Transcranial Doppler Flow Velocity Research Articles

Ventricular Volume Load Reveals the Mechanoelastic Impact of Communicating Hydrocephalus on Dynamic Cerebral Autoregulation.

Several studies have shown that the progression of communicating hydrocephalus is associated with diminished cerebral perfusion and microangiopathy. If communicating hydrocephalus similarly alters the cerebrospinal fluid circulation and cerebral blood flow, both may be related to intracranial mechanoelastic properties as, for instance, the volume pressure compliance. Twenty-three shunted patients with communicating hydrocephalus underwent intraventricular constant-flow infusion with Hartmann’s solution. The monitoring included transcranial Doppler (TCD) flow velocities (FV) in the middle (MCA) and posterior cerebral arteries (PCA), intracranial pressure (ICP), and systemic arterial blood pressure (ABP). The analysis covered cerebral perfusion pressure (CPP), the index of pressure-volume compensatory reserve (RAP), and phase shift angles between Mayer waves (3 to 9 cpm) in ABP and MCA-FV or PCA-FV. Due to intraventricular infusion, the pressure-volume reserve was exhausted (RAP) 0.84+/-0.1 and ICP was increased from baseline 11.5+/-5.6 to plateau levels of 20.7+/-6.4 mmHg. The ratio dRAP/dICP distinguished patients with large 0.1+/-0.01, medium 0.05+/-0.02, and small 0.02+/-0.01 intracranial volume compliances. Both M wave phase shift angles (r = 0.64; p<0.01) and CPP (r = 0.36; p<0.05) displayed a gradual decline with decreasing dRAP/dICP gradients. This study showed that in communicating hydrocephalus, CPP and dynamic cerebral autoregulation in particular, depend on the volume-pressure compliance. The results suggested that the alteration of mechanoelastic characteristics contributes to a reduced cerebral perfusion and a loss of autonomy of cerebral blood flow regulation. Results warrant a prospective TCD follow-up to verify whether the alteration of dynamic cerebral autoregulation may indicate a progression of communicating hydrocephalus.

Long-Term, Continuous Intra-Arterial Nimodipine Treatment of Severe Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Secondary vasospasm and disturbances in cerebrovascular autoregulation are associated with the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. An intra-arterial application of nimodipine has been shown to increase the vessel diameter, although this effect is transient. The feasibility of long-term, continuous, intra-arterial nimodipine treatment and its effects on macrovasospasm, autoregulation parameters, and outcome were evaluated in patients with refractory severe macrovasospasm. Ten patients were included with refractory macrovasospasm despite bolus nimodipine application (n= 4) or with primary severe vasospasm (n= 6). The patients were assessed with continuous multimodal neuromonitoring (mean arterial pressure, intraceranial pressure, cerebral perfusion pressure, brain tissue oxygen tension probe), daily transcranial Doppler examinations, and computed tomography angiography/perfusion. Autoregulation indices, the pressure reactivity index, and oxygen reactivity index were calculated. Indwelling microcatheters were placed in the extracranial internal carotid arteries and 0.4 mg nimodipine was continuously infused at 50 mL/hour. The duration of continuous, intra-arterial nimodipine ranged from 9 to 15 days. During treatment intracranial pressure remained stable, transcranial Doppler flow velocity decreased, and brain tissue oxygen tension improved by 37%. Macrovasospasm, as assessed via computed tomography angiography, had improved (n= 5) or disappeared (n= 5) at the end of treatment. Cerebrovascular autoregulation according to the pressure reactivity index and oxygen reactivity index significantly worsened during treatment. All patients showed a favorable outcome (median Glasgow Outcome Scale 5) at 3 months. In well-selected patients with prolonged severe macrovasospasm, continuous intra-arterial nimodipine treatment can be applied as a rescue therapy with relative safety for more than 2 weeks to prevent secondary cerebral ischemia. The induced impairment of cerebrovascular autoregulation during treatment seems to have no negative effects.

Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia—TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial

BackgroundFor children with sickle cell anaemia and elevated transcranial Doppler (TCD) flow velocities, regular blood transfusions effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxyurea in this setting is unknown.MethodsTWiTCH was a multicentre Phase III randomised open label, non-inferiority trial comparing standard treatment (transfusions) to alternative treatment (hydroxyurea) in children with abnormal TCD velocities but no severe vasculopathy. Iron overload was managed with chelation (Standard Arm) and serial phlebotomy (Alternative Arm). The primary study endpoint was the 24-month TCD velocity calculated from a general linear mixed model, with non-inferiority margin = 15 cm/sec.FindingsAmong 121 randomised participants (61 transfusions, 60 hydroxyurea), children on transfusions maintained <30% sickle haemoglobin, while those taking hydroxyurea (mean 27 mg/kg/day) averaged 25% fetal haemoglobin. The first scheduled interim analysis demonstrated non-inferiority, and the sponsor terminated the study. Final model-based TCD velocities (mean ± standard error) on Standard versus Alternative Arm were 143 ± 1.6 and 138 ± 1.6 cm/sec, respectively, with difference (95% CI) = 4.54 (0.10, 8.98), non-inferiority p=8.82 × 10−16 and post-hoc superiority p=0.023. Among 29 new neurological events adjudicated centrally by masked reviewers, no strokes occurred but there were 3 transient ischaemic attacks per arm. Exit brain MRI/MRA revealed no new cerebral infarcts in either arm, but worse vasculopathy in one participant (Standard Arm). Iron burden decreased more in the Alternative Arm, with ferritin difference −1047 ng/mL (−1524, −570), p<0.001 and liver iron difference −4.3 mg Fe/gm dry weight (−6.1, −2.5), p=0.001.InterpretationFor high-risk children with sickle cell anaemia and abnormal TCD velocities, after four years of transfusions and without severe MRA vasculopathy, hydroxyurea therapy can substitute for chronic transfusions to maintain TCD velocities and help prevent primary stroke.

G306 Hydroxyurea lowers transcranial Doppler flow velocities in Nigerian children with sickle cell anaemia

BackgroundTranscranial Doppler (TCD) flow velocities predict stroke risk in children with sickle cell disease (SCD) and give a chance for primary stroke prevention. Elevated velocities ≥ 170 cm/sec are present...

Intra-aortic balloon pump (IABP) counterpulsation improves cerebral perfusion in patients with decreased left ventricular function

The current goal of treatment after acute ischemic stroke is the increase of cerebral blood flow (CBF) in ischemic brain tissue. Intra-aortic balloon pump (IABP) counterpulsation in the setting of cardiogenic shock is able to reduce left ventricular afterload and increase coronary blood flow. The effects of an IABP on CBF have not been sufficiently examined. We hypothesize that the use of an IABP especially enhances cerebral blood flow in patients with pre-existing heart failure. In this pilot study, 36 subjects were examined to investigate the effect of an IABP on middle cerebral artery (MCA) transcranial Doppler (TCD) flow velocity change and relative CBF augmentation by determining velocity time integral changes (ΔVTI) in a constant caliber of the MCA compared to a baseline measurement without an IABP. Subjects were divided into two groups according to their left ventricular ejection fraction (LVEF): Group 1 LVEF >30% and Group 2 LVEF ≤30%. Both groups showed an increase in CBF using an IABP. Patients with a LVEF ≤30% showed a significantly higher increase of ΔVTI in the MCA under IABP augmentation compared to patients with a LVEF >30% (20.9% ± 3.9% Group 2 vs.10.5% ± 2.2% Group 1, p<0,05). The mean arterial pressure (MAP) increased only marginally in both groups under IABP augmentation. IABP improves cerebral blood flow, particularly in patients with pre-existing heart failure and highly impaired LVEF. Hence, an IABP might be a treatment option to improve cerebral perfusion in selected patients with cerebral misperfusion and simultaneously existing severe heart failure.

