Reduction In Cerebral Perfusion Pressure Research Articles

The Effect of Oral Nimodipine on Cerebral Metabolism and Hemodynamic Parameters in Patients Suffering Aneurysmal Subarachnoid Hemorrhage.

Nimodipine is routinely administered to aneurysmal subarachnoid hemorrhage patients to improve functional outcomes. Nimodipine can induce marked systemic hypotension, which might impair cerebral perfusion and brain metabolism. Twenty-seven aneurysmal subarachnoid hemorrhage patients having multimodality neuromonitoring and oral nimodipine treatment as standard of care were included in this retrospective study. Alterations in mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), brain tissue oxygen tension (pbtO2), and brain metabolism (cerebral microdialysis), were investigated up to 120 minutes after oral administration of nimodipine (60mg or 30mg), using mixed linear models. Three thousand four hundred twenty-five oral nimodipine administrations were investigated (126±59 administrations/patient). After 60mg of oral nimodipine, there was an immediate statistically significant (but clinically irrelevant) drop in MAP (relative change, 0.97; P<0.001) and CPP (relative change: 0.97; P<0.001) compared with baseline, which lasted for the whole 120 minutes observation period (P<0.001). Subsequently, pbtO2 significantly decreased 50 minutes after administration (P=0.04) for the rest of the observation period; the maximum decrease was -0.6mmHg after 100 minutes (P<0.001). None of the investigated cerebral metabolites (glucose, lactate, pyruvate, lactate/pyruvate ratio, glutamate, glycerol) changed after 60mg nimodipine. Compared with 60mg nimodipine, 30mg induced a lower reduction in MAP (relative change, 1.01; P=0.02) and CPP (relative change, 1.01; P=0.03) but had similar effects on pbtO2 and cerebral metabolism (P>0.05). Oral nimodipine reduced MAP, which translated into a reduction in cerebral perfusion and oxygenation. However, these changes are unlikely to be clinically relevant, as the absolute changes were minimal and did not impact cerebral metabolism.

Prediction of cerebral hyperperfusion following carotid endarterectomy using intravoxel incoherent motion magnetic resonance imaging

ObjectivesOne of the risk factors for cerebral hyperperfusion following carotid endarterectomy (CEA) is a chronic reduction in cerebral perfusion pressure due to internal carotid artery (ICA) stenosis, which is clinically detected as increased cerebral blood volume (CBV). The perfusion fraction (f) is one of the intra-voxel incoherent motion (IVIM) parameters obtained using magnetic resonance (MR) imaging that theoretically reflects CBV. The present study aimed to determine whether preoperative IVIM-f on MR imaging predicts development of cerebral hyperperfusion following CEA. Materials and MethodsSixty-eight patients with unilateral ICA stenosis (≥ 70%) underwent preoperative diffusion-weighted 3-T MR imaging, and IVIM-f maps were generated from these data. Quantitative brain perfusion single-photon emission computed tomography (SPECT) was performed before and immediately after CEA. Regions-of-interest (ROIs) were automatically placed in the bilateral middle cerebral artery territories in all images using a three-dimensional stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on IVIM-f maps. ResultsNine patients (13%) exhibited postoperative hyperperfusion (cerebral blood flow increases of ≥ 100% compared with preoperative values in the ROIs on brain perfusion SPECT). Only high IVIM-f ratios were significantly associated with the occurrence of postoperative hyperperfusion (95% confidence interval, 253.8–6774.2; p = 0.0031) on logistic regression analysis. The sensitivity, specificity, and positive and negative predictive values of the IVIM-f ratio to predict the occurrence of postoperative hyperperfusion were 100%, 81%, 45%, and 100%, respectively. ConclusionsPreoperative IVIM-f on MR imaging can predict development of cerebral hyperperfusion following CEA.

