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Henrik Engquist, Anders Lewén, Lars Hillered, Elisabeth Ronne-Engström, Pelle Nilsson, Per Enblad and Elham Rostami


Despite the multifactorial pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH), augmentation of cerebral blood flow (CBF) is still considered essential in the clinical management of DCI. The aim of this prospective observational study was to investigate cerebral metabolic changes in relation to CBF during therapeutic hypervolemia, hemodilution, and hypertension (HHH) therapy in poor-grade SAH patients with DCI.


CBF was assessed by bedside xenon-enhanced CT at days 0–3, 4–7, and 8–12, and the cerebral metabolic state by cerebral microdialysis (CMD), analyzing glucose, lactate, pyruvate, and glutamate hourly. At clinical suspicion of DCI, HHH therapy was instituted for 5 days. CBF measurements and CMD data at baseline and during HHH therapy were required for study inclusion. Non-DCI patients with measurements in corresponding time windows were included as a reference group.


In DCI patients receiving HHH therapy (n = 12), global cortical CBF increased from 30.4 ml/100 g/min (IQR 25.1–33.8 ml/100 g/min) to 38.4 ml/100 g/min (IQR 34.2–46.1 ml/100 g/min; p = 0.006). The energy metabolic CMD parameters stayed statistically unchanged with a lactate/pyruvate (L/P) ratio of 26.9 (IQR 22.9–48.5) at baseline and 31.6 (IQR 22.4–35.7) during HHH. Categorized by energy metabolic patterns during HHH, no patient had severe ischemia, 8 showed derangement corresponding to mitochondrial dysfunction, and 4 were normal. The reference group of non-DCI patients (n = 11) had higher CBF and lower L/P ratios at baseline with no change over time, and the metabolic pattern was normal in all these patients.


Global and regional CBF improved and the cerebral energy metabolic CMD parameters stayed statistically unchanged during HHH therapy in DCI patients. None of the patients developed metabolic signs of severe ischemia, but a disturbed energy metabolic pattern was a common occurrence, possibly explained by mitochondrial dysfunction despite improved microcirculation.

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Tim Howells, Kristin Elf, Patricia A. Jones, Elisabeth Ronne-Engström, Ian Piper, Pelle Nilsson, Peter Andrews and Per Enblad

Object. The aim of this study was to compare the effects of two different treatment protocols on physiological characteristics and outcome in patients with brain trauma. One protocol was primarily oriented toward reducing intracranial pressure (ICP), and the other primarily on maintaining cerebral perfusion pressure (CPP).

Methods. A series of 67 patients in Uppsala were treated according to a protocol aimed at keeping ICP less than 20 mm Hg and, as a secondary target, CPP at approximately 60 mm Hg. Another series of 64 patients in Edinburgh were treated according to a protocol aimed primarily at maintaining CPP greater than 70 mm Hg and, secondarily, ICP less than 25 mm Hg for the first 24 hours and 30 mm Hg subsequently.

The ICP and CPP insults were assessed as the percentage of monitoring time that ICP was greater than or equal to 20 mm Hg and CPP less than 60 mm Hg, respectively. Pressure reactivity in each patient was assessed based on the slope of the regression line relating mean arterial blood pressure (MABP) to ICP. Outcome was analyzed at 6 months according to the Glasgow Outcome Scale (GOS).

The prognostic value of secondary insults and pressure reactivity was determined using linear methods and a neural network. In patients treated according to the CPP-oriented protocol, even short durations of CPP insults were strong predictors of death. In patients treated according to the ICP-oriented protocol, even long durations of CPP insult—mostly in the range of 50 to 60 mm Hg—were significant predictors of favorable outcome (GOS Score 4 or 5). Among those who had undergone ICP-oriented treatment, pressure-passive patients (MABP/ICP slope ≥ 0.13) had a better outcome. Among those who had undergone CPP-oriented treatment, the more pressure-active (MABP/ICP slope < 0.13) patients had a better outcome.

Conclusions. Based on data from this study, the authors concluded that ICP-oriented therapy should be used in patients whose slope of the MABP/ICP regression line is at least 0.13, that is, in pressure-passive patients. If the slope is less than 0.13, then hypertensive CPP therapy is likely to produce a better outcome.

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Elisabeth Ronne-Engström, Kristina Giuliana Cesarini, Per Enblad, Göran Hesselager, Niklas Marklund, Pelle Nilsson, Konstantin Salci, Lennart Persson and Lars Hillered

Object. When evaluating the results of intracerebral microdialysis, the in vivo performance of the microdialysis probe must be considered, because this determines the fraction of the interstitial concentration obtained in the microdialysis samples. The in vivo performance is dependent on several factors, for example, the interstitial compartment's diffusion characteristics, which may vary during the course of the acute brain injury process. In the present study the authors investigated the method of controlling the in vivo performance by using urea, which is evenly distributed in all body fluid compartments, as an endogenous reference compound and by comparing the urea levels in three compartments: the brain (CNS), abdominal subcutaneous tissue (SC), and blood serum (BS).

Methods. Sixty-nine patients with traumatic brain injury or cerebrovascular disease were included in the study. In 63 of these patients a CNS probe was used, an SC probe was used in 40, and both were used in 34. Urea was measured by enzymatic methods, at bedside for the microdialysis samples and in routine clinical laboratory studies for the BS samples, with the probe calibrated to give identical results. The correlation coefficient for CNS/SC urea was 0.88 (2414 samples), for CNS/BS urea it was 0.89 (180 samples), and for SC/BS urea it was 0.98 (112 samples).

Conclusions. Urea levels in the CNS, SC, and BS were highly correlated, which supports the assumption that urea is evenly distributed. The CNS/SC urea ratio can therefore be used for monitoring the CNS probe's in vivo performance. Fluctuations in other substances measured with microdialysis are probably caused by biological changes in the brain, as long as the CNS/SC urea ratio remains constant.

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Elham Rostami, Henrik Engquist, Timothy Howells, Ulf Johnson, Elisabeth Ronne-Engström, Pelle Nilsson, Lars Hillered, Anders Lewén and Per Enblad


Delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is one of the major contributors to poor outcome. It is crucial to be able to detect early signs of DCI to prevent its occurrence. The objective of this study was to determine if low cerebral blood flow (CBF) measurements and pathological microdialysis parameters measured at the bedside can be observed early in patients with SAH who later developed DCI.


The authors included 30 patients with severe SAH. The CBF measurements were performed at Day 0–3 after disease onset, using bedside xenon-CT. Interstitial glucose, lactate, pyruvate, glycerol, and glutamate were measured using microdialysis.


Nine of 30 patients developed DCI. Patients with DCI showed significantly lower global and regional CBF, and lactate was significantly increased in these patients. A high lactate/pyruvate ratio was also detected in patients with DCI.


Early low CBF measurements and a high lactate and lactate/pyruvate ratio may be early warning signs of the risk of developing DCI. The clinical value of these findings needs to be confirmed in larger studies.