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Errors in injectable preparations with high-risk drugs can be fatal. This study aimed to identify the factors influencing the accuracy of high-risk injectable drug concentrations in appliances used for intensive care unit preparation practices. Norepinephrine (NE) was chosen as an example of a high-risk medication drug. The concentration (0.2 and 0.5 mg/mL), the diluent (sodium chloride 0.9% and 5% dextrose), and the container type (prefilled- and empty-infusion bag and syringe) were tested as potential variability factors. An ultraviolet spectrophotometric method was used for NE dosage. 108 NE solutions were prepared by five individuals (pharmacists or laboratory technicians) with clinical experience as well as experience in the aseptic preparation of solutions. The container type was found to be the only factor influencing the accuracy of NE concentration. NE solutions in syringes proved to be the most accurate while preparations in prefilled bags tended to underdose NE.

Objectives Norepinephrine is a vasopressor frequently administered after dilution to treat hypotension and shocks in intensive care units. The stability of norepinephrine is known to be highly sensitive to storage conditions. Moreover, medication errors linked to the dilution step are frequent and may be deleterious for critically-ill patients, especially in intensive care units. This study aimed to evaluate the stability of ready-to-use diluted norepinephrine solutions prepared at two target concentrations (0.2 and 0.5 mg/mL), according to the summary of product characteristics, and stored for 365 days in two containers: AT-closed cyclic olefin copolymer vials, and polypropylene syringes. Methods A fast reversed-phase liquid chromatography method coupled with an ultra-violet detector was developed to assess the chemical stability of norepinephrine solutions. Validation was conducted according to the linearity of the calibration ranges, selectivity, sensitivity, accuracy and precision. Dosage, sub-visible particle contamination, pH monitoring and sterility assays were performed. Chemical stability was maintained if the measured concentration respected the lower limit of 90% of the initial concentration. Containers were stored at −20±5°C, +5±3°C and +25±2°C with 60±5% relative humidity in a dark closed enclosure. Results Stability was successfully maintained for every concentration and container tested when stored at −20±5°C and +5±3°C. In these storage conditions, particle contamination, pH monitoring and sterility assay respected the required criteria. Chemical degradation and colouring of solutions appeared before the end of the 1 year study period for most norepinephrine solutions stored at room temperature. Conclusions Ready-to-use solutions containing 0.2 and 0.5 mg/mL norepinephrine in polypropylene syringes or cyclic olefin copolymer vials must be stored at refrigerated or frozen temperatures to obtain acceptable 1 year shelf-stability. Exposure to higher temperatures significantly decreases shelf-stability. Our study protocol for compounding polypropylene syringes and cyclic olefin copolymer vials containing norepinephrine is adapted to implementation in centralised intravenous additive services.

Vancomycin hydrochloride is an antibiotic belonging to the glycopeptide family and acts by inhibiting the synthesis of the peptidoglycan wall. This antibiotic is active against Gram-positive aerobic and anaerobic bacteria1 2 and is commonly used in hospitals to treat serious infections.3 4 Vancomycin has slow bactericidal time-dependent activity and can be administered by continuous or intermittent intravenous infusion. In France, administering vancomycin by continuous infusion over 24 hours is recommended.5 6 The Summary of Product Characteristics (SmPC) recommends reconstituting a 1 g vial with 20 mL of water for injection (WFI), then diluting it in 100 mL of saline solution. The amount of vancomycin to treat an adult infection is superior to 1 g and so the volume administered can be higher than 100 mL. This volume must be limited in children or in patients on water restriction, such as those suffering from hyponatraemia and cardiovascular diseases or are in intensive care.7 Some studies on vancomycin stability have already been performed. Solutions at 5 and 10 mg/mL were stable for 58 days at +4°C in 100 mL polyvinyl chloride (PVC) infusion bags with no specification with regard to protection from light.8 Vancomycin was stable at 5 mg/mL in PVC bags for 48 hours at +22°C without protection from light and for 7 days at +4°C with protection from light.9 Raverdy et al 10 examined the stability of vancomycin diluted in 5% dextrose at high concentration (83 mg/mL) and was stable for 72 hours at +37°C. However, none of these studies reflects real infusion conditions as vancomycin is usually administered at 30 mg/kg/day.11 12 In practice, clinical services infuse vancomycin into electric syringe pumps using 50 mL (for adults) or 20 mL (for children) syringes. No stability study has yet been performed for such concentrations, in 50 or 20 mL syringes, at room temperature, nor has the reconstitution procedure13 been …

