Abstract
Background
The study focuses on three questions related to the clinical usefulness of microdialysis in severe brain trauma: (1) How frequently is disturbed cerebral energy metabolism observed in various types of lesions? (2) How often does the biochemical pattern indicate cerebral ischaemia and mitochondrial dysfunction? (3) How do these patterns relate to mortality?
Method
The study includes 213 consecutive patients with severe brain trauma (342 intracerebral microdialysis catheters). The patients were classified into four groups according to the type of lesion: extradural haematoma (EDH), acute subdural haematoma (SDH), cerebral haemorrhagic contusion (CHC) and no mass lesion (NML). Altogether about 150,000 biochemical analyses were performed during the initial 96 h after trauma.
Results
Compromised aerobic metabolism occurred during 38 % of the study period. The biochemical pattern indicating mitochondrial dysfunction was more common than that of ischaemia. In EDH and NML aerobic metabolism was generally close to normal. In SDH or CHC it was often severely compromised. Mortality was increased in SDH with impaired aerobic metabolism, while CHC did not exhibit a similar relation.
Conclusions
Compromised energy metabolism is most frequent in patients with SDH and CHC (32 % and 49 % of the study period, respectively). The biochemical pattern of mitochondrial dysfunction is more common than that of ischaemia (32 % and 6 % of the study period, respectively). A correlation between mortality and biochemical data is obtained provided the microdialysis catheter is placed in an area where energy metabolism reflects tissue outcome in a large part of the brain.
Similar content being viewed by others
References
Ungerstedt U, Pycock CH (1974) Functional correlates of dopamine neurotransmission. Bull der Schweiz Akad Med Wiss 30:44–55
Nelson DW, Thornquist B, MacCallum RM, Nyström H, Holst A, Rudehill A, Wanecek M, Bellander BM, Weitzberg E (2011) Analyses of cerebral microdialysis in patients with traumatic brain injury: relations to intracranial pressure, cerebral perfusion pressure and catheter placement. BMC Med 9:21
Timofeev I, Carpenter KL, Nortje J, Al-Rawi PG, O’Connell MT, Czosnyka M, Smielewski P, Pickard JD, Menon DK, Gupta AK, Kirkpatrick PJ, Hutchinson PJ (2011) Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients. Brain 134:484–494
Dienel GA (2012) Brain lactate metabolism: the discoveries and the controversies. J Cereb Blood Flow Metab 32:1107–1138
Dienel GA (2014) Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations. J Cereb Blood Flow Metab 34:1736–1748
Siesjö BK (1978) Brain energy metabolism. Wiley, Chichester, pp 192–194
Jacobsen A, Nielsen TH, Nilsson O, Schalén W, Nordström CH (2014) Bedside diagnosis of mitochondrial dysfunction in aneurysmal subarachnoid hemorrhage. Acta Neurol Scand 130:156–163
Nielsen TH, Olsen NV, Toft P, Nordström CH (2013) Cerebral energy metabolism during mitochondrial dysfunction induced by cyanide in piglets. Acta Anaesthesiol Scand 57:793–801
Nielsen TH, Schalén W, Ståhl N, Toft P, Reinstrup P, Nordström CH (2014) Bedside diagnosis of mitochondrial dysfunction after malignant middle cerebral artery infarction. Neurocrit Care 21:35–42
Teasdale G, Jennett B (1974) Assessment of coma and impaired consciousness. A practical scale. Lancet 7872:81–84
Lundberg N (1960) Continuous recording and control of ventricular fluid pressure in neurosurgical practice. Acta Psychiatr Scand Suppl 36(149):1–193
Grände PO, Asgeirsson B, Nordström CH (2002) Volume targeted therapy of increased intracranial pressure: the Lund concept unifies surgical and non-surgical treatments. Acta Anaesthesiol Scand 46:929–941
Nordström CH, Reinstrup P, Xu W, Gärdenfors A, Ungerstedt U (2003) Assessment of the lower limit for cerebral perfusion pressure in severe head injuries by bedside monitoring of regional energy metabolism. Anesthesiology 98:809–814
Reinstrup P, Stahl N, Mellergard P, Uski T, Ungerstedt U, Nordström CH (2000) Intracerebral microdialysis in clinical practice: baseline values for chemical markers during wakefulness, anesthesia, and neurosurgery. Neurosurgery 47:701–709
Engström M, Polito A, Reinstrup P, Romner B, Ryding E, Ungerstedt U, Nordström CH (2005) Intracerebral microdialysis in clinical routine—the importance of catheter location. J Neurosurg 102:460–469
Nedergaard M, Takano T, Hansen AJ (2002) Beyond the role of glutamate as a neurotransmitter. Nat Rev Neurosci 3:748–755
Samuelsson C, Hillered L, Zetterling M, Enblad P, Hesselager G, Ryttlefors M, Kumlien E, Lewén A, Marklund N, Nilsson P, Salci K, Ronne-Engström E (2007) Cerebral glutamine and glutamate levels in relation to compromised energy metabolism: a microdialysis study in subarachnoid hemorrhage patients. J Cereb Blood Flow Metab 27:1309–1317
