Search

Background: This study aimed to investigate renal replacement therapy (RRT) practices in a representative nationwide sample of French intensive care units (ICUs). Methods: From July 1 to October 5 2021, 67 French ICUs provided data regarding their ICU and RRT implementation. We used an online questionnaire to record general data about each participating ICU, including the type of hospital, number of beds, staff ratios, and RRT implementation. Each center then prospectively recorded RRT parameters from 5 consecutive acute kidney injury (AKI) patients, namely the indication, type of dialysis catheter used, type of catheter lock used, type of RRT (continuous or intermittent), the RRT parameters initially prescribed (dose, blood flow, and duration), and the anticoagulant agent used for the circuit. Results: A total of 303 patients from 67 ICUs were analyzed. Main indications for RRT were oligo-anuria (57.4%), metabolic acidosis (52.1%), and increased plasma urea levels (47.9%). The commonest insertion site was the right internal jugular (45.2%). In 71.0% of cases, the dialysis catheter was inserted by a resident. Ultrasound guidance was used in 97.0% and isovolumic connection in 90.1%. Citrate, unfractionated heparin, and saline were used as catheter locks in 46.9%, 24.1%, and 21.1% of cases, respectively. Conclusions: Practices in French ICUs are largely compliant with current national guidelines and international literature. The findings should be interpreted in light of the limitations inherent to this type of study.

Ceftazidime is used for the treatment of many bacterial infections, including severeThe objective of this review is to assess the current state of knowledge about the impact of obesity on ceftazidime treatment. A literature search was conducted on PubMed-MEDLINE (2016-2021) to retrieve pharmacokinetic studies published in English, matching the terms 'ceftazidime' AND 'pharmacokinetics.'The impact of obesity on pharmacokinetics is generally poorly known, mainly because obese patients are often excluded from clinical studies. However, the published literature clearly shows that obese patients have significantly lower ceftazidime concentrations. This could be explained by increased volume of distribution and clearance. This low exposure represents a major factor of therapeutic failure, potentially fatal for critically ill patients. While further studies would be useful to better assess the magnitude and understanding of this variability, the use of higher doses of ceftazidime is needed in obese patients. Moreover, therapeutic drug monitoring for dose adaptation is of major interest for these patients, as the efficacy of ceftazidime seems to be directly related to its plasma concentration.

The performance of new-generation high-power electronic nicotine delivery system (ENDS) for the administration of inhaled terbutaline was assessed.The formulation of e-liquid was carried out using terbutaline in combination with 1, 3- propanediol. Several terbutaline concentrations (from 0.3125 to 2.500 mg / mL) and power levels (from 15 to 35 W) were assessed using a box type ENDS. The respirable drug dose was determined using a Glass Twin Impinger and quantified by liquid chromatography coupled with a UV-detector. The Next Generation Impactor and the Dekati Low Pressure Impactor were used to measure the aerosol particle size distribution in drug mass. The results were compared with a jet nebulizer (Cirrus TM 2) similar to the usual clinical conditions (2 mL at [terbutaline] of 2.5 mg / mL).The optimal conditions to maximize terbutaline delivery using ENDS are a drug concentration at 1 mg/mL, and a power level at 30 W, to reach a respirable dose of 8.73 ± 0.90 µg/puff. By contrast, during a 5 min nebulization, the respirable dose of terbutaline was 1040 ± 33 µg whatever the cascade impactors and the aerosol devices used. The mass median aerodynamic diameter (MMAD) remains similar for jet nebulizer and ENDS in the 1.74-2.07 µm range.Compared to the jet nebulizer, a same respirable dose of terbutaline at the same range of aerosol size distribution was delivered by ENDS if 120 puffs were performed. The ENDS can be considered as an alternative aerosol device for terbutaline delivery.

