Intracranial pressure monitoring with and without brain tissue oxygen pressure monitoring for severe traumatic brain injury in France (OXY-TC): an open-label, randomised controlled superiority trial.

BACKGROUND: Optimisation of brain oxygenation might improve neurological outcome after traumatic brain injury. The OXY-TC trial explored the superiority of a strategy combining intracranial pressure and brain tissue oxygen pressure (PbtO2) monitoring over a strategy of intracranial pressure monitoring only to reduce the proportion of patients with poor neurological outcome at 6 months. METHODS: We did an open-label, randomised controlled superiority trial at 25 French tertiary referral centres. Within 16 h of brain injury, patients with severe traumatic brain injury (aged 18-75 years) were randomly assigned via a website to be managed during the first 5 days of admission to the intensive care unit either by intracranial pressure monitoring only or by both intracranial pressure and PbtO2 monitoring. Randomisation was stratified by age and centre. The study was open label due to the visibility of the intervention, but the statisticians and outcome assessors were masked to group allocation. The therapeutic objectives were to maintain intracranial pressure of 20 mm Hg or lower, and to keep PbtO2 (for those in the dual-monitoring group) above 20 mm Hg, at all times. The primary outcome was the proportion of patients with an extended Glasgow Outcome Scale (GOSE) score of 1-4 (death to upper severe disability) at 6 months after injury. The primary analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew consent or had protocol violations. This trial is registered with ClinicalTrials.gov, NCT02754063, and is completed. FINDINGS: Between June 15, 2016, and April 17, 2021, 318 patients were randomly assigned to receive either intracranial pressure monitoring only (n=160) or both intracranial pressure and PbtO2 monitoring (n=158). 27 individuals with protocol violations were not included in the modified intention-to-treat analysis. Thus, the primary outcome was analysed for 144 patients in the intracranial pressure only group and 147 patients in the intracranial pressure and PbtO2 group. Compared with intracranial pressure monitoring only, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with GOSE score 1-4 (51% [95% CI 43-60] in the intracranial pressure monitoring only group vs 52% [43-60] in the intracranial pressure and PbtO2 monitoring group; odds ratio 1·0 [95% CI 0·6-1·7]; p=0·95). Two (1%) of 144 participants in the intracranial pressure only group and 12 (8%) of 147 participants in the intracranial pressure and PbtO2 group had catheter dysfunction (p=0.011). Six patients (4%) in the intracranial pressure and PbtO2 group had an intracrebral haematoma related to the catheter, compared with none in the intracranial pressure only group (p=0.030). No significant difference in deaths was found between the two groups at 12 months after injury. At 12 months, 33 deaths had occurred in the intracranial pressure group: 25 (76%) were attributable to the brain trauma, six (18%) were end-of-life decisions, and two (6%) due to sepsis. 34 deaths had occured in the intracranial pressure and PbtO2 group at 12 months: 25 (74%) were attributable to the brain trauma, six (18%) were end-of-life decisions, one (3%) due to pulmonary embolism, one (3%) due to haemorrhagic shock, and one (3%) due to cardiac arrest. INTERPRETATION: After severe non-penetrating traumatic brain injury, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with poor neurological outcome at 6 months. Technical failures related to intracerebral catheter and intracerebral haematoma were more frequent in the intracranial pressure and PbtO2 group. Further research is needed to assess whether a targeted approach to multimodal brain monitoring could be useful in subgroups of patients with severe traumatic brain injury-eg, those with high intracranial pressure on admission. FUNDING: The French National Program for Clinical Research, La Fondation des Gueules Cassées, and Integra Lifesciences.

Corticosteroid treatment for refractory intracranial hypertension: a rescue therapy in patients with severe traumatic brain injury with contusional lesions-a feedback.

