Perioperative infusions in paediatric patients: rationale for using Ringer-lactate solution with low dextrose concentration.

To assess the usefulness of Ringer-lactate solution with 0.9% dextrose, fluid therapy during surgery in paediatric patients was reviewed. From the literature, the need for intravenous (i.v.) infusion and water could be established. The need for sodium was also evident and use of normonatraemic i.v. solutions should be recommended to avoid hyponatraemia. Little data were found about the value of the other electrolytes. Dextrose requirements have been the subject of debate for the last two decades. The choice of dextrose concentration is a compromise between avoiding hypoglycaemia and hyperglycaemia. Four clinical trials assessing the use of Ringer-lactate solution with 0.9 or 1% dextrose in paediatric patients suggest that it is appropriate for routine infusion in paediatric patients during the perioperative period. However, fluid therapy during surgery has rarely been studied, probably because it is inexpensive, rarely leads to problems and is used in very different clinical settings. Development of consensus clinical guidelines on the use of electrolyte infusions in paediatric surgery would be helpful.

Effect of multifaceted intervention promoting early switch from intravenous to oral acetaminophen for postoperative pain: controlled, prospective, before and after study.

PROBLEM: Need to improve the efficiency of postoperative pain management by early switching from intravenous to oral acetaminophen. DESIGN: Implementation of local guidelines aimed at improving nurses' and doctors' behaviour. A controlled, prospective, before and after study evaluated its impact on appropriateness and costs. BACKGROUND AND SETTING: Orthopaedic surgery department (intervention) and all other surgical departments (control) of a university hospital. Five anaesthetists and 30 nurses of orthopaedic department participated in study. KEY MEASURES FOR IMPROVEMENT: Reducing number of acetaminophen injections per patient, reducing consumption of acetaminophen injections; cost savings over a one year period. STRATEGIES FOR IMPROVEMENT: Multifaceted intervention included a local consensus process, short educational presentation, poster displayed in all nurses' offices, and feedback of practices six months after implementation of guidelines. EFFECTS OF CHANGE: Mean number of acetaminophen injections per patient decreased from 6.81 before intervention to 2.36 six months after. Monthly consumption of acetaminophen injections per 100 patients decreased by 320.9 (95% confidence interval 192.4 to 449.4) in intervention department and remained unchanged in control departments. Annual cost reduction was projected to be pound 15,100. LESSONS LEARNT: Simple and locally implemented guidelines can improve practices and cut costs. Educational interventions can improve professionals' behaviour when they are based on actual working practices, use interactive techniques such as discussion groups, and are associated with other effective implementation strategies.

Pharmacokinetics of superoxide dismutase in rats after oral administration.

The kinetic behaviour of bovine erythrocyte Cu-Zn SOD was investigated in Sprague Dawley male rats after subcutaneous and oral administrations of doses ranging from 0 center dot 5 to 20 mg kg-1. Studies have been carried out with SOD and SOD encapsulated into liposomes containing or not containing ceramides. The maximum concentration (Cmax) in blood cell pellets ranged from 8 center dot 65 to 11 center dot 03 U/mg haemoglobin (Hb) after subcutaneous injection, and from 4 center dot 48 to 8 center dot 23 U/mg Hb after oral administration. The maximum concentrations were reached in 5 h (t max) for the two routes. Comparison between the areas under the curves (AUCs) obtained after subcutaneous and oral administration allowed the calculation of relative bioavailability (F'). The maximum bioavailability after oral administration was 14% for free SOD, 22% for SOD encapsulated into liposomes, and 57% when ceramides were added to liposomes. Poor SOD bioavailability was enhanced by liposome encapsulation, and ceramide addition seemed to be beneficial for oral encapsulated SOD administration.

Effect of encapsulation on the anti-inflammatory properties of superoxide dismutase after oral administration.

Anti-inflammatory properties of free superoxide dismutase and superoxide dismutase encapsulated into liposomes, with or without ceramides, have been investigated. Two models were investigated: carrageenan paw oedema and pleurisy. Animals were fed by repeated doses, twice daily from day 1 until day 4. Evaluation consisted of measurement of paw oedema volume with determination of prostaglandin E2, thromboxane B2 and 6-keto-prostaglandin F1 alpha levels. Polymorphonuclear oxidative metabolism was evaluated by measurement of superoxide anion production. Levels of superoxide dismutase were determined in cells and pleural exudates. Higher anti-inflammatory effects were obtained after eight administrations of encapsulated forms (0.5 mg/kg) whereas free superoxide dismutase have shown no effects. Ceramides enhanced the results obtained.

[Physicochemical incompatibility of injectable drugs: practical considerations]. / Incompatibilités physico-chimiques des médicaments injectables: considérations pratiques.

