Martin Seule

THERAPEUTIC HYPOTHERMIA IN PATIENTS WITH ANEURYSMAL SUBARACHNOID HEMORRHAGE, REFRACTORY INTRACRANIAL HYPERTENSION, OR CEREBRAL VASOSPASM

OBJECTIVETo evaluate the feasibility and safety of mild hypothermia treatment in patients with aneurysmal subarachnoid hemorrhage (SAH) who are experiencing intracranial hypertension and/or cerebral vasospasm (CVS). METHODSOf 441 consecutive patients with SAH, 100 developed elevated intracranial pressure and/or symptomatic CVS refractory to conventional treatment. Hypothermia (33–34°C) was induced and maintained until intracranial pressure normalized, CVS resolved, or severe side effects occurred. RESULTSThirteen patients were treated with hypothermia alone, and 87 were treated with hypothermia in combination with barbiturate coma. Sixty-six patients experienced poor-grade SAH (Hunt and Hess Grades IV and V) and 92 had Fisher Grade 3 and 4 bleedings. The mean duration of hypothermia was 169 ± 104 hours, with a maximum of 16.4 days. The outcome after 1 year was evaluated in 90 of 100 patients. Thirty-two patients (35.6%) survived with good functional outcome (Glasgow Outcome Scale [GOS] score, 4 and 5), 14 (15.5%) were severely disabled (GOS score, 3), 1 (1.1%) was in a vegetative state (GOS score, 2), and 43 (47.8%) died (GOS score, 1). The most frequent side effects were electrolyte disorders (77%), pneumonia (52%), thrombocytopenia (47%), and septic shock syndrome (40%). Of 93 patients with severe side effects, 6 (6.5%) died as a result of respiratory or multi-organ failure. CONCLUSIONProlonged systemic hypothermia may be considered as a last-resort option for a carefully selected group of SAH patients with intracranial hypertension or CVS resistant to conventional treatment. However, complications associated with hypothermia require elaborate protocols in general intensive care unit management.

Correlation among systemic inflammatory parameter, occurrence of delayed neurological deficits, and outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND The role and impact of systemic inflammatory response after aneurysmal subarachnoid hemorrhage remain to be elucidated. OBJECTIVE To assess the time course and correlation of systemic inflammatory parameters with outcome and the occurrence of delayed ischemic neurological deficits (DINDs) after subarachnoid hemorrhage. METHODS Besides the baseline characteristics, daily interleukin-6 (IL-6), procalcitonin, C-reactive protein levels, and leukocyte counts were prospectively measured until day 14 after subarachnoid hemorrhage. Occurrence of infectious complications and application of therapeutic hypothermia were assessed as confounding factors. The primary end point was outcome after 3 months, assessed by Glasgow outcome scale; the secondary end point was the occurrence of DINDs. RESULTS During a 3-year period, a total of 138 patients were included. All inflammatory parameters measured were higher in patients with unfavorable outcome (Glasgow outcome scale score, 1-3). After adjustment for confounding factors, elevated IL-6 and leukocyte counts remained significant risk factors for unfavorable outcome. The odds ratio for log IL-6 was 4.07 (95% confidence interval, 1.18 to 14.03; P = .03) and for leukocyte counts was 1.24 (95% confidence interval, 1.06-1.46, P = .008). The analysis of the time course established that IL-6 was the only significantly elevated parameter in the early phase in patients with unfavorable outcome. Higher IL-6 levels in the early phase (days 3-7) were associated with the occurrence of DINDs. The adjusted odds ratio for log IL-6 was 4.03 (95% confidence interval, 1.21-13.40; P = .02). CONCLUSION Higher IL-6 levels are associated with worse clinical outcome and the occurrence of DINDs. Because IL-6 levels were significantly elevated in the early phase, they might be a useful parameter to monitor.

Novel treatments for vasospasm after subarachnoid hemorrhage.

Purpose of reviewCerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage remains a considerable challenge in neurocritical care medicine. This review aims to cover the recent novel aspects and results in CVS treatment. Recent findingsOn the basis of the recent literature, treatment focusing on CVS alone is outdated. A considerable amount of evidence suggests CVS not to be the sole cause of delayed cerebral ischemia (DCI) and poor outcome. Early brain injury, cortical spreading depolarization, inflammation and microthrombosis have recently been discussed as additional factors. The results of a well designed phase III trial, using an endothelin-1 antagonist, indicated a decrease in the occurrence of CVS but did not change the clinical outcome significantly. Induced hypertension is currently recommended for treating suspected DCI, whereas hemodilution and hypervolemia are not. Endovascular intervention is only recommended in case of refractory symptomatic CVS. A couple of newer treatment strategies are under evaluation. Phase III trials are underway for magnesium sulfate and statins. Clinical trials aiming specifically at recently discussed factors other than CVS have not been reported. SummaryReviewing the recent literature, there have been some updates on recommendations and newer treatment modalities are under evaluation. However, a novel treatment with convincing evidence has not been reported so far.

