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.

Report of the first AKI Round Table meeting: an initiative of the ESICM AKI Section.

PURPOSE: Critical Care Nephrology is an emerging sub-specialty of Critical Care. Despite increasing awareness about the serious impact of acute kidney injury (AKI) and renal replacement therapy (RRT), important knowledge gaps persist. This report represents a summary of a 1-day meeting of the AKI section of the European Society of Intensive Care Medicine (ESICM) identifying priorities for future AKI research. METHODS: International Members of the AKI section of the ESICM were selected and allocated to one of three subgroups: "AKI diagnosis and evaluation", "Medical management of AKI" and "Renal Replacement Therapy for AKI." Using a modified Delphi methodology, each group identified knowledge gaps and developed potential proposals for future collaborative research. RESULTS: The following key research projects were developed: Systematic reviews: (a) epidemiology of AKI with stratification by patient cohorts and diagnostic criteria; (b) role of higher blood pressure targets in patients with hypertension admitted to the Intensive Care Unit, and (c) specific clearance characteristics of different modalities of continuous renal replacement therapy (CRRT). Observational studies: (a) epidemiology of critically ill patients according to AKI duration, and (b) current clinical practice of CRRT. Intervention studies:( a) Comparison of different blood pressure targets in critically ill patients with hypertension, and (b) comparison of clearance of solutes with various molecular weights between different CRRT modalities. CONCLUSION: Consensus was reached on a future research agenda for the AKI section of the ESICM.

Team planning discussion and clinical performance: a prospective, randomised, controlled simulation trial.

Planning held before emergency management of a critical situation might be an invaluable asset for optimising team preparation. The purpose of this study was to investigate whether a brief planning discussion improved team performance in a simulated critical care situation. Forty-four pairs of trainees in anaesthesia and intensive care were randomly allocated to either an intervention or control group before participating in a standardised simulated scenario. Twelve different scenarios were utilised. Groups were stratified by postgraduate year and simulated scenario, and a facilitator was embedded in the scenario. In the intervention group, the pairs had an oral briefing followed by a 4-min planning discussion before starting the simulation. The primary end-point was clinical performance, as rated by two independent blinded assessors on a score of 0-100 using video records and pre-established scenario-specific checklists. Crisis resource management and stress response (cognitive appraisal ratio) were also assessed. Two pairs were excluded for technical reasons. Clinical performance scores were higher in the intervention group; mean (SD) 51 (9) points vs. 46 (9) in the control group, p = 0.039. The planning discussion was also associated with higher crisis resource management scores and lower cognitive appraisal ratios, reflecting a positive response. A 4-min planning discussion before a simulated critical care situation improved clinical team performance and cognitive appraisal ratios. Team planning should be integrated into medical education and clinical practice.

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.

Use of a hand-held digital cognitive aid in simulated crises: the MAX randomized controlled trial.

BACKGROUND: Cognitive aids improve the technical performance of individuals and teams dealing with high-stakes crises. Hand-held electronic cognitive aids have rarely been investigated. A randomized controlled trial was conducted to investigate the effects of a smartphone application, named MAX (for Medical Assistance eXpert), on the technical and non-technical performance of anaesthesia residents dealing with simulated crises. METHODS: This single-centre randomized, controlled, unblinded trial was conducted in the simulation centre at Lyon, France. Participants were anaesthesia residents with >1 yr of clinical experience. Each participant had to deal with two different simulated crises with and without the help of a digital cognitive aid. The primary outcome was technical performance, evaluated as adherence to guidelines. Two independent observers remotely assessed performance on video recordings. RESULTS: Fifty-two residents were included between July 2015 and February 2016. Six participants were excluded for technical issues; 46 participants were confronted with a total of 92 high-fidelity simulation scenarios (46 with MAX and 46 without). Mean (sd) age was 27 (1.8) yr and clinical experience 3.2 (1.0) yr. Inter-rater agreement was 0.89 (95% confidence interval 0.85-0.92). Mean technical scores were higher when residents used MAX [82 (11.9) vs 59 (10.8)%; P<0.001]. CONCLUSION: The use of a hand-held cognitive aid was associated with better technical performance of residents dealing with simulated crises. These findings could help digital cognitive aids to find their way into daily medical practice and improve the quality of health care when dealing with high-stakes crises. CLINICAL TRIAL REGISTRATION: NCT02678819.

Is decompression illness possible during hyperbaric therapy? a case report.

