A Diabetes-specific Oral Nutritional Supplement Improves Glycaemic Control in Type 2 Diabetes Patients.

AIMS: Reducing the intake of low molecular weight carbohydrates with artificial nutrition may lower glycaemic response in patients with diabetes. We evaluated effects of a diabetes-specific carbohydrate modified oral nutritional supplement (ONS) during 12 weeks administration in 40 elderly type 2 normal weight patients with diabetes with previous involuntary weight loss. METHODS: Prospective, randomised, double-blind, controlled trial. Patients ingested 2×200 ml/day diabetes-specific or isocaloric standard ONS (control) in addition to their regular diet. Parameters of glucose and lipid metabolism, functional and nutritional status were assessed at baseline, weeks 6 and 12. RESULTS: Postprandial glucose incremental area under the curve (iAUC0-240 min) was comparable between treatment groups on day 1 (467.9±268.4 vs. 505.1±206.1 mmol/l*min, n.s. - arithmetic means±standard deviation) and was significantly lower with the diabetes-specific ONS vs. controls in weeks 6 and 12 (355.2±115.8 vs. 634.9±205.9 and 364.9±153.1 vs. 743.4±202.7; both P<0.0001). Postprandial peak glucose was significantly lower with the diabetes-specific ONS vs. controls in weeks 6 and 12 (P<0.0001) and the decrease in HbA1c, (baseline to week 12) was markedly pronounced (P=0.028). There were no differences between groups in insulin, HOMA-IR, lipid parameters, nutritional and performance status. Body weight and body mass index (BMI) increased significantly over time in both groups. CONCLUSIONS: Administration of a diabetes-specific ONS for 12 weeks reduced postprandial glycaemia after ingestion of the study treatment and improved long-term glycaemic control in elderly patients with type 2 diabetes and involuntary weight loss, thereby reducing their risk for diabetes-associated long-term complications.

Arterial lactate above 2 mM is associated with increased brain lactate and decreased brain glucose in patients with severe traumatic brain injury.

BACKGROUND: Lactate fuels cerebral energy-consuming processes and it is neuroprotective. The impact of arterial lactate on brain metabolism determined by microdialysis was investigated retrospectively in patients with severe traumatic brain injury (TBI). METHODS: Cerebral microdialysis (glucose, lactate), neuromonitoring (ICP, CPP, ptiO2, SjvO2) and blood gas data collected in 20 patients during pharmacologic coma were grouped within predefined arterial lactate clusters (<1, 1-2, >2 mM). Microdialysis samples were only taken from time points characterized by normoventilation (paCO2 34.5-42 mmHg), sufficient oxygenation (paO2 >75 mmHg) and hematocrit (≥24%) to exclude confounding influences. RESULTS: Elevated arterial lactate ≥2 mM was associated with significantly increased brain lactate which coincided with markedly decreased brain glucose despite significantly increased arterial glucose levels and sufficient cerebral perfusion indirectly determined by normal SjvO2 and ptiO2 values. At elevated arterial lactate levels signs of significantly increased cerebral lactate uptake coincided with markedly decreased cerebral glucose uptake. Infused lactate above 50 mM per 24 hours was associated with significantly decreased cerebral glucose. CONCLUSION: Increased arterial lactate levels were associated with increased cerebral lactate uptake and elevated brain lactate. At the same time brain glucose uptake and brain glucose were significantly reduced. It remains unclear whether arterial lactate is the driving force for the increased cerebral lactate levels or if the reduced glucose uptake also contributed to the increased cerebral lactate levels. Further studies are required to assess the impact of lactate infusion under clinical conditions.

Resuscitative emergency thoracotomy in a Swiss trauma centre.