Monitoring of the Inflammatory Response After Aneurysmal Subarachnoid Haemorrhage in the Clinical Setting: Review of Literature and Report of Preliminary Clinical Experience

BACKGROUND Clinical and experimental studies showed a marked inflammatory response in aneurysmal subarachnoid haemorrhage (SAH), and it has been proposed to play a key role in the development of cerebral vasospasm (CVS). Inflammatory response and occurrence of CVS may represent a common pathogenic pathway allowing point of care diagnostics of CVS. Therefore, monitoring of the inflammatory response might be useful in the daily clinical setting of an ICU. The aim of the current report is to give a summary about factors contributing to the complex pathophysiology of inflammatory response in SAH and to discuss possible monitoring modalities. METHODS Review and analysis of the existing literature and definition of own study protocols. RESULTS In cerebrospinal fluid, interleukin (IL)-6 has been found to be significantly higher in patients with CVS during the peri-vasospasm period. While systemic inflammatory response syndrome, high C-reactive protein levels and leukocyte counts has been linked with the occurrence of CVS, less has been reported about cytokines levels in the jugular bulb of the internal jugular vein and in the peripheral blood. Preliminary evaluation of own data suggests, that IL-6 values in the peripheral blood and the arterio-jugular differences of IL-6 are increased with the inflammatory response after SAH. CONCLUSION Monitoring of the inflammatory response, in particular IL-6, might be a useful tool for the daily clinical management of patients with SAH and CVS.

Theoretical evaluations of therapeutic systemic and local cerebral hypothermia

PURPOSE To simulate cerebral temperature behaviour with hypothermia treatment applying different cooling devices and to find the optimal brain temperature monitoring. METHODS Models 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. RESULTS Systemic hypothermia by endovascular cooling leads to an uniform temperature decrease within the brain tissue. Cooling with head caps lead to 33 degrees C only in the superficial brain while the deep brain remains higher than 36 degrees C. Cooling with neckbands lead to 35.8 degrees C for dry and 32.8 degrees C for wet skin in the deep brain. CONCLUSIONS With head caps temperatures below 36 degrees 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 2 cm below the cortical surface to give values representative for deep brain tissue.

Introducing a nationwide registry: the Swiss study on aneurysmal subarachnoid haemorrhage (Swiss SOS)

BackgroundAneurysmal subarachnoid haemorrhage (aSAH) is a haemorrhagic form of stroke and occurs in a younger population compared with ischaemic stroke or intracerebral haemorrhage. It accounts for a large proportion of productive life-years lost to stroke. Its surgical and medical treatment represents a multidisciplinary effort. Due to the complexity of the disease, the management remains difficult to standardise and quality of care is accordingly difficult to assess.ObjectiveTo create a registry to assess management parameters of patients treated for aSAH in Switzerland.MethodsA cohort study was initiated with the aim to record characteristics of patients admitted with aSAH, starting January 1st 2009. Ethical committee approval was obtained or is pending from the institutional review boards of all centres. In the study period, seven Swiss hospitals (five university [U], two non-university medical centres) harbouring a neurosurgery department, an intensive care unit and an interventional neuroradiology team so far agreed to participate in the registry (Aarau, Basel [U], Bern [U], Geneva [U], Lausanne [U], St. Gallen, Zürich [U]). Demographic and clinical parameters are entered into a common database.DiscussionThis database will soon provide (1) a nationwide assessment of the current standard of care and (2) the outcomes for patients suffering from aSAH in Switzerland. Based on data from this registry, we can conduct cohort comparisons or design diagnostic or therapeutic studies on a national level. Moreover, a standardised registration system will allow healthcare providers to assess the quality of care.

Aneurysmatische Subarachnoidalblutung – Diagnostik und Therapie zerebraler und systemischer Komplikationen

The management of patients with aneurysmal subarachnoid hemorrhage (SAH) requires a fundamental knowledge of the disease, its therapeutic options and possible complications. The preoperative goal is to prevent rebleeding by controlling blood pressure and treating pain and anxiety as well as stabilizing cardiopulmonary functions. An acute hydrocephalus has to be treated immediately. Microsurgical clipping or endovascular coiling are the therapeutic options available. The postoperative goal aims at securing cardiopulmonary functions as well as recognizing and treating cerebral (cerebral vasospasm, hydrocephalus, epilepsy) and systemic complications (electrolyte disorder, cardiac dysfunction). This article provides an overview about the pre-, peri- and postoperative management of patients with SAH.