Background: Parenteral nutrition (PN) is a complex medium in which added insulin can become unstable. The aim of this study is, therefore, to evaluate the stability of insulin in PN and to identify influencing factors. Methods: A total of 20 IU/L of regular insulin was added to PN in either glass or Ethylene Vinyl Acetate (EVA) containers. A 24 h stability study was performed via an electrochemiluminescence immunoassay in different media: A ternary PN admixture, separate compartments of the PN bag and a binary admixture. This study was repeated in the absence of zinc, with the addition of serum albumin or tween and with pH adjustment (3.6 or 6.3). Insulin concentration at t time was expressed as a percentage of the initial insulin concentration. Analysis of covariance (ANCOVA) was applied to determine the factors that influence insulin stability. Results: In all PN admixtures, the insulin concentration ratio decreased, stabilising at a 60% and then plateauing after 6 h. At pH 3.6, the ratio was above 90%, while at pH 6.3 it decreased, except in the amino acid solution. ANCOVA (r2 = 0.68, p = 0.01) identified dextrose and pH as significant factors influencing insulin stability. Conclusion: A low pH level seems to stabilise insulin in PN admixtures. The influence of dextrose content suggests that insulin glycation may influence stability.

Bacteriophages are a promising therapeutic strategy among cystic fibrosis and lung-transplanted patients, considering the high frequency of colonization/infection caused by pandrug-resistant bacteria. However, little clinical data are available regarding the use of phages for infections with Achromobacter xylosoxidans. A 12-year-old lung-transplanted cystic fibrosis patient received two rounds of phage therapy because of persistent lung infection with pandrug-resistant A. xylosoxidans. Clinical tolerance was perfect, but initial bronchoalveolar lavage (BAL) still grew A. xylosoxidans. The patient’s respiratory condition slowly improved and oxygen therapy was stopped. Low-grade airway colonization by A. xylosoxidans persisted for months before samples turned negative. No re-colonisation occurred more than two years after phage therapy was performed and imipenem treatment was stopped. Whole genome sequencing indicated that the eight A. xylosoxidans isolates, collected during phage therapy, belonged to four delineated strains, whereby one had a stop mutation in a gene for a phage receptor. The dynamics of lung colonisation were documented by means of strain-specific qPCRs on different BALs. We report the first case of phage therapy for A. xylosoxidans lung infection in a lung-transplanted patient. The dynamics of airway colonization was more complex than deduced from bacterial culture, involving phage susceptible as well as phage resistant strains.

Insulin aspart (Novorapid) is a rapid-acting insulin analog that is maintained in hexameric form by phenolic preservatives (phenol and metacresol) and stabilized by insulin-zinc complex. According to the manufacturers, insulin can be independently diluted either in 5% dextrose solution (D5%) or 0.9% sodium chloride solution. In reality, in most clinical units, such as the neonatal intensive care unit (NICU), insulin aspart is more frequently diluted in D5% than in saline solution due to sodium restriction. However, injectable dextrose solutions contain glucose degradation products (1) that are capable of binding proteins—like insulin—through a glycation phenomenon. Therefore, dilution of Novorapid in D5% would be more likely to cause glycated insulin and may raise a worrisome problem in terms of insulin stability. The objective of this study was to investigate the stability of insulin aspart diluted in D5% at both adult and neonate therapeutic concentrations in order to ensure its appropriateness in the preparation of insulin aspart. To address this issue, insulin aspart diluted in D5% was assayed by a stability-indicating method using high-performance liquid chromatography (HPLC) coupled with an ultraviolet (UV) detector. The nature of the formed product was determined by HPLC coupled with a mass spectrometer. The effect of …

