Autoregulation of Cerebral Blood Flow in Response to Adenosine-Induced Hypotension in Dogs
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During induced hypotension for surgical procedures, cerebral blood flow (CBF) autoregulation and cerebrovascular responsivity to CO2 may be impaired-changes that appear to be agent-specific. Adenosine is a potent endogenous systemic vasodilator and has been investigated as a hypotensive agent. In this study in dogs we investigated cerebral vascular responses to graded decreases of cerebral perfusion pressure (CPP) (100%, 60%, 45%, and 35% of control CPP) during normocapnia (PaCO2 = 37 mm Hg) and hypocapnia (PaCO2 = 21 mm Hg). CBF was measured using the venous outflow technique. Six mongrel dogs were anesthetized with halothane (0.6% inspired) and nitrous oxide (70%) in oxygen and studied during both normocapnic and hypocapnic hypotension. The entry sequence was randomized with >/= 1 h of recovery between normocapnia and hypocapnia. Hypocapnia reduced control CBF from 60.6 +/- 7.1 to 45.1 +/- 5.4 ml 100 g min (mean +/- SEM, p <0.05) during normotension. CBF was unchanged from control values during both graded normocapnic and hypocapnic hypotension until CPP reached 60% of control CPP (50 and 47 mm Hg for normocapnia and hypocapnia, respectively). Thereafter CBF decreased significantly from control values at 45% (37 mm Hg for both groups) and 35% (29 mm Hg for both groups) of control CPP. The lower limit of CBF autoregulation derived by applying linear regression analysis to the CBF-CPP relationship above and below the inflexion point was similar under both experimental conditions (60 +/- 1% of control CPP during normocapnia and 63 +/- 3% of control CPP during hypocapnia). CBF was significantly greater during normocapnia compared with hypocapnia at all levels of CPP, except at 35% of control when the values were similar. Cerebral metabolic rate was unchanged throughout the study. We conclude that neither CBF nor CO2 responsivity is appreciably altered during adenosine-induced hypotension when GPP remains above the lower limit of autoregulation of CBF.Keywords:
Normocapnia
Hypocapnia
Cerebral autoregulation
Cerebral microvascular changes are influenced by intracranial pressure (ICP) as well as mean arterial blood pressure (MAP). The mechanism maintaining blood flow despite changes in either pressure is called cerebral autoregulation. This mechanism is known to be impaired in many diseases, including traumatic brain injury and stroke. Maintaining adequate cerebral blood flow and autoregulation is known to improve long term patient outcomes. However, the influence on the microvasculature and autoregulation of blood pressure vs. fluid increase, hence intracranial pressure, is not well understood. Furthermore, while blood pressure changes can readily be measured, intracranial pressure sensors are invasive and there is a need to overcome this invasiveness. We have recently shown that changes in cerebral perfusion pressure, which is the difference between blood pressure and intracranial pressure, can be correlated to total hemoglobin concentration, as measured non-invasively with near-infrared spectroscopy (NIRS) in non-human primates. These results showed that non-invasive intracranial pressure monitoring should be possible by means of vascular changes as measured with NIRS. In order to quantify autoregulation and differentiate between blood pressure and fluid increase driven vascular changes, we collected data on non-human primates. The primates' brains were cannulated to induce rapid changes in ICP. Exsanguination was performed to reduce blood pressure. Data was collected with a combined frequency domain NIRS (OxiplexTS, ISS Inc.) and diffuse correlation spectroscopy (DCS) system for measuring hemoglobin concentration changes as well as blood flow changes, respectively. We will present on the experimental implementation as well as data analysis for quantifying cerebral autoregulation.
Cerebral autoregulation
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Cerebral autoregulation
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Normocapnia
Hypocapnia
Cerebral autoregulation
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This comprehensive review summarizes the evidence regarding use of cerebral autoregulation-directed therapy at the bedside and provides an evaluation of its impact on optimizing cerebral perfusion and associated functional outcomes. Multiple studies in adults and several in children have shown the feasibility of individualizing mean arterial blood pressure and cerebral perfusion pressure goals by using cerebral autoregulation monitoring to calculate optimal levels. Nine of these studies examined the association between cerebral perfusion pressure or mean arterial blood pressure being above or below their optimal levels and functional outcomes. Six of these nine studies (66%) showed that patients for whom median cerebral perfusion pressure or mean arterial blood pressure differed significantly from the optimum, defined by cerebral autoregulation monitoring, were more likely to have an unfavorable outcome. The evidence indicates that monitoring of continuous cerebral autoregulation at the bedside is feasible and has the potential to be used to direct blood pressure management in acutely ill patients.
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✓ Increased brain tissue stiffness following severe traumatic brain injury is an important factor in the development of raised intracranial pressure (ICP). However, the mechanisms involved in brain tissue stiffness are not well understood, particularly the effect of changes in systemic blood pressure. Thus, controversy exists as to the optimum management of blood pressure in severe head injury, and diverging treatment strategies have been proposed. In the present study, the effect of induced alterations in blood pressure on ICP and brain stiffness as indicated by the pressure-volume index (PVI) was studied during 58 tests of autoregulation of cerebral blood flow in 47 comatose head-injured patients. In patients with intact autoregulation mechanisms, lowering the blood pressure caused a steep increase in ICP (from 20 ± 3 to 30 ± 2 mm Hg, mean ± standard error of the mean), while raising blood pressure did not change the ICP. When autoregulation was defective, ICP varied directly with blood pressure. Accordingly, with intact autoregulation, a weak positive correlation between PVI and cerebral perfusion pressure was found; however, with defective autoregulation, the PVI was inversely related to cerebral perfusion pressure. The various blood pressure manipulations did not significantly alter the cerebral metabolic rate of oxygen, irrespective of the status of autoregulation. It is concluded that the changes in ICP can be explained by changes in cerebral blood volume due to cerebral vasoconstriction or dilatation, while the changes in PVI can be largely attributed to alterations in transmural pressure, which may or may not be attenuated by cerebral arteriolar vasoconstriction, depending on the autoregulatory status. The data indicate that a decline in blood pressure should be avoided in head-injured patients, even when baseline blood pressure is high. On the other hand, induced hypertension did not consistently reduce ICP in patients with intact autoregulation and should only be attempted after thorough assessment of the cerebrovascular status and under careful monitoring of its effects.
