Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial.

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.

Effectiveness of Lumbar Cerebrospinal Fluid Drain Among Patients With Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.

Importance: After aneurysmal subarachnoid hemorrhage, the use of lumbar drains has been suggested to decrease the incidence of delayed cerebral ischemia and improve long-term outcome. Objective: To determine the effectiveness of early lumbar cerebrospinal fluid drainage added to standard of care in patients after aneurysmal subarachnoid hemorrhage. Design, Setting, and Participants: The EARLYDRAIN trial was a pragmatic, multicenter, parallel-group, open-label randomized clinical trial with blinded end point evaluation conducted at 19 centers in Germany, Switzerland, and Canada. The first patient entered January 31, 2011, and the last on January 24, 2016, after 307 randomizations. Follow-up was completed July 2016. Query and retrieval of data on missing items in the case report forms was completed in September 2020. A total of 20 randomizations were invalid, the main reason being lack of informed consent. No participants meeting all inclusion and exclusion criteria were excluded from the intention-to-treat analysis. Exclusion of patients was only performed in per-protocol sensitivity analysis. A total of 287 adult patients with acute aneurysmal subarachnoid hemorrhage of all clinical grades were analyzable. Aneurysm treatment with clipping or coiling was performed within 48 hours. Intervention: A total of 144 patients were randomized to receive an additional lumbar drain after aneurysm treatment and 143 patients to standard of care only. Early lumbar drainage with 5 mL per hour was started within 72 hours of the subarachnoid hemorrhage. Main Outcomes and Measures: Primary outcome was the rate of unfavorable outcome, defined as modified Rankin Scale score of 3 to 6 (range, 0 to 6), obtained by masked assessors 6 months after hemorrhage. Results: Of 287 included patients, 197 (68.6%) were female, and the median (IQR) age was 55 (48-63) years. Lumbar drainage started at a median (IQR) of day 2 (1-2) after aneurysmal subarachnoid hemorrhage. At 6 months, 47 patients (32.6%) in the lumbar drain group and 64 patients (44.8%) in the standard of care group had an unfavorable neurological outcome (risk ratio, 0.73; 95% CI, 0.52 to 0.98; absolute risk difference, -0.12; 95% CI, -0.23 to -0.01; P = .04). Patients treated with a lumbar drain had fewer secondary infarctions at discharge (41 patients [28.5%] vs 57 patients [39.9%]; risk ratio, 0.71; 95% CI, 0.49 to 0.99; absolute risk difference, -0.11; 95% CI, -0.22 to 0; P = .04). Conclusion and Relevance: In this trial, prophylactic lumbar drainage after aneurysmal subarachnoid hemorrhage lessened the burden of secondary infarction and decreased the rate of unfavorable outcome at 6 months. These findings support the use of lumbar drains after aneurysmal subarachnoid hemorrhage. Trial Registration: ClinicalTrials.gov Identifier: NCT01258257.

Safety Profile and Complication Rates in Emergency Off-label Use of Tirofiban in Interventional Neuroradiology : An Observational Dual Center Study.

PURPOSE: Tirofiban has been approved for the treatment of acute coronary syndrome. Meanwhile, tirofiban is frequently applied in emergency situations in interventional neuroradiology (INR). The objective of this study was to analyze the risk profile for the off-label use of tirofiban in INR patients. METHODS: Data of 86 patients, who underwent neurointerventional therapy and were treated with tirofiban at 2 neuroendovascular centers between January 2016 and July 2017 were retrospectively analyzed. Despite off-label use, recent stroke (< 30 days), recent hemorrhage, thrombocytopenia (< 150,000/µl), activated partial thromboplastin time (aPTT) > 1.3-fold, internation normalised ratio (INR) < 1.5, severe liver insufficiency (Child-Pugh C), and preceding intravenous thrombolysis were considered as contraindications. RESULTS: Median patient age was 62 years (range 26-88 years). Patients received tirofiban for extracranial (n = 35) or intracranial stenting (n = 35), coiling of ruptured cerebral aneurysms (n = 6), continuous intra-arterial nimodipine infusion via microcatheters for subarachnoid hemorrhage (SAH)-related vasospasm (n = 5), or thrombotic complications during neuroendovascular procedures (n = 5). The desired effect of preventing thrombotic complications when applying tirofiban off-label was achieved in 81 of 86 patients (94.2%). Relevant tirofiban-associated complications occurred in 14 patients (16.3%), of which 9 patients received i.v. thrombolysis for treatment of acute ischemic stroke shortly before starting therapy with tirofiban. Of the 86 patients 12 died, while the overall tirofiban-related mortality was 2.3% (2 patients died due to ICH). Logistic regression analysis revealed age to be the only parameter significantly associated with development of tirofiban-associated complications (p = 0.026). CONCLUSION: Whereas the safety profile of tirofiban when applied off-label in INR is acceptable, the highest risk for relevant tirofiban-associated complications is observed in older patients treated by emergency stenting for acute stroke.

