What drives the increasing utilisation of hemicraniectomy in acute ischaemic stroke?

BACKGROUND: Survival after malignant middle cerebral artery infarcts is dismal. In 2007, a pooled analysis of randomised trials in Europe demonstrated a substantial survival benefit from decompressive hemicraniectomy, with a number needed to treat of 2 for survival. Our objective was to review factors driving the nationwide utilisation of this potentially lifesaving procedure in the USA. METHODS: Data from the Nationwide Inpatient Sample for 2001-2009 were reviewed. Hospitalisations with a discharge diagnosis of an acute ischaemic stroke were included. Hemicraniectomy utilisation was determined within this subset. Nationwide estimates of utilisation were calculated for each year. Trends across the years were estimated for various subgroups. RESULTS: From 2001 to 2009, there were an estimated 4 909 519 acute ischaemic stroke discharges. The estimated frequency of hemicraniectomy increased from 118 (0.02% of stroke discharges in 2001) to 804 (0.15% of stroke discharges in 2009) (trend p<0.001). The increased utilisation was greatest for younger subjects (age<45 years; trend p<0.001) and men (trend p<0.001). Urban teaching hospitals were responsible for the greatest increase in hemicraniectomy utilisation: from 0.05% of stroke discharges in 2001 to 0.28% in 2009. The increase was steady and sustained over the decade. In comparison, rural and urban non-teaching hospitals showed a much smaller improvement in utilisation. CONCLUSION: Utilisation of hemicraniectomy in the USA has increased significantly, in line with compelling results from European clinical trials. Early transfer of patients with malignant infarctions to urban teaching centres could potentially extend the survival benefit to a larger population.

A prospective evaluation of labetalol versus nicardipine for blood pressure management in patients with acute stroke.

INTRODUCTION: Acute hypertension is common following stroke and contributes to poor outcomes. Labetalol and nicardipine are often used for acute hypertension but there are little data comparing the two. This study is to evaluate the therapeutic response and tolerability of these two agents following acute stroke. METHODS: This is a prospective, pseudo-randomized study comparing labetalol and nicardipine for blood pressure (BP) management in acute stroke patients. Patients who presented to the emergency department (ED) with confirmed hemorrhagic or ischemic stroke received either labetalol or nicardipine for 24 h from ED admission. Therapeutic response was assessed by achievement of goal BP, time spent within goal, and variability in BP. Clinical outcomes including length of stay, clinical status at discharge, and in-hospital mortality were recorded. RESULTS: 54 patients were enrolled (labetalol = 28; nicardipine = 26) with 25 ± 6 BP measurements per patient. Majority of patients had a hemorrhagic stroke and baseline characteristics were similar between groups. All patients who received nicardipine achieved goal BP compared to 17 (61 %) in the labetalol group (p < 0.001) with 89 % nicardipine-treated patients achieved goal BP within 60 min of drug initiation versus 25 % in labetalol group (p < 0.001). Nicardipine group had better maintenance of BP, a greater percentage of time spent within goal, and significantly less BP variability compared to labetalol group (p < 0.001). Less rescue antihypertensive agents were given to nicardipine group than labetalol group (p < 0.001). The incidences of adverse drug events were similar between groups and there were no differences in clinical outcomes. CONCLUSION: In acutely hypertensive stroke patients, superior therapeutic response was achieved with nicardipine versus labetalol. Despite this, there was no demonstrable difference in clinical outcomes.

Low-dose recombinant tissue-type plasminogen activator enhances clot resolution in brain hemorrhage: the intraventricular hemorrhage thrombolysis trial.

BACKGROUND AND PURPOSE: Patients with intracerebral hemorrhage and intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events, and for its effect on the rate of intraventricular clot lysis. METHODS: Forty-eight patients were enrolled at 14 centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen activator (rtPA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the 2 groups. RESULTS: Severity factors, including admission Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume, and blood pressure were evenly distributed, as were adverse events, except for an increased frequency of respiratory system events in the placebo-treated group. Neither intracranial pressure nor cerebral perfusion pressure differed substantially between treatment groups on presentation, with external ventricular device closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the prespecified threshold for mortality (18% rtPA; 23% placebo), ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo, which approached statistical significance; P=0.1). The median duration of dosing was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial effect of rtPA on rate of clot resolution. CONCLUSIONS: Low-dose rtPA for the treatment of intracerebral hemorrhage with intraventricular hemorrhage has an acceptable safety profile compared to placebo and historical controls. Data from a well-designed phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment.

