Standards of scoring, monitoring, and parameter targeting in German neurocritical care units: a national survey.

BACKGROUND: Optimal management of physiological parameters in neurological/neurosurgical intensive care units (NICUs) is largely unclear as high-quality evidence is lacking. The aim of this survey was to investigate if standards exist in the use of clinical scores, systemic and cerebral monitoring and the targeting of physiology values and in what way this affects clinical management in German NICUs. METHODS: National survey, on-line anonymized questionnaire. German departments stating to run a neurological, neurosurgical or interdisciplinary neurological/neurosurgical intensive care unit were identified by a web-based search of all German hospitals and contacted via email. RESULTS: Responses from 78 German NICUs were obtained. Of 19 proposed clinical/laboratory/radiological scores only 5 were used regularly by >60 %. Bedside neuromonitoring (NM) predominantly consisted of transcranial Doppler sonography (94 %), electroencephalography (92 %) and measurement of intracranial pressure (ICP) (90 %), and was installed if patients had or were threatened by elevated ICP (86 %), had specific diseases like subarachnoid hemorrhage (51 %) or were comatose (35 %). Although mean trigger values for interventions complied with guidelines or wide-spread customs, individual trigger values varied widely, e.g., for hyperglycemia (maximum blood glucose between 120 and 250 mg/dl) or for anemia (minimum hemoglobin values between 5 and 10 g/dl). CONCLUSIONS: Although apparently aiming for standardization in neurocritical care, German NICUs show substantial differences in NM and monitoring-associated interventions. In terms of scoring and monitoring methods, German NICUs seem to be quite conservative. These survey results suggest a need of prospective and randomized interventional trials in neurocritical care to help define standards and target values.

[News and perspectives in neurocritical care]. / Neuigkeiten und Perspektiven der Neurointensivmedizin.

Neurocritical care is an ever-evolving discipline and its implementation in intensive care leads to reduction in mortality and to improvement of functional outcome in patients with devastating injuries to the nervous system. However, the decisive elements of the complete field of neurocritical care remain relatively unclear, as well as the exact ways to optimize them. During recent years new insights have been gained and new exciting studies have been initiated from which results are soon to be expected. This review focuses on the following management aspects: neuromonitoring, airway and ventilation, endovascular therapy, cerebrospinal fluid drainage, decompressive craniectomy, hematoma evacuation, blood pressure, and targeted temperature management. The application of these measures to brain diseases and injuries frequently treated in neurointensive care units will be addressed in the context of current studies.

The role of spreading depolarization in subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a devastating disease associated with death and poor functional outcome. Despite decades of intense research and improvements in clinical management, delayed cerebral ischaemia (DCI) remains the most important cause of morbidity and mortality after SAH. The key role of angiographic cerebral vasospasm, thought to be the main cause of DCI, has been questioned. Emerging evidence suggests that DCI is likely to have a multifactorial etiology. Over the last few years, spreading depolarization (SD) has been identified as a potential pathophysiological mechanism contributing to DCI. The presence of cortical spreading ischaemia, due to an inverse hemodynamic response to SD, offers a possible explanation for DCI and requires more intensive research. Understanding the role of SD as another mechanism inducing DCI and its relationship with other pathological factors could instigate the development of new approaches to the diagnosis and treatment of DCI in order to improve the clinical outcome.

[Multimodal monitoring in neurointensive care medicine: state of the art]. / Multimodales Monitoring in der Neurointensivmedizin : Eine Standortbeschreibung.

