Diagnostic value of a ghrelin test for the diagnosis of GH deficiency after subarachnoid hemorrhage

ObjectiveTo determine the diagnostic value of a ghrelin test in the diagnosis of GH deficiency (GHD) shortly after aneurysmal subarachnoid hemorrhage (SAH).DesignProspective single-center observational cohort study.MethodsA ghrelin test was assessed after the acute phase of SAH and a GH-releasing hormone (GHRH)–arginine test 6 months post SAH. Primary outcome was the diagnostic value of a ghrelin test compared with the GHRH–arginine test in the diagnosis of GHD. The secondary outcome was to assess the safety of the ghrelin test, including patients' comfort, adverse events, and idiosyncratic reactions.ResultsForty-three survivors of SAH were included (15 males, 35%, mean age 56.6±11.7). Six out of 43 (14%) SAH survivors were diagnosed with GHD by GHRH–arginine test. In GHD subjects, median GH peak during ghrelin test was significantly lower than that of non-GHD subjects (5.4 vs 16.6,P=0.002). Receiver operating characteristics analysis showed an area under the curve of 0.869. A cutoff limit of a GH peak of 15 μg/l corresponded with a sensitivity of 100% and a false-positive rate of 40%. No adverse events or idiosyncratic reactions were observed in subjects undergoing a ghrelin test, except for one subject who reported flushing shortly after ghrelin infusion.ConclusionOwing to its convenience, validity, and safety, the ghrelin test might be a valuable GH provocative test, especially in the early phase of SAH.

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Abstract W MP37: Novel Prognostic Scores for Early Prediction of Outcome Following Aneurysmal Subarachnoid Hemorrhage

Stroke ◽

10.1161/str.46.suppl_1.wmp37 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Blessing Jaja ◽

Hester Lingsma ◽

Ewout Steyerberg ◽

R. Loch Macdonald ◽

Keyword(s):

Subarachnoid Hemorrhage ◽

Cross Validation ◽

Prediction Models ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Model Performance ◽

Predictor Variable ◽

Predictive Ability ◽

Prognostic Scores ◽

Operating Characteristics ◽

Fisher Grade

Background: Aneurysmal subarachnoid hemorrhage (SAH) is a cerebrovascular emergency. Currently, clinicians have limited tools to estimate outcomes early after hospitalization. We aimed to develop novel prognostic scores using large cohorts of patients reflecting experience from different settings. Methods: Logistic regression analysis was used to develop prediction models for mortality and unfavorable outcomes according to 3-month Glasgow outcome score after SAH based on readily obtained parameters at hospital admission. The development cohort was derived from 10 prospective studies involving 10936 patients in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository. Model performance was assessed by bootstrap internal validation and by cross validation by omission of each of the 10 studies, using R2 statistic, Area under the receiver operating characteristics curve (AUC), and calibration plots. Prognostic scores were developed from the regression coefficients. Results: Predictor variable with the strongest prognostic strength was neurologic status (partial R2 = 12.03%), followed by age (1.91%), treatment modality (1.25%), Fisher grade of CT clot burden (0.65%), history of hypertension (0.37%), aneurysm size (0.12%) and aneurysm location (0.06%). These predictors were combined to develop 3 sets of hierarchical scores based on the coefficients of the regression models. The AUC at bootstrap validation was 0.79-0.80, and at cross validation was 0.64-0.85. Calibration plots demonstrated satisfactory agreement between predicted and observed probabilities of the outcomes. Conclusions: The novel prognostic scores have good predictive ability and potential for broad application as they have been developed from prospective cohorts reflecting experience from different centers globally.

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Abstract 194: Cognitive Outcome in Acute Simvastatin Treatment for Aneurysmal Subarachnoid Hemorrhage

Stroke ◽

10.1161/str.47.suppl_1.194 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

George Wong ◽

Keyword(s):

Cognitive Impairment ◽

Subarachnoid Hemorrhage ◽

Cerebral Infarction ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Primary Outcome Measure ◽

