Neurointensive Care Patients Research Articles

Review of central-line-related sepsis in neurointensive care patients

Central venous catheterisation is a core component of intensive care management. Despite advances in medicine, central venous catheters are associated with infection rates ranging between 2.5 and 70% [1,2]. There is, however, little isolated information regarding rates of central line sepsis in neurointensive patients. Microbiology results from the 3 months preceding this study identified six line-related infections. Following implementation of a new evidence-based medicine technique for central lines, this study set out to review central line sepsis in patients at Walton Neurological ITU.

A review of central venous catheter-related infections in neurointensive care patients in a tertiary referral centre

Intravenous catheter-related bloodstream infections (ICR-BSI) are a major contributing factor to in-hospital mortality and morbidity, extending the inpatient stay by 10 days and expenditure per patient by £2,000 to £30,000 [1]. A prospective survey was conducted in our unit on all patients with central venous catheters to ascertain the incidence of ICR-BSI, identify the organisms and determine the occurrence of infection from the various sites - femoral, internal jugular and subclavian lines.

Conivaptan for Hyponatremia in the Neurocritical Care Unit

Conivaptan is the first arginine vasopressin antagonist to be FDA-approved for the treatment of euvolemic hyponatremia, a common complication in neurointensive care patients. Due to risks for cerebral edema and seizures, sodium levels are generally aggressively maintained within normal levels (135-145 meq/l) in this patient population. To assess the safety and efficacy of conivaptan for the treatment of euvolemic hyponatremia in the neurocritical care unit. Data were obtained retrospectively on 22 patients treated with conivaptan for euvolemic hyponatremia. End points evaluated included time to [Na] increase of >or=6 meq/l; incidences of rapid overcorrection of [Na] (defined as an increase of >12 meq/l in a 24-h period while on conivaptan), infusion site reactions, or other adverse events; and whether sodium levels decreased after discontinuation of conivaptan. A [Na] increase of >or=6 meq/l was reached in 19/22 (86%) patients, with an average time to goal of 13.1 h. No patients experienced a rapid overcorrection of [Na]. Five patients had an infusion site reaction necessitating an IV change. One patient experienced hypotension and another complained of thirst during infusion. Conivaptan was initiated in 11/22 patients (50%) who were hyponatremic despite already being on conventional therapies. Conivaptan was safe and effective in this small series of neurointensive care patients, including many patients who were hyponatremic despite traditional treatments to maintain normal sodium levels. Further studies are needed to clarify the role of conivaptan as an adjunctive and/or alternative therapy for hyponatremia in this patient population.

Cerebral Glutamine and Glutamate Levels in Relation to Compromised Energy Metabolism: A Microdialysis Study in Subarachnoid Hemorrhage Patients

Astrocytic glutamate (Glt) uptake keeps brain interstitial Glt levels low. Within the astrocytes Glt is converted to glutamine (Gln), which is released and reconverted to Glt in neurons. The Glt-Gln cycle is energy demanding and impaired energy metabolism has been suggested to cause low interstitial Gln/Glt ratios. Using microdialysis (MD) measurements from visually noninjured cortex in 33 neurointensive care patients with subarachnoid hemorrhage, we have determined how interstitial Glt and Gln, as a reflection of the Glt-Gln cycle turnover, relate to perturbed energy metabolism. A total of 3703 hourly samples were analyzed. The lactate/pyruvate (L/P) ratios correlated to the Gln/Glt ratios (r=-0.66), but this correlation was not stronger than the correlation between L/P and Glt (r=0.68) or the correlation between lactate and Glt (r=0.65). A novel observation was a linear relationship between interstitial pyruvate and Gln (r=0.52). There were 13 periods (404 h) of 'energy crisis', defined by L/P ratios above 40. All were associated with high interstitial Glt levels. Periods with L/P ratios above 40 and low pyruvate levels were associated with decreased interstitial Gln levels, suggesting ischemia and failing astrocytic Gln synthesis. Periods with L/P ratios above 40 and normal or high pyruvate levels were associated with increased interstitial Gln levels, which may represent an astrocytic hyperglycolytic response to high interstitial Glt levels. The results imply that moderately elevated L/P ratios cannot always be interpreted as failing energy metabolism and that interstitial pyruvate levels may discriminate whether or not there is sufficient astrocytic capacity for Glt-Gln cycling in the brain.

