Less Stress: Oxidatieve Stress bij Prematuren · blender. This is a schematic presentation of the...
Transcript of Less Stress: Oxidatieve Stress bij Prematuren · blender. This is a schematic presentation of the...
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Less Stress: Oxidatieve Stress bij Prematuren
Denise Rook
Arts-onderzoeker Neonatologie
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Geschiedenis van zuurstof (1)
1774 Ontdekking “vital air” door J. Priestly
Kaarsen brandden feller en muizen waren actiever
1775 J. Priestly tevens al bewust van de gevaren
“A candle burns out much faster in vital air than in common air, so we might also live out too fast and be too soon exhausted in this pure kind of air”
1938 Couveuse met 100% O2
Sophia Children’s Hospital
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Geschiedenis van zuurstof (2)
1951 Campbell Associatie O2 en ROP
50-60 Restrictie O2 Toegenomen sterfte en spasticiteit
1980 Introductie pulse oximetrie op NICU’s
2011 Nog geen duidelijkheid over saturatie grenzen!!!
Sophia Children’s Hospital
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Optimale saturatie grenzen
Laag (85-89%) vs hoog (91-95%)
SUPPORT trial minder risico op ROP
hogere mortaliteit
BOOST trial eerder gestopt voor analyse
3631 prematuren (GA<28 wkn)
Hogere mortaliteit (21.8 vs 13.3%)
Sophia Children’s Hospital
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Zuurstof Paradox
“Hoewel zuurstof noodzakelijk is voor de mens, is het tegelijkertijd ook schadelijk.”
Sophia Children’s Hospital
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Waarom is zuurstof gevaarlijk?Sophia Children’s Hospital
O2 H2 O
energie
Elektronentransportketen
H2 O2 2-O. OH.
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Reactive Oxygen Species (ROS)
H2 O2
2-O.
OH.Kumar et al. Basic Pathology, 6th edition, Saunders
lipid peroxidationprotein damageDNA damage
cell injury
Sophia Children’s Hospital
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Gevolgen van ROS
Schade celmembranen schade / celdood- witte stof schade- nierschade- Etc.
Veranderingen van signalen in de cel
DNA mutaties kanker
Veranderde enzym activiteit- bv surfactant synthese
Sophia Children’s Hospital
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Bescherming tegen ROS
Antioxidanten
“any substance that delays, prevents
or removes oxidative damage”
Sophia Children’s Hospital
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AntioxidantenSophia Children’s Hospital
Shoji et al 2007
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Sophia Children’s Hospital
Reactive Oxygen Species
Antioxidanten
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Oxidatieve Stress bij prematuren (1)
Toegenomen aanmaak vrije radicalen
Toename PaO2 bij geboorte
Extra zuurstof
Infecties
Bloedtransfusies?
Voeding?
Sophia Children’s Hospital
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Oxidatieve Stress bij prematuren (2)
Minder antioxidanten
Tijdens laatste trimester zwangerschap
Rijping antioxidant enzymen
Verhoogde transfer via placenta
Geen upregulatie van antioxidanten in de long in reactie
op O2 bij geboorte
Suboptimale voeding
Sophia Children’s Hospital
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Sophia Children’s Hospital
Reactive Oxygen Species
AntioxidantenOXIDATIEVE STRESS
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Oxidatieve Stress bij prematuren
Oxidatieve Stress
“Oxygen Radical Diseases in Neonatology”(O.D. Saugstad)
Sophia Children’s Hospital
Brain(IVH, PVL)
Lungs (BPD)
Eyes(ROP)
Gut (NEC)
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Sophia Children’s Hospital
MortaliteitHersenschade
ROP, BPD, Hersenschade
, Mortaliteit
HYPOXIE HYPEROXIE
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Zuurstof therapie op NICU
Wat meet je?
Hoe meet je?