The prognosis of neurointensive care patients depends largely on the occurrence of secondary ischemic/hypoxic tissue damage, which is mediated by different pathomechanisms, such as edema formation or increased intracranial pressure. Due to the cerebral damage and need for sedation as well as intubation, clinical assessment of these patients is limited. Furthermore, clinical signs of secondary damage, such as advanced herniation syndromes are often delayed and therefore mostly indicate irreversible brain damage. To adequately predict and detect secondary neuronal damage, various neuromonitoring techniques have been developed in recent years with ongoing technical refinement. These can be used for bedside and ideally continuous monitoring of various functional systems of the brain. Neuromonitoring is used to implement early therapeutic measures before irreversible brain damage has occurred, to monitor therapeutic effects, for evaluation of the prognosis and to improve the neurological outcome of patients. Different monitoring techniques are often combined in multimodal neuromonitoring. This article gives an overview of the most promising neuromonitoring techniques available.

Multiparametric characterisation of the perihemorrhagic zone in a porcine model of lobar ICH.

OBJECTIVES: To describe early perihemorrhagic changes after lobar intracerebral hemorrhage (ICH) using multiparametric neuromonitoring [intracranial pressure (ICP), cerebral blood flow (CBF), tissue oxygenation (PbrO2), microdialysis (MD)]. METHODS: Seven anaesthetized male swine were examined over 12 h. Four cerebral probes were inserted around the ICH (ICP, MD, CBF and PbrO2). A right frontal autologous arterial ICH (1.5 mL) was induced in all animals. RESULTS: Initial ICH creation was hampered by using a soft 22-G cannula. A modified injection technique with a 90° bent steel cannula (20 G) allowed for an 87.5% success rate in ICH formation. After induction of ICH, ICP significantly increased from 2 mmHg to 9 mmHg. No significant PbrO2 or CBF reduction occurred during the monitoring period. Consequently, microdialysis did not indicate overall mean deterioration in the hematoma group over time. The indicator of ischemia (extracellular lactate) did not increase significantly during the monitoring period. Individual monitoring episodes demonstrated hypoxic episodes with consecutive metabolic derangement. These effects were reversible by optimizing CPP and FiO2. CONCLUSION: We established a reproducible cortical ICH model using multiparametric neuromonitoring. Subtle changes in ICP were observed. No evidence for the existence of a perihemorrhagic ischemic area was found, hypothetically because of the small hematoma size. Individual animals underwent critical PbrO2 and CBF decreases with consecutive metabolic derangement. The effect of larger hematoma volumes should be evaluated with this setup in future studies to study volume-dependent deterioration.

Cerebral microdialysis in acutely brain-injured patients with spreading depolarizations.

Multimodal cerebral monitoring was utilized to examine the relationship between pathological changes in microdialysis parameters and the occurrence of spreading depolarizations (SD) in brain-injured patients. SD are a relatively newly discovered phenomenon in man found to be linked to secondary insults and infarct growth and they can be detected via electrocorticography (ECoG). A total of 24 brain-injured patients (mean age: 52±11 years) requiring craniotomy took part in this prospective observational study. Each patient was monitored with a linear strip electrode for ECoG data and a cerebral microdialysis probe. SD were detected in 13 of the 24 patients. Pathological concentrations of glucose and lactate in brain parenchyma were significantly correlated with various time points prior to and/or immediately following the SD. Severe systemic hyperglycemia and systemic hypoglycemia were also found to be correlated with the occurrence of SD. The present study shows a clear relationship between SD and pathological changes in cerebral metabolism; further studies are needed to elucidate these complex interactions with the ultimate goal of developing therapeutic strategies for improving outcome in brain-injured patients.

[Intracranial pressure-volume relationship. Physiology and pathophysiology]. / Intrakranielle Druck-Volumen-Beziehung. Physiologie und Pathophysiologie.

