Critical Evaluation of the Lund Concept for Treatment of Severe Traumatic Head Injury, 25 Years after Its Introduction.

When introduced in 1992, the Lund concept (LC) was the first complete guideline for treatment of severe traumatic brain injury (s-TBI). It was a theoretical approach, based mainly on general physiological principles-i.e., of brain volume control and optimization of brain perfusion and oxygenation of the penumbra zone. The concept gave relatively strict outlines for cerebral perfusion pressure, fluid therapy, ventilation, sedation, nutrition, the use of vasopressors, and osmotherapy. The LC strives for treatment of the pathophysiological mechanisms behind symptoms rather than just treating the symptoms. The treatment is standardized, with less need for individualization. Alternative guidelines published a few years later (e.g., the Brain Trauma Foundation guidelines and European guidelines) were mainly based on meta-analytic approaches from clinical outcome studies and to some extent from systematic reviews. When introduced, they differed extensively from the LC. We still lack any large randomized outcome study comparing the whole concept of BTF guidelines with other guidelines including the LC. From that point of view, there is limited clinical evidence favoring any of the s-TBI guidelines used today. In principle, the LC has not been changed since its introduction. Some components of the alternative guidelines have approached those in the LC. In this review, I discuss some important principles of brain hemodynamics that have been lodestars during formulation of the LC. Aspects of ventilation, nutrition, and temperature control are also discussed. I critically evaluate the most important components of the LC 25 years after its introduction, based on hemodynamic principles and on the results of own an others experimental and human studies that have been published since then.

Isolated Brain Trauma in Cats Triggers Rapid Onset of Hypovolemia.

BACKGROUND: Hemodynamic instability responsive to fluid resuscitation is common after a traumatic brain injury (TBI), also in the absence of systemic hemorrhage. The present study tests if an isolated severe TBI induces a decrease in plasma volume (PV). METHODS: The study was performed in three groups of anesthetized and tracheostomized male cats (n = 21). In one group (n = 8), the cats were prepared with a cranial borehole (10 mm i.d) used to expose the brain to a fluid percussion brain injury (FPI) (1.90-2.20 bar), and two smaller cranial boreholes (4 mm i.d) for insertion of an intracranial pressure (ICP) and a microdialysis catheter. To differentiate the effect of FPI from that of the surgical preparation, a sham group was exposed to the same surgical preparation but no FPI trauma (n = 8). A control group had no brain trauma and no surgical preparation (n = 5). PV was determined by a 125I-albumin dilution technique. PV, electrolytes, pH, BE (base excess), hematocrit (Hct), PaO2, and PaCO2 were measured at baseline and after 3 h. Mean arterial pressure (MAP) was measured continuously. ICP was measured in the FPI and the sham group. RESULTS: In the FPI group, PV decreased by 11.2 mL/kg from 31.7 mL/kg (p < 0.01) with a simultaneous increase in Hct and decrease in pH. In the sham group, PV decreased by 5.7 mL/kg from 32.7 mL/kg (p < 0.01). The control group showed no PV reduction. CONCLUSIONS: The results support that an isolated severe head trauma triggers a significant and rapid reduction in PV, most likely due to vascular leak.

A Consensus-Based Interpretation of the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure Trial.

Widely-varying published and presented analyses of the Benchmark Evidence From South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial of intracranial pressure (ICP) monitoring have suggested denying trial generalizability, questioning the need for ICP monitoring in severe traumatic brain injury (sTBI), re-assessing current clinical approaches to monitored ICP, and initiating a general ICP-monitoring moratorium. In response to this dissonance, 23 clinically-active, international opinion leaders in acute-care sTBI management met to draft a consensus statement to interpret this study. A Delphi method-based approach employed iterative pre-meeting polling to codify the group's general opinions, followed by an in-person meeting wherein individual statements were refined. Statements required an agreement threshold of more than 70% by blinded voting for approval. Seven precisely-worded statements resulted, with agreement levels of 83% to 100%. These statements, which should be read in toto to properly reflect the group's consensus positions, conclude that the BEST TRIP trial: 1) studied protocols, not ICP-monitoring per se; 2) applies only to those protocols and specific study groups and should not be generalized to other treatment approaches or patient groups; 3) strongly calls for further research on ICP interpretation and use; 4) should be applied cautiously to regions with much different treatment milieu; 5) did not investigate the utility of treating monitored ICP in the specific patient group with established intracranial hypertension; 6) should not change the practice of those currently monitoring ICP; and 7) provided a protocol, used in non-monitored study patients, that should be considered when treating without ICP monitoring. Consideration of these statements can clarify study interpretation.

