[First French-speaking days of users of decision support system in clinical pharmacy: Feedback and perspectives]. / Premières journées francophones des utilisateurs de système d'aide à la décision en pharmacie clinique : retour d'expériences et perspectives.

Clinical decision support systems (CDSS) are tools that have been used for several years by clinical pharmacy teams to support pharmaceutical analysis, with a perspective of contributing to the quality of care in collaboration with the other health care team members. These tools require both technical, logistical and human resources. The growing use of these systems in different establishments in France and in Europe gave birth to the idea of meeting to share our experiences. The days organized in Lille in September 2021 aimed at proposing a time of exchange and reflection on the use of these CDSS in clinical pharmacy. A first session was devoted to feedback from each establishment. These tools are essentially used to optimize pharmaceutical analysis and to secure patient medication management. This session outlined the clear advantages and common limitations of these CDSS. Two research projects were also presented to put the use of these tools into perspective. The second session of these days, in the form of workshops, addressed 4 themes that surround the implementation of CDSS: their usability, the legal aspect, the creation of rules and their possible valorization. Common problems were raised, the resolution of which requires close collaboration. This is a first step proposing a beginning of harmonization and sharing that should be deepened in order not to lose the dynamics created between the different centers. This event ended with the proposal to set up two working groups around these systems: the creation and structuring of rules for the detection of risk situations and the common valorization of the work.

[Standardized computer recording of clinical pharmacy procedures in health care institution: Feedback and evaluation of potential economic value]. / Enregistrement informatique normalisé des actes de pharmacie clinique en établissement de santé : retour d'expérience et évaluation de la valorisation économique potentielle.

Clinical pharmacy procedures are clearly defined by the French society of clinical pharmacy. However, clinical pharmacists do not have efficient tools for their traceability. This need has increased following the publication of the instruction on the day hospital management of patients. Indeed, the action of the clinical pharmacist is included in it. In order to improve our traceability of clinical pharmacy acts and to take advantage of the implementation of the instruction, we worked with the medical information department to integrate our activity into their business software and to model the pathways valued by the intervention of the clinical pharmacist in outpatient care and in day hospital.

[Evaluation of the training of clinical pharmacy residents in prescription analysis using an ergonomic approach]. / Évaluation de la formation des internes en pharmacie clinique à l'analyse des prescriptions selon une approche ergonomique.

OBJECTIVES: To perform an ergonomic intervention using the methodology of the analysis of the activity of the training process of clinical pharmacy residents in the analysis of prescriptions. METHODS: The evaluation was carried out over two semesters: from May to October 2016 (first study) and from November 2016 to April 2017 (second study). The interviews and observations were conducted by an ergonomist who is an expert in this type of evaluation. The first study was based on observations of the training process and interviews at different time. The second study allowed to support pharmacists and evaluate the changes following the recommendations of the previous study. RESULTS: A total of 6 and 9 residents participated in the first and second study, respectively. During the first study, 6 difficulties were raised which allowed implementation decisions. Feedback from residents on the training process was generally positive for the first part of the training but negative for the last part. The average number of fears expressed by the residents was higher at the beginning (2.9 fears) than at the end (1 fear). CONCLUSIONS: The training process has been adapted to the expectations and feelings of the residents. Follow-up at the beginning and throughout the internship was essential. The next stage of this work will be to evaluate the contribution of the dashboards for monitoring clinical pharmacy skills in the new degree for hospital pharmacy.

The clinical pharmacist's role in enhancing the relevance of a clinical decision support system.

