Advances in neuro-monitoring

Abstract

Neuromonitoring aims to detect harmful physiologic events, early enough to guide the treatment instituted. Evidences encourage us to implement multimodal monitoring, as no single monitor is capable of providing a complete picture of dynamic cerebral state. This review highlights the role of intracranial pressure monitoring, cerebral oxygenation (jugular venous oximetry, brain tissue oxygenation, near infrared oximetry, cerebral microdialysis) and cerebral blood flow monitoring (direct and indirect methods) in the management of neurologically injured patients. In this context, the recent developments of these monitors along with the relevant clinical implications have been discussed. Nevertheless, the diverse range of data obtained from these monitors needs to be integrated and simplified for the clinician. Hence, the future research should focus on identification of a most useful monitor for integration into multimodal system.

INTRODUCTION

Neuro-monitoring assumes paramount significance because the condition of neurologically impaired patients may change rapidly within a short period of time impacting the outcome. The main concern in these patients is to maintain cerebral perfusion and hence, meeting with the metabolic demands of brain for oxygen and glucose. This holds good for patients with acute neurological conditions such as traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), stroke etc., Hence, the goal of monitoring should include detection of harmful physiologic events before they cause irreversible damage to brain and providing on-line feedback to guide treatment instituted. As the secondary injuries are either systemic or intracranial in nature, the monitoring modalities must include detection of both these components. The systemic and routine neurointensive monitoring variables include electrocardiography, arterial oxygen tension (SpO₂), arterial blood pressure, temperature, arterial blood gases and electrolytes. However, this article aims to review the recent developments of intracranial monitoring modalities with relevant clinical implications.

INTRACRANIAL PRESSURE MONITORING

Measurement of ICP is essential to determine cerebral perfusion pressure (CPP). Normal ICP in supine position is 5-15 mmHg in adults, 3-7 mmHg in children and 1.5-6 mmHg in infants.[1] The treatment threshold for raised ICP is considered as 15-20 mmHg.[1] Management of raised ICP is an integral part of neurointensive care practice. For this there has been a continuous effort for developing an ideal method for measuring ICP. The development of strain gauges and an external transducer revolutionized the ICP monitoring technique and has been widely adopted. The Richmond and Leeds screw once widely used, has now declined in popularity. The intraventricular technique remains the gold standard for ICP measurement. This invasive method measures the global ICP with additional advantages of periodic external calibration, therapeutic cerebrospinal fluid drainage, and instillation of drugs or antibiotics directly into the ventricle. However, the placement of catheter may be difficult in cases of severe brain swelling and also runs the risk of infection.[2] Currently, catheter-tipped transducers are widely used. These microtransducer-tipped ICP sensors can be placed in brain parenchyma, intraventricular or subdural space through a burr-hole or during a neurosurgical procedure. They are almost as accurate as ventricular catheters. Fiberoptic (Camino ICP Monitor), Strain gauge (Codman Microsensor, Neurovent-P ICP Monitor), or pneumatic (Spiegelberg ICP Monitor) technologies are used to transduce pressure in these modern devices. However, most of these devices do not allow in vivo pressure calibration (exception Spiegelberg monitor). After a pre-insertion calibration (zeroed with atmospheric pressure), their output is subject to the zero drift of the sensor though the drift is as low as 0.6 ± 0.9 mmHg during in vivo testing. The ICP monitoring allows measurement of absolute ICP value, calculation of CPP, identification and analysis of pathological waveforms (Lundberg A wave or Plateau waves), calculation of cerebrovascular pressure reactivity and pressure-volume compensatory reserve.[1]

Noninvasive methods of measuring ICP do not involve risk of hemorrhage or infection. Various methods such as transcranial Doppler (TCD) ultrasonography,[3,4] tympanic membrane displacement,[5,6] optic nerve sheath diameter,[7,8] and transcranial color-coded duplex sonography.[9] Noninvasive techniques lack the accuracy of their invasive counterparts thus they cannot be used as an alternative to the invasive techniques.[10]