INTRODUCTION: Refractory intracranial hypertension (rICH) is a severe complication among patients with severe traumatic brain injury (sTBI). Medical treatment may be insufficient, and in some cases, the only viable treatment option is decompressive hemicraniectomy. The assessment of a corticosteroid therapy against vasogenic edema secondary to severe brain injuries seems interesting to prevent this surgery in sTBI patients with rICH caused by contusional areas. METHODS: This is a monocentric retrospective observational study including all consecutive sTBI patients with contusion injuries and a rICH requiring cerebrospinal fluid drainage with external ventricular drainage between November 2013 and January 2018. Patient inclusion criterium was a therapeutic index load (TIL; an indirect measure of TBI severity) > 7. Intracranial pressure (ICP) and TIL were assessed before and 48 h after corticosteroid therapy (CTC). Then, we divided the population into two groups according to the evolution of the TIL: responders and non-responders to corticosteroid therapy. RESULTS: During the study period, 512 patients were hospitalized for sTBI, and among them, 44 (8.6%) with rICH were included. They received 240 mg per day [120 mg, 240 mg] of Solu-Medrol for 2 days [1; 3], 3 days after the sTBI. The average ICP in patients with rICH before the CTC bolus was 21 mmHg [19; 23]. After the CTC bolus, the ICP fell significantly to less than 15 mmHg (p < 0.0001) for at least 7 days. The TIL decreased significantly the day after the CTC bolus and until day 2. Among these 44 patients, 68% were included in the responder group (n = 30). DISCUSSION: Short and systemic corticosteroid therapy in patients with refractory intracranial hypertension secondary to severe traumatic brain injury seems to be a potentially useful and efficient treatment for lowering intracranial pressure and decreasing the need for more invasive surgeries.

Long-Term Cangrelor Administration in Neurology Intensive Care: A Case Series.

Cangrelor is a P2Y12 inhibitor antiplatelet agent, with a rapid onset and offset. The available literature only reviews short-term administration over a few hours. We describe 5 patients who received cangrelor for >1 month in a neurosurgical intensive care unit due to a very high likelihood of requiring emergency revision surgery. Despite multiple therapeutic interruptions for surgical procedures, no hemorrhagic events occurred, and there was only one transient ischemic event, which occurred during transition from cangrelor to ticagrelor. Cangrelor can be a therapeutic option for patients with a high likelihood of requiring revision neurosurgery after intracranial stenting.

Preliminary Experience with Cangrelor for Endovascular Treatment of Challenging Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Cangrelor is a P2Y12 inhibitor that presents the advantage of having a short half-life. Its use may be helpful in the management of antiplatelet therapy for patients with intracranial aneurysms treated by stent-assisted coiling or flow-diverter stents. The purpose of this study was to report early experiences in using cangrelor for such indications. MATERIAL AND METHODS: From October 2017 to November 2018, 7 consecutive patients (5 females, 2 males, mean age = 56 years) were managed with cangrelor as antiplatelet therapy, combined with aspirin, for stent-assisted coiling embolization and flow-diverter embolization of challenging intracranial aneurysms. Anti-aggregation protocols, including cangrelor, were systematically recorded. Treatment-related complications (minor/major hemorrhagic complications, ischemic complications) as well as clinical and angiographic outcomes (evaluated at 8.7 ± 4.2 and 8.75 ± 10 months, respectively) were retrospectively analyzed. RESULTS: Of the aneurysms 71.4% (5 out of 7) were ruptured and treated in the acute phase. In one case cangrelor was used as an alternative to clopidogrel in an asymptomatic hemorrhagic complication after stent-assisted coiling for better control of a possible worsening of the intracranial bleeding. Of the patients, 1 (14%) with a complex ruptured MCA aneurysm treated with a flow-diverter stent experienced a severe intracranial hemorrhage, which occurred after switching the cangrelor to ticagrelor and eventually led to death. No hemorrhagic complications under cangrelor were recorded for the six remaining patients. No mRS worsening was observed at discharge, except for the patient who died and six out of the seven patients had a mRS ≤2 at follow-up. CONCLUSION: Cangrelor is a new antiplatelet therapy with a P2Y12 inhibiting effect, with a rapid onset and offset of action, owing to its short half-life. This cases series presents a pilot experience with promising results in terms of antiplatelet management for challenging intracranial aneurysms treated by stent assisted coiling or flow-diverter stents.

Management of severe traumatic brain injury (first 24hours).