A STUDY ON HAEMODYNAMIC RESPONSE ATTENUATION DURING HEAD HOLDER APPLICATION FOR CRANIOTOMY COMPARING IV DEXMEDITOMIDINE AND LOCAL LIGNOCAINE

Background; One of the goals of neuro anesthesia is to ensure stable perioperative cerebral hemodynamics, thus avoiding a sudden rise in intracranial pressure and prevent acute brain swelling.1 The intense surgical stimuli associated with craniotomy frequently causes sympathetic activation, which results in changes in heart rate (HR), blood pressure (BP), and cerebral blood ow (CBF). These changes may increase intracranial pressure (ICP) and a reduction in cerebral perfusion pressure (CPP). Finally, it leads to cerebral ischemia, especially in patients with impaired autoregulation and compromised cerebral compliance2,3. Thus, it is essential to preserve cerebral homeostasis and to prevent abrupt changes in hemodynamics. Smooth and rapid recovery from anesthesia allows immediate neurological assessment. Application of skull pin head holder is a necessity for stabilizing the head during craniotomy. Mayeld device or head holder is a clamp thatconsists of a C-shaped metal piece with three sharp interchangeable metal pins arranged triangularly to one another.4 These pins forced through the layers of scalp and periosteuminto the external lamina of the skull. Skull pins support the head without allowing any direct pressure on the face, allow access to the airway, and hold head rmly in one position that can nely be adjusted for optimal neurosurgical exposure. This study was conducted in fty ASA grade 1 or 2 patients who were adm Methods: itted at Government General Hospital, Guntur afliated to Guntur Medical College, Guntur, to undergo elective craniotomies under general anesthesia. After getting Ethical committee approval, a total of fty patients were allocated into two groups of 25 each. They were connected to the non-invasive monitors, and the basal heart rate and mean arterial pressure were recorded.Patients randomized to group dexmedetomidine received 1mcg/kg of dexmedetomidine diluted to 10ml with 0.9% saline over 10 min through a syringe pump, after recording pre-induction baseline hemodynamic parameters. Before the pin application, these patients received inltration of the pin sites with 0.9% saline (3ml for each site). Patients randomized to group lidocaine received infusion of 10ml of 0.9% saline over 10min, after recording baseline hemodynamic parameters. They then received inltration of the pre-marked pin sites with 2% lidocaine (without adrenaline), 3ml for each site. Heart rate and mean arterial pressure were recorded at various time intervals.Baseline, preinltration, post inltration, pre pin, 1 minute after post pin, 2minutes after post pin, 3 minutes, 5 miutes, 10 minutes and 15 minutes after post pin application. The result was analyzed using student t-test, and a P value of less than 0.05 was taken as signicant. ResultsWith patients matched for demographic data, the results showed there was no signicant difference in baseline values between the two groups. Heart rate and mean arterial pressure were comparable between the groups at various time intervals in the study. Thus both dexmedetomidine and lidocaine are equally effective in controlling the hemodynamic response to skull pin application. Despite being comparable to lidocaine inltration, dexmedetomidine causes signicantlymore episodes of hypotension and bradycardia, which could be detrimental in neurosurgical patients. Dexmedetomidine 1mcg/kg infusion and 2% li Conclusion gnocaine inltration both are equally effective in controlling the hemodynamic response to skull pin placement. Despite being comparable to lignocaine inltration, dexmedetomidine causes signicantly more episodes of bradycardia and hypotension, so they need rescue medication, which could be detrimental in a neurosurgical patient. We conclude that 2% of local lignocaine inltration is better in controlling hemodynamic responses to skull pin head holder application and does not cause any adverse effects in any of the patients.

