Trends in monitoring patients with aneurysmal subarachnoid haemorrhage

J. B. Springborg1,*, H.-J. Frederiksen1, V. Eskesen2 and N. V. Olsen1

1 Department of Neuroanaesthesia and 2 Department of Neurosurgery, The Neuroscience Centre, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark

* Corresponding author. E-mail: rh13842{at}rh.dk


    Abstract
 Top
 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
After aneurysmal subarachnoid haemorrhage (SAH), the clinical outcome depends upon the primary haemorrhage and a number of secondary insults in the acute post-haemorrhagic period. Some secondary insults are potentially preventable but prevention requires prompt recognition of cerebral or systemic complications. Currently, several neuro-monitoring techniques are available; this review describes the most frequently used techniques and discusses indications for their use, and their value in diagnosis and prognosis. None of the techniques, when considered in isolation, has proved sufficient after SAH. Furthermore, the use of multi-modality monitoring is hampered by a lack of clinical studies that identify combinations of specific techniques in terms of clinical information and reliability. However, ischaemia at the tissue level can be detected by intracerebral microdialysis technique. Used together with the conventional monitoring systems, for example intracranial pressure measurements, transcranial Doppler ultrasound and modern neuro-imaging, direct assessment of biochemical markers by intracerebral microdialysis is promising in the advancement of neurointensive care of patients with SAH. A successfully implemented monitoring system provides answers but it also raises valuable new questions challenging our current understanding of the brain injury after SAH.

Keywords: complications, subarachnoid haemorrhage ; intensive care ; monitoring


    Introduction
 Top
 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
In the last 30 yr the incidence of spontaneous subarachnoid haemorrhage (SAH), mostly from rupture of intracranial aneurysms, has remained at around 6–10 per 100 000 persons per year.79 SAH accounts for about 3% of all strokes and about 5% of stroke deaths, and as SAH often affects younger adults it is estimated to account for up to 25% of potential life years lost through stroke.56 126 Despite advances in the treatment and prevention of complications, SAH remains one of the most life-threatening acute neurological diseases. Overall outcome has improved only modestly during the last decades.12 31 46 74 115 Case mortality is around 50% (including pre-hospital deaths) and one-third of survivors remain dependent.46

Neurointensive care of patients with SAH is based on the theory that the clinical outcome is the consequence of the primary haemorrhage and a number of secondary insults in the acute post-haemorrhage period. Some secondary insults are potentially preventable and can be influenced by therapeutic measures. To prevent and treat delayed neurological deficits early aneurysm closure in good-grade patients and the use of nimodipine and ‘Triple-H treatment’ have been suggested in guidelines for the management of patients with SAH.87 Nevertheless, systemic and neurological complications are still common.27 90 120 However, some clinical studies suggest that aggressive peri- and postoperative intensive care of patients with SAH using invasive monitoring is associated with improved outcome.12 46 74

Clinical surveillance of the neurological condition remains an important diagnostic measure but contrary to a true monitoring (warning) system ‘neurochecks’ only recognize neurological deterioration when it has already occurred and is limited by coma, sedation, and neuromuscular block. Currently, the monitoring of a number of physiological and chemical neuroparameters is possible, and the use of one or more of these techniques is a regular part of neurointensive care. However, few of these monitoring techniques have been thoroughly evaluated in clinical settings, which indicates the need for a sceptical implementation and further evaluation in clinical studies. Also, the additional diagnostic or prognostic value of invasive or non-invasive monitoring of patients who are sufficiently alert to allow more detailed neurological assessment has never been demonstrated.

In this review, we have described the most common neuro-monitoring methods in patients with SAH (Table 1) and discussed their indications, uses, and diagnostic value. The focus has been on techniques available for use in the intensive care unit as transportation of critically ill patients out of the intensive care setting poses an important safety concern.


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Table 1 Possible secondary insults after SAH and the available monitoring techniques

 
Because of a high incidence of non-neurological complications after SAH, it is important to remember that neurological monitoring is only part of the problem and that systemic physiological monitoring is as important in a patient with SAH as in any patient in the intensive care setting. A recent review by Vender and Franklin135 has dealt with the trends in systemic physiological monitoring.


    Neuro-monitoring
 Top
 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
SAH is a complex disease involving a number of intracranial and systemic perturbations. These perturbations are more evident in poor-grade patients where they are often associated with delayed neurological deficits (Fig. 1).



