Search

Background: Sildenafil is a phosphodiesterase-5 inhibitor considered for antenatal use for a variety of indications. We sought to assess sildenafil pharmacokinetics in the pregnant ewe and fetus and evaluate its physiological fetal effects. Methods: Twelve fetal lambs (127–133 days GA, term 145) were chronically catheterized in utero. Ewes received different doses of sildenafil, either via subcutaneous injection (1.6, 2.0 mg/kg/day) or intravenous (IV) infusion (3, 5, 7, 10, and 12 mg/kg/day). Maternal and fetal sildenafil concentrations and metabolic status (blood gas analysis) were measured at given intervals. The fetal heart rate, pulmonary blood flow, systemic and aortic pressure, and maternal uterine artery pressure were continuously monitored. Results: The transplacental sildenafil transfer was 2.9% (range: 1.4–7.8%), preventing attainment of fetal target concentrations without toxic maternal levels. IV sildenafil infusion induced an immediate, temporary, dose-dependent reduction of pulmonary vascular resistance (38–78%) and increased both pulmonary blood flow (32–132%) and heart rate (13–49%), with limited nonlinear dose-dependent effects on systemic and pulmonary pressures. Fetal and maternal blood gases and maternal uterine artery pressures were unaffected by sildenafil infusion. Conclusion: In sheep, transplacental transfer of sildenafil is extremely low. Though, minimal fetal sildenafil concentrations induce an acute transient pulmonary vasodilation, well-tolerated by the fetus and ewe.

International audience; The use of immunomodulatory and/or immunosuppressive therapy (IT) is increasingly common in the management of chronic inflammatory disease. Skin reactions to any drug (IT or not) are not rare in these patients, justifying allergological investigations. The influence of IT on allergological tests for drugs is not clearly described. IT cannot be interrupted due to the underlying disease. The data assessing the benefit and the safety of allergological test for drug allergy in patients under IT are missing.

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: Transforming a drug from its commercial form into a ready-to-use drug is common practice, especially in pediatrics. However, the risk of compounding error is real and data on drug stability in practice are not always available. OBJECTIVE: The aim of this study was to assess, in real conditions, both the error rate and stability of three drugs: ketamine, remifentanil, and sufentanil. METHODS: A new rapid and easy-to-use high-performance liquid chromatography method with a diode array detector has been developed and validated to quantify these drugs and detect their degradation products. Over a 1-month period, 151 syringes were collected in the postanesthesia care unit. Seventy-three were stock solution syringes containing a 10-fold dilution of commercial drugs and 78 were serial dilution syringes made from successive dilutions of stock solutions. A comparison between real and expected concentrations as well as the detection of possible degradation products was carried out on these samples. RESULTS: All stock solution syringes had good chemical stability throughout the working day. A 4-µg/mL remifentanil serial dilution syringe, however, had to be discarded as a degradation peak was detected. Overall, 15.3% (95% CI, 9.5-21.1%) of syringes had a drug concentration outside the ±10% acceptability range, that is, 11.0% (95% CI, 3.7-18.2%) and 19.5% (95% CI, 10.6%-28.4%) of stock and diluted syringes respectively, with drug amounts ranging from -25.3% to 22.0%. The highest error rates were observed with sufentanil syringes: 20% and 28% for stock solution and serial dilution, respectively. CONCLUSIONS: The study shows that stock solution syringes prepared in advance are chemically stable throughout the day, unlike certain serial dilution syringes, indicating that the latter should be prepared just before administration to ensure chemical stability. Our results show that the error rate for serial dilution syringes is twice that of stock solution. Different safety measures are under discussion and have to be further studied.

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.

The use of long-term taurolidine locks (LTTL) seems to be effective in preventing catheter-related blood stream infections (CRBSI), especially in patients on home parenteral nutrition (HPN). This work targets the cost-effectiveness of LTTL in a cohort of adult HPN patients.A monocentric mirror-image design study was conducted in our referral centre among long-term HPN patients experiencing recurrent CRBSI. From 7th January 2011, LTTL were started after the third CRBSI episode within 12 months. CRBSI data was prospectively collected until 7th January 2013, in the same way as it had retrospectively been done before initiating LTTL. A cost-effective analysis was conducted to estimate the incremental costs and effects on CRBSI with LTTL. The efficacy of LTTL on CRBSI rate was assessed over 1000 days of catheter use.A total of 31,100 catheter days were analysed in 37 patients (median [interquartile range (IQR)]) aged 58 [42-68] years. The mean ± SD proven CRBSI rate was 3.18 ± 3.51 per 1000 catheter days before the introduction of LTTL and 0.39 ± 1.50 per 1000 catheter days after its introduction (p 0.0001). Considering both proven and probable CRBSI requiring hospital management, LTTL reduced by (mean [bootstrap CI 95%]) -2.63 [-3.26 to -2.06] infections per patient (from 2.89 [2.31 to 3.49] before to 0.26 [0.13 to 0.41] after) as well as incremental costs by -7 258 [-10 450 to -4 016] € (from 11 176 [8 004 to 14 968] € before to 3 918 [2 390 to 5 445] € after).Implementing LTTL to prevent recurrent CRBSI is cost-effective by dramatically decreasing their incidence.

