Mexican Americans (MAs) have shown lower post-stroke mortality compared to non-Hispanic whites (NHWs). Limited evidence suggests race/ethnic differences exist in intensive care unit (ICU)admissions following stroke. Our objective was to investigate the association of ethnicity with admission to the ICU following stroke.
Cases of intracerebral hemorrhage and acute ischemic stroke were prospectively ascertained as part of the Brain Attack Surveillance in Corpus Christi (BASIC) project for the period January, 2000 through December, 2009. Logistic regression models fitted within the generalized additive model framework were used to test associations between ethnicity and ICU admission and potential confounders. An interaction term between age and ethnicity was investigated in the final model.
A total 1,464 cases were included in analysis. MAs were younger, more likely to have diabetes, and less likely to have atrial fibrillation, health insurance, or high school diploma than NHWs. On unadjusted analysis, there was a trend toward MAs being more likely to be admitted to ICU than NHWs (34.6% versus 30.3%; OR=1.22; 95% CI 0.98–1.52; p=0.08). However, on adjusted analysis, no overall association between MA ethnicity and ICU admission (OR=1.13; 95% CI 0.85–1.50) was found. When an interaction term for age and ethnicity was added to this model, there was only borderline evidence for effect modification by age of the ethnicity/ICU relationship (p=0.16).
No overall association between ethnicity and ICU admission was observed in this community. ICU utilization alone does not likely explain ethnic differences in survival following stroke between MAs and NHWs.
Intracerebral hemorrhage; Acute ischemic stroke; Mexican Americans; Intensive care unit
Prolonged emergency department length of stay (EDLOS) has been associated with worse patient outcomes, longer inpatient stays, and failure to meet quality measures in several acute medical conditions, but these findings have not been consistently reproduced. We performed this study to explore the hypothesis that longer EDLOS would be associated with worse outcomes in a large cohort of patients presenting with spontaneous intracerebral hemorrhage (ICH).
We performed a secondary analysis of a prospective cohort of consecutive patients with spontaneous ICH who presented to a single academic referral center from February 2005 to October 2009. The primary exposure variable was EDLOS, and our primary outcome was neurologic status at hospital discharge, measured with a modified Rankin scale (mRS). Secondary outcomes were ICU length of stay, total hospital length of stay, and total hospital costs.
Our cohort included 616 visits of which 42 were excluded, leaving 574 patient encounters for analysis. Median age was 75 years (IQR 63–82), median EDLOS 5.1 h (IQR 3.7–7.1) and median discharge mRS 4 (IQR 3–6). Thirty percent of the subjects died in-hospital. Multivariable proportional odds logistic regression, controlling for age, initial Glasgow Coma Scale, initial hematoma volume, ED occupancy at registration, and the need for intubation or surgical intervention, demonstrated no association between EDLOS and outcome. Furthermore, multivariable analysis revealed no association of increased EDLOS with ICU or hospital length of stay or hospital costs.
We found no effect of EDLOS on neurologic outcome or resource utilization for patients presenting with spontaneous ICH.
Emergency medicine; Emergency department crowding; Emergency department length of stay; Intracerebral hemorrhage
Hematoma expansion after acute intracerebral hemorrhage occurs most frequently in patients presenting within 3 h of symptom onset. However, the majority of patients present outside this window or with an unknown onset time. We investigated the prevalence of hematoma expansion in these patients and assessed the accuracy of the CT angiography (CTA) spot sign for identifying risk of hematoma expansion.
We analyzed 391 consecutive patients undergoing CTA and a followup CT. CTA spot sign readings were performed by two experienced readers and hematoma expansion was assessed by means of semi-automated software.
Hematoma expansion occurred in 18 % of patients. When stratified by time from symptom onset to initial CT, hematoma expansion rates were: 39 % within 3 h; 11 % between 3 and 6 h, 11 % beyond 6 h (but with known onset), and 20 % in patients with unknown symptom onset. Of patients who developed hematoma expansion, only 38 % presented within 3 h. The accuracy of the spot sign in predicting hematoma expansion was 0.67 for patients presenting within 3 h, 0.83 between 3 and 6 h, 0.88 after 6 h, and 0.76 for patients presenting with an unknown onset time.
A substantial number of patients destined to suffer from hematoma expansion present either late or with an unknown symptom onset time. The CTA spot sign accurately identifies patients destined to expand regardless of time from symptom onset, and may therefore open a path to offer clinical trials and novel therapies to the many patients who do not present acutely.
Intracerebral hemorrhage; CT angiography; CTA spot sign; Hematoma expansion; Late presentation
The objectives of this study were to determine effects of severe traumatic brain injury (TBI) on cerebrospinal fluid (CSF) concentrations of myelin basic protein (MBP) and to assess relationships between clinical variables and CSF MBP concentrations.
