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Biomedical subjects

Dominique Chassard

Publications and source records attributed to Dominique Chassard.

At least 19 recordsLinked to original sources

Erythromycin promotes gastric emptying during acute pain in volunteers.

In this double-blind cross-over study, we assessed whether erythromycin infusion is effective as a prokinetic drug against gastroparesis from acute pain. The effect of erythromycin on gastric emptying (GE) was measured in seven volunteers subjected to a standardized acute painful stimulus. The GE rate for solids was measured using the octanoic acid breath test. An acetaminophen absorption test measured the GE rate for liquids. Five minutes after ingestion of a 13C-labeled meal, the subjects received in randomized order either a test (placebo and erythromycin groups) or a control (control group) stimulus consisting of repeated 1-min immersion of a hand into 4 degrees C (test) or 37 degrees C (control) water, with 15 s for recovery between immersions, for a total of 20 min. While the stimulus was applied, 250 mL saline (control and placebo groups) or 250 mg erythromycin (erythromycin group) was infused. Pain and stress were evaluated using visual analog scales, and standard hemodynamic values were recorded throughout the study. Our results show that acute stress decreased GE for solids, which was significantly accelerated in the erythromycin group in comparison with the placebo group. GE for liquids was similar in the three groups. We conclude that erythromycin is effective as a prokinetic drug for solids in acute painful situations.

Acetaminophen↗

Validation of a Pseudomonas aeruginosa porcine model of septic shock.

OBJECTIVES: To develop a standardized bacteraemic porcine model of septic shock with cardiovascular and immunological profiles similar to those observed in human clinical states. METHODS: Sepsis was induced by an intravenous challenge of 18 anaesthetized pigs with live Pseudomonas aeruginosa. The pulmonary arterial pressure was monitored and the bacterial infusion was stopped when the systolic pulmonary arterial pressure reached 45 mmHg. Septic shock was treated with fluid resuscitation and epinephrine infusion. The haemodynamic parameters and the rate of different inflammatory cytokines were recorded during 6 h of observation. RESULTS: The mean+/-SD cardiac output increased from 2.4+/-1.2 to 5.7+/-2.1 L/min while the mean+/-SD systemic vascular resistance index decreased from 1957+/-744 to 709+/-221 dyn/s/cm5/m2. The pharmacokinetic profile of the inflammatory cytokines was similar to the one observed in human studies. CONCLUSIONS: The control of the systolic pulmonary arterial pressure during a P. aeruginosa infusion leads to a hyperdynamic, reproducible cardiovascular profile similar to the one observed in human septic shock. Since the immunological profile of the inflammatory cytokines is also similar to the human one, this standardized porcine model appears to be appropriate for experimental research concerning sepsis.

Animals↗

Immediate postoperative refeeding in orthopedic surgery is safe.

The purpose of this retrospective study was to investigate the morbidity of immediate postoperative refeeding after orthopedic surgery. We included all the 1077 patients who underwent orthopedic surgery between January and December 2003 at our military teaching hospital. General anesthesia was performed in 37% of the patients (n = 398), 24% (n = 259) had combined general and regional anesthesia, and 39% (n = 420) had isolated regional anesthesia (spinal anesthesia and/or peripheral regional anesthesia). After surgery, each patient was allowed free access to solid and liquid food immediately after discharge from the postanesthetic care unit. Although no systematic nausea and vomiting prophylaxis was performed, only 7% (n = 75) of the patients had postoperative nausea and vomiting during the first 48 h. Moreover, neither deglutition trouble nor aspiration syndrome was observed during that period. Our results suggest that immediate postoperative refeeding after orthopedic surgery is safe, does not increase postoperative nausea and vomiting, and probably increases the comfort of patients.

Anesthesia↗

Spinal muscarinic and nicotinic subtypes activated by clonidine in postincisional pain.

