The neurocritical care research network: NCRN.

Neurocritical care diseases carry a high morbidity and mortality. Therapeutic and technological advances in neurocritical care have greatly improved the outcome of a variety of life-threatening disorders including traumatic brain injury, acute ischemic stroke, intracerebral and subarachnoid hemorrhage, and anoxic injury following cardiac arrest. These advances have stemmed from a better understanding of the physiology of neurocritical care illnesses, improved neuromonitoring techniques, and the introduction of more efficacious treatments. Despite all the advances in neuromonitoring, diagnostic imaging, and emerging treatments, much research needs to be undertaken in neurocritical care. Many of the clinical trials carried out in the general critical care population have excluded neurocritical care patients. For instance, the landmark ARDSNET trial that demonstrated the beneficial effects of low tidal volume ventilation in patients with ARDS cannot be directly applied to neurocritical care patients who frequently may experience this pulmonary complication. There is a need for a more cohesive and integrated research system or network to establish a track record for high-quality, investigator-initiated clinical research in neurocritical care. Such a system may help us overcome potential impediments to the future advancement of neurocritical care research. We propose the creation of the neurocritical care research network. The mission of the Network is to facilitate multicenter and multidisciplinary collaboration and patient enrollment in clinical trials of specific neurocritical care diseases.

Clinical trial design in the neurocritical care unit.

Clinical trials provide a robust mechanism to advance science and change clinical practice across the widest possible spectrum. Fundamental in the Neurocritical Care Society's mission is to promote Quality Patient Care by identifying and implementing best medical practices for acute neurological disorders that are consistent with the current scientific knowledge. The next logical step will be to foster rapid growth of our scientific body of evidence, to establish and disseminate these best practices. In this manuscript, five invited experts were impaneled to address questions, identified by the conference organizing committee as fundamental issues for the design of clinical trials in the neurological intensive care unit setting.

The critical care research networks experience.

Neurocritical care is a subspecialty of critical care medicine, dedicated to the care and the advancement of care of critically ill patients with neurosurgical or neurological diseases. Neurocritical care patients are heterogeneous, in both their disease process and the therapies they receive, however, several studies demonstrate that care of these patients in dedicated NeuroIntensive Care Units (neuroICUs) by neurointensivists, who coordinate their care is associated with reduced mortality and resource utilization. NeuroICUs foster innovation, and yet despite all the recent advances, much research needs to be undertaken in neurocritical care to better understand the disease pathophysiology and to demonstrate improved outcome with the use of goal-directed therapy based on evolving techniques and therapies.

Research and technology in neurocritical care.

The daily practice of neurointensivists focuses on the recognition of subtle changes in the neurological examination, interactions between the brain and systemic derangements, and brain physiology. Common alterations such as fever, hyperglycemia, and hypotension have different consequences in patients with brain insults compared with patients of general medical illness. Various technologies have become available or are currently being developed. The session on "research and technology" of the first neurocritical care research conference held in Houston in September of 2009 was devoted to the discussion of the current status, and the research role of state-of-the art technologies in neurocritical patients including multi-modality neuromonitoring, biomarkers, neuroimaging, and "omics" research (proteomix, genomics, and metabolomics). We have summarized the topics discussed in this session. We have provided a brief overview of the current status of these technologies, and put forward recommendations for future research applications in the field of neurocritical care.

Neurocritical care nursing research priorities.

The science of nursing has long been discussed as a blending of the art and science of caring, and nursing research builds the evidence of support for nursing practice. Nurses and nursing care are key to successful neurocritical care research endeavors. Ideally nursing care should be evidence based and supported by solid research. The goal of nursing research is to expand the knowledge of caring for patients. Within the scope of nursing research, the priorities for research in neurocritical care should support this goal. In this manuscript, we discuss what we believe are the priorities of neurocritical care nursing research, the obstacles, and some possible solutions.

Role of the NR2A/2B subunits of the N-methyl-D-aspartate receptor in glutamate-induced glutamic acid decarboxylase alteration in cortical GABAergic neurons in vitro.

