randomly assigned to receive PCA with morphine (0.75, 1.0, or 1.5 mg bolus dose size) or meperidine (9, 12, or 18 mg) for pain control. Postoperative assessments included pain at rest and on sitting, nausea, unusual dreams, the Multiple Affect Adjective Check List (a measure of mood), and the trailmaking tests A and B (measures of ability to concentrate). Pain on sitting (P = 0.037) but not pain at rest (P = 0.8) was significantly less in patients receiving morphine. Meperidine use was associated with poorer performance in the trailmaking tests and a greater incidence of dryness of the mouth. Severity of nausea, mood, and incidence of unusual dreams did not differ significantly between drugs. We conclude that meperidine should be reserved for those patients in whom morphine is judged inappropriate.

Abdomen↗
PubMedDate not supplied

Comparison of hydromorphone and meperidine for ureteral colic.

OBJECTIVE: To compare the efficacies of meperidine and hydromorphone in the treatment for ureteral colic in the emergency department (ED). METHODS: A prospective, double-blind, randomized clinical trial was conducted over six months at a tertiary referral center with 93,000 annual ED visits. Seventy-three patients completed the study. The patients received either 1 mg of hydromorphone or 50 mg of meperidine IV at t = 0. Pain intensity was determined using a 10-cm visual analog scale at t = 0, 15, 30, 60, and 120 minutes. A second dose of the study drug could be given between t = 15 and t = 120 minutes when the clinician believed the initial dose was ineffective. Patients requiring more than one additional dose of analgesia were treated as nonresponders and were removed from the study. RESULTS: Thirty-six patients received hydromorphone and 37 received meperidine. The initial pain intensities (hydromorphone group = 8.4 +/- 1.5; meperidine group = 8.5 +/- 2.1), age distributions, sex distributions, and side effects of the two groups were comparable. Pain relief was better (p < 0.05) with hydromorphone at t = 15, 30, 60, and 120 minutes. The hydromorphone group required rescue analgesia less often (31% vs 68%, p < 0.01), had fewer IV pyelographies (IVPs) (28% vs 54%, p < 0.05), and had a lower proportion of hospital admissions (25% vs 49%, p = 0.08). CONCLUSIONS: For the fixed doses used in this study, the adult ureteral colic patients receiving hydromorphone achieved more pain relief, required less rescue medication, underwent fewer IVPs, and avoided hospital admission more frequently than did those receiving meperidine.

Adolescent↗
PubMed1978

Effects of 6-hydroxydopamine-induced depletions of brain catecholamines or dopamine on meperidine antinociception in rats.

The participation of brain norepinephrine (NE) and dopamine (DA) in the production of the antinociceptive effect of meperidine was investigated. Rats were permanently depleted of brain catecholamines via 6-hydroxydopamine treatments at 2 weeks of age. 6-8 weeks later, the antinociceptive activity of meperidine was determined in control, NE- and DA-depleted, and DA-depleted rats by both the tail-flick and hot-plate methods. The antinociceptive activity of meperidine was reduced in DA-depleted male rats. In DA-depleted female rats, however, the antinociceptive activity was increased at low doses of meperidine and decreased only at higher doses of the drug. In male NE + DA-depelted rats, the activity was generally intermediate between that seen in DA-depleted and control rats. No consistent change in the activity of meperidine was observed in female NE + DA-depleted rats.

Analgesics↗
PubMed1976

Effect of meperidine on occlusion pressure responses to hypercapnia and hypoxia with and without external inspiratory resistance.

