Critical Care 2020, 24(Suppl 1):87 https://doi.org/10.1186/s13054-020-2772-3 MEETING ABSTRACTS Open Access 40th International Symposium on Intensive Care & Emergency Medicine Brussels, Belgium. 24-27 March 2020 Published: 24 March 2020 P001 Physiological emergence of amyloid-β1-40 with mechanical ventilation-induced cerebral immunochallenge S Lahiri1, N Sparrow2, L Mangiacotti2, PS Rajput2, M Koronyo2 1Cedars-Sinai Medical Center, Neurocritical Care, Los Angeles, United States; 2Cedars-Sinai Medical Center, Departments of Neurology, Neurosurgery, and Biomedical Sciences, Los Angeles, United States Critical Care 2020, 24(Suppl 1):P001 Introduction: A long-term cognitive impairment that resembles Alzheimer’s disease (AD) is a known complication of acute critical illnesses that affects up to 2 million individuals annually in the US. Mechanical ventilation (MV) is a hallmark critical care intervention that is strongly associated with cognitive decline. Fig. 1 (abstract P001). (1) Representative images from ADtg mouse Methods: showing markedly increased distribution of Aβ1-40 in a “banding” We subjected double transgenic Alzheimer’sdisease(Adtg) pattern within a region of acute vascular disruption. Graph showing (APP/PSEN1) and wild-type (WT) mice to MV for 4 hours and significant increase in Aβ1-40 bands/% area of FITC in ADtg mice compared to spontaneously breathing (SB) controls. Cerebral subjected to MV compared to SB ADtg mice. (2) Increased cleaved soluble/insoluble amyloid-β (Aβ) and neurological and systemic caspase-3 in the entorhinal cortices of WT mice subjected to MV markers of inflammation were quantified. Hippocampal blood- compared to SB controls. (3) Significantly decreased activation of brain barrier permeability was quantified using a novel meth- cleaved caspase-3 in the entorhinal cortices of ADtg mice subjected odology that enabled assessment of small and large molecule to MV compared to SB ADtg controls permeability across the blood-brain barrier. Immunohistochem- istry was used to assess the regional relationship between amyloid-β1–40 and acute vascular disruption and neuronal injury. Results: P002 See image Withdrawn Conclusions: Short-term MV resulted in increased cerebral soluble Aβ1-40 P003 and increased cerebral TNF-α and IL-6 concentrations. BBB per- Molecular mechanisms of xenon neuroprotection (experimental meability and neuronal injury were decreased in mechanically data) ventilated ADtg mice, whereas BBB permeability and neuronal A Kuzovlev1, O Grebenchikov1, A Shabanov2, I Kasatkina1, L Nikolaev3,I injury were increased in mechanically ventilated WT mice com- Molchanov4 pared to their respective SB controls. There was increased distri- 1Federal Research and Clinical Center of Intensive Care Medicine and bution of Aβ1-40 in regions of acute vascular disruption, Rehabilitology, Moscow, Russia; 2Federal Research and Clinical Center of resulting in lower BBB permeability. Overall, these results sup- Intensive Care Medicine and Rehabilitology; N.V. Sklifosofsky Research port a possible physiological role for Aβ1-40 to decrease BBB Institute of Emergency Medicine, Moscow, Russia; 3Russian Academy of permeability and neuronal injury during the acute stress of MV, Postgraduate Education, Moscow, Russia; 4Federal Research and Clinical however it is expected that long-term sustained of this putative Center of Intensive Care Medicine and Rehabilitology; Russian Academy protective pathway will contribute to neurodegeneration and of Postgraduate Education, Moscow, Russia cognitive impairment. Critical Care 2020, 24(Suppl 1):P003 © The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Critical Care 2020, 24(Suppl 1):87 Page 2 of 213 Introduction: was low and significantly lower than in the group no-VRI (0.16 ug/l and The aim of the study was to investigate into the molecular mecha- 2.61ug/l, p=0.03 in the group VRI and no-VRI, respectively) (panel C). WBC nisms of neuroprotection with 50 vol% xenon in an in vivo model in CSF were similar between groups (710.14/ul and 675.16/ul p=0.93 in the experiments. group VRI and no-VRI, respectively). Methods: Conclusions: Eight rats were anesthestized (Combi-Vet machine; induction chloral- In this study, serum-inflammatory markers were not able to screen hydrate 300 mg/kg intraabdominally; then 30 mins of 50 vol% xenon patients with VRIs. Their routine measurement should be carefully inhalation (95% O2 0.5 l/min, 100% xenon 0.5 l/min; O2 50%, Xe evaluated. 