Urinary F2-Isoprostane Concentration as a Poor Prognostic Factor After Subarachnoid Hemorrhage.

BACKGROUND: The role of isoprostanes in cerebral vasospasm (CVS) following aneurysmal subarachnoid hemorrhage (aSAH) is controversial. Recent studies have suggested that the level of isoprostanes in cerebrospinal fluid could play a role in outcomes of patients with aSAH. We measured concentration of urinary F2-isoprostanes (F2-IsoPs), which is simple and noninvasive. METHODS: A prospective analysis was performed of clinical data and urine samples of 20 patients with aSAH who underwent microsurgical clipping of the aneurysmal neck between May 2016 and January 2017. The role of F2-IsoPs as a CVS biomarker was analyzed with regard to clinical conditions of patients. Outcome was assessed at discharge and 1-month and 4-month follow-up using the Glasgow Outcome Scale and modified Rankin Scale. RESULTS: The concentration of urinary F2-IsoPs was significantly greater in patients with aSAH than in healthy control subjects (P < 0.001). Additionally, increased F2-IsoP levels on day 3 after aSAH were associated with development of CVS (P = 0.015) and worse neurologic performance after 1 month (P = 0.042) and 4 months (P = 0.027). The prognostic value of urinary F2-IsoPs on day 3 in terms of CVS was found to be high (area under the curve 0.864, 95% confidence interval 0.691-1.000). CONCLUSIONS: Urinary F2-IsoPs may be used as a noninvasive prognostic biochemical marker in patients with aSAH. F2-IsoP levels in urine may have significant implications in pathogenesis of CVS.

Urine Test Strips as a Bedside Diagnostic Aid to Rule out Blood in CSF: A Validation.

INTRODUCTION: Patients presenting to the emergency department with acute-onset, atypical headaches require an evaluation for subarachnoid hemorrhage (SAH). The standard evaluation for SAH includes noncontrast computed tomography of the head and, if negative, a lumbar puncture to determine the presence of blood in the cerebrospinal fluid (CSF). In austere environments without full laboratory capabilities, a rapid bedside diagnostic test allowing clinicians to rule out SAH would reduce costly transfers of patients requiring further evaluation. CSF samples obtained while evaluating patients for potential SAH were tested with the blood panel of Bayer Multistix urine test strips. METHODS: We compared the test strip color change to the number of red blood cells per high power field found on laboratory analysis of the CSF. RESULTS: The sensitivity of the Multistix for detecting red blood cells in the CSF was 100%, with a specificity of 56%. The positive predictive value was 37%, and the negative predictive value was 100%. CONCLUSION: These results are encouraging and may form the basis for potential use of urine test strips as a tool to rule out subarachnoid blood in austere environments, but the test strips' low specificity limits their usefulness as a practical clinical tool at this time.

Polyuria and cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Natriuresis with polyuria is common after aneurysmal subarachnoid hemorrhage (aSAH). Previous studies have shown an increased risk of symptomatic cerebral vasospasm or delayed cerebral ischemia (DCI) in patients with hyponatremia and/or the cerebral salt wasting syndrome (CSW). However, natriuresis may occur in the absence of hyponatremia or hypovolemia and it is not known whether the increase in DCI in patients with CSW is secondary to a concomitant hypovolemia or because the physiology that predisposes to natriuretic peptide release also predisposes to cerebral vasospasm. Therefore, we investigated whether polyuria per se was associated with vasospasm and whether a temporal relationship existed. METHODS: A retrospective review of patients with aSAH was performed. Exclusion criteria were admission more than 48 h after aneurysmal rupture, death within 5 days, and the development of diabetes insipidus or acute renal failure. Polyuria was defined as > 6 liters of urine in a 24 h period. Vasospasm was defined as a mean velocity > 120 m/s on Transcranial Doppler Ultrasonography (TCDs) or by evidence of vasospasm on computerized tomography (CT) or catheter angiography. Multivariable logistic regression was performed to assess the relationship between polyuria and vasospasm. RESULTS: 95 patients were included in the study. 51 had cerebral vasospasm and 63 met the definition of polyuria. Patients with polyuria were significantly more likely to have vasospasm (OR 4.301, 95% CI 1.378-13.419) in multivariate analysis. Polyuria was more common in younger patients (52 vs 68, p <.001) but did not impact mortality after controlling for age and disease severity. The timing of the development of polyuria was clustered around the diagnosis of vasospasm and patients with polyuria developed vasospasm faster than those without polyuria. CONCLUSIONS: Polyuria is common after aSAH and is significantly associated with cerebral vasospasm. The development of polyuria may be temporally related to the development of vasospasm. An increase in urine volume may be a useful clinical predictor of patients at risk for vasospasm.