Effects of prostacyclin on cerebral blood flow and vasospasm after subarachnoid hemorrhage: randomized, pilot trial.

BACKGROUND AND PURPOSE: Delayed ischemic neurological deficits (DINDs) are a major contributing factor for poor outcome in patients with subarachnoid hemorrhage. In this trial, we investigated the therapeutic potential of prostacyclin, an endogen substance with known effect on vascular tone and blood flow regulation, on factors related to DIND. METHODS: This trial is a single-center, randomized, blinded, clinical, pilot trial with 3 arms. Ninety patients were randomized to continuous infusion of prostacyclin 1 ng/kg per minute, prostacyclin 2 ng/kg per minute, or placebo. The intervention was initiated day 5 after subarachnoid hemorrhage and discontinued day 10. Primary outcome was the difference in change from baseline in global cerebral blood flow. Secondary outcome measures were occurrence of DIND, angiographic vasospasm, and clinical outcome at 3 months. RESULTS: No statistically significant difference in change of global cerebral blood flow was found between the intervention groups. The observed incidence of DIND and angiographic vasospasm was markedly higher in the placebo group, although this difference was not statistically significant. No statistically significant differences in safety parameters or clinical outcome were found between the 3 groups. CONCLUSIONS: Administration of prostacyclin to patients with subarachnoid hemorrhage may be safe and feasible. Global cerebral blood flow after subarachnoid hemorrhage is not markedly affected by administration of prostacyclin in the tested dose range. It may be possible that the observed reduction in the point estimates of DIND and vasospasm in the prostacyclin groups represents an effect of prostacyclin as this trial was not powered to investigate the effect of prostacyclin on these outcomes. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01447095.

Therapeutic Hypothermia in Children and Adults with Severe Traumatic Brain Injury.

Great expectations have been raised about neuroprotection of therapeutic hypothermia in patients with traumatic brain injury (TBI) by analogy with its effects after heart arrest, neonatal asphyxia, and drowning in cold water. The aim of this study is to review our present knowledge of the effect of therapeutic hypothermia on outcome in children and adults with severe TBI. A literature search for relevant articles in English published from year 2000 up to December 2013 found 19 studies. No signs of improvement in outcome from hypothermia were seen in the five pediatric studies. Varied results were reported in 14 studies on adult patients, 2 of which reported a tendency of higher mortality and worse neurological outcome, 4 reported lower mortality, and 9 reported favorable neurological outcome with hypothermia. The quality of several trials was low. The best-performed randomized studies showed no improvement in outcome by hypothermia-some even indicated worse outcome. TBI patients may suffer from hypothermia-induced pulmonary and coagulation side effects, from side effects of vasopressors when re-establishing the hypothermia-induced lowered blood pressure, and from a rebound increase in intracranial pressure (ICP) during and after rewarming. The difference between body temperature and temperature set by the biological thermostat may cause stress-induced worsening of the circulation and oxygenation in injured areas of the brain. These mechanisms may counteract neuroprotective effects of therapeutic hypothermia. We conclude that we still lack scientific support as a first-tier therapy for the use of therapeutic hypothermia in TBI patients for both adults and children, but it may still be an option as a second-tier therapy for refractory intracranial hypertension.

The effect of vitamin C on plasma volume in the early stage of sepsis in the rat.

