Abstract

Circulation of perfluorocarbon (PFC) through corporeal cavities has received interest by virtue of its potential to supplement oxygenation via mechanical ventilation. However, the technology is not mature enough for clinical application, due to the knowledge gaps regarding the limiting factors hampering oxygen transport from PFC to blood. In this paper, we investigate a novel hypothesis that hypothermic peritoneal perfusion of cold oxygenated PFC may improve oxygenation of blood by facilitating the diffusion of oxygen from PFC to blood. Our hypothesis originates from physics-inspired insights that both hypothermia and PFC cooling may increase PFC-to-blood oxygen tension gradient: (i) hypothermia may decrease venous oxygen tension while (ii) cooling PFC may increase oxygen tension therein by increasing its oxygen solubility. Using a physics-based mathematical model capable of simulating oxygen tension responses to mechanical ventilation and peritoneal PFC perfusion under normothermic and hypothermic conditions, we analyzed the effect of hypothermic peritoneal cold PFC perfusion on blood oxygenation. The results predicted that peripheral oxygen saturation may be improved by 5–10% by peritoneal perfusion of oxygenated 15 °C PFC at 32 °C body temperature compared with peritoneal perfusion of oxygenated 37.5 °C PFC at 37.5 °C body temperature. The results also predicted that cooling PFC may play a more meaningful role than hypothermia. Pending the investigation of adverse impact of hypothermia and cold PFC on homeostasis, hypothermic cold PFC perfusion may improve peritoneal oxygenation by facilitating diffusion.

References

1.
Grotberg
,
J. C.
,
Reynolds
,
D.
, and
Kraft
,
B. D.
,
2023
, “
Management of Severe Acute Respiratory Distress Syndrome: A Primer
,”
Crit. Care
,
27
(
1
), p.
289
.10.1186/s13054-023-04572-w
2.
Chiu
,
L.-C.
, and
Kao
,
K.-C.
,
2021
, “
Mechanical Ventilation During Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome: A Narrative Review
,”
J. Clin. Med.
,
10
(
21
), p.
4953
.10.3390/jcm10214953
3.
Factora
,
F. N. F.
,
Bustamante
,
S.
,
Spiotta
,
A.
, and
Avitsian
,
R.
,
2011
, “
Intracranial Hemorrhage Surgery on Patients on Mechanical Circulatory Support: A Case Series
,”
J. Neurosurg. Anesthesiol.
,
23
(
1
), pp.
30
34
.10.1097/ANA.0b013e3181eee55e
4.
Wrisinger
,
W. C.
, and
Thompson
,
S. L.
,
2022
, “
Basics of Extracorporeal Membrane Oxygenation
,”
Surg. Clin.
,
102
(
1
), pp.
23
35
.10.1016/j.suc.2021.09.001
5.
Gattinoni
,
L.
,
Carlesso
,
E.
, and
Langer
,
T.
,
2011
, “
Clinical Review: Extracorporeal Membrane Oxygenation
,”
Crit. Care
,
15
(
6
), pp.
243
246
.10.1186/cc10490
6.
Chaves
,
R. C. D. F.
,
Rabello
,
R.
,
Timenetsky
,
K. T.
,
Moreira
,
F. T.
,
Vilanova
,
L. C. D. S.
,
Bravim
,
B. D. A.
,
Serpa
,
A.
, and
Corrêa
,
T. D.
,
2019
, “
Extracorporeal Membrane Oxygenation: A Literature Review
,”
Rev. Bras. Ter. Intensiva
,
31
(
3
), pp.
410
424
.10.5935/0103-507X.20190063
7.
Biffi
,
S.
,
Di Bella
,
S.
,
Scaravilli
,
V.
,
Peri
,
A. M.
,
Grasselli
,
G.
,
Alagna
,
L.
,
Pesenti
,
A.
, and
Gori
,
A.
,
2017
, “
Infections During Extracorporeal Membrane Oxygenation: Epidemiology, Risk Factors, Pathogenesis and Prevention
,”
Int. J. Antimicrob. Agents
,
50
(
1
), pp.
9
16
.10.1016/j.ijantimicag.2017.02.025
8.
Jin
,
Y.
,
Zhang
,
Y.
, and
Liu
,
J.
,
2023
, “
Ischemic Stroke and Intracranial Hemorrhage in Extracorporeal Membrane Oxygenation for COVID-19: A Systematic Review and Meta-Analysis
,”
Perfusion
,
38
(
8
), pp.
1722
1733
.10.1177/02676591221130886
9.
Solass
,
W.
,
Horvath
,
P.
,
Struller
,
F.