We measured serial CSF MBP concentrations in children enrolled in a randomized controlled trial evaluating therapeutic hypothermia (TH) after severe pediatric TBI. Control CSF was obtained from children evaluated, but found not to be having CNS infection. Generalized estimating equation models and Wilcoxon Rank-Sum test were used for comparisons of MBP concentrations.
There were 27 TBI cases and 57 controls. Overall mean (±SEM) TBI case MBP concentrations for 5 days after injury were markedly greater than controls (50.49 ± 6.97 vs. 0.11 ± 0.01 ng/ml, p < 0.01). Mean MBP concentrations were lower in TBI patients < 1 year versus >1 year (9.18 ± 1.67 vs. 60.22 ± 8.26 ng/ml, p = 0.03), as well as in cases with abusive head trauma (AHT) versus non-abusive TBI (14.46 ± 3.15 vs. 61.17 ± 8.65 ng/ml, p = 0.03). TH did not affect MBP concentrations.
Mean CSF MBP increases markedly after severe pediatric TBI, but is not affected by TH. Infancy and AHT are associated with low MBP concentrations, suggesting that age-dependent myelination influences MBP concentrations after injury. Given the magnitude of MBP increases, axonal injury likely represents an important therapeutic target in pediatric TBI.
Axonal injury; Pediatrics; Secondary injury
Intracerebral hemorrhage (ICH) is a highly fatal disease with few proven treatments. Data to guide clinician decisions for therapies, including antiepileptic drugs (AED), are limited. Published studies on AED treatment in ICH have provided conflicting results. We investigated the effect of AED treatment on 90-day mortality after ICH in a large prospectively ascertained cohort.
We conducted a retrospective analysis of a prospectively assembled cohort of patients with ICH in the Electronic supplementary material The online version of this article (doi:10.1007/s12028-012-9776-z) contains supplementary material, which is available to authorized users. supratentorial regions, comparing 90-day mortality and modified Rankin Score among 543 patients treated with AED during hospitalization and 639 AED-free ICH. Supratentorial ICH location was categorized as lobar or deep hemispheric.
Multivariate analysis demonstrated an association between AED treatment and reduced 90-day mortality in supratentorial ICH (OR = 0.62, 95 % CI 0.42–0.90, p = 0.01) and the subset of lobar ICH (OR = 0.49, 95 % CI 0.25–0.96, p = 0.04). When analyses were restricted to subjects surviving longer than 5 days from ICH, however, no association between AED treatment and a 90-day outcome, regardless of hemorrhage location (all p > 0.15), was detected, despite more than adequate power to detect the originally observed association.
These results suggest that AED treatment in acute ICH is not associated with 90-day mortality or outcome and that any detected association could arise by confounding by indication, in which the most severely affected patients are those in whom AEDs are prescribed. They provide a cautionary example of the limitations of drawing conclusions about treatment effects from observational data.
Intracerebral hemorrhage; Antiepileptic; Outcome; Confounding; Confounding by indication
Accurate prediction of successful extubation in patients with Guillain-Barré syndrome (GBS) is an important clinical problem. We hypothesized that reversal of clinical indices used to intubate a patient (i.e., declining vital capacity [VC]) predict extubation.
This was a retrospective study in neurocritical care units at two teaching hospitals identifying all mechanically-ventilated patients with GBS.
A total of 44 patients with GBS were included. Of these, 14 patients were successfully extubated. There were 10 failed extubations among six patients; and 20 patients underwent tracheostomy without an extubation trial. On the day of extubation, lower negative inspiratory force (NIF) (−50.3 ± 12.7 versus −28.6 ± 16.5 cm H2O, p = 0.0005) and higher VC (21.9 ± 8.4 versus 13.0 ± 5.9 mL/kg, p = 0.003) correlated with successful extubation. Change in VC preintubation to preextubation by greater than 4 mL/kg correlated with 82% sensitivity and 90% positive predictive value for successful extubation. Failed extubations were associated with the presence of pulmonary comorbidities (79 versus 36%, p = 0.008) and autonomic dysfunction (73 versus 27%, p = 0.008). Length of stay (LOS) in the intensive care unit (ICU) was increased in patients who failed extubation and in those patients who underwent tracheostomy (21.5 ± 11.1 versus 12.5 ± 8.7, p = 0.005). In multivariate analysis, higher VC at extubation was associated with successful extubation (p = 0.05).
In mechanically-ventilated patients with respiratory failure secondary to GBS, NIF less than −50 cm H2O, and VC improvement preextubation to preintubation by 4 mL/kg were significantly associated with successful extubation. Failed extubation or need for tracheostomy correlated with autonomic dysfunction, pulmonary comorbidities, and prolonged LOS in the ICU. Such parameters may be helpful in identifying patients with GBS likely to succeed extubation versus early referral for tracheostomy.
