Impact of fludrocortisone on the outcomes of subarachnoid hemorrhage patients: A retrospective analysis.

BACKGROUND: Whether the use of fludrocortisone affects outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We conducted a retrospective analysis of 78 consecutive patients with a ruptured aSAH at a single academic center in the United States. The primary outcome was the score on the modified Rankin scale (mRS, range, 0 [no symptoms] to 6 [death]) at 90 days. The primary outcome was adjusted for age, hypertension, aSAH grade, and time from aSAH onset to aneurysm treatment. Secondary outcomes were neurologic and cardiopulmonary dysfunction events. RESULTS: Among 78 patients at a single center, the median age was 58 years [IQR, 49 to 64.5]; 64 % were female, and 41 (53 %) received fludrocortisone. The adjusted common odds ratio, aOR, of a proportional odds regression model of fludrocortisone use with mRS was 0.33 (95 % CI, 0.14-0.80; P = 0.02), with values <1.0 favoring fludrocortisone. Organ-specific dysfunction events were not statistically different: delayed cerebral ischemia (22 % vs. 39 %, P = 0.16); cardiac dysfunction (0 % vs. 11 %; P = 0.10); and pulmonary edema (15 % vs. 8 %; P = 0.59). CONCLUSIONS: The risk of disability or death at 90 days was lower with the use of fludrocortisone in aSAH patients.

Low plasma citrulline levels are associated with acute respiratory distress syndrome in patients with severe sepsis.

INTRODUCTION: The role of nitric oxide synthase (NOS) in the pathophysiology of acute respiratory distress syndrome (ARDS) is not well understood. Inducible NOS is upregulated during physiologic stress; however, if NOS substrate is insufficient then NOS can uncouple and switch from NO generation to production of damaging peroxynitrites. We hypothesized that NOS substrate levels are low in patients with severe sepsis and that low levels of the NOS substrate citrulline would be associated with end organ damage including ARDS in severe sepsis. METHODS: Plasma citrulline, arginine and ornithine levels and nitrate/nitrite were measured at baseline in 135 patients with severe sepsis. ARDS was diagnosed by consensus definitions. RESULTS: Plasma citrulline levels were below normal in all patients (median 9.2 uM, IQR 5.2 - 14.4) and were significantly lower in ARDS compared to the no ARDS group (6.0 (3.3 - 10.4) vs. 10.1 (6.2 - 16.6), P = 0.002). The rate of ARDS was 50% in the lowest citrulline quartile compared to 15% in the highest citrulline quartile (P = 0.002). In multivariable analyses, citrulline levels were associated with ARDS even after adjustment for covariates including severity of illness. CONCLUSIONS: In severe sepsis, levels of the NOS substrate citrulline are low and are associated with ARDS. Low NOS substrate levels have been shown in other disease states to lead to NOS uncoupling and oxidative injury suggesting a potential mechanism for the association between low citrulline and ARDS. Further studies are needed to determine whether citrulline supplementation could prevent the development of ARDS in patients with severe sepsis and to determine its role in NOS coupling and function.

Impact of Fludrocortisone on the Outcomes of Subarachnoid Hemorrhage Patients: A Retrospective Analysis.

Background: Whether the use of fludrocortisone affects outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) and its usage rate in the United States remain unknown. Methods: We conducted a retrospective analysis of 78 consecutive patients with a ruptured aSAH at a single academic center in the United States. The primary outcome was the score on the modified Rankin scale (mRS, range, 0 [no symptoms] to 6 [death]) at 90 days. We adjusted the primary outcome for age, hypertension, aSAH grade, and time from aSAH onset to aneurysm treatment. Secondary outcomes were brain and cardiopulmonary dysfunction events. Results: Among 78 patients at a single center, the median age was 58 years [IQR, 49 to 64.5]; 64% were female, and 41 (53%) received fludrocortisone. The adjusted common odds ratio, aOR, of a proportional odds regression model of fludrocortisone use with mRS was 0.33 (95% CI, 0.14-0.80; P=0.02), with values <1.0 favoring fludrocortisone. Organ-specific dysfunction events were not statistically different: delayed cerebral ischemia (22% vs. 39%, P=0.16); cardiac dysfunction (0% vs. 11%; P=0.10); and pulmonary edema (15% vs. 8%; P=0.59). Conclusions: The risk of disability or death at 90 days was lower with the use of fludrocortisone in aSAH patients.

