Severe Aneurysmal Subarachnoid Hemorrhage Research Articles

The venous delay phenomenon in computed tomography angiography: a novel imaging outcome predictor for poor cerebral perfusion after severe aneurysmal subarachnoid hemorrhage.

Diverse treatment results are observed in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH). Significant initial perfusion compromise is thought to predict a worse treatment outcome, but this has scant support in the literature. In this cohort study, the authors correlate the treatment outcomes with a novel poor-outcome imaging predictor representing impaired cerebral perfusion on initial CT angiography (CTA). The authors reviewed the treatment results of 148 patients with poor-grade aSAH treated at a single tertiary referral center between 2007 and 2016. Patients with the "venous delay" phenomenon on initial CTA were identified. The outcome assessments used the modified Rankin Scale (mRS) at the 3rd month after aSAH. Factors that may have had an impact on outcome were retrospectively analyzed. Compared with previously identified outcome predictors, the venous delay phenomenon on initial CTA was found to have the strongest correlation with posttreatment outcomes on both univariable (p < 0.0001) and multivariable analysis (OR 4.480, 95% CI 1.565-12.826; p = 0.0052). Older age and a higher Hunt and Hess grade at presentation were other factors that were associated with poor outcome, defined as an mRS score of 3 to 6. The venous delay phenomenon on initial CTA can serve as an imaging predictor for worse functional outcome and may aid in decision making when treating patients with poor-grade aSAH.

Stereotactic Catheter Ventriculocisternostomy for Clearance of Subarachnoid Hemorrhage: A Matched Cohort Study.

Delayed cerebral infarction (DCI) is a major source of morbidity and mortality after aneurysmal subarachnoid hemorrhage. We report a novel intervention-stereotactic catheter ventriculocisternostomy (STX-VCS) and fibrinolytic/spasmolytic lavage therapy-for DCI prevention. Outcomes of 20 consecutive patients are compared with 60 matched controls. On the basis of individual treatment decisions, STX-VCS was performed in 20 high-risk aneurysmal subarachnoid hemorrhage patients admitted to our department between September 2015 and October 2016. Three controls matched for age, sex, aneurysm treatment method, and admission Hunt and Hess grade were assigned to each case treated by STX-VCS. DCI was the primary outcome. Mortality and mRS at rehabilitation discharge were secondary outcome parameters. The association between STX-VCS and DCI, mortality, and mRS was assessed by conditional logistic regression. Stereotactic procedures were performed without surgical complications. Continuous cisternal lavage was feasible in 17 of 20 patients (85%). One adverse event because of cisternal lavage was without sequelae. DCI occurred in 25 of 60 (42%) controls and 3 of 20 (15%) patients with STX-VCS (odds ratio, 0.15; 95% confidence interval, 0.04-0.64). Mortality occurred in 20 of 60 (33%) controls and 1 of 20 (5%) patients with STX-VCS, respectively (odds ratio, 0.08; 95% confidence interval, 0.01 - 0.66). Favorable outcome (mRS≤3) at rehabilitation discharge was observed in 12 of 20 patients with STX-VCS (60%) versus 21 of 60 (35%) matched controls (odds ratio, 0.26; 95% confidence interval, 0.8-0.86). STX-VCS was feasible and safe in patients with severe aneurysmal subarachnoid hemorrhage. Initial results indicate that DCI and mortality can be reduced, and neurological outcome may be improved with this method.

Speckle tracking analysis allows sensitive detection of stress cardiomyopathy in severe aneurysmal subarachnoid hemorrhage patients.