The vulnerability of brain neuronal cell subpopulations to neurologic insults varies greatly. Among cells that survive a pathological insult, for example ischemia or brain trauma, some may undergo morphological and/or biochemical changes that may compromise brain function. The present study is a follow-up of our previous studies that investigated the effect of glutamate-induced excitotoxicity on the GABA synthesizing enzyme glutamic acid decarboxylase (GAD65/67)'s expression in surviving DIV 11 cortical GABAergic neurons in vitro [Monnerie and Le Roux, (2007) Exp Neurol 205:367-382, (2008) Exp Neurol 213:145-153]. An N-methyl-D-aspartate receptor (NMDAR)-mediated decrease in GAD expression was found following glutamate exposure. Here we examined which NMDAR subtype(s) mediated the glutamate-induced change in GAD protein levels. Western blotting techniques on cortical neuron cultures showed that glutamate's effect on GAD proteins was not altered by NR2B-containing diheteromeric (NR1/NR2B) receptor blockade. By contrast, blockade of triheteromeric (NR1/NR2A/NR2B) receptors fully protected against a decrease in GAD protein levels following glutamate exposure. When receptor location on the postsynaptic membrane was examined, extrasynaptic NMDAR stimulation was observed to be sufficient to decrease GAD protein levels similar to that observed after glutamate bath application. Blocking diheteromeric receptors prevented glutamate's effect on GAD proteins after extrasynaptic NMDAR stimulation. Finally, NR2B subunit examination with site-specific antibodies demonstrated a glutamate-induced, calpain-mediated alteration in NR2B expression. These results suggest that glutamate-induced excitotoxic NMDAR stimulation in cultured GABAergic cortical neurons depends upon subunit composition and receptor location (synaptic vs. extrasynaptic) on the neuronal membrane. Biochemical alterations in surviving cortical GABAergic neurons in various disease states may contribute to the altered balance between excitation and inhibition that is often observed after injury.

Intracranial pressure and cerebral oxygenation changes after decompressive craniectomy in children with severe traumatic brain injury.

INTRODUCTION: There has been a resurgence of interest in decompressive craniectomy for traumatic brain injury (TBI), but the impact of craniectomy on intracranial pressure (ICP) and cerebral oxygenation has not been well described for diffuse injury in children. METHODS: ICP and brain tissue oxygenation (PbtO2) changes after decompressive craniectomy for diffuse brain swelling after TBI in children were analysed. FINDINGS: Decompressive craniectomy was performed for diffuse brain swelling in 18 children under 15 years old. For 8 patients, craniectomy was performed as an emergency for malignant brain swelling, and in 10, for sustained ICP > 25 mmHg refractory to conventional medical treatment. In 6 of these patients, PbtO2 was also monitored. Median ICP was reduced from 40 mmHg before craniectomy to 16 mmHg for 24 hours thereafter, and PbtO2 improved from a median of 17.4 to 43.4 mmHg. Clinical outcome was favourable in 78%. CONCLUSIONS: In selected pediatric patients with TBI, craniectomy for diffuse brain swelling can significantly improve ICP and cerebral oxygenation control. The use of the procedure in appropriate settings does not appear to increase the proportion of disabled survivors.

Intracranial pressure and cerebral oxygenation changes after decompressive craniectomy in a child with traumatic brain swelling.

CASE REPORT: The authors present the case of a 5-year-old child with severe traumatic brain injury in whom decompressive hemicraniectomy was performed for progressive increased intracranial pressure (ICP) unresponsive to medical treatment. Data from ICP and cerebral tissue oxygenation monitoring in the contralateral hemisphere were recorded, which demonstrated the immediate and delayed mechanical and physiological changes occurring after bony and dural decompression. DISCUSSION: The role of the procedure and that of the monitoring approach are discussed.

Robot-assisted microsurgery: a feasibility study in the rat.

OBJECTIVE: Telerobotic surgery is a novel technology that can improve a surgeon's manual dexterity as well as the results achieved with microsurgical procedures. METHODS: A prototype Robot-Assisted MicroSurgery (RAMS) microdexterity enhancement system developed by the Jet Propulsion Laboratory and MicroDexterity Systems, Inc., was tested in 10 rats. Carotid arteriotomies were created and closed using either the RAMS system or conventional microsurgical techniques. The time required, the technical quality (vessel patency and suture line integrity), the error rate, and subjective difficulty were compared. RESULTS: All procedures were successfully completed using the RAMS system to manipulate the vessel but not to hold the needle or place the sutures. The precision, technical quality, and error rate of telerobotic surgery were similar to those of conventional techniques. However, the use of the RAMS system was associated with a twofold increase in the length of the procedure. CONCLUSION: Surgery using a microdexterity enhancement system, or RAMS prototype, is feasible. With further development, such as a stereotelevisualization and haptic feedback system, this system could be used for telerobotic surgery in neurosurgical practice.

