Julian Bösel

Hemicraniectomy in Older Patients with Extensive Middle-Cerebral-Artery Stroke

BACKGROUND Early decompressive hemicraniectomy reduces mortality without increasing the risk of very severe disability among patients 60 years of age or younger with complete or subtotal space-occupying middle-cerebral-artery infarction. Its benefit in older patients is uncertain. METHODS We randomly assigned 112 patients 61 years of age or older (median, 70 years; range, 61 to 82) with malignant middle-cerebral-artery infarction to either conservative treatment in the intensive care unit (the control group) or hemicraniectomy (the hemicraniectomy group); assignments were made within 48 hours after the onset of symptoms. The primary end point was survival without severe disability (defined by a score of 0 to 4 on the modified Rankin scale, which ranges from 0 [no symptoms] to 6 [death]) 6 months after randomization. RESULTS Hemicraniectomy improved the primary outcome; the proportion of patients who survived without severe disability was 38% in the hemicraniectomy group, as compared with 18% in the control group (odds ratio, 2.91; 95% confidence interval, 1.06 to 7.49; P=0.04). This difference resulted from lower mortality in the surgery group (33% vs. 70%). No patients had a modified Rankin scale score of 0 to 2 (survival with no disability or slight disability); 7% of patients in the surgery group and 3% of patients in the control group had a score of 3 (moderate disability); 32% and 15%, respectively, had a score of 4 (moderately severe disability [requirement for assistance with most bodily needs]); and 28% and 13%, respectively, had a score of 5 (severe disability). Infections were more frequent in the hemicraniectomy group, and herniation was more frequent in the control group. CONCLUSIONS Hemicraniectomy increased survival without severe disability among patients 61 years of age or older with a malignant middle-cerebral-artery infarction. The majority of survivors required assistance with most bodily needs. (Funded by the Deutsche Forschungsgemeinschaft; DESTINY II Current Controlled Trials number, ISRCTN21702227.).

Effect of Conscious Sedation vs General Anesthesia on Early Neurological Improvement Among Patients With Ischemic Stroke Undergoing Endovascular Thrombectomy: A Randomized Clinical Trial

Importance Optimal management of sedation and airway during thrombectomy for acute ischemic stroke is controversial due to lack of evidence from randomized trials. Objective To assess whether conscious sedation is superior to general anesthesia for early neurological improvement among patients receiving stroke thrombectomy. Design, Setting, and Participants SIESTA (Sedation vs Intubation for Endovascular Stroke Treatment), a single-center, randomized, parallel-group, open-label treatment trial with blinded outcome evaluation conducted at Heidelberg University Hospital in Germany (April 2014-February 2016) included 150 patients with acute ischemic stroke in the anterior circulation, higher National Institutes of Health Stroke Scale (NIHSS) score (>10), and isolated/combined occlusion at any level of the internal carotid or middle cerebral artery. Intervention Patients were randomly assigned to an intubated general anesthesia group (n = 73) or a nonintubated conscious sedation group (n = 77) during stroke thrombectomy. Main Outcomes and Measures Primary outcome was early neurological improvement on the NIHSS after 24 hours (0-42 [none to most severe neurological deficits; a 4-point difference considered clinically relevant]). Secondary outcomes were functional outcome by modified Rankin Scale (mRS) after 3 months (0-6 [symptom free to dead]), mortality, and peri-interventional parameters of feasibility and safety. Results Among 150 patients (60 women [40%]; mean age, 71.5 years; median NIHSS score, 17), primary outcome was not significantly different between the general anesthesia group (mean NIHSS score, 16.8 at admission vs 13.6 after 24 hours; difference, -3.2 points [95% CI, -5.6 to -0.8]) vs the conscious sedation group (mean NIHSS score, 17.2 at admission vs 13.6 after 24 hour; difference, -3.6 points [95% CI, -5.5 to -1.7]); mean difference between groups, -0.4 (95% CI, -3.4 to 2.7; P = .82). Of 47 prespecified secondary outcomes analyzed, 41 showed no significant differences. In the general anesthesia vs the conscious sedation group, substantial patient movement was less frequent (0% vs 9.1%; difference, 9.1%; P = .008), but postinterventional complications were more frequent for hypothermia (32.9% vs 9.1%; P < .001), delayed extubation (49.3% vs 6.5%; P < .001), and pneumonia (13.7% vs 3.9%; P = .03). More patients were functionally independent (unadjusted mRS score, 0 to 2 after 3 months [37.0% in the general anesthesia group vs 18.2% in the conscious sedation group P = .01]). There were no differences in mortality at 3 months (24.7% in both groups). Conclusions and Relevance Among patients with acute ischemic stroke in the anterior circulation undergoing thrombectomy, conscious sedation vs general anesthesia did not result in greater improvement in neurological status at 24 hours. The study findings do not support an advantage for the use of conscious sedation. Trial Registration clinicaltrials.gov Identifier: NCT02126085.

