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Ketorolac vs meperidine for the management of pain in the emergency department.

OBJECTIVE: To compare the pain relief, sedation, and common side effect profiles of ketorolac tromethamine and meperidine for the management of acute pain in the emergency department (ED). METHODS: A prospective, double-blind, randomized clinical trial was conducted over a 12-month period using consecutive adult patients presenting to a university teaching hospital ED (annual census: 32,000), who required IM analgesia for acute pain. Adult patients with acute pain of various etiologies were randomly assigned to receive a single fixed IM dose of ketorolac (60 mg) or meperidine (100 mg). RESULTS: Ninety-three patients were enrolled in the study; 46 were randomized to meperidine and 47 to ketorolac. Using a visual analog scale, there was no difference in pain relief between the ketorolac and meperidine groups even after adjusting for baseline pain level. Ketorolac caused significantly (p < 0.005) less sedation than did meperidine at one hour. Rescue analgesia was required for seven of the 46 (15.2%) patients receiving meperidine and five of the 47 (10.6%) patients receiving ketorolac (p = NS). Seventeen of 45 (38%) patients receiving meperidine experienced side effects compared with eight of the 47 (17%) patients receiving ketorolac (p = 0.0452). CONCLUSIONS: When used to treat patients who had acute pain states, 60 mg of IM ketorolac produced analgesia similar to that produced by 100 mg of IM meperidine; however, the ketorolac produced fewer subjective side effects and less sedation than did the meperidine.

Adolescent↗

Patient-controlled analgesia with epidural meperidine after elective cesarean section.

BACKGROUND AND OBJECTIVES: We report the first controlled analysis of the use of patient-controlled epidural meperidine. This randomized, prospective study compares the efficacy and safety of patient-controlled epidural meperidine to conventional intramuscular meperidine for the management of postoperative pain after elective cesarean delivery. METHODS: After delivery, 60 patients were randomly assigned to receive either conventional intramuscular meperidine therapy or epidural meperidine by a patient-controlled analgesia pump, which was programmed to deliver bolus doses in addition to a continuous background infusion. RESULTS: Patients in the patient-controlled epidural analgesia group used significantly less meperidine in the first 24 hours after surgery (p < 0.05) and had significantly lower visual analog pain scores (p < 0.05) from three hours postoperatively until study completion at 24 hours. Patients in the patient-controlled epidural analgesia group ambulated sooner (19 +/- 7.8 versus 29.2 +/- 2.2 hours, p < 0.005) and cared for their infants earlier (4.6 +/- 0.9 versus 8.1 +/- 6.8 hours, p < 0.05) than patients receiving intramuscular meperidine. One patient developed a respiratory rate of four breaths per minute, 25 minutes after receiving 75 mg epidural meperidine in the operating room. This was treated with intravenous naloxone. No other serious side effects occurred in either group. Both groups were similar with regard to minor intraoperative and postoperative side effects. CONCLUSIONS: Patient-controlled epidural meperidine after cesarean delivery more effectively manages postoperative pain than conventional intramuscular use. The technique is preferred by both patients and nursing staff and can be used in the ward setting with appropriate organization and education. Respiratory depression, if it occurs, should present early after epidural bolus administration.

Adult↗

Diazepam enhances fentanyl and diminishes meperidine antinociception.

