Cerebral Autoregulation Function Research Articles

Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study.

The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation. Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP. Individualized limits of autoregulation were computed in 55 patients (mean age 38years, mean monitoring time 92h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14mm Hg to 79 ± 17mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6mm Hg to 21.9 ± 5.6mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60min after compared with before an intervention (11% vs. 23%, p = 0.05). Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes.

Assessment of cerebral autoregulatory function and inter-hemispheric blood flow in older adults with internal carotid artery stenosis using transcranial Doppler sonography-based measurement of transient hyperemic response after carotid artery compression

Unhealthy vascular aging promotes atherogenesis, which may lead to significant internal carotid artery stenosis (CAS) in 5 to 7.5% of older adults. The pathogenic factors that promote accelerated vascular aging and CAS also affect the downstream portion of the cerebral microcirculation in these patients. Primary treatments of significant CAS are eversion endarterectomy or endarterectomy with patch plasty. Factors that determine adequate hemodynamic compensation and thereby the clinical consequences of CAS as well as medical and surgical complications of carotid reconstruction surgery likely involve the anatomy of the circle of Willis (CoW), the magnitude of compensatory inter-hemispheric blood flow, and the effectiveness of cerebral microcirculatory blood flow autoregulation. This study aimed to test two hypotheses based on this theory. First, we hypothesized that patients with symptomatic and asymptomatic CAS would exhibit differences in autoregulatory function and inter-hemispheric blood flow. Second, we predicted that anatomically compromised CoW would associate with impaired inter-hemispheric blood flow compensation. We enrolled older adults with symptomatic or asymptomatic internal CAS (>70% NASCET criteria; n = 46) and assessed CoW integrity by CT angiography. We evaluated transient hyperemic responses in the middle cerebral arteries (MCA) after common carotid artery compression (CCC; 10 s) by transcranial Doppler sonography (TCD). We compared parameters reflecting autoregulatory function (e.g., transient hyperemic response ratio [THRR], return to baseline time [RTB], changes of vascular resistance) and inter-hemispheric blood flow (residual blood flow velocity). Our findings revealed that CAS was associated with impaired cerebral vascular reactivity. However, we did not observe significant differences in autoregulatory function or inter-hemispheric blood flow between patients with symptomatic and asymptomatic CAS. Moreover, anatomically compromised CoW did not significantly affect these parameters. Notably, we observed an inverse correlation between RTB and THRR, and 49% of CAS patients exhibited a delayed THRR, which associated with decreased inter-hemispheric blood flow. Future studies should investigate how TCD-based evaluation of autoregulatory function and inter-hemispheric blood flow can be used to optimize surgical techniques and patient selection for internal carotid artery revascularization.

Comparison of Near-Infrared Spectroscopy-Based Cerebral Autoregulatory Indices in Extremely Low Birth Weight Infants.

Premature infants are born with immature cerebral autoregulation function and are vulnerable to pressure passive cerebral circulation and subsequent brain injury. Measurements derived from near-infrared spectroscopy (NIRS) have enabled continuous assessment of cerebral vasoreactivity. Although NIRS has enabled a growing field of research, the lack of clear standardization in the field remains problematic. A major limitation of current literature is the absence of a comparative analysis of the different methodologies. To determine the relationship between NIRS-derived continuous indices of cerebral autoregulation in a cohort of extremely low birth weight (ELBW) infants. Premature infants of birth weight 401-1000 g were studied during the first 72 h of life. The cerebral oximetry index (COx), hemoglobin volume index (HVx), and tissue oxygenation heart rate reactivity index (TOHRx) were simultaneously calculated. The relationship between each of the indices was assessed with Pearson correlation. Fifty-eight infants with a median gestational age of 25.8 weeks and a median birth weight of 738 g were included. Intraventricular hemorrhage (IVH) was detected in 33% of individuals. COx and HVx demonstrated the highest degree of correlation, although the relationship was moderate at best (r = 0.543, p < 0.001). No correlation was found either between COx and TOHRx (r = 0.318, p < 0.015) or between HVx and TOHRx (r = 0.287, p < 0.029). No significant differences in these relationships were found with respect to IVH and no IVH in subgroup analysis. COx, HVx, and TOHRx are not numerically equivalent. Caution must be applied when interpreting or comparing results based on different methodologies for measuring cerebral autoregulation. Uniformity regarding data acquisition and analytical methodology are needed to firmly establish a gold standard for neonatal cerebral autoregulation monitoring.