,
Königsrainer
,
I.
,
Beckert
,
S.
,
Königsrainer
,
A.
,
Weinreich
,
F.-J.
, and
Schenk
,
M.
,
2019
, “
Functional Vascular Anatomy of the Peritoneum in Health and Disease
,”
Pleura Peritoneum
,
1
(
3
), pp.
145
158
.10.1515/pp-2016-0015
10.
Klein
,
J.
,
Faithfull
,
N. S.
,
Salt
,
P. J.
, and
Trouwborst
,
A.
,
1986
, “
Transperitoneal Oxygenation With Fluorocarbons
,”
Anesth. Analg.
,
65
(
7
), pp.
734
738
.10.1213/00000539-198607000-00005
11.
Faithfull
,
N. S.
,
Klein
,
J.
,
Vanderzee
,
H. T.
, and
Salt
,
P. J.
,
1984
, “
Whole Body Oxygenation Using Intraperitoneal Perfusion of Fluorocarbons
,”
Br. J. Anaesth.
,
56
(
8
), pp.
867
872
.10.1093/bja/56.8.867
12.
Lowe
,
K. C.
,
1987
, “
Perfluorocarbons as Oxygen-Transport Fluids
,”
Comp. Biochem. Physiol. Part A: Physiol.
,
87
(
4
), pp.
825
838
.10.1016/0300-9629(87)90001-6
13.
Chiba
,
T.
,
Harrison
,
M. R.
,
Ohkubo
,
T.
,
Rollins
,
M. D.
,
Albanese
,
C. T.
, and
Jennings
,
R. W.
,
1999
, “
Transabdominal Oxygenation Using Perfluorocarbons
,”
J. Pediatr. Surg.
,
34
(
5
), pp.
895
901
.10.1016/S0022-3468(99)90394-9
14.
Fiala
,
A.
,
Slagle
,
C.
,
Legband
,
N.
,
Aghabaglou
,
F.
,
Buesing
,
K.
,
Borden
,
M.
,
Harris
,
S.
, and
Terry
,
B.
,
2020
, “
Treatment of a Rat Model of LPS-Induced ARDS Via Peritoneal Perfusion of Oxygen Microbubbles
,”
J. Surg. Res.
,
246
, pp.
450
456
.10.1016/j.jss.2019.09.017
15.
Legband
,
N.
,
Hatoum
,
L.
,
Thomas
,
A.
,
Kreikemeier-Bower
,
C.
,
Hostetler
,
D.
,
Buesing
,
K.
,
Borden
,
M.
, and
Terry
,
B.
,
2016
, “
Peritoneal Membrane Oxygenation Therapy for Rats With Acute Respiratory Distress Syndrome
,”
ASME J. Med. Devices
,
10
(
2
), p.
020905
.10.1115/1.4033201
16.
Matsutani
,
N.
,
Takase
,
B.
,
Nogami
,
Y.
,
Ozeki
,
Y.
,
Ishihara
,
M.
, and
Maehara
,
T.
,
2008
, “
The Peritoneum as a Novel Oxygenation Organ: Revitalization of Intraperitoneal Oxygenation
,”
Shock
,
30
(
3
), pp.
250
253
.10.1097/SHK.0b013e318162be0a
17.
Jägers
,
J.
,
Wrobeln
,
A.
, and
Ferenz
,
K. B.
,
2021
, “
Perfluorocarbon-Based Oxygen Carriers: From Physics to Physiology
,”
Pflügers Arch.-Eur. J. Physiol.
,
473
(
2
), pp.
139
150
.10.1007/s00424-020-02482-2
18.
Barr
,
J.
,
Livne
,
A.
,
Lushkov
,
G.
,
Vinograd
,
I.
,
Efrati
,
Y.
,
Ballin
,
A.
,
Lahat
,
E.
, and
Eshel
,
G.
,
1994
, “
Peritoneal Ventilation: An Animal Model of Extrapulmonary Ventilation in Experimental Adult Respiratory Distress Syndrome
,”
Pediatr. Res.
,
35
(
6
), pp.
682
684
.10.1203/00006450-199406000-00012
19.
Legband
,
N.
,
Feshitan
,
J.
,
Borden
,
M.
, and
Terry
,
B.
,
2014
, “
Peritoneal Microbubble Oxygenation: An Extrapulmonary Respiration Treatment in Rabbits
,”
ASME J. Med. Devices
,
8
(
3
), p.
030944
.10.1115/1.4027112
20.
Singh
,
I.
,
1934
, “
Absorption of Oxygen From the Peritoneal Cavity and the Stomach
,”
Q. J. Exp. Physiol.: Transl. Integr.
,
24
(
1
), pp.
