Experimental Models of Posterior Reversible Encephalopathy Syndrome: A Review From Pathophysiology to Therapeutic Targets.

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity characterized by nonspecific symptomatology (eg, headache, visual disturbances, encephalopathy, and seizures) and classically cortical and subcortical vasogenic edema predominantly affecting the parietooccipital region. PRES etiologies are usually dichotomized into toxic PRES (eg, antineoplastic drugs, illicit drugs) and clinical condition-associated PRES (eg, acute hypertension, dysimmune disorders). Although the pathophysiology of PRES remains elusive, 2 main pathogenic hypotheses have been suggested: cerebral hyperperfusion due to acute hypertension and cerebral hypoperfusion related to endothelial dysfunction. Research into the pathogenesis of PRES has emerged through the development of animal models in the last decade. The motivation for developing a suitable PRES model is 2-fold: to fill in knowledge gaps of the pathophysiological mechanisms involved, and to open new perspectives for clinical assessment of pharmacological targets to improve therapeutic management of PRES. All current models of PRES have a hypertensive background, on which other triggers (acute hypertension, inflammatory, drug toxicity) have been added to address specific facets of PRES (eg, seizures). The initial model consisted in inducing a reduced uterine perfusion pressure that mimics preeclampsia, a leading cause of PRES. More recently, a model of stroke-prone spontaneously hypertensive rats on high-salt diet, originally developed for hypertensive small vessel disease and vascular cognitive impairment, has been studied in PRES. This review aims to discuss, depending on the research objective, the benefits and limitations of current experimental approaches and thus to define the desirable characteristics for studying the pathophysiology of PRES and developing new therapies.

Kidney Increase Natriuresis but Not Glomerular Filtration Under Veno-venous ECMO, a Retrospective Study.

PURPOSE: Acute kidney injury is a frequent complication of acute respiratory distress syndrome (ARDS). We aim to study the evolution of kidney function in patients presenting severe ARDS and requiring veno-venous extracorporeal membrane oxygenation (VV ECMO). METHODS: We conducted a multicenter retrospective study, including adult patients requiring VV ECMO for ARDS. The primary outcome was the evolution of the serum creatinine level after VV ECMO initiation. Secondary outcomes were change in urine output, and urine biochemical parameters after VV ECMO initiation. RESULTS: One hundred and two patients were included. VV ECMO was initiated after a median of 6 days of mechanical ventilation, mainly for ARDS caused by COVID-19 (73%). Serum creatinine level did not significantly differ after VV ECMO initiation (P = .20). VV ECMO was associated with a significant increase in daily urine output (+6.6 mL/kg/day, [3.8;9.3] P < .001), even after adjustment for potential confounding factors; with an increase in natriuresis. The increase in urine output under VV ECMO was associated with a reduced risk of receiving kidney replacement therapy (OR 0.4 [0.2;0.8], P = .026). CONCLUSIONS: VV ECMO initiation in severe ARDS is associated with an increase in daily urine output and natriuresis, without change in glomerular filtration rate.

A single Bayesian estimator for iohexol clearance estimation in ICU, liver failure and renal transplant patients.

AIMS: Iohexol clearance has been proposed to estimate the glomerular filtration rate (GFR). A population pharmacokinetics (popPK) model was developed from heterogeneous patients. A Bayesian estimator (MAP-BE) based on a limited sampling strategy (LSS) was derived and evaluated in external patients. METHODS: Full pharmacokinetic data (7-12 samples) from 172 patients receiving iohexol for measurement of their GFR (unstable and stable ICU patients, liver failure patients and kidney transplant patients) were split into development (n = 136) and validation (n = 36) datasets. A PopPK model was developed in Monolix and was used to develop MAP-BE based on LSS. Its performance for GFR estimation was evaluated in the validation set. RESULTS: A two-compartment model with first-order elimination best described the data. The final model included the type of patients on volume of distribution (Vd), clearance and intercompartmental constants, serum creatinine on clearance and body weight on Vd. The best LSS included samples at 0.1-1-9 h exhibiting a relative mean prediction error (MPE) (RMSE) = -3.7% (14.3%) and better performance than the Bröchner-Mortensen formula (-3.0%/17%). Split by type of patients, the highest interindividual variability and imprecision was observed in unstable ICU patients (MPE (RMSE) = 3.7% (18.8%)) while the best performances were obtained for renal transplant patients (MPE (RMSE) = 1.0% (5.8%)). All LSS that included samples before 9 hours for the third sample were associated with an increased imprecision. CONCLUSION: A single MAP-BE of iohexol based on a three-sample LSS for four heterogeneous populations was developed and allowed accurate estimation of GFR in kidney transplant patients, slightly biased in stable ICU patients and slightly imprecise in unstable ICU patients.

