Influence of arterial blood gases on the renal arterial resistive index in intensive care unit.

BACKGROUND: Renal artery Doppler sonography with resistive index (RI) determination is a noninvasive, fast, and reliable diagnostic tool increasingly used in the intensive care unit (ICU) to predict and assess the reversibility of acute kidney injury (AKI). However, interpreting the RI can be challenging due to numerous influencing factors. While some studies have explored various confounding factors, arterial blood gases have received limited attention. Therefore, our study aims to evaluate the impact of arterial blood gases on the RI in the ICU setting. METHODS: This prospective observational study enrolled ICU patients who required blood gas analysis and had not experienced significant hemodynamic changes recently. The RI was measured using standardized Doppler ultrasound within an hour of the arterial blood gases sampling and analysis. RESULTS: A total of sixty-four patients were included in the analysis. Univariate analysis revealed a correlation between the RI and several variables, including PaCO2 (R = 0.270, p = 0.03), age (R = 0.574, p < 0.0001), diastolic arterial pressure (DAP) (R = - 0.368, p = 0.0028), and SaO2 (R = - 0.284, p = 0.0231). Multivariate analysis confirmed that age > 58 years and PaCO2 were significant factors influencing the RI, with respective odds ratios of 18.67 (p = 0.0003) and 1.132 (p = 0.0267). CONCLUSION: The interpretation of renal arterial RI should take into account thresholds for PaCO2, age, and diastolic arterial pressure. Further studies are needed to develop a comprehensive scoring system that incorporates all these cofactors for a reliable analysis of RI levels. Trial registration This observational study, registered under number 70-0914, received approval from local Ethical Committee of Toulouse University Hospital.

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.

A study of patients' quality of life more than 5 years after trauma: a prospective follow-up.

BACKGROUND: The long-term fate of severely injured patients in terms of their quality of life is not well known. Our aim was to assess the quality of life of patients who have suffered moderate to severe trauma and to identify primary factors of long-term quality of life impairment. METHODS: A prospective monocentric study conducted on a number of patients who were victims of moderate to severe injuries during the year 2012. Patients were selected based on an Injury Severity Score (ISS) more than or equal to 9. Quality of life was assessed by the MOS SF-36 and NHP scores as a primary evaluation criterion. The secondary evaluation criteria were the determination of the socio-economic impact on quality of life and the identification of factors associated with disability. RESULTS: Two hundred and eight patients were contacted by e-mail or telephone. Fifty-five patients participated in this study (with a participation level of 26.4%), including 78.2% men, with a median age of 46. Significant alterations in quality of life were observed with the NHP and MOS SF-36 scale, including physical and psychological components. This resulted in a major socio-economic impact as 26% of the patients could not resume their professional activities (n = 10), 20% required retraining in other lines of work, and 36.4% had a disability status. The study showed that scores ≤ 85 on the physical functioning variable of the MOS SF 36 scale was associated with disability. CONCLUSION: More than five years after a moderate to severe injury, patients' quality of life was significantly impacted, resulting in significant socio-economic consequences. Disability secondary to major trauma seems to be associated with a score ≤ 85 on the physical functioning dimension of the MOS SF-36 scale. This study raises the question of whether or not early rehabilitation programs should be implemented in order to limit the long-term impact of major trauma.

Hydroxychloroquine in Coronavirus Disease 2019 Patients: What Still Needs to Be Known About the Kinetics.

Different dosage regimens of hydroxychloroquine are used to manage coronavirus disease 2019 (COVID-19) patients, without information on the pharmacokinetics in this population. Blood samples (n = 101) were collected from 57 COVID-19 patients for 7 days, and concentrations were compared with simulated kinetic profiles. Hydroxychloroquine exposure is low and cannot be predicted by other populations.

