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F Servin

Publications and source records attributed to F Servin.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Diprivan and liver].

No evidence of hepatoxicity has been demonstrated with propofol. Propofol can be used for anaesthesia in patients suffering from moderate cirrhosis of the liver. Liver blood flow is preserved. Propofol dosage must be titrated to each patient's needs. Data concerning the use of propofol in patients suffering from severe hepatic failure or cholestasis are lacking. Propofol dosage in chronic alcoholic patients without cirrhosis must be increased.

Humans↗
PubMed1993

Plasma concentrations of midazolam after i.v., nasal or rectal administration in children.

Midazolam is used frequently for premedication in children, preferably by non-parenteral administration. We have compared plasma concentrations of midazolam after nasal, rectal and i.v. administration in 45 children (aged 2-9 yr; weight 10-30 kg) undergoing minor urological surgery. General anaesthesia consisted of spontaneous respiration of halothane and nitrous oxide in oxygen via a face mask. After administration of atropine and fentanyl i.v., children were allocated randomly to receive midazolam 0.2 mg kg-1 by the nasal, rectal or i.v. route. In the nasal group, children received 50% of the dose of midazolam in each nostril. In the rectal group, midazolam was given rectally via a cannula. Venous blood samples were obtained before and up to 360 min after administration of the drug. Plasma concentrations of midazolam were measured by gas chromatography and electron capture detection. After nasal and rectal administration, midazolam Cmax was 182 (SD 57) ng ml-1 within 12.6 (5.9) min, and 48 (16) ng ml-1 within 12.1 (6.4) min, respectively. Rectal administration resulted in smaller plasma concentrations. In the nasal group, a plasma concentration of midazolam 100 ng ml-1 occurred at about 6 min. After 45 min, the concentration curves after i.v. and nasal midazolam were similar.

Administration, Intranasal↗
PubMed1993

Propofol infusion for maintenance of anesthesia in morbidly obese patients receiving nitrous oxide. A clinical and pharmacokinetic study.

BACKGROUND: The pharmacokinetic and pharmacodynamic properties of propofol indicate that this may be an appropriate agent for induction and maintenance of anesthesia in obese patients. This study was designed to assess the rates of recovery and the pharmacokinetics of propofol infusions in morbidly obese patients. METHODS: Anesthesia was induced and maintained using a stepwise infusion regimen of propofol in eight morbidly obese patients. The patients' lungs were ventilated with nitrous oxide:oxygen (66:34%). Pharmacokinetic parameters were calculated from iterative blood sampling during the propofol infusion and during 8 h after its completion. RESULTS: Results were compared with those from a concurrent study of propofol pharmacokinetics in nonobese adults. The initial volume of distribution of propofol was not modified in obese patients. Total body clearance increase was correlated to body weight (R = 0.76, 25.4 +/- 6.5 ml.kg-1.min-1, mean +/- SD). Volume of distribution at steady state was also correlated to body weight (R = 0.61, 1.63 +/- 0.54 l.kg-1, mean +/- SD). Propofol concentration at the time of eye opening in response to verbal command was 0.94 +/- 0.26 mg.l-1. CONCLUSIONS: Results from this study confirm the absence of propofol accumulation in morbidly obese patients when the current dosing scheme is used. Dosing schemes expressed in mg.kg-1 are the same as those in normal patients.

Adult↗
PubMed1993

Chronic alcoholism increases the induction dose of propofol in humans.

The doses of propofol that produce loss of consciousness were investigated in 26 patients with chronic alcoholism and in 20 patients with a history of small alcoholic intake undergoing ear, nose, and throat surgery under general anesthesia. Last ethanol consumption by the alcoholics was 24 h preoperatively, as they had no access to alcohol when admitted to the hospital. Propofol was infused at a rate of 1200 mL/h (200 mg/min). The doses required to produce (a) loss of verbal contact and (b) loss of ability to grasp a 20-mL syringe filled with water were recorded. At this time a 2-mL venous blood sample was collected to detect propofol blood concentrations. A painful stimulus was applied to the abdomen, and a positive or negative response was noted. The mean +/- SD dose of propofol required for loss of verbal contact was 2.7 +/- 0.42 mg/kg in the alcoholic group and 2.2 +/- 0.43 mg/kg in the control group (P < 0.001). The dose of propofol required for dropping the syringe was significantly higher in the alcoholic group, 4.2 +/- 1.02 mg/kg versus 3.2 +/- 0.75 mg/kg in the control group (P < 0.01). The two groups did not differ significantly regarding the propofol blood concentrations at loss of consciousness, or the frequency of response or no response to painful stimulus. These findings suggest that the doses of propofol required to induce anesthesia in chronic alcoholic patients are more than in patients who drink socially.

