Lise Bernard

Migrability of PVC plasticizers from medical devices into a simulant of infused solutions.

Medical devices (MD) for infusion and artificial nutrition are essentially made of plasticized PVC. The plasticizers in the PVC matrix can leach out into the infused solutions and may enter into contact with the patients. In order to assess the risk of patient exposure to these plasticizers we evaluated the migration performance of DEHP, DEHT, DINCH, and TOTM using a model adapted to the clinical use of the MDs. Each PVC tubing sample was immersed in a simulant consisting of a mixture of ethanol/water (50/50v/v) at 40°C and migration tests were carried out after 24h, 72h, and 10 days.DEHP had the highest migration ability, which increased over time. The amount of TOTM released was more than 20 times less than that of DEHP, which makes it an interesting alternative. DEHT is also promising, with a migration level three times smaller than DEHP. However, the migration ability of DINCH was similar to DEHP, with the released amounts equaling 1/8th of the initial amount in the tubing after 24h of contact. Taking into account the available toxicological data, TOTM and DEHT appear to be of particular interest. However, these data should be supplemented and correlated with clinical and toxicological studies on plasticizers and their metabolites.

Analysis of PVC plasticizers in medical devices and infused solutions by GC–MS

In 2008, di-(2-ethylhexyl) phthalate (DEHP), was categorized as CMR 1B under the CLP regulations and its use in PVC medical devices (MD) was called into question by the European authorities. This resulted in the commercialization of PVC MDs plasticized with the DEHP alternative plasticizers tri-octyl trimellitate (TOTM), di-(2-ethylhexyl) terephthalate (DEHT), di-isononyl cyclohexane-1,2-dicarboxylate (DINCH), di-isononyl phthalate (DINP), di-(2-ethylhexy) adipate (DEHA), and Acetyl tri-n-butyl citrate (ATBC). The data available on the migration of these plasticizers from the MDs are too limited to ensure their safe use. We therefore developed a versatile GC-MS method to identify and quantify both these newly used plasticizers and DEHP in MDs and to assess their migration abilities in simulant solution. The use of cubic calibration curves and the optimization of the analytical method by an experimental plan allowed us to lower the limit of plasticizer quantification. It also allowed wide calibration curves to be established that were adapted to this quantification in MDs during migration tests, irrespective of the amount present, and while maintaining good precision and accuracy. We then tested the developed method on 32 PVC MDs used in our hospital and evaluated the plasticizer release from a PVC MD into a simulant solution during a 24h migration test. The results showed a predominance of TOTM in PVC MDs accompanied by DEHP (<0.1% w/w), DEHT, and sometimes DEHA. The migration tests showed a difference in the migration ability between the plasticizers and a non-linear kinetic release.

Epidural analgesia in critically ill patients with acute pancreatitis: the multicentre randomised controlled EPIPAN study protocol

Background Acute pancreatitis (AP) is associated with high morbidity and mortality in its most severe forms. Most patients with severe AP require intubation and invasive mechanical ventilation, frequently for more than 7 days, which is associated with the worst outcome. Recent increasing evidence from preclinical and clinical studies support the beneficial effects of epidural analgesia (EA) in AP, such as increased gut barrier function and splanchnic, pancreatic and renal perfusion, decreased liver damage and inflammatory response, and reduced mortality. Because recent studies suggest that EA might be a safe procedure in the critically ill, we sought to determine whether EA reduced AP-associated respiratory failure and other major clinical outcomes in patients with AP. Methods and analysis The Epidural Analgesia for Pancreatitis (EPIPAN) trial is an investigator-initiated, prospective, multicentre, randomised controlled two-arm trial with assessor-blinded outcome assessment. The EPIPAN trial will randomise 148 patients with AP requiring admission to an intensive care unit (ICU) to receive EA (with patient-controlled epidural administration of ropivacaine and sufentanil) combined with standard care based on current recommendations on the treatment of AP (interventional group), or standard care alone (reference group). The primary outcome is the number of ventilator-free days at day 30. Secondary outcomes include main complications of AP (eg, organ failure and mortality, among others), levels of biological markers of systemic inflammation, epithelial lung injury, renal failure, and healthcare-associated costs. Ethics and dissemination The study was approved by the appropriate ethics committee (CPP Sud-Est VI). Informed consent is required. If the combined application of EA and standard care proves superior to standard care alone in patients with AP in the ICU, the use of EA may become standard practice in experienced centres, thereby decreasing potential complications related to AP and its burden in critically ill patients. The results will be disseminated in a peer-reviewed journal. Trial registration number NCT02126332.