BACKGROUND: A recent model of acute incisional pain has been characterized that strongly parallels the postoperative period in patients experiencing evoked pain. In that setting, abundant literature has revealed antihypersensitive effects produced by intrathecally administered alpha2-adrenergic receptor agonists, such as clonidine, in both animals and humans. Recent reports have suggested an obligatory role of spinal acetylcholine receptors in the analgesic action of intrathecal clonidine. The authors sought to determine the involvement of spinal muscarinic and nicotinic receptor subpopulations in the antihypersensitivity effect of intrathecal clonidine in a rodent model for human postoperative pain. METHODS: After intrathecal catheterization, rats underwent superficial plantar incision. Clonidine or a combination of clonidine and muscarinic receptor subtype antagonists (M1, M2, M3, and M4) or nicotinic receptor subtype antagonists (alpha4beta2 and alpha7) were intrathecally administered, and withdrawal thresholds to mechanical stimuli were examined. RESULTS: Spinal clonidine maximally reduced hypersensitivity adjacent to the wound 30 min after its injection. When animals were intrathecally pretreated with the M1 muscarinic antagonist toxin MT-7, the M3 muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine, and the M4 muscarinic antagonist toxin MT-3, clonidine lost its antihypersensitive action. When animals were intrathecally pretreated with the alpha4beta2 nicotinic receptor antagonist dihydro-beta-erythroidine, but not with the alpha7 nicotinic receptor antagonist methyllycaconitine, the antihypersensitivity action of clonidine was abolished. CONCLUSIONS: These data indicate for the first time that the clonidine-induced increase in punctuate mechanical threshold is mediated via the activation of all but M2 muscarinic receptor subtypes, and via the activation of alpha4beta2 but not alpha7 nicotinic receptor subtypes in a rodent model for human postoperative pain.

Aconitine↗

Pharmacokinetics and intrapulmonary diffusion of levofloxacin in critically ill patients with severe community-acquired pneumonia.

OBJECTIVE: To determine the steady-state plasma and epithelial lining fluid concentrations of intravenous levofloxacin, 500 mg, administered once or twice daily in critically ill patients with severe community-acquired pneumonia. DESIGN: Prospective, open-label study. SETTING: An intensive care unit and a clinical pharmacokinetic laboratory in two university hospitals. PATIENTS: Twenty-four adult patients with severe community-acquired pneumonia and receiving mechanical ventilation were enrolled. INTERVENTIONS: All subjects received 1-hr intravenous infusions of 500 mg levofloxacin once or twice daily. The plasma and epithelial lining fluid levofloxacin concentrations were determined at steady-state after 2 days of therapy with high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: The median (interquartile range [IQR]) plasma and epithelial lining fluid peak levofloxacin concentrations were 12.6 (IQR, 12.0-14.1) and 11.9 (IQR, 8.7-13.7) mg/L, respectively, in the once-daily group and 19.7 (IQR, 19.0-22.0) and 17.8 (IQR, 16.2-23.5) mg/L in the twice-daily group, showing a pulmonary percentage penetration of >100% in both groups. The median (IQR) total body exposures were 151 (IQR, 137-174) and 416 (IQR, 406-472) mg.hr/L, respectively, in the once-daily and twice-daily groups. CONCLUSIONS: Our results suggest that in critically ill patients who are receiving mechanical ventilation and have severe community-acquired pneumonia and creatinine clearance of >40 mL/min, the administration of 500 mg of intravenous levofloxacin once and twice daily allows for the exceeding of pharmacodynamic thresholds predictive of outcome (i.e., peak concentration to minimum inhibitory concentration ratio of >10 or area under concentration-time curve to minimal inhibitory concentration ratio of >125 hrs) both in serum and epithelial lining fluid for pathogens with minimum inhibitory concentration values of < or =1 mg/L and >1 mg/L, respectively.

Aged↗

Pharmacokinetics and intrapulmonary concentrations of linezolid administered to critically ill patients with ventilator-associated pneumonia.

