Mechanical ventilation and long-term neurocognitive impairment after acute respiratory distress syndrome

Giordano, Giovanni; Pugliese, Francesco; Bilotta, Federico

doi:10.1186/s13054-020-2736-7

Cited by 5 publications

(2 citation statements)

References 7 publications

(9 reference statements)

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“…In order to lessen the acute and long-term detrimental effects of the allostatic load imposed during vital organ support, as emerged in various studies on critically ill patients requiring ventilation, early administration of GCs is essential, ideally within six hours of diagnosis [ 40 , 41 , 42 , 43 , 44 , 45 ]. A study performed in 2016 on ARDS proved that when fibroproliferation is still in the early stages of disease (cellular with a predominance of type III procollagen), early (72 h) as opposed to late (seven days) beginning of methylprednisolone administration is linked with quicker disease remission (extubation and ICU discharge) at the same dose (1 mg/kg/day vs. 2 mg/kg/day) [ 29 ].…”

Section: Glucocorticoid Administration: Principles and Evidencementioning

confidence: 99%

Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints

et al. 2023

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Prolonged, low-dose glucocorticoids (GCs) have shown the highest efficacy among pharmacological and non-pharmacological treatments for COVID-19. Despite the World Health Organization’s recommendation against their use at the beginning of the pandemic, GCs at a dose equivalent to dexamethasone 6 mg/day for 10 days are now indicated in all COVID-19 cases who require respiratory support. However, the efficacy of the intervention depends on the timing of initiation, the dose, and other individual factors. Indeed, patients treated with similar GC protocols often experience different outcomes, which do not always correlate with the presence of comorbidities or with the severity of respiratory involvement at baseline. This prompted us to critically review the literature on the rationale, pharmacological principles, and clinical evidence that should guide GC treatment. Based on these data, the best treatment protocol probably involves an initial bolus dose to saturate the glucocorticoid receptors, followed by a continuous infusion to maintain constant plasma levels, and eventually a slow tapering to interruption. Methylprednisolone has shown the highest efficacy among different GC molecules, most likely thanks to its higher ability to penetrate the lung. Decreased tissue sensitivity to glucocorticoids is thought to be the main mechanism accounting for the lower response to the treatment in some individuals. We do not have a readily available test to identify GC resistance; therefore, to address inter-individual variability, future research should aim at investigating clinical, physiological, and laboratory markers to guide a personalized GC treatment approach.

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Section: Glucocorticoid Administration: Principles and Evidencementioning

confidence: 99%

Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints

et al. 2023

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“…While these data provide mechanistic insights to explain the high rates of cognitive decline after mechanical ventilation, they reveal additional unexpected results. Despite an increase in both soluble Aβ 1−40 accumulation and cognition-relevant neuroin ammation, mechanical ventilation of double transgenic AD (ADtg) mice signi cantly decreased cortical BBB permeability, while the same mechanical ventilation intervention signi cantly increased cortical BBB permeability in wild-type (WT) mice 1,6 . These ndings were contrary to the a priori hypothesis, as BBB permeability was expected to be more signi cantly increased in mechanically ventilated ADtg mice who are considered more susceptible to acute systemic and cerebral stressors.…”

Section: Introductionmentioning

confidence: 99%

Physiological Emergence of Amyloid-β During the Acute Cerebral Stress of Mechanical Ventilation Reduces Peri-Hippocampal and Cortical Blood-Brain Barrier Permeability and Neuronal Injury

Gezalian¹,

Rajput²,

Sparrow³

et al. 2020

Preprint

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Background: Prior published data show that short-term mechanical ventilation contributes to pathological hallmarks of Alzheimer’s Disease (AD) by increasing cerebral accumulation of the amyloid-β1-40 (Aβ1-40) peptide and neuroinflammation while unexpectedly decreasing blood-brain barrier permeability. In this study, we hypothesized that the acute cerebral immunochallenge of mechanical ventilation promotes physiological emergence of Aβ1-40 to regions of acute vascular disruption, resulting in reduced neuronal injury.Methods: Immunohistology was used to assess the regional relationship between cerebral Aβ1-40 accumulation, acute vascular disruption, and neuronal inflammation and apoptosis as measured by cleaved caspase-3 (CC3) expression from mechanically ventilated double transgenic AD-model (ADtg) mice and compared to mechanically ventilated wild-type (WT) controls.Results: There was significantly decreased expression of CC3 in regions of cortical and hippocampal Aβ1-40 accumulation in mechanically ventilated ADtg animals (p=0.0224). In contrast, CC3 expression was significantly increased in cortical and hippocampal regions of mechanically ventilated WT controls (p=0.0260). Aβ1-40 accumulation occurred in regions of acute vascular disruption in a characteristic banding pattern and reduced blood-brain barrier permeability. The banding pattern was significantly increased in ADtg mice subjected to mechanical ventilation compared to non-mechanically ventilated ADtg mice (p=0.0002). Additionally, no evidence of irreversible neurological injury is seen in mechanically ventilated ADtg and WT mice, as demonstrated by the absence of TUNEL positive staining. Conclusions: This study provides first evidence that acute short-term mechanical ventilation-induced cerebral immunochallenge promotes physiological emergence of Aβ1-40 to reduce blood-brain barrier permeability and neuronal injury. While it is expected that sustained or long-term activation of this normally protective pathway leads to dysregulated Aβ1-40 accumulation, neurodegeneration, and cognitive impairment, these data suggest that a window of opportunity may exist within which implementation of timely interventions may limit cognition-relevant cerebral injury.

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General adaptation in critical illness 1: The glucocorticoid signaling system as master rheostat of homeostatic corrections in concerted action with nuclear factor-κB

Umberto Meduri,

Chrousos

2024

Stress: Immunology and Inflammation

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Mechanical ventilation and long-term neurocognitive impairment after acute respiratory distress syndrome

Cited by 5 publications

References 7 publications

Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints

Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints

Physiological Emergence of Amyloid-β During the Acute Cerebral Stress of Mechanical Ventilation Reduces Peri-Hippocampal and Cortical Blood-Brain Barrier Permeability and Neuronal Injury

General adaptation in critical illness 1: The glucocorticoid signaling system as master rheostat of homeostatic corrections in concerted action with nuclear factor-κB

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