The latest French Guidelines for the management in the first 24hours of patients with severe traumatic brain injury (TBI) were published in 1998. Due to recent changes (intracerebral monitoring, cerebral perfusion pressure management, treatment of raised intracranial pressure), an update was required. Our objective has been to specify the significant developments since 1998. These guidelines were conducted by a group of experts for the French Society of Anesthesia and Intensive Care Medicine (Société francaise d'anesthésie et de réanimation [SFAR]) in partnership with the Association de neuro-anesthésie-réanimation de langue française (ANARLF), The French Society of Emergency Medicine (Société française de médecine d'urgence (SFMU), the Société française de neurochirurgie (SFN), the Groupe francophone de réanimation et d'urgences pédiatriques (GFRUP) and the Association des anesthésistes-réanimateurs pédiatriques d'expression française (ADARPEF). The method used to elaborate these guidelines was the Grade® method. After two Delphi rounds, 32 recommendations were formally developed by the experts focusing on the evaluation the initial severity of traumatic brain injury, the modalities of prehospital management, imaging strategies, indications for neurosurgical interventions, sedation and analgesia, indications and modalities of cerebral monitoring, medical management of raised intracranial pressure, management of multiple trauma with severe traumatic brain injury, detection and prevention of post-traumatic epilepsia, biological homeostasis (osmolarity, glycaemia, adrenal axis) and paediatric specificities.

Computed tomography-estimated specific gravity at hospital admission predicts 6-month outcome in mild-to-moderate traumatic brain injury patients admitted to the intensive care unit.

BACKGROUND: It is clear that patients with a severe traumatic brain injury (TBI) develop secondary, potentially lethal neurological deterioration. However, it is difficult to predict which patients with mild-to-moderate TBI (MM-TBI), even after intensive care unit (ICU) admission, will experience poor outcome at 6 months. Standard computed tomography (CT) imaging scans provide information that can be used to estimate specific gravity (eSG). We have previously demonstrated that higher eSG measurements in the standard CT reading were associated with poor outcomes after severe TBI. The aim of this study was to determine whether eSG of the intracranial content predicts 6-month outcome in MM-TBI. METHODS: We analyzed admission clinical and CT scan data (including eSG) of 66 patients with MM-TBI subsequently admitted to our neurosurgical ICU. Primary outcome was defined as a Glasgow Outcome Scale score of 1 to 3 after 6 months. Discriminating power (area under the receiver operating characteristic curve [ROC-AUC], 95% confidence interval) of eSG to predict 6-month poor outcome was calculated. The correlation of eSG with the main ICU characteristics was then compared. RESULTS: Univariate and stepwise multivariate analyses showed an independent association between eSG and 6-month poor outcome (P = 0.001). ROC-AUC of eSG for the prediction of 6-month outcomes was 0.87 (confidence interval: 0.77-0.96). Admission eSG values were correlated with the main ICU characteristics, specifically 14-day mortality (P = 0.004), length of mechanical ventilation (P = 0.01), length of ICU stay (P = 0.045), and ICU procedures such as intracranial pressure monitoring (P < 0.001). CONCLUSIONS: In this MM-TBI cohort admitted to the ICU, eSG of routine CT scans was correlated with mortality, ICU severity, and predicted 6-month poor outcome. An external validation with studies that include the spectrum of TBI severities is warranted to confirm our results.

Admission risk factors for cerebral vasospasm in ruptured brain arteriovenous malformations: an observational study.

INTRODUCTION: Cerebral vasospasm is a well-documented complication of aneurismal subarachnoid hemorrhage but has not been extensively studied in brain arteriovenous malformations (BAVMs). Here, our purpose was to identify risk factors for cerebral vasospasm after BAVM rupture in patients requiring intensive care unit (ICU) admission. METHODS: Patients admitted to our ICU from January 2003 to May 2010 for BAVM rupture were included in this observational study. Clinical, laboratory and radiological features from admission to ICU discharge were recorded. The primary endpoint was cerebral vasospasm by transcranial Doppler (TCD-VS) or cerebral infarction (CI) associated with vasospasm. Secondary endpoints included the Glasgow Outcome Scale (GOS) at ICU discharge. RESULTS: Of 2,734 patients admitted to our ICU during the study period, 72 (2.6%) with ruptured BAVM were included. TCD-VS occurred in 12 (17%) and CI in 6 (8%) patients. All patients with CI had a previous diagnosis of TCD-VS. A Glasgow Coma Scale score <8 was a risk factor for both TCD-VS (relative risk (RR), 4.7; 95% confidence interval (95% CI), 1.6 to 26) and CI (RR, 7.8; 95% CI, 0.1 to 63). Independent risk factors for TCD-VS by multivariate analysis were lower Glasgow Coma Scale score (odds ratio (OR) per unit decrease, 1.38; 95% CI, 1.13 to 1.80), female gender (OR, 4.86; 95% CI, 1.09 to 25.85), and younger age (OR per decade decrease, 1.39; 95% CI, 1.05 to 1.82). The risk of a poor outcome (GOS <4) at ICU discharge was non-significantly increased in the patients with TCD-VS (RR, 4.9; 95% CI, 0.7 to 35; P = 0.09). All six patients with CI had poor outcomes. CONCLUSIONS: This is the first cohort study describing the incidence and risk factors for cerebral vasospasm after BAVM rupture. Larger studies are needed to investigate the significance of TCD-vasospasm and CI in these patients.

