Cerebral Pressure Autoregulation Research Articles

Intravenous labetalol versus oral nifedipine for acute hypertension in pregnancy: effects on cerebral perfusion pressure

Pregnant women with preeclampsia have been found to have elevated cerebral perfusion pressure and impaired cerebral autoregulation compared with normal pregnant women. Transcranial Doppler is a noninvasive technique used to estimate cerebral perfusion pressure. The effects of different antihypertensive medications on cerebral perfusion pressure in preeclampsia are unknown. To compare the change in cerebral perfusion pressure before and after intravenous labetalol vs oral nifedipine in the setting of acute severe hypertension in pregnancy. This is a prospective cohort study of pregnant women between 24 and 42 weeks' gestation with severe hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥110 mm Hg). Women who consented to the study and received either intravenous labetalol or oral nifedipine were included. Exclusion criteria included active labor or receipt of any antihypertensive medication within 2 hours of initial cerebral perfusion pressure measurement. Peripheral blood pressure and transcranial Doppler studies for middle cerebral artery hemodynamics were performed prior to the administration of antihypertensive medications and repeated 30 minutes after medication administration. A total of 16 women with acute severe hypertension were enrolled; 8 received intravenous labetalol and 8 received oral nifedipine. There were no significant differences between the labetalol and nifedipine groups in baseline characteristics such as maternal age, race and ethnicity, payment, hospital site, body mass index, nulliparity, gestational age, preexisting diabetes mellitus or chronic hypertension, fetal growth restriction, magnesium sulfate administration, and symptomatology (P>.05). When examined 30 minutes after the administration of either intravenous labetalol or oral nifedipine, there was a significantly greater decrease in systolic blood pressure (-9.8 mm Hg vs-39 mm Hg; P=.003), mean arterial pressure (-7.1 mm Hg vs-22.3 mm Hg; P=.02), and cerebral perfusion pressure (-2.5 mm Hg vs-27.7 mm Hg; P=.01) in the nifedipine group. There was no statistically significant decrease in diastolic blood pressure (-12.9 mm Hg vs-5.4 mm Hg; P=.15). The change in middle cerebral artery velocity by transcranial Doppler was compared between the groups and was not different (0.07 cm/s vs 0.16 cm/s; P=.64). Oral nifedipine resulted in a significant decrease incerebral perfusion pressure, whereas labetalol did not, after administration for acute severe hypertension among women with preeclampsia. This decrease seems to be driven by a decrease in peripheral arterial blood pressure rather than a direct change in cerebral blood flow.

Regional heterogeneity of cerebral hemodynamics in mild neonatal encephalopathy measured with multichannel near-infrared spectroscopy.

Neuromonitoring at the bedside is the key to understand the pathophysiological mechanisms of brain injury associated with neonatal encephalopathy. The current practice is to monitor the forehead using a noninvasive cerebral oximetry-it remains unknown to what extent cerebral hemodynamics in other brain regions is different to the frontal region. A multichannel near-infrared spectroscopy (NIRS) system was used to monitor neonates (n = 14) with fetal acidosis and mild neonatal encephalopathy at four brain regions (the frontal, posterior, left temporal, and right temporal lobes). The data were compared to delineate the regional difference in (1) cerebral hemodynamics and (2) pressure autoregulation. For both analyses, wavelet transform coherence was applied. We observed frontal-posterior heterogeneity as indicated by significantly lower coherence between these two regions (p = 0.02). Furthermore, areas with regional magnetic resonance imaging (MRI)-detected lesions showed greater hemodynamic variations compared to non-affected areas (p = 0.03), while cerebral autoregulation was not affected and showed no difference. Cerebral hemodynamics in mild neonatal encephalopathy is heterogeneous across different brain regions, while cerebral autoregulation remains intact. These findings indicate the robustness of the wavelet measure of cerebral autoregulation in this population, but need to be further investigated in the presence of severe injury. This proof-of-concept study is the first to investigate the regional difference of cerebral hemodynamics and autoregulation in mild neonatal encephalopathy. Study findings confirm that brain functions are complex in the developing neonatal brain and that cerebral hemodynamics are region specific in newborns with frontal-posterior heterogeneity among brain regions probed by multichannel NIRS. Regional MRI lesions were associated with differences across NIRS regional channels among the affected side. Cerebral autoregulation with multichannel NIRS is not affected by regional MRI abnormalities.