Extubation; Guillain-Barré syndrome; mechanical ventilation; vital capacity
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; Neuromonitoring; Genomics; Neuroimaging; Biomarkers
Intracerebral hemorrhage (ICH) expansion is common during the first 24 hours after onset, but the pattern and pace of hyperacute hemorrhage growth have not been described because serial imaging is typically performed over the course of hours and days, not minutes. The purpose of this study is to elucidate the spatial and temporal characteristics of hyperacute hemorrhage expansion within minutes of ICH onset.
An 86-year-old man with probable cerebral amyloid angiopathy developed an ICH while in the MRI scanner. Hyperacute hemorrhage growth was captured at three time points over a 14-minute interval of MRI data acquisition and at a fourth time point with CT 22 hours later. MRI and CT datasets were spatially coregistered, and three-dimensional models of ICH expansion were generated.
Longitudinal analysis revealed that the spatial pattern of ICH growth was asymmetric at each time point. Maximal expansion occurred along the anterior-posterior plane during the first four minutes but along the superior-inferior plane during the next 10 minutes. The temporal pace of ICH expansion was also non-uniform, as growth along the anterior-posterior plane outpaced medial-lateral growth during the first 4 minutes (2.8 cm vs. 2.5 cm), but medial-lateral growth outpaced anterior-posterior growth over the next 10 minutes (1.0 cm vs. 0.2 cm).
We provide evidence for asymmetric, non-uniform expansion of a hyperacute hemorrhage. These serial imaging observations suggest that hemorrhage expansion may be caused by local cascades of secondary vessel rupture as opposed to ongoing bleeding from a single ruptured vessel.
intracerebral hemorrhage; MRI; cerebral amyloid angiopathy; cerebral microbleed
To address the question: does non-convulsive status epilepticus warrant the same aggressive treatment as convulsive status epilepticus?
We used a decision model to evaluate the risks and benefits of treating non-convulsive status epilepticus with intravenous anesthetics and ICU-level aggressive care. We investigated how the decision to use aggressive versus non-aggressive management for non-convulsive status epilepticus impacts expected patient outcome for four etiologies: absence epilepsy, discontinued antiepileptic drugs, intraparenchymal hemorrhage, and hypoxic ischemic encephalopathy. Each etiology was defined by distinct values for five key parameters: baseline mortality rate of the inciting etiology; efficacy of non-aggressive treatment in gaining control of seizures; the relative contribution of seizures to overall mortality; the degree of excess disability expected in the case of delayed seizure control; and the mortality risk of aggressive treatment.
Non-aggressive treatment was favored for etiologies with low morbidity and mortality such as absence epilepsy and discontinued antiepileptic drugs. The risk of aggressive treatment was only warranted in etiologies where there was significant risk of seizure-induced neurologic damage. In the case of post-anoxic status epilepticus, expected outcomes were poor regardless of the treatment chosen. The favored strategy in each case was determined by strong interactions of all five model parameters.
Determination of the optimal management approach to non-convulsive status epilepticus is complex and is ultimately determined by the inciting etiology.
Non-convulsive status epilepticus; Risk benefit analysis; NCSE; Decision analysis
Clinical monitoring of cerebral blood flow (CBF) autoregulation in patients undergoing liver transplantation may provide a means for optimizing blood pressure to reduce the risk of brain injury. The purpose of this pilot project is to test the feasibility of autoregulation monitoring with transcranial Doppler (TCD) and near infrared spectroscopy (NIRS) in patients undergoing liver transplantation and to assess changes that may occur perioperatively.
We performed a prospective observational study in 9 consecutive patients undergoing orthotopic liver transplantation. Patients were monitored with TCD and NIRS. A continuous Pearson’s correlation coefficient was calculated between mean arterial pressure (MAP) and CBF velocity and between MAP and NIRS data, rendering the variables mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Both Mx and COx were averaged and compared during the dissection phase, anhepatic phase, first 30 mins of reperfusion, and remaining reperfusion phase. Impaired autoregulation was defined as Mx ≥ 0.4.
Autoregulation was impaired in one patient during all phases of surgery, in two patients during the anhepatic phase, and in one patient during reperfusion. Impaired autoregulation was associated with a MELD score > 15 (p=0.015) and postoperative seizures or stroke (p<0.0001). Analysis of Mx categorized in 5-mmHg bins revealed that MAP at the lower limit of autoregulation (MAP when Mx increased to ≥ 0.4) ranged between 40 and 85 mmHg. Average Mx and average COx were significantly correlated (p=0.0029). The relationship between COx and Mx remained when only patients with bilirubin > 1.2 mg/dL were evaluated (p=0.0419). There was no correlation between COx and baseline bilirubin (p=0.2562) but MELD score and COx were correlated (p=0.0458). Average COx was higher for patients with a MELD score > 15 (p=0.073) and for patients with a neurologic complication than for patients without neurologic complications (p=0.0245).
These results suggest that autoregulation is impaired in patients undergoing liver transplantation, even in the absence of acute, fulminant liver failure. Identification of patients at risk for neurologic complications after surgery may allow for prompt neuroprotective interventions, including directed pressure management.