BACKGROUND: Previous experimental studies have shown that vitamin C has several beneficial effects in sepsis and burns, such as decreased tissue oedema, improved endothelial barrier function and decreased transcapillary leakage of plasma markers. It has still not been investigated, though, if vitamin C has any impact specifically on plasma volume. The present study aims at testing the hypothesis that vitamin C decreases plasma volume loss in sepsis. METHODS: Anaesthetized male adult Sprague-Dawley rats were used in this prospective randomized study. All experiments were carried out at a university hospital laboratory. Sepsis was induced by caecal ligation and incision. After 3 h, vitamin C was given either as a bolus dose (66 mg/kg) followed by a continuous infusion (33 mg/kg/h) (n = 9), or as a single bolus dose (200 mg/kg) (n = 9). A sham group (n = 9) underwent the same surgical procedure, but no vitamin C was given. Plasma volume was measured ((125)I-dilution technique) at baseline, at 3 h after end of initiation of sepsis and at the end of the experiment 3 h later. Arterial blood samples for analyses of electrolytes, blood gases, haematocrit and lactate were taken at the same time points. RESULTS: There were no significant differences in plasma volumes or the physiological parameters analysed between any of the three groups at any time point. There was a significantly larger urine production in the single bolus dose group (200 mg/kg) compared to the sham group. CONCLUSIONS: Vitamin C treatment did not decrease the loss of plasma volume in the septic rat. The diuretic effect of vitamin C was in accordance with previous studies.

Treatment with the sphingosine-1-phosphate analogue FTY 720 reduces loss of plasma volume during experimental sepsis in the rat.

BACKGROUND: Increased vascular leakage leading to hypovolaemia and tissue oedema is common in severe sepsis. Hypovolaemia together with oedema formation may contribute to hypoxia and result in multiorgan failure and death. To improve treatment during sepsis, a potential therapeutic target may be to reduce the vascular leakage. Substances affecting the endothelial barrier are interesting in this respect, as it is suggested that increase in vascular leakage depends on reorganisation of the endothelial cells and breakdown of the endothelial barrier. The agonist of the bioactive lipid sphingosine-1-phosphate, FTY720, has been shown to modulate the integrity of the endothelium and reduce permeability both in vitro and in vivo. The aim of the present study was to determine if FTY720 could reduce the loss of plasma volume during experimental sepsis in rats. METHODS: Sepsis was induced by ligation and incision of the caecum in the rat. Plasma volume was determined before and 4.5 h after induction of sepsis by a dilution technique using (125) I-labelled albumin. RESULTS: FTY720 in a dose of 0.2 mg/kg reduced the loss of plasma during sepsis by approximately 30% compared with vehicle, without any adverse effects on haemodynamic and physiological parameters. The increase in hematocrit and haemoglobin concentration was also found to be higher in the vehicle group. CONCLUSION: FTY720 in a dose without haemodynamic side effects reduces loss of plasma volume during experimental sepsis most likely because of reduction in permeability and may therefore be beneficial in sepsis.

Plasma volume expansion by 0.9% NaCl during sepsis/systemic inflammatory response syndrome, after hemorrhage, and during a normal state.

OBJECTIVE: The objective of this study was to determine the degree of plasma volume expansion by 0.9% NaCl in relation to the infused volume, in sepsis/systemic inflammatory response syndrome (SIRS), after a standardized hemorrhage, and in a normal condition. DESIGN: Prospective, randomized animal study. SETTING: The study was performed at a university hospital laboratory. SUBJECTS: Thirty anesthetized adult male rats were included in the study. INTERVENTIONS: The study was performed in three groups: a sepsis/SIRS group (the S group), in which sepsis/SIRS was induced by cecal ligation and incision; a hemorrhage group (the H group), in which the rats were left without intervention for 4 h and bled 8 mL/kg thereafter; and a group that was left without intervention (the N group). Then, 4 h after baseline, all three groups were given an infusion of 0.9% NaCl (32 mL/kg) for 15 min. Baseline was defined as the time point when the surgical preparation was finished. MEASUREMENTS AND MAIN RESULTS: Plasma volumes were measured using I-albumin dilution technique at baseline, after 4 h, and 20 min after the end of infusion. The plasma volume-expanding effect 20 min after end of infusion was 0.6% ± 2.9% in the S group, 20% ± 6.4% in the H group, and 12% ± 11% in the N group, compared with just before start of infusion. CONCLUSIONS: The present study in rats showed that the plasma volume-expanding effect after an infusion of 0.9% NaCl was smaller in a septic/SIRS state than after hemorrhage and in a normal state. This indicates that the plasma volume-expanding effect of a crystalloid is dependent on pathophysiologic changes in sepsis/SIRS.