Identifying Cognitive Impairment in Elderly Using Coupling Functions Between Cerebral Oxyhemoglobin and Arterial Blood Pressure.

BackgroundThis study aimed to assess brain oxygenation status and cerebral autoregulation function in subjects with cognitive dysfunction.MethodsThe Montreal Cognitive Assessment (MoCA) was applied to divide the subjects into three groups: cognitive impairment (Group CI, 72.50 ± 10.93 y), mild cognitive impairment (Group MCI, 72.02 ± 9.90 y), and normal cognition (Group NC, 70.72 ± 7.66 y). Near-infrared spectroscopy technology and a non-invasive blood pressure device were used to simultaneously measure changes in cerebral tissue oxygenation signals in the bilateral prefrontal lobes (LPFC/RPFC) and arterial blood pressure (ABP) signals from subjects in the resting state (15 min). The coupling between ABP and cerebral oxyhemoglobin concentrations (Δ [O2Hb]) was calculated in very-low-frequency (VLF, 0.02–0.07 Hz) and low-frequency (LF, 0.07–0.2 Hz) bands based on the dynamical Bayesian inference approach. Pearson correlation analyses were used to study the relationships between MoCA scores, tissue oxygenation index, and strength of coupling function.ResultsIn the interval VLF, Group CI (p = 0.001) and Group MCI (p = 0.013) exhibited significantly higher coupling strength from ABP to Δ [O2Hb] in the LPFC than Group NC. In the interval LF, coupling strength from ABP to Δ [O2Hb] in the LPFC was significantly higher in Group CI than in Group NC (p = 0.001). Pearson correlation results showed that MoCA scores had a significant positive correlation with the tissue oxygenation index and a significant negative correlation with the coupling strength from ABP to Δ [O2Hb].ConclusionThe significantly increased coupling strength may be evidence of impaired cerebral autoregulation function in subjects with cognitive dysfunction. The Pearson correlation results suggest that indicators of brain oxygenation status and cerebral autoregulation function can reflect cognitive function. This study provides insights into the mechanisms underlying the pathophysiology of cognitive impairment and provides objective indicators for screening cognitive impairment in the elderly population.

Cerebral Autoregulatory Function Before, During, and After Therapeutic Interventions Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study (S21.001)

Cerebral Autoregulatory Function Before, During, and After Therapeutic Interventions Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study (S21.001)

Time-evolving coupling functions for evaluating the interaction between cerebral oxyhemoglobin and arterial blood pressure with hypertension.

This study aimed to investigate the network coupling between arterial blood pressure (ABP) and changes in cerebral oxyhemoglobin concentration (Δ [O2 Hb]/Δ [HHb]) oscillations based on dynamical Bayesian inference in hypertensive subjects. Two groups of subjects, consisting of 30 healthy (Group Control, 55.1±10.6y), and 32 hypertensive individuals (Group AH, 58.9±8.7y), participated in this study. A functional near-infrared spectroscopy system was used to measure the Δ [O2 Hb] and Δ [HHb] signals in the bilateral prefrontal cortex (LPFC/RPFC), motor cortex (LMC/RMC), and occipital lobe (LOL/ROL) during the resting state (12min). Based on continuous wavelet analysis and coupling functions, the directed coupling strength (CS) between ABP and cerebral hemoglobin was identified and analyzed in three frequency intervals (I: 0.6-2Hz, II: 0.145-0.6Hz, III: 0.01-0.08Hz). The Pearson correlations between the CS and blood pressure parameters were calculated in the hypertension group. In interval I, Group AH exhibited a significantly higher CS for the coupling from ABP to Δ [O2 Hb] than Group Control in LMC, RMC, LOL, and ROL. In interval III, the CS from ABP to Δ [O2 Hb] in LPFC, RPFC, LMC, RMC, LOL, and ROL was significantly higher in Group AH than in Group Control. For the patients with hypertension, diastolic blood pressure was negatively and pulse pressure was positively related to the CS from ABP to Δ [O2 Hb] oscillations in interval III. The higher CS from ABP to Δ [O2 Hb] in interval I indicated that the components of cardiac activity in cerebral hemoglobin oscillations were more directly responsive to the changes in systematic ABP in patients with hypertension than in healthy subjects. Meanwhile, the higher CS from ABP to Δ [O2 Hb] in interval III indicated that the cerebral hemoglobin oscillations were susceptible to changes in blood pressure in hypertensive subjects. The results may serve as evidence of impairment in cerebral autoregulation after hypertension. The Pearson correlation results showed that diastolic blood pressure and pulse pressure might be regarded as predictors of cerebral autoregulation function in patients with hypertension, and may be useful for hypertension stratification. This study provides novel insights into the interaction mechanism between ABP and cerebral hemodynamics and could help in the development of new assessment techniques for cerebral vascular disease.