Abstract W P227: Cerebral Hyperperfusion Syndrome after Intravenous Thrombolysis for Acute Ischemic Stroke

Background: Cerebral hyperperfusion syndrome (CHS) is a recognized complication after surgical revascularization of a chronically atherosclerotic artery. However, this phenomenon is unexpected when an acutely occluded artery is recanalized by IV-TPA for acute ischemic stroke (AIS).In patients with discrepant neuroimaging and clinical findings, our multimodal evaluations revealed CHS in a series of 7 patientsmafter IV- TPA therapy. Methods: Patients in whom the occluded ICA or MCA in pre-TPA CT-angiogram (CTA) showed recanalization in the day-2 CTA, were observed for any new unexpected neuropsychiatric symptoms/signs. If these were present they underwent multimodal evaluation including serial transcranial Doppler (TCD), quantitative electroencephalography (QEEG) and HMPAO-SPECT. Patients with considerable mismatch between clinical and neuroimaging findings were also included. CHS was deemed to have occurred if the unexpected neuropsychiatric signs corresponded with TCD flow velocity &gt;100% of the contralateral vessel, EEG showed abnormal activity and HMPAO-SPECT scan showed markedly increased cerebral perfusion compared to the contralateral side. Results: Out of 155 patients treated with IV-TPA, 7 (4.5%) patients fulfilled our definition of CHS. All 7 patients developed the symptoms 2-3 days after IV-TPA. Abnormalities on TCD, QEEG and HMPAO-SPECT were observed in all patients. The unexpected symptoms included generalized headache (4 cases), unexplained persistent drowsiness (3 cases), visual neglect (2 cases), aphasia (2 cases) and severe suicidal thoughts despite complete neurological recovery (1 case). All cases had hypertension prior to the index stroke. Upright posture, fluid restriction and aggressive blood pressure control resulted in rapid resolution of abnormal features in all cases within a week. All patients achieved modified Rankin score 0-1 with no intracranial hemorrhage. Conclusion: CHS after intravenous thrombolysis in acute ischemic stroke should be suspected in patients that achieve arterial recanalization with unexplained new neuropsychiatric manifestations. Early diagnosis and appropriate management might prevent hemorrhage and achieve good functional outcomes.

Abstract T P87: Does an Increased Pulsatility of the Intracranial Blood Flow Spectral Waveform on Transcranial Doppler (TCD) Point to Peripheral Arterial Disease in Stroke Patients?

Background: Peripheral arterial disease (PAD) is common in patients with acute cerebral ischemia, yet little testing, if any, is done during in-hospital stay. The pulsatility index (PI) from the systolic and diastolic velocity measurements on TCD is routinely used in stroke patients to assess resistance to flow and thereby intracranial atheromatous disease. We sought to explore whether the PI can indirectly predict the presence of PAD in these patients. Methods: We prospectively evaluated consecutive patients with acute cerebral ischemia by TCD and ankle-brachial-index (ABI) measurements. Clinical variables were collected at baseline. On TCD, peak systolic, end-diastolic and mean flow velocities in both middle cerebral and basilar arteries were manually measured. According to a complete four-cardiac cycle sweep without arrhythmias, PI was automatically calculated for each of the 3 arteries and the average was used for analysis. Bilateral brachial, tibial and pedal systolic blood pressures were measured using a 4-MHz continuous-wave Doppler (average over two measurements). ABI 0.91 to 0.99 was considered as borderline, ABI &lt;=0.9 as abnormal and predictive of PAD. All examinations were done in supine position. Results: We enrolled a total of 53 patients: 68% ischemic stroke, 32% TIA, 60% Caucasians, 42% male, mean age 64±10 yrs, median NIHSS 4 (range 0-20). ABI was borderline or abnormal in 26/53 (49%) including 12/53 (23%) patients with ABIs consistent with PAD. Baseline characteristics were similar between patients with and without PAD. The mean PI did not differ among patients with and without PAD (0.92±0.08 vs. 1.01±0.04, p=0.24). The PI was not found to be an independent predictor of PAD (OR=0.21, 95% CI 0.01-3.64, p=0.285). Similarly, the PI did not predict ABI (p=0.96). PI strongly predicted history of arterial hypertension (OR=530.04, 95%CI 5.18-54215.57, p=0.008). Conclusions: Our findings do not suggest that the presence of PAD can be inferred from intracranial flow parameters predictive of atheromatous disease and risk factors such as hypertension among patients with acute cerebral ischemia. However, the high frequency of PAD in these patients warrants further investigation to facilitate routine and early detection of this disease.