Influence of extracorporeal membrane oxygenation on the pharmacokinetics of ceftolozane/tazobactam: an ex vivo and in vivo study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in intensive care units and can modify drug pharmacokinetics and lead to under-exposure associated with treatment failure. Ceftolozane/tazobactam is an antibiotic combination used for complicated infections in critically ill patients. Launched in 2015, sparse data are available on the influence of ECMO on the pharmacokinetics of ceftolozane/tazobactam. The aim of the present study was to determine the influence of ECMO on the pharmacokinetics of ceftolozane-tazobactam. METHODS: An ex vivo model (closed-loop ECMO circuits primed with human whole blood) was used to study adsorption during 8-h inter-dose intervals over a 24-h period (for all three ceftolozane/tazobactam injections) with eight samples per inter-dose interval. Two different dosages of ceftolozane/tazobactam injection were studied and a control (whole blood spiked with ceftolozane/tazobactam in a glass tube) was performed. An in vivo porcine model was developed with a 1-h infusion of ceftolozane-tazobactam and concentration monitoring for 11 h. Pigs undergoing ECMO were compared with a control group. Pharmacokinetic analysis of in vivo data (non-compartmental analysis and non-linear mixed effects modelling) was performed to determine the influence of ECMO. RESULTS: With the ex vivo model, variations in concentration ranged from - 5.73 to 1.26% and from - 12.95 to - 2.89% respectively for ceftolozane (concentrations ranging from 20 to 180 mg/l) and tazobactam (concentrations ranging from 10 to 75 mg/l) after 8 h. In vivo pharmacokinetic exploration showed that ECMO induces a significant decrease of 37% for tazobactam clearance without significant modification in the pharmacokinetics of ceftolozane, probably due to a small cohort size. CONCLUSIONS: Considering that the influence of ECMO on the pharmacokinetics of ceftolozane/tazobactam is not clinically significant, normal ceftolozane and tazobactam dosing in critically ill patients should be effective for patients undergoing ECMO.

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.

Anticoagulation Monitoring Under ECMO Support: A Comparative Study Between the Activated Coagulation Time and the Anti-Xa Activity Assay.

PURPOSE: Extra Corporeal Membrane Oxygenation (ECMO) is used in cases of severe respiratory and/or circulatory failure over periods of several days to several weeks. Its circuitry requires a closely monitored anticoagulation therapy that is empirically supported by activated clotting time (ACT)-a method often associated with large inter- and intraindividual variability. We aimed to compare the measurement of heparin activity with ACT and the direct measurement of the heparin activity (anti-Xa) in a large ECMO population. METHODS: All patients treated by venoarterial or venovenous ECMO in our intensive care unit between January 2014 and December 2015 were prospectively included. A concomitant measurement of the anti-Xa activity and ACT was performed on the same sample collected twice a day (morning-evening) for unfractionated heparin adaptation with an ACT target range of 180 to 220 seconds. RESULTS: One hundred and nine patients (men 69.7%, median age 54 years) treated with ECMO (70.6% venoarterial) were included. Spearman analysis found no correlation between anti-Xa and ACT (ρ < 0.4) from day 1 and worsened over time. Kappa analysis showed no agreement between the respective target ranges of ACT and anti-Xa. CONCLUSIONS: We demonstrate that concomitant measurement of ACT and anti-Xa activity is irrelevant in ECMO patients. Since ACT is poorly correlated with heparin dosage, anti-Xa activity appears to be a more suitable assay for anticoagulation monitoring.

Outcome of community- versus hospital-acquired intra-abdominal infections in intensive care unit: a retrospective study.

BACKGROUND: To compare patients hospitalised in the intensive care unit (ICU) after surgery for community-acquired intra-abdominal infection (CA-IAI) and hospital-acquired intra-abdominal infection (HA-IAI) in terms of mortality, severity and complications. METHODS: Retrospective study including all patients admitted to 2 ICUs within 48 h of undergoing surgery for peritonitis. RESULTS: Two hundred twenty-six patients were enrolled during the study period. Patients with CA-IAI had an increased 28-day mortality rate compared to those with HA-IAI (30% vs 15%, respectively (p = 0.009)). At 90 days, the mortality rates were 36.7 and 37.5% in the CA-IAI group and HA-IAI group, respectively, with a similar APACHE II score on admission (median: 21 [15-25] vs. 21 [15-24] respectively, p = 0.63). The patients with HA-IAI had prolonged ICU and hospital stays (median: 17 [7-36] vs. 6[3-12] days, p < 0.001 and 41 [24-66] vs. 17 [7-32] days, p = 0.001), and experienced more complications (reoperation and reintubation) than those with CA-IAI. CONCLUSION: CA-IAI group had higher 28-day mortality rate than HA-IAI group. Mortality was similar at 90 days but those with HA-IAI had a prolonged ICU and hospital stay. In addition, they developed more complications.

Risk factors for acquisition of carbapenem-resistance during treatment with carbapenem in the intensive care unit: a prospective study.