Blood transfusion during aneurysm surgery.

INTRODUCTION: Increasing costs and concerns about blood supply safety have led to a reevaluation of blood transfusion practices. This study was undertaken to examine blood use during aneurysm surgery. METHODS: We performed a retrospective analysis of hospital records including operative, anesthetic, and nursing notes, computed tomographic scans, and four-vessel angiographic films of 547 patients undergoing surgery for ruptured and unruptured cerebral aneurysms at Harborview Medical Center in Seattle. During the review period, the transfusion threshold was not altered. RESULTS: A total of 134 patients (24.5%) received an intraoperative blood transfusion (median number of units, 2; range, 1-17). Preoperative factors associated with intraoperative blood use included older patient age (P < 0.001), lower hematocrit level on admission (P = 0.007), ruptured rather than unruptured aneurysm (P = 0.004), severe intraventricular hemorrhage (P = 0.03), and larger aneurysm size (P = 0.004). Factors not associated with intraoperative blood transfusion included past medical history (including cardiac or pulmonary disease), admission clinical grade after aneurysm rupture, findings such as hydrocephalus on computed tomographic scanning, and aneurysm location and aneurysm neck-to-fundus ratio. Also associated with blood transfusion during surgery were intraoperative aneurysm rupture (P < 0.0001), intracerebral hematoma evacuation (P = 0.02), and obliteration of multiple aneurysms (P = 0.002). Among patients who received an intraoperative transfusion, those who experienced an aneurysm rupture required an average of 3.6 +/- 0.35 units, whereas patients who did not have a rupture required 1.9 +/- 0.12 units (P = 0.001). Postoperatively, a total of 244 patients (44.6%), including 77 who received blood intraoperatively, required a blood transfusion (median number of units, 2; range, 1-31). Postoperative blood transfusion was associated with the treatment of patients with subarachnoid hemorrhage (P < 0.0001), particularly among poor-grade patients who developed medical complications. CONCLUSION: Blood transfusion can be expected in one in five patients undergoing aneurysm surgery. Reducing intraoperative rupture may reduce the need for blood products.

Cerebral cortical neuron apoptosis after mild excitotoxic injury in vitro: different roles of mesencephalic and cortical astrocytes.

OBJECTIVE: Increasing evidence supports the presence of neuronal apoptosis after ischemic or excitotoxic brain injury. Astrocytes, which exhibit significant regional differences in function, may exert a protective effect on neurons exposed to ischemic injury. We examined the effects of astrocytes derived from different regions of the central nervous system on neuronal apoptosis after mild excitotoxic injury in tissue culture. METHODS: Purified astrocyte cultures derived from P4 rat cerebral cortex or mesencephalon showed transient cell swelling but no cell death when exposed to 50 micromol/L glutamate for 5 minutes. When mixed neuronal/glial cocultures were exposed to the same glutamate dose, neuron death was observed. Necrotic and apoptotic cell death during 24 hours was examined using morphological criteria, nuclear staining, triphosphate nick end labeling, and trypan blue exclusion. RESULTS: We found that cortical neurons that elaborate a more extensive dendritic arbor when grown on homotypic astrocytes are more likely to undergo apoptosis than neurons with a limited dendritic arbor grown on heterotypic astrocytes. By contrast, a similar number of neurons undergo necrotic cell death. CONCLUSION: This finding may be associated with 1) increased vulnerability of neurons with a more elaborate dendrite structure to mild excitotoxic injury, or 2) regional differences in the ability of astrocytes to attenuate apoptosis.

Intracranial aneurysms and subarachnoid hemorrhage management of the poor grade patient.