Care Around Medical Devices: Infusion Sets and Devices

Patients who receive intravenous (IV) medications as a rule should be given special attention. As pharmacists we want to assist to optimize the treatment and prevent medication errors. Intravenous drug administration is complex and subject to iatrogenic risk. The choice of the appropriate medical devices is therefore important in each infusion setup. By his knowledge of injectable drugs and medical devices, the pharmacist can contribute to the selection of appropriate tools to control infusion rates, avoid drug incompatibilities, container–content interactions, prevent allergies or infectious complications, and improve the patient comfort.

Effects of flow rate on the migration of different plasticizers from PVC infusion medical devices

Infusion medical devices (MDs) used in hospitals are often made of plasticized polyvinylchloride (PVC). These plasticizers may leach out into infused solutions during clinical practice, especially during risk-situations, e.g multiple infusions in Intensive Care Units and thus may enter into contact with the patients. The migrability of the plasticizers is dependent of several clinical parameters such as temperature, contact time, nature of the simulant, etc… However, no data is available about the influence of the flow rate at which drug solutions are administrated. In this study, we evaluated the impact of different flow rates on the release of the different plasticizers during an infusion procedure in order to assess if they could expose the patients to more toxic amounts of plasticizers. Migration assays with different PVC infusion sets and extension lines were performed with different flow rates that are used in clinical practice during 1h, 2h, 4h, 8h and 24h, using a lipophilic drug simulant. From a clinical point of view, the results showed that, regardless of the plasticizer, the faster the flow rate, the higher the infused volume and the higher the quantities of plasticizers released, both from infusion sets and extension lines, leading to higher patient exposure. However, physically, there was no significant difference of the migration kinetics linked to the flow rate for a same medical device, reflecting complex interactions between the PVC matrix and the simulant. The migration was especially dependent on the nature and the composition of the medical device.

Patients’ exposure to PVC plasticizers from ECMO circuits

ABSTRACT Background: ECMO is a therapeutic act with a high risk of exposure to diethylhexylphthalate (DEHP), plasticizer from PVC tubings. The replacement of this plasticizer with alternative compounds is recommended but the risks associated with the use of new plasticizers have not been evaluated in ECMO situations. Methods: Ex vivo ECMO models were performed with different flow rates over 6 days to evaluate the migration of plasticizers and their potential toxic risk for patient. The release of plasticizers during ECMO was measured and compared to reference value (derived no effect level, DNEL) and to cytotoxic concentration carried out with MTT test. Results: Trioctyltrimellitate (TOTM), main plasticizer present in circuit (44% w/w), is weakly released during ECMO. Concentrations are not cytotoxic and exposure doses are lower than DNEL. In contrast, DEHP doses are higher than the DNEL despite a lower presence of DEHP in the circuit (0.2%). We have shown that DEHP is not coming from the circuit but from the priming bag. Replacing this bag with a multilayer one avoids the exposure to DEHP. Conclusion: Our study shows that circuits made of PVC plasticized with TOTM against DEHP improves the safety of ECMO.

6ER-033 Pharmacy residents’ training to on-call duties in hospital pharmacies: survey of french training programmes and optimisation of a local training programme

Background During their residency pharmacy residents may attend a hospital on-call programme to ensure the continuum of care for inpatients. This hazardous activity, especially because of the diversity of services provided, requires adapted training. Purpose With a goal based on securing the medication process and improving quality in our hospital, our project was to optimise residents’ training for in-house on-call duties to allow them to receive a strong, clear and complete training, including more practical training. Material and methods We first established a baseline survey of the existing training methods in our university hospital and in the different hospitals of France (September to December 2016), and we identified the pharmacists and students’ needs in our structure (respectively in December 2016 and July 2017). From this assessment and on the basis of the evolving pedagogical methods, we developed a transverse, structured and harmonised training programme. It has been developed in our hospital pharmacy, starting with the most critical sectors since May 2016. Results Our national survey’s results highlighted the great disparities of training between the establishments and point out the lack of structure, organisation and harmonisation of the training. Some training programmes are only composed of a theoretical (13%) or practical part (6%). An evaluation of knowledge occurs in only 47% of hospitals. All the training occurs at the beginning of each 6 month period and only 6% of the hospitals set up continuous training. The duration of the theoretical (10 to 15 hours) and practical training (5 to 10 hours) seem to be short. Training support is mainly oral explanations: residents have no written trace of trainings except for their own notes. Residents hope the training will be improved. Our programme is divided into three parts: initial theoretical training, initial practical training and continuous training. Beyond the harmonisation of theoretical training’s support between the pharmacy’s sectors, new tools were introduced such as an in-house on-call duty notebook complementary to training, simulations’ workshops and interactive quizzes. Conclusion The next steps of our work are the implementation of our programme in each pharmacy’s sector and its assessment. If successful, a possible extension to the other hospitals in our region will be considered. No conflict of interest