Despite lack of class I evidence supporting its efficacy in TBI, there are large number of scientific publications which supports this monitoring not only for guiding therapeutic interventions but also for early detection of mass lesions and prediction of prognosis.[1] However, in patients with severe TBI, Chesnut et al. observed that the care focused on maintaining monitored ICP at 20 mmHg or less was not superior to the care based on imaging and clinical examination.[11]

CEREBRAL OXYGENATION MONITORING

Jugular venous oximetry[12]

Cannulation of the jugular bulb allows assessment of the global oxygenation status of the brain and adequacy of cerebral blood flow (CBF). The dominant jugular vein is cannulated and the catheter tip is placed at the level of body of first cervical vertebra, medial to mastoid process which can be confirmed by lateral X-ray of skull.[13] This intends to minimize contamination from extracerebral venous drainage (about 3%). Normal jugular venous oxygenation (SjvO₂) ranges is between 55% and 75%.[13] The ischemic threshold has been reported to be a SjvO₂ < 50% for at least 10 min[14] which is associated with poor outcome following TBI. Low SjvO₂ indicates either an increase in oxygen demand (fever, seizures) or a reduction in oxygen delivery due to vasospasm or hypotension, or inadequate CPP. A high SjvO₂ indicates hyperemia, or decreased metabolic demand of the brain. SjvO₂ monitoring has been used commonly in patients with TBI for detection of reduced cerebral perfusion and by some to titrate hyperventilation in patients with increased ICP. Brain trauma foundation guidelines recommend maintenance of SjvO₂ greater than 50%.

A significant association exists between arterio-jugular difference of oxygen content and poor neurological outcome.[15] However, it has low sensitivity to regional changes, and studies using positron emission tomography (PET) scan indicate that a relatively large volume of tissue must be affected (approximately 13%), before SjvO₂ levels decrease below 50%.[16] Intraoperative jugular venous oximetry has been used intraoperatively during pediatric intracranial neurosurgery to optimize cerebral physiology.[17]

Brain tissue oxygen monitoring (PbO₂)

PbO₂ monitoring probe (diameter 0.8 mm) is a miniature Clark electrode inserted into the brain parenchyma and measures brain tissue PO₂ in vivo. It represents the balance between oxygen delivery and consumption. The two most commonly used systems to date are the Licox and the Neurotrend. The Licox system provides PbO₂ with or without brain temperature, in an estimated 7.1-15 mm² area. In addition to PbO₂, Neurotrend provides information on brain tissue partial pressure of carbon dioxide (PbCO₂), pH and temperature. Currently, only Licox system is available commercially to monitor PbO₂. Post insertion computed tomographic (CT) scan confirms probe position in the brain parenchyma. The inspired oxygen concentration (F_iO₂) is increased transiently and a corresponding increase PbO₂ is ensured to exclude the presence of surrounding micro-hemorrhages or sensor damage at the point of insertion. A ‘run in’ or equilibration time of up to 1 h is required before readings are considered stable. The normal values are in the range of 35-50 mmHg.[18] Generally PbO₂ < PaO₂ (extravascular sensor placement and high metabolic activity), PbCO₂ (40-70 mmHg) > PaCO₂ (high metabolism), pH brain (7.05-7.25) < pH blood (high brain metabolism).[13] A PbO₂ value less than 10 mmHg (Licox) should be corrected within 30 min to prevent poor outcome.[19] Placement near the injury or penumbra will yield values reflecting the local measure of brain tissue oxygen to guide therapy, whereas placement within a contusion or clot will give erroneous readings. Ponce et al. studied retrospectively, 405 severe TBI patients in whom PbO₂ probe was placed either in normal or abnormal brain. They noted that PbO₂ and outcome were related only when probe was placed in abnormal brain.[20]

