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Biomedical subjects

J Y Lepage

Publications and source records attributed to J Y Lepage.

At least 19 recordsLinked to original sources

[Adequate prescription of antibiotic therapy for urinary tract infections in hospital: identifying and correcting non-observance of guidelines].

OBJECTIVE: We analyzed the adequacy of antibiotic therapy prescribed for urinary tract infections (UTI): prostatitis, pyelonephritis, indwelling catheter-associated UTIs, or other undefined UTIs. DESIGN: The adequacy of prescriptions to local guidelines was assessed retrospectively in two wards (Internal Medicine and Surgical Urology) of the Nantes University Hospital. The principal criteria involved simultaneously: choice of the molecule, dose, and treatment duration. Non-observances of guidelines were major (non-adequacy of the molecule, prescription of a non-active molecule according to in vitro susceptibility tests, non-appropriate treatment abstention), or minor (non-justified treatment, non-justified bitherapy, no prescription of bitherapy when requested, no treatment adaptation when requested, too short or too long treatment length, dosage mistakes). RESULTS: One thousand eighty-six infections were collected over a 24-month period. The overall rate of adequate prescriptions was 40.1% (46.6% in Internal Medicine and 36.5% in Surgical Urology). In Internal Medicine (226 non observance among 389 prescriptions), the ratio of major non-observance of guidelines was 9.8%. Among them, 44.7% were non-appropriate treatment abstentions. In Surgical Urology (539 non observance out of 695 prescriptions), non-observance related to treatment length were the most frequent. The ratio of major non-observance was 19.9%. Among them, non-adequacy of the molecule reached 60.7%. Non-justified treatment and non-appropriate bitherapies were frequent. CONCLUSIONS: For both units, indwelling catheter-related UTIs and other UTIs accounted for more than 50% of the infections although not detailed in the local guidelines. Identifying and analyzing Non observance may lead to targeted correcting actions to improve prescription quality.

Adult↗

[Anaesthesia and prostate surgery].

OBJECTIVES: To review the current data about anaesthetic management in prostate surgery with special regards on analysis and prevention of specific risks, appropriate anaesthetic procedure keeping with surgery and patient, recognition and treatment of adverse events. DATA SOURCES AND EXTRACTION: The Pubmed database was searched for articles (1990-2004) combined with references analysis of major articles on the field. DATA SYNTHESIS: It is strongly recommended to settle germfree urine in the preoperative period. The thromboembolic risk of radical retropubic prostatectomy for cancer parallels lower abdomen oncologic surgery and is prolonged. Preoperative evaluation of cardiovascular, respiratory, neurological and metabolic comorbidity is a source of prognostic information and an essential tool in the management of elderly patients with prostate disease. Extreme patient positioning applied in prostate surgery induces haemodynamic and respiratory changes and are associated with severe muscular and nervous injuries. The laparoscopic access for radical prostatectomy is a growing alternative to the open surgical procedure. Acute normovolaemic haemodilution is a consistent and cost-effective blood conservation strategy in reducing allogenic blood transfusion for radical retropubic prostatectomy. Whether open transvesical or transurethral prostatectomy for treatment of benign hypertrophy depends on the size of the gland: transurethral resection is safe up to 80 g. Intrathecal anaesthesia with a T9 cephalad spread of sensory block, produces adequate conditions for transurethral prostatectomy and allows a rapid diagnosis of irrigating fluid absorption syndrome. In spite of recommended preoperative antibiotic prophylaxis, bacteriemias are frequent during transurethral prostate resection.

Adenoma↗

Intrathecal anesthesia: ropivacaine versus bupivacaine.

