Biomedical subjects

France Varin

Publications and source records attributed to France Varin.

11 recordsLinked to original sources

PubMed2006

Pharmacokinetics and pharmacodynamics of a 0.1 mg/kg dose of cisatracurium besylate in children during N2O/O2/propofol anesthesia.

We studied the pharmacokinetics and pharmacodynamics of cisatracurium in 9 children (mean weight, 17.1 kg) aged 1-6 yr (mean, 3.75 yr) during propofol-nitrous oxide anesthesia. Neuromuscular monitoring was performed. Venous samples were taken before injection of a 0.1 mg/kg dose of cisatracurium and then at 2, 5, 10, 30, 60, 90, and 120 min. Cisatracurium plasma concentrations were determined by high performance liquid chromatography. Onset time was 2.5 +/- 0.8 min, recovery to 25% of baseline twitch height was 37.6 +/- 10.2 min, and the 25%-75% recovery index was 10.9 +/- 3.7 min. Distribution and elimination half-lives were 3.5 +/- 0.9 min and 22.9 +/- 4.5 min, respectively. Steady-state volume of distribution (0.207 +/- 0.031 L/kg) and total body clearance (6.8 +/- 0.7 mL/min/kg) were significantly larger than those published for adults. Pharmacodynamic results were comparable to those obtained in pediatric studies during halothane or opioid anesthesia with the exception of a longer recovery to 25% baseline. Although the plasma-effect compartment equilibration rate constant was twofold faster (0.115 +/- 0.025 min(-1)) than that published for cisatracurium in adults, the effect compartment concentration corresponding to 50% block was similar (129 +/- 27 ng/mL).

Anesthesia, Inhalation↗

PubMed2006

A multimodal analgesia protocol for total knee arthroplasty. A randomized, controlled study.

BACKGROUND: Although numerous methods of postoperative analgesia have been investigated in an attempt to improve pain control after total knee arthroplasty, parenteral narcotics still play a major role in postoperative pain management. Local anesthetics have the advantage of blocking pain conduction at its origin and minimizing the systemic side effects associated with postoperative narcotic use. This study was performed to evaluate the benefits and safety of a multimodal analgesia protocol that included periarticular injection of large doses of local anesthetics in patients undergoing total knee arthroplasty. METHODS: We compared morphine consumption during the first twenty-four hours after unilateral total knee arthroplasty in forty-two patients who had been randomized to receive either (1) a perioperative infiltration mixture, consisting principally of local anesthetic, and self-administered morphine or (2) self-administered morphine only. Narcotics consumption, pain control, medication-related side effects, plasma levels of the local anesthetic (ropivacaine), and postoperative rehabilitation were monitored. RESULTS: Although there was high satisfaction and good pain control in both groups, morphine consumption was significantly lower in the local analgesia group than it was in the control group (28.8 +/- 17.4 mg compared with 50.3 +/- 25.4 mg twenty-four hours after surgery, and 46.7 +/- 19.4 mg compared with 68.6 +/- 38.6 mg forty hours after surgery). Both groups achieved a similar amount of knee flexion on the fifth postoperative day. Over the five-day period after the procedure, the patients in the local analgesia group reported a total of 2.6 +/- 3.9 hours of nausea compared with 7.1 +/- 12.2 hours in the control group. No complications related to the infiltration of the local anesthetic were observed, and all plasma concentrations of the local anesthetic were below the toxic range. CONCLUSIONS: This multimodal perioperative analgesia protocol that included infiltration of a local anesthetic offered improved pain control and minimal side effects to patients undergoing total knee arthroplasty. Our study also confirmed the safety of the protocol.

Analgesia, Patient-Controlled↗

PubMed2005

Pharmacokinetics and pharmacodynamics of mivacurium in patients phenotypically homozygous for the atypical plasma cholinesterase variant: effect of injection of human cholinesterase.

BACKGROUND: In patients homozygous for atypical plasma cholinesterase, mivacurium causes a long-lasting neuromuscular block, but injection of human cholinesterase has been proven effective in antagonizing the block. The purpose of this study was to evaluate the pharmacodynamics and pharmacokinetics of mivacurium in such patients, as well as the effect of cholinesterase injected early or late after mivacurium. METHODS: Eleven patients phenotypically homozygous for the atypical variant received 0.075 mg/kg (1 patient) or 0.15 mg/kg (10 patients) mivacurium. The neuromuscular block was monitored using train-of-four nerve stimulation and mechanomyography. Cholinesterase, 2.8-10.0 mg/kg, was administered approximately 30 or 120 min after mivacurium. The times to different levels of neuromuscular recovery and the venous concentrations of the isomers of mivacurium were measured. RESULTS: Injection of cholinesterase increased plasma cholinesterase activity to normal and the clearances of the active isomers and the elimination rate constants by a factor of 10-15. The first response was seen in 13.5 min (3.7-44.2 min). Time to a train-of-four ratio of 0.8 ranged from 30 to 60 min (n = 6). Neostigmine injected after cholinesterase shortened recovery further, and a train-of-four ratio of 0.8 was reached in 10-30 min. CONCLUSION: As expected, the duration of action of mivacurium is markedly prolonged in homozygous atypical patients. Injection of cholinesterase significantly increases the metabolism of mivacurium, leading to a shorter duration of action. Injection of neostigmine after the administration of cholinesterase speeds up recovery.