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Fig 1 Schematic review of the complex interplay of secondary insults leading to secondary brain damage after SAH. ICH, intracerebral haemorrhage; IVH, intraventricular haemorrhage.

 
No single monitoring technique can describe the entire clinical condition of a patient. Furthermore, successive steps from the measurement of a neuroparameter to the implementation of a response from the neurointensive team depend upon human skills and vigilance, which ultimately determine the success or failure of a monitoring system. Therefore, the successful implementation of any new monitoring system depends on a thorough introduction and continuous training of the professional team.

Problems with agitated patients who accidentally remove the monitoring equipment are well known in the neurointensive care unit. Most of the monitoring techniques discussed will require co-operative or sedated patients and, when deciding to initiate invasive monitoring, this should always be taken into consideration.

The scientific interest elicited by neuro-monitoring or neuro-imaging techniques should not cloud the issue of their practical relevance. Consequently, a review of monitoring techniques should aim to address the following questions: accuracy and reliability of the technique, theoretical and practical limitations and risks, impact on decision-making and influence on patient outcome. While some neuro-monitoring techniques have been tested in traumatic brain injury and stroke, their application to patients with SAH is a more recent development. Thus, while the risks and complications are rather well documented, data on accuracy and reliability in patients with SAH are incomplete at best. In addition, the impact of any monitoring technique on patient management and outcome is often unresolved, and when studied, even generally accepted routine techniques might prove disappointing. As for example, pulse oximetry monitoring influenced patient treatment but not patient outcome in a study of 20 802 patients randomly assigned to pulse oximetry in the operating room and intensive care unit.94


    Intracranial pressure/cerebral perfusion pressure
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 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
The overall aim of intracranial pressure (ICP) monitoring is to alert the clinician to rises in ICP and thereby allow him/her to protect cerebral perfusion by maintaining an adequate cerebral perfusion pressure (CPP). In patients with SAH common causes of increased ICP are hydrocephalus, intracerebral haemorrhage and brain oedema. Intracranial compliance may be reduced even when ICP is normal, leaving the patient susceptible to small changes in intracranial volume. In patients with severely compromised intracranial compliance even routine procedures such as turning or suctioning can produce deleterious elevations of ICP.

It has been debated whether ICP or CPP should be used to target therapy and predict outcome. In patients with SAH they seem of equal value.27 A number of different ICP monitoring techniques are available (for details see Czosnyka and Pickard20 and Piper and co-workers105). Briefly, fluid-filled catheter transducer systems based on the pioneer work of Lundberg in the 1960s are generally considered gold standard.81 Alternatively, various catheter tip ICP monitoring systems are available (e.g. Camino®, Codman®, and Spiegelberg®).

Intracranial compliance can be studied through the relation between ICP and changes in volume of the intracerebral space. One method depends on injection of sterile saline into the ventricular system but it is rarely used because of the associated risk of infection or disruption of intracranial dynamics. An alternative method, relying on inflating and deflating a balloon in the cerebrospinal space, is implemented in the Spiegelberg® monitor.20 71 Alternatively, altered ICP wave morphology may be a clue to a compromised cerebral compliance.20

Indwelling intraventricular catheters are recommended in all patients with SAH presenting with acute hydrocephalus and a depressed level of consciousness.87 Cerebrospinal fluid (CSF) drainage can be intermittently discontinued and ICP measurements performed using pressure transducers in a closed circuit system where ICP waveform analysis is also possible.

The introduction of a ventricular catheter poses risks of bleeding, damage to parenchyma, and an infection rate close to 10%.43 80 125 Furthermore, there has been concern about an increased risk of aneurysm re-bleeding if vetriculostomy is performed before aneurysm repair but data are contradicting.43 89 138 After ventriculostomy ICP should be maintained above 15 mm Hg to reduce the risk of re-bleeding.138

The catheter tip devices are generally safe40 84 but pose the risk of infection and intra-parenchymal damage. Also, questions have been raised about accuracy given that most catheters cannot be recalibrated once implanted.84 105 This problem might be solved with the Spiegelberg® monitor, which uses a small air pouch system and is unique in performing automatic zeroing in situ every hour.20 71 The Camino® and Codman® systems allow evaluation of ICP waveforms similar to ventricular catheters, but they cannot drain CSF.105 Because of their inferior frequency properties many methods of ICP waveform analysis are not possible with the Spiegelberg® monitor, but the intraventricular version of the system allows access to the CSF space for drainage.20 71

Diagnostic and prognostic values have not been reported. As there is persuasive evidence that aggressive treatment of increased ICP improves outcome it may, because of ethical constrains, never be demonstrated that ICP monitoring in itself improves outcome.