Nauwkeurigheid
Praktijk
Sophia Children’s Hospital
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Zuurstof therapie: Wat meet je (1)
SpO2 Saturatie d.m.v. pulse oximeter
PaO2 Partiële druk van zuurstof
Sophia Children’s Hospital
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SaO
2[%
]
PaO2 [kPa]
Bohr-effect:• pH• Temperatuur• Foetaal Hb
9485
Sophia Children’s Hospital
Zuurstof therapie: Wat meet je (2)
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Ligh
t abs
orba
nce
W.J. Salyer, 2003
Zuurstof therapie: Hoe meet jeSophia Children’s Hospital
Pulse oximetrie
Absorptie licht
2 golflengtes
Meet verschil in absorptie
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Zuurstof therapie: NauwkeurigheidSophia Children’s Hospital
SpO2 =87 89 91 93 95
68%
95%
nauwkeurigheid (1 SD)
70-100% +/- 2 cijfers
60-80% +/- 3 cijfers
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15%7% 8%
15% 14%
54% 69%74%
84%
61%
30%24%
17%25%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
88‐94 88‐96 88‐98 88‐100 92‐98
>bovengrensbinnen grenzen71‐ondergrenslager 71
Zuurstof therapie: de praktijk (1)Sophia Children’s Hospital
Anne van der Eijk, TU Delft, dep. BioMechanical Engineering
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Zuurstof therapie: de praktijk (2)Sophia Children’s Hospital
Anne van der Eijk, TU Delft, dep. BioMechanical Engineering
15%7% 8%
15%5%
54%
37% 38%
43%
25%
30%
55% 53%41%
69%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
88‐94 88‐96 88‐98 88‐100 92‐98
95‐10088‐9471‐87lager 71nul
15%7% 8%
15% 14%
54% 69%74%
84%
61%
30%24%
17%25%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
88‐94 88‐96 88‐98 88‐100 92‐98
>bovengrensbinnen grenzen71‐ondergrenslager 71
Binnen grenzen Binnen 88-94%
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Conclusies
Zowel hypoxie als hyperoxie gevaarlijk
Weet wat je meet!
Pulse oximetrie niet geschikt voor voorkomen van hoge PaO2 ’s (hyperoxie)
Sophia Children’s Hospital
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Less stress: Zuurstofstudie
Intra-uterien SaO2 ~ 40%
Geboorte hyperoxic challenge
Plotselinge stijging PaO2
Vorming ROS
Prematuren O2 toediening
Sophia Children’s Hospital
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Oxygen @ resuscitation - Term infants
Room Air
N = 762
100% O2
N = 740
p-value
Mortality 44 (5.8%) 70 (9.5%) 0.008
Apgar after 5 min* 6.6 (1.9) 6.4 (1.9) 0.048
HR after 90 sec* 116 (24) 111 (25) < 0.001
Time to first breath (min)* 1.8 (3.2) 2.3 (3.7) 0.001
* Presented as mean (SD) Adapted from Saugstad et al 2005
Term, asphyxiated infants:
Sophia Children’s Hospital
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Oxygen @ resuscitation - Preterm infants
Wang et al. Pediatrics 2008
Sophia Children’s Hospital
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Aim & Objective
Resuscitation of preterm infants with 30% vs 65% oxygen
Sophia Children’s Hospital
Safe resuscitation of preterm infants, while minimizing oxidative stress
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Study design
Subjects
Preterm infants: gestational age < 32 wks
N = 200
Prenatal informed consent
Resuscitation
Computerized randomization to 30 or 65% oxygen
Blinded resuscitation
Goal: oxygen saturation 88-94% after 10 minutes
Sophia Children’s Hospital
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Study designSophia Children’s Hospital
preterm infant21% O2
100% O2
21% 100%
O2 blender
30% O2
or
65% O2
O2 blender
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Outcome
Safety and efficacy of resuscitation
FiO2 , SaO2 and HR, Apgar Score
Long term outcome
Mortality
Incidence ‘Oxygen Radical Diseases’
Mental and psychomotor development at age 2
Oxidative stress
Glutathione synthesis rates
Oxidative stress markers
Sophia Children’s Hospital
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Vragen??Sophia Children’s Hospital