Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

Topographical and cytological evolution of the glial phase during prenatal development of the human brain: histochemical and electron microscopic study.

An ultrastructural analysis of prenatal gliogenesis and neuronal-glial relationships in the developing fetal brain was carried out using reduced osmium and periodic acid-thiocarbohydrazide-silver proteinate to stain selectively the glycogen content of the glial population. Gliophilic neuronal migration was confirmed in the human fetus, with radial glial fibers (RGF) acting as obligatory corridors for neuronal migration in the prospective neocortex and underlying intermediate zone (IZ). With this method, the entire glial phase was differentiated from neuronal elements; this permitted a description of the evolutionary distribution pattern of RGF: in the cortical plate, glial fascicles fully dissociate by 18 weeks gestation, whereas in the IZ, they remain grouped in fascicles until their transformation into astrocytes. The most conspicuous and constant developmental feature observed in the maturing glial cytoplasm between 21 and 30 weeks gestation was a radical enhancement in the abundance and activity of the lysosomal apparatus and autophagic vacuoles observed in the RGF, a cytological basis for the transformation of radial glial cells into astrocytes. These data have implications for the understanding of the ontogenesis of the neocortical vertical modules in the human brain and for the phylogenetic analysis of the vertical cortical units in terms of comparative mammalian anatomy

Prevention by magnesium of excitotoxic neuronal death in the developing brain:an animal model for clinical intervention studies

Excitotoxic disturbances during brain development were studied in the mouse using intracerebral injections of ibotenate, a glutamatergic agonist of the N-methyl-D-aspartate (NMDA) complex receptor, to analyse the protective effect of a systemic bolus of MgSO4, a non-competitive antagonist of the NMDA ionophore-complex receptor. MgSO4 did not prevent microgyia, induced by ibotenate when injected at P0 immediately after the post-migratory settlement of layer V, but did prevent ulegyrias, porencephalic cysts, and other cortical and cortical-subcortical hypoxic-like lesions arising after completion of the neocortical cyto-architectonic development at P5. Protection was optimal in 80 per cent of mice at 600mg/kg, with no mortality due to MgSO4; thereafter mortality increased with dosage. The protective effect appears after the developmental acquisition of two properties of the excitotoxic cascade, namely the coupling of the massive calcium influx with NMDA-receptor overstimulation and the predominance of magnesium-obliterable calcium channels. This animal model supports the clinical intervention studies with magnesium in hypoxias/perfusion failures and has implications for their design. If maturation of the excitotoxic cascade follows the same sequence in humans, protection is probably low before 26 weeks of gestational age

The germinative zone produces the most cortical astrocytes after neuronal migration in the developing mammalian brain.

The origin of astrocytes of the mouse neocortex during the fetal and early postnatal periods as determined by immunocytological, autoradiographic, electron microscopic and antimitotic methods is described. Most astrocytes destined for the white matter and the infragranular cortical layers are derived from the transformation of radial glial cells between P0 and P10 with an inside-out pattern. This cell metamorphosis is not directly preceded by mitosis and involves the activation of the radial glial lysosomal apparatus. In opposition to recent hypotheses, our findings suggest that most astrocytes destined for the supragranular cortical layers are produced in the germinative zone after the migration of the infragranular neurons and themselves migrate afterwards to the upper cortex between E16 and the first postnatal days. These astrocytes do not display an intermediate stage of the radial glial cell and do not participate in the pattern of appearance of the deeper astrocytes. This second step of astrocytogenesis is a condition for normal cytoarchitectonic development and the maintenance of the supragranular layers, since the deprivation of the astrocytic equipment of the supragranular layers by an antimitotic drug drastically reduces the number of supragranular neurons

Brain defects in infants with Potter syndrome (oligohydramnios sequence)

Defects of neuronal migration were detected in the brains of five unrelated infants with Potter syndrome (oligohydramnios sequence). These consisted of abnormal lamination of cerebral cortex, white matter heterotopias, and meningeal and molecular zone neuronal-glial ectopias. Besides, various other brain anomalies were sometimes found. They comprised one or more of the followings: abnormal gyration patterns (gyral fusion, cerebellar microgyria), cerebellar granule and Purkinje cell heterotopias, brain stem heterotopias, adysplasia of basal ganglia, gliosis, mineralization, and hydrocephalus. Detailed investigations, using standard neuropathologic stains, immunohistochemical and Golgi methods, and a new electron microscopic histochemical technique that we applied to study the developing human brain, suggest that migration defects of neurons are caused by an abnormality in their glial guides, the radial glial fibers, during the period of cortical histogenesis. We hypothesize that abnormally and precociously induced radial glial transformation into astrocytes is the pathogenic mechanism for the defects in neuronal migration. The etiological factor(s) that precipitates such abnormal glial transformation seems to be heterogeneous. Its relation to the Potter anomaly is discussed

Prolonged dysphagia caused by congenital pharyngeal dysfunction.

We describe two patients with severe, isolated, congenital dysphagia caused by paralysis of the pharyngeal muscles, who recovered at the ages of 40 months and 20 months, respectively. No other evidence of neurologic or muscular dysfunction was present except for a transient paralysis of the adductors of the vocal cords in one child. Radiocinematographic studies showed paralysis of the pharyngeal stage of swallowing, with minimal involvement of the oral stage. One child refused oral feeding for several months after apparent radiologic recovery. Two other patients with a similar disorder died of tracheal aspiration at the ages of 8 months and 4 months, respectively. Autopsies showed no abnormality of the central nervous system, and the cranial nerves involved in swallowing were normal. Only five other well-studied cases of this syndrome have been reported. These observations demonstrate the existence of a type of severe, idiopathic, congenital dysphagia related to paralysis of the constrictor muscles of the pharynx, with a propensity to recover after several months or years if properly managed. The cause of the disorder is obscure, but it is probably related to a dysfunction of the central nervous system

Glial organization in the developing reeler neocortex

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