Mechanical Ventilation Triggers Hippocampal Apoptosis by Vagal and Dopaminergic Pathways

González-López, Adrián; López-Alonso, Inés; Aguirre, Alina; Amado-Rodríguez, Laura; Batalla-Solís, Estefanía; Astudillo, Aurora; Tomás-Zapico, Cristina; Fueyo, Antonio; Santos, Claudia C. dos; Talbot, Konrad; Albaiceta, Guillermo M.

doi:10.1164/rccm.201304-0691oc

Cited by 76 publications

(108 citation statements)

References 50 publications

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“…Expanding preclinical evidence suggests mechanical lung injury may cause brain injury via several complex pathways (17)(18)(19)(20)(21), paralleling clinical trials data that have revealed lungprotective ventilation attenuates other extrapulmonary organ dysfunctions (8,9).…”

mentioning

confidence: 86%

“…Insults ranging from acute myocardial infarction (44,45) to sepsis (46,47) have been shown to increase intracerebral proinflammatory cytokine levels and associated neuronal injury. Several studies similarly have implicated lung injury as a precipitant of neuroinflammation and brain injury (17)(18)(19)(20). Even absent preexisting lung injury, recent data suggest lung mechanotransduction during high-VT ventilation may induce vagal afferentmediated apoptotic pathways in the brain (17,18).…”

Section: Original Articlementioning

confidence: 99%

“…Several studies similarly have implicated lung injury as a precipitant of neuroinflammation and brain injury (17)(18)(19)(20). Even absent preexisting lung injury, recent data suggest lung mechanotransduction during high-VT ventilation may induce vagal afferentmediated apoptotic pathways in the brain (17,18).…”

Section: Original Articlementioning

confidence: 99%

See 2 more Smart Citations

Favorable Neurocognitive Outcome with Low Tidal Volume Ventilation after Cardiac Arrest

Beitler

Ghafouri

Jinadasa

et al. 2017

Am J Respir Crit Care Med

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Rationale: Neurocognitive outcome after out-of-hospital cardiac arrest (OHCA) is often poor, even when initial resuscitation succeeds. Lower tidal volumes (VTs) attenuate extrapulmonary organ injury in other disease states and are neuroprotective in preclinical models of critical illness.Objective: To evaluate the association between VT and neurocognitive outcome after OHCA.Methods: We performed a propensity-adjusted analysis of a twocenter retrospective cohort of patients experiencing OHCA who received mechanical ventilation for at least the first 48 hours of hospitalization. VT was calculated as the time-weighted average over the first 48 hours, in milliliters per kilogram of predicted body weight (PBW). The primary endpoint was favorable neurocognitive outcome (cerebral performance category of 1 or 2) at discharge.Measurements and Main Results: Of 256 included patients, 38% received time-weighted average VT greater than 8 ml/kg PBW during the first 48 hours. Lower VT was independently associated with favorable neurocognitive outcome in propensityadjusted analysis (odds ratio, 1.61; 95% confidence interval [CI], 1.13-2.28 per 1-ml/kg PBW decrease in VT; P = 0.008). This finding was robust to several sensitivity analyses. Lower VT also was associated with more ventilator-free days (b = 1.78; 95% CI, 0.39-3.16 per 1-ml/kg PBW decrease; P = 0.012) and shockfree days (b = 1.31; 95% CI, 0.10-2.51; P = 0.034). VT was not associated with hypercapnia (P = 1.00). Although the propensity score incorporated several biologically relevant covariates, only height, weight, and admitting hospital were independent predictors of VT less than or equal to 8 ml/kg PBW.Conclusions: Lower VT after OHCA is independently associated with favorable neurocognitive outcome, more ventilator-free days, and more shock-free days. These findings suggest a role for low-VT ventilation after cardiac arrest.

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mentioning

confidence: 86%

Section: Original Articlementioning

confidence: 99%

See 1 more Smart Citation

Favorable Neurocognitive Outcome with Low Tidal Volume Ventilation after Cardiac Arrest

Beitler

Ghafouri

Jinadasa

et al. 2017

Am J Respir Crit Care Med

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“…Specifically, despite the potential to improve long-term cognitive outcomes by improving oxygenation (33) or reducing lung stretch (35,36) in the case of proning or indirectly by shifting the balance between oxygen delivery and oxygen consumption to a more favorable position in the case of neuromuscular blocking agents (32), the effects of these interventions on long-term outcomes remain speculative.…”

Section: Perspectivesmentioning

confidence: 99%

“…Cognitive impairment, an outcome of vital importance to ARDS survivors and their caregivers (37), is common after ARDS (11,13,15,16). Emerging evidence suggests that mechanical ventilation per se may trigger neuronal apoptosis via vagal and dopaminergic pathways (36). In contrast to mechanical ventilation, which is required to support life in ARDS, the selected oxygenation target range may be a potentially modifiable risk factor for long-term cognitive impairment after ARDS.…”

Section: Perspectivesmentioning

confidence: 99%

Can We Optimize Long-Term Outcomes in Acute Respiratory Distress Syndrome by Targeting Normoxemia?

et al. 2014

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Since its original description in 1967, acute respiratory distress syndrome (ARDS) has been recognized as a devastating condition associated with significant morbidity and mortality. Advances in critical care medicine and ARDS management have led to a substantial increase in the number of ARDS survivors. Longterm cognitive impairment after critical illness is a significant public health concern. ARDS survivors frequently experience long-term cognitive impairment, as well as physical impairment, psychiatric morbidity, and reduced health-related quality of life. At present, no intensive care unit-based intervention has been proven to reduce the risk of long-term cognitive impairment after ARDS. To address the urgent need to identify strategies to preserve long-term health, investigators have advocated the measurement of short-and long-term outcomes in clinical trials. Maintaining adequate oxygen delivery to preserve organ function is of vital importance in ARDS management. The optimal target range for arterial oxygenation in ARDS remains unknown, due in part to the challenge to maintain adequate tissue oxygenation and to minimize harm, such as oxygen toxicity. An approach targeted to subnormal oxygenation values (partial pressure of arterial oxygen, 55-80 mm Hg) has emerged as a means to accomplish these aims. In this perspective, we critically evaluate this strategy from short-and long-term perspectives, with a focus on the potential long-term cognitive effects of the strategy. We conclude with a proposal to consider resetting the target range for arterial oxygenation higher (85-110 mm Hg) as a potential strategy to improve the long-term outcomes of ARDS survivors.

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Sepsis‐Associated Encephalopathy

Verdonk¹,

Mazeraud²,

Chrétien³

et al. 2020

Infections of the Central Nervous System

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Mechanical Ventilation Triggers Hippocampal Apoptosis by Vagal and Dopaminergic Pathways

Abstract: These results prove the existence of a pathogenic mechanism of lung stretch-induced hippocampal apoptosis that could explain the neurological changes in ventilated patients and may help to identify novel therapeutic approaches.

Cited by 76 publications

References 50 publications

Favorable Neurocognitive Outcome with Low Tidal Volume Ventilation after Cardiac Arrest

Favorable Neurocognitive Outcome with Low Tidal Volume Ventilation after Cardiac Arrest

Can We Optimize Long-Term Outcomes in Acute Respiratory Distress Syndrome by Targeting Normoxemia?

Sepsis‐Associated Encephalopathy

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