Importance of the infusion rate for the plasma expanding effect of 5% albumin, 6% HES 130/0.4, 4% gelatin, and 0.9% NaCl in the septic rat.

OBJECTIVES: To compare the plasma volume (PV) expanding effect of a fast infusion rate with that of a slow infusion rate of a fixed volume of 5% albumin, of the synthetic colloids, 6% hydroxyethyl starch 130/0.4 and 4% gelatin, and of 0.9% NaCl in a rat sepsis model and to compare the plasma-expanding effect among these fluids. DESIGN: Prospective, randomized animal study. SETTING: University hospital laboratory. SUBJECTS: One hundred and twelve adult male rats. INTERVENTIONS: Sepsis was induced by cecal ligation and incision followed by closure of the abdomen. After 3 hrs, an infusion of the PV expander under study was started at a volume of 12mL/kg for the colloids and of 48mL/kg for 0.9% NaCl, either for 15 mins or for 3 hrs. A control group underwent the same experimental procedure but no fluid was given. MEASUREMENTS AND MAIN RESULTS: Three hours after start of the infusion (end of experiment), the plasma-expanding effect was better with a slow than a fast infusion rate for the colloids, especially albumin, but the NaCl groups did not differ significantly from the control group. The PV for the control group was 28.7±3mL/kg. In the slow and the fast infusion groups, it was 38.9±4.3 and 32.6±4.2mL/kg for albumin (p < 0.001), 32.9±4.3 and 29.5±4.4mL/kg for hydroxyethyl starch 130/0.4 (p < 0.05), 31.8±3.9 and 28.2±4.1mL/kg for gelatin (p < 0.05), and 31.8±5.3 and 30.7±6.6mL/kg for NaCl (n.s), respectively. CONCLUSIONS: The study showed that the PV expansion by a colloid was greater when given at a slow than at a fast infusion rate, an effect more pronounced for albumin. This difference was not seen for NaCl. The PV-expanding effect was poor for NaCl and better for albumin than for the other colloids.

Prostacyclin reduces plasma volume loss after skeletal muscle trauma in the rat.

BACKGROUND: Trauma induces transcapillary leakage of fluid and proteins because of increased microvascular permeability. Based on studies showing that prostacyclin (PGI2) has permeability-reducing properties, in the present study, we investigated whether PGI2 reduces plasma volume (PV) loss after a nonhemorrhagic trauma. METHODS: The study was performed on anesthetized Sprague-Dawley rats exposed to a controlled standardized blunt trauma to the abdominal rectus muscle. Thereafter, the animals were randomized to treatment with either PGI2 (2 ng/kg per minute) or 0.9% NaCl. PV was estimated before and 3 hours after the trauma using I-albumin as tracer. In separate experiments, the transcapillary escape rate of I-albumin was calculated and plasma concentrations of cytokines were measured after both treatments. RESULTS: Average PV at baseline was 41.6 mL/kg ± 2.5 mL/kg and 42.3 mL/kg ± 1.7 mL/kg in the PGI2 and NaCl animals, respectively. PV was decreased by 22% ± 8% in the NaCl animals and by 11% ± 9% in the PGI2 animals 3 hours after the trauma (p < 0.05). Trauma induced a decrease in mean arterial blood pressure and an increase in hematocrit in both groups. There were no differences in urine production and mean arterial blood pressure between the PGI2 and NaCl animals. The transcapillary escape rate for albumin was calculated for one hour starting 30 minutes after the trauma and was 15.1% ± 2.4% per hour in the PGI2 animals and 17.4% ± 3.3% per hour in the NaCl animals (p = 0.09). Interleukin 6 concentration 3 hours after the trauma was lower in the PGI2 animals than in the NaCl animals (p < 0.05). CONCLUSION: We conclude that PGI2 attenuates PV loss after blunt muscle trauma. The vascular effects of PGI2 are associated with a modulation of the trauma-induced inflammatory response.