Experience of diffusion tensor imaging and 1H spectroscopy for outcome prediction in severe traumatic brain injury: Preliminary results.

OBJECTIVE: The objective of the study is to test whether multimodal magnetic resonance imaging can provide a reliable outcome prediction of the clinical status, focusing on consciousness at 1 year after severe traumatic brain injury (TBI). DESIGN: Single center prospective cohort with consecutive inclusions. SETTING: Critical Care Neurosurgical Unit of a university hospital. PATIENTS: Forty-three TBI patients not responding to simple orders after sedation cessation and 15 healthy controls. INTERVENTIONS: A multimodal magnetic resonance imaging combining morphologic sequences, diffusion tensor imaging (DTI), and H proton magnetic resonance spectroscopy (MRS) was performed 24 +/- 11 days after severe TBI. The ability of DTI and MRS to predict 1-year outcome was assessed by linear discriminant analysis (LDA). Robustness of the classification was tested using a bootstrap procedure. MEASUREMENTS AND MAIN RESULTS: Fractional anisotropy (FA) was computed as the mean of values at discrete brain sites in the infratentorial and supratentorial regions. The N-acetyl aspartate/creatine (NAA/Cr) ratio was measured in the thalamus, lenticular nucleus, insular cortex, occipital periventricular white matter, and pons. After 1 year, 19 (44%) patients had unfavorable outcomes (death, persistent vegetative state, or minimally conscious state) and 24 (56%) favorable outcomes (normal consciousness with or without functional impairments). Analysis of variance was performed to compare FA and NAA/Cr in the two outcome groups and controls. FA and MRS findings showed highly significant differences between the outcome groups, with significant variables by LDA being supratentorial FA, NAA/Cr (pons), NAA/Cr (thalamus), NAA/Cr (insula), and infratentorial FA. LDA of combined FA and MRS data clearly separated the unfavorable outcome, favorable outcome, and control groups, with no overlap. Unfavorable outcome was predicted with up to 86% sensitivity and 97% specificity; these values were better than those obtained with DTI or MRS alone. CONCLUSION: FA and NAA/Cr hold potential as quantitative outcome-prediction tools at the subacute phase of TBI.

S100B as an additional prognostic marker in subarachnoid aneurysmal hemorrhage.