Reliable and efficient data repositories are essential for the advancement of research in Neurocritical care. Various factors, such as the large volume of patients treated within the Neuro ICU, their differing length and complexity of hospital stay and the substantial amount of desired information can complicate the process of data collection.
We adapted the tools of process improvement to the data collection and database design of a research repository for a Neuroscience intensive care unit. Using the Shewhart-Deming method, we implemented an iterative approach to improve the process of data collection for each element. After an initial design phase, we re-evaluated all data fields that were challenging or time-consuming to collect. We then applied root-cause analysis to optimize the accuracy and ease of collection, and to determine the most efficient manner of collecting the maximal amount of data.
During a six month period, we iteratively analyzed the process of data collection for various data elements. For example, the pre-admission medications were found to contain numerous inaccuracies after comparison with a gold standard (sensitivity 71% and specificity 94%). Also, our first method of tracking patient admissions and discharges contained higher than expected errors (sensitivity 94% and specificity 93%). In addition to increasing accuracy, we focused on improving efficiency. Through repeated incremental improvements, we reduced the number of subject records that required daily monitoring from 40 to 6 per day, and decreased daily effort from 4.5 to 1.5 hours per day.
By applying process improvement methods to the design of a Neuroscience ICU data repository, we achieved a three-fold improvement in efficiency and increased accuracy. Although individual barriers to data collection will vary from institution to institution, a focus on process improvement is critical to overcoming these barriers.
Cerebral edema following ischemic stroke is frequently treated with mannitol and hypertonic saline (HS) although their relative cerebrovascular and metabolic effects are incompletely understood, and may operate independent of their ability to lower intracranial pressure. We compared the effects of 20% mannitol and 23.4% saline on cerebral blood flow (CBF), blood volume (CBV), oxygen extraction fraction (OEF) and oxygen metabolism (CMRO2), in nine ischemic stroke patients who deteriorated and had >2 mm midline shift on imaging. 15O-PET was performed before and one hour after randomly assigned equi-osmolar doses of mannitol (1.0 g/kg) or 23.4% saline (0.686 mL/kg). Baseline CBF (ml/100g/min) in the infarct core, peri-infarct region, remaining ipsilateral hemisphere and contralateral hemisphere in the mannitol group was 5.0±3.9, 25.6±4.4, 35.6±8.6 and 45.5±2.2 and in the HS group was 8.3±9.8, 35.3±10.9, 38.2±15.1, and 35.2±12.4. There was a trend for CBF to rise in the contralateral hemisphere after mannitol from 45.5±12.2 to 57.6±21.7, p=0.098, but not HS. CBV, OEF and CMRO2 did not change after either agent. Change in CBF in the contralateral hemisphere following osmotic therapy was strongly correlated with baseline blood pressure (R2= 0.879, p=0.002). We conclude that at higher perfusion pressures osmotic agents may raise CBF in non-ischemic tissue.
osmotic; hypertonic saline; mannitol; cerebral blood flow; cerebral blood volume
Background and Purpose
The perihematomal hyperintensity is commonly interpreted to represent cerebral edema following ICH, but the accuracy of this interpretation is unknown. We therefore investigated the relationship between changes in PHH and changes in hemispheric brain volume as a measure of edema during the first week after ICH.
Fifteen individuals aged 66±13 with baseline hematoma size of 13.1 mL (range 3–43) were prospectively studied with sequential MRI 1.0±0.5, 2.6±0.9, and 6.5±1.0 days after spontaneous supratentorial ICH. Changes in hemispheric brain volume were assessed on MPRAGE using the Brain-Boundary Shift Integral. Hematoma and PHH volumes were measured on T2-weighted images.
Brain volume increased a small but statistically significant amount (6.3±8.0 mL, 0.6±0.7%) between the first and second scans relative to 10 normal controls (−0.9±4.1 mL, p=0.02) and returned toward baseline at the third scan (1.5±9.5 mL vs. controls 0.9±4.0 mL, p=0.85). There were no significant differences in the volume changes between the two hemispheres at scan 2 or scan 3. At both scan 2 (p=0.04) and scan 3 (p=0.004), the change in PHH was significantly greater than and poorly correlated with the change in ipsilateral hemispheric volume. There were no significant correlations between change in NIHSS and change in PHH, ipsilateral, or total brain volume at scan 2 or scan 3 (all p> 0.05).
In patients with small-to-moderate-sized hematomas, change in PHH was a poor measure of brain edema in the first week following ICH. A small degree of bihemispheric brain swelling occurred but was of little clinical significance.
Hyperthermia following a severe traumatic brain injury (TBI) is common, potentiates secondary injury, and worsens neurological outcome. Conventional fever treatment is often ineffective. An induced normothermia protocol, utilizing intravascular cooling, was used to assess the impact on fever incidence and intracranial pressure (ICP) in patients with severe TBI.