Pharmacokinetics of Intravenous Linezolid in Cerebrospinal Fluid and Plasma in Neurointensive Care Patients with Staphylococcal Ventriculitis Associated with External Ventricular Drains

The pharmacokinetic profile of linezolid in cerebrospinal fluid (CSF) in five neurointensive care patients with staphylococcal ventriculitis was studied. The mean area under concentration-time curve (+/- standard deviation) was 63 +/- 18.9 mg x h/liter, with a CSF-to-plasma ratio of 0.8 +/- 0.3. Times above MIC in CSF were 99.8% and 57.2% for pathogens with MICs of 2 mg/liter and 4 mg/liter, respectively.

Analysis of near-infrared spectroscopy and indocyanine green dye dilution with Monte Carlo simulation of light propagation in the adult brain

Near-infrared spectroscopy (NIRS) combined with indocyanine green (ICG) dilution is applied externally on the head to determine the cerebral hemodynamics of neurointensive care patients. We applied Monte Carlo simulation for the analysis of a number of problems associated with this method. First, the contamination of the optical density (OD) signal due to the extracerebral tissue was assessed. Second, the measured OD signal depends essentially on the relative blood content (with respect to its absorption) in the various transilluminated tissues. To take this into account, we weighted the calculated densities of the photon distribution under baseline conditions within the different tissues with the changes and aberration of the relative blood volumes that are typically observed under healthy and pathologic conditions. Third, in case of NIRS ICG dye dilution, an ICG bolus replaces part of the blood such that a transient change of absorption in the brain tissues occurs that can be recorded in the OD signal. Our results indicate that for an exchange fraction of Delta=30% of the relative blood volume within the intracerebral tissue, the OD signal is determined from 64 to 74% by the gray matter and between 8 to 16% by the white matter maximally for a distance of d=4.5 cm.

‘ICM+’: software for on-line analysis of data from bedside monitors in neurosurgical and neurointensive care patients

Smielewski, P.1,2; Czosnyka, M.1; Piechnik, S.1; Steiner, L.1; Momhjan, S.1; Pickard, J. D.1,2 Author Information

Volume Measurement of Cerebral Blood Flow: Assessment of Cerebral Circulatory Arrest

Cerebral blood flow (CBF) volume can be measured at bedside by color duplex flowmetry of the extracranial cerebral arteries. In neurointensive care patients, we prospectively tested the hypothesis that a CBF volume <100 ml/min indicates imminent cerebral circulatory arrest. CBF volume was determined as sum of flow volumes in the internal carotid and vertebral arteries of both sides. In 192 neurointensive care patients, 829 measurements were taken. When CBF volume fell short of 100 ml/min, common carotid and external carotid artery flow volumes were also measured, and transcranial color-coded duplex sonography (TCCD) of basal cerebral arteries was performed. Results were compared with actual clinical conditions, outcome, and previously published reference data. All 41 patients with CBF volume <100 ml/min (range, 0-89 ml/min) were officially declared brain dead 2-126 hours after the measurement (median, 23 hours). TCCD revealed signs of cerebral circulatory arrest in all patients with a patent acoustic bone window. External carotid artery flow volumes were normal. The lowest CBF volume rate recorded in a surviving patient was 208 ml/min. Early confirmation of cerebral circulatory arrest is of decisive importance if the patient is a potential organ donor. CBF volume measurement allows confirming the arrest of cerebral circulation even in patients without a patent acoustic bone window for TCCD. Because the critical lower threshold for survival appears to lie at 200 ml/min, bedside monitoring of CBF volume in neurointensive care patients may indicate a therapeutic window before irreversible circulatory arrest occurs.

