Noninvasive cardiac output monitor to quantify hydration status in ischemic stroke patients: A feasibility study.

BACKGROUND: Individuals who are dehydrated, volume contracted or both at the time of hospitalization for acute ischemic stroke have worse clinical outcomes than do individuals with optimal volume status. Currently, there is no gold standard method for measuring hydration status, except indirect markers of a volume contracted state (VCS) including elevated blood urea nitrogen (BUN)/creatinine ratio. We sought to test the feasibility and acceptability of a non-invasive cardiac output monitor (NICOM) for the measurement of hydration status in a group of hospitalized ischemic stroke patients, and explore the relationship with a common indirect laboratory-based measure of VCS. METHODS: We performed a prospective observational feasibility study of hospitalized acute ischemic stroke patients. We collected hemodynamic parameters using the NICOM device before and after fluid auto-bolus via passive leg raise and BUN/creatinine ratio. Successful acquisition of relevant hemodynamic data was the primary objective of this study. We explored agreement between the NICOM results and BUN/creatinine ratio using Cohen's kappa statistic. RESULTS: Thirty patients hospitalized with acute ischemic stroke were enrolled. We found that 29/30 patients tolerated assessment with NICOM. Hemodynamic data were collected in all 30 patients. Data capture took an average of 10 min(SD ± 112 s). Agreement between NICOM and BUN/creatinine ratio was 70%; (expected agreement 51%; kappa 0.38). Agreement was stronger in the cohort without history of diabetes (81% agreement, kappa 0.61). CONCLUSIONS: NICOM assessment was feasible in hospitalized stroke patients. The identification of an objective, real-time measure of hydration status would be clinically useful, and could allow precise, goal-directed care.

The Future of Neurocritical Care Research: Proceedings and Recommendations from the Fifth Neurocritical Care Research Network Conference.

The Fifth Neurocritical Care Research Network (NCRN) Conference held in Boca Raton, Florida, in September of 2018 was devoted to challenging the current status quo and examining the role of the Neurocritical Care Society (NCS) in driving the science and research of neurocritical care. The aim of this in-person meeting was to set the agenda for the NCS's Neurocritical Care Research Central, which is the overall research arm of the society. Prior to the meeting, all 103 participants received educational content (book and seminar) on the 'Blue Ocean Strategy®,' a concept from the business world which aims to identify undiscovered and uncontested market space, and to brainstorm innovative ideas and methods with which to address current challenges in neurocritical care research. Three five-member working groups met at least four times by teleconference prior to the in-person meeting to prepare answers to a set of questions using the Blue Ocean Strategy concept as a platform. At the Fifth NCRN Conference, these groups presented to a five-member jury and all attendees for open discussion. The jury then developed a set of recommendations for NCS to consider in order to move neurocritical care research forward. We have summarized the topics discussed at the conference and put forward recommendations for the future direction of the NCRN and neurocritical care research in general.

Multimodal MRI characterization of experimental subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is associated with significant morbidity and mortality. We implemented an in-scanner rat model of mild SAH in which blood or vehicle was injected into the cistern magna, and applied multimodal MRI to study the brain prior to, immediately after (5min to 4h), and upto 7days after SAH. Vehicle injection did not change arterial lumen diameter, apparent diffusion coefficient (ADC), T2, venous signal, vascular reactivity to hypercapnia, or foot-fault scores, but mildly reduce cerebral blood flow (CBF) up to 4h, and open-field activity up to 7days post injection. By contrast, blood injection caused: (i) vasospasm 30min after SAH but not thereafter, (ii) venous abnormalities at 3h and 2days, delayed relative to vasospasm, (iii) reduced basal CBF and to hypercapnia 1-4h but not thereafter, (iv) reduced ADC immediately after SAH but no ADC and T2 changes on days 2 and 7, and (v) reduced open-field activities in both SAH and vehicle animals, but no significant differences in open-field activities and foot-fault tests between groups. Mild SAH exhibited transient and mild hemodynamic disturbances and diffusion changes, but did not show apparent ischemic brain injury nor functional deficits.

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.

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.

Research priorities in neurocritical care.