BACKGROUND: Clinical decision support systems (CDSSs) can improve the quality of patient care by helping physicians to review their prescriptions and thus to optimize drug treatments. Nevertheless, the "alert fatigue" brought on by a large number of irrelevant alerts can decrease a CDSS's effectiveness and thus clinical value. Involving a clinical pharmacist in the development and management of a CDSS can reduce the number of irrelevant alerts presented to physicians. Clinical pharmacists screen alerts and suggest PIs for physicians, corresponding to any proposed therapeutic change about health products, only for relevant alerts could improve the relevance and the acceptance of the information given to physicians about the risks faced by their patients. OBJECTIVE: To assess the value of involving clinical pharmacists in the development and maintenance of decision support rules for generating alerts and pharmaceutical interventions (PIs) and to describe the level of acceptance of these PIs by the physicians. METHOD: In a retrospective, single-centre study, we evaluated the number of PIs accepted from alerts generated by the CDSS when a clinical pharmacist had developed and managed this tool. During the first 7 months of development of the CDSS, a clinical pharmacist analyzed alerts triggered by the CDSS according to its technical validity and pharmaceutical relevance. Lastly, for alerts that led to a PI, the level of acceptance by physicians was documented. RESULTS: During the study, 1430 alerts were analysed: 186 (13%) were considered to be technically invalid - mainly due to the characteristics of the interface. Of the 1244 (87.0%) technically valid alerts, 353 (24.6%) were pharmaceutically relevant and led to a PI. The three main causes of pharmaceutical irrelevance were a lack of specificity in the CDSS (70.8%), lack of relevance with regard to the ward's habits (15.6%), and the pharmacist's decision to recommend monitoring for the patient rather than sending a PI immediately (10.8%). 64.6% of the submitted PIs were accepted by the physicians. CONCLUSION: The standardized analysis of alerts by a clinical pharmacist appears to be a good way of improving the development of CDSS by limiting the generation of irrelevant alerts and the latter's transmission to physicians. The involvement of a clinical pharmacist in the development and implementation of a CDSS appears to be novel and may help to optimize drug treatment.

Traces pilot pharmacokinetic study dataset.

The dataset displays the pharmacokinetics data obtained from the TRACES pilot study. The nine patients included were undergoing haemorrhagic caesarean section (blood loss > 800 mL) and receiving a single i.v dose of tranexamic acid (0.5, 1 or 2 g over 1 min). The dataset gathers the tranexamic acid blood and urinary concentrations. With these first elements, a pharmacokinetic compartment model was built as described in Gilliot et al. and the individual pharmacokinetic parameters were estimated. In parallel, the patients anthropometric, biological, and clinical characteristics were collected. The correlation between the patient data and the estimated individual pharmacokinetic parameters were tested. The correlation tests revealed that the dose, the height, the body weight, and the ideal bodyweight had and impact on the volume of distribution of tranexamic acid. According to these results, these latter covariates were explored using a multi-regression analysis in Gilliot et al.

Hypothesis for a partially non urinary elimination of tranexamic acid in haemorrhagic caesarean section: Traces pilot pharmacokinetic study: Pharmacokinetics of tranexamic acid in obstetrics.

BACKGROUND: In previous studies, the choice of doses of tranexamic acid was empirically defined as no pharmacokinetic study had been conducted in haemorrhagic caesarean section. OBJECTIVE: The objective was to build a pharmacokinetic model in patients receiving a single 0.5, 1 or 2 g intravenous bolus. METHOD: A preliminary monocentric open study was performed in the Lille centre. Blood samples and one urinary sample were collected in the 6 h following the injection. Nine patients were included. Tranexamic acid concentration was measured using liquid chromatography system coupled with tandem mass spectrometry. We used Monolix 2019R1 for population pharmacokinetic modelling. A structural model was constructed followed by the investigation of potential covariates. RESULTS: Data were best described with a two-compartment model with a double first-order elimination from the central compartment. The model was improved when the variable ideal weight per dose was affected as a covariate for the apparent volume of distribution. Assuming a dose of 1 g and a height of 160 cm, the pharmacokinetic parameters were estimated at 10.26 L.h-1 for total clearance, 11.5 L for the volume of the central compartment, 15.8 L for the volume of the second compartment, a diffusional clearance of 30.36 L.h-1 , and a urinary excretion fraction of 25.8%. CONCLUSIONS: The population pharmacokinetic model of tranexamic acid in haemorrhagic caesarean section was successfully established in our tiny sample of patients. The results of this preliminary TRACES pharmacokinetic study suggested that elimination of tranexamic acid is partially non urinary in contrast with healthy patients.

[Evaluation of knowledge and perceptions of pharmacists and residents pharmacists about bibliometric indicators applied to the scientific literature in pharmacy]. / Évaluation des connaissances et perceptions des pharmaciens et internes en pharmacie sur les indicateurs de notoriété appliqués à la publication scientifique en pharmacie.