    Cerebral blood flow
 Top
 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
Under normal conditions cerebral blood flow (CBF) is coupled to cerebral metabolism. Particularly in the poor-grade patients with SAH, the cerebral metabolic rate is reduced probably as a result of ischaemic damage from the flow stop occurring in the first short period after aneurysm rupture or direct toxic effects of subarachnoid blood.10 44 53 129 Thus, ischaemic damage from the reduced CBF soon after rupture of an aneurysm is limited. In some patients relatively high CBF (luxury perfusion) early after SAH suggests a post-ischaemic condition, but in others CBF is low because of either increased ICP or reduced metabolic rate.10 44 53 129 Later the CBF level approaches the metabolic demands of the brain, but in poor-grade patients uncoupling between flow and metabolism may continue for a longer period.10 129 139 Vasospasm may decrease CBF to below metabolic demand depending on the severity and duration.10 129 139 Regional variation in metabolic rate and CBF is immense, which challenges choice of monitoring.50 132

Bedside evaluation of CBF has been a long-lasting aim of neurointensivists. It could assess flow reductions suggestive of cerebral ischaemia, measure the effects of treatment, and evaluate the integrity of autoregulatory mechanisms. Several techniques are available but none have established the position of a practical bedside monitoring system.

Using nitrous oxide as a marker, Kety and Schmidt made the first determinations of CBF almost 60 yr ago.65 Lassen and Ingvar later used intravascular injections of a radioactive tracer to determine CBF in multiple small regions of the brain from the clearance curve.73 Today 133Xe inhalation or injection techniques are the most widely used for bedside CBF measurements.54 72 98 However, both techniques are discontinuous and, in essence, not capable of detecting all the ischaemic events. Moreover these are invasive, expensive and available only in research centres.

Xenon-enhanced CT,33 133Xe emission CT,91 single photon emission computed tomography (SPECT)51 75 and positron computed tomography10 44 75 142 have all been used for measuring CBF in patients with SAH. The CBF measurements can determine the net effect of the initial bleeding and vasospasm on cerebral perfusion. The normal mean hemispheric CBF is about 50 ml 100 g–1 min–1; neurological deficits normally do not occur until CBF decreases below approximately 25 ml 100 g–1 min–1.50 57 Reservations related to the 133Xe inhalation or injection methods apply equally to the imaging techniques, and they all pose the important safety concern of transporting critically ill patients. The diagnostic or prognostic values have never been reported.

Laser Doppler flowmetry (LDF) provides reliable measurements of local cortical non-directional CBF.4 7 However, the technique is limited by extremely local measurements, arbitrary units of measurements, and artifacts that can be induced by a large number of external derangements.4 7 Furthermore, the reliability depends on probe position and patient cooperation and the technique is invasive.4 7 In patients with SAH the LDF technique has been used concomitant with transcranial Doppler ultrasound (TCD) in the detection of secondary ischaemia and therapeutic management of vasospasm, confirming that high Doppler flow velocities and ischaemia are often not correlated.55 A thermal diffusion flowmetry technique for continuous and quantitative assessment of regional CBF has been developed, but difficulties in clinical practice with respect to accuracy and reliability have been encountered and again the technique is invasive.11 132

Neither technique has gained significant clinical acceptance. Diagnostic or prognostic values have not been reported.


    Brain temperature
 Top
 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
The ischaemic brain is very sensitive to the variations in the temperature. Even a small increase in temperature can have significant negative effects and, though not documented in patients with SAH, many neurointensivists use mild to moderate hypothermia as part of their management strategy.36 61 However, temperature gradients may exist between different regions of the brain. Brain temperature is normally approximately 1°C higher than core temperature, and even greater regional differences in temperature may exist when the core temperature is elevated.109 Thus information on local brain temperature is required for the optimal use of temperature as a monitoring tool. Different systems are commercially available and the systems use stand-alone temperature sensitive probes or probes integrated with ventricular drains or other monitoring equipment (e.g. ICP, microdialysis, or brain tissue oxygenation).61 99 Diagnostic or prognostic values of these devices in patients with SAH have not been reported.