Cerebral Blood Flow Measurement in Healthy Children and Children Suffering Severe Traumatic Brain Injury—What Do We Know?

Traumatic brain injury is the leading cause of death in children. Children with severe TBI are in need of neurointensive care where the goal is to prevent secondary brain injury by avoiding secondary insults. Monitoring of cerebral blood flow (CBF) and autoregulation in the injured brain is crucial. However, there are limited studies performed in children to investigate this. Current studies report on age dependent increase in CBF with narrow age range. Low initial CBF following TBI has been correlated to poor outcome and may be more prevalent than hyperemia as previously suggested. Impaired cerebral pressure autoregulation is also detected and correlated with poor outcome but it remains to be elucidated if there is a causal relationship. Current studies are few and mainly based on small number of patients between the age of 0–18 years. Considering the changes of CBF and cerebral pressure autoregulation with increasing age, larger studies with more narrow age ranges and multimodality monitoring are required in order to generate data that can optimize the therapy and clinical management of children suffering TBI.

Cerebral venous volume changes and pressure autoregulation in critically ill infants.

ObjectiveTo determine whether ventilator-related fluctuations in cerebral blood volume (CBV) are associated with cerebral pressure passivity.Study designIn a prospective study of newborns undergoing positive-pressure ventilation, we calculated coherence between continuous mean arterial pressure (MAP) and cerebral near-infrared spectroscopy hemoglobin difference (HbD). Significant HbD–MAP coherence indicated cerebral pressure passivity. CBV changes were measured as the spectral power of total hemoglobin (SHbT) at the ventilator frequency. A regression model tested whether SHbT predicts cerebral pressure passivity and/or death/brain injury, controlling for birth gestational age and other factors.ResultsWe studied 68 subjects with prematurity (n = 19), congenital heart disease (n = 11), and hypoxic–ischemic encephalopathy (n = 38). SHbT, sedative use, and pCO2 were positively associated, and circulating hemoglobin negatively associated, with cerebral pressure passivity (p < 0.001), which was positively associated with brain injury (p < 0.001).ConclusionIn sick newborns, ventilator-related CBV fluctuations may predispose to cerebral pressure passivity, which may predispose to an adverse neonatal outcome.

Mild Hyperventilation in Traumatic Brain Injury—Relation to Cerebral Energy Metabolism, Pressure Autoregulation, and Clinical Outcome

Hyperventilation is a controversial treatment in traumatic brain injury (TBI). Prophylactic severe hyperventilation (below 3.3 kPa/25 mm Hg) is generally avoided, due to the risk of cerebral ischemia. Mild hyperventilation (arterial pCO2 within 4.0-4.5 kPa/30-34 mm Hg) in cases of intracranial hypertension is commonly used, but its safety and benefits are not fully elucidated. The aim of this study was to evaluate the use of mild hyperventilation and its relation to cerebral energy metabolism, pressure autoregulation, and clinical outcome in TBI. This retrospective study was based on 120 patients with severe TBI treated at the neurointensive care unit, Uppsala University Hospital, Sweden, between 2008 and 2018. Data from cerebral microdialysis (glucose, pyruvate, and lactate), arterial pCO2, and pressure reactivity index were analyzed for the first 3 days post-injury. Mild hyperventilation, 4.0-4.5 kPa (30-34 mm Hg), was more frequently used early and the patients were gradually normoventilated. Low pCO2 was associated with slightly higher intracranial pressure and slightly lower cerebral perfusion pressure (P < 0.01). There was no univariate correlation between low pCO2 and worse cerebral energy metabolism. Multiple linear regression analysis showed that mild hyperventilation was associated with lower pressure reactivity index on day 2 (P= 0.03), suggesting better pressure autoregulation. Younger age and lower intracranial pressure were also associated with lower pressure reactivity index. These findings support the notion that mild hyperventilation is safe and may improve cerebrovascular reactivity.