Continuous Intraarterial Nimodipine Infusion for the Treatment of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Retrospective, Single-Center Cohort Trial.

Background: Delayed cerebral ischemia (DCI) occurs after aneurysmal subarachnoid hemorrhage (aSAH). Continuous intraarterial nimodipine infusion (CIAN) is a promising approach in patients with intracranial large vessel vasospasm (LVV). The objective of this retrospective single-center cohort study was to evaluate the outcome in aSAH-patients treated with CIAN. Methods: CIAN was initiated and ended based on the clinical evaluation and transcranial Doppler (TCD), CT-angiography, CT-perfusion (PCT), and digital subtraction angiography (DSA). Nimodipine (0.5-2.0 mg/h) was administered continuously through microcatheters placed in the extracranial internal carotid and/or vertebral artery. Primary outcome measures were Glasgow Outcome Scale (GOS) at discharge and within 1 year after aSAH, and the occurrence of minor and major (<⅓ and >⅓ of LVV-affected territory) DCI-related infarctions in subsequent CT/MRI-scans. Secondary outcome measures were CIAN-associated complications. Results: A total of 17 patients underwent CIAN. Median onset of CIAN was 9 (3-13) days after aSAH, median duration was 5 (1-13) days. A favorable outcome (GOS 4-5) was achieved in 9 patients (53%) at discharge and in 13 patients within 1 year (76%). One patient died of posthemorrhagic cerebral edema. Minor cerebral infarctions occurred in five and major infarctions in three patients. One patient developed cerebral edema possibly due to CIAN. Normalization of PCT-parameters within 2 days was observed in 9/17 patients. Six patients showed clinical response and thus did not require PCT imaging. Conclusion: The favorable outcome in 76% of patients after 1 year is in line with previous studies. CIAN thus may be used to treat patients with severe therapy-refractory DCI.

The Influence of Oxidative Stress on Neurological Outcomes in Spontaneous Intracerebral Hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) causes, besides the primary brain injury, a secondary brain injury (SBI), which is induced, amongst other things, by oxidative stress (OS) and inflammation, determining the patient's outcome. This study aims to assess the impact of OS in plasma and cerebrospinal fluid (CSF) on clinical outcomes in patients with ICH. A total of 19 ICH (volume > 30 cc) patients and 29 control patients were included. From day one until seven, blood and CSF samples were obtained, and ICH volume was calculated. OS markers, like malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-sulfhydryl (GSH), and the total antioxidant status (TAS) were measured. Clinical data on treatment and outcome were determined. Patients with mRS ≤ 4 showed significantly elevated SOD and GSH-Px levels in plasma compared to patients with poor CO (p = 0.004; p = 0.002). Initial increased TAS in plasma and increased MDA in CSF were linked to an unfavorable outcome after six months (p = 0.06, r = 0.45; p = 0.05, r = 0.44). A higher ICH volume was associated with a worse outcome at week six (p = 0.04, r = 0.47). OS plays a significant role in SBI. Larger ICHs, elevated MDA in CSF, and TAS in plasma were associated with a detrimental outcome, whereas higher plasma-SOD and -GSH-Px were associated with a favorable outcome.