Cerebral interstitial levels of glutamate and glutamine after intravenous administration of nutritional amino acids in neurointensive care patients

After severe trauma or disease glutamine (GLN) is mobilised from all muscles, including the heart and smooth muscles. The result is weakness and fatigue which affects recovery. The breakdown of muscle tissue can be counteracted by external GLN supply. There are concerns, however, that increasing the blood glutamine (Blood-GLN) concentration in patients with acute brain diseases is harmful by elevating the CNS interstitial (IS) concentration of glutamate (CNS-GLT), and that this may result in a secondary excitotoxic injury. We therefore studied the IS CNS-GLN and CNS-GLT when a commercially available nutritional amino acid solution was given intravenously. Ten NICU patients were included. The IS concentrations of amino acids in the brain were measured using intracerebral microdialysis. Blood concentrations of amino acids were measured before and after the amino acid infusion. The change in Blood-GLN was 2.14 (median; range 1.34–3.22) times the basal levels and Blood-GLT increased 1.37 (median; range 0.93–3.45) times basal levels. Both changes were statistically significant. The changes in CNS-GLN was 1.21 (median; range 0.72–1.92) and for CNS-GLT 0.96 (median; range 0.45–1.53) times the basal levels. This was statistically significant for CNS-GLN but not for CNS-GLT. A high initial CNS-GLT (55.3 μmol/l) in one patient increased even further to 84.4 μmol/l after infusion of amino acid solution. We submit that nutritional amino acid solutions can be administrated to some patients with acute brain disease without increasing the CNS-GLT values. However, since BBB function was not quantified in our study, further evaluation of this issue is warranted.

Non-invasive measurement of systolic blood pressure on the arm utilising photoplethysmography: development of the methodology

Photoplethysmography (PPG) can be used to measure systolic blood pressure at the brachial artery. With a specially designed probe, positioned in the most distal position beneath a pressure cuff on the upper arm, this is possible. The distance between the light source (880 nm) and the photodetector was 20 mm. A test was performed on neuro-intensive care patients by determining blood pressure from the PPG curves, and, when it was compared with systolic blood pressure obtained from inserted indwelling arterial catheters, a correlation factor of r = 0.95 was achieved. The difference between blood pressure obtained using PPG and invasive blood pressure measurement was 3.9 +/- 9.1 mmHg (mean +/- SD), n = 19. The depth to the brachial artery was 13.9 +/- 4.1 mm (mean +/- SD), n = 18. A digital PPG system utilising pulsating light was also developed.

Bedside monitoring of CBF with xenon-CT and a mobile scanner: a novel method in neurointensive care

Combining previously independently established techniques our objective was to develop and evaluate a method for bedside qualitative assessment of cerebral blood flow in neurointensive care (NICU) patients. The CT-protocol was optimized using phantoms and comparing a mobile CT-scanner (Tomoscan-M, Philips) with two stationary CT scanners. Thirty-two per cent xenon was delivered with standard equipment (Enhancer 3000). Mean cortical flow in volunteers was 48 ml/min/100 g, with the mean vascular territorial flow varying between 45 and 66 ml/min/100 g. The potential clinical usefulness was illustrated in three patients with vasospasm following subarachnoid haemorrhage. Our conclusion is that quantitative bedside measurements of CBF can be repeatedly performed in an easy and safe way in a standard NICU-setting, using xenon-inhalation and a mobile CT-scanner. The method is useful for the decision-making, and is a good example of how the quality of multi-modality monitoring in the NICU can be developed and further diversified.

A reply

We note with interest the comments of Dr Wendy Fallis. She challenges our view that the mouth is not ideal for temperature measurement in patients with severe head injury. We presume Dr Fallis includes her own ‘state-of–the-science review [1] to support mouth temperature monitoring in orally intubated patients. We agree that the mouth is a valid monitoring site, long used in healthy and sick adults and children. Perhaps Dr Fallis has missed the point we were making in our short correspondence that in patients with severe head injury, other issues frequently of a practical nature influence the choice of a) the site and b) the method for temperature measurement. In this respect the unique issues relating to the management of head-injured patients have been overlooked by Dr Fallis. Our reasons for suggesting that mouth temperature is not ideal are two-fold. First, maintaining accurate placement of thermistors within the sublingual pocket when neurosurgical patients start to wake up is difficult. Patients become agitated and disorientated and chew on probes in situ in the mouth. Accurate temperature monitoring remains important, but it is difficult to ensure that an oral thermistor remains optimally placed, particularly when regular mouth care may disturb the position. In addition, mucosal ulceration is common in orally intubated patients. Additional probes in the mouth exacerbate this problem. The second reason is that neurointensive care patients are often haemodynamically unstable. Indeed, Dr Fallis herself raises a note of caution for the use of the sublingual pocket in such patients [1]. Oral gastric tubes are also, of necessity, placed in the mouth, often delivering iced cold fluids to the stomach (as an aid to intragastric cooling). Little is known of the impact of ice cold feeds on mouth temperature. From our own detailed monitoring of brain and body temperature in patients with severe brain injury, it is our considered opinion that when accurate temperature monitoring is essential, as it is in brain injured patients, other sites for continuous core temperature measurement, e.g. rectum or bladder, are more appropriate than the mouth.