Surgical treatment of unruptured intracranial aneurysms in a low-volume hospital – Outcome and review of literature

BACKGROUND The aim of this study was to evaluate surgical outcome of unruptured intracranial aneurysms (UIAs) in a low-volume hospital and compare the results with the recent literature. METHODS A retrospective review of all consecutive craniotomies for UIA from July 1999 through June 2009 was performed. Morbidity was defined as modified Rankin Scale (mRS) ≥ 3 and evaluated six weeks after surgery. Cognitive function was evaluated at rehabilitation-to-home discharge. A PubMed database search (2001-2011) seeking retrospective, single-center studies reporting on surgical outcome of UIAs was performed. RESULTS There were 47 procedures performed in 42 patients to treat 50 UIAs (mean of 5 annual craniotomies). The mean age was 54.7 ± 12.1 years and mean aneurysm size was 7.6 ± 4.0mm. Favorable outcome (mRS 0-2) at six weeks after surgery was achieved in 45 of 47 procedures (95.7%). Aneurysm size ≥ 12 mm was statistically significant related to adverse outcome defined as mRS change ≥ 1 (71% vs. 29%; p = 0.018). Five patients (10.6%) with favorable neurological outcome (mRS 2) presented with cognitive impairment at rehabilitation-to-home discharge. There was no significant difference in overall morbidity and mortality comparing low- and high-volume hospitals (4.0% vs. 4.8%; p = 0.85). CONCLUSIONS Low-volume hospitals may achieve good results for surgical treatment of UIAs. The results indicate that defining numeric operative volume thresholds is not feasible to guide centralization of aneurysm treatment.

Long-term neurological and neuropsychological outcome in patients with severe traumatic brain injury.

BACKGROUND Severe traumatic brain injury (TBI) remains a major cause of death and disability worldwide. The aim of the study was to evaluate predictors for neurological and neuropsychological long-term outcome in patients with severe TBI treated according to an intracranial pressure (ICP-) targeted therapy. METHODS From 08/2005 to 12/2008, 46 patients with severe TBI and more than 12h of intensive care treatment were included in this study. Neurological outcome was assessed with the Glasgow Outcome Scale (GOS). Neuropsychological performance assessing 9 different domains was evaluated at long-term follow-up (median 20.5 months; range 10-46). Logistic regression was used to identify favourable outcomes according to the GOS and Fishers exact tests were used to identify predictors of severe neuropsychological impairments at follow-up. RESULTS Twenty-nine patients were available for neuropsychological assessment at long-term follow-up. Only 2 out of 29 patients presented normal or average neuropsychological findings throughout all 9 neuropsychological domains at long-term follow-up. The percentage of a favourable outcome (GOS 4-5) increased from 13.8% at hospital discharge to 75.8% at rehabilitation discharge to 79.3% at long-term follow-up, respectively. Age ≤40 was found to be a strong predictor of favourable outcome at follow-up (OR 5.95, 95% CI 1.41 25.00, p=0.015). The GOS at hospital discharge was not a predictor for severe impairments in any of the 9 different neuropsychological domains (all p-values were p>0.268). In contrast, the GOS at rehabilitation discharge was found to be a predictor of severe impairments at follow-up in all but one domain assessed (all p-values less than p<0.038). CONCLUSIONS The GOS at rehabilitation discharge should be regarded as a better predictor for neuropsychological impairments at long-term follow-up than the GOS at hospital discharge. Even in patients with favourable GOS after finishing a course of rehabilitation, three quarters of these patients may have at least one severe neuropsychological deficit. Therefore, it remains of paramount importance to provide long-term neuropsychological support to further improve outcome after TBI.

Monitoring of Cerebral Hemodynamics and Oxygenation to Detect Delayed Ischemic Neurological Deficit After Aneurysmal Subarachnoid Hemorrhage

One of the major goals in the treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH) is early detection and treatment of delayed ischemic neurologic deficits (DINDs) to prevent cerebral infarction and thus poor outcome or even death. The complex changes of cerebral metabolism, hemodynamics, and oxygenation after SAH are underestimated if they are considered exclusively based on angiographic cerebral vasospasm (CVS). The discrepancies on one hand may arise from the heterogeneous and complex pathophysiology of DINDs. On the other hand, the occurrence of DINDs may depend on the relationship between local cerebral oxygen delivery and demand, which can only be determined if cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO(2)) can be measured. We briefly review the most relevant methods for monitoring cerebral hemodynamics and oxygenation and discuss the limitations associated with early diagnosis of DINDs in patients with severe aSAH not amenable for clinical neurological examination.