PaO2 target
CPR 2015 :
- routinely
> 60 mmHg
- ALI - ARDS
- chronic hypercapnia
- paraquat intoxication
55 - 80 mmHg
~ 50 mmHg
~ 40 mmHg (lactate)
- acute myoc. infarction
- acute brain injury
80 - 100 mmHg
80 - 100 mmHg
how much oxygen ?
Serge Brimioulle
Department of Intensive Care
ir
is
Erasme Hospital, Brussels, Belgium
O2 pressure
Cell respiration
in
ai
re
s
Oxygenation
(mmHg)
- atmospheric
- alveolar
- arterial
- capillary
- muscle (rest)
- muscle (work)
- mitochondrial
160
100
97
…
40
4
1
100
Alv.
Gnaiger, AEMB 2003
Wagner, ERJ 2008
Art.
- at rest, PcO2 40 mmHg (Mb sat. 100%), PmO2 2
- at work, PcO2 4 mmHg (Mb sat. 50%), PmO2 0.3
Cap.
75
50
Mus.
rest
25
Mus.
work Mit.
se
m
0
Advantages of low PcO2
- optimal : maximal mitoch. energy production
prevents excessive ROS production
- maximal RBC - cell gradient (diffusion limitation)
- arteriolar vasodilation (tissue autoregulation)
- HIF-stimulated VEGF and angiogenesis
Oxygen is good
Falkowski, Science 2005
Hypoxia - HIF
Smith, BJH 2008
- HIF = transcription factors (hundreds of genes)
- continuous HIF production and degradation
normal : PHD-modified, VHL-bound, metabolized
hypoxia : PHD inhibition
At organ level
- ventilation
- HPV
- erythropoiesis
- cardiac output
At cell level
- energy metabolism
- vasomotor regulation
- angiogenesis (VEGF)
- cell growth & apoptosis
Hypoxia
West, AAS 1990
- Everest 1981, Everest-II 1986
Hypoxia - brain ischemia
Miyamoto, Neurology 2000
- rats, ischemia < transient MCA occlusion
- blood gases: 7.65 - 8 - 30 and 7.56 - 11 - 30
- left shift of ODC, quicker pulm. oxygen loading
PaO2
- hypoxia
- normoxia
- hyperoxia
- preserved contractility and hemodynamics
- (relatively) preserved exercise capacity
46 ± 1
120 ± 4
214 ± 6
% necrosis
hemisph.
cortex
24 ± 5 *
13 ± 3 *
17 ± 7
8±5
8±2*
1±1*
ir
is
- impairment of cognitive function
- persistence for more than 12 months
Hypoxia - brain trauma
Hypoxia - stroke
in
ai
re
s
Diringer, COCC 2008
- mitochondrial dysfunction, low PbO2
- secondary brain injury due to ischemia
- many animal studies, often hyperbaric
- may be effective in selected conditions
- hyperbaric oxygen well-known toxicity
- pulmonary, ocular, … and cerebral
- 3 clinical studies on hyperbaric oxygen
- Anderson, Stroke 1991
- Nighoghossian, Stroke 1995
- Rusyniak, Stroke 2003
- no evident clinical benefit
- questionable trials design
se
m
- normobaric oxygen
- animal and clinical studies
- better ICP, PbO2, microdialysis data
- no clinical or PET benefit
Singhal, IJS 2006
Oxygen holocaust
Oxygen holocaust
- anaerobic reactions and unicellular organisms
- photosystem (CO2 + H2S) : green & purple bacteria
- photosystem (CO2 + H2O) : cyanobacteria
- photosynthesis by plants < chloroplasts (~ cyanob.)
