Pressure Autoregulation Research Articles

The relationship of intracranial pressure Lundberg waves to electroencephalograph fluctuations in patients with severe head trauma

Lundberg (or B) waves, defined as repetitive changes in intracranial pressure (ICP) occurring at frequencies of 0.5 to 2 waves/min, have been attributed to cerebral blood flow fluctuations induced by central nervous system pace-makers or cerebral pressure autoregulation. We prospectively recorded and digitalized at a frequency rate of 10 Hz (AcqKnowledge software) the following parameters in 6 brain injured patients: mean arterial pressure, heart rate, ICP, mean flow velocity of the middle cerebral artery (MFVMCA) (transcranial Doppler WAKI) and left and right spectral edge frequency (SEFl, SEFr) of continuous electroencephalogram (EEG) recordings (Philips technologies). All patients were sedated using a combination of sufentanil and midazolam and mechanically ventilated. Cerebral electrical activity (oscillations of SEF at a mean frequency of 26+/-9 mHz) and MFVMCA fluctuations were found strongly correlated with the intracranial Lundberg B waves (mean frequency 23+/-7 mHz). These result support the existence of a neuropacemaker at the origin of the Lundberg B waves. The change in cerebral electrical activity, resulting from cerebral pacemakers, could increase cerebral metabolic rate of oxygen (CMRO2) and thus lead to an increase in cerebral blood flow and secondarily of ICP through a change in cerebral blood volume.

Identification of Pressure Passive Cerebral Perfusion and Its Mediators after Infant Cardiac Surgery

Cerebrovascular pressure autoregulation (CPA) regulates cerebral blood flow (CBF) in relation to changes in mean arterial blood pressure (MAP). Identification of a pressure-passive cerebral perfusion and the potentially modifiable physiologic factors underlying it has been difficult to achieve in sick infants. We previously validated the near-infrared spectroscopy-derived hemoglobin difference (HbD) signal (cerebral oxyhemoglobin - deoxyhemoglobin) as a reliable measure of changes in CBF in animal models. We now sought to determine whether continuous measurements of DeltaHbD would correlate to middle cerebral artery flow velocity (CBFV), allow identification and quantification of pressure-passive state, and help to delineate potentially modifiable factors. We enrolled 43 infants (2 d to 7 mo old) who were undergoing open cardiac surgery and cardiopulmonary bypass. At 6 and 20 h after surgery, we measured changes in HbD, CBFV (by transcranial Doppler), and MAP at different end-tidal CO(2) levels. We assigned a pressure-passive index (PPI) to each study on the basis of the relative duration of significant coherence between DeltaMAP and DeltaHbD. We found a significant relationship between DeltaHbD and DeltaCBFV at both time points. At 6 h after surgery, we showed high concordance (coherence > 0.5; PPI > or = 41%) between DeltaMAP and DeltaHbD, consistent with disturbed CPA in 13% of infants. End-tidal CO(2) values > or = 40 mm Hg and higher MAP variability both were associated with increased odds (p < 0.001) of autoregulatory failure. This approach provides a means to identify and quantify disturbances of CPA. High CO(2) levels and fluctuating MAP are two important preventable factors associated with disturbed CPA.

Cerebral Pressure Autoregulation Is Intact and Is Not Influenced by Hypothermia after Traumatic Brain Injury in Rats

Cerebral Pressure Autoregulation Is Intact and Is Not Influenced by Hypothermia after Traumatic Brain Injury in Rats

The Effects of Large-dose Propofol on Cerebrovascular Pressure Autoregulation in Head-injured Patients

The Effects of Large-dose Propofol on Cerebrovascular Pressure Autoregulation in Head-injured Patients