English

BACKGROUND Anaesthesia for neurosurgery requires special considerations. The brain is enclosed in a rigid cranium, so the rise in intracranial pressure (ICP) which impairs cerebral perfusion pressure (CPP), results in irrepairable damage to various vital areas in the brain. Stable head position is required in long neurosurgical procedures. This is obtained with the use of clamps which fix the head rigidly. This is done usually under general anaesthesia because it produces intense painful stimuli leading to stimulation of sympathetic nervous system which in turn causes release of vasoconstrictive agents. This can impair perfusion in all organ systems. The increase in blood pressure due to sympathetic nervous system causes increase in blood flow. This causes increases in intracranial pressure which result in reduction in cerebral perfusion pressure once the auto regulatory limits are exceeded. We compared the effects of dexmedetomidine 1 µgm/kg and propofol 100 µgm/kg given as infusion over a period of 10 minutes before the induction of anaesthesia and continued till 5 minutes after pinning to attenuate the stress response while cranial pinning. In this study, we wanted to compare the effects of dexmedetomidine and propofol as infusion to attenuate the stress response while cranial pinning in patients undergoing neurosurgical procedures. METHODS This is a randomized interventional trial. Patients were divided into 2 groups of 20 each. Group 1 receiving dexmedetomidine and group 2 receiving propofol, both drugs given as infusion. Haemodynamic variables were monitored before and after cranial pinning. Data was analysed using IBM statistical package for social sciences (SPSS) statistics. The parameters recorded were analysed with the help of a statistician. RESULTS The two groups were comparable in demographic data. Incidence of tachycardia between group 1 and 2 showed that tachycardia to pinning was better controlled with propofol than dexmedetomidine (P &lt; 0.05) which is statistically significant. There is no statistically significant difference in blood pressure values between group 1 and 2 after pinning. CONCLUSIONS From our study, we came to a conclusion that propofol was superior to dexmedetomidine in attenuating the heart rate response to cranial pinning. The effect of propofol and dexmedetomidine was comparable in attenuating the blood pressure response to cranial pinning. KEYWORDS Cranial Pinning, Dexmedetomidine, Propofol

Prone Position Ventilation in Neurologically Ill Patients: A Systematic Review and Proposed Protocol.

Prone positioning has been shown to be a beneficial adjunctive supportive measure for patients who develop acute respiratory distress syndrome. Studies have excluded patients with reduced intracranial compliance, whereby patients with concomitant neurologic diagnoses and acute respiratory distress syndrome have no defined treatment algorithm or recommendations for management. In this study, we aim to determine the safety and feasibility of prone positioning in the neurologically ill patients. A systematic review of the literature, performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses 2009 guidelines, yielded 10 articles for analysis. Using consensus from these articles, in combination with review of multi-institutional proning protocols for patients with nonneurologic conditions, a proning protocol for patients with intracranial pathology and concomitant acute respiratory distress syndrome was developed. Among 10 studies included in the final analysis, we found that prone positioning is safe and feasible in the neurologically ill patients with acute respiratory distress syndrome. Increased intracranial pressure and compromised cerebral perfusion pressure may occur with prone positioning. We propose a prone positioning protocol for the neurologically ill patients who require frequent neurologic examinations and intracranial monitoring. Although elevations in intracranial pressure and reductions in cerebral perfusion pressure do occur during proning, they may not occur to a degree that would warrant exclusion of prone ventilation as a treatment modality for patients with acute respiratory distress syndrome and concomitant neurologic diagnoses. In cases where intracranial pressure, cerebral perfusion pressure, and brain tissue oxygenation can be monitored, prone position ventilation should be considered a safe and viable therapy.

Effect of magnesium sulphate on the intracranial pressure of preeclampsia patients using ultrasound-guided optic nerve sheath diameter: A pilot study.

Background:Increased intracranial pressure (ICP) is a known complication of pre-eclampsia with severe features. The use of magnesium sulphate (MgSO4) is the standard treatment and is associated with marked reduction of cerebral perfusion pressure (CPP) and prevention of cerebral damage. Optic nerve sheath diameter (ONSD) ultrasonography is a bedside tool used to reflect changes in the ICP. The aim of this study is to detect the effect of MgSO4 administration on ICP in severe preeclampsia through measuring changes in the ONDS.Methods:Thirty pregnant female patients suffering from severe pre-eclampsia were enrolled in this prospective pilot study. Ultrasound measurement of ONSD was measured before the commencement of MgSO4 and after 1, 6, and 24 h after the administration.Results:There was a significant difference in ONSD measurements between that at baseline and post magnesium administration at 1, 6, and 24 h (P-value 0.001). Additionally, a significant difference in measurements between 1 and 6 and 6 and 24 h after magnesium initiation (P-value 0.001).Conclusions:Ultrasound ONSD measurement in patients with severe preeclampsia is a non-invasive easy tool to detect increased intracranial pressure and monitor the response to magnesium sulphate infusion.

Escalation therapy in severe traumatic brain injury: how long is intracranial pressure monitoring necessary?