A rabbit tooth pulp antinociceptive model was used to investigate the effect of prior administration of diazepam or muscimol on the potency and duration of fentanyl and meperidine Potency experiments compared ED(50) values in all-or-none dose-response assays between both muscimol (0.25 mg/kg) and saline, and diazepam (1.5 mg/kg) and propylene glycol vehicle. An all-or-none effect was defined as doubling of voltage threshold to elicit a lick/chew evoked response. Duration experiments compared time (minutes) to 50% maximum possible effect (MPE) of an ED(90) dose of fentanyl (0.04 mg/kg) and to 50% and 20% MPE of an ED(98) dose of meperidine (17 mg/kg) 10 minutes after pretreatment with diazepam (1.5 mg/kg). Prior (10 minutes) injection of diazepam (1.5 mg/kg) increased the ED(50) value for meperidine (3.06 mg/kg) compared with its control (1.48 mg/kg), indicating a decrease in antinociceptive potency. The same dose of diazepam decreased the ED(50) value for fentanyl (1.1 μg/kg) compared with its control (13.1 μg/kg), indicating an increase in antinociceptive potency. Muscimol also had a similar effect on fentanyl (ED(50), 1.8 μg/kg) compared with saline control (ED(50), 13.8 μg/kg). Diazepam, vehicle, and muscimol by themselves had no effect on voltage thresholds to elicit a lick/chew response. Time to 50% MPE for diazepam-fentanyl was 38 minutes vs. 25 minutes for vehicle-fetanyl; time to 20% MPE for diazepam-meperidine was 38 minutes vs. 54 minutes for vehicle-meperidine (maximum percentage of MPE produced by diazepam-meperidine was 40% compared with 100% MPE for vehicle-meperidine). Percentages of MPE for diazepam-meperidine were significantly lower than those for vehicle-meperidine at all time intervals, whereas percentages of MPE for diazepam-fentanyl were significantly greater than those for vehicle-fentanyl over time.

Animals↗

Neonatal neurobehavior in the first 48 hours of life: effect of the administration of meperidine with and without naloxone in the mother.

The early neonatal neurobehavioral scale was administered to three groups of newborns at 2, 4, and 24 hours of age. Group 1 consisted of 28 babies whose mothers had received no narcotics during labor, group 2 of 33 babies whose mothers had received meperidine hydrochloride alone during labor, and group 3 of 40 babies whose mothers had received meperidine followed by 0.4 mg of naloxone hydrochloride intravenously approximately 15 minutes before delivery. Babies who were not exposed to meperidine showed a statistically significantly greater percentage of high scores than those exposed to meperidine alone for all items on the neurobehavioral scale at 2 and 4 hours and for all items except tone and Moro response at 24 hours. Similarly, babies whose mothers had received meperidine and naloxone showed a significantly greater percentage of high scores than those whose mothers had received meperidine alone at 2 hours of age. At 4 hours a difference was found for tone and rooting and at 24 hours for overall score, placing, and total decrement score. It is concluded that naloxone given intravenously to the mother reverses the effect of meperidine on neonatal neurobehavior for approximately two hours after birth. At 4 and 24 hours, however, the neurobehavior of neonates exposed to meperidine and naloxone is depressed almost as much as that of babies exposed to meperidine alone.

Child Behavior↗

Intrathecal meperidine for labor analgesia: preliminary communication.

The authors administered intrathecal meperidine 10 mg to 10 healthy laboring women to determine its analgesic quality, onset, duration, and side-effect profile. When patients requested pain relief, we injected 10 mg preservative-free meperidine in 1 ml normal saline through a 32 gauge spinal catheter. We administered a second dose of meperidine 10 mg if analgesia was inadequate at 10 min. Additional doses of intrathecal meperidine or bupivacaine were administered on request. All patients received local anesthetic intrathecally or by infiltration for delivery. Eight patients were pain-free following meperidine 10 mg, the other 2 patients were comfortable after the second 10 mg meperidine dose. Three patients did not request further labor analgesics and delivered 58, 66 and 244 min following their initial injection of intrathecal meperidine. The mean duration of analgesia in the other 7 patients was 136 +/- 58 (mean +/-SD) min. Six of the 10 women in the study delivered vaginally; 3 spontaneously and 3 with vacuum or forceps assistance. Four patients delivered by cesarean section for failure to progress. Side-effects (which were easily treated) consisted of: pruritus (n = 1), vomiting (n = 2), hypotension (n = 2) and changes in fetal heart rate pattern (n = 5). All infants were vigorous and had good Apgar scores at birth. In conclusion, intrathecal meperidine is a promising labor analgesic, but the effect of meperidine on maternal blood pressure, fetal heart rate pattern, and the progress of labor need to be determined.