    Transcranial Doppler ultrasound
 Top
 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
Since its introduction two decades ago2 the use of TCD has widely expanded in neurointensive care. In patients with SAH the technique has one major objective, namely to detect elevated flow velocities in the basal cerebral arteries suggesting vasospasm, and thereby to identify patients at risk for delayed neurological deficits.

Briefly, a low-frequency (2 MHz) pulsed wave probe is used to insonate a major cerebral basal artery through cranial windows: areas of the skull with little attenuation and scattering of the signal because of sparse or no cancellous bone. This allows computer assisted generation of information on peak systolic, end diastolic and mean flow velocities along with a pulsatility index from the recorded waveforms.58 83 In 1984 Aaslid, Huber, and Nornes presented data from 40 patients with recent spontaneous SAH demonstrating an inverse relationship between blood-flow velocity in the middle cerebral artery (MCA) and arterial lumen diameter measured on angiographies.1 They suggested mean velocities of more than 120 cm s–1 as a lower limit indicating MCA vasospasm and today this is generally the most accepted threshold value. After SAH, CBF may deviate considerably from normal.10 44 53 129 139 As CBF in itself affects the flow velocities, the assessment of vasospasm from flow velocities alone may be insufficient. Lindegaard an co-workers suggested the use of a ‘Hemispheric Index’ between flow velocities in the MCA and internal carotid artery on the same side.78 It is resistant to changes in CBF and therefore predictive of MCA lumen narrowing. An index of more than 3.0 is indicative of MCA vasospasm and values more than 6.0 suggest severe MCA vasospasm.78

The transcranial Doppler seems most reliable in detecting vasospasm of the MCA. With angiography or symptomatic vasospasm as a reference standard for final diagnosis, the reported sensitivity and specificity is generally high: around 60–100% and 80–100%, respectively.18 85 118 The reported positive predictive value (PPV) is high (100%) whereas the negative predictive value (NPV) is low (30%) when angiography is used as reference standard.118 On the contrary, the PPV is low (39%) and the NPV is high (90%) when symptomatic vasospasm is used as reference standard.124 Because of anatomical variations, the lack of correlation between flow velocities and lumen diameter, and frequent participation in collateral blood flow, TCD is less reliable in detecting vasospasm in the major cerebral arteries other than MCA.18 118 Vasospasm in smaller arteries beyond the detection capacity of TCD is rare and does not lead to delayed neurological deficits.96 Just as the frequency of angiographically documented vasospasm is higher than symptomatic cases, also high TCD flow velocities may be well tolerated in some patients and vice versa. Integrity of the CBF autoregulation, the number of arteries involved, and the anatomy of the circle of Willis are some of the factors that determine the clinical condition of the patient. This makes treatment decisions based on TCD findings alone difficult. Supplementary CBF examinations can identify flow reductions caused by vasospasm.21 39 116 Blood flow and vessel diameter may be directly estimated from the Doppler curve through calculated indices.35

Consecutive TCD measurements and calculation of the hemispheric index are routinely used in many neurointensive care units. Steep velocity increases (>25 cm s–1 day–1) from baseline level are generally accepted as a warning of the development of vasospasm.26 39 Furthermore, TCD measurements are helpful in deciding whether a clinical worsening is a result of vasospasm or if other causes should be excluded by for example a CT scan. In patients with SAH additional applications of the TCD technique include studies of CBF autoregulation integrity by the carotid artery compression test or induced hypertension,34 70 77 119 and indirect evaluation of ICP through the use of the pulsatility index.58 83 The major advantage is its bedside non-invasive nature allowing serial measurements. Limitations are the operator dependency along with the lack of an established relationship between flow velocities and delayed neurological deficits.


    Microdialysis
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 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
In clinical practice many diagnostic and therapeutic decisions are based on blood concentrations of endogenous substances. However, most biochemical and pharmacological events take place in the tissues. The function and pathology of the brain are reflected by alterations in intra- and extracellular molecular biology;5 130 therefore, assessing tissue chemistry directly in the brain may provide valuable data in patients in neurointensive care.