Purpose To assess the physico-chemical stability of Voriconazole Eye-Drops (VED), when stored frozen and refrigerated once thawed, in 3 containers: Amber glass with a Low-Density PolyEthylene (LDPE) eyedropper, and two types of LDPE bottles: one classical and one with an innovative insert that maintains sterility after opening (Novelia® from Nemera). Methods Three batches of 1% VED (10 mL) were aseptically compounded from marketed injectable voriconazole (Vfend®) diluted in sterile water for injection. VEDs were stored for three months at -20 °C in amber glass (n = 32), classical LDPE (n = 32) or innovative LDPE (n = 31) bottles. Stability-indicating (HPLC-UV-DAD) and chiral chromatography methods were developed. The stability study was conducted according to GERPAC-SFPC guidelines. At each study time, the following parameters were controlled: visual aspect, voriconazole concentration, pH and osmolality. In addition, non-visible particle count, sterility and absence of racemisation (impurity D – (2S,3R)-voriconazole) were assessed at the beginning and end of the study. Results are expressed as mean ± standard deviation. Statistical analyses were performed using non-parametric tests (α Results When stored frozen, concentration was between 95.2 ± 1.4% and 103.6 ± 1.3% of the initial concentration (C0) with no difference between the three containers (p = 0.564; non-significant). Fifteen days after thawing, concentration was between 97.1 ± 1.6% and 98.6 ± 0.8% of C0 with no difference between containers (p = 0.278 and 0.368 for VED thawed at room temperature and at 2–8 °C, respectively). pH remained stable between each time. Osmolality was slightly higher in glass (533.17 ± 8.93 mOsm/Kg) than in plastic containers (522.17±3.31mOsm/Kg, classical LDPE; 517.5 ± 12.42 mOsm/Kg, innovative LDPE) (p = 0.022). Sterility was preserved. Degradation product areas increased slightly but remained below the limit of quantification. Impurity D was never detected. Conclusion We have demonstrated that the ability of the innovative container Novelia® to maintain VED physicochemical and microbiological stability does not differ from that of amber glass and classical LDPE containers. Real life studies are required to find out if there is a potential difference between Novelia® and other containers in terms of sterility preservation.

Background Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are innovative digestive endoscopic approaches allowing ‘en bloc’ tumour removal – which facilitates histological analysis and lowers the risks of local relapse. To ease complete tumour removal, both techniques require submucosal fluid injections. Nevertheless, no ready-to-use commercial solutions for submucosal injection are available. Purpose To implement a simple production of a ready-to-use 5% fructose and 10% glycerol sterile solution (FGSS) for submucosal injection and appropriate quality controls. Material and methods FGSS were aseptically compounded according to good manufacturing practices. Fructose and glycerol were mixed with isotonic sodium chloride in an ISO 5 controlled atmosphere area. The solution was sterile-filtered using rapid flow 0.22 µm filter units (ThermoScientific) and aseptically-filled into glass containers (125 mL) in a vertical laminar flow hood. An alternative method, using terminal sterilisation (121°C for 20 min), was also tested. Quality controls were performed on three vials (beginning-middle-end of production). Fructose and glycerol concentrations were assessed by colorimetric-enzymatic methods adapted on a chemistry analyser (acceptance limits±10%). We developed a method of quantifying two fructose degradation products (5-hydroxymethylfurfural (5HMF) and 2-furaldehyde (2FA)) in FGSS, using a high-performance liquid chromatography UV Diode-Array-Detector. Accuracy profile serves for validation (relative acceptance limits:±10%). Sterility assay and endotoxin testing (kinetic chromogenic method) were performed. Sub-visible particles contamination was assessed using a light-obscuration method (European pharmacopoeia (EP) 2.9.19 threshold: respectively 25 and 3 particles/mL for particles size ≥10 µm and ≥25 µm). Results Our sterile-filtered compounding method allows the production of a sterile and bacterial-endotoxin-free FGSS. Particle load was 9.99 and 0.37 particles/ml respectively for ≥10 µm and ≥25 µm particles. Fructose and glycerol concentrations (g/L) were respectively at (mean (min-max)) 48.99 (47.04–50.39) and 127.39 (123.4–129.8)). Both 5HMF and 2FA concentrations were below our method’s limits of quantification (3.39 and 1.69 ng/mL respectively). When using the moist heat sterilisation method, the solution became light yellow and 5-HMF was 19.61 mg/L (far above EP specification). Conclusion Our compounding method is simple, limits 5HMF production and can be implemented in any hospital. Produced FGSS complies with the EP quality requirements. We developed the first specific and sensitive method for 5HMF and 2FA concentrations measurement in a FGSS preparation. References and/or acknowledgements No conflict of interest.