Options to restrict hematoma expansion after spontaneous intracerebral hemorrhage.

Background and Purpose— Secondary expansion of hematoma after spontaneous intracerebral hemorrhage occurs frequently and early with the potential sequelae of functional deterioration or death. The aim of this topical review is to give a summary of current evidence- and experience-based options to avoid or attenuate hematoma expansion. Method— We reviewed the literature of the past 10 years on efforts to restrict spontaneous intracerebral hemorrhage expansion by searching Medline and adding related articles known to us. Based on evidence, current guidelines, and our own clinical practice, we have collected consistent and inconsistent pieces of data. These were differentiated according to surgical versus medical approaches, weighed and discussed with regard to expectable benefit, potential risk, and practicability. Finally, we have outlined promising future approaches. Results— Although consistent evidence on the topic is generally limited, some important studies have provided data on risk factors predicting spontaneous intracerebral hemorrhage expansion implying ways of directing therapy toward these risk factors. Large trials have shed light on 4 major efforts to avoid hematoma expansion: surgical hematoma treatment, reduction of hypertension, reversal of coagulopathies or anticoagulants, and hemostatic therapy. The results were largely disappointing but provide insights for new trials. Future strategies include the combination of surgical and medical treatment and the use of neuroprotectants. Conclusions— Early restriction of intracerebral hemorrhage is of paramount importance because secondary volume expansion leads to outcome deterioration and death. Although there appear to be few indications for neurosurgical measures, nonsurgical measures such as reduction of hypertension and normalization of altered coagulation seem to be beneficial. However, the routine use of coagulation factors outside of warfarin-associated spontaneous intracerebral hemorrhage cannot generally be recommended at present. The same applies for future approaches such as combined medical–surgical approaches and neuroprotective therapies at this point.

Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial

BACKGROUND Haematoma expansion is a major cause of mortality in intracranial haemorrhage related to vitamin K antagonists (VKA-ICH). Normalisation of the international normalised ratio (INR) is recommended, but optimum haemostatic management is controversial. We assessed the safety and efficacy of fresh frozen plasma (FFP) versus prothrombin complex concentrate (PCC) in patients with VKA-ICH. METHODS We did an investigator-initiated, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Patients aged at least 18 years with VKA-ICH who presented within 12 h after symptom onset with an INR of at least 2·0 were randomly assigned (1:1) by numbered sealed envelopes to 20 mL/kg of intravenous FFP or 30 IU/kg of intravenous four-factor PCC within 1 h after initial cerebral CT scan. The primary endpoint was the proportion of patients with INR 1·2 or lower within 3 h of treatment initiation. Masking of treatment was not possible, but the primary analysis was observer masked. Analyses were done using a treated-as-randomised approach. This trial is registered with EudraCT, number 2008-005653-37, and ClinicalTrials.gov, number NCT00928915. FINDINGS Between Aug 7, 2009, and Jan 9, 2015, 54 patients were randomly assigned (26 to FFP and 28 to PCC) and 50 received study drug (23 FFP and 27 PCC). The trial was terminated on Feb 6, 2015, after inclusion of 50 patients after a safety analysis because of safety concerns. Two (9%) of 23 patients in the FFP group versus 18 (67%) of 27 in the PCC group reached the primary endpoint (adjusted odds ratio 30·6, 95% CI 4·7-197·9; p=0·0003). 13 patients died: eight (35%) of 23 in the FFP group (five from haematoma expansion, all occurring within 48 h after symptom onset) and five (19%) of 27 in the PCC group (none from haematoma expansion), the first of which occurred on day 5 after start of treatment. Three thromboembolic events occurred within 3 days (one in the FFP group and two in the PCC group), and six after day 12 (one and five). 43 serious adverse events (20 in the FFP group and 23 in the PCC group) occurred in 26 patients. Six serious adverse events were judged to be FFP related (four cases of haematoma expansion, one anaphylactic reaction, and one ischaemic stroke) and two PCC related (ischaemic stroke and pulmonary embolism). INTERPRETATION In patients with VKA-related intracranial hemorrhage, four-factor PCC might be superior to FFP with respect to normalising the INR, and faster INR normalisation seemed to be associated with smaller haematoma expansion. Although an effect of PCC on clinical outcomes remains to be shown, our data favour the use of PCC over FFP in intracranial haemorrhage related to VKA. FUNDING Octapharma.