Stress cardiomyopathy is a common life-threatening complication after aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that left ventricular (LV) longitudinal strain alterations assessed with speckle tracking could identify early systolic function impairment. This was an observational single-center prospective pilot controlled study conducted in a neuro-intensive care unit. Forty-six patients with severe SAH with a World Federation of Neurological Surgeons grade (WFNS) ≥ III were included. Transthoracic echocardiography (TTE) was performed on day 1, day 3, and day 7 after the patient's admission. A cardiologist blinded to the patient's management analyzed the LV global longitudinal strain (GLS). The control group comprised normal subjects matched according to gender and age. On day 1 median (25th-75th percentile) GLS was clearly impaired in SAH patients compared to controls [-16.7 (-18.7/-13.7) % versus -20 (-22/-19) %, p < 0.0001], whereas LVEF was preserved [65 (59-70) %]. GLS was severely impaired in patients with a WFNS score of V versus III-IV [-15.6 (-16.9/-12.3) % versus -17.8 (-20.6/-15.8) %, p = 0.008]. Seventeen (37 %) patients had a severe GLS alteration (>- 16 %). In these patients, GLS improved from day 1 [-12.4 (-14.8/-10.9) %] to last evaluation [-16.2 (-19/-14.6) %, p = 0.0007] in agreement with the natural evolution of stress cardiomyopathy. On the basis of LV GLS assessment, we demonstrated for the first time that myocardial alteration compatible with a stress cardiomyopathy is detectable in up to 37 % of patients with severe SAH while LVEF is preserved. GLS could be used for sensitive detection of stress cardiomyopathy. This is critical because cardiac impairment remains a major cause of morbidity and mortality after SAH.

Biochemical neuromonitoring of poor-grade aneurysmal subarachnoid hemorrhage: comparative analysis of metabolic events detected by cerebral microdialysis and by retrograde jugular vein catheterization

Objectives:In severe aneurysmal subarachnoid hemorrhage (aSAH), pathological changes in cerebral energy metabolism can be detected either by local measurements using cerebral microdialysis (cMD) together with brain tissue oxygen probe or by global measurements of arterio-jugular difference performed with retrograde jugular vein catheter. Our main objective was to compare the two methods of detection and assess whether combining biomarkers from both procedures could improve outcome prediction, which has never been studied before.Methods:This study included 400 sets of paired arterial and jugular venous samples and 3138 brain microdialyzates obtained from 18 poor-grade aSAH patients. Using Glasgow outcome scale (GOS), neurochemical data from unfavorable (GOS 1–3) and favorable (GOS 4–5) outcome groups were compared.Results:The lactate/pyruvate ratio was found as the most sensitive marker for predicting unfavorable outcome (90%), although not specific. In contrast, hypoxic lactate events and those of metabolic ratio (MR) < 3.44, most frequently observed in the unfavorable outcome group than in the favorable one (13.9 vs 0.9% and 33.3 vs 3.75% respectively), were shown to be more specific biomarkers (86%) to predict unfavorable outcome, but less sensitive ( < 70%). The combination of these three biomarkers improved the accuracy of outcome prediction (sensitivity 90% and specificity 71%).Discussion:Both retrograde jugular venous catheterization (RJVC) and cMD contribute to monitor poor-grade aSAH patients. In this preliminary study, we show that these two techniques are complementary and their combination increases the accuracy of outcome prediction.

Effects of intravenous infusion of hydrogen-rich fluid combined with intra-cisternal infusion of magnesium sulfate in severe aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial.

BackgroundThe failures of recent studies intended to prevent cerebral vasospasm have moved the focus of research into delayed cerebral ischemia away from cerebral artery constriction towards other mechanisms. Recent accumulating evidence has suggested that early brain injury is also involved in the development of delayed cerebral ischemia, and that hydrogen can prevent early brain injury. Therefore, we have established a combination therapy of intravenous hydrogen infusion and intra-cisternal magnesium sulfate infusion for the treatment of both early brain injury and cerebral vasospasm. The present randomized controlled clinical trial is designed to investigate the effects of this novel therapeutic strategy on the occurrence of cerebral vasospasm, delayed cerebral ischemia, and clinical outcomes after high-grade subarachnoid hemorrhage.MethodsThis study is a randomized, double-blind, placebo-controlled design to be conducted in two hospitals. A total of 450 patients with high-grade subarachnoid hemorrhage will be randomized to one of three arms: (i) Mg + H2 group, (ii) Mg group, and (iii) control group. Patients who are assigned to the Mg + H2 group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous hydrogen-rich fluid infusion (200 mL) twice a day for 14 days. Patients who are assigned to the Mg group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Patients who are assigned to the control group will receive intra-cisternal Ringer solution without magnesium sulfate at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Primary outcome measures will be occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures will be modified Rankin scale score at 3, 6, and 12 months and biochemical markers.DiscussionThe present protocol for a randomized, placebo-controlled study of intravenous hydrogen therapy with intra-cisternal magnesium infusion is expected to establish the efficacy and safety of this therapeutic strategy.Trial registrationUMIN-CTR: UMIN000014696

