The IMPACT Score: A New Score to Predict the Risk of Early Mortality in Cardiogenic Shock Patients Treated With Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) requires considerable human and financial resources. Few studies have focused on early mortality (ie, occurring within 72 hours after VA-ECMO implantation). The objective of this study was to establish a prognosis score-the IMPACT score (prediction of early mortality associated with VA-ECMO using preimplantation characteristics)-by determining the risk factors associated with early mortality. DESIGN: This was a retrospective and observational study. SETTING: The study was conducted at a University hospital. PARTICIPANTS: This single-center retrospective study included 147 patients treated with VA-ECMO for cardiogenic shock between 2014 and 2021. METHODS: The primary outcome was early mortality (ie, occurring within 72 hours after VA-ECMO implantation). Multivariate logistic regression was performed using a bootstrapping methodology to identify factors independently associated with early mortality. To construct the score, identified variables had points (pts) assigned corresponding to their odds ratio. RESULTS: A total of 147 patients were included in the study. Early mortality (<72 hours) was 26% (38 patients). Four variables were established: cardiac arrest (2 pts), lactate levels (3 pts), platelet count <100 g/L (4 pts), and renal-replacement therapy (5 pts). The IMPACT score had an area under the receiver operating characteristic curve of 0.78 (95% CI 0.86-0.70) to predict early mortality. CONCLUSIONS: In the authors' experience, 26% of patients treated with VA-ECMO presented early mortality. The IMPACT score is a reliable predictor of early mortality and may assist with VA-ECMO initiation decision-making.

Effect of Body Mass Index on the Clinical Outcomes of Adult Patients Treated With Venoarterial ECMO for Cardiogenic Shock.

OBJECTIVE: Current guidelines consider obesity to be a relative contraindication to venoarterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. The authors investigated the effect of body mass index (BMI) on clinical outcomes in patients treated with VA-ECMO for cardiogenic shock. DESIGN: This was a retrospective and observational study. SETTING: University hospital. PARTICIPANTS: The study comprised 150 adult patients who underwent VA-ECMO for cardiogenic shock. MEASUREMENTS AND MAIN RESULTS: The primary outcome was intensive care unit (ICU) mortality. Of the 150 included patients, 10 were underweight (BMI < 18.5 kg/m²), 62 were normal weight (BMI = 18.5-24.9 kg/m²), 34 were overweight (BMI = 25.0-29.9 kg/m²), 34 were obese class I (BMI = 30.0-34.9 kg/m²), and 10 were obese class II (BMI = 35.0-39.9 kg/m²). All-cause ICU mortality was 62% (underweight, 70%; normal weight, 53%; overweight, 65%; class I obese, 71%; class II obese, 70%). After multivariate logistic regression, BMI was not associated with ICU mortality (adjusted odds ratio [aOR] 0.99 [0.92-1.07], p = 0.8). Analysis by BMI category showed unfavorable mortality trends in underweight patients (aOR 3.58 [0.82-19.6], p = 0.11) and class I obese patients (aOR 2.39 [0.95-6.38], p = 0.07). No statistically significant differences were found among BMI categories in the incidences of complications. CONCLUSION: The results suggested that BMI alone should not be considered an exclusion criterion for VA-ECMO. The unfavorable trend observed in underweight patients could be the result of malnutrition.

Predictive risk factors for postoperative pneumonia after heart transplantation.

BACKGROUND: Pneumonia is a frequent complication in patients undergoing heart transplantation (HTx) that increases morbidity and mortality in this population. Nevertheless, the risk factors for postoperative pneumonia (POP) are still unknown. The aim of this study was to investigate the predictive risk factors for POP in HTx recipients. METHODS: In this retrospective study, all patients undergoing HTx between January 2014 and December 2015 were included. All cases of POP occurring until hospital discharge were investigated. The study aimed to determine risk factors using univariate and multivariate Cox regression models. Data are expressed in Odds Ratio [95% CI]. P < 0.05 was necessary to reject the null hypothesis. RESULTS: A total of 175 patients were included without any patients being lost to follow-up, and 89 instances of POP were diagnosed in 59 (34%) patients. Enterobacteriaceae and Pseudomonas aeruginosa were the most common pathogens. In the multivariate analysis, the risk factors were preoperative mechanical ventilation (OR 1.42 [1.12-1.80], P < 0.01) and perioperative blood transfusion (OR 1.42 [95% CI: 1.20-1.70], P < 0.01). POP significantly impacted mortality at 30 days (OR: 4 [1.3-12.4], P = 0.01) and 1 year (OR: 6.8 [2.5-8.4], P < 0.01) and was associated with a longer duration of mechanical ventilation, time to weaning from venoarterial extracorporeal membrane oxygenation and stay in an intensive care unit. Plasma exchanges and intravenous administration of immunoglobulins did not increase the risk of POP. CONCLUSION: After HTx, preoperative mechanical ventilation and blood transfusion were risk factors for POP and were associated with increased mortality. Enterobacteriaceae and Pseudomonas aeruginosa are the most common pathogens of POP.