BACKGROUND: Resuscitative emergency thoracotomy (ET) is performed as a salvage manoeuvre for selected patients with trauma. However, reports from European trauma centres are scarce. METHODS: A retrospective analysis was undertaken of injured patients who underwent resuscitative ET in the emergency department (ED) or operating room (OR) between January 1996 and September 2008. Survival in the ED and to hospital discharge was analysed using logistic regression. RESULTS: During the study interval 121 patients required a resuscitative thoracotomy, of which 49 (40·5 per cent) were performed in the ED and 72 (59·5 per cent) in the OR. Patients in the OR had higher blood pressure on arrival (median 110 versus 60 mmHg; P < 0·001), were less often in severe haemorrhagic shock (63 versus 94 per cent; P < 0·001), had fewer serious head injuries (Abbreviated Injury Score of 3 or above in 33 versus 53 per cent; P = 0·031) and more often had a penetrating stab wound as the dominating mechanism (25 versus 10 per cent; P = 0·042) compared with those in the ED. Ten patients (20 per cent) survived to hospital discharge after ED thoracotomy, compared with 53 (74 per cent) of those treated in the OR. Penetrating injury and Glasgow Coma Scale score above 8 were independent predictors of hospital survival following ED thoracotomy. No patient with a blunt injury and no detectable signs of life on admission survived. Three of 26 patients with blunt trauma and signs of life on admission survived to hospital discharge. CONCLUSION: Resuscitative ET may be life-saving in selected patients. Location of the procedure is dictated by injury severity and vital parameters. Outcome is best when signs of life are present on admission, even for blunt injuries.

Changes in calculated arterio-jugular venous glutamate difference and SjvO2 in patients with severe traumatic brain injury.

BACKGROUND: Cerebral metabolic impairment is feared to induce secondary brain damage following traumatic brain injury (TBI). The present study was designed to assess the temporal profile of calculated arterio- jugular venous differences in glutamate (AJVDglu) and SjvO(2) in patients subjected to continuous pharmacologic coma. Metabolic impairment was assumed to be reflected by increased jugular venous glutamate levels and decreased jugular venous oxygen saturation (SjvO(2)). METHODS: Arterial and jugular venous blood was drawn once daily for up to 14 days from 14 patients to assess the temporal profile. Plasma glutamate was measured by high performance liquid chromatography. SjvO(2), lactate and paCO(2) were determined in routine blood gas analysis. Calculated AJVD indirectly reflects cerebral uptake (positive values) or cerebral release (negative values). RESULTS: During pharmacologic coma an increase in ICP approaching 20 mmHg was associated with significantly reduced paCO(2) (4.7 ± 0.5 kPa; mean ± standard deviation), markedly decreased SjvO(2) (66.0 ± 4.2%) without reaching ischemic values, and a trend to more negative AJVDglu values (-6.0 ± 14.3 µmol/L), suggesting cerebral glutamate release. Arterio- jugular venous lactate difference (AJVDlac) remained unchanged. CONCLUSION: During pharmacologic coma increased ICP was associated with significantly decreased SjvO(2) which coincided only with a trend to increased cerebral glutamate release. Calculated AJVDglu appears to be inferior in unmasking altered brain metabolism compared to SjvO(2) whenever ICP is increased.

Insulin differentially influences brain glucose and lactate in traumatic brain injured patients.

BACKGROUND: Hypo- and hyperglycemia must be avoided to prevent additional brain damage following traumatic brain injury (TBI). However, the optimal blood glucose range requiring insulin remains unknown. Cerebral microdialysis is helpful in unmasking signs of metabolic impairment, thereby identifying deleterious blood glucose levels. METHODS: A retrospective analysis of prospectively collected cerebral microdialysis samples obtained from 20 non-diabetic patients with severe TBI treated at the trauma surgical intensive care unit at the University Hospital Zürich, Switzerland. RESULTS: The impact of different arterial blood glucose values and concomitant insulin administration on cerebral interstitial glucose and lactate levels was investigated. In addition, energetic impairment was determined by calculating lactate-to-glucose ratios. Insulin administration was associated with significantly reduced cerebral glucose concentrations and significantly increased lactate-to-glucose ratios with arterial blood glucose levels <5 mM. At arterial blood glucose levels >7 mM, insulin administration was associated with significantly increased interstitial glucose values, significantly decreased lactate concentrations, and markedly diminished lactate-to-glucose ratios. CONCLUSION: Insulin exerts differential effects that depend strongly on the underlying arterial blood glucose concentrations. To avoid energetic impairment, insulin should not be administered at arterial blood glucose levels <5 mM. However, at arterial blood glucose levels >7-8 mM, insulin administration appears to be encouraged to increase extracellular glucose concentrations and decrease energetic impairment reflected by reduced interstitial brain lactate and decreased lactate-to-glucose ratios. Nevertheless, frequent analysis is required to minimize the risk of inducing impaired brain metabolism.

