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Subarachnoid meperidine (Pethidine) causes significant nausea and vomiting during labor. The Duke Women's Anesthesia Research Group.

BACKGROUND: The combined spinal-epidural (CSE) technique using bupivicaine-fentanyl has become an established method of pain control during parturition. One limitation is the relatively short duration of effective analgesia produced by bupivicaine-fentanyl. In contrast, subarachnoid meperidine has been shown to provide a long duration of anesthesia in nonobstetric patients. Therefore, the authors tested the hypothesis that subarachnoid meperidine produces a significant increase in the duration of analgesia compared with bupivicaine-fentanyl. METHODS: Based on a power analysis of preliminary data, the authors intended to recruit 90 patients for the study, randomized to three groups: 2.5 mg bupivicaine-25 microg fentanyl, 15 mg meperidine, or 25 mg meperidine. However, after enrolling 34 patients, the study was discontinued because of a significant increase in nausea or vomiting in the study patients. RESULTS: Nausea or vomiting was substantially increased in both meperidine groups compared with the bupivicaine-fentanyl group: 16 with nausea or vomiting in the meperidine groups (n = 21), compared with 1 in the bupivicaine-fentanyl group (n = 11), P = 0.0011. The mean duration of analgesia provided by 25 mg meperidine was 126 +/- 51 min, compared with 98 +/- 29 min for bupivicaine-fentanyl and 90 +/- 67 min for 15 mg meperidine. These data were not significant (P = 0.27). CONCLUSIONS: Although intrathecal meperidine could potentially prolong subarachnoid analgesia during labor, its use was associated with a significant incidence of nausea or vomiting. These data do not support the use of subarachnoid meperidine in doses of 15 or 25 mg for labor analgesia.

Adult↗

Meperidine: a critical review.

Meperidine was initially synthesized as an anticholinergic agent but was soon discovered to have analgesic properties. Although meperidine's anticholinergic effects were demonstrated in vivo, the anticholinergic effects on the biliary and renal tracts have not been demonstrated in vivo. Studies have clearly demonstrated that meperidine is no more efficacious in treating biliary or renal tract spasm than comparative mu opioids. The initial studies demonstrating the analgesic efficacy of meperidine were mostly case reports and not double-blind, randomized, controlled trials in specific populations. Subsequent comparative studies failed to demonstrate any advantages of meperidine over comparable doses of other analgesics. Meperidine was portrayed in practice and teaching as having unique clinical advantages. The analgesic effects of meperidine are not pronounced, and, in addition, meperidine use is complicated by unique side effects including serotonergic crisis and normeperidine toxicity. Meperidine's poor efficacy, toxicity, and multiple drug interactions have resulted in a movement to replace meperidine with more efficacious and less toxic opioid analgesics.

Adjuvants, Anesthesia↗

Meperidine binding to isolated alpha 1-acid glycoprotein and albumin.

Interpatient variability in response to a given dose of meperidine, a synthetic opiate analgesic, may be partially explained by variability in plasma protein binding. Alpha 1-acid glycoprotein (AAG), a plasma protein that primarily binds basic drugs, has been shown to increase in patients during stress such as trauma or surgery. The objective of this study was to determine the extent of meperidine binding to AAG and albumin as a function of both protein and meperidine concentrations. We performed a simple extraction procedure and a highly sensitive gas chromatograph analytical procedure. The results indicated that meperidine binding did not vary significantly with meperidine concentration at a given AAG concentration. However, meperidine binding increased significantly (p less than 0.01) as AAG concentration increased. Conversely, meperidine binding to albumin appeared to be independent of concentration of either meperidine or albumin. In conclusion, alpha 1-acid glycoprotein is a major plasma protein which binds meperidine in patients during stress. Further studies are suggested to elucidate the role of AAG on the pharmacologic effects of meperidine.

Cholinesterase Inhibitors↗

Effects of low doses of meperidine on neonatal behavior.

