Ken Kazumata

Performance of Bedside Transpulmonary Thermodilution Monitoring for Goal-Directed Hemodynamic Management After Subarachnoid Hemorrhage

Background and Purpose— Early goal-directed hemodynamic therapy is of particular importance for adequate cerebral circulation of patients with vasospasm after subarachnoid hemorrhage but is often precluded by the invasiveness of established cardiac output determination using a pulmonary artery catheter. This study was undertaken to validate the usefulness of less invasive goal-directed hemodynamic monitoring by transpulmonary thermodilution technique in patients after subarachnoid hemorrhage. Methods— One hundred sixteen patients with subarachnoid hemorrhage who underwent surgical clipping within 24 hours of ictus were investigated. Validation of transpulmonary thermodilution-derived intermittent/continuous cardiac output and cardiac preload (global end diastolic volume) were compared with pulmonary artery catheter-derived reference cardiac output and pulmonary capillary wedge pressure or central venous pressure in 16 patients diagnosed with vasospasm. In a subsequent trial of 100 consecutive cases, clinical results between the new and standard management paradigms were compared. Results— Transpulmonary thermodilution-derived intermittent cardiac output and transpulmonary thermodilution-derived continuous cardiac output showed close agreement to catheter-derived reference cardiac output with high correlation (r=0.85 and 0.77) and low percentage error (13.5% and 18.0%). Fluid responsiveness to defined volume loading was predicted better with global end diastolic volume than with pulmonary capillary wedge pressure and central venous pressure for larger receiver operating characteristic curve area. Patients receiving early goal-directed management by transpulmonary thermodilution experienced reduced frequencies of vasospasm and cardiopulmonary complications compared with those managed with standard therapy (P<0.05), whereas their functional outcomes at 3 months were not different (P=0.06). Conclusions— Goal-directed hemodynamic management guided by transpulmonary thermodilution appears to have a therapeutic advantage for optimizing the prognosis of patients with subarachnoid hemorrhage with vasospasm over conventional methods.

Goal-Directed Fluid Management by Bedside Transpulmonary Hemodynamic Monitoring After Subarachnoid Hemorrhage

Background and Purpose— Optimal monitoring of cardiac output and intravascular volume is of paramount importance for good fluid management of patients with subarachnoid hemorrhage (SAH). The aim of this study was to demonstrate the feasibility of advanced hemodynamic monitoring with transpulmonary thermodilution and to provide descriptive data early after SAH. Methods— Forty-six patients with SAH treated within 24 hours of the ictus were investigated. Specific targets for cardiac index (≥3.0 L · min−1 · m−2), global end-diastolic volume index (700 to 900 mL/m2), and extravascular lung water index (≤14 mL/kg) were established by the single-indicator transpulmonary thermodilution technique, and a fluid management protocol emphasizing supplemental colloid administration was used to attain these targets. Plasma hormones related to stress and fluid regulation were also measured. Results— A higher cardiac index (mean value of 5.3 L · min−1 · m−2) and a lower global end-diastolic volume index (555 mL/m2) were observed on initial measurement, for which elevations of plasma adrenaline, noradrenaline, and cortisol were also detected. Cardiac index was progressively decreased (3.5 L · min−1 · m−2) and global end-diastolic volume index was normalized by fluid administration aimed at normovolemia. The extent of the initial hemodynamic and hormonal profile was greater in patients with a poor clinical status (P<0.05). The extravascular lung water index was mildly elevated but within the target range throughout the study period. No patients developed pulmonary edema or congestive heart failure. Conclusions— The impact of sympathetic hyperactivity after SAH predisposes patients to a hyperdynamic and hypovolemic state, especially in those whose clinical status is poor. Bedside monitoring with the transpulmonary thermodilution system may be a powerful tool for the systemic management of such patients.