Osmotherapy in brain edema: a questionable therapy.

Despite the fact that it has been used since the 1960s in diseases associated with brain edema and has been investigated in >150 publications on head injury, very little has been published on the outcome of osmotherapy. We can only speculate whether osmotherapy improves outcome, has no effect on outcome, or leads to worse outcome. Here we describe the action and potentially beneficial and adverse effects of the 2 most commonly used osmotic solutions, mannitol and hypertonic saline, and present some critical aspects of their use. There is a well-documented transient intracranial pressure (ICP)-reducing effect of osmotherapy, but an adverse rebound increase in ICP after its withdrawal has been discussed extensively in the literature and is an expected pathophysiological phenomenon. From side effects related to renal and pulmonary failure, electrolyte disturbances, and a rebound increase in ICP, osmotherapy can be negative for outcome, which may explain why we lack scientific support for its use. These drawbacks, and the fact that the most recent Cochrane meta-analyses of osmotherapy in brain edema and stroke could not find any beneficial effects on outcome, make routine use of osmotherapy in brain edema doubtful. Nevertheless, the use of osmotherapy as a temporary measure may be justified to acutely prevent brain stem compression until other measures, such as evacuation of space-occupying lesions or decompressive craniotomy, can be performed. This article is the Con part in a Pro-Con debate in the present journal on the general routine use of osmotherapy in brain edema.

The effects of continuous prostacyclin infusion on regional blood flow and cerebral vasospasm following subarachnoid haemorrhage: study protocol for a randomised controlled trial.

BACKGROUND: One of the main causes of mortality and morbidity following subarachnoid haemorrhage (SAH) is the development of cerebral vasospasm, a frequent complication arising in the weeks after the initial bleeding. Despite extensive research, to date no effective treatment of vasospasm exists. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. In vitro models have shown a relaxing effect of prostacyclin after induced contraction in cerebral arteries, and a recent pilot trial showed a positive effect on cerebral vasospasm in a clinical setting. No randomised, clinical trials have been conducted, investigating the possible pharmacodynamic effects of prostacyclin on the human brain following SAH. METHODS: This trial is a single-centre, randomised, placebo-controlled, parallel group, blinded, clinical, pilot trial. A total of 90 patients with SAH will be randomised to one of three intervention arms: epoprostenol 1 ng/kg/min, epoprostenol 2 ng/kg/min or placebo in addition to standard treatment. Trial medication will start day 5 after SAH and continue to day 10. The primary outcome measure is changes in regional cerebral blood flow from baseline in the arterial territories of the anterior cerebral artery, medial cerebral artery and the posterior cerebral artery, measured by CT perfusion scan. The secondary outcomes will be vasospasm measured by CT angiography, ischaemic parameters measured by brain microdialysis, flow velocities in the medial cerebral artery, clinical parameters and outcome (Glasgow Outcome Scale) at 3 months. TRIAL REGISTRATION: Clinicaltrials.gov NCT01447095.

The G protein-coupled oestrogen receptor 1 agonist G-1 disrupts endothelial cell microtubule structure in a receptor-independent manner.