Implications of habitual endurance and resistance exercise for dynamic cerebral autoregulation.

What is the central question of this study? Does habitual resistance and endurance exercise modify dynamic cerebral autoregulation? What is the main finding and its importance? To the authors' knowledge, this is the first study to directly assess dynamic cerebral autoregulation in resistance-trained individuals, and potential differences between exercise training modalities. Forced oscillations in blood pressure were induced by repeated squat-stands, from which dynamic cerebral autoregulation was assessed using transfer function analysis. These data indicate that dynamic cerebral autoregulatory function is largely unaffected by habitual exercise type, and further document the systemic circulatory effects of regular exercise. Regular endurance and resistance exercise produce differential but desirable physiological adaptations in both healthy and clinical populations. The chronic effect of these different exercise modalities on cerebral vessels' ability to respond to rapid changes in blood pressure (BP) had not been examined. We examined dynamic cerebral autoregulation (dCA) in 12 resistance-trained (mean±SD, 25±6years), 12 endurance-trained (28±9years) and 12 sedentary (26±6years) volunteers. The dCA was assessed using transfer function analysis of forced oscillations in BP vs. middle cerebral artery blood velocity (MCAv), induced via repeated squat-stands at 0.05 and 0.10Hz. Resting BP and MCAv were similar between groups (interaction: both P≥0.544). The partial pressure of end-tidal carbon dioxide ( ) was unchanged (P=0.561) across squat-stand manoeuvres (grouped mean for absolute change +0.6±2.3mmHg). Gain and normalized gain were similar between groups across all frequencies (both P≥0.261). Phase showed a frequency-specific effect between groups (P=0.043), tending to be lower in resistance-trained (0.63±0.21 radians) than in endurance-trained (0.90±0.41, P=0.052) and -untrained (0.85±0.38, P=0.081) groups at slower frequency (0.05Hz) oscillations. Squat-stands induced mean arterial pressure perturbations differed between groups (interaction: P=0.031), with greater changes in the resistance (P<0.001) and endurance (P=0.001) groups compared with the sedentary group at 0.05Hz (56±13 and 49±11vs. 35±11mmHg, respectively). The differences persisted at 0.1Hz between resistance and sedentary groups (49±12vs. 33±7mmHg, P<0.001). These results indicate that dCA remains largely unaltered by habitual endurance and resistance exercise with a trend for phase to be lower in the resistance exercise group at lower fequencies.

Delayed cord clamping is associated with improved dynamic cerebral autoregulation and decreased incidence of intraventricular hemorrhage in preterm infants.

