PubMed Health⌕ Search

Biomedical subjects

J X Mazoit

Publications and source records attributed to J X Mazoit.

54 records · Page 3Linked to original sources
PubMed1993

[Analgesia after thoracotomy by extrapleural administration of continuous bupivacaine].

This study was aimed to assess the efficiency and the side effects of a continuous administration of bupivacaine into the paravertebral space. Twenty patients, ranked ASA 2 or 3, with a mean age of 57.9 years, and having had a posterolateral thoracotomy for resection of lung tissue, were randomly assigned to one of two groups, B or C. At the end of the surgical procedure, a 22 gauge catheter was inserted into the paravertebral extrapleural space, at T4 levels As soon as pain occurred during recovery (T0), the patients were given two-hourly intravenous boluses of buprenorphine. The patients in group B were also given, through the paravertebral catheter, a 20 ml bolus of 0.25% bupivacaine, followed by a continuous steady rate infusion (10 ml.h-1). Group C patients were given normal saline in the same way. All patients could improve their analgesia with 0.05 ml boluses of buprenorphine given by an auto-analgesia pump (Pharmacia). The following parameters were assessed during the 72 h which followed the first injection: pain with a visual analogic scale, quality of sedation (5 grades), heart and breathing rate, systolic and diastolic blood pressure, arterial blood gases. In group B, plasma bupivacaine concentrations were measured throughout the infusion, and for an 8-hour period after its end. The statistical analysis included 15 patients only, as the catheter had moved into the chest cavity in the other 5. Analgesia was qualified to be adequate by all patients, but there was no statistically significant difference in the amounts of self-administered buprenorphine between groups B and C.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1993

Myocardial uptake of bupivacaine: I. Pharmacokinetics and pharmacodynamics of lidocaine and bupivacaine in the isolated perfused rabbit heart.

Bupivacaine, but not lidocaine, may cause severe cardiac dysrrhythmias in case of accidental intravascular injection. In an attempt to discriminate between a pharmacokinetic and a pharmacodynamic (or both) origin to these differences, we used an isolated rabbit heart model with constant coronary inflow to compare the myocardial uptake and disposition kinetics of lidocaine and bupivacaine. Drug concentration in the outflow perfusate was assayed and surface electrocardiogram was recorded. Drug uptake and disposition kinetics were modeled with a two-compartment open model. An Emax model was used to describe the increase in QRS duration in relation with drug concentration in the central compartment. Lidocaine and bupivacaine exhibited similar myocardial pharmacokinetics (i.e., a rapid decrease in the outflow concentration upon drug administration discontinuation). Bupivacaine-induced maximum increase in QRS duration (Emax) was 15 times superior to lidocaine Emax. The steady-state perfusate concentration producing half Emax was the same for both drugs. We conclude that bupivacaine-induced QRS widening decreases almost at the same rate as does lidocaine-induced QRS widening when drug administration is terminated. Therefore, the different cardiac effects of lidocaine and bupivacaine are not due to differences in myocardial uptake and disposition kinetics.

Animals↗
PubMed1993

Myocardial uptake of bupivacaine: II. Pharmacokinetics and pharmacodynamics of bupivacaine enantiomers in the isolated perfused rabbit heart.

The enantiomers of a racemic drug generally differ in their pharmacokinetic and/or pharmacodynamic properties. Because bupivacaine is a mixture of two optical isomers known to exert different toxic properties on isolated nerve preparations, we decided to use an isolated rabbit heart model with constant coronary inflow to compare the myocardial uptake kinetics of the R(+)-, S(-)-enantiomers and the racemic mixture of bupivacaine. The increase in QRS duration was also measured, and the inflow concentration-effect relationship was analyzed for the three drugs. The racemic and the two enantiomers of bupivacaine exhibited similar myocardial pharmacokinetics with a two-compartment profile for all hearts except one. All drugs showed a rapid decrease in the outflow concentration when drug administration was discontinued. The tissue/perfusate concentration ratio at steady state was similar for the three drugs. QRS widening, as well as the occurrence of severe arrhythmias, was much less pronounced in the hearts receiving the S(-) isomer than in the hearts receiving the R(+) isomer or the racemic mixture. Despite the occurrence of arrhythmias, QRS widening was adequately modelled with an Emax model. C50, the inflow perfusate concentration producing half Emax (maximal theoretical increase in QRS duration) was the same for all three drugs. The authors conclude that the S(-)-bupivacaine exerts less detrimental effects on the isolated heart of the rabbit perfused at a constant coronary flow with protein-free buffer.

Animals↗
PubMed1992

Serum concentrations of local anaesthetics following intraperitoneal administration during laparoscopy.

