Search

Twenty-one children undergoing surgery received a caudal block using 1 ml kg-1 of a mixture of 50% lignocaine (1%) and 50% bupivacaine (0.25%). They were randomized into two groups, one of which received diazepam 10 mg rectally as premedication. Diazepam administration resulted in significantly higher Cmax and AUC values for bupivacaine but did not influence the plasma concentrations of lignocaine. [ABSTRACT FROM AUTHOR]

Background: The pharmacokinetic profile of local anaesthetics is influenced by the mode of administration. We sought to compare the pharmacokinetics of two doses of ropivacaine after fascia iliaca compartment (FIC) block in children., Methods: In this prospective, double-blind study, children received an FIC block as a part of their anaesthetic management during elective orthopaedic surgery on the thigh. They were randomized to receive ropivacaine 0.7 ml x kg(-1) using either a 0.375% or 0.5% solution. Venous blood samples were drawn up to 6 h after injection. Plasma concentrations of ropivacaine were measured by gas-liquid chromatography., Results: Six children (10.2 (range 5-15) yr, 35.6 (sd 10) kg were included. FIC block provided satisfactory peroperative pain relief. No signs of toxicity were observed, but high maximal plasma concentrations (C(max) 4.33-5.6 microg ml(-1)), were observed for three of four patients in the ropivacaine 0.5% group. The two patients in the 0.375% group showed values within the safe range (C(max) 0.66 and 0.98 microg ml(-1) respectively). Even though no toxic effects were observed, these results led us to discontinue the study., Conclusions: The administration of ropivacaine 3.5 mg x kg(-1) can be associated with sustained high plasma concentrations of ropivacaine, outside the tolerable range. In view of these results, we recommend the use of lower ropivacaine dosage during FIC block in children.

The pharmacokinetics of moxifloxacin was studied in 17 mechanically ventilated patients with pneumonia. Patients were given 400 mg of moxifloxacin intravenously. Blood samples and bronchial secretions were taken on days 1 and 4. A dose of 400 mg of moxifloxacin allows one to achieve efficient concentrations in bronchial secretions and plasma.

1. Tacrolimus and sirolimus are potent immunosuppressors used in transplantation. Tacrolimus has been suspected to alter mitochondrial respiration of different tissues but sirolimus has not been evaluated. 2. We evaluated the in vitro effect of tacrolimus and sirolimus on oxidative phosphorylation of isolated rat kidney mitochondria. 3. Oxygen consumption was measured with a Clark-type electrode. Tacrolimus and sirolimus increased the resting rate (state 4) and had no significant effect on ADP-stimulated respiration (state 3). The decrease of respiratory control ratio was concentration-dependent with a biphasic curve for tacrolimus. The EC(50)s were 3.4 x 10(-11) M and 2.3 x 10(-8) M for tacrolimus and 4.4 x 10(-10) M for sirolimus. The maximal inhibition was 20 and 14% for tacrolimus and sirolimus, respectively. 4. Tacrolimus and sirolimus had an uncoupling effect on oxidative phosphorylation related to a decrease of the inner membrane fluidity. At the opposite of cyclosporin A, no effect on swelling or Ca(2+) fluxes was observed. 5. All events occurred at therapeutic concentrations and then could appear during long-term treatment. Cellular consequences such as chronic nephrotoxicity with tacrolimus are suggested. The risk of cyclosporin A nephrotoxicity potentiation by sirolimus is discussed.

Unlabelled: We sought to determine the plasma concentrations of bupivacaine and its main metabolite after continuous fascia iliaca compartment (FIC) block in children. Twenty children (9.9 +/- 4 yr, 38 +/- 19 kg) received a continuous FIC block for either postoperative analgesia (n = 16) or femoral shaft fracture (n = 4). A bolus dose of 0.25% bupivacaine (1.56 +/- 0.3 mg/kg) with epinephrine was followed by a continuous administration of 0.1% bupivacaine (0.135 +/- 0.03 mg. kg(-)(1). h(-)(1)) for 48 h. Plasma bupivacaine levels were determined at 24 h and 48 h by using gas liquid chromatography. Heart rate, arterial blood pressure, respiratory rate, side effects, and pain scores were recorded at 4-h intervals during 48 h. No significant differences were found between mean plasma bupivacaine levels at 24 h (0.71 +/- 0.4 microg/mL) and at 48 h (0.84 +/- 0.4 microg/mL) (P = 0.33). FIC block provided adequate analgesia in most cases. No severe adverse effects were noted. We conclude that the bupivacaine plasma concentrations during continuous FIC block in children are within the safety margins. FIC block is well tolerated, and provides satisfactory pain relief in most cases., Implications: In this study, we have shown that, in children, continuous fascia iliaca compartment block, a technique providing neural blockade of the thigh and the anterior part of the knee, was associated with safe plasma bupivacaine concentrations, was well tolerated, and provided satisfactory pain scores in most cases.