Saline versus Balanced Crystalloids for Adults with Aneurysmal Subarachnoid Hemorrhage: A Subgroup Analysis of the SMART Trial.

Background: Whether the composition of intravenous crystalloid solutions affects outcomes in adults with aneurysmal subarachnoid hemorrhage (aSAH) remains unknown. Therefore, we determined whether the use of saline is associated with lower risk of disability and death in aSAH patients compared to balanced crystalloids. Methods: We conducted a post hoc subgroup analysis of the Isotonic Solutions and Major Adverse Renal Events Trial (SMART), a pragmatic, unblinded, cluster-randomized, multiple-crossover clinical trial that enrolled 15,802 adults between June 2015 and April 2017. We compared intravenous administration of saline to balanced crystalloids in consecutively enrolled aSAH patients aged 18 years or older whose ruptured aneurysm was procedurally secured at a single academic center in the United States. The primary outcome was the score on the modified Rankin scale (mRS, range, 0 [no symptoms] to 6 [death]) at 90 days obtained from a prospective institutional stroke registry. Secondary outcome included death by 90 days. Logistic or proportional odds regression models were used to test for between-group differences adjusted for age, hypertension, aSAH grade, and procedure type. Results: Of the 79 aSAH patients procedurally treated during the SMART study period, 78 were enrolled (median age, 58 years; IQR, 49 to 64.5; 64% female), with 41 (53%) assigned to saline and 37 (47%) to balanced crystalloids. Plasma-Lyte was the primary balanced crystalloid used. Among 72 patients with 90-day mRS assessment, the adjusted common odds ratio, aOR, for mRS was 0.68 (95% CI, 0.28-1.63; P=0.39), with values less than 1.0 favoring saline. By 90 days, 2/39 patients (5%) in the saline group and 9/35 (26%) in the balanced-crystalloids group had died (aOR, 0.06; 95% CI, 0.00-0.50; P=0.02). Conclusions: Among procedurally treated aSAH patients, the risk of disability or death at 90 days did not significantly differ between saline and balanced crystalloids. Death occurred less frequently with saline than balanced crystalloids.

Bone Cement Cranioplasty Reduces Cerebrospinal Fluid Leak Rate after Microvascular Decompression: A Single-Institutional Experience.

Background Microvascular decompression (MVD) is a common surgical treatment for cranial nerve compression, though cerebrospinal fluid (CSF) leak is a known complication of this procedure. Bone cement cranioplasty may reduce rates of CSF leak. Objective To compare rates of CSF leak before and after implementation of bone cement cranioplasty for the reconstruction of cranial defects after MVD. Methods Retrospective chart review was performed of patients who underwent MVD through retrosigmoid craniectomy for cranial nerve compression at a single institution from 1998 to 2017. Study variables included patient demographics, medical history, type of closure, and postoperative complications such as CSF leak, meningitis, lumbar drain placement, and ventriculoperitoneal shunt insertion. Cement and noncement closure groups were compared, and predictors of CSF leak were assessed using a multivariate logistic regression model. Results A total of 547 patients treated by 10 neurosurgeons were followed up for more than 20 years, of whom 288 (52.7%) received cement cranioplasty and 259 (47.3%) did not. Baseline comorbidities were not significantly different between groups. CSF leak rate was significantly lower in the cement group than in the noncement group (4.5 vs. 14.3%; p < 0.001). This was associated with significantly fewer patients developing postoperative meningitis (0.7 vs. 5.2%; p = 0.003). Multiple logistic regression model demonstrated noncement closure as the only independent predictor of CSF leak (odds ratio: 3.55; 95% CI: 1.78-7.06; p < 0.001). Conclusion CSF leak is a well-known complication after MVD. Bone cement cranioplasty significantly reduces the incidence of postoperative CSF leak and other complications. Modifiable risk factors such as body mass index were not associated with the development of CSF leak.