Low Plasma Arginine:Asymmetric Dimethyl Arginine Ratios Predict Mortality After Intracranial Aneurysm Rupture

Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, predicts mortality in cardiovascular disease and has been linked to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In this prospective study, we assessed whether circulating ADMA, arginine:ADMA ratio, and nitrite/nitrate levels were associated with survival and cerebral vasospasm in SAH patients. One hundred and eleven patients were observed day 1 to 15 after SAH, with serial measurements of transcranial Doppler flow velocities (VMCA) and plasma biomarkers. Clinical status was assessed by the World Federation of Neurosurgical Societies grading scale. Overall 30-day mortality was 18%, but differed between patients grouped by low, midrange, and high arginine:ADMA ratio in the first week after SAH. Mortality rates were 14/37, 1/37, and 5/37 in the 3 groups, respectively (P-logrank=0.0003). Cox regression showed that low versus midrange or high arginine:ADMA was associated with a hazard ratio of 4.1 independent of World Federation of Neurosurgical Societies grade (95% confidence interval, 1.5-10.9; P=0.006). ADMA or arginine:ADMA had no association to VMCA, but there was an inverse relationship between VMCA and nitrite/nitrate levels (P<0.0001). The NOS3 894G/G genotype was associated with 15% lower VMCA (P=0.01). ATbG-NOS3 haplotype homozygosity was associated with up to 64% higher nitrite/nitrate levels (P=0.003). This study suggests that plasma arginine:ADMA ratios predict mortality after SAH. Both clinical and physiological measures of changes in cerebral hemodynamics are coupled to the nitric oxide system.

Evaluation of transcranial Doppler flow velocity changes in intracerebral hemorrhage rats using ultrasonography

This study investigated the blood flow velocity changes in seven major arteries in rat brain before and after intracerebral hemorrhage (ICH) using high frequency transcranial Doppler (TCD) ultrasonography (13–4MHz). Eighteen adult Sprague Dawley rats received either the collagenase-injection surgery (ICH, n=12) or the saline-injection surgery (control, n=6) after baseline TCD flow velocity values were recorded. The TCD flow velocity changes were measured at 0.5h after the surgery and daily for the following 8days in seven major cerebral arteries, including bilateral internal carotid arteries, bilateral middle cerebral arteries (MCAs), bilateral posterior cerebral arteries (PCAs), and basilar artery. The results showed a significant decrease of TCD flow velocity in the right MCA at 0.5h and 24h after the collagenase-injection surgery, and in the right PCA at 0.5h in the ICH group rats. The TCD flow velocities in these two arteries gradually increased and then returned to the baseline values in the following days. The control group rats did not show significant changes in TCD flow velocity in all monitored arteries. This study demonstrates the feasibility and reliability of monitoring TCD flow velocity in cerebral arteries using ultrasonography technique in a rat ICH model. The results of this study extend our knowledge in the cerebrovascular changes during intracranial hemorrhage and suggest a possibility of clinical application of TCD ultrasonography in studying the dynamic cerebral circulation after strokes. Moreover, this method could be extensively applied in further studies using potential neuroprotective treatments that affect the cerebral dynamics in the intracerebral hemorrhage.