Fulminant arterial vasculitis as an unusual complication of disseminated staphylococcal disease due to the emerging CC1 methicillin-susceptible Staphylococcus aureus clone: a case report.

BACKGROUND: Staphylococcus aureus has emerged as a leading cause of invasive severe diseases with a high rate of morbidity and mortality worldwide. The wide spectrum of clinical manifestations and outcome observed in staphylococcal illness may be a consequence of both microbial factors and variability of the host immune response. CASE PRESENTATION: A 14-years old child developed limb ischemia with gangrene following S. aureus bloodstream infection. Histopathology revealed medium-sized arterial vasculitis. The causing strain belonged to the emerging clone CC1-MSSA and numerous pathogenesis-related genes were identified. Patient's genotyping revealed functional variants associated with severe infections. A combination of virulence and host factors might explain this unique severe form of staphylococcal disease. CONCLUSION: A combination of virulence and genetic host factors might explain this unique severe form of staphylococcal disease.

Antibody-mediated rejection induced cardiogenic shock: Too late for conventional therapy.

BACKGROUND: Data are scarce on the prognosis of heart allograft antibody-mediated rejection (AMR) with cardiogenic shock (CS). METHODS: We performed a retrospective, single center, observational study. We included patients with biopsy-proven AMR and CS. We aimed to analyze the characteristics, treatment, and prognosis of patients treated for CS due to AMR. Patients alive after AMR were followed to analyze recurrences of AMR, graft function, and cardiac allograft vasculopathy (CAV). RESULTS: Seventeen patients met the inclusion criteria. Patients were mostly males (70%). Median age at diagnosis was 56 years, and median time between heart transplantation and AMR was 21 months. AMR was mostly due to high-level de novo class II DSA. Only 2 patients had past history of biopsy-proven AMR. Despite aggressive immunosuppressive therapies, in-hospital and 1-year mortality were as high as 76% and 82%, respectively. Four patients were discharged from hospital. Two of them were diagnosed with recurrent subclinical AMR: one died suddenly and the other presented rapidly progressive CAV. CONCLUSION: CS due to AMR occurred mostly in patients without history of AMR who developed de novo class II DSA. Despite aggressive conventional immunosuppressive therapies, prognosis after CS due to AMR was poor.

Noninvasive cardiac output measurement using bioreactance in postoperative pediatric patients.

BACKGROUND: Thoracic bioreactance is a noninvasive and continuous method of cardiac output (CO) measurement that is being developed in adult patients. Very little information is available on thoracic bioreactance use in children. OBJECTIVE: The aim of the study was to evaluate the ability of a bioreactance device (NICOM(®) ; Cheetah Medical, Tel Aviv, Israel) to estimate CO and to track changes in CO induced by volume expansion (VE) in children. METHODS: Cardiac output values obtained using the NICOM(®) device (CONICOM ) and measured by trans-thoracic echocardiography (COTTE ) were compared in pediatric neurosurgical patients during the postoperative period. RESULTS: Seventy-three pairs of measurements of CO obtained in 30 children were available for analysis. The bias (lower and upper limits of agreement) between CONICOM and COTTE was -0.11 (-1.4 to 1.2) l·min(-1). The percentage error (PE) was 55%. The precision of the NICOM(®) device was 45%. A significant correlation was observed between the CO values obtained using the two methods (r = 0.89, <0.001). The concordance percentage between changes in COTTE and CON icom induced by VE was 84% following exclusion of patients with changes in CO <15% (n = 5). CONCLUSIONS: The PE observed is too large, and the limits of agreement too wide, to enable us to comment on the equivalence of the two techniques of CO measurements. However, the NICOM(®) device performs well in tracking changes in CO following VE.