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.

Trace minerals in experimental subarachnoid haemorrhage: zinc, copper and manganese levels in rat brain tissue, blood and urine.

BACKGROUND: Zinc (Zn), copper (Cu) and manganese (Mn) are involved in regulatory systems in the cell. Their role in neuromodulator activities and redox reactions has been implicated in the pathogenesis of neurological disorders. The aim of this study was to determine changes of Zn, Cu and Mn levels in brain tissue, blood and urine after experimental subarachnoid haemorrhage (SAH). The possible importance of these trace minerals on the pathogenesis of SAH was also discussed. METHOD: Rats were divided into three groups; namely a SAH group, a control group and a normal group. Blood samples in the SAH group and normal saline in the control group were injected into the cisterna magna. No surgical procedures were performed on the normal group. Brain tissue, blood and urine samples were measured for trace minerals by atomic absorption spectrophotometry. Measurements were taken on days 3, 7 and 10 after the onset in the control and SAH groups, and on the first day in the normal group. FINDINGS: The reduced blood Zn levels and increased Zn urine loss observed in the SAH group were conspicuously significant. Furthermore, significant changes in Mn levels were also seen at different stages of the trial in the SAH group. However, differences found in the Cu levels between the groups were not significant enough to explain the results. INTERPRETATION: These results suggest that the low blood Zn levels seen throughout the stages, the low brain tissue Mn levels seen during the latter part of the trial, and the low blood Mn levels observed during the early stages, may all be related to an increased risk in experimental SAH in rats. These differences may have possible role in the pathogenesis of SAH, and further investigations into the reduced blood Mn levels observed during the study may lead to new insight into the treatment of SAH.

A method to estimate urinary electrolyte excretion in patients at risk for developing cerebral salt wasting.

OBJECT: Two major criteria are necessary to diagnose cerebral salt wasting (CSW): a cerebral lesion and a large urinary excretion of Na+ and Cl- at a time when the extracellular fluid (ECF) volume is contracted. Nevertheless, it is difficult for the physician to confirm from bedside observation that a patient has a contracted ECF volume. Hyponatremia, although frequently present, should not be a criterion for a diagnosis of salt wasting. A contracted ECF volume is unlikely if there are positive balances of Na+ and Cl-. The goal of this study was to assess the accuracy of calculating balances for Na+ plus K+ and of Cl- over 1 to 10 days in an intensive care unit (ICU) setting. METHODS: A prospective comparison of measured and estimated quantities of Na+ plus K+ and of Cl- excreted over 1 to 10 days in 10 children and 12 adults who had recently received a traumatic brain injury or undergone recent neurosurgery. Plasma concentrations of electrolytes were recorded at the beginning and end of the study period. The total volumes infused and excreted and the concentrations of Na+, K+, and Cl- in the infusate were obtained from each patient's ICU chart. The electrolytes in the patients' urine were measured and calculated. Correlations between measured and calculated values for excretions of Cl- and of Na+ plus K+ were excellent. CONCLUSIONS: Mass balances for Na+ plus K+ and for Cl- can be accurately estimated. These data provide information to support or refute a clinical diagnosis of CSW. The danger of relying on balances for these electrolytes measured within a single day to diagnose CSW is illustrated.

[Elevation of total urinary catecholamines in patients with subarachnoid hemorrhage]. / Elevación de catecolaminas urinarias totales en pacientes con hemorragia subaracnoidea.