This summary of the last session of the First Neurocritical Care Research Conference reviews the discussions about research priorities in neurocritical care. The first presentation reviewed current projects funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health and potential models to follow including an independent Neurocritical Care Network or the creation of such a network with the goal of collaborating with already existing ones. Experienced neurointensivists then presented their views on the most common and important research questions that need to be answered and investigated in the field. Finally, utility of clinical registries was discussed emphasizing their importance as hypothesis generators. During the group discussion, interests in comparative effectiveness research, the use of physiological endpoints from monitoring and alternate trial design were expressed.

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.

Asymptomatic middle cerebral artery stenosis diagnosed by magnetic resonance angiography.

We reviewed 1440 MRA studies to identify patients with middle cerebral artery stenosis (MCAS). We identified 99 cases, and after reviewing the clinical records, classified 28 as asymptomatic MCAS (AMCAS), a prevalence of 2%. Suspected stroke was the most frequent indication for MRA. Follow-up was available for 21, mean 46.7 months (range 2.4-75.6 months). One stroke occurred in the AMCAS territory (5%), other strokes in five patients (24%). There were five deaths in patients with MCAS; age > 69 (P = 0.045) was the only associated risk factor. This study suggests that patients in whom MRA is performed and shows AMCAS may be at increased risk of strokes in any vascular distribution or of death.

Thrombolytic therapy for acute extra-cranial artery dissection: report of two cases.

Extra-cranial arterial dissection accounts for 10% of strokes in young people. Information on safety of thrombolytic administration in this group is limited. The literature, however, does not favor use of thrombolytics for myocardial ischemia when peripheral arterial dissection coexists. Based on the clinical and radiological features, two patients who presented with acute stroke secondary to arterial dissection were considered for thrombolysis. One of them received intra-venous recombinant tissue plasminogen activator (rtPA), and the other patient received intra-arterial rtPA. There were no post thrombolysis complications. This report supports feasibility of administering thrombolytics in acute ischemic strokes resulting from extra-cranial arterial dissection. Future larger studies are necessary to determine the efficacy, safety and long-term outcome in this patient population.

Risk factors for subarachnoid hemorrhage.

OBJECTIVE: Cigarette smoking has been demonstrated to increase the risk of subarachnoid hemorrhage (SAH). Whether cessation of smoking decreases this risk remains unclear. We performed a case-control study to examine the effect of smoking and other known risk factors for cerebrovascular disease on the risk of SAH. METHODS: We reviewed the medical records of all patients with a diagnosis of SAH (n = 323) admitted to Johns Hopkins Hospital between January 1990 and June 1997. Controls matched for age, sex, and ethnicity (n = 969) were selected from a nationally representative sample of the Third National Health and Nutrition Examination Survey. We determined the independent association between smoking (current and previous) and various cerebrovascular risk factors and SAH by use of multivariate logistic regression analysis. A separate analysis was performed to determine associated risk factors for aneurysmal SAH. RESULTS: Of 323 patients admitted with SAH (mean age, 52.7+/-14 yr; 93 were men), 173 (54%) were hypertensive, 149 (46%) were currently smoking, and 125 (39%) were previous smokers. In the multivariate analysis, both previous smoking (odds ratio [OR], 4.5; 95% confidence interval [CI], 3.1-6.5) and current smoking (OR, 5.2; 95% CI, 3.6-7.5) were significantly associated with SAH. Hypertension was also significantly associated with SAH (OR, 2.4; 95% CI, 1.8-3.1). The risk factors for 290 patients with aneurysmal SAH were similar and included hypertension (OR, 2.4; 95% CI, 1.8-3.2), previous smoking (OR, 4.1; 95% CI, 2.7-6.0), and current smoking (OR, 5.4; 95% CI, 3.7-7.8). CONCLUSION: Hypertension and cigarette smoking increase the risk for development of SAH, as found in previous studies. However, the increased risk persists even after cessation of cigarette smoking, which suggests the importance of early abstinence from smoking.

Safety of intra-arterial thrombolysis in the postoperative period.