Cerebrospinal fluid (CSF) penetration and the pharmacokinetics of vancomycin were studied after continuous infusion (50 to 60 mg/kg of body weight/day after a loading dose of 15 mg/kg) in 13 mechanically ventilated patients hospitalized in an intensive care unit. Seven patients were treated for a sensitive bacterial meningitis and the other six patients, who had a severe concomitant neurologic disease with intracranial hypertension, were treated for various infections. Vancomycin CSF penetration was significantly higher (P < 0.05) in the meningitis group (serum/CSF ratio, 48%) than in the other group (serum/CSF ratio, 18%). Vancomycin pharmacokinetic parameters did not differ from those obtained with conventional dosing. No adverse effect was observed, in particular with regard to renal function.

Unlabelled: Delayed recovery has been advocated to limit the postoperative stress linked to awakening from anesthesia, but data on this subject are lacking. In this study, we measured oxygen consumption (V(O2)) and plasma catecholamine concentrations as markers of postoperative stress. We tested the hypothesis that delayed recovery and extubation would attenuate metabolic changes after intracranial surgery. Thirty patients were included in a prospective, open study and were randomized into two groups. In Group I, the patients were tracheally extubated as soon as possible after surgery. In Group II, the patients were sedated with propofol for 2 h after surgery. V(O2), catecholamine concentration, mean arterial pressure (MAP), and heart rate (HR) were measured during anesthesia, at extubation, and 30 min after extubation. V(O2) and noradrenaline on extubation and mean V(O2) during recovery were significantly higher in Group II than in Group I (V(O2) for Group I: preextubation 215 +/- 46 mL/min, recovery 198 +/- 38 mL/min; for Group II: preextubation 320 +/- 75 mL/min, recovery 268 +/- 49 mL/min; noradrenaline on extubation for Group I: 207 +/- 76 pg/mL, for Group II: 374 +/- 236 pg/ mL). Extubation induced a significant increase in MAP. MAP, HR, and adrenaline values were not statistically different between groups. In conclusion, delayed recovery after neurosurgery cannot be recommended as a mechanism of limiting the metabolic and hemodynamic consequences from emergence from general anesthesia., Implications: In this study, we tested the hypothesis that delayed recovery after neurosurgery would attenuate the consequences of recovery from general anesthesia. As markers of stress, oxygen consumption and noradrenaline blood levels were higher after delayed versus early recovery. Thus, delayed recovery cannot be recommended as a mechanism of limiting the metabolic and hemodynamic consequences from emergence after neurosurgery.

Background: Studies of the effects of tobacco smoke often rely on reported exposure to cigarette smoke, a measure that is subject to bias. We describe here the relationship between parental smoking exposure as assessed by urinary cotinine excretion and lung function in children with asthma., Methods: We studied 90 children 4-14 years of age, who reported a confirmed diagnosis or symptoms of asthma. In each child, we assessed baseline pulmonary function (spirometry) and bronchial responsiveness to carbachol stimulation. Urinary cotinine was measured by HPLC with ultraviolet detection., Results: Urinary cotinine concentrations in the children were significantly correlated (P <0.001) with the number of cigarettes the parents, especially the mothers, smoked. Bronchial responsiveness to carbachol (but not spirometry test results) was correlated (P <0.03) with urinary cotinine in the children., Conclusion: Passive smoke exposure increases the bronchial responsiveness to carbachol in asthmatic children., (Copyright 1999 American Association for Clinical Chemistry)