The present study is a comparison of the pharmacokinetics of four local anaesthetics injected double blind in the right subdiaphragmatic area during outpatient laparoscopy performed under standard general anaesthesia in 28 young women. 80 ml of one of the following solutions was injected: Group A 0.5% plain lidocaine (n = 7), Group B 0.5% lidocaine with 1/320.000 adrenaline (n = 8), Group C 0.5% lidocaine with 1/800.000 adrenaline (n = 7), and Group D 0.125% bupivacaine with 1/800.000 adrenaline (n = 6). Blood samples were collected over 360 min from an iv catheter and serum concentrations were measured by gas chromatography. No adverse effects occurred in the study period. In Group A (plain lidocaine), Cmax was significantly higher and tmax significantly earlier than in Groups B and C (lidocaine with adrenaline). A toxic level was not found after either solution in any patient. The intraperitoneal use of doses of 400 mg lidocaine or 100 mg bupivacaine for perioperative analgesia was safe and solutions of lidocaine containing adrenaline appeared to pose even less risk than plain solutions.

Adult↗
PubMed1992

Effects of epinephrine and clonidine on plasma concentrations of spinal bupivacaine.

ASA II-III patients, scheduled for peripheral vascular surgery, were included in a study designed to assess the effect of spinal epinephrine and clonidine on plasma concentrations of spinally administered 0.5% glucose-free bupivacaine. Patients were allocated randomly to three groups to receive via a spinal catheter 22.5 mg (4.5 ml) of bupivacaine alone (Group B, 9 patients) or combined with 0.3 mg epinephrine (Group BE, 10 patients) or 0.15 mg clonidine (Group BC, 10 patients). Sensory blockade was assessed by pin-prick and motor blockade on the Bromage scale. Bupivacaine plasma concentrations were measured by gas chromatography. A trend to prolongation of local anaesthetic blockade was documented in patients receiving bupivacaine plus epinephrine or clonidine. (Time to regression of sensory blockade to L2: 170 +/- 75 min in Group B, 230 +/- 50 min in Group BE, 232 +/- 64 min in Group BC.) The maximum peak concentration (Cmax), the time to reach Cmax (Tmax) and the time-concentration curve from 0-180 min (AUC) were not different for the three groups (Cmax 228 +/- 112 ng.ml-1 in Group B, 215 +/- 103 ng.ml-1 in Group BE, 234 +/- 159 ng.ml-1 in Group BC; Tmax 41 +/- 34 min in Group B, 59 +/- 31 min in Group BE, 68 +/- 32 min in Group BC; AUC 31.0 +/- 1.7 mg.ml-1.min-1 in Group B, 27.3 +/- 1.1 mg.ml-1.min-1 in Group BE, 27.0 +/- 1.1 mg.ml-1.min-1 in Group BC). The results of this study suggest that epinephrine and clonidine do not decrease blood resorption of spinal bupivacaine.

Aged↗
PubMed1991

Heart rate response to an i.v. test dose of adrenaline and lignocaine with and without atropine pretreatment.

In order to evaluate the sensitivity of an adrenaline test dose for detecting intravascular injection and the effect of atropine pretreatment, 90 ASA physical status I and II patients were allocated randomly to two groups, to receive i.v. saline 1 ml (n = 46) or i.v. atropine 0.5 mg (n = 44). Five minutes later, all patients received an i.v. test dose of 2% lignocaine 3 ml with adrenaline 15 micrograms at a rate of 1 ml s-1. The groups were similar with respect to basal heart rate (HR). HR remained unchanged after saline injection, but increased slightly 5 min after atropine injection (mean 78 (SD 15) beat min-1 vs 87 (20) beat min-1 (P less than 0.05). After the test dose of lignocaine with adrenaline, HR increased significantly in both groups at 30 s, 1 and 2 min, and remained increased at 3 min in the atropine group. The maximum increase in HR was greater in the atropine group than in the saline group (31 (4) beat min-1 vs 26 (11) beat min-1 (P less than 0.05). However, when individual maximum HR changes are considered, five patients in the saline group and four in the atropine group had an increase less than or equal to 10 beat min-1, and three patients in the saline group had no change or a decrease in HR. Defining a positive result to a test dose as an increase in HR of greater than 10 beat min-1, the sensitivity of the adrenaline test dose was 83 (5.5)% in the saline group and 91 (3.5)% in the atropine group (ns).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Extrahepatic metabolism of morphine occurs in humans.