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 …

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 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.

Background In the paediatric surgery unit, low doses of opioid analgesics are used daily for anaesthesia. Because dilutions in series are required, potential preparation errors may occur. Thus stock solution (SS) syringes are prepared each morning in the post anaesthesia care units, resulting from a 10-fold dilution of commercial products. SS syringes are then extemporaneously diluted all day long by a factor of 2, 2.5, 5 or 10 to obtain serial dilution (SD) syringes used in the operating ward. Purpose We quantified the concentration of ketamine (Ket), remifentanil (Rem) and sufentanil (Suf) in prepared syringes to evaluate the compounding accuracy of the anaesthetic staff before injection to children. Material and methods Over a 1 month period, Ket, Rem and Suf samples were collected from SS and SD syringes prepared in the care unit. Samples were quantified by a HPLC-UV-DAD method, previously validated according to the SFSTP-Pharma requirements. Results were expressed as bias (%) and were considered acceptable if included between acceptance limits of ±10% of the theoretical concentration (drugs with a narrow therapeutic margin). Results 150 syringes were collected on 31 days: 73 SS (25 Suf; 24 Rem; 24 Ket) and 77 SD (36 Suf; 24; Rem; 17 Ket). Biases were not within acceptance limits for 15 of the 31 days, representing 25 syringes (17%). Focusing on dilution modalities, the total error rate and extremes biases (min; max) obtained for the 17 SD syringes out of 77 were 28% (−17%; +12%), 21% (−10%; +15%) and 14% (−7%; +14%) for Suf, Rem and Ket, respectively. For the SS syringes, the total error rate and extremes biases (min; max) obtained were 20% (−25%; +22%), 4% (−23%; +2%) and 8% (−23%; +3%) for Suf, Rem and Ket, respectively, representing 8 syringes (11%). Whatever the drug, the error rate was higher with the SD syringes compared with the SS syringes. Conclusion We found that 22% of syringes administered to children were not within acceptance limits. In order to reduce the occurrence of compounding error in the ward, a preparation procedure will be defined. Its impact will be further assessed. No conflict of interest

Purpose The aims of the study are to make an inventory of fixtures of aseptic compounding structures, to compare, using real examples, the design and operating costs of controlled atmosphere area (CAA) with isolators and CAA with laminar flow biological safety cabinets (BSCs) in order to determine the most economical scheme in hospitals and to give a final facilities cost calculated for one workstation. Methods Forty-three hospitals were interviewed (21 French and 22 from four European countries) over seven months. Hospital pharmacists completed a form with 390 items. Hospitals are compared according to their workstation type: BSCII or BSCIII (group B) and isolator (group I), using Mann and Whitney’s statistical test and Monte-Carlo modeling. Results Twenty-one hospitals responded (11 French and 10 from other European countries). All European compounding unit organizations are not significantly different. The study compared items such as infrastructure cost, equipment cost, staff cost, consumable cost, cleaning cost and control cost. A synthesis of all costs has been drafted to calculate an estimated preparation cost which seemed to be higher for group B than for group I when staff costs were included ($46 and $31, respectively, in study conditions). Conclusions The different costs studied have revealed little significant difference between group B and I. The preparation cost in group B appears higher than in group I. This pilot study has resulted in the calculation of an estimated manufactured preparation cost but this work should be completed to help optimize resources and save money.

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.

Objective The aims are to identify critical parameters influencing the drug mass flow rate of infusion delivery to patients during multidrug infusion and to discuss their clinical relevance. Data sources A review of literature was conducted in January 2016 using Medline, Google Scholar, ScienceDirect, Web of Science and Scopus online databases. Data extraction References relating to the accuracy of fluid delivery via gravity-flow intravenous (IV) infusion systems and positive displacement pumps, components of IV administration sets, causes of flow rate variability, potential complications due to flow rate variability, IV therapies especially at low flow rates and drug compatibilities were considered relevant. Data synthesis Several parameters impact the delivery of drugs and fluids by IV infusion. Among them are the components of infusion systems that particularly influence the flow rate of medications and fluids being delivered. By their conception, they may generate significant start-up delays and flow rate variability. Performing multidrug infusion requires taking into account two main points: the common dead volume of drugs delivered simultaneously with potential consequences on the accuracy and amount of drug delivery and the prevention of drug incompatibilities and their clinical effects. Conclusion To prevent the potentially serious effects of flow rate variability on patients, clinicians should receive instruction on the fluid dynamics of an IV administration set and so be able to take steps to minimise flow rate changes during IV therapy.