OBJECTIVES: Evaluate the level of knowledge and perceptions of French and Quebec hospital's pharmacists/residents about bibliometrics indicators applied in pharmacy. Identify the determinants associated with this knowledge. METHODS: This is a descriptive cross-sectional study. An anonymous questionnaire of 17 questions answers was developed. The questionnaire was published on the SurveyMonkey site (www.SurveyMonkey.com, SurveyMonkey, Portland, OR, USA) and released from March 19 to April 9, 2018. We calculated and compared the proportion of respondents in Quebec and France by using a Chi2 test. A value less than 0.05 is considered statistically significant. RESULTS: A total of 899 pharmacists (646 in Quebec and 253 in France) and 147 residents (70 in Quebec and 77 in France) were contacted by email. The survey was completed by 401 respondents, e.g., 301 in Quebec (participation rate: 42%) and 100 in France (30%). Overall 26% (106/401) of respondents (67/301 in Quebec vs. 39/100 in France) reported having knowledge or good knowledge of those indicators. These data are corroborated by many other results. CONCLUSIONS: Small proportions are aware of those indicators. A good knowledge is associated with being a French pharmacist, working in a teaching hospital or university, having a professional experience of 10 years or more, be involved in a research project, having a scientific watch or having an online profile on database. It appears necessary to inform pharmacists and residents on notoriety indicators.

A new pharmacokinetic model for 90Y-ibritumomab tiuxetan based on 3-dimensional dosimetry.

Monoclonal antibodies (mAbs) are key components in several therapies for cancer and inflammatory diseases but current knowledge of their clinical pharmacokinetics and distribution in human tissues remains incomplete. Consequently, optimal dosing and scheduling in clinics are affected. With sequential radiolabeled mAb-based imaging, radiation dosing in tissues/organs can be calculated to provide a better assessment of mAb concentrations in tissues. This is the first pharmacokinetic model of 90Y-Ibritumomab tiuxetan (90Y-IT) in humans to be described, based on three-dimensional (3D) dosimetry using single-photon emission computed-tomography coupled with computed-tomography. 19 patients with follicular lymphoma were treated initially with 90Y-IT in the FIZZ trial. Based on a compartmental approach individualising the vascular compartment within studied organs, this study proposes a reliable pharmacokinetic (PK) five-compartment model replacing the currently used two-compartment model and constitutes a new direction for further research. This model provides exchange constants between the different tissues, Area Under the Curve of 111In-IT in blood (AUC) and Mean Residence Time (MRT) that have not been reported so far for IT. Finally, the elimination process appears to occur in a compartment other than the liver or the spleen and suggests the metabolism of mAbs may take place mainly on the vascular compartment level.

Development and validation of an UHPLC-MS/MS method for simultaneous quantification of ibrutinib and its dihydrodiol-metabolite in human cerebrospinal fluid.

Ibrutinib is an orally administered first-in-class irreversible Bruton's tyrosine kinase (BTK) covalent inhibitor for the treatment of patients with B-cell malignancies. Several isolated clinical observations reported its efficacy in central nervous system dissemination. Herein, we described the development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) procedure for the quantification of ibrutinib and its active metabolite PCI-45227 in cerebrospinal fluid (CSF). This is the first complete validated method for quantification of ibrutinib and PCI-45227 in CSF. The compounds were eluted on a Waters BEH C18 column (50.0 × 2.1 mm; 1.7 µm) using a gradient elution with a mobile phase composed of ammonium formate buffer 5 mM pH 3.2 and acetonitrile +0.1% formic acid with a flow rate of 400 µL·min-1. Two deuterated internal standards were used to obtain the most accurate quantification. The CSF samples were prepared by a simple and rapid dilution. The method was validated by testing the selectivity, response function, intra-day and inter-day precisions, trueness, limits of detection (LOD) and lower limits of quantification (LLOQ). The validation results proved that the methods were suitable to quantify ibrutinib and PCI-45227 in real biological CSF samples from 0.50 (ibrutinib) or 1.00 (PCI-45227) to 30.00 ng·mL-1. Furthermore, the developed method was adapted to allow the quantification of both compounds in plasma and the results were compared to those reported in literature. The plasmatic samples were treated by protein precipitation and the method was validated to quantify ibrutinib and PCI-45227 in real biological plasmatic samples from 5.00 to 491 ng·mL-1. Lastly, for both matrices, accuracy profiles were plotted from the trueness and precision results using a 20% α-risk (ß = 80%) and the tolerance intervals were comprised within the acceptance limits fixed at ±25% for the LLOQ and ±15% for the other concentrations. Finally, these methods were successfully applied to quantify ibrutinib and PCI-45227 in real human CSF and plasma samples.

