Impaired autoregulation of cerebral blood flow in the distressed newborn infant
TL;DR: Cerebral blood flow was measured, using the 133Xe clearance technique, a few hours after birth in 19 infants with varying degrees of respiratory distress syndrome, showing a linear relationship that was identical in infants with asphyxia at birth and infants with RDS only.
About: This article is published in The Journal of Pediatrics.The article was published on 1979-01-01. It has received 631 citations till now. The article focuses on the topics: Cerebral blood flow & Asphyxia.
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TL;DR: NIRS can be used in a noninvasive manner at the bedside to identify premature infants with impaired cerebrovascular autoregulation, which is relatively common in such infants, and that the presence of this impairment is associated with a high likelihood of occurrence of severe GMH-IVH/PVL.
Abstract: Objectives. Premature infants experience brain injury, ie, germinal matrix–intraventricular hemorrhage (GMH-IVH) and periventricular leukomalacia (PVL), in considerable part because of disturbances in cerebral blood flow (CBF). Because such infants are susceptible to major fluctuations in mean arterial blood pressure (MAP), impaired cerebrovascular autoregulation would increase the likelihood for the changes in CBF that could result in GMH-IVH and PVL. The objectives of this study were to determine whether a state of impaired cerebrovascular autoregulation could be identified reliably and conveniently at the bedside, the frequency of any such impairment, and the relation of the impairment to the subsequent occurrence of severe GMH-IVH and PVL. Patients and Methods. To monitor the cerebral circulation continuously and noninvasively, we used near-infrared spectroscopy (NIRS) to determine quantitative changes in cerebral concentrations of oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin (Hb) from the first hours of life. Our previous experimental study showed a strong correlation between a measure of cerebral intravascular oxygenation (HbD), ie, HbD = HbO2 − Hb, determined by NIRS, and volemic CBF, determined by radioactive microspheres. We studied 32 very low birth weight premature infants (gestational age: 23–31 weeks; birth weight: 605-1870 g) requiring mechanical ventilation, supplemental oxygen, and invasive blood pressure monitoring by NIRS from 1 to 3 days of age. MAP measured by arterial catheter pressure transducer and arterial oxygen saturation measured by pulse oximetry were recorded simultaneously. The relationship of MAP to HbD was quantitated by coherence analysis. Results. Concordant changes (coherence scores >.5) in HbD and MAP, consistent with impaired cerebrovascular autoregulation, were observed in 17 of the 32 infants (53%). Eight of the 17 infants (47%) developed severe GMH-IVH or PVL or both. Of the 15 infants with apparently intact autoregulation, ie, coherence scores .5. Conclusions. We conclude that NIRS can be used in a noninvasive manner at the bedside to identify premature infants with impaired cerebrovascular autoregulation, that this impairment is relatively common in such infants, and that the presence of this impairment is associated with a high likelihood of occurrence of severe GMH-IVH/PVL.
526 citations
01 Aug 1998
TL;DR: More research on reproducibility and inter-method comparisons is urgently needed, particularly involving the assessment of pressure autoregulation in individuals rather than patient groups, and it is not clear whether the two approaches are interchangeable.
Abstract: Assessment of cerebral autoregulation is an important adjunct to measurement of cerebral blood flow for diagnosis, monitoring or prognosis of cerebrovascular disease. The most common approach tests the effects of changes in mean arterial blood pressure on cerebral blood flow, known as pressure autoregulation. A 'gold standard' for this purpose is not available and the literature shows considerable disparity of methods and criteria. This is understandable because cerebral autoregulation is more a concept rather than a physically measurable entity. Static methods utilize steady-state values to test for changes in cerebral blood flow (or velocity) when mean arterial pressure is changed significantly. This is usually achieved with the use of drugs, shifts in blood volume or by observing spontaneous changes. The long time interval between measurements is a particular concern in many of the studies reviewed. Parallel changes in other critical variables, such as pCO2, haematocrit, brain activation and sympathetic tone, are rarely controlled for. Proposed indices of static autoregulation are based on changes in cerebrovascular resistance, on parameters of the linear regression of flow/velocity versus pressure changes, or only on the absolute changes in flow. The limitations of studies which assess patient groups rather than individual cases are highlighted. Newer methods of dynamic assessment are based on transient changes in cerebral blood flow (or velocity) induced by the deflation of thigh cuffs, Valsalva manoeuvres, tilting and induced or spontaneous oscillations in mean arterial blood pressure. Dynamic testing overcomes several limitations of static methods but it is not clear whether the two approaches are interchangeable. Classification of autoregulation performance using dynamic methods has been based on mathematical modelling, coherent averaging, transfer function analysis, crosscorrelation function or impulse response analysis. More research on reproducibility and inter-method comparisons is urgently needed, particularly involving the assessment of pressure autoregulation in individuals rather than patient groups.