Case Report: Severe Community-Acquired Pneumonia in Réunion Island due to Acinetobacter baumannii.

Acinetobacter baumannii (Ab) is a well-known nosocomial pathogen that has emerged as a cause of community-acquired pneumonia (CAP) in tropical regions. Few global epidemiological studies of CAP-Ab have been published to date, and no data are available on this disease in France. We conducted a retrospective chart review of severe cases of CAP-Ab admitted to intensive care units in Réunion University Hospital between October 2014 and October 2022. Eight severe CAP-Ab cases were reviewed. Median patient age was 56.5 years. Sex ratio (male-to-female) was 3:1. Six cases (75.0%) occurred during the rainy season. Chronic alcohol use and smoking were found in 75.0% and 87.5% of cases, respectively. All patients presented in septic shock and with severe acute respiratory distress syndrome. Seven patients (87.5%) presented in cardiogenic shock, and renal replacement therapy was required for six patients (75.0%). Five cases (62.5%) presented with bacteremic pneumonia. The mortality rate was 62.5%. The median time from hospital admission to death was 3 days. All patients received inappropriate initial antibiotic therapy. Acinetobacter baumannii isolates were all susceptible to ceftazidime, cefepime, piperacillin-tazobactam, ciprofloxacin, gentamicin, and imipenem. Six isolates (75%) were also susceptible to ticarcillin, piperacillin, and cotrimoxazole. Severe CAP-Ab has a fulminant course and high mortality. A typical case is a middle-aged man with smoking and chronic alcohol use living in a tropical region and developing severe CAP during the rainy season. This clinical presentation should prompt administration of antibiotic therapy targeting Ab.

Duration of Invasive Mechanical Ventilation before Veno-Venous ExtraCorporeal Membrane Oxygenation for Covid-19 related Acute Respiratory Distress Syndrome: The experience of a tertiary care center.

Background: Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) is an efficient ventilatory support in patients with refractory Covid-19-related Acute Respiratory Distress Syndrome (ARDS), however the duration of invasive mechanical ventilation (IMV) before ECMO initiation as a contraindication is still controversial. The aim of this study was to investigate the impact of prolonged IMV prior to VV-ECMO in patients suffering from refractory Covid-19-related ARDS. Methods: This single-center retrospective study included all patients treated with VV-ECMO for refractory Covid-19-related ARDS between January 1, 2020 and May 31, 2022. The impact of IMV duration was investigated by comparing patients on VV-ECMO during the 7 days (and 10 days) following IMV with those assisted after 7 days (and 10 days). The primary endpoint was in-hospital mortality. Results: Sixty-four patients were hospitalized in the ICU for Covid-19-related refractory ARDS requiring VV-ECMO. Global in-hospital mortality was 55 %. Median duration of IMV was 4 [2; 8] days before VV-ECMO initiation. There was no significant difference in in-hospital mortality between patients assisted with IMV pre-VV-ECMO for a duration of ≤7 days (≤10 days) and those assisted after 7 days (and 10 days) ((p = 0.59 and p = 0.45). Conclusion: This study suggests that patients assisted with VV-ECMO after prolonged IMV had the same prognosis than those assisted earlier in refractory Covid-19-related ARDS. Therefore, prolonged mechanical ventilation of more than 7-10 days should not contraindicate VV-ECMO support. An individual approach is necessary to balance the risks and benefits of ECMO in this population.

Impact of the COVID-19 pandemic on severe non-SARS-CoV-2 community-acquired pneumonia in Reunion Island: a multicenter retrospective observational study, 2016-2021.