[Particulate contamination associated with the manipulation of drugs in glass ampules: A literature review]. / Présence de particules associées à la préparation de médicaments provenant d'ampoules de verre : revue de littérature.

OBJECTIVES: The manipulation of drugs from glass ampules can generate particles when the ampule is broken. Several authors recommend the use of filter needle to withdraw the drug content. The aim of this study is to make an assessment of the presence of particles during the manipulation of glass ampules and to discuss the current practices. METHODS: Literature review based on a search strategy (Pubmed, Google Scholar) and a summary table of available data. Analysis to evaluate the efficacy of the filtration when data are available. RESULTS: Eighteen articles have been included. Most of study shows the presence of particles in glass ampules. Important discrepancies reported regarding the number of particles per ampule. Analysis of data from seven studies: decrease of 83% of the total number of particles (>10µm) identified when drugs are removed with filter needle. All studies but two confirm the efficacy of filter needles. CONCLUSIONS: Studies show the presence of particles when drugs are removed from glass ampules. They do not allow to make a conclusion on human clinical consequences associated with the presence of particles. It is necessary to evaluate in human the risks associated with particle contamination to determine the optimal use of filter needle.

[Comparative profile of the use of filter needles in Quebec and France in healthcare facility]. / Profil comparé de l'utilisation des aiguilles filtrantes au Québec et en France en établissement de santé.

OBJECTIVES: The manipulation of drugs from glass ampules can generate particles when the ampule is broken. Several authors recommend the use of filter needle to withdraw the drug content. The main objective is to establish an inventory of the use of filter needles and the perception of pharmacists in Quebec and in France. METHODS: This is a cross-sectional descriptive study. A questionnaire was sent to all health facilities in Quebec (n=30) and a selection of hospitals in France (n=100). Respondents were asked to answer a questionnaire that included policies and procedures on the use of these medical devices and the conditions of their use at the pharmacy and in healthcare services. RESULTS: In total, 27 respondents from Quebec (response rate: 90%) and 41 respondents from France (response rate: 41%) participated in our survey. In Quebec, all exploitable questionnaires except one (42/43) used five micron filter needles at the pharmacy against 28% of utilisation in healthcare services. In France, this practice is nearly ignored. CONCLUSIONS: Action should be taken to decide on the use of filter needles including studies to confirm the consequences of the presence of these particles on an animal model, discussions with regulatory authorities to clarify the situation, incentives for manufacturers to use vials.

Prospective assessment of patients' knowledge and informational needs and of surgeon-to-patient information transfer before and after knee or hip arthroplasty.

BACKGROUND: Patients are playing an increasingly large role in their own management and must therefore receive clear, complete, and comprehensible information. In the field of hip and knee arthroplasty, little is known about the level of patient knowledge and effectiveness of surgeon-to-patient information transfer. We therefore designed a prospective observational study with the objective of assessing four factors: patient knowledge during management, quality of information transfer, informational needs, and factors associated with the level of knowledge. HYPOTHESIS: The level of patient knowledge changes during the management process. PATIENTS AND METHODS: A prospective single-centre study was conducted between January 2014 and March 2015 during the outpatient visits and inpatient stays of 63 patients who underwent arthroplasty of the hip (n=36) or knee (n=27). A single observer attended all patient visits and recorded the information provided by the surgeon. Each patient completed a self-questionnaire after the outpatient visit (T1), at admission (T2), and at discharge after surgery (T3). Semi-quantitative scores were used to assess knowledge and informational needs. The effectiveness of information transfer was evaluated by comparing the information provided by the surgeon to the replies made by the patients. RESULTS: The mean overall knowledge score (on a 0-42 scale) increased from 17.22±6.33 at T1 to 19.44±6.89 at T3 (P=0.0028). In contrast, knowledge about complications was better at T1 than at T3 (2.67±1.98 vs. 2.19±1.91; P<0.05). Agreement between information given by the surgeon and replies made by patients varied across items from 23% to 100%. The mean informational needs score (on a scale from 0 to 21) ranged from 3.67 to 4.83 and was higher at T3 than at T2 (4.83±3.77 vs. 3.67±4.86; P=0.03). The proportion of patients who wanted written information was higher at T3. Most patients sought information before the outpatient visit. At each step of the management process, the main areas about which the patients wanted information were the surgical procedure, the rehabilitation programme, and the prosthesis. Several socio-demographic or management-related factors influenced the level of knowledge. Thus, older age and lower educational attainment were associated with lower knowledge scores, whereas previous lower-limb orthopaedic surgery and amount of information provided by the surgeon were associated with higher knowledge scores. Knowledge scores were not associated with being employed vs. retired, gender, replacement of a hip vs. a knee, the surgeon, or being accompanied by another person. DISCUSSION: Our study is original in that we assessed changes in patient knowledge during the management process for hip or knee arthroplasty. The level of patient knowledge was fairly low and varied considerably across individuals and time points in the management process. These data highlight the importance of providing patients with information throughout their management and particularly at discharge, when the desire for information seems greatest. LEVEL OF EVIDENCE: IV, prospective observational study with no control group.