- sea – air – land poisoning by oxygen
- death of most oxygen-sensitive organisms
cyanobacteria
25
O2 atm (%)
De Duve, 2002
20
15
10
5
0
-4
-3
-2
-1
time (billions years)
0
- integration of oxygen-using bacteria : mitochondrias
- energy-efficient (ATP) aerobic cell respiration
- multicellular animals, land invasion
Oxygen is bad
Nathan, BMB 1999
- oxidative phosphorylation in mitochondrias (COX)
- glucose + O2 + ADP ==> H2O + CO2 + ATP
- production of ROS : O2-, OH•, H2O2
Nathan, BMB 1999
- production of ROS : O2-, OH•, H2O2
- antioxidative protective mechanisms
If imbalance
- hypoxia or ischemia : "reductive" stress
- hyperoxia or reperfusion : "oxidative" stress
- intramitochondrial dysfunction (Ca++, Fe++)
- mitochondrial permeabilization and swelling
- cellular toxicity …
ir
is
Antioxidative protective mechanisms
- superoxide dismutase
- GSH
- glutathione peroxidase
- NADPH
- glutathione reductase
- vitamin C
- NAD(P) transhydrogenase
- vitamin E
Oxygen is bad
Chalhoub, AAS 2011
Huet, CCM 2011
Hyperoxia - surgery
in
ai
re
s
ROS production
- Proxi trial, n = 1386
perop 80 vs 30% O2
- no diff. in infection
- MLR predictor (OR 1.3)
2-yr mortality, %
*
20
10
0
NO2
HO2
se
m
Surgery
- 32 pts after low- and intermediate-risk surgery
- perfusion of serum on endothelial cells
- unchanged cytokines production
- ROS production, related to surgery "magnitude"
Cardiac arrest
- 12 pts after cardiac arrest (vs septic shock)
- ROS production, antioxidant activity
- impaired mitochondrial chain activity
- increased anaerobic metabolism
Meyhoff, AA 2012
Hyperoxia - cardiac arrest
Pilcher, Resusc 2012
Hyperoxia - cardiac arrest
- extrahosp CA (Finland)
witnessed, VF, ROSC,
n = 28 (± hypothermia)
survival 20 / 28
- FiO2 100 vs 30% (1 hr)
maintain SpO2 95%
- suppl. O2 in 5 / 14
Animal studies - hyperoxia vs normoxia - effect on mortality
Kuisma, Resusc 2006
30
100
PaO2 - 10' 158 ± 30 373 ± 42*
PaO2 - 60'
109 ± 7
349 ± 47*
NSE - 24h
11 ± 2
13 ± 2
NSE - 48h
14 ± 5
19 ± 5
S100 - 24h
21 ± 4
73 ± 30
S100 - 48h
23 ± 5
49 ± 16
Hyperoxia - cardiac arrest
- 120 US hospitals, 5 yrs
- nontraumatic CA
first PaO2 in 24 h
n = 6326
- hypoxia < 60 mmHg
- hyperoxia > 300 mmHg
- MLR predictor (OR 1.8)
Kilgannon, JAMA 2010
hosp. mortality, %
*
*
60
Hyperoxia - cardiac arrest
- 125 ICUs, Aust-NZ
n = 12108
worst PaO2 in 24 h
20
- MLR predictor (OR 1.2)
Cox non-predictor
0
NO2
*
*
40
20
0
HO2
hO2
NO2
HO2
ir
is
hO2
hosp. mortality, %
60
- hypoxia < 60 mmHg
- hyperoxia > 300 mmHg
40
Bellomo, CC 2011
Hyperoxia - cardiac arrest
Hyperoxia - cardiac arrest
in
ai
re
s
Ferguson, Circ 2012
- PICAnet, 2003-2010
n = 1875
PaO2 in 1 hr
ICU mortality, %
40
*
*
- MLR predictor (OR 1.3)
- Aust-NZ, 2007-2011
CA < VF, n = 584
most aN PaO2 in 24 h
- hypoxia < 60 mmHg
- hyperoxia > 300 mmHg
20
Ihle, CCR 2012
hosp. mortality, %
60
40
20
- MLR : no effect
0
NO2
HO2
0
hO2
NO2
HO2
se
m
hO2
Hyperoxia - cardiac arrest
Guerra-Wallace, PCCM 2013
- PICU, 2004-2008
surv > 48 h, n = 74
PaO2 in 24 hr
6-mo mortality, %
20
- hypoxia < 60 mmHg
- hyperoxia > 300 mmHg
10
- no difference
0
hO2
NO2
HO2
Hyperoxia - cardiac arrest
Wang, Resusc 2014
Hyperoxia - cardiac arrest
Wang, Resusc 2014
Hyperoxia - cardiac arrest
Elmer, ICM 2015
- Pittsburgh, 2008-2010
surv > 24 h, n = 184
PaO2 exposure (h)
- hypoxia < 60 mmHg
- hyperoxia > 300 mmHg
ir
is
- 1-hr HO2 ind. predictor
of survival (OR 0.83)
Hyperoxia - brain trauma
Hyperoxia - stroke
in
ai
re
s
Rincon, JNNP 2013
- 61 US hospitals, 5 yrs
n = 12121
PaO2 in 24 h
hosp. mortality, %
- 84 US hospitals, 5 yrs
n = 2894
PaO2 in 24 h
*
40
- hypoxia < 60 mmHg
- hyperoxia > 300 mmHg
*
- hypoxia < 60 mmHg
- hyperoxia > 300 mmHg
20
- MLR predictor (OR 1.5)
Rincon, CCM 2014
hosp. mortality, %
60
*
*
40
20
- MLR predictor (OR 1.2)
0
NO2
HO2
0
hO2
NO2
se
m
hO2
Hyperoxia - cardiac arrest
- 120 US hospitals, 5 yrs
- same as before
highest PaO2 in 24 h
n = 4459 (excl. hO2)
- continuous trend
- MLR indep. predictor
(OR 1.24 / 100 mmHg)
Kilgannon, Circ 2011
PaO2 target
- routinely
> 60 mmHg
- ALI - ARDS
- chronic hypercapnia
- paraquat intoxication
55 - 80 mmHg
~ 50 mmHg
~ 40 mmHg (lactate)
- acute myoc. infarction
- acute brain injury
80 - 100 mmHg
80 - 100 mmHg
HO2