BACKGROUND AND PURPOSE: Limited systemic fibrinolysis and reduced dosage are features of intra-arterial thrombolyis (IAT) that may be advantageous in the treatment of postoperative strokes. However, IAT may increase the risk of surgical bleeding. We sought to determine the safety of postoperative IAT. METHODS: This was a retrospective case series from 6 university hospitals. All cases of IAT within 2 weeks of surgery were identified. Demographics, stroke mechanism, stroke severity, imaging and angiographic findings, time between surgery and lysis, thrombolytic agent used, surgical site bleeding, intracranial bleeding, and mortality rates were determined. Death or complications directly related to IAT were determined. RESULTS: Thirty-six patients (median age, 71.5 years; range, 45 to 85) were identified. Median time from surgery to stroke was 21.5 hours (range, 1 to 120). Open heart surgery was done in 18 (50%), carotid endarterectomy in 6 (17%), craniotomy in 3 (8%), ophthalmologic-ear, nose and throat surgery in 2 (6%), urologic-gynecologic surgery in 4 (11%), orthopedic surgery in 2 (6%), and plastic surgery in 1 (3%). The stroke causes were cardioembolism in 24 (67%), large-vessel atherosclerosis in 4 (11%), dissection in 3 (8%), postendarterectomy occlusion in 4 (11%), and radiation arteriopathy in 1 (3%). Median time to angiogram was 2.5 hours (0.1 to 5.5). Occlusion sites were M1 in 19 (53%), M2 in 9 (25%), internal carotid artery in 5 (14%), basilar artery in 2 (6%), and posterior communicating artery in 1 (3%). Thrombolysis was completed at a median of 4.5 hours (range, 1 to 8.0). Tissue plasminogen activator was used in 19 (53%) and urokinase in 17 (47%). Nine (26%) patients died. Surgical site bleeding occurred in 9 (25%) cases (minor in 6, major in 3). The major surgical bleeds were 2 post-craniotomy intracranial hemorrhages and 1 hemopericardium after coronary artery bypass grafting; all were fatal. Six deaths were non-IAT related: 3 caused by cerebral edema and 3 by systemic causes. Major bleeding complications were significantly more common among patients with craniotomy (P<0.02). CONCLUSIONS: Postoperative IAT carries a risk of bleeding in up to 25% of patients but is usually minor surgical site bleeding. Avoiding IAT in intracranial surgery patients may reduce complications. Mortality rate in this series was similar to that reported in prior IAT trials. IAT remains a viable therapeutic option for postoperative strokes.

Benefits of perfusion MR imaging relative to diffusion MR imaging in the diagnosis and treatment of hyperacute stroke.

BACKGROUND AND PURPOSE: The development of thrombolytic agents for use with compromised cerebral blood flow has made it critical to quickly identify those patients to best treat. We hypothesized that combined diffusion and perfusion MR imaging adds vital diagnostic value for patients for whom the greatest potential benefits exist and far exceeds the diagnostic value of diffusion MR imaging alone. METHODS: The cases of patients with neurologic symptoms of acute ischemic stroke who underwent ultra-fast emergent MR imaging within 6 hours were reviewed. In all cases, automatic processing yielded isotropic diffusion images and perfusion time-to-peak maps. Images with large vessel distribution ischemia and with mismatched perfusion abnormalities were correlated with patient records. All follow-up images were reviewed and compared with outcomes resulting from hyperacute therapies. RESULTS: For 16 (26%) of 62 patients, hypoperfusion was the best MR imaging evidence of disease distribution, and for 15 of the 16, hypoperfusion (not abnormal diffusion) comprised the only imaging evidence for disease involving large vessels. For seven patients, diffusion imaging findings were entirely normal, and for nine, diffusion imaging delineated abnormal signal in either small vessel distributions or in a notably smaller cortical branch in one case. In all cases, perfusion maps were predictive of eventual lesions, as confirmed by angiography, CT, or subsequent MR imaging. CONCLUSION: If only diffusion MR imaging is used in assessing patients with hyperacute stroke, nearly one quarter of the cases may be incorrectly categorized with respect to the distribution of ischemic at-risk tissue. Addition of perfusion information further enables better categorizing of vascular distribution to allow the best selection among therapeutic options and to improve patient outcomes.

[Treatment of acute brain edema]. / Tratamiento del edema cerebral agudo.