Cognitive Outcomes ◽

Cognitive Outcome ◽

Secondary Outcome ◽

Modified Rankin Scale ◽

Simvastatin Treatment

Objectives: Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid haemorrhage (SAH). Recently, acute simvastatin treatment was not shown to be beneficial in neurological outcome using modified Rankin Scale. Cognitive function is another important dimension of outcome assessment and yet had not been investigated in statin studies for aneurysmal subarachnoid hemorrhage. We therefore explored whether acute simvastatin treatment would improve cognitive outcomes. Methods: The study recruited SAH patients with acute simvastatin treatment enrolled in a randomized controlled double-blinded clinical trial (ClinicalTrials.gov Identifier: NCT01038193). A control cohort of SAH patients without simvastatin treatment was identified with propensity score matching of age and admission grade. Primary outcome measure was Montreal Cognitive Assessment (MoCA). Secondary outcome measures were delayed ischaemic deficit (DID), delayed cerebral infarction, modified Rankin Scale (mRS), and Mini-Mental State Examination( MMSE). Results: Fifty-one SAH patients with acute simvastatin treatment and 51 SAH patients without simvastatin treatment were recruited for analysis. At 3 months, there were no differences in MoCA scores (MoCA: 21+/-6 vs. 21+/-5, p=0.772). MoCA-assessed cognitive impairment (MoCA<26) was not different (75% vs. 80%, OR 0.7, 95%CI 0.3 to 1.8, p=0.477). There were also no differences in DID, delayed cerebral infarction, favorable mRS outcome, and MMSE scores, and MMSE-assessed cognitive impairment between both groups. Conclusions: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage.

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Invasive Multimodal Neuromonitoring in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review

Stroke ◽

10.1161/strokeaha.121.034633 ◽

2021 ◽

Author(s):

Michael Veldeman ◽

Walid Albanna ◽

Miriam Weiss ◽

Soojin Park ◽

Anke Hoellig ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Trend Analysis ◽

Oxygen Tension ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Case Series ◽

Diagnostic Value ◽

Cerebral Microdialysis ◽

Treatment Support ◽

Patients At Risk

Background and Purpose: Aneurysmal subarachnoid hemorrhage is a devastating disease leaving surviving patients often severely disabled. Delayed cerebral ischemia (DCI) has been identified as one of the main contributors to poor clinical outcome after subarachnoid hemorrhage. The objective of this review is to summarize existing clinical evidence assessing the diagnostic value of invasive neuromonitoring (INM) in detecting DCI and provide an update of evidence since the 2014 consensus statement on multimodality monitoring in neurocritical care. Methods: Three invasive monitoring techniques were targeted in the data collection process: brain tissue oxygen tension (p ti O 2 ), cerebral microdialysis, and electrocorticography. Prospective and retrospective studies as well as case series (≥10 patients) were included as long as monitoring was used to detect DCI or guide DCI treatment. Results: Forty-seven studies reporting INM in the context of DCI were included (p ti O 2 : N=21; cerebral microdialysis: N=22; electrocorticography: N=4). Changes in brain oxygen tension are associated with angiographic vasospasm or reduction in regional cerebral blood flow. Metabolic monitoring with trend analysis of the lactate to pyruvate ratio using cerebral microdialysis, identifies patients at risk for DCI. Clusters of cortical spreading depolarizations are associated with clinical neurological worsening and cerebral infarction in selected patients receiving electrocorticography monitoring. Conclusions: Data supports the use of INM for the detection of DCI in selected patients. Generalizability to all subarachnoid hemorrhage patients is limited by design bias of available studies and lack of randomized trials. Continuous data recording with trend analysis and the combination of INM modalities can provide tailored treatment support in patients at high risk for DCI. Future trials should test interventions triggered by INM in relation to cerebral infarctions.

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Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Meta-analysis of Randomized Controlled Trials

10.21203/rs.3.rs-711779/v1 ◽

2021 ◽

Author(s):

Tao Liu ◽

Huiru Ding ◽

Renmin Xue

Keyword(s):

Subarachnoid Hemorrhage ◽

Adverse Events ◽

Tranexamic Acid ◽

Randomized Controlled Trials ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Heterogeneous Data ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Controlled Trials ◽