Posttraumatic increase of intracranial pressure (ICP) is a strong prognostic factor for the outcome of patients after traumatic brain injury. After exhausting all compensatory mechanisms ICP increases exponentially, where ICP(norm)=(CSF production*CSF flow resistance)+venous pressure((sinus sagittalis))=10-15 mmHg. The ICP curve is influenced by the compliance (DeltaV/DeltaP) and elasticity (DeltaP/DeltaV) of the brain. Marmarou could demonstrate that the non-linear cranio-spinal pressure-volume relationship describes a logarithmic, mono-exponential, strongly linear relationship between pressure and volume and named this the pressure volume index (PVI=log ICP/DeltaV). The pressure volume index describes the volume necessary to increase ICP by a factor of 10. Additionally to PVI the measurement of volume-pressure response (VPR) was introduced. The continuous intracranial compliance could be determined on the principle of pulsatile volume increases as an equivalent of very small intra-cranial volume increases. However, to ascertain functional status of the injured brain a combination of measurements of different parameters, such as tissue oxygen partial pressure (p(ti)O2), cerebral blood flow (CBF), microdialysis and electrocorticography (ECoG) is recommended.

Serial diffusion and perfusion MRI analysis of the perihemorrhagic zone in a rat ICH model.

OBJECTIVES: Cerebral ischemia has been proposed as a contributing mechanism to secondary neuronal injury after intracranial hemorrhage (ICH). We aimed to examine perihemorrhagic changes with an animal experimental MRI study using a stroke-MRI protocol. In a subset of animals the feasibility and effects of stereotactic hematoma evacuation was investigated. METHODS: An MRI compatible setup for rats was established using a double injection model. ICH was stereotactically placed into the right basal ganglia of 49 Wistar rats. Coronal T2-WI, T2*-WI, DWI and PWI were generated with a 2.35T animal MRI scanner at 3 time points. Clot volumes, normalized ADC and relative MTT values were analysed in 3 hematoma regions (periphery, outer rim, healthy ipsilateral tissue) in all sequences. RESULTS: There were no perihemorrhagic ADC decreases consistent with ischemic cytotoxic edema but a mild vasogenic edema surrounding the ICH could be observed. This improved partially with evacuation. Reduced perfusion was seen in the periphery and outer rim. This disappeared with lysis and evacuation of the clot. CONCLUSION: No evidence for the existence of a perihemorrhagic ischemic area was found. But, reversible perfusion reduction in this model indicates that early evacuation may help reducing secondary neuronal changes.

Guidelines for the Treatment of Head Injury in Adults.

The workshop of scientific medical faculties (Arbeitsgemeinschaft wissenschaftlicher medizinischer Fakultäten [AWMF]) of Germany has asked societies of specific medical disciplines to jointly publish guidelines on the treatment of diseases and injuries. On behalf of the Deutsche Gesellschaft für Neurochirurgie, its commission on guidelines initiated an interdisciplinary approach to publish guidelines on the treatment of head injury in adults. These guidelines were published in German by the AWMF in late 2015. Because these guidelines have received widespread attention in Germany and became fundamental for research in head injuries, we have translated the German version into English to make it accessible to the international scientific community.

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.

Relation of cerebral energy metabolism and extracellular nitrite and nitrate concentrations in patients after aneurysmal subarachnoid hemorrhage.

In a prospective clinical investigation on neurochemical intensive care monitoring, the authors' aim was to elucidate the temporal profile of nitric oxide metabolite concentrations-that is, nitrite and nitrate (NO(x))--and compounds related to energy-metabolism in the cerebral interstitium of patients after aneurysmal subarachnoid hemorrhage (SAH). During aneurysm surgery, microdialysis probes were implanted in cerebral white matter of the vascular territory most likely affected by vasospasm. Temporal profiles of NO(x) were analyzed in a subset of 10 patients (7 female, 3 male, mean age = 47 +/- 14 years). Microdialysis was performed for 152 +/- 63 hours. Extracellular metabolites (glucose, lactate, pyruvate, glutamate) were recovered from the extracellular fluid of the cerebral parenchyma. NO(x) was measured using a fluorometric assay. After early surgery, SAH patients revealed characteristic decreases of NO(x) from initial values of 46.2 +/- 34.8 micromol/L to 23.5 +/- 9.0 micromol/L on day 7 after SAH (P < 0.05). Decreases in NO(x) were seen regardless of development of delayed ischemia (DIND). Overall NO(x) correlated intraindividually with glucose, lactate, and glutamate (r = 0.58, P < 0.05; r = 0.32, P < 0.05; r = 0.28, P < 0.05; respectively). After SAH, cerebral extracellular concentrations of NO metabolites decrease over time and are associated with concomitant alterations in energy-or damage-related compounds. This could be related to reduced NO availability, potentially leading to an imbalance of vasodilatory and vasoconstrictive factors. On the basis of the current findings, however, subsequent development of DIND cannot be explained by a lack of vasodilatory NO alone.