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In Response: We thank Dr. Nordström for his concern about two important issues. First, he questions whether trial manipulations of arterial blood pressure can be helpful in determining optimal perfusion pressure after head injury. In our study we varied arterial pressure across a wide range and measured intracranial pressure, autoregulation capacity, and brain tissue oxygenation. We found that the combined responses of these variables could be interpreted in a consistent way using autoregulation theory. Thus, from these observations we inferred whether cerebral perfusion pressure was within autoregulation limits or whether it was at or below the lower autoregulation threshold. We did not explore the upper threshold. Although we agree that sustained blood pressure interventions are necessary to determine the long-term effects on intracranial pressure, the concern that increased perfusion pressure will aggravate intracranial hypertension may only be warranted if both the blood-brain barrier is disrupted and arteriolar vasomotor responses are abolished after injury. The latter was not observed in our study. Second, Dr. Nordström suggests the use of microdialysis techniques at the bedside. This is a promising research tool, but it may not be as readily available in a clinical setting as the monitors we used. However, we encourage researchers to study the cerebral physiological responses to induced (not spontaneous) variations in arterial pressure at regular time intervals after head injury using multiple available tools. O. L. Cremer, MD Department of Anesthesiology University Medical Center Utrecht, The Netherlands. [email protected]
Cerebral autoregulation
Vasomotor
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Cerebral autoregulation maintains a relatively constant blood flow despite changes of blood pressure in the brain. Linear models have been extensively applied to identify this mechanism, using spontaneous arterial blood pressure (ABP) fluctuation as input and cerebral blood flow velocity (CBFV) change as output. Although valuable measurements have been achieved by these models, accuracy and consistency are of great concern due to the large variability of results. We therefore investigated whether more reliable measurements can be achieved by selecting only those recordings (or parts of recordings) with relatively high spontaneous variability of ABP. Twenty-four recordings, 7 from hypercapnia and 17 from normocapnia, of ABP and CBFV from 9 healthy adults were analyzed. Two conventional autoregulatory parameters were used to assess cerebral autoregulation. In the absence of a 'gold' standard for the study of dynamic cerebral autoregulation, lower variability of the parameters and higher correlation with pCO(2) were considered as criteria for identifying improved measures of autoregulation. Both significantly lower variability of the parameters, and higher correlation between the parameters and pCO(2) were achieved from the data with higher variability of blood pressure. We therefore conclude that ABP with high variability may effectively stimulate regulatory response in blood flow resulting in improved assessment of cerebral autoregulation.
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Normocapnia
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Vascular pressure reactivity is the ability of vascular smooth muscle to respond to changes in transmural pressure. In the cerebral circulation this reactivity - or autoregulation - limits cerebral blood flow variation over a range of cerebral perfusion pressures ensuring adequate perfusion and oxygenation to the brain. In adults cerebrovascular pressure reactivity can be determined by observing the response of intracranial pressure (ICP) to changes in mean arterial blood pressure. Non-invasive techniques such as transcranial Doppler ultrasound and near-infrared spectroscopy have been validated against ICP measurements, which have enabled continuous assessment of cerebral autoregulation to be investigated in newborn infants. A number of different techniques have been described, including static and dynamic measurements and analysis in the time and frequency domain, yet despite many years of research the characteristics of cerebral autoregulation in the newborn are still not clear. Both the presence and limits of autoregulation has been much debated although there is increasing evidence that autoregulation, while present in healthy infants, is impaired in sick term and preterm neonates and that this impairment may be a predictor of poor outcome. In clinical practice there is a reliance on blood pressure measurements alone to make informed clinical decisions, which ignores the complex circulatory control mechanisms that exist to optimize oxygen delivery to the brain. The ability to obtain continuous quantitative information on cerebral autoregulation at the cotsie would represent a significant advance in the management of these patients.
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Transcranial Doppler
Cerebral circulation
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Purpose of review Severe traumatic brain injury (TBI) remains the most prevalent neurological condition worldwide. Observational and interventional studies provide evidence to recommend monitoring of intracranial pressure (ICP) in all severe TBI patients. Existing guidelines focus on treating elevated ICP and optimizing cerebral perfusion pressure (CPP), according to fixed universal thresholds. However, both ICP and CPP, their target thresholds, and their interaction, need to be interpreted in a broader picture of cerebral autoregulation, the natural capacity to adjust cerebrovascular resistance to preserve cerebral blood flow in response to external stimuli. Recent findings Cerebral autoregulation is often impaired in TBI patients, and monitoring cerebral autoregulation might be useful to develop personalized therapy rather than treatment of one size fits all thresholds and guidelines based on unidimensional static relationships. Summary Today, there is no gold standard available to estimate cerebral autoregulation. Cerebral autoregulation can be triggered by performing a mean arterial pressure (MAP) challenge, in which MAP is increased by 10% for 20 min. The response of ICP (increase or decrease) will estimate the status of cerebral autoregulation and can steer therapy mainly concerning optimizing patient-specific CPP. The role of cerebral metabolic changes and its relationship to cerebral autoregulation is still unclear and awaits further investigation.
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Intracranial pressure monitoring
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