Impaired dynamic cerebral autoregulation in patients with cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) might disturb the sensitive mechanism of cerebral pressure autoregulation. This study examines whether dynamic cerebral autoregulation (CA) is impaired in the posterior or anterior circulation of CAA patients. Fifteen patients with known CAA on magnetic resonance imaging (MRI) and 14 age-matched controls were examined with transcranial Doppler. Dynamic CA was assessed in the middle (MCA) and posterior cerebral artery (PCA) via transfer function phase and gain during respiratory-induced 0.1 Hz oscillations of arterial pressure. Within the patient group, 4 patients showed additional microbleeds in the basal ganglia on the MRI performed within the study (pure CAA vs mixed microbleeds). PCA phase was significantly lower in patients compared with controls (p = 0.018), particularly in patients with pure CAA (p = 0.0034). MCA values showed a similar but non-significant trend towards lower phase in patients with pure CAA. Poorer phase was associated with a higher number of microbleeds on MRI (MCA r = −0.57, p = 0.027; PCA r = −0.52, p = 0.098) and superficial cortical siderosis (PCA: p = 0.0025). In conclusion, dynamic cerebral autoregulation is impaired in patients with CAA. The degree of impairment is associated with the extent of cerebral microbleeds.

Ensuring signal quality of cerebral near infrared spectroscopy during continuous longterm monitoring

BackgroundNear infrared spectroscopy (NIRS) derived hemoglobin difference (HbD: oxygenated [HbO2] – reduced hemoglobin [Hb]) and total hemoglobin (HbT: HbO2+Hb) have been used as surrogate measures of cerebral blood flow and volume, respectively. Statistically, a lack of HbD-blood pressure (BP) or negative HbT-BP association is regarded as a state of intact cerebral pressure autoregulation (CPA). In contrast, a co-variation of HbD/HbT and systemic blood pressure (BP) in the same direction is thought of as a failure of CPA. If the quality of one (NIRS/BP) or both signals is compromised, the reliability of the results may be adversely affected. In this work, we develop an analytic approach to assess the quality of the NIRS signals. New methodGiven that cardiac pulses cause hemodynamic changes that are transmitted through the peripheral vasculature, cerebral NIRS signals should exhibit cyclical changes at the pulse frequency. Therefore, we propose that an association between HbD/HbT and electrocardiogram (EKG) signals would be an indicator of NIRS quality. We demonstrate the application of this approach with data collected from six newborns undergoing therapeutic hypothermia for neonatal encephalopathy. ResultsWe observed an intermittent lack of association between NIRS signals and EKG data over the course of several hours of continuous records, indicating a loss in the strength in NIRS signals. Comparison with existing methodExisting CPA characterization suffers from Type-II error which the current preprocessing approach can mitigate. ConclusionsThe proposed approach will allow for real-time assessment of NIRS signal quality that is essential for accurate CPA monitoring.

Individualizing Thresholds of Cerebral Perfusion Pressure Using Estimated Limits of Autoregulation.

In severe traumatic brain injury, cerebral perfusion pressure management based on cerebrovascular pressure reactivity index has the potential to provide a personalized treatment target to improve patient outcomes. So far, the methods have focused on identifying "one" autoregulation-guided cerebral perfusion pressure target-called "cerebral perfusion pressure optimal". We investigated whether a cerebral perfusion pressure autoregulation range-which uses a continuous estimation of the "lower" and "upper" cerebral perfusion pressure limits of cerebrovascular pressure autoregulation (assessed with pressure reactivity index)-has prognostic value. Single-center retrospective analysis of prospectively collected data. The neurocritical care unit at a tertiary academic medical center. Data from 729 severe traumatic brain injury patients admitted between 1996 and 2016 were used. Treatment was guided by controlling intracranial pressure and cerebral perfusion pressure according to a local protocol. None. Cerebral perfusion pressure-pressure reactivity index curves were fitted automatically using a previously published curve-fitting heuristic from the relationship between pressure reactivity index and cerebral perfusion pressure. The cerebral perfusion pressure values at which this "U-shaped curve" crossed the fixed threshold from intact to impaired pressure reactivity (pressure reactivity index = 0.3) were denoted automatically the "lower" and "upper" cerebral perfusion pressure limits of reactivity, respectively. The percentage of time with cerebral perfusion pressure below (%cerebral perfusion pressure < lower limit of reactivity), above (%cerebral perfusion pressure > upper limit of reactivity), or within these reactivity limits (%cerebral perfusion pressure within limits of reactivity) was calculated for each patient and compared across dichotomized Glasgow Outcome Scores. After adjusting for age, initial Glasgow Coma Scale, and mean intracranial pressure, percentage of time with cerebral perfusion pressure less than lower limit of reactivity was associated with unfavorable outcome (odds ratio %cerebral perfusion pressure < lower limit of reactivity, 1.04; 95% CI, 1.02-1.06; p < 0.001) and mortality (odds ratio, 1.06; 95% CI, 1.04-1.08; p < 0.001). Individualized autoregulation-guided cerebral perfusion pressure management may be a plausible alternative to fixed cerebral perfusion pressure threshold management in severe traumatic brain injury patients. Prospective randomized research will help define which autoregulation-guided method is beneficial, safe, and most practical.

