[NRFit: A new standard to prevent wrong-route medication errors]. / NRFit : une nouvelle norme de connexion pour prévenir les erreurs médicamenteuses concernant les voies d'administration.

Wrong route medication errors due to tubing misconnections can lead to serious adverse events, especially when they concern the neuraxial and perineural routes. It has been favoured by the use of the universal Luer connector for medical devices with a risk of confusion with the intravenous route. The prevention of these errors is based on passive measures such as using specific small-bore connectors, and active measures such as reading Specific labelling which must be systematically affixed to the routes. NRFit connectors are a type of small-bore connector specifically intended for neuraxial and perineural applications. They are based on the International Organization for Standardization (ISO) standard 80369-6. They are physically incompatible with other small-bore connectors, like the Luer connectors used for intra-venous and enteral medication administration, and thus help prevent inadvertent misconnections. While some countries have already implemented this standard, France is behind schedule in implementing the NRFit connectors due to the absence of strong recommendations or obligations from the authorities. However, NRFit connectors represents real progress for the prevention of medication errors.

Suboptimal exposure to fluconazole in critically ill patients: Pharmacokinetic analysis and determinants.

OBJECTIVES: This study aims at evaluating fluconazole exposure in critically ill patients and identifying variables associated with the latter. PATIENTS AND METHODS: This was a 2-year (2018-2019) retrospective multicenter cohort study. Adult patients > 18 years-old with at least one fluconazole concentration measurement during their ICU stay were included. RESULTS: Twenty patients were included. Only 11 patients had a fluconazole trough concentration (Cmin) within the target range (≥15 mg/L). According to bivariable analysis, SOFA score, GGT, fluconazole clearance, Ke, and Vd, were independently associated with a decrease in fluconazole Cmin. The median loading dose required to achieve the Cmin target appeared to be greater in patients with higher SOFA or GGT level and in patients undergoing renal replacement therapy. CONCLUSIONS: This study supports recommendation for routine fluconazole therapeutic drug monitoring in ICU patients so as to avoid underexposure, especially if SOFA score is ≥ 7 and/or GGT is ≥ 100 U/L.

Serious adverse events and deaths linked to poor ventilator use: A report of four closed claims.

Through this series of four closed claims, we highlight examples of accidents stemming from poor ventilator use. We then review the main issues in this regard as reported in the literature and by learned societies. This case series has led us to emphasise the need for safety procedures involving systematic checks prior to use, declaration and analysis of the risk, as well as feedback and teaching regarding ventilation systems.

Postauthorization safety study of Clottafact® , a triply secured fibrinogen concentrate in acquired fibrinogen deficiency: a prospective observational study.

BACKGROUND AND OBJECTIVES: A postauthorization safety study was performed between 2009 and 2012 to describe the use of Clottafact® in acquired fibrinogen deficiency in real-life medical practice in France. MATERIALS AND METHODS: One hundred and fifty patients were planned for 28 days of prospective follow-up after infusion. The analysis of this observational study was descriptive and performed according to the type of treatment (curative or preventive) and the origin of the bleed. RESULTS: One hundred and fifty-six patients (16-87 years) were included in 13 centres and treated in five different medical bleeding situations: postpartum (59), other gynaecological/obstetrical (6), trauma (34), liver (13), cardiovascular (23) and other various bleeding situations (21). The mean follow-up time was 18·9 ± 12·3 days. Two patients presented adverse drug reactions: one a pulmonary embolism and the other a four-site venous thromboembolic episode. All were serious with a dubious causal relationship with the study treatment. Efficacy data were collected as a secondary objective. In 150 patients receiving curative treatment, 117 of 159 infusions (73·6%) were considered as successful by the investigators, 35 as moderate (22%) and seven as no response (4·4%). CONCLUSION: The Clottafact® safety profile observed during the study matched the known profile of fibrinogen during use.

A systematic review of interventions and performance measures for antifungal stewardship programmes.