Risk factors and pathogens involved in early ventilator-acquired pneumonia in patients with severe subarachnoid hemorrhage

Ventilator-acquired pneumonia (VAP) is a common burden in intensive care unit (ICU) patients, but, to date, specific data are not available in patients with severe aneurysmal subarachnoid hemorrhage (SAH). A single neuro-ICU retrospective analysis of 193 patients with SAH requiring mechanical ventilation (MV) ≥48 h admitted from January 2005 to May 2010 was undertaken. The diagnosis of early VAP was prospectively upheld during a multidisciplinary staff meeting, according to the American Thoracic Society (ATS) 2005 guidelines with a threshold of 7 days after the onset of MV. Patients had a median age of 53 (44-62) years and 70 (36 %) were male. The median Glasgow coma scale (GCS) score before MV was 9 (5-14). 142 (74 %) patients had a World Federation of Neurosurgeons (WFNS) score ≥III. Aneurysm was secured with an endovascular coiling procedure in 162 (84 %) patients. 81 (48.7 %) patients declared an early VAP. On multivariate analysis, male sex (odds ratio [OR] 2.26, 95 % confidence interval [CI] [1.14-4.46]), use of mannitol before day 7 (OR 3.03, 95 % CI [1.54-5.95]), and achieving enteral nutrition ≥20 kcal kg(-1) day(-1) after day 7 (OR 2.91, 95 % CI [1.27-6.67]) remained independent risk factors of VAP. The main pathogens involved were methicillin-susceptible Staphylococcus aureus (MSSA) (34.9 %), Haemophilus influenzae (28.1 %), Streptococcus pneumoniae (15.5 %), and Enterobacteriaceae (10.7 %). Early VAP was associated with a longer duration of MV and ICU stay, but not with an excess of mortality. Early VAP bears significant morbidity in patients with severe SAH. Pathogens involved in early VAP are susceptible to antibiotics. Among modifiable risk factors of VAP, early enteral nutrition could be an easy and effective target.

Therapeutic Hypothermia Reduces Middle Cerebral Artery Flow Velocity in Patients with Severe Aneurysmal Subarachnoid Hemorrhage

Transcranial Doppler (TCD) is widely used to detect and follow up cerebral vasospasm after subarachnoid hemorrhage (SAH). Therapeutic hypothermia might influence blood flow velocities assessed by TCD. The aim of the study was to evaluate the effect of hypothermia on Doppler blood flow velocity after SAH. In 20 patients treated with hypothermia (33°) due to refractory intracranial hypertension or delayed cerebral ischemia (DCI), mean flow velocity of the middle cerebral artery (MFV(MCA)) was assessed by TCD. Thirteen patients were treated with combined hypothermia and barbiturate coma and seven with hypothermia alone. MFV(MCA) was obtained within 24 h before and after induction of hypothermia as well as before and after rewarming. Hypothermia was induced on average 5 days after SAH (range 1-12) and maintained for 144 h (range 29-270). After hypothermia induction, MFV(MCA) decreased from 113.7 ± 49.0 to 93.8 ± 44.7 cm/s (p = 0.001). The decrease was independent of SAH-related complications and barbiturate coma. MFV(MCA) further decreased by 28.2 cm/s between early and late hypothermia (p < 0.001). This second decrease was observed in patients with DCI (p < 0.001), but not in patients with intracranial hypertension (p = 0.715). Compared to late hypothermia, MFV(MCA) remained unchanged after rewarming (65.6 ± 32.1 vs 70.3 ± 36.8 cm/s; p = 0.219). However, patients treated with hypothermia alone showed an increase in MFV(MCA) after rewarming (p = 0.016). Therapeutic hypothermia after SAH decreases Doppler blood flow velocity in both intracranial hypertension and DCI cases. The results can be the effect of hypothermia-related mechanisms or resolving cerebral vasospasm during prolonged hypothermia.