Preservatives and additives are needed to prepare stable solutions for injection. They may provoke physiochemical reactions when these solutions are mixed. End-products may be either inactive or toxic to the patient. Information on allowed mixtures is scarce. Compatibility analyses are difficult to perform in a short time and are usually expensive. The best way would be to inject the drugs separately with 50 or 100 ml infusions. Moreover, some laboratories supply prepared infusion solutions such as buflomedil, pefloxacine, metronidazole.

[Cost of intensive treatment followed by autograft of circulating stem cells. Application to multiple myeloma]. / Coût d'un traitement intensif suivi d'une autogreffe de cellules souches circulantes. Application au myélome multiple.

OBJECTIVES: Legitimate efforts to reduce health care costs, especially of intensive protocols including transplantation for haematological diseases, require realistic economic evaluations. We determined the direct cost of intensive chemotherapy associated with total body irradiation and autologous blood stem cell transplantation in patients with multiple myeloma. METHODS: Ten consecutive patients (7 males, 3 females) with Stage II or II multiple myeloma, who had received no prior treatment and were under the age of 55, were included in the study. Peripheral blood stem cells were collected by successive cytaphereses after a short period of aplasia induced by a CHOP protocol. During this period, the patients were in normal hospital rooms. A VAMP protocol was then administered in three 4-day sessions. Intensive therapy was started 1 month later with CCNU, etoposide, cyclophosphamide and melphalan. Total body irradiation (12 Gy) was performed on days -3, -2, -1. Autologous grafting was done on day 0. The intensive therapy was followed by a period of aplasia and the patients were protected in laminar flow rooms. Regular antibiotic and haematologic protocols were applied. Growth hormone was not given. The patients were seen regularly for follow-up and interferon alpha 2b was prescribed for 5. RESULTS: The mean cost of the two year treatment was 468,392 +/- 167,467 French francs. Personnel accounted for 36% of the total cost, marrow collection 13%, blood products 9.8%, laboratory tests 8.2% and drugs 7.2%. Little data are available in the literature of comparable cost analyses in other French hospitals or in other countries. CONCLUSION: Controlled cost/benefit studies should be conducted to enable a rigorous comparison between different therapeutic strategies.

[Treatment of mucositis with vitamin E during administration of neutropenic antineoplastic agents]. / Traitement des mucites par la vitamine E lors de l'administration d'anti-néoplasiques neutropéniants.

Mucositis represents one of the most frequent complications during chemotherapy or radiotherapy. Few studies have showed effective prevention against mucositis in this setting. In this randomized study, we tested the efficacy of vitamin E in the treatment of chemotherapy-induced mucositis. Twenty patients with malignant haemopathies were included; 19 patients were evaluable for the prevention of mucositis. Ten patients were treated with induction therapy for acute myelogenous leukaemia and 9 were treated with intensive therapy followed by autologous bone marrow transplantations. The severity of mucositis was evaluated according to World Health Organization classification. Our results showed that vitamin E may be of therapeutical value in the prevention of mucositis especially during induction therapy for acute myelogenous leukaemia.

Influence of beta carotene, vitamin E, and vitamin C on endogenous antioxidant defenses in erythrocytes.

OBJECTIVE: To evaluate the in vivo radical scavenger activity of vitamin E, vitamin C, and beta carotene on erythrocyte membranes. DESIGN: A prospective, open trial without placebo. SETTING: Department of Clinical Pharmacy. PATIENTS: Ten healthy volunteers being supplemented with beta carotene, vitamin E, and vitamin C. MEASUREMENTS: Erythrocytes were incubated in water bath with 2,2' azobis (2 amidinopropane) hydrochloride (AAPH). AAPH decomposes spontaneously at 37 degrees C to generate free radicals inducing membrane cellular damage and hemolysis. The absorbance was measured at 405 nm at 0, 30, and 60 min, and then every 20 minutes for four hours. The time for 50 percent of maximal hemolysis (T50%), which expresses the radical scavenger activity of erythrocytes, was determined. RESULTS: The physiologic T50% value determined in 52 healthy volunteers is 117 +/- 12 min. Patients receiving these supplements have a higher value of T50% (143.2 +/- 11.6 min at 30 d and 145.7 +/- 10.5 min at 60 d) than the physiologic value (p < 0.001). CONCLUSIONS: These data suggest that vitamin C, vitamin E, and beta carotene stimulate the radical scavenger activity of erythrocyte membranes after 30 days.

Thermal desorption-gas chromatographic determination of ethane and pentane in breath as potential markers of lipid peroxidation.

Formation of free radicals and lipoperoxidation occur at the onset of cellular damage. These effects are produced during normal metabolism and in pathological states. The peroxidation of polyunsaturated fatty acids, i.e. linoleic acid and linolenic acid, which are both cellular membrane compounds, induces ethane and pentane formation in pulmonary air exhalation. These two volatile hydrocarbons can be considered as potential lipoperoxidation markers. Methodological difficulties limit the use of these gases for assessment of free oxygen radical activity but we have developed and validated a non-invasive technique. A study was performed with ten healthy volunteers.

