Assessment of lung ultrasound for early detection of respiratory complications in thoracic surgery.

BACKGROUND AND OBJECTIVES: To assess lung ultrasound for the diagnosis and monitoring of respiratory complications in thoracic surgery. METHODS: Prospective observational study in a University hospital, single institution. Adult patients scheduled for pulmonary resection surgery excluding pneumonectomy. An ultrasound follow-up was performed from the day before the surgery to the third day after surgery with calculation of B-line and lung score (reaeration and loss of aeration scores). Respiratory complications were collected throughout the hospitalization period. RESULTS: Fifty-six patients were included. Eighteen patients presented a respiratory complication (32%), and they presented significantly higher BMI and ASA scores. Patients operated by videothoracoscopy were less at risk of complications. At day 3, a reaeration score ≤ 2 on the ventilated side or ≤ -2 on the operated side, and a B-line score>6 on the operated side were in favor of a complication. CONCLUSION: Lung ultrasound can help in the diagnosis of respiratory complications following pulmonary resection surgery.

Assessment of Magnetic Resonance Imaging Changes and Functional Outcomes Among Adults With Severe Herpes Simplex Encephalitis.

Importance: Current guidelines recommend brain magnetic resonance imaging (MRI) for clinical management of patients with severe herpes simplex encephalitis (HSE). However, the prognostic value of brain imaging has not been demonstrated in this setting. Objective: To investigate the association between early brain MRI data and functional outcomes of patients with HSE at 90 days after intensive care unit (ICU) admission. Design, Setting, and Participants: This multicenter cohort study was conducted in 34 ICUs in France from 2007 to 2019 and recruited all patients who received a clinical diagnosis of encephalitis and exhibited cerebrospinal fluid positivity for herpes simplex virus DNA in the polymerase chain reaction analysis. Data analysis was performed from January to April 2020. Exposures: All patients underwent a standard brain MRI during the first 30 days after ICU admission. Main Outcomes and Measures: MRI acquisitions were analyzed by radiologists blinded to patients' outcomes, using a predefined score. Multivariable logistic regression and supervised hierarchical classifiers methods were used to identify factors associated with poor outcome at 90 days, defined by a score of 3 to 6 (indicating moderate-to-severe disability or death) on the Modified Rankin Scale. Results: Overall, 138 patients (median [interquartile range {IQR}] age, 62.6 [54.0-72.0] years; 75 men [54.3%]) with an admission median (IQR) Glasgow Coma Scale score of 9 (6-12) were studied. The median (IQR) delay between ICU admission and MRI was 1 (1-7) days. At 90 days, 95 patients (68.8%) had a poor outcome, including 16 deaths (11.6%). The presence of fluid-attenuated inversion recovery MRI signal abnormalities in more than 3 brain lobes (odds ratio [OR], 25.71; 95% CI, 1.21-554.42), age older than 60 years (OR, 7.62; 95% CI, 2.02-28.91), and the presence of diffusion-weighted MRI signal abnormalities in the left thalamus (OR, 6.90; 95% CI, 1.12-43.00) were independently associated with poor outcome. Machine learning models identified bilateral diffusion abnormalities as an additional factor associated with poor outcome (34 of 39 patients [87.2%] with bilateral abnormalities had poor outcomes) and confirmed the functional burden of left thalamic lesions, particularly in older patients (all 11 patients aged >60 years had left thalamic lesions). Conclusions and Relevance: These findings suggest that in adult patients with HSE requiring ICU admission, extensive MRI changes in the brain are independently associated with poor functional outcome at 90 days. Thalamic diffusion signal changes were frequently observed and were associated with poor prognosis, mainly in older patients.

Diaphragmatic speckle tracking imaging for 2D-strain assessment in mechanical ventilation weaning test.

Ultrasound (US) is recognized as a useful tool for detecting lung physiology and pathology. Lung US is compared with standard techniques for evaluating lung structure and function such as computed tomography and pulmonary function tests. At present, markers of normal physiology and pathology are detected using expected image patterns. Detecting the latter depends on the experience of the operator. Diaphragmatic dysfunction is a particularly frequent problem in intensive care. Diaphragmatic dysfunction is easily assessed using lung US. Speckle tracking analysis, a known method for assessing tissue displacement and deformation in cardiology, is proposed to be utilized in lung US for detecting and quantifying lung sliding. Using speckle tracking analysis to diaphragmatic deformation quantification could be an informative and new tool for weaning from mechanical ventilation.