Traumatic brain injury frequently causes an elevation of intracranial pressure (ICP) that could lead to reduction of cerebral perfusion pressure and cause brain ischemia. Invasive ICP monitoring is recommended by international guidelines, in order to reduce the incidence of secondary brain injury; although rare, the complications related to ICP probes could be dependent on the duration of monitoring. The aim of this manuscript is to clarify the appropriate timing for removal and management of invasive ICP monitoring, in order to reduce the risk of related complications and guarantee adequate cerebral autoregulatory control. There is no universal consensus concerning the duration of invasive ICP monitoring and its related complications, although the pertinent literature seems to show that the longer is the monitoring maintenance, the higher is the risk of technical issues. Besides, upon 72 h of normal ICP values or less than 72 h if the first computed tomography scan is normal (none or minimal signs of injury) and the neurological exam is available (allowing to observe variations and possible occurrence of new-onset pathological response), the removal of invasive ICP monitoring can be justified. The availability of non-invasive monitoring systems should be considered to follow up patients’ clinical course after invasive ICP probe removal or for substituting the invasive monitoring in case of contraindication to its placement. Recently, optic nerve sheath diameter and straight sinus systolic flow velocity evaluation through ultrasound methods showed a good correlation with ICP values, demonstrating their potential role in place of invasive monitoring or in the early weaning phase from the invasive ICP monitoring.

Immunomodulatory Effect of Hypertonic Saline Solution in Traumatic Brain-Injured Patients and Intracranial Hypertension

AbstractTraumatic brain injury (TBI) is often associated with an increase in the intracranial pressure (ICP). This increase in ICP can cross the physiological range and lead to a reduction in cerebral perfusion pressure (CPP) and the resultant cerebral blood flow (CBF). It is this reduction in the CBF that leads to the secondary damage to the neural parenchyma along with the physical axonal and neuronal damage caused by the mass effect. In certain cases, a surgical intervention may be required to either remove the mass lesion (hematoma of contusion evacuation) or provide more space to the insulted brain to expand (decompressive craniectomy). Whether or not a surgical intervention is performed, all these patients require some form of pharmaceutical antiedema agents to bring down the raised ICP. These agents have been broadly classified as colloids (e.g., mannitol, glycerol, urea) and crystalloids (e.g., hypertonic saline), and have been used since decades. Even though mannitol has been the workhorse for ICP reduction owing to its unique properties, crystalloids have been found to be the preferred agents, especially when long-term use is warranted. The safest and most widely used agent is hypertonic saline in various concentrations. Whatever be the concentration, hypertonic saline has created special interest among physicians owing to its additional property of immunomodulation and neuroprotection. In this review, we summarize and understand the various mechanism by which hypertonic saline exerts its immunomodulatory effects that helps in neuroprotection after TBI.

Effects of Routine Position Changes and Tracheal Suctioning on Intracranial Pressure in Traumatic Brain Injury Patients.

Patient position change and tracheal suctioning are routine interventions in mechanically ventilated traumatic brain injury (TBI) patients. We sought to better understand the impact of these interventions on intracranial pressure (ICP) and cerebral hemodynamics. We conducted a prospective study in TBI patients requiring ICP monitoring. The timing of position changes and suctioning episodes were recorded with concurrent blood pressure and ICP measurements. We collected data on 460 patient position changes and 204 suctioning episodes over 2404 h in 18 ventilated patients (mean age 34 [13] years, median Glasgow Coma Score 4 [3-7]). We recorded 24 (20-31) positioning and 11 (6-18) suctioning episodes per patient, with 54% and 39% of position changes associated with ICP ≥22 mm Hg and cerebral perfusion pressure (CPP) <60 mm Hg, respectively, and 22% and 27% of suctioning episodes associated with an ICP ≥22 mm Hg and CPP <60 mm Hg. The median change in ICP was 11 (6-16) mm Hg after position changes and 3 (1-9) mm Hg after suctioning. Reduction in CPP to <60 mm Hg lasted ≥10 min in 17% of positioning and 11% of suctioning episodes. The baseline ICP and its amplitude were both predictive of a rise in ICP ≥22 mm Hg after positioning and suctioning episodes, whereas cerebral autoregulation was not. Baseline CPP was predictive of a decrease in CPP <60 mm Hg after both interventions. Increases in ICP and reductions in CPP are common following patient positioning and tracheal suctioning episodes. Frequently, these changes are substantial and sustained.

