Enhanced renal clearance impacts levetiracetam concentrations in patients with traumatic brain injury with and without augmented renal clearance.

BACKGROUND: The purpose of this study was to examine the impact of ARC on levetiracetam concentrations during the first week following acute TBI. The hypothesis was levetiracetam concentrations are significantly lower in TBI patients with augmented renal clearance (ARC) compared to those with normal renal clearance. METHODS: This is a prospective cohort pharmacokinetic study of adults with moderate to severe TBI treated with levetiracetam during the first week after injury. Serial blood collections were performed daily for analysis of levetiracetam, cystatin C, and 12-hr creatinine clearance (CrCl) determinations. Patients were divided into two cohorts: with (CrCl ≥130 ml/min/1.73 m2) and without ARC. RESULTS: Twenty-two patients with moderate to severe TBI were included. The population consisted primarily of young male patients with severe TBI (mean age 40 years old, 68% male, median admission GCS 4). Each received levetiracetam 1000 mg IV every 12 h for the study period. ARC was present in 77.3% of patients, with significantly lower levetiracetam concentrations in ARC patients and below the conservative therapeutic range (< 6mcg/mL) for all study days. In patients without ARC, the serum concentrations were also below the expected range on all but two study days (Days 4 and 5). Four of the 22 (18.2%) patients exhibited seizure activity during the study period (two of these patients exhibited ARC). Cystatin C concentrations were significantly lower in patients with ARC, though the mean for all patients was within the typical normal range. CONCLUSIONS: ARC has a high prevalence in patients with moderate to severe TBI. Levetiracetam concentrations after standard dosing were low in all TBI patients, but significantly lower in patients with ARC. This study highlights the need to consider personalized drug dosing in TBI patients irrespective of the presence of ARC. CLINICAL TRIAL REGISTRATION: This study was registered at cliicaltrials.gov (NCT02437838) Registered on 08/05/2015, https://clinicaltrials.gov/ct2/show/NCT02437838 .

Multicenter Comparison of the Safety and Efficacy of Clopidogrel Versus Ticagrelor for Neuroendovascular Stents.

BACKGROUND: Dual antiplatelet therapy (DAPT) is commonly employed for neuroendovascular stenting due to the significant risk of thromboembolism. Clopidogrel and aspirin are most often selected as initial DAPTs; however, there is limited literature available to support guidance of DAPT in this setting. The objective of this study was to evaluate safety and efficacy in patients whose final regimen included either DAPT with aspirin and clopidogrel (DAPT-C) or DAPT with aspirin and ticagrelor (DAPT-T). METHODS: This was a multicenter, retrospective cohort of patients who underwent neuroendovascular stenting and received DAPT between July 1, 2017, and October 31, 2020. Study participants were allocated into groups based on discharge DAPT regimen. The primary outcome was incidence of stent thrombosis at 3-6 months on DAPT-C versus DAPT-T, as defined by the presence of thrombus on imaging or new onset stroke. Secondary outcomes included major and minor bleeding and death within 3-6 months after the procedure. RESULTS: Five hundred and seventy patients were screened across 12 sites. Of those, 486 were included (DAPT-C n = 360, DAPT-T n = 126). There was no difference in the primary outcome of stent thrombosis between the DAPT-C and DAPT-T groups (8% vs. 8%, p = 0.97) and no difference in any of the secondary safety outcomes. CONCLUSIONS: Using DAPT-C or DAPT-T regimens in a broad population of neuroendovascular stenting procedures appears to have similar safety and efficacy profiles. Further prospective evaluation is warranted to streamline the practice of DAPT selection and monitoring to determine the impact on clinical outcomes.

Factor Xa Inhibitor-Related Intracranial Hemorrhage: Results From a Multicenter, Observational Cohort Receiving Prothrombin Complex Concentrates.