Background Congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome (CHILD) syndrome is a rare X-linked dominant disorder of cholesterol metabolism that clinically expresses as an epidermical hamartoma. Using co-application of topical formulation of simvastatin and cholesterol (TFSC) on skin lesions after previous failures has recently been reported.1 Purpose To describe protocol of use, efficacy and safety of TFSC. Material and methods A woman, born in 1988, presented at birth with an extensive epidermal hamartoma due to CHILD syndrome. The cutaneous presentation was ichtyosiform erythroderma with sharp midline demarcation involving the right side of the body and a homolateral lower limb. She had skeletal malformations of her upper and lower limbs. Partial lower limb amputation was necessary when she was 2 years’ old. In February 2016, since skin lesions did not improve with acitretine, topical corticoid and various types of dressings, TFSC was began after obtaining informed consent. We developed an original ethanol-free formulation with simvastatin, cholesterol in Excipial Lipocreme (Galderma). The preparation consists of incorporating simvastatin in powder and triturated ground powder of cholesterol with Excipial: physical stability was satisfactory for at least 30 days. We used the following protocol1: in the first month, 0.5% simvastatin and cholesterol in Excipial Lipocreme, twice per day on a limited area to test tolerance; then afterwards at 2%, twice per day on a wider area. Efficacy was clinically assessed (aspect and extension of the skin lesion) and tolerance was clinically and biologically assessed. Results TFSC was started in February 2016. Erythema whitened after 10 months and totally disappeared after 18 months. After 24 months, improvement began on the papillomatous aspect of the stump. After 30 months, whitening areas were stable, with persisting papillomatosis in the stump and flexion areas. A 2 month supply disruption of simvastatin powder during the first year led to the reappearance of erythema. When TFSC resumed, the lesions improved again. The main reported side effect was the skin’s dryness on application, leading to emollient use. Complete blood counts, electrolytes, urea, triglycerides, cholesterol, CPK and liver function remained normal. Conclusion This case shows the interest and safety of TFSC in hamartoma lesions, indicating a potential interest in other types of hamartoma. Reference and/or acknowledgements Alexopoulos A, Kakourou T. Pediatr Dermatol 2015;32:e145–7. No conflict of interest.

Background In hospital, medications for infusion are mostly diluted in saline. In neonatal resuscitation, glycaemic instabilities are frequently observed in premature newborns, hence insulin treatment is started. In our establishment, insulin aspart is used and diluted in a 5% dextrose solution (D5%), due to sodium restrictions in newborns. Purpose To evaluate the impact of the choice of D5% diluent on the stability of the insulin aspart at 1 U/mL. Material and methods The pharmaceutical specialty composed of insulin aspart and its two preservatives (phenol and metacresol) were diluted in saline or D5%. The impact of the diluent on the stability of insulin aspart was studied by high-performance liquid chromatography with UV detection (HPLC-UV). A stability indicator method,1 adapted from the method of Poulsen et al.2 and developed for insulin aspart diluted in saline, was used. The prospective formation of a new compound in the different diluents was evaluated by HPLC with a mass spectrometry detection (HPLC-MS) in full-scan mode. The kinetic of the new compound’s appearance was studied by relative evaluation of HPLC-UV signals during 1 week for insulin at 1 U/mL diluted in D5% (n=4). Results The three products contained in the pharmaceutical specialty diluted in saline correspond to the three signals identified in HPLC-UV (elution order: phenol, metacresol and insulin aspart). After dilution of insulin aspart in D5%, we noted a fourth signal. pH influence and forced degradation tests failed to attribute this signal to insulin or preservatives’ degradation. HPLC-MS analysis revealed a mass difference of 162 daltons between insulin and this product, which corresponds to a glycation phenomenon of insulin aspart. Finally, the kinetics shows that the insulin glycation phenomenon seems to increase with the contact time between insulin and glucose until a plateau is reached after 24 hour of contact. Conclusion This work highlighted the instability of insulin in D5% and showed the phenomenon of insulin aspart glycation. To better characterise this phenomenon, the biological effect of glycation on insulin activity have to be determined, since a decrease in activity has been observed for human insulin. References and/or acknowledgements 1. Methodological guidelines for stability studies of hospital pharmaceutical preparations. https://www.gerpac.eu/IMG/pdf/guide_stabilite_anglais.pdf 2. Poulsen, et al. Pharmal Res2008. No conflict of interest.

