Systematic review of cognitive impairment and brain insult after mechanical ventilation

Abstract

We conducted a systematic review following the PRISMA protocol primarily to identify publications that assessed any links between mechanical ventilation (MV) and either cognitive impairment or brain insult, independent of underlying medical conditions. Secondary objectives were to identify possible gaps in the literature that can be used to inform future studies and move toward a better understanding of this complex problem. The preclinical literature suggests that MV is associated with neuroinflammation, cognitive impairment, and brain insult, reporting higher neuroinflammatory markers, greater evidence of brain injury markers, and lower cognitive scores in subjects that were ventilated longer, compared to those ventilated less, and to never-ventilated subjects. The clinical literature suggests an association between MV and delirium, and that delirium in mechanically ventilated patients may be associated with greater likelihood of long-term cognitive impairment; our systematic review found no clinical study that demonstrated a causal link between MV, cognitive dysfunction, and brain insult. More studies should be designed to investigate ventilation-induced brain injury pathways as well as any causative linkage between MV, cognitive impairment, and brain insult.

Transvenous Diaphragm Neurostimulation Mitigates Ventilation-associated Brain Injury

“…3,5,6,8 Two recently published systematic reviews on MV associated with brain injury reported thirteen preclinical papers that describe hippocampal apoptosis and neuroinflammation as experimental findings linked to VABI. 9,10 In a porcine model, our group showed that even lung-protective MV settings were associated with brain injury after 50 hours of MV; 5 moreover, in the same study our group showed that serum concentrations of glial fibrillary acid protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) were greater in the MV subjects than in the never-ventilated subjects, revealing an opportunity for the use of these markers for VABI. 5,6 It has been hypothesized that either an inflammatory or a neural pathway might lead to the development of VABI.…”

“…Heart rate variability is a wellaccepted surrogate marker of the balance between vagal (parasympathetic) activity and sympathetic activity. 9 Root mean square of the standard deviation (RMSSD), a time-domain method of HRV analysis, was measured in our study (Figure 6). 9 All mechanically ventilated groups had two time periods analyzed during the 50 hours of the experiment, the first six hours after initiating the experiment (hours 0-6) and the last six hours before the end of the experiment (hours 44-50).…”

“…9 Root mean square of the standard deviation (RMSSD), a time-domain method of HRV analysis, was measured in our study (Figure 6). 9 All mechanically ventilated groups had two time periods analyzed during the 50 hours of the experiment, the first six hours after initiating the experiment (hours 0-6) and the last six hours before the end of the experiment (hours 44-50). Each subject had the same number of R-R intervals analyzed: 21,600 R-R intervals from hours 0-6, and 21,600 R-R intervals from hours 44-50.…”

“…However, preclinical studies investigating VABI in fully grown subjects have shown that mechanically ventilated subjects have greater numbers of microglia, greater numbers of reactive astrocytes, and a higher incidence of cellular apoptosis compared with never-ventilated subjects ( 3 , 5 , 6 , 8 ). Two recently published systematic reviews on MV associated with brain injury reported 13 preclinical papers that describe hippocampal apoptosis and neuroinflammation as experimental findings linked to VABI ( 9 , 10 ). In a porcine model, our group showed that even lung-protective MV settings were associated with brain injury after 50 hours of MV ( 5 ); moreover, in the same study, our group showed that serum concentrations of GFAP (glial fibrillary acid protein) and UCHL1 (ubiquitin carboxy-terminal hydrolase L1) were greater in the MV subjects than in the never-ventilated subjects, revealing an opportunity for the use of these markers for VABI ( 5 , 6 ).…”

Pathophysiology of Brain Injury and Neurological Outcome in Acute Respiratory Distress Syndrome: A Scoping Review of Preclinical to Clinical Studies

“…Also, included studies did not report some important factors such as stroke risk factors that may have confounded the reported ABIs. A recent systematic review demonstrated that delirium and cognitive impairment were associated with mechanical ventilation, and therefore, it is possible that poor neurological outcome may be attributed to mechanical ventilation alone [ 69 ]. However, that study was not focused on subjects with ARDS and our study only included animals and patients with ARDS and provides a comprehensive review of ABI after ARDS.…”