Adult↗
PubMed1990

[Pharmacology in elderly patients].

The increasing population of elderly patients has special anesthesia care needs. In order to meet those, the pharmacological aspects of aging must be defined. A drug entering the body will generate a blood concentration, then be distributed to the tissues, inducing a pharmacological response. The determinants of blood concentration are absorption when the drug is not administered intravenously, distribution and elimination. Absorption is scarcely affected by ageing. On the contrary, the reduction of the lean mass as well as modifications of the plasma protein concentrations of binding deeply modify distribution. The main organ of drug metabolism is liver. Liver size and hepatic blood flow are reduced in elderly patients. Ageing induces heterogeneous modifications of metabolic pathways. Phase I reactions (oxidation, reduction and hydrolysis) are often slowed down, while phase II reactions (acetylation and conjugation) remain unaffected. Glomerular filtration rate is also reduced in elderly patients. Nevertheless plasma creatinine concentration remains close to the values observed in young healthy patients because of the reduction of the lean mass. The pharmacological response can be affected by the physiological modifications observed with ageing: metabolic rate is reduced, which diminishes the amount of drug necessary to achieve anesthesia. Cardiac index is very often reduced, but the major fact is a very large variability of cardiovascular function and an important reduction of functional reserve. Vascular compliance is diminished, and peroperative arterial pressure can be unstable. Respiratory function is also altered: vital capacity is reduced and hypoxemia frequently observed. Airway protective reflexes are impaired, enhancing the risk of inhalation particularly during recovery.

Aged↗
PubMed1990

Pharmacokinetics of propofol infusions in patients with cirrhosis.

We have compared the pharmacokinetics of propofol as an infusion in 10 control and 10 patients with cirrhosis. Anaesthesia was induced within 3-4 min during administration of an infusion of propofol 21 mg kg-1 h-1. After 5 min, the infusion was decreased in a stepwise manner to 12 mg kg-1 h-1 and subsequently 6 mg kg-1 h-1. The mean recovery time after discontinuation of the infusion was significantly longer in the cirrhotic group; however, when patients opened their eyes, blood concentrations of propofol were similar in both groups (1 micrograms ml-1). Pharmacokinetic analysis was performed from the beginning of infusion to 8 h after termination. Total body clearance was not reduced significantly in cirrhotic (1.56 (SD 0.48) litre min-1) compared with control (1.75 (0.32) litre min-1) patients. The volume of distribution at steady state was significantly greater in patients with cirrhosis than in control patients (202 (82) litre vs 121 (49) litre). However, this difference did not change terminal elimination half-life. The pharmacokinetics of propofol given by infusion to maintain general anaesthesia were not affected markedly by moderate cirrhosis.

Adult↗
PubMed1988

Midazolam infusion for basal sedation in intensive care: absence of accumulation.

This study was designed to: (1) determine plasma midazolam concentrations producing adequate sedation in ICU patients; (2) establish an intravenous regimen to provide continuous sedation and rapid recovery after discontinuation of infusion. Initially, 13 ICU patients were given midazolam as a bolus injection, 0.20 mg.kg-1 over 30 s in order to define the midazolam plasma concentration corresponding to an adequate level of sedation. The optimal level was reached in a mean time of 61 +/- 26 min and the mean corresponding midazolam plasma concentration was 163 +/- 62 ng.ml-1. Estimations of the main pharmacokinetic parameters (elimination half life: 230 +/- 102 min, total body clearance: 520 +/- 283 ml.min-1, total volume of distribution: 2.23 +/- 1.15 l.kg-1) showed no marked differences with normal patients. From those variables, an infusion regimen (loading dose and maintenance rate) to provide long term (24 to 80 h) sedation was derived in 9 patients. The mean loading dose was 0.33 +/- 0.18 mg.kg-1 over 30 min and the mean continuous infusion dose was 0.06 +/- 0.02 mg.kg-1.h-1. The mean midazolam plasma concentration during infusion was 215 +/- 61 ng.ml-1, and the mean midazolam plasma concentration at the end of infusion was 199 +/- 93 ng.ml-1. The level of sedation was considered as optimal in most patients throughout the study. After discontinuation of infusion, the mean time for normalization of the mental state was 97 min.