We compared intrathecal ropivacaine to bupivacaine in patients scheduled for transurethral resection of bladder or prostate. Doses of ropivacaine and bupivacaine were chosen according to a 3:2 ratio found to be equipotent in orthopedic surgery. One hundred patients were randomly assigned to blindly receive either 10 mg of isobaric bupivacaine (0.2%, n = 50) or 15 mg of isobaric ropivacaine (0.3%, n = 50) over 30 s through a 27-gauge Quincke needle at the L2-3 level in the sitting position. Onset and offset times for sensory and motor blockades and mean arterial blood pressure were recorded. Pain at surgical site requiring supplemental analgesics was recorded. Cephalad spread of sensory blocks was higher with bupivacaine (median level, cold T(4) and pinprick T(7)) than with ropivacaine (cold T(6) and pinprick T(9)) (P<0.001). Eight patients in Group Ropivacaine received IV alfentanil (P<0.01). Onset time (mean +/- SD) to T(10) anesthesia and offset time at L2 were not different (bupivacaine = 13 +/-8 min, 127+/-41 min; ropivacaine = 11+/-7 min, 105+/-29 min). Complete motor blockade occurred in 43 patients with bupivacaine and in 41 patients with ropivacaine (not significant). Total duration of motor blockade was not different. No difference in hemodynamic effects was detected between groups. No patient reported back pain. We conclude that 15 mg of intrathecal ropivacaine provided similar motor and hemodynamic effects but less potent anesthesia than 10 mg of bupivacaine for endoscopic urological surgery.

Aged↗

Intrathecal bupivacaine in humans: influence of volume and baricity of solutions.

BACKGROUND: The effects of volume and baricity of spinal bupivacaine on block onset, height, duration, and hemodynamics were studied. METHODS: Ninety patients undergoing endoscopic urologic procedures were randomized to receive 10 mg of intrathecal bupivacaine at L2-L3 level in sitting position. In the operating room, commercial products were diluted as needed with NaCl 0.9% to obtain isobaric solutions (density, 1.005-1.008) or with NaC 10.9% and glucose 30% to obtain hyperbaric solutions (density, 1.031-1.037) of 2, 5, or 10 ml (six groups of 15 patients each). Three minutes after spinal injection the patients were placed in lithotomy position. Sensory blockade was assessed using pinprick and cold sensation tests, and motor blockade was assessed using a four-point scale. RESULTS: Onset times to maximal cephalad spread of spinal blockade were similar with isobaric and hyperbaric solutions. A greater maximal cephalad spread of anesthesia was obtained with diluted isobaric bupivacaine but was not associated with more hypotension. Volume had no effect on cephalad extent of anesthesia with hyperbaric bupivacaine. Times for regression of anesthesia to L2 and offset of motor block were longer with isobaric than with hyperbaric solutions of bupivacaine. The intensity of motor blockade was decreased with diluted hyperbaric bupivacaine. No patient reported back pain. CONCLUSION: In this study, volume had no significant influence on either cephalad spread or duration of sensory blockade for either isobaric or hyperbaric bupivacaine. Time for offset of anesthesia was shorter with hyperbaric bupivacaine compared with isobaric solutions.

Aged↗

The urodynamic effects of intravenous opioids and ketoprofen in humans.

UNLABELLED: We used a double-blind design to study urodynamic changes induced by mu-agonists (fentanyl, morphine), a partial mu-agonist antagonist (buprenorphine), a putative mu-antagonist, kappa-agonist (nalbuphine), and ketoprofen, an injectable nonsteroidal antiinflammatory drug. Men (20-55 yr old) were randomly assigned to receive one of the following i.v. before anesthesia for endoscopic extraction of a ureteral stone: 10 mg of morphine, 0.3 mg of buprenorphine, 0.35 mg of fentanyl, 20 mg of nalbuphine, 100 mg of ketoprofen, or 10 mL of 0.9% sodium chloride. The urodynamic study consisted of cystometry followed by urethral pressure profile. Measurements were taken before the i.v. infusion of drugs and 15 min thereafter. Statistical comparisons were performed by using analysis of variance with repeated measurements (P < 0.05). Ketoprofen and saline did not induce any urodynamic changes. Opioids altered bladder sensations, and the residual volume after voiding increased, except after morphine. Detrusor contraction decreased only after the administration of fentanyl and buprenorphine. Some patients could not micturate after receiving morphine, fentanyl, and buprenorphine. Compliance and urethral pressures did not change with any drug. This study suggests that ketoprofen and nalbuphine are useful analgesics in terms of their urodynamics. IMPLICATIONS: We compared the urodynamic effects of opioids and ketoprofen used as analgesics in surgical patients. In contrast to ketoprofen, opioids altered urodynamics. The opioid nalbuphine had no effect on detrusor contraction. This study suggests that ketoprofen and nalbuphine are useful analgesics in terms of their urodynamics.