Dissociation of Vasoreactivity to Acetazolamide and Hypercapnia Comparative Study in Patients With Chronic Occlusive Major Cerebral Artery Disease

BACKGROUND AND PURPOSE The aim of this study was to compare the effect of vasodilative stimuli for the measurement of cerebrovascular reactivity obtained by acetazolamide and hypercapnia in patients with chronic occlusive major cerebral artery disease. METHODS We examined 24 patients with unilateral occlusive lesions of a major cerebral artery using the 133Xe inhalation technique and single-photon emission CT. Regional cerebral blood flow (CBF) was measured during a resting state, during inhalation of 5% CO2, and 15 minutes after the administration of acetazolamide consecutively in the same patients. Normative values of resting CBF and acetazolamide reactivity were obtained in 21 normal subjects. RESULTS All patients with the exception of 1 showed an increase in CBF during hypercapnia ipsilateral to the occlusive lesion. Ipsilateral acetazolamide reactivity was preserved in 13 patients. Conversely, 11 patients showed an absent response or paradoxical CBF reduction. Ipsilateral CO2 reactivity did not correlate with acetazolamide reactivity when all 24 patients were considered. However, there was a significant correlation between acetazolamide and CO2 in the 13 patients who showed preserved acetazolamide reactivity (r = .60, P < .05). No significant correlation was present in the remaining 11 patients with reduced acetazolamide reactivity. Although significant blood pressure augmentation was observed in hypercapnia, we could not find a correlation between change of blood pressure and CO2 reactivity. CONCLUSIONS Acetazolamide identified patients with reduced vasomotor reactivity who appeared to have preserved CO2 reactivity. Acetazolamide testing may be useful in the assessment of cerebral hemodynamics. However, further investigations are necessary to assess the clinical utility of these tests.

The frequency of postoperative stroke in moyamoya disease following combined revascularization: a single-university series and systematic review

OBJECT Although combined direct and indirect anastomosis in patients with moyamoya disease immediately increases cerebral blood flow, the surgical procedure is more complex. Data pertinent to the postoperative complications associated with combined bypass are relatively scarce compared with those associated with indirect bypass. This study investigated the incidence and characteristics of postoperative stroke in combined bypass and compared them with those determined from a literature review to obtain data from a large population. METHODS A total of 358 revascularization procedures in 236 patients were retrospectively assessed by reviewing clinical charts and radiological data. PubMed was searched for published studies on surgical treatment to determine the incidence of postoperative complications in a larger population. RESULTS Seventeen instances of postoperative stroke were observed in 16 patients (4.7% per surgery, 95% CI 2.8%-7.5%). Postoperative stroke was more frequent (7.9% per surgery) in adults than in pediatric patients (1.7% per surgery, OR 4.07, 95% CI 1.12-14.7; p < 0.05). Acute progression of stenoocclusive changes were identified in the major cerebral arteries (anterior cerebral artery, n = 3; middle cerebral artery, n = 1; posterior cerebral artery, n = 2). The postoperative stroke rate was comparable with that (5.4%) determined from a literature search that included studies reporting more than 2000 direct/combined procedures. No differences in the stroke rates between the direct/combined and indirect procedures were found. In the literature review, direct/combined bypass was more often associated with excellent revascularization (angiographic opacification greater than two-thirds) than indirect bypass (p < 0.05). CONCLUSIONS This experience of 358 consecutive procedures is one of the largest series for which the postoperative stoke rate for direct/combined bypass performed with a unified strategy has been reported. A systematic review confirmed that the postoperative stroke rate for the direct/combined procedure was comparable to that for the indirect procedure.

Early Intensive Versus Minimally Invasive Approach to Postoperative Hemodynamic Management After Subarachnoid Hemorrhage

Background and Purpose— The results of previous studies suggest that early goal-directed fluid therapy (EGDT) reduces delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage, but the effects of EGDT on clinical outcomes are still unclear. This study aimed to determine whether EGDT improves outcomes compared with standard less-invasive hemodynamic therapy. Methods— This study included 160 patients treated within 24 hours after subarachnoid hemorrhage, randomized to receive either (1) EGDT guided by preload volume and cardiac output monitored by transpulmonary thermodilution (treatment group) or (2) standard therapy guided by fluid balance or central venous pressure, assisted by uncalibrated less-invasive cardiac output monitoring during hyperdynamic therapy in patients with clinical or radiological indications of DCI (control group). DCI determined by clinical or radiological findings and functional outcome determined by the modified Rankin Scale score at 3 months were compared between groups. Results— For all clinical grades combined, there were no significant differences in the rates of DCI (33% versus 42%; P=0.33) or modified Rankin Scale score of 0 to 3 at 3 months (67% versus 57%; P=0.22) between the 2 groups. For patients with poor clinical grade, those who received EGDT had a significantly lower rate of DCI (5% versus 14%; P=0.036), modified Rankin Scale score of 0 to 3 at 3 months (52% versus 36%; P=0.026), and shorter length of intensive care unit stay (14 versus 17 days; P=0.043) than those who received standard therapy. Conclusions— EGDT is beneficial for reducing DCI and improving postoperative functional outcome in patients with poor clinical grade. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: UMIN000007509.