BACKGROUND: Since the approval of the oral factor Xa inhibitors, there have been concerns regarding the ability to neutralize their anticoagulant effects after intracranial hemorrhage (ICH). Multiple guidelines suggest using prothrombin complex concentrates (PCCs) in these patients on the basis of research that includes a limited number of patients with ICH. Given this, we aimed to evaluate the safety and efficacy of PCCs for factor Xa inhibitor-related ICH in a large, multicenter cohort of patients. METHODS: This was a multicenter, retrospective, observational cohort study of patients with apixaban- or rivaroxaban-related ICH who received PCCs between January 1, 2015, and March 1, 2019. The study had 2 primary analysis groups: safety and hemostatic efficacy. The safety analysis evaluated all patients meeting inclusion criteria for the occurrence of a thrombotic event, which were censored at hospital discharge or 30 days after PCC administration. Patients with intracerebral, subarachnoid, or subdural hemorrhages who had at least 1 follow-up image within 24 hours of PCC administration were assessed for hemostatic efficacy. The primary efficacy outcome was the percentage of patients with excellent or good hemostasis on the basis of the modified Sarode criteria. Secondary outcomes included an evaluation of in-hospital mortality, length of stay, infusion-related reactions, and thrombotic event occurrence during multiple predefined periods. RESULTS: A total of 663 patients were included and assessed for safety outcomes. Of these, 433 patients met criteria for hemostatic efficacy evaluation. We observed excellent or good hemostasis in 354 patients (81.8% [95% CI, 77.9-85.2]). Twenty-five (3.8%) patients had a total of 26 thrombotic events, of which 22 occurred in the first 14 days after PCC administration. One patient had documentation of an infusion-related reaction. For the full cohort of patients, in-hospital mortality was 19.0%, and the median intensive care unit and hospital lengths of stay were 2.0 and 6.0 days, respectively. CONCLUSIONS: Administration of PCCs after apixaban- and rivaroxaban-related ICH provided a high rate of excellent or good hemostasis (81.8%) coupled with a 3.8% thrombosis rate. Randomized, controlled trials evaluating the clinical efficacy of PCCs in patients with factor Xa inhibitor-related ICH are needed.

Identifying errors and safety considerations in patients undergoing thrombolysis for acute ischemic stroke.

BACKGROUND & PURPOSE: Alteplase is the standard of care for early pharmacologic thrombolysis after acute ischemic stroke (AIS). Alteplase is also considered a high-alert medication and is fraught with potential for error. We sought to describe the difference in medication error rates in in patients receiving alteplase for acute ischemic stroke from regional hospitals compared to patients receiving alteplase at the Comprehensive Stroke Center. METHODS: This was a retrospective cohort comparison of patients who were greater than 18 years old that received intravenous alteplase for the treatment of AIS from June 2015 to June 2018. Several institution specific databases were utilized to obtain pertinent data. A standardized taxonomy was utilized to classify medication errors. Patients were excluded if they received any fibrinolytic other than alteplase or if alteplase was used for a non-stroke indication. Two cohorts (from regional hospitals or the Comprehensive Stroke Center (CSC)) were compared. RESULTS: A total of 676 patients received alteplase during the study period (34% from the CSC and 66% from regional hospitals). There were 133 (19.8%) errors identified. Ten errors (1.6%) occurred at the CSC and 123 (18.2%) errors occurred at regional hospitals. More patients who had an error with alteplase administration (12.7%) experienced a hemorrhagic conversion compared to those with no error in administration (7.2%, p= 0.04). CONCLUSION: The error rate of alteplase infusion for ischemic stroke is high, particularly in patients from referring centers. Errors may be associated with adverse events. Further education and administration safeguards should be implemented to decrease the risk of medication errors.

Alcohol Withdrawal Syndrome in Neurocritical Care Unit: Assessment and Treatment Challenges.