The emergence of carbapenemases in gram-negative aerobes is worrying. The aim of this prospective study was to estimate the incidence of acquisition of carbapenem-resistance during treatment in ICU and to identify the risk factors. This was a prospective, observational, cohort study. This study was conducted at intensive care unit, academic medical center, Toulouse Rangueil University Hospital. Patients were included if they received antibiotic treatment with carbapenem for more than 48 h. Biological samples were taken in accordance with current practice in the unit. The main endpoint was the occurrence of bacterial resistance to carbapenems occurring between the onset of treatment and the patient's exit from the ICU. Uni- and multi-variate analyses were carried out. Of the 364 patients admitted to the unit between May and November 2014, 78 were included in our study and 16 (20.51%) developed resistance. The two main risk factors were a length of stay in ICU of more than 29 days (HR = 3.61, p = 0.01) and the presence of Pseudomonas aeruginosa in the samples taken before the start of treatment (HR = 5.31, p = 0.002). No resistance due to carbapenemase production was observed in this study. The prescription of carbapenems in the ICU setting must adhere to the expert guidelines. In light of our results, special attention must be paid to patients whose stay in intensive care is prolonged, and those in whom Pseudomonas aeruginosa is isolated from bacteriological samples taken before the beginning of antibiotic therapy.

Neurally adjusted ventilatory assist (NAVA) versus pressure support ventilation: patient-ventilator interaction during invasive ventilation delivered by tracheostomy.

BACKGROUND: Prolonged weaning is a major issue in intensive care patients and tracheostomy is one of the last resort options. Optimized patient-ventilator interaction is essential to weaning. The purpose of this study was to compare patient-ventilator synchrony between pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA) in a selected population of tracheostomised patients. METHODS: We performed a prospective, sequential, non-randomized and single-centre study. Two recording periods of 60 min of airway pressure, flow, and electrical activity of the diaphragm during PSV and NAVA were recorded in a random assignment and eight periods of 1 min were analysed for each mode. We searched for macro-asynchronies (ineffective, double, and auto-triggering) and micro-asynchronies (inspiratory trigger delay, premature, and late cycling). The number and type of asynchrony events per minute and asynchrony index (AI) were determined. The two respiratory phases were compared using the non-parametric Wilcoxon test after testing the equality of the two variances (F-Test). RESULTS: Among the 61 patients analysed, the total AI was lower in NAVA than in PSV mode: 2.1% vs 14% (p < 0.0001). This was mainly due to a decrease in the micro-asynchronies index: 0.35% vs 9.8% (p < 0.0001). The occurrence of macro-asynchronies was similar in both ventilator modes except for double triggering, which increased in NAVA. The tidal volume (ml/kg) was lower in NAVA than in PSV (5.8 vs 6.2, p < 0.001), and the respiratory rate was higher in NAVA than in PSV (28 vs 26, p < 0.05). CONCLUSION: NAVA appears to be a promising ventilator mode in tracheotomised patients, especially for those requiring prolonged weaning due to the decrease in asynchronies.

Cost Effectiveness of Candida Polymerase Chain Reaction Detection and Empirical Antifungal Treatment among Patients with Suspected Fungal Peritonitis in the Intensive Care Unit.

BACKGROUND: Mortality from intra-abdominal candidiasis in intensive care units (ICUs) is high. It takes many days for peritoneal-fluid fungal culture to become positive, and the recommended empirical antifungal therapy involves excessive costs. Polymerase chain reaction (PCR) should produce results more rapidly than fungal culture. OBJECTIVES: To perform a cost-effectiveness analysis of the combination of several diagnostic and therapeutic strategies to manage Candida peritonitis in non-neutropenic adult patients in ICUs. METHODS: We constructed a decision tree model to evaluate the cost effectiveness. Cost and effectiveness were taken into account in a 1-year time horizon and from the French National Health Insurance perspective. Six strategies were compared: fluconazole or echinocandin as an empirical therapy, plus diagnosis by fungal culture or detection by PCR of all Candida species, or use of PCR to detect most fluconazole-resistant Candida species (i.e., Candida krusei and Candida glabrata). RESULTS: The use of fluconazole empirical treatment and PCR to detect all Candida species is more cost effective than using fluconazole empirical treatment without PCR (incremental cost-effectiveness ratio of €40,055/quality-adjusted life-year). Empirical treatment with echinocandin plus PCR to detect C. krusei and C. glabrata is the most effective strategy, but has an incremental cost-effectiveness ratio of €93,776/quality-adjusted life-year. If the cost of echinocandin decreases, then strategies involving PCR plus empirical echinocandin become more cost-effective. CONCLUSIONS: Detection by PCR of all Candida species and of most fluconazole-resistant Candida species could improve the cost-effectiveness of fluconazole and echinocandin given to non-neutropenic patients with suspected peritoneal candidiasis in ICUs.