Implication of altered autonomic control for orthostatic tolerance in SCI.

Neural output from the sympathetic and parasympathetic branches of the autonomic nervous system (ANS) are integrated to appropriately control cardiovascular responses during routine activities of daily living including orthostatic positioning. Sympathetic control of the upper extremity vasculature and the heart arises from the thoracic cord between T1 and T5, whereas splanchnic bed and lower extremity vasculature receive sympathetic neural input from the lower cord between segments T5 and L2. Although the vasculature is not directly innervated by the parasympathetic nervous system, the SA node is innervated by post-ganglionic vagal nerve fibers via cranial nerve X. Segmental differences in sympathetic cardiovascular innervation highlight the effect of lesion level on orthostatic cardiovascular control following spinal cord injury (SCI). Due to impaired sympathetic cardiovascular control, many individuals with SCI, particularly those with lesions above T6, are prone to orthostatic hypotension (OH) and orthostatic intolerance (OI). Symptomatic OH, which may result in OI, is a consequence of episodic reductions in cerebral perfusion pressure and the symptoms may include: dizziness, lightheadedness, nausea, blurred vision, ringing in the ears, headache and syncope. However, many, if not most, individuals with SCI who experience persistent and episodic hypotension and OH do not report symptoms of cerebral hypoperfusion and therefore do not raise clinical concern. This review will discuss the mechanism underlying OH and OI following SCI, and will review our knowledge to date regarding the prevalence, consequences and possible treatment options for these conditions in the SCI population.

Quantitative estimation of a ratio of intracranial cerebrospinal fluid volume to brain volume based on segmentation of CT images in patients with extra-axial hematoma.

Background Diminishing volume of intracranial cerebrospinal fluid (CSF) in patients with space-occupying masses have been attributed to unfavorable outcome associated with reduction of cerebral perfusion pressure and subsequent brain ischemia. Objective The objective of this article is to employ a ratio of CSF volume to brain volume for longitudinal assessment of space-volume relationships in patients with extra-axial hematoma and to determine variability of the ratio among patients with different types and stages of hematoma. Patients and methods In our retrospective study, we reviewed 113 patients with surgical extra-axial hematomas. We included 28 patients (age 61.7 +/- 17.7 years; 19 males, nine females) with an acute epidural hematoma (EDH) ( n = 5) and subacute/chronic subdural hematoma (SDH) ( n = 23). We excluded 85 patients, in order, due to acute SDH ( n = 76), concurrent intraparenchymal pathology ( n = 6), and bilateral pathology ( n = 3). Noncontrast CT images of the head were obtained using a CT scanner (2004 GE LightSpeed VCT CT system, tube voltage 140 kVp, tube current 310 mA, 5 mm section thickness) preoperatively, postoperatively (3.8 ± 5.8 hours from surgery), and at follow-up clinic visit (48.2 ± 27.7 days after surgery). Each CT scan was loaded into an OsiriX (Pixmeo, Switzerland) workstation to segment pixels based on radiodensity properties measured in Hounsfield units (HU). Based on HU values from -30 to 100, brain, CSF spaces, vascular structures, hematoma, and/or postsurgical fluid were segregated from bony structures, and subsequently hematoma and/or postsurgical fluid were manually selected and removed from the images. The remaining images represented overall brain volume-containing only CSF spaces, vascular structures, and brain parenchyma. Thereafter, the ratio between the total number of voxels representing CSF volume (based on values between 0 and 15 HU) to the total number of voxels representing overall brain volume was calculated. Results CSF/brain volume ratio varied significantly during the course of the disease, being the lowest preoperatively, 0.051 ± 0.032; higher after surgical evacuation of hematoma, 0.067 ± 0.040; and highest at follow-up visit, 0.083 ± 0.040 ( p < 0.01). Using a repeated regression analysis, we found a significant association ( p < 0.01) of the ratio with age (odds ratio, 1.019; 95% CI, 1.009-1.029) and type of hematoma (odds ratio, 0.405; 95% CI, 0.303-0.540). Conclusion CSF/brain volume ratio calculated from CT images has potential to reflect dynamics of intracranial volume changes in patients with space-occupying mass.