Alcohol withdrawal syndrome (AWS) can range from mild jittery movements, nausea, sweating to more severe symptoms such as seizure and death. Severe AWS can worsen cognitive function, increase hospital length of stay, and in-hospital mortality and morbidity. Due to a lack of reliable history of present illness in many patients with neurological injury as well as similarities in clinical presentation of AWS and some commonly encountered neurological syndromes, the true incidence of AWS in neurocritical care patients remains unknown. This review discusses challenges in the assessment and treatment of AWS in patients with neurological injury, including the utility of different scoring systems such as the Clinical Institute Withdrawal Assessment and the Minnesota Detoxification Scale as well as the reliability of admission alcohol levels in predicting AWS. Treatment strategies such as symptom-based versus fixed dose benzodiazepine therapy and alternative agents such as baclofen, carbamazepine, dexmedetomidine, gabapentin, phenobarbital, ketamine, propofol, and valproic acid are also discussed. Finally, a treatment algorithm considering the neurocritical care patient is proposed to help guide therapy in this setting.

Stress-Related Gastrointestinal Bleeding in Patients with Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Observational Study.

BACKGROUND/OBJECTIVE: Stress-related mucosal bleeding (SRMB) occurs in approximately 2-4% of critically ill patients. Patients with aneurysmal subarachnoid hemorrhage (aSAH) have a (diffuse) space-occupying lesion, are critically ill, often require mechanical ventilation, and frequently receive anticoagulation or antiplatelet therapy after aneurysm embolization, all of which may be risk factors for SRMB. However, no studies have evaluated SRMB in patients with aSAH. Aims of the study were to determine the incidence of SRMB in aSAH patients, evaluate the effect of acid suppression on SRMB, and identify specific risk factors for SRMB. METHODS: This was a multicenter, retrospective, observational study conducted across 17 centers. Each center reviewed up to 50 of the most recent cases of aSAH. Patients with length of stay (LOS) < 48 h or active GI bleeding on admission were excluded. Variables related to demographics, aSAH severity, gastrointestinal (GI) bleeding, provision of SRMB prophylaxis, adverse events, intensive care unit (ICU), and hospital LOS were collected for the first 21 days of admission or until hospital discharge, whichever came first. Descriptive statistics were used to analyze the data. A multivariate logistic regression modeling was utilized to examine the relationship between specific risk factors and the incidence of clinically important GI bleeding in patients with aSAH. RESULTS: A total of 627 patients were included. The overall incidence of clinically important GI bleeding was 4.9%. Of the patients with clinically important GI bleeding, 19 (61%) received pharmacologic prophylaxis prior to evidence of GI bleeding, while 12 (39%) were not on pharmacologic prophylaxis at the onset of GI bleeding. Patients who received an acid suppressant agent were less likely to experience GI bleeding than patients who did not receive pharmacologic prophylaxis prior to evidence of bleeding (OR 0.39, 95% CI 0.18-0.83). The multivariate regression analysis identified any instance of elevated intracranial pressure, creatinine clearance < 60 ml/min and the incidence of cerebral vasospasm as specific risk factors associated with GI bleeding. Cerebral vasospasm has not previously been described as a risk for GI bleeding (OR 2.5 95% CI 1.09-5.79). CONCLUSIONS: Clinically important GI bleeding occurred in 4.9% of patients with aSAH, similar to the general critical care population. Risk factors associated with GI bleeding were prolonged mechanical ventilation (> 48 h), creatinine clearance < 60 ml/min, presence of coagulopathy, elevation of intracranial pressure, and cerebral vasospasm. Further prospective research is needed to confirm this observation within this patient population.

Guidelines for the Acute Treatment of Cerebral Edema in Neurocritical Care Patients.

BACKGROUND: Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety. METHODS: The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy. RESULTS: The panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy. CONCLUSION: The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in therapeutic response and safety may exist between HTS and mannitol. The use of these agents in these critical clinical situations merits close monitoring for adverse effects. There is a dire need for high-quality research to better inform clinicians of the best options for individualized care of patients with cerebral edema.

