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Predictors of increased cumulative serum levels of the N-terminal prohormone of brain natriuretic peptide 4 days after acute spontaneous subarachnoid hemorrhage
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
2014 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 120, no 3, 599-604 p.Article in journal (Refereed) Published
Abstract [en]

Object. The rupture of an intracranial aneurysm is followed by increased intracranial pressure and decreased cerebral blood flow. A major systemic stress reaction follows, presumably to restore cerebral blood flow. However, this reaction can also cause adverse effects, including myocardial abnormalities, which are common and can be serious, and increased levels of natriuretic peptides, especially brain natriuretic peptide (BNP). The association of BNP with fluid and salt balance, vasospasm, brain ischemia, and cardiac injury has been studied but almost exclusively regarding events after admission. Brain natriuretic peptide has also been measured at various time points and analyzed in different ways statistically. The authors approached BNP measurement in a new way; they used the calculated area under the curve (AUC) for the first 4 days to quantitatively measure the BNP load during the first critical part of the disease state. Their rationale was a suspicion that early BNP load is a marker of the severity of the ictus and will influence the subsequent course of the disease by disturbing the fluid and salt balance. Methods. The study included 156 patients with acute spontaneous subarachnoid hemorrhage (SAH). Mean patient age was 59.8 +/- 11.2 years, and 105 (67%) of the patients were female. An aneurysm was found in 138 patients. A total of 82 aneurysms were treated by endovascular coiling, 50 were treated by surgery, and 6 were untreated. At the time of admission, serum samples were collected for troponin-I analysis and for the N-terminal prohormone of BNP (NT-proBNP); daily thereafter, samples were collected for the NT-proBNP analysis. The cumulative BNP load was calculated as the AUC for NT-proBNP during the first 4 days. The following variables were studied in terms of their influence on the AUC for NT-proBNP: sex, age, World Federation of Neurosurgical Societies grade of SAH, Fisher grade, angiographic result, treatment of aneurysm,'clinical neurological deterioration, verified infections, vasospasm treatment, and 6-month outcome. Results. The AUC for NT-proBNP was larger when variables indicated a more severe SAH. These variables were higher Fisher and World Federation of Neurosurgical Societies grades, high levels of troponin-I at admission, an aneurysm, neurological deficits, and infections. The AUC for NT-proBNP was also larger among women, older patients, and patients with poor outcomes. Linear regression showed that the best predicting model for large AUC for NT-proBNP was the combination of the following: female sex, high levels of troponin-I, an aneurysm, neurological deficits, and advanced age. Conclusions. The cumulative BNP load during the first days after SAH can be predicted by variables describing the severity of the disease already known at the time of admission. This information can be used to identify patients at risk for an adverse course of the disease.

Place, publisher, year, edition, pages
2014. Vol. 120, no 3, 599-604 p.
Keyword [en]
subarachnoid hemorrhage, NT-proBNP, vascular disorders, brain natriuretic peptide, troponin-I
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-222748DOI: 10.3171/2013.8.JNS13625ISI: 000332048800003OAI: oai:DiVA.org:uu-222748DiVA: diva2:712219
Available from: 2014-04-14 Created: 2014-04-14 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Metabolic and Endocrine Response in the Acute Stage of Subarachnoid Hemorrhage
Open this publication in new window or tab >>Metabolic and Endocrine Response in the Acute Stage of Subarachnoid Hemorrhage
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The rupture of an aneurysm in subarachnoid hemorrhage (SAH) is a dramatic event causing a severe impact on the brain and a transient or permanent ischemic condition. Several types of responses to meet the challenges of SAH have been found in the acute phase, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system, elevated levels of brain natriuretic peptide (BNP), and disturbances in cerebral and systemic metabolism.

Cerebral metabolism and the endocrine stress response in the ultra-early phase was investigated in a novel porcine model of SAH in which autologous blood was injected to the anterior skull base. Early activation of the HPA axis was found with rapid elevation of adrenocorticotrophic hormone, cortisol and aldosterone. The peak values of these hormones were early and may be impossible to catch in patients. There were indications of a sympathetic nervous response with excretion of catecholamines in urine as well as plasma chromogranin-A elevation. Cerebral microdialysis suggested immediate substrate failure followed by hypermetabolism of glucose. The animal model seems suited for further studies of aneurysmal SAH.

NT-proBNP was investigated in 156 patients with SAH, there was a dynamic course with increasing levels during the first 4 days of the disease. Factors predicting high NT-proBNP load included female sex, high age, high Troponin-I at admission, angiographic finding of an aneurysm and worse clinical condition at admission. High levels of NT-proBNP were correlated to factors indicating a more severe disease, suggesting the initial injury in aneurysmal SAH is an important factor in predicting high NT-proBNP during the acute stage of the disease.

Measurements with indirect calorimetry were performed daily during the first week after SAH on 32 patients with SAH. There was a dynamic course with increasing energy expenditure (EE) the first week after SAH. Comparisons with three predictive equations indicated that measured EE generally is higher than predicted, but considerable variation exists within and between patients, indicating that prediction of EE in SAH is difficult.

Altogether, the studies demonstrate a complicated response in acute SAH that needs to be further studied to increase possibility of good outcome in SAH patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 61 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1357
Keyword
Subarachnoid hemorrhage, Energy Expenditure, BNP, Animal Model, Cortisol, Microdialysis
National Category
Neurology Anesthesiology and Intensive Care
Research subject
Neurosurgery
Identifiers
urn:nbn:se:uu:diva-328121 (URN)978-91-513-0038-2 (ISBN)
Public defence
2017-10-06, Grönwallsalen, Akademiska sjukhuset, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2017-09-15 Created: 2017-08-17 Last updated: 2017-10-17

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Nyberg, ChristofferKarlsson, TorbjörnRonne-Engström, Elisabeth

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