Journal Article↗

The effect of phenobarbital on the metabolism of meperidine in normal volunteers.

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.

Adult↗

Urinary excretion of meperidine and its metabolites.

The urine of male and female mice, rats, guinea pigs, rabbits, cats, and dogs, given meperidine hydrochloride, 20--40 mg/kg ip, was analyzed by GLC for meperidine, normeperidine, p-hydroxymeperidine, and total (free and conjugated) meperidinic and normeperidinic acids. More than 90% of the excreted drugs was found in the 24-hr urine. Meperidine was observed in the urine of mice, rats, guinea pigs, and cats, but only a trace amount was observed in the urine of rabbits and dogs. Normeperidine, p-hydroxymeperidine (except in the mice), and total meperidinic and normeperidinic acids were observed in all species. All of the species studied have the capacity to N-demethylate meperidine to normeperidine and to hydrolyze meperidine and normeperidine to their respective acids. The male has a higher N-demethylating activity that the female with the exception of mice. Ester hydrolysis is a major metabolic pathway for meperidine metabolism.

Animals↗

Subjective, behavioral and physiological responses to intravenous meperidine in healthy volunteers.

Meperidine is a mu opiate agonist that is frequently used to treat pain. We examined in healthy volunteers (N = 10) the effects of intravenous meperidine (0, 0.25, 0.5, and 1.0 mg/kg) on mood and psychomotor performance. A randomized, placebo-controlled, crossover design was used in which subjects were injected with meperidine or saline in a double-blind fashion. Subjects completed several subjective effects questionnaires commonly used in abuse liability testing studies before drug injection and at periodic intervals for up to 5 h after drug injection. Subjects also completed several psychomotor tests. Meperidine produced a constellation of subjective effects in a dose-related fashion, including increases in ratings of "sedated," "coasting or spaced out" and "feel drug effect" ratings. Many of the drug's subjective effects persisted up to 4 or 5 h after administration of the 1.0 mg/kg dose. Drug liking ratings assessed on a visual analog scale were increased after meperidine injection in about half of the subjects (P = 0.09). Eye-hand coordination was affected slightly by meperidine but other indices of psychomotor functioning were unaffected. Miosis increased in a dose-related fashion. Other physiological parameters, such as vital signs, were not affected by meperidine. We conclude that meperidine in healthy volunteers has robust and long-lasting effects on mood, but may have weaker effects on psychomotor performance.

Adult↗

Disposition of meperidine and normeperidine following multiple doses during labor. I. Mother.

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.

Adolescent↗

Disposition of meperidine and normeperidine following multiple doses during labor. II. Fetus and neonate.

It has been suggested that continued diffusion gradients from mother to fetus would exist and that both meperidine and normeperidine would accumulate in the fetus following multiple doses of meperidine to the mother during labor. However, no pharmacokinetic data are available. Therefore, the purpose of this study was to document the disposition of meperidine and normeperidine in the fetus and neonate following multiple doses of meperidine to the mother over long time periods. Twelve infants were studied. The results show surprisingly high concentrations of both meperidine and normeperidine in fetal blood at delivery. In addition, the amount of normeperidine increased with time in umbilical cord blood, the ratio of normeperidine to meperidine increased with time, and the umbilical artery-to-vein ratio of meperidine (but not normeperidine) was greater than one following long drug-to-delivery intervals. The data also suggest that with long drug-to-delivery intervals the levels of normeperidine may become clinically important and that the elimination of both compounds by the neonate is prolonged. The study suggests that multiple doses to the mother over long time periods result in maximum accumulation of both meperidine and normeperidine in fetal tissues.

Female↗

The cocaine-like behavioral effects of meperidine are mediated by activity at the dopamine transporter.