Bisensory stimulation increases gamma-responses over multiple cortical regions.

In the framework of the discussion about gamma (approx. 40 Hz) oscillations as information carriers in the brain, we investigated the relationship between gamma responses in the EEG and intersensory association. Auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) were compared with bisensory evoked potentials (BEPs; simultaneous auditory and visual stimulation) in 15 subjects. Gamma responses in AEPs, VEPs and BEPs were assessed by means of wavelet decomposition. Overall maximum gamma-components post-stimulus were highest in BEPs (P < 0.01). Bisensory evoked gamma-responses also showed significant central, parietal and occipital amplitude-increases (P < 0.001, P < 0.01, P < 0.05, respectively; prestimulus interval as baseline). These were of greater magnitude when compared with the unisensory responses. As a correlate of the marked gamma responses to bimodal stimulation we suggest a process of 'intersensory association', i.e. one of the steps between sensory transmission and perception. Our data may be interpreted as a further example of function-related gamma responses in the EEG.

Oscillatory frontal theta responses are increased upon bisensory stimulation.

OBJECTIVES: To investigate the functional correlation of oscillatory EEG components with the interaction of sensory modalities following simultaneous audio-visual stimulation. METHODS: In an experimental study (15 subjects) we compared auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) to bimodal evoked potentials (BEPs; simultaneous auditory and visual stimulation). BEPs were assumed to be brain responses to complex stimuli as a marker for intermodal associative functioning. RESULTS: Frequency domain analysis of these EPs showed marked theta-range components in response to bimodal stimulation. These theta components could not be explained by linear addition of the unimodal responses in the time domain. Considering topography the increased theta-response showed a remarkable frontality in proximity to multimodal association cortices. Referring to methodology we try to demonstrate that, even if various behavioral correlates of brain oscillations exist, common patterns can be extracted by means of a systems-theoretical approach. CONCLUSIONS: Serving as an example of functionally relevant brain oscillations, theta responses could be interpreted as an indicator of associative information processing.

Wavelet Transform in the analysis of the frequency composition of evoked potentials.

This technical paper deals with the application of the Wavelet Transform to the study of evoked potentials. In particular, Wavelet Transform gives an optimal time-dependent frequency decomposition of the evoked responses, something difficult to be achieved with previous methods such as the Fourier Transform. We describe in detail the protocol for implementing the decomposition based on the Wavelet Transform and apply it to two different types of evoked potentials. In the first case we study alpha responses in pattern visual evoked potentials and in the second case, we study gamma responses to bimodal (auditory and visual) stimulation. Although in this study we focus on methodological issues, we briefly discuss physiological implications of the present time-frequency analysis. Furthermore, we show examples of the better performance of the wavelet decomposition in comparison with Fourier-based methods.