OBJECTIVE: To review the basic concepts and mechanisms of cerebral edema and to analyze current management of this complex clinical problem. DEVELOPMENT: Cerebral edema is a stereotyped reaction of the brain to any aggression and is a very common complication in patients with alterations of the blood-brain barrier. The cerebral edema should be recognized and treated early and aggressively to avoid disastrous results such as cerebral herniation. The most important types of edema are the vasogenic and cytotoxic. The first implies primary alterations of the blood-brain barrier, whilst in the second they are of cellular homeostasis. We have reviewed how various pro-inflammatory substances interact to stimulate the mechanisms causing edema, and also the importance of cerebrovascular autoregulation for maintenance of a normal intracranial volume. The measures necessary for good cerebral reanimation are the following: evaluation of the airway, controlled hyperventilation, maintenance of the cerebral perfusion pressure > 70 mmHg, suitable position of the head, administration of hypertonic solutions, dexamethasone, and possibly barbiturates. We have shown that a body temperature > 37.5 degrees C and blood glucose > 150 mg/dl are related to worsening of the cerebral edema. Finally, we have reviewed other experimental treatments which seem promising, such as hemicraniectomy, hypertonic saline solutions, hypothermia and other neuroprotector agents. CONCLUSIONS: All patients with acute cerebral edema should be evaluated early and treated with therapy which will solve the underlying pathological problem. Good medical management of these patients is of vital importance to assure a satisfactory clinical outcome. Recently new, effective therapy has been evaluated which may substantially change current concepts of the treatment of patients with acute cerebral edema.

[Management of closed head injury]. / Manejo del traumatismo craneal cerrado.

OBJECTIVE: To review current concepts regarding the management of severe closed head injury and determine the possible causes of brain damage in these patients. DEVELOPMENT: Severe closed head injury causes a high rate of mortality and disability in developed countries. The diagnosis and management of these patients has progressed in recent years, from the availability of brain scanning to varied therapeutic methods based on brain metabolism and intracranial dynamics. We have reviewed the different neuropathological processes in relation to closed head injury and emphasized the importance of recognition and control of the secondary lesions, which may have disastrous consequences for the patient. After clinical evaluation and early cardiorespiratory stabilization, the patients are taken to a critical care unit for continuous monitoring of the intracranial pressure, cerebral perfusion pressure and cerebral extraction of oxygen. We have discussed several therapeutic interventions taking into account the values obtained by continuous monitoring of these patients. As well as traditional measures (hyperventilation, manitol and barbiturate coma), there are other possibilities for treatment of these patients such as hypothermia, hypertonic saline solutions and neuroprotector agents. CONCLUSIONS: All patients with closed head injuries should be evaluated and treated as emergencies, and admitted to a critical care unit to avoid secondary lesions such as hypoxemia, arterial hypotension and cerebral edema. Treatment should be aimed at maintenance of the intracranial pressure and cerebral perfusion within normal limits and also maintenance satisfactory jugular saturation.

Acute motor-sensory axonal neuropathy associated with active systemic lupus erythematosus and anticardiolipin antibodies.

Acute motor-sensory axonal neuropathy (AMSAN) is an axonal variant of Guillian-Barré syndrome (GBS) that presents with acute ascending quadriparesis. This has generally been described in association with Campylobacter jejuni infections or with anti-ganglioside antibodies. Known cases have shown a slow recovery and a poor prognosis. We report a case with clinical and electrophysiological evidence of AMSAN in association with active systemic lupus erythematosus (SLE) and anticardiolipin antibodies but not the other associations, with a rapid response to combination immunosuppressant and intravenous immunoglobulin (IVIg) therapy. The association between AMSAN and SLE has not been previously described. This case illustrates that early recognition and the utilization of electrophysiologic techniques may be beneficial in the diagnosis and management of GBS associated with SLE. Fulminant or rapidly progressive cases should be managed in specialized intensive care units. Combination therapy of immunosuppressants and IVIg may be beneficial in non-vasculitic axonal radiculo-neuropathies associated with SLE, resulting in good outcomes.

Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension.

