Search

Background: Meperidine has been shown to exhibit a sensory block in peripheral nerves. However, its motor blockade ability is controversial. The aim of this study was to investigate, electroneurographically, the ability of meperidine to inhibit conduction in both sensory and motor fibres in the ulnar nerve., Materials and Methods: The study was conducted in a double-blind, placebo-controlled fashion. Eighteen healthy volunteers were randomized into three groups (Saline, meperidine 1% and meperidine 2%). Three millilitre of the study solution was administered to the ulnar nerve perineurally at the level of the wrist by the guidance of a nerve stimulator. Sensory nerve action potential (SNAP) and compound motor action potential (CMAP) amplitudes were recorded. At least a 20% decrease in the initial response amplitude was accepted as a block., Results: The number of individuals with sensory and motor block with saline, meperidine 1% and meperidine 2% were 0/6, 6/6, 6/6 and 0/6, 5/6, 6/6, respectively (P<0.05). The maximum decrease in the median SNAP and CMAP amplitude values were 4.7% and 8.3% with saline; 38.5% and 46.4% with meperidine 1%; and 100% and 97.8% with meperidine 2%, respectively (P<0.05). Median values for the duration of sensory and motor block with meperidine 1% and meperidine 2% were 45, 52.5 and 30, 32.5 min, respectively., Conclusion: Meperidine blocks sensory and motor nerve conduction in a dose-related manner.

Background: Opioid-induced vasodepressor responses have been reported in a variety of species and laboratory models. The aim of this study was to ascertain the relative potencies of different clinically relevant opioids compared with traditional vasodepressor agents in the feline pulmonary vascular bed. A second aim was to study the effects of morphine and to identify the receptors involved in the mediation or the modulation of these effects., Methods: This was a prospective vehicle-controlled study involving an intact chest preparation of adult mongrel cats. The effects of various opioids, morphine, fentanyl, remifentanil, sufentanil, and meperidine were compared with other vasodepressor agents. Additionally, the effects of L-N(5)-(1-iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), nimesulide [selective cyclooxygenase (COX)-2 inhibitor], glibenclamide (ATP-sensitive K+ channel blocker), naloxone (non-selective opioid receptor antagonist), and diphenhydramine (histamine H(1)-receptor antagonist) were investigated on pulmonary arterial responses to morphine and other selected agonists in the feline pulmonary vascular bed. The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and recorded., Results: In the cat pulmonary vascular bed of the isolated left lower lobe, morphine, remifentanil, fentanyl, sufentanil, and meperidine induced a dose-dependent moderate vasodepressor response and it appeared that sufentanil was the most potent on a nanomolar basis. The effects of morphine were not significantly altered after administration of L-NIO, nimesulide, and glibenclamide. However, the vascular responses to morphine were significantly attenuated following administration of naloxone and diphenhydramine., Conclusion: The results of the present study suggest that sufentanil appears to have slightly more potency and morphine the least of the five opioid agonists studied on a nanomolar basis. Morphine-induced vasodilatory responses appeared to be mediated or modulated by both opioid receptor and histamine-receptor-sensitive pathways.

Background: The research on conductive analgesia induced by perineural opioids generated a large body of conflicting data. In this study we reassessed the antinociceptive response to perineural administration of morphine, fentanyl or meperidine in a rat model., Methods: Analgesia was assessed using the hind paw withdrawal latency (HPWL) response to radiant heat. The opioid dose producing 20% of maximal possible effect (20%MPE) for systemic analgesia was calculated for each drug. Then sciatic blockade was performed with the dose corresponding to 20%MPE. The injected hind paw was used to measure direct perineural effect and the contralateral hind paw was used as an indicator of systemic effect., Results: The response latency produced by morphine or fentanyl was not significantly different for ipsilateral (perineural effect) or contralateral (systemic effect) paw (27+/-11 vs. 28+/-16 and 3l+/-16 vs. 23+/-16 s, respectively). However, the meperidine group showed significantly higher %MPE for the ipsilateral paw (79+/-32 s) than for the contralateral paw (27+/-22 s)., Conclusions: The results indicate that perineural fentanyl or morphine do not produce analgesia. Perineural block produced by meperidine was attributed to local anesthetic-like effect, rather than to drug interaction with opioid receptor.