Adult↗

Ketamine and norketamine plasma concentrations after i.v., nasal and rectal administration in children.

It has been suggested that nasal administration of ketamine may be used to induce anaesthesia in paediatric patients. We have examined the pharmacokinetics of ketamine and norketamine after nasal administration compared with rectal and i.v. administration in young children. During halothane anaesthesia, 32 children, aged 2-9 yr, weight 10-30 kg, were allocated randomly to receive ketamine 3 mg kg-1 nasally (group IN3) or ketamine 9 mg kg-1 nasally (group IN9); ketamine 9 mg kg-1 rectally (group IR9); or ketamine 3 mg kg-1 i.v. (group IV3). Venous blood samples were obtained before and up to 360 min after administration of ketamine. Plasma concentrations of ketamine and norketamine were measured by gas liquid chromatography. Statistical comparisons were performed using ANOVA and the Kruskall-Wallis test, with P < 0.05 as significant. Mean plasma concentrations of ketamine peaked at 496 ng ml-1 in group IN3 within 20 min, 2104 ng ml-1 in group IN9 within 21 min, and 632 ng ml-1 in group IR9 within 42 min. Plasma concentrations of norketamine peaked at approximately 120 min after nasal ketamine, but appeared more rapidly after rectal administration of ketamine and were always higher than ketamine concentrations in the same situation. Calculated bioavailability was 0.50 in groups IN3 and IN9 and 0.25 in group IR9. We conclude that nasal administration of low doses of ketamine produced plasma concentrations associated with analgesia, but using high doses via the nasal route produced high plasma concentrations of ketamine similar to those that induce anaesthesia. However, the large volume of ketamine required was partly swallowed and led to an unacceptable variability of effect that precludes this route for induction of anaesthesia.

Administration, Intranasal↗

Pharmacodynamic dose-response and safety study of cisatracurium (51W89) in adult surgical patients during N2O-O2-opioid anesthesia.

After administration of doses ranging from 0.025 to 0.25 mg/kg, the neuromuscular blocking effect of cisatracurium was assessed in 119 adult surgical patients receiving N2O-opioid-midazolam-thiopental anesthesia. The calculated 95% effective dose (ED95) for inhibition of adductor pollicis twitch evoked at 0.1 Hz was 0.053 mg/kg. With 0.10 mg/kg injected over 5-10 and 20-30 s, median onset times (range) were 5.8 (3.0-7.7) and 4.8 (1.2-10.2) min, respectively, and median times to 5% and 95% recovery (range) were 27 (19-46) and 48 (25-68) min, respectively. For doses of 0.10, 0.20, and 0.25 mg/kg, median 5%-95% and 25%-75% recovery indexes ranged from 48 to 90 min and 8 to 9 min, respectively. After administration of neostigmine (0.06 mg/kg) at 10%-15% or 16%-30% recovery, the median times to 95% recovery (range) were 6 (2-22) and 4 (2-5) min, respectively. There were no changes in heart rate, blood pressure, or plasma histamine concentrations during the first 5 min after administration of cisatracurium at doses up to 5 x ED95 injected over 5-10 s. No cutaneous flushing or bronchospasm was noted. In summary, cisatracurium is a potent neuromuscular blocking drug with an intermediate duration of action, characterized by excellent cardiovascular stability, with no apparent histamine release.