Granulocyte colony-stimulating factor does not affect contusion size, brain edema or cerebrospinal fluid glutamate concentrations in rats following controlled cortical impact.

INTRODUCTION: Granulocyte colony-stimulating factor (G-CSF) is an established treatment in the neutropenic host. Usage in head-injured patients at risk for infection may aggravate brain damage. In contrast, evidence of G-CSF neuroprotective effects has been reported in rodent models of focal cerebral ischemia. We investigated effects of G-CSF in acute focal traumatic brain injury (TBI) in rats. METHODS: Thirty-six male Sprague-Dawley rats were anesthetized with 1.2%) to 2.0% isoflurane and subjected to controlled cortical impact injury (CCII). Thirty minutes following CCII, either vehicle or G-CSF was administered intravenously. Animals were sacrificed 24 hours following CCII. Glutamate concentrations were determined in cisternal cerebrospinal fluid (CSF). Brain edema was assessed gravimetrically. Contusion size was estimated by 2,3,5-triphenyltetrazolium chloride staining and volumetric analysis. RESULTS: Dose-dependent leukocytosis was induced by infusion of G-CSF. Physiological variables were unaffected. Water content of the traumatized hemisphere and CSF glutamate concentrations were unchanged by treatment. Contusion volume was similar in all groups. CONCLUSIONS: A single injection of G-CSF did not influence cortical contusion volume, brain edema, or glutamate concentrations in CSF determined 24 hours following CCII in rats. G-CSF, administered 30 minutes following experimental TBI, failed to exert neuroprotective effects.

The use of neuronavigation in transnasal transsphenoidal pituitary surgery.

BACKGROUND: Recurrent pituitary adenomas and localisation of microadenomas potentially cause difficulties during transsphenoidal pituitary surgery. Neuronavigation might improve tumour removal in such cases. METHODS: Between 12/98 and 04/01 transnasal transsphenoidal adenomectomies were performed in 152 patients at our department. In 16 of these patients neuronavigation was chosen as a means of safely approaching the tumour and improving the efficacy of tumour localisation and removal. Mean age of the 7 female and 9 male patients was 51.8 +/- 13.7 years. Patients were subdivided according to the underlying pathology, i. e. microadenomas (n = 8, mean diameter: 5.75 +/- 2.1 mm), and recurrent adenomas (n = 8). The imaging of adenomas was achieved in preoperatively obtained 1 mm transversely reconstructed magnetic resonance sections from a dynamic enhanced 3D-FFE sequence (Gyroscan 1.5 Tesla, Philips). Contour-guided surgery via a transnasal transsphenoidal approach to the sella region was performed using the MKM navigation microscope (Zeiss). RESULTS: Endocrinologic studies revealed secretion of growth hormone (GH), ACTH, and follicle stimulating hormone (FSH) in 5, 4, and 1 patient, respectively. The remaining 7 adenomas did not secrete any hormones. All pituitary tumours were accurately localised by neuronavigation. In all recurrent macroadenomas, the tumours were rapidly and safely approached through the scarred tissue and the tumour volume was significantly reduced. Neither intraoperative nor postoperative complications occurred in these patients. In hormone-secreting pituitary tumours with far lateral localisation, endocrinologic abnormalities were corrected in 5 patients, while hormone secretion was significantly decreased in 3 patients. In 1 patient with histologically verified adenoma, hormone secretion did not significantly change following surgical removal. CONCLUSIONS: Neuronavigation in pituitary surgery is of use in only a small number of cases. Nevertheless, we suggest that contour-guided, transsphenoidal adenomectomy may prove helpful in approaching recurrent adenomas and localising lateral microadenomas.