DESTINY II: DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY II.

Background Patients with severe space-occupying – so-called malignant – middle cerebral artery infarcts have a poor prognosis even under maximum intensive care treatment. Randomised trials demonstrated that early hemicraniectomy reduces mortality from about 70% to 20% without increasing the risk of being very severely disabled. Hemicraniectomy increases the chance to survive completely independent more than fivefold and doubles the chance to survive at least partly independent. Only patients up to 60-years have been included in these trials. However, patients older than 60-years represent about 50% of all patients with malignant middle cerebral artery infarcts. Data from observational studies, suggesting that older patients may not profit from hemicraniectomy, are inconclusive, because these patients have generally been treated later and less aggressively. This leads to great uncertainty in everyday clinical practice. Aims To investigate the efficacy of early hemicraniectomy in patients older than 60-years with malignant MCA infarcts. Materials & Methods DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY II is a randomised controlled trial including patients 61-years and older with malignant middle cerebral artery infarcts. Patients are randomised to either maximum conservative treatment alone or in addition to early hemicraniectomy within 48 h after symptom onset. The trial uses a sequential design with a maximum number of 160 patients to be enrolled (ISRCTN 21702227). Discussion In the face of an ageing population, the potential benefit of hemicraniectomy in older patients is of major clinical relevance, but remains controversial. Conclusion The results of this trial are expected to directly influence decision making in these patients.

Stroke-Related Early Tracheostomy Versus Prolonged Orotracheal Intubation in Neurocritical Care Trial (SETPOINT): A Randomized Pilot Trial.

Background and Purpose— Optimal timing of tracheostomy in ventilated patients with severe stroke is unclear. We aimed to investigate feasibility, safety, and potential advantages of early tracheostomy in these intensive care unit (ICU) patients. Methods— This prospective, randomized, parallel-group, controlled, open, and outcome-masked pilot trial was conducted in neurological/neurosurgical ICUs of a university hospital. Patients with severe ischemic or hemorrhagic stroke and an estimated need for at least 2 weeks of ventilation were randomized to either early tracheostomy (within day 1–3 from intubation; early) or to standard tracheostomy (between day 7–14 from intubation if extubation could not be achieved or was not feasible; standard). The primary outcome was length of stay in the ICU; secondary outcomes were diverse aspects of the ICU course. Results— Sixty patients were randomized and analyzed. No differences were observed with regard to the primary outcome length of stay in the ICU (median 18 [interquartile range 16–28] versus 17 [interquartile range 13–22] days, median difference: 1 [−2 to 6]; P=0.38) or to most secondary outcomes, including adverse effects. Instead, use of sedatives (62% versus 42% of ICU stay, median difference 17.5 [3.3–29.2]; P=0.02), ICU mortality (ICU deaths 3 [10%] versus 14 [47%]; P<0.01) and 6-month mortality (deaths 8 [27%] versus 18 [60%]; P=0.02) were lower in the early group than in the standard group, respectively. Conclusions— Early tracheostomy in ventilated intensive care stroke patients is feasible, and safe, and presumably reduces sedation need. Whether the suggested benefits in mortality and outcome truly exist has to be determined by a larger multicenter trial. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT01261091.

Emergency Cervical Internal Carotid Artery Stenting in Combination with Intracranial Thrombectomy in Acute Stroke

BACKGROUND AND PURPOSE: In past years, thrombectomy has become a widely used procedure in interventional neuroradiology for the treatment of acute intracranial occlusions. However, in 10–20% of patients, there are additional occlusions or stenotic lesions of the ipsilateral cervical internal carotid artery. The purpose of this study was to evaluate the feasibility of emergency carotid artery stent placement in combination with intracranial thrombectomy and the clinical outcome of the treated patients. MATERIALS AND METHODS: We analyzed clinical and angiographic data of patients who underwent emergency cervical ICA stent placement and intracranial thrombectomy with stent-retriever devices in our institution between November 2009 and July 2012. Recanalization was assessed according to the Thrombolysis in Cerebral-Infarction score. Clinical outcome was evaluated at discharge (NIHSS) and after 3 months (mRS). RESULTS: Overall, 24 patients were treated. The mean age was 67.2 years; mean occlusion time, 230.2 minutes. On admission, the median NIHSS score was 18. In all patients, the Thrombolysis in Cerebral Infarction score was zero before the procedure. Stent implantation was feasible in all cases. In 15 patients (62.5%), a Thrombolysis in Cerebral Infarction score ≥ 2b could be achieved. Six patients (25%) improved ≥10 NIHSS points between admission and discharge. After 90 days, the median mRS score was 3.0. Seven patients (29.2%) had a good clinical outcome (mRS 0–2), and 4 patients (16.6%) died, 1 due to fatal intracranial hemorrhage. Overall, symptomatic intracranial hemorrhage occurred in 4 patients (16.6%). CONCLUSIONS: Emergency ICA stent implantation was technically feasible in all patients, and the intracranial recanalization Thrombolysis in Cerebral Infarction score of ≥2b was reached in a high number of patients. Clinical outcome and mortality seem to be acceptable for a cohort with severe stroke. However, a high rate of symptomatic intracranial hemorrhage occurred in our study.