Adolescent↗

Retroperitoneal laparoscopic nephrectomy: animal and human anatomic studies.

Retroperitoneal laparoscopic nephrectomy with CO2 insufflation was performed in 11 goats. The hemodynamic and blood gas repercussions of retroperitoneal laparoscopy were compared during the first 30 minutes with those induced by intraperitoneal laparoscopy. With the animal placed in the left lateral supine position, the hemodynamic and blood gas changes were similar with the two techniques and had a similar time course. The technical feasibility of retroperitoneal laparoscopy in animals was confirmed in the fresh human cadaver. The technical feasibility of retroperitoneal laparoscopy and the absence of any particular hemodynamic and blood gas repercussions encourage us to develop this approach for clinical upper urinary tract surgery.

Animals↗

Motor and blood pressure effects of epidural sustained-release bupivacaine from polymer microspheres: a dose-response study in rabbits.

The incorporation of local anesthetics into injectable polymer microspheres can be useful in providing prolonged regional effects. This randomized study was designed to compare the effects of bupivacaine and bupivacaine-loaded microspheres on the time course of motor block in rabbits injected epidurally. Bupivacaine-loaded microspheres and drug-free microspheres 1-10 microns in size were devised from poly-d,l-lactic acid by using a solvent evaporation/extraction method. The effects of bupivacaine and of similar amounts of bupivacaine-loaded microspheres were studied in 26 rabbits as follows: 0.9% sodium chloride, followed by drug-free microspheres, then 1.25 mg of bupivacaine and 1.25 mg of bupivacaine-loaded microspheres (Group I; n = 8); 2.5 mg of bupivacaine, then 2.5 mg of bupivacaine-loaded microspheres (Group II; n = 8); and 5 mg of bupivacaine and 5 mg of bupivacaine-loaded microspheres (Group III; n = 10). Motor block was evaluated blindly by observation of walking disturbances, using a scale from 0 (free movements) to 3 (total limb paralysis). A period of 3 days elapsed between each injection. No limitation on movements was observed after 0.9% sodium chloride and drug-free microsphere injection. With 5 mg, both bupivacaine solutions provided complete motor block which was significantly more prolonged (+244% +/- 129%, mean +/- SD) with bupivacaine-loaded microspheres than bupivacaine. With 2.5 and 1.25 mg, block intensity was less marked, and block duration was shorter after administration of bupivacaine-loaded microspheres than after bupivacaine. We concluded that blocks resulting from bupivacaine-loaded microspheres are highly influenced by the amount of drug initially released by the polymer.

Animals↗

Premedication with midazolam in children. Effect of intranasal, rectal and oral routes on plasma midazolam concentrations.

We report a study performed to compare the time and plasma drug concentrations necessary to achieve a similar state of sedation after midazolam premedication given by various routes in children of 2-5 years old. Children were randomly allocated to one of three groups to receive midazolam 0.2 mg.kg-1 given intranasally, 0.5 mg.kg-1 given orally or 0.3 mg.kg-1 given rectally. Sedation was measured regularly until venepuncture was possible in a cooperative child. At this time, a first blood sample was taken to measure plasma concentration, followed by another 10 min later. Anaesthesia consisted of intravenous propofol supplemented with regional analgesia. At recovery from anaesthesia, a third blood sample was taken. Adequate sedation occurred sooner (7.7, SD 2.4 min) with intranasal than oral (12.5, SD 4.9 min) or rectal (16.3, SD 4.2 min) midazolam. The initial blood levels were lower when the drug was given by the alimentary routes despite higher doses (146, SD 51 ng.ml-1 in 11.5, SD 3.9 min; 104, SD 34 ng.ml-1 in 21 +/- 6 min; and 93, SD 63 ng.ml-1 in 23.1, SD 3.5 min for the intra nasal, rectal and oral routes respectively). Duration of surgical procedures, and of propofol infusion, and recovery from anaesthesia was similar for the three groups. The only problem arose in a 30-month-old boy in the intranasal group who developed respiratory depression with a plasma midazolam concentration of 169 ng.ml-1. Intranasal midazolam is an excellent alternative for rapid premedication provided that respiratory monitoring is used.