Meperidine has atypical opioid receptor agonist effects and shares some structural features with the phenyltropane (WIN) analogs of cocaine. In combination with 0.1 mg/kg naltrexone, meperidine produced cocaine-like discriminative stimulus effects in monkeys, whereas morphine was inactive. Both cocaine and meperidine inhibited [3H]dopamine uptake in chopped rat caudate putamen with comparable potencies; meperidine differed from cocaine in that its effects could be characterized as having predominantly a single high-affinity component. Morphine was not active in inhibiting [3H]dopamine uptake, indicating that the effect of meperidine was not via a classic mu-opioid receptor agonist action. Further, meperidine but not morphine displaced [3H]WIN 35,428 (2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane) binding. These data suggest that the actions of meperidine that are atypical of opioids are due to activity at the dopamine transporter. In addition, meperidine appears to interact predominantly with the high-affinity component of the dopamine transporter, and this high-affinity component may be the site of importance for the production of cocaine's behavioral effects.

Animals↗

Eliminating analgesic meperidine use with a supported formulary restriction.

PURPOSE: Meperidine is a commonly used analgesic despite unique disadvantages compared with other opioid analgesics. The objective of this study was to measure the effects of a meperidine formulary restriction on the prescribing of parenteral opioid analgesics. MATERIALS AND METHODS: The study was performed at a single 750-bed tertiary care teaching hospital in Rochester, NY. The formulary restriction limited meperidine to use exclusively for rigors or procedural sedation and was supported by an educational initiative and a computerized order entry system. Independent computerized pharmacy records were used to capture all doses of parenteral morphine, meperidine, and hydromorphone administered to patients in the emergency department or on a medical or surgical inpatient floor during data-collection periods. Baseline data were collected during two 3-day periods before the formulary restriction; then comparison data were collected during three 3-day periods over 15 months after the formulary restriction. RESULTS: The number of administered doses of meperidine per day decreased from 37.5 (20.8% of parenteral opioid doses before the restriction) to 0.22 (0.1% of parenteral opioid doses, P = .001). The total number of opioid doses and morphine doses given did not change, whereas the number of hydromorphone doses increased significantly postrestriction, from 16.0 doses per day (8.9% of total) to 59.7 doses per day (29.5%) (P = .009). CONCLUSION: Meperidine formulary restriction, supported by an educational program and computerized order entry, effectively eliminated analgesic meperidine use. Hydromorphone use increased proportionately to offset the decreased use of meperidine.

Analgesics, Opioid↗

Effects of meperidine on the pancreatic and biliary sphincter.

BACKGROUND: Opioids are traditionally avoided during sphincter of Oddi manometry because of indirect evidence suggesting that these agents cause sphincter of Oddi spasm. This study was undertaken to determine the direct effects of meperidine on the biliary and pancreatic sphincter. METHODS: Forty-seven patients were prospectively evaluated by sphincter of Oddi manometry in the conventional retrograde fashion. Manometry was initially performed with intravenous diazepam sedation alone. The manometry was repeated 3 to 5 minutes after meperidine was administered. RESULTS: The basal sphincter pressure of the biliary sphincter, pancreatic sphincter, and the combined sphincter group were not significantly altered by meperidine. Concordance (normal versus abnormal) between the basal sphincter pressure before and after meperidine was seen in 44 of 47 patients (94%). Meperidine produced a significant increase in the pancreatic, biliary, and combined sphincter phasic frequency and a significant decrease in the phasic duration. The pancreatic and combined sphincter phasic pressures were significantly reduced following meperidine administration. Seventeen manometry tracings (36%) were believed to be qualitatively better after meperidine, while only four (8.5%; p < .001) were qualitatively better with diazepam alone. CONCLUSION: Meperidine can be used for additional analgesia during sphincter of Oddi manometry if the basal sphincter pressure is the parameter used to determine therapy.

Humans↗

Comparison of intravenous ketorolac and meperidine in the treatment of biliary colic.