Decreased Superoxide Dismutase Concentrations (SOD) in Plasma and CSF and Increased Circulating Total Antioxidant Capacity (TAC) Are Associated with Unfavorable Neurological Outcome after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a devastating disease with high morbidity and mortality. Hypoxia-induced changes and hemoglobin accumulation within the subarachnoid space are thought to lead to oxidative stress, early brain injury, and delayed vasospasm. This study aimed to evaluate the antioxidant status and its impact on neurological outcome in patients with aneurysmal SAH. METHODS: In this prospective observational study, 29 patients with aneurysmal SAH were included (mean age 54.7 ± 12.4). Blood and cerebrospinal fluid (CSF) samples were collected on days (d) 1, 3, and 7. In addition, 29 patients without intracranial hemorrhage served as controls. The antioxidant system was analyzed by glutathione peroxidase (GSH-Px; U/L) and total and free glutathione-sulfhydryl (GSH; mg/L) in the plasma. Superoxide dismutase (SOD, U/mL) and total antioxidant capacity (TAC, µmol/L) were measured in the serum and CSF. Clinical data were compiled on admission (Hunt and Hess grade, Fisher grade, and GCS). Neurological and cognitive outcome (modified Rankin scale (mRS), Glasgow Outcome Scale Extended (GOSE) and Montreal Cognitive Assessment (MoCA)) was assessed after 6 weeks (6 w) and 6 months (6 m). RESULTS: Plasma levels of SOD increased from day 1 to 7 after SAH (d1: 1.22 ± 0.36 U/L; d3: 1.25 ± 0.33 U/L, p = 0.99; d7: 1.52 ± 0.4 U/L, p = 0.019) and were significantly higher compared to controls (1.11 ± 0.27 U/L) at day 7 (p < 0.001). Concordantly, CSF levels of SOD increased from day 1 to 7 after SAH (d1: 1.22 ± 0.41 U/L; d3: 1.77 ± 0.73 U/L, p = 0.10; d7: 2.37 ± 1.29 U/L, p < 0.0001) without becoming significantly different compared to controls (1.74 ± 0.8 U/L, p = 0.09). Mean plasma TAC at day 1 (d1: 77.87 ± 49.72 µmol/L) was not statistically different compared to controls (46.74 ± 32.42 µmol/L, p = 0.25). TAC remained unchanged from day 1 to 7 (d3: 92.64 ± 68.58 µmol/L, p = 0.86; d7: 74.07 ± 54.95 µmol/L, p = 0.8) in plasma. TAC in CSF steeply declined from day 1 to 7 in patients with SAH becoming significantly different from controls at days 3 and 7 (d3: 177.3 ± 108.7 µmol/L, p = 0.0046; d7: 85.35 ± 103.9 µmol/L, p < 0.0001). Decreased SOD levels in plasma and CSF are associated with a worse neurological outcome 6 weeks (mRS: CSF p = 0.0001; plasma p = 0.027/GOSE: CSF p = 0.001; plasma p = 0.001) and 6 months (mRS: CSF p = 0.001; plasma p = 0.09/GOSE: CSF p = 0.001; plasma p = 0.001) after SAH. Increased plasma TAC correlated with a worse neurological outcome 6 weeks (mRS: p = 0.001/GOSE p = 0.001) and 6 months (mRS p = 0.001/GOSE p = 0.001) after SAH. CONCLUSION: In our study, a reduction in the antioxidative enzyme SOD and elevated TAC were associated with a poorer neurological outcome reflected by mRS and GOSE at 6 weeks and 6 months after SAH. A lower initial SOD CSF concentration was associated with the late deterioration of cognitive ability. These findings support the mounting evidence of the role of oxidative stress in early brain injury formation and unfavorable outcome after SAH.

High CSF thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage.