A comparative cohort study of 21 adult patients with severe TBI (GCS ≤ 8) treated with induced normothermia [36–36.5°C rectal probe setting; intravascular cooling catheter (CoolLine®, Alsius Corporation, Irvine, CA)] were matched by age, gender, and severity of injury to 21 historical control severe TBI patients treated with conventional fever control methods. ICP was measured via an external ventricular catheter and time duration for ICP > 25 mmHg was calculated for the initial 72-h monitoring period. Non-parametric rank tests were performed.
Mean (±SD) or median [range] demographics did not differ between groups [total N = 42 (6 female, 36 male, age 36.4 ± 14.8 years and initial GCS 7 [3-8], median and range]. Fever burden in the first 3 days (time >38°C) in the induced normothermia versus control group was significantly less at 1.6% versus 10.6%, respectively (P = 0.03). Mean ICP for patients with induced normothermia versus control was 12.74 ± 4.0 and 16.37 ± 6.9 mmHg, respectively. Furthermore, percentage of time with ICP > 25 mmHg was significantly less in the induced normothermia group (P = 0.03).
Induced normothermia (fever prophylaxis via intravascular cooling catheter) is effective in reducing fever burden and may offer a means to attenuate secondary injury, as evidenced by a reduction in the intracranial hypertension burden.
Traumatic brain injury; Fever; Normothermia; Intracranial pressure; Critical care medicine
Drowning is a leading cause of accidental death. Survivors may sustain severe neurologic morbidity. There is negligible research specific to brain injury in drowning making current clinical management non-specific to this disorder. This review represents an evidence-based consensus effort to provide recommendations for management and investigation of the drowning victim. Epidemiology, brain-oriented prehospital and intensive care, therapeutic hypothermia, neuroimaging/monitoring, biomarkers, and neuroresuscitative pharmacology are addressed. When cardiac arrest is present, chest compressions with rescue breathing are recommended due to the asphyxial insult. In the comatose patient with restoration of spontaneous circulation, hypoxemia and hyperoxemia should be avoided, hyperthermia treated, and induced hypothermia (32–34 °C) considered. Arterial hypotension/hypertension should be recognized and treated. Prevent hypoglycemia and treat hyperglycemia. Treat clinical seizures and consider treating non-convulsive status epilepticus. Serial neurologic examinations should be provided. Brain imaging and serial biomarker measurement may aid prognostication. Continuous electroencephalography and N20 somatosensory evoked potential monitoring may be considered. Serial biomarker measurement (e.g., neuron specific enolase) may aid prognostication. There is insufficient evidence to recommend use of any specific brain-oriented neuroresuscitative pharmacologic therapy other than that required to restore and maintain normal physiology. Following initial stabilization, victims should be transferred to centers with expertise in age-specific post-resuscitation neurocritical care. Care should be documented, reviewed, and quality improvement assessment performed. Preclinical research should focus on models of asphyxial cardiac arrest. Clinical research should focus on improved cardiopulmonary resuscitation, re-oxygenation/reperfusion strategies, therapeutic hypothermia, neuroprotection, neurorehabilitation, and consideration of drowning in advances made in treatment of other central nervous system disorders.
Drowning; Brain; Asphyxia; Cardiac arrest
Cardiac morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH) are attributable to myocardial injury, decreased ventricular function, and ventricular arrhythmia (VA). Our objective was to test the relationships between QTc prolongation, VA, and survival after SAH.
In 200 subjects with acute aneurysmal SAH, electrocardiograms, echocardiograms, and telemetry were evaluated. Serum electrolytes and troponin were also evaluated.
Initial QTc (mean 460 ± 45 ms) was prolonged (≥470 ms) in 38% of subjects and decreased on follow-up (469 ± 49 initial vs. 435 ± 31 ms follow-up; N = 89; P < 0.0001). VA was present in 14% of subjects, 52% of subjects with VA had QTc ≥ 470 ms, and initial QTc trended toward longer duration in subjects with VA (474 ± 61 vs. 457 ± 42 ms; P = 0.084). Multivariate analysis demonstrated significant predictors of VA after SAH were increasing age (OR 1.3/5 years; P = 0.025), increasing stroke severity (OR 1.8; P = 0.009), decreasing heart rate (OR 0.5/10 beats/min; P= 0.006), and the absence of angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist use at SAH onset (OR 0.10; P = 0.027). All-cause mortality was 19% (25/135) at 3 months and subjects with VA had significantly higher mortality than those without VA (37% vs. 16%; P = 0.027).
These data demonstrate that QTc prolongation and arrhythmias are frequently noted after SAH, but arrhythmias are often not associated with QTc prolongation. In addition, the presence of VA identified subjects at greater risk of mortality following their SAH.