506 citations
453 citations
01 Jan 1989
TL;DR: A view of brain pathophysiology and therapy from the perspective of the blood-brain barrier is presented, showing how future brain treatments with regulatory peptides, immune mediators, and gene components will require selective methods to deliver these agents to specific brain regions.
Abstract: As a neurologist and student of the microvasculature, I find great pleasure in introducing this treatise Presented here is a view of brain pathophysiology and therapy from the perspective of the blood-brain barrier (BBB) Virtually every disease process that affects the brain-traumatic, neoplastic, infectious, inflammatory, toxic, metabolic, degenera tive, vascular, and epileptic-affects the BBB Damage to this homeostatic system often leads to disruption of the composition and volume of brain fluid compartments, thereby contributing to neurologic symptoms and pathology Furthermore, in disorders in which the integrity of the barrier is not breached, its normal restrictive nature may limit therapeu tic approaches For example, the barrier appears to function normally in Parkinson dis ease, but its ability to compensate for striatal dopamine depletion is in part determined by the activity of transporters and enzymes operative in the brain microvasculature of antibiotics, anticonvulsants, antineoplastic agents, and neurolep Similarly, the choice tics requires attention to these drugs' interaction with the BBB Thus, the barrier inter faces with virtually all nervous system diseases and therapies Future brain treatments with regulatory peptides, immune mediators, and gene components will require selective methods to deliver these agents to specific brain regions The second volume of this text successfully provides a thorough review of BBB function and failure in a variety of clinical situations"
438 citations
TL;DR: Cerebral pressure-passivity was significantly associated with low gestational age and birth weight, systemic hypotension, and maternal hemodynamic factors, but not with markers of maternal infection.
Abstract: Cerebral blood flow pressure-passivity results when pressure autoregulation is impaired, or overwhelmed, and is thought to underlie cerebrovascular injury in the premature infant. Earlier bedside observations suggested that transient periods of cerebral pressure-passivity occurred in premature infants. However, these transient events cannot be detected reliably by intermittent static measurements of pressure autoregulation. We therefore used continuous bedside recordings of mean arterial pressure (MAP; from an indwelling arterial catheter) and cerebral perfusion [using the near-infrared spectroscopy (NIRS) Hb difference (HbD) signal) to detect cerebral pressure-passivity in the first 5 d after birth in infants with birth weight <1500 g. Because the Hb difference (HbD) signal [HbD = oxyhemoglobin (HbO2) - Hb] correlates with cerebral blood flow (CBF), we used coherence between MAP and HbD to define pressure-passivity. We measured the prevalence of pressure-passivity using a pressure-passive index (PPI), defined as the percentage of 10-min epochs with significant low-frequency coherence between the MAP and HbD signals. Pressure-passivity occurred in 87 of 90 premature infants, with a mean PPI of 20.3%. Cerebral pressure-passivity was significantly associated with low gestational age and birth weight, systemic hypotension, and maternal hemodynamic factors, but not with markers of maternal infection. Future studies using consistent serial brain imaging are needed to define the relationship between PPI and cerebrovascular injury in the sick premature infant.
352 citations
Cites methods or result from "Impaired autoregulation of cerebral..."
...Static and/or intermittent measurements of CPA used in previous studies (2,7,13) are likely to miss transient cerebral pressurepassivity....
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...In this respect our findings are similar to previous work that suggested that cerebral pressurepassivity may be present despite normal blood pressure (2)....
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References
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TL;DR: The hypothesis that electrical failure in ischemia may be directly associated with a massive release of intracellular K+ or with a critical degree of extracellular acidosis is tested and the concept of an ischemic penumbra during which the neurons remain structurally intact but functionally inactive is supported.
Abstract: As shown previously, the electrical function of the brain is critically dependent on cerebral blood flow in the sense that reduction beyond an ischemic threshold of approximately 15 ml/100 gm per minute (approximately 35% of control) in the baboon leads to complete failure of the somatosensory evoked response. This study tests the hypothesis that electrical failure in ischemia may be directly associated with a massive release of intracellular K+ or with a critical degree of extracellular acidosis. By microelectrode techniques, measurements of blood flow, extracellular activity of K+ and H+ as well as evoked potential were made in the baboon neocortex. Reductions in blood flow were obtained by occlusion of the middle cerebral artery and depression beyond the ischemic threshold of electrical function achieved by a reduction of systemic blood pressure which, in the ischemic zones, changed local cerebral blood flow proportionally. Abolition of evoked response could not be explained by depolarization by release of intracellular K+, nor was it critically dependent on cortical pH. However, the massive release of intracellular K+ was by itself critically dependent on cortical blood flow and occurred at 18 greater than 6 greater than 2 ml/100 gm per minute (median with 5% confidence limits). Thus a dual threshold in ischemia for neuronal function is described, the threshold for release of K+ being clearly lower than the threshold for complete electrical failure. Further, the findings support the concept of an ischemic penumbra during which the neurons remain structurally intact but functionally inactive. That neurons can survive for some time in this state of lethargy is evidenced by the observations that an increase in rCBF, if sufficient, can restore evoked potential and normalize extracellular K+ activity as well as pH.