Background Continuous compensation of dopamine represents an ideal symptomatic treatment for Parkinson's disease (PD). The feasibility in intracerebroventricular administration (i.c.v.) of dopamine previously failed because of unresolved dopamine oxidation. Objectives We aim to test the feasibility, safety margins and efficacy of continuous i.c.v. of anaerobic-dopamine (A-dopamine) with a pilot translational study in a non-human primate model of PD. Methods Continuous and circadian i.c.v. of A-dopamine was administered through a micro-pump connected to a subcutaneous catheter implanted into the right frontal horn of 8 non-human primates treated with 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP). A-dopamine was assessed at acute doses previously reported for dopamine as well as evaluating the long term therapeutic index of A-dopamine in comparison to anaerobically prepared L-dopa or methyl ester L-dopa. Results Over 60 days of a continuous circadian i.c.v. of A-dopamine improved motor symptoms (therapeutic index from 30 to 70 mg/day) without tachyphylaxia. No dyskinesia was observed even with very high doses. Death after 1 to 10 days (without neuronal alteration) was only observed with doses in excess of 160 mg whereas L-dopa i.c.v. was not effective at any dose. The technical feasibility of the administration regimen was confirmed for an anaerobic preparation of dopamine and for administration of a minimal infusion volume by micro-pump at a constant flow that prevented obstruction. Conclusion Continuous circadian i.c.v. of A-dopamine appears to be feasible and shows efficacy without dyskinesia with a safe therapeutic index.

Objective The aim of this review is to analyse the clinical consequences of intravenous drug incompatibilities in critically ill patients, especially the incidence of organ dysfunctions and mortality. Methods A review of literature was conducted according to the PRISMA statement in June 2017, using Medline, ISI Web of Science and Clinicaltrials.gov. Data extraction Eligible studies were case reports and randomised controlled trials (RCTs) that assessed the effects of drug incompatibilities in critically ill patients on morbidity or mortality as primary or secondary outcomes, or adverse events. Two investigators independently reviewed the eligibility of the study from abstracts or manuscript data. Data synthesis Twelve articles met the selection criteria. The six articles reporting RCTs concern only four RCTs. RCTs were single-centre studies comparing infusion with or without filter. One of them included adult patients. The others included paediatric and neonatal intensive care unit patients. Primary endpoints were SIRS, organ failure, overall complication rate, bacteraemia, sepsis, phlebitis and length of stay. The results are mixed with one RCT reporting a reduction in SIRS, organ failure and overall complication rate, two studies in disagreement over the occurrence of sepsis and one study reporting no impact on length of hospital stay. The six articles on case reports show different drug incompatibility situations. They report pulmonary toxicity. Conclusion Little data is available on this topic. Infused particles may induce organ failure, in particular pulmonary toxicity and SIRS. Further studies are needed to establish a link between the level of exposure to drug incompatibilities and clinical implication.