After meperidine administration during labor, meperidine reaches its highest level in fetal tissues within 2-3 hr. The highest levels of normeperidine, the active metabolite of meperidine, are, on the other hand, determined in fetal tissues by the time between administration of meperidine to the mother and delivery: the greater the drug-to-delivery interval (DDI), the higher the fetal levels of normeperidine. Because of the different times to peak fetal levels of meperidine and normeperidine, it may be possible to partially separate the effects of meperidine and its metabolite on the neonate using the DDI. The purpose of this study was to determine whether low doses of meperidine affected performance on the Brazelton Neonatal Behavioral Assessment Scale (BNBAS), and whether this performance is related to the DDI or to levels of meperidine or to normeperidine. Sixteen control neonates whose mothers received no meperidine and 41 study infants whose mothers received 25-100 mg meperidine intravenously (mean 39 +/- 19 mg) were studied. Comparisons of BNBAS scores of control and study infants measured at less than 12 hr, again at 3 days of age, and the effect of DDI were made using repeated measures analyses of variance (ANOVA). Correlation techniques were used to examine relationships between BNBAS performance and clinical and pharmacological variables related to drug administration. The BNBAS cluster scores representing regulation of state and number of abnormal reflexes were significantly different in study neonates from control neonates. Performance depended upon test day. Further analysis showed that longer DDIs resulted in less optimal BNBAS performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Respiratory and analgesic effects of meperidine and tramadol in patients undergoing orthopedic surgery.

The respiratory and analgesic effects of i.v. meperidine, tramadol and their correlation with plasma concentrations of meperidine, tramadol and O-demethyltramadol were determined. Forty-eight patients after total hip or knee replacement were randomly distributed into 3 groups (n = 16 each). At the time of analgesia request, they received in a double-blind manner, i.v. single doses of 100 mg meperidine, 100 mg tramadol, or saline. Thirty minutes after treatment, patients who requested additional analgesia were rescued with 75 mg diclofenac and morphine as required. Patients were evaluated at the time of analgesia request and at set intervals during 4 h. Meperidine induced sedation (p < 0.05), respiratory depression (tidal volume, p < 0.047; respiratory rate, p < 0.004; % O2 Sat, p < 0.036), and hypercapnia (PaCO2, p < 0.002). Incidence of nausea and vomiting was higher with tramadol (p < 0.02). For the first 30 min, meperidine produced lower pain intensity scores than tramadol or saline (p < 0.05). At this time, 14/16 patients on saline, 8/16 on meperidine and 11/16 on tramadol were rescued. Onset for meperidine analgesia was 10 min and > 30 min for tramadol. Both opioids produced similar degree of analgesia in patients who were not rescued. A negative correlation (r = -0.99) between analgesia and tramadol concentrations and a poor positive correlation (r = +0.54) with O-demethyltramadol (a metabolite of tramadol) was observed. Pain intensity differences correlated negatively with meperidine plasma concentrations during the first 30 min (r = -0.97) and positively thereafter (r = +0.92). In the present study, meperidine and tramadol produced comparable analgesia, with a different time course profile, but meperidine induced sedation and respiratory depression while tramadol did not.

Aged↗

The production and characterization of antibodies reactive with meperidine.

Meperidinic acid was converted to O-meperidinyl-glycollic acid and covalently attached to bovine serum albumin. Rabbits injected with this conjugate produced antibodies reactive with meperidine which were measured by the ammonium sulfate method. The specificities of these antisera were studied by competitive inhibition of the binding of 100 pmol/ml of 3H-meperidine to antibody by the prior addition of increasing concentrations of various unlabeled compounds. The concentrations in nanomoles per milliliter of various unlabeled opiods required to inhibit 3H-meperidine binding by 50% (I50) were: meperidine, 0.08; O-meperidinyl-glycollic acid, 1.7; methadone, 580; heroin, 1750; codeine, 2600; and morphine, 4200. Several psychopharmacologically active compounds were found to have I50 values comparable to the nonmeperidine opioids: hydroxyzine. HCl, 460; propoxyphene, 4,500; diazepam, 6,500; and cocaine, 10,800. The metabolites of meperidine exhibited the following I50 values: normeperidine, 0.7; meperidinic acid and normeperidinic acid, 210. A radioimmunoassay for meperidine which employs this antiserum was shown to be approximately 100 times more sensitive than the spectrophotometric method of Burns et al. (J. Pharmacol. Exp Ther. 114: 289-293, 1955). In this assay only normeperidine and some of the meperidine congeners might be expected to interfere with the measurement of meperidine. The degree of normeperidine interference was shown to be comparable to that present in the existing assay method.