Developed and refined since the late 1960s, microdialysis has changed from a ‘bench’ to a bedside technique. Instruments for performing microdialysis in the human brain were labelled according to the European Medical Device in 1995 and have been approved for use in the USA by the Food and Drug Administration in 2002. Microdialysis is a chemical sampling method, which allows endogenous low-molecular-weight substances to passively diffuse and equilibrate across a semi-permeable membrane into a dialysate where concentrations can be analysed (Fig. 2). Depending on the permeability of the membrane, essentially all smaller water-soluble substances can diffuse and be analysed by high-performance liquid chromatography. Today bedside equipment, allowing spectrophotometric analysis of some substances of interest, is commercially available. The dialysate is normally collected every hour and thus the measured concentrations are average concentrations in that hour.130 Using a 10-mm dialysis membrane and a perfusion flow of 0.3 µl min–1, the ‘recovery’ of glucose in the dialysate will reach approximately 70% of the concentration in the interstitial fluid with a flow delay of about 20 min.48 130 Provided that microdialysis catheters are implanted in relevant positions in relation to affected tissue, the technique contributes prompt information on metabolism and its consequences for cell survival.5 130



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Fig 2 Microdialysis catheter (CMA 70, CMA Microdialysis, Sweden). (1) Connection for pump; (2) inlet tube; (3) shaft (tunnelated): (4) microdialysis membrane; (5) outlet tube; (6) microvial holder; (7) microvial for collection of dialysis samples.

 
A variety of substances have been monitored, but focus has been mainly on three different areas: (i) ischaemia by measuring energy-related metabolic substances such as glucose, pyruvate, and lactate; (ii) excitotoxines such as glutamate and aspartate; and (iii) membrane degrading products such as glycerol.28 47 63 64 97 110 122 130 131 Taken together, ischaemia within the region of the microdialysis catheter is associated with pathological changes in energy-related metabolites, excitotoxines and membrane degrading products, but conflicting results concerning which markers are the most sensitive or predictive have been reported.28 47 63 97 130 Biochemical changes that accompany brain tissue ischaemia mostly involve a change in the redox potential, evident from an increase in the lactate/pyruvate ratio.5 130 In patients with traumatic brain injury, increases in the lactate/pyruvate ratio correlates with the severity of clinical symptoms and outcome.121 More important, the biochemical changes detected by intracerebral microdialysis appear before significant increases in ICP.121 Similar findings have been reported in patients with SAH where the lactate/pyruvate ratio is found to be a more reliable marker than lactate alone.103 Another study indicates that in patients with SAH elevated concentrations of glutamate is the earliest marker of vasospasm followed over time by lactate, the lactate/pyruvate ratio and glycerol.97

Interest has focused on the ability of microdialysis to monitor the development of vasospasm and delayed neurological deficits. In 40 patients with SAH or complex unruptured aneurysm surgery microdialysis detected but failed to predict the development of delayed neurological deficits.64 In contrast, in a study on 97 patients with SAH, changes in metabolites indicative of ischaemia occurred before the onset of symptoms in 83% of patients with delayed neurological deficits.110 In 60 patients with SAH microdialysis was compared with TCD and angiography, and it was found to have the highest specificity and positive likelihood ratio in terms of confirming delayed neurological deficits.131 Only intermediate sensitivity was found, probably because of the regional nature of the microdialysis measurements.131 Using a predefined ischaemic pattern, with increases in lactate/glucose and lactate/pyruvate followed by increases in glycerol, a high sensitivity (94%), specificity (88%), and PPV (85%) in terms of detecting delayed neurological deterioration can be found. The ischaemic pattern precedes the occurrence of delayed neurological deficits by a mean interval of 11 h.117 Besides, patients with poor-grade SAH or an unfavourable outcome have higher (pathological) concentrations of markers than less affected patients.64 110 122 Peerdeman, van Tulder and Vandertop attempted to determine the diagnostic accuracy of microdialysis by systematically reviewing clinical studies: a quantitative analysis could not be performed because of insufficient data, but a qualitative analysis gave a positive impression with regard to diagnostic accuracy in detecting ischaemic events.100 However, they concluded that there was insufficient evidence at the time for routine use of microdialysis in clinical practice.

Microdialysis is an invasive technique but acute tissue reaction to catheter implantation is insignificant.140 Bleeding and infection are potential adverse complications but so far no cases have been reported. Prolonged catheter placement might result in oedema in the surrounding tissue and infiltration of the dialysis membrane by inflammatory cells making the measurements obtained after several days more difficult to interpret.6 140 However, assessment of the lactate/pyruvate ratio is independent of the recovery of the microdialysis catheter.