Pharmacokinetics of single-dose daptomycin in patients with suspected or confirmed neurological infections.

There are currently few or no published data on the amount of cerebrospinal fluid (CSF) penetration of daptomycin in patients with suspected or documented neurosurgical infections. We conducted a prospective study, assessing the pharmacokinetics and CSF penetration of a single intravenous daptomycin dose administered at 10 mg/kg, based on total body weight (TBW), in six neurosurgical patients with indwelling external CSF shunts with suspected or documented meningitis or ventriculitis. Each patient had four blood and CSF samples drawn simultaneously at specific times after the end of infusion: 30 min, 6 h, 12 h, and 24 h. Pharmacokinetic parameters of daptomycin in serum were calculated using standard noncompartmental methods, and daptomycin was assayed using high-performance liquid chromatography (for serum) or liquid chromatography with mass spectrometry (for CSF). The mean (± standard deviation [SD]) maximum measured daptomycin concentrations were 93.7 ± 17.3 mg/liter in serum at 0.5 h postinfusion and 0.461 ± 0.51 mg/liter in CSF at 6 h postinfusion. The mean (± SD) daptomycin minimum concentrations were 13.8 ± 4.8 mg/liter in serum at 24 h postinfusion and 0.126 ± 0.12 mg/liter in CSF at 0.5 h postinfusion. The mean daptomycin penetration, determined by the area under the concentration-time curve in CSF (AUC(CSF))/(AUC(serum) ratio), was 0.8%. Corrected for protein binding, the overall CSF penetration was 11.5%. Additional pharmacokinetic studies evaluating multiple and/or higher dosages of daptomycin are necessary in human subjects to better characterize the CSF penetration of daptomycin in neurosurgical patients.

Time of day, outcome, and response to thrombolytic therapy: the National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Trial experience.

OBJECTIVE: Circadian pattern for the onset of acute ischemic stroke has been described; however, data assessing an association between thrombolytic therapy efficacy and circadian rhythm are limited. We assessed the relationship between the time of stroke onset and neurologic outcomes after thrombolytic therapy for acute ischemic stroke in the National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator (rt-PA) Stroke Trial. METHODS: We conducted exploratory, post hoc analysis of 624 patients in the NINDS rt-PA Stroke Trial. Variables assessed included presenting time of day (4- and 6-hour time blocks), outcome variables, stroke subtypes, treatment assignment, and biological markers. Outcome variables included 3-month mortality, clinical outcome at 3 months, intracranial hemorrhage (ICH), computed tomography lesion volume at 3 months, and deterioration at 24 hours. RESULTS: The distribution of patients in the time blocks was balanced between the rt-PA and placebo groups. There was not a clear circadian variation in the stroke onset time. There were no associations detected between stroke onset time and clinical outcome, computed tomography lesion volume, and asymptomatic hemorrhage. Patients treated with rt-PA whose stroke onset was between 0401 and 0800 hours had less symptomatic ICH, whereas those who received rt-PA between 0000 and 0400 hours had a 43% incidence of symptomatic ICH. Patients in the placebo group who had stroke onset between 1801 and 2400 hours had lower chances for neurologic deterioration. Patients who had a stroke between 0001 and 0400 hours had the highest fibrinogen concentrations. CONCLUSIONS: We did not find a circadian pattern to time of day of stroke onset in the patients included in the NINDS rt-PA Stroke Trial. The effect of rt-PA treatment on favorable outcome was independent of time of day of stroke onset. Patients who received rt-PA between 4 and 8 am were less likely to develop symptomatic ICH.

Effect of prophylactic transluminal balloon angioplasty on cerebral vasospasm and outcome in patients with Fisher grade III subarachnoid hemorrhage: results of a phase II multicenter, randomized, clinical trial.