Animals↗

The production and characterization of antibodies reactive with meperidine.

Meperidinic acid was converted to O-meperidinyl-glycollic acid and covalently attached to bovine serum albumin. Rabbits injected with this conjugate produced antibodies reactive with meperidine which were measured by the ammonium sulfate method. The specificities of these antisera were studied by competitive inhibition of the binding of 100 pmol/ml of 3H-meperidine to antibody by the prior addition of increasing concentrations of various unlabeled compounds. The concentrations in nanomoles per milliliter of various unlabeled opiods required to inhibit 3H-meperidine binding by 50% (I50) were: meperidine, 0.08; O-meperidinyl-glycollic acid, 1.7; methadone, 580; heroin, 1750; codeine, 2600; and morphine, 4200. Several psychopharmacologically active compounds were found to have I50 values comparable to the nonmeperidine opioids: hydroxyzine-HC1, 460; propoxyphene, 4,500; diazepam, 6,500; and cocaine, 10,800. The metabolites of meperidine exhibited the following I50 values: normeperidine, 0.7; meperidinic acid and normeperidinic acid, 210. A radioimmunoassay for meperidine which employs this antiserum was shown to be approximately 100 times more sensitive than the spectrophotometric method of Burns et al. (J. Pharmacol. Exp. Ther. 114:289-293, 1955). In this assay only normeperidine and some of the meperidine congeners might be expected to interfere with the measurement of meperidine. The degree of normeperidine interference was shown to be comparable to that present in the existing assay method.

Animals↗

Assessment of the relative intrinsic efficacy of profadol and meperidine in a pigeon drug discrimination procedure: relevance to partial substitution patterns.

Substitution and antagonism patterns of butorphanol, meperidine and profadol were examined in pigeons trained to discriminate either a 0.056 (low) or 0.18 (high) mg/kg dose of fentanyl from saline. In the low-dose group, fentanyl, meperidine, profadol and butorphanol substituted completely (>/=85% fentanyl-appropriate responding) for the fentanyl stimulus. For fentanyl and butorphanol, complete substitution was obtained at doses that had little effect on rates of responding, whereas profadol substituted at doses that moderately decreased rates and meperidine substituted at doses that markedly decreased rates. Although naloxone antagonized the stimulus effects of meperidine and profadol, it failed to alter their rate-decreasing effects. In the high-dose group, fentanyl and butorphanol substituted completely and meperidine and profadol partially (approximately 50% fentanyl-appropriate responding) for the fentanyl stimulus. During antagonism tests, meperidine and profadol produced only small decreases (less than 15%) in the percentage of fentanyl-appropriate responding produced by the training dose of fentanyl. Analysis of individual data indicated that meperidine and profadol produced three patterns of substitution and antagonism. In one subgroup of pigeons, meperidine and profadol substituted completely for but failed to antagonize the fentanyl stimulus; in another, these opioids failed to substitute for but did antagonize the fentanyl stimulus; and in another, these opioids failed to substitute for or antagonize the fentanyl stimulus. In this latter subgroup, meperidine and profadol produced leftward shifts in the dose-effect function for the stimulus effects of fentanyl and butorphanol. The present findings suggest that the failure of meperidine and profadol to substitute completely for the high-dose fentanyl stimulus was a direct consequence of their rate-decreasing effects rather than low efficacy at the mu receptor.

Journal Article↗

Prevalence of meperidine use in older surgical patients.

