Summary Background Clazosentan, an endothelin receptor antagonist, significantly and dose-dependently reduced angiographic vasospasm after aneurysmal subarachnoid haemorrhage (aSAH). We investigated ...whether clazosentan reduced vasospasm-related morbidity and all-cause mortality. Methods In this randomised, double-blind, placebo-controlled, phase 3 study, we randomly assigned patients with aSAH secured by surgical clipping to clazosentan (5 mg/h, n=768) or placebo (n=389) for up to 14 days (27 countries, 102 sites, inpatient and outpatient settings) using an interactive web response system. The primary composite endpoint (week 6) included all-cause mortality, vasospasm-related new cerebral infarcts, delayed ischaemic neurological deficit due to vasospasm, and rescue therapy for vasospasm. The main secondary endpoint was dichotomised extended Glasgow outcome scale (GOSE; week 12). This trial is registered with ClinicalTrials.gov , number NCT00558311. Findings In the all-treated dataset, the primary endpoint was met in 161 (21%) of 764 clazosentan-treated patients and 97 (25%) of 383 placebo-treated patients (relative risk reduction 17%, 95% CI −4 to 33; p=0·10). Poor functional outcome (GOSE score ≤4) occurred in 224 (29%) clazosentan-treated patients and 95 (25%) placebo-treated patients (−18%, −45 to 4; p=0·10). Lung complications, anaemia, and hypotension were more common with clazosentan. Mortality (week 12) was 6% in both groups. Interpretation Clazosentan at 5 mg/h had no significant effect on mortality and vasospasm-related morbidity or functional outcome. Further investigation of patients undergoing endovascular coiling of ruptured aneurysms is needed to fully understand the potential usefulness of clazosentan in patients with aSAH. Funding Actelion Pharmaceuticals.
Wider use of oral anticoagulants has led to an increasing frequency of warfarin-related intracerebral hemorrhage (ICH). The high early mortality of approximately 50% has remained stable in recent ...decades. In contrast to spontaneous ICH, the duration of bleeding is 12 to 24 hours in many patients, offering a longer opportunity for intervention. Treatment varies widely, and optimal therapy has yet to be defined. An OVID search was conducted from January 1996 to January 2006, combining the terms warfarin or anticoagulation with intracranial hemorrhage or intracerebral hemorrhage. Seven experts on clinical stroke, neurologic intensive care, and hematology were provided with the available information and were asked to independently address 3 clinical scenarios about acute reversal and resumption of anticoagulation in the setting of warfarin-associated ICH. No randomized trials assessing clinical outcomes were found on management of warfarin-associated ICH. All experts agreed that anticoagulation should be urgently reversed, but how to achieve it varied from use of prothrombin complex concentrates only (3 experts) to recombinant factor VIIa only (2 experts) to recombinant factor VIIa along with fresh frozen plasma (1 expert) and prothrombin complex concentrates or fresh frozen plasma (1 expert). All experts favored resumption of warfarin therapy within 3 to 10 days of ICH in stable patients in whom subsequent anticoagulation is mandatory. No general agreement occurred regarding subsequent anticoagulation of patients with atrial fibrillation who survived warfarin-associated ICH. For warfarin-associated ICH, discontinuing warfarin therapy with administration of vitamin K does not reverse the hemostatic defect for many hours and is inadequate. Reasonable management based on expert opinion includes a wide range of additional measures to reverse anticoagulation in the absence of solid evidence.