The CT-Defined Hyperdense Arterial Sign as a Marker for Acute Intracerebral Large Vessel Occlusion.

BACKGROUND AND PURPOSE: To determine the sensitivity and specificity of the hyperdense artery sign (HAS) on thin-slice non-contrast computed tomography (NCCT), combined with brief clinical history, as an indicator for large vessel occlusion (LVO) in the setting of acute ischemic stroke. METHODS: Ninety-nine LVO and 102 non-LVO acute ischemic stroke patients were retrospectively identified from a prospective database at a single institution. After reviewing each patient's neurologic presentation based on his or her initial National Institute of Health Stroke Scale (NIHSS) and neurologic evaluation, all thin (1 mm) and thick (5 mm) NCCT scans were reviewed for the HAS. Analysis of sensitivity and specificity was conducted to determine the utility of the HAS sign as a reliable marker for LVO in acute ischemic stroke patients. RESULTS: Of the 99 LVO stroke patients, 66 HASs were identified on NCCT. Of the 102 non-LVO patients, 18 false-positive HASs were identified. The sensitivity and specificity of the HAS, respectively, was 67% and 82%. By anatomic distribution, the sensitivity of identifying basilar artery occlusions was 75%, and the sensitivity of identifying middle cerebral artery (MCA) M1 branch occlusions was 76%. Among patients with an NIHSS > 10, the sensitivity was 79%; whereas sensitivity was 50% if NIHSS was ≤ 10. CONCLUSIONS: The HAS on thin-slice NCCT has a reasonably high sensitivity and specificity for identifying LVO in acute ischemic stroke patients presenting with an NIHSS > 10 and suspected MCA M1 or basilar artery occlusion.

Comparison of a pressure-sensing sheath and radial arterial line for intraoperative blood pressure monitoring in neurointerventional procedures.

PURPOSE: The efficiency of neuroendovascular procedures may partly depend on the time devoted to placement of a radial arterial line (RAL) for intraoperative blood pressure monitoring. An alternative approach is to use a pressure-sensing sheath (PSS) that serves to provide invasive blood pressure monitoring without requiring a separate procedure for placement. We compared the use of a RAL versus PSS and assessed procedure time, anesthetist and patient satisfaction, and cost. METHODS: We performed a single-center, prospective, blockwise, comparative trial of procedure start time using traditional RAL placement versus the EndoPhys PSS for invasive blood pressure monitoring. Endpoints included time from room arrival to groin puncture, patient and anesthetist satisfaction ratings, and costs associated with RAL placement. RESULTS: Twenty patients were enrolled in the PSS+RAL arm and 20 in the PSS-alone arm. Mean time from arrival in the room until groin puncture was 61.9±14.0 min in the RAL group and 51.2±10.8 min in the PSS-alone group (P=0.01; difference=10.7 min). Patients in the PSS-alone group reported less pain than those in the RAL group. Furthermore, anesthetists reported accurate blood pressure in the PSS group. The average cost estimate of RAL placement was US$774.70, with a range of US$743 to US$1171. CONCLUSIONS: Placement of a RAL at the start of the neuroendovascular procedures resulted in increased delays to procedure start time and more patient-reported pain compared with the PSS, which may offer a more efficient means of blood pressure monitoring for neurointerventional procedures. CLINICAL TRIAL REGISTRATION: NCT03239847.

Predicting Resident Performance from Preresidency Factors: A Systematic Review and Applicability to Neurosurgical Training.

