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OBJECTIVE: Acute kidney injury (AKI) is associated with death in critically ill patients, but this complication has not been well characterized after aneurysmal subarachnoid hemorrhage (aSAH). The purpose of this study was to determine the incidence of AKI after aSAH and to identify risk factors for renal dysfunction. Secondary objectives were to examine what effect AKI has on patient mortality and functional outcome at 12 weeks post-aSAH. METHODS: The authors performed a post hoc analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial data set (clinical trial registration no.: NCT00111085, https://clinicaltrials.gov). The primary outcome of interest was the development of AKI, which was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Secondary outcomes of interest were death and a modified Rankin Scale score greater than 2 at 12 weeks post-aSAH. Propensity score matching was used to assess for a significant treatment effect related to clazosentan administration and AKI. Univariate analysis, locally weighted scatterplot smoothing (LOWESS) curves, and stepwise logistic regression models were used to evaluate for associations between baseline or disease-related characteristics and study outcomes. RESULTS: One hundred fifty-six (38%) of the 413 patients enrolled in the CONSCIOUS-1 trial developed AKI during their ICU stay. A history of hypertension (p < 0.001) and the number of nephrotoxic medications administered (p = 0.029) were independent predictors of AKI on multivariate analysis. AKI was an independent predictor of death (p = 0.028) but not a poor functional outcome (p = 0.21) on multivariate testing. Unresolved renal dysfunction was the strongest independent predictor of death in this cohort (p < 0.001). CONCLUSIONS: AKI is a common complication following aSAH. Patients with premorbid hypertension and those treated with nephrotoxic medications may be at greater risk for renal dysfunction. AKI appears to confer an increased probability of death after aSAH.
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OBJECTIVEDelayed ischemic neurological deficit (DIND) is a leading cause of mortality and morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Arginine vasopressin (AVP) is a hormone released by the posterior pituitary. It is known to cause cerebral vasoconstriction and has been implicated in hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion. Direct measurement of AVP is limited by its short half-life. Copeptin, a cleavage product of the AVP precursor protein, was therefore used as a surrogate marker for AVP. This study aimed to investigate the temporal relationship between changes in copeptin concentrations and episodes of DIND and hyponatremia.METHODSCopeptin concentrations in cerebrospinal fluid were quantified using enzyme-linked immunosorbent assay in 19 patients: 10 patients with DIND, 6 patients without DIND (no-DIND), and 3 controls.RESULTSCopeptin concentrations were higher in DIND and no-DIND patients than in controls. In hyponatremic DIND patients, copeptin concentrations were higher compared with hyponatremic no-DIND patients. DIND was associated with a combination of decreasing sodium levels and increasing copeptin concentrations.CONCLUSIONSIncreased AVP may be the unifying factor explaining the co-occurrence of hyponatremia and DIND. Future studies are indicated to investigate this relationship and the therapeutic utility of AVP antagonists in the clinical setting.
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OBJECTIVE Delayed cerebral ischemia (DCI) is an important complication after aneurysmal subarachnoid hemorrhage (aSAH). Although intrathecal milrinone injection via lumbar catheter to prevent DCI has been previously reported to be safe and feasible, its effectiveness remains unknown. The goal of this study was to evaluate whether intrathecal milrinone injection treatment after aSAH significantly reduced the incidence of DCI. METHODS The prospectively maintained aSAH database was used to identify patients treated between January 2010 and December 2015. The cohort included 274 patients, with group assignment based on treatment with intrathecal milrinone injection or not. A propensity score model was generated for each patient group, incorporating relevant patient variables. RESULTS After propensity score matching, 99 patients treated with intrathecal milrinone injection and 99 without treatment were matched on the basis of similarities in their demographic and clinical characteristics. There were significantly fewer DCI events (4% vs 14%, p = 0.024) in patients treated with intrathecal milrinone injection compared with those treated without it. However, there were no significant differences between the 2 groups with respect to their 90-day functional outcomes (46% vs 36%, p = 0.31). The likelihood of chronic secondary hydrocephalus, meningitis, and congestive heart failure as complications of intrathecal milrinone injection therapy was also similar between the groups. CONCLUSIONS In propensity score-matched groups, the intrathecal administration of milrinone via lumbar catheter showed significant reduction of DCI following aSAH, without an associated increase in complications.