Delayed cord clamping (DCC) improves neurologic outcomes in preterm infants through a reduction in intraventricular hemorrhage (IVH) incidence. The mechanism behind this neuroprotective effect is not known. Infants born <28 wk gestation were recruited for longitudinal monitoring. All infants underwent 72 h of synchronized near-infrared spectroscopy (NIRS) and mean arterial blood pressure (MABP) recording within 24 h of birth. Infants with DCC were compared with control infants with immediate cord clamping (ICC), controlling for severity of illness [clinical risk index for babies (CRIB-II) score], chorioamnionitis, antenatal steroids, sedation, inotropes, and delivery mode. Autoregulatory dampening was calculated as the transfer function gain coefficient between the MABP and NIRS signals. Forty-five infants were included (DCC; n = 15, paired 2:1 with ICC controls n = 30). ICC and DCC groups were similar including gestational age (25.5 vs. 25.2 wk, P = 0.48), birth weight (852.3 vs. 816.6 g, P = 0.73), percent female (40 vs. 40%, P = 0.75), and dopamine usage (27 vs. 23%, P = 1.00). There was a significant difference in IVH incidence between the DCC and ICC groups (20 vs. 50%, P = 0.04). Mean MABP was not different (35.9 vs. 35.1 mmHg, P = 0.44). Compared with the DCC group, the ICC group had diminished autoregulatory dampening capacity (-12.96 vs. -15.06 dB, P = 0.01), which remained significant when controlling for confounders. Dampening capacity was, in turn, strongly associated with decreased risk of IVH (odds ratio = 0.14, P < 0.01). The results of this pilot study demonstrate that DCC is associated with improved dynamic cerebral autoregulatory function and may be the mechanism behind the decreased incidence of IVH. NEW & NOTEWORTHY The neuroprotective mechanism of delayed cord clamping in premature infants is unclear. Delayed cord clamping was associated with improved cerebral autoregulatory function and a marked decrease in intraventricular hemorrhage (IVH). Improved dynamic cerebral autoregulation may decrease arterial baroreceptor sensitivity, thereby reducing the risk of IVH.

Cerebral Autoregulation-Guided Optimal Blood Pressure in Sepsis-Associated Encephalopathy: A Case Series.

Impaired cerebral autoregulation and cerebral hypoperfusion may play a critical role in the high morbidity and mortality in patients with sepsis-associated encephalopathy (SAE). Bedside assessment of cerebral autoregulation may help individualize hemodynamic targets that optimize brain perfusion. We hypothesize that near-infrared spectroscopy (NIRS)-derived cerebral oximetry can identify blood pressure ranges that enhance autoregulation in patients with SAE and that disturbances in autoregulation are associated with severity of encephalopathy. Adult patients with acute encephalopathy directly attributable to sepsis were followed using NIRS-based multimodal monitoring for 12 consecutive hours. We used the correlation in time between regional cerebral oxygen saturation and mean arterial pressure (MAP) to determine the cerebral oximetry index (COx) as a measure of cerebral autoregulation. Autoregulation curves were constructed for each patient with averaged COx values sorted by MAP in 3 sequential 4-hour periods; the optimal pressure (MAPOPT), defined as the MAP associated with most robust autoregulation (lowest COx), was identified in each period. Severity of encephalopathy was measured with Glasgow coma scale (GCS). Six patients with extracranial sepsis met the stringent criteria specified, including no pharmacological sedation or neurologic premorbidity. Optimal MAP was identified in all patients and ranged from 55 to 115 mmHg. Additionally, MAPOPT varied within individual patients over time during monitoring. Disturbed autoregulation, based on COx, was associated with worse neurologic status (GCS < 13) both with and without controlling for age and severity of sepsis (adjusted odds ratio [OR]: 2.11; 95% confidence interval [CI]: 1.77-2.52; P < .001; OR: 2.97; 95% CI: 1.63-5.43; P < .001). In this high-fidelity group of patients with SAE, continuous, NIRS-based monitoring can identify blood pressure ranges that improve autoregulation. This is important given the association between cerebral autoregulatory function and severity of encephalopathy. Individualizing blood pressure goals using bedside autoregulation monitoring may better preserve cerebral perfusion in SAE than current practice.