Background: There is a current interest in local anaesthetic drugs/formulations exhibiting long durations of sensory block and minor motor-blocking effects., Objectives: To compare the duration of sensory and motor blockade in peripheral nerve blocks induced by the new agents ropivacaine and levobupivacaine, with that of racemic bupivacaine and pethidine., Methods: Groups of 8 male Sprague-Dawley rats were subjected to infraorbital (IONB) or sciatic nerve block (SNB) employing 0.2 ml of differently concentrated solutions of bupivacaine, levobupivacaine, ropivacaine or pethidine. The sensory blocking effect in IONB is expressed as (i) the time to elicitation of an abdominal jerk by electrical stimulation at arbitrarily chosen (threshold) intensities (IONB degree 3, 5, 8 and 10), and as (ii) the area under the curve (AUC, threshold intensities vs time). The duration of motor block in SNB is given as the time from injection to regained ability to walk and grip normally with the toes. Comparisons of the dose-effect relationships for the investigated agents were made by analysis of covariance., Results: In IONB the log (dose)-log (effect) lines for bupivacaine, levobupivacaine and ropivacaine did not deviate from parallelism. The duration of sensory block induced by equimolar doses of these agents was similar, although bupivacaine exerted more pronounced effects than levobupivacaine (AUC by 25%, P=0.001; IONB degree 3 by 14%, P=0.03). In SNB only the log (dose)-log (duration) lines for bupivacaine vs levobupivacaine were found not to deviate from parallelism, both agents exerting similar durations of action. The motor-blocking effects of ropivacaine showed an inverse dose-duration relationship (P=0.019)., Conclusions: Equimolar doses of the investigated local anaesthetics exerted similar durations of sensory blockade in a peripheral nerve block model in the rat.

Background: Objectives were to study the effects of variations in the pH and the buffer capacity of solutions of lignocaine or pethidine on their analgesic efficacy in peripheral nerve block., Methods: Infraorbital nerve blocks (IONB) were induced in rats during light pentobarbitone anaesthesia employing 0.2 ml of test solutions containing 10 mg center dot ml-1 of lignocaine or pethidine dissolved in normal saline, 50 mmol and 150 mmol tris-hydroxymethylaminomethane (THAM) hydrochloride (THAM center dot HCl) of pH 4.8 and 4.5, respectively, or 100 mmol THAM + THAM center dot HCl of pH 7.4. The pH of solutions in saline was varied from 3.0 to 9.3 by adding HCl or NaHCO3. The analgesic efficacy is expressed as the interval from injection to elicitation of a minimal response to electric stimulation at various intensities (threshold intensities) within the blocked area (IONB 3 to 10), and in terms of the area under the curve (AUC, threshold intensities vs. time)., Results: When dissolved in saline, pH 7.4, pethidine exerted more pronounced effects than lignocaine [AUC by 3.5 times (P<0.001), IONB 3 to 10 by 2.7 (P<0.05) to 3.6 (P<0.001) times]. Variations of the pH of solutions did not affect their analgesic efficacy. Lignocaine exerted more pronounced local analgesic effects when mixed with 150 mmol THAM center dot HCl than when mixed with saline (pH 7.4), but manifested even more pronounced effects when dissolved in THAM + THAM center dot HCl [AUC by 3.7 times (P<0.001), IONB 3 to 10 by 2.7 (P<0.01) to 3.8 (P<0.001) times]. When dissolved in THAM + THAM center dot HCl, the analgesic efficacy of pethidine increased by 2.0 to 2.8 times (P<0.001), as compared to a solution in saline at the same pH., Conclusions: It is concluded that variations in the pH of solutions of lignocaine or pethidine in saline does not affect the analgesic efficacy of the drugs, presumably due to the low buffer capacity of the medium, whereas when dissolved in THAM + THAM center dot HCl, their effect is enhanced.