Administration, Intranasal↗

Acute effects of urapidil on left ventricular function in hypertensive patients: comparison with clonidine using radionuclide angiography.

We have studied the effects of urapidil 0.4 mg kg-1 i.v. and clonidine 2.5 micrograms kg-1 i.v. on left ventricular volume and function in 20 patients with chronic coronary artery disease and essential hypertension. Patients were studied using 99mtechnetium radionuclide angiography with first-pass and ECG-gated equilibrium blood-pool techniques and non-invasive sphygmomanometry. Administration of both urapidil and clonidine caused a similar decrease in mean arterial pressure (20%), associated with an equivalent reduction in systemic vascular resistance. Despite the decrease in mean arterial pressure, heart rate did not change after administration of clonidine, but there was an early and transient increase of 13% after urapidil. There were no changes in cardiac index, but in contrast with clonidine, urapidil caused a decrease in stroke index. In both groups, global left ventricular ejection fraction did not change. Urapidil produced a mean decrease in end-diastolic volume of 8% and a mean decrease in end-systolic volume of 13%, in contrast with clonidine which caused little change. Reduced arterial pressure, systemic vascular resistance and preload after urapidil 0.4 mg kg-1 i.v., associated with lack of prolonged tachycardia and preserved global left ventricular performance, may have obvious clinical implications in anaesthesia.

Adrenergic alpha-Antagonists↗

[Is urapidil a venodilator?].

This study aimed to assess and compare the effects of urapidil and clonidine on right ventricular volumes and function in 20 physical status ASA III patients, with a borderline untreated essential hypertension and with or without chronic coronary artery disease. The patients were randomly assigned to two equal groups to receive either urapidil (0.4 mg.kg-1) or clonidine (2.5 micrograms.kg-1). Neither patient had congestive heart failure, valvular heart disease, previous myocardial infarction, nor was any being treated with beta-blocking agents or with amiodarone. Usual anti-anginal medication (nifedipine and isosorbide) was maintained up to the time of the procedure. Monitoring was obtained from ECG, Swan-Ganz catheter fitted out with a fast response-thermistor, and radial artery cannula. Blood samples were withdrawn for plasma atrial natriuretic factor determination. Thirty minutes after catheter insertion, baseline data were collected in supine and 45 degrees head-up tilt positions. Following urapidil or clonidine i.v. injection, three series of measurements (3, 8 and 13 min) were made in supine and tilt positions according to a randomized sequence. The two groups were similar with regard to age, weight, height, coronary artery disease and treatment. Urapidil and clonidine elicited a similar decrease in mean arterial pressure of 14% in supine position and 20% in head-up tilt position, combined with an exclusive decrease in systolic index i.e. not associated with a change in peripheral vascular resistances. Despite the decrease in arterial pressure, heart rate remained unchanged. Right ventricular ejection fraction was maintained after both urapidil and clonidine, however end-diastolic and end-systolic volumes decreased, with no modification by tilting.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗

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↗

Is ketamine or its preservative responsible for neurotoxicity in the rabbit?