A 57-year-old woman was admitted to the intensive care unit in a state of severe hypotensive shock following a session of hyperbaric oxygen (HBO2) therapy. Shock was attributed to gastric barotrauma, which resulted in a massive venous gas embolism. Gastric barotrauma was attributed to the presence of a filled gastric band/cuff during the HBO2 therapy that prevented expanding gas from escaping on decompression. After deflation of the gastric band, two additional HBO2 sessions were performed and resulted in complete symptom resolution. Vasoactive drugs could be weaned, and the patient was discharged from hospital on Day Three with complete symptom resolution. Given the risk of gastric barotrauma and venous gas embolism, physicians should be aware of gastric band history before HBO2 therapy.

Perioperative management of a bilateral forearm allograft.

Composite tissue allotransplantation (CTA) is a complex procedure requiring a multidisciplinary collaboration between surgeons, anesthetists, and transplantation specialists. We will describe the perioperative management of a bilateral forearm allograft performed at our facility. A 40-year-old man who lost both forearms was registered on the transplant waiting list; a suitable graft was available 11months later. Anesthesia required planning for vascular access, hemodynamic monitoring, fluid therapy management and prevention of deep vein thrombosis. Blood loss was not quantifiable, which made coagulation management challenging. Reperfusion syndrome required the use of vasopressors. Postoperatively, moderate rhabdomyolysis without acute renal failure was observed. No complications such as thrombosis, hemorrhage, or opportunistic infections occurred during the early postoperative period. A comprehensive, protocol-driven, patient care strategy is crucial for the proper conduct of the surgical procedure and graft survival.

[Impact of a program designed to improve continuous renal replacement therapy stability]. / Impact d'un programme d'amélioration de la stabilité de l'épuration extrarénale continue.

OBJECTIVES: During continuous renal replacement therapy (CRRT), circuit clotting increases nursing workload, cost of the therapy and blood loss. The aim of this study was to assess the impact of a program designed to improve CRRT stability on unexpected circuit clotting. STUDY DESIGN: Retrospective and observational study. PATIENTS AND METHODS: In January 2011, several changes have been adopted regarding CRRT management. Regional citrate anticoagulation, continuous hemodialysis using super high-flux membranes and a specific training for intensive care unit nurses were implemented. CRRT sessions before (year 2009 and 2010, "Before group") and after (year 2011 and 2012, "After group") were analyzed. The primary endpoint was the incidence of unexpected CRRT session end. RESULTS: During the study period, 401 sessions performed in 152 patients were analyzed. Sixty-three unexpected session's end (40%) occurred before and 43 (17%) after the implementation of the program (P<0.0001). Median filter life time was 33 (13-48) hours before and 55 (27-67) hours after (P<0.0001). CONCLUSION: Our program designed to improve CRRT stability reduced filter losses by reducing unexpected circuit clotting.

[The acute pulmonary renal syndrome: An unusual presentation of granulomatosis with polyangiitis]. / Le syndrome pneumo-rénal aigu : un mode de révélation rare de la granulomatose avec polyangéite.

INTRODUCTION: We report a case of acute pulmonary renal syndrome mimicking septic shock, which led to the diagnosis of granulomatosis with polyangiitis. CASE REPORT: A 70-year-old man was hospitalized because of acute kidney injury and acute respiratory distress syndrome with diffuse alveolar hemorrhage associated with a serum procalcitonin level of 18 µg/L. Initially, septic shock was suspected and antibiotic therapy was started. The absence of microbiological isolates and the patient's rapid clinical deterioration prompted laboratory testing for autoimmune disease, which confirmed the diagnosis of granulomatosis with polyangiitis. Immunosuppressive therapy was promptly initiated with corticosteroids, cyclophosphamide and several plasma exchanges, which resulted in a rapid clinical improvement and ICU discharge. CONCLUSIONS: Granulomatosis with polyangiitis is a systemic necrotizing vasculitis with antineutrophil cytoplasmic antibodies, which can present with acute pulmonary renal syndrome, combining acute respiratory distress syndrome and acute kidney injury. This misleading presentation must prompt an autoimmune disease testing in order to yield an early diagnosis of a vasculitis, allowing for timely initiation of immunosuppressive treatment. Serum procalcitonin levels can be markedly elevated and this must not override the possibility of a vasculitis where the patient shows a compatible symptomatology.

[Integration of a hospital pharmacist in the ICU]. / Intégration d'un pharmacien hospitalier en service de réanimation.

The French regulatory system strongly encourages strict regulation of health products' production and distribution, especially concerning risk management and economic aspects. An ICU is an unusual environment for a local pharmacy practice (a nurse for every 2.5 patients, continuous adaptation of therapeutics…). However, a literature review reports interesting data concerning risk management and economics. This article aims to relate the experience of a pharmacist integration in a French teaching hospital ICU (half-time position).