Randomized Controlled

Abstract BackgroundTranexamic acid, as a hemostatic drug, is widely used to treat or prevent excessive blood loss. The efficacy of tranexamic acid in promoting good clinical outcomes, reducing mortality, and the occurrence of adverse events during treatment of aneurysmal subarachnoid hemorrhage remains unclear.MethodsPubMed, Web of Science, Embase, and The Cochrane Library were searched for randomized-controlled trials (from1980 to 2021) following strict inclusion and exclusion criteria. We performed STATA 16.0 and RevMan 5.3 for statistical analysis. Fixed-effect model (M-H method) and effect size RR (95% CI) were used as a pooled measure to combine the heterogeneous data. We also performed post hoc sensitivity analyses and conducted subgroup analyses to evaluate each outcome with low heterogeneity results.ResultsMeta-analysis showed that tranexamic acid was associated with reduced rebleeding(RR 0.72 [0.59, 0.87], p= 0.0008; I2:0%, p = 0.51). Tranexamic acid probably has no effect on good clinical outcome or mortality (RR 0.98 [0.92,1.04], p = 0.51; I2: 0%, p = 0.60; RR 1.01 [0.88,1.15], p=0.91; I2:0%, p = 0.51).TXA was associated with increased hydrocephalus (RR 1.13 [1.02, 1.24], p = 0.02; I2:0%, p = 0.61), DCI (RR 1.70 [1.34, 2.16], p < 0.0001; I2: 0%, p= 0.84) and seizure (RR 1.46 [1.00, 2.14], p= 0.05),The rate for thromboembolic complications were similar in both groups(RR 0.91 [0.63, 1.31], p = 0.62;I2: 0%, p = 0.73). There was significant drug related overall adverse events (RR 1.21 [1.11, 1.32], p < 0.0001; I2: 29%, p = 0.14).ConclusionsIn patients with aneurysmal subarachnoid hemorrhage, these findings indicate that it does not support the routine use of TXA.

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A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency

Acta Endocrinologica ◽

10.1530/eje-07-0066 ◽

2007 ◽

Vol 157 (1) ◽

pp. 19-27 ◽

Cited By ~ 53

Author(s):

Kazuo Chihara ◽

Akira Shimatsu ◽

Naomi Hizuka ◽

Toshiaki Tanaka ◽

Yoshiki Seino ◽

...

Keyword(s):

Diagnostic Test ◽

Gh Deficiency ◽

High Reliability ◽

Diagnostic Value ◽

Tolerance Test ◽

World Health ◽

Elderly Subjects ◽

Provocative Test ◽

Adult Gh Deficiency ◽

Serum Gh

Objective: The international, first-line diagnostic test for adult GH deficiency is the insulin tolerance test (ITT), which is contraindicated in some patients due to severe adverse events. Alternatives such as GH-releasing hormone combined with arginine or GH-releasing peptides (GHRP) have been proposed. We validated the use of GHRP-2 for diagnosing adult GH deficiency (GHD). Methods: Seventy-seven healthy subjects and 58 patients with peak GH<3 μg/l by ITT were enrolled. After overnight fasting, a 100 μg dose of GHRP-2 was administered intravenously; blood samples were taken during the subsequent 2 h and GH measured by immunoradiometric assay. Results: Serum GH peak occurred within 60 min after GHRP-2 administration in all subjects. GH responses to GHRP-2 were not affected by gender, but were slightly lower in elderly subjects and those with adiposity, although these did not influence diagnosis of GHD. Repeated tests showed favourable reproducibility. Peak GH concentrations after GHRP-2 were significantly (P<0.001) lower in patients (1.36±2.60 μg/l) than the healthy group (84.6±60.9 μg/l) with no difference between hypothalamic and pituitary diseases. Serum GH concentration at the point where sensitivity of response crossed with specificity ranged from 15 to 20 μg/l. A cut-off value of 15 μg/l for diagnosing GHD with GHRP-2 corresponded to the diagnostic value of 3 μg/l in the ITT. Conclusions: The GHRP-2 provocative test showed favourable reproducibility and was mildly influenced by age and adiposity. Severe GH deficiency could be diagnosed with high reliability using a 15 μg/l (9 μg/l when GH calibrated with recombinant World Health Organization 98/574 standard) cut-off for peak GH concentration.