Aspects on the Physiological and Biochemical Foundations of Neurocritical Care.

Neurocritical care (NCC) is a branch of intensive care medicine characterized by specific physiological and biochemical monitoring techniques necessary for identifying cerebral adverse events and for evaluating specific therapies. Information is primarily obtained from physiological variables related to intracranial pressure (ICP) and cerebral blood flow (CBF) and from physiological and biochemical variables related to cerebral energy metabolism. Non-surgical therapies developed for treating increased ICP are based on knowledge regarding transport of water across the intact and injured blood–brain barrier (BBB) and the regulation of CBF. Brain volume is strictly controlled as the BBB permeability to crystalloids is very low restricting net transport of water across the capillary wall. Cerebral pressure autoregulation prevents changes in intracranial blood volume and intracapillary hydrostatic pressure at variations in arterial blood pressure. Information regarding cerebral oxidative metabolism is obtained from measurements of brain tissue oxygen tension (PbtO2) and biochemical data obtained from intracerebral microdialysis. As interstitial lactate/pyruvate (LP) ratio instantaneously reflects shifts in intracellular cytoplasmatic redox state, it is an important indicator of compromised cerebral oxidative metabolism. The combined information obtained from PbtO2, LP ratio, and the pattern of biochemical variables reveals whether impaired oxidative metabolism is due to insufficient perfusion (ischemia) or mitochondrial dysfunction. Intracerebral microdialysis and PbtO2 give information from a very small volume of tissue. Accordingly, clinical interpretation of the data must be based on information of the probe location in relation to focal brain damage. Attempts to evaluate global cerebral energy state from microdialysis of intraventricular fluid and from the LP ratio of the draining venous blood have recently been presented. To be of clinical relevance, the information from all monitoring techniques should be presented bedside online. Accordingly, in the future, the chemical variables obtained from microdialysis will probably be analyzed by biochemical sensors.

Posterior Reversible Encephalopathy Syndrome Due To Carcinoid Crisis Complicating Transarterial Chemoembolization for Metastatic Carcinoid Tumour

Posterior Reversible Encephalopathy Syndrome Due To Carcinoid Crisis Complicating Transarterial Chemoembolization for Metastatic Carcinoid Tumour

Relationships between cerebral autoregulation and markers of kidney and liver injury in neonatal encephalopathy and therapeutic hypothermia.

ObjectiveWe studied whether cerebral blood pressure autoregulation and kidney and liver injuries are associated in neonatal encephalopathy (NE).Study DesignWe monitored autoregulation of 75 newborns who received hypothermia for NE in the neonatal intensive care unit to identify the mean arterial blood pressure with optimized autoregulation (MAPOPT). Autoregulation parameters and creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were analyzed using adjusted regression models.ResultsGreater time with blood pressure within MAPOPT during hypothermia was associated with lower creatinine in girls. Blood pressure below MAPOPT related to higher ALT and AST during normothermia in all neonates and boys. The opposite occurred in rewarming when more time with blood pressure above MAPOPT related to higher AST.ConclusionsBlood pressures that optimize cerebral autoregulation may support the kidneys. Blood pressures below MAPOPT and liver injury during normothermia are associated. The relationship between MAPOPT and AST during rewarming requires further study.

Bedside Xenon-CT Shows Lower CBF in SAH Patients with Impaired CBF Pressure Autoregulation as Defined by Pressure Reactivity Index (PRx).