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.

[Continuous haemodialysis with citrate anticoagulation in patients with liver failure: three cases]. / Hémodialyse continue avec anticoagulation au citrate chez l'insuffisant hépatique : à propos de trois cas.

Regional citrate anticoagulation for continuous renal replacement therapy provides an efficient alternative to heparin as it reduces the likelihood of haemorrhage in critically ill patients with bleeding risk or coagulopathy and increases the haemofilter survival time. Liver failure is a classic contraindication of regional citrate anticoagulation since it carries the risk of citrate accumulation and its metabolic complications, although it could be attractive for this population of patients with high bleeding risk. We report three cases of continuous haemodialysis with regional citrate anticoagulation performed in patients with severe acute liver failure, without accumulation in two cases and with a suspected beginning of accumulation in the third case. For these patients, close monitoring of the total-to-ionized calcium ratio, pH and anion gap is particularly essential to control the safety of citrate infusion. Increasing effluent flow rate eliminates more calcium-bound citrate and therefore limits citrate accumulation and its consequences.

[Incidental finding of phaeochromocytoma during surgery: the anaesthesiologist's nightmare]. / Découverte fortuite d'un phéochromocytome en peropératoire : le cauchemar de l'anesthésiste.

We report the case of a patient who presented hypertension paroxysmal with acute pulmonary oedema followed by cardiocirculatory arrest during gynaecological surgery for resection of latero-aortic lymph nodes suspected to be cervical cancer metastases. This intervention, originally oncologic, has discovered ectopic phaeochromocytoma a posteriori. The management of perioperative serious adverse events revealing the undiagnosed phaeochromocytoma is discussed.

[Management of bradykinin-mediated angioedema]. / Prise en charge en urgence de l'angiœdème à bradykinine.

OBJECTIVES: Present the clinical signs of bradykinin-mediated angioedema, a disease little known to intensive care anaesthesiologists, and develop their scientific basis with recent data on management in emergency and perioperative care. DATA SOURCES: International recommendations and recent general reviews. Data collection was performed using the Medline database with the keyword: angioedema. STUDY SELECTION AND DATA EXTRACTION: Research studies published during the last 10 years were reviewed. Relevant clinical information was extracted and discussed. DATA SYNTHESIS: Angioedema is a clinical syndrome characterized by episodes of transitory recurrent submucosal and subcutaneous oedema, called attacks. During an attack, the oedema may be localized at the level of the skin and/or ENT and digestive tract mucosa. This syndrome is not due to an allergic reaction. It is related to a C1 complement inhibitor deficiency or an increase in factor XII resulting in the excessive release of bradykinin, which leads to capillary permeability. There are hereditary and acquired forms, notably associated with the use of ACE inhibitors and sartans. This rare disease should be recognized by anaesthesiologists and intensive care and emergency physicians because, in the absence of specific treatment, it can be life-threatening due to the appearance of laryngeal oedema. In addition, there is a risk that the patient may have an attack during the perioperatory period, due to surgical trauma. International recommendations exist, and there are new molecules available in France. For moderate attacks, treatment is based on tranexamic acid. For hereditary forms, according to the localization and gravity of the attacks, emergency treatment is based on the use of Icatibant, a bradykinin B2 receptor inhibitor, and C1 inhibitor concentrate. For pregnant women and acquired forms, C1 inhibitor concentrate is the treatment of reference. Antalgic and perfusion treatments should not be neglected, and should be modified as a function of clinical signs. High-risk situations (perioperatory period, birthing, dental care) should be identified and short-term prophylaxis put in place before any procedure that may trigger an attack. Algorithms are proposed for the diagnosis, treatment and prevention of attacks. Recommendations exist for during childbirth, in which case C1 inhibitor concentrate should be used. CONCLUSION: Bradykinin-mediated angioedema should be evoked in the case of recurrent and transitory oedema. Emergency management has evolved thanks to the commercialization of new molecules. Prevention of attacks during surgery and for during childbirth is important. The availability of C1 inhibitor concentrate in sufficient doses should be verified prior to the procedure. A multi-site reference centre (CREAK) has been created to help clinicians manage this disease. Patients with this disease should be identified in emergency departments. Health establishments, which cannot all have emergency stocks, should set up procedures for rapid provision or the transfer of patients to reference sites.

[Does the second cycle of French medical studies prepare students to be future anesthesiologists and intensivists?]. / Le deuxième cycle des études médicales prépare-t-il de futurs anesthésistes-réanimateurs?

