Augmented renal clearance in the ICU: estimation, incidence, risk factors and consequences-a retrospective observational study.

BACKGROUND: Augmented renal clearance (ARC) remains poorly evaluated in ICU. The objective of this study is to provide a full description of ARC in ICU including prevalence, evolution profile, risk factors and outcomes. METHODS: This was a retrospective, single-center, observational study. All the patients older than 18 years admitted for the first time in Medical ICU, Bichat, University Hospital, APHP, France, between January 1, 2017, and November 31, 2020 and included into the Outcomerea database with an ICU length of stay longer than 72 h were included. Patients with chronic kidney disease were excluded. Glomerular filtration rate was estimated each day during ICU stay using the measured creatinine renal clearance (CrCl). Augmented renal clearance (ARC) was defined as a 24 h CrCl greater than 130 ml/min/m2. RESULTS: 312 patients were included, with a median age of 62.7 years [51.4; 71.8], 106(31.9%) had chronic cardiovascular disease. The main reason for admission was acute respiratory failure (184(59%)) and 196(62.8%) patients had SARS-COV2. The median value for SAPS II score was 32[24; 42.5]; 146(44%) and 154(46.4%) patients were under vasopressors and invasive mechanical ventilation, respectively. The overall prevalence of ARC was 24.6% with a peak prevalence on Day 5 of ICU stay. The risk factors for the occurrence of ARC were young age and absence of cardiovascular comorbidities. The persistence of ARC during more than 10% of the time spent in ICU was significantly associated with a lower risk of death at Day 30. CONCLUSION: ARC is a frequent phenomenon in the ICU with an increased incidence during the first week of ICU stay. Further studies are needed to assess its impact on patient prognosis.

Neurologic Outcomes of Survivors of COVID-19-Associated Acute Respiratory Distress Syndrome Requiring Intubation.

OBJECTIVES: To describe 3-6-month neurologic outcomes of survivors of COVID-19-associated acute respiratory distress syndrome, invasively ventilated in the ICU. DESIGN: A bicentric prospective study during the two first waves of the pandemic (March to May and September to December, 2020). SETTING: Two academic hospital ICUs, Paris, France. PATIENTS: Adult COVID-19-associated acute respiratory distress syndrome survivors, invasively ventilated in the ICU, were eligible for a neurologic consultation between 3 and 6 months post ICU discharge. INTERVENTIONS: Follow-up by face-to-face neurologic consultation. MEASURES AND MAIN RESULTS: The primary endpoint was favorable functional outcome defined by a modified Rankin scale score less than 2, indicating survival with no significant disability. Secondary endpoints included mild cognitive impairment (Montreal Cognitive Assessment score < 26), ICU-acquired weakness (Medical Research Council score < 48), anxiety and depression (Hospital Anxiety and Depression score > 7), and posttraumatic stress disorder (posttraumatic stress disorder checklist for Diagnostic and Statistical Manual of Mental Disorders 5 score > 30). Of 54 eligible survivors, four non-French-speaking patients were excluded, eight patients were lost-to-follow-up, and one died during follow-up. Forty-one patients were included. Time between ICU discharge and neurologic consultation was 3.8 months (3.6-5.9 mo). A favorable functional outcome was observed in 16 patients (39%) and mild cognitive impairment in 17 of 33 patients tested (52%). ICU-acquired weakness, depression or anxiety, and posttraumatic stress disorder were reported in six of 37 cases (16%), eight of 31 cases (26%), and two of 27 cases (7%), respectively. Twenty-nine patients (74%) required rehabilitation (motor, cognitive, or psychologic). ICU and hospital lengths of stay, tracheostomy, and corticosteroids were negatively associated with favorable outcome. By contrast, use of alpha-2 agonists during ICU stay was associated with favorable outcome. CONCLUSIONS: COVID-19-associated acute respiratory distress syndrome requiring intubation led to slight-to-severe functional disability in about 60% of survivors 4 months after ICU discharge. Cognitive impairment, muscle weakness, and psychologic symptoms were frequent. A large multicenter study is warranted to allow identification of modifiable factors for improving long-term outcome.

Sepsis and septic shock in France: incidences, outcomes and costs of care.