Objectives: Antifungal resistance is a significant and emerging threat. Stewardship programmes (SPs) have been proposed as an opportunity to optimize antifungal use. While examples of antifungal SP implementation have been recently described, there is yet to be an overview of interventions and their impacts on performance measures. Methods: We systematically reviewed published articles using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses check-list 2009. MEDLINE was searched using the term 'antifungal stewardship' on 15 February 2017. Eligible studies were those that described an antifungal SP and included an intervention and an evaluation of performance measures. Results: A total of 97 studies were identified and 14 were included. Only five studies reported an antifungal stewardship team composed of all the recommended members. The main intervention was the formulation of recommendations to change treatment (12 of 14). The main performance measure collected was antifungal consumption (10 of 14), followed by antifungal expenditure (7 of 14), adherence to therapeutic advice (4 of 14) and impact on mortality (4 of 14). Antifungal consumption was reduced by 11.8% to 71% and antifungal expenditure by as much as 50%. Adherence to therapeutic advice ranged from 40% to 88%, whereas antifungal SPs had no impact on mortality. Conclusions: All antifungal SPs had an impact, in particular on antifungal consumption and antifungal expenditure. Active intervention including a review of prescriptions seems to have more impact than implementation of treatment guidelines only. According to available published studies, antifungal consumption appears to be the most achievable performance measure to evaluate the impact of an antifungal SP.

Current trends in vasopressor use to the operating room: A pharmacoepidemiologic study in French teaching and military hospitals.

OBJECTIVES: Phenylephrine, ephedrine and norepinephrine are the vasopressors most commonly used in the operating room to treat anaesthesia-induced hypotension. Two new diluted forms of phenylephrine were released in 2011 (500µg/10mL and 500µg/5mL). We initiated a study to evaluate trends in the use of vasopressors in the operating room in French hospitals over the period 2011-2014. METHODS: We conducted a longitudinal, retrospective, observational study between 2011 and 2014 in French teaching and military hospitals. A questionnaire was sent in February 2015 to hospital pharmacists of each centre to retrospectively collect the consumption of each type of vasopressor. Yearly numbers of vasopressor ampoules were divided by the yearly numbers of anaesthetics recorded. For each vasopressor, we calculated the number of ampoules per 100 anaesthetics recorded (/100A). RESULTS: Thirty-two hospitals (82%) completed the questionnaire. One hundred per cent of hospitals had registered the diluted form of phenylephrine (61% had chosen the dilution 500µg/10mL), whereas concentrated ampoules were available in 68% of hospitals. Over the period, an exponential increase in the use of diluted phenylephrine was observed (from 1.0 ampoule/100A in 2012 to 31.7 in 2014), the use of ephedrine remained stable (26 ampoules and 17 prefilled syringe/100A), and use of norepinephrine trended upwards (from 6.7 to 8.2 ampoules/100A). CONCLUSIONS: The use of diluted phenylephrine has exponentially increased without reducing consumption of other vasopressors. This trend might be secondary to practice changes in hypotension treatment following the release of French guidelines in 2013 related to fluid management, the restriction of indications of hydroxylethyl-starch solutions in 2013, and a better knowledge of the benefit of blood pressure optimisation to reduce postoperative morbidity.

Prevalence of drug-related problems associated with direct oral anticoagulants in hospitalized patients: a multicenter, cross-sectional study.

WHAT IS KNOWN AND OBJECTIVE: The complex dose regimens of the direct-acting oral anticoagulants (DOAC) make their appropriate prescribing highly challenging. Inappropriate prescribing of the DOAC remains poorly addressed. We studied the patterns of DOAC prescription and estimated the prevalence of drug-related problems (DRPs) associated with their use. METHODS: A cross-sectional study was conducted using data from medical records system of the Lyon teaching hospitals. DRPs, identified among patients who received a DOAC, between 1 January 2010 and 31 July 2013, were categorized according to the Pharmaceutical Care Network Europe Classification System. The prevalence of hospital stays with a DRP was estimated, and a subgroup analysis according to DOAC and their indication for use was provided. Clinical outcomes were not assessed. RESULTS: Of the 4154 hospital stays with at least one DOAC administration [3412 patients; median age (range): 71 years (14-98), 57% female], 70·8% were excluded from the analysis mainly due to missing information for renal function and/or patient weight. Of the 1188 hospital stays that were screened, 100 DRPs were identified (prevalence 8·4%; 95% CI, 6·8-10·0). The highest prevalence was found among patients who received rivaroxaban for atrial fibrillation (14·6%; 95% CI, 10·7-18·5). A too low drug dose was the most frequent DRP (n = 56; 4·7%), followed by a too high drug dose (n = 37; 3·1%), contraindication (n = 5; 0·4%), and pharmacokinetic problem requiring dose adjustment (n = 2; 0·2%). WHAT IS NEW AND CONCLUSION: Drug-related problems associated with the DOACs occur quite commonly among hospitalized patients. Although these DRPs were considered to be of minor severity, prescribing protocols to support better prescribing should be disseminated to reduce the risk to patients. Renal function and body weight data should be mandatory on prescriptions to allow cross-checking.