There are important limitations to the microdialysis technique. The most important is the fact that the technique monitors metabolic changes in the vicinity of the catheter only. Unless the catheter is placed in an area where secondary insults are affecting nerve cells, ‘normal’ concentrations will be measured. Basing the catheter placement solely on the initial CT scan might result in catheter placement in ‘normal’ tissue, as the prediction of aneurysm location based on the admission CT scan alone can be difficult.134 Furthermore, the most informative placement of the catheter can be compromised because of the fact that vasospasm and infarction after SAH are not limited to the area of aneurysm location, but can be found in other areas of the brain depending on the distribution of the haemorrhage.9 Nonetheless, in patients with SAH the most informative placement of the catheter seems to be the vascular territory of the artery harbouring the ruptured aneurysm.64 110 131 Alternatively, more than one catheter can be placed.130

Whether microdialysis will establish a routine part in neurointensive care will depend on future experimental and clinical research clarifying which substances should be measured and the most informative placement of the catheters. A potential area of interest is the measurement of endogenous substances associated with neuronal damage, for example protein S-100, nitric oxide, and free oxygen radicals, and small-molecule mediators of inflammation. In addition, intracerebral microdialysis may provide important bedside information on the effect of interventional therapy and, perhaps even more intriguing, a hitherto unseen opportunity to assess pharmacokinetics of drugs administered on either side of the blood–brain barrier. As with most neuro-monitoring techniques, clinical studies evaluating the actual positive impact of microdialysis monitoring on patient outcome are lacking.


    Jugular venous oximetry
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 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
Calculations of the arterial to jugular vein oxygen concentration difference (AVDO2) may serve as an indirect measure of relative changes in CBF.106 114 Assuming an unchanged metabolic rate of oxygen (CMRO2), AVDO2 changes in inverse proportion to CBF, because , where and denote arterial and jugular venous oxygen content, respectively. Thus, an increase in CBF will elicit a proportional decrease in (), which during short study intervals may be replaced by the difference in arterial and jugular venous saturation ().106 114 In general, low vaues indicate hypoperfusion and elevated values relative hyperaemia.29 88

A retrograde catheter can be placed in the internal jugular vein for serial measurements or continuous fibre-optic monitoring of .29 52 88 The fibre-optic technique can give a lot of erroneous readings and questions about its usefulness have been raised.22 29 88 Because anatomical data suggest that blood from the cortex might preferably drain into the right jugular vein and blood from the subcortex into the left, it is debated which side should be monitored.29 88 123 However, unless the patient has lateralizing pathology the difference in oxygen saturation on the two sides is small.29 88 123 Indeed, measurements reflect global CBF and cannot detect focal CBF changes.22 29 88

Generally, values of less than 50–60% are considered the threshold for cerebral hypoxaemia.22 29 88 This corresponds to an intraparenchymal brain tissue partial pressure of oxygen () of around 1.3–2 kPa.66 The catheter can, in addition, be used in the assessment of CBF autoregulation and vasoreactivity.106

Few studies have used measurements in patients with SAH. Using concomitant and 133Xe CBF measurements uncoupling between flow and metabolism, leading to luxury perfusion, has been demonstrated in the acute state after SAH, suggesting a post-ischaemic condition.53 139 In nine of 26 patients with SAH at least one episode of desaturation is found.13 Abnormal reductions in are observed in 10% of total serial measurements and ICP is significantly elevated during these episodes.13

Possible complications from retrograde jugular catheterization are similar to anterograde catheterization including carotid artery puncture, haematoma formation, infection, jugular vein occlusion, and increases in ICP during placement.88 The risk of carotid artery puncture is 1–3%, but no adverse sequelae have been reported when local pressure is applied to the puncture site for 10 min.88

No study has evaluated the diagnostic or clinical relevance of jugular venous oximetry in the management of patients with SAH. In head trauma patients, the use of catheters seems promising19 107 and concomitant use of brain tissue oxygenation monitoring may further improve the clinical relevance.38


    Brain tissue oxygenation
 Top
 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
Bedside on-line monitoring of brain tissue oxygenation () is possible with intraparenchymal oxygen-sensitive or combined oxygen-, carbon dioxide- and pH-sensitive microelectrodes. Whereas only provides information on oxygen tension, the combined microelectrodes present indirect information on the metabolic status of the brain.