Hillered L, Valtysson J, Enblad P, Persson L (1998) Interstitial glycerol as a marker for membrane phospholipid degradation in the acutely injured human brain. J Neurol Neurosurg Psychiatry 64:486–491
Ungerstedt U, Bäckström T, Hallström Å, Grände PO, Mellergård P, Nordström CH (1997) Microdialysis in normal and injured human brain. In: Kinney JM, Tucker HN (eds) Physiology, stress, and malnutrition: functional correlates, nutritional intervention. Lippincott-Raven, Philadelphia, pp 361–374
Halestrap AP (2012) The monocarboxylate transporter family—structure and functional characterization. IUBMB Life 64:1–9
Xiong Y, Gu Q, Peterson PL, Muizelaar JP, Lee CP (1997) Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury. J Neurotrauma 14:23–34
Reinstrup P, Nordström CH (2011) Prostacyclin infusion may prevent secondary damage in pericontusional brain tissue. Neurocrit Care 14:441–446
Alessandri B, Rice AC, Levasseur J, DeFord M, Hamm RJ, Bullock MR (2002) Cyclosporin A improves brain tissue oxygen consumption and learning/memory performance after lateral fluid percussion injury in rats. J Neurotrauma 19:829–841
Moroa N, Suttona RL (2010) Beneficial effects of sodium or ethyl pyruvate after traumatic brain injury in the rat. Exp Neurol 225:391–401
Uchino H, Elmer E, Uchino K, Lindvall O, Siesjö BK (1998) Amelioration by cyclosporin A of brain damage in transient forebrain ischemia in the rat. Brain Res 812:216–226
Nordström CH, Rehncrona S, Siesjö BK (1978) Restitution of cerebral energy state, as well as of glycolytic metabolites, citric acid cycle intermediates and associated amino acids after 30 minutes of complete ischemia in rats anaesthetized with nitrous oxide or phenobarbital. J Neurochem 30:479–486
Nordström CH, Rehncrona S, Siesjö BK (1978) Effects of phenobarbital in cerebral ischemia. Part II: restitution of cerebral energy state, as well as of glycolytic metabolites, citric acid cycle intermediates and associated amino acids after pronounced incomplete ischemia. Stroke 9:335–343
Rehncrona S, Mela L, Siesjo BK (1979) Recovery of brain mitochondrial function in the rat after complete and incomplete cerebral ischemia. Stroke 10:437–446
Soane L, Kahraman S, Kristian T, Fiskum G (2007) Mechanisms of impaired mitochondrial energy metabolism in acute and chronic neurodegenerative disorders. J Neurosci Res 85:3407–3415
MacMillan VH (1989) Cerebral energy metabolism in cyanide encephalopathy. J Cereb Blood Flow Metab 9:156–162
Thelin EP, Nelson DW, Ghatan PH, Bellander BM (2014) Microdialysis monitoring of CSF parameters in severe traumatic brain injury patients: a novel approach. Front Neurol 5:159
Jacobsen R, Nielsen TH, Granfeldt A, Toft P, Nordström CH (2016) A technique for continuous bedside monitoring of global cerebral energy state. Intensive Care Med Exp 4:3
Vespa P, Bergsneider M, Hattori N, Wu HM, Huang SC, Martin NA, Glenn TC, McArthur DL, Hovda DA (2005) Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab 25:763–774
Vespa PM, O’Phelan K, McArthur D, Miller C, Eliseo M, Hirt D, Glenn T, Hovda DA (2007) Pericontusional brain tissue exhibits persistent elevation of lactate/pyruvate ratio independent of cerebral perfusion pressure. Crit Care Med 35:1153–1160
Stein NR, McArthur DL, Etchepare M, Vespa PM (2012) Early cerebral metabolic crisis after TBI influences outcome despite adequate hemodynamic resuscitation. Neurocrit Care 17:49–57
Lakshmanan R, Loo JA, Drake T, Leblanc J, Ytterberg AJ, McArthur DL, Etchepare M, Vespa PM (2010) Metabolic crisis after traumatic brain injury is associated with a novel microdialysis proteome. Neurocrit Care 12:324–336
Acknowledgments
We thank Katarina Nielsen, Department of Neurosurgery, Lund University Hospital, for help with the microdialysis equipment and biochemical analyses.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
No funding was received for this research.
Conflict of interest
Carl-Henrik Nordström is consulting for MDialysis Stockholm, Sweden. All other authors certify that they have no affiliations with or involvement in any organisation or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
Ethical approval
All procedures performed in studies involving human participants were in accordance with ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.
Rights and permissions
About this article
Cite this article
Nordström, CH., Nielsen, T.H., Schalén, W. et al. Biochemical indications of cerebral ischaemia and mitochondrial dysfunction in severe brain trauma analysed with regard to type of lesion. Acta Neurochir 158, 1231–1240 (2016). https://doi.org/10.1007/s00701-016-2835-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00701-016-2835-z