Ventricular arrhythmia; Subarachnoid hemorrhage; Gender; QTc prolongation
Animal studies have shown that even a small temperature elevation of one degree Celsius can cause detrimental effects after brain injury. Since the skull acts as a potential thermal insulator, we hypothesized that decompressive hemicraniectomy facilitates surface cooling and lowers brain temperature.
Forty-eight patients with severe brain injury (TBI=38, ICH=10) with continuous brain temperature monitoring were retrospectively studied and grouped into “hemicraniectomy” (n=20) or “no hemicraniectomy” (n=28) group. The paired measurements of core body (TCore) and brain (TBr) temperature were recorded at 1-min intervals over 12±7 days. As a surrogate measure for the extent of surface heat loss from the brain, ΔTCore-Br was calculated as the difference between TCore and TBr with each recording. In order to accommodate within-patient temperature correlations, mixed-model regression was used to assess the differences in ΔTCore-Br between those with and without hemicraniectomy, adjusted for core body temperature and diagnosis.
A total of 295,883 temperature data pairs were collected (median [IQR] per patient: 5047 [3125–8457]). Baseline characteristics were similar for age, sex, diagnosis, incidence of sepsis, Glasgow Coma Scale score, ICU mortality, and ICU length of stay between the two groups. The mean difference in ΔTCore-Br, was 1.29±0.87 °C for patients with and 0.80±0.86 °C for patients without hemicraniectomy (p<0.0001). In mixed-model regression, accounting for temperature correlations within patients, hemicraniectomy and higher TCore were associated with greater ΔTCore-Br (hemicraniectomy: estimated effect=0.60, p=0.003; TCore: estimated effect=0.21, p<0.0001).
Hemicraniectomy is associated with modestly but significantly lower brain temperature relative to core body temperature.
Decompressive hemicraniectomy; brain temperature; brain tissue oxygen monitor
Delayed deterioration associated with vasospasm (DDAV) after aneurismal subarachnoid hemorrhage (SAH) is a major cause of morbidity. We have previously shown that myeloid cell depletion before experimental SAH in a murine model ameliorates DDAV. In this study, we address whether systemic administration of lipopolysaccharide (LPS) worsens DDAV in a myeloid cell-dependent fashion.
We challenged mice in our experimental SAH model with LPS before hemorrhage and evaluated the degree of vasospasm on day 6 with India ink angiography; behavioral deficits by rotorod, Y-maze and Barnes maze testing; microglial activation early after SAH by immunohistochemistry; and the brain levels of the chemokines CCL5 and KC at the time of vasospasm. Another group of animals were given the myeloid cell-depleting antibody against the neutrophil antigen Ly6G/C prior to LPS administration and SAH.
LPS followed by SAH significantly worsens angiographic vasospasm as well as performance on the Barnes maze but not the Y-maze or rotorod tests. There was an increased activation of microglia in animals with LPS before SAH compared to SAH alone. Depletion of myeloid cells before LPS administration inhibited the development of vasospasm, improved the performance on behavioral tests and reduced microglial activation. The chemokines CCL5 and KC were incrementally elevated in SAH and LPS SAH but suppressed in animals with myeloid cell depletion.
LPS administration before SAH worsens DDAV through a myeloid cell-dependent mechanism supporting studies in humans which show that systemic inflammation increases the likelihood of developing DDAV.
Subarachnoid hemorrhage; LPS; Delayed cerebral vasospasm; Innate immunity; Behavior
Therapeutic hypothermia (TH) improves outcomes in comatose patients resuscitated from cardiac arrest. However, nonconvulsive status epilepticus (NCSE) may cause persistent coma. The frequency and timing of NCSE after cardiac arrest is unknown.
Review of consecutive subjects treated with TH and receiving continuous EEG (cEEG) monitoring between 8/1/2009 and 11/16/2010. Demographic data, survival, and functional outcome were prospectively recorded. Each cEEG file was analyzed using standard definitions to define NCSE. Data were analyzed using descriptive and non-parametric statistics.
Mean age of the 101 subjects was 57 years (SD 15) with most subjects being male (N = 55, 54%) and experiencing out-of-hospital cardiac arrest (N = 78; 77%). Ventricular fibrillation was the initial cardiac rhythm in 39 (38%). All subjects received TH. Thirty subjects (30%) awoke at a median of 41 h (IQR 30, 61) after cardiac arrest. A total of 29/30 (97%) subjects surviving to hospital discharge were awake. Median interval from arrest to placement of cEEG was 9 h (IQR 6, 12), at which time the mean temperature was 33.9°C. NCSE occurred in 12 (12%) subjects. In 3/12 (25%) subjects, NCSE was present when the cEEG recording began. In 4 subjects, NCSE occurred within 8 h of cEEG recording. One (8%) subject with NCSE survived in a vegetative state.
NCSE is common in comatose post-cardiac arrest subjects receiving TH. Most seizures occur within the first 8 h of cEEG recording and within the first 12 h after resuscitation from cardiac arrest. Outcomes are poor in those who experience NCSE.