BACKGROUND Ceftazidime (CAZ) is commonly used as pivotal antibiotic against pseudomonas aeruginosa in critically ill patients. ICU patients have severely altered and variable antibiotic pharmacokinetics, resulting in lower antimicrobial concentrations and potentially poor outcome. Several factors, including obesity and renal function, may influence pharmacokinetics. Thus, the objective of the study was to evaluate impact of obesity and renal function on CAZ plasma concentrations and dosing regimen in ICU patients. METHODS All consecutive adult patients from 6 ICUs, treated with continuous CAZ infusion and under Therapeutic Drug Monitoring evaluation were included. Obesity was defined as body mass index ≥ 30 kg/m². Glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease Epidemiology Collaboration formula. CAZ recommended levels for plasma concentrations were between 35 and 80 mg/L. RESULTS A total of 111 patients (45 obese), weighted 90 (±24,4) kg, were included. Mean GFR was 82 mL/min/1,73m2 (±40,3). Recommended CAZ plasma concentrations were achieved only for 49,6% patients, with median dosing regimen of 6g/d. Obese patients had lower CAZ plasma concentrations compared to non-obese patients (37.8 vs 56.3 mg/L; p=0.0042*) despite similar dosing regimens (5.83g/d vs 5.52 g/d, p= 0.2529). Almost all Augmented Renal Clearance patients were underdosed despite CAZ dosing of 6,6g/d (±0,8). Considering weight-based CAZ dosing seemed to attenuate such obesity-related discrepancies, regardless of GFR. CONCLUSIONS ICU obese patients required significantly greater CAZ amount to achieve target range. Tailored dosing regimen may be considered based on weight and GFR. Future prospective studies should be performed to confirm this individualized dosing approach.

Background Successful aerosol therapy in mechanically ventilated patients depends on multiple factors. Among these, position of nebulizer in ventilator circuit and humidification of inhaled gases can strongly influence the amount of drug deposited in airways. Indeed, the main objective was to preclinically evaluate impact of gas humidification and nebulizer position during invasive mechanical ventilation on whole lung and regional aerosol deposition and losses. Methods Ex vivo porcine respiratory tracts were ventilated in controlled volumetric mode. Two conditions of relative humidity and temperature of inhaled gases were investigated. For each condition, four different positions of vibrating mesh nebulizer were studied: (i) next to the ventilator, (ii) right before humidifier, (iii) 15 centimeters to the Y-piece adapter and (iv) right after the Y-piece. Aerosol size distribution were calculated using cascade impactor. Nebulized dose, lung regional deposition and losses were assessed by scintigraphy using 99mtechnetium-labeled diethylene-triamine-penta-acetic acid. Results Mean nebulized dose was 95% ± 6%. For dry conditions, the mean respiratory tract deposited fractions reached 18% (± 4%) next to ventilator and 53% (± 4%) for proximal position. For humidified conditions, it reached 25% (± 3%) prior humidifier, 57% (± 8%) before Y-piece and 43% (± 11%) after this latter. Conclusions Optimal nebulizer position is proximal before the Y-piece adapter showing a more than two-fold higher lung dose than positions next to the ventilator. Dry conditions tend to more peripheral lung deposition of aerosol. But gas humidification appears hard to interrupt efficiently and safely in clinical use. Considering the impact of optimized positioning, this study argues to maintain humidification.

In this article, we present a case of apixaban elimination prolonged by 450% in a patient with coronavirus disease 2019 because of multiple conditions, including drug–drug interaction, severe inflammation, and acute kidney injury. Therapeutic drug monitoring was used to explain unusual routine coagulation assays. This grand round highlights the importance of dialog between the clinician and a therapeutic drug monitoring consultant for optimal patient care.

Several technical features influencing bronchodilator delivery were evaluated using different vaping drug delivery systems (VDDS).Terbutaline in powder form, combined with 1, 3- propanediol used as e-liquid was tested at different concentrations (1 and 2.5 mg/mL), power levels (15 W and 30 W), and set applied resistances (0.15 to 1.5 O) to compare the efficiency of three VDDS (GS AIR2, GS TANK, CUBIS). Samples were collected with a Glass Twin Impinger (GTI). A High Performance Liquid Chromatography (HPLC) was used for drug quantification. The Next Generation Impactor (NGI) measured particle size distribution. Results were also considered with a clinical jet nebulizer (CirrusGS AIR2 with resistance = 1.5 O; power = 15 W, and [Terbutaline] = 2.5 mg/mL represents the optimal VDDS conditions to deliver a respirable dose of 20.05 ± 4.2 µg/puff with a mass median aerodynamic diameter (MMAD) of 1.41 ± 0.03 µm. Thus, 52 puffs were required (lasting approximately 15 min of vaping) to reach similar respirable dose and MMAD compared to nebulization.We proved that several crucial VDDS technical parameters govern the performance of respiratory bronchodilator delivery including the resistance, power level and atomizer design.