BACKGROUND AND PURPOSE: Cerebral vasospasm continues to be a major cause of poor outcome in patients with ruptured aneurysms. Prophylactic Transluminal Balloon Angioplasty (pTBA) appeared to prevent delayed ischemic neurological deficit in a pilot study. A phase II multicenter randomized clinical trial was subsequently designed. METHODS: One hundred and seventy patients with Fisher Grade III subarachnoid hemorrhage were enrolled in the study. Of these, 85 patients were randomized to the treatment group and underwent pTBA within 96 hours after subarachnoid hemorrhage. Main end points of the study included the 3-month dichotomized Glasgow Outcome Score (GOS), development of delayed ischemic neurological deficit (DIND), occurrence of Transcranial Doppler (TCD) vasospasm, and length of stay in the ICU and hospital. RESULTS: The incidence of DIND was lower in the pTBA group (P=0.30) and fewer patients required therapeutic angioplasty to treat DIND (P=0.03). Overall pTBA resulted in an absolute risk reduction of 5.9% and a relative risk reduction of 10.4% unfavorable outcome (P=0.54). Good grade patients had absolute and relative risk reductions of respectively 9.5 and 29.4% (P=0.73). Length of stay in ICU and hospital was similar in both groups. Four patients had a procedure-related vessel perforation, of which three patients died. CONCLUSIONS: While the trial is unsuccessful as defined by the primary end point (GOS), proof of concept is confirmed by these results. Fewer patients tend to develop vasospasm after treatment with pTBA and there is a statistically significantly decreased need for therapeutic angioplasty. pTBA does not improve the poor outcome of patients with Fisher grade III subarachnoid hemorrhage.

Global white matter analysis of diffusion tensor images is predictive of injury severity in traumatic brain injury.

Conventional clinical neuroimaging is insensitive to axonal injury in traumatic brain injury (TBI). Immunocytochemical staining reveals changes to axonal morphology within hours, suggesting potential for diffusion-weighted magnetic resonance (MR) in early diagnosis and management of TBI. Diffusion tensor imaging (DTI) characterizes the three-dimensional (3D) distribution of water diffusion, which is highly anisotropic in white matter fibers owing to axonal length. Recently, DTI has been used to investigate traumatic axonal injury (TAI), emphasizing regional analysis in more severe TBI. In the current study, we hypothesized that a global white matter (WM) analysis of DTI data would be sensitive to TAI across a spectrum of TBI severity and injury to scan interval. To investigate this, we compared WM-only histograms of a scalar, fractional anisotropy (FA), between 20 heterogeneous TBI patients recruited from Detroit Medical Center, including six mild TBI (GCS 13-15), and 14 healthy age-matched controls. FA histogram parameters were correlated with admission GCS and posttraumatic amnesia (PTA). In all cases, including mild TBI, patients' FA histograms were globally decreased compared with control histograms. The shape of the TBI histograms also differed from controls, being more peaked and skewed. The mean FA, kurtosis and skewness were highly correlated suggesting a common mechanism. FA histogram properties also correlated with injury severity indexed by GCS and PTA, with mean FA being the best predictor and duration of PTA (r = 0.64) being superior to GCS (r = 0.47). Therefore, in this heterogeneous sample, the FA mean accounted for 40% of the variance in PTA. Increased diffusion in the short axis dimension, likely reflecting dysmyelination and swelling of axons, accounted for most of the FA decrease. FA is globally deceased in WM, including mild TBI, possibly reflecting widespread involvement. FA changes appear to be correlated with injury severity suggesting a role in early diagnosis and prognosis of TBI.

Energy expenditure in patients with nontraumatic intracranial hemorrhage.