BACKGROUND: The cerebral thrombin system is activated in the early stage after intracerebral hemorrhage (ICH). Expression of thrombin leads to concentration dependent secondary neuronal damage and detrimental neurological outcome. In this study we aimed to investigate the impact of thrombin concentration and activity in the cerebrospinal fluid (CSF) of patients with ICH on clinical outcome. METHODS: Patients presenting with space-occupying lobar supratentorial hemorrhage requiring extra-ventricular drainage (EVD) were included in our study. The CSF levels of thrombin, its precursor prothrombin and the Thrombin-Antithrombin complex (TAT) were measured using enzyme linked immune sorbent assays (ELISA). The oxidative stress marker Superoxide dismutase (SOD) was assessed in CSF. Initial clot size and intraventricular hemorrhage (IVH) volume was calculated based on by computerized tomography (CT) upon admission to our hospital. Demographic data, clinical status at admission and neurological outcome were assessed using the modified Rankin Scale (mRS) at 6-weeks and 6-month after ICH. RESULTS: Twenty-two consecutive patients (9 females, 11 males) with supratentorial hemorrhage were included in this study. CSF concentrations of prothrombin (p < 0.005), thrombin (p = 0.005) and TAT (p = 0.046) were statistical significantly different in patients with ICH compared to non-hemorrhagic CSF samples. CSF concentrations of thrombin 24h after ICH correlated with the mRS index after 6 weeks (r2 = 0.73; < 0.005) and 6 months (r2 = 0.63; < 0.005) after discharge from hospital. Thrombin activity, measured via TAT as surrogate parameter of coagulation, likewise correlated with the mRS at 6 weeks (r2 = 0.54; < 0.01) and 6 months (r2 = 0.66; < 0.04). High thrombin concentrations coincide with higher SOD levels 24h after ICH (p = 0.01). CONCLUSION: In this study we found that initial thrombin concentration and activity in CSF of ICH patients did not correlate with ICH and IVH volume but are associated with a poorer functional neurological outcome. These findings support mounting evidence of the role of thrombin as a contributor to secondary injury formation after ICH.

Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany-Updated series of 120 cases.

BACKGROUND: Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth. AIMS: To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage. METHODS: Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used. RESULTS: One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in n = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0-3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay. CONCLUSION: Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.

Cerebrospinal fluid penetration of very high-dose meropenem: a case report.

BACKGROUND: Standard dosing of meropenem (2 g t.i.d.) produces CSF concentrations of only 1-2 mg/L which is inferior to the clinical breakpoint for most Gram-negative bacteria. There is therefore concern that dosing must be increased in order to achieve therapeutic CSF concentrations for bacteria with susceptibility close to clinical breakpoints. Yet, the effects of high-dose meropenem on CSF concentrations are not well described in literature. We therefore determined meropenem CSF-levels in a patient who was treated with 15 g/day of meropenem. CASE PRESENTATION: Our patient suffered from a brain trauma and an external ventricular drainage was implanted. Later, a carbapenemase-producing Acinetobacter baumannii (OXA-23, NDM-1) was isolated from blood cultures and CSF. The MIC for meropenem was > 32 mg/L (R), and we opted for a combination therapy of meropenem, colistin and fosfomycin. Meropenem was given at an unusual high-dose (15 g/day) with the aim of achieving high CSF concentrations. CSF concentrations peaked at 64 mg/L. Yet, the patient succumbed to an intracranial bleed into a preexisting cerebral contusion. CONCLUSIONS: High-dose meropenem can achieve CSF levels largely superior to those achieved with commonly recommended dosing regimens. Though our patient succumbed to an intracranial bleed which could be regarded as a severe adverse event, we suggest that meropenem dosing can be increased when pathogens with increased MICs are found in the CSF. More in vivo data are however needed to determine the safety of high-dose meropenem.

Endovascular therapy for vasospasm after aneurysmatic subarachnoid hemorrhage.