OBJECTIVES: To review the literature on the use of hypertonic saline (HS) in treating cerebral edema and intracranial hypertension. DATA SOURCES: Review of scientific and clinical literature retrieved from a computerized MEDLINE search from January 1965 through November 1999. STUDY SELECTION: Pertinent literature is referenced, including clinical and laboratory investigations, to demonstrate principles and efficacy of treatment with HS in patients with intracranial space-occupying pathology. DATA EXTRACTION: The literature was reviewed to summarize the mechanisms of action, efficacy, adverse effects, systemic effects, and comparisons with standard treatments in both clinical and laboratory settings. DATA SYNTHESIS: HS has an osmotic effect on the brain because of its high tonicity and ability to effectively remain outside the bloodbrain barrier. Numerous animal studies have suggested that fluid resuscitation with HS bolus after hemorrhagic shock prevents the intracranial pressure (ICP) increase that follows resuscitation with standard fluids. There may be a minimal benefit in restoring cerebral blood flow, which is thought to be mitigated through local effects of HS on cerebral microvasculature. In animal models with cerebral injury, the maximum benefit is observed in animals with focal injury associated with vasogenic edema (cryogenic injury). The ICP reduction is seen for < or =2 hrs and may be maintained for longer periods by using a continuous infusion of HS. The ICP reduction is thought to be caused by a reduction in water content in areas of the brain with intact blood-brain barrier such as the nonlesioned hemisphere and cerebellum. Most comparisons with mannitol suggest almost equal efficacy in reducing ICP, but there is a suggestion that mannitol may have a longer duration of action. Human studies published to date reporting on the use of HS in treating cerebral edema and elevated ICP include case reports, case series, and small controlled trials. Results from studies directly comparing HS with standard treatment in regard to safety and efficacy are inconclusive. However, the low frequency of side effects and a definite reduction of ICP observed with use of HS in these studies are very promising. Systemic effects include transient volume expansion, natriuresis, hemodilution, immunomodulation, and improved pulmonary gas exchange. Adverse effects include electrolyte abnormalities, cardiac failure, bleeding diathesis, and phlebitis. Although unproven, a potential for central pontine myelinolysis and rebound intracranial hypertension exists with uncontrolled administration. CONCLUSIONS: HS demonstrates a favorable effect on both systemic hemodynamics and intracranial pressure in both laboratory and clinical settings. Preliminary evidence supports the need for controlled clinical trials evaluating its use as resuscitative fluid in brain-injured patients with hemorrhagic shock, as therapy for intracranial hypertension resistant to standard therapy, as firstline therapy for intracranial hypertension in certain intracranial pathologies, as small volume fluid resuscitation during spinal shock, and as maintenance intravenous fluid in neurocritical care units.

Long-term outcome after medical reversal of transtentorial herniation in patients with supratentorial mass lesions.

OBJECTIVE: To determine the short- and long-term outcomes after successful reversal of transtentorial herniation by medical treatment. Although it has been recognized that aggressive medical management can reverse transtentorial herniation, it is believed that overall outcome in such patients is poor. DESIGN: Prospective cohort study. SETTING: Neurocritical care unit of a university hospital. PATIENTS: A total of 28 consecutive patients who underwent an episode of transtentorial herniation (defined as decrease in level of consciousness accompanied by pupillary dilation) secondary to a supratentorial mass lesion followed by successful reversal. INTERVENTION: Herniation was reversed by using a combination of hyperventilation, mannitol and hypertonic saline. MEASUREMENTS AND MAIN RESULTS: The following outcomes were analyzed: risk of second herniation, radiologic evidence of structural damage or vascular compromise related to herniation on post-herniation computed tomographic scan, in-hospital mortality, and long-term functional outcome using Rankin score and Barthel index. A total of 32 episodes of transtentorial herniations were reversed in 28 patients during a 14-month period. The most common precipitating cause were edema (n = 23) or new/expanding intracerebral hematoma (n = 5). After first reversal of transtentorial herniation in 28 patients, a second herniation episode was observed in 16 patients after a mean interval of 88.2 hrs (range, 23-432 hrs); four were successfully reversed. On follow-up computed tomographic scan, hypodense lesion in midbrain (n = 6), temporal lobe contusion (n = 2), posterior cerebral artery (n = 3), and middle cerebral artery (n = 1) infarction were visualized in a minority of patients. The in-hospital mortality was 60% (n = 15) with brain death being the cause of death in 13 patients; care was withdrawn in eight patients. Second episode of herniation (p = .002) and midbrain involvement during herniation (p = .02) were associated with in-hospital mortality. During a mean follow-up period of 11.4+/-4.2 months, two patients died of cerebral neoplasm and human immunodeficiency virus-related sepsis, respectively. Of the 11 survivors, 7 were functionally independent (Rankin score <3 and Barthel index >60). CONCLUSIONS: Although mortality after transtentorial herniation is high, we found a prominent potential for meaningful recovery with aggressive medical reversal of transtentorial herniation. Our study implies that timely medical intervention for reversing transtentorial herniation can result in preservation of neurologic function.