OBJECTIVE: To determine the steady-state plasma pharmacokinetic variables and epithelial lining fluid concentrations of linezolid administered to critically ill patients with ventilator-associated pneumonia. DESIGN: Prospective, open-label study. SETTING: An intensive care unit and research ward in a university hospital. PATIENTS: Sixteen critically ill adult patients with ventilator-associated pneumonia. INTERVENTIONS: All subjects received 1-hr intravenous infusions of linezolid 600 mg twice daily. After 2 days of therapy, the steady-state plasma pharmacokinetic variables and epithelial lining fluid concentrations of linezolid were determined by high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: The mean +/- sd linezolid peak and trough concentrations were 17.7 +/- 4.0 mg/L and 2.4 +/- 1.2 mg/L in plasma and 14.4 +/- 5.6 mg/L and 2.6 +/- 1.7 mg/L in epithelial lining fluid, respectively, showing a mean linezolid percentage penetration in epithelial lining fluid of approximately 100%. The mean +/- sd area under concentration-time curve during the observational period (AUC0-12) was 77.3 +/- 23.7 mg x hr/L, corresponding to a mean AUC0-24 of 154.6 mg x hr/L. CONCLUSIONS: Our study shows satisfactory results, with linezolid concentrations exceeding the susceptibility breakpoint for Gram-positive bacteria in both plasma and epithelial lining fluid. This suggests that a dosage of 600 mg administered intravenously twice daily to critically ill patients with Gram-positive ventilator-associated pneumonia would achieve success against organisms with minimum inhibitory concentrations as high as 2-4 mg/L in both plasma and epithelial lining fluid.

Acetamides↗

Antibacterial activity of clonidine and neostigmine in vitro.

We conducted an in vitro study to investigate the antibacterial activity of clonidine and neostigmine on common microorganisms encountered during infectious complications after regional anesthesia. Standardized suspensions of Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli were incubated during 1, 3, 6, and 24 h at 37 degrees C with concentrations of 37.5, 75, and 150 microg/mL of clonidine and 125, 250, and 500 microg/mL of neostigmine. After 24 h incubation at 37 degrees C, the colony counts were compared by two-way analysis of variance. The mean colony counts for S. aureus decreased significantly from control as the exposure to clonidine increased (P < 0.05), with a approximately 100% kill at 6 h for the largest concentration (150 microg/mL) and at 24 h for the intermediate concentration (75 microg/mL). Similar results were observed for S. epidermidis, with a approximately 100% kill at 6 h for the largest concentrations (75 and 150 microg/mL). No bactericidal activity of clonidine was observed for E. coli and no bactericidal activity of neostigmine was observed for any of the tested strains. In the conditions of this experiment, clonidine, but not neostigmine, exhibited a concentration-dependent and time-dependent bactericidal activity in vitro on the microorganisms most frequently encountered in infectious complications after regional anesthesia.

Anesthesia, Conduction↗

Steady-state plasma and intrapulmonary concentrations of piperacillin/tazobactam 4 g/0.5 g administered to critically ill patients with severe nosocomial pneumonia.

OBJECTIVE: To determine the steady-state plasma and epithelial lining fluid (ELF) concentrations of piperacillin/tazobactam (P/T) administered to critically ill patients with severe bacterial pneumonia. DESIGN: Prospective, open-label study. SETTING: An intensive care unit and research ward in a university hospital. PATIENTS: Ten adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation. INTERVENTIONS: All subjects received a 30-min intravenous infusion of P/T 4 g/0.5 g every 8 h. The steady-state plasma and ELF concentrations of P/T were determined by high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: The mean+/-SD steady-state plasma trough, peak, and intermediate concentrations were 8.5+/-4.6 microg/ml, 55.9+/-21.6 microg/ml, and 24.0+/-13.8 microg/ml for piperacillin, and 2.1+/-1.0 microg/ml, 4.8+/-2.1 microg/ml, and 2.4+/-1.2 microg/ml for tazobactam, respectively. The mean+/-SD steady-state intermediate ELF concentrations were 13.6+/-9.4 microg/ml for piperacillin and 2.1+/-1.1 microg/ml for tazobactam, respectively, showing a mean percentage penetration of piperacillin and tazobactam into ELF of 56.8% and 91.3 %, respectively, with a P/T ratio of 6.5:1. CONCLUSION: Our results show that during the treatment of severe nosocomial pneumonia, a regimen of P/T 4 g/0.5 g every 8 h might provide insufficient concentrations into lung tissue to exceed the MIC of many causative pathogens. This suggests that higher doses of P/T should be administered in order to maximize the antibiotic concentration at the site of infection, or that a second antimicrobial agent should be used in association.