The Coronavirus 2019 (COVID-19) pandemic has had a considerable impact on the incidence of severe community-acquired pneumonia (CAP) worldwide. The aim of this study was to assess the early impact of the COVID-19 pandemic in the Reunion Island. This multicenter retrospective observational study was conducted from 2016 to 2021 in the hospitals of Reunion Island. The incidence of severe non-SARS-CoV-2 CAP, microorganisms, characteristics and outcomes of patients hospitalized in intensive care unit were compared between the pre-COVID-19 period (January 1, 2016 to February 29, 2020) and the early COVID-19 period (March 1, 2020 to October 31, 2021). Over the study period, 389 patients developed severe non-SARS-CoV-2 CAP. The incidence of severe non-SARS-CoV-2 CAP significantly decreased between the two periods (9.16 vs. 4.13 cases per 100,000 person-years). The influenza virus was isolated in 43.5% patients with severe non-SARS-CoV-2 CAP in the pre-COVID-19 period and in none of the 60 patients in the early COVID-19 period (P < 0.0001). The only virus that did not decrease was rhinovirus. Streptococcus pneumoniae was the most frequently isolated bacterial microorganism, with no significant difference between the two periods. In Reunion Island, the COVID-19 pandemic led to a significant decrease in the incidence of influenza, which likely explains the observed decrease in the incidence of severe non-SARS-CoV-2 CAP. The pandemic had no impact on the incidence of other viral and bacterial severe non-SARS-CoV-2 CAP. Monitoring influenza incidence is crucial now that COVID-19 control measures have been removed.

Prognosis of patients with acute respiratory failure due to the SARS-CoV-2 501Y.V2 variant: a multicenter retrospective matched cohort study.

The aim of this study was to compare the prognosis of patients with acute respiratory failure (ARF) due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant 501Y.V2 to that of patients with ARF due to the original strain. This retrospective matched cohort study included all consecutive patients who were hospitalized for ARF due to SARS-CoV-2 in Reunion Island University Hospital between March 2020 and March 2021. Twenty-eight in hospital mortality was evaluated before and after matching. A total of 218 patients with ARF due to SARS-CoV-2 were enrolled in the study. Of these, 83 (38.1%) were infected with the 501Y.V2 variant. During intensive care unit stay, 104 (47.7%) patients received invasive mechanical ventilation and 20 (9.2%) patients were supported by venovenous extracorporeal membrane oxygenation. Patients infected with the 501Y.V2 variant were younger (58 [51-68] vs. 67 [56-74] years old, P = 0.003), had less hypertension (54.2% vs 68.1%, P = 0.04), and had less chronic kidney disease (13.3% vs. 31.9%, P = 0.002) than patients infected with the original strain. After controlling for confounding variables (62 matched patients in each group), 28-day mortality was higher in the group of patients infected with the 501Y.V2 variant (30.6%) than in the group of patients infected with the original strain (19.4%, P = 0.04). In Reunion Island, where SARS-CoV-2 incidence remained low until February 2021 and the health care system was never saturated, mortality was higher in patients with ARF infected with the 501Y.V2 variant than in patients infected with the original strain.

Severe community-acquired pneumonia in Reunion Island: Epidemiological, clinical, and microbiological characteristics, 2016-2018.

PURPOSE: No data are available on severe community-acquired pneumonia (CAP) in the French overseas department of Reunion Island. This is unfortunate as the microorganisms responsible for the disease are likely to differ from those in temperate regions due to a tropical climate and proximity to other islands of the Indian Ocean region. The aim of this study was to assess the epidemiological, clinical, prognosis, and microbiological characteristics of patients with severe CAP in Reunion Island. MATERIALS AND METHODS: This retrospective study evaluated all patients with CAP aged >18 years and hospitalized in one of the two intensive care units of Reunion Island between 2016 and 2018. Microorganisms were identified by culture from blood and respiratory samples, multiplex polymerase chain reaction from respiratory samples, urinary antigen tests, and serology. RESULTS: Over the study period, 573 cases of severe CAP were recorded, with a mean incidence of 22 per 100,000 person-years. The most frequently isolated microorganism was influenza (21.9%) followed by Streptococcus pneumoniae (12%). The influenza virus was detected in affected patients all year round. Twenty-four patients with severe CAP came from another island of the Indian Ocean region (4.2%), mainly Madagascar (>50%). Two of these patients presented with melioidosis and 4 were infected with Acinetobacter spp. CONCLUSIONS: Our findings have major implications for the management of severe CAP in tropical regions. The most frequently isolated microorganism in patients with severe CAP in Reunion Island is influenza followed by S. pneumoniae. Physicians should be aware that influenza is the main cause of severe CAP in patients living in or returning from Reunion Island, where this virus circulates all year round.

Modeling small remotely piloted aircraft system to head impact for investigating craniocerebral response.