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Isquemia Encefálica/prevención & control , Milrinona/administración & dosificación , Hemorragia Subaracnoidea/complicaciones , Vasodilatadores/administración & dosificación , Vasoespasmo Intracraneal/prevención & control , Anciano , Isquemia Encefálica/etiología , Catéteres , Femenino , Humanos , Inyecciones Espinales , Masculino , Persona de Mediana Edad , Milrinona/uso terapéutico , Resultado del Tratamiento , Vasodilatadores/uso terapéutico , Vasoespasmo Intracraneal/etiologíaRESUMEN
OBJECTIVE Clipping of a ruptured intracranial aneurysm requires some degree of vessel manipulation, which in turn is believed to contribute to vasoconstriction. One of the techniques used during surgery is temporary clipping of the parent vessel. Temporary clipping may either be mandatory in cases of premature rupture (rescue) or represent a precautionary or facilitating surgical step (elective). The aim of this study was to study the association between temporary clipping during aneurysm surgery and the incidence of vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH) in a large clinical series. METHODS Seven hundred seventy-eight patients who underwent surgical aneurysm treatment after aSAH were retrospectively included in the study. In addition to surgical parameters, the authors recorded transcranial Doppler (TCD) sonography-documented vasospasm (TCD-vasospasm, blood flow acceleration > 120 cm/sec), delayed ischemic neurological deficits (DINDs), and delayed cerebral infarction (DCI). Multivariate binary logistic regression analysis was applied to assess the association between temporary clipping, vasospasm, DIND, and DCI. RESULTS Temporary clipping was performed in 338 (43.4%) of 778 patients during aneurysm surgery. TCD sonographic flow acceleration developed in 370 (47.6%), DINDs in 123 (15.8%), and DCI in 97 (12.5%). Patients with temporary clipping showed no significant increase in the incidence of TCD-vasospasm compared with patients without temporary clipping (49% vs 48%, respectively; p = 0.60). DINDs developed in 12% of patients with temporary clipping and 18% of those without temporary clipping (p = 0.01). DCI occurred in 9% of patients with temporary clipping and 15% of those without temporary clipping (p = 0.02). The need for rescue temporary clipping was a predictor for DCI; 19.5% of patients in the rescue temporary clipping group but only 11.3% in the elective temporary clipping group had infarcts (p = 0.02). Elective temporary clipping was not associated with TCD-vasospasm (p = 0.31), DIND (p = 0.18), or DCI (p = 0.06). CONCLUSIONS Temporary clipping did not contribute to a higher rate of TCD-vasospasm, DIND, or DCI in comparison with rates in patients without temporary clipping. In contrast, there was an association between temporary clipping and a lower incidence of DINDs and DCI. There is no reason to be hesitant in using elective temporary clipping if deemed appropriate.
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Aneurisma Roto/cirugía , Isquemia Encefálica/epidemiología , Isquemia Encefálica/etiología , Infarto Cerebral/epidemiología , Infarto Cerebral/etiología , Aneurisma Intracraneal/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Hemorragia Subaracnoidea/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Procedimientos Quirúrgicos Vasculares/métodos , Adulto JovenRESUMEN
OBJECTIVE Plasma D-dimer levels elevate during acute stages of aneurysmal subarachnoid hemorrhage (SAH) and are associated with poor functional outcomes. However, the mechanism in which D-dimer elevation on admission affects functional outcomes remains unknown. The aim of this study is to clarify whether D-dimer levels on admission are correlated with systemic complications after aneurysmal SAH, and to investigate their additive predictive value on conventional risk factors for poor functional outcomes. METHODS A total of 187 patients with aneurysmal SAH were retrospectively analyzed from a single-center, observational cohort database. Correlations of plasma D-dimer levels on admission with patient characteristics, initial presentation, neurological complications, and systemic complications were identified. The authors also evaluated the additive value of D-dimer elevation on admission for poor functional outcomes by comparing predictive models with and without D-dimer. RESULTS D-dimer elevation on admission was associated with increasing age, female sex, and severity of SAH. Patients with higher D-dimer levels had increased likelihood of nosocomial infections (OR 1.22 [95% CI 1.07-1.39], p = 0.004), serum sodium disorders (OR 1.11 [95% CI 1.01-1.23], p = 0.033), and cardiopulmonary complications (OR 1.20 [95% CI 1.04-1.37], p = 0.01) on multivariable analysis. D-dimer elevation was an independent risk factor of poor functional outcome (modified Rankin Scale Score 3-6, OR 1.50 [95% CI 1.15-1.95], p = 0.003). A novel prediction model with D-dimer had significantly better discrimination ability for poor outcomes than conventional models without D-dimer. CONCLUSIONS Elevated D-dimer levels on admission were independently correlated with systemic complication, and had an additive value for outcome prediction on conventional risk factors after aneurysmal SAH.