Der erhöhte intrakranielle Druck – Multimodales Neuromonitoring – Indikationen und Methoden

Managing patients after severe traumatic brain injury and aneurysmal subarachnoid hemorrhage is a challenging task of modern intensive care. Most patients do require sedation for mechanical ventilation due to respiratory distress or treatment of increased intracranial pressure. Besides standard ICP monitoring, a variety of continuous monitoring technologies for bedside use exists. The paper discusses the 5 methods most frequently used and their significance for multimodal neuromonitoring.

Continuous intra-arterial infusion of nimodipine at the onset of resistant vasospasm in aneurysmal subarachnoidal haemorrhage. Technical report

<title/>Cerebral vasospasm complicating the aneurysmal subarachnoid haemorrhage is a well known medical entity. The delayed ischemic neurological deficits (DINDs) as a result of vasospasm, remain the main cause of morbidity among patients who manage to survive this severe disease pattern. When the traditional treatment options either medical or interventional, fail to reverse the vasospasm, continuous intra-arterial infusion of nimodipine through catheters direct in the spastic arteries, presents a promising treatment modality. We treated in our clinic four patients with severe aneurysmal subarachnoid haemorrhage and refractory vasospasms with continuous nimodipine infusion via catheters in both internal carotid arteries and discussed the efficacy of the method presenting an illustrative case and discussing the effect based on doppler examinations.

Endocrine Response After Severe Subarachnoid Hemorrhage Related to Sodium and Blood Volume Regulation

Hyponatremia is often associated with, and worsens, the prognosis of severe aneurysmal subarachnoid hemorrhage (SAH). Several possible endocrine perturbations of variable severity and variable sodium and water intake have been described in SAH. However, a comprehensive study of the different hormonal systems involved in sodium and water homeostasis and circulating blood volume modifications is still needed. Our aim was to assess water and sodium regulation after severe SAH by investigating blood volume and several hormonal regulatory systems in the context of hyponatremia prevention by controlled sodium intake. Nineteen mechanically ventilated patients with severe SAH, were prospectively studied. Replacement of sodium was at least 4.5 mmol x kg(-1) x d(-1) and adjusted on natriuresis. Hormones involved in electrolyte and water homeostasis: vasopressin, renin, angiotensin, aldosterone, and natriuretic peptides were assessed every 3 days for 12 days. Red blood cell volume was measured by the isotopic method (technetium-labeled red blood cells), in the first 48 h after admission and at day 7. Cardiac function was assessed using electrocardiogram, transthoracic echocardiography, and troponin Ic (cTnI). Outcome was assessed at 3 mo. After SAH onset, hyponatremia, but not decreased circulating blood volume, was prevented by high sodium and water infusion adapted to renal excretion. The hormonal profiles were characterized by an increase in renin, angiotensin II, natriuretic peptide concentrations associated with increased troponin Ic, stable low levels of vasopressin, and the absence of increased aldosterone concentrations. There were no correlations between hormone concentrations and natriuresis. After severe SAH, in the context of multiple clinical interventions, increased natriuresis and low blood volume are consistent with cerebral salt wasting syndrome, probably related to the sequence of severe SAH, highly increased sympathetic tone, hyperreninemic hypoaldosteronism syndrome, and increased natriuretic peptides release.

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.