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Reduction of inflammation after administration of interleukin-1 receptor antagonist following aneurysmal subarachnoid hemorrhage: results of the Subcutaneous Interleukin-1Ra in SAH (SCIL-SAH) study

Journal of Neurosurgery ◽

10.3171/2016.9.jns16615 ◽

2018 ◽

Vol 128 (2) ◽

pp. 515-523 ◽

Cited By ~ 33

Author(s):

James Galea ◽

Kayode Ogungbenro ◽

Sharon Hulme ◽

Hiren Patel ◽

Sylvia Scarth ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Receptor Antagonist ◽

Inflammatory Markers ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Interleukin 1 ◽

Area Under The Curve ◽

Phase Iii ◽

Secondary Outcome ◽

Cerebrovascular Event

OBJECTIVEAneurysmal subarachnoid hemorrhage (aSAH) is a devastating cerebrovascular event with long-term morbidity and mortality. Patients who survive the initial bleeding are likely to suffer further early brain injury arising from a plethora of pathological processes. These may result in a worsening of outcome or death in approximately 25% of patients and may contribute to longer-term cognitive dysfunction in survivors. Inflammation, mediated by the cytokine interleukin-1 (IL-1), is an important contributor to cerebral ischemia after diverse forms of brain injury, including aSAH. Its effects are attenuated by its naturally occurring antagonist, IL-1 receptor antagonist (IL-1Ra [anakinra]). The authors hypothesized that administration of additional subcutaneous IL-1Ra would reduce inflammation and associated plasma markers associated with poor outcome following aSAH.METHODSThis was a randomized, open-label, single-blinded study of 100 mg subcutaneous IL-1Ra, administered twice daily in patients with aSAH, starting within 3 days of ictus and continuing until 21 days postictus or discharge from the neurosurgical center, whichever was earlier. Blood samples were taken at admission (baseline) and at Days 3–8, 14, and 21 postictus for measurement of inflammatory markers. The primary outcome was difference in plasma IL-6 measured as area under the curve between Days 3 and 8, corrected for baseline value. Secondary outcome measures included similar area under the curve analyses for other inflammatory markers, plasma pharmacokinetics for IL-1Ra, and clinical outcome at 6 months.RESULTSInterleukin-1Ra significantly reduced levels of IL-6 and C-reactive protein (p < 0.001). Fibrinogen levels were also reduced in the active arm of the study (p < 0.002). Subcutaneous IL-1Ra was safe, well tolerated, and had a predictable plasma pharmacokinetic profile. Although the study was not powered to investigate clinical effect, scores of the Glasgow Outcome Scale–extended at 6 months were better in the active group; however, this outcome did not reach statistical significance.CONCLUSIONSSubcutaneous IL-1Ra is safe and well tolerated in aSAH. It is effective in reducing peripheral inflammation. These data support a Phase III study investigating the effect of IL-1Ra on outcome following aSAH.Clinical trial registration no.: EudraCT: 2011-001855-35 (www.clinicaltrialsregister.eu)

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Elevated Glucose-Potassium Ratio Predicts Preoperative Rebleeding in Patients With Aneurysmal Subarachnoid Hemorrhage

Frontiers in Neurology ◽

10.3389/fneur.2021.795376 ◽

2022 ◽

Vol 12 ◽

Author(s):

Jiayin Wang ◽

Qiangqiang Feng ◽

Yinbin Zhang ◽

Weizhi Qiu ◽

Hongzhi Gao

Keyword(s):

Subarachnoid Hemorrhage ◽

Poor Prognosis ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Pearson Correlation ◽

Multivariable Analysis ◽

Area Under The Curve ◽

Serum Glucose ◽

Diabetic Patients ◽

Operating Characteristics ◽

Preoperative Serum

Introduction: Recent reports revealed that higher serum glucose-potassium ratio (GPR) levels at admission were significantly associated with poor outcomes at 3 months following aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the association between GPR and the risk of rebleeding following aSAH.Methods: This single-center retrospective study of patients with aSAH was conducted in our hospital between January 2008 and December 2020. Patients meeting the inclusion criteria were divided into the rebleed group and the non-rebleed group. Univariate and multivariate analyses were implemented to assess the association between risk factors of rebleeding and outcomes.Results: A total of 1,367 patients experiencing aSAH, 744 patients who met the entry criteria in the study [mean age (54.89 ± 11.30) years; 60.50% female patients], of whom 45 (6.05%) developed rebleeding. The patients in the rebleed group had significantly higher GPR levels than those of patients without rebleeding [2.13 (1.56–3.20) vs. 1.49 (1.23–1.87); p < 0.001]. Multivariable analysis revealed that higher mFisher grade and GPR were associated with rebleeding [mFisher grade, odds ratios (OR) 0.361, 95% CI 0.166–0.783, p = 0.01; GPR, OR 0.254, 95% CI 0.13–0.495, p < 0.001]. The receiver operating characteristics (ROCs) analysis described that the suitable cut-off value for GPR as a predictor for rebleeding in patients with aSAH was determined as 2.09 (the area under the curve [AUC] was 0.729, 95% CI 0.696–0.761, p < 0.0001; the sensitivity was 53.33%, and the specificity was 83.98%). Pearson correlation analysis showed a significant positive correlation between GPR and mFisher grade, between GPR and Hunt–Hess grade (mFisher grade r = 0.4271, OR 0.1824, 95% CI 0.3665–0.4842, p < 0.001; Hunt–Hess grade r = 0.4248, OR 0.1836, 95% CI 0.3697–0.4854, p < 0.001). The patients in the poor outcome had significantly higher GPR levels than those of patients in the good outcome [1.87 (1.53–2.42) vs. 1.45 (1.20–1.80); p < 0.001]. Multivariable analysis demonstrated that GPR was an independent predictor for poor prognosis. The AUC of GPR was 0.709 (95% CI 0.675–0.741; p < 0.0001) (sensitivity = 77.70%; specificity = 55.54%) for poor prognosis.Conclusion: Higher preoperative serum GPR level was associated with Hunt–Hess grade, mFisher grade, rebleeding, and unfunctional outcome, and that they predicted preoperative rebleeding and the 90-days outcome of non-diabetic patients with aSAH, who had potentially relevant clinical implications in patients with aSAH.