PbO₂ monitoring is useful in various clinical situations where cerebral ischemia is a risk. Correctly positioned PbO₂ monitoring allows not only assessment of the effect and reversibility of temporary aneurysm clipping, but can also be indicative of the correct positioning of the subsequent permanent clip.[21] Jödicke et al. found that PbO₂ monitoring during aneurysm clipping supplemented somatosensory evoked potentials (SSEP) monitoring in identifying ischemia, especially in those patients where the baseline SEP was absent. Using a threshold of 15 mmHg, PbO₂ was found more effective than SSEP monitoring for predicting ischemia.[22] Low intraoperative PbO₂ values indicate high risk of occurrence of postoperative TCD detected vasospasm in cases of aneurysmal SAH.[23]

In patients with TBI, PbO₂ has been shown to be a good indicator of treatment effects and correlates well with clinical outcome measures.[24] ICP/CPP and Pbto₂-based therapy is associated with better outcome after severe TBI than ICP/CPP – based therapy alone.[25] However, it further needs to be proved by a randomized controlled trial.[26] The change in trend of PbO₂ values is helpful in detecting secondary insult and guiding specific therapy. However, the disadvantages of this monitor are: It gives a local measure of PbO₂ and is invasive.

Regional and global oxygenation monitoring techniques are not competitive or mutually exclusive. Neither Jugular venous oxygen saturation nor PbO₂ monitoring alone identifies all episodes of ischemia and they should be considered complementary with monitoring strategies taking advantage of the unique features of each technique.

Near-infrared spectroscopy

NIRS is a noninvasive method of estimating cerebral oxygenation.[12,27] It is based on reflectance oximetry and measures the light reflected from chromophobes in the brain (hemoglobin) to derive the regional oxygen saturation (rSO₂). It interrogates arterial, venous and capillary blood and hence, the oxygen saturation represents an average value for these compartments. However, most of the NIRS signal is from the venous blood which contributes to approximately 70% of intracranial blood volume. This technique indirectly measures changes in CBF and cerebral blood volume (CBV) by detecting changes in venous saturation.[26] Two types of NIRS instruments commonly available for clinical use: The INVOS series (Somanetics Corporation USA) and the NIRO series (Hamamatsu Photonics Japan). The former presents a single numerical value for regional cerebral oxygen saturation whereas the latter provides tissue oxygen index in percentage terms and changes in oxyhemoglobin and deoxyhemoglobin variables and oxidized cytochrome-c oxidase.

The sensors illuminate up to a volume of 10 ml of hemispherical tissue. The radial depth will depend on the interoptode distance. The optodes are placed on one side of the forehead with an interoptode spacing of 4-7 cm. Near infrared time resolved spectroscopy with functional maximal optode spacing of 4 cm measure cerebral hemodynamic responses optimally and quantitatively.[28] Taussky et al. demonstrates that CT perfusion CBF has a significant linear correlation with NIRS measurement.[29] The normal values of rSO₂ is reported to be 60-80% and the ischaemic threshold is estimated to be 47% saturation.[30] This critical cerebral oxygen saturation was observed by comparing cerebral oxygen saturation with EEG during controlled episodes of venticular fibrillation in humans. The investigators found EEG evidence of cerebral ischemia in 47% of patients under anesthesia.

Despite problems of extracranial contamination, limitation for placement on the forehead, and interference by ambient light, NIRS has several applications. Bhatia et al. studied 32 SAH patients during coil embolization and found that angiographic cerebral vasospasm was strongly associated with decrease in trend of ipsilateral NIRS values.[31] In patients undergoing carotid endarterectomy, cerebral co-oximeter helps in detecting cerebral ischemia.[32] A relative decrease in rSO₂ of 16-20% during carotid endarterectomy (CEA) predicted neurological compromise.[33] Mille et al. identified a cutoff point of 12% decrease in rSO₂ as optimal for defining ischemia secondary to internal carotid artery clamping during CEA.[34] Increase in rSO₂ value immediately after declamping of the internal carotid artery (cutoff point, 5%) is useful for detection post-CEA hyperperfusion syndrome with a sensitivity of 100% and specificity of 86.4%[35] In addition, it has been used to detect a low cardiac output state and utilized for noninvasive cerebral autoregulation assessment. A new technology employing ultrasound guided NIRS holds promise for non-invasive and real-time bedside CBF monitoring.[36] It has found utility even in monitoring CBF autoregulation.[37]