HYPOTHESIS: The unique toxic and adverse effects of meperidine hydrochloride have prompted a number of expert panels convened by national health care policy organizations to recommend that meperidine not be used in older patients. We hypothesized that the prescription of meperidine was less likely to reflect these recommendations in older surgical patients than in older medical patients. The current study examined the use of meperidine in 2 urban hospitals as 1 quality indicator of the care of older adults, measuring the prevalence of its use and characteristics of the patients to whom it is administered. DESIGN: Retrospective analysis. SETTING: Two urban hospitals: a large private tertiary care teaching hospital and a smaller academically affiliated Veterans Affairs medical center. PATIENTS: Patients 65 years or older and hospitalized on medical and surgical services between February 19, 2001, and February 14, 2003. MAIN OUTCOME MEASURES: Patient demographics, medication administration, and department of admitting physician. RESULTS: Meperidine was administered to approximately 1 in 8 older surgical patients at both institutions. Surgical patients were more likely than medical patients to receive a dose of meperidine (hospital A, 12.2% vs 4.3%, P<.001; hospital B, 12.9% vs 1.9%, P<.001). Of those administered meperidine, surgical patients were also more likely than medical patients to receive multiple doses (hospital A, 86.0% vs 65.5%, P = .045; hospital B, 73.8% vs 48.4%, P = .02). CONCLUSIONS: Contrary to national recommendations, meperidine continues to be administered to many hospitalized older adults, particularly those on surgical services. Several alternatives to meperidine exist that provide equal or better pain relief with fewer toxic effects. Hospitals and, in particular, departments of surgery should address this cause of preventable morbidity in this vulnerable population.

Aged↗

A double-blind study comparing single dose of intramuscularly injected zomepirac to meperidine in the treatment of postoperative pain.

Eighty-eight patients with moderate or severe postoperative pain were entered into a double-blind, single-injection trial designed to assess the analgesic efficacy of intramuscular zomepirac 100 mg. Patients were randomly selected to receive zomepirac injection, meperidine 100 mg or meperidine 50 mg. By most criteria of analgesic efficacy, zomepirac was superior to meperidine 50 mg and as effective as meperidine 100 mg. In terms of peak analgesia (and of patients' global evaluations), both meperidine 100 mg and zomepirac were superior to meperidine 50 mg. Total analgesia provided by zomepirac was greater than that with meperidine 100 mg, which was greater than that with meperidine 50 mg. Significantly fewer patients needed remedication during the observation period, and mean time to remedication was significantly longer for the zomepirac group than for either meperidine group. No serious adverse effects were reported.

Adult↗

Clinical and pharmacokinetic aspects of the combination of meperidine and prilocaine for spinal anaesthesia.

The aim of this study was to determine whether the addition of a small dose of prilocaine could augment the spinal block induced by meperidine and affect intrathecal meperidine pharmacokinetic behaviour. Spinal anaesthesia was performed in 60 men scheduled for endoscopic resection of a prostatic adenoma or bladder tumour under spinal anaesthesia. They were allocated randomly to receive either 1 mg.kg-1 meperidine (Group 1, n = 30), or 1 mg.kg-1 meperidine plus 0.5 mg.kg-1 prilocaine (Group 2, n = 30). Blood samples were collected prior to and for 24 hr after spinal injection in 24 patients (12 in each group). Plasma meperidine levels were assayed by gas chromatography. Complete motor block was achieved in all Group 2 patients, but was incomplete in seven of Group 1 (P less than 0.05). The onset of both motor and sensory blocks was shorter (P less than 0.01) in Group 2 and the duration was longer (P less than 0.05). Coadministration of prilocaine modifies meperidine pharmacokinetic behaviour. The area under curve was 48% greater (P less than 0.01) and Cmax was higher in Group 2 than in Group 1, 145.8 +/- 42.2 vs 107 +/- 20.5 ng.ml-1 (P less than 0.001). No evidence of respiratory depression was noted in any of the patients. Despite the increase in plasma meperidine concentrations, no side effects were observed. The plasma concentrations remained at one third to one sixth the levels reported to induce a respiratory depression. It is concluded that the addition of prilocaine to meperidine improves motor and sensory block during surgery and alters meperidine kinetics without producing major side effects.

Aged↗

Intrathecal meperidine for elective caesarean section: a comparison with lidocaine.