Hypothermia; Cardiac arrest; Seizures; Status epilepticus; Coma; Anoxic brain injury; Outcomes
The December 2003 report from the National Institute of Neurological Disorders and Stroke (NINDS) Workshop on priorities for clinical research in intracerebral hemorrhage (ICH) recommended clinical trials for evaluation of blood pressure management in acute ICH as a leading priority. The Special Writing Group of the Stroke Council of the American Heart Association in 1999 and 2007 emphasized the need for clinical trials to ensure evidence-based treatment of acute hypertensive response in ICH. To address important gaps in knowledge, we conducted a pilot study funded by the NINDS, Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) I Trial, during 2004–2008 to determine the appropriate level of systolic blood pressure (SBP) reduction. We now have initiated a multicenter, randomized Phase III trial, the ATACH II Trial, to definitively determine the efficacy of early, intensive, anti-hypertensive treatment using intravenous (IV) nicardipine initiated within 3 h of onset of ICH and continued for the next 24 h in subjects with spontaneous supratentorial ICH. The primary hypothesis of this large (N = 1,280), streamlined, and focused trial is that SBP reduction to ≤140 mm Hg reduces the likelihood of death or disability at 3 months after ICH, defined by modified Rankin scale score of 4–6, by at least 10% absolute compared to standard SBP reduction to ≤180 mm Hg. The ATACH II trial is a natural extension of numerous case series, the subsequent ATACH I pilot trial, and a preliminary, randomized, and controlled trial in this patient population funded by the Australian National Health and Medical Research Council. Both trials recently confirmed the safety and tolerability of both the regimen and goals of antihypertensive treatment in acutely hypertensive patients with ICH, as proposed in the present trial. The underlying mechanism for this expected beneficial effect of intensive treatment is presumably mediated through reduction of the rate and magnitude of hematoma expansion observed in approximately 73% of the patients with acute ICH. The Australian trial provided preliminary evidence of attenuation of hematoma expansion with intensive SBP reduction. The ATACH II trial will have important public health implications by providing evidence of, or lack thereof, regarding the efficacy and safety of acute antihypertensive treatment in subjects with ICH. This treatment represents a strategy that can be made widely available without the need for specialized equipment and personnel, and therefore, can make a major impact upon clinical practice for treating patients with ICH.
Intracerebral hemorrhage; Clinical trial; Randomization; Acute hypertensive response; Hematoma enlargement
Intracranial pressure (ICP) remains a pivotal physiological signal for managing brain injury and subarachnoid hemorrhage (SAH) patients in neurocritical care units. Given the vascular origin of the ICP, changes in ICP waveform morphology could be used to infer cerebrovascular changes. Clinical validation of this association in the setting of brain trauma, and SAH is challenging due to the multi-factorial influences on, and uncertainty of, the state of the cerebral vasculature.
To gain a more controlled setting, in this articel, we study ICP signals recorded in four uninjured patients undergoing a CO2 inhalation challenge in which hypercapnia induced acute cerebral vasodilatation. We apply our morphological clustering and analysis of intracranial pressure (MOCAIP) algorithm to identify six landmarks on individual ICP pulses (based on the three established ICP sub-peaks; P1, P2, and P3) and extract 128 ICP morphological metrics. Then by comparing baseline, test, and post-test data, we assess the consistency and rate of change for each individual metric.
Acute vasodilatation causes consistent changes in a total of 72 ICP pulse morphological metrics and the P2 sub-region responds to cerebral vascular changes in the most consistent way with the greatest change as compared to P1 and P3 sub-regions.
Since the dilation/constriction of the cerebral vasculature resulted in detectable consistent changes in ICP MOCIAP metrics, by an extended monitoring practice of ICP that includes characterizing ICP pulse morphology, one can potentially detect cerebrovascular changes, continuously, for patients under neurocritical care.
Intracranial pressure; Hemodynamic signal; Cerebral vasodilation; Hypercapnia; Waveform morphology
Elevated levels of B-type natriuretic peptide (BNP) have been associated with cardiac dysfunction and adverse neurological outcomes after subarachnoid hemorrhage (SAH). We sought to determine whether elevated levels of BNP are independently associated with radiographic cerebral infarction after SAH.
Plasma BNP levels were measured after admission, a mean of 5.5 ± 3.0 days after SAH onset. Cerebral infarction was determined by retrospective review of computerized tomography (CT) scans. Cerebral vasospasm was confirmed by the presence of vascular narrowing on cerebral angiogram. The association between BNP and cerebral infarction was quantified using multivariable logistic regression and reverse stepwise elimination of clinical covariates. A stratified analysis was performed to quantify the association between BNP levels and infarction in patients with and without angiographic vasospasm.
BNP levels were measured from 119 subjects. The median BNP level was 105 pg/ml (interquartile range 37–275 pg/ml). In our multivariable model, the top quartile of BNP levels (≥276 pg/ml) were associated with an increased odds of cerebral infarction (OR 4.2, P = 0.009). The stratified analysis showed that the association between BNP and infarction was strongest in patients without angiographic vasospasm (OR 7.8, P = 0.006).