INTRODUCTION: Balloon angioplasty and/or selective intra-arterial vasodilator therapies are treatment options in patients with vasospasm after subarachnoid hemorrhage (SAH). We analyzed the effect of balloon angioplasty and/or selective intra-arterial vasodilator therapy in our patients. METHODS: Twenty-six patients (vasodilation group, VDT) were treated with intra-arterial nimodipine. The balloon angioplasty with nimodiopine-group (BAP-N group) comprised 21 patients. The primary endpoint of this study was successful angiographic vessel dilation in vasospastic vessels after balloon angioplasty, together with nimodipine (BAP-N group), compared to intra-arterial vasodilator therapy (VDT group) with nimodipine alone. RESULTS: A significant effect of angioplasty plus nimodipine was found in the central arteries (composite endpoint) with an OR of 2.4 (95% CI: 1.4-4.2], p = 0.002), indicating a chance of improvement of the BAP-N group of more than twice compared to nimodipine infusions alone. Significant advantages for BAP-N-therapy were also encountered in the internal carotid artery (OR 5.4, p < 0.001) and basilar artery (OR 29.7, p = 0.003). A joint analysis of all arteries combined failed to show significant benefit of BAP-N therapy (OR 1.5, p = 0.079), which was also true for cerebral peripheral arteries (OR 0.77, p = 0.367). There was no difference in clinical outcome between both groups. CONCLUSIONS: In SAH patients with vasospasm, a combination therapy of balloon angioplasty and intra-arterial nimodipine resulted in a more than doubled vasodilative effect in the central cerebral arteries compared to the sole infusion of nimodipine. Regarding the ICA and BA arteries, this beneficial effect was even more pronounced. Although there was a tendency of better effects of the BAP-N group, regarding the overall effect in all territories combined, this failed to reach statistical evidence. In cerebral peripheral arteries, no differences were observed, and there was no difference in clinical outcome, too.

Continuous-wave near-infrared spectroscopy is not related to brain tissue oxygen tension.

Near-infrared spectroscopy (NIRS) has gained acceptance for cerebral monitoring, especially during cardiac surgery, though there are few data showing its validity. We therefore aimed to correlate invasive brain tissue oxygen measurements (PtiO2) with the corresponding NIRS-values (regional oxygen saturation, rSO2). We also studied whether NIRS was able to detect ischemic events, defined as a PtiO2-value of <15 mmHg. Eleven patients were studied with invasive brain tissue oxygen monitoring and continuous-wave NIRS. PtiO2-correlation with corresponding NIRS-values was calculated. We found no correlation between PtiO2- and NIRS-readings. Measurement of rSO2 was no better than flipping a coin in the detection of cerebral ischemia when a commonly agreed ischemic PtiO2 cut-off value of <15 mmHg was chosen. Continuous-wave-NIRS was unable to reliably detect ischemic cerebral episodes, defined as a PtiO2 value <15 mmHg. Displayed NIRS-values did not correlate with invasively measured PtiO2-values. CW-NIRS should not be used for the detection of cerebral ischemia.

Direct effects of Facio-Oral Tract Therapy(®) on swallowing frequency of non-tracheotomised patients with acute neurogenic dysphagia.

OBJECTIVES: The aim of this study was to investigate the direct effect of Facio-Oral Tract Therapy(®) on swallowing frequency of non-tracheotomised patients with acute neurogenic dysphagia. METHODS: Within a pre-, post-/during and follow-up study design, 19 non-tracheotomised dysphagic patients were included consecutively and treated according to three specific preselected Facio-Oral Tract Therapy stimulation techniques. RESULTS: The primary outcome was the direct effect of the three different Facio-Oral Tract Therapy stimulation techniques on the number of swallows. We found a significant effect of Facio-Oral Tract Therapy on swallowing frequency as compared to baseline with an increase by 65.63% and medium effect size of D = 0.62. No significant difference could be demonstrated when comparing baseline to follow-up. CONCLUSION: For the first time, this positive therapy effect could be demonstrated on a population of non-tracheotomised patients. Facio-Oral Tract Therapy seems to be an appropriate means for improving effectiveness and safety of swallowing. Since improvement was not long lasting, it appears to be reasonable to apply therapy frequently during the day with the plausible result of minimising the amount of aspirated saliva and thereby reducing the risk of aspiration pneumonia. Further studies may consider choosing a randomised controlled trial design to demonstrate that change in swallow frequency is related to the target intervention only.

Computed tomographic angiography as a useful adjunct in the diagnosis of brain death.