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Systemic Immune-Inflammation Index Predicts the Outcome After Aneurysmal Subarachnoid Hemorrhage

10.21203/rs.3.rs-687534/v1 ◽

2021 ◽

Author(s):

Fushu Luo ◽

Yuanyou Li ◽

Yutong Zhao ◽

Mingjiang Sun ◽

Qiuguang He ◽

...

Keyword(s):

Logistic Regression ◽

Subarachnoid Hemorrhage ◽

Inflammatory Response ◽

Early Stage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Area Under The Curve ◽

Systemic Inflammatory Response ◽

Unfavorable Outcome ◽

Operating Characteristics ◽

Immune Inflammation

Abstract Objectives: Systemic inflammatory response is closely related to the pathogenesis and prognosis in critical patients. Recently, systemic immune-inflammation index (SII), an indicator of systemic inflammatory response, was proved to predict the outcome in cancerous and non-cancerous diseases. The aim of this study is to evaluate the relationship between SII on admission and 6-month outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH).Methods: The clinical data and prognosis of 76 patients with aSAH was analyzed. Patients were divided into high SII group and low SII group. The 6-month outcome was assessed by the modified Rankin scale (mRS).The unfavorable outcome was defined as mRS score ≥3. Receiver operating characteristics (ROC), area under the curve (AUC) and logistic regression were used to examine the relations between SII levels and 6-month clinical outcomes.Results: Thirty-six patients (47.4%) in our study had a unfavorable outcome (mRS ≥3) at 6 months, and twenty-four (66.7%) of them had high SII. Spearman correlation analysis showed that the SII was correlated with mRS (r=0.418, P＜0.05). Binary logistic regression showed that there was an independent association between SII on admission and 6-month clinical outcome (OR=4.271, 95%CI: 1.047-17.422, P＜0.05). The AUC of the SII for predicting unfavorable outcome was 0.692(95% CI:0.571–0.814, P＜0.05).Conclusion: Systemic immune-inflammation index (SII) could be a novel independent prognostic factor for aSAH patients at the early stage of the disease.

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Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a preliminary report

Journal of Neurosurgery ◽

10.3171/jns.2000.93.5.0743 ◽

2000 ◽

Vol 93 (5) ◽

pp. 743-752 ◽

Cited By ~ 300

Author(s):

Daniel F. Kelly ◽

Irene T. Gaw Gonzalo ◽

Pejman Cohan ◽

Nancy Berman ◽

Ronald Swerdloff ◽

...