Excluding the first hour after insertion, monitoring is a reliable technique with good quality of data.24 133 In patients with SAH a low level is associated with the severity of the haemorrhage, ischaemic events and a poor clinical outcome.45 47 63 A specific hypoxic lower limit, below which the brain is at risk of being damaged, is undetermined. Different authors find different cut-off points.45 63 133 However, a lower level of around 1.3–2 kPa is probably rational, corresponding to values of around 60%.66 Similar to microdialysis monitoring only provides information on local tissue changes, and reservations concerning changes in other areas of the brain apply equally to this technique.

monitoring is an invasive technique but the acute tissue reaction to catheter implantation seems insignificant.24 133 Infection is a potential adverse complication but so far no cases have been reported. Prolonged catheter placement might result in oedema in the surrounding tissue and infiltration of the catheter by inflammatory cells making the measurements obtained after several days more difficult to interpret. The diagnostic and prognostic value has not been reported and the influence on patient outcome is undetermined.


    Near infrared spectroscopy
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 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
Transcranial near infrared spectroscopy (NIRS) is a continuous non-invasive method to determine cerebral oxygen saturation. The near infrared light penetrates biological tissue and is absorbed differently by the chromophores oxyhaemoglobin and deoxyhaemoglobin.82 Commercially available equipment uses different technology and mathematical algorithms, which makes general assessment of the technique complex: comparison between monitors is difficult, and it is impossible to understand output from monitors supplied by manufacturers who do not publish their algorithms.

In healthy volunteers NIRS detects cerebral hypoxia41 and the technique has been implemented in the care of patients with head trauma.37 67 Using an intravascular tracer such as indocyanine green, local CBF can be calculated from the clearance curve.62 82 Both uses may be inaccurate because of insufficient light shielding, optode displacement, and CSF or extracerebral blood contamination. Placing the optodes in the subdural space, together with for example a ICP monitor, could eliminate some of these problems, and preliminary results from patients with SAH have been presented.62 Also, newer spatially resolved spectrometers might overcome the problem of extracranial contamination.3 In patients with SAH cerebral hypoxia detected by NIRS correlates to increased flow velocity detected by TCD.25 Further studies evaluating the clinical use of NIRS in patients with SAH have not been reported, and at the moment NIRS is not established in routine clinical practice. The clinical relevance of NIRS is debated.8 76 95 The diagnostic and prognostic value has not been reported.


    Continuous electroencephalography
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 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
Continuous electroencephalographic (CEEG) monitoring is potentially interesting in the neurointensive care setting. The technique is non-invasive and the changes in CEEG closely correlate with cerebral metabolism and are sensitive to ischaemia.16 59 136 Also, CEEG is the best available method for detection of seizure activity and a high frequency of non-convulsive seizures has been reported after SAH.16 23 58 59 136 In addition, CEEG correlates with cerebral topography, which makes it attractive for the detection focal dysfunction or vasospasm.16 59 136

Comparing CEEG changes with clinical and radiological findings in 11 patients with SAH, the most sensitive ischaemia parameter was changes in total power (91%). In four of 11 patients CEEG changes appeared before clinical deterioration.69 Comparing CEEG and angiographical data from 32 patients with SAH, CEEG was highly sensitive (100%) and had a high PPV (76%) and NPV (100%) in terms of detecting vasospasm. In 10 of 19 patients the CEEG changes were present before the diagnosis of vasospasm for a period of about 3 days.137

As yet, CEEG is not included in routine neurointensive monitoring. Scepticism because of the supposed vulnerability to artifacts and dependence on trained neurophysiologists has so far outweighed the potential usefulness. New technological improvements, including digital processing and automated analysis, might facilitate the implementation and expand credibility.16 59 136 The prognostic value and influence on patient outcome remains undetermined.


    Evoked potentials
 Top
 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
Evoked potentials measure the neuronal activity and conduction pathways and indirectly reflect the functional effects of CBF changes.

Somatosensory evoked potentials change during cerebral aneurysm surgery, and the relationship with postoperative neurological complications has been studied on many occasions. However, whether evoked potentials are really helpful in detecting or preventing neurological complications has been questioned. In 87 patients undergoing aneurysm surgery somatosensory evoked potentials were monitored in 60 and no difference was found in the frequency of postoperative neurological complications in the monitored (15% [9/60]) and unmonitored patients (22% [6/27]).92 In 32 patients with SAH CBF and somatosensory evoked potential were monitored intermittently. Patients with central conduction time prolongation over 7.5 ms within 10 days after SAH tended to have poor recovery of CBF and an unfavourable outcome.49 In 43 patients with SAH somatosensory and brainstem auditory evoked potentials were used to diagnose cerebral ischaemia and predict clinical outcome. Compared with outcome sensitivity was 73%, specificity 81%, PPV 57%, and NPV 90%.112 Despite the high diagnostic and prognostic values, the technique is impractical, discontinuous and, in essence, not capable of detecting all ischaemic events.