System Identification of Human Cerebral Blood Flow Regulatory Mechanisms

Regulation of cerebral blood flow (CBF) is important to protect the brain against ischemia or excessive capillary pressure and hyperperfusion. In addition to the myogenic and metabolic mechanisms of pressure autoregulation, which tend to maintain CBF relatively constant with changes in arterial blood pressure (ABP), several other variables, like CO2, intracranial pressure, metabolic demand, sympathetic activity, cerebrovascular resistance, and endothelial metabolites are also involved in the dynamic control of CBF. Increasingly, system identification techniques are being used to shed light on the physiology of CBF regulation and to provide clinical tools for diagnosis, monitoring, and prognosis of patients with cerebrovascular conditions. In the frequency domain, the transfer function between ABP and CBF for normal subjects, is characterized by a reduced coherence, below 0.1 Hz, a positive phase response, below 0.2 Hz, and an amplitude frequency response that tends to rise continuously with frequency. One or more of these functions have been shown to be altered in patients with prematurity, carotid artery disease, severe head injury, and subarachnoid hemorrhage. Time-domain approaches are becoming more popular, involving autoregressive moving average structures (ARMA), cross-correlation analysis, or linear system models, such as the second-order differential equation used to calculate the dynamic autoregulation index (ARI), which has been adopted in many clinical studies. Nonlinear methods, based on the Wiener–Volterra approach have also been proposed, including new implementations based on dedicated neural networks. One trend in this area is the use of multivariate time-domain models to include other variables, such as CO2, in addition to ABP. However, the inclusion of other key variables, such as intracranial pressure, metabolic demand, and sympathetic activity, will depend on refinements of noninvasive measurement techniques to quantify their input load. Open access databases, containing representative recording from patients with different conditions, would be important to standardize the validation of system identification techniques by different research groups. The use of hybrid models, incorporating elements of mathematical modeling of well-known physiological phenomena, might also be a worthwhile approach in the future.

Microvasculature in acute myocardial ischemia: part I: evolving concepts in pathophysiology, diagnosis, and treatment.

Microvasculature in acute myocardial ischemia: part I: evolving concepts in pathophysiology, diagnosis, and treatment.

Comparisons of Hemodynamic and Respiratory Parameters, and Outcomes between High and Low Cerebral Perfusion Pressure Groups in a Severe Head Injury

A secondary hypoxic brain injury is one of the most important determinants of a neurological outcome after a head injury. In the absence of a specific therapy to normalize cerebral blood flow (CBF), some advocators decided that one approach toward preventing cerebral ischemia was to monitor and maintain the cerebral perfusion pressure (CPP). To date, there is no evidence to support which level of CPP is needed to keep an adequate CBF in the management of severe head injuries. Furthermore, some studies suggested that side effects like acute respiratory distress syndrome (ARDS) or a respiratory complication with intentional CPP management therapy affected the patient's outcome. To examine the relationship between CPP and CBF, we analyzed CBF using the Kety-Schmidt N2O technique, and studied the patient's outcome and respiratory complications. We studied forty patients with severe head injuries (Glasgow Coma Scale<8), who were treated at the Musashino Red Cross Hospital between years 1999 to 2001. We divided the patients into the “high-CPP group (group-H), ” in which CPP was kept above 70mmHg as a threshold of CBF, and the “low-CPP group (group-L), ” in which CPP was kept from 50 to 70mmHg. We analyzed the patients' CBFs and their outcomes, and examined their cardiac indices (CI) and pulmonary arterial diastoric pressures with a thermo-dilution catheter. We also calculated the patients' cerebral vascular resistances (CVR) and compared the results in the two groups. There was no statistical significance concerning CBF, neurological outcomes, pulmonary hemodynamics, or the existence rate of pulmonary complications. The mean CVR in group-H was higher than that of group-L, and we considered that the CBF would be affected by both CVR and CPP. We concluded that the threshold of CPP at 70mmHg is not always appropriate for patients. CPP is affected by certain factors, such as the degree of pressure autoregulation. We should consider both CPP and CVR in the treatments of head injury patients. CPP management is one of the optional therapies that should be chosen with sufficient consideration.

Asymmetry of pressure autoregulation after traumatic brain injury.