Current Practices of Intraventricular Antibiotic Therapy in the Treatment of Meningitis and Ventriculitis: Results from a Multicenter Retrospective Cohort Study.

BACKGROUND: Central nervous system (CNS) infections are particularly prevalent in the adult neurocritical care patient population and are associated with significant morbidity and mortality. Factors relevant to the nature of CNS infections pose significant challenges to clinicians treating afflicted patients. Intraventricular (IVT) administration of antibiotics may offer several benefits over systemic therapy; however, the outcomes and current practices of such treatments are poorly described in the literature. OBJECTIVE: To describe current practices and outcomes of patients receiving intraventricular antibiotic treatment for CNS infections in neurological intensive care units of academic medical centers nationwide. METHODS: A retrospective cohort study was conducted on patients admitted to intensive care units who received IVT antibiotic treatment at participating centers in the USA between January 01, 2003, and December 31, 2013. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were collected and described. RESULTS: Of the 105 patients included, all received systemic antimicrobial therapy along with at least one dose of IVT antimicrobial agents. Intraventricular vancomycin was used in 52.4% of patients. The average dose was 12.2 mg/day for a median duration of 5 days. Intraventricular aminoglycosides were used in 47.5% of the patients, either alone or in combination with IVT vancomycin. The average dose of gentamicin/tobramycin was 6.7 mg/day with a median duration of 6 days. Overall mortality was 18.1%. Cerebrospinal fluid (CSF) culture sterilization occurred in 88.4% of the patients with a rate of recurrence or persistence of positive cultures of 9.5%. CONCLUSION: Intraventricular antimicrobial agents resulted in a high CSF sterilization rate. Contemporary use of this route typically results in a treatment duration of less than a week. Prospective studies are needed to establish the optimal patient population, as well as the efficacy and safety of this route of administration.

Management of Chronic Hypertension Following Intracerebral Hemorrhage.

Acute blood pressure control after a cerebrovascular event is integral in the immediate care of these patients to preserve perfusion to ischemic areas and prevent intracerebral bleeding. The majority of patients with ischemic stroke or intracerebral hemorrhage (ICH) present with preexisting hypertension and therefore require a treatment plan after the acute phase. The presence of chronic hypertension after ICH has often been discussed as a modifiable risk factor for recurrent events. Clinical evidence is relatively lacking for clinicians to understand the extent of blood pressure lowering and the optimal agents to use in this setting. Limited data exist describing the long-term management of hypertension in patients after cerebrovascular events. This review provides nurses with a summary of the available literature on long-term blood pressure management to minimize the risk of secondary ICH and ischemic stroke. It focuses on oral antihypertensive medications available in the United States that may be utilized to manage chronic hypertension immediately after the postacute phase of care to lower blood pressure and to improve long-term outcomes.

Fever Burden in Patients With Subarachnoid Hemorrhage and the Increased Use of Antibiotics.

BACKGROUND: Fever occurs in the majority of subarachnoid hemorrhage (SAH) patients. Nearly 50% of SAH patients have noninfectious fevers. Data are lacking describing the effects of fever burden in the SAH patient population. METHODS: This was a single-center, retrospective observational cohort study in patients more or equal to 18 years of age with a diagnosis of nontraumatic SAH admitted to an ICU between January 1, 2010 and September 1, 2015. Exclusion criteria were SAH secondary to trauma or admission for more than 48 hours. Temperature measurements, demographic data, and other pertinent information were collected from Day 0 to Day 13. Daily fever burden was calculated for each patient by calculating an area under the curve. RESULTS: A total of 194 subjects were included. The mean study period maximum temperature (Tmax) for all 194 patients was 40.8 ± 0.83°C. The mean overall fever burden for all 194 patients was 89.2 ± 99.59°C h more than 37°C. The overall fever burden peaked on day 5 and declined thereafter. Fever burden, Tmax, and length of stay in the hospital were all significantly associated with receipt of antibiotics. Only Tmax was associated with poor outcome. The 31 patients who had fever but no identified cause of infection received 1000 doses of antibiotics or 32.25 doses per patient. CONCLUSION: Fever is common in SAH patients and is associated with antibiotic use, infection, vasospasm, and poor outcome. Some SAH patients may receive antibiotics unnecessarily for noninfectious fever. Clinicians should consider using site-specific parameters related to infection rather than systemic symptoms such as fever to evaluate infection in SAH patients.