Between 20 and 30% of patients who suffer cerebral aneurysm rupture are in poor clinical grade when first evaluated. Management of these patients is controversial and challenging but can be successful with an aggressive proactive approach that begins with in the field resuscitation and continues through rehabilitation. In this article we review the epidemiology, pathology and pathophysiology, clinical features, evaluation, surgical and endovascular management, critical care, cost, and outcome prediction of patients in poor clinical grade after subarachnoid hemorrhage.

Postoperative pain after lumbar disc surgery: a comparison between parenteral ketorolac and narcotics.

OBJECTIVE: Lumbar discectomy is a common elective surgical procedure but many patients still experience postoperative back pain which may delay hospital discharge. We therefore evaluated the efficacy of a parenteral non-steroidal antiinflammatory agent, ketorolac, for the management of post-surgical pain. METHODS: Fifty three patients undergoing lumbar discectomy at a Medical School affiliated Veterans Administration hospital were randomly assigned to receive either: 1) 30 mg intramuscular ketorolac upon surgical closure and every 6 hours for 36 hours and narcotic analgesics as needed (PRN); or 2) only narcotic analgesics as needed. A blinded observer recorded the average, minimum and maximum postoperative pain intensity using a Numeric Pain Intensity Scale; total postoperative narcotic consumption, complications, length of hospitalization (from surgery to discharge) and outcome at 6 weeks. RESULTS: The patients who received ketorolac reported significantly lower average (p < 0.001), minimum (p < 0.001), and maximum (p < 0.001) pain scores than patients receiving only narcotic analgesics. Cumulative narcotic doses (standardized to parenteral morphine) were significantly lower in the ketorolac group (p < 0.001). There was no significant difference between groups in the frequency of side effects, and no complication specifically associated with ketorolac use was observed. Mean length of hospitalization was significantly shorter (p = 0.05) in patients receiving ketorolac than in patients receiving only narcotics. Six weeks after surgery 5 (19.2%) patients who received only narcotics were troubled by persistent back pain. By contrast, all patients who received ketorolac were free of back pain at follow-up (p = 0.03). CONCLUSIONS: These results suggest that ketorolac, when used with PRN narcotics, is more effective than PRN narcotics alone for postoperative pain following lumbar disc surgery. In addition, this strategy also may contribute to early discharge from hospital after lumbar disc surgery.

Surgical approaches to basilar bifurcation aneurysms.

Basilar bifurcation aneurysms are technically challenging and their treatment is often associated with greater morbidity than aneurysms located in the anterior circulation. These lesions can be treated using surgical, endovascular, or a combination of techniques. Several surgical approaches have evolved to treat basilar bifurcation aneurysms; none, however, is suitable for all aneurysms in this location. This article reviews the natural history, clinical presentation, evaluation, and selection of treatment approach and details various surgical techniques. The use of endovascular techniques is reviewed briefly.

Management of cerebral aneurysms. How can current management be improved?

In the present article, we have reviewed potential avenues for improvement in the care of and present management of patients with cerebral aneurysms. Opportunities exist in areas of prevention, systems approach and organization of centers, physician and patient education, screening, and advances in surgical and endovascular therapy. All such advances, however, depend on rigorous academic evaluation. This issue represents a review of the current management of cerebral aneurysms, hopefully providing a basis for future improvements in the treatment of these lesions.

Management of the ruptured aneurysm.

Rupture of cerebral aneurysms is a complex and devastating pathophysiologic event. The successful management of aneurysm rupture requires a dedicated multidisciplinary team. This article reviews pathophysiology; clinical grading that can be used to predict outcome and guide therapy; factors that may affect outcome such as rebleeding, poor clinical grade, intracerebral hemorrhage, intraventricular hemorrhage, and acute hydrocephalus; preoperative care and assessment; pharmacological therapy; anesthetic, surgical, and endovascular considerations; and postoperative care following aneurysm rupture.

Perioperative and intensive care unit care of patients with aneurysmal subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a complex pathophysiological event that results in a number of intracranial and systemic alterations. The effective management of SAH has its foundation in the prevention, early diagnosis, and correction of complications. Successful outcome in these compromised patients requires close monitoring and intensive care. This article will review the pathophysiology of SAH, identify the most common medical and neurological events that complicate SAH, examine the impact of secondary cerebral insults after aneurysm rupture, and outline current ICU care for SAH.