Kinetic Glomerular Filtration Rate Equations in Patients With Shock: Comparison With the Iohexol-Based Gold-Standard Method.

OBJECTIVES: Static glomerular filtration rate formulas are not suitable for critically ill patients because of nonsteady state glomerular filtration rate and variation in the volume of distribution. Kinetic glomerular filtration rate formulas remain to be evaluated against a gold standard. We assessed the most accurate kinetic glomerular filtration rate formula as compared to iohexol clearance among patients with shock. DESIGN: Retrospective multicentric study. SETTING: Three French ICUs in tertiary teaching hospitals. PATIENTS: Fifty-seven patients within the first 12 hours of shock. MEASUREMENTS AND MAIN RESULTS: On day 1, we compared kinetic glomerular filtration rate formulas with iohexol clearance, with or without creatinine concentration correction according to changes in volume of distribution and ideal body weight. We analyzed three static glomerular filtration rate formulas (Cockcroft and Gault, modification of diet in renal disease, and Chronic Kidney Disease-Epidemiology Collaboration), urinary creatinine clearance, and seven kinetic glomerular filtration rate formulas (Jelliffe, Chen, Chiou and Hsu, Moran and Myers, Yashiro, Seelhammer, and Brater). We evaluated 33 variants of these formulas after applying corrective factors. The bias ranged from 12 to 47 mL/min/1.73 m2. Only the Yashiro equation had a lower bias than urinary creatinine clearance before applying corrective factors (15 vs 20 mL/min/1.73 m2). The corrected Moran and Myers formula had the best mean bias, 12 mL/min/1.73 m2, but wide limits of agreement (-50 to 73). The corrected Moran and Myers value was within 30% of iohexol-clearance-measured glomerular filtration rate for 27 patients (47.4%) and was within 10% for nine patients (15.8%); other formulas showed even worse accuracy. CONCLUSIONS: Kinetic glomerular filtration rate equations are not accurate enough for glomerular filtration rate estimation in the first hours of shock, when glomerular filtration rate is greatly decreased. They can both under- or overestimate glomerular filtration rate, with a trend to overestimation. Applying corrective factors to creatinine concentration or volume of distribution did not improve accuracy sufficiently to make these formulas reliable. Clinicians should not use kinetic glomerular filtration rate equations to estimate glomerular filtration rate in patients with shock.

Glomerular Hyper- and Hypofiltration During Acute Circulatory Failure: Iohexol-Based Gold-Standard Descriptive Study.