Anesthesia increases circulating glutamate in neurosurgical patients.

BACKGROUND: The excitotoxic amino acid glutamate is known to aggravate pre-existing neuropathology. Since volatile anesthetics increase plasma amino acid levels, we investigated if the anesthetics isoflurane and propofol increase plasma and cerebrospinal fluid (CSF) glutamate in neurosurgical patients. METHODS: In discectomized patients (n = 15), plasma glutamate was determined at 30 minute intervals before and during isoflurane anesthesia. In craniotomized patients (n = 66), plasma glutamate was assessed during and up to 24 hours after routine isoflurane or propofol anesthesia. CSF samples were withdrawn upon opening of the dura, before surgical manipulations. FINDINGS: During isoflurane anesthesia, plasma glutamate was significantly and reversibly increased in discectomized and craniotomized patients compared to healthy controls (56+/-6 microM; p<0.05), which was mostly sustained in male patients (males: 126+/-12 vs. females: 96+/-6 microM; p<0.05). With propofol, plasma glutamate was increased equally in men and women but to a lesser extent than with isoflurane (mean: 72+/-7 microM). CSF glutamate was significantly increased during isoflurane and propofol anesthesia compared to control lumbar CSF (1.2+/-0.1 microM; p<0.0001), being more prominent in patients with pre-existing brain edema receiving isoflurane (76+/-8 vs. propofol: 40+/-6 microM; p<0.05). CONCLUSIONS: The significant increases in plasma and CSF glutamate which were mostly sustained during isoflurane compared to propofol anesthesia should prompt the identification of anesthetic agents which do not impose a possible burden of glutamate-mediated excitotoxicity in patients with underlying compromised cerebral homeostasis. Detailed neuropsychological investigations following different anesthesia regimen are important to determine if transient elevations in CSF and plasma glutamate levels are of clinical relevance.

Assessment of the relationship between age and continuous intracranial compliance.

The aim of this open, descriptive and prospective study was to determine if the new monitoring parameter "continuous intracranial compliance (cICC)" decreases with age in patients with traumatic brain injury (TBI). 30 patients with severe and moderate TBI (Glasgow Coma Scale score < or = 10) contributing to a European multicenter study, organized by the Brain-IT group, underwent computerized monitoring of blood pressure, intracranial pressure (ICP), cerebral perfusion pressure and cICC. Regression analyses of individual median ICP and median cICC versus patients' age revealed no significant dependency. Median cICC declined significantly with increasing ICP (when median ICP = 10, 20 and 30 mmHg, cICC = 0.64, 0.56 and 0.42 ml/mmHg respectively, p < 0.05). These three ICP groups were then subdivided according to age (0-20, 21-40, 41-60 and 61-80 years). Median cICC declined with age in both high ICP groups (median ICP = 20,30 mmHg). Percentage cICC values below a set pathological threshold of lower than 0.05 ml/mmHg across the four age groups were 28% (0-20 yrs), 59% (21-40 yrs), 60% (41-60 yrs) and 70% (61-80 yrs) respectively. The observed phenomenon of decreased intracranial volume challenge compensation with advancing age may contribute to the well-known fact of a worse outcome in elderly patients after TBI.

The antioxidant effect of N-acethylcysteine on experimental contusion in rats.

N-acethylcysteine (NAC) is known to have direct and indirect antioxidant abilities. We investigated the potential protective effect of NAC on ICP, brain edema and contusion volume after Controlled Cortical Impact (CCI) injury. A moderate CCI injury was induced on the left hemisphere in 48 Sprague Dawley rats. The animals were treated with intraperitoneal injection of NAC (163 mg/kg/KG) or physiological saline. Measurements of intracranial pressure (ICP) were performed and brains were removed at 24 hours. Gravimetric analysis of post-traumatic edema and morphometric measurements (TTC staining) of contusion volume were carried out in 24 animals, respectively. ICP measurements increased significantly over time with no significant differences between both groups. The relative difference in water content in NAC treated animals (1.45 +/- 0.1%) did not differ significantly versus placebo (1.47 +/- 0.2%). The contusion volume was diminished by 19% in the NAC group (53.52 +/- 5.3 mm3) versus placebo (66.28 +/- 4.7 mm3) without showing statistical significance. The antioxidant properties of NAC did not affect intracranial pressure or posttraumatic brain edema formation, although the moderate reduction of contusion volume might reveal beneficial effects on focal contusion.