The purpose of this study was to determine the efficacy of intrathecal meperidine in patients undergoing Caesarean section, and also to compare meperidine with heavy lidocaine. Fifty full-term pregnant women, ASA physical status I or II, presenting for elective Caesarean section under spinal anaesthesia were randomly divided into two groups with 25 in each, to receive either intrathecal meperidine or lidocaine. All patients received premedication with oral ranitidine, 150 mg, the night before surgery, and again two hours before surgery. Patients in the meperidine group were also given metoclopramide iv 10 mg one hour before surgery. After iv 20 ml.kg-1 Ringer's lactate, patients were given either 5% meperidine 1 mg.kg-1 or 5% heavy lidocaine 1.2 to 1.4 ml intrathecally. The sensory and motor blockades in all except two patients in each group who required sedation at the time of skin incision were adequate for surgery. None of the mothers suffered from any major side effects. The incidence of hypotension was higher in the lidocaine group than in meperidine group (P < 0.05). Pruritus and drowsiness were more common in meperidine group than in lidocaine group (P < 0.01). All the newborns in both groups cried immediately after birth and had an Apgar score > 7. The mean duration of postoperative analgesia was six hours in the meperidine group and one hour in the lidocaine group (P < 0.01). Postoperative analgesia requirement was less in the meperidine than in the lidocaine group (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ketorolac versus meperidine: ED treatment of severe musculoskeletal low back pain.

The study objective was to assess the efficacy and patient acceptance of ketorolac as an alternative to meperidine for the treatment of severe musculoskeletal low back pain (LBP). A double blinded prospective trial in a convenience sample of patients >18 years of age presenting to an urban university hospital emergency department (ED) was conducted over a 19-month period. Patients were included if the pain was musculoskeletal in origin and was severe enough to warrant parenteral analgesics. Patients were randomized to receive 1 mg/kg meperidine intramuscularly (IM) or 60 mg ketorolac IM. Pain intensity was measured preadministration and at 60 minutes via a 100 mm Visual Analog Scale (VAS). Outcomes measured at 60 minutes were pain intensity decrease (PID), patient satisfaction, rescue analgesia requirement, sedation level, and adverse effects. Clinically significant pain reduction was defined as a PID of at least 13 mm or a reduction in pain of least 30%. One hundred fifty-five patients were enrolled (meperidine = 75, ketorolac = 80) and 153 patients completed the study. At 60 minutes the mean PID was 7 mm less in the ketorolac group (95% confidence interval [CI] - 15 mm to 2.6 mm). Pain reduction of at least 30% occurred in 63% of the ketorolac group versus 67% of the meperidine group (95% CI, odds ratio [OR] .43 to 1.61). Rescue analgesia was required in 35% of the ketorolac group versus 37% of the meperidine group (95% CI, OR .47 to 1.74). Patient satisfaction was less in the ketorolac group (ketorolac 68% satisfied versus meperidine 74% satisfied) however this was not significant (95% CI, OR .66 to 2.72). Sedation level and adverse effects were significantly greater in the meperidine group. Ketorolac shows comparable single dose analgesic efficacy to a single moderate dose of meperidine with less sedation and adverse effects in an ED population with severe musculoskeletal LBP. The trend for greater pain reduction and patient satisfaction with meperidine needs further investigation.

Adult↗

A comparison among nalbuphine, meperidine, and placebo for treating postanesthetic shivering.

UNLABELLED: Postanesthetic shivering (PS) is distressing for patients and may induce a variety of complications. In this prospective, double-blinded, randomized study, we evaluated the value of nalbuphine, compared with meperidine and saline, for treating PS. Ninety adult patients were included in the study. Group 1 (n = 30) received i.v. nalbuphine 0.08 mg/kg, Group 2 (n = 30) received i.v. meperidine 0.4 mg/kg, and Group 3 (n = 30) received i.v. saline. Treatment that stopped shivering was considered to have been successful. The results demonstrated that, 5 min after treatment, both nalbuphine and meperidine provided a rapid and potent anti-shivering effect on PS, with high response rates of 80% and 83%, compared with those of saline (0%) (P < 0.01). Thirty minutes after injection, the response rates of nalbuphine and meperidine were 90% and 93%, respectively, compared with 17% in the saline group (P < 0.01). The differences between nalbuphine and meperidine were not significant. We conclude that nalbuphine may be an alternative to meperidine for treating PS. IMPLICATIONS: We evaluated nalbuphine versus meperidine and saline for treating postanesthetic shivering. Our results demonstrate that both nalbuphine and meperidine provide a similar rapid and potent anti-shivering effect. Nalbuphine may be an alternative to meperidine for treating postanesthetic shivering.