The aim of this study was to assess the asymmetry of autoregulation between the left and right sides of the brain by using bilateral transcranial Doppler ultrasonography in a cohort of patients with head injuries. Ninety-six patients with head injuries comprised the study population. All significant intracranial mass lesions were promptly removed. The patients were given medications to induce sedation and paralysis, and artificial ventilation. Arterial blood pressure (ABP) and intracranial pressure (ICP) were monitored in an invasive manner. A strategy based on the patient's cerebral perfusion pressure (CPP = ABP - ICP) was applied: CPP was maintained at a level higher than 70 mm Hg and ICP at a level lower than 25 mm Hg. The left and right middle cerebral arteries were insonated daily, and bilateral flow velocities (FVs) were recorded. The correlation coefficient between the CPP and FV, termed Mx, was calculated and time-averaged over each recording period on both sides. An Mx close to 1 signified that slow fluctuations in CPP produced synchronized slow changes in FV, indicating a defective autoregulation. An Mx close to 0 indicated preserved autoregulation. Computerized tomography scans in all patients were reviewed; the side on which the major brain lesion was located was noted and the extent of the midline shift was determined. Outcome was measured 6 months after discharge. The left-right difference in the Mx between the hemispheres was significantly higher in patients who died than in those who survived (0.16 +/- 0.04 compared with 0.08 +/- 0.01; p = 0.04). The left-right difference in the Mx was correlated with a midline shift (r = -0.42; p = 0.03). Autoregulation was worse on the side of the brain where the lesion was located (p < 0.035). The left-right difference in autoregulation is significantly associated with a fatal outcome. Autoregulation in the brain is worse on the side ipsilateral to the lesion and on the side of expansion in cases in which there is a midline shift.

Assessment of critical thresholds for cerebral perfusion pressure by performing bedside monitoring of cerebral energy metabolism.

An intractable increase in intracranial pressure (ICP) leading to a progressive decrease in cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) is the dominating cause of death in patients with severe brain trauma. Arterial hypotension may further compromise CPP (and CBF) and significantly contributes to death. In addition, the injured brain is sensitive to raised CPP due to an increased permeability of the blood-brain barrier (BBB) to crystalloids and an impaired pressure autoregulation of the CBF. Given these circumstances, an increase in CPP will cause a net transport of water across the BBB and a further elevation in ICP. Accordingly, the assessment of the lower critical threshold for CPP is important for neurological intensive care. This level varies among different patients and different areas of the brain. In fact, the penumbral zones surrounding focal brain lesions appear to be the most sensitive. In the individual patient, preservation of normal cerebral energy metabolism within areas at risk during a decrease in CPP can be guaranteed by performing intracerebral microdialysis and bedside biochemical analyses.

Hemispheric asymmetry and temporal profiles of cerebral pressure autoregulation in head injury.

A moving correlation index (Mx-ABP) between arterial blood pressure (ABP) and mean middle cerebral artery blood flow velocity (CBFV) can be used to monitor dynamic cerebrovascular autoregulation (CA) after traumatic brain injury (TBI). In this study we examined hemispheric CA asymmetry and temporal CA profiles, their relationship with ABP and CBFV, and their prognostic relevance. Mx-ABP was calculated for each hemisphere in 25 TBI patients second-daily for as long as they were receiving sedation and analgesia. Forty-nine recordings were obtained, between one and six per patient. Four time periods were defined: immediate--postinjury days (PID) 0 and 1; early--PID 2 and 3; intermediate--PID 4 and 5, and late--PID 6 and later. GOS was estimated at discharge, GOS 4 and 5 were considered favorable (15 patients) and GOS 1-3 unfavorable outcome (10 patients). A Mx difference >0.2 was classified as hemispheric asymmetry (HA). HA was observed at least once in 12 of the 25 patients (48%) and in 18 of 49 recordings (37%). It was observed during all time periods: 35%, 43%, 25%, 43%, respectively, and was not related to outcome. There was no difference in mean CBFV or ABP between patients with and without HA. HA was not related to interhemispheric CBFV differences. A significant improvement in Mx was seen over time. Hemispheric CA asymmetry is common after traumatic brain injury. It does not bear significant clinical or predictive relevance, and it is unrelated to CBFV or ABP. CA is most profoundly disturbed during the immediate postinjury phase and improves gradually during the ICU course. Further studies are needed to investigate CA during post ICU recovery and rehabilitation.

The role of arterial hypertension in the progression of non-diabetic glomerular diseases.

