Rivaroxaban and intracranial haemorrhage after mild traumatic brain injury: A dangerous combination?

OBJECTIVES: Despite several advantages of the novel anticoagulant rivaroxaban compared with vitamin K antagonists (VKA), its lack of specific antidotes to reverse anticoagulant effects may increase the risk profile of patients with bleeding complications. The purpose of this study was to analyze the effects of pre-injury treatment with rivaroxaban on patients with mild traumatic brain injury (TBI) and traumatic intracranial haemorrhage (tICH). METHODS: A total of 70 patients with tICH after mild TBI were included in this retrospective analysis and were categorized into three groups: group A (no antithrombotics n=37), group B (antiplatelet medication n=22, VKA=5), and group C (rivaroxaban n=6). Medical charts were reviewed for baseline characteristics, laboratory values, intracranial haemorrhage, repeated computed tomography (CT) scans, re-haemorrhage, Glasgow Coma Scale (GCS) scores and in-hospital mortality. RESULTS: No significant differences were observed for baseline characteristics. The rate of re-haemorrhage was significantly higher in group C (50%) than in group A (11%) (p<0.05). Two patients died and both had been treated with rivaroxaban which resulted in a significantly higher mortality rate of 33% in group C compared with groups A (0%) and B (0%). No significant differences were observed for GCS at discharge and length of hospital stay between survivors of groups A-C. CONCLUSIONS: Despite major limitations of retrospective design and small patient numbers, our results suggest that rivaroxaban may exacerbate intracranial haemorrhage in patients with mild TBI. Further studies are needed to characterize the risk profile of this drug in patients with tICH.

Brain tissue oxygen monitoring and hyperoxic treatment in patients with traumatic brain injury.

Cerebral ischemia is a well-recognized contributor to high morbidity and mortality after traumatic brain injury (TBI). Standard of care treatment aims to maintain a sufficient oxygen supply to the brain by avoiding increased intracranial pressure (ICP) and ensuring a sufficient cerebral perfusion pressure (CPP). Devices allowing direct assessment of brain tissue oxygenation have showed promising results in clinical studies, and their use was implemented in the Brain Trauma Foundation Guidelines for the treatment of TBI patients in 2007. Results of several studies suggest that a brain tissue oxygen-directed therapy guided by these monitors may contribute to reduced mortality and improved outcome of TBI patients. Whether increasing the oxygen supply to supraphysiological levels has beneficial or detrimental effects on TBI patients has been a matter of debate for decades. The results of trials of hyperbaric oxygenation (HBO) have failed to show a benefit, but renewed interest in normobaric hyperoxia (NBO) in the treatment of TBI patients has emerged in recent years. With the increased availability of advanced neuromonitoring devices such as brain tissue oxygen monitors, it was shown that some patients might benefit from this therapeutic approach. In this article, we review the pathophysiological rationale and technical modalities of brain tissue oxygen monitors, as well as its use in studies of brain tissue oxygen-directed therapy. Furthermore, we analyze hyperoxia as a treatment option in TBI patients, summarize the results of clinical trials, and give insights into the recent findings of hyperoxic effects on cerebral metabolism after TBI.

Detecting and treating microvascular ischemia after subarachnoid hemorrhage.

PURPOSE OF REVIEW: To provide an overview of the current management of cerebral vasospasm following subarachnoid hemorrhage, emphasizing the detection and treatment of delayed ischemia. RECENT FINDINGS: Sensitive and specific monitoring methods are necessary to register the onset of cerebral vasospasm early to prevent long-term morbidity and mortality. Therefore, various techniques to measure cerebral perfusion and/or surrogate parameters have been developed. Prophylaxis with calcium antagonists such as nimodipine is administered for neuroprotection. Resolution of ongoing cerebral vasospasm can be achieved by either dilating constricted vessels or optimizing hemodynamics. Therapeutic treatment with hypertension, hypervolemia and hemodilution (HHH) has a direct influence on cerebral vasospasm, ischemic sequelae and outcome, while prophylactic HHH leads to excess complications. Other treatments, for example endothelin antagonists, statins or magnesium salts, used to prevent or treat cerebral vasospasm, are being tested. Endovascular treatment options can be used for therapy-refractory cerebral vasospasm, but they carry procedure-related risks and may be short-acting. SUMMARY: Diagnosis of microvascular ischemia following subarachnoid hemorrhage involves clinical observation, non-invasive determination of cerebral hemodynamic variables, autoregulation studies and invasive online monitoring of cerebral oxygenation and metabolism. Nimodipine is administered prophylactically, while HHH is initiated therapeutically. New causal therapies are being evaluated.

Wavelet entropy analysis of event-related potentials indicates modality-independent theta dominance.

Sensory/cognitive stimulation elicits multiple electroencephalogram (EEG)-oscillations that may be partly or fully overlapping over the time axis. To evaluate co-existent multi-frequency oscillations, EEG responses to unimodal (auditory or visual) and bimodal (combined auditory and visual) stimuli were analyzed by applying a new method called wavelet entropy (WE). The method is based on the wavelet transform (WT) and quantifies entropy of short segments of the event-related brain potentials (ERPs). For each modality, a significant transient decrease of WE emerged in the post-stimulus EEG epoch indicating a highly-ordered state in the ERP. WE minimum was always determined by a prominent dominance of theta (4-8 Hz) ERP components over other frequency bands. Event-related 'transition to order' was most pronounced and stable at anterior electrodes, and after bimodal stimulation. Being consistently observed across different modalities, a transient theta-dominated state may reflect a processing stage that is obligatory for stimulus evaluation, during which interfering activations from other frequency networks are minimized.