Changing treatment strategy from clipping to radial artery graft bypass and parent artery sacrifice in patients with ruptured blister-like internal carotid artery aneurysms.

BACKGROUND: Blood blister-like aneurysms (BBAs) are aneurysms with ill-defined fragile necks arising from an internal carotid artery (ICA) and associated with high mortality. OBJECTIVE: To describe strategies and outcomes in patients in whom radial artery (RA) graft bypass with ICA sacrifice was considered as the primary treatment during the acute phase of subarachnoid hemorrhage. METHODS: The authors analyzed the clinical records of 20 patients who were treated between 2004 and 2011 at their hospital and affiliate institutions. RESULTS: A majority of the patients were treated during the acute phase (<24 hours, n = 15). A favorable outcome was achieved in 18 (90%) patients. The treatment strategies used were as follows: (1) ICA trapping/external carotid artery (ECA)-RA-middle cerebral artery (MCA) bypass (n = 13), (2) ICA trapping/superficial temporal artery-MCA bypass (n = 2), (3) aneurysm clipping with RA-MCA temporary bypass (n = 3), (3) aneurysm clipping with proximal ICA ligation and ECA-RA-MCA bypass (n = 1), and (4) direct clipping (n = 1). Postoperative infarction was observed in 6 patients and was ascribed to vasospasm (n = 1), retrograde thrombosis associated with trapping (n = 2), and reasons unrelated to the surgical procedures (n = 3). CONCLUSION: Trapping with RA graft bypass demonstrated favorable results in patients with internal carotid BBAs. Although trapping/RA graft bypass is a definitive treatment for BBAs located proximal to the origin of the posterior communicating artery, some distal BBAs preclude ICA trapping to spare the perforating arteries. ABBREVIATIONS: BBA, blister-like aneurysm DCI, delayed cerebral ischemia ECA, external carotid artery ICA, internal carotid artery MCA, middle cerebral artery mRS, modified Rankin scale Pcom, posterior communicating RA, radial artery SAH, subarachnoid hemorrhage; STA, superficial temporal artery

Chronic ischemia alters brain microstructural integrity and cognitive performance in adult moyamoya disease.

Background and Purpose— The mechanisms underlying frontal lobe dysfunction in moyamoya disease (MMD) are unknown. We aimed to determine whether chronic ischemia induces subtle microstructural brain changes in adult MMD and evaluated the association of changes with neuropsychological performance. Methods— MRI, including 3-dimensional T1-weighted imaging and diffusion tensor imaging, was performed in 23 adult patients with MMD and 23 age-matched controls and gray matter density and major diffusion tensor imaging indices were compared between them; any alterations in the patients were tested for associations with age, ischemic symptoms, hemodynamic compromise, and neuropsychological performance. Results— Decrease in gray matter density, associated with hemodynamic compromise (P<0.05), was observed in the posterior cingulate cortex of patients with MMD. Widespread reduction in fractional anisotropy and increases in radial diffusivity and mean diffusivity in some areas were also observed in bilateral cerebral white matter. The fractional anisotropy (r=0.54; P<0.0001) and radial diffusivity (r=−0.41; P<0.01) of white matter significantly associated with gray matter density of the cingulate cortex. The mean fractional anisotropy of the white matter tracts of the lateral prefrontal, cingulate, and inferior parietal regions were significantly associated with processing speed, executive function/attention, and working memory. Conclusions— In adult MMD, there were more white matter abnormalities than gray matter changes. Disruption of white matter may play a pivotal role in the development of cognitive dysfunction.

Synergistic Interactions Between Direct and Indirect Bypasses in Combined Procedures: The Significance of Indirect Bypasses in Moyamoya Disease.