Cluster randomized trial to evaluate the impact of team training on surgical outcomes.

BACKGROUND: The application of safety principles from the aviation industry to the operating room has offered hope in reducing surgical complications. This study aimed to assess the impact on major surgical complications of adding an aviation-based team training programme after checklist implementation. METHODS: A prospective parallel-group cluster trial was undertaken between September 2011 and March 2013. Operating room teams from 31 hospitals were assigned randomly to participate in a team training programme focused on major concepts of crew resource management and checklist utilization. The primary outcome measure was the occurrence of any major adverse event, including death, during the hospital stay within the first 30 days after surgery. Using a difference-in-difference approach, the ratio of the odds ratios (ROR) was estimated to compare changes in surgical outcomes between intervention and control hospitals. RESULTS: Some 22 779 patients were enrolled, including 5934 before and 16 845 after team training implementation. The risk of major adverse events fell from 8·8 to 5·5 per cent in 16 intervention hospitals (adjusted odds ratio 0·57, 95 per cent c.i. 0·48 to 0·68; P < 0·001) and from 7·9 to 5·4 per cent in 15 control hospitals (odds ratio 0·64, 0·50 to 0·81; P < 0·001), resulting in the absence of difference between arms (ROR 0·90, 95 per cent c.i. 0·67 to 1·21; P = 0·474). Outcome trends revealed significant improvements among ten institutions, equally distributed across intervention and control hospitals. CONCLUSION: Surgical outcomes improved substantially, with no difference between trial arms. Successful implementation of an aviation-based team training programme appears to require modification and adaptation of its principles in the context of the the surgical milieu. Registration number: NCT01384474 (http://www.clinicaltrials.gov).

No impact on long-term survival of prolonged ICU stay and re-admission for patients undergoing cytoreductive surgery with HIPEC.

BACKGROUND: Cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC) are promising new approaches of peritoneal metastases. However these surgical procedures are associated with a high morbidity rate thus intensive care (IC) management following serious complications may be warranted for these patients. The impact of the prolonged IC stay or re-admission on long-term survival remains unknown. METHODS: We retrospectively analysed 122 consecutive HIPEC procedures over a one year period (2010-2011) in a single academic hospital. We analysed complications that would lead to prolonged stay or re-admission into ICU and analysed long term follow-up in patients whether they required intensive care (ICU group) or not (Control group). RESULTS: ICU group represented 26.2% of the cohort mainly due to septic or haemorrhagic shock. Among them acute kidney injury and respiratory failure were present in 50% and 47% respectively. Cohort overall mortality rate was of 5.7%. Patients were followed for 4 years and survival analysis was performed adjusting for main confounding factors in a Cox survival model. Survival was not different between groups, with a median survival of 38 months [32; 44] vs. 33 months [26; 39] in the ICU group and Control group respectively. CONCLUSION: Prolonged stay or re-admission into ICU does not seem to statistically impact long term prognosis of patients undergoing CRS with HIPEC.

Estimated economic impact of pre-filled ephedrine syringes in the operating room.