Keyword(s):

Risk Factors ◽

Subarachnoid Hemorrhage ◽

Head Injury ◽

Severe Head Injury ◽

Gh Deficiency ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Content Type ◽

Pituitary Dysfunction ◽

Function Testing ◽

Fine Print

Object. Recognition of pituitary hormonal insufficiencies after head injury and aneurysmal subarachnoid hemorrhage (SAH) may be important, especially given that hypopituitarism-related neurobehavioral problems are typically alleviated by hormone replacement. In this prospective study the authors sought to determine the rate and risk factors of pituitary dysfunction after head injury and SAH in patients at least 3 months after insult.Methods. Patients underwent dynamic anterior and posterior pituitary function testing. Results of the tests were compared with those of 18 age-, sex-, and body mass index—matched healthy volunteers. The 22 head-injured patients included 18 men and four women (mean age 28 ± 10 years at the time of injury) with initial Glasgow Coma Scale (GCS) scores of 3 to 15. Eight patients (36.4%) had a subnormal response in at least one hormonal axis. Four were growth hormone (GH) deficient. Five patients (four men, all with normal testosterone levels, and one woman with a low estradiol level) exhibited an inadequate gonadotroph response. One patient had both GH and thyrotroph deficiency and another had both GH deficiency and borderline cortisol deficiency. At the time of injury, all eight patients with pituitary dysfunction had an initial GCS score of 10 or less and, compared with the 14 patients without dysfunction, were more likely to have had diffuse swelling, seen on initial computerized tomography scans (p < 0.05), and to have sustained a hypotensive or hypoxic insult (p = 0.07). Of two patients with SAH who were studied (Hunt and Hess Grade IV) both had GH deficiency.Conclusions. From this preliminary study, some degree of hypopituitarism appears to occur in approximately 40% of patients with moderate or severe head injury, with GH and gonadotroph deficiencies being most common. A high degree of injury severity and secondary cerebral insults are likely risk factors for hypopituitarism. Pituitary dysfunction also occurs in patients with poor-grade aneurysms. Postacute pituitary function testing may be warranted in most patients with moderate or severe head injury, particularly those with diffuse brain swelling and those sustaining hypotensive or hypoxic insults. The neurobehavioral effects of GH replacement in patients suffering from head injury or SAH warrant further study.

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Intravenous Magnesium versus Nimodipine in the Treatment of Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized Study

Neurosurgery ◽

10.1227/01.neu.0000215868.40441.d9 ◽

2006 ◽

Vol 58 (6) ◽

pp. 1054-1065 ◽

Cited By ~ 91

Author(s):

Robert Schmid-Elsaesser ◽

Matthias Kunz ◽

Stefan Zausinger ◽

Stefan Prueckner ◽

Josef Briegel ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Transcranial Doppler ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Randomized Study ◽

Fatal Outcome ◽

Neuron Specific Enolase ◽

Neurological Deficits ◽

Secondary Outcome ◽

Neuronal Markers ◽

Angiographic Vasospasm

Abstract OBJECTIVE: The prophylactic use of nimodipine in patients with aneurysmal subarachnoid hemorrhage reduces the risk of ischemic brain damage. However, its efficacy seems to be rather moderate. The question arises whether other types of calcium antagonists offer better protection. Magnesium, nature's physiological calcium antagonist, is neuroprotective in animal models, promotes dilatation of cerebral arteries, and has an established safety profile. The aim of the current pilot study is to evaluate the efficacy of magnesium versus nimodipine to prevent delayed ischemic deficits after aneurysmal subarachnoid hemorrhage. METHODS: One hundred and thirteen patients with aneurysmal subarachnoid hemorrhage were enrolled in the study and were randomized to receive either magnesium sulfate (loading 10 mg/kg followed by 30 mg/kg daily) or nimodipine (48 mg/d) intravenously until at least postoperative Day 7. Primary outcome parameters were incidence of clinical vasospasm and infarction. Secondary outcome measures were the incidence of transcranial Doppler/angiographic vasospasm, the neuronal markers (neuron-specific enolase, S-100), and the patients' Glasgow Outcome Scale scores at discharge and after 1 year. RESULTS: One hundred and four patients met the study requirements. In the magnesium group (n = 53), eight patients (15%) experienced clinical vasospasm and 20 (38%) experienced transcranial Doppler/angiographic vasospasm compared with 14 (27%) and 17 (33%) patients in the nimodipine group (n = 51). If clinical vasospasm occurred, 75% of the magnesium-treated versus 50% of the nimodipine-treated patients experienced cerebral infarction resulting in fatal outcome in 37 and 14%, respectively. Overall, the rate of infarction attributable to vasospasm was virtually the same (19 versus 22%). There was no difference in outcome between groups. CONCLUSION: The efficacy of magnesium in preventing delayed ischemic neurological deficits in patients with aneurysmal subarachnoid hemorrhage seems to be comparable with that of nimodipine. The difference in their pharmacological properties makes studies on the combined administration of magnesium and nimodipine seem promising.

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