Background Limited data are available on the care of patients with acute severe hypertension requiring hospitalization. We characterized contemporary practice patterns and outcomes for this ...population. Methods STAT is a 25-institution, US registry of consecutive patients with acute severe hypertension (>180 mm Hg systolic and/or >110 mm Hg diastolic; >140 and/or >90 for subarachnoid hemorrhage) treated with intravenous therapy in a critical care setting. Results One thousand five hundred eighty-eight patients were enrolled (January 2007 to April 2008). Median age was 58 years (interquartile range 49-70 years), 779 (49%) were women, and 892 (56%) were African American; 27% (n = 425) had a prior admission for acute hypertension and 486 (31%) had chronic kidney disease. Median qualifying blood pressure (BP) was 200 (186, 220) systolic and 110 (93, 123) mm Hg diastolic. Initial intravenous antihypertensive therapies used to control BP varied, with 1,009 (64%) patients requiring multiple drugs. Median time to achieve a systolic BP <160 mm Hg (<140 mm Hg for subarachnoid hemorrhage) was 4.0 (0.8, 12) hours; 893 (60%) had reelevation to >180 (>140 for subarachnoid hemorrhage) after initial control; and 63 (4.0%) developed iatrogenic hypotension. Hospital mortality was 6.9% (n = 109) with an aggregate 90-day mortality rate of 11% (174/1,588); 59% (n = 943) had acute/worsening end-organ dysfunction during hospitalization. The 90-day readmission rate was 37% (523/1,415), of which one quarter (132/523) was due to recurrent acute severe hypertension. Conclusion This study highlights heterogeneity in care, BP control, and outcomes of patients hospitalized with acute severe hypertension.
Although urgent surgical hematoma evacuation is necessary for most patients with subdural hematoma (SDH), well-orchestrated, evidenced-based, multidisciplinary, postoperative critical care is ...essential to achieve the best possible outcome. Acute SDH complicates approximately 11% of mild to moderate traumatic brain injuries (TBIs) that require hospitalization, and approximately 20% of severe TBIs. Acute SDH usually is related to a clear traumatic event, but in some cases can occur spontaneously. Management of SDH in the setting of TBI typically conforms to the Advanced Trauma Life Support protocol with airway taking priority, and management breathing and circulation occurring in parallel rather than sequence.
Highlights • Intraventricular Nicardipine injection may be considered in patients with refractory vasospasm after subarachnoid hemorrhage. • Intraventricular Nicardipine transiently increases ...intracranial pressure. • Doppler study suggests that intraventricular nicardipine dilates resistance vessels.
The prevention and management of medical complications are important for improving outcomes after subarachnoid hemorrhage (SAH). Fever, anemia requiring transfusion, hyperglycemia, hyponatremia, ...pneumonia, hypertension, and neurogenic cardiopulmonary dysfunction occur frequently after SAH. There is increasing evidence that acute hypoxia and extremes of blood pressure can exacerbate brain injury during the acute phase of bleeding. There are promising strategies to minimize these complications. Randomized controlled trials are needed to evaluate the risks and benefits of these and other medical management strategies after SAH.
Multimodality monitoring of cerebral physiology encompasses the application of different monitoring techniques and integration of several measured physiologic and biochemical variables into ...assessment of brain metabolism, structure, perfusion, and oxygenation status. Novel monitoring techniques include transcranial Doppler ultrasonography, neuroimaging, intracranial pressure, cerebral perfusion, and cerebral blood flow monitors, brain tissue oxygen tension monitoring, microdialysis, evoked potentials, and continuous electroencephalogram. Multimodality monitoring enables immediate detection and prevention of acute neurologic injury as well as appropriate intervention based on patients' individual disease states in the neurocritical care unit. Real-time analysis of cerebral physiologic, metabolic, and cardiovascular parameters simultaneously has broadened knowledge about complex brain pathophysiology and cerebral hemodynamics. Integration of this information allows for more precise diagnosis and optimization of management of patients with brain injury.
This article addresses current critical care management strategies for patients with aneurysmal subarachnoid hemorrhage (SAH) and ischemic stroke. The chronology of typical SAH care is discussed, ...with an emphasis on the treatment of poor-grade SAH and on current monitoring techniques. Acute diagnosis and treatment of the life-threatening ischemic strokes is reviewed, emphasizing the care of patients with acute basilar artery occlusion and the malignant middle cerebral artery syndrome. Up-to-date estimates of the long-term outcomes of these syndromes are reviewed.