Cerebral Blood Flow and Transcranial Doppler Sonography Measurements of CO2-Reactivity in Acute Traumatic Brain Injured Patients

Cerebral blood flow (CBF) measurements are helpful in managing patients with traumatic brain injury (TBI), and testing the cerebrovascular reactivity to CO(2) provides information about injury severity and outcome. The complexity and potential hazard of performing CBF measurements limits routine clinical use. An alternative approach is to measure the CBF velocity using bedside, non-invasive, and transcranial Doppler (TCD) sonography. This study was performed to investigate if TCD is a useful alternative to CBF in patients with severe TBI. CBF and TCD flow velocity measurements and cerebrovascular reactivity to hypocapnia were simultaneously evaluated in 27 patients with acute TBI. Measurements were performed preoperatively during controlled normocapnia and hypocapnia in patients scheduled for hematoma evacuation under general anesthesia. Although the lack of statistical correlation between the calculated reactivity indices, there was a significant decrease in TCD-mean flow velocity and a decrease in CBF with hypocapnia. CBF and TCD do not seem to be directly interchangeable in determining CO(2)-reactivity in TBI, despite both methods demonstrating deviation in the same direction during hypocapnia. TCD and CBF measurements both provide useful information on cerebrovascular events which, although not interchangeable, may complement each other in clinical scenarios.

Cerebral haemodynamic physiology during steep Trendelenburg position and CO2 pneumoperitoneum

The steep (40°) Trendelenburg position optimizes surgical exposure during robotic prostatectomy. The goal of the current study was to elucidate the influence of this patient positioning on cerebral blood flow and zero flow pressure (ZFP), and to assess the validity of different methods of evaluating ZFP. In 21 consecutive patients who underwent robotic endoscopic radical prostatectomy under general anaesthesia, transcranial Doppler flow velocity waveforms and invasive arterial and central venous pressure (CVP) waveforms suitable for analysis were recorded throughout the whole operative procedure in 14. The ZFP was determined by regression analysis of the pressure-flow plot and by different simplified formulas. The effective cerebral perfusion pressure (eCPP), pulsatility index (PI), and resistance index (RI) were determined. While patients were in the Trendelenburg position, the ZFP increased in parallel with the CVP. The PI, RI, gradient between the ZFP and CVP, and the gradient between the CPP and the eCPP did not increase significantly (P<0.05) after 3 h of the steep Trendelenburg position. Using the formula described by Czosnyka and colleagues, the ZFP correlated closely with that calculated by linear regression throughout the course of the operation. Prolonged steep Trendelenburg positioning and CO(2) pneumoperitoneum does not compromise cerebral perfusion. ZFP and eCPP are reliable variables for assessing brain perfusion during prolonged steep Trendelenburg positioning.

Effect of age on intraoperative cerebrovascular autoregulation and near-infrared spectroscopy-derived cerebral oxygenation

Age is an important risk factor for perioperative cerebral complications such as stroke, postoperative cognitive dysfunction, and delirium. We explored the hypothesis that intraoperative cerebrovascular autoregulation is less efficient and brain tissue oxygenation lower in elderly patients, thus, increasing the vulnerability of elderly brains to systemic insults such as hypotension. We monitored intraoperative cerebral perfusion in 50 patients aged 18-40 and 77 patients >65 yr at two Swiss university hospitals. Mean arterial pressure (MAP) was measured continuously using a plethysmographic method. An index of cerebrovascular autoregulation (Mx) was calculated based on changes in transcranial Doppler flow velocity due to changes in MAP. Cerebral oxygenation was assessed by the tissue oxygenation index (TOI) using near-infrared spectroscopy. End-tidal CO₂, O₂, and sevoflurane concentrations and peripheral oxygen saturation were recorded continuously. Standardized anaesthesia was administered in all patients (thiopental, sevoflurane, fentanyl, atracurium). Autoregulation was less efficient in patients aged >65 yr [by 0.10 (se 0.04; P=0.020)] in a multivariable linear regression analysis. This difference was not attributable to differences in MAP, end-tidal CO₂, or higher doses of sevoflurane. TOI was not significantly associated with age, sevoflurane dose, or Mx but increased with increasing flow velocity [by 0.09 (se 0.04; P=0.028)] and increasing MAP [by 0.11 (se 0.05; P=0.043)]. Our results do not support the hypothesis that older patients' brains are more vulnerable to systemic insults. The difference of autoregulation between the two groups was small and most likely clinically insignificant.