45
54
.10.1113/expphysiol.1934.sp000624
21.
Mohammed
,
R. U. R.
,
Zollinger
,
N. T.
,
McCain
,
A. R.
,
Romaguera‐Matas
,
R.
,
Harris
,
S. P.
,
Buesing
,
K. L.
,
Borden
,
M. A.
, and
Terry
,
B. S.
,
2022
, “
Testing Oxygenated Microbubbles Via Intraperitoneal and Intrathoracic Routes on a Large Pig Model of LPS‐Induced Acute Respiratory Distress Syndrome
,”
Physiol. Rep.
,
10
(
17
), p.
e15451
.10.14814/phy2.15451
22.
Carr
,
S. R.
,
Cantor
,
J. P.
,
Rao
,
A. S.
,
Lakshman
,
T. V.
,
Collins
,
J. E.
, and
Friedberg
,
J. S.
,
2006
, “
Peritoneal Perfusion With Oxygenated Perfluorocarbon Augments Systemic Oxygenation
,”
Chest
,
130
(
2
), pp.
402
411
.10.1378/chest.130.2.402
23.
Feshitan
,
J. A.
,
Legband
,
N. D.
,
Borden
,
M. A.
, and
Terry
,
B. S.
,
2014
, “
Systemic Oxygen Delivery by Peritoneal Perfusion of Oxygen Microbubbles
,”
Biomaterials
,
35
(
9
), pp.
2600
2606
.10.1016/j.biomaterials.2013.12.070
24.
Giffin
,
D. M.
,
Gow
,
K. W.
,
Warriner
,
C. B.
,
Walley
,
K. R.
, and
Phang
,
P. T.
,
1998
, “
Oxygen Uptake During Peritoneal Ventilation in a Porcine Model of Hypoxemia
,”
Crit. Care Med.
,
26
(
9
), pp.
1564
1568
.10.1097/00003246-199809000-00025
25.
Biederman-Thorson
,
M. A.
,
Schmidt
,
R. F.
, and
Thews
,
G.
,
2013
,
Human Physiology
,
Springer Science & Business Media
, New York.
26.
Valkov
,
S.
,
Mohyuddin
,
R.
,
Nilsen
,
J. H.
,
Schanche
,
T.
,
Kondratiev
,
T. V.
,
Sieck
,
G. C.
, and
Tveita
,
T.
,
2019
, “
Organ Blood Flow and O2 Transport During Hypothermia (27 °C) and Rewarming in a Pig Model
,”
Exp. Physiol.
,
104
(
1
), pp.
50
60
.10.1113/EP087205
27.
Tveita
,
T.
, and
Sieck
,
G. C.
,
2022
, “
Physiological Impact of Hypothermia: The Good, the Bad, and the Ugly
,”
Physiology
,
37
(
2
), pp.
69
87
.10.1152/physiol.00025.2021
28.
Dias
,
A. M. A.
,
Freire
,
M.
,
Coutinho
,
J. A. P.
, and
Marrucho
,
I. M.
,
2004
, “
Solubility of Oxygen in Liquid Perfluorocarbons
,”
Fluid Phase Equilib.
,
222–223
, pp.
325
330
.10.1016/j.fluid.2004.06.037
29.
Doosthosseini
,
M.
,
Aroom
,
K.
,
Aroom
,
M.
,
Culligan
,
M.
,
Naselsky
,
W.
,
Thamire
,
C.
, and
Haslach
,
H. W.
, et al.,
2022
, “
Monitoring, Control System Development, and Experimental Validation for a Novel Extrapulmonary Respiratory Support Setup
,”
IEEE/ASME Trans. Mechatron.
,
27
(
5
), pp.
4177
4187
.10.1109/TMECH.2022.3145832
30.
Costanzo
,
L. S.
,
2021
,
Costanzo Physiology E-Book
,
Elsevier Health Sciences
, Richmond, VA.
31.
Brewer
,
L. M.
,
Orr
,
J. A.
, and
Pace
,
N. L.
,
2008
, “
Anatomic Dead Space Cannot Be Predicted by Body Weight
,”
Respir. Care
,
53
(
7
), pp.
885
891
.http://rc.rcjournal.com/content/53/7/885.abstract
32.
Pittman
,
R. N.
,
2016
,
Regulation of Tissue Oxygenation
,
Morgan Claypool Life Science
, San Rafael, CA.
33.
Kim
,
C.-S.
,
Ansermino
,
J. M.
, and
Hahn
,
J.-O.