Subarachnoid hemorrhage (SAH) is a disease with a high rate of unfavorable outcome, often related to delayed cerebral ischemia (DCI), i.e., ischemic injury that develops days-weeks after onset, with a multifactorial etiology. Disturbances in cerebral pressure autoregulation, the ability to maintain a steady cerebral blood flow (CBF), despite fluctuations in systemic blood pressure, have been suggested to play a role in the development of DCI. Pressure reactivity index (PRx) is a well-established measure of cerebral pressure autoregulation that has been used to study traumatic brain injury, but not extensively in SAH. To study the relation between PRx and CBF in SAH patients, and to examine if PRx can be used to predict DCI. Retrospective analysis of prospectively collected data. PRx was calculated as the correlation coefficient between mean arterial blood pressure (MABP) and intracranial pressure (ICP) in a 5min moving window. CBF was measured using bedside Xenon-CT (Xe-CT). DCI was diagnosed clinically. 47 poor-grade mechanically ventilated patients were studied. Patients with disturbed pressure autoregulation (high PRx values) had lower CBF, as measured by bedside Xe-CT; both in the early (day 0-3) and late (day 4-14) acute phase of the disease. PRx did not differ significantly between patients who developed DCI or not. In mechanically ventilated and sedated SAH patients, high PRx (more disturbed CBF pressure autoregulation) is associated with low CBF, both day 0-3 and day 4-14 after onset. The role of PRx as a monitoring tool in SAH patients needs further studying.

Transcranial Doppler ultrasonography: From methodology to major clinical applications.

Non-invasive Doppler ultrasonographic study of cerebral arteries [transcranial Doppler (TCD)] has been extensively applied on both outpatient and inpatient settings. It is performed placing a low-frequency (≤ 2 MHz) transducer on the scalp of the patient over specific acoustic windows, in order to visualize the intracranial arterial vessels and to evaluate the cerebral blood flow velocity and its alteration in many different conditions. Nowadays the most widespread indication for TCD in outpatient setting is the research of right to left shunting, responsable of so called "paradoxical embolism", most often due to patency of foramen ovale which is responsable of the majority of cryptogenic strokes occuring in patients younger than 55 years old. TCD also allows to classify the grade of severity of such shunts using the so called "microembolic signal grading score". In addition TCD has found many useful applications in neurocritical care practice. It is useful on both adults and children for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoidal haemorrhage (caused by aneurysm rupture or traumatic injury), traumatic brain injury, brain stem death. It is used also to evaluate cerebral hemodynamic changes after stroke. It also allows to investigate cerebral pressure autoregulation and for the clinical evaluation of cerebral autoregulatory reserve.

Impaired cerebral autoregulation and brain injury in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

Impaired cerebral autoregulation may contribute to secondary injury in newborns with hypoxic-ischemic encephalopathy (HIE). Continuous, noninvasive assessment of cerebral pressure autoregulation can be achieved with bedside near-infrared spectroscopy (NIRS) and systemic mean arterial blood pressure (MAP) monitoring. This study aimed to evaluate whether impaired cerebral autoregulation measured by NIRS-MAP monitoring during therapeutic hypothermia and rewarming relates to outcome in 36 newborns with HIE. Spectral coherence analysis between NIRS and MAP was used to quantify changes in the duration [pressure passivity index (PPI)] and magnitude (gain) of cerebral autoregulatory impairment. Higher PPI in both cerebral hemispheres and gain in the right hemisphere were associated with neonatal adverse outcomes [death or detectable brain injury by magnetic resonance imaging (MRI), P < 0.001]. NIRS-MAP monitoring of cerebral autoregulation can provide an ongoing physiological biomarker that may help direct care in perinatal brain injury.

Normal perfusion pressure breakthrough theory: a reappraisal after 35 years.

The intrinsic ability of the brain to maintain constant cerebral blood flow (CBF) is known as cerebral pressure autoregulation. This ability protects the brain against cerebral ischemia and hyperemia within a certain range of blood pressures. The normal perfusion pressure breakthrough (NPPB) theory described by Spetzler in 1978 was adopted to explain the edema and hemorrhage that sometimes occur after resection of brain arteriovenous malformations (AVMs). The underlying pathophysiology of edema and hemorrhage after AVM resection still remains controversial. Over the last three decades, advances in neuroimaging, CBF, and cerebral perfusion pressure (CPP) measurement have both favored and contradicted the NBBP theory. At the same time, other theories have been proposed, including the occlusive hyperemia theory. We believe that both theories are related and complementary and that they both explain changes in hemodynamics after AVM resection. The purpose of this work is to review the current status of the NBBP theory 35 years after its original description.