Elevated levels of BNP are strongly and independently associated with cerebral infarction, and the association is most pronounced in patients without angiographic vasospasm. These results provide further evidence that other mechanisms can contribute to infarction, and BNP may be a useful biomarker in detecting patients at risk for adverse outcomes without large vessel vasospasm.
Subarachnoid hemorrhage; Cerebral infarction; Cerebral vasospasm; B-type natriuretic peptide
We describe institutional vasopressor usage, and examine the effect of vasopressors on hemodynamics: heart rate (HR), mean arterial blood pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation (PbtO2), and jugular venous oximetry (SjVO2) in adults with severe traumatic brain injury (TBI).
We performed a retrospective analysis of 114 severely head injured patients who were admitted to the neurocritical care unit of Level 1 trauma center and who received vasopressors (phenylephrine, norepinephrine, dopamine, vasopressin or epinephrine) to increase blood pressure
Phenylephrine was the most commonly used vasopressor (43%), followed by norepinephrine (30%), dopamine (22%), and vasopressin (5%). Adjusted for age, gender, injury severity score, vasopressor dose, baseline blood pressure, fluid administration, propofol sedation, and hypertonic saline infusion, phenylephrine use was associated with 8 mmHg higher mean arterial pressure (MAP) than dopamine (P = 0.03), and 12 mmHg higher cerebral perfusion pressure (CPP) than norepinephrine (P = 0.02) during the 3 h after vasopressor start. There was no difference in ICP between the drug groups, either at baseline or after vasopressor treatment.
Most severe TBI patients received phenylephrine. Patients who received phenylephrine had higher MAP and CPP than patients who received dopamine and norepinephrine, respectively.
Traumatic brain injury; Vasopressor; Phenylephrine; Norepinephrine; Dopamine; Cerebral perfusion pressure
Continuous EEG (cEEG) monitoring is being used with increasing frequency in critically ill patients, most often to detect non-convulsive seizures. While cEEG is non-invasive and feasible in the critical care setting, it is also expensive and labor intensive, and there has been little study of its impact on clinical care. We aimed to determine prospectively the impact of cEEG on clinical management in critically ill children.
Critically ill children (non-neonates) with acute encephalopathy underwent cEEG. Study enrollment and data collection were prospective.
100 children were studied. EEG monitoring led to specific clinical management changes in 59 children. These included initiating or escalating anti-seizure medications in 43 due to seizure detection, demonstrating that a specific event (subtle movement or vital sign change) was not a seizure in 21, or obtaining urgent neuroimaging that led to a clinical change in 3. In the remaining 41 children, cEEG ruled out the presence of non-convulsive seizures but did not lead to a specific change in clinical management.
EEG monitoring led to changes in clinical management in the majority of patients, suggesting it may have an important role in management of critically ill children. Further study is needed to determine whether the management changes elicited by cEEG improve outcome.
Seizure; Status epilepticus; Pediatric; Critically Ill; Electroencephalogram; EEG monitoring
Endothelin-1 (ET-1) is a potent vasoconstrictor implicated in the pathogenesis of vasospasm and delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients. The aim of this study was to investigate the relationship between cerebrospinal fluid (CSF) ET-1 levels and angiographic vasospasm and DCI.
Patients with aSAH were consented (n = 106). Cerebral vasospasm was determined by angiography. DCI was determined by transcranial Doppler (TCD) results and/or angiogram results with corresponding clinical deterioration. CSF ET-1 levels over 14 days after the initial insult was quantified by ELISA. ET-1 analysis included a group-based trajectory analysis and ET-1 exposure rate during 24, 48, and 72 h prior to, as well as 72 h post angiography, or clinical deterioration.
Trajectory analysis revealed two distinct groups of subjects with 56% of patients in the low ET-1 trajectory group (mean at day 1 = 0.31 pg/ml; SE = 0.04; mean at day 14 = 0.41 pg/ml; SE = 0.15) and 44% of patients in the high ET-1 trajectory group (mean at day 1 = 0.65 pg/ml; SE = 0.08; mean at day 14 = 0.61 pg/ml; SE = 0.06). Furthermore, we observed that ET-1 exposure rate 72 h before angiography and clinical spasm was a significant predictor of both angiographic vasospasm and DCI, whereas, ET-1 exposure after angiography and clinical spasm was not associated with either angiographic vasospasm or DCI.
Based on these results we conclude that ET-1 concentrations are elevated in a sub-group of patients and that the acute (72 h prior to angiography and clinical neurological deterioration), but not chronic, elevations in CSF ET-1 concentrations are indicative of the pathogenic alterations of vasospasm and DCI in aSAH patients.
aSAH; CSF; Endothelin-1; Vasospasm; DCI