BACKGROUND: Syringes of ephedrine are usually prepared ahead of time in order to reduce the time to injection. Commercial pre-filled syringes of ephedrine have been introduced to minimize the amount of waste. Our primary objective was to determine the economic impact of commercial syringes. We hypothesized that costs could be reduced compared to standard syringes. METHODS: Using data extracted from our medical records system, we retrospectively measured the total dose of ephedrine received per patient in 2013 to estimate the number of administered standard syringes. The proportion of administered standard syringes was calculated as the total number of administered standard syringes divided by the number of delivered ampoules in 2013. Thereafter, we calculated the annual cost difference as the difference between the cost for commercial syringes and the cost for standard syringes. Endpoints were calculated overall and for each operating room. RESULTS: At least one dose of ephedrine was given in 19,422 patients (44,943 administrations). The overall proportion of administered standard syringes was estimated to 52.8%. The threshold proportion of administered standard syringes for which commercial syringes would add no extra cost was 20.4%. In 30/32 operating rooms, the proportion of administered standard syringes was higher than 20.4%. The overall cost increase with commercial syringes was estimated to 51,567 €. Among operating rooms, incremental costs varied between -703 and 5086 €. CONCLUSION: Based on our findings, pre-filled ephedrine commercial syringes do not appear to reduce costs.

[Technical criteria of central venous catheters: Anaesthesiologist/intensivist and pharmacist opinions]. / Critères de choix d'un cathéter veineux central : points de vue de l'anesthésiste-réanimateur et du pharmacien.

INTRODUCTION: The lack of technical information from suppliers and from the literature, a wide variety of features and the absence of medical device reference document explain the difficulty for medical and pharmaceutical staffs to choose a central venous catheter (CVC). The aim of this study was to establish the specifications to choose a CVC according to the clinician needs. METHODS: An analysis of suppliers' technical documentation and a literature review was performed to identify criteria and to collect them in a questionnaire to conduct semi-structured interviews between 1 pharmacist and 5 anaesthesiologists/intensivists. With these interviews, the technical criteria were classified according to their importance in 3 levels. RESULTS: Thirteen technical criteria were identified after reading the technical documents and the literature. Among them, 8 were classified as "essential criteria" (level I) by the physicians: J-shaped guide, one clamp on each way, identified lumen, radiopacity, graduation every centimeter by 5 to 20 cm from the distal extremity, a length of 15 to 25 cm, a single-lumen catheter with a 14 to 16G way and a three-lumen catheter with 14 to 18G way. Finally, three criteria were classified as "intermediate criteria" (level II) and two as "optional criteria" (level III). CONCLUSIONS: This collaborative approach allowed to reference new medical devices according to the clinicians needs. These CVC are a mean to respect guidelines for physicians and nurses and to secure the patient's care.

[Impact of sugammadex on neuromuscular blocking agents use: a multicentric, pharmaco-epidemiologic study in French university hospitals and military hospitals]. / Impact du sugammadex sur les consommations de curares : étude pharmaco-épidémiologique multicentrique dans les centres hospitalo-universitaires et hôpitaux d'instructions des armées français.

INTRODUCTION: Seven Neuromuscular Blocking Agents (NMBA) are commercialized in France. Four of them have an intermediate duration of action. Sugammadex required the use of NMBA slightly employed in clinical practice in France. Its introduction in routine practice could have an impact on NMBA use in clinical practice. This study was then conducted to assess and compare NMBA use before and after the commercialization of sugammadex. MATERIALS AND METHODS: A longitudinal, retrospective, observational study was conducted between 2008 and 2011 in French university hospitals and military hospitals. The consumption data for sugammadex and NMBA were collected using a collection grid which was filled by pharmacists or anesthesiologists. Drug use was measured by the number of vials used divided by the annual number of hospitalizations in surgery and obstetrics (HSO). An overall analysis of the annual frequency of NMBA use was firstly performed, then individual data of each hospital were analyzed. Descriptive statistical analysis including mean, standard deviation, median, minimum and maximum was achieved. RESULTS: Thirty-four out of 39 hospitals participated in the study (87%) and analysis was performed on 26 of them (7%). The data of eight institutions were excluded due to missing values or because of the non-admission of sugammadex in their formulary. The NMBA mostly used were non-steroidal NMBA (75% of market share) with an increased use between 2008 and 2011 concerning atracurium (from 41 to 51 vials of 50mg atracurium used per 100 HSO). The overall analysis revealed an increase of the occurrence of rocuronium (between 2008 and 2011: from 1 to 4.8 vials of 50mg rocuronium used per 100 HSO). Individual analyses on each hospital showed a possible effect of sugammadex introduction on NMBA use in nine hospitals. DISCUSSION AND CONCLUSIONS: The commercialization of sugammadex seems to have induced a discrete increase of steroidal NMBA but non-steroidal NMBA remain the leading agent in France. A long-term follow-up is deserved.