Sedation interruption in neurointensive care

The reasons for sedation in neurointensive care can be divided into two main groups: (i) general indications, as for other intensive care patients, such as to allow the necessary treatments (therapeutic facilitation), controlling the states of agitations em leader; (ii) specific indications due to the neuro-physiologic effect of the sedatives: facilitation of the control of the intracranial pressure and lowering of the cortical excitability during the epileptic fits and thereby helping the recovery of the cerebral tissue and diminishing the secondary brain insults. It is important to remember that sedation is usually combined with the administration of opioids, which can potentiate the effect of the sedative drugs. The interruption of the sedation can be long- or short-termed. The definitive interruption is possible once the clinical and cerebral state of the patient does not justify any sedation, whereas the brief interruption allows a neurological reassessment. The amount of literature on sedation in intensive care is opposed to the few studies on neurointensive care: in January 2003, the American Society of Intensive Care has published recommendations for this topic without mentioning the interruption of sedation in neurointensive care patients. The aim of this article is to review the literature about the effects of the interruption of the sedation in neurointensive care patients.

Concentrations of fosfomycin in the cerebrospinal fluid of neurointensive care patients with ventriculostomy-associated ventriculitis.

The present study was performed to test the ability of fosfomycin to penetrate into the CSF of neurointensive care patients with ventriculostomy-associated ventriculitis. Six patients requiring neurointensive care monitoring, including extraventricular drainage due to secondary obstructive hydrocephalus, were enrolled into the study. All patients received 8 g of fosfomycin intravenously three times a day over a period of at least 5 days. Concentrations of fosfomycin in the CSF and plasma were measured after single-dose administration and at steady state. Mean values of the fosfomycin area under the time-concentration curves for the dosing interval of 8 h (AUC(8)) were 929 +/- 280 and 225 +/- 131 mg.h/L for plasma and CSF after single-dose administration, respectively (P < 0.03). The ratios of the AUC(8) for CSF to the AUC(8) for plasma were 0.23 +/- 0.07 after a single dose and 0.27 +/- 0.08 following multiple doses (P > 0.05, not significant). Additional in vitro experiments have shown that fosfomycin exerts non-concentration-dependent microbial growth inhibition. At steady state, the time above MIC (t > MIC) values were 98%, 92% and 61% for pathogens with MIC values of 8, 16 and 32 mg/L, respectively. The present pharmacokinetic study indicates that 8 g of fosfomycin three times per day should provide sufficient antimicrobial concentrations in the CSF for the overall treatment period. Thus, the co-administration of fosfomycin could be useful for the treatment of ventriculitis caused by susceptible pathogens.

Sedation in neurointensive care: advances in understanding and practice.

To evaluate the rationale and the pharmacologic options for sedating neurointensive care patients. Sedation is a fundamental element in the neurointensive care unit. Even if the sedative strategy in the neurointensive care unit shares the same general aims with intensive care, the characteristics of the patients in the neurointensive care unit pose other unique challenges and some specific indications. The primary aim of neurointensive care is to maintain adequate cerebral perfusion pressure, to control intracranial pressure, and to maintain an adequate mean arterial pressure. Reducing the brain's metabolic demand is an important treatment strategy, and analgesic and sedative agents are used to prevent undesirable increases in intracranial pressure. There are many different pharmacologic agents available, each with distinct advantages and disadvantages. The pharmacokinetic and pharmacologic effects of the available sedatives used in neurointensive care patients are reviewed.

Can a critical lower threshold of cerebral perfusion be determined? A pilot observational study.