Neuronal activity and cortical perfusion determined by quantitative EEG analysis and laser doppler flowmetry are uncoupled in brain injured rats.

Following traumatic brain injury uncoupling of metabolism from perfusion, reflected by an increase in cellular activity in face of reduced perfusion contributes to secondary tissue damage. Standard autoradiographic techniques employed to study metabolism and perfusion are limited by the inability to perform longitudinal investigations. Therefore, the aims of this study were to investigate if metabolic uncoupling can be studied by applying noninvasive and non-radioactive methods. For this, quantitative EEG analysis and laser Doppler flowmetry were employed to determine changes in EEG activity as a global measure of neuronal activity and pericontusional cortical perfusion during the early phase following controlled cortical impact injury (CCII). In eight rats changes in neuronal activity and pericontusional cortical perfusion were determined before, at 4 and 24 hours after CCII. Neuronal activity was significantly increased by 40% at 4 hours after CCII followed by a significant decrease by 60% at 24 hours compared to pre-trauma levels. Pericontusional cortical perfusion was significantly reduced by 45% and 18% at 4 and 24 hours after CCII. respectively. Non-radioactive methods like quantitative EEG analysis and laser Doppler flowmetry can be used to reveal underlying uncoupling of EEG activity from cortical perfusion which is mostly sustained in the early phase following CCII.

Differential effects of prolonged isoflurane anesthesia on plasma, extracellular, and CSF glutamate, neuronal activity, 125I-Mk801 NMDA receptor binding, and brain edema in traumatic brain-injured rats.

BACKGROUND: Volatile anesthetics reduce neuronal excitation and cerebral metabolism but can also increase intracellular water accumulation in normal and injured brains. While attenuation of neuronal excitation and glutamate release are beneficial under pathological conditions, any increase in edema formation should be avoided. In the present study we investigated duration-dependent effects of the commonly used isoflurane/nitrous oxide (N2O) anesthesia on EEG activity, specific NMDA receptor binding, extracellular, CSF, and plasma glutamate, and cerebral water content in brain-injured rats subjected to short (30 minutes) or prolonged (4 hours) anesthesia. METHODS: Before controlled cortical impact injury (CCI), during prolonged (4-8 hours) or short anesthesia (7.5-8 hours after CCI), and before brain removal, changes in neuronal activity were determined by quantitative EEG analysis and glutamate was measured in arterial plasma. Brains were processed to determine acute and persisting changes in cerebral water content and 125I-Mk801 NMDA receptor binding at 8 and 32 hours after CCI, i.e., immediately or 24 hours after short or prolonged anesthesia. During prolonged anesthesia glutamate was measured via microdialysis within the cortical contusion. CSF was sampled before brain removal. FINDINGS: Prolonged isoflurane (1.8 vol%) anesthesia significantly increased EEG activity, plasma, cortical extracellular, and CSF glutamate, cortical and hippocampal 125I-Mk801 NMDA receptor binding, and cerebral water content in brain-injured rats. These changes were partially reversible within 24 hours after prolonged anesthesia. At 24 hours, CSF glutamate was significantly reduced following long isoflurane anesthesia compared to rats previously subjected to short anesthesia despite an earlier significant increase. Conclusions. The partially reversible increases in EEG activity, 125I-Mk801 NMDA receptor binding, cerebral water content, plasma and CSF glutamate appear important for physiological, pathophysiological, and pharmacological studies requiring prolonged anesthesia with isoflurane. Increases in extracellular cortical and plasma glutamate could contribute to acute aggravation of underlying tissue damage.

Continuous monitoring of intracranial compliance after severe head injury: relation to data quality, intracranial pressure and brain tissue PO2.