OBJECTIVE: To assess glomerular filtration rate in the early phase of acute circulatory failure by measuring iohexol plasma clearance. DESIGN: Interventional prospective multicentric study. SETTING: Three French ICUs in tertiary teaching hospitals. PATIENTS: Patients with acute circulatory failure within 12 hours after ICU admission. INTERVENTIONS: IV administration of a nontoxic 5-mL dose of iohexol. Collection of nine arterial blood samples over 24 hours for iohexol plasma concentration measurements. Iohexol clearance calculation with a population pharmacokinetic model. Iohexol clearance was an estimation of the mean glomerular filtration rate over 24 hours. MEASUREMENTS AND MAIN RESULTS: Among 99 included patients, we could calculate iohexol clearance for 85. The median iohexol clearance was 31 mL/min (interquartile range, 16-44). According to iohexol clearance, 41 patients (48%) had severe hypofiltration (clearance, < 30 mL/min), 29 (34%) had moderate hypofiltration, and 10 (12%) had mild hypofiltration (clearance, 30-60 and 60-90 mL/min, respectively). Four patients (5%) had normal glomerular filtration rate, and only one (1%) showed hyperfiltration (clearance, > 130 mL/min). Urinary creatinine clearance underestimated renal impairment in one patient out of two; the bias of iohexol clearance toward 24-hour urinary creatinine clearance over the same period was -18.1 mL/min (limits of agreement, -73.5 to 37.4). CONCLUSIONS: We demonstrated the feasibility of iohexol clearance measurement in unstable critically ill patients. Normal kidney function is exceptional during the early phase of acute circulatory failure. Glomerular filtration rate estimation by urinary creatinine clearance frequently fails to detect renal impairment. Hyperfiltration is very infrequent.

Lack of impact of iodinated contrast media on kidney cell-cycle arrest biomarkers in critically ill patients.

BACKGROUND: Iodinated contrast media may contribute to acute kidney injury. However, several recent works suggest that this toxicity is minimal in the clinical setting. Recently, urinary G1 cell-cycle arrest proteins tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin like growth factor binding protein 7 (IGFBP-7) were identified as highly sensitive and specific biomarkers for early detection of kidney aggression. The impact of contrast administration on those biomarkers has not been specifically evaluated but could provide clues about the toxicity of contrast media. This study aimed at measuring changes in TIMP-2 and IGFBP-7 urinary concentrations before and after a contrast-enhanced computed tomography in critically ill patients. METHODS: 77 patients were included in a prospective observational cohort study. Urinary [TIMP -2]·[IGFBP-7] was measured before, 6 and 24 h after contrast infusion. Urine output and serum creatinine were followed 3 days. RESULTS: Median [TIMP-2]·[IGFBP-7] was 0.06 [interquartile range 0.04;0.26], 0.07 [0.03;0.34] and 0.10 [0.04;0.37] (ng/mL)2/1000 respectively before, 6 and 24 h after contrast infusion. Individual changes from baseline were - 0.01 [- 0.11;0.11] and 0.00 [- 0.10;0.09] (ng/ml)2/1000 at 6 and 24 h. These changes were not higher among the patients increasing their Kidney Disease Improving Global Outcome (KDIGO) classification within 3 days after contrast infusion (n = 14 [18%] based on creatinine criterion only, n = 42 [55%] based on creatinine and urine output). CONCLUSIONS: Changes in [TIMP-2]·[IGFBP-7] urinary concentration after contrast-enhanced computed tomography were insignificant, suggesting minimal kidney aggression by modern iodinated contrast media.

Hypoxia/Reoxygenation Inhibits P2Y11 Receptor Expression and Its Immunosuppressive Activity in Human Dendritic Cells.

High concentrations of extracellular ATP (eATP) resulting from cell damage may be found during an ischemia/reperfusion (I/R) episode at the site of injury. eATP activates purinergic receptors in dendritic cells (DCs) and may inhibit inflammation. This immunosuppressive activity could be of interest in the field of I/R, which is an inflammatory condition involved in myocardial infarction, stroke, and solid organ transplantation. However, the specific purinergic receptor responsible for this effect remains to be identified. In this study, we report that eATP induced maturation of human monocyte-derived DCs. Additionally, eATP inhibited IL-12 production whereas IL-10 levels remained unchanged in activated DCs. These effects were prevented by the P2Y11R antagonist NF340. Interestingly, a 5-h hypoxia prevented the effects of eATP on cytokine production whereas a 1-h hypoxia did not affect the eATP-mediated decrease of IL-12 and IL-6. We showed a time-dependent downregulation of P2Y11R at both mRNA and protein levels that was prevented by knocking down hypoxia-inducible factor-1α. In this study, we showed an immunosuppressive role of P2Y11R in human DCs. Additionally, we demonstrated that the time-dependent downregulation of P2Y11R by hypoxia orientates DCs toward a proinflammatory phenotype that may be involved in post-I/R injuries as observed after organ transplantation.