The G protein-coupled oestrogen receptor GPER1, also known as GPR30, has been implicated in oestrogen signalling, but the physiological importance of GPER1 is not fully understood. The GPER1 agonist G-1 has become an important tool to assess GPER1-mediated cellular effects. Here, we report that this substance, besides acting via GPER1, affects the microtubule network in endothelial cells. Treatment with G-1 (3 µM) for 24 h reduced DNA synthesis by about 60 % in mouse microvascular endothelial bEnd.3 cells. Treatment with 3 µM G-1 prevented outgrowth of primary endothelial cells from mouse aortic explants embedded in Matrigel. Treatment with G-1 (0.3-3 µM) for 24 h disrupted bEnd.3 cell and HUVEC microtubule structure in a concentration-dependent manner as assessed by laser-scanning confocal immunofluorescence microscopy. G-1-induced (3 µM) disruption of microtubule was observed also after acute (3 and 6 h) treatment and in the presence of the protein synthesis inhibitor cycloheximide. Disruption of microtubules by 3 µM G-1 was observed in aortic smooth muscle cells obtained from both GPER1 knockout and wild-type mice, suggesting that G-1 influences microtubules through a mechanism independent of GPER1. G-1 dose dependently (10-50 µM) stimulated microtubule assembly in vitro. On the other hand, microtubules appeared normal in the presence of 10-50 µM G-1 as determined by electron microscopy. We suggest that G-1-promoted endothelial cell anti-proliferation is due in part to alteration of microtubule organization through a mechanism independent of GPER1. This G-1-promoted mechanism may be used to block unwanted endothelial cell proliferation and angiogenesis such as that observed in, e.g. cancer.

The Lund concept for the treatment of patients with severe traumatic brain injury.

Two different main concepts for the treatment of a severe traumatic brain injury have been established during the last 15 years, namely the more conventional concept recommended in well-established guidelines (eg, U.S. Guideline, European Guideline, Addelbrook's Guideline from Cambridge), on the one hand, and the Lund concept from the University Hospital of Lund, Sweden, on the other. Owing to the lack of well-controlled randomized outcome studies comparing these 2 main therapeutic approaches, we cannot conclude that one is better than the other. This paper is the PRO part in a PRO-CON debate in this journal on the Lund concept. Although the Lund concept is based on a physiology-oriented approach dealing with the hemodynamic principles of brain volume and brain perfusion regulation, traditional treatments are primarily based on a meta-analytic approach from clinical studies. High cerebral perfusion pressure has been an essential goal in the conventional treatments (the cerebral perfusion pressure-guided approach), even though it has been modified in a recent up date of U.S. guidelines. The Lund concept has instead concentrated on management of brain edema and intracranial pressure, along with improvement of cerebral perfusion and oxygenation (the intracranial pressure and perfusion-guided approach). Although conventional guidelines are restricted to clinical data from meta-analytic surveys, the physiological approach of Lund therapy finds support in both experimental and clinical studies. It offers a wider base and can also provide recommendations regarding fluid therapy, lung protection, optimal hemoglobin concentration, temperature control, the use of decompressive craniotomy, and ventricular drainage. This paper puts forward arguments in support of Lund therapy.

PRO: the "Lund concept" for treatment of patients with severe traumatic brain injury.

Two different main concepts for the treatment of severe traumatic brain injury have been established during the last 15 years, namely the more conventional concept recommended in well-established guidelines (eg, the US Guideline, European Guideline, Addelbrook's Guideline from Cambridge) on the one hand, and the Lund concept from the University Hospital of Lund, Sweden on the other. Owing to the lack of well-controlled randomized outcome studies comparing these 2 main therapeutic approaches, we cannot conclude that one is better than the other. This study is the PRO part in a PRO-CON debate on the Lund concept in the present journal. Although the Lund concept is based on a physiology-oriented approach dealing with hemodynamic principles of brain volume and brain perfusion regulation, traditional treatments are primarily based on a meta-analytic approach from clinical studies. High cerebral perfusion pressure has been an essential goal in the conventional treatments (the cerebral perfusion pressure-guided approach), even though it has been modified in a recent update of US guidelines. The Lund concept has instead concentrated on management of brain edema and intracranial pressure, simultaneously with improvement of cerebral perfusion and oxygenation (the intracranial pressure and perfusion-guided approach). Although conventional guidelines are restricted to clinical data from meta-analytic surveys, the physiological approach of the Lund therapy finds support in both experimental and clinical studies. It offers a wider base and can also give recommendations regarding fluid therapy, lung protection, optimal hemoglobin concentration, temperature control, the use of decompressive craniotomy, and ventricular drainage. This study puts forward arguments in support of the Lund therapy.