BACKGROUND: Sepsis is one of the leading causes of death worldwide. The associated incidence, mortality and trends do not differ greatly between documented reports. The purpose of this study was to provide an in-depth description of patients with sepsis and septic shock hospitalized in France from 2010 to 2015 and to explore the temporal trends of their clinical characteristics, costs and outcomes. METHODS: Retrospective cohort study of the French hospital administrative database in which organ failure therapies and severity scores are systematically registered. All patients admitted between 2010 and 2015 for sepsis and septic shock as defined by an ICD-10 code for infection, and for organ failure or the use of organ failure supplementation were included. Incidence, outcomes and trends were analyzed. Subgroup analyses based on several coding strategies and adjusted for severity scores were performed. RESULTS: A total of 737,147 patients with sepsis and 492,902 patients with septic shock were included. From 2010 to 2015, the incidence of sepsis and septic shock increased, respectively, from 206 to 243 and from 135 to 171 cases per 100,000 population. Case fatality remained at 34% for sepsis, but decreased from 46 to 44% for septic shock. Median hospital stay costs amounted to €11,400 (IQR: 5036; 24,364) for patients with sepsis and €16,439 (IQR: 7339; 29,360) for patients with septic shock. After adjustment for case-mix and illness severity, the risk of death was stable for sepsis (0.08% [- 0.04; 0.20] per year), but decreased for sepsis patients admitted to the intensive care unit and for cases of septic shock (- 0.33%[ - 0.40; - 0.27] per year). CONCLUSIONS: Sepsis is common, frequently fatal and expensive to treat. Its incidence has increased. Case fatality has decreased in most severely affected patients, owing partly to general improvements in care.

Early EEG for Prognostication Under Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND/OBJECTIVES: Tools for prognostication of neurologic outcome of adult patients under venoarterial ECMO (VA-ECMO) have not been thoroughly investigated. We aimed to determine whether early standard electroencephalography (stdEEG) can be used for prognostication in adults under VA-ECMO. METHODS: Prospective single-center observational study conducted in two intensive care units of a university hospital, Paris, France. Early stdEEG was performed on consecutive adult patients treated with VA-ECMO for refractory cardiogenic shock or refractory cardiac arrest. The association between stdEEG findings and unfavorable outcome was investigated. The primary endpoint was 28-day mortality. The secondary endpoint was severe disability or death at 90 days, defined by a score of 4-6 on the modified Rankin scale. RESULTS: A total of 122 patients were included, of whom 35 (29%) received cardiopulmonary resuscitation before VA-ECMO cannulation. Main stdEEG findings included low background frequency ≤ 4 Hz (n = 27, 22%) and background abnormalities, i.e., a discontinuous (n = 20, 17%) and/or an unreactive background (n = 12, 10%). Background abnormalities displayed better performances for prediction of unfavorable outcomes, as compared to clinical parameters at time of recording. An unreactive stdEEG background in combination with a background frequency ≤ 4 Hz had a false positive rate of 0% for prediction of unfavorable outcome at 28 days and 90 days, with sensitivities of 8% and 6%, respectively. After adjustment for confounders, a lower background frequency was independently associated with unfavorable outcome at 28 days (adjusted odds ratio per 1-Hz increment, 95% CI 0.71, 0.52-0.97), whereas no such independent association was observed at 90 days. CONCLUSION: Standard EEG abnormalities recorded at time of VA-ECMO initiation are predictive of unfavorable outcomes. However, the low sensitivity of these parameters highlights the need for a multimodal evaluation for improving management of care and prognostication.

Immune Alterations in a Patient with SARS-CoV-2-Related Acute Respiratory Distress Syndrome.

We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19 in Europe. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2-3-fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in γδ T cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a pro-inflammatory cytokine storm, Th1 and Th2 activation, and markers of T cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response. The investigation was conducted as part of an overall French clinical cohort assessing patients with COVID-19 and registered in clinicaltrials.gov under the following number: NCT04262921.

Correction to: Changes in the clinical presentation and outcomes of patients treated for severe malaria in a referral French university intensive care unit from 2004 to 2017.

After publication of the original article [1], we were notified that family names have been exchanged with the first names for all authors. Below the name are tagged correctly.

Changes in the clinical presentation and outcomes of patients treated for severe malaria in a referral French university intensive care unit from 2004 to 2017.

