41
ONSD measured with MRI
MR imaging is a suitable tool for measuring the optic nerve diameter and that of its surrounding sheath, by using a fat-suppressed T2-weighted sequence (47).
ONSD acquired on MR images decreases in response to measures to reduce hydrocephalus in pediatric patients and thus can be a good indicator of improved hydrocephalus following pediatric neurosurgical interventions (48).
The value of ONSD changes in children on MR as a radiological screening for outcome after endoscopic third ventriculostomy, demonstrated a good accuracy (49). Further, a study on TBI patients requiring ICP monitoring with a parenchymal sensor, evidenced a significant relationship between ONSD and ICP (r = 0.71) with very good sensitivity and specificity (90 and 92%, respectively) (50).
For measuring ONSD, an acceptable agreement has been found between US and MR (r = 0.72, p = 0.002, mean difference < 5%) has been found (51), as well as between CT and MR (52).
ONSD assessed with CT
CT imaging has the advantage of being more available than MR and less operator dependent as compared to US (37, 52).
ONSD increases detected on brain CT correlated with mortality (53, 54) and with neurological outcome in hypoxic ischemic encephalopathy after cardiac arrest (55).
In a retrospective cohort study on TBI patients with continuous ICP monitoring and simultaneous brain CT, a strong correlation between ONSD and ICP was found (r = 0.74, P = 0.001); for ONSD a cut-off of 6.0 mm provided a sensitivity of 97%, and a specificity of 42%, with a positive predictive value of 67 %, and a negative predictive value of 92% (42).
42
INDIRECT PRESSURE TRANSMISSION Pupillometry
Optic disc swelling (papilledema), due to raised ICP can be visualized by fundoscopy. The entity of the swelling can be graded by Frisén scale which includes 5 categories and it is built on ophtalmoscopic signs related to an increased mass or to swollen axons (56). This method showed a good accuracy for ICP detection in severe head injured patients (57).
Although fundoscopy is often used as a screening method for suspected increased ICP, it has several limits. The grading scale is not widely accepted (58) and there is a considerable variability between individuals with respect to normal ophtalmoscopic morphology.
Moreover, optic disc swelling in cases of raised ICP takes time (59), and therefore this technique is not suitable for emergency conditions or when acute ICP increases are suspected.
Tympanic membrane displacement
Tympanic membrane displacement (TMD) technique is based on the communication of the perilymph and the CSF via the perilymphatic duct (60). Acoustic stimuli are transmitted through the ossicular chain of the middle ear, to the tympanic membrane and then ultimately activate the acoustic sensor cells. CSF pressure is transmitted to the perilymph of the cochlea affecting the excursion of tympanic membrane and stapes. Indirect measurement of perilymphatic pressure may be investigated by observing TMD during stapedial reflex contraction (figure 2.3) (61, 62).
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Figure 2.3. A schematic representation of the communication between the subarachnoid space and the inner ear through the cochlear aqueduct.
Marchbanks et al. (60) first studied the effects of ICP changes on cochlear fluid pressure measuring TMD demonstrating that this technique was sensitive to ICP variations. A significant negative relationship (r = -0.57, p = 0.0013) between mean TMD and invasively measured ICP was demonstrated, despite wide predictive limits (± 25 mm Hg), precluding the clinical use of this technique as an absolute number (63).
This method helped to detect shunt dysfunction in patients treated for hydrocephalus with suggestive symptoms (62), showing good sensitivity and specificity (64).
This technique may present several methodological limitations (63) and is associated with a low success rate (up to 40% (63)).
The perilymphatic duct becomes less patent with age, and this can compromise the correct estimation of the pressure of the perilymph (63)).
Moreover, the magnitude of TMD can also depend on other several anatomic factors (integrity of the ossicles, presence of masses in the middle ear, or patency of the Eustachian tube), which can affect the acoustic impedance or the strength of the acoustic reflex (63)).
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CEREBRAL BLOOD FLOW CHARACTERISTICS AND ALTERATIONS
Arterial TCD
Transcranial Doppler Ultrasonography (TCD) is a safe, repeatable technique to assess ICP and CPP, detecting specific changes in cerebral blood flow velocity (FV). Gosling Pulsatility Index (gPI) is probably the most widely investigated measure derived from the TCD waveform (65) and is defined as the difference between systolic and diastolic flow velocities, divided by the mean flow velocity.
Some authors (66) demonstrated a good performance of PI in detecting increased ICP, with the best reported correlation coefficient between the ICP and the PI of 0.938, and a sensitivity and specificity of 0.89 and 0.92 to detect ICP higher than 20 mm Hg (66). Other authors have been far more reserved on this subject (67, 68). Zweifel et al. (68), in a cohort of 290 patients, found a weak correlation between PI and ICP (0.31,P 0, 001) and between PI and CPP (-0.41, P 0, 0001), with a large 95% CI , concluding that the value of PI to assess ICP and CPP noninvasively is very limited. Other TCD derived formulas have the primary objective of non –invasively estimating cerebral perfusion pressure (nCPP) and to consequently obtain non-invasive ICP (nICP) based on the assumption that nICP = MAP - nCPP.
Aaslid et al. (69) have determined CPP with TCD parameters using a formula (nCPP=FVm*A/F) based on the amplitude (F) of the fundamental frequency components of flow velocity and the amplitude of the fundamental frequency components of arterial pressure (A) and found a strong correlation between estimated CPP with the calculated CPP changes (69).
Schmidt et al. (70) studied a method for nICP assessment applying a mathematical “black- box” model (based not on physiological structure, but based on a set of formal mathematical expressions) to estimate ICP from cerebral blood flow velocity (FV) and arterial blood pressure (MAP). Such parameters act as coefficients to calculate and continuously update a transformation of MAP into ICP, providing full waveform of nICP. This method (70) showed a maximum 95% confidence interval (CI) of 12.8 mmHg for prediction of increased ICP in TBI patients.
45
Schmidt, Czosnyka et al. (71) proposed a new formula for CPP estimation and demonstrated an absolute difference between real CPP and nCPP lower than 10 mm Hg in 89% of measurements and less than 13 mmHg in 92% of measurements.
Finally, Varsos et al. proposed a method to calculate nCPP using the concept of Critical Closing Pressure (CrCP) (72): applied on a series of 280 head-injured patients, nCPP showed a good correlation with measured CPP (R = 0.851, p < 0.001), with only a small estimation error.
According to a recent study by Cardim et al. (73) Schmidt’s method (70) demonstrated to be the best estimator for ICP in TBI patients.
TCD is a safe and repeatable technique, with no major complications. However, TCD practice requires training and there are also intra- and inter-observer variations (74).
Moreover, on 10–15% of the patients the technique