Theoretical evaluations of therapeutic systemic and local cerebral hypothermia

PurposeTo simulate cerebral temperature behaviour with hypothermia treatment applying different cooling devices and to find the optimal brain temperature monitoring. MethodsModels based on hourly temperature values recorded in patients with severe aneurysmal subarachnoid hemorrhage, taking MRI data, thermal conductive properties, metabolism and blood flow into account were applied to different scenarios of hypothermia. ResultsSystemic hypothermia by endovascular cooling leads to an uniform temperature decrease within the brain tissue. Cooling with head caps lead to 33°C only in the superficial brain while the deep brain remains higher than 36°C. Cooling with neckbands lead to 35.8°C for dry and 32.8°C for wet skin in the deep brain. ConclusionsWith head caps temperatures below 36°C cannot be reached in the deep brain tissue, whereas neckbands, covering the carotid triangles, may lead to hypothermic temperatures in the deep brain tissue. Temperature sensors have to be applied at least 2cm below the cortical surface to give values representative for deep brain tissue.

Effects of the selective endothelin A (ETA) receptor antagonist Clazosentan on cerebral perfusion and cerebral oxygenation following severe subarachnoid hemorrhage – preliminary results from a randomized clinical series

To study the effects of clazosentan, a new selective endothelin receptor subtype A antagonist, on cerebral perfusion and cerebral oxygenation following severe aneurysmal subarachnoid haemorrhage (aSAH). All 12 patients treated at our institution in the context of a phase IIa, multicenter, randomized trial on clazosentan's safety and efficacy in reducing the incidence of angiographic cerebral vasospasm were included in this substudy. The phase IIa study (n = 34) consisted of two parts: a double-blind, randomized Part A (clazosentan 0.2 mg/kg/h versus placebo) and an open-label Part B (clazosentan 0.4 mg/kg/h for 12 h followed by 0.2 mg/kg/h) for patients with established vasospasm. In parallel to the phase IIa study protocol, which included assessment of vasospasm by angiography and transcranial Doppler sonography, we determined regional cerebral blood flow (rCBF), cerebrovascular resistance, and regional tissue oxygenation. Cerebral perfusion was comparable between treatment groups during the early post-bleeding period (rCBF placebo, 22.6 +/- 3.5 ml/100 g/min versus rCBF clazosentan, 23.9 +/- 1.1 ml/100 g/min). By the time of control angiography (day 8 after aSAH), rCBF decreased by 50% in the placebo group (11.3 +/- 6.7 ml/ 100 g/min) while it remained stable in the clazosentan group (23.5 +/- 12.9 ml/100 g/min). During Part B of the study, all 3 patients who developed haemodynamically relevant vasospasm during placebo treatment, showed a sustained improvement in rCBF upon conversion to clazosentan. These preliminary data suggest that clazosentan reduces the extent of vasospasm-associated impairment of cerebral perfusion following aSAH. Furthermore, clazosentan may exert beneficial actions on overt vasospasm-associated hypoperfusion.

Effect of Nicardipine Prolonged-Release Implants on Cerebral Vasospasm and Clinical Outcome After Severe Aneurysmal Subarachnoid Hemorrhage

The purpose of this study was to investigate the effect of nicardipine prolonged-release implants (NPRIs) on cerebral vasospasm and clinical outcome after severe subarachnoid hemorrhage. Thirty-two patients with severe subarachnoid hemorrhage and undergoing aneurysm clipping were included into this single center, randomized, double-blind trial. Sixteen patients received NPRIs implanted into the basal cisterns in direct contact to the exposed proximal blood vessels; in 16 control patients, the basal cisterns were opened and washed out only without leaving implants. Angiography was performed preoperatively and at day 8+/-1. Computed tomography imaging was analyzed for the incidence of territorial infarcts unrelated to surgery. Patient outcome was assessed using the modified Rankin and National Institute of Health Stroke scales. The incidence of angiographic vasospasm in proximal vessel segments was significantly reduced after implantation of NPRIs (73% control versus 7% NPRIs). Significant differences occurred also for the majority of distal vessel segments. Computed tomography scans revealed a lower incidence of delayed ischemic lesions (47% control versus 14% NPRIs). The NPRI group demonstrated more favorable modified Rankin and National Institute of Health Stroke scales as well as a significantly lower incidence of deaths (38% control versus 6% NPRIs). Implantation of NPRIs reduces the incidence of cerebral vasospasm and delayed ischemic deficits and improves clinical outcome after severe subarachnoid hemorrhage.

