We read with great interest the review article by Eckenhoff et al. on the different approaches used in preclinical perioperative neurocognitive disorder research.1  In this review, the authors provided data on the various preclinical models used in scientific literature to study perioperative neurocognitive disorder that include molecular, cell culture, brain slices, and animal models. Surprisingly, the possible role of mechanical ventilation as cause of perioperative neurocognitive disorder is not mentioned.

There is growing preclinical and clinical evidence on the relevance of mechanical ventilation–induced neurocognitive damage.2–5  Various mechanisms have been described to explain how mechanical ventilation–induced alveolar stretching might trigger neuroinflammation: local brain action of systemic lung-derived inflammatory cytokines, afferent neuronal signaling by vagal-mediated dopaminergic lung–brain axis, and histopathologic changes in blood–brain barrier and brain deposition of β-amyloid.2  These are also known as “brain–lung” cross-talk.2  Despite the ample preclinical evidence on mechanical ventilation–induced neurocognitive damage, there are no clinical studies designed to evaluate the effect of mechanical ventilation on neuroinflammation and perioperative neurocognitive disorder, but there is evidence that mechanical ventilation duration is a risk factor for neurocognitive impairment in critically ill patients and that, in neurocritical care patients, mechanical ventilation setting is associated with functional outcome.3,4  Furthermore, a retrospective study in patients resuscitated after out-of-hospital cardiac arrest proved that lower tidal volume associates with better neurocognitive outcome.5 

We wonder if, considering this evidence, Eckenhoff et al. agree that mechanical ventilation–related neuroinflammation might ultimately contribute to perioperative neurocognitive disorder and therefore deserves to be addressed in appropriately designed preclinical and clinical studies.

The authors declare no competing interests.

1.
Eckenhoff
RG
,
Maze
M
,
Xie
Z
,
Culley
DJ
,
Goodlin
SJ
,
Zuo
Z
,
Wei
H
,
Whittington
RA
,
Terrando
N
,
Orser
BA
,
Eckenhoff
MF
.
Perioperative neurocognitive disorder: State of the preclinical science.
Anesthesiology
.
2020
;
132
:
55
68
2.
Bilotta
F
,
Giordano
G
,
Sergi
PG
,
Pugliese
F
.
Harmful effects of mechanical ventilation on neurocognitive functions.
Crit Care
.
2019
;
23
:
273
3.
Sakusic
A
,
O’Horo
JC
,
Dziadzko
M
,
Volha
D
,
Ali
R
,
Singh
TD
,
Kashyap
R
,
Farrell
AM
,
Fryer
JD
,
Petersen
R
,
Gajic
O
,
Rabinstein
AA
.
Potentially modifiable risk factors for long-term cognitive impairment after critical illness: A systematic review.
Mayo Clin Proc
.
2018
;
93
:
68
82
4.
Borsellino
B
,
Schultz
MJ
,
Gama de Abreu
M
,
Robba
C
,
Bilotta
F
.
Mechanical ventilation in neurocritical care patients: A systematic literature review.
Expert Rev Respir Med
.
2016
;
10
:
1123
32
5.
Beitler
JR
,
Ghafouri
TB
,
Jinadasa
SP
,
Mueller
A
,
Hsu
L
,
Anderson
RJ
,
Joshua
J
,
Tyagi
S
,
Malhotra
A
,
Sell
RE
,
Talmor
D
.
Favorable neurocognitive outcome with low tidal volume ventilation after cardiac arrest.
Am J Respir Crit Care Med
.
2017
;
195
:
1198
206