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.

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.

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.

Possible removal of topiramate by continuous renal replacement therapy.

BACKGROUND: Topiramate is primarily renally eliminated and requires dosage adjustment based upon renal function. While there is data to suggest drug removal during intermittent hemodialysis (IHD), little is known regarding its clearance and dosing during continuous renal replacement therapy (CRRT). CASE DESCRIPTION: We describe a 59-year-old man with refractory status epilepticus who was started on continuous venovenous hemodiafiltration (CVVHDF) for acute renal failure while receiving topiramate with a series of serum concentrations to assess for removal during CVVHDF. CONCLUSION: Our data suggest clinically important amounts of topiramate are removed by CRRT, and higher topiramate dosage may be needed for these patients instead of the current recommended 50% of normal dosage. Unfortunately, there is no antiepileptic drug dosing recommendation when used during CRRT due to the paucity of data. This case highlights a need for research evaluating the effect of CRRT on AED elimination in order to optimize therapy for seizure control.

A comparison of nicardipine and labetalol for acute hypertension management following stroke.

OBJECTIVE: Evaluate the ease of use and tolerability of labetalol (L) and nicardipine (N) for hypertension management in patients with acute stroke. METHODS: This is a retrospective, non-randomized study. Consecutive adults within 24 h of hospital admission who received intravenous bolus labetalol or nicardipine infusion as first-line antihypertensive therapy were identified. Hemodynamic data were collected through 24 h of therapy. RESULTS: Ninety patients received either labetalol (N = 64) or nicardipine (N = 26) initially for blood pressure (BP) management. Stroke types were 54% intracerebral hemorrhage (ICH), 22% subarachnoid hemorrhage, and 23% ischemic stroke and were similar between the two drug groups. Baseline patient characteristics and disease severity (APACHE II and GCS) were similar between groups. The average total daily labetalol dose was 40 (10-340) mg and nicardipine infusion was 5 (1-14) mg/h. Initial BP was similar in the two groups. The nicardipine group had less BP variability (N 8.19 vs. L 10.78 mmHg; p = 0.003), fewer dosage adjustments [L 4 (1-17), N 2 (0-5); p < 0.001] and fewer additional antihypertensive agents (L 33%, N 8%; p = 0.013) administered during the 24-h observation period. In patients with ICH, 33% of nicardipine-treated patients achieved target BP within the first 60 min versus 6% of the L group (p = 0.02). Overall, incidence of hypotension (SBP < 90 mmHg) (L 3%; N 0%) and bradycardia (HR < 60 beats per min) (L 20.6%; N 12%) were comparable between the groups. CONCLUSIONS: Nicardipine offers an alternative to labetalol with similar tolerability and appears to provide a smoother blood pressure control compared to labetalol.

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.

Frameless stereotactic aspiration and thrombolysis of spontaneous intracerebral hemorrhage.

INTRODUCTION: To test the feasibility and safety of a minimally invasive technique, we report our experience in treating spontaneous intracerebral hemorrhage (ICH) patients by using frameless stereotactic clot aspiration-thrombolysis and its effects on their 30-day survival. We compared the observed cohort mortality with its predicted 30-day ICH mortality, by using previously validated methods. METHODS: Selection criteria were diagnosis of hypertensive ICH > or =35 cc, reduced level of consciousness, and no brainstem compression. Frameless stereotactic puncture/clot aspiration followed by intraclot external catheter placement was performed. Two milligrams of recombinant tissue plasminogen activator (rtPA) was administered q12 hours until ICH volume < or =10 cc, or the catheter fenestrations were no longer in continuity with the clot. RESULTS: Fifteen patients were treated, mean age was 60.7 years. Hemorrhage locations included basal ganglia (13), thalamic (1), and lobar (1); mean systolic blood pressure; and admission ICH volumes were 229.3 mmHg and 59.1 cc, respectively. Median time from ictus to clot aspiration/thrombolysis was 1 (range 0-3) day. Mean hematoma volume was reduced to 17% of pretreatment size. Complications were ventriculitis (6.6%) and clot enlargement (13.3%). Two patients were dead at 30 days. Median Glasgow Coma Scale (GCS) scores were 10.5 (4-15) at admission and 11.0 (3-15) at discharge. By using the most conservative estimate for analysis, probability of observing two or fewer deaths among 15 patients with an overall probability of dying calculated at 0.33 was p = 0.079. CONCLUSIONS: In this selected cohort of patients with ICH, stereotactic aspiration and thrombolytic washout seemed to be feasible and to have a trend towards improved 30-day survival, when using their predicted mortality data as "historical control." Complications did not exceed expected incidence rates. Based on the experience presented here as well as previous similar reports, a larger, randomized study addressing dose escalation, patient selection, and best therapeutic window is needed.