Changes in cerebral hemodynamics in different body positions in healthy volunteers

Objective To investigate the changes in cerebral hemodynamics in different body positions in healthy volunteers.Methods Sixty right-handed healthy male volunteers,aged 22-26,height 167-178 cm,weighing 51-67 kg,were randomly divided into 4 groups ( n =15 each): 15 degrees head-down tilt group (group Ⅰ ),30 degrees head-down tilt group (group Ⅱ ),15 degrees head-up tilt group (group Ⅲ) and 30 degrees head-up tilt group (group Ⅳ ).Blood flow signals of right middle cerebral artery (MCA) and extracranial internal carotid artery (EICA) were detected by transcranial Doppler and systolic blood flow velocity (Vs),diastolic blood flow velocity (Vd ),mean blood flow velocity (Vm),pulsatility index (PI) and resistance index (RI) were recorded at supine position (baseline),immediately,10 and 30 min after body position change(T1-3 ).Lindegaard index was calculated.Results Compared with the baseline,in group [Ⅱ Lindegaard index was increased at T2,while Vs and Vm of MCA were decreased at T2,3,in group Ⅳ Vs of MCA and PI of EICA at T2,Vd and Vm of MCA at T2,3 were decreased ( P ＜ 0.05),while there was no significant difference in the variables mentioned above in the other two groups ( P ＞ 0.05 ).Conclusion In healthy adults,cerebral blood flow velocity decreases in 30 degrees headdown and head-up tilt positions,however there is no change in cerebral blood flow velocity in 15 degrees headdown and head-up tilt positions. Key words: Posture ; Hemodynamics ; Brain

Monitoring cerebral autoregulation after head injury. Which component of transcranial Doppler flow velocity is optimal?

Cerebral autoregulation assessed using transcranial Doppler (TCD) mean flow velocity (FV) in response to various physiological challenges is predictive of outcome after traumatic brain injury (TBI). Systolic and diastolic FV have been explored in other diseases. This study aims to evaluate the systolic, mean and diastolic FV for monitoring autoregulation and predicting outcome after TBI. 300 head-injured patients with blood pressure (ABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and FV recordings were studied. Autoregulation was calculated as a correlation of slow changes in diastolic, mean and systolic components of FV with CPP (Dx, Mx, Sx, respectively) and ABP (Dxa, Mxa, Sxa, respectively) from 30 consecutive 10s averaged values. The relationship with age, severity of injury, and dichotomized 6months outcome was examined. Association with outcome was significant for Mx and Sx. For favorable/unfavorable and death/survival outcomes Sx showed the strongest association (F=20.11; P=0.00001 and F=13.10; P=0.0003, respectively). Similarly, indices derived from ABP demonstrated the highest discriminatory value when systolic FV was used (F=12.49; P=0.0005 and F=5.32; P=0.02, respectively). Indices derived from diastolic FV demonstrated significant differences (when calculated using CPP) only when comparing between fatal and non-fatal outcome. Systolic flow indices (Sx and Sxa) demonstrated a stronger association with outcome than the mean flow indices (Mx and Mxa), irrespective of whether CPP or ABP was used for calculation.

Left Ventricular Dysfunction and Cerebral Infarction from Vasospasm After Subarachnoid Hemorrhage

Although neurogenic stunned myocardium (NSM) after aneurysmal subarachnoid hemorrhage (SAH) is well described, its clinical significance remains poorly defined. We investigated the influence of left ventricular (LV) dysfunction and cerebral vasospasm on cerebral infarction, serious cardiovascular events, and functional outcome after SAH. Of the 481 patients enrolled in the University Columbia SAH Outcomes Project between 10/96 and 05/02, we analyzed a subset of 119 patients with at least one echocardiogram, serial transcranial Doppler (TCD) data, and with no prior history of cardiac disease. LV dysfunction was defined as an ejection fraction <40% on echocardiography. Infarction from vasospasm was adjudicated by the study team after comprehensive review of all clinical and imaging data. Functional outcome was assessed at 15 and 90 days with the modified Rankin Scale (mRS). Eleven percent of patients had LV dysfunction (N = 13). Younger age, hydrocephalus, and complete filling of the quadrigeminal and fourth ventricles were associated with LV dysfunction (all P < 0.05). Despite a similar frequency of pre-existing hypertension, 0% of patients with LV dysfunction reported taking antihypertensive medication, compared to 35% of those without (P = 0.009). There was a significant association between LV dysfunction and infarction from vasospasm after adjusting for clinical grade, age, and peak TCD flow velocity (P = 0.03). Patients with LV dysfunction also had higher rates of hypotension requiring vasopressors (P = 0.001) and pulmonary edema (P = 0.002). However, there was no association between LV dysfunction and outcome at 14 days after adjustment for established prognostic variables. LV dysfunction after SAH increases the risk of cerebral infarction from vasospasm, hypotension, and pulmonary edema, but with aggressive ICU support does not affect short-term survival or functional outcome. Antihypertensive medication may confer cardioprotection and reduce the risk of catecholamine-mediated injury after SAH.