Background Evidence increases that a high or a standard dose of tranexamic acid (TA) reduces postpartum bleeding. The TRACES pharmacobiological substudy aims to establish a therapeutic strategy in hemorrhagic (H) Cesarean section (CS) with respect to the intensity of fibrinolysis by using innovative assays. Method/Design The TRACES trial is a multicenter, randomized, double-blind, placebo-controlled, TA dose-ranging study that measures simultaneously plasmatic and uterine and urine TA concentrations and the plasmin peak inhibition tested by a simultaneous thrombin plasmin generation assay described by Van Geffen (novel hemostasis assay [NHA]). Patients undergoing H CS (>800 mL) will receive blindly TA 0.5 g or 1 g or placebo. A non-hemorrhagic (NH) group will be recruited to establish plasmin generation profile. Venous blood will be sampled before, at the end, and then at 30, 60, 120, and 360 min after injection. Uterine bleeding will be sampled after injection. Urine will be sampled 2 h and 6 h after injection. The number of patients entered into the study will be 114 H + 48 NH out of the 390 patients of the TRACES clinical trial. Discussion To explore the two innovative assays, a preliminary pilot study was conducted. Blood samples were performed repeatedly in patients undergoing either a H (>800 mL) or NH (

Background Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide. Tranexamic acid (TA), an antifibrinolytic drug, reduces bleeding and transfusion need in major surgery and trauma. In ongoing PPH following vaginal delivery, a high dose of TA decreases PPH volume and duration, as well as maternal morbidity, while early fibrinolysis is inhibited. In a large international trial, a TA single dose reduced mortality due to bleeding but not the hysterectomy rate. TA therapeutic dosages vary from 2.5 to 100 mg/kg and seizures, visual disturbances and nausea are observed with the highest dosages. TA efficiency and optimal dosage in haemorrhagic caesarean section (CS) has not been yet determined. We hypothesise large variations in fibrinolytic activity during haemorrhagic caesarean section needing targeted TA doses for clinical and biological efficacy. Methods/design The current study proposal is a blinded, randomised controlled trial with the primary objective of determining superiority of either 1 g of TXA or 0.5 g of TXA, in comparison to placebo, in terms of 30% blood-loss reduction at 6 h after non-emergency haemorrhagic caesarean delivery (active PPH > 800 mL) and to correlate this clinical effect in a pharmacokinetics model with fibrinolysis inhibition measured by an innovative direct plasmin measurement regarding plasmatic TA concentration. A sample size of 342 subjects (114 per group) was calculated, based on the expected difference of 30% reduction of blood loss between the placebo group and the low-dose group, out of which 144 patients will be included blindly in the pharmaco-biological substudy. A non-haemorrhagic reference group will include 48 patients in order to give a reference for peak plasmin level. Discussion TRACES trial is expected to give the first pharmacokinetics data to determinate the optimal dose of tranexamic acid to reduce blood loss and inhibit fibrinolysis in hemorrhagic cesarean section. Trial registration ClinicalTrials.gov, ID: NCT02797119. Registered on 13 June 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2420-7) contains supplementary material, which is available to authorized users.

Stopping and resuming carrier fluid flow can lead to potentially dangerous transient disturbances in drug mass flow rate. We compared the impact of 2 infusion sets, one with very low dead-space volume and the other with greater dead-space volume, on the amount of drug delivered during stop-and-go carrier fluid flows.Two infusion sets, both with antireflux, connected to an angiocatheter and with dead-space volumes of 6.185 mL and 0.071 mL, respectively, were assessed. Two protocols were studied: carrier fluid flow of 90 mL/h associated with noradrenaline infused at 7 mL/h and carrier fluid flow of 350 mL/h with a noradrenaline infusion flow of 65 mL/h. During both protocols, the carrier fluid was stopped and resumed at the same rate 30 minutes later. Effluent noradrenaline concentration was measured using UV spectrophotometry. Flow change efficiency was calculated from the ratio of the area under the experimental mass flow rate curve to the area under the theoretical instantaneous mass flow rate curve.For both flow rate conditions, flow change efficiency was significantly different for the 2 infusion sets during the 10-minute period after stopping carrier fluid flow and the 10-minute period after restarting it. The major phenomena were sudden decreases in drug delivery after stopping carrier flow and sudden, temporary increases when it was resumed. The very low dead-space volume infusion set resulted in significant reduction in changes in drug delivery compared with the standard set, even at high flow rates.The use of a very low dead-space volume set attenuates disturbances in drug delivery caused by interrupting and resuming carrier fluid flow.