Development of a Coprecepting Model for a Preceptor-in-Training Program for New Practitioners.

Background: Preceptor development is a focus of pharmacy residency programs across the country. Graduation from residency into the role of preceptor can be a challenge, as it is one of many transitions junior practitioners make in their early careers. Literature in recent years has brought attention to the need to establish preceptor development programs that adequately allow newer preceptors to develop their skills in experiential education, for both pharmacy residents and students. Furthermore, many preceptor development programs as implemented are often didactic in nature, and include readings, webinars, and other passive learning regarding the art of precepting. Objective: Given the need to develop a preceptor development program in our service line that met the needs of preceptors-in-training and full preceptors, we offer a description of our preceptor development program in the intensive care unit. Methods: We focused on active development of preceptor skills for multiple layers of resident and student learners. In addition, this model incorporated instructing, modeling, coaching, and facilitating, as the relationship between full preceptor and preceptor-in-training evolved. It also offered the opportunity for real-time feedback and discussion on precepting performance. Conclusions: We describe our coprecepting model as an opportunity that succeeded for us in helping to transition our preceptors-in-training to full preceptors. It met the needs of our department, staff, and patients, and we believe it has the potential to be valuable as a tool extrapolated to the preceptor development programs of other institutions.

Treatment of Hyponatremia in Patients with Acute Neurological Injury.

BACKGROUND: Little data exist regarding the practice of sodium management in acute neurologically injured patients. This study describes the practice variations, thresholds for treatment, and effectiveness of treatment in this population. METHODS: This retrospective, multicenter, observational study identified 400 ICU patients, from 17 centers, admitted for ≥48 h with subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), intraparenchymal hemorrhage, or intracranial tumors between January 1, 2011 and July 31, 2012. Data collection included demographics, APACHE II, Glascow Coma Score (GCS), serum sodium (Na+), fluid rate and tonicity, use of sodium-altering therapies, intensive care unit (ICU) and hospital length of stay, and modified Rankin score upon discharge. Data were collected for the first 21 days of ICU admission or ICU discharge, whichever came first. Sodium trigger for treatment defined as the Na+ value prior to treatment with response defined as an increase of ≥4 mEq/L at 24 h. RESULTS: Sodium-altering therapy was initiated in 34 % (137/400) of patients with 23 % (32/137) having Na+ >135 mEq/L at time of treatment initiation. The most common indications for treatment were declining serum Na+ (68/116, 59 %) and cerebral edema with mental status changes (21/116, 18 %). Median Na+ treatment trigger was 133 mEq/L (IQR 129-139) with no difference between diagnoses. Incidence and treatment of hyponatremia was more common in SAH and TBI [SAH (49/106, 46 %), TBI (39/97, 40 %), ICH (27/102, 26 %), tumor (22/95, 23 %); p = 0.001]. The most common initial treatment was hypertonic saline (85/137, 62 %), followed by oral sodium chloride tablets (42/137, 31 %) and fluid restriction (15/137, 11 %). Among treated patients, 60 % had a response at 24 h. Treated patients had lower admission GCS (12 vs. 14, p = 0.02) and higher APACHE II scores (12 vs. 10, p = 0.001). There was no statistically significant difference in outcome when comparing treated and untreated patients. CONCLUSION: Sodium-altering therapy is commonly employed among neurologically injured patients. Hypertonic saline infusions were used first line in more than half of treated patients with the majority having a positive response at 24 h. Further studies are needed to evaluate the impact of various treatments on patient outcomes.