Although the effects of local anaesthetics (LA) on motor and sensory transmission in the spinal cord have been described, the effects of opioids are controversial. Our aim was to evaluate the action of clinically relevant doses of subarachnoid (SA) meperidine (MP) and fentanyl (FN), on somatosensory (SSEP) and cortical motor evoked responses (CMER) in awake subjects. Thirty ASA I-II patients scheduled for infra umbilical surgery received SA (N = 10/group): 1 mg/kg lidocaine (LD), 1 mg/kg MP or 25 mu g FN. SSEP elicited by stimulation of the posterior tibial nerve at the ankle, and cortical motor evoked response at rest (r-CMER) and during facilitation (f-CMER) were obtained prior and 30 min after treatment. Conduction at the proximal segment of the motor nerve (F-wave) was evaluated by stimulation of the posterior tibial nerve at the popliteal fossa. Motor/sensory block and side effects were clinically assessed. LD completely abolished SSEP and CMER. At the same dose, MP abolished SSEP in 40% of the patients, while r-CMER and f-CMER were absent in 70% and 30%, respectively; in addition, the F-wave was absent in 50% of the patients. Fentanyl induced small changes in the latencies of SSEP and F-wave; however, a 28% decrease in the amplitude of the f-CMER (P<0.05) was observed. Pruritus was present in 60% of patients in the FN group (P<0.006). Our results show that while LD and MP block sensory and motor conduction at the spinal roots, FN seems to decrease the excitability of the spinal interneurons in the corticospinal tract.

In order to evaluate the anticholinergic effect of fentanyl and pethidine, the influence of these drugs on the cumulative dose-response curves of carbacholine on the guinea-pig ileum has been investigated. Fentanyl and pethidine displaced the dose-response curve for carbacholine to the right in a parallel fashion, indicating competitive antagonism. Dissociation constants determined by an agonist EC versus antagonist plot were 0.22 mumol/l for fentanyl and 1.4 mumol/l for pethidine. It is concluded that during high-dose fentanyl anaesthesia, fentanyl may bind to muscarinic receptors and thereby produce a central anticholinergic syndrome. An additional finding was that the maximal response to carbacholine increased significantly when combined with pethidine.

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.

The respiratory depressant actions of pethidine and tilidine during anaesthesia were compared in 18 surgical patients anaesthetized with N2O + O2 after thiopental induction. Five minutes after thiopental, 0.5 mg/kg pethidine or 1.5 mg/kg tilidine were each given intravenously to six patients, the remaining six patients serving as controls. Minute ventilation, respiratory rate, end-tidal CO2 and PCO2 from arterialized venous blood were measured up to 30 min. Pethidine caused the following maximal changes: V -0.98 +/- 0.24 (s.e. mean) 1/min, rate -5.5 +/- 0.7/min, CO2ET + 0.7 +/- 0.1 vol % and PCO2 + 5.7 +/- 1.1 mm Hg. These changes occurred within 10 min of the injection.

Anileridine and pethidine have a spasmolytic action on animal intestine. Pethidine is known to have a spasmogenic effect at the choledocho-duodenal junction of man, but there is no study of the effect of anileridine on the biliary tract. In the present study the effects of anileridine and pethidine on the intracholedochal pressure during constant fluid perfusion in man were compared. The maximal elevation of the choledochal passage pressure was significantly greater after anileridine than after pethidine. However, the difference between anileridine and pethidine seemed to be less than that reported previously between morphine and pethidine. The effect of anileridine was of shorter duration than of pethidine. Anileridine and pethidine are not ideal analgesics when the normal activity of the biliary ductal system has to be maintained in pain or during cholangiography.

The influence of a sedative dose of "lytic cocktail" (chlorpromazine, promethazine and pethidine) on cerebral blood flow (CBF) and oxygen consumjtion (CMRO2) was tested in artificially ventilated rats, maintained on either 70% N2 or 70% N2O. When given alone, the lytic cocktail had no significant effect on CBF or CMRO2. However, in the presence of nitrous oxide there was a 25% reduction in blood flow and oxygen consumption.