The effects of sevoflurane on cerebral blood flow autoregulation and flow-metabolism coupling during cardiopulmonary bypass

previous studies on non-cardiac surgical patients have shown that cerebral pressure-flow autoregulation and cerebral flow-metabolism coupling are maintained with sevoflurane. The effects of sevoflurane on cerebral blood flow (CBF) autoregulation and flow-metabolism coupling during cardiopulmonary bypass (CPB) have not been studied previously. the effects of sevoflurane-induced burst suppression, monitored with electroencephalography (EEG), on cerebral blood flow velocity (CBFV), cerebral oxygen extraction (COE) and flow autoregulation, were studied in 16 patients undergoing cardiac surgery. The experimental procedure was performed during non-pulsatile CPB with mild hypothermia (34 degreesC) in fentanyl/droperidol-anesthetized patients. Middle cerebral artery transcranial Doppler flow velocity, right jugular vein bulb oxygen saturation and jugular venous pressure were measured continuously. Autoregulation was tested during changes in the mean arterial pressure (40-90 mmHg), induced by sodium nitroprusside and norepinephrine before (control), and during additional sevoflurane administration, in a dose that resulted in an EEG burst-suppression level of 4-6/min. sevoflurane, at an inspired concentration of 3.36 ± 0.03%, induced a 17% decrease in CBFV (P<0.05) and a 22% decrease in COE (P<0.05) compared with the control. The slope of the positive relationship between CBFV and cerebral perfusion pressure was steeper with sevoflurane (p<0.01) compared with control measurements, as was the slope of the negative relationship between cpp and coe (p<0.01). burst-suppression doses of sevoflurane exert an intrinsic cerebral vasodilatory effect, which impairs CBF autoregulation during mildly hypothermic CPB. Furthermore, during sevoflurane administration, CBF is in excess relative to oxygen demand, indicating a partial loss of the cerebral flow-metabolism coupling.

Resolution of cerebral artery stenosis in a child with sickle cell anemia treated with hydroxyurea

Stroke is a major cause of morbidity and mortality in individuals with sickle cell anemia (SCA) [1]. Transcranial Doppler (TCD) ultrasound can identify patients at increased risk of stroke [2,3], and chronic transfusion therapy decreases stroke risk by 92% in the highest risk group, defined by abnormal [time average mean of the maximum velocity (TAMV) > 200 cm/sec] TCD flow velocities [4]. However, chronic transfusions can lead to serious complications, and the optimal management strategy for patients with cerebral artery stenosis whose TCD flow velocities are conditional (TAMV = 170-199 cm/sec) is unknown. Hydroxyurea effectively prevents several complications of SCA [5], but there are no controlled studies demonstrating its effectiveness in cerebral artery stenosis or primary stroke prevention in SCA. We report the case of a 4-year-old child with SCA found to have left middle cerebral artery stenosis on evaluation for unilateral conditional TCD flow velocities. Hydroxyurea therapy was followed by normalization of TCD flow velocities and resolution of vascular stenosis. This case adds to the literature suggesting that hydroxyurea can successfully reverse cerebral artery stenosis in patients with SCA, further supporting the need for controlled clinical trials of hydroxyurea for cerebral vasculopathy and primary stroke prevention in SCA.