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Productos de Degradación de Fibrina-Fibrinógeno/análisis , Aneurisma Intracraneal/sangre , Aneurisma Intracraneal/fisiopatología , Hemorragia Subaracnoidea/sangre , Hemorragia Subaracnoidea/fisiopatología , Anciano , Estudios de Cohortes , Femenino , Humanos , Aneurisma Intracraneal/complicaciones , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Hemorragia Subaracnoidea/complicacionesRESUMEN
OBJECTIVE The efficacy of statin therapy in treating aneurysmal subarachnoid hemorrhage (SAH) remains controversial. In this meta-analysis, the authors investigated whether statin treatment significantly reduced the incidence of cerebral vasospasm and delayed neurological deficits, promoting a better outcome after aneurysmal SAH. METHODS A literature search of the PubMed, Ovid, and Cochrane Library databases was performed for randomized controlled trials (RCTs) and prospective cohort studies investigating the effect of statin treatment. The end points of cerebral vasospasm, delayed ischemic neurological deficit (DIND), delayed cerebral infarction, mortality, and favorable outcome were statistically analyzed. RESULTS Six RCTs and 2 prospective cohort studies met the eligibility criteria, and a total of 1461 patients were included. The meta-analysis demonstrated a significant decrease in the incidence of cerebral vasospasm (relative risk [RR] 0.76, 95% confidence interval [CI] 0.61-0.96) in patients treated with statins after aneurysmal SAH. However, no significant benefit was observed for DIND (RR 0.88, 95% CI 0.70-1.12), delayed cerebral infarction (RR 0.66, 95% CI 0.33-1.31), mortality (RR 0.69, 95% CI 0.39-1.24) or favorable outcome, according to assessment by the modified Rankin Scale or Glasgow Outcome Scale (RR 0.99, 95% CI 0.92-1.17). CONCLUSIONS Treatment with statins significantly decreased the occurrence of vasospasm after aneurysmal SAH. The incidence of DIND, delayed cerebral infarction, and mortality were not affected by statin treatment. Future research should focus on DIND and how statins influence DIND.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Aneurisma Intracraneal/tratamiento farmacológico , Hemorragia Subaracnoidea/tratamiento farmacológico , Vasoespasmo Intracraneal/tratamiento farmacológico , Humanos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/fisiopatología , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/fisiopatología , Resultado del Tratamiento , Vasoespasmo Intracraneal/etiologíaRESUMEN
OBJECT Delayed ischemic neurological deficits (DINDs) and cerebral vasospasm (CVS) are responsible fora poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), most likely because of a decreased availability of nitric oxide (NO) in the cerebral microcirculation. In this study, the authors examined the effects of treatment with the NO donor molsidomine with regard to decreasing the incidence of spasm-related delayed brain infarctions and improving clinical outcome in patients with SAH. METHODS Seventy-four patients with spontaneous aneurysmal SAH were included in this post hoc analysis. Twenty-nine patients with SAH and proven CVS received molsidomine in addition to oral or intravenous nimodipine. Control groups consisted of 25 SAH patients with proven vasospasm and 20 SAH patients without. These patients received nimodipine therapy alone. Cranial computed tomography (CCT) before and after treatment was analyzed for CVS-related infarcts. A modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) were used to assess outcomes at a 3-month clinical follow-up. RESULTS Four of the 29 (13.8%) patients receiving molsidomine plus nimodipine and 22 of the 45 (48%) patients receiving nimodipine therapy alone developed vasospasm-associated brain infarcts (p < 0.01). Follow-up revealed a median mNIHSS score of 3.0 and a median mRS score of 2.5 in the molsidomine group compared with scores of 11.5 and 5.0, respectively, in the nimodipine group with CVS (p < 0.001). One patient in the molsidomine treatment group died, and 12 patients in the standard care group died (p < 0.01). CONCLUSIONS In this post hoc analysis, patients with CVS who were treated with intravenous molsidomine had a significant improvement in clinical outcome and less cerebral infarction. Molsidomine offers a promising therapeutic option in patients with severe SAH and CVS and should be assessed in a prospective study.