Adolescent↗

PubMed2005

Cisatracurium-induced neuromuscular blockade is affected by chronic phenytoin or carbamazepine treatment in neurosurgical patients.

The effect of chronic anticonvulsant therapy (CAT) on the maintenance and recovery profiles of cisatracurium-induced neuromuscular blockade has not been adequately studied. In this study, we compared the pharmacokinetics and pharmacodynamics of cisatracurium after a prolonged infusion in patients with or without CAT. Thirty patients undergoing intracranial surgery were enrolled in the study: 15 patients under CAT (carbamazepine and phenytoin, Group A) and 15 controls receiving no anticonvulsant therapy (Group C). Anesthesia was standardized and both groups received a bolus of cisatracurium followed by an infusion to maintain a 95% twitch depression. A steady-state was obtained and the infusion was kept constant for 2 additional hours. Neuromuscular blockade was then allowed to spontaneously recover. Blood samples were taken for measurement of cisatracurium plasma concentration during the steady-state period (Cp(ss)95) and at various times during recovery. Demographic and intraoperative data were similar. CAT resulted in faster 25% and 75% recovery of the first twitch. The rate of infusion of cisatracurium needed to maintain a 95% twitch depression at steady-state was 44% faster in Group A (P < 0.001). The clearance of cisatracurium was significantly faster in Group A when compared with Group C (7.12 +/- 1.87 versus 5.72 +/- 0.70 L . kg(-1) . min(-1), P = 0.01). The Cp(ss)95 was also significantly larger in Group A (191 +/- 45 versus 159 +/- 36 ng/mL, P = 0.04). In addition, patients receiving CAT had a 20% increase in the clearance of cisatracurium that, in turn, resulted in a faster recovery of neuromuscular blockade after an infusion of the drug. Also, patients under CAT had a 20% increase in their Cp(ss)95, indicating an increased resistance to the effect of cisatracurium.

Adolescent↗

PubMed2004

Ropivacaine plasma concentrations are similar during continuous lumbar plexus blockade using the anterior three-in-one and the posterior psoas compartment techniques.

PURPOSE: To compare ropivacaine blood concentrations obtained after a continuous lumbar plexus block performed either by the anterior three-in-one femoral (FEM) technique or the posterior (psoas compartment; PSOAS) technique. METHODS: As a substudy of a larger clinical trial, 24 patients were randomly allocated to receive a bolus of 30 mL of ropivacaine 0.5% plus epinephrine 1:200,000 followed by an infusion of ropivacaine 0.2% at 12 mL.hr(-1) for 48 hr via one of the two continuous lumbar plexus block techniques. Plasma ropivacaine concentrations, up to 48 hr, were measured by high performance liquid chromatography. RESULTS: Mean plasma ropivacaine concentrations were higher in the PSOAS group at 15, 30, and 60 min (two-way analysis of variance, P < 0.0001) but areas under the curve were similar for both groups (FEM 452.4 +/- 253.6 mg.hr(-1).L(-1), PSOAS 433.4 +/- 99.0 mg.hr(-1).L(-1)). Mean maximal plasma concentrations were observed at 48 hr and were comparable for the two techniques (FEM 2630.9 +/- 1470.3 ng.L(-1), PSOAS 2325.1 +/- 604.2 ng.mL(-1)). There was no correlation between blood concentrations at 48 hr and body weight (r2 = 0.085, P = 0.21). One patient in the FEM group achieved a concentration of 6201 ng.mL(-1) at 48 hr. CONCLUSIONS: Although the posterior PSOAS block results in higher early plasma concentrations of local anesthetic than the anterior three-in-one FEM block, both techniques are equivalent with regards to their potential toxicity when a continuous infusion is administered. Local anesthetic accumulation occurs with an infusion of ropivacaine 0.2% at 12 mL.hr(-1) and can lead to potentially dangerous concentrations at 48 hr.