A whole-body physiologically based pharmacokinetic (WB-PBPK) model of ciprofloxacin: a step towards predicting bacterial killing at sites of infection.

The purpose of this study was to develop a whole-body physiologically based pharmacokinetic (WB-PBPK) model for ciprofloxacin for ICU patients, based on only plasma concentration data. In a next step, tissue and organ concentration time profiles in patients were predicted using the developed model. The WB-PBPK model was built using a non-linear mixed effects approach based on data from 102 adult intensive care unit patients. Tissue to plasma distribution coefficients (Kp) were available from the literature and used as informative priors. The developed WB-PBPK model successfully characterized both the typical trends and variability of the available ciprofloxacin plasma concentration data. The WB-PBPK model was thereafter combined with a pharmacokinetic-pharmacodynamic (PKPD) model, developed based on in vitro time-kill data of ciprofloxacin and Escherichia coli to illustrate the potential of this type of approach to predict the time-course of bacterial killing at different sites of infection. The predicted unbound concentration-time profile in extracellular tissue was driving the bacterial killing in the PKPD model and the rate and extent of take-over of mutant bacteria in different tissues were explored. The bacterial killing was predicted to be most efficient in lung and kidney, which correspond well to ciprofloxacin's indications pneumonia and urinary tract infections. Furthermore, a function based on available information on bacterial killing by the immune system in vivo was incorporated. This work demonstrates the development and application of a WB-PBPK-PD model to compare killing of bacteria with different antibiotic susceptibility, of value for drug development and the optimal use of antibiotics .

Early Prediction of 3-month Survival of Patients in Refractory Cardiogenic Shock and Cardiac Arrest on Extracorporeal Life Support.

BACKGROUND: Extracorporeal life support (ECLS) holds the promise of significant improvement of the survival of patient in refractory cardiogenic shock (CS) or cardiac arrest (CA). Nevertheless, it remains to be shown to which extent these highly invasive supportive techniques could improve long-term patient's outcome. METHODS: The outcomes of 82 adult ECLS patients at our institution between January 2012 and December 2013 were retrospectively analyzed. RESULTS: Patients were essentially men (64.7%) and are 54 years old. Preexisting ischemic (53.7%) and dilated cardiomyopathy (14.6%) were frequent. ECLS indications were shared equally between CA and CS. ECLS-specific adverse effects as hemorrhage (30%) and infection (50%) were frequent. ECLS was effective for 43 patients (54%) with recovery for 35 (43%), 5 (6%) heart transplant, and 3 (4%) left ventricular assist device support. Mortality rate at 30 days was 59.8%, but long-term and 3-month survival rates were similar of 31.7%. Initial plasma lactate levels >5.3 mmol/L and glomerular filtration rate <43 ml/min/1.73 m2 were significantly associated with 3-month mortality (risk ratio [RR] 2.58 [1.21-5.48]; P = 0.014; RR 2.10 [1.1-4]; P = 0.024, respectively). Long-term follow-up had shown patients paucisymptomatic (64% New York Heart Association 1-2) and autonomic (activities of daily living [ADL] score 6 ± 1.5). CONCLUSION: In case of refractory CA or CS, lactates and renal function at ECLS initiation could serve as outcome predictor for risk stratification and ECLS indication.

Patient-ventilator synchrony in Neurally Adjusted Ventilatory Assist (NAVA) and Pressure Support Ventilation (PSV): a prospective observational study.

