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Subarachnoid hemorrhage (SAH) is a devastating type of stroke, leading to high mortality and morbidity rates. Cerebral vasospasm and delayed cerebral ischemia (DCI) are common complications following SAH that contribute significantly to the poor outcomes observed in these patients. Intrathecal (IT) nicardipine delivered via an existing external ventricular drain is an off‐label intervention that has been shown to be correlated with reduced DCI and improved patient outcomes. The current study aims to characterize the population pharmacokinetic (popPK) properties of intermittent IT nicardipine. Following informed consent, serial cerebrospinal fluid (CSF) samples were obtained from 16 SAH patients (50.4 ± 9.3 years old; 13 females) treated with IT nicardipine every 6 h (q6h, n = 8) or every 8 h (q8h, n = 8) for an average of 72 ± 21 doses. High‐performance liquid chromatography was used to quantify CSF concentration from each sample. Our popPK analysis showed that the CSF pharmacokinetics of IT nicardipine in the cohort was adequately described by a two‐compartment model with a lag time. Model parameter estimates were reliable (relative standard error <50%). Intracranial pressure influenced both the total clearance and the central volume of nicardipine (i.e., negative correlation, P <−.001). Calculated PK parameters were similar between q6h and q8h dosing regimens. Despite a small cohort of SAH patients, we successfully developed a popPK model to describe the nicardipine disposition kinetics in the CSF following IT administration. These findings may help inform future clinical trials designed to examine the optimal dosing of IT nicardipine. [ABSTRACT FROM AUTHOR]

One of the common complications of non-traumatic subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI). Intrathecal (IT) administration of nicardipine, a calcium channel blocker (CCB), upon detection of large-artery cerebral vasospasm holds promise as a treatment that reduces the incidence of DCI. In this observational study, we prospectively employed a non-invasive optical modality called diffuse correlation spectroscopy (DCS) to quantify the acute microvascular cerebral blood flow (CBF) response to IT nicardipine (up to 90min) in 20 patients with medium-high grade non-traumatic SAH. On average, CBF increased significantly with time post-administration. However, the CBF response was heterogeneous across subjects. A latent class mixture model was able to classify 19 out of 20 patients into two distinct classes of CBF response: patients in Class 1 (n = 6) showed no significant change in CBF, while patients in Class 2 (n = 13) showed a pronounced increase in CBF in response to nicardipine. The incidence of DCI was 5 out of 6 in Class 1 and 1 out of 13 in Class 2 (p < 0.001). These results suggest that the acute (<90min) DCS-measured CBF response to IT nicardipine is associated with intermediate-term (up to 3 weeks) development of DCI. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is a neurological emergency because it may lead to sudden neurological decline and death and, depending on the cause, has treatment options that can return a patient to normal. Because there are interventions that can be life-saving in the first few hours after onset, SAH was chosen as an Emergency Neurological Life Support (ENLS) protocol. [ABSTRACT FROM AUTHOR]

Background: Epsilon aminocaproic acid (EACA) has been used in the past to prevent cerebral aneurysm rerupture. Recent studies have indicated that short-term treatment with EACA can lower rebleeding rates without significantly increasing ischemic or thrombotic complications or permanent shunt rates. The goal of this study is to determine the efficacy of EACA in the prevention of aneurysm rerupture at a high volume subarachnoid hemorrhage center. Methods: We conducted a retrospective study of 355 consecutive subarachnoid hemorrhage patients over a 2-year period under our current protocol for EACA use. Patients were divided by presentation time to our institution and whether the patient received EACA. The primary endpoints of the study were rebleeding rates, ischemic complications, thrombotic complications, vasospasm, shunt rates, and outcomes. Results: Rerupture rates were reduced by half in the entire pool of patients on EACA after controlling for Hunt and Hess Scores and Fisher Scores. In patients who received early aneurysm treatment, this effect persisted but was non-statistically significant due to the small numbers of reruptures. In addition, there was no evidence to suggest that EACA increased ischemic or thrombotic complications, vasospasm, or VPS rates. In patients presenting earlier than 24 h to our institution, there was a non-significant trend toward worse outcomes after EACA use. This trend was reversed in patients arriving after 24 h. Conclusion: There is evidence to suggest that EACA is protective from aneurysm rerupture without significant ischemic or thrombotic complications when used for less than 72 h. However, if the aneurysm is treated, this effect is modest indicating that early aneurysm treatment remains the gold standard for rerupture prevention. [ABSTRACT FROM AUTHOR]

Purpose Subarachnoid hemorrhage (SAH) is a rare but life-threatening clinical event for pediatric patients. Cerebral vasospasm is a common complication of SAH that often leads to poor outcomes. This case report describes the use of dual intraventricular (IVT) vasodilators in a pediatric patient. Summary An 11-year-old male presented with traumatic diffuse SAH and cerebral vasospasm. Despite treatment with IVT nicardipine, intravenous (IV) milrinone by continuous infusion, enteral nimodipine, and intraarterial verapamil and milrinone given during digital subtraction angiography, transcranial Doppler (TCD) mean velocities continued to rise. IVT milrinone was then added to IVT nicardipine and IV milrinone. The combination of IVT nicardipine, IV milrinone, and rescue therapy with IVT milrinone was continued for a total of 7 days. TCD mean velocities decreased into the mild to moderate range within 2 days of the patient receiving this combined regimen and remained globally low thereafter. Conclusion This case illustrates the potential benefit of using dual IVT vasodilators to improve outcomes for pediatric patients with refractory cerebral vasospasm. [ABSTRACT FROM AUTHOR]