To compare the analgesic efficacy and tolerability of intravenous (IV) ketorolac tromethamine with IV meperidine in the treatment of biliary colic, a prospective, randomized, double blind study was carried out upon a convenience sample of patients at a large inner city facility. Patients between the ages of 18 and 65 years of age with a history and physical examination consistent with biliary colic were enrolled over a 2-year period. Patients were randomly assigned to receive ketorolac 30 mg IV or meperidine 50 mg IV. Pain was quantified using a 4-point verbal rating system (VRS) as well as a visual analog scale (VAS). Patients were queried about their pain at times 0, 12 h, 1 h, and 2 h after administration of the study medication. Adverse effects were also recorded. A total of 324 patients completed the study protocol with 175 patients receiving ketorolac and 149 receiving meperidine. Patient demographics were similar for both groups with mean age for the ketorolac group of 36.1 years and for the meperidine group of 34.6 years. Both groups were predominantly Latino and over 80% of patients in both groups were female. No significant difference in pain control was found between ketorolac and meperidine in either the VAS or VRS for any time interval studied. The mean change in the VAS at time 2 h was 6.2 cm +/- 3.6 cm for the ketorolac group, compared with 6.7 cm +/- 3.6 cm for the meperidine group (p = 0.25). Although no significant difference was found in overall drug tolerability, patients receiving meperidine reported higher incidences of nausea and of dizziness than those receiving ketorolac (p = 0.009 and 0.003, respectively). Ketorolac tromethamine is a well-tolerated, effective medication in the treatment of acute biliary colic. It showed similar efficacy to meperidine with a decreased number of adverse effects.

Adult↗

Effects of tramadol and meperidine on respiration, plasma catecholamine concentrations, and hemodynamics.

STUDY OBJECTIVE: To evaluate the effects of high analgesic doses of tramadol and meperidine on respiration, plasma catecholamine concentrations, and hemodynamic parameters. STUDY DESIGN: Randomized, double-blind, cross-over, controlled volunteer study. SETTING: Laboratory at a university hospital. SUBJECTS: 8 healthy male volunteers. INTERVENTIONS: Tramadol was given as a 150 mg bolus plus a succeeding 3-hour steady infusion of 250 mg (83.3 mg/hr). Meperidine was given in a similar manner as a bolus dose of 112.5 mg plus 187.5 mg in a 3-hour steady infusion (62.5 mg/hr). Experimental pain was induced using a tourniquet. MEASUREMENTS AND MAIN RESULTS: Respiration was studied noninvasively with respiratory inductive plethysmography and pulse oximetry. Arterial line was used for measurement of hemodynamics and blood sampling. Tramadol did not have any clinically significant effects on respiration, breathing pattern, or hemodynamics, but an increase in plasma epinephrine levels was noted. Meperidine bolus decreased tidal volume (p < 0.05, difference from baseline) and pulse oxygen saturation (from 97% to 94%, p < 0.05), but during the succeeding infusion, the respiratory drive, measured as mean inspiratory flow, was enhanced (p < 0.05 difference from baseline), and the respiratory parameters returned to baseline level. No change in hemodynamics was noted, but a significant increase in plasma norepinephrine and epinephrine levels (from 0.9 to 1.6 nmol/L and from 0.3 to 0.8 nmol/L, respectively; p < 0.05) was observed after meperidine administration. Tramadol caused nausea more often than meperidine (p < 0.05, between treatments). CONCLUSIONS: Tramadol exhibited a minimal effect on respiration and breathing pattern in healthy volunteers. The respiratory effects of meperidine bolus were predictable with decreasing tidal volume and pulse oxygen saturation. In contrast, during meperidine infusion, adequate respiration was preserved despite the large amount of meperidine infused.

Adult↗

Effect of phenytoin on meperidine clearance and normeperidine formation.