BACKGROUND: Because of its widespread accessibly, computed tomographic angiography (CT-A) is a promising technique in the detection of intracranial circulatory arrest in brain death (BD). Several studies assessed this tool, but neither have standardized evaluation parameters been developed nor has information about specificity become available. METHODS: We conducted a prospective study between January 2008 and April 2012. Thirty patients were admitted to our University Hospital (16 men and 14 women; age, 18-88 years) and underwent CT-A scanning at two occasions: immediately after the first signs of loss of brain stem reflexes and after definitive determination of brain. The results of CT-A were compared with transcranial Doppler ultrasonography and electroencephalogram. RESULTS: In 3 of 30 patients, we observed a termination of contrast flow at the level of the skull base and foramen magnum in arterial scanning series before the clinical determination of BD. After the clinical determination of BD, the opacification of all vascular territories in arterial phase scanning was found in one case, but venous phase scanning revealed no blood return in internal cerebral veins. In all other cases, contrast filling ceased at level of skull base or below. The specificity of CT-A in the detection of intracranial circulatory arrest was 90%, and sensitivity was 97%. CONCLUSION: CT-A is reliable and appropriate technical investigation to detect intracranial circulatory arrest in BD. The evaluation of contrast enhancement in arterial phase scanning seems to be more reliable than that in venous phase. An international consensus about a uniformly applied CT-A protocol for the evaluation of BD should be established.

Technical aids in the diagnosis of brain death: a comparison of SEP, AEP, EEG, TCD and CT angiography.

BACKGROUND: The use of technical aids to confirm brain death is a controversial matter. Angiography with the intra-arterial administration of contrast medium is the international gold standard, but it is not allowed in Germany except in cases where it provides a potential mode of treatment. The currently approved tests in Germany are recordings of somatosensory evoked potentials (SSEP), brain perfusion scintigraphy, transcranial Doppler ultrasonography (TCD), and electroencephalography (EEG). CT angiography (CTA), a promising new alternative, is being increasingly used as well. METHODS: In a prospective, single-center study that was carried out from 2008 to 2011, 71 consecutive patients in whom brain death was diagnosed on clinical grounds underwent recording of auditory evoked potentials (AEP) and SSEP as well as EEG, TCD and CTA. RESULTS: The validity of CTA for the confirmation of brain death was 94%; the validity of the other tests was: 94% for EEG, 92% for TCD, 82% for SSEP, and 2% for AEP. In 61 of the 71 patients (86%), the EEG, TCD and CTA findings all accorded with the clinical diagnosis. The diagnosis of brain death was established beyond doubt in all patients. CONCLUSION: In this study, the technical aids yielded discordant results in 14% of cases, necessitating interpretation by an expert examiner. The perfusion tests, in particular, can give false-positive results in patients with large cranial defects, skull fractures, or cerebrospinal fluid drainage. In such cases, electrophysiologic tests or a repeated clinical examination should be performed instead. CTA is a promising, highly reliable new method for demonstrating absent intracranial blood flow. In our view, it should be incorporated into the German guidelines for the diagnosis of brain death.

CT angiography as a confirmatory test in brain death.

OBJECTIVE: From recent studies, it remains unclear whether CT angiography could be an alternative to other established ancillary tests for the diagnosis of brain death. We examined intracranial contrast enhancement in CT angiography after clinically established brain death and compared the results with EEG and TCD findings. MATERIALS AND METHODS: Prospective study between April 2008 and January 2010. EEG, TCD and CT angiography were performed in 40 patients aged between 18 and 88 years (mean 56 years) who fulfilled the clinical criteria of brain death. RESULTS: In all cases, the common carotid artery, cervical internal carotid artery, cervical vertebral artery and superficial temporal artery opacified in an arterial CT angiography series. 37 out of 40 cases demonstrated no opacification of both MCA-M4, ACA-A3, PCA-P2 segments, and BA. CONCLUSION: CT angiography is a promising method of evaluating intracranial circulatory arrest in brain death with a high spatial and temporal resolution, superior to all other established technical procedures. The examination is easily accessible in most hospitals, operator independent, minimally invasive and inexpensive. Therefore, CT angiography has the potential to enlarge the existing armamentarium of confirmatory brain death tests.

Effect of intraarterial papaverine or nimodipine on vessel diameter in patients with cerebral vasospasm after subarachnoid hemorrhage.