BACKGROUND: Patients with intracerebral (ICH), intraventricular (IVH) and subarachnoid hemorrhage (SAH) have increased morbidity and mortality compared with other forms of stroke. We postulate that the systemic inflammatory state triggered by these forms of nontraumatic intracranial hemorrhage (IH) translates into higher nutrition requirements than traditionally assumed. In order to test this hypothesis, we performed a retrospective study comparing the resting energy expenditure (REE) of 14 mechanically ventilated IH patients with the REE of 6 severe traumatic brain injury (sTBI) patients (a disease known to induce an increased metabolic state). METHODS: Using nonparametric analysis, we compared 2 contemporary cohorts of patients-IH and sTBI-who required mechanical ventilation and who underwent indirect calorimetry (IC) within 7 days after the ictus. RESULTS: Fourteen patients with nontraumatic IH (IVH, 2; SAH, 9; SAH/ICH, 1; ICH/SAH/IVH, 2) who underwent IC within 7 days from injury were identified; median age: 59 (28-84) years, median admission Glasgow Coma Scale (GCS): 6 (4-9), and median APACHE II: 19.5 (15-28). A control cohort of 6 patients with sTBI was identified; median age: 57.5 (18-80) years, admission GCS: 6.5 (4-8), and APACHE II: 16 (11-31). Sedation was used in 11/14 patients with IH and in 5/6 severe TBI patients. No patient was pharmacologically paralyzed. Median REE was 1810 (1124-2806) and 2238 (1860-2780) kcal/d for the IH and for the sTBI patient cohorts, respectively. Using Wilcoxon signed ranks test, the 2 patient groups were found comparable in regard to baseline clinical variables and disease severity (APACHE II). We did not identify a statistically significant difference in the REE between these 2 cohorts of patients (p = .25). CONCLUSIONS: Patients with severe TBI and patients with IH have similar increments in metabolic rate during the initial phase (1 week from onset) of their disease. This information needs to be confirmed in a larger cohort of patients. If reproduced, our results suggest that nontraumatic IH patients are at high risk of inadequate nutrition if their metabolic rate is estimated after conventional nutrition practice.

A Consensus-Based Interpretation of the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure Trial.

Widely-varying published and presented analyses of the Benchmark Evidence From South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial of intracranial pressure (ICP) monitoring have suggested denying trial generalizability, questioning the need for ICP monitoring in severe traumatic brain injury (sTBI), re-assessing current clinical approaches to monitored ICP, and initiating a general ICP-monitoring moratorium. In response to this dissonance, 23 clinically-active, international opinion leaders in acute-care sTBI management met to draft a consensus statement to interpret this study. A Delphi method-based approach employed iterative pre-meeting polling to codify the group's general opinions, followed by an in-person meeting wherein individual statements were refined. Statements required an agreement threshold of more than 70% by blinded voting for approval. Seven precisely-worded statements resulted, with agreement levels of 83% to 100%. These statements, which should be read in toto to properly reflect the group's consensus positions, conclude that the BEST TRIP trial: 1) studied protocols, not ICP-monitoring per se; 2) applies only to those protocols and specific study groups and should not be generalized to other treatment approaches or patient groups; 3) strongly calls for further research on ICP interpretation and use; 4) should be applied cautiously to regions with much different treatment milieu; 5) did not investigate the utility of treating monitored ICP in the specific patient group with established intracranial hypertension; 6) should not change the practice of those currently monitoring ICP; and 7) provided a protocol, used in non-monitored study patients, that should be considered when treating without ICP monitoring. Consideration of these statements can clarify study interpretation.

Clinical trials in head injury.

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate significant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

Free fatty acids in cerebrospinal fluids from patients with traumatic brain injury.

Free fatty acid (FFA) concentrations in cerebrospinal fluid (CSF) are recognized as markers of brain damage in animal studies. There is, however, relatively little information regarding FFA concentrations in human CSF in normal and pathological conditions. The present study examined FFA concentrations in CSF from 15 patients with traumatic brain injury (TBI) and compared the data with values obtained from 73 contemporary controls. Concentrations of specific FFAs from TBI patients, obtained within 48 h of the insult were significantly greater than those in the control group (arachidonic, docosahexaenoic and myristic, P<0.001; oleic, palmitic, P<0.01; linoleic, P<0.05). Higher concentrations of total polyunsaturated fatty acids (P<0.001) and of arachidonic, myristic and palmitic acids measured individually in CSF (P<0.01) obtained 1 week after the insult were associated with a worse outcome at the time of hospital discharge using the Glasgow Outcome Scale. This preliminary investigation suggests that CSF FFA concentrations may be useful as a predictive marker of outcome following TBI.