The pharmacokinetics of morphine was studied in six patients in whom a radiologic localization of an insulinoma was to be performed under general anesthesia. Sampling was done in the peripheral artery, the mesenteric vein in five of the six patients, the hepatic vein, and the peripheral vein, as well as in urine. Hepatic blood flow was estimated by an indocyanine green infusion technique at the end of the radiologic procedure. Morphine terminal half-life was 92 +/- 9 minutes, total body clearance was 1260 ml.min-1, and the hepatic extraction ratio was 0.65 +/- 0.11. No concentration gradient was observed between the artery and the superior mesenteric vein, showing that no gut wall metabolism of morphine occurred. The total body clearance exceeded the hepatic clearance by 38%. It was concluded that the extrahepatic extraintestinal clearance of morphine probably occurred through the kidney.

Adolescent↗
PubMed1990

Myocardial uptake of lignocaine: pharmacokinetics and pharmacodynamics in the isolated perfused heart of the rabbit.

1. The uptake kinetics and pharmacodynamics of lignocaine were studied in isolated perfused heart of the rabbit. 2. Six hearts were perfused with increasing concentrations of lignocaine in a modified Krebs-Henseleit buffer. The effluent concentration together with the increase in QRS duration were measured during lignocaine infusion and during 20 min after cessation of lignocaine infusion. 3. Lignocaine disposition and elimination were best described by a two-compartment open model. Terminal half-life was 11.0 +/- 2.9 min. The unidirectional transfer was slower from central to peripheral compartment than from peripheral to central compartment (T1/2.12 = 42.6 +/- 10.5 min whereas T1/2.21 = 10.7 +/- 2.8 min). The myocardium/perfusate concentration-ratio was 4.7 +/- 0.4. 4. The pharmacodynamic effect was best described in the central compartment by using the Hill equation. Calculated maximum QRS duration (Emax) was 77 +/- 8 ms. Emax was also directly measured in four additional rabbits by infusing ten times the dose of lignocaine used in the main experiment: the value of Emax measured in these conditions was 92.5 +/- 9.6 ms, i.e. a QRS widening of 150%. The steady-state perfusate concentration producing half the effect (C50) was 15.7 +/- 7.6 micrograms ml-1. 6. In conclusion, the specific lignocaine binding leading to increase in QRS duration appeared to be more closely related to the vascular stream than non specific binding leading to a deeper accumulation process.

Animals↗
PubMed1988

[Are combinations of local anesthetics dangerous?].

Although local anaesthetic mixtures are often used, there is often no scientific basis for this. Interactions between the local anaesthetics in the mixture can even increase their toxicity. Such interactions may be due to the physical chemical properties of each constituent (this is not a real problem for amide local anaesthetics), to a mutual displacement from the binding sites on the plasma proteins or to an additional effect on membrane receptors. This displacement would seem to benefit the least toxic drug: the toxicity of local anaesthetic mixtures may therefore be reduced; for example, lidocaine and mepivacaine are displaced by bupivacaine. Moreover, the fraction of drug which leaves the blood vessel is greater than the serum free fraction. During chronic administration, neurological toxicity and free fraction are narrowly linked. When using local anaesthetic mixtures, it must be remembered that potency and toxicity of a local anaesthetic are closely correlated and that the toxic effects are, at least, additive.

Anesthetics, Local↗
PubMed1988

Pharmacokinetics of bupivacaine following caudal anesthesia in infants.

Pharmacokinetics and protein binding of bupivacaine were studied after caudal injection of 2.5 mg/kg in 13 ASA PS 1 infants (1-6 months of age) scheduled for elective hernia repair. Blood was sampled at frequent intervals from 5 min to 600 min in all but one patients. Additional samples were taken at 720 and 840 min in five patients. Bupivacaine concentration was measured using gas chromatography. Protein binding was measured using ultrafiltration. Peak serum concentrations ranged between 0.55 and 1.93 micrograms/ml. The time to reach the peak ranged from 10 to 60 min. Terminal half-life (T1/2 beta) was 7.7 +/- 2.4h (mean +/- SD), the volume of distribution (Vss) was 3.9 +/- 2.01.kg, and the total body clearance (CL) was 7.1 +/- 3.2 ml.min.kg-1. The free fraction was markedly increased (0.16 +/- 0.07) when compared with published adult values, and showed a highly significant negative correlation with age. Alpha 1 acid glycoprotein measured in the same infants correlated significantly with age. In conclusion, pharmacokinetics of caudal bupivacaine in infants are characterized by Cmax of total drug similar to those observed in adults after epidural injection. The free fraction is increased at least until 6 months of life. This suggests caution in the use of bupivacaine in infants until we understand the clinical significance of this increased free fraction.