Iohexol clearance in unstable critically ill patients: a tool to assess glomerular filtration rate.

BACKGROUND: Acute kidney injury (AKI) is associated with significant morbidity and mortality, particularly in unstable critically ill patients. In this context, serum creatinine concentration is an imperfect tool for estimating glomerular filtration rate (GFR), an index of renal function. The objective of this pilot study was to evaluate the feasibility of measuring iohexol clearance for GFR assessment in critically ill patients with acute circulatory failure at intensive care unit (ICU) admission. METHODS: ICU patients were prospectively included within 12 h of acute circulatory failure; a non-toxic dose of iohexol (5 mL) was infused intravenously and iohexol plasma concentration decrease was measured over 24 h. Urinary iohexol concentration was measured in urine samples collected four times, every 6 h for 24 h. The Kidney Disease Improving Global Outcome score, measuring AKI, was calculated each day. RESULTS: Among 18 patients with acute circulatory failure, AKI developed in 15; 14 showed decreased serum creatinine concentration during the first 24 h even though 10 presented AKI. The absolute variation in serum creatinine concentration was correlated with fluid balance over 24 h. Median [min; max] plasma clearance of iohexol was 39.4 mL/min [6.1; 154.0] and iohexol urinary clearance 32.8 mL/min [0.8-170.4]. The correlation between plasma and urinary clearance was ρ=0.97, p<0.0001. CONCLUSIONS: GFR may be estimated by plasma iohexol clearance in unstable critically ill patients. This method is reliable, correlates very well with urinary iohexol clearance and does not depend on input/output fluid balance and fluid infusion, as compared with serum creatinine concentration.

Influence of socio-economic status on functional recovery after ARDS caused by SARS-CoV-2: the multicentre, observational RECOVIDS study.

PURPOSE: Survivors after acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) are at high risk of developing respiratory sequelae and functional impairment. The healthcare crisis caused by the pandemic hit socially disadvantaged populations. We aimed to evaluate the influence of socio-economic status on respiratory sequelae after COVID-19 ARDS. METHODS: We carried out a prospective multicenter study in 30 French intensive care units (ICUs), where ARDS survivors were pre-enrolled if they fulfilled the Berlin ARDS criteria. For patients receiving high flow oxygen therapy, a flow ≥ 50 l/min and an FiO2 ≥ 50% were required for enrollment. Socio-economic deprivation was defined by an EPICES (Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé - Evaluation of Deprivation and Inequalities in Health Examination Centres) score ≥ 30.17 and patients were included if they performed the 6-month evaluation. The primary outcome was respiratory sequelae 6 months after ICU discharge, defined by at least one of the following criteria: forced vital capacity < 80% of theoretical value, diffusing capacity of the lung for carbon monoxide < 80% of theoretical value, oxygen desaturation during a 6-min walk test and fibrotic-like findings on chest computed tomography. RESULTS: Among 401 analyzable patients, 160 (40%) were socio-economically deprived and 241 (60%) non-deprived; 319 (80%) patients had respiratory sequelae 6 months after ICU discharge (81% vs 78%, deprived vs non-deprived, respectively). No significant effect of socio-economic status was identified on lung sequelae (odds ratio (OR), 1.19 [95% confidence interval (CI), 0.72-1.97]), even after adjustment for age, sex, most invasive respiratory support, obesity, most severe P/F ratio (adjusted OR, 1.02 [95% CI 0.57-1.83]). CONCLUSIONS: In COVID-19 ARDS survivors, socio-economic status had no significant influence on respiratory sequelae 6 months after ICU discharge.

