Pharmacological Prevention of Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Causes of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH) include early brain injury and delayed neurologic deterioration, which may result from delayed cerebral ischemia (DCI). Complex pathophysiological mechanisms underlie DCI, which often includes angiographic vasospasm (aVSP) of cerebral arteries. METHODS: Despite the study of many pharmacological therapies for the prevention of DCI in aSAH, nimodipine-a dihydropyridine calcium channel blocker-remains the only drug recommended universally in this patient population. A common theme in the research of preventative therapies is the use of promising drugs that have been shown to reduce the occurrence of aVSP but ultimately did not improve functional outcomes in large, randomized studies. An example of this is the endothelin antagonist clazosentan, although this agent was recently approved in Japan. RESULTS: The use of the only approved drug, nimodipine, is limited in practice by hypotension. The administration of nimodipine and its counterpart nicardipine by alternative routes, such as intrathecally or formulated as prolonged release implants, continues to be a rational area of study. Additional agents approved in other parts of the world include fasudil and tirilazad. CONCLUSIONS: We provide a brief overview of agents currently being studied for prevention of aVSP and DCI after aSAH. Future studies may need to identify subpopulations of patients who can benefit from these drugs and perhaps redefine acceptable outcomes to demonstrate impact.

Guidelines for the Neurocritical Care Management of Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The neurointensive care management of patients with aneurysmal subarachnoid hemorrhage (aSAH) is one of the most critical components contributing to short-term and long-term patient outcomes. Previous recommendations for the medical management of aSAH comprehensively summarized the evidence based on consensus conference held in 2011. In this report, we provide updated recommendations based on appraisal of the literature using the Grading of Recommendations Assessment, Development, and Evaluation methodology. METHODS: The Population/Intervention/Comparator/Outcome (PICO) questions relevant to the medical management of aSAH were prioritized by consensus from the panel members. The panel used a custom-designed survey instrument to prioritize clinically relevant outcomes specific to each PICO question. To be included, the study design qualifying criteria were as follows: prospective randomized controlled trials (RCTs), prospective or retrospective observational studies, case-control studies, case series with a sample larger than 20 patients, meta-analyses, restricted to human study participants. Panel members first screened titles and abstracts, and subsequently full text review of selected reports. Data were abstracted in duplicate from reports meeting inclusion criteria. Panelists used the Grading of Recommendations Assessment, Development, and Evaluation Risk of Bias tool for assessment of RCTs and the "Risk of Bias In Nonrandomized Studies - of Interventions" tool for assessment of observational studies. The summary of the evidence for each PICO was presented to the full panel, and then the panel voted on the recommendations. RESULTS: The initial search retrieved 15,107 unique publications, and 74 were included for data abstraction. Several RCTs were conducted to test pharmacological interventions, and we found that the quality of evidence for nonpharmacological questions was consistently poor. Five PICO questions were supported by strong recommendations, one PICO question was supported by conditional recommendations, and six PICO questions did not have sufficient evidence to provide a recommendation. CONCLUSIONS: These guidelines provide recommendations for or against interventions proven to be effective, ineffective, or harmful in the medical management of patients with aSAH based on a rigorous review of the available literature. They also serve to highlight gaps in knowledge that should guide future research priorities. Despite improvements in the outcomes of patients with aSAH over time, many important clinical questions remain unanswered.

Impact of Pharmacists to Improve Patient Care in the Critically Ill: A Large Multicenter Analysis Using Meaningful Metrics With the Medication Regimen Complexity-ICU (MRC-ICU) Score.

OBJECTIVES: Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not optimized in the ICU. Medication regimen complexity (as measured by the Medication Regimen Complexity-ICU [MRC-ICU] scoring tool) has been proposed as a potential metric to optimize critical care pharmacist workload but has lacked robust external validation. The purpose of this study was to test the hypothesis that MRC-ICU is related to both patient outcomes and pharmacist interventions in a diverse ICU population. DESIGN: This was a multicenter, observational cohort study. SETTING: Twenty-eight ICUs in the United States. PATIENTS: Adult ICU patients. INTERVENTIONS: Critical care pharmacist interventions (quantity and type) on the medication regimens of critically ill patients over a 4-week period were prospectively captured. MRC-ICU and patient outcomes (i.e., mortality and length of stay [LOS]) were recorded retrospectively. MEASUREMENTS AND MAIN RESULTS: A total of 3,908 patients at 28 centers were included. Following analysis of variance, MRC-ICU was significantly associated with mortality (odds ratio, 1.09; 95% CI, 1.08-1.11; p < 0.01), ICU LOS (ß coefficient, 0.41; 95% CI, 00.37-0.45; p < 0.01), total pharmacist interventions (ß coefficient, 0.07; 95% CI, 0.04-0.09; p < 0.01), and a composite intensity score of pharmacist interventions (ß coefficient, 0.19; 95% CI, 0.11-0.28; p < 0.01). In multivariable regression analysis, increased patient: pharmacist ratio (indicating more patients per clinician) was significantly associated with increased ICU LOS (ß coefficient, 0.02; 0.00-0.04; p = 0.02) and reduced quantity (ß coefficient, -0.03; 95% CI, -0.04 to -0.02; p < 0.01) and intensity of interventions (ß coefficient, -0.05; 95% CI, -0.09 to -0.01). CONCLUSIONS: Increased medication regimen complexity, defined by the MRC-ICU, is associated with increased mortality, LOS, intervention quantity, and intervention intensity. Further, these results suggest that increased pharmacist workload is associated with decreased care provided and worsened patient outcomes, which warrants further exploration into staffing models and patient outcomes.

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.

Comparison of Amphotericin B Bladder Irrigations Versus Fluconazole for the Treatment of Candiduria in Intensive Care Unit Patients.

BACKGROUND: Funguria occurs often in hospitalized patients and is most commonly caused by Candida species. Fluconazole is the agent of choice for most Candida urinary tract infections. Amphotericin B bladder irrigations (ABBI) are an alternative treatment option. OBJECTIVE: The purpose of this study is to assess the efficacy of ABBI compared to fluconazole for the treatment of candiduria in the intensive care unit (ICU) setting. METHODS: We conducted a retrospective chart review of patients admitted to ICUs at our institution with a positive urine culture for Candida species between 2005 and 2012. All patients receiving ABBI were included; patients receiving fluconazole for treatment of candiduria were matched by year. The primary endpoint was achievement of cure. RESULTS: There was no difference in cure between the ABBI and fluconazole groups (59.6% vs. 52.8%, p = 0.55). Clearance was higher in patients receiving ABBI (92.3% vs. 67.9%, p < 0.001). Logistic regression found that renal dysfunction predicted greater cure with ABBI therapy compared to fluconazole (OR 7.63, 95% CI 1.81-32.1). CONCLUSION: ABBI was equally efficacious in achieving overall cure, and resulted in greater clearance of candiduria compared to fluconazole. ABBI may be considered an alternative to fluconazole for the treatment of candiduria and may be preferred over fluconazole in patients with renal dysfunction.