Objectives: A paucity of treatments to prevent delayed cerebral ischemia (DCI) has stymied recovery after aneurysmal subarachnoid hemorrhage (aSAH). Nicardipine has long been recognized as a potent cerebrovascular vasodilator with a history off-label use to prevent vasospasm and DCI. Multiple centers have developed nicardipine prolonged release implants (NPRI) that are directly applied during clip ligation to locally deliver nicardipine throughout the vasospasm window. Here we perform a systematic review and meta-analysis to assess whether NPRI confers protection against DCI and improves functional outcomes after aSAH.Materials and Methods: A systematic search of PubMed, Ovid Embase, and Cochrane databases was performed for studies reporting the use of NPRI after aSAH published after January 1, 1980. We included all studies assessing the association of NPRI with DCI and or functional outcomes. Findings from studies with control arms were analyzed using a random effects model. A separate network meta-analysis was performed, including controlled NPRI studies, single-arm NPRI reports, and the control-arms of modern aSAH randomized clinical trials as additional comparators.Results: The search identified 214 unique citations. Three studies with 284 patients met criteria for the random effects model. The pooled summary odds ratio for the association of NPRI and DCI was 0.21 (95% CI 0.09-0.49, p = 0.0002) with no difference in functional outcomes (OR 1.80, 95% CI 0.63 - 5.16, p = 0.28). 10 studies of 866 patients met criteria for the network meta-analysis. The pooled summary odds ratio for the association of NPRI and DCI was 0.30 (95% CI 0.13-0.89,p = 0.017) with a trend towards improved functional outcomes (OR 1.68, 0.63 - 4.13 95% CI, p = 0.101).Conclusions: In these meta-analyses, NPRI decreases the incidence of DCI with a non-significant trend towards improvement in functional outcomes. Randomized trials on the role of intrathecal calcium channel blockers are warranted to evaluate these observations in a prospective manner. [ABSTRACT FROM AUTHOR]

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition that results from a ruptured cerebral vessel. Cerebral edema and vasospasm are common complications and frequently require treatment with hypertonic solutions, in particular hypertonic sodium chloride (NaCl). We have previously shown that hyperchloremia in patients with aSAH given hypertonic NaCl is associated with the development of acute kidney injury (AKI), which leads to higher morbidity and mortality. Our current trial aims to study the effect of two hypertonic solutions with different chloride content on serum chloride concentrations in patients with aSAH who are at risk for AKI.Methods: A low ChloridE hyperTonic solution for brain Edema (ACETatE) is a single center, double-blinded, double-dummy pilot trial comparing bolus doses of 23.4% NaCl and 16.4% NaCl/Na-Acetate for the treatment of cerebral edema in patients with aSAH. All patients will be enrolled within 36 h following admission. Randomization will occur once patients who receive hypertonic treatment for cerebral edema develop hyperchloremia (serum Cl- concentration ≥ 109 mmol/L). Subsequent treatment will consist of either NaCl 23.4% or NaCl/Na-Acetate 16.4%. The primary outcome of this study will be the change in serum Cl- concentrations during treatment. Secondary outcomes will include incidence of AKI, mortality, changes in intracranial pressure, and extent of hypernatremia.Discussion: In patients with aSAH, hyperchloremia is a known risk factor for subsequent development of AKI. The primary goal of this pilot study is to determine the effect of two hypertonic solutions with different Cl- content on serum Cl- concentrations in patients with aSAH who have already developed hyperchloremia. Data will be collected prospectively to determine the extent to which the choice of hypertonic saline solution affects subsequent serum Cl- concentrations and the occurrence of AKI. This approach will allow us to obtain preliminary data to design a large randomized trial assessing the effects of chloride-sparing hypertonic solutions on development of AKI in patients with SAH. This pilot study is the first to prospectively evaluate the relationship between hypertonic solution chloride content and its effect on serum electrolytes and renal function in aSAH patients at risk of AKI due to hyperchloremia.Trial Registration: Clinicaltrials.gov, NCT03204955 . Registered on 28 June 2017. [ABSTRACT FROM AUTHOR]

Moreover, these patients often have external ventricular drains (EVDs) and direct ICP measurements. B Introduction: b Jugular access for central venous catheterization (CVC) is usually avoided in neurocritically ill patients due to an inferred risk of increasing intracranial pressure (ICP). Here we test whether CVC-access site correlates with ICP measurements and catheter-associated complications in aSAH patients. [Extracted from the article]

Regional microvascular CBF in the frontal cortex was measured with diffuse correlation spectroscopy for up to 90 min after the first treatment dose, and for a subset of patients, on days 2 and 3 of treatment as well. B Introduction: b A common complication of subarachnoid hemorrhage is cerebral vasospasm, which is associated with delayed cerebral ischemia, a predictor of poor functional outcome. [Extracted from the article]

On the 3rd day of treatment, trough concentrations were similar before and after the dose, suggesting approximate steady state (171.6±145.2 pg/mL pre-dose vs. 151.7±181.5 pg/mL post dose, p=0.8). B Introduction: b Cerebral vasospasm is a common complication following non-traumatic subarachnoid hemorrhage. Spontaneously draining cerebrospinal fluid (CSF) was collected hourly following the first dose and after a scheduled dose on the third day of treatment. [Extracted from the article]

The article examines the efficacy of intrathecally (IT) nicardipine in treating cerebral vasospasm. Methodology-wise, the treatment was administered to six patients with aneurysmal subarachnoid hemorrhage. Based on the results, the researchers concluded that larger scale studies evaluating the efficacy of IT nicardipine are warranted.