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.

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.

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.

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.

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.

Critical Care Medicine: May 2006 - Volume 34 - Issue 5 - p 1582-1583 doi: 10.1097/01.CCM.0000216697.37348.FC

Objectives: Posttraumatic hypotension is believed to increase morbidity and mortality in traumatically brain-injured patients. Using a clinically relevant model of combined traumatic brain injury with superimposed hemorrhagic hypotension in rats, the present study evaluated whether a reduction in mean arterial blood pressure aggravates regional brain edema formation, regional cell death, and neurologic motor/cognitive deficits associated with traumatic brain injury.Design: Experimental prospective, randomized study in rodents.Setting: Experimental laboratory at a university hospital.Subjects. One hundred nineteen male Sprague-Dawley rats weighing 350-385 g.Interventions. Experimental traumatic brain injury of mild to moderate severity was induced using the lateral fluid percussion brain injury model in anesthetized rats (n = 89). Following traumatic brain injury, in surviving animals one group of animals was subjected to pressure-controlled hemorrhagic hypotension, maintaining the mean arterial blood pressure at 50-60 mm Hg for 30 mins (n = 47). The animals were subsequently either resuscitated with lactated Ringer's solution (three times shed blood volume, n = 18) or left uncompensated (n = 29). Other groups of animals included those with isolated traumatic brain injury (n = 34), those with isolated hemorrhagic hypotension (n = 8), and sham-injured control animals receiving anesthesia and surgery alone (n = 22).Measurements and Main Results: The withdrawal of 6-7 mL of arterial blood significantly reduced mean arterial blood pressure by 50% without decreasing arterial oxygen saturation or PaO2. Brain injury induced significant cerebral edema (p <.001) in vulnerable brain regions and cortical tissue loss (p <.01) compared with sham-injured animals. Neither regional brain edema formation at 24 hrs postinjury nor the extent of cortical tissue loss assessed at 7 days postinjury was significantly aggravated by superimposed hemorrhagic hypotension. Brain injury-induced neurologic deficits persisted up to 20 wks after injury and were also not aggravated by the hemorrhagic hypotension. Cognitive dysfunction persisted for up to 16 wks postinjury. The superimposition of hemorrhagic hypotension significantly delayed the time course of cognitive recovery.Conclusions. A single, acute hypotensive event lasting 30 mins did not aggravate the short- and long-term structural and motor deficits but delayed the speed of recovery of cognitive function associated with experimental traumatic brain injury.

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.

Pancreatitis remains to be a major complication following clinical pancreas transplantation. We performed orthogonal polarized spectral (OPS) imaging for direct in vivo visualization and quantification of human pancreatic microcirculation in six healthy donors for living donor liver transplantation and 13 patients undergoing simultaneous pancreas-kidney transplantation. We further determined the impact of microvascular dysfunction during early reperfusion on pancreatic graft injury. Exocrine and endocrine pancreatic impairment was determined by analysis of serum lipase, amylase and C-peptide levels. Compared to normal pancreas in liver donors (homogeneous acinar perfusion) functional capillary density (FCD) and capillary red blood flow velocity of reperfused grafts were significantly decreased. Elevated CRP concentrations on day 2 post-transplant and serum lipase and amylase levels determined on days 4-5 significantly correlated with microvascular dysfunction during the first 30 min of graft reperfusion. Post-transplant serum C-peptide also correlated significantly with pancreatic capillary perfusion. OPS imaging allows to intra-operatively assess physiologic pancreatic microcirculation and to determine microcirculatory impairment during early graft reperfusion. This impairment correlated with the manifestation of post-transplant dysfunction of both exocrine and endocrine pancreatic tissue. OPS imaging may be used clinically to determine the efficacy of interventions, aiming at attenuating microcirculatory impairment during the acute post-transplant reperfusion phase.

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.

Trauma-induced microcirculatory dysfunction, formation of free radicals and decreased endothelial release of nitric oxide (NO) contribute to evolving tissue damage following skeletal muscle injury. Administration of N-acetylcysteine (NAC) known to A-avenge free radicals and generate NO is considered a valuable therapeutic approach. Thus, the objective of this study was to quantitatively analyze the acute effects of NAC oil skeletal muscle microcirculation and leukocyte-endothelial cell interaction following severe standardized closed soft tissue injury (CSTI). Severe CSTI was induced in the hindlimbs of 14 male anesthetized Sprague-Dawley rats using the controlled impact injury technique. Rats were randomly assigned (n = 7) to high-dose intravenous infusion of NAC (400 mg/kg body weight) or isovolemic normal saline (NS). Non-injured, sham-operated animals (n = 7) were subjected to (he same surgical procedures but did not receive any additional fluid. Creatin kinase (CK) activity was assessed at baseline. I h before and 2 h following posttraumatic NAC or NS infusion. Microcirculation of the extensor digitorum longus (EDL) muscle was analyzed using intravital microscopy and Laser-Doppler flowmetry (LDF). Edema index (El) was calculated by measuring the EDL wet-to-dry weight ratio (El = injured/contralateral limb). EDL-muscles were analyzed for desmin immunoreactivity and granulocyte infiltration. Microvascular deteriorations observed following NS-infusion were effectively reversed by NAC: Functional capillary density was restored to levels found in sham-operated animals and leukocyte adherence was significantly (p < 0.05) reduced compared to the NS group. NAC significantly (p < 0.05) increased erythrocyte flux determined by Laser-Doppler flowmetry. Posttraumatic serum CK levels and El were significantly (p < 0.05) decreased by NAC. During the posttraumatic acute phase, single infusion of NAC markedly reduced posttraumatic microvascular dysfunction. attenuated both leukocyte adherence and tissue infiltration. NAC also decreased CSTI-induced edema formation and myonecrosis as reflected by attenuated serum CK levels and attenuated loss of desmin inuminoreactivity. NAC may serve as an effective therapeutic strategy by supporting microvascular blood supply and tissue viability in the early posttraumatic period. Additional studies aimed at long-term analysis and investigation of injury severity-or dosage dependency are needed. (C) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

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.

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.

The efficacy of topiramate, a novel therapeutic agent approved for the treatment of seizure disorders, was evaluated in a model of traumatic brain injury (TBI). Adult male rats were anesthetized (sodium pentobarbital, 60 mg/kg, i.p.), subjected to lateral fluid percussion brain injury (n = 60) or sham injury (n = 47) and randomized to receive either topiramate or vehicle at 30 min (30 mg/kg, i.p.), and 8, 20 and 32 h postinjury (30 mg/kg, p.o.). In Study A, memory was evaluated using a Morris water maze at 48 h postinjury, after which brain tissue was evaluated for regional cerebral edema. In Study B, animals were evaluated for motor function at 48 h and 1, 2, 3, and 4 weeks postinjury using a composite neuroscore and the rotating pole test and for learning ability at 4 weeks. Brains were analyzed for hemispheric tissue loss and hippocampal CA3 cell loss. Topiramate had no effect on posttraumatic cerebral edema or histologic damage when compared to vehicle. At 48 h, topiramate treatment improved memory function in sham but not brain-injured animals, while at one month postinjury it impaired learning performance in brain-injured but not sham animals. Topiramate significantly improved composite neuroscores at 4 weeks postinjury and rotating pole performance at 1 and 4 weeks postinjury, suggesting a potentially beneficial effect on motor function following TBI.

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.