Assessment of Electrical Impedance Tomography to Set Optimal Positive End-Expiratory Pressure for Venoarterial Extracorporeal Membrane Oxygenation-Treated Patients.

OBJECTIVES: Patients on venoarterial extracorporeal membrane oxygenation have many risk factors for pulmonary complications in addition to their heart failure. Optimal positive end-expiratory pressure is unknown in these patients. The aim was to evaluate the ability of electrical impedance tomography to help the physician to select the optimal positive end-expiratory pressure in venoarterial extracorporeal membrane oxygenation treated and mechanically ventilated patients during a positive end-expiratory pressure trial. DESIGN: Observational prospective monocentric. SETTING: University hospital. PATIENTS: Patients (n = 23) older than 18 years old, on mechanical ventilation and venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: A decreasing positive end-expiratory pressure trial (20-5 cm H2O) in increments of 5 cm H2O was performed and monitored by a collection of clinical parameters, ventilatory and ultrasonographic (cardiac and pulmonary) to define an optimal positive end-expiratory pressure according to respiratory criteria (optimal positive end-expiratory pressure selected by physician with respiratory parameters), and then adjusted according to hemodynamic and cardiac tolerances (optimal positive end-expiratory pressure selected by physician with respiratory, hemodynamic, and echocardiographic parameters). At the same time, electrical impedance tomography data (regional distribution of ventilation, compliance, and overdistension collapse) were recorded and analyzed retrospectively to define the optimal positive end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS: The median of this optimal positive end-expiratory pressure was 10 cm H2O in our population. Electrical impedance tomography showed that increasing positive end-expiratory pressure promoted overdistention of ventral lung, maximum at positive end-expiratory pressure 20 cm H20 (34% [interquartile range, 24.5-40]). Decreasing positive end-expiratory pressure resulted in collapse of dorsal lung (29% [interquartile range, 21-45.8]). The optimal positive end-expiratory pressure selected by physician with respiratory parameters was not different from the positive end-expiratory pressure chosen by the electrical impedance tomography. However, there is a negative impact of a high level of intrathoracic pressure on hemodynamic and cardiac tolerances. CONCLUSIONS: Our results support that electrical impedance tomography appears predictive to define optimal positive end-expiratory pressure on venoarterial extracorporeal membrane oxygenation, aided by echocardiography to optimize hemodynamic assessment and management.

Assessment of electrical impedance tomography to set optimal positive end-expiratory pressure for veno-venous ECMO-treated severe ARDS patients.

PURPOSE: Ultra-protective ventilation with low tidal volume is used in severe acute respiratory distress syndrome (ARDS) patients under extracorporeal membrane oxygenation (ECMO). However, the optimal positive end-expiratory pressure (PEEP) is unknown. The aim of our study was to assess electrical impedance tomography's (EIT) ability to choose the best PEEP for these patients. MATERIALS AND METHODS: A recruitment maneuver and after a decremental PEEP trial from 20 to 5 cmH20 were monitored by EIT, with lung images divided into four ventral-to-dorsal horizontal regions of interest. For each patient, three EIT-based PEEP were defined: PEEP ODCLmin (lowest pressure with the least EIT-based collapse lung [CL] and overdistension [OD]), PEEP ODCL15 (lowest pressure able to limit EIT-based collapse to less than or equal to 15% with the least overdistension) and PEEP Comp (PEEP with the highest EIT-based compliance). RESULTS: High PEEP levels were significantly associated with more overdistension while decreasing PEEP led to more collapsed zones. PEEP ODCL15 and PEEP Comp were in complete agreement with the reference Pulmonary PEEP (chosen according to usual respiratory clinical and ultrasound criteria), PEEP ODCLmin was in average agreement with the Pulmonary PEEP. CONCLUSION: EIT may be a useful real-time monitoring technique to optimize the PEEP level in severe ARDS patients under ECMO. TAKE-HOME MESSAGE: Ultra-protective ventilation with low tidal volume is used in severe acute respiratory distress syndrome patients under extracorporeal membrane oxygenation (ECMO), but the optimal positive end-expiratory pressure is unknown. This trial shows that electrical impedance tomography may be an interesting non-invasive bedside tool to provide real-time monitoring of PEEP impact in severe ARDS patients under ECMO. The Pulmovista® electrical impedance tomography was provided by Dräger (Lübeck, Germany) during the study period. Dräger had no role in the study design, collection, analysis and interpretation of the data, writing the article, or the decision to submit the article for publication.