BACKGROUND: Although ketamine has been administered spinally in humans, previous neurotoxicity studies have shown that it can induce spinal cord lesions in various animal models. The aim of this work was to evaluate by histologic and blood-brain barrier studies whether different components of the commercial ketamine solution might be responsible for the microscopic lesions observed. METHODS: Forty white New Zealand rabbits were randomly assigned to four groups of 10. One-percent preservative-free ketamine (0.3 ml), 1% d-ketamine, 0.05% chlorobutanol, and 1% lidocaine were intrathecally injected through the atlantooccipital membrane. Laminectomy was performed on day 8, and the dura was preserved using paraformaldehyde-glutaraldehyde fixative. Light and fluorescence microscopy were performed on transverse spinal cord sections by a neuropathologist unaware of injected agents used. Specimens were then graded as normal or abnormal as compared with a control group receiving lidocaine. RESULTS: Isomers of ketamine did not induce spinal cord lesions in either study, but chlorobutanol (the preservative used in the ketamine solution) induced significant severe spinal cord lesions in both studies. CONCLUSIONS: The appearance of spinal cord lesions after intrathecal chlorobutanol strongly suggests that this preservative is responsible for apparent toxicity of ketamine and therefore should not be used in any solution intrathecally injected into humans.

Animals↗

Identification of factors affecting in vivo aminoglycoside activity in an experimental model of gram-negative endocarditis.

Aminoglycoside bactericidal activity during the first 24 h of treatment probably is a determining parameter in the prognosis of severe gram-negative infections in immunocompromised patients. To identify the predictive factors involved in the definition of the best therapeutic regimen for Enterobacter cloacae and Serratia marcescens infections, we studied different gentamicin, tobramycin, and amikacin regimens by using an experimental model of rabbit endocarditis. Two factors appear to play an important role in predicting in vivo efficacy: (i) the level of in vivo bactericidal activity, which can differ widely from one aminoglycoside to another for the same bacterial strain and from one strain to another of the same species, and (ii) the critical serum drug concentration (CSC, in milligrams per liter), defined as the lowest serum antibiotic concentration capable of producing a significant CFU reduction (P less than 0.05) in endocarditis vegetations 24 h after the beginning of a continuous infusion. Stepwise regression analysis showed that for gentamicin and S. marcescens, the area under the concentration-time curve above the CSC and then the time above the CSC are the determining parameters for efficacy (R = 0.69; F = 13.5; P = 0.001), whereas for amikacin and S. marcescens, the time above the CSC and then the area under the concentration-time curve above the CSC predict efficacy (R = 0.74; F = 24.0; P = 0.0001). The lowest CSC is that of amikacin (about 8 mg/liter); those of gentamicin and tobramycin are about 15 mg/liter. In severe S. marcescens infections, intermittent amikacin dosing offers excellent bactericidal activity within the first 24 h.

Amikacin↗

[Comparative effects of diazepam, ranitidine , sodium citrate and enprostil on pH and gastric volume in preanesthetic medication].

A study was designed to assess the efficacy of oral premedication with diazepam or enprostil in preventing the gastric aspiration syndrome in fasted patients scheduled for elective surgery, and to compare the results with those obtained with ranitidine and sodium citrate. The study included 120 consecutive patients undergoing urological or plastic surgery, randomly assigned to four groups of 30. Two hours before anaesthesia, the patients from three groups were given, with 30 ml of water, either 10 mg diazepam, or 150 mg ranitidine, or 35 micrograms enprostil. Those in the fourth group were given 30 ml of 0.5 M sodium citrate, ten minutes before induction. Anaesthesia consisted in the administration of thiopentone, fentanyl, vecuronium and nitrous oxide in oxygen. After endotracheal intubation, a gastric tube was inserted. The stomach fluid content was completely aspirated, and then again 60 and 120 min after induction, as well as at the end of surgery. Age, weight and duration of surgery were comparable in the four groups. Mean pH in the diazepam group was much lower than that in the other groups, both just after induction (2.3 +/- 1.54; p less than 0.001 vs. ranitidine and sodium citrate; p less than 0.01 vs. enprostil) and at the end of surgery (3.2 +/- 2.03; p less than 0.01 vs. ranitidine and sodium citrate; p less than 0.05 vs. enprostil). There was more than 0.4 ml.kg-1 gastric juice in the sodium citrate group.(ABSTRACT TRUNCATED AT 250 WORDS)

Antacids↗