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Infarto Encefálico/prevención & control , Isquemia Encefálica/prevención & control , Molsidomina/uso terapéutico , Enfermedades del Sistema Nervioso/prevención & control , Hemorragia Subaracnoidea/cirugía , Vasodilatadores/uso terapéutico , Vasoespasmo Intracraneal/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Infarto Encefálico/etiología , Isquemia Encefálica/etiología , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/etiología , Nimodipina/uso terapéutico , Estudios Prospectivos , Accidente Cerebrovascular/epidemiología , Hemorragia Subaracnoidea/complicaciones , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Vasoespasmo Intracraneal/mortalidad , Adulto JovenRESUMEN
OBJECT: The literature has conflicting reports about the prognostic value of premorbid hypertension and neurological status in aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to investigate the prognostic value of premorbid hypertension and neurological status in the SAH International Trialists repository. METHODS: Patient-level meta-analyses were conducted to investigate univariate associations between premorbid hypertension (6 studies; n = 7249), admission neurological status measured on the World Federation of Neurosurgical Societies (WFNS) scale (10 studies; n = 10,869), and 3-month Glasgow Outcome Scale (GOS) score. Multivariable analyses were performed to sequentially adjust for the effects of age, CT clot burden, aneurysm location, aneurysm size, and modality of aneurysm repair. Prognostic associations were estimated across the ordered categories of the GOS using proportional odds models. Nagelkerke's R(2) statistic was used to quantify the added prognostic value of hypertension and neurological status beyond those of the adjustment factors. RESULTS: Premorbid hypertension was independently associated with poor outcome, with an unadjusted pooled odds ratio (OR) of 1.73 (95% confidence interval [CI] 1.50-2.00) and an adjusted OR of 1.38 (95% CI 1.25-1.53). Patients with a premorbid history of hypertension had higher rates of cardiovascular and renal comorbidities, poorer neurological status (p ≤ 0.001), and higher odds of neurological complications including cerebral infarctions, hydrocephalus, rebleeding, and delayed ischemic neurological deficits. Worsening neurological status was strongly independently associated with poor outcome, including WFNS Grades II (OR 1.85, 95% CI 1.68-2.03), III (OR 3.85, 95% CI 3.32-4.47), IV (OR 5.58, 95% CI 4.91-6.35), and V (OR 14.18, 95% CI 12.20-16.49). Neurological status had substantial added predictive value greater than the combined value of other prognostic factors (R(2) increase > 10%), while the added predictive value of hypertension was marginal (R(2) increase < 0.5%). CONCLUSIONS: This study confirmed the strong prognostic effect of neurological status as measured on the WFNS scale and the independent but weak prognostic effect of premorbid hypertension. The effect of premorbid hypertension could involve multifactorial mechanisms, including an increase in the severity of initial bleeding, the rate of comorbid events, and neurological complications.
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Hipertensión/complicaciones , Examen Neurológico/métodos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/cirugía , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Escala de Consecuencias de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Valor Predictivo de las Pruebas , Pronóstico , Sistema de Registros , Hemorragia Subaracnoidea/fisiopatología , Resultado del TratamientoRESUMEN
OBJECT: Experimental studies have demonstrated the crucial role of posthemorrhagic erythrocyte catabolism in the pathogenesis of subarachnoid hemorrhage (SAH). The authors of this study aimed to investigate the prognostic value of a series of CSF biomarkers linked to heme metabolism in SAH patients. METHODS: Patients with Fisher Grade III aneurysmal SAH undergoing early aneurysm obliteration were enrolled. The levels of heme oxygenase-1 (HO-1), oxyhemoglobin, ferritin, and bilirubin in intrathecal CSF were measured on the 7th day posthemorrhage. The associations of functional outcome with clinical and CSF parameters were analyzed. RESULTS: The study included 41 patients (mean age 59 ± 14 years; 16 male, 25 female), 17 (41.5%) of whom had an unfavorable outcome (Glasgow Outcome Scale score ≤ 3) 3 months after SAH. In terms of the clinical data, age > 60 years, admission World Federation of Neurosurgical Societies Grade ≥ III, and the presence of acute hydrocephalus were independent factors associated with an unfavorable outcome. After adjusting for clinical parameters, a higher level of HO-1 appeared to be the most significant CSF parameter related to an unfavorable outcome among all tested CSF molecules (OR 0.934, 95% CI 0.883-0.989, p = 0.018). Further analysis using a generalized additive model identified a cutoff HO-1 value of 81.2 µM, with higher values predicting unfavorable outcome (82.4% accuracy). CONCLUSIONS: The authors propose that the level of intrathecal CSF HO-1 at Day 7 post-SAH can be an effective outcome indicator in patients with Fisher Grade III aneurysmal SAH.