The presystemic metabolism of meperidine to normeperidine was examined in four healthy men before, during, and 3 wk after phenytoin. The results from the two control periods were similar. Meperidine systemic clearance rose from 1017 +/- 225 ml/min (mean +/- SD) to 1280 +/- 130 ml/min during phenytoin dosing (P less than 0.01). Meperidine elimination half-life fell from 6.4 +/- 1.0 hr to 4.3 +/- 0.4 hr during phenytoin dosing (P less than 0.05). Bioavailability fell from 0.61 +/- 0.08 to 0.43 +/- 0.14 (P less than 0.07). Meperidine volume of distribution, renal clearance, and protein binding did not change. The normeperdine area under the blood concentration-time curve from 0 to 24 hr after intravenous meperidine rose from 385 +/- 105 ng/hr/ml-1 to 589 +/- 108 ng/hr/ml-1 during phenytoin dosing (P less than 0.01); after oral meperidine it rose from 592 +/- 50 ng/hr/ml-1 to 738 +/- 178 ng/hr/ml-1. Normeperidine renal clearance was approximately four times that of meperidine, but was not altered by phenytoin. Because analgesia relates to meperidine blood concentrations, patients on long-term phenytoin therapy may require more frequent parenteral doses and larger and more frequent oral doses than usual.

Adult↗

Effects of intraoperative i.v. acetaminophen vs i.m. meperidine on post-tonsillectomy pain in children.

BACKGROUND: Enteral acetaminophen, when used alone, is not very effective for postoperative analgesia because of delayed absorption and sub-therapeutic plasma concentrations. In contrast, i.v. acetaminophen is devoid of these shortcomings and could potentially provide adequate postoperative analgesia as a single agent. This randomized double-blind study compared the analgesic effects of i.v. acetaminophen and i.m. meperidine in paediatric patients undergoing tonsillectomy. METHODS: Eighty children undergoing tonsillectomy were randomized to receive either acetaminophen 15 mg kg(-1) i.v. (acetaminophen group) or meperidine 1 mg kg(-1) i.m. (meperidine group), intraoperatively. Anaesthesia was induced with either sevoflurane inhalation or propofol, and was maintained with sevoflurane. After operation, the objective pain scale (OPS), Ramsay sedation score and Aldrete score were recorded every 5 min, and nurses' satisfaction was determined on a 7-point scale (1-7). RESULTS: On admission to the recovery room, OPS scores were 3.1 (sem 0.3) for the acetaminophen group and 2.1 (sem 0.3) for the meperidine group (P=0.147); however, Ramsay sedation scores were 3 (sem 0.2) and 4 (sem 0.3) for the acetaminophen and meperidine groups, respectively (P<0.05). Patients in the meperidine group continued to be more sedated 5 min after arrival in recovery (P<0.05). Acetaminophen group patients achieved an Aldrete score of 10 min sooner than those in the meperidine group [median (IQR) time: 15 (0-20) min vs 25 (15-30) min, respectively, P=0.005]. Adjusted nurse satisfaction scores were similar in both groups [6.1 (sem 0.2) vs 5.7 (sem 0.2) min, P=0.311]. CONCLUSION: Compared with i.m. meperidine, i.v. acetaminophen provided adequate analgesia, less sedation and earlier readiness for recovery room discharge among paediatric patients undergoing tonsillectomy.

Acetaminophen↗

Patient-controlled epidural analgesia after thoracotomy: a comparison of meperidine with and without bupivacaine.

The purpose of this study was to compare meperidine to meperidine with bupivacaine when used for patient-controlled epidural analgesia (PCEA) after thoracotomy. For 3 days after thoracotomy patients received thoracic PCEA with meperidine 0.1% plain or with added bupivacaine 0.1% or 0.01%. No background infusion was used. All patients received indomethacin postoperatively for the duration of the study. Patients were assessed with respect to meperidine consumption, analgesia, and side effects. Sixty-six patients participated. Patients in all three groups obtained effective analgesia with median meperidine consumption of 5-6 mg/h. There were no significant differences between groups in meperidine consumption or pain scores at rest or with coughing. The addition of bupivacaine 0.1% reduced the incidence of pruritus (P = 0.036), but 5 of 23 patients in this group were with-drawn from the study because of significant hypotension, oliguria, and/or motor or sensory block (P = 0.006). We conclude that the addition of bupivacaine 0.1% or 0.01% to thoracic PCEA meperidine 0.1% does not affect meperidine requirements or analgesia after thoracotomy. The addition of bupivacaine 0.1% may reduce pruritus, but is associated with signs of excessive sensory, motor, or autonomic blockade in a significant number of patients.

Adult↗