BACKGROUND: In France, the incidence of severe imported malaria cases increased since early 2000. Artesunate was available (temporarily use authorization) since mid-2011 in France and commonly used for severe malaria since early 2013. Thus, the study objectives were to describe the patients with severe imported malaria admitted in intensive care unit (ICU) and assess the changes in clinical presentation and outcomes before and after this date. METHODS: Retrospective observational single-center study in the infectious diseases ICU of a referral university hospital, conducted on patients admitted for severe imported malaria from 2004 to 2017. Demographic variables, severity scores, WHO's severity criteria on admission, treatment, and ICU and hospital lengths of stay were collected. Patients' characteristics and outcomes were compared between both periods. A poor outcome was defined as the composite endpoint of death, or requirement for vasopressors, invasive mechanical ventilation and/or renal replacement therapy. RESULTS: 189 patients were included, 98 in 2004-2012 and 91 in 2013-2017, most often from West and Central African countries (96%). The number of WHO criteria for severe malaria was comparable in both groups, but SAPS II, SOFA and ICU length of stay were significantly higher in 2004-2012, while patients of African origin living in France were less frequent (p < 0.01). The outcome was poor for 41/98 cases in 2004-2012 and 12/91 cases in 2013-2017 (p < 0.01). The risk factors of poor outcome on the multivariate logistic regression were a neurological failure (adjusted odds ratio (adjOR = 3.23; 95% CI (1.03-10.08), p = 0.004), cardio-circulatory failure (adjOR = 9.92; 95% CI (2.34-42), p = <0.01) and creatinine blood levels > 265 µmol/L (adjOR = 10.76; 95% CI (3.17-36.53), p < 0.01). In the multivariate analysis, IV artesunate was not associated with a better outcome. Patients of African origin did not seem to have a better outcome than Caucasian patients or those from other origins (adjOR = 0.59; 95% CI (0.21-1.65), p = 0.31). CONCLUSION: Patients with imported malaria admitted in ICU in 2013-2017 were less severely ill than those in 2004-2012. These trends could be partially explained by the increasing proportion of African patients visiting friends or relatives or living in endemic areas.

Early Electroencephalography Findings in Cardiogenic Shock Patients Treated by Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: We aimed to assess early electroencephalography findings in patients treated by venoarterial extracorporeal membrane oxygenation and their association with neurologic outcome. DESIGN: Single-center observational study. SETTING: Medical ICU of a university hospital. PATIENTS: An early standardized electroencephalography assessment, that is, standard electroencephalography followed by continuous electroencephalography, was performed in consecutive cardiogenic shock patients requiring venoarterial extracorporeal membrane oxygenation. Associations between electroencephalography findings and outcome, defined as a composite of acute brain injury or death at 14 days, were investigated. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients with a median Full Outline of Unresponsiveness score of 4 (interquartile range, 3-6) were studied. Pupillary light reflex, corneal reflex, and cough reflex were preserved in 20 (90%), 17 (77%), and 17 (77%) patients, respectively. Overall, standard electroencephalography findings consisted of diffuse slowing in 21 patients (95%) and severe background abnormalities in 13 patients (59%) (i.e., a discontinuous [n = 5; 23%] and/or an unreactive background [n = 9; 41%]). Severe background abnormalities on standard electroencephalography (poor outcome rate: 69% vs 22%; p = 0.03) and absence of sleep transients on continuous electroencephalography (poor outcome rate: 67% vs 14%; p = 0.02) were associated with a poor outcome, whereas neurologic findings and doses of sedation were not. Patients without sleep transients on continuous electroencephalography tended to have lower Full Outline of Unresponsiveness scores than patients with preserved sleep transients-appearing patterns. CONCLUSIONS: In patients treated by venoarterial extracorporeal membrane oxygenation, early severe background abnormalities on standard electroencephalography provide important information on neurologic outcome. The lack of sleep transients on continuous electroencephalography reflects the severity of brain dysfunction and might represent an additional prognostic marker.

Incremental research approach to describing the pharmacokinetics of ciprofloxacin during extracorporeal membrane oxygenation.

BACKGROUND: Significant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and critical illness may affect the pharmacokinetic properties of antibiotics in critically ill patients receiving ECMO. OBJECTIVE: To describe the pharmacokinetic properties of ciprofloxacin during ECMO by integrating pre-clinical findings (ie, ex vivo and in vivo ovine models) to a critically ill patient. DESIGN, PARTICIPANTS AND INTERVENTION: An ex vivo model of an ECMO circuit was used to describe ciprofloxacin concentration changes over 24 hours. An in vivo ovine model of ECMO was used to describe the population pharmacokinetic properties of ciprofloxacin in three different groups of sheep, and to investigate sources of pharmacokinetic variability. In the final phase, data from a 39-year-old critically ill man was used to validate the findings from the ovine pharmacokinetic model. RESULTS: In the ex vivo model of ECMO circuits, the median concentrations of ciprofloxacin at baseline and at 24 hours after ciprofloxacin infusion were similar. The time course of ciprofloxacin in the in vivo ovine on ECMO model was adequately described by a two-compartment model. The final population primary parameter mean estimates were: clearance (CL), 0.21 L/kg/h (SD, 0.09 L/kg/h) and volume of distribution (Vd), 0.84 L/kg (SD, 0.12 L/kg). In the critically ill ECMO patient, the primary pharmacokinetic parameter estimates were: CL, 0.15 L/kg/h and Vd, 0.99 L/kg. CONCLUSIONS: We provide preliminary evidence that ciprofloxacin dosing in ECMO patients should remain in line with the recommended dosing strategies for critically ill patients not receiving ECMO.