Anesthesia, Caudal↗
PubMed1988

Pharmacokinetics of bupivacaine after short and prolonged infusions in conscious dogs.

A conscious dog model was used to study pharmacokinetics of bupivacaine after a short infusion (SI) (15 min) and a prolonged infusion (PI) (24 hours). Bupivacaine was infused in six mongrel dogs at least 10 days after implantation of femoral arterial and venous catheters. Each dog received both the SI and the PI in a random crossover design at a one week interval. Bupivacaine concentration was measured in serum sampled during the SI, during the last hour of the PI, and at frequent intervals during eight hours after cessation of infusion. Indocyanine green (ICG) clearance also was measured during the last hour of the PI and 90 min after cessation of both the SI and the PI. The terminal half-life (T1/2Z) of bupivacaine increased after the PI compared with the SI, 167 +/- 86 vs 53 +/- 13 min, respectively (mean +/- SD; P less than 0.05), and total body clearance (Cl) decreased, 3.4 +/- 1.2 vs 9.5 +/- 4.5 ml.min-1.kg-1, (P less than 0.05), although the volumes of distribution (VZ and VSS) did not change. A decrease in hepatic blood flow did not cause the decrease in Cl because ICG clearance did not change during the three sets of measurements. Thus, the observed increase in T1/2Z and decrease in Cl after the PI as compared with the SI are due to a decrease in hepatic intrinsic clearance of bupivacaine. Differences in the kinetic profile of the two enantiomers of bupivacaine cannot be excluded as a cause. We conclude that the extrapolation of kinetic data of bupivacaine obtained after a short infusion (or a bolus injection) to prolonged dosage must be done with care.

Anesthetics, Local↗
PubMed1987

Pharmacokinetics of unchanged morphine in normal and cirrhotic subjects.

Published reports of morphine pharmacokinetics differ, perhaps because of analytical discrepancies and different study protocols. A highly specific radioimmunoassay (N-carboxymethylnormorphine RIA) was used to measure unchanged morphine in plasma in six normal subjects and in eight cirrhotic patients with hypoalbuminemia, hyperbilirubinemia, and prolonged prothrombin time. All subjects received a single intravenous bolus of morphine hydrochloride (0.1 mg/kg). Peripheral blood samples were collected at frequent intervals from 2 min to 36 hr after injection. In cirrhotic patients as compared with normal subjects, terminal half-life of unchanged morphine was longer (201 +/- 39 vs 111 +/- 32 min (mean +/- SD), P less than 0.01) and total body clearance was slower (21 +/- 7.5 vs 33.5 +/- 8 ml X min-1 X kg-1, P less than 0.05). The apparent volume of distribution and the steady-state volume of distribution did not differ in the two groups. In conclusion, cirrhotic patients have a prolonged terminal half-life of unchanged morphine that is attributable to a decrease in total body clearance.

Aged↗
PubMedDate not supplied

Additivity of bupivacaine and morphine for peripheral analgesia in rats.

Infiltration of the surgical wound is a classical technique for post-operative analgesia. Recent studies have suggested that local anaesthetic may be combined with other drugs such as opioids. This study has evaluated, in rat, the infiltration with morphine, bupivacaine and their combination. In all groups, the two hind paws were injected with carrageenin. The left hind paw was used as control. The vocalisation threshold to paw pressure (VTPP) of both hind paws was evaluated 2 h after induction of carrageenin inflammation (baseline value), then every 10 min until the return to baseline value after injection of analgesic drugs. The development of oedema was evaluated in both hind paws by measurement of paw circumference (PC) before, then after, carrageenin injection. All analgesic drugs were injected in the right inflamed paw diluted in 0.2 mL of normal saline. The analgesic effect of bupivacaine (0.1, 0.25 and 0.5%), morphine (25, 50 and 100 microg) and their combination (bupivacaine 0.1%/morphine 20 microg, bupivacaine 0.2%/morphine 40 microg and bupivacaine 0.4%/morphine 80 microg) was tested. The effect of naloxone on morphine induced analgesia was tested. The interaction between bupivacaine and morphine was evaluated with an isobolographic analysis. Bupivacaine produced a dose-dependent antinociceptive effect. Morphine infiltration produced a peripheral, dose-dependent analgesic effect antagonised by naloxone. This analgesic effect of morphine was associated with an anti-inflammatory effect. The isobolographic analysis revealed only additivity between bupivacaine and morphine. The infiltration with morphine offers a peripheral analgesic effect which is additive with the effect of bupivacaine. An anti-inflammatory effect of morphine participates in this peripheral analgesic effect.

Analgesics, Opioid↗