Brain Injury in Premature Brain Injury in Premature Infants: The Role of Infants: The Role of Cerebral Autoregulation Cerebral Autoregulation Jeffrey R. Kaiser, Jeffrey R. Kaiser, MD, MA MD, MA Pediatrics, Neonatology UAMS College of Medicine Little Rock, AR Perinatal Conference February 17, 2005
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Brain Injury in Premature Infants: The Role of Cerebral Autoregulation Jeffrey R. Kaiser, MD, MA Pediatrics, Neonatology UAMS College of Medicine Little.
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Brain Injury in Premature Brain Injury in Premature Infants: The Role of Cerebral Infants: The Role of Cerebral
AutoregulationAutoregulation
Jeffrey R. Kaiser, MD, MAJeffrey R. Kaiser, MD, MAPediatrics, Neonatology
UAMS College of MedicineLittle Rock, AR
Perinatal ConferenceFebruary 17, 2005
BackgroundBackground
Advances in obstetric & newborn intensive care over the last 4 decades have led to dramatic improvements in survival for the most premature of infants
of the Middle Cerebral Arteryof the Middle Cerebral Artery
% Change From Baseline% Change From BaselineDuring Surfactant During Surfactant
AdministrationAdministration
CBF
PaCO2
MABP
PaO2
n=14
MABP’s Effect on the MABP’s Effect on the Cerebral VasculatureCerebral Vasculature
• Changes in MABP had much less impact on CBF than PaCO2
• In fact, a majority of infants displayed intact cerebral autoregulation--constant CBF with changes in MABP
• 2 of 14 infants had ↑CBF that was associated with ↑ MABP (impaired autoregulation)
PaCOPaCO22’s Effect on the ’s Effect on the
Cerebral VasculatureCerebral Vasculature
• Changes in PaCO2 highly associated with changes in CBF in VLBW infants
• Consistent with PaCO2’s effect
CBF
CBF
The Effects of Hypercapnia on The Effects of Hypercapnia on Cerebral Autoregulation of Cerebral Autoregulation of
Ventilated VLBW InfantsVentilated VLBW Infants
Jeffrey R. Kaiser, MD, MA
C. Heath Gauss, MS
D. Keith Williams, PhDIn preparation, Pediatric Research
• Permissive hypercapnia is being utilized in intubated VLBW infants to minimize ventilator-induced lung injury
• The effects of permissive hypercapnia, (PaCO2, 45-55 mm Hg), on CBF and cerebral autoregulation as well as neurologic outcome of such infants have not been primarily examined
(Mariana, et al, 1999)
Pediatrics 1999;104:1082-88
Hypercapnia and Cerebral Hypercapnia and Cerebral AutoregulationAutoregulation
• Studies in animals and adults indicate the following:– Hypercapnia is associated with impaired
autoregulation
– Impaired autoregulation can be restored by hypocapnia
Cerebral Autoregulation in Cerebral Autoregulation in Preterm InfantsPreterm Infants
0
20
40
60
80
50
70
20 40 60 80 55
Lower
Limit
Upper
Limit
0
10
20
30
40
60
15 25 35 45
Lower Limit
Upper Limit
MABP (mm Hg)
CBF (cm/s)
30 40
Hypercapnia StudyHypercapnia Study
HypothesisHypothesis
Cerebral autoregulation in VLBW infants becomes progressively impaired with increasing PaCO2
Hypercapnia StudyHypercapnia Study
ObjectiveObjective
Examine the effects of increasing PaCO2 on the
cerebral autoregulatory capacity of ventilated VLBW infants
Hypercapnia StudyHypercapnia Study
Statistical MethodsStatistical Methods
• The slope of the relationship between mean CBF velocity and MABP was estimated for all suctioning sessions (117, n = 43 VLBW infants)
• BP range: 30-40 mm Hg • PaCO2 was statistically fixed at 30, 35, 40, 45,
50, 55, and 60 mm Hg • Slope near 0: intact cerebral autoregulation• Slope > 0: impaired cerebral autoregulation
Hypercapnia StudyHypercapnia Study
ResultsResults(Discrete Values)(Discrete Values)
PaCO2 (mm Hg)
30 35 40 45 50 55 60
Slo
pe
-1.0
-0.5
0.0
0.5
1.0
Mean 95% CI
p = 0.0041
,
Effects of Increasing PaCOEffects of Increasing PaCO22
on the Relationship between on the Relationship between Mean CBF Velocity & MABPMean CBF Velocity & MABP
MABP (mm Hg)
CB
F V
elo
city
(cm
/s)
30
35
40
45*
50*
55*60*
*Slope >0
Relationship between Highest Relationship between Highest PaCOPaCO22 in VLBW Infants in the in VLBW Infants in the
Permissive Hypercapnia Era & IVHPermissive Hypercapnia Era & IVH
• No IVH 60.8 20.4 mm Hg• Grade 1 IVH 62.2 17.4 mm Hg• Grade 2 IVH 73.7 24.4 mm Hg• Grade 3 IVH 74.2 25.6 mm Hg• Grade 4 IVH 80.6 25.3 mm Hg
P < 0.001, n = 995
Hypercapnia StudyHypercapnia Study ConclusionConclusion
• The slope of mean CBF velocity vs. MABP progressively increases with increasing PaCO2
• The cerebral circulation becomes more pressure- passive with increasing PaCO2
Hypercapnia StudyHypercapnia Study
SpeculationSpeculation
These novel data describing the effects of elevated PaCO2 on the capacity for cerebral autoregulation should raise concerns regarding the liberal use of permissive hypercapnea in VLBW infants during the first week of life
AcknowledgementsAcknowledgements
• NINDS • Gerald A. Dienel, PhD• D. Keith Williams, PhD• Heath Gauss, MS• K.J.S. Anand, MBBS,
DPhil• Jeffrey M. Perlman, MD• Robert W. Arrington, MD
• Neonatologists• Carol Sikes, RN• GCRC (M01RR14288)• ACHRI, UAMS, and