Ten actions to achieve gender equity among intensivists: the French Society of Intensive Care (FICS) model.

In our recent survey, we aimed to collect information on perceived inequity as well as professional and personal fulfillment among women intensivists in France. For the 371 respondents out of the 732 persons who received the survey, the findings were unequivocal: for one-third of the respondents, being a woman was considered as an obstacle to careers or academic advancement, and for two thirds, pregnancy was viewed as a barrier to their career advancement. Gender discrimination had been experienced by 55% of the respondents. In 2019, to promote and achieve gender equity in the French Intensive Care Society (FICS), ten actions were initiated and are detailed in the present manuscript together with supporting data: (1) creation of a working group: the FEMMIR group; (2) promotion of mentorship; (3) implementation of concrete sponsorship; (4) transparency and public reporting of gender ratios in editorial boards; (5) workshops dedicated to unconscious gender bias; (6) workshops dedicated to improved women assertiveness; (7) role models; (8) creation of educational/information programs for young intensivists; (9) development of research on gender inequity and, as a perspective; and (10) development of a wide-ranging program. This review is aimed at providing a toolbox of organizational best practices designed to achieve gender equity. It is particularly important to share promising practical action engaged in our FEMMIR group with other concerned professionals around the world.

Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges.

BACKGROUND: Post-intensive care syndrome (PICS) encompasses physical, cognition, and mental impairments persisting after intensive care unit (ICU) discharge. Ultimately it significantly impacts the long-term prognosis, both in functional outcomes and survival. Thus, survivors often develop permanent disabilities, consume a lot of healthcare resources, and may experience prolonged suffering. This review aims to present the multiple facets of the PICS, decipher its underlying mechanisms, and highlight future research directions. MAIN TEXT: This review abridges the translational data underlying the multiple facets of chronic critical illness (CCI) and PICS. We focus first on ICU-acquired weakness, a syndrome characterized by impaired contractility, muscle wasting, and persisting muscle atrophy during the recovery phase, which involves anabolic resistance, impaired capacity of regeneration, mitochondrial dysfunction, and abnormalities in calcium homeostasis. Second, we discuss the clinical relevance of post-ICU cognitive impairment and neuropsychological disability, its association with delirium during the ICU stay, and the putative role of low-grade long-lasting inflammation. Third, we describe the profound and persistent qualitative and quantitative alteration of the innate and adaptive response. Fourth, we discuss the biological mechanisms of the progression from acute to chronic kidney injury, opening the field for renoprotective strategies. Fifth, we report long-lasting pulmonary consequences of ARDS and prolonged mechanical ventilation. Finally, we discuss several specificities in children, including the influence of the child's pre-ICU condition, development, and maturation. CONCLUSIONS: Recent understandings of the biological substratum of the PICS' distinct features highlight the need to rethink our patient trajectories in the long term. A better knowledge of this syndrome and precipitating factors is necessary to develop protocols and strategies to alleviate the CCI and PICS and ultimately improve patient recovery.

Influence of socioeconomic status on functional recovery after ARDS caused by SARS-CoV-2: a multicentre, observational study.