Adult↗
PubMed1988

Pharmacokinetics of midazolam in anaesthetized cirrhotic patients.

The pharmacokinetics of midazolam were compared in cirrhotic patients (n = 10) and control patients (n = 9), during general anaesthesia. Total plasma clearance was 637 +/- 223 ml min-1 (mean +/- SD) in control patients and 402 +/- 170 ml min-1 in cirrhotic patients (P less than 0.05). The total volume of distribution was similar. Elimination half-life was 135 +/- 40 min in controls and 168 +/- 30 min in cirrhosis (P less than 0.05). Protein binding was evaluated by equilibrium dialysis in both groups at two concentrations of midazolam: 20 and 500 micrograms litre-1. No saturation occurred, but the free fraction was 4.9 +/- 1.7% in cirrhotic patients, compared with 1.9 +/- 0.6% in controls (P less than 0.01). Despite its mainly hepatic elimination, midazolam disposition appears to be only slightly impaired in cirrhotic patients.

Adult↗
PubMed1988

Pharmacokinetics and protein binding of propofol in patients with cirrhosis.

The pharmacokinetics and protein binding of propofol were studied in ten patients with cirrhosis and in ten control patients undergoing elective surgery. All patients received 2.5 mg.kg-1 propofol as an intravenous bolus injection for the induction of anesthesia. Whole blood propofol concentrations were measured at intervals up to 12 h, using a high-performance liquid chromatography (HPLC) technique. Propofol protein binding was estimated by equilibrium dialysis 10 min after injection of propofol. Individual propofol profiles for all patients were best described by a three-compartment open mammillary model. Rapid and slow propofol distribution half-times were observed, followed by an elimination phase with a half-time of 4-5 h. Propofol total body clearance was reduced (1.99 +/- 0.68 l.min-1) in the patients with cirrhosis but did not differ significantly from that in the control patients (2.30 +/- 0.61 l.min-1). The apparent volume of distribution at steady state (Vdss) was similar in the two groups. No significant difference in elimination half-life was observed between the two groups. Propofol was extensively bound (mean: 97-98%) to the plasma protein of both cirrhotic and control groups. This study shows that propofol pharmacokinetics and protein binding of propofol following a single intravenous bolus dose were not markedly affected by uncomplicated cirrhosis of the liver.

Adult↗
PubMed1988

Pharmacokinetics of propofol administered by continuous infusion in patients with cirrhosis. Preliminary results.

Anaesthesia was provided by an infusion of propofol in six healthy patients and six patients with hepatic cirrhosis. There were no significant differences between the groups with regard to the central compartment volume, distribution volume at steady state, total apparent distribution volume, total body clearance or elimination half-life, although the values were always greater in the cirrhotic patients. Recovery times were significantly longer in the patients with cirrhosis.

Anesthesia, Intravenous↗
PubMed1987

[Use of a continuous infusion of propofol in maintaining anesthesia].

This open, non comparative study was designed to establish a suitable dose regime for propofol when used as the main anaesthetic agent and given as a continuous infusion. Thirty patients (ASA I and II) were studied; five received muscle relaxants and were excluded from the analysis of maintenance and recovery. Immediately after an i.v. bolus dose of fentanyl (2 micrograms X kg-1), anaesthesia was induced in all patients with a mean dose of 2.03 mg X kg-1 propofol. Apnoea at induction was seen in 14 patients, with a mean duration of 151 s (range: 20 to 360 s). Mean, systolic and diastolic arterial pressures and heart rate decreased slightly but statistically significantly following induction. Fourteen patients, four of whom received propofol into a vein of the hand, noted pain on the injection site without venous sequelae immediately nor 24 h after anaesthesia. The mean duration of anaesthesia from induction to the patient ability to obey a simple command was approximately 40 min (range: 10 to 95 min). The mean infusion rate of propofol during maintenance was 0.86 +/- 0.04 mg X kg-1 X min-1. During maintenance, a satisfactory depth of anaesthesia was achieved in 23 patients without any further bolus injection of propofol. The mean time from stopping the infusion to eye opening on verbal command was 6.2 min, whilst that for orientation was 8.4 min. The anaesthesist assessed the quality of recovery as good or adequate in all the patients, who all were satisfied by the anaesthesia. No major adverse reactions occurred during or after anaesthesia and the incidence of minor side-effects was low.

Adult↗