,
2016
, “
A Comparative Data-Based Modeling Study on Respiratory CO2 Gas Exchange During Mechanical Ventilation
,”
Front. Bioeng. Biotechnol.
,
4
, p.
8
.10.3389/fbioe.2016.00008
34.
Willford
,
D. C.
,
Hill
,
E. P.
, and
Moores
,
W. Y.
,
1986
, “
Theoretical Analysis of Oxygen Transport During Hypothermia
,”
J. Clin. Monit.
,
2
(
1
), pp.
30
43
.10.1007/BF01619175
35.
Willford
,
D. C.
,
Hill
,
E. P.
,
White
,
F. C.
, and
Moores
,
W. Y.
,
1986
, “
Decreased Critical Mixed Venous Oxygen Tension and Critical Oxygen Transport During Induced Hypothermia in Pigs
,”
J. Clin. Monit.
,
2
(
3
), pp.
155
168
.10.1007/BF01620548
36.
Krogh
,
A.
,
1922
,
The Anatomy and Physiology of Capillaries
,
Yale University Press
, New Haven, CT.
37.
Benitez
,
J.
,
2016
,
Principles and Modern Applications of Mass Transfer Operations
,
Wiley
, Hoboken, NJ.
38.
Dias
,
A. M. A.
,
Bonifacio
,
R. P.
,
Marrucho
,
I. M.
,
Pádua
,
A. A. H.
, and
Gomes
,
M. F. C.
,
2003
, “
Solubility of Oxygen in N-Hexane and in N-Perfluorohexane. Experimental Determination and Prediction by Molecular Simulation
,”
Phys. Chem. Chem. Phys.
,
5
(
3
), pp.
543
549
.10.1039/b207512c
39.
Tivay
,
A.
,
Kramer
,
G. C.
, and
Hahn
,
J.-O.
,
2022
, “
Collective Variational Inference for Personalized and Generative Physiological Modeling: A Case Study on Hemorrhage Resuscitation
,”
IEEE Trans. Biomed. Eng.
,
69
(
2
), pp.
666
677
.10.1109/TBME.2021.3103141
40.
Kingma
,
D. P.
, and
Welling
,
M.
,
2019
, “
An Introduction to Variational Autoencoders
,”
Found. Trends® Mach. Learn.
,
12
(
4
), pp.
307
392
.10.1561/2200000056
41.
Blei
,
D. M.
,
Kucukelbir
,
A.
, and
McAuliffe
,
J. D.
,
2017
, “
Variational Inference: A Review for Statisticians
,”
J. Am. Stat. Assoc.
,
112
(
518
), pp.
859
877
.10.1080/01621459.2017.1285773
42.
Hoffman
,
M. D.
,
Blei
,
D. M.
,
Wang
,
C.
, and
Paisley
,
J.
,
2013
, “
Stochastic Variational Inference
,”
J. Mach. Learn. Res.
, 14, pp.
1303
1347
.https://jmlr.org/papers/volume14/hoffman13a/hoffman13a.pdf
43.
Ranganath
,
R.
,
Gerrish
,
S.
, and
Blei
,
D.
,
2014
, “
Black Box Variational Inference
,” 17th International Conference on Artificial Intelligence and Statistics (
AISTATS
),
Reykjavik, Iceland
, Apr. 22–25, pp.
814
822
.https://proceedings.mlr.press/v33/ranganath14.pdf
44.
Walley
,
K. R.
,
2011
, “
Use of Central Venous Oxygen Saturation to Guide Therapy
,”
Am. J. Respir. Crit. Care Med.
,
184
(
5
), pp.
514
520
.10.1164/rccm.201010-1584CI
45.
Mohyuddin
,
R.
,
Dietrichs
,
E. S.
,
Sundaram
,
P.
,
Kondratiev
,
T.
,
Figenschou
,
M. F.
,
Sieck
,
G. C.
, and
Tveita
,
T.
,
2021
, “
Cardiovascular Effects of Epinephrine During Experimental Hypothermia (32 C) With Spontaneous Circulation in an Intact Porcine Model
,”
Front. Physiol.
,
12
, p.
718667
.10.3389/fphys.2021.718667
46.
Schou
,
H.
,
Perez de Sa
,
V.
,
Sigurdardottir
,
M.
,
Roscher
,
R.
,
Jonmarker
,
C.
, and
Werner
,
O.
,
1996
, “
Circulatory Effects of Hypoxia, Acute Normovolemic Hemodilution, and Their Combination in Anesthetized Pigs
,”
J. Am. Soc. Anesthesiol.
,
84
(
6
), pp.
1443
1454
.10.1097/00000542-199606000-00021
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