Cerebral Vasospasm: New Strategies in Research and Treatment

Cerebral Vasospasm: New Strategies in Research and Treatment

A Multimodal Concept in Patients after Severe Aneurysmal Subarachnoid Hemorrhage: Results of a Controlled Single Centre Prospective Randomized Multimodal Phase I/II Trial on Cerebral Vasospasm

Recent publications suggest that a combination of head-shaking and cisternal irrigation might reduce symptomatic cerebral vasospasm after subarachnoid hemorrhage (SAH). The present clinical prospective randomized phase I/II study was initiated in order to analyze the prophylactic effect of intracisternal lysis in combination with kinetic treatment followed by intrathecal nimodipine lavage. Twenty patients with aneurysmal SAH, WFNS grade 2 to 5 (GCS 13-3) and Fisher grade 3 or 4 were included in this prospective randomized study which had been approved by the local Ethics Research Committee. Following insertion of a ventricular drain, securing of the aneurysm by a microsurgical or endovascular route and the insertion of two lumbar catheters, intracisternal lysis with urokinase 120 000 IU/d was performed for 48 h in the patients of the study group. Intrathecal pressure was monitored by the second lumbar catheter. After intracisternal lysis, intrathecal nimodipine lavage was applied for 7 d. For comatose patients kinetic head-rotation was also performed. Vasospasm was clinically identified with a focus on delayed neurological deficits (DINDs) by daily transcranial Doppler (TCD), computerized tomography (CT), perfusion CT (pCT) and cerebral angiography (DSA). There was no DIND in the study group among the patients who were awake, while two DINDs occurred in the control group. The pooled TCD flow velocities over an average period of 14 d revealed no statistically significant difference between the groups. Vasospasm-related infarction on CT was seen in two patients of the control group. Evident vasospasm on DSA appeared in three patients of the study group compared with 7 patients in the control group. Moreover there was a neurological improvement in the study population as measured by mRS at 3-month follow-up (P=0.266). In two consecutive patients randomized to the study group a paresis of the lower extremities of unknown origin occurred. As a result of these complications the study was stopped in accordance with the local Ethics Research Committee guidelines. A multimodal approach with translumbar lysis in combination with kinetic therapy followed by intrathecal nimodipine lavage proved to be effective against cerebral vasospasm and for clinical outcome. However, due to the observed complications with the occurrence of paraparesis in two patients of the study group the trial was stopped. Nevertheless, the promising preliminary results suggest a further development of the clinical protocol using a modified multimodal concept to prevent and treat cerebral vasospasm after severe SAH.

Critical Closing Pressure: Comparison of Three Methods

Critical closing pressure (CCP) is an arterial pressure threshold below which small arterial vessels collapse. Our aim was to compare different methods to estimate CCP in the cerebrovascular circulation using the relationships between transcranial Doppler flow velocity (FV), laser-Doppler flux (LDF), and arterial blood pressure (ABP). A total of 116 experiments in rabbits were analyzed retrospectively. At the end of each recording, cardiac arrest (CA) was induced. Arterial blood pressure in femoral artery, basilar artery FV, cortical blood LDF, intracranial pressure (ICP) was recorded. Critical closing pressure was estimated using linear regression between decreasing mean ABP values, FV, and LDF during CA. In addition, CCP was calculated from FV waveform just before CA. The correlation between CCP evaluated using LDF and FV during CA was 0.98 (P<0.0001). The correlation between CCP measured during CA and CCP estimated from the transcranial Doppler ultrasonography (TCD) waveform was weaker (R=0.39; P<0.001), with CCP calculated from waveform being significantly greater than CCP from CA (median difference 9 mm Hg; P<0.003). Critical closing pressures obtained from FV waveform and CA correlated with mean ICP before CA (R=0.40; P=0.001). In conclusion strong correlation exists between CCP values obtained by means of FV and LDF during cardiac arrest. However, predictions of CCP using TCD waveform analysis show substantial differences from values of CCP recorded during cardiac arrest.