The objective of the present study was to test the new continuous intracranial compliance (cICC) device in terms of data quality, relationship to intracranial pressure (ICP) and brain tissue oxygenation (PtiO2). A total of 10 adult patients with severe traumatic brain injury underwent computerized monitoring of arterial blood pressure, ICP, cerebral perfusion pressure, end-tidal CO2, cICC and PtiO2 providing a total of 1726 h of data. (1) The data quality assessed by calculating the 'time of good data quality' (TGDQ, %), i.e. the median duration of artefact-free time as a percentage of total monitoring time reached 98 and 99% for ICP and PtiO2, while cICC measurements were free of artefacts in only 81%. (2) Individual regression analysis showed broad scattered correlation between cICC and ICP ranging from low (r = 0.05) to high (r = 0.52) correlation coefficients. (3) From 225 episodes of increased ICP (ICP > 20 mmHg > 10 min), only 37 were correctly predicted by a preceding decline in cICC to pathological values (< 0.5 ml/mmHg). (4) In all episodes of cerebral hypoxia (PtiO2 < 10 mmHg > 10 min), cICC was not pathologically altered. Based on the present results, we conclude that the current hardware and software version of the cICC monitoring system is unsatisfactory concerning data quality, prediction of increased ICP and revelance of cerebral hypoxic episodes.

Noninvasive analysis of conjunctival microcirculation during carotid artery surgery reveals microvascular evidence of collateral compensation and stenosis-dependent adaptation.

OBJECTIVE: Hemodynamically relevant internal carotid artery (ICA) stenosis is a major cause of ischemic stroke. Despite its long-term benefit, carotid endarterectomy may also be associated with severe neurologic deficits. Intraoperative and early recognition of ischemia in the region of the ICA may reduce this risk. To date, direct imaging and quantitative analysis of microvascular structures and function in the human ICA region have not been possible. We purposed to visualize and quantify ischemia/reperfusion-induced microcirculatory changes in the terminal vascular bed of the ICA in patients undergoing unilateral ICA endarterectomy. METHODS: Sequential analysis of the ipsilateral and contralateral conjunctival microcirculation was performed with orthogonal polarized spectral imaging in 33 patients undergoing unilateral ICA endarterectomy because of moderate or severe ICA stenosis (North American Symptomatic Carotid Endarterectomy Trial score, 75% +/- 13%), before clamping the ICA (baseline), during clamping of the external carotid artery and ICA, during reperfusion of the ICA (intraluminal shunt), during the second clamping of the ICA (shunt removal), after declamping (reperfusion) of the external carotid artery and ICA, and 15 to 20 minutes after the second ICA reperfusion. RESULTS: During ICA clamping for shunt placement, ipsilateral and contralateral conjunctival capillary perfusion was significantly decreased, but it was completely restored after reperfusion with carotid shunting. Reclamping of the ICA for shunt removal caused microvascular dysfunction, which was significantly less pronounced than that observed during the first clamping. The individual degree of ICA stenosis was inversely correlated with the ipsilateral and contralateral decrease in conjunctival functional capillary density during the first ICA clamping. CONCLUSIONS: These results suggest adaptive mechanisms of capillary perfusion with increasing stenosis and development of collateral compensatory circulation in the vascular region of the human ICA. Conjunctival orthogonal polarized spectral imaging during unilateral ICA reconstruction enables continuous noninvasive analysis of bilateral conjunctival microcirculation in the terminal region of the ICA and enables monitoring for efficient carotid shunt perfusion during and after endarterectomy.

Pharmacology of traumatic brain injury.

The intensity of experimental and clinical research to identify a neuroprotective drug for the treatment of traumatic brain injury is motivated by the devastating morbidity and mortality of this condition. Encouraging experimental work has led so far to disappointing clinical trials and the identification of new potential therapeutic targets is critically dependent on a better understanding of the chronic pathophysiology triggered by the initial insult. Future advances in the pharmacological treatment of traumatic brain injury are likely to include the evaluation of sequentially timed therapies combining multiple and targeted agents, and manipulation of the newly discovered neurogenic potential of the adult brain together with the refinement of traditional interventions to block specific cytotoxic cascades.