Factors Generating Glucose Degradation Products In Sterile Glucose Solutions For Infusion: Statistical Relevance Determination Of Their Impacts.

Sterilising glucose solutions by heat promotes the generation of a large number of glucose degradation products (GDPs). It has been shown that high levels of GDPs may result in Advanced Glycation End products that have an impact on cellular homeostasis and health in general. If data is available for peritoneal dialysis solutions, little has been published for glucose infusion fluids. It is essential to identify the parameters causing the formation of GDPs and so limit the risk of exposing patients to them. After quantifying both 5-hydroxymethyl-2-furfural, considered as an important indicator of degradation, and 2-furaldehyde, an ultimate GDP of one degradation pathway, in marketed solutions, the aim of this work is to build a model integrating all the parameters involved in the formation rates of these two GDPs: supplier, glucose amount, container material, oxygen permeability coefficient and time-lapse since manufacture. Our results show a good logarithmic relationship between GDP formation rates and time-lapse since manufacture for both GDPs. The amount of GDPs in the glucose solutions for infusion depends on the initial glucose amount, the polymer of the container, the time elapsed since manufacturing and the supplier.

Analysis of plasticizers in PVC medical devices: Performance comparison of eight analytical methods.

A wide variety of medical devices (MDs) used in hospitals are made of flexible plasticized polyvinylchloride (PVC). Different plasticizers are present in variable amounts in the PVC matrix of the devices and can leach out into the infused solutions and may enter into contact with the patients. The ARMED1 project aims to assess the migration of these plasticizers from medical devices and therefore the level of exposure in patients. For the first task of the project, eight methods were developed to directly detect and quantify the plasticizers in the PVC matrix of the MDs. We compared the overall performances of the analytical methods using standardized and validated criteria in order to provide the scientific community with the guidance and the technical specifications of each method for the intended application. We have shown that routine rapid screening could be performed directly on the MDs using the FTIR technique, with cost-effective analyses. LC techniques may also be used, but with limits and only with individual quantification of the main plasticizers expected in the PVC matrix. GC techniques, especially GC-MS, are both more specific and more sensitive than other techniques. NMR is a robust and specific technique to precisely discriminate all plasticizers in a MD but is limited by its cost and its low ability to detect and quantify plasticizer contamination, e.g. by DEHP. All these results have been confirmed by a real test, called the " blind test " carried out on 10 MD samples.

Evaluation of Pentravan®, Pentravan® Plus, Phytobase®, Lipovan® and Pluronic Lecithin Organogel for the transdermal administration of antiemetic drugs to treat chemotherapy-induced nausea and vomiting at the hospital.

The objective of this study was to evaluate five commercial ready-to-use transdermal vehicles (Phytobase®, Lipovan®, Pentravan®, Pentravan® Plus and Pluronic Lecithin Organogel (PLO)), for the compounding of three antiemetic drugs (ondansetron, dexamethasone and aprepitant) and their administration in combination to treat chemotherapy-induced nausea and vomiting (CINV) at the hospital. Drugs were individually formulated in these vehicles and in mixture in Pentravan® Plus using different penetration enhancers. Quality control of the forms has demonstrated that formulation process was mastered and convenient for the hospital (time required: 20min). Diffusion experiments through synthetic membranes and pig ear epidermis performed using Franz-type diffusion cells, have shown that the release and permeation process were greater for ondansetron than for dexamethasone and aprepitant, with a release step not limiting. As permeation of aprepitant was too low, it was discarded of the study. When ondansetron and dexamethasone were compounded in combination in Pentravan® Plus, the most efficient vehicle, a permeation decrease was observed. Finally, the use of tween 20 instead of EtOH as chemical enhancer has led to 2-fold factor increase in the flux of dexamethasone, resulting in fluxes convenient for transdermal administration of ondansetron to a child, but insufficient for an adult and for dexamethasone.