Endothelial nitric oxide synthase mediates the cerebrovascular effects of erythropoietin in traumatic brain injury.

Background: Erythropoietin (Epo) improves post-traumatic cerebral blood flow (CBF), pressure autoregulation, and vascular reactivity to l-arginine. This study examines the dependence of these cerebral hemodynamic effects of Epo on nitric oxide generated by endothelial nitric oxide synthase (eNOS).Methods: Using laser Doppler flow imaging, CBF was monitored in wild-type (WT) and eNOS-deficient mice undergoing controlled cortical impact followed by administration of Epo (5000 U/kg) or normal saline.Results: Cerebral blood flow decreased in all groups post-injury with the greatest reductions occurring at the impact site. Epo administration resulted in significantly higher CBF in the peri-contusional sites in the WT mice [70.2 ± 3.35% in Epo-treated compared to 53 ± 3.3% of baseline in saline-treated mice (p < 0.0001)], but no effect was seen in the eNOS-deficient mice. No CBF differences were found at the core impact site where CBF dropped to 20–25% of baseline in all groups.Conclusion: These differences between eNOS-deficient and WT mice indicate that the Epo mediated improvement in CBF in traumatic brain injury is eNOS dependent.

A conceptual approach to managing severe traumatic brain injury in a time of uncertainty.

Current controversies in the literature suggest that a reassessment of the current management of severe traumatic brain injury (sTBI) is necessary. This article presents a conceptual framework toward individualizing sTBI treatment with respect to targeting thresholds and strategies on the basis of known physiologic processes and available monitors. Intracranial pressure (ICP) is modeled as an epiphenomenon of cerebral compliance and herniation tendency, as well as cerebral ischemia. By combining serial neurological examinations, imaging studies, and ICP measurements (values, trends, and area-under-the-curve calculations) over time, evidence can be accrued on the necessity of maintaining ICP at a given threshold in the realm of physical changes in the brain. Similarly, by collecting and trending clinical, imaging, and monitoring data on the status of cerebral blood flow, the balance of oxygen consumption and delivery, and the status of cerebral static pressure autoregulation, and analyzing them with respect to measured parameters, such as blood pressure, ICP, and cerebral perfusion pressure, one can attempt to fine-tune these variables as well. Such individualization of management optimizes the possibility of successfully treating demonstrated pathophysiological processes while avoiding unnecessary interventions and treatment toxicity. Monitor values must not be seen as targets but rather as indicators of targetable pathology.

An optimal frequency range for assessing the pressure reactivity index in patients with traumatic brain injury

The objective of this study was to identify the optimal frequency range for computing the pressure reactivity index (PRx). PRx is a clinical method for assessing cerebral pressure autoregulation based on the correlation of spontaneous variations of arterial blood pressure (ABP) and intracranial pressure (ICP). Our hypothesis was that optimizing the methodology for computing PRx in this way could produce a more stable, reliable and clinically useful index of autoregulation status. The patients studied were a series of 131 traumatic brain injury patients. Pressure reactivity indices were computed in various frequency bands during the first 4 days following injury using bandpass filtering of the input ABP and ICP signals. Patient outcome was assessed using the extended Glasgow Outcome Scale (GOSe). The optimization criterion was the strength of the correlation with GOSe of the mean index value over the first 4 days following injury. Stability of the indices was measured as the mean absolute deviation of the minute by minute index value from 30-min moving averages. The optimal index frequency range for prediction of outcome was identified as 0.018-0.067 Hz (oscillations with periods from 55 to 15 s). The index based on this frequency range correlated with GOSe with ρ=-0.46 compared to -0.41 for standard PRx, and reduced the 30-min variation by 23%.

Critical Thresholds for Cerebrovascular Reactivity: Fact or Fiction?