Specialized Neurocritical Care, Severity Grade, and Outcome of Patients With Aneurysmal Subarachnoid Hemorrhage

To evaluate the impact of specialized neurocritical care on the population admitted to a neurovascular center and on the outcome of patients with severe aneurysmal subarachnoid hemorrhage (aSAH). After exclusion of patients treated with endovascular techniques, between 1999 and 2003, 198 patients with aSAH treated with early aneurysm clipping were analysed. In 1999, a new standardized protocol for intensive care treatment was established in the Department of Neurosurgery, University Hospital Zurich. The results were compared to the earlier time period (1993-1994) immediately after introduction of early aneurysm clipping. Out of 198 patients with aSAH, 90 patients (45.5%) suffered from mild aSAH World Federation of Neurosurgical Societies (WFNS) grade 1 and 2, 41 (27.3%) from aSAH WFNS grade 3, 36 (18.2%) from grade 4, and 57 (28.8%) from grade 5. From 1999 to 2003, significantly more patients with severe aSAH WFNS grade 4 and 5 underwent (further) treatment (93 out of 198 patients; 47.0%) compared to the former time-period after introduction of early surgery (23 out of 150 patients; 15.3%) (p < 0.0001). In the early series, 10 out of 23 patients (43.5%) with WFNS 4 recovered with good outcome Glasgow Outcome Score 4 and 5, whereas in the later series 23 out of 36 (63.9%) with WFNS grade 4 survived in a good functional state. Before 1999, all patients with WFNS grade 5 died or survived in a vegetative state. From 1999 to 2003, 20 out of 57 patients (35.1%) with aSAH WFNS grade 5 survived with good outcome. The availability of extended specialized neurocritical care seems to induce a change within the patient population towards a higher severity grade. Patients with highgrade aSAH might benefit most from highly specialized neurocritical care treatment.

Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation*

Acute respiratory dysfunction frequently occurs following severe aneurysmal subarachnoid hemorrhage requiring positive end-expiratory pressure (PEEP) ventilation to maintain adequate oxygenation. High PEEP levels, however, may negatively affect cerebral perfusion. The goal of this study was, to examine the influence of various PEEP levels on intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, and systemic hemodynamic variables. Animal research and clinical intervention study. Surgical intensive care unit of a university hospital. Experiments were carried out in five healthy pigs, followed by a clinical investigation of ten patients suffering subarachnoid hemorrhage. Under continuous monitoring of intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, mean arterial pressure, and cardiac output, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O in the experimental part and from baseline to 20 cm H2O in the clinical part. In animals, high PEEP levels had no adverse effect on intracranial pressure, brain tissue oxygen tension, or regional cerebral blood flow. In patients with severe subarachnoid hemorrhage, stepwise elevation of PEEP resulted in a significant decrease of mean arterial pressure and regional cerebral blood flow. Analyses of covariance revealed that these changes of regional cerebral blood flow depended on mean arterial pressure changes as a result of a disturbed cerebrovascular autoregulation. Consequently, normalization of mean arterial pressure restored regional cerebral blood flow to baseline values. Application of high PEEP does not impair intracranial pressure or regional cerebral blood flow per se but may indirectly affect cerebral perfusion via its negative effect on macrohemodynamic variables in case of a disturbed cerebrovascular autoregulation. Therefore, following severe subarachnoid hemorrhage, a PEEP-induced decrease of mean arterial pressure should be reversed to maintain cerebral perfusion.