Abstract Background context Spinal deformity surgery in elderly patients is associated with an increased risk of implant loosening due to failure at the screw-bone interface. Several techniques can ...be used to increase the screw anchorage characteristics. Cement-augmented screw fixation was shown to be the most efficient method; however, this technique is associated with a risk of complications related to vertebral cement deposition and leakage. Hence, there is a need to further elaborate the alternative screw augmenting techniques to reduce the indications for bone cement. Purpose To analyze surgical alternatives to cement augmentation, the present study sought to quantify the impact of a distal expansion mechanism added to a standard pedicle screw on an axial pullout resistance. Study design A biomechanical laboratory study on the uniaxial pullout resistance of a standard pedicle screw versus a customized pedicle screw with a distal expansion mechanism. Methods A total of 40 vertebrae from seven fresh-frozen human specimens were harvested and subjected to a computed tomography scanning and an analysis of the bone mineral density (BMD). The vertebrae were instrumented with a standard 6.0-mm pedicle screw and a modified 6.0-mm pedicle screw with a distal expansion mechanism added. The actual working length of both screws inside the vertebrae was identical. The distal expansion mechanism made up one-fifth of the shaft length. The accuracy of the screw insertion was assessed using biplanar radiographs and by inspection. Analysis of resistance to pullout was performed by a coaxial alignment of the pedicle screws and attachment to an electromechanical testing machine. The pullout rate was 5 mm/min, and the load-displacement curve was recorded until the force of the pullout resistance peaked. The peak load-to-failure was measured in Newtons and reported as the ultimate failure load. With each test, the mode of failure was noted and analyzed descriptively. Results A total of 17 vertebrae with matched pairs of standard and expansion pedicle screws were eligible for the final statistical analysis. The BMD of the vertebrae tested was 0.67±0.19 g/cm³. The screw length was 50 mm, and the actual working length of both screws was 40.3±4.2 mm. The ultimate failure load of the standard screw was 773.8±529.4 N and that of the expansion screw was 910.3±488.3 N. Statistical analysis revealed a strong trend toward an increased failure load with the expansion screw (p=.06). The mean increase of the ultimate failure load was 136.5±350.4 N. Abrupt vertebral fracture at the vertebral body-pedicle junction and the pedicle occurred seven times with the expansion screw and only five times with the standard screw (p=.16). Conclusions Our study indicates that adding a distal expansion mechanism to a standard pedicle screw increases the failure load by one-fifth. Modern expansion screws might offer an intermediate solution for the augmentation of screw-rod constructs in osteoporotic bone while reducing the need for cement-augmented screws and avoiding the related risks.
Abstract Background Transient loss of consciousness (LOC) is one of the most common presentations of aneurysmal subarachnoid hemorrhage (SAH) and may be an indicator of early brain injury. The aim of ...the current study was to examine the association of LOC to functional outcomes in patients with good-grade SAH. Methods We searched the Subarachnoid Hemorrhage International Trialists Repository for patients that presented with LOC at ictus of SAH. A propensity score analysis was performed on good-grade patients (defined as World Federation of Neurosurgical Societies grades 1-3) to balance selected covariates between those with and without LOC. Primary outcome was Glasgow Outcome Score (GOS) at 3 months (with poor outcome defined as GOS of 1-3). Secondary outcomes were delayed cerebral ischemia (DCI), rebleed, length of hospital stay, and time to death. Results A propensity score-matching algorithm identified 337 patients (168 with LOC at ictus, and 168 without). The proportion of patients with poor functional outcome at 3-months was significantly higher in those who had LOC at ictus compared to the matched cohort without LOC (30% vs. 19%; P = 0.02). There was a non-significant trend toward higher mortality in patients with LOC (19% vs. 13%; P = 0.14). There were no differences in the secondary outcomes. Conclusions LOC of at ictus of SAH is associated with higher rate of unfavorable functional outcomes but not mortality, DCI or rebleed in good-grade SAH patients. Future studies should further investigate the putative mechanisms by which LOC mediates early brain injury in SAH.
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