Cross Infection↗

Plasma and lung concentrations of ceftazidime administered in continuous infusion to critically ill patients with severe nosocomial pneumonia.

OBJECTIVE: To determine the steady-state plasma and epithelial lining fluid (ELF) concentrations of ceftazidime administered in continuous infusion to critically ill patients with severe nosocomial pneumonia. DESIGN: Prospective, open-label study. SETTING: An intensive care unit and research ward in a university hospital. PATIENTS: A total of 15 adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation were enrolled. INTERVENTIONS: All subjects received a 30 min intravenous infusion of 2 g ceftazidime followed by a continuous infusion of 4 g over 24 h. The concentrations of ceftazidime in plasma and ELF were determined at steady-state after 2 days of therapy by high performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: The mean +/-SD steady-state plasma and ELF concentrations of 4 g ceftazidime in continuous infusion were 39.6+/-15.2 microg/mL and 8.2+/-4.8 microg/mL, respectively, showing a mean +/-SD percentage penetration of ceftazidime into ELF of 20.6+/-8.9%. CONCLUSION: The administration of 4 g ceftazidime in continuous infusion in critically ill patients with severe nosocomial pneumonia provides concentrations in excess of the minimal inhibitory concentration of many susceptible organisms over the course of therapy both in serum and ELF. However, for some pathogens such as P. aeruginosa, higher doses of ceftazidime should be administered, or another agent should be used in combination.

Anti-Bacterial Agents↗

[Remifentanil is an effective alternative to propofol for patient-controlled analgesia during digestive endoscopic procedures].

PURPOSE: Unlike propofol, the self-administration of remifentanil for sedation in gastrointestinal endoscopies has never been evaluated formally. We wanted to compare the efficacy and tolerance of patient self-administration of remifentanil vs propofol during gastrointestinal endoscopy. METHOD: This prospective randomized, single-blinded study, included 77 patients undergoing gastrointestinal endoscopy. Patients were divided into two groups: group R received remifentanil (5 microg.kg(-1).hr(-1) infusion, 25 microg boli, refractory period of five minutes) and group P received propofol (2 mg.kg(-1).hr(-1) infusion, 0.5 mg.kg(-1) boli, refractory period of ten minutes). A 1 mg.kg(-1) bolus of propofol was administered before the procedure began in cases of marked anxiety. Additional boli of 25 microg of remifentanil or 0.5 mg.kg(-1) of propofol were administered when patients complained during the refractory period. The evaluation targeted analgesic efficacy during the procedure and patient satisfaction. The degree of sedation during the procedure and the occurrence of adverse reactions were analyzed. RESULTS: Patient satisfaction was high and comparable in both groups, with the number of awake and oriented patients being significantly higher in group R. Hemodynamic and respiratory tolerance was comparable in both groups, despite two episodes of desaturation in group R. The incidence of nausea was significantly higher in group R. CONCLUSIONS: The self-administration of remifentanil for sedation during gastrointestinal endoscopies is as effective as the self-administration of propofol and can be offered to patients, especially when it is desirable that they remain conscious during the procedure.