Unpeeling the Evidence for the Banana Bag: Evidence-Based Recommendations for the Management of Alcohol-Associated Vitamin and Electrolyte Deficiencies in the ICU.

OBJECTIVE: Patients with a chronic alcohol use disorder presenting to the ICU may be deficient in important vitamins and electrolytes and are often prescribed a "banana bag" as a reflexive standard of therapy. The difficulty of diagnosing Wernicke's encephalopathy in the critical care setting is reviewed. Furthermore, whether the contents and doses of micronutrients and electrolytes in standard banana bags meet the needs of critically ill patients with an alcohol use disorder is assessed based on available evidence. DATA SOURCE: MEDLINE/PubMed (1966 to June 2015) database search, the Cochrane Database of Systematic Reviews, and manual selection of bibliographies from selected articles. STUDY SELECTION AND DATA EXTRACTION: Articles relevant to Wernicke's encephalopathy, vitamin and electrolyte deficiencies in patients with alcohol use disorders, and alcoholic ketoacidosis were selected. Articles were narratively synthesized for this review. DATA SYNTHESIS: Of these deficiencies, thiamine is the most important for the practicing clinician to assess and prescribe replacement in a timely manner. Based on a pharmacokinetic assessment of thiamine, the banana bag approach likely fails to optimize delivery of thiamine to the central nervous system. Folic acid and magnesium may also merit supplementation although the available data do not allow for as strong a recommendation as for prescribing thiamine in this setting. There is no available evidence supporting the prescription of a multivitamin. CONCLUSIONS: Based on the published literature, for patients with a chronic alcohol use disorder admitted to the ICU with symptoms that may mimic or mask Wernicke's encephalopathy, we suggest abandoning the banana bag and utilizing the following formula for routine supplementation during the first day of admission: 200-500 mg IV thiamine every 8 hours, 64 mg/kg magnesium sulfate (approximately 4-5 g for most adult patients), and 400-1,000 µg IV folate. If alcoholic ketoacidosis is suspected, dextrose-containing fluids are recommended over normal saline.

Neuroleptic Malignant Syndrome.

OBJECTIVE: To review evidence for the treatment of neuroleptic malignant syndrome (NMS) and to discuss how to rechallenge patients with neuroleptics when continued pharmacotherapy for chronic psychological illness is required. DATA SOURCES: A PubMed search was conducted through March 2016 using available medical subject heading (MeSH) terms and keywords that included neuroleptic malignant syndrome, treatment, dantrolene, and bromocriptine. A manual search of article reference sections followed. STUDY SELECTION AND DATA EXTRACTION: Case reports and case series in English that discussed NMS and atypical NMS treatment as well as neuroleptic rechallenge were included for review. DATA SYNTHESIS: The reported incidence of NMS was 0.02% to 0.03%, with a mortality rate of 5.6%. Current literature on NMS is primarily retrospective and emphasizes diagnostic criteria, causative agents, and potential pharmacotherapy. Details regarding timing of administration, dose, and duration of pharmacotherapy are inconsistently reported. Reported dosing strategies and outcomes have been summarized. Instances of rechallenge were infrequently reported but demonstrate that recurrence may happen at any time after NMS resolution. Recommendations regarding safe rechallenge are provided. CONCLUSION: NMS is a rare adverse drug reaction, with a complex pathophysiology and presentation. Timely diagnosis and discontinuation of antipsychotic therapy is the first-line treatment, followed by supportive care and pharmacotherapy. Antipsychotic rechallenge is often required and should be attempted only after a drug-free period and with a different agent, slowly titrated with close monitoring.

Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine.