Disposition of cefepime in the central nervous system of patients with external ventricular drains.

STUDY OBJECTIVE: To assess central nervous system (CNS) penetration of cefepime in adults with external ventricular drains and to compare the achieved cerebrospinal fluid (CSF) concentrations with the usual minimum inhibitory concentrations (MICs) of common pathogens. DESIGN: Open-label, prospective study. SETTING: University-affiliated medical center. PATIENTS: Seven patients with external ventricular drains and normal renal function (documented creatinine clearance > 60 ml/min) who received cefepime 2 g intravenously every 12 hours for treatment of nosocomial pneumonia. INTERVENTION: Serial serum and CSF samples were obtained concurrently after the fourth dose during one dosing interval. MEASUREMENTS AND MAIN RESULTS: The concentration-time profiles in serum and CSF were comodeled by using a two-compartment model with zero-order infusion to the central compartment. The CSF concentration-time profiles of the individual patients were compared with published MIC90 of common pathogens isolated in nosocomial meningitis. Our model reasonably characterized the disposition of cefepime in serum and CSF. Penetration into the CNS was 4-34% based on area under the curve and was 5-58% based on minimum concentration. CONCLUSION: Penetration of cefepime into the CNS was variable among the patients (4-34%) but appeared similar to that reported for other cephalosporins given to treat meningitis. The concentrations attained by most patients in this study were above the MIC90 of many common nosocomial organisms.

Free fatty acids in human cerebrospinal fluid following subarachnoid hemorrhage and their potential role in vasospasm: a preliminary observation.

OBJECT: The mechanisms leading to vasospasm following subarachnoid hemorrhage (SAH) remain unclear. Accumulation in cerebrospinal fluid (CSF) of free fatty acids (FFAs) may play a role in the development of vasospasm; however, in no previous study have concentrations of FFAs in CSF been examined after SAH. METHODS: We collected samples of CSF from 20 patients with SAH (18 cases of aneurysmal SAH and two cases of spontaneous cryptogenic SAH) and used a high-performance liquid chromatography assay to determine the FFA concentrations in these samples. We then compared these findings with FFA concentrations in the CSF of control patients. All FFA concentrations measured 24 hours after SAH were significantly greater than control concentrations (p < 0.01 for palmitic acid and < 0.001 for all other FFAs). All measured FFAs remained elevated for the first 48 hours after SAH (p < 0.05 for linoleic acid, p < 0.01 for palmitic acid, and p < 0.001 for the other FFAs). After 7 days, a second elevation in all FFAs was observed (p < 0.05 for linoleic acid, p < 0.01 for palmitic acid, and p < 0.001 for the other FFAs). Samples of CSF collected within 48 hours after SAH from patients in whom angiography and clinical examination confirmed the development of vasospasm after SAH were found to have significantly higher concentrations of arachidonic, linoleic, and palmitic acids than samples collected from patients in whom vasospasm did not develop (p < 0.05). CONCLUSIONS: Following SAH, all FFAs are initially elevated. A secondary elevation occurs between 8 and 10 days after SAH. This study provides preliminary evidence of FFA elevation following SAH and of a potential role for FFAs in SAH-induced vasospasm. A prospective study is warranted to determine if CSF concentrations of FFAs are predictive of vasospasm.

Critical care issues in stroke and subarachnoid hemorrhage.