Adult↗

Patient-controlled regional analgesia is effective in children: a preliminary report.

PURPOSE: To report a preliminary analysis of prospectively recorded data in 27 children in whom patient-controlled regional analgesia (PCRA) was used for postoperative pain control following lower limb surgery. METHODS: Under general anesthesia, perineural catheters (popliteal and fascia iliaca compartment block) were inserted and infused with ropivacaine 0.2% (0.02 mL.kg(-1).hr(-1)). Additional demand doses were left to the child's discretion (0.1 mL.kg(-1)and a 30-min lockout interval). RESULTS: The average total dose of ropivacaine administered was 4.9 +/- 2 mg.kg(-1)over 48 hr. Visual analogue scale and Children's Hospital of Eastern Ontario Pain Scale scores were always inferior to 5/10 and 6/13, respectively. Motor block was observed in two children and two children needed rescue analgesia. CONCLUSIONS: Our preliminary observations indicate that PCRA in children provides satisfactory postoperative pain relief following lower limb surgery.

Adolescent↗

Background infusion is not beneficial during labor patient-controlled analgesia with 0.1% ropivacaine plus 0.5 microg/ml sufentanil.

BACKGROUND: Although patient-controlled epidural analgesia (PCEA) during labor has been extensively studied in recent clinical trials, the role of a background infusion associated with self-administered boluses is still debated. The authors designed a study to assess whether the use of PCEA with or without background infusion could improve the comfort of parturients and their satisfaction during labor and delivery without affecting the total consumption of local anesthetics. METHODS: One hundred thirty-three laboring parturients requesting epidural analgesia administered via PCEA with a solution of 0.1% ropivacaine plus 0.5 microg/ml sufentanil were randomly assigned to four groups, according to the rate of background infusion used (0, 3, 6, and 9 ml/h). Local anesthetic requirements, maternal satisfaction, verbal pain scores, incidence of side effects, and outcome of labor were compared among groups. RESULTS: Patient demographics, labor characteristics, side effects, and Apgar scores were similar in each group. No significant differences were observed between groups in verbal pain scores during labor, number of supplemental boluses, or maternal satisfaction. A significantly greater overall total drug consumption with a 6-ml/h or a 9-ml/h background infusion (74 and 78 ml, respectively) was observed in comparison with PCEA without a background infusion (55 ml). A similar relation was observed for hourly use during both the first and the second stage of labor. CONCLUSION: The results of this study suggest that the use of a background infusion with PCEA during labor leads to a greater consumption of anesthetic solution without improving comfort and satisfaction of parturients. Moreover, not using a background infusion does not provide an increased incidence of supplemental boluses (which might cause problems in a busy unit) and allows for a substantial reduction in the cost of analgesia.

Adult↗

Chronopharmacology of intrathecal sufentanil for labor analgesia: daily variations in duration of action.

BACKGROUND: The pharmacokinetic and pharmacodynamic characteristics of opioids vary throughout the day, as demonstrated for oral morphine in chronic pain. However, little is known about the chronobiology of intrathecal lipid soluble opioids used for labor analgesia. The aim of this prospective study was to determine whether the duration of action of intrathecally administered sufentanil is influenced by the time of administration. METHODS: Ninety-one women in the first stage of labor were enrolled. Labor analgesia was first provided by 10 microg intrathecal sufentanil. The duration of action of intrathecal sufentanil was measured and analyzed by the cosinor method to determine periodic intraday variation. RESULTS: Pain assessed by a visual analog score was not different among patients (70 +/- 17 mm) before the injection of intrathecal sufentanil. Rhythm analysis revealed a mean ( +/- SD) duration of analgesia (mesor) of 93.0 +/- 3.8 min. A highly significant 12-h rhythm was found, with two peaks: One was near midnight (0.78 +/- 0.6 h), and the other was near noon (12.78 +/- 0.6 min) (P < 0.01). The amplitude of this 12-h component was 16.1 +/- 5.5 min. CONCLUSIONS: The duration of intrathecal sufentanil analgesia exhibited a temporal pattern with 30% variations throughout the day period. The authors point out that the lack of consideration of chronobiological conditions in intrathecally administered analgesia studies can cause significant statistical bias. Further studies dealing with intrathecal opioids should consider the time of drug administration.