1,066 citations
TL;DR: Experimental results demonstrate the theoretically expected close relationship between rCBFinitial and flow of gray substance (r CBFinitial 20% to 30% lower than Fg) and how the cerebral clearance curve (normally biexponential) with low flow values becomes gradually monoexponential.
Abstract: The regional cerebral blood flow can be calculated from the initial slope of the logarithmically displayed clearance curve following intra-arterial injection of 133Xe (rCBFinitial). The relationship between this parameter and the values resulting from stochastic (height over area) and compartmental analyses is extensively discussed. Experimental results demonstrate the theoretically expected close relationship between rCBFinitial and flow of gray substance (rCBFinitial 20% to 30% lower than Fg). It is shown how the cerebral clearance curve (normally biexponential) with low flow values becomes gradually monoexponential. Thus only flow of gray substance changes, whereas flow of white substance is independent of CBF∞. CBF10 was shown to overestimate CBF∞ with about 15% independent of the flow level. Correlation between CBFinitial and CBF10 was linear (r=0.98) at CBF10 values above 20 ml/100 gm/min.
The CBFinitial normal value is found to be 64±9 ml/100 gm/min, and the interchannel coefficient of variation is 8.2%. A correction for remaining radioactivity from previous measurements is described. Using this, no significant difference was found between repeated resting state measurements.
The CBFinitial-Paco2 relationship was found to be best described as exponential. In a group of patients with various intracranial diseases, 1 mm Hg change in Paco2 resulted in 4% change of CBFinitial quite independent of the CBFinitial level.
498 citations
TL;DR: It is suggested that the capillaries within the germinal layer may be ruptured by a rise in arterial pressure, particularly in conditions of hypercapnia and hypoxia.
Abstract: A technique has been developed for the injection and stereomicroscopic examination of blood vessels in the preterm newborn brain. Using this technique it can be seen that in the immature brain there is a rich capillary bed in the germinal layer region supplied mainly by Heubner's artery. Capillary channels drain directly into the terminal vein and its main branches. Study of 19 cases with spontaneous germinal layer haemorrhage (GLH) with or without intraventricular haemorrhage (IVH) failed to show rupture of the terminal vein or germinal layer infarction. In babies of up to 28 weeks' gestation GLH developed most frequently over the body of the caudate nucleus, whereas in babies of 29 weeks' gestation or more the haemorrhages were usually over the head of the caudate nucleus. Histological study of 10 cases of GLH failed to show rupture either of arteries or veins, though evidence of rupture at a capillary-vein junction was seen in one case and masses of fibrin adjacent to the vein wall in 2 others. Injection through the carotid artery caused prominent leaks of injection mass within the germinal layer capillary bed, often adjacent to the veins. Injection through the jugular veins in 2 cases failed to rupture the terminal vein but caused multiple vein ruptures at the junction of deep and cortical venous systems. Additional small ruptures in the germinal layer occurred in one of the cases only. It is suggested that the capillaries within the germinal layer may be ruptured by a rise in arterial pressure, particularly in conditions of hypercapnia and hypoxia.
343 citations
TL;DR: Severe mental retardation and extensive neurological deficits appear in children who survive after the first few months of life, due to episodes of impaired circulatory perfusion during the first weeks of life.
Abstract: A survey of postmortem material related to cerebral injury at birth disclosed 13 cases of periventricular leukomalacia. Six patients survived for three months or longer; one reached adulthood. Our observations suggest that the lesions are infarcts located in the periventricular arterial end zones, between the ventriculopetal and ventriculofugal branches of deep penetrating arteries. They apparently are due to episodes of impaired circulatory perfusion during the first weeks of life. In children who survive the neonatal period, these infarcts appear as cavitations or as bands of gliosis in the periventricular regions, with extreme thinning of the white matter and secondary enlargement of the lateral ventricles. Whereas the clinical manifestations in the neonatal period are not distinctive, severe mental retardation and extensive neurological deficits appear in children who survive after the first few months of life.
269 citations