OBJECTIVE: To analyze the factors influencing the choice of the specialty "anesthesiology and intensive care" by medical students at the end of the second cycle of the French medical curriculum. This study had three aims: to measure the attraction of students for this specialty, to assess the perception of this specialty at this stage of the medical studies, and to study the influence of the teaching of "anesthesiology and intensive care" during this second cycle on student perceptions of the specialty. STUDY DESIGN: Descriptive study. MATERIAL AND METHODS: We conducted an anonymous survey among 407 medical students who were at the end of their sixth year of their medical studies, and who were enrolled in one of the four schools of medicine in Lyon, France, for the university year 2007-2008. RESULTS: Three hundred and twenty-eight surveys were analyzed. The specialty "anesthesiology and intensive care" was ranked third overall in terms of preferred specialties. Intensive care was rated the most attractive component, and respondents in particular noted its multisystem perspective and perceived utility. Anesthesiology was in general seen as highly technical and potentially lucrative, but holding increased medicolegal risk. The hospital training courses were highly rated by the students, who believed these to be the best way to learn about this specialty. However, respondents indicated that not enough hospital training courses were available, and only training courses in the intensive care units and the prehospital care department led the students towards this specialty. Accordingly, the nature and practice of anesthesiology were less well-known by students. CONCLUSION: Numerous medical students want to become intensivists. Anesthesiology is less well-known at this stage of the medical studies. The teaching of the "anesthesiology and intensive care" specialty needs to be optimized.

[Posterior reversible encephalopathy related to tacrolimus in a liver transplanted HIV patient]. / Encéphalopathie postérieure réversible liée au tacrolimus chez un patient transplanté hépatique infecté par le VIH.

Tacrolimus-related posterior reversible leukoencephalopathy (PRLE) is a rare complication which should be recognized by clinicians who regularly use immunosuppressive therapy. We report the case of an HIV-positive, hepatitis C-positive liver transplant patient who presented with this complication. Immunosuppression with tacrolimus was started after postsurgery. On the 20th day, the patient suffered two tonic-clonic convulsive attacks against a background of hypertension. Cerebral magnetic resonance imaging and lumbar puncture led to diagnosis of tacrolimus-related PRLE after eliminating other possible diagnoses. Therapeutic management consisted of withdrawing tacrolimus and initiating treatment with antiepileptogenic and antihypertensive drugs, supplemented with magnesium sulphate. The symptoms regressed in the days following withdrawal of tacrolimus and the majority of lesions on magnetic resonance imaging disappeared within two weeks. The aim of which should be to identify patients at risk of developing this complication. This would enable targeted prevention involving magnesium supplementation, strict control of blood pressure and serial monitoring of tacrolimus blood concentrations.

[Antimicrobial prophylaxis for caesarean delivery: before or after cord clamping? A meta-analysis]. / Antibioprophylaxie pour césarienne avant incision ou après clampage du cordon? Méta-analyse.

OBJECTIVE: The objective of this systematic review was to assess the effect of preoperative rather than after umbilical cord clamping antimicrobial prophylaxis for caesarean delivery on maternal and neonatal infectious postoperative morbidity. STUDY DESIGN: Meta-analysis. METHODS: Three electronic databases (Pubmed, Cochrane Central Register of Randomized Controlled Trials and Embase) were searched without language restriction and retrieved 201 potentially relevant trials. Five randomized controlled trials (n=1108) studying the timing of antimicrobial prophylaxis for caesarean section were included. The quality of included trials was assessed on the modified Oxford validity scale. RESULTS: Preoperative administration of antibiotics (n=456) rather than after cord clamping (n=563) provides a significant reduction in the incidence of endometritis (Odds Ratio (OR) 0.59 [95% Confidence Interval (CI) 0.35-0.98]) and of total maternal infectious morbidity (OR 0.51 [95% CI 0.32-0.82]). This benefit was not observed regarding the incidence of wound infection (Peto OR 0.58 [95% CI 0.29-1.16]), neonatal infection (Peto OR 1.06 [95% CI 0.57-1.96]), neonatal sepsis workup (OR 1.02 [95% CI 0.67-1.54]), neonatal documented sepsis (Peto OR 0.93 [95% CI 0.43-2.02]) or neonatal intensive care unit admission (OR 0.97 [95% CI 0.61-1.56]). No significant heterogeneity was observed between the included studies. CONCLUSION: This meta-analysis provides strong evidence that the preoperative rather than after cord clamping administration of antimicrobial prophylaxis for caesarean delivery provides a reduction in the incidence of endometritis and maternal total infectious morbidity without affecting the incidence of wound infection and neonatal infectious morbidity.