Understanding small remotely piloted aircraft system (sRPAS) to human head impacts is needed to better protect human head during sRPAS ground collision accidents. Recent literature reported cadaveric data on sRPAS to human head impacts, which provided a unique opportunity for developing validated computational models. However, there lacks an understanding of skull stress and brain strain during these impacts. Meanwhile, how slight changes in sRPAS impact setting could affect human head responses remains unknown. Hence, a representative quadcopter style sRPAS finite element (FE) model was developed and applied to a human body model to simulate a total of 45 impacts. Among these 45 simulations, 17 were defined according to cadaveric setting for model validation and the others were conducted to understand the sensitivity of impact angle, impact location, and impacted sRPAS components. Results demonstrated that FE-model-predicted head linear acceleration and rotational velocity agreed with cadaveric data with average predicted linear acceleration 4.5% lower than experimental measurement and average predicted of rotational velocity 2% lower than experimental data. Among validated simulations, high skull stresses and moderate level of brain strains were observed. Also, sensitivity study demonstrated significant effect of impact angle and impact location with 3° variation inducing 30% changes in linear acceleration and 29% changes in rotational velocity. Arm-first impact was found to generate more than two times higher skull stresses and brain strains compared to regular body-shell-first impact.

Case Report: Transmission of Dengue Virus from a Deceased Donor to a Kidney Transplant Recipient Previously Infected by Dengue Virus.

Since 2018, a dengue epidemic has been ongoing in the French overseas department of Reunion Island, in the Indian Ocean, with more than 25,000 serologically confirmed cases. Currently, three dengue serotypes have been identified in Réunion Island (DENV-1, DENV-2, and DENV-3) progressing in the form of epidemic outbreaks. This arbovirus is mainly transmitted by mosquitoes of the genus Aedes and may be responsible for serious clinical forms. To date, very few cases of kidney transplant-related dengue virus infection have been described. Here we report the first case of severe dengue virus infection related to kidney transplantation from a patient previously infected with dengue. Testing for dengue fever with PCR search in donor's urine may help complete the pretransplant assessment in areas where this disease occurs.

Case Report: Refractory Acute Respiratory Distress Syndrome Supported by Extracorporeal Membrane Oxygenation due to Coinfection with Chlamydia pneumoniae and Leptospirosis in Reunion Island.

Infection with Leptospira spp. is common in Réunion, a tropical island in the Indian Ocean. However, respiratory coinfections between strains of Leptospira spp. and other microorganisms are rarely described. Here, we describe the first reported case of coinfection between Leptospira spp. and Chlamydia pneumoniae, responsible for refractory acute respiratory distress syndrome requiring extracorporeal membrane oxygenation with a favorable outcome. In a case of leptospirosis with severe respiratory illness, testing for respiratory coinfection, especially with atypical pathogens, could explain the seriousness of the clinical condition and lead to specific treatment.

Emergency air evacuation of patients with acute respiratory failure due to SARS-CoV-2 from Mayotte to Reunion Island.

ABSTRACT: In February 2021, an explosion of cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia overwhelmed the only hospital in Mayotte. To report a case series of patients with acute respiratory failure (ARF) due to SARS-CoV-2 who were evacuated by air from Mayotte to Reunion Island.This retrospective observational study evaluated all consecutive patients with ARF due to SARS-CoV-2 who were evacuated by air from Mayotte Hospital to the intensive care unit (ICU) of Félix Guyon University Hospital in Reunion Island between February 2, and March 5, 2021.A total of 43 patients with SARS-CoV-2 pneumonia were evacuated by air, for a total flight time of 2 hours and a total travel time of 6 hours. Of these, 38 patients (88.4%) with a median age of 55 (46-65) years presented with ARF and were hospitalized in our ICU. Fifteen patients were screened for the SARS-CoV-2 501Y.V2 variant, all of whom tested positive. Thirteen patients (34.2%) developed an episode of severe hypoxemia during air transport, and the median paO2/FiO2 ratio was lower on ICU admission (140 [102-192] mmHg) than on departure (165 [150-200], P = .022). Factors associated with severe hypoxemia during air transport was lack of treatment with curare (P = .012) and lack of invasive mechanical ventilation (P = .003). Nine patients (23.7%) received veno-venous extracorporeal membrane oxygenation support in our ICU. Seven deaths (18.4%) occurred in hospital.Emergency air evacuation of patients with ARF due to SARS-CoV-2 was associated with severe hypoxemia but remained feasible. In cases of ARF due to SARS-CoV-2 requiring emergency air evacuation, sedated patients receiving invasive mechanical ventilation and curare should be prioritized over nonintubated patients. It is noteworthy that patients with SARS-CoV-2 pneumonia related to the 501Y.V2 variant were very severe despite their young age.