Risk factor analysis for linezolid-associated thrombocytopenia in critically ill patients.

Linezolid is an antibiotic used against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Its primary adverse effect is haematotoxicity. The objective of this study was to analyse the risk factors for onset of thrombocytopenia in critically ill patients treated with linezolid. This was a retrospective, single-centre study of 72 patients. Platelets were measured from D0 to D20 after the start of treatment. The risk factors for thrombocytopenia were identified using a multivariate logistic regression analysis following a Monte Carlo simulation. Following ROC curve analysis, a baseline platelet count lower than 108 × 109/L and a Cmin higher than 4 mg/L, with respective odds ratios of 117 (95% CI [97-206]) and 3 (95% CI [1.5-6.2]) in the simulated population, were identified as risk factors. Among the source population patients combining these 2 factors, a significantly higher number developed thrombocytopenia (66.7% vs. 33.3%, p = 0.0042). A baseline platelet count lower than 108 × 109/L and a Cmin higher than 4 mg/L are risk factors for the onset of thrombocytopenia in critically ill patients treated with linezolid.

Ceftazidime dosage recommendations in burn patients: from a population pharmacokinetic approach to clinical practice via Monte Carlo simulations.

BACKGROUND: Ceftazidime dosage regimen recommendations based on pharmacokinetic/pharmacodynamic approaches are not available for burn patients. OBJECTIVE: The goal of this study was to propose a continuous dosage regimen of ceftazidime in burn patients, taking into account different MICs and pharmacokinetic covariates. METHODS: The population pharmacokinetic analysis was conducted by using software dedicated to the analysis of nonlinear mixed effects models. The population pharmacokinetic model was first developed and validated in 70 adult burn patients. Taking into account various MICs of pathogens, 3 Monte Carlo simulation trials were conducted by using target concentration intervals (10-100, 20-100, and 40-100 mg/L). The recommended dosages were defined as the minimum dose leading to the highest percentage of patients whose ceftazidime concentrations were included in the target interval. RESULTS: Serum creatinine and age were identified as covariates of ceftazidime clearance. Age was also involved in volume of distribution. The simulations showed that a dose of 6 g/d did not allow achievement of the target interval in most patients. Regardless of dosage regimen, age, and serum creatinine, the mean percentage of patients reaching the 10- to 100-mg/L and the 20- to 100-mg/L target intervals were 99.4% (0.3%) and 96.1% (0.8%), respectively. For the 40- to 100-mg/L target interval, this percentage was only 76.4% (2.1%) (range, 65%-80%). CONCLUSIONS: Age and serum creatinine level can be used at the bedside to determine the initial doses of ceftazidime. These Monte Carlo simulations highlight the need of a reappraisal of ceftazidime's use in burn patients. Doses between 3 and 16 g/d are proposed, taking into account the pathogens' MICs. However, for sepsis caused by a pathogen with an MIC ≥ 8 mg/L, an insufficient percentage of burn patients will reach the therapeutic target with the recommended dosages.

Noninvasive assessment of hemodynamic response to a fluid challenge using femoral Doppler in critically ill ventilated patients.

PURPOSE: The purpose of the study is to determine if femoral artery blood flow Doppler parameters can assess cardiac response to a fluid challenge (FC). MATERIALS AND METHODS: We prospectively recorded in 52 critically ill ventilated patients' velocity time integral variation (%VTIf) and maximal systolic velocity variation (%Vfmax) derived from femoral Doppler analysis and aortic velocity time integral variation registered on transthoracic echocardiography before and after an FC of 500-mL saline. RESULTS: According to Pearson coefficient, %Vfmax and %VTIf were found to be positively correlated with aortic velocity time integral variation (r(2) = 0.46 and 0.51, respectively; P < .0001) and were significantly different between responder patients and nonresponders (11% ± 3.4% vs 5.9% ± 4.3% and 14.9% ± 4.2% vs 5.5% ± 5.5%, respectively; P < .0001). Increase of %VTIf 10% or higher and %Vfmax 7% or higher after an FC showed a sensitivity of 80% and 84%, a specificity of 85% and 73%, and an area under the curve of 0.905 and 0.851, respectively, for discriminating responder and nonresponder patients. CONCLUSION: Variation of femoral Doppler parameters before and after FC mirrors cardiac response to fluid loading. This tool could be considered as an alternative to transthoracic echocardiography in case of poor thoracic insonation.