Role of bedside microdialysis in the diagnosis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

OBJECT: Ischemia due to vasospasm is a feared complication in patients following aneurysmal subarachnoid hemorrhage (SAH). Cerebral online microdialysis monitoring may detect the metabolic changes in the extracellular fluid associated with ischemia. The aims of the present study were to correlate clinical course, microdialysis-recorded data, transcranial Doppler (TCD) ultrasonography findings, and angiographic findings in patients with SAH. METHODS: In 60 patients a microdialysis catheter was inserted into the brain parenchyma that is most likely to be affected by vasospasm directly after aneurysm clipping. Hourly analyses of glucose, pyruvate, lactate, and glutamate levels were performed using a bedside device. Blood-flow velocities were obtained using serial TCD measurements. Cerebral angiography was routinely performed on Day 7 after aneurysm clipping or earlier in cases of clinical deterioration (30 patients). In all patients the results of microdialysis monitoring, TCD ultrasonography, and angiography were correlated. The mean duration of monitoring was 7.3+/-2.5 days. In patients with acute ischemic neurological deficits (18 patients) immediate microdialysis-recorded alterations were observed if the probe was placed close to the malperfused region. In 13 of 15 patients with symptomatic vasospasm (delayed ischemic neurological deficit [DIND]), the microdialysis-recorded values revealed secondary deterioration. In terms of confirming DIND, microdialysis had the highest specificity (0.89, 95% confidence interval [CI] 0.78-1) compared with TCD ultrasonography (0.63, 95% CI 0.46-0.8) and angiography (0.53, 95% CI 0.35-0.7). For microdialysis, the positive likelihood ratio was 7.8, whereas this was significantly lower for TCD ultrasonography (1.7) and angiography (2.1). CONCLUSIONS: Although angiography also demonstrates vessel narrowing in asymptomatic patients, online microdialysis reveals characteristic metabolic changes that occur during vasospasm. Thus, online microdialysis may be used to confirm the diagnosis of vasospasm.

Effects of tacrolimus on hemispheric water content and cerebrospinal fluid levels of glutamate, hypoxanthine, interleukin-6, and tumor necrosis factor-alpha following controlled cortical impact injury in rats.

OBJECT: Disturbance of calcium homeostasis contributes to evolving tissue damage and energetic impairment following traumatic brain injury (TBI). Calcium-mediated activation of calcineurin results in production of tissue-damaging nitric oxide and free oxygen radicals. Inhibition of calcineurin induced by the immunosuppressant tacrolimus (FK506) has been shown to reduce structural and functional damage after ischemia. The aims of the present study were to investigate time- and dose-dependent short-term antiedematous effects of tacrolimus following TBI. METHODS: A left temporoparietal contusion (controlled cortical impact injury [CCII]) was induced in 51 male Sprague-Dawley rats. Tacrolimus (1 or 3 mg/kg body weight) was administered by a single intraperitoneal injection at 5 minutes, 30 minutes, or 4 hours after CCII occurred. Control rats received physiological saline. Water contents of traumatized and nontraumatized hemispheres, as well as cerebrospinal fluid (CSF) levels of mediators reflecting tissue damage (the proinflammatory cytokines interleukin [IL]-6 and tumor necrosis factor [TNF]-alpha, the excitotoxin glutamate, and the adenosine triphosphate-degradation product hypoxanthine), were determined 24 hours after trauma. Although CSF levels of IL-6 and TNFalpha were completely suppressed by tacrolimus at all time points and at both concentrations, CSF levels of glutamate and hypoxanthine, as well as edema formation, were only marginally influenced. Significant reduction of cerebral water content was confined to nontraumatized hemispheres. In addition, the higher dose of tacrolimus failed to exert significant antiedematous effects on traumatized hemispheres. CONCLUSIONS: Under the present study design, the potency of tacrolimus in reducing edema formation following CCII seems limited. However, its immunosuppressive effects could be of value in influencing the posttraumatic inflammatory response known to aggravate tissue damage.

The selectively distributed theta system: functions.

The present paper provides three interwoven or interrelated approaches: (1) the dependence of frontal theta response from the spontaneous activity will be pointed out. This helps in understanding that 'frontal theta' is a major oscillation of the human frontal cortex and has a response-controlling function; (2) it will be shown that complex stimulations such as bimodal stimulation enhances the theta response; and by bringing together the results outlined in a number of previous reviews the so-called 'selectively distributed theta system of the brain' is described.

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.

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.

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.