A new non-craniotomy model of subarachnoid hemorrhage in the pig: a pilot study.

Subarachnoid hemorrhage (SAH) from rupture of an intracranial arterial aneurysm is a devastating disease affecting young people, with serious lifelong disability or death as a frequent outcome. Large animal models that exhibit all the cardinal clinical features of human SAH are highly warranted. In this pilot study we aimed to develop a non-craniotomy model of SAH in pigs suitable for acute intervention studies. Six Norwegian Landrace pigs received advanced invasive hemodynamic and intracranial pressure (ICP) monitoring. The subarachnoid space, confirmed by a clear cerebrospinal fluid (CSF) tap, was reached by advancing a needle below the ocular bulb through the superior orbital fissure and into the interpeduncular cistern. SAH was induced by injecting 15 mL of autologous arterial blood into the subarachnoid space. Macro- and microanatomical investigations of the pig brain showed a typical blood distribution consistent with human aneurysmal SAH (aSAH) autopsy data. Immediately after SAH induction ICP sharply increased with a concomitant reduction in cerebral perfusion pressure (CPP). ICP returned to near normal values after 30 min, but increased subsequently during the experimental period. Signs of brain edema were confirmed by light microscopy post-mortem. None of the animals died during the experimental period. This new transorbital injection model of SAH in the pig mimics human aSAH and may be suitable for acute intervention studies. However, the model is technically challenging and needs further validation.

The correlation between brain near-infrared spectroscopy and cerebral blood flow in piglets with intracranial hypertension.

Cerebral perfusion pressure (CPP) is used as a surrogate for measurement of cerebral blood flow (CBF) but its determination requires that intracranial pressure be directly measured. Near-infrared spectroscopy (NIRS) can noninvasively measure tissue oxygenation. We hypothesized that NIRS would correlate well with CBF, with cerebral metabolism of oxygen (CMRO2) and glucose and with lactate production as CPP was reduced. Seven anesthetized piglets were subjected to reductions in CPP to 60, 50, 40, 30, and 20 mmHg by infusing an artificial cerebral spinal fluid into the lateral ventricle of the brain. After a period of equilibration, NIRS over the left temporal cortex and regional CBF (microspheres) were measured at each CPP level as well as arterial and internal jugular PaO2 , glucose, and lactate. CMRO2 and glucose consumption and lactate production were calculated by standard formulae. NIRS correlated very well (P < 0.05) with CBF in the left temporal cortex [mean r (95% CI) = 0.95 (0.91-0.99)] and with left hemispheric CMRO2 [0.94 (0.90-0.98)], glucose consumption [0.87 (0.76-0.97)], and lactate production [0.89 (0.81-0.97)]. The correlation of NIRS with CBF was slightly better (P < 0.05) than that of CPP with CBF [0.89 (0.84-0.94)]. In this model of global cerebral hypertension, NIRS correlated well with CBF and measures of cerebral metabolism, and might be useful as a surrogate for CPP. Further studies are warranted to determine if NIRS is associated with these variables in focal cerebral injury.

Intracranial pressure and cerebral perfusion pressure in patients developing brain death

PurposeWe investigated whether a critical rise of intracranial pressure (ICP) leading to a loss of cerebral perfusion pressure (CPP) could serve as a surrogate marker of brain death (BD). Materials and methodsWe retrospectively analyzed ICP and CPP of patients in whom BD was diagnosed (n = 32, 16-79 years). Intracranial pressure and CPP were recorded using parenchymal (n = 27) and ventricular probes (n = 5). Data were analyzed from admission until BD was diagnosed. ResultsIntracranial pressure was severely elevated (mean ± SD, 95.5 ± 9.8 mm Hg) in all patients when BD was diagnosed. In 28 patients, CPP was negative at the time of diagnosis (−8.2 ± 6.5 mm Hg). In 4 patients (12.5%), CPP was reduced but not negative. In these patients, minimal CPP was 4 to 18 mm Hg. In 1 patient, loss of CPP occurred 4 hours before apnea completed the BD syndrome. ConclusionsBrain death was universally preceded by a severe reduction of CPP, supporting loss of cerebral perfusion as a critical step in BD development. Our data show that a negative CPP is neither sufficient nor a prerequisite to diagnose BD. In BD cases with positive CPP, we speculate that arterial blood pressure dropped below a critical closing pressure, thereby causing cessation of cerebral blood flow.