Background Whether additional indirect bypasses effectively contribute to revascularization in combined procedures remains unclear in patients with moyamoya disease. Objective To evaluate the longitudinal changes associated with combined procedures while following up pediatric and adult patients long term and to assess whether any other clinical factors or hemodynamic parameters affected these changes to determine an optimal surgical strategy. Methods We studied 58 hemispheres in 43 adults and 39 hemispheres in 26 children who underwent combined revascularization for moyamoya disease. To evaluate bypass development, we assessed the sizes of the superficial temporal artery and middle meningeal artery using magnetic resonance angiography. Multivariate analysis determined the effects of multiple variables on bypass development. Results Indirect bypass (middle meningeal artery) development occurred in 95% and 78% of the pediatric and adult hemispheres, respectively. Of these, dual development of direct and indirect bypasses occurred in 54% of the pediatric hemispheres and in 47% of the adult hemispheres. Reciprocal superficial temporal artery regression occurred in 28% of the hemispheres during the transition from the postoperative acute phase to the chronic phase during indirect bypass development. Good indirect bypass development was associated with adult hemispheres at Suzuki stage 4 or greater (odds ratio, 7.4; 95% confidence interval, 1.4-39.4; P = .02). Disease onset type and preoperative hemodynamic parameters were not considered predictors for the development of surgical revascularization. Conclusion Simultaneous direct and indirect bypass development was most frequently observed, regardless of patient age and hemodynamic status. Applying indirect bypass as an adjunct to direct bypass could maximize revascularization in adults and children.

Edaravone Reduces Hyperperfusion-Related Neurological Deficits in Adult Moyamoya Disease Historical Control Study

Background and Purpose— Postoperative hyperperfusion-related transient neurological deficits (TNDs) are frequently observed in adult patients with moyamoya disease who undergo direct bypass procedures. The present study evaluated the effect of the free radical scavenger edaravone on postoperative hyperperfusion in adult moyamoya disease. Methods— This study included 92 hemispheres in 72 adult patients who underwent direct bypass for moyamoya disease. Serial measurements of cerebral blood flow were conducted immediately after surgery and on postoperative days 2 and 7. In 40 hemispheres for 36 patients, edaravone (60 mg/d) was administered from the day of surgery to postsurgical day 7. The incidence of postoperative hyperperfusion and associated TNDs were compared with a control group that included 52 hemispheres in 36 patients. Results— Radiological hyperperfusion was observed in 28 of 40 (70.0%) and 39 of 52 (75.0%) hemispheres in the edaravone and control groups, respectively (P=0.30). Hyperperfusion-related TND incidences were significantly lower in the edaravone group compared with the control group (12.5% versus 32.7%; P=0.024). Multivariate analysis demonstrated that edaravone administration (P=0.009) and left-sided surgery (P=0.037) were significantly correlated with hyperperfusion-related TNDs (odds ratios, 0.3 and 4.2, respectively). Conclusions— Perioperative administration of edaravone reduced the incidence of hyperperfusion-related TNDs after direct bypass procedures in adult patients with moyamoya disease.

Post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin can reduce ischemia reperfusion injury.

Despite successful revascularization, reperfusion after prolonged ischemia causes ischemia reperfusion (I/R) injury. Recruitment and activation of neutrophils is thought to be a key event causing I/R injury. We examined whether post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier without neutrophils, could reduce I/R injury in a rat transient middle cerebral artery occlusion (MCAO) model. Male Sprague-Dawley rats were subjected to 2-h MCAO and then were divided into three groups: (1) LEH group (n=7) infused with LEH (Hb concentration of 6g/dl, 10ml/kg/h) through the recanalized internal carotid artery for 2h, (2) vehicle group (n=8) infused with saline (10ml/kg/h) in the same manner as the LEH group, and (3) control group (n=9) subjected to recanalization only. After 24-h reperfusion, all rats were tested for neurological score and then sacrificed to examine infarct and edema volumes, myeloperoxidase (MPO) expression, matrix metalloproteinase-9 (MMP-9) expression and activity, and reactive oxygen species (ROS) production. Compared with the control group and the vehicle group, the LEH group showed a significantly better neurological score and significantly smaller infarct and edema volumes. MPO expression, MMP-9 expression and activity, and ROS production in the LEH group were also significantly lower than those in the control and vehicle groups. The results in the present study suggest that post-ischemic intra-arterial infusion of LEH can reduce I/R injury through reducing the effect of MMP-9, most likely produced by neutrophils. This therapeutic strategy may be a promising candidate to prevent I/R injury after thrombolysis and/or thromboectomy.