BACKGROUND: Weaning from mechanical ventilation is associated with the presence of asynchronies between the patient and the ventilator. The main objective of the present study was to demonstrate a decrease in the total number of patient-ventilator asynchronies in invasively ventilated patients for whom difficulty in weaning is expected by comparing neurally adjusted ventilatory assist (NAVA) and pressure support ventilation (PSV) ventilatory modes. METHODS: We performed a prospective, non-randomized, non-interventional, single-center study. Thirty patients were included in the study. Each patient included in the study benefited in an unpredictable way from both modes of ventilation, NAVA or PSV. Patients were successively ventilated for 23 h in NAVA or in PSV, and then they were ventilated for another 23 h in the other mode. Demographic, biological and ventilatory data were collected during this period. The two modes of ventilatory support were compared using the non-parametric Wilcoxon test after checking for normal distribution by the Kolmogorov-Smirnov test. The groups were compared using the chi-square test. RESULTS: The median level of support was 12.5 cmH2O (4-20 cmH2O) in PSV and 0.8 cmH2O/µvolts (0.2-3 cmH2O/µvolts) in NAVA. The total number of asynchronies per minute in NAVA was lower than that in PSV (0.46 vs 1, p < 0.001). The asynchrony index was also reduced in NAVA compared with PSV (1.73 vs 3.36, p < 0.001). In NAVA, the percentage of ineffective efforts (0.77 vs 0.94, p = 0.036) and the percentage of auto-triggering were lower compared with PSV (0.19 vs 0.71, p = 0.038). However, there was a higher percentage of double triggering in NAVA compared with PSV (0.76 vs 0.71, p = 0.046). CONCLUSION: The total number of asynchronies in NAVA is lower than that in PSV. This finding reflects improved patient-ventilator interaction in NAVA compared with the PSV mode, which is consistent with previous studies. Our study is the first to analyze patient-ventilator asynchronies in NAVA and PSV on such an important duration. The decrease in the number of asynchronies in NAVA is due to reduced ineffective efforts and auto-triggering.

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.

Co-Infection and Ventilator-Associated Pneumonia in Critically Ill COVID-19 Patients Requiring Mechanical Ventilation: A Retrospective Cohort Study.

Considering virus-related and drug-induced immunocompromised status of critically ill COVID-19 patients, we hypothesize that these patients would more frequently develop ventilator-associated pneumonia (VAP) than patients with ARDS from other viral causes. We conducted a retrospective observational study in two intensive care units (ICUs) from France, between 2017 and 2020. We compared bacterial co-infection at ICU admission and throughout the disease course of two retrospective longitudinally sampled groups of critically ill patients, who were admitted to ICU for either H1N1 or SARS-CoV-2 respiratory infection and depicted moderate-to-severe ARDS criteria upon admission. Sixty patients in the H1N1 group and 65 in the COVID-19 group were included in the study. Bacterial co-infection at the endotracheal intubation time was diagnosed in 33% of H1N1 and 16% COVID-19 patients (p = 0.08). The VAP incidence per 100 days of mechanical ventilation was 3.4 (2.2−5.2) in the H1N1 group and 7.2 (5.3−9.6) in the COVID-19 group (p < 0.004). The HR to develop VAP was of 2.33 (1.34−4.04) higher in the COVID-19 group (p = 0.002). Ten percent of H1N1 patients and 30% of the COVID-19 patients had a second episode of VAP (p = 0.013). COVID-19 patients have fewer bacterial co-infections upon admission, but the incidence of secondary infections increased faster in this group compared to H1N1 patients.

Mass Training In Situ During COVID-19 Pandemic: Enhancing Efficiency and Minimizing Sick Leaves.

INTRODUCTION: Avoiding coronavirus disease 2019 (COVID-19) work-related infection in frontline healthcare workers is a major challenge. A massive training program was launched in our university hospital for anesthesia/intensive care unit and operating room staff, aiming at upskilling 2249 healthcare workers for COVID-19 patients' management. We hypothesized that such a massive training was feasible in a 2-week time frame and efficient in avoiding sick leaves. METHODS: We performed a retrospective observational study. Training focused on personal protective equipment donning/doffing and airway management in a COVID-19 simulated patient. The educational models used were in situ procedural and immersive simulation, peer-teaching, and rapid cycle deliberate practice. Self-learning organization principles were used for trainers' management. Ordinary disease quantity in full-time equivalent in March and April 2020 were compared with the same period in 2017, 2018, and 2019. RESULTS: A total of 1668 healthcare workers were trained (74.2% of the target population) in 99 training sessions over 11 days. The median number of learners per session was 16 (interquartile range = 9-25). In the first 5 days, the median number of people trained per weekday was 311 (interquartile range = 124-385). Sick leaves did not increase in March to April 2020 compared with the same period in the 3 preceding years. CONCLUSIONS: Massive training for COVID-19 patient management in frontline healthcare workers is feasible in a very short time and efficient in limiting the rate of sick leave. This experience could be used in the anticipation of new COVID-19 waves or for rapidly preparing hospital staff for an unexpected major health crisis.