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.

Safety and efficacy of combined epidural/general anesthesia during major abdominal surgery in patients with increased intracranial pressure: a cohort study

BackgroundThe increased intracranial pressure can significantly complicate the perioperative period in major abdominal surgery, increasing the risk of complications, the length of recovery from the surgery, worsening the outcome. Epidural anesthesia has become a routine component of abdominal surgery, but its use in patients with increased intracranial pressure remains controversial. The goal of the study was to evaluate the safety and efficacy of epidural anesthesia, according to monitoring of intracranial pressure in patients with increased intracranial pressure.MethodsThe study includes 65 surgical patients who were routinely undergone the major abdominal surgery under combined epidural/general anesthesia. Depending on the initial ICP all patients were divided into 2 groups: 1 (N group) - patients with the normal intracranial pressure (≤12 mm Hg, n = 35) and 2 (E group) – patients with the elevated intracranial pressure (ICP > 12 mm Hg, n = 30). During the surgery we evaluated ICP, blood pressure, cerebral perfusion pressure (CPP). The parameters of recovery from anesthesia and the effectiveness of postoperative analgesia were also assessed.ResultsIn N group ICP remained stable. In E group ICP decreased during anesthesia, the overall decline was 40 % at the end of the operation (from 15 to 9 mm Hg (P <0.05)). The correction of MAP with vasopressors to maintain normal CPP was required mainly in patients with increased ICP (70 % vs. 45 %, p <0.05). CPP declined by 19 % in N group. In E group the CPP reduction was 23 %, and then it remained stable at 60 mm Hg. No significant differences in time of the recovery of consciousness, effectiveness of postoperative analgesia and complications between patients with initially normal levels of ICP and patients with ICH were noted.ConclusionsThe combination of general and epidural anesthesia is safe and effective in patients with increased intracranial pressure undergoing elective abdominal surgery under the condition of maintaining the arterial pressure. Its use is not associated with the increase in intracranial pressure during the anesthesia, but it needs an intraoperative monitoring of ICP in order to prevent CPP reduction.

Evidence for Cerebral Hemodynamic Measurement-based Therapy in Symptomatic Major Cerebral Artery Disease.

In patients with atherosclerotic internal carotid artery or middle cerebral artery occlusive disease, chronic reduction in cerebral perfusion pressure (chronic hemodynamic compromise) increases the risk of ischemic stroke and can be detected by directly measuring hemodynamic parameters. However, strategies for selecting treatments based on hemodynamic measurements have not been clearly established. Bypass surgery has been proven to improve hemodynamic compromise. However, the benefit of bypass surgery for reducing the stroke risk in patients with hemodynamic compromise is controversial. The results of the two randomized controlled trials were inconsistent. Hypertension is a major risk factor for stroke, and antihypertensive therapy provides general benefit to patients with symptomatic atherosclerotic major cerebral artery disease. However, the benefit of strict control of blood pressure for reducing the stroke risk in patients with hemodynamic compromise is a matter of debate. The results of the two observational studies were different. We must establish strategies for selecting treatments based on hemodynamic measurements in atherosclerotic major cerebral artery disease.

Early brain injury linearly correlates with reduction in cerebral perfusion pressure during the hyperacute phase of subarachnoid hemorrhage.