Adversarial attack on deep learning-based dermatoscopic image recognition systems: Risk of misdiagnosis due to undetectable image perturbations.

Deep learning algorithms have shown excellent performances in the field of medical image recognition, and practical applications have been made in several medical domains. Little is known about the feasibility and impact of an undetectable adversarial attacks, which can disrupt an algorithm by modifying a single pixel of the image to be interpreted. The aim of the study was to test the feasibility and impact of an adversarial attack on the accuracy of a deep learning-based dermatoscopic image recognition system.First, the pre-trained convolutional neural network DenseNet-201 was trained to classify images from the training set into 7 categories. Second, an adversarial neural network was trained to generate undetectable perturbations on images from the test set, to classifying all perturbed images as melanocytic nevi. The perturbed images were classified using the model generated in the first step. This study used the HAM-10000 dataset, an open source image database containing 10,015 dermatoscopic images, which was split into a training set and a test set. The accuracy of the generated classification model was evaluated using images from the test set. The accuracy of the model with and without perturbed images was compared. The ability of 2 observers to detect image perturbations was evaluated, and the inter observer agreement was calculated.The overall accuracy of the classification model dropped from 84% (confidence interval (CI) 95%: 82-86) for unperturbed images to 67% (CI 95%: 65-69) for perturbed images (Mc Nemar test, P < .0001). The fooling ratio reached 100% for all categories of skin lesions. Sensitivity and specificity of the combined observers calculated on a random sample of 50 images were 58.3% (CI 95%: 45.9-70.8) and 42.5% (CI 95%: 27.2-57.8), respectively. The kappa agreement coefficient between the 2 observers was negative at -0.22 (CI 95%: -0.49--0.04).Adversarial attacks on medical image databases can distort interpretation by image recognition algorithms, are easy to make and undetectable by humans. It seems essential to improve our understanding of deep learning-based image recognition systems and to upgrade their security before putting them to practical and daily use.

Case Report: Refractory Shock due to Fulminant Dengue Myocarditis Treated with Venoarterial Extracorporeal Membrane Oxygenation: A Report of Four Cases.

Dengue disease is found worldwide and has been spreading exponentially in the past decades. Severe forms affect about 2% of patients, sometimes leading to organ failure. Recent studies have shown that fulminant dengue myocarditis is more common than previously thought, and fatal cases have been reported. The treatment of fulminant dengue myocarditis remains supportive and is very challenging in cases of cardiogenic shock. Here, we describe four cases presenting with fulminant dengue myocarditis treated with extracorporeal membrane oxygenation, among two survived.

PHARMECMO: Therapeutic drug monitoring and adequacy of current dosing regimens of antibiotics in patients on Extracorporeal Life Support.

INTRODUCTION: Optimisation of antibiotic therapy for extracorporeal membrane oxygenation (ECMO) patients remains a pharmacological challenge. The objective of this study was to observe the plasma concentrations of commonly used antibiotics in intensive care for patients treated with extracorporeal membrane oxygenation. PATIENTS AND METHODS: The PHARMECMO study was a pilot, prospective study, conducted in a cardiac surgery intensive care unit. Every adult patient under ECMO support, with known or suspected sepsis and receiving antibiotic therapy, was eligible for inclusion. Plasma concentrations of antibiotics were determined by a combination of liquid chromatography and mass spectrometry. RESULTS: Forty-four eligible patients were enrolled for 68 inclusions on a twelve-month period. For the association piperacillin-tazobactam (n=19), 68.7% of CT50 and 93.7% of Cmin reached the pharmacokinetic goals defined (64 mg.L-1 for CT50 and 16 mg.L-1 for Cmin). For cefotaxime (n=12), the pharmacokinetic goals (4 mg.L-1 for CT50 and 1 mg.L-1 for Cmin) were achieved in 100% of the cases for CT50 and in 81.8% of the cases for Cmin. Regarding imipenem (n=10), the pharmacokinetic goals were 16 mg.L-1 for CT50 and 4 mg.L-1 for Cmin. Only one CT50 was above 16 mg.L-1. For Cmin, 60% of the doses did not reach the target concentration. In our 10 patients, only one patient was considered as reaching the pharmacokinetic goals. Finally, for amikacin (n=6), four Cmax (66.7%) were infra-therapeutics for a target between 60 and 80 mg.L-1. CONCLUSION: These preliminary results suggest that therapeutic drug monitoring could optimise the achievement of pharmacokinetic objectives associated with an effective antibiotic therapy. For most patients, the recommended doses of imipenem and amikacin did not achieve the pK targets.