BACKGROUND: Neurosurgical educators strive to identify the best applicants, yet formal study of resident selection has proved difficult. We conducted a systematic review to answer the following question: What objective and subjective preresidency factors predict resident success? METHODS: PubMed, ProQuest, Embase, and the CINAHL databases were queried from 1952 to 2015 for literature reporting the impact of preresidency factors (PRFs) on outcomes of residency success (RS), among neurosurgery and all surgical subspecialties. Due to heterogeneity of specialties and outcomes, a qualitative summary and heat map of significant findings were constructed. RESULTS: From 1489 studies, 21 articles met inclusion criteria, which evaluated 1276 resident applicants across five surgical subspecialties. No neurosurgical studies met the inclusion criteria. Common objective PRFs included standardized testing (76%), medical school performance (48%), and Alpha Omega Alpha (43%). Common subjective PRFs included aggregate rank scores (57%), letters of recommendation (38%), research (33%), interviews (19%), and athletic or musical talent (19%). Outcomes of RS included faculty evaluations, in-training/board exams, chief resident status, and research productivity. Among objective factors, standardized test scores correlated well with in-training/board examinations but poorly correlated with faculty evaluations. Among subjective factors, aggregate rank scores, letters of recommendation, and athletic or musical talent demonstrated moderate correlation with faculty evaluations. CONCLUSION: Standardized testing most strongly correlated with future examination performance but correlated poorly with faculty evaluations. Moderate predictors of faculty evaluations were aggregate rank scores, letters of recommendation, and athletic or musical talent. The ability to predict success of neurosurgical residents using an evidence-based approach is limited, and few factors have correlated with future resident performance. Given the importance of recruitment to the greater field of neurosurgery, these data provide support for a national, prospective effort to improve the study of neurosurgery resident selection.

Evaluation of previously embolized intracranial aneurysms: inter-and intra-rater reliability among neurosurgeons and interventional neuroradiologists.

BACKGROUND: The angiographic evaluation of previously coiled aneurysms can be difficult yet remains critical for determining re-treatment. OBJECTIVE: The main objective of this study was to determine the inter-rater reliability for both the Raymond Scale and per cent embolization among a group of neurointerventionalists evaluating previously embolized aneurysms. METHODS: A panel of 15 neurointerventionalists examined 92 distinct cases of immediate post-coil embolization and 1 year post-embolization angiographs. Each case was presented four times throughout the study, along with alterations in demographics in order to evaluate intra-rater reliability. All respondents were asked to provide the per cent embolization (0-100%) and Raymond Scale grade (1-3) for each aneurysm. Inter-rater reliability was evaluated by computing weighted kappa values (for the Raymond Scale) and intraclass correlation coefficients (ICC) for per cent embolization. RESULTS: 10 neurosurgeons and 5 interventional neuroradiologists evaluated 368 simulated cases. The agreement among all readers employing the Raymond Scale was fair (κ=0.35) while concordance in per cent embolization was good (ICC=0.64). Clinicians with fewer than 10 years of experience demonstrated a significantly greater level of agreement than the group with greater than 10 years (κ=0.39 and ICC=0.70 vs κ=0.28 and ICC=0.58). When the same aneurysm was presented multiple times, clinicians demonstrated excellent consistency when assessing per cent embolization (ICC=0.82), but moderate agreement when employing the Raymond classification (κ=0.58). CONCLUSIONS: Identifying the per cent embolization in previously coiled aneurysms resulted in good inter- and intra-rater agreement, regardless of years of experience. The strong agreement among providers employing per cent embolization may make it a valuable tool for embolization assessment in this patient population.

Implementation of an institution-wide acute stroke algorithm: Improving stroke quality metrics.