Aminoglycosides are broad-spectrum antibiotics with peak-dependent bactericidal activity, administered by gravity infusion or for more accuracy by electronic pump infusion. The aim of this study was to assess the difference between the two systems and its pharmacokinetic impact. Twenty-four patients hospitalised for community-acquired pulmonary infections received amikacin by IV route over 1 h with a targeted peak concentration of 35 mg/L. They were randomly distributed into two groups, one receiving infusion through a pump system, the other by gravity. Amikacin serum levels were determined at the end of infusion and 24 h later. C(max) values were significantly lower with gravity than pump (40.2 +/- 12.3 vs. 50.6 +/- 17.6 mg/L, respectively; p = 0.04). Elimination half-life time, volume of distribution and clearance did not differ significantly from one group to the other. The percentage of patients who failed to achieve the targeted peak concentration was significantly higher with gravity than pump (41.7% vs. 16.7%, respectively; p < 0.001). Improving infusion flow-rate provides better control over amikacin C(max). This study underlines the fact that infusion device characteristics should be added to the physiopathological information of a patient if we are to make a better estimation of pharmacokinetic parameters.

Summary New treatments for relapse of acute myeloid leukaemia (AML), include gemtuzumab ozogamicin (GO), an anti-CD33 monoclonal antibody. We describe a second case of GO-induced sinusoidal obstructive syndrome (SOS) effectively treated with defibrotide (DF). No stem-cell transplantation was involved. On day 23 after the first GO dose, a patient presented with ascites, weight gain, liver enlargement and pain in the right upper quadrant. Sudden hepatic cytolysis (transaminases at six times the normal range: grade 3) and cholestasis [alkaline phosphatase ALP and gamma-glutamyltransferase (GGT) respectively at four and eight times the normal range: grade 2] were observed but there was no evidence of increase serum bilirubin. Treatment with DF (Prociclide®, Crinos; 10 mg/kg/day, or 200 mg, q.i.d.) improved the hepatic abnormality within a few days (serum transaminases decreased from 312 to 103 IU/L for aspartate aminotransferase (AST) and from 141 to 80 IU/L for alanine aminotransferase (ALT) within 3 days ALP increased from 253 to 383 IU/L and gamma-GT from 238 to 417 IU/L 4 days after administration of DF. The clinical and biological features of our case suggest a direct involvement of GO in causing SOS, even when used as monotherapy, without allogenic stem-cell transplantation. Low dose DF (10 mg/kg/day) given early during the development of SOS associated with GO was effective. Unfortunately, in our case the patient eventually died of multi-organ failure probably because of failure of GO.

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.

PURPOSE/OBJECTIVES To assess the PCHIMX-1 (Doran International), a new sterile medical device intended by its manufacturer to improve the quality and safety of cytotoxic drug infusions, as well as its influence on manipulation times required for pharmacy technicians and nurses and its effect on infusion line outflow parameters. DESIGN PCHIMX-1 assemblies were compared to standard infusion sets. SETTING Pharmacy and oncology units of a French general hospital. METHODS Reference assemblies (an infusion bag connected to an infusion set) were compared to PCHIMX-1 assemblies (PCHIMX-1 connected to two bags and to an infusion set). Two assessments were performed: (a) comparison of the times of manipulation during both preparation and administration of 5-fluorouracil infusion bags (n = 40) and (b) effect of PCHIMX-1 on infusion quality. MAIN RESEARCH VARIABLES Manipulation times in the pharmacy (TP) and in the ward (TW) were measured, as well as flow rate and infusion efficiency. FINDINGS The results showed that TW was significantly increased, whereas TP was significantly decreased; total time was unchanged. Results also showed that PCHIMX-1 significantly changed infusion efficiency; flow rate was not affected. CONCLUSIONS PCHIMX-1 obliges pharmacy technicians and nurses to change their handling procedures. The device does not have any influence on infusion flow rate but considerably improves infusion quality by ensuring that the full quantity of medication prescribed is administered. IMPLICATIONS FOR NURSING PCHIMX-1 guarantees that the complete prescribed dose of chemotherapy is administered without any change in infusion quality and adheres to the latest recommendations concerning occupational exposure protection.