INTRODUCTION: Prognosis of patients with COVID-19 depends on the severity of the pulmonary affection. The most severe cases may progress to acute respiratory distress syndrome (ARDS), which is associated with a risk of long-term repercussions on respiratory function and neuromuscular outcomes. The functional repercussions of severe forms of COVID-19 may have a major impact on quality of life, and impair the ability to return to work or exercise. Social inequalities in healthcare may influence prognosis, with socially vulnerable individuals more likely to develop severe forms of disease. We describe here the protocol for a prospective, multicentre study that aims to investigate the influence of social vulnerability on functional recovery in patients who were hospitalised in intensive care for ARDS caused by COVID-19. This study will also include an embedded qualitative study that aims to describe facilitators and barriers to compliance with rehabilitation, describe patients' health practices and identify social representations of health, disease and care. METHODS AND ANALYSIS: The "Functional Recovery From Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: Influence of Socio-Economic Status" (RECOVIDS) study is a mixed-methods, observational, multicentre cohort study performed during the routine follow-up of post-intensive care unit (ICU) functional recovery after ARDS. All patients admitted to a participating ICU for PCR-proven SARS-CoV-2 infection and who underwent chest CT scan at the initial phase AND who received respiratory support (mechanical or not) or high-flow nasal oxygen, AND had ARDS diagnosed by the Berlin criteria will be eligible. The primary outcome is the presence of lung sequelae at 6 months after ICU discharge, defined either by alterations on pulmonary function tests, oxygen desaturation during a standardised 6 min walk test or fibrosis-like pulmonary findings on chest CT. Patients will be considered to be socially disadvantaged if they have an "Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé" (EPICES) score ≥30.17 at inclusion. ETHICS AND DISSEMINATION: The study protocol and the informed consent form were approved by an independent ethics committee (Comité de Protection des Personnes Sud Méditerranée II) on 10 July 2020 (2020-A02014-35). All patients will provide informed consent before participation. Findings will be published in peer-reviewed journals and presented at national and international congresses. TRIAL REGISTRATION NUMBER: NCT04556513.

A Machine Learning Approach to Estimate the Glomerular Filtration Rate in Intensive Care Unit Patients Based on Plasma Iohexol Concentrations and Covariates.

OBJECTIVE: This work aims to evaluate whether a machine learning approach is appropriate to estimate the glomerular filtration rate in intensive care unit patients based on sparse iohexol pharmacokinetic data and a limited number of predictors. METHODS: Eighty-six unstable patients received 3250 mg of iohexol intravenously and had nine blood samples collected 5, 30, 60, 180, 360, 540, 720, 1080, and 1440 min thereafter. Data splitting was performed to obtain a training (75%) and a test set (25%). To estimate the glomerular filtration rate, 37 candidate potential predictors were considered and the best machine learning approach among multivariate-adaptive regression spline and extreme gradient boosting (Xgboost) was selected based on the root-mean-square error. The approach associated with the best results in a ten-fold cross-validation experiment was then used to select the best limited combination of predictors in the training set, which was finally evaluated in the test set. RESULTS: The Xgboost approach yielded the best performance in the training set. The best combination of covariates comprised iohexol concentrations at times 180 and 720 min; the relative deviation from these theoretical times; the difference between these two concentrations; the Simplified Acute Physiology Score II; serum creatinine; and the fluid balance. It resulted in a root-mean-square error of 6.2 mL/min and an r2 of 0.866 in the test set. Interestingly, the eight patients in the test set with a glomerular filtration rate < 30 mL/min were all predicted accordingly. CONCLUSIONS: Xgboost provided accurate glomerular filtration rate estimation in intensive care unit patients based on two timed blood concentrations after iohexol intravenous administration and three additional predictors.

Perceived inequity, professional and personal fulfillment by women intensivists in France.

BACKGROUND: The medical workforce has been feminized for the last two decades worldwide. Nonetheless, women remain under-represented among intensivists. We conducted a survey among French women intensivists to assess their professional and personal quality of life and their perception of potential gender discrimination at work. METHODS: We conducted an observational descriptive study by sending a survey, designed by the group FEMMIR (FEmmes Médecins en Médecine Intensive Réanimation), to women intensivists in France, using primarily the Société de Réanimation de Langue Française (SRLF) mailing list. The questionnaire was also available online between September 2019 and January 2020 and women intensivists were encouraged to answer through email reminders. It pertained to five main domains, including demographic characteristics, work position, workload and clinical/research activities, self-fulfillment scale, perceived discrimination at work and suggested measures to implement. RESULTS: Three hundred and seventy-one women responded to the questionnaire, among whom 16% had an academic position. Being a woman intensivist and pregnancy were both considered to increase difficulties in careers' advancement by 31% and 73% of the respondents, respectively. Almost half of the respondents (46%) quoted their quality of life equal to or lower than 6 on a scale varying from 1 (very bad quality of life) to 10 (excellent quality of life). They were 52% to feel an imbalance between their personal and professional life at the cost of their personal life. Gender discrimination has been experienced by 55% of the respondents while 37% confided having already been subject of bullying or harassment. Opportunities to adjust their work timetable including part-time work, better considerations for pregnant women including increasing the number of intensivists and the systematic replacement during maternity leave, and the respect of the law regarding the paternity leave were suggested as key measures to enable better professional and personal accomplishment by women intensivists. CONCLUSION: In this first large French survey in women intensivists, we pointed out issues felt by women intensivists that included an imbalance between professional and personal life, a perceived loss of opportunity due to the fact of being a woman, frequent reported bullying or harassment and a lack of consideration of the needs related to pregnancy and motherhood.