BACKGROUND: In May 2012, an updated stroke algorithm was implemented at Vanderbilt University Medical Center. The current study objectives were to: (1) describe the process of implementing a new stroke algorithm and (2) compare pre- and post-algorithm quality improvement (QI) metrics, specificaly door to computed tomography time (DTCT), door to neurology time (DTN), and door to tPA administration time (DTT). METHODS: Our institutional stroke algorithm underwent extensive revision, with a focus on removing variability, streamlining care, and improving time delays. The updated stroke algorithm was implemented in May 2012. Three primary stroke QI metrics were evaluated over four separate 3-month time points, one pre- and three post-algorithm periods. RESULTS: The following data points improved after algorithm implementation: average DTCT decreased from 39.9 to 12.8 min (P < 0.001); average DTN decreased from 34.1 to 8.2 min (P ≤ 0.001), and average DTT decreased from 62.5 to 43.5 min (P = 0.17). CONCLUSION: A new stroke protocol that prioritized neurointervention at our institution resulted in significant lowering in the DTCT and DTN, with a nonsignificant improvement in DTT.

Utilization of Pipeline embolization device for treatment of ruptured intracranial aneurysms: US multicenter experience.

OBJECTIVE: Utilization of the Pipeline embolization device (PED) in complex ruptured aneurysms has not been well studied. We evaluated the safety and effectiveness data from five participating US centers. METHODS: Records of patients with ruptured cerebral aneurysms who underwent PED treatment between 2011 and 2013 were retrospectively reviewed. RESULTS: 26 patients with ruptured aneurysms underwent PED treatment (mean age 51.4 ± 13.2 years;16 women). At presentation, 8 patients (30.8%) had a Hunt-Hess grade of IV or above; 11 required extraventricular drain placement. Aneurysm morphologies were: 8 dissecting, 8 blister-like, 6 fusiform, and 4 saccular. There were 22 anterior circulation and 4 posterior circulation aneurysms. PED deployment was successful in all patients, with adjunctive coiling utilized in 12. Periprocedural complications occurred in 5 (19.2%), including 3 inhospital deaths. 23 patients (88.5%) had postoperative angiography at a mean of 5.9 months: 18 aneurysms (78.3%) were completely occluded, 3 (13.0%) had residual neck filling, and 2 (8.7%) had residual dome filling. All blister-type aneurysms were completely occluded at follow-up. Clinical follow-up was available for an average of 10.1 months (range 2-21 months), with one asymptomatic in-stent stenosis and one asymptomatic thromboembolic stroke noted. Good outcome (modified Rankin Scale (mRS) score of 0-2) was achieved in 20 patients (76.9%), fair (mRS 3-4) in 3 (11.5%), and 3 died (11.5%). CONCLUSIONS: The PED can be utilized for ruptured aneurysms and is a good option for blister-type aneurysms. However, due to periprocedural complications, it should be reserved for lesions that are difficult to treat by conventional clipping or coiling.

γ-Glutamylcysteine ameliorates oxidative injury in neurons and astrocytes in vitro and increases brain glutathione in vivo.

γ-Glutamylcysteine (γ-GC) is an intermediate molecule of the glutathione (GSH) synthesis pathway. In the present study, we tested the hypothesis that γ-GC pretreatment in cultured astrocytes and neurons protects against hydrogen peroxide (H(2)O(2))-induced oxidative injury. We demonstrate that pretreatment with γ-GC increases the ratio of reduced:oxidized GSH levels in both neurons and astrocytes and increases total GSH levels in neurons. In addition, γ-GC pretreatment decreases isoprostane formation both in neurons and astrocytes, as well as nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation in astrocytes in response to H(2)O(2)-induced oxidative stress. Furthermore, GSH and isoprostane levels significantly correlate with increased neuron and astrocyte viability in cells pretreated with γ-GC. Finally, we demonstrate that administration of a single intravenous injection of γ-GC to mice significantly increases GSH levels in the brain, heart, lungs, liver, and in muscle tissues in vivo. These results support a potential therapeutic role for γ-GC in the reduction of oxidant stress-induced damage in tissues including the brain.