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.

Tobramycin disposition in ICU patients receiving a once daily regimen: population approach and dosage simulations.

UNLABELLED: WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT? It is well known that tobramycin given as an once daily dose according to the usual recommendations needs therapeutic drug monitoring by measurement of peak and trough concentrations. In the literature, there are only few published studies on the population pharmacokinetics of once daily tobramycin in critically ill patients. Glomerular filtration rate and bodyweight were identified as covariates contributing to the inter-individual variability in the disposition of aminoglycosides. The study, by Peris-Marti et al. [24], only evaluated the pharmacodynamic effectiveness of a 4 mg kg(-1) dose of tobramycin given once daily in critically ill patients. The authors concluded with a simulation showing that for a theoretical MIC of 1 or 2 mg l(-1) , a 7 mg kg(-1) dose was required. WHAT THIS STUDY ADDS: Our results confirm the high variability of tobramycin disposition in intensive care patients and consequently the possible lack of effectiveness. By using a population pharmacokinetic approach, two explicative covariates (height and Cockcroft creatinine clearance) added to a two-compartment model with proportional error, explained much of the inter-individual variability of tobramycin disposition in the critically ill patient population. In a median ICU patient, simulations were performed at various dosage regimens and peak and AUC pharmacodynamic targets could not be reached simultaneously in more than 45% of the ICU patient population. Drug monitoring is required to manage efficacy and toxicity. AIM: The aim of this study was to evaluate the disposition of tobramycin (TOB) in critically ill patients (ICU) by a population pharmacokinetic approach, to determine the covariates involved, and to simulate tobramycin dosage regimens. METHODS: Forty-nine adult ICU patients received TOB (5 mg kg(-1) ) once daily. NonMem modelling was performed on 32 patients. The 17 other patients were used for the qualification process by normalized prediction distribution error. Then Monte Carlo simulations (MCS) were performed. RESULTS: A two-compartment model with a proportional error best fitted the data. TOB total clearance (CL(TOB) ) was significantly correlated with Cockcroft creatinine clearance (COCK) and height. TOB clearance was 4.8 ± 1.9 l h(-1) (range 1.22-8.95), the volume of distribution of the central compartment was 24.7 ± 3.7 l (range 17.34-32.83) and that of the peripheral compartment and the inter-compartmental clearance were 30.6 l and 4.74 l h(-1) , respectively. Only 29% of the patients presented a target AUC between 80 and 125 mg l(-1) h and 61% were lower than 80 mg l(-1) h. After considering COCK and height, MCS showed that only 50% of the population could achieve the target AUC for the 375 and 400 mg dosages. CONCLUSION: Even after taking into account COCK and height, for strains with an MIC ≤ 1 mg l(-1) , MCS doses evidenced that peak and AUC pharmacodynamic targets could not be reached simultaneously in more than 45% of the ICU patient population. Combination therapy in addition to drug monitoring are required to manage efficacy and toxicity.

Increased creatinine clearance in polytrauma patients with normal serum creatinine: a retrospective observational study.

INTRODUCTION: The aim of this study, performed in an intensive care unit (ICU) population with a normal serum creatinine, was to estimate urinary creatinine clearance (CLCR) in a population of polytrauma patients (PT) through a comparison with a population of non trauma patients (NPT). METHODS: This was a retrospective, observational study in a medical and surgical ICU in a university hospital. A total of 284 patients were consecutively included. Two different groups were studied: PT (n = 144) and NPT (n = 140). Within the second week after admission to the ICU, renal function was assessed using serum creatinine, 24 h urinary CLCR . RESULTS: Among the 106 patients with a CLCR above 120 mL minute(-1) 1.73 m(-2), 79 were PT and 27 NPT (P < 0.0001). Only 63 patients had a CLCR below 60 mL minute(-1) 1.73 m(-2) with 15 PT and 48 NPT (P < 0.0001). Patients with CLCR greater than 120 mL minute(-1). 1.73 m(-2) were younger, had a lower SAPS II score and a higher male ratio as compared to those having CLCR lower than 120 mL minute(-1). 1.73 m(-2). Through a logistic regression analysis, age and trauma were the only factors independently correlated to CLCR. CONCLUSIONS: In ICU patients with normal serum creatinine, CLCR, is higher in PT than in NPT. The measure of CLCR should be proposed as routine for PT patients in order to adjust dose regimen, especially for drugs with renal elimination.