Ceftazidime dosage regimen in intensive care unit patients: from a population pharmacokinetic approach to clinical practice via Monte Carlo simulations.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The large variability in drug pharmacokinetic disposition has already been described in ICU patients leading to important variations in drugs concentrations. The usual recommended dosage of ceftazidime is not adapted for all ICU situations and ceftazidime should be monitored closely. New recommendations have to be given for some specific cases. WHAT THIS STUDY ADDS: Our results propose individual therapeutic drug monitoring taking into account: For the patient: the reason of admission in the ICU, the mechanical ventilation status and the creatinine clearance calculated by the modified diet in renal disease (MDRD). • For the antibiotics: the lung distribution, the minimal inhibitory concentration (MIC) of the strain to eradicate and the potential toxicity. AIM To predict the ceftazidime dosage regimen as a function of the glomerular filtration rate expressed by the modification of the diet in renal disease (MDRD), reason for admission and mechanical ventilation in intensive care unit (ICU) patients to treat Pseudomonas aeruginosa pneumonia. METHOD: A published and qualified population pharmacokinetic model was used to perform Monte Carlo simulations of ceftazidime concentrations. The serum target of 40-100 mg l(-1) was defined based on the minimal inhibitory concentration (MIC), the European break point (EBP), the pulmonary drug diffusion and toxicity. The recommended dosage regimens were based on the maximum percentile of the patients with simulated steady state concentrations reaching the target. RESULTS: Steady-state was reached at 72 h whatever the MDRD. The simulations of serum concentrations generated higher percentiles of the population reaching the target after continuous administration. We recommend a 4 g continuous dose after the usual 2 g loading dose for patients with MDRD from 10 to 30 ml min(-1) , 6 g for MDRD between 40 and 80 ml min(-1) , 8 g for MDRD from 90 to 110 ml min(-1) , 10 g for MDRD from 120 to 190 ml min(-1) and 12 g day(-1) for patients with MDRD higher than 200 ml min(-1) . CONCLUSION: Our study demonstrated that in ICU patients for a given MDRD, steady-state takes longer to reach in polytrauma patients than in patients with medical or post surgery reasons for admission. Continuous infusion ensures that a higher percentage of patients reaches the target than the same dose given by discontinuous administration and this only depends on MDRD.

Optimizing ciprofloxacin dosing in intensive care unit patients through the use of population pharmacokinetic-pharmacodynamic analysis and Monte Carlo simulations.

OBJECTIVES: To explore different ciprofloxacin dosage regimens for the treatment of intensive care unit (ICU) patients with respect to clinical outcome and the development of bacterial resistance for the major Gram-negative pathogens. METHODS: A population pharmacokinetic model was first developed on ciprofloxacin serum concentrations obtained in 102 ICU patients. Then, based on this model, pharmacokinetic-pharmacodynamic Monte Carlo simulations (MCSs) were carried out to explore the appropriateness of different ciprofloxacin dosage regimens in ICU patients. The defined targets were free AUC(24)/MIC ≥90 h (as a predictor of clinical outcome) and T(MSW) ≤20% (as a predictor of selecting resistance), where T(MSW) is the time spent within the mutant selection window over 24 h. Two simulation trials were conducted: Trial 1 took into account the whole MIC distribution for each causative pathogen in line with empirical antibiotherapy; Trial 2 used MIC breakpoints given by the Antibiogram Committee of the French Microbiology Society in order to treat the 'worst-case' scenario. RESULTS: Trial 1 showed that for Pseudomonas aeruginosa and Acinetobacter baumannii, the common dosage regimens of 400 mg twice or three times a day did not achieve the desired target attainment rates (TARs) with respect to T(MSW), while suboptimal TARs were found for AUC(24)/MIC. Trial 2 showed that ≤ 18% of patients reached the target of T(MSW) ≤ 20% for MIC breakpoints of 0.5 and 1 mg/L, regardless of the administered dose. CONCLUSIONS: Based on the mutant selection window concept, our simulations truly question the use of ciprofloxacin for the treatment of P. aeruginosa and A. baumannii infections in ICU patients due to the potential for developing resistance.