Clazosentan (AXV-034343), a selective endothelin A receptor antagonist, in the prevention of cerebral vasospasm following severe aneurysmal subarachnoid hemorrhage: results of a randomized, double-blind, placebo-controlled, multicenter Phase IIa study

The goal of this study was to investigate the safety and tolerability of the novel endothelin A (ETA) receptor antagonist clazosentan in patients with subarachnoid hemorrhage (SAH) and its potential to reduce the incidence and severity of cerebral vasospasm following surgical clipping of the aneurysm. This Phase IIa multicenter study had two parts: a double-blind, randomized Part A (some patients given clazosentan [0.2 mg/kg/hr] and others given placebo), in which statistical inference was performed, and an open-label Part B (patients with established vasospasm given clazosentan [0.4 mg/kg/hr for 12 hours followed by 0.2 mg/kg/hr]) for exploratory purposes only. Primary end points were the incidence and severity of angiographic vasospasm on Day 8 after SAH and the safety and tolerability of the drug. Thirty-four patients (Hunt and Hess Grades III and IV and Fisher Grade > or = 3) were recruited and 32 (15 in the clazosentan group and 17 in the placebo group) were retained in the intent-to-treat population; 19 patients entered Part B. In Part A, treatment with clazosentan resulted in a reduced incidence of angiographically evident cerebral vasospasm (40% compared with 88% of patients, p = 0.008). In addition, the severity of vasospasm was reduced in the clazosentan group (p = 0.012). In Part B of the study, in 50% of assessable patients who were initially treated with placebo reversal of vasospasm was observed following the initiation of clazosentan therapy. The incidence of new infarctions was 15% in the clazosentan group and 44% in the placebo group (p = 0.130). There was no adverse event pattern indicating a specific organ toxicity of clazosentan. This study indicates that clazosentan reduces the frequency and severity of cerebral vasospasm following severe aneurysmal SAH with the incidence and severity of adverse events comparable to that of placebo.

Monitoring of brain tissue oxygenation following severe subarachnoid hemorrhage

The purpose of this prospective observational study was to investigate the relation between the frequency of critical neuromonitoring parameters (brain tissue pO2, (PtiO2) ≤ 10 mmHg, intracranial pressure (ICP) > 20 mmHg, cerebral perfusion pressure (CPP) ≤ 70 mmHg) and outcome after severe aneurysmal subarachnoid hemorrhage (SAH). In a prospective study on 42 patients monitoring of ICP, CPP, and PtiO2 (in the area at risk for vasospasm) was performed. All patients were primarily classified as Hunt and Hess grade 4 or with secondary deterioration to this grade. Relative proportions of PtiO2 ≤ 10 mmHg (n = 42), ICP > 20 mmHg (n = 25) and CPP ≤ 70 mmHg (n = 23) were derived from multimodal neuromonitoring data sets for different time intervals, i.e. 1. the total monitoring time; 2. the total monitoring time without the last two monitoring days; 3. the second last monitoring day; and 4. the last monitoring day. Patients were divided into nonsurvivors (GOS = 1) and survivors (GOS = 3-5). For the total monitoring time, significant differences in the relative proportion of critical values were found for all neuromonitoring parameters (p < 0.05). The detailed analysis of consecutive time intervals revealed significantly increased proportions of critical values in nonsurvivors for all neuromonitoring parameters during the last day only. Additionally, ICP > 20 mmHg was significantly more frequent during the second last day (p < 0.01). For other time periods no differences were observed. We conclude, that critical neuromonitoring values are not early predictors of nonsurvival in patients suffering from severe SAH.

血管内治療を施行した肺水腫合併くも膜下出血の１例

We report a case of severe aneurysmal subarachnoid hemorrhage (SAH) associated with pulmonary edema (PE) that was treated using endovascular surgery. A 65-year-old female was brought to our hospital with a history of disturbed consciousness. She was diagnosed as suffering from SAH in association with PE. An angiography examination revealed a ruptured anterior communicating artery aneurysm; an intraaneurysmal embolization using Guglielmi detachable coils was performed about 6 hours after the onset of the event. The partient's PE worsened during the first 12 hours after the procedure, necessitating artificial ventilation with a positive end-expiratory pressure. The patient's condition resolved in about 5 days. Endovascular surgery may be useful for the teatment of aneurysmal SAH episodes associated with cardiopulmonary complications. Careful cardiopulmonary monitoring and patient management are necessary in such cases.