BACKGROUND: The use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased over the last decade and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes. METHODS: The Neurocritical Care Society, in conjunction with the Society of Critical Care Medicine, organized an international, multi-institutional committee with expertise in neurocritical care, neurology, neurosurgery, stroke, hematology, hemato-pathology, emergency medicine, pharmacy, nursing, and guideline development to evaluate the literature and develop an evidence-based practice guideline. Formalized literature searches were conducted, and studies meeting the criteria established by the committee were evaluated. RESULTS: Utilizing the GRADE methodology, the committee developed recommendations for reversal of vitamin K antagonists, direct factor Xa antagonists, direct thrombin inhibitors, unfractionated heparin, low-molecular weight heparin, heparinoids, pentasaccharides, thrombolytics, and antiplatelet agents in the setting of intracranial hemorrhage. CONCLUSIONS: This guideline provides timely, evidence-based reversal strategies to assist practitioners in the care of patients with antithrombotic-associated intracranial hemorrhage.

Accuracy of nimodipine gel extraction.

INTRODUCTION: Until recently, use of nimodipine in aneurysmal subarachnoid hemorrhage patients unable to swallow required extraction of gel from inside the commercially available capsule. Despite the Black-Box warning against inadvertent intravenous administration, bedside extraction of the gel from the capsule continues to be a common practice in some institutions. The accuracy of bedside extraction has not been formally evaluated. METHODS: Twenty-eight nurses from the neurology and neurosurgical ICUs at a single center attempted to extract nimodipine gel from 2 capsules, each using the method currently approved by the US FDA. The primary outcome was mean weight of extracted gel per capsule, which was compared to both gel weight from batch compounded pharmacy syringes and a pre-calculated appropriate weight for 30 mg nimodipine gel. RESULTS: Simulated bedside extraction provided lower yield than pharmacy-compounded syringes (22.6 ± 4.6 mg vs 30.4 ± 0.59 mg, p = 0.001). Bedside extraction provided inconsistent and low yield (75.4 ± 15.32 % of possible dose extracted, p = 0.0001 for comparison of means between bedside extraction syringes and predicted gel weight). Pharmacy-compounded syringes provided consistent high yield (101.3 ± 2.0 % of possible dose extracted, p = 0.14 for comparison of means between pharmacy syringes and predicted gel weight). CONCLUSION: Combined with reports of significant patient harm and death with inadvertent intravenous administration, this study suggests that there is no role for bedside extraction of nimodipine in clinical practice.

Augmented Renal Clearance in Patients with Subarachnoid Hemorrhage.

BACKGROUND: Patients with subarachnoid hemorrhage (SAH) typically exhibit hyperdynamic cardiovascular hemodynamics, which may lead to increased medication clearance. The aims of this study were to evaluate the actual creatinine clearance (CrClA) in an aneurysmal SAH population and the effect of the development of cerebral vasospasm (CV) along with its treatment to better understand if this population exhibits augmented renal clearance (ARC). METHODS: This was a prospective, single-center study in a neurosciences ICU at a university hospital. A total of 20 patients were consented and provided a 24-h urine sample to measure the CrClA. If patients experienced CV, a 24-h urine collection was repeated during vasospasm treatment. CrClA was measured using a modified Jaffe assay. RESULTS: Among the 20 patients enrolled, the mean SAH CrClA was 325.93 ± 135.20 ml/min 1.73 m(2) and this differed significantly from the SAH estimated creatinine clearance (CrClE) 144.93 ± 42.82 ml/min 1.73 m(2) (p < 0.001). Four patients developed CV; the mean CV CrClA was 558.43 ± 356.12 ml/min 1.73 m(2) and there was no significant difference when compared to those patients' mean SAH CrClA (246.91 ± 84.14 ml/min 1.73 m(2), p = 0.16). CONCLUSIONS: ARC was present in 100 % of the patients with recent SAH enrolled. Although ARC remained present in the patients who experienced CV, their creatinine clearance was not significantly further augmented. Further work is needed to clarify the impact of such clearances on renally excreted medications and how the development and treatment of CV further augment these findings.