Posterior Reversible Encephalopathy Syndrome in Clinical Toxicology: A Systematic Review of Published Case Reports.

Background: Posterior reversible encephalopathy syndrome (PRES) is a rare clinical and radiological entity characterized by a typical brain edema. Although several case reports have described PRES in a context of poisoning, to our knowledge, a comprehensive assessment has not been performed. The aim of this systematic review was to raise awareness on poisoning-specific PRES features and to encourage consistent and detailed reporting of substance abuse-and drug overdose-associated PRES. Methods: Medline/PubMed, Web of Science, and PsycINFO were screened through May 31, 2019, to systematically identify case reports and case series describing PRES associated with poisoning (i.e., alcohol, drugs, illicit drugs, natural toxins, chemical substances) in accidental context, intentional overdose, and substance abuse. The methodological quality of eligible case reports/series was assessed. Patients and exposure characteristics were recorded; relevant toxicological, radiological, and clinical data were extracted. Results: Forty-one case reports and one case series reporting 42 unique cases were included. The median time to PRES onset from the start of exposure was 3 days (IQR 2-10). Acute high blood pressure, visual disturbance, and seizure were reported in 70, 55, and 50% of patients, respectively. The initial clinical presentation was alertness disorders in 64% of patients. Nine patients (21%) required mechanical ventilation. One-third of patients had at least one risk factor for PRES such as chronic hypertension (17%) or acute/chronic kidney failure (24%). The main imaging pattern (67%) was the combination of classical parieto-occipital edema with another anatomical region (e.g., frontal, basal ganglia, posterior fossa involvement). Vasogenic edema was found in 86% of patients. Intracranial hemorrhage occurred in 14% of patients. Both brain infarction and reversible cerebral vasoconstriction syndrome were diagnosed in 5% of patients. Three patients (12%, 3/25) had non-reversible lesions on follow-up magnetic resonance imaging. The median time required to hospital discharge was 14 days (IQR 7-18). Mortality and neurological recurrence rate were null. Conclusions: Comorbidities such as chronic hypertension and kidney failure were less frequent than in patients with other PRES etiologies. Imaging analysis did not highlight a specific pattern for poisoning-induced PRES. Although less described, PRES in the context of poisoning, which shares most of the clinical and radiological characteristics of other etiologies, is not to be ignored.

Arginine Vasopressin and Posterior Reversible Encephalopathy Syndrome Pathophysiology: the Missing Link?

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity characterized by a typical brain edema. Its pathogenesis is still debated through hypoperfusion and hyperperfusion theories, which have many limitations. As PRES occurs almost exclusively in clinical situations with arginine vasopressin (AVP) hypersecretion, such as eclampsia and sepsis, we hypothesize that AVP plays a central pathophysiologic role. In this review, we discuss the genesis of PRES and its symptoms through this novel approach. We theorize that AVP axis stimulation precipitates PRES development through an increase in AVP secretion or AVP receptor density. Activation of vasopressin V1a receptors leads to cerebral vasoconstriction, causing endothelial dysfunction and cerebral ischemia. This promotes cytotoxic edema through hydromineral transglial flux dysfunction and may increase endothelial permeability, leading to subsequent vasogenic brain edema. If our hypothesis is confirmed, it opens new perspectives for better patient monitoring and therapies targeting the AVP axis in PRES.