We designed a prospective study in order to evaluate total urinary catecholamines in patients with subarachnoid hemorrhage (SAH) and correlate them with some prognostic factors and its complications. We studied 24 patients: 19 were normotensive, five had had a previous arterial hypertension that persisted during the SAH, and five developed the hypertension during the SAH. The latter showed cardiac complications with a more severely affected Hunt and Hess scale and a higher level of excretion of urinary catecholamines than the normotensive patients (p < 0.003). The cases with previous arterial hypertension that persisted during the SAH had more complications than the normotensive patients but in a lesser degree compared to chose who developed the hypertension during the SAH.

Long term monitoring of immunoreactive endothelin-1 and endothelin-3 in ventricular cerebrospinal fluid, plasma, and 24-h urine of patients with subarachnoid hemorrhage.

Endothelins (ETs), peptides that were originally isolated from endothelial cells, have extremely potent and long-lasting vasoconstricting effects on cerebral vessels in vitro and in vivo. Observations that astrocytes produce these peptides and that their ET production can be stimulated, e.g. by thrombin, and potentiated via a self-enhancing autoregulatory mechanism may have shed new light upon the pathogenesis of cerebrovasospasm (CVS). ETs are present at low levels in normal human cerebrospinal fluid (CSF). Few and contradictory reports exist on ET levels in subarachnoid hemorrhage (SAH)-associated CVS. We monitored ventricular CSF, plasma, and 24-h urine levels of immunoreactive endothelin-1 (ET-1) and endothelin-3 (ET-3) in seven patients with SAH, who did (five) or did not (two) develop CVS in the course of their disease, as well as in two patients with different conditions (acoustic neuroma/postoperative meningitis; hydro-/hematocephalus) over 7-19 days. A distinct peak of both ET-1 and ET-3 in CSF of patients with SAH coincided with clinically documented signs of CVS and was absent in CSF of patients with SAH but no CVS. CSF levels of ET-1 and ET-3 displayed a striking parallelism in all subjects. Plasma ET-1 levels were essentially in the normal range. ET-3 was not detectable in plasma under our assay conditions. The excretion profiles of ET-1 and ET-3 in 24-h urine revealed again a predominantly parallel behavior of the two peptides. Interestingly, patients with high ET levels in CSF showed simultaneous peaks in urinary ET excretion, expressed as nanograms per gram of creatinine. Our findings support an association of ETs with the pathogenic events following SAH. The well-documented effects of these peptides on cerebral vessels suggest they are mediators rather than markers of disease.

The effect of fludrocortisone acetate on plasma volume and natriuresis in patients with aneurysmal subarachnoid hemorrhage.

In order to prevent hypovolemia fludrocortisone acetate treatment was started on admission in 39 consecutive patients with CT evidence of subarachnoid hemorrhage. In 28 patients an aneurysm was proven or probable, and in 21 of these the effects of fludrocortisone acetate on sodium balance and on plasma volume could be studied. In the first five days plasma volume decreased more than 10% in four patients, decreased less than 10% in five and increased in 12. The cumulative sodium balance measured over five days was negative in seven of the 21 patients. Plasma renin values were measured in 15 of the 21 patients and also in stored samples of 18 patients who were not treated with fludrocortisone acetate. Plasma renin values were less high in patients treated with fludrocortisone acetate, regardless of the presence of a negative sodium balance. In three of the 39 patients signs of pulmonary edema developed, and low serum potassium values were observed in four of the 21 patients. In comparison with previous studies, these findings suggest that fludrocortisone acetate is an effective method of decreasing the incidence of volume depletion and negative sodium balance.

Cyclic AMP excretion in urines of patients with subarachnoid hemorrhages.

Urinary excretion of cAMP was closely monitored for several days in 74 patients with subarachnoid hemorrhages. A rise in urinary cAMP up to 45 microM/24h was observed (normal values being 1 to 5 microM/24h). Patients with associated metabolic disorders were excluded from this study. We have found a correlation between the severity of the clinical conditions, recovery from acute disorder and cAMP excretion, thus suggesting that an increase of urinary cAMP level is related to the extent and the evolution of the acute cerebral damage.