Arterial hypertension (AH) per se is, together with diabetes mellitus, the most important cause of renal failure and of dialysis in the western world. AH is also a well known consequence of chronic renal disease, and at the same time one of the main factors which causes diabetic and/or non-diabetic chronic renal failure progression. AH is mostly registered in patients with focal segmental glomerulosclerosis and with membranoproliferative glomerulonephritis. The pathophysiology and the mechanism of AH within primary glomerular diseases are complex, including activation of the sympathetic nervous system, the renin-angiotensin system (RAS), sodium retention, volume expansion and decreased synthesis of vasodilatatory substances. As autoregulation of glomerular pressure in chronic glomerular disease is disturbed, the increment in systemic blood pressure leads to the rise in glomerular pressure. Glomerular hypertension results in glomerular capillary wall stretch, endothelial damage and a rise in protein glomerular filtration. These processes, in turn, cause changes of mesangial and proximal tubular cells, ultimately resulting in the replacement of functional by non-functional connective tissue and the development of fibrosis. One of the most important factors in the progression of chronic renal failure is activation of the RAS. Its effect is not only elevated blood pressure, but also the promotion of cell proliferation, inflammation and matrix accumulation. Many studies, first in experimental animals and later in humans, have shown that the lowering of blood pressure (and proteinuria) is associated with a slower progression of kidney disease. It seems that angiotensin-converting enzyme inhibitors (ACEIs) are more renoprotective than other antihypertensives (the protection beyond the antihypertensive effect), although some studies have also confirmed a comparatively beneficial effect of non-dihydropiridine calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs). Moreover, it seems that a combination of antihypertensives (e.g. ACEI + CCB, ACEI + ARB) has a more effective action than either of the drugs alone. However, the effects depend first on the degree of blood pressure reduction. According to comprehensive studies, the achievement of adequate blood pressure (not higher than 130/85 mmHg) is the most important factor. An even lower blood pressure (125/75 mmHg) has been suggested as the limit value in patients with proteinuria of >1 g/24 h and in Blacks.

Autoregulation of blood pressure and thought: preliminary results of an application of brain imaging to psychosomatic medicine.

This presentation seeks to demonstrate the use of brain imaging techniques for understanding the interaction between hypertension and psychosocial function. The historical background for the study of brain function among hypertensive patients is reviewed. An initial and a current project examining rCBF with 15O water radiotracer and PET in unmedicated hypertensives and normotensives are described. The rCBF response is assessed during the performance of spatial and verbal working memory tasks of increasing memory load. The assessment also addresses the influence on rCBF and performance of white matter hyperintensities and the presence of carotid artery thickening. Initial results suggest that hypertensives relative to normotensives show less CBF and less posterior parietal rCBF in response to increases in memory load. Hypertensives, however, increase lateral prefrontal (Broca's area)/insula and amygdala/hippocampal rCBF more than normotensives. Initial results are sufficient to show that hypertension induces changes in rCBF. A tentative hypothesis is that a relatively general decrease in rCBF responsivity induces specific compensatory cognitive strategies as well as subcortical activation. The rCBF changes appear to have implications for information processing and, as such, hold promise for understanding prior reports relating hypertension to affective regulation and cardiovascular reactivity. Imaging techniques provide a powerful tool for psychosomatic research.

Functions of the mastoid cell system: auto-regulation of temperature and gas pressure.

This article presents a new approach to understanding the physiological functions of the mastoid cell system. It is suggested that the cell system, in combination with the continuous blood flow through the adjacent large vessels, makes up a compound functional unit that serves to protect the sensitive vestibular part of the inner ear from inadequate stimulation by external temperature changes. By virtue of the large surface area of the cell system mucosa with respect to the enclosed gas volume, the mastoid cell system may also work as a pressure regulator. Variations of the bi-directional exchange of fluid over the capillary network in the mucosa will change the size of the lumen that is available for the gas in the cell system. Volumes of gas and fluid can thus be exchanged to keep the intratympanic pressure within physiological limits. The process is most effective in a cell system with a high area-to-volume ratio.

The relationship of electroencephalograph fluctuations to intracranial pressure B waves

Lundberg B waves, characterized as repetitive changes in intracranial pressure occurring at frequencies of 8–33 mHz, have been attributed to cerebral blood flow fluctuations induced by central nervous system pacemakers and cerebral pressure autoregulation.

Volume-targeted therapy of increased intracranial pressure.