Adult↗

The effects of three graded doses of meperidine for spinal anesthesia in African men.

UNLABELLED: The intrathecal injection of 0.7-1 mg/kg meperidine provides spinal anesthesia of only short duration. In this study, we investigated the effects of three different doses of meperidine for spinal anesthesia on the duration and level of sensory block and the incidence of side effects. Forty-five African men were randomly allocated to receive one of three doses of intrathecal meperidine: Group A = 1.2 mg/kg, Group B = 1.5 mg/kg, and Group C = 1.8 mg/kg. The duration of sensory block was significantly longer after 1.5 mg/kg compared with 1.2 mg/kg meperidine (112 +/- 19 vs 79 +/- 27 min; P = 0.001). Increasing the dose to 1.8 mg/kg did not further increase the duration of block. The level and the onset of the block were not affected by the dose. Common side effects were fatigue (27%), pruritus (20%), and nausea (7%). Seven patients had respiratory depression and seven had a decrease of systolic arterial blood pressure (SAP) >30% from baseline. There was no difference in the incidence of any side effect among groups. Respiratory depression and decreases in SAP were observed 5-50 min after meperidine injection. Twenty-two patients had no pain after the sensory block had terminated. We conclude that increasing the dose of meperidine from 1.2 to 1.5 mg/kg increased the duration, but not the level, of sensory block without an increase in side effects. IMPLICATIONS: Intrathecal meperidine 1 mg/kg provides surgical anesthesia for only 40-90 min. We investigated the effects of three larger doses of meperidine in 45 African men. The 1.5 and 1.8 mg/kg doses provide a longer duration of anesthesia compared with 1.2 mg/kg. Nausea, pruritus, and respiratory depression were common in all dose groups. We conclude that increasing the dose of meperidine from 1.2 to 1.5 mg/kg increased the duration, but not the level, of sensory block without an increase in side effects.

Analgesics, Opioid↗

Meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold.

BACKGROUND: Meperidine administration is a more effective treatment for shivering than equianalgesic doses of other opioids. However, it remains unknown whether meperidine also profoundly impairs other thermoregulatory responses, such as sweating or vasoconstriction. Proportional inhibition of vasoconstriction and shivering suggests that the drug acts much like alfentanil and anesthetics but possesses greater thermoregulatory than analgesic potency. In contrast, disproportionate inhibition would imply a special antishivering mechanism. Accordingly, the authors tested the hypothesis that meperidine administration produces a far greater concentration-dependent reduction in the shivering than vasoconstriction threshold. METHODS: Nine volunteers were each studied on three days: 1) control (no opioid); 2) a target total plasma meperidine concentration of 0.6 microgram/ml (40 mg/h); and 3) a target concentration of 1.8 micrograms/ml (120 mg/h). Each day, skin and core temperatures were increased to provoke sweating and then subsequently reduced to elicit vasoconstriction and shivering. Core-temperature thresholds (at a designated skin temperature of 34 degrees C) were computed using established linear cutaneous contributions to control sweating (10%) and vasoconstriction and shivering (20%). The dose-dependent effects of unbound meperidine on thermoregulatory response thresholds was then determined using linear regression. Results are presented as means +/- SDs. RESULTS: The unbound meperidine fraction was approximately 35%. Meperidine administration slightly increased the sweating threshold (0.5 +/- 0.8 degree C.microgram-1.ml; r2 = 0.51 +/- 0.37) and markedly decreased the vasoconstriction threshold (-3.3 +/- 1.5 degrees C.microgram-1.ml; r2 = 0.92 +/- 0.08). However, meperidine reduced the shivering threshold nearly twice as much as the vasoconstriction threshold (-6.1 +/- 3.0 degrees C.microgram-1.ml; r2 = 0.97 +/- 0.05; P = 0.001). CONCLUSIONS: The special antishivering efficacy of meperidine results at least in part from an uncharacteristically large reduction in the shivering threshold rather than from exaggerated generalized thermoregulatory inhibition. This pattern of thermoregulatory impairment differs from that produced by alfentanil, clonidine, propofol, and the volatile anesthetics, all which reduce the vasoconstriction and shivering thresholds comparably.

