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Persistent Metabolic Disturbance in the Perihemorrhagic Zone Despite a Normalized Cerebral Blood Flow Following Surgery for Intracerebral Hemorrhage.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
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2019 (English)In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, no 6, p. 1269-1278Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: We hypothesized that reduced cerebral blood flow (CBF) and/or energy metabolic disturbances exist in the tissue surrounding a surgically evacuated intracerebral hemorrhage (ICH). If present, such CBF and/or metabolic impairments may contribute to ongoing tissue injury and the modest clinical efficacy of ICH surgery.

OBJECTIVE: To conduct an observational study of CBF and the energy metabolic state in the perihemorrhagic zone (PHZ) tissue and in seemingly normal cortex (SNX) by microdialysis (MD) following surgical ICH evacuation.

METHODS: We evaluated 12 patients (median age 64; range 26-71 yr) for changes in CBF and energy metabolism following surgical ICH evacuation using Xenon-enhanced computed tomography (n = 10) or computed tomography perfusion (n = 2) for CBF and dual MD catheters, placed in the PHZ and the SNX at ICH surgery.

RESULTS: CBF was evaluated at a mean of 21 and 58 h postsurgery. In the hemisphere ipsilateral to the ICH, CBF improved between the investigations (36.6 ± 20 vs 40.6 ± 20 mL/100 g/min; P < .05). In total, 1026 MD samples were analyzed for energy metabolic alterations including glucose and the lactate/pyruvate ratio (LPR). The LPR was persistently elevated in the PHZ compared to the SNX region (P < .05). LPR elevations in the PHZ were predominately type II (pyruvate normal-high; indicating mitochondrial dysfunction) as opposed to type I (pyruvate low; indicating ischemia) at 4 to 48 h (70% vs 30%) and at 49 to 84 h (79% vs 21%; P < .05) postsurgery.

CONCLUSION: Despite normalization of CBF following ICH evacuation, an energy metabolic disturbance suggestive of mitochondrial dysfunction persists in the perihemorrhagic zone.

Place, publisher, year, edition, pages
Oxford University Press, 2019. no 6, p. 1269-1278
National Category
Neurology
Identifiers
URN: urn:nbn:se:liu:diva-150994DOI: 10.1093/neuros/nyy179ISI: 000471247000038PubMedID: 29788388OAI: oai:DiVA.org:liu-150994DiVA, id: diva2:1246685
Note

Funding agencies: STROKE-Riksforbundet (Skarholmen, Sweden); local hospital ALF-funds (Region Ostergotland, Linkoping, Sweden); Anaesthesia, Operations and Specialty Surgery Centre

Available from: 2018-09-10 Created: 2018-09-10 Last updated: 2019-07-15
In thesis
1. Surgically Treated Intracerebral Haemorrhage: Pathophysiology and Clinical Aspects
Open this publication in new window or tab >>Surgically Treated Intracerebral Haemorrhage: Pathophysiology and Clinical Aspects
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mortality and morbidity of intracerebral haemorrhage (ICH) is excessively high, and the case fatality rate has not improved in the last decades. Although surgery for ICH can be life-saving, no positive effect on functional outcome has been found in large cohorts of ICH patients. Increased understanding of the pathophysiology of ICH is needed to develop improved treatment strategies.

In 17 ICH patients, paired cerebral microdialysis (CMD) catheters were inserted in the perihaemorrhagic zone (PHZ) and in normal uninjured cortex at time of surgery. Despite normalisation of cerebral blood flow, a persistent metabolic crisis indicative of mitochondrial dysfunction was detected in the PHZ. This metabolic pattern was not observed in the uninjured cortex.

CMD was also used to sample proteins for proteomic analysis. A distinct proteome profile that changed over time was found in the PHZ when compared to the seemingly normal, uninjured cortex. However, protein adsorption to CMD membranes, which may interfere with concentration measurements, was substantial.

Surgical treatment of 578 ICH patients was analysed in a nation-wide retrospective multi-centre study in Sweden over five years. Patients selected for surgery had similar age, pre-operative level of consciousness and co-morbidity profiles, but ICH volume and the proportion of deep-seated ICH differed among the six neurosurgical centres. Furthermore, there was variability in the post-operative care, including the use and duration of intracranial pressure monitoring, cerebrospinal fluid drainage and mechanical ventilation.

In conclusion, the results of this thesis show that:

(i) Despite surgical removal of an ICH a metabolic crisis caused by mitochondrial dysfunction, a potential future therapeutic target, persists in the perihaemorrhagic zone.

(ii-iii) CMD is a valuable tool in ICH research for sampling novel biomarkers using proteomics, which may aid in the development of improved therapeutic interventions. However, caveats of the technique, such as protein adsorption to the CMD membrane, must be considered.

(iv) The nation-wide study illustrates similar clinical features in patients selected for ICH surgery, but substantial variability in ICH volume and location as well as neurocritical care strategies among Swedish neurosurgical centres. Development of refined clinical guidelines may reduce such intercentre variability and lead to improved functional outcome for ICH patients.  

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2019. p. 108
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1663
National Category
Anesthesiology and Intensive Care Surgery
Identifiers
urn:nbn:se:liu:diva-156369 (URN)10.3384/diss.diva-156369 (DOI)9789176851272 (ISBN)
Public defence
2019-05-24, Berzeliussalen, Campus US, Linköping, 13:00 (English)
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Available from: 2019-04-17 Created: 2019-04-17 Last updated: 2019-04-17Bibliographically approved

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Tobieson, LovisaRossitti, SandroZsigmond, PeterHillman, Jan

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