Healthcare trajectories before and after critical illness: population-based insight on diverse patients clusters.

BACKGROUND: The post intensive care syndrome (PICS) gathers various disabilities, associated with a substantial healthcare use. However, patients' comorbidities and active medical conditions prior to intensive care unit (ICU) admission may partly drive healthcare use after ICU discharge. To better understand retative contribution of critical illness and PICS-compared to pre-existing comorbidities-as potential determinant of post-critical illness healthcare use, we conducted a population-based evaluation of patients' healthcare use trajectories. RESULTS: Using discharge databases in a 2.5-million-people region in France, we retrieved, over 3 years, all adult patients admitted in ICU for septic shock or acute respiratory distress syndrome (ARDS), intubated at least 5 days and discharged alive from hospital: 882 patients were included. Median duration of mechanical ventilation was 11 days (interquartile ranges [IQR] 8;20), mean SAPS2 was 49, and median hospital length of stay was 42 days (IQR 29;64). Healthcare use (days spent in healthcare facilities) was analyzed 2 years before and 2 years after ICU admission. Prior to ICU admission, we observed, at the scale of the whole study population, a progressive increase in healthcare use. Healthcare trajectories were then explored at individual level, and patients were assembled according to their individual pre-ICU healthcare use trajectory by clusterization with the K-Means method. Interestingly, this revealed diverse trajectories, identifying patients with elevated and increasing healthcare use (n = 126), and two main groups with low (n = 476) or no (n = 251) pre-ICU healthcare use. In ICU, however, SAPS2, duration of mechanical ventilation and length of stay were not different across the groups. Analysis of post-ICU healthcare trajectories for each group revealed that patients with low or no pre-ICU healthcare (which represented 83% of the population) switched to a persistent and elevated healthcare use during the 2 years post-ICU. CONCLUSION: For 83% of ARDS/septic shock survivors, critical illness appears to have a pivotal role in healthcare trajectories, with a switch from a low and stable healthcare use prior to ICU to a sustained higher healthcare recourse 2 years after ICU discharge. This underpins the hypothesis of long-term critical illness and PICS-related quantifiable consequences in healthcare use, measurable at a population level.

Nasal high-flow bronchodilator nebulization: a randomized cross-over study.

BACKGROUND: There is an absence of controlled clinical data showing bronchodilation effectiveness after nebulization via nasal high-flow therapy circuits. RESULTS: Twenty-five patients with reversible airflow obstruction received, in a randomized order: (1) 2.5 mg albuterol delivered via a jet nebulizer with a facial mask; (2) 2.5 mg albuterol delivered via a vibrating mesh nebulizer placed downstream of a nasal high-flow humidification chamber (30 L/min and 37 °C); and (3) nasal high-flow therapy without nebulization. All three conditions induced significant individual increases in forced expiratory volume in one second (FEV1) compared to baseline. The median change was similar after facial mask nebulization [+ 350 mL (+ 180; + 550); + 18% (+ 8; + 30)] and nasal high flow with nebulization [+ 330 mL (+ 140; + 390); + 16% (+ 5; + 24)], p = 0.11. However, it was significantly lower after nasal high-flow therapy without nebulization [+ 50 mL (- 10; + 220); + 3% (- 1; + 8)], p = 0.0009. FEV1 increases after facial mask and nasal high-flow nebulization as well as residual volume decreases were well correlated (p < 0.0001 and p = 0.01). Both techniques showed good agreement in terms of airflow obstruction reversibility (kappa 0.60). CONCLUSION: Albuterol vibrating mesh nebulization within a nasal high-flow circuit induces similar bronchodilation to standard facial mask jet nebulization. Beyond pharmacological bronchodilation, nasal high flow by itself may induce small but significant bronchodilation.