In intensive care units, nebulization is a usual route for drug administration to patients under mechanical ventilation (MV). The effectiveness of inhalation devices as well as depositions sites of aerosols for ventilated patients remain poorly documented. In vivo human inhalation studies are scarce due to ethical restrictions because imaging techniques require radioaerosols to assess regional aerosol deposition. Thus, we developed an ex vivo respiratory model under invasive MV for preclinical aerosol deposition studies. The model was composed of ex vivo porcine respiratory tracts. MV was achieved thanks to a tracheal intubation and a medical ventilator under controlled conditions. Respiratory features were studied using analogical sensors. Then regional homogeneity of gas-ventilation was assessed with 81mKrypton scintigraphies. Finally, a proof of concept study for aerosol deposition was performed. Obtained respiratory features as well as gamma-imaging techniques, which demonstrated a homogenous regional ventilation and about 18% ± 4% of the nebulized dose deposited the respiratory tract, were in good agreement with human data available in the literature. This original ex vivo respiratory model provides a feasible, reproducible and cost-effective preclinical tool to achieve aerosol deposition studies under MV.

International audience; The new high-power Electronic Nicotine Delivery System (ENDS) can generate aerosols with higher nicotine concentrations than older ENDS . Aerosol particle sizes affect deposition patterns and then plasma nicotine levels in vapers. Consequently, understanding the factors influencing particle size distribution of high-power ENDS is relevant to assess their performance in terms of nicotine delivery. The particle size distribution and the aerosol output (aerosol mass) were measured using cascade impactors. The effects of the refill liquid composition (80% PG/20% VG vs. 80% VG/20% PG; PG refers to propylene glycol and VG to vegetable glycerin) and the power level of the battery (from 7 W to 22 W) were investigated. The aerosol output increases significantly with the power level following a logarithmic law. The PG/VG ratio also has an impact on the aerosol output. The higher the VG content in the refill liquid, the higher is the aerosol output. Besides, particle size distribution is positively related to the power level, following linear correlations between the mass median aerodynamic diameter (MMAD) and the power level in the range of 7-22 W. A moderate impact of the PG/VG ratio on size distribution is equally observed. Changes in the power level allow the transition between a dominant mode with MMAD from 613 nm to 949 nm. We demonstrated that the power level can strongly change the aerodynamic properties of high-power ENDS, especially at high voltage. Associated with the aerosol nicotine level assessment, MMAD could be determined as a means for comparing ENDS devices and nicotine delivery.