Adult↗

PubMed2002

Spatial effects in modeling pharmacokinetics of rapid action drugs.

We develop a model to describe the time course of plasma concentration of neuromuscular blocking agents used as anesthetics during surgery. This model, which overcomes the limitations of the classical compartment models routinely used in pharmacokinetics, incorporates spatial effects due to heterogeneity in the circulation: it takes the form of a dispersion equation on a circular domain, with a time-dependent leakage term. This term is fitted to the functional form desired once first-stage transients have died out. Comparisons are made with clinical data by adjusting three parameters in the model.

Body Fluid Compartments↗

PubMed2002

Rocuronium pharmacokinetic-pharmacodynamic relationship under stable propofol or isoflurane anesthesia.

PURPOSE: To compare the pharmacokinetics, pharmacodynamics and the concentration-effect relationship of rocuronium in patients under stable propofol or isoflurane anesthesia. METHODS: Ten patients were randomized to receive fentanyl, propofol and nitrous oxide (60%) or fentanyl, thiopental, isoflurane (1.2% end-tidal concentration) and nitrous oxide (60%). To obtain good intubation conditions and maintain adequate muscle relaxation during surgery, patients received two bolus doses of rocuronium: 0.5 mg x kg(-1) (1.7 x ED95) at induction followed one hour later by 0.3 mg x kg(-1) (1 x ED95). Arterial blood samples were obtained over six hours after the second bolus dose. Plasma concentrations of rocuronium were measured using high pressure liquid chromatography. Muscle twitch tension was monitored by mechanomyography for the two doses. Pharmacokinetic and pharmacodynamic parameters were determined. RESULTS: No differences in rocuronium pharmacokinetic parameters were observed between both groups. After the second bolus, clinical duration was 20 +/- 6 min in the propofol group vs 39 +/- 8 min in the isoflurane group (P <0.05). The effect compartment concentration corresponding to 50% block, EC50, was higher under propofol anesthesia: 1008 vs 592 microg x L(-1) (P <0.05). CONCLUSION: Rocuronium body disposition is similar under stable propofol or isoflurane anesthesia. In contrast to isoflurane, propofol does not prolong the neuromuscular block. Therefore, the potentiating effect of isoflurane is of pharmacodynamic origin only, as explained by an increased sensitivity at the neuromuscular junction. In contrast with isoflurane anesthesia where the dose of rocuronium has to be decreased under stable conditions, no dose adjustment is required under propofol anesthesia.

Adult↗

PubMed2002

Mivacurium arteriovenous gradient during steady state infusion in anesthetized patients.

BACKGROUND: Mivacurium and isomers undergo rapid hydrolysis by plasma cholinesterase. As this enzyme is largely distributed, it cannot be excluded that these isomers might undergo peripheral elimination. This hypothesis was investigated in patients by measuring the difference between arterial and venous concentrations under a constant-rate continuous infusion of mivacurium. METHODS: During propofol-remifentanil anesthesia, eight adult consenting patients received an intravenous bolus dose of 0.2 mg/kg mivacurium, followed by a constant infusion (3, 5, or 7 microg. kg. min ) into the brachial vein. One hour after starting the infusion, arterial (radial artery) and venous (contralateral brachial vein) blood samples were drawn simultaneously at 15-min intervals for 45 min. Mivacurium isomers and metabolite plasma concentrations were determined by stereospecific high-performance liquid chromatography. Using the corresponding arterial and venous concentrations, the tissue extraction coefficient as well as total body clearance were calculated. RESULTS: During steady state conditions, the venous concentrations of the and isomers were 34 +/- 13% and 42 +/- 11% (mean +/- SD) lower than the corresponding arterial concentrations (P < 0.05), respectively. For the isomer, the difference between venous and arterial concentrations was 3 +/- 4% (P = 0.063). Total body clearances of the and isomers were greater when based on venous sampling (P < 0.05). CONCLUSION: Pharmacokinetic parameters derived from a constant infusion of mivacurium depend heavily on the sampling site (arterial or venous) for the rapidly hydrolyzed isomers. These results strongly suggest a significant metabolism of mivacurium within muscle tissue that may account for the large interpatient variability in response to mivacurium.

Algorithms↗

PubMed2002

Concentration-effect relation of succinylcholine chloride during propofol anesthesia.