Cerebral microdialysis

CMD is one of the promising bed-side neuro-monitors which provide analysis of biochemical markers for occurrence of hypoxia/ischemia. It helps in identifying impending secondary injury and thus early implementation of neuroprotective strategies. Hence, its use has been recommended in severe cases of TBI.[38] CMD measures metabolic products locally in the area of the catheter, hence it should be placed in ‘at-risk’ tissue following TBI, in area around a mass lesion or in the nondominant frontal lobe following diffuse axonal injury. Energy metabolites (glucose, lactate, pyruvate), the lactate/pyruvate ratio (LPR), toxic neurotransmitters (glutamate, aspartate), tissue damage indices (glycerol, potassium) are the most commonly measured biochemical variables. The normal values of glucose 1.7-2.1 mmol/l, Lactate 2.9-3.1 mmol/l, pyruvate 151-166 μmol/l, LPR 19-23, glycerol is 50-100 μmol/l, and glutamate 14-16 μmol/l.[39,40] The trend is however more useful than absolute measures.

Online continuous dialysate analysis can detect changes 9 min after they have occurred as compared to 30 min required for probe-to-detection time using an offline analyzer.[41] However, intraoperative CMD monitoring still has a long way to go.[42]

Intracranial hypertension results in reduced brain pyruvate and elevated LPR. When autoregulation is deranged, the increase in LPR with CPP reduction is even more pronounced.[43] A high LPR correlates with severity of clinical symptoms and poor outcome after severe head injury. A rise in glycerol levels, indicating progression to cell damage has been found after severe head injury.[43] Schlenk et al. found that cerebral glucose increases when blood level is > 140 mg/dl. Glucose level above 7.8 mmol/l (140 mg/dl) were independent predictors of unfavorable outcome and mortality in SAH patients.[44]

CBF MONITORING

CBF monitoring offers a rational approach to detect and prevent secondary insults and improve the outcome of these patients. Normal value of CBF in young adults is 50 ml/100 g of brain tissue/min (range 20-70 ml). The ischemic threshold for CBF is 18 ml/100 g/min and below 10 ml/100 g/min, irreversible damage ensues.[45]

The CBF monitors may be discussed in two broad categories: Direct CBF measurements and Indirect CBF measurements.

Direct CBF monitoring

These methods are invasive, more quantitative and often require transport of the patients from the ICU.

PET

PET (positron emission tomography) provides quantitative in vivo measurement of CBF, cerebral metabolic rate of oxygen (CMRO₂), CBV, oxygen extraction fraction, and is considered the gold standard for studying cerebral hemodynamics.[46] Isotopes commonly used are ¹¹C, ¹³N, ¹⁵O and require on-site production. Several limitation of this technique are use of radioactive compounds, requires shifting of the patient to a radiology facility, needs cyclotron, is expensive, not universally available, and gives a single shot assessment.

Perfusion weighted magnetic resonance imaging

Diffusion weighted MRI (DWI) detects irreversibly infarcted tissue whereas perfusion weighted MRI (PWI) also identifies potential ischemic areas.[46] It can assess vascular patency if magnetic resonance angiography (MRA) is added. It requires either an exogenous gadolinium contrast agent or an endogenous diffusible tracer No ionizing radiation is used. Values of rCBF measured by MRI and PET methods correlate well.[47] PWI is time consuming and more expensive than CT scan.

Xenon-enhanced computed tomography

In xenon-enhanced computed tomography (XeCT) the non-radioactive Xe is inhaled for 4-5 min which is radiodense on subsequent CT scan.[46] It is based on the Kety algorithm to quantitatively measure regional and global CBF. The ability of Xe (33%) itself to modify CBF is minimal.[48] However, it requires transfer of the patients, measurement times are long, provide non-continuous measure of CBF and are available in few centers only.