Background Predicting fluid responsiveness may help to avoid unnecessary fluid administration during acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the diagnostic performance of the following methods to predict fluid responsiveness in ARDS patients under protective ventilation in the prone position: cardiac index variation during a Trendelenburg maneuver, cardiac index variation during an end-expiratory occlusion test, and both pulse pressure variation and change in pulse pressure variation from baseline during a tidal volume challenge by increasing tidal volume (VT) to 8 ml.kg-1. Methods This study is a prospective single-center study, performed in a medical intensive care unit, on ARDS patients with acute circulatory failure in the prone position. Patients were studied at baseline, during a 1-min shift to the Trendelenburg position, during a 15-s end-expiratory occlusion, during a 1-min increase in VT to 8 ml.kg-1, and after fluid administration. Fluid responsiveness was deemed present if cardiac index assessed by transpulmonary thermodilution increased by at least 15% after fluid administration. Results There were 33 patients included, among whom 14 (42%) exhibited cardiac arrhythmia at baseline and 15 (45%) were deemed fluid-responsive. The area under the receiver operating characteristic (ROC) curve of the pulse contour-derived cardiac index change during the Trendelenburg maneuver and the end-expiratory occlusion test were 0.90 (95% CI, 0.80–1.00) and 0.65 (95% CI, 0.46–0.84), respectively. An increase in cardiac index ≥ 8% during the Trendelenburg maneuver enabled diagnosis of fluid responsiveness with sensitivity of 87% (95% CI, 67–100), and specificity of 89% (95% CI, 72–100). The area under the ROC curve of pulse pressure variation and change in pulse pressure variation during the tidal volume challenge were 0.52 (95% CI, 0.24–0.80) and 0.59 (95% CI, 0.31–0.88), respectively. Conclusions Change in cardiac index during a Trendelenburg maneuver is a reliable test to predict fluid responsiveness in ARDS patients in the prone position, while neither change in cardiac index during end-expiratory occlusion, nor pulse pressure variation during a VT challenge reached acceptable predictive performance to predict fluid responsiveness in this setting. Trial registration ClinicalTrials.gov, NCT01965574. Registered on 16 October 2013. The trial was registered 6 days after inclusion of the first patient. Electronic supplementary material The online version of this article (doi:10.1186/s13054-017-1881-0) contains supplementary material, which is available to authorized users.

Limiting tidal volume (TV) in ARDS patients may not be achieved once assisted modes are used. We systematically investigated on the bench effect of assisted modes on size and variability of TV at different breathing frequencies (BF), patient effort and ARDS severity. We used V500 Infinity ICU ventilator connected to ASL 5000 lung model mimicking mild, moderate and severe ARDS. Thirteen assisted modes were tested falling into three categories, namely volume controlled ventilation with mandatory minute ventilation (VCV-MMV), pressure-controlled ventilation (PCV) including airway pressure release ventilation (APRV) and pressure support ventilation (PSV). Two levels of BF and effort were tested for each ARDS severity in each mode. Median (first-third quartiles) TV was compared across modes using non parametric tests. Probability of TV > 6 ml/kg ideal body weight was assessed by binomial regression and expressed as odds ratio (OR) with 95% confidence intervals. TV variability was measured from coefficient of variation. TV distribution over all BF, effort and ARDS categories significantly differed across modes (P 6ml/kg was significantly increased with spontaneous breaths assisted by PSV (OR 19.36 [12.37-30.65]) and significantly reduced in APRV (OR 0.44 [0.26-0.72]) and PSV with guaranteed volume mode. Coefficient of variation of TV was greater for low BF and VCV-MMV and PCV modes. Risk of TV > 6ml/kg was significantly reduced in APRV and PSV with guaranteed volume mode. APRV had the highest variability.

Legionella are bacteria responsible for severe lung pathologies but how they are aerosolized and enter the respiratory tract remains poorly documented. Previous data using animal experimentations (especially through intratracheal instillations) led to the establishment of mathematical models allowing the estimation of aerosol dispersion risks. But direct extrapolation to humans is questionable and a model more representative of a physiological route (for example inhalation of aerosols) should be developed. The aim of this study was to determine the deposition pattern of aerosolized Legionella in a model as close as possible to the human anatomy and to the physiological respiratory function while limiting in vivo experiments. To that purpose, we used a human-porcine respiratory tract model previously published. This chimeric model consists of a replica of the upper respiratory airways made by additive manufacturing connected to ex vivo porcine lungs ventilated by passive expansion, as for humans in physiological conditions. In 6 independent experiments, fluorescent Legionella were aerosolized in the model and visualized using the Cellvizio Lab technology (probe-based confocal fluorescence microscope). Legionella were found in the whole respiratory tract. Broncho-alveolar lavages were also performed and the amount of Legionella reaching the thoracic region was quantified by culture and quantitative PCR. 0.3 to 21% of aerosolized Legionella reached the left upper lobe while only 0.003 to 0.06% the right lower lobe. To the best of our knowledge, it is the first time that experiments mimicking a real human physiological exposure are performed while limiting animal experiments.