The outcomes of devastating neurological emergencies such as stroke and subarachnoid hemorrhage may be measurably improved by timely treatment in a neurointensive care unit (NICU). Optimal care requires a multidisciplinary approach, with attention to a wide range of treatment issues. This review examines the key therapeutic concerns in the NICU management of acute ischemic and hemorrhagic stroke and subarachnoid hemorrhage, including mechanical ventilation, blood pressure management, cardiac monitoring, intracranial pressure assessment, vasospasm, seizures, sedation, fluids, electrolytes, and nutrition. The discussion of mechanical ventilation includes rapid sequence induction and intubation, indication for intubation and extubation, and prognostic factors in mechanical ventilation. Differing blood pressure management concerns in hemorrhagic and ischemic events are discussed, and specific target blood pressures and pharmacologic interventions are reviewed. The discussion of cardiac monitoring includes concurrent stroke and cardiac ischemia and arrhythmias, cardiac imaging, anticoagulation, and vasopressor therapy. The importance, monitoring and management of cerebral blood flow and intracranial pressure (ICP) are discussed, and strategies for treatment of elevated ICP are outlined in detail. The discussion of vasospasm includes evaluation, prophylaxis, and treatment with medications, hypervolemic hemodilution, and angioplasty. Management of seizure and status epilepticus in stroke and subarachnoid hemorrhage are reviewed and current algorithms are presented. The management of fluids, electrolytes and enteral nutrition are also reviewed.

Tolerability of bolus versus continuous gastric feeding in brain-injured patients.

Brain injured patients may exhibit altered gastric emptying; thus, some believe post-pyloric feeding to be tolerated better than gastric feeding. Reliable post-pylorus access can be difficult to obtain, so gastric feeding remains the preferred route for administering nutrition. Feeding intolerance may be associated with increased complications and costs. We sought to compare bolus (B) versus continuous (C) gastric feeding in brain injured patients. This retrospective cohort study was carried out at a neurological/neurosurgical intensive care unit at a Level 1 trauma and tertiary referral center. Our subjects were 152 consecutive patients over two years. Use of B or C feedings was based on clinicians' preferences. Abdominal examination and gastric residuals (> 75 mL over four hours) defined feeding intolerance (FI). Putative risks for FI were compared between the groups. Demographic characteristics were similar between groups B (n = 86) and C (n = 66). Feeding intolerance occurred more often in group B than in group C (60.5% vs. 37.9%, p = 0.009). Group C patients achieved 75% of nutritional goals faster than group B patients (median 3.3 vs. 4.6 days; p = 0.03). Prokinetic agent use was similar between the groups and did not reduce the time to achieve nutritional goals. There was a trend towards a reduction in the incidence of infections in group C (p = 0.05). Independent predictors of FI included: sucralfate (OR 2.3), propofol (OR 2.1), pentobarbital (OR 3.9) or paralytic (OR 3) use; older age (OR 5); days receiving mechanical ventilation (OR 1.2); and admission diagnosis of either intracerebral hemorrhage (OR 2.2) or ischemic stroke (OR 1.9). Continuous gastric feeding is better tolerated than B feedings in patients with acute brain injuries. Use of prokinetic agents did not affect time to achievement of nutritional goals. Use of common medications including sucralfate and propofol were associated with FI.

Randomized evaluation of adverse events and length-of-stay with routine emergency department use of phenytoin or fosphenytoin.

Intravenous phenytoin has come under increased scrutiny with the introduction of the prodrug, fosphenytoin. We evaluated adverse events and length-of-stay using parenteral the two drugs in routine emergency department use. Open-label randomization of phenytoin or fosphenytoin in 256 Emergency Department patients prescribed 279 parenteral doses of a phenytoin-equivalent. All phenytoin was administered intravenously, and fosphenytoin was given intravenously or intramuscularly (physician preference). Adverse events and Emergency Department length-of-stay were recorded; re-presentation to the Emergency Department within three months was reviewed for evidence of the purple glove syndrome. Nonparametric statistics were used to analyze the data. Seventy-seven patients received phenytoin and 202 fosphenytoin; 28 (10.0%) received intramuscular fosphenytoin. The mean phenytoin-equivalent dose was similar between the groups. Eighteen patients required reduction in infusion rates because of an adverse event (phenytoin = 6.5%, fosphenytoin = 6.4%; OR 0.9, 95% CI 0.4 2.6; p = 1.0). Adverse events occurred with similar frequency (phenytoin 9.1%, fosphenytoin 15.8%; OR 0.7, 95% CI 0.3 1.4; p = 0.3). The most common events were: pruritus, pain on infusion, and paresthesias. One patient developed hypotension (fosphenytoin); there were no other serious adverse events, including phlebitis. Median Emergency Department length-of-stay was 6.7 h for phenytoin and 5.7 h for fosphenytoin (p = 0.6). In routine Emergency Department use, our data do not support formulary conversion from phenytoin to fosphenytoin, based on the incidence of adverse events or Emergency Department length-of-stay.