The circulatory effects of anileridine, a derivative of pethidine, have been little studied. Therefore we compared the haemodynamic effects of equianalgesic doses of pethidine (1 mg/kg i.v.) and anileridine (0.25 mg/kg) in matched patients requiring myocardial revascularization. Cardiac output was significantly increased 5 min after the administration of pethidine, mainly due to an increase in heart rate. A transient rise in the systolic pulmonary-arterial pressure was found after anileridine. No remarkable changes were found in systemic arterial pressures, central venous pressure, balloon-occluded pulmonary-arterial pressure, stoke volume, systemic or pulmonary vascular resistances and derived oxygen consumption. Further, 20 min after drug administration, there were no significant differences in any circulatory parameters between the two groups. One patient developed acute cardiac failure after anileridine, though as he had very severe coronary heart disease it remains an open question whether this was spontaneous or drug-induced. Since the rate-pressure product tended to increase after pethidine, this drug may not be considered an ideal analgesic for patients with ischaemic heart disease. Anileridine had less influence on this variable. Since the circulatory effects of pethidine seem to depend on the haemodynamic status of the patient, the haemodynamic properties of anileridine may also deserve further investigation.

To assess the effect of epidural block on plasma catecholamines and cortisol during labour and delivery, plasma epinephrine, norepinephrine and cortisol levels were determined in 26 healthy parturients, all of whom delivered vaginally (18 received an epidural block, eight had meperidine 50 mg intramuscularly). We found a significant drop of plasma epinephrine and cortisol and no significant reduction of plasma norepinephrine 1 h after administration of epidural block compared to preblock values. Observing the data during the whole course of labour in correlation with cervical dilatation, in the control group, where the parturients received meperidine, all hormones rose progressively up to the moment of delivery. One hour after delivery the catecholamines returned to normal levels; cortisol returned more slowly. In the epidural group the increase of plasma epinephrine and cortisol was significantly inhibited but not that of norepinephrine.

The respiratory effects of lorazepam (a 1, 4 benzodiazepine) were studied using a modified Read rebreathing technique in healthy adult males about to undergo elective surgery. Lorazepam 0.05 mg/kg (IV) produced an increase in slope and a shift to the left of the CO2 response curve. These effects were also detectable but of smaller magnitude when the same lorazepam dose (IV) was given with meperidine (IV). End-expiratory CO2 (PeCO2), which was significantly elevated in all drug groups, is not a sensitive indicator of either the time course or the degree of respiratory depression.

Haemodynamic effects of equianalgesic doses of pethidine (1 mk kg -1) and anileridine (0.25 mg kg -1) were compared in patients with coronary artery disease, after induction of anaesthesia with flunitrazepam - N2O - pancuronium. Contrary to previous findings made in conscious patients, these analgesics produced a moderate circulatory depression. Heart rate, cardiac index and rate-pressure product were decreased by both drugs, and anileridine alone decreased mean arterial pressure. The only statistically significant differences in the haemodynamic changes between the two groups were those in pulmonary capillary wedge pressure and rate pressure product, which were slightly lower after anileridine than after pethidine.

The effects of repeated sedative i.v. doses of midazolam and diazepam in combination with meperidine on breathing pattern and thoracoabdominal motion were studied in eight healthy male volunteers. At 20-min intervals in a randomized double-blind crossover design the subjects initially received two doses of midazolam 0.05 mg/kg or diazepam 0.15 mg/kg followed by meperidine 0.5 mg/kg and then naloxone 0.4 mg. Breathing pattern and thoracoabdominal motion were measured non-invasively, utilizing a computerized strain gauge technique. The initial injection of both benzodiazepines caused significant decreases in tidal volume, inspiratory time and expiratory time. There were no significant differences between the two drugs in any of these variables. Minute ventilation, mean inspiratory flow and respiratory timing were not significantly affected. The second injection of both benzodiazepines caused only insignificant additional changes. When meperidine was added, the effects on inspiratory time and tidal volume were small and not significant. However, expiratory time increased and was no longer significantly different from control. The injection of naloxone reversed the meperidine-induced changes only, and the breathing pattern was no longer different from that obtained during benzodiazepines alone. The decrease in tidal volume after the benzodiazepines was almost exclusively mediated by a decrease in the abdominal contribution. Additional doses of benzodiazepines did not enhance these changes. However, meperidine caused a further decrease in the abdominal contribution. This decrease was reversed by naloxone. This indicates that the combination of benzodiazepines and meperidine caused a profound decrease in diaphragmatic performance.