Alfentanil↗

Cesarean delivery: a randomized trial of epidural analgesia versus intravenous meperidine analgesia during labor in nulliparous women.

BACKGROUND: Controversy concerning increased cesarean births as a result of epidural analgesia for relief of labor pain has been attributed, in large part, to difficulties interpreting published studies because of design flaws. In this study, the authors compared epidural analgesia to intravenous meperidine analgesia using patient-controlled devices during labor to evaluate the effects of labor epidural analgesia, primarily on the rate of cesarean deliveries while minimizing limitations attributable to study design. METHODS: Four hundred fifty-nine nulliparous women in spontaneous labor at term were randomly assigned to receive either epidural analgesia or intravenous meperidine analgesia. Epidural analgesia was initiated with 0.25% bupivacaine and was maintained with 0.0625% bupivacaine and fentanyl 2 microg/ml at 6 ml/h with 5-ml bolus doses every 15 min as needed using a patient-controlled pump. Women in the intravenous analgesia group received 50 mg meperidine with 25 mg promethazine hydrochloride as an initial bolus, followed by 15 mg meperidine every 10 min as needed, using a patient-controlled pump. A written procedural manual that prescribed the intrapartum obstetric management was followed for each woman randomized in the study. RESULTS: A total of 226 women were randomized to receive epidural analgesia, and 233 women were randomized to receive intravenous meperidine analgesia. Protocol violations occurred in 8% (38 of 459) of women. There was no difference in the rate of cesarean deliveries between the two analgesia groups (epidural analgesia, 7% [16 of 226; 95% confidence interval, 4-11%] vs. intravenous meperidine analgesia, 9% [20 of 233; 95% confidence interval, 5-13%]; P = 0.61). Significantly more women randomized to epidural analgesia had forceps deliveries compared with those randomized to meperidine analgesia (12% [26 of 226] vs. 3% [7 of 233]; P < 0.001). Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received intravenous meperidine analgesia. CONCLUSIONS: Epidural analgesia compared with intravenous meperidine analgesia during labor does not increase cesarean deliveries in nulliparous women.

Adult↗

The peripheral analgesic effect of meperidine in reducing propofol injection pain is not naloxone-reversible.

BACKGROUND AND OBJECTIVES: Meperidine is frequently used in general anesthesia and perioperative analgesia. In addition to its opioid action, meperidine possesses some local anesthetic properties. A preliminary study using the tourniquet venous retention technique found meperidine to be more effective in reducing propofol injection pain than fentanyl or morphine, both of which were slightly better than placebo. This study was undertaken to evaluate whether this peripheral analgesic effect of meperidine is affected by naloxone. METHODS: In a randomized, double-blind manner, after venous occlusion with a tourniquet, meperidine 40 mg was given intravenously to patients in group A (n = 31), meperidine 40 mg followed by naloxone 0.04 mg to group B (n = 32), meperidine 40 mg followed by naloxone 0.2 mg to group C (n = 30), and normal saline placebo to group D (n = 30). The venous retention of drug(s) was maintained for 1 minute, followed by tourniquet release and intravenous administration of propofol 100 mg. Pain assessment was made immediately after the propofol injection. RESULTS: All three groups given meperidine had significantly less propofol injection pain (P < .01 ) than the group given saline placebo, and there was no difference among groups A, B, and C. CONCLUSION: The peripheral analgesic effect of meperidine in reducing propofol injection pain is not mediated by its opioid activity.

Adjuvants, Anesthesia↗