OBJECTIVES: Studies of new neuroprotective approaches in patients with subarachnoid aneurysmal hemorrhage and better family information would benefit from the development of laboratory markers of brain ischemia. The goal of this study was to evaluate mean 15-day S100B for predicting outcomes after subarachnoid aneurysmal hemorrhage. DESIGN: Single center prospective cohort with consecutive inclusions. SETTING: Anesthesiology and Critical Care Neurosurgical Unit of a university hospital. PATIENTS: One hundred nine patients admitted within 48 hrs after subarachnoid aneurysmal hemorrhage onset and treated by surgical clipping or coiling within 48 hrs following admission. INTERVENTIONS: We recorded initial World Federation of Neurologic Surgeons and Fisher grades; comorbidities; initial severity; aneurysm location; presence of acute hydrocephalus; presence of intraventricular hemorrhage; initial seizures and neurogenic lung edema; initial troponin values; treatment of aneurysm; and occurrence of vasospasm. MEASUREMENTS AND MAIN RESULTS: S100B was assayed daily over the first 15 days. Glasgow Outcome Scores were recorded at intensive care unit discharge and after 6 and 12 months. The main outcome criterion was the 12-month Glasgow Outcome Scale score dichotomized as poor (Glasgow Outcome Scale 1-3) or good (Glasgow Outcome Scale 4-5). Seventy percent of patients had good 12-month outcome. Poor outcome was associated with higher initial World Federation of Neurologic Surgeons and Fisher scores, neurogenic lung edema, high mean 15-day S100B but not initial, troponin initial value, intraventricular hemorrhage, angiographically documented vasospasm, all in an univariate manner. After multivariate analysis, only mean 15-day S100B value significantly predicted outcome (p < 0.0005). The best cutoff for the mean 15-day S100B value was 0.23 microg/L (specificity 0.90, 95% confidence interval [CI] 0.81-0.95; sensitivity 0.91, 95% CI 0.75-0.98; area under the curve 0.98, 95% CI 0.87-0.99). CONCLUSION: S100B elevation over the first 15 days after subarachnoid aneurysmal hemorrhage is associated with poor outcome after subarachnoid aneurysmal hemorrhage. This result supports the use of S100B as a surrogate marker for brain ischemia in patients with subarachnoid aneurysmal hemorrhage.

Treatment of intracranial hypertension.

PURPOSE OF REVIEW: The review provides key points and recent advances regarding the treatments of intracranial hypertension as a consequence of traumatic brain injury. The review is based on the pathophysiology of brain edema and draws on the current literature as well as clinical bedside experience. RECENT FINDINGS: The review will cite baseline literature and discuss emerging data on cerebral perfusion pressure, sedation, hypothermia, osmotherapy and albumin as treatments of intracranial hypertension in traumatic brain-injured patients. SUMMARY: One of the key issues is to consider that traumatic brain injury is more likely a syndrome than a disease. In particular, the presence or absence of a high contusional volume could influence the treatments to be implemented. The use of osmotherapy and/or high cerebral perfusion pressure should be restricted to patients without major contusions. Some physiopathological, experimental and clinical data, however, show that corticosteroids and albumin--therapies that have been proven deleterious if administered systematically--are worth reconsidering for this subgroup of patients. The current Pitié-Salpêtrière algorithm, where treatments are stratified according to their potential side effects, will be added at the end of the review as an example of an integrated strategy.

Effect of loxapine on electrical brain activity, intracranial pressure, and middle cerebral artery flow velocity in traumatic brain-injured patients.

INTRODUCTION: Delirium is a frequent complication of traumatic brain injury, especially during the weaning period. Antipsychotic drugs are often used in this case. Loxapine is a tricyclic antipsychotic drug with sedating properties. The effects of intravenous loxapine on EEG as well as on systemic and cerebral hemodynamics after traumatic brain injury are unknown. METHODS: Seven sedated and mechanically ventilated traumatic brain injured patients were studied 11 +/- 5 days after trauma. They were on continuous perfusion of sufentanil and midazolam. Left and right spectral edge frequency (SEFl, SEFr) of continuous EEG recording, intracranial pressure (ICP), mean flow velocity of the middle cerebral artery (MFV(MCA)) and mean arterial pressure (MAP) were simultaneously recorded and digitalized before and after loxapine infusion (10 mg in 10 min of continuous infusion). RESULTS: Loxapine induced no significant change on MAP, MFV. On the contrary, it decreased ICP and both SEFl, SEFr. ETCO(2 )and the dose of vasopressors were not altered during the study period. CONCLUSION: 10 mg of loxapine administered intravenously over 10 min decreased brain electrical activity. There is a concomitant reduction in ICP without any significant change in cerebral blood flow velocity. The use of intravenous loxapine to control agitation is not accompanied by deleterious hemodynamic or systemic effects in ICU's traumatic brain injured patients.

Predictors of 1-year outcome after coiling for poor-grade subarachnoid aneurysmal hemorrhage.