Assessment of anti-factor Xa activity of heparin in binary parenteral nutrition admixtures for premature neonates.

An in vitro study was carried out to determine the anti-Xa activity of heparin in binary parenteral nutrition (BPN) admixtures for premature neonates in our neonatal intensive care unit (NICU) after a 24-hour infusion, as well as to assess drug interaction with a 50% glucose solution. Two types of bags were prepared: (1) BPN admixtures (composition defined in the NICU) including sodium heparin at 77 UI/mL and (2) bags containing only G50% with sodium heparin at 193 UI/mL. The anti-Xa activity of heparin was measured in bags at T0, after the 24-hour infusion and in eluates at the outlet of the infusion line after 24hours, using a validated chromogenic anti-Xa method. Comparisons of the mean concentration observed with the theoretical value for anti-Xa activity were performed with the Student t-test. Mean values of anti-Xa activity do not differ significantly from the values expected for all conditions. We found a slight variation in anti-Xa activity when infused over 24hours for both types of bags, with and without in-line filtration, showing that heparin remains stable during this infusion period in both BPN admixtures and G50%.

An in vitro evaluation of infusion methods using a syringe pump to improve noradrenaline administration.

BACKGROUND: International guidelines recommend noradrenaline (NA) as the vasopressor of choice to treat septic shock. The aim of this study was to determine the best way to infuse patients with NA. METHODS: The in vitro study was designed to measure NA concentration at the end of each studied assembly line. Three infusion systems used the double pump method and three single pumps, which differed as regards NA concentrations (0,2 - 0,5 - 1 mg/h), dead space volume of the devices and the use of saline. Infusion systems were compared according to the time necessary to reach an NA mass flow rate steady-state plateau after the onset of infusion or after a flow change. RESULTS: Times were significantly different between the six methods for infusing NA. The system using the double syringe method with a standard extension set was the longest to reach the steady state after the onset of infusion [40.00 min (19.57 - 49.22)]. The steady-state plateau was obtained most rapidly with the double-syringe pump systems using very low dead-space volume extension sets and single-syringe pump systems containing diluted noradrenaline at the beginning of NA infusion. CONCLUSION: A combination of a low dead-space volume extension set and a double pump method with a constant saline flow rate at 5 ml/h might be the solution to provide the most reliable NA infusion delivery.

Complementarity of UV-PLS and HPLC for the simultaneous evaluation of antiemetic drugs.

This work was dedicated to the development of a simple and direct multivariate UV spectrophotometric method for the simultaneous determination of three antiemetic drugs (ondansetron, dexamethasone and aprepitant) in a new organogel formulation developed for their simultaneous transdermal administration. This method that does not require separation of the drugs and sophisticated instrument will permit to control quality of this new transdermal form both during the optimization step and for a further routine control of this preparation at the pharmacy department of the hospital. Hence, a partial least squares regression model using the spectral data record from 260 to 288 nm and 5 components, has firstly been validated thanks to the evaluation of the REP% (under 7.9%) and secondly using an accuracy profile approach (acceptance limit of ±10%). Thereby, the method allows the quantitation of the drugs in the ranges (5-15 mg L(-1)), (4-8 mg L(-1)) and (20-50 mg L(-1)) for ondansetron, dexamethasone and aprepitant, respectively. An HPLC/UV reference method has also been developed. Optimal separation (2.52

Impact of infusion set characteristics on the accuracy of patient-controlled morphine administration: a controlled in-vitro study.

The aim of our in-vitro study was to assess the impact of infusion set characteristics on the accuracy of morphine doses in patient-controlled analgesia. Two infusion sets differing in conception and dead-space volume were assessed: a standard set and a low dead-space volume Y-set. The patient-controlled analgesia programme parameters were as follows: bolus equal to 1 ml at 100 ml.h(-1) ; lockout intervals equal to 5 and 10 min; and carrier fluid flow rate equal to 10 and 50 ml.h(-1) . Morphine concentration was determined by an ultraviolet spectrophotometric method. The morphine doses were significantly different from one set to the other during bolus and lockout intervals, whatever the patient-controlled analgesia programme. The average doses were approximately 1.3-6.0 times higher with the low dead-space volume Y-set during bolus. Our study underlines the impact of infusion set characteristics on the accuracy of morphine patient-controlled analgesia doses.