An attempt to validate the modification of the American-European consensus definition of acute lung injury/acute respiratory distress syndrome by the Berlin definition in a university hospital.

PURPOSE: The Berlin definition for acute respiratory distress syndrome (ARDS) is a new proposal for changing the American-European consensus definition but has not been assessed prospectively as yet. In the present study, we aimed to determine (1) the prevalence and incidence of ARDS with both definitions, and (2) the initial characteristics of patients with ARDS and 28-day mortality with the Berlin definition. METHODS: We performed a 6-month prospective observational study in the ten adult ICUs affiliated to the Public University Hospital in Lyon, France, from March to September 2012. Patients under invasive or noninvasive mechanical ventilation, with PaO2/FiO2 <300 mmHg regardless of the positive end-expiratory pressure (PEEP) level, and acute onset of new or increased bilateral infiltrates or opacities on chest X-ray were screened from ICU admission up to discharge. Patients with cardiogenic pulmonary edema were excluded. Patients were further classified into specific categories by using the American-European Consensus Conference and the Berlin definition criteria. The complete data set was measured at the time of inclusion. Patient outcome was measured at day 28 after inclusion. RESULTS: During the study period 3,504 patients were admitted and 278 fulfilled the American-European Consensus Conference criteria. Among them, 18 (6.5 %) did not comply with the Berlin criterion PEEP ≥ 5 cmH2O and 20 (7.2 %) had PaO2/FiO2 ratio ≤200 while on noninvasive ventilation. By using the Berlin definition in the remaining 240 patients (n = 42 mild, n = 123 moderate, n = 75 severe), the overall prevalence was 6.85 % and it was 1.20, 3.51, and 2.14 % for mild, moderate, and severe ARDS, respectively (P > 0.05 between the three groups). The incidence of ARDS amounted to 32 per 100,000 population per year, with values for mild, moderate, and severe ARDS of 5.6, 16.3, and 10 per 100,000 population per year, respectively (P < 0.05 between the three groups). The 28-day mortality was 35.0 %. It amounted to 30.9 % in mild, 27.9 % in moderate, and 49.3 % in severe categories (P < 0.01 between mild or moderate and severe, P = 0.70 between mild and moderate). In the Cox proportional hazard regression analysis ARDS stage was not significantly associated with patient death at day 28. CONCLUSIONS: The present study did not validate the Berlin definition of ARDS. Neither the stratification by severity nor the PaO2/FiO2 at study entry was independently associated with mortality.

[Preoperative cardiac-risk assessment for non-cardiac surgery: The French RICARDO survey]. / Évaluation du Risque CARDiaque de l'Opéré (RICARDO) : enquête nationale auprès des anesthésistes-réanimateurs concernant la prise en charge périopératoire du patient à risque cardiaque.

