Troels Halfeld Nielsen

Cerebral energy metabolism during mitochondrial dysfunction induced by cyanide in piglets

Mitochondrial dysfunction is an important factor contributing to tissue damage in both severe traumatic brain injury and ischemic stroke. This experimental study explores the possibility to diagnose the condition bedside by utilising intracerebral microdialysis and analysis of chemical variables related to energy metabolism.

Bedside diagnosis of mitochondrial dysfunction in aneurysmal subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) is frequently associated with delayed neurological deterioration (DND). Several studies have shown that DND is not always related to vasospasm and ischemia. Experimental and clinical studies have recently documented that it is possible to diagnose and separate cerebral ischemia and mitochondrial dysfunction bedside. The study explores whether cerebral biochemical variables in SAH patients most frequently exhibit a pattern indicating ischemia or mitochondrial dysfunction.

Cerebral energy metabolism during induced mitochondrial dysfunction

In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in brain tissue oxygen tension (PbtO2) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets.

Exogenous lactate supplementation to the injured brain: misleading conclusions with clinical implications

Dear Editor, In their study Bouzat et al. [1] conclude that following traumatic brain injury lactate may be used by the brain as a preferential energy substrate and that intravenous infusion of hypertonic sodium lactate had positive effects on cerebral energy metabolism and intracranial pressure (ICP). The biochemical conclusions are based on data obtained from microdialysis (MD) indicating that the therapy increased the intracerebral levels of glucose and pyruvate while glutamate and ICP decreased. The conclusions are partly misleading which may lead to inappropriate clinical decisions. The lactate/pyruvate (LP) ratio obtained during MD reflects cytoplasmatic redox state which can be described according to the equation

Critical thresholds for cerebrovascular reactivity: fact or fiction?

To the Editor, We read with interest the recent publication by Sorrentino et al. [1] entitled: ‘‘Critical Thresholds for Cerebrovascular Reactivity after Traumatic Brain Injury’’. The study is based on the hypothesis that bedside real-time calculation of the pressure-reactivity index (PRx) allows a continuous estimation of cerebral pressure autoregulation [1–3]. From measurements of hydrostatic pressure alone the authors define threshold levels for survival as well as favorable outcome in patients with severe traumatic brain lesions. Pressure autoregulation is present in many tissues but it is most pronounced in the brain and the kidney. The main ‘‘physiological purpose’’ of pressure autoregulation is probably to keep intracapillary hydrostatic pressure relatively constant [4]. Changes in precapillary resistance (R) underlying cerebral pressure autoregulation are calculated from cerebral perfusion pressure (CPP) divided by cerebral blood flow (F): R = (Pa ICP)/F [5]. Accordingly, to describe cerebral vasoreactivity it is necessary to assess not only arterial blood pressure (Pa) and intracranial pressure (ICP) but also F. The authors behind the PRx method claim that cerebrovascular pressure reactivity may be estimated by observing the response of ICP to changes in Pa. PRx is in this study determined by calculating the correlation coefficient between 30 consecutive data points resulting from the time averaging of ICP and Pa signals with a width of the moving-average window of 8 s [1]. However, in our opinion it is obvious from the equation above that cerebrovascular resistance cannot be calculated unless cerebral blood flow is also assessed. The method of PRx is based on the assumption that the observed change in Pa is the primary and independent cause of the variations in the other three monitored variables. In the validity study of the PRx method Pa was increased by i.v. vasopressor infusion and F was measured utilizing PET-technique [3]. In this defined, experimental situation it is possible that the increase in Pa is the primary and independent cause of the variations in the other variables. Under clinical conditions this is, however, often not the case. During neurocritical care fluctuations in pain, sedation, stress level, local neuronal excitation, etc., will cause changes in cerebral energy metabolism resulting in variations in precapillary vasoconstriction and cerebral blood flow that are not a function of simultaneously occurring changes in Pa. All these sources of error are neglected when PRx is interpreted as a measure of cerebral pressure autoregulation. As the Cambridge group has also suggested that PRx is correlated to cerebral energy metabolism [6] it seems unlikely that this index might be used for continuous estimation pressure autoregulation as well. In their analyses of prognostic threshold levels the authors use mean values for the entire monitoring period for each parameter: ICP, CPP, and PRx. In the study, the monitoring periods vary between 6 h and 20 days. The authors comment on this fact in the section of limitations. However, in our opinion the consequences are more serious than mentioned by the authors and may invalidate the threshold levels arrived at. In patients with brain trauma mortality is usually caused by an increase in ICP and patients who die within the first few days of admission usually have a high ICP. However, patients who initially may have equally high ICP (in this C.-H. Nordstrom (&) T. H. Nielsen Department of Neurosurgery, Odense University Hospital, Odense, Denmark e-mail: carl-henrik.nordstrom@med.lu.se

Recirculation usually precedes malignant edema in middle cerebral artery infarcts

In patients with large middle cerebral artery (MCA) infarcts, maximum brain swelling leading to cerebral herniation and death usually occurs 2–5 days after onset of stroke. The study aimed at exploring the pattern of compounds related to cerebral energy metabolism in infarcted brain tissue.

Bedside Monitoring of Cerebral Energy State During Cardiac Surgery-A Novel Approach Utilizing Intravenous Microdialysis.

OBJECTIVES This study investigated whether the lactate-to-pyruvate (LP) ratio obtained by microdialysis (MD) of the cerebral venous outflow reflected a derangement of global cerebral energy state during cardiopulmonary bypass (CPB). DESIGN Interventional, prospective, randomized study. SETTING Single-center, university teaching hospital. PARTICIPANTS The study included 10 patients undergoing primary, elective coronary artery bypass grafting. INTERVENTIONS Patients were randomized blindly to low mean arterial pressure (MAP) (40-60 mmHg; n = 5) or high MAP (60-80 mmHg; n = 5) during CPB. The MD catheters were positioned in a retrograde direction into the jugular bulb, and a reference catheter was inserted into the brachial artery. The correlations among LP ratio, MAP, data obtained from bifrontal near-infrared spectroscopy (NIRS), and postoperative neurologic outcome measures were assessed. MEASUREMENTS AND MAIN RESULTS The correlated difference between pooled LP ratio (low and high MAP) of the jugular venous and the arterial blood was significant (LParterial 17 [15-20] v LPvenous 26 [23-27]; p = 0.0001). No cerebral desaturations (decrease in rSO2>20% from baseline) were observed in either group during CPB. In each group, 50% of the patients showed significant cognitive decline (mini-mental state examination, 3 points) 2 days after surgery. CONCLUSION The LP ratio of cerebral venous blood increased significantly during CPB, indicating compromised cerebral oxidative metabolism. Conventional monitoring of rSO2 by NIRS did not show a corresponding decrease in cerebral oxygenation. As the patients exhibited decreased cognitive functions after CPB, increases in jugular venous LP ratio may be a sensitive indicator of impending cerebral damage.