BackgroundIt is unclear how complex pathophysiological mechanisms that result in early brain injury (EBI) after subarachnoid hemorrhage (SAH) are triggered. We investigate how peak intracranial pressure (ICP), amount of subarachnoid blood, and hyperacute depletion of cerebral perfusion pressure (CPP) correlate to the onset of EBI following experimental SAH.MethodsAn entire spectrum of various degrees of SAH severities measured as peak ICP was generated and controlled using the blood shunt SAH model in rabbits. Standard cardiovascular monitoring, ICP, CPP, and bilateral regional cerebral blood flow (rCBF) were continuously measured. Cells with DNA damage and neurodegeneration were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB).ResultsrCBF was significantly correlated to reduction in CPP during the initial 15 min after SAH in a linear regression pattern (r2 = 0.68, p < 0.001). FJB- and TUNEL-labeled cells were linearly correlated to reduction in CPP during the first 3 min of hemorrhage in the hippocampal regions (FJB: r2 = 0.50, p < 0.01; TUNEL: r2 = 0.35, p < 0.05), as well as in the basal cortex (TUNEL: r2 = 0.58, p < 0.01). EBI occurred in animals with severe (relative CPP depletion >0.4) and moderate (relative CPP depletion >0.25 but <0.4) SAH. Neuronal cell death was equally detected in vulnerable and more resistant brain regions.ConclusionsThe degree of EBI in terms of neuronal cell degeneration in both the hippocampal regions and the basal cortex linearly correlates with reduced CPP during hyperacute SAH. Temporary CPP reduction, however, is not solely responsible for EBI but potentially triggers processes that eventually result in early brain damage.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-014-0030-1) contains supplementary material, which is available to authorized users.

Paradoxical reduction of cerebral blood flow after acetazolamide loading: a hemodynamic and metabolic study with (15)O PET.

Paradoxical reduction of cerebral blood flow (CBF) after administration of the vasodilator acetazolamide is the most severe stage of cerebrovascular reactivity failure and is often associated with an increased oxygen extraction fraction (OEF). In this study, we aimed to reveal the mechanism underlying this phenomenon by focusing on the ratio of CBF to cerebral blood volume (CBV) as a marker of regional cerebral perfusion pressure (CPP). In 37 patients with unilateral internal carotid or middle cerebral arterial (MCA) steno-occlusive disease and 8 normal controls, the baseline CBF (CBF(b)), CBV, OEF, cerebral oxygen metabolic rate (CMRO2), and CBF after acetazolamide loading in the anterior and posterior MCA territories were measured by (15)O positron emission tomography. Paradoxical CBF reduction was found in 28 of 74 regions (18 of 37 patients) in the ipsilateral hemisphere. High CBF(b) (> 47.6 mL/100 mL/min, n = 7) was associated with normal CBF(b)/CBV, increased CBV, decreased OEF, and normal CMRO2. Low CBF(b) (< 31.8 mL/100 mL/min, n = 9) was associated with decreased CBF(b)/CBV, increased CBV, increased OEF, and decreased CMRO2. These findings demonstrated that paradoxical CBF reduction is not always associated with reduction of CPP, but partly includes high-CBF(b) regions with normal CPP, which has not been described in previous studies.

Metabolic pattern of the acute phase of subarachnoid hemorrhage in a novel porcine model: studies with cerebral microdialysis with high temporal resolution.

BackgroundAneurysmal subarachnoid hemorrhage (SAH) may produce cerebral ischemia and systemic responses including stress. To study immediate cerebral and systemic changes in response to aneurysm rupture, animal models are needed.ObjectiveTo study early cerebral energy changes in an animal model.MethodsExperimental SAH was induced in 11 pigs by autologous blood injection to the anterior skull base, with simultaneous control of intracranial and cerebral perfusion pressures. Intracerebral microdialysis was used to monitor concentrations of glucose, pyruvate and lactate.ResultsIn nine of the pigs, a pattern of transient ischemia was produced, with a dramatic reduction of cerebral perfusion pressure soon after blood injection, associated with a quick glucose and pyruvate decrease. This was followed by a lactate increase and a delayed pyruvate increase, producing a marked but short elevation of the lactate/pyruvate ratio. Glucose, pyruvate, lactate and lactate/pyruvate ratio thereafter returned toward baseline. The two remaining pigs had a more severe metabolic reaction with glucose and pyruvate rapidly decreasing to undetectable levels while lactate increased and remained elevated, suggesting persisting ischemia.ConclusionThe animal model simulates the conditions of SAH not only by deposition of blood in the basal cisterns, but also creating the transient global ischemic impact of aneurysmal SAH. The metabolic cerebral changes suggest immediate transient substrate failure followed by hypermetabolism of glucose upon reperfusion. The model has features that resemble spontaneous bleeding, and is suitable for future research of the early cerebral and systemic responses to SAH that are difficult to study in humans.