To the Editor, We read with interest the recent publication by Sorrentino et al. [1] entitled: ‘‘Critical Thresholds for Cerebrovascular Reactivity after Traumatic Brain Injury’’. The study is based on the hypothesis that bedside real-time calculation of the pressure-reactivity index (PRx) allows a continuous estimation of cerebral pressure autoregulation [1–3]. From measurements of hydrostatic pressure alone the authors define threshold levels for survival as well as favorable outcome in patients with severe traumatic brain lesions. Pressure autoregulation is present in many tissues but it is most pronounced in the brain and the kidney. The main ‘‘physiological purpose’’ of pressure autoregulation is probably to keep intracapillary hydrostatic pressure relatively constant [4]. Changes in precapillary resistance (R) underlying cerebral pressure autoregulation are calculated from cerebral perfusion pressure (CPP) divided by cerebral blood flow (F): R = (Pa ICP)/F [5]. Accordingly, to describe cerebral vasoreactivity it is necessary to assess not only arterial blood pressure (Pa) and intracranial pressure (ICP) but also F. The authors behind the PRx method claim that cerebrovascular pressure reactivity may be estimated by observing the response of ICP to changes in Pa. PRx is in this study determined by calculating the correlation coefficient between 30 consecutive data points resulting from the time averaging of ICP and Pa signals with a width of the moving-average window of 8 s [1]. However, in our opinion it is obvious from the equation above that cerebrovascular resistance cannot be calculated unless cerebral blood flow is also assessed. The method of PRx is based on the assumption that the observed change in Pa is the primary and independent cause of the variations in the other three monitored variables. In the validity study of the PRx method Pa was increased by i.v. vasopressor infusion and F was measured utilizing PET-technique [3]. In this defined, experimental situation it is possible that the increase in Pa is the primary and independent cause of the variations in the other variables. Under clinical conditions this is, however, often not the case. During neurocritical care fluctuations in pain, sedation, stress level, local neuronal excitation, etc., will cause changes in cerebral energy metabolism resulting in variations in precapillary vasoconstriction and cerebral blood flow that are not a function of simultaneously occurring changes in Pa. All these sources of error are neglected when PRx is interpreted as a measure of cerebral pressure autoregulation. As the Cambridge group has also suggested that PRx is correlated to cerebral energy metabolism [6] it seems unlikely that this index might be used for continuous estimation pressure autoregulation as well. In their analyses of prognostic threshold levels the authors use mean values for the entire monitoring period for each parameter: ICP, CPP, and PRx. In the study, the monitoring periods vary between 6 h and 20 days. The authors comment on this fact in the section of limitations. However, in our opinion the consequences are more serious than mentioned by the authors and may invalidate the threshold levels arrived at. In patients with brain trauma mortality is usually caused by an increase in ICP and patients who die within the first few days of admission usually have a high ICP. However, patients who initially may have equally high ICP (in this C.-H. Nordstrom (&) T. H. Nielsen Department of Neurosurgery, Odense University Hospital, Odense, Denmark e-mail: carl-henrik.nordstrom@med.lu.se

Effects of Hypothermia on Cerebral Autoregulatory Vascular Responses in Two Rodent Models of Traumatic Brain Injury

Traumatic brain injury (TBI) can trigger disturbances of cerebral pressure autoregulation that can translate into the generation of secondary insults and increased morbidity/mortality. Few therapies have been developed to attenuate the damaging consequences of disturbed autoregulatory control, although some suggest that hypothermia may exert such protection. Here we reexamine this issue of traumatically induced autoregulatory disturbances and their modulation by hypothermic intervention, examining these phenomena in two different models of TBI. Adult rats were subjected to either impact acceleration injury (IAI) or lateral fluid percussion injury (LFPI) followed by the insertion of cranial windows to assess the pial arteriolar cerebral autoregulatory vascular response to the post-traumatic induction of sequential reductions of arterial blood pressure. The potential for continued pial vasodilation in response to declining blood pressure was directly measured post-injury and compared with that in injured groups subjected to 33° C of hypothermia of 1-2 h duration initiated 1 h post-injury. We observed that the TBI resulted in either impaired or abolished cerebral vascular dilation in response to the sequential declines in blood pressure. Following IAI there was a 50% reduction in the vasculature's ability to dilate in response to the induced hypotension. In contrast, following LFPI, the vascular response to hypotension was abolished both ipsilateral and contralateral to the LFPI. In animals sustaining IAI, the use of 1 h post-traumatic hypothermia preserved vascular dilation in response to declines in blood pressure in contrast to the LFPI in which the use of the same strategy afforded no improvement. However, with LFPI, the use of 2 h of hypothermia provided partial vascular protection. These results clearly illustrate that TBI can alter the cerebral autoregulatory vascular response to sequentially induced hypotensive insult, whereas the use of post-traumatic hypothermia provides benefit. Collectively, these studies also demonstrate that different animal models of TBI can evoke different biological responses to injury.