Autonomic Dysfunction in Dizziness Clinic

Orthostatic dizziness is a common type of dizziness. In general, orthostatic dizziness is provoked by standing or tilting, and subsided by supine position. The patient with orthostatic intolerance complains multiple symptoms such as dizziness, palpitation, lightheadness, fatigue and rarely syncope. Common orthostatic intolerance is orthostatic hypotension (classic, initial, transient, and delayed orthostatic hypotension) and postural orthostatic tachycardia syndrome. Transcranial Doppler is a noninvasive technique that provides real-time measurement of cerebral blood flow velocity. It can be useful for understanding the relationship between orthostatic symptoms and cerebral autoregulatory function. The reciprocal causal relationship between vestibular and autonomic dysfunction should always be kept in mind. Keywords: Orthostatic dizziness; Orthostatic hypotension; Postural orthostatic tachycardia syndrome; Transcranial Doppler; Autonomic dysfunction 중심 단어: 기립어지럼, ê¸°ë¦½ì €í˜ˆì••, 기립자세빈맥증후군, 경두개도플러, ìžìœ¨ì‹ ê²½ë¶€ì „

Effect of Cerebral Flow Autoregulation Function on Cerebral Flow Rate Under Continuous Flow Left Ventricular Assist Device Support.

Neurological complications in continuous flow left ventricular assist device (CF-LVAD) patients are the second-leading risk of death after multi-organ failure. They are associated with altered blood flow in the cardiovascular system because of CF-LVAD support. Moreover, an impaired cerebral autoregulation function may also contribute to complications such as hyperperfusion in the cerebral circulation under mechanical circulatory support. The aim of this study is to evaluate the effect of cerebral autoregulatory function on cerebral blood flow rate under CF-LVAD support. A lumped parameter model was used to simulate the cardiovascular system including the heart chambers, heart valves, systemic and pulmonary circulations and cerebral circulation which includes entire Circle of Willis. A baroreflex model was used to regulate the systemic arteriolar and cerebral vascular resistances and a model of the Micromed CF-LVAD was used to simulate the pump dynamics at different operating speeds. Additionally, preserved and impaired cerebral autoregulatory functions were simulated in heart failure and under CF-LVAD support. Cerebral blood flow rate was restored under CF-LVAD support at 10500 rpm pump operating speed which generated a similar arterial blood pressure and blood flow as in a healthy condition for the impaired cerebral autoregulatory function while the preserved cerebral autoregulatory function regulated the cerebral flow rate within a relatively low range for the applied pump operating speeds. Relatively low or high pump operating speeds may cause underpefusion or hyperperfusion for a failing cardiovascular system with impaired cerebral autoregulatory function under CF-LVAD support whichwill contribute to the worsening of cerebral complications.

The Link Between Cerebrovascular Hemodynamics and Rehabilitation Outcomes After Aneurysmal Subarachnoid Hemorrhage

The aim of the study was to assess the relation between cerebrovascular function early after aneurysmal subarachnoid hemorrhage onset and functional and rehabilitation outcomes. Observational cohort study of subarachnoid hemorrhage patients (n = 133) admitted to rehabilitation (n = 49), discharged home (n = 52), or died before discharge (n = 10). We obtained hemodynamic markers of cerebral autoregulatory function from blood flow velocities in the middle cerebral artery and arterial pressure waveforms, recorded daily on days 2-4 after symptom onset, and functional independence measure (FIM) scores and FIM efficiency for those admitted to acute rehabilitation. Compared to those discharged home, the range of pressures within which autoregulation is effective was lower in patients admitted to rehabilitation (4.6 [0.2] vs. 3.9 [0.2] mm Hg) and those who died (2.7 [0.4], P = 0.04). For those admitted to rehabilitation, autoregulatory range and the ability of cerebrovasculature to increase flow were related to discharge FIM score (R = 0.33 and 0.43, P < 0.01) and efficiency (R = 0.33 and 0.47 P < 0.01). The latter marker, along with subarachnoid hemorrhage severity and admission FIM, explained 84% and 69% of the variability in discharge FIM score and efficiency, respectively, even after accounting for age. Early cerebrovascular function is a major contributor to functional outcomes after subarachnoid hemorrhage and may represent a modifiable target to develop therapeutic approaches. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Define cerebral autoregulation; (2) Explain the importance of the integrity of cerebral autoregulation for longer-term functional and rehabilitation outcomes after aneurysmal subarachnoid hemorrhage; and (3) Theorize why treatment strategies that may be effective in reducing large-vessel vasospasms after an aneurysmal subarachnoid hemorrhage might not always translate into improved functional outcomes. Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Acute Effect of Intravenous Sildenafil on Cerebral Blood Flow in Patients with Vasospasm After Subarachnoid Hemorrhage.

