6 The Effects Of Hypercapnia On Cerebral Autoregulation And Neonatal Brain Injury
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6 The Effects Of Hypercapnia On Cerebral Autoregulation And Neonatal Brain Injury
- 1. The Effects of Hypercapnia on Cerebral Autoregulation and Neonatal Brain Injury Jeffrey R. Kaiser, MD, MA Department of Pediatrics, Section of Neonatology UAMS College of Medicine Maternal Fetal Network Meeting October 7, 2005 Supported by NINDS 1 K23 NS43185
- 7. PaCO 2 is a Potent Regulator of Cerebral Arterioles and CBF CBF CBF
- 8. Changes in CBF are Highly Associated with Changes in PaCO 2 in VLBW Infants CBF PaCO 2 Kaiser et al, J Pediatr 2004 r 2 = 0.96
- 9. Maximum PaCO 2 is associated with Worst Grade IVH in VLBW Infants P < 0.001, n = 574 Kaiser et al, In Submission 72-91 81 4 71-84 78 3 69-84 76 2 63-73 68 1 64-68 66 0 95% CI Max PaCO 2 (mm Hg) Worst Grade
- 11. Experimental Setup: Continuous Measurement of CBF velocity, Blood Gases, and BP Setup
- 12. Experimental Setup: Continuous Measurement of CBF velocity, Blood Gases, and BP Transcranial Doppler Setup
- 13. Experimental Setup: Continuous Measurement of CBF velocity, Blood Gases, and BP Transcranial Doppler Fiber Optic Sensor Setup
- 14. Experimental Setup: Continuous Measurement of CBF velocity, Blood Gases, and BP Transcranial Doppler Fiber Optic Sensor Setup Umbilical Arterial Catheter Cardio-respiratory Monitor
- 15. How can we securely fix the Doppler transducer to the newborn head for continuous monitoring?
- 16. First we used tape…
- 17. VLBW Infant During the Study Courtesy of the Arkansas Homemakers Extension Service Crocheted Hats
- 22. Effects of Increasing PaCO 2 on the Autoregulatory Plateau of VLBW Infants Intact 0 20 40 60 80 100 120 140 20 40 60 80 100 Autoregulatory Plateau Lower Limit Upper Limit Mean Carotid Arterial Blood Pressure (mm Hg) CBF (ml•100 gm – 1 min – 1 ) 0 20 40 60 80 100 120 140 20 40 60 80 100 Autoregulatory Plateau Lower Limit Upper Limit Mean Carotid Arterial Blood Pressure (mm Hg) CBF (ml•100 gm – 1 min – 1 )
- 23. Effects of Increasing PaCO 2 on the Autoregulatory Plateau of VLBW Infants Impaired
- 26. VLBW Infants ->
- 27. VLBW Infants ->
- 28. Thank You
- 30. Maximum PaCO 2 Distribution
- 31. Multivariate Predictors of Severe IVH * Compared to Max PaCO 2 <56 mm Hg .003 1.7-12.8 4.7 Max PaCO 2 >75* .009 1.4-11.1 3.9 Max PaCO 2 63-75* .037 1.1-8.9 3.1 Max PaCO 2 56-63* .019 1.1-3.4 2.0 Vasopressors .035 1.0-3.2 1.8 Multiples NS .39-1.1 .64 Apgar 1 min >3 .003 .71-.93 .81 Gestational age (w) P value 95% CI OR Factor
Editor's Notes
- While the etiology of neonatal brain injury is multifactorial, including vascular, extravascular, and intravascular factors, disturbances of CBF and cerebral autoregulation play an important role, and will be discussed here.
- Cerebral autoregulation is an essential physiologic mechanism that… This process is achieved in the normal brain by constriction or relaxation of cerebral arterioles induced, respectively, by increases or decreases of BP. The BP range over which CBF remains constant is known as the autoregulatory plateau. In this portion of the curve,the slope is 0. Below and above this range, CBF changes in a pressure-passive manner.
- Although cerebral autoregulation is generally considered to be impaired in sick newborn ventilated premature infants. Recent evidence, however, suggests that many premature newborns have intact autoregulation.
- PCO2 changes were highly associated with changes in CBF. This is consistent with PCO 2 ‘s known effects on the cerebral vasculature, where hypercapnia produces vasodilation thus increasing CBF.
- We observed… ~75% increase in CBF ( Increased in every VLBW infant, Average % increase 75 %) Significant hypercapnia (~50% increase) , Average ∆ from baseline 21 mm Hg From logistic regression analysis, CBF changes were predominantly associated with changes in PaCO2 and not BP
- In the determination of cerebral autoregulatory capacity in VLBW infants, we compare changes in CBF to changes in BP after routine neonatal care procedures. Autoregulation testing employed in adults is too invasive for use in premature infants and in fact may induce brain injury in infants lacking autoregulation Surfactant administration and endotracheal suctioning were chosen since they are commonly used procedures in ventilated VLBW infants and are known to affect BP, gas exchange, and CBF.
- Continuous Doppler measurements of the middle cerebral artery CBF velocity were made using a transcranial Doppler ultrasound system. The system performs fast Fourier transformation analysis enabling real-time display and calculation of of the blood flow spectra and values for mean CBF velocity, as well as peak systolic and end-diastolic velocities.
- Baseline monitoring of physiological variables begins 15 minutes before surfactant administration or endotracheal suctioning and continued for about 45 minutes post-procedure.
- Based upon the previous studies in adults and animals, we hypothesized
- Permissive hypercapnia, a strategy allowing high PaCO 2 (45−55 mm Hg), is widely used by neonatologists to minimize lung damage in very low birth weight infants. Randomized controlled trials of permissive hypercapnia, however, failed to demonstrate significant improvements in survival without chronic lung disease over routine ventilation strategies.
- For each suctioning session, the slope of the relationship between mCBFv and MABP was estimated over the presumed autoregulatory plateau between 30 and 40 mm Hg, when PaCO 2 was statistically fixed at 30, 35, 40, 45, 50, 55, and 60 mm Hg using a multiple regression model. A slope near or equal to 0 suggests intact cerebral autoregulation. Progressive values >0 represent increasing impaired autoregulation.
- Here you can see the slopes of the autoregulatory plateau with increasing PaCO2 levels. Again, the slopes for CO2 30-40 are not statistically different from 0, while the slopes for PaCO2 levels >40 progressively increase.
- The results are displayed here in a different way. Here you can see the slopes of the autoregulatory plateau with increasing PaCO2 levels. Again, the slopes for CO2 30-40 are not statistically different from 0, while the slopes for PaCO2 levels >40 progressively increase.
- The slope of the relationship between mCBFv and MABP increases with increasing PaCO 2 levels, suggesting that the cerebral circulation becomes more pressure passive with increasing PaCO 2 .
- With increasing hypercapnia, there is maximal vasodilation of resistance arterioles, such that: further vasodilation becomes inadequate during hypotension. Sufficient vasoconstriction is not possible when BP increases. The cerebral circulation becomes pressure-passive.