Treatment of refractory fever in the neurosciences critical care unit using a novel, water-circulating cooling device. A single-center pilot experience.

Fever after acute brain injury affects neuronal function and recovery. Standard therapies have proven to be inadequate in treating hyperthermia in this patient population. We report on safety/efficacy pilot data collected using a noninvasive, novel, water-circulating cooling device in febrile acute brain injury patients. We enrolled patients who developed fever (rectal temperature > or =38.0 degrees C) refractory to pharmacological therapy. The treatment device uses an ice water circulating system embedded in hydrogel-coated, energy transfer pads. Its thermoregulatory feedback control uses cold water (4.0 degrees C-42.0 degrees C) and was set at 36.5 degrees C for this study. We analyzed the temperature response during 600 consecutive minutes of treatment. Six consecutive patients were enrolled and seven episodes of fever were recorded; the mean age of the patients was 59.7 years (range 46-71 years; five male, one female). Diagnoses were as follows: subarachnoid hemorrhage (two), severe traumatic brain injury (two), status epilepticus following massive cerebral infarction (one), and intracerebral/intraventricular hemorrhage (one). Hand warming was applied at treatment onset on all patients; shivering only responsive to meperidine occurred in five of them. Fever of 38.4 degrees C (range 38.0 degrees C-38.9 degrees C) was reduced to 36.9 degrees C (range 36.0 degrees C-38.0 degrees C) after 120 minutes (P<0.001). Core temperature remained "locked" during the remainder of the treatment (36.6 degrees C, P=0.5; 36.6 degrees C, P=0.9; and 36.5 degrees C, P=0.9 at 180, 300, and 600 minutes, respectively). Skin integrity under the pads was preserved in all study subjects. Our results indicate that use of this novel technique is safe, rapidly effective, and able to maintain sustained normothermia following fever in a cohort of critically ill neurologic/neurosurgical patients.

Critical care management of acute ischemic stroke.

PURPOSE OF REVIEW: Acute ischemic stroke (AIS) can have profound and devastating effects on the CNS and several other organs. Approximately 15% to 20% of patients with AIS are admitted to an intensive care unit and cared for by a multidisciplinary team. This article discusses the critical care management of patients with AIS. RECENT FINDINGS: Patients with AIS require attention to airway, pulmonary status, blood pressure, glucose, temperature, cardiac function, and, sometimes, life-threatening cerebral edema. SUMMARY: The lack of disease-specific data has led to numerous management approaches and limited guidance on choosing among them. Existing guidelines emphasize risk factors, prevention, natural history, and prevention of bleeding but provide little discussion of the complex critical care issues involved in caring for patients with AIS.

Arrival by ambulance is associated with acute stroke intervention in young adults.

BACKGROUND AND PURPOSE: Timely intervention in young stroke patients minimizes long term disability. We hypothesized that arrival to the emergency department by ambulance would be associated with increased rate of stroke intervention with intravenous t-PA or intra arterial procedures. METHODS: Charts of 77 patients aged 15-49 years diagnosed with ischemic stroke were analyzed. Data was collected on demographics, arrival to emergency department by ambulance, whether initial hospital at presentation was a Primary Stroke Center, and intervention by intravenous t-PA or intra arterial procedures. Data was analyzed by Fisher's exact test, and significant variables were included in multivariable analysis. RESULTS: Arrival by ambulance was significantly associated with acute stroke intervention in young adults (p=0.016). Gender and Primary Stroke Center certification did not make a difference in patients getting stroke intervention. CONCLUSION: Young adults with stroke symptoms were more likely to receive acute stroke intervention if they arrived by ambulance. Larger multi-center studies should address whether Primary Stroke Centers are more likely to provide either IV thrombolysis or interventional therapies in young patients with acute ischemic stroke.