Adult↗

Steady-state plasma and intrapulmonary concentrations of cefepime administered in continuous infusion in critically ill patients with severe nosocomial pneumonia.

OBJECTIVE: To determine the steady-state plasma and epithelial lining fluid concentrations of cefepime administered in continuous infusion in critically ill patients with severe bacterial pneumonia. DESIGN: Prospective, open-label study. SETTING: An intensive care unit and research ward in a university hospital. PATIENTS: Twenty adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation were enrolled. INTERVENTIONS: All subjects received a 30-min intravenous infusion of cefepime 2 g followed by a continuous infusion of 4 g over 24 hrs. The concentrations of cefepime in plasma and epithelial lining fluid were determined at steady state after 48 hrs of therapy with high performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: The mean +/- sd steady-state plasma and epithelial lining fluid concentrations of cefepime 4 g in continuous infusion were 13.5 +/- 3.3 microg/mL and 14.1 +/- 2.8 microg/mL, respectively, with a mean percentage penetration of cefepime into epithelial lining fluid of about 100%. CONCLUSIONS: The administration of 4 g of cefepime in continuous infusion in critically ill patients with severe nosocomial pneumonia appears to optimize the pharmacodynamic profile of this beta-lactam by constantly providing concentrations in excess of minimal inhibitory concentration of most of susceptible organisms over the course of therapy in both serum and epithelial lining fluid.

Aged↗

Ropivacaine 0.15% plus sufentanil 0.5 microg/mL and ropivacaine 0.10% plus sufentanil 0.5 microg/mL are equivalent for patient-controlled epidural analgesia during labor.

UNLABELLED: We compared the administration of 0.15% ropivacaine plus 0.5 microg/mL of sufentanil with that of 0.10% ropivacaine plus 0.5 microg/mL of sufentanil for labor analgesia with patient-controlled epidural analgesia (PCEA) to determine whether a decreased concentration of ropivacaine could produce equally effective analgesia. One-hundred-thirty healthy pregnant women at term were randomized in a double-blinded fashion. The PCEA settings were as follows: 12-mL initial bolus, 5-mL bolus dose, 5-min lockout interval, and 10 mL/h basal infusion. Patient demographics and labor characteristics were comparable in both groups. No differences were observed for pain scores, maternal satisfaction, volume of anesthetic solution administered, number of boluses requested and delivered, need for supplemental boluses, mode of delivery, motor block, side effects, or Apgar scores. Patients in the 0.10% ropivacaine group used significantly less drug than those in the 0.15% group (mean, 57 mg; 95% confidence interval, 50.5-63.5 mg; versus mean, 88.0 mg; 95% confidence interval, 74.4-93.3 mg, respectively; P < 0.0001). Ropivacaine 0.10% plus 0.5 microg/mL of sufentanil administered via PCEA for labor analgesia is equally effective as ropivacaine 0.15% plus 0.5 microg/mL of sufentanil, with a 30% local anesthetic-sparing effect and a 40% reduction in cost. However, this reduction in local anesthetic is not associated with a decrease in the incidence of motor block, side effects, or instrumental deliveries. IMPLICATIONS: Ropivacaine 0.10% plus 0.5 microg/mL of sufentanil given via patient-controlled epidural anesthesia for labor analgesia is equally as effective as ropivacaine 0.15% plus 0.5 microg/mL of sufentanil, with a 30% local anesthetic-sparing effect and a 40% reduction in cost. This reduction in ropivacaine concentration is not associated with a decrease in the incidence of motor block, side effects, or instrumental deliveries.

Adult↗