The phosphodiesterase-5 inhibitor sildenafil has been shown to attenuate delayed cerebral ischemia (DCI) and improve neurologic function in experimental subarachnoid hemorrhage (SAH). We recently demonstrated that it could improve cerebral vasospasm (CVS) in humans after SAH. However, successful therapies for DCI must also restore cerebral blood flow (CBF) and/or autoregulatory capacity. In this study, we tested the effects of sildenafil on CBF in SAH patients at-risk for DCI. Six subjects with angiographically confirmed CVS received 30-mg of intravenous sildenafil (mean 9±2days after aneurysmal SAH). Each underwent (15)O-PET imaging to measure global and regional CBF at baseline and post-sildenafil. Mean arterial pressure declined by 10mm Hg on average post-sildenafil (8%, p=0.01), while ICP was unchanged. There was no change in global CBF (mean 34.5±7ml/100g/min at baseline vs. 33.9±8.0ml/100g/min post-sildenafil, p=0.84). The proportion of brain regions with low CBF (<25ml/100g/min) was also unchanged after sildenafil infusion. Infusion of sildenafil does not lead to a change in global or regional perfusion despite a significant reduction in cerebral perfusion pressure. While this could reflect the ineffectiveness of sildenafil-induced proximal vasodilatation to alter brain perfusion, it also suggests that cerebral autoregulatory function was preserved in this group. Future studies should assess whether sildenafil can restore or enhance autoregulation after SAH.

Identifying stable phase coupling associated with cerebral autoregulation using the synchrosqueezed cross-wavelet transform and low oscillation morlet wavelets.

A novel method of identifying stable phase coupling behavior of two signals within the wavelet transform time-frequency plane is presented. The technique employs the cross-wavelet transform to provide a map of phase coupling followed by synchrosqueezing to collect the stable phase regime information. The resulting synchrosqueezed cross-wavelet transform method (Synchro-CrWT) is illustrated using a synthetic signal and then applied to the analysis of the relationship between biosignals used in the analysis of cerebral autoregulation function.

Fixing Hearts and Protecting Minds

Ischemic heart disease is a significant cause of mortality and morbidity in Western populations. Consistent with this, coronary artery bypass graft (CABG) surgery remains one of the most frequently performed major surgeries. Improved survival rates mean that our research focus now extends beyond surgical technique to include quality of postoperative outcome. Postoperative cognitive dysfunction (POCD) has emerged as one of the most challenging and hotly debated issues, with increasing impetus to answer the unresolved question: does fixing the heart come at a cost to the brain? CABG surgery is associated with neurological events including stroke in 1.6%1 and delirium in 5.8%2 of patients. Beyond these severe and marked alterations to neurological function, there has been a widely held belief that CABG surgery is associated with POCD, which may presage a decline toward dementia. Research has been influenced by the 1995 Consensus Statement3 into the study of POCD in patients undergoing CABG surgery. Although the methods of investigation set forth by the Consensus Statement achieved widespread acknowledgment, its specific recommendations have not always been followed.4 Despite significant methodological issues, it seems that the balance of interpretation has historically been in favor of CABG surgery as a cause of significant POCD. More recently, however, a review of a series of publications from a well-controlled longitudinal cohort study conducted at Johns Hopkins5 and a meta-analysis6 suggested that cognition is in fact stable or may even show some improvement after CABG surgery in the majority of patients, at least within the first year (Figures 1 and 2). There is little doubt that POCD affects some patients in the short term, but the pathophysiological mechanisms underlying this and the influence on longer-term cognitive function remain uncertain. For research to progress, we require a paradigmatic shift in our focus from …

Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage

Vasospasm is one of the leading causes of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Radiographic vasospasm usually develops between 5 and 15 days after the initial hemorrhage, and is associated with clinically apparent delayed ischemic neurological deficits (DID) in one-third of patients. The pathophysiology of this reversible vasculopathy is not fully understood but appears to involve structural changes and biochemical alterations at the levels of the vascular endothelium and smooth muscle cells. Blood in the subarachnoid space is believed to trigger these changes. In addition, cerebral perfusion may be concurrently impaired by hypovolemia and impaired cerebral autoregulatory function. The combined effects of these processes can lead to reduction in cerebral blood flow so severe as to cause ischemia leading to infarction. Diagnosis is made by some combination of clinical, cerebral angiographic, and transcranial doppler ultrasonographic factors. Nimodipine, a calcium channel antagonist, is so far the only available therapy with proven benefit for reducing the impact of DID. Aggressive therapy combining hemodynamic augmentation, transluminal balloon angioplasty, and intra-arterial infusion of vasodilator drugs is, to varying degrees, usually implemented. A panoply of drugs, with different mechanisms of action, has been studied in SAH related vasospasm. Currently, the most promising are magnesium sulfate, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, nitric oxide donors and endothelin-1 antagonists. This paper reviews established and emerging therapies for vasospasm.

Cerebral Syncope: Insights from Valsalva Maneuver

Background and Purpose: Cerebral syncope refers to a loss of consciousness associated with cerebral vasoconstriction in the absence of systemic hypotension. The diagnosis of cerebral syncope could be established by the head-up tilt test (HUT) and transcranial Doppler ultrasonography. Valsalva maneuver (VM) permitted assessment of cerebral autoregulatory function by provoking blood pressure (BP) changes. To develop a path-physiological approach for vasomotor reactivity of cerebral syncope, the authors combined these maneuvers (HUT/transcranial Doppler/VM). Methods: Using transcranial Doppler ultrasonography, we simultaneously recorded systemic arterial BP in the radial artery and flow velocities in both middle cerebral arteries (MCAFV) in 10 cerebral syncope patients (4 males and 6 females, 35.24 ± 4.5 years old) during the Valsalva maneuver. Results: The characteristic changes in BP (phases I–IV) were seen in all subjects, accompanying distinct changes in cerebral blood flow velocity. The BP/heart rate responding to VM was within normal limit in all subjects. There was no orthostatic hypotension. Instead, BP increased during the tilting test in 2 subjects (20.00%). The MCAFV dropped 25.4 ± 2.3% from baseline. Abnormal flattening of MCAFV during late phase II (IIb), the paradoxical drop of flow velocity despite restoration of BP, was noted in 9 subjects (90.00%). Conclusion: During VM there are complex changes in relevant cardiovascular and cerebrovascular variables within a short time span. The paradoxical drop of MCAFV during phase IIb was the result of complex parameters. Among them, a failure in cerebrovascular resistance reduction and even paradoxical vasoconstriction might further compromise cerebral perfusion pressure and lead to syncope.

Cerebral blood flow during cardiac operations: Comparison of Kety-Schmidt and xenon-133 clearance methods

This study simultaneously compared the standard Kety-Schmidt and the modified xenon-133 (133Xe) clearance techniques for measuring cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) during cardiac operations. The validity of the CBF method is important because our management of the patient during cardiopulmonary bypass (CPB) is based, in part, on our understanding of the cerebral hemodynamics during CPB. In 20 patients undergoing coronary artery bypass grafting, CBF and CMRO2 were determined by both methods. Measurements were made before onset of CPB and once during CPB. Ten patients underwent CPB with systemic normothermia (37 degrees C) and 10 with systemic hypothermia (27 degrees C). Anesthesia consisted of fentanyl and midazolam. CPB pump flows were kept at 2.2 to 2.4 L.min-1.m-2 and alpha-stat pH management was used. Xenon-133 clearance significantly underestimated CBF and CMRO2 relative to the Kety-Schmidt technique before CPB and at both bypass temperatures. Values obtained by 133Xe clearance were approximately 50% of that measured by the Kety-Schmidt method. The modified 133Xe technique as typically used during cardiac operations does not appear to measure CBF accurately; this leads to corresponding errors in CMRO2 calculations. Determination of CMRO2 and cerebral autoregulatory function during cardiac operations appears to be more appropriate if based on the more direct Kety-Schmidt technique. Accordingly, our management of CPB with respect to cerebral perfusion as it has been determined by the modified 133Xe clearance method may require reassessment.