OBJECTIVE: To describe features in patients admitted to the intensive care unit (ICU) for poor-grade aneurysmal subarachnoid hemorrhage (SAH) and to identify predictors of 12-month outcome. METHODS: We conducted a controlled observational study of 51 consecutive patients treated with endovascular coiling within 96 h of rupture for poor-grade aneurysmal SAH (20 men and 31 women, age 54 +/- 12 years). We recorded co-morbidities; initial severity; aneurysm location; occurrence of acute hydrocephalus, initial seizures, and/or neurogenic lung edema; troponin values, Fisher grade; computed tomography (CT) findings; treatment intensity; and occurrence of vasospasm. The brain injury marker S100B was assayed daily over the first 8 days. Glasgow Outcome Scores (GOS) were recorded at ICU discharge, at 6 and 12 months. The main outcome criterion was the 1-year GOS score, which we used to classify patients as having a poor outcome (GOS 1-3) or a good outcome (GOS 4-5). RESULTS: Overall, clinical status after 1 year was very good (GOS 5) in 41% of patients and good (GOS 4) in 16%. Neither baseline characteristics nor interventions differed significantly between patients with good outcome (GOS 4-5) and those with poor outcome (GOS 1-3). Persistent intracranial pressure elevation and higher mean 8-day S100B value significantly and independently predicted the 1-year GOS outcome (P = 0.008 and P = 0.001, respectively). CONCLUSIONS: Patients in poor clinical condition after SAH have more than a 50:50 chance of a favorable outcome after 1 year. High mean 8-day S100B value and persistent intracranial hypertension predict a poor outcome (GOS 1-3) after 1 year.

[Management of severe traumatic brain injury]. / Réanimation des patients traumatisés crâniens graves.

Severe brain injuries, most often occurring in young subjects, are a major source of lost work years. These injuries are medical and surgical emergencies. Prehospital management of severe brain injuries requires intubation and mechanical ventilation aimed at normal arterial carbon dioxide pressure. Signs of transtentorial herniation: Uni- or bilateral mydriasis requires immediate perfusion of 20% mannitol or hypertonic sodium chloride. Neurological disorders after head injury justify emergency cerebral computed tomography. The presence of a mass syndrome or signs of transtentorial herniation are in principle indications for surgery. Specialized hospital management is essential. In the case of refractory intracranial hypertension, the cerebral perfusion pressure and osmotherapy should be adapted to the volume of the cerebral contusion. The use of deep hypothermia and barbiturates should be minimized as much as possible. Magnetic resonance imaging makes it possible to identify the cerebral lesions.

Gabapentin-induced coma: A MR-spectrometry analysis.

As for the majority of antiepileptic drugs, encephalopathy, manifested by transient somnolence, mood and motor disorders, is a possible side-effect. To our knowledge, there is little information about gabapentin-induced coma. We report a third case of gabapentin-induced coma where magnetic resonance-spectrometry was performed in diagnosis assessment.

Intra-arterial nimodipine for the treatment of symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage: preliminary results.

BACKGROUND AND PURPOSE: Cerebral vasospasm remains a major problem in patients recovering from aneurysmal subarachnoid hemorrhage despite advances in medical, surgical, and endovascular care. Our purpose was to assess the efficacy of intra-arterial nimodipine, a calcium-channel blocker acting mainly on cerebral vessels, in preventing delayed neurologic deficits in patients with symptomatic vasospasm. METHODS: Clinical charts of 25 consecutively treated patients were retrospectively reviewed. A multifactorial decision tree was used to determine the indication for angiography and subsequent endovascular treatment. Nimodipine was infused intra-arterially via a diagnostic catheter in the internal carotid artery or vertebral artery at a rate of 0.1 mg/min. Angiographic vasospasm before endovascular treatment, immediate vessel caliber modifications, and short- and long-term clinical efficacy of the procedure were assessed. RESULTS: Thirty procedures were performed in 25 patients. Clinical improvement was observed in 19 (76%), 16 of whom improved after the first endovascular procedure, two after the second intra-arterial treatment, and one after the third. Of these 19 patients, only 12 (63%) had notable vascular dilatation at postprocedural angiography. Dilatation of infused vessels occurred in only 13 (43%) of 30 procedures. After follow-up of 3-6 months, 18 (72%) of 25 patients had a favorable outcome (Glasgow outcome scale score of 1-2 and modified Rankin scale score of 0-2). No complications were observed. CONCLUSION: Intra-arterial nimodipine is effective and safe for the treatment of symptomatic vasospasm after subarachnoid hemorrhage. Further prospective randomized studies of cerebral blood flow are needed to confirm these results.