A scoping review protocol on brain PaCO2 levels at altitude for stroke airplane transport

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 A scoping review protocol on brain PaCO2 levels at altitude

STUDY PROTOCOL
A scoping review protocol on brain PaCO2
levels at altitude
Hanna TangID1,2☯*, Laurel CharlesworthID1,2,3☯, Manoj Lalu3,4, Brian Dewar3, Risa Shorr5,
Dariush Dowlatshahi1,2,3
1 Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada, 2 Faculty
of Medicine, University of Ottawa, Ottawa, Ontario, Canada, 3 Ottawa Hospital Research Institute, Ottawa,
Ontario, Canada, 4 Department of Anesthesiology and Pain Medicine, Department of Cellular and Molecular
Medicine, University of Ottawa, Ottawa, Ontario, Canada, 5 Learning Services, The Ottawa Hospital, Ottawa,
Ontario, Canada
☯ These authors contributed equally to this work.
* hatang@toh.ca
Abstract                                       
Background
Aeromedical transfer of patients with ischemic stroke to access hyperacute stroke treatment is
becoming increasingly common. Little is known about how rapid changes of altitude and atmo-
spheric pressure can impact cerebral perfusion and ischemic burden. In patients with ischemic
stroke, there is a theoretical possibility that this physiologic response of hypoxia-driven hyper-
ventilation at higher altitude can lead to a relative drop in PaCO2. This would ultimately result in
cerebral vasoconstriction, and therefore worsening of the ischemic burden in patients with
ischemic stroke. Currently, there are no specific recommendations in stroke guidelines for opti-
mizing altitude of aeromedical transportation to minimize the rate of ischemic burden. In this
scoping review, we aim to map the available literature that addressed whether PaCO2 changes
with altitude. This would be the steppingstone for more in-depth analyses into the cerebral auto-
regulatory consequences of high altitude on cerebral ischemia to form future guidelines.
Methods and analysis
We will follow scoping review methods recommended by the Joanna Briggs Institute. Elec-
tronic databases MEDLINE, Embase, Web of Science, and Cochrane Central Register of
Systematic will be systematically searched to identify articles that report on the acute
response of PaCO2 on acute change in altitude. Two independent investigators will perform
duplicate title and abstract screening and full-text review, followed by duplicate data extrac-
tion. We will present quantitative data using descriptive statistics. Key textual information
will be synthesized in a tabular format Simple statistics on the frequency of papers, data will
be presented via histogram.
Ethics and dissemination
This scoping review does not require ethical approval. The results of our scoping review will
be published in academic medical journals and presented at medical conferences. The find-
ings will highlight the current availability of literature on PaCO2 changes with altitude.

Registration

This scoping review protocol has been registered in Open Science Framework (DOI 10.

17605/OSF.IO/UVK83).

Introduction

Aeromedical transfer of patients with ischemic stroke allows access to hyperacute therapies

that are not otherwise geographically available [1, 2]. Since 2018, when the Thrombectomy 6

to 24 Hours after Stroke with a Mismatch between Deficit and Infarct Trial demonstrated a

90-day mortality and recovery benefit with endovascular therapy (EVT) in patients who pres-

ent with acute stroke within 24 hours of onset [3], the treatment window for ischemic stroke

was extended to 24 hours from last seen well. This led to an expansion of catchment areas of

EVT-capable comprehensive stroke centres. To this end, aeromedical transport is increasingly

used worldwide to reduce the overall time to treatment for patients with strokes suspected to

be secondary to a large vessel occlusion [4]. However, little is known about how rapid changes

of altitude and atmospheric pressure can impact cerebral perfusion and ischemic burden.

At sea level, ventilation is driven by predominantly by arterial pressure of carbon dioxide

(PaCO2) with a secondary ventilatory response to hypoxia with lower arterial pressures of oxy-

gen (PaO2). The partial pressure of oxygen (pO2) decreases at higher altitudes when atmo-

spheric pressure decreases, leading to relative hypoxia; this hypobaric hypoxic environment

causes hypoxia-driven hyperventilation, in an attempt to normalize PaO2 [5, 6]. In patients

with ischemic stroke, there is a theoretical possibility that this physiologic response of hyp-

oxia-driven hyperventilation at higher altitude can lead to a relative drop in PaCO2. There is a

nearly direct linear relationship between PaCO2 and cerebral autoregulation, with hypocarbia

causing vasoconstriction. In the hypobaric hypoxic environment, hypoxia-drive hyperventila-

tion lowers PaCO2 which could lead to decreased cerebral blood flow and therefore worsening

of the ischemic burden in patients with ischemic stroke. Although the use of supplemental

oxygen could mitigate some of the effects of the hypobaric hypoxic environment during aero-

medical transport, there are no current protocols for how this should be implemented, and it

is currently unknown what blood oxygen saturation (spO2) should be targeted. Furthermore,

in patients with concurrent diseases impacting blood oxygenation, supplemental oxygen alone

may not be sufficient to optimize PaO2 and could require modifications in the cabin pressure

and cruising altitude which could delay air transfer.

Currently, there are no specific recommendations in stroke guidelines for optimizing alti-

tude of aeromedical transportation to minimize the rate of ischemic burden [7–11]. However,

before these guidelines can be established, there are some knowledge gaps that will need to be

addressed. The physiologic relationship between PaO2, PaCO2, altitude and cerebral autoregu-

lation during aeromedical transfer is not well known. In this scoping review, we aim to map

the available literature that addresses whether PaCO2 changes with altitude. This scoping

review will provide essential foundational information for future investigations into the cere-

bral autoregulatory consequences of high altitude on cerebral ischemia.

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