Subarachnoid hemorrhage and cerebral aneurysms in the elderly.

Advanced age is associated with a less favorable outcome following aneurysmal SAH, in large part, because of associated medical conditions. Nevertheless, available data suggest that elderly patients often benefit from aggressive treatment and that a reasonable outcome at a reasonable cost can be expected in selected patients. Emerging technologies such as endovascular treatment of ruptured and unruptured aneurysms continue to improve treatment options in the elderly population. Physiologic rather than chronologic age together with the patient's clinical condition and personal and family considerations should form the basis of any recommended treatment approach in the elderly patient with a cerebral aneurysm.

Risks and benefits of diagnostic angiography after aneurysm surgery: a retrospective analysis of 597 studies.

INTRODUCTION: Cerebral angiography performed after aneurysm surgery can identify causes of morbidity and mortality that may be corrected. The risks and benefits of angiography that is performed after aneurysm surgery, however, have not been clearly defined. We therefore reviewed our experience with postoperative angiography to determine its dangers and benefits. METHODS: During 10 years, 543 consecutive patients received treatment for cerebral aneurysms. A retrospective analysis of 597 diagnostic angiograms obtained after aneurysm surgery for 494 of these patients was performed. RESULTS: Catheter-induced vessel spasm and dissection, occurring most frequently in the internal carotid artery, were observed in seven (1.2%) and six (1%) studies, respectively. No angiography-associated strokes were identified. No association between age, smoking, hypertension, blood pressure, atherosclerosis, or severe vasospasm and angiographic complications was observed. Aneurysm remnants were identified in 36 (5.7%) of the 637 aneurysms that were surgically treated. Atherosclerosis (P < 0.01) or multiple clip applications (P < 0.01) were significantly associated with aneurysm remnants. Angiographic vessel occlusion was observed in 28 (5.7%) patients and resulted in stroke in 14 of these patients. Vessel occlusion was significantly associated with increasing aneurysm size (P < 0.001), atherosclerosis (P < 0.001), temporary clips (P < 0.001), multiple clips (P=0.03), multiple clip applications (P=0.001), and a new postoperative neurological deficit (P=0.002). Severe vasospasm and newly identified aneurysms were observed in 51 and 16 patients, respectively. CONCLUSION: Angiography after aneurysm surgery is safe and can be routinely performed. Angiography after aneurysm surgery should be particularly considered for patients with large aneurysms or cerebrovascular atherosclerosis and for those who develop new postoperative neurological deficits.

Comparison of balloon angioplasty and papaverine infusion for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage.

OBJECT: The purpose of this study was to test the hypothesis that balloon angioplasty is superior to papaverine infusion for the treatment of proximal anterior circulation arterial vasospasm following subarachnoid hemorrhage (SAH). Between 1989 and 1995, 125 vasospastic distal internal carotid artery or proximal middle cerebral artery vessel segments were treated in 52 patients. METHODS: Blood flow velocities of the involved vessels were assessed by using transcranial Doppler (TCD) monitoring in relation to the day of treatment with balloon angioplasty or papaverine infusion. Balloon angioplasty and papaverine infusion cohorts were compared based on mean pre- and posttreatment velocity at 24 and 48 hours using the one-tailed, paired-samples t-test. Balloon angioplasty alone was performed in 101 vessel segments (81%) in 39 patients (75%), whereas papaverine infusion alone was used in 24 vessel segments (19%) in 13 patients (25%). Although repeated treatment after balloon angioplasty was needed in only one vessel segment, repeated treatment following papaverine infusion was required in 10 vessel segments (42%) in six patients because of recurrent vasospasm (p < 0.001). Seven vessel segments (29%) with recurrent spasm following papaverine infusion were treated with balloon angioplasty. Although vessel segments treated with papaverine demonstrated a 20% mean decrease in blood flow velocity (p < 0.009) on posttreatment Day 1, velocities were not significantly lower than pretreatment levels by posttreatment Day 2 (p = 0.133). Balloon angioplasty resulted in a 45% mean decrease in velocity to a normal level following treatment (p < 0.001), a decrease that was sustained. CONCLUSIONS: Balloon angioplasty is superior to papaverine infusion for the permanent treatment of proximal anterior circulation vasospasm following aneurysmal SAH.