The ability of an infusion set to deliver a specific amount of drug to the patient can be directly related to the presence of an antireflux valve and dead-space volume. In this study we quantified separately the impact of these 2 components on drug delivery.Various infusion sets were assessed differing in length, in dead-space volume, and with or without an antireflux valve. Noradrenaline was infused with a syringe pump simultaneously with a carrier flow. Effluent drug concentration was measured using ultraviolet spectrophotometry. Flow change efficiency (FCE) was calculated from the ratio of the area under the experimental mass flow rate curve to the area under the theoretical instantaneous mass flow rate curve.The FCE for infusion sets with or without antireflux valves were significantly different 10 to 15 minutes after the start of an infusion at flow rates of 7 mL/h for noradrenaline and 35 mL/h to 70 mL/h for the carrier fluid. They were not different with a carrier flow of 115 mL/h.These findings suggest that antireflux valves have a significant impact on FCE when the ratio of drug flow rate to carrier fluid flow rate is high. Infusion sets with very low dead-space volume connectors yield better FCE. There is a nonlinear relationship between dead-space volume and FCE 5 to 10 minutes after the onset of drug infusion.Care providers must consider dead-space volume and the presence of an antireflux valve when choosing their infusion sets.

Background Multiaccess infusion sets allow multiple simultaneous infusions but may induce interference in drug delivery resulting from large variations in the delivery rate of potent drugs. In this study, we sought to understand the influence of multiaccess infusion device properties (dead space volume and antireflux valve [ARV]) on drug delivery during multi-infusion therapy. Methods Infusion sets differing in length, dead space volume, and presence of an ARV were assessed. Three drugs were infused simultaneously through different access points, and their concentrations were obtained using UV spectrophotometric analysis of the effluent. Different infusion configurations were compared by assessing (1) the amount of drug delivered to the patient per unit of time, (2) the mean amount of drug delivered to the patient per unit of time during the steady-state infusion (mass flow rate plateau), and (3) flow change efficiency calculated from the ratio of the area under the experimental instant mass flow rate curve to the area corresponding to theoretical instant mass flow rate curve. Results Infusion sets with lower dead space volumes offered significantly higher flow change efficiency (53.0% +/- 15.4% with a dead space volume equal to 0.046 mL 5 min after the start of infusion) than infusion sets with higher dead space volume (5.6% +/- 8.2% with a dead space volume equal to 6.16 mL), whatever the flow rate changes. Even in case of large dead space volumes, the presence of an ARV significantly increased the mass flow rate plateau (from 92.4% to 99.3% of the theoretical plateau without and with the presence of an ARV, respectively). Conclusions Multi-infusion therapy induces perturbation in drug delivery. These perturbations (lag time, backflow, and bolus) could be reduced by using infusion sets including very low dead space volume and an ARV.

Background Adverse drug reactions on skin affect approximately 2% of patients. Skin and drug challenge tests were performed in the dermatology department to assess these reactions and pharmacy-compounded drugs were tested through patches, pricks and intradermal (IDR) tests. Purpose To assess the incidence of positive allergic reactions in tested patients and to define the culprit drugs and their potential allergic role in these reactions. Materials and Methods The study was conducted between 2007 and 2010 on patients from our hospital. We collected information on the characteristics of the adverse drug reaction on skin, the drugs tested, the tests performed and their results. Results In the period studied, 220 patients referred by other practitioners (from the hospital or from ambulatory practitioners) for serious cutaneous reactions were tested and 3225 preparations were performed by the pharmacy. 92 patients had an immediate reaction to the drug and 128 had a non-immediate reaction. 64 (29%) patients developed a positive response: 48 (75%) through skin tests (patch, prick and IDR) and 16 (25%) through a Drug Challenge Test (DCT). The drugs most often involved in the positive tests were anti-infectious drugs (46%), paracetamol (16%) and iodinated contrast media (10%). Conclusions The percentage of positive tests in this cohort agrees with the data found in the literature (3–76%). The large difference is due to the variability in patient recruitment. However, it is difficult to compare these data because the preparation and interpretation of the tests are not standardised. Allergology tests still improve the care of patients as with negative skin tests and DPTs many patients were able to continue with their treatment. Manufacturing tests by the pharmacy standardise preparation conditions within the hospital and reduce cross contamination and microbial contamination. No conflict of interest.