50%); 8 rats were in the control group (Combi-Vet anesthesia ma- chine; induction chloralhydrate 300 mg/kg intraabdominally; then 30 mins of 95% O2 0.5 l/min). Rats were euthanized and brain homoge- nates were made. Content of the phosphorylated (inactivated form) of the GSK-3 beta enzyme and key antioxidant enzymes (hemoxy- genase, superoxide dismutase, catalase) in rat brain homogenates was assessed by western - immunoblotting. Statistica 6.0, parametric methods were used for data analysis. Results: The research results showed that xenon inhalation anesthesia re- sulted in a 2-fold increase of the phosphorylated (inactivated form) of the GSK-3 beta enzyme (р<0.05); increased the content of the key antioxidant enzymes (hemoxygenase (by 50%, р<0.05), superoxide dismutase (by 60%, р<0.05), catalase (by 20%, р>0.05) in rat brain homogenates compared to the controls. Conclusions: An increase of the phosphorylated GSK-3 beta enzyme and pool of antioxidant enzymes (hemoxigenase, superoxide dismutase, cata- lase) in the brain under the xenon anesthesia was proved which sug- Fig. 1 (abstract P004). Box-plots of WBC (panel A), CRP (panel B), gests a new molecular mechanism for the realization of its and PCT (panel C) in the groups neuroprotective properties and has a great clinical outlook. P004 P005 Procalcitonin and C-reactive protein are not increased in Central nervous system infections in an intensive care unit: a ventriculostomy-related infections in patients with hemorrhagic retrospective study stroke A Martinho, E Trigo, M Miranda, P Martins S Wang, E Pietrzko, E Keller, G Brandi Centro Hospitalar e Universitário de Coimbra - CHUC, Medicina Intensiva, University Hospital Zurich, Neurocritical Care Unit, Dept. of Neurosurgery Coimbra, Portugal and Institute of Intensive Care Medicine, Zurich, Switzerland Critical Care 2020, 24(Suppl 1):P005 Critical Care 2020, 24(Suppl 1):P004 Introduction: Introduction: Central nervous system (CNS) infections constitute a potentially life- Ventriculostomy-related infection (VRI) is a serious complication in threatening neurological emergency. Patients admitted to the inten- patients with hemorrhagic stroke. In such patients, diagnosis of VRIs sive care unit (ICU) usually present with a severe disease and organ is complicated by blood contamination of CSF following ventricular failure, leading to high mortality and morbidity. hemorrhage. We aimed to evaluate the diagnostic potential of white Methods: blood cells count (WBC), C-reactive protein (CRP), and procalcitonin We have performed a retrospective analysis during a 5-year period of (PCT) to identify VRIs in patients with hemorrhagic stroke during the patients admitted to a polyvalent ICU. Clinical, demographic and out- time of external ventricular drain (EDV) in situ. come data were collected to evaluate its clinical impact on the out- Methods: come of patients with CNS infections. This retrospective study was conducted at the Neurosurgical-ICU, University Results: Hospital of Zurich. A total of 347 patients with hemorrhagic stroke and an We identified 30 patients with the diagnosis of meningitis, meningo- external ventricular drain (EVD) were admitted over a 6 years period at the encephalitis and ventriculitis, where the median age was 57,6 years (range ICU. Of those, 14 patients with VRIs (“VRI”), defined by positive CSF bacterial 24-80). Upon clinical presentation, their most frequent signs were fever culture and increased WBC in CSF (>250/ul), and 115 patients without VRIs (70%), meningeal signs (40%), seizures (30%), and a Glasgow Coma Scale and with serial CSF sampling (“no-VRI”) were analyzed. Patients with CSF- score <8 (66%). All needed ventilation support and 66% needed cardiovas- contamination or suspected VRI (negative CSF cultures but antibiotic treat- cular support. A definitive microbiological diagnosis was achieved on 22 ments) were excluded. WBC, CRP, and PCT were measured daily. CSF was patients and antibiotic therapy was adjusted on 18 of them. Most common sampled routinely twice a week or by T>38°C. For the analysis, mean peak microorganisms were Streptococcus pneumoniae (n=7), Listeria (n=5) and values of WBC, CRP, PCT during the time of EVD in situ were compared be- Pseudomonas aeruginosa (n=4) (Figure 1). Other gram negative microorgan- tween groups (t test). Data are expressed as mean with CI 95%. isms were detected and lead to more adverse outcomes. Meningitis was Results: the cause of admission on 26 patients and on a minority (n=4) meningitis Between groups, WBC and CRP were similar (WBC: 15.13 G/L and 14.55 G/ was considered to be a secondary diagnosis on patients admitted for other L, p=0.68 and CRP: 115.93 mg/l and 129.44 mg/l, p=0.56 in the group VRI causes (traumatic brain injury, subarachnoid or intraparenchymal and no-VRI, respectively) (Figure 1, panel A and B). In the group VRI, PCT hemorrhage, postoperatively of neurosurgical tumor). Patients that Critical Care 2020, 24(Suppl 1):87 Page 3 of 213 eventually died had at least one risk factor (age>65, immunocompromised control group was 21.4 ± 1.6, mkg/l on day 30 in the control group due to diabetes, corticotherapy, HIV or heart transplantation).