Single-photon emission computed tomography

Single-photon emission computed tomography (SPECT) is the 3-D image produced by gamma scintillation counting.[46] It utilizes ¹³³Xe or 99mTc as the radioisotopes for CBF estimation. Other lipophilic tracers used are SPECTamine and Ceretac. By comparing an ischemic area with presumably normal area, relative CBF can be measured with this technique. Though cheaper than PET, it also requires transfer of the patients, has limited spatial resolution and provides single-shot measure of CBF.

Computed tomography perfusion scan

In computed tomography perfusion (CTP) scan, the concentration of the contrast agent used is proportional to the perfusion parameters.[46] After iodinated contrast is infused, concurrent images are acquired using a helical CT multislice scanner and thus CBF, CBV, mean transit time, time-to-peak can be calculated. Along with absolute values of CBF, it helps in detecting preservation of autoregulation. It also provides only regional CBF values.[49]

Indirect (bedside) CBF monitoring

Thermal diffusion flowmetry

Thermal conductivity of cerebral cortical tissues varies directly with CBF. Probe consists of a thermistor which is heated and a sensor which measures temperature. The temperature difference between the two reflects local CBF.[50] As cerebral temperature increases, the temperature difference decreases. In patients with severe TBI, it has been used for assessment of autoregulation and vasoreactivity.[51] It provides continuous, quantitative assessment of cortical perfusion. Its main limitations are potential complications of acute tissue damage, bleeding, and infection and erroneous readings due to external thermal factors.

Laser doppler flowmetry

A craniotomy or burr hole is needed to insert a laser Doppler flowmeter to detect cortical blood flow.[50] The depth and area of the tissue involved limit the technique. Laser Doppler flowmetry (LDF) provides continuous and real-time measurements of regional CBF changes are relatively inexpensive and non-radioactive. It has been used to assess autoregulation, CO₂ reactivity and to detect ischemic injury.

TCD ultrasonography

Transcranial doppler (TCD) is a non-invasive, bed-side technique, which uses pulsed-doppler ultrasound beam of 2 MHz frequency to measure relative changes in CBF in the basal cerebral arteries provided angle of insonation and the diameter of the insonated vessel remain constant.[12,52,53] Reasonable correlations have been reported between TCD and Xe CT and PET CBF measurements.[54] It has also found utility for detecting cerebral vasospasm after SAH, for evaluation of autoregulation, for noninvasive estimation of ICP and to confirm brain death.

The pulsatility index (PI), also called Gosling index, reflects the cerebrovascular resistance, mainly ICP. It is derived from following formula:

Where FV dias is diastolic blood flow velocity and FV sys is systolic blood flow velocity

Higher the value of PI more is the resistance. Normal PI is independent of angle of insonation and ranges between 0.6 and 1.0. PI is inversely proportional to CPP. Hence, PI provides the best TCD correlate of CPP and ICP.

Schmidt and associates[55] assessed noninvasive CPP (nCPP) from the following formula with satisfactory accuracy (error < 10 mmHg in more than 80% cases).

nCPP = (Mean arterial pressure × Diastolic flow velocity)/Mean flow velocity + 14

The drawbacks of TCD are measurement of relative flow velocity, operator dependent, and failure to insonate the temporal window in 5-10% of cases.

Others

An ultrasonic perivascular flow probe has recently been developed for direct intraoperative CBF measurement.[56] CBF can also be estimated from NIRS assessment of indocyanine green clearance.[57]

CONCLUSION

Most of the monitoring modalities described above have drawbacks when considered in isolation. Invasive techniques provide continuous information on a particular area of brain with associated risk of complications whereas noninvasive techniques provide non-continuous information of multiple sites. Therefore, the challenge is to integrate all these modalities (Multimodal monitoring) in order to combine their strengths and allow greater confidence in the decision making for patient management. Modern multimodality monitoring systems provide the clinicians with diverse range of data. Interpretation of these data is complex and may require computer assisted methods. The future research should focus on identification of most useful monitor for integration into multimodal system.