Ventilator-associated pneumonia in patients assisted by veno-arterial extracorporeal membrane oxygenation support: Epidemiology and risk factors of treatment failure.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is frequent in Intensive Care Unit (ICU) patients. In the specific case of patients treated with Veno-Arterial Extracorporeal Membrane Oxygenation Support (VA-ECMO), VAP treatment failures (VAP-TF) have been incompletely investigated. METHODS: To investigate the risk factors of treatment failure (VAP-TF) in a large cohort of ICU patients treated with VA-ECMO, we conducted a retrospective study in a Surgical ICU about patients assisted with VA-ECMO between January 1, 2013, and December 31, 2014. Diagnosis of VAP was confirmed by a positive quantitative culture of a respiratory sample. VAP-TF was defined as composite of death attributable to pneumonia and relapse within 28 days of the first episode. RESULTS: In total, 152 patients underwent ECMO support for > 48h. During the VA-ECMO support, 85 (55.9%) patients developed a VAP, for a rate of 60.6 per 1000 ECMO days. The main pathogens identified were Pseudomonas aeruginosa and Enterobacteriaceae. VAP-TF occurred in 37.2% of patients and was associated with an increased 28-day mortality (Hazard Ratio 3.05 [1.66; 5.63], P<0.001), and VA-ECMO assistance duration (HR 1.47 [1.05-2.05], P = 0.025). Risk factors for VAP-TF were renal replacement therapy (HR 13.05 [1.73; 98.56], P = 0.013) and documentation of Pseudomonas aeruginosa (HR 2.36 [1.04; 5.35], P = 0.04). CONCLUSIONS: VAP in patients treated with VA-ECMO is associated with an increased morbidity and mortality. RRT and infection by Pseudomonas aeruginosa appear as strong risks factors of treatment failure. Further studies seem necessary to precise the best antibiotic management in these patients.

Effect of severe acidosis on vasoactive effects of epinephrine and norepinephrine in human distal mammary artery.

OBJECTIVE: Acidosis is a very common pathologic process in perioperative management. However, how to correct severe acidosis to improve the efficacy of vasoconstrictors in hemodynamically unstable patients is still debated. The present study investigated whether severe extracellular acidosis influences the vasoactive properties of vasoconstrictors on human isolated arteries. METHODS: Segments of intact distal internal mammary arteries were removed from 41 patients undergoing artery bypass grafting. The arterial rings were washed in Krebs-Henseleit solution and suspended in an organ bath. The rings were set at a pretension equivalent of 100 mm Hg, and the relaxation response to 10 µM acetylcholine was verified. Concentration-response curves for epinephrine, norepinephrine, methoxamine (α1A/D-adrenoceptor agonist), phenylephrine (equipotent agonist of α1A/B-adrenoceptors), and clonidine (α2-adrenoceptor agonist) were achieved under control conditions (pH 7.40) and under acidic conditions by substitution of the Krebs-Henseleit solution with a modified solution. RESULTS: Decreasing the pH from 7.40 to 7.20, 7.0, or 6.80 did not significantly alter the potency and efficacy of epinephrine and norepinephrine, although the standardized effect size was sometimes large. Severe acidosis (pH 6.80) did not significantly change the potency and efficacy of phenylephrine and clonidine, although it increased the efficacy and potency of methoxamine (P < .001 and P = .04 vs paired control conditions, respectively). CONCLUSIONS: Extracellular acidosis did not impair the vasoactive properties of epinephrine and norepinephrine in human medium-size arteries until pH 6.80. The results of the present study also suggest that acidosis might potentiate arterial responsiveness to vasoconstrictors, mostly by way of the α1D-adrenoceptor.