Fluid exchange across the intact blood-brain barrier (BBB) is counteracted by the low permeability to crystalloids (mainly Na+ and Cl-) combined with the high osmotic pressure (5,700 mm Hg) on both sides of the BBB. If the BBB is disrupted transcapillary water transport will be determined by the differences in hydrostatic and colloid osmotic pressure between the intra- and extracapillary compartments. Under these pathological conditions pressure autoregulation of cerebral blood flow is likely to be impaired and intracapillary hydrostatic pressure will depend on variations in systemic blood pressure. The volume targeted "Lund concept" can be summarized under four headings: A. Reduction of stress response and cerebral energy metabolism: B. Reduction of capillary hydrostatic pressure; C. Maintenance of colloid osmotic pressure and control of fluid balance: D. Reduction of cerebral blood volume. The efficacy of the protocol has been evaluated in experimental and clinical studies regarding the physiological and biochemical (utilizing intracerebral microdialysis) effects and the clinical experiences have been favourable.

ERRATUM

For the article by Jones et al. in the August 2002 issue of Anesthesiology (2002; 97:488–96), the correct title should read as follows:“Variability in the Magnitude of the Cerebral Blood Flow Response and the Shape of the Cerebral Blood Flow–Pressure Autoregulation Curve during Hypotension in Normal Rats”

Progressive renal and cardiovascular disease: Optimal treatment strategies

Progressive renal and cardiovascular disease: Optimal treatment strategies

Effect of xenon on cerebral autoregulation in pigs.

There are little data on the effect of anaesthetic concentrations of xenon on cerebral pressure autoregulation. In this study, we have investigated the effect of 79% xenon inhalation on cerebral pressure autoregulation and CO2 response in pigs. Ten pigs were randomly allocated to receive xenon 79% or halothane anaesthesia, respectively, in a crossover designed study. Halothane was used to validate the experimental set-up. Transcranial Doppler was performed to determine the mean flow velocities in the middle cerebral artery (vMCA) during defined cerebral perfusion pressures and during normo-, hyper- and hypoventilation. The results showed that the inhalation of 79% xenon preserved cerebral autoregulation during conditions of normo-, hyper- and hypoventilation and at different cerebral perfusion pressures in pigs. These results suggest that with the inhalation of xenon, in the highest concentration suitable for a safe clinical use, cerebral autoregulation is preserved.

Assessment of cerebral pressure autoregulation

Cerebral pressure autoregulation, a sensitive homeostatic mechanism important for the control of cerebral blood flow, is impaired by disease pathology and some drugs commonly used during anaesthesia. Therefore, the assessment of cerebral pressure autoregulation can help optimize cerebral blood flow in patients who have suffered neurological insults. In this article, we outline the means available for testing cerebral pressure autoregulation, thus allowing the reader to decide on the best strategy to adopt in their particular operating theatre and intensive care setting.

Volume-targeted therapy of increased intracranial pressure: the Lund concept unifies surgical and non-surgical treatments.

Opinions differ widely on the various treatment protocols for sustained increase in intracranial pressure (ICP). This review focuses on the physiological volume regulation of the intracranial compartments. Based on these mechanisms we describe a protocol called 'volume-targeted' ('Lund concept') for treatment of increased ICP. The driving force for transcapillary fluid exchange is determined by the balance between effective transcapillary hydrostatic and osmotic pressures. Fluid exchange across the intact blood-brain barrier (BBB) is counteracted by the low permeability to crystalloids (mainly Na+ and Cl-) combined with the high osmotic pressure (5500 mmHg) on both sides of the BBB. This contrasts to most other capillary regions where the osmotic pressure is mainly derived from the plasma proteins (approximately 25 mmHg). Accordingly, the level of the cerebral perfusion pressure (CPP) is of less importance under physiological conditions. In addition cerebral intracapillary hydrostatic pressure (and cerebral blood flow) is physiologically tightly autoregulated, and variations in systemic blood pressure are generally not transmitted to these capillaries. If the BBB is disrupted, transcapillary water transport will be determined by the differences in hydrostatic and colloid osmotic pressure between the intra- and extracapillary compartments. Under these pathological conditions, pressure autoregulation of cerebral blood flow is likely to be impaired and intracapillary hydrostatic pressure will depend on variations in systemic blood pressure. The volume-targeted 'Lund concept' can be summarized under four headings: (1) Reduction of stress response and cerebral energy metabolism; (2) reduction of capillary hydrostatic pressure; (3) maintenance of colloid osmotic pressure and control of fluid balance; and (4) reduction of cerebral blood volume. The efficacy of the protocol has been evaluated in experimental and clinical studies regarding the physiological and biochemical (utilizing intracerebral microdialysis) effects, and the clinical experiences have been favorable.