Evidence-based guidelines for the management of large hemispheric infarction : a statement for health care professionals from the Neurocritical Care Society and the German Society for Neuro-intensive Care and Emergency Medicine.

Large hemispheric infarction (LHI), also known as malignant middle cerebral infarction, is a devastating disease associated with significant disability and mortality. Clinicians and family members are often faced with a paucity of high quality clinical data as they attempt to determine the most appropriate course of treatment for patients with LHI, and current stroke guidelines do not provide a detailed approach regarding the day-to-day management of these complicated patients. To address this need, the Neurocritical Care Society organized an international multidisciplinary consensus conference on the critical care management of LHI. Experts from neurocritical care, neurosurgery, neurology, interventional neuroradiology, and neuroanesthesiology from Europe and North America were recruited based on their publications and expertise. The panel devised a series of clinical questions related to LHI, and assessed the quality of data related to these questions using the Grading of Recommendation Assessment, Development and Evaluation guideline system. They then developed recommendations (denoted as strong or weak) based on the quality of the evidence, as well as the balance of benefits and harms of the studied interventions, the values and preferences of patients, and resource considerations.

Sedation vs. Intubation for Endovascular Stroke TreAtment (SIESTA) - a randomized monocentric trial.

Background The optimal peri-interventional management of sedation and airway for endovascular stroke treatment (EST) appears to be a crucial factor for treatment success. According to retrospective studies, the widely favored general anesthesia with intubation seems to be associated with poor functional outcome compared to a slightly sedated non-intubated condition (conscious sedation). Method SIESTA is a monocentric, prospective, randomized parallel-group, open-label treatment trial with blinded endpoint evaluation (PROBE design). The study compares the non-intubated with the intubated state in patients receiving endovascular treatment of acute ischemic anterior circulation stroke. The primary endpoint is early neurological improvement as by National Institutes of Health Stroke Scale (NIHSS) after 24 h (difference between NIHSS on admission and NIHSS after 24 h). Secondary endpoints include: functional outcome after three-months as by modified Rankin Scale (mRS), mortality, parameters of ventilation and critical care, feasibility, and safety, i.e. complications related to endovascular stroke treatment. Conclusion The aims of this study are to prospectively clarify whether the non-intubated state of conscious sedation is feasible, safe, and superior with regard to early neurological improvement compared to the intubated state of general anesthesia in patients receiving acute endovascular stroke treatment.

Monitoring of Brain and Systemic Oxygenation in Neurocritical Care Patients

Maintenance of adequate oxygenation is a mainstay of intensive care, however, recommendations on the safety, accuracy, and the potential clinical utility of invasive and non-invasive tools to monitor brain and systemic oxygenation in neurocritical care are lacking. A literature search was conducted for English language articles describing bedside brain and systemic oxygen monitoring in neurocritical care patients from 1980 to August 2013. Imaging techniques e.g., PET are not considered. A total of 281 studies were included, the majority described patients with traumatic brain injury (TBI). All tools for oxygen monitoring are safe. Parenchymal brain oxygen (PbtO2) monitoring is accurate to detect brain hypoxia, and it is recommended to titrate individual targets of cerebral perfusion pressure (CPP), ventilator parameters (PaCO2, PaO2), and transfusion, and to manage intracranial hypertension, in combination with ICP monitoring. SjvO2 is less accurate than PbtO2. Given limited data, NIRS is not recommended at present for adult patients who require neurocritical care. Systemic monitoring of oxygen (PaO2, SaO2, SpO2) and CO2 (PaCO2, end-tidal CO2) is recommended in patients who require neurocritical care.