BACKGROUND: Limiting tidal volume (VT) in patients with ARDS may not be achieved once patient-triggered breaths occur. Furthermore, ICU ventilators offer numerous patient-triggered modes that work differently across brands. We systematically investigated, using a bench model, the effect of patient-triggered modes on the size and variability of VT at different breathing frequencies (f), patient effort, and ARDS severity. METHODS: We used a V500 Infinity ICU ventilator connected to an ASL 5000 lung model whose compliance was mimicking mild, moderate, and severe ARDS. Thirteen patient-triggered modes were tested, falling into 3 categories, namely volume control ventilation with mandatory minute ventilation; pressure control ventilation, including airway pressure release ventilation (APRV); and pressure support ventilation. Two levels of f and effort were tested for each ARDS severity in each mode. Median (first-third quartiles) VT was compared across modes using non-parametric tests. The probability of VT > 6 mL/kg ideal body weight was assessed by binomial regression and expressed as the odds ratio (OR) with 95% CI. VT variability was measured from the coefficient of variation. RESULTS: VT distribution over all f, effort, and ARDS categories significantly differed across modes (P 6 mL/kg was significantly increased with spontaneous breaths patient-triggered by pressure support (OR 19.36, 95% CI 12.37–30.65) and significantly reduced in APRV (OR 0.44, 95% CI 0.26–0.72) and pressure support with guaranteed volume mode. The risk increased with increasing effort and decreasing f. Coefficient of variation of VT was greater for low f and volume control-mandatory minute ventilation and pressure control modes. APRV had the greatest within-mode variability. CONCLUSIONS: Risk of VT > 6 mL/kg was significantly reduced in APRV and pressure support with guaranteed volume mode. APRV had the highest variability. Pressure support with guaranteed volume could be tested in patients with ARDS.

Purpose A need remains for alternative devices for aerosol drug delivery that are low cost, convenient and easy to use for the patient, but also capable of producing small-sized aerosol particles. This study investigated the potential of recent high power electronic nicotine delivery systems (ENDS) as aerosol generation devices for inhaled bronchodilators. Methods The particle size distribution was measured using a cascade impactor. The delivery of terbutaline sulfate, a current bronchodilator used for asthma or COPD therapy by inhalation, was studied. This drug was quantified by liquid chromatography coupled with tandem mass spectrometry. Results The particle size distribution in terms of mass frequency (in two ways, gravimetrically and quantitatively through drug assay on each stage) and the terbutaline sulfate concentration in the aerosol were elucidated. The mass median aerodynamic diameter (MMAD) and the drug delivery rose when the power level increased, to reach 5.6 ± 0.4 μg/puff with a MMAD of 0.78 ± 0.03 μm at 25 W. Conclusion New generation high-power ENDS are very efficient to generate carrier-droplets in the submicron range containing drug molecules with a constant drug concentration whatever the size-fractions. ENDS appear to be highly patient-adaptive.

Introduction: Respiratory models to assess aerosol regional deposition on human are often irrelevant or difficult to use. On the other hand, in vivo human experimentations have ethical restrictions. Objectives: This study aims to develop an ex vivo human-like respiratory tract model relevant to compare to human in vivo data, cheaper and easy to use. The main objective of this work is the validation of this model. Methods: This model includes a human plastinated head connected to an ex vivo porcine pulmonary tract ventilating artificially by passive expansion. First, a physiological study measures “pleural” depressions, tidal volumes and minute ventilation for the three respiratory rates chosen (10, 15 and 20 per minute) with three inspiratory / exiratory ratios (1/1, 1/2 and 1/3). Finally, a scintigraphy with 81m Krypton assesses the homogenous of the ventilation. Results: 36 different experiments were set for validation. At a respiratory rate of 15/minute with Inspiratory / Expiratory ratio of 1/2, the tidal volume average was 824mL (standard deviation 207mL). The scintigraphy performed on 16 ex vivo models (44.4%), showed homogenous ventilation with great similarity with human physiologic studies. Conclusion: This new model provides a realistic approach of human inhalation. Moreover, it allows variations of ventilation parameters permitting comparison to different human in vivo data. Consequently, it will likely become an indispensable work tool in aerosol deposition studies by combining research feasibility and human physiology likeness.