BACKGROUND: The pharmacokinetics and pharmacodynamics of succinylcholine were studied simultaneously in anesthetized patients to understand why the drug has a rapid onset and short duration of action. A quantitative model describing the concentration-effect relation of succinylcholine was proposed. The correlation between hydrolysis in plasma and elimination was also examined. METHODS: Before induction of anesthesia, blood was drawn for analysis in seven adults. Anesthesia was induced with propofol and remifentanil. Single twitch stimulation was applied at the ulnar nerve every 10 s, and the force of contraction of the adductor pollicis was measured. Arterial blood was drawn frequently after succinylcholine injection to characterize the front-end kinetics. Plasma concentrations were measured by mass spectrometry, and pharmacokinetic parameters were derived using compartmental and noncompartmental approaches. Pharmacokinetic-pharmacodynamic relations were estimated. RESULTS: The mean degradation rate constant in plasma (1.07 +/- 0.49 min(-1)) was not different from the elimination rate constant (0.97 +/- 0.30 min(-1)), and an excellent correlation (r2 = 0.94) was observed. Total body clearance derived using noncompartmental (37 +/- 7 ml x min(-1) x kg(-1)) and compartmental (37 +/- 9 ml x min(-1) x kg(-1)) approaches were similar. The plasma-effect compartment equilibration rate constant (k(eo)) was 0.058 +/- 0.026 min(-1), and the effect compartment concentration at 50% block was 734 +/- 211 ng/ml. CONCLUSION: Succinylcholine is a low-potency drug with a very fast clearance that equilibrates relatively slowly with the effect compartment. Its disappearance is greatly accountable by a rapid hydrolysis in plasma.

Adult↗

PubMedDate not supplied

The number of injections does not influence local anesthetic absorption after paravertebral blockade.

PURPOSE: The aims of this study are to determine if the injection of a single large dose of local anesthetics into the paravertebral space increases the risks of inducing toxicity compared with multiple small injections and to describe ropivacaine plasma concentrations resulting from paravertebral blockade. METHODS: Paravertebral blockade was performed using a solution of 10 mL ropivacaine 0.75%, 10 mL lidocaine CO2 2% plus 0.1 mL epinephrine 1:1000 either by a single injection at T3 or T4 (Group S, n = 6) or by five injections of 4 mL each at T2 to T6 (Group M, n = 8). Blood samples were taken at zero, five, ten, 15, 20, 30, 45, 60 and 90 min and at two, three, four, five, six and eight hours. Ropivacaine and lidocaine plasma concentrations were measured by high performance liquid chromatography. RESULTS: Maximal plasma concentrations were comparable for lidocaine: 2.6 +/- 1.3 (S) vs 2.6 +/- 0.8 microg x mL(-1) (M) and for ropivacaine: 1.3 +/- 0.2 (S) vs 1.3 +/- 0.1 microg x mL(-1) (M). Area under the plasma concentration-time curve was higher in Group M for lidocaine: 577.6 +/- 146.1 vs 401.7 +/- 53.2 mg x min(-1) x mL(-1) (P = 0.04) but similar for ropivacaine: 381.1 +/- 95.4 (M) vs 363.1 +/- 85.3 mg x min(-1) x L(-1) (S). CONCLUSIONS: The injection of a single large bolus of local anesthetics into the paravertebral space does not increase its absorption. Maximal ropivacaine plasma concentrations resulting from paravertebral blockade are similar to those reported with equivalent doses of bupivacaine.

Absorption↗

PubMedDate not supplied

Determination of interstitial rocuronium concentrations in the muscle tissue of anesthetized dogs by microdialysis.

INTRODUCTION: The objective was to establish and validate a microdialysis technique for the quantification of interstitial concentrations of the neuromuscular blocker, rocuronium, in the muscle tissue of dogs under steady-state conditions. METHODS: The standard and combined retrodialysis approaches were used for in vivo microdialysis probe calibration. After induction of anesthesia with pentobarbital (30 mg/kg), the left femoral vein was cannulated and blood drawn for protein binding determination. Microdialysis probes were inserted in the muscle and calibrated in vivo, using vecuronium as the calibrator. Each dog received a short 2-min infusion followed by a 120-min infusion of rocuronium via the right jugular vein and three microdialysis samples were collected at steady-state during a 2-h period. Samples were stored at -70 degrees C until HPLC analysis. RESULTS: Using combined retrodialysis, rocuronium unbound interstitial (C(ISFu)) and venous plasma (C(pssuv)) concentrations are in good agreement; with a ratio C(ISFu)/C(pssuv) of 100+/-11%. Using standard retrodialysis, this ratio was 47+/-7%. CONCLUSIONS: Combined retrodialysis is a more reliable and accurate technique for quantitative assessment of rocuronium interstitial concentrations especially for lengthy anesthetic procedures. These findings have potential implications, as drug concentrations in the site of action would be more relevant for concentration-effect relation of muscle relaxants.

Androstanols↗