In 5 normal subjects we measured ventilation and P0.1, the pressure generated by the first 0.1 sec of inspiratory effort against a closed airway, in response to hypercapnia and hypoxia with and without added inspiratory resistance before and after oral meperidine (1.1 to 1.3 mg per kg). CO2 responses were studied in the steady state, whereas progressive hypoxia was used to elicit hypoxic responses. In general, resistance decreased ventilatory responses to hypercapnia but increased P0.1 responses to both hypoxia and hypercapnia. Meperidine depressed both ventilatory and P0.1 responses, more so in hypoxia than in hypercapnia. The combination of resistance and merperidine was additive in depressing responses to hypercapnia but in hypoxia produced little more depression than did meperidine alone. In both hypercapnia and hypoxia, meperidine decreased the augmentation of P0.1 that was associated with increased resistance. Normal subjects responded to acute increases of inspiratory resistance by increasing inspiratory motor output; this increase was distinctly blunted by meperidine.

Adult↗
PubMed1987

Meperidine-induced delirium.

Despite the widespread use of meperidine as an analgesic, its potential for producing delirium has been overlooked. Six cases demonstrating meperidine-induced behavioral toxicity are reported. Toxicity was more likely when meperidine was combined with cimetidine or drugs having anticholinergic activity. Discontinuation of meperidine and substitution of morphine for analgesia were usually successful in treating the delirium. Physostigmine reversed the delirium in one patient. The authors suggest that the delirium results from the excessive anticholinergic activity of meperidine or its only active metabolite, normeperidine.

Adult↗
PubMed1999

Low frequency of meperidine-associated seizures in sickle cell disease.

Pain control measures in sickle cell diseases are not uniform. Most clinicians use parenteral morphine or meperidine for severe pain. Reports of seizures associated with meperidine have led to a growing reliance on intravenous morphine, usually with patient-controlled devices. Acceptance of morphine has been poor among patients, and many prefer meperidine. The aim of this retrospective study was to determine the incidence of meperidine-associated seizures in a large, mostly pediatric population with sickling disorders. The results suggest that the incidence of seizures with meperidine is extremely small (0.4% of patients; 0.06% of admissions). The risk of seizures should not dissuade clinicians from using this drug.

Adolescent↗
PubMed1992

Neonatal pattern of breathing during active and quiet sleep after maternal administration of meperidine.

The aim of this study was to reappraise the effects of maternal meperidine administration on breathing pattern during the first hours of life taking into account the state of alertness. Because breathing instability is more pronounced during active sleep, we hypothesized that meperidine administration might create a greater risk for respiratory instability during active sleep, the prominent sleep state in newborns. We studied eight full-term, healthy newborns whose mothers had received a continuous i.v. infusion of meperidine (81 +/- 9 mg) that was terminated 5.5 +/- 2.1 h before delivery. These infants were compared with a control group of eight full-term newborns whose mothers did not receive any opioids. In both groups, all babies were delivered vaginally after a normal labor and had Apgar scores of 9 or 10 at 1 and 5 min. Neonatal gastric secretion and maternal venous and umbilical venous blood were sampled at delivery for determination of meperidine concentration. From 60 to 300 min after delivery, behavioral sleep states and thoracic and abdominal movement as well as transcutaneous arterial oxygen saturation (SaO2) were monitored continuously. The number of apneic spells lasting more than 3 s during 100 min of recording and the percentage of time with SaO2 below 90% in each sleep state were recorded. During quiet sleep, all respiratory variables were similar in both groups. During active sleep, there were significantly more apneic episodes (37.1 +/- 25.1 versus 11.2 +/- 13.9) and a higher percentage of time with SaO2 less than 90% (14.3 +/- 16.7% versus 1.3 +/- 1.5%) in the meperidine group than in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMedDate not supplied

Cardiovascular effects of meperidine-N2O anesthesia before and after pancuronium.