Cortical hypoperfusion precedes hyperperfusion following controlled cortical impact injury.

Impaired cerebral perfusion contributes to tissue damage following traumatic brain injury. In this longitudinal study persistence of reduced cortical perfusion employing laser doppler flowmetry was investigated following controlled cortical impact injury (CCII). Before, 30 minutes, 6, 24, and 48 hours after CCII, perfusion in pericontusional cortex was determined by moving a laser doppler probe in 50 x 0.2 mm steps over the traumatized hemisphere in 5 rats. Arterial blood gases and mean arterial blood pressure were monitored. Mean arterial blood pressure and arterial blood gases remained stable during the entire experiments. At 30 minutes and 6 hours following CCII, cortical perfusion was significantly diminished by 24% and 43% (p < 0.05), respectively compared to pre-trauma levels. At 24 and 48 hours after CCII, pericontusional blood flow was significantly increased by 64% and 123%. Cortical hypoperfusion found within the early phase following trauma is reversible and precedes a long lasting phase of hyperperfusion. Changes in tissue mediators (endothelin, acidosis, NO) could account for these findings.

Neuronal activity determined by quantitative EEG and cortical microdialysis is increased following controlled cortical impact injury in rats.

Following brain injury increased glutamate release is linked to sustained neuronal activation resulting in excitotoxic tissue damage. Isoflurane anesthesia has been shown to decrease electroencephalographic (EEG) activity and extracellular (e.c.) glutamate, possibly attenuating excitotoxic tissue damage. However, based on clinical experience EEG activity can fluctuate despite stable isoflurane concentrations. Therefore, the aims of this study were to investigate the impact of neuronal activity assessed by quantitative EEG on e.c. glutamate during isoflurane anesthesia following controlled cortical impact injury (CCII). In 10 rats balanced anesthesia using isoflurane was induced at 4 hours after CCII. Under steady-state conditions maintaining isoflurane at 1.8 vol%, EEG was recorded for 3 hours. During this period, e.c. glutamate was sampled in the pericontusional cortex by microdialysis. Despite maintaining isoflurane at 1.8 vol%, neuronal activity expressed as low frequency EEG power showed marked fluctuations. Spontaneous increases in neuronal activity coincided with elevated e.c. glutamate levels and vice versa. Overall, EEG power correlated significantly with pathologically elevated e.c. glutamate levels (n = 58; R2 = 0.54; p < 0.05). Despite unchanged isoflurance concentrations fluctuations in neuronal activity were reflected by altered EEG power and e.c. glutamate concentrations. Therefore, neuronal activity needs to be considered for the interpretation of e.c. glutamate levels.

Norepinephrine is superior to dopamine in increasing cortical perfusion following controlled cortical impact injury in rats.

Following traumatic brain injury catecholamines are routinely applied to increase cerebral perfusion. To date, it remains controversial if infusion of catecholamines is associated with diminished cerebral perfusion due to catecholamine-mediated vasoconstriction. The aims of the present study were to investigate the effects of norepinephrine and dopamine on cortical perfusion and brain edema following controlled cortical impact injury (CCII) in rats. Four hours after CCII, rats (n = 22) received either norepinephrine or dopamine with the aim of increasing MABP to 120 mm Hg for 90 minutes. Control rats were given NaCl. Cortical perfusion was measured before, during, and after catecholamine infusion using Laser Doppler flowmetry. Brain swelling was determined directly after the study period (8 hrs after CCII). Following CCII cortical perfusion was reduced by 40% compared to pre-trauma values in all rats. Parallel to the increases in MABP, cortical perfusion was significantly elevated under norepinephrine and dopamine, respectively (p < 0.05). Despite similar MABP values this increase was mostly sustained under norepinephrine. In control rats cortical perfusion remained diminished. Brain swelling was similar in all groups. Both norepinephrine and dopamine significantly increased cortical perfusion following CCII. Norepinephrine, however, was superior to dopamine in CBF. Based on increased CBF and unchanged brain swelling catecholamine-mediated vasoconstriction does not seem to occur under the present study design.