    Imaging techniques
 Top
 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
In 1980 Fisher, Kistler, and Davis determined that the amount and distribution of blood detected on admission CT correlates with the later development of vasospasm in patients with SAH.30 The ‘Fisher scale’ proposed by this group is still used.30 Other groups have identified further CT-verified risks of delayed neurological deficits and proposed modifications of the scale.14 15 32 Serial CT scans yield information on the intracranial dynamics. Diffusion- and perfusion-weighted MRI is highly sensitive to ischaemia and in patients with SAH it may prove useful in the detection of vasospasm.17 75 104 108 The use of other imaging techniques in the evaluation of CBF has already been mentioned. However, all imaging techniques require transportation of the patient out of the intensive care unit limiting the clinical relevance of these methods as monitors. Whether bedside technology will be available in the near future remains undetermined.


    Biochemical markers
 Top
 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
Finding a biochemical marker highly sensitive to neuronal damage and predictive of outcome has been a long-standing experimental objective in neuroscience. Several promising markers have been evaluated, but none have achieved a part in routine practice.

In patients with SAH, initial high serum and CSF S-100 concentrations are related to the severity of the haemorrhage and to a poor outcome of the patient.42 101 102 128 Furthermore, serial CSF S-100 measurements increase parallel to the development of delayed neurological deficits42 128 indicating a possible use of this marker in the determination of vasospasm and evaluation of therapeutic measures. Among others, CSF and serum neurone-specific enolase,102 CSF lipid peroxides,60 CSF cytokines,68 86 CSF and serum angiogenic factors,111 CSF fibrin and fibrinogen degrading products,113 CSF endothelin-1,127 CSF nitric oxide metabolites141 and serum intercellular adhesion molecule-193 have been examined in preliminary clinical studies. The clinical relevance awaits further evaluation and none of the markers are routinely used in the monitoring of patients with SAH.


    Conclusions
 Top
 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
The clinical care of patients with SAH should focus on prevention, early identification and immediate treatment of the secondary insults that adversely affect outcome. Often patients are unable to communicate and evaluation of their neurological condition may be restricted by coma, medical sedation, and neuromuscular block. Currently, several monitoring techniques aiding decision-making are available, and studies demonstrate that aggressive intensive care using invasive monitoring may improve patient outcome.12 46 74 Nevertheless, no physiological or biological marker or variable, however sophisticated, has been unequivocally predictive of delayed neurological deficits in a manner timely enough that preventive interventions might be effectively instituted. Furthermore, multi-modality monitoring is hampered by the lack of clinical studies that identify a combined specific use of the most informative and reliable techniques. Consequently, there is no general recommendation concerning a multi-modality monitoring profile in patients with SAH. When deciding whether to monitor the patient with SAH, the decision should depend on the clinical condition of the patient, the risk of complications and a sceptical attitude towards the available techniques. As it appears few of the available monitoring techniques have been thoroughly validated in patients with SAH and the influence on patient outcome is undetermined.

Interestingly, ischaemia at the tissue level can be detected by intracerebral microdialysis. Secondary brain ischaemia is an important cause of a poor outcome after SAH and together with more conventional neuroparameters, for example ICP, CBF, and blood-flow velocity, direct monitoring of biochemical markers by intracerebral microdialysis is promising. Furthermore, invasive monitoring techniques will be useful in the evaluation of new potentially neuroprotective substances, as well as improve our understanding of the brain's response to SAH and changes induced by therapy. A successfully implemented monitoring system provides answers but in addition raises valuable new questions challenging our current understanding.


    References
 Top
 Abstract
 Introduction
 Neuro-monitoring
 Intracranial pressure/cerebral...
 Cerebral blood flow
 Brain temperature
 Transcranial Doppler ultrasound
 Microdialysis
 Jugular venous oximetry
 Brain tissue oxygenation
 Near infrared spectroscopy
 Continuous...
 Evoked potentials
 Imaging techniques
 Biochemical markers
 Conclusions
 References
 
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