Plasma concentrations of beta-carotene, vitamin A and vitamin E after beta-carotene and vitamin E intake.

We have studied the metabolism (absorption) of beta-carotene and vitamin E by assigning eleven volunteers to receive daily two capsules of OENOBIOL, each containing 15 mg of beta-carotene and 15 mg of vitamin E, over 60 days. The beta-carotene, vitamin E and vitamin A plasma levels were then determined using new methods developed in our laboratory. After two months, the actively treated group's median beta-carotene and vitamin E levels were significantly higher than those of a control group. However, no significant change between treated and control groups in the mean of vitamin A (retinol) plasma levels were observed. Treatment with beta-carotene, a vitamin A precursor, does not significantly modify the vitamin A levels. This conclusion had already been observed and it is assumed that a plasma level of beta-carotene equal or higher than 0.3 mg/L reflects a nutritional intake of provitamins sufficient to support homeostasis of retinol (Brubacher et al., 1982).

[Resumption of function of the liver graft. Controlled comparative study of UW solution and SLF Cochin]. / Reprise de fonction du greffon hépatique. Etude contrôlée comparant la solution UW et le SLF Cochin.

Nowadays the UW solution is usually used in liver transplantation for graft preservation. The importance of each of its components has not been fully resolved. The omission of some of the components does not result in poor hepatic function. The aim of this controlled study was to assess the early graft function (ALAT, factor V and total bilirubin at days 1, 2, 3 and 6) after use of the UW solution and SLF Cochin. SLF Cochin is a modified UW solution without hydroxyethyl starch, adenosine, penicillin, dexamethazone and allopurinol. No significant difference was observed in the early graft function between the two solutions for a cold ischemia time below 15 hours. Considering the qualities of the SLF Cochin and its three fold lower cost, it is concluded that the use of the SLF Cochin solution is justified for liver transplantation in which foreseeable cold ischemia time is less than 15 hours.

[Pharmacist drug dispensing in clinical trials]. / La dispensation pharmaceutique dans les essais cliniques.

Dispensing experimental drugs in part of a pharmacist's task in the hospital since the 20.12.1988 law. A 13 month critical evaluation dispensing drugs for clinical trials is presented. Drug management, distribution and control in 61 new studies included 1,165 patients need a full time pharmacist. This new organization is well accepted by sponsors and investigators. The hospital pharmacist's contributions to clinical trials are: protocol application in hospital practice, nurses information, efficient and safe storage and distribution to patients. The pharmacist facilitates good clinical practices and quality assurance. The problem is that in many french hospitals the pharmaceutical department is chiefly a wholesale dealer for pharmaceutical products. Our opinion is that the pharmacists should deliver drugs to improve patient compliance.

Determination of the enantiomers of mefloquine in plasma and whole blood using a coupled achiral-chiral high-performance liquid chromatographic system.

A coupled achiral-chiral high-performance liquid chromatographic system has been developed for the determination of the enantiomers of mefloquine, (+)-MFQ and (-)-MFQ, in plasma and whole blood. The MFQ was separated from the interfering components in the biological matrix and quantified on a cyano-bonded phase, and the enantiomeric composition was determined on an (S)-naphthylurea chiral stationary phase. The two columns were connected by a switching valve equipped with a silica precolumn. The precolumn was used to concentrate the MFQ in the eluent from the achiral column before backflushing onto the chiral phase. The coupled-column system was validated and applied to the analysis of a pilot study of the pharmacokinetics of (+)- and (-)-MFQ in plasma and whole blood.

Comparison of rat liver preservation with Eurocollins and a modified University of Wisconsin solution: transplantation and isolation of hepatocytes for culture.

The efficiency of Eurocollins or modified University of Wisconsin (UW) solution (MUW) in preserving rat livers was compared. After cold storage with one of the solutions, the livers were transplanted or perfused by collagenase for isolation of hepatocytes. Five of the 6 rats receiving a graft preserved with MUW versus none of the 6 rat receiving a graft preserved with Eurocollins solution survived 24 h or more. A significantly greater number of hepatocytes were isolated from livers preserved with MUW than from livers preserved with Eurocollins solution. This suggests a better reperfusion of MUW-preserved livers by collagenase resulting from less endothelial injury. LDH release by cultured hepatocytes, ketone body production and stimulation by glucagon were not significantly different between the two groups. These results confirm the superiority of MUW solution over Eurocollins in preserving liver grafts. They suggest that the advantage of MUW solution results from better protection of vascular endothelium rather than of hepatocytes.