Intracranial pressure following resuscitation with albumin or saline in a cat model of meningitis.

OBJECTIVE: To compare the intracranial pressure after resuscitation to normovolemia by using 20% albumin or normal saline in a cat model of meningitis. DESIGN: Prospective, randomized animal study. SETTING: University hospital laboratory. SUBJECTS: Twenty adult, male cats. INTERVENTIONS: Meningitis was induced by intrathecal injection of Escherichia coli-derived lipopolysaccharide (0.8 × 10 units/kg). Four hours after the lipopolysaccharide injection, the animals were randomized to intravenous treatment with 0.4 mL/kg/hr of 20% albumin or 7.5 mL/kg/hr of 0.9% sodium chloride for 6 hrs (n = 7 per group). A control group receiving lipopolysaccharide but no fluid was also studied (n = 6). MEASUREMENTS AND MAIN RESULTS: Effects on intracranial pressure, mean arterial pressure, plasma volume (I-albumin technique), plasma oncotic pressure, and brain metabolism via cerebral interstitial lactate/pyruvate ratio and glycerol and glucose levels (microdialysis technique) were evaluated. Plasma volume decreased by approximately 20% and intracranial pressure increased from 10 to approximately 20 mm Hg at 4 hrs after the lipopolysaccharide injection. Six hours later, plasma volume had returned to baseline in both fluid groups while there was a further reduction in the control group. Intracranial pressure was higher in the saline group than in the albumin and control groups and was 25.8 ± 2.8 mm Hg, 18.3 ± 0.6 mm Hg, and 20.4 ± 1.7 mm Hg, respectively. Plasma oncotic pressure was higher in the albumin group than in the saline and control groups. Mean arterial pressure and microdialysis data were within normal range and did not differ among the groups. CONCLUSIONS: The results showed that the choice of resuscitation fluid may influence intracranial pressure in meningitis. The lower intracranial pressure in the colloid group may be explained by a higher plasma oncotic pressure and less fluid distribution to the brain interstitium.

Segmental cerebral vasoconstriction: successful treatment of secondary cerebral ischaemia with intravenous prostacyclin.

We describe a 23-year-old male patient who presented with spontaneous intermittent and increasing attacks of severe, left-sided thunderclap headache combined with rapidly progressive muscle weakness and dysphasia, including gradual loss of consciousness. Subsequent CT, MRI and DSA showed progressive brain ischaemia and oedema within the left cerebral hemisphere with strict ipsilateral segmental arterial vasoconstriction. Despite extensive medical care, including steroids, the patient deteriorated rapidly. However, the clinical course changed dramatically within 15 h after the start of an intravenous infusion of prostacyclin at a dose of 0.9 ng/kg/min, with an almost complete recovery of consciousness and speech. In addition the pathophysiological alterations seen on magnetic resonance (imaging and digital) subtraction angiography including diffusion-weighted imaging and apparent diffusion coefficient maps shortly before prostacyclin treatment were clearly reduced when the patient was examined 3-4 days later and he continued to recover thereafter. Although not fully compatible, our case had several clinical characteristics and radiological findings reminiscent of those of the 'segmental reversible vasoconstriction syndrome', sometimes called the Call-Fleming syndrome.

[Actively induced hypothermia following severe traumatic brain injury]. / Aktivt induceret hypotermi efter svaer traumatisk hjerneskade.

A Cochrane metaanalysis and a study performed on children have recently confirmed that therapeutic hypothermia does not improve outcome after severe traumatic brain injury (TBI). TBI is not comparable to a short episode of global ischemia, where therapeutic hypothermia has been shown to improve outcome. The difference may be explained by the fact that hypothermia-induced stress after a traumatic brain injury reduces cerebral perfusion in the penumbra zone, where local circulation is already reduced. Thus, to date there is no indication for therapeutic hypothermia in TBI patients.