INTRODUCTION: Papaverine (P) and nimodipine (N) are the most widely used vasodilators when angiographic and symptomatic vasospasm is present after subarachnoid aneurysmatic hemorrhage (SAH). Their effect is only short-lived and no direct comparisons have been undertaken to evaluate the action of both substances directly. We retrospectively assessed the effect of either P or N on angiographic diameter reduction and capillary blood flow. METHODS: Fifteen SAH patients with secured aneurysms and cerebral vasospasm received intraarterial P, fifteen similar patients received N. As the primary endpoint, pre- and post-infusion arterial diameters and capillary blood flow were rated retrospectively on angiographies and compared by RM-ANOVA. Secondary endpoints were the difference in the modified Rankin Scale between the two groups on admission and at discharge, the occurrence of delayed cerebral ischemia, the separate effects on angiographic diameter and capillary blood flow and the overall response rate to the vasodilator infusion. RESULTS: Angiographic resolution of diameter reduction and angiographically assessed capillary blood flow together differed not significantly between both groups. P infusion dilated all angiographic demonstrable vessels while N infusion was ineffective in 16% of the patients. Capillary flow on pre- and post-infusion angiographies was not different between the two groups. CONCLUSION: P and N seem to differ in the effect on cerebral diameter reduction in patients with vasospasm after SAH. The clinical implications remain to be established. A multimodal approach, perhaps combining different agents for intraarterial infusion in such patients, needs to be evaluated.

Postoperative nausea and vomiting in patients after craniotomy: incidence and risk factors.

OBJECT: The purpose of this study was to assess the incidence and risk factors of postoperative nausea and vomiting (PONV) after craniotomy because most available data about PONV in neurosurgical patients are retrospective in nature or derive from small prospective studies. METHODS: Postoperative nausea and vomiting was prospectively assessed within 24 hours after surgery in 229 patients requiring supratentorial or infratentorial craniotomy. To rule out the relevance of the neurosurgical procedure itself to the development of PONV, the observed incidence of vomiting was compared with the rate of vomiting predicted with a surgery-independent risk score (Apfel postoperative vomiting score). RESULTS: The overall incidence of PONV after craniotomy was 47%. Logistic regression identified female sex as a risk factor for postoperative nausea (OR 4.25, 95% CI 2.3-7.8) and vomiting (OR 2.62, 95% CI 1.4-4.9). Both the incidence of nausea (OR 3.76, 95% CI 2.06-6.88) and vomiting (OR 4.48, 95% CI 2.4-8.37) were increased in patients not receiving steroids. Postoperative nausea and vomiting occurred after infratentorial as well as after supratentorial procedures. The observed incidence of vomiting within 24 hours after surgery was higher (49%) than would be predicted with the Apfel surgery-independent risk score (31%; p = 0.0004). CONCLUSIONS: The overall incidence of PONV within 24 hours after craniotomy was approximately 50%. One possible reason is that intracranial surgeries pose an additional and independent risk factor for vomiting, especially in female patients. Patients undergoing craniotomy should be identified as high-risk patients for PONV.

Prospective assessment of postoperative pain after craniotomy.

UNLABELLED: Pain after craniotomy may be underdiagnosed, despite the fact that it can increase postoperative complications for example arterial hypertension and postoperative hemorrhage. This study investigates the incidence and intensity of pain after craniotomy and characterizes the influencing parameters. During a 1-year period 256 patients undergoing elective craniotomy were prospectively included in the study. Intensity of pain was evaluated 1, 4, and 24 hours after extubation using a verbal numerical rating scale (NRS) ranging from 0 (no pain) to 10 (maximal pain). Routine perioperative pain management was not influenced by the investigators. Parameters including patient-related factors, drug administration, and surgical factors were correlated with incidence and intensity of postcraniotomy pain. STATISTICAL ANALYSIS: logistic regression and chi using SPSS program (Windows, version 12.0). During the first 24 hours 87% of the patients experienced pain (NRS 1 to 3: 32%, NRS 4 to 7: 44%, NRS 8 to 10: 11%). For postoperative analgesia, the opioid piritramide (a mu-receptor agonist) was administered to 70% and nonopiod analgesics to 73% of the patients. The probability of experiencing postcraniotomy pain was reduced by 3% for each year of life. Maintenance of anesthesia with sevoflurane increased the probability of suffering from postcraniotomy pain by 147% and the absence of corticosteroids by 119%. Other investigated parameters did not influence pain after craniotomy. This study shows that pain is experienced by the majority of patients after craniotomy, despite conventional pain management, emphasizing the necessity for improved and individualized pain management in this special group of patients.