OBJECTIVES: Professional practice evaluation of anaesthesiologist for high cardiac-risk patient cares in non-cardiac surgery, and assess disparities between results and recommendations. MATERIALS AND METHODS: Since June to September 2011, a self-questionnaire was sent to 5000 anesthesiologist. They were considered to be representative of national anesthesiology practitioner. Different items investigated concerned: demography, preoperative cardiac-risk assessment, modalities of specialized cardiologic advice, per- and postoperative care, and finally knowledge of current recommendations. RESULTS: We collected 1255 questionnaire, that is to say 25% of answers. Men were 73%, 38% were employed by public hospital; 70% worked in a shared operating theatre with a general activity. With regards to preoperative assessment, 85% of anaesthetists referred high cardiac-risk patient to a cardiologist. In only 16% of answer, Lee's score appeared in anaesthesia file to assess perioperative cardiac-risk. Only 61% considered the six necessary items to optimal estimate of cardiac-risk. On the other hand, 91% measured routinely the exercise capacities by interrogation. The most frequently doing exam (49% of anaesthetist) was an electrocardiogram in elderly patient. In 96% of case, beta-blockers were given in premedication if they were usually thought. Clopidogrel was stopped by 62% of anesthetist before surgery. In this case, 38% used another medication to take over from this one. Only 7% considered revascularization in coronary patient who were effectively treated. POISE study was know by 40% of practitioner, and 18% estimated that they have changed their practice. Preoperatively, 21% organized multidisciplinary approach for high-risk patient. During surgery, 63% monitored the ST-segment. In postoperative period for cardiac-risk patient, only 11% prescribed systematically an ECG, a troponin dosage, a postoperative monitoring of ST-segment, a cardiologic advice. In case of moderate troponin elevation, they were 70% to realize at least an ECG and/or an echocardiography. CONCLUSION: This study highlights some difference between current recommendation concerning assessment of cardiac-risk patient in non-cardiac surgery and daily practice of anesthetist, justifying regular update of this one.

[Implementation of morbidity and mortality conferences in French intensive care units: a survey]. / Enquête nationale sur la pratique des "Revues de morbi-mortalité" en réanimation.

OBJECTIVE: A national survey was conducted by the "Collège français d'anesthésie et de réanimation (CFAR)" and the "Collège des bonnes pratiques en réanimation (CBPR)", to analyze the implementation of morbidity and mortality conferences (MMCs) in French intensive care units (ICUs). STUDY DESIGN: An electronic questionnaire was set up. We directed the survey at French ICUs physicians registered in the two Colleges directories, only one form was filled in by each participating unit. RESULTS: From December 2009 to February 2010, Among the 170 replies, 120 ICUs (71%) practiced MMC. No difference in the typology of the two groups was found. The median annual number of MMCs was 4 per year (1-15). The perimeter of the MMCs concerned only the ICU unit in 70 cases (58%), more than one ICU unit in the same department in 11 cases (9.8%), more than one department of ICU in 16 cases (13%) and other departments in 57 cases (48%). The events analyzed were: all deaths in 45 cases (37.5%), unexpected deaths in 50 cases (41.7%), severe adverse events in 67 cases (55.8%) and other events in 19 cases (15.8%). At least one adverse event defined by the two colleges in the process of "accreditation" was analyzed in 86 cases (72%). Participation of a physician of at least one other unit was reported in 56 cases (47%) and of medical students in 62 cases (52%). The low rate of participation of ICU nurses was reported in 62 cases (69.2%) and their absence in 35 cases (29%). MMCs consequences were drafting of new procedure in 99 cases (83%), changes in procedures in 75 cases (63%), conducting training programs in 60 cases (50%), organizational changes in 86 cases (72%), adverse event declaration in 21 cases (18%) and monitoring indicators in 40 cases (33%). Among units which did not practice MMCs, Identified obstacles were organizational causes in 25 cases (50%), inexperience in seven cases (14%), lack of methodology in 4 cases (8%), realization of other methods of formative assessment in 4 cases (8%) and physician's refusal in three cases (6%). The fear of medico-legal problem was never reported as a barrier to MMCs practice. Forty-five units (90%) projected to practice MMR. CONCLUSION: This survey showed that the practice of MMR is common in French ICUs, allowing the identification of organizational problems, but also of training needs, joining one of the initial concerns that have led to their implementation. Expanding the participation to non-physician members of the units should be encouraged, without underestimating the difficulties particularly in the organizational domains that represent an obstacle to development of MMCs.

[Bacterial parotitis in an immunocompromised patient in adult ICU]. / Parotidite bactérienne chez une patiente immunodéprimée en réanimation adulte.

Bacterial parotitis is a common childhood disease with a favorable outcome. Staphylococcus aureus is the most frequently involved pathogen. Clinical presentation in adult patients can be misleading, Onset occurs in patients with multiple comorbidities, making diagnosis difficult--particularly in ICU. Different pathogens are found in adults with worse outcomes observed. We report here the case of a critically ill patient and discuss diagnosis and management of bacterial parotitis.