Better prognostic indicators are needed for predicting the chances of survival in neurointensive care patients. Brain perfusion, usually assessed using nuclear medicine techniques, is considered a prognostic indicator. We showed that global cerebral blood flow (CBF) volume can be measured by sonography of the extracranial arteries.1 These measurements are noninvasive and can be repeatedly performed at the bedside. Reference data in children2 and in adults3,4⇓ correspond closely to those obtained with other techniques. Interobserver test-retest difference of global CBF volume measurement has been shown to be 1.7 ± 9.2%, which was comparable to a test-retest difference of 2.3 ± 8.7% found with H215O-PET measurement of CBF.5,6⇓ In this pilot observational study we determined CBF volume in neurointensive care patients in order to find out whether a critical lower threshold of cerebral perfusion can be defined above which patients eventually recovered and could be discharged and below which patients eventually died. In 128 patients (59 men, 69 women; mean age ± SD, 49 ± 18 years) admitted to the anesthesiologic and neurosurgical intensive care units of the University Hospital …

Room C, 10/17/2000 9: 00 AM - 11: 00 AM (PS) Measured, Calculated and Effective Plasma Osmolality in Neurointensive Care Patients

Room C, 10/17/2000 9: 00 AM - 11: 00 AM (PS) Measured, Calculated and Effective Plasma Osmolality in Neurointensive Care Patients

Magnetic evoked potentials in neurocritical care patients with acute brainstem lesions

Motor evoked potentials (MEPs) are widely used in various neurological diseases, but have not been systematically employed in neurocritical care patients. We evaluated the clinical and predictive value of MEPs by magnetic transcranial stimulation in intensive care patients with acute brainstem lesions of predominantly vascular origin. In a prospective trial, a total of 30 patients with acute brainstem lesions were studied. Diagnoses were brainstem infarction (n=15), brainstem hemorrhage (n=3), encephalitis (n=1), basilar artery aneurysm (n=1), and space-occupying cerebellar infarct (n=5), cerebellar hemorrhage (n=3), and brainstem contusion (n=2). We performed MEP tests by transcranial stimulation to the abductor pollicis brevis bilaterally, bilateral somatosensory (SEPs) and auditory evoked (BAEPs) potentials. We determined motor function at the time of electrophysiological testing and after 3 months, the presence of radiologically confirmed lesions, and clinical outcome after 3 months. At the time of MEP recordings, ten patients were comatose, twelve stuporous, seven somnolent and one awake. MEPs were present bilaterally in seventeen, absent unilaterally in eight and bilateral absent in five patients. Absent MEP highly correlated with the presence of persisting motor deficit 3 months later (P<0.0001). Absent MEPs predicted motor deficit after 3 months with a high specificity and more precisely than the clinical examination at the time of MEP testing. MEP findings correlated with the presence of radiologically confirmed lesions within the brainstem (P<0.0001). Combined with SEP and BAEP data, MEPs predicted the presence of unilateral brainstem lesions with high accuracy. MEP recordings can be safely performed in neurointensive care patients and yield utilizable results. In patients with brainstem lesions, MEPs correlate with radiological findings and predict final motor function more accurately than clinical findings. MEPs are a reliable diagnostic tool for assessing motor function in otherwise unresponsive patients.

Neurochemical monitoring of the acutely injured human brain.

The main goal of modern neurointensive care (NIC) of patients with acute brain injury (traumatic brain injury, neurovascular disease) is to prevent additional loss of viable brain tissue due to secondary injury processes. It is generally held that secondary injury, mediated by, for example, cerebral hypoxia/ischemia and destructive molecular cascades on the cellular level, contributes significantly to the extent of brain damage after head injury and stroke. The basic concept is that improved knowledge of the secondary injury processes will lead to new therapeutic approaches in NIC. New methods by which secondary injury processes can be detected and monitored in NIC patients are therefore greatly needed. This paper describes intracerebral microdialysis as a novel approach to neurochemical monitoring of the human brain. The main objectives are (i) to monitor cortical energy metabolism in order to detect secondary ischemia and (ii) to monitor secondary injury processes, such as glutamate receptor overactivation and increased free radical production, in NIC patients.

51 Effect of Head Elevation on Cerebral Hemodynamics in Neurointensive Care Patients

Moraine, Jean-Jacques PT, PhD; Berre, Jacques MD; Mélot, Christian MD, PhD, MSciBiostat Author Information