The cardiovascular effects of 2 and 3 mg/kg of meperidine plus 60 to 67% N2O in O2 on cardiovascular dynamics in man were measured before and after the administration of 0.08 mg/kg of IV pancuronium. N2O and 2 mg/kg of meperidine did not change heart rate (HR) but produced a marked reduction (-49%) in cardiac output (QT) plus significant decreases in stroke volume (SV) and blood pressure (BP) and an increase in peripheral arterial resistance (PVR). Additional meperidine did not further alter any of the variables; however, surgical stimulation caused significant increases in HR, BP, and PVR. SV and QT were not significantly changed by surgical stimulation and were still markedly depressed when compared to control values. Pancuronium produced marked increases in HR, SV, QT, and BP and a reduction in PVR. These changes were maximal 4 to 8 minutes after pancuronium and returned toward pre-pancuronium values thereafter. These data demonstrate that N2O-meperidine anesthesia results in a moderate reduction in BP but a marked depression in QT. The findings also indicate that pancuronium reverses the cardiovascular depression produced by N2O-meperidine and is therefore, a desirable muscle relaxant when the above technic is employed.

Anesthesia, General↗
PubMed1991

Prolongation of the pharmacologic effect of intrathecal meperidine by the use of a lipid solution of it.

The possibility of prolonging the effect of intrathecally injected meperidine by the use of a lipid solution was examined in this study. An aqueous solution of 5% meperidine HCl, 250 micrograms/kg, and an equimolar solution of meperidine dissolved in iophendylate (Pantopaque) were injected subarachnoidally in two groups of rabbits (n = 9 in each) with chronically implanted catheters in the subarachnoid space at the level of L7-8. The effect of each injection was assessed by evaluation of the pain threshold in the animal's hind limbs and of the degree of motor blockade produced. The duration of analgesia and of motor blockade were significantly longer when the lipid solution was used. Six of nine animals that received the aqueous solution of 5% meperidine HCl exhibited temporary signs of agitation (i.e., biting of hind limbs). None of the animals given the lipid solution of the drug did. The findings are attributed to the slow release of meperidine from the lipid phase that serves as a drug depot in the cerebrospinal fluid. The approach presented is suggested as a basis for the development of lipid solutions that might prolong the duration of spinal analgesia produced by a single intrathecal injection.

Animals↗
PubMed1992

Comparison among intrathecal fentanyl, meperidine, and sufentanil for labor analgesia.

This study compared the analgesic efficacy of intermittent injections of intrathecal fentanyl (10 micrograms), meperidine (10 mg), or sufentanil (5 micrograms) administered to 65 parturients during the first stage of labor. The groups did not differ in onset or duration of effective analgesia. The meperidine group, however, had significantly lower pain scores once cervical dilation progressed beyond 6 cm. Side effects included mild pruritus and nausea. After intrathecal drug injection, variable decelerations of the fetal heart rate increased in the fentanyl and meperidine groups. All neonates had a 5-min Apgar score of 7 or more. We conclude that intermittent intrathecal injections of fentanyl, meperidine, or sufentanil can provide adequate first-stage labor analgesia. Meperidine appears to provide more reliable analgesia as the first stage of labor progresses.

Adult↗
PubMedDate not supplied

Comparison of ketorolac-chlorpromazine with meperidine-promethazine for treatment of exacerbations of chronic pain.

BACKGROUND: The aim was to compare the efficacy and safety of a combination of intramuscular ketorolac and chlorpromazine for the treatment of acute exacerbations of chronic pain with the more commonly used regimen of intramuscular meperidine and promethazine. METHODS: Use-effective case series were drawn from a real-life, rural emergency department practice, in which 200 consecutive patients coming to a rural emergency department with acute exacerbations of chronic pain syndromes were assigned on an every-other basis in a single-blind fashion to one of the two treatment conditions. Patients were given intramuscular doses of either 60 mg of ketorolac plus 50 mg of chlorpromazine (75 mg of chlorpromazine for patients weighing more than 100 kg), or 50 mg of meperidine plus 25 mg of promethazine (50 mg of promethazine for patients weighing more than 75 kg); patients weighing more than 100 kg were given 1.5 doses. Patients older than 65 years or whose blood pressure at the time of injection was less than 110/70 mmHg were given half-doses. Patients could receive one additional half-dose injection if they had no results within 30 to 60 minutes after the first injection. Patients were assessed on self-report and on a verbal and visual analog scale of pain rating. Temperature, blood pressure, heart rate, and respirations were monitored every 15 minutes. RESULTS: Both regimens performed well, with more than 90 percent of patients reporting good or excellent improvement on acute exacerbations of chronic pain. Ketorolac-chlorpromazine offered significant advantages compared with meperidine-promethazine when patients rated their pain on a visual analog pain scale (P < 0.05) but not on a verbal scale. Adverse reactions were minimal and consisted of more respiratory tract depression with meperidine and more vertigo or dizziness with chlorpromazine. There was no difference in incidence of hypotension between the two groups. CONCLUSIONS: The combination of ketorolac and chlorpromazine is a safe and efficacious alternative to meperidine plus promethazine for the treatment of exacerbations of chronic pain in the rural emergency department setting.

Adolescent↗
PubMed1989

Intrathecal meperidine as the sole agent for cesarean section.

Recently several reports have described the usefulness of meperidine as the sole agent for spinal anesthesia. In this study, meperidine 50mg mixed with 10% dextrose 0.5ml was used for the spinal anesthetic agent for Cesarean section in 182 cases. The subarachnoid injection of meperidine resulted in anesthesia similar to that noted with the intrathecal administration of local anesthetics. Sensory and motor blockades in all patients with meperidine spinal anesthesia were obtained. Prolonged analgesic effect (453.7 +/- 158.1 minutes) and rapid motor recovery (75.9 +/- 17.2 minutes) were obtained. Side effects included nausea (49 patients), hypotension (95 patients) and pruritus (30 patients). Hypotension was easily treated with rapid hydration and ephedrine. Eighteen patients complained of mild pain during the last period of operation. At birth, all newborns cried immediately and the mean Apgar scores were 9.8 +/- 0.4 at one minute and 10 at 5 minutes. It is concluded that meperidine, which has advantages such as rapid motor recovery, prolonged postoperative analgesia, and mild complications which may be easily treated, can serve as a good alternative agent for spinal anesthesia for Cesarean section.

Adult↗
PubMed1977

Accumulation of normeperidine, an active metabolite of meperidine, in patients with renal failure of cancer.

Concentrations of meperidine and its active metabolite, normeperidine, were measured in plasma of patients receiving the drug for analgesia. Meperidine levels in cancer patients were 0.10 to 0.55 microng/ml 1 h after a dose and were 0.05 to 0.14 in patients in the oliguric period after renal transplantation. Normeperidine levels were 0.05 to 0.28 microng/ml in the cancer patients and 0.13 to 0.36 in the renal failure patients. The ratio of normeperidine to meperidine levels was always higher in the renal failure patients than in the cancer patients. Additionally, two patients receiving multiple doses of meperidine had high normeperidine levels and very high normeperidine/meperidine ratios when they showed signs of central nervous system excitation. These data indicate that normeperidine can contribute to the excitatory effects seen after multiple doses of meperidine and suggest that patients with renal failure are particularly susceptible to this problem.

Acute Kidney Injury↗
PubMed1975

Production and characterization of antibodies to meperidine.

A mepridine-bovine serum albumin (Mep-BSA) conjugate with 15-20 moles of meperidine per mole of BSA was synthesized and characterized. Rabbits immunized with Mep-BSA produced antibodies that were assayed utilizing saturated ammonium sulfate to separate 3H-meperidine (3H-M) bound to antibody from free 3H-M. Antibody specificity was assessed by competitive inhibition studies. The nanomoles of inhibitor required to decrease the binding of 3H-M by 50% were: meperidine .046; meperidine acid, 3.2; alphaprodine, 7.8; dextromethorphan, 20; codeine, 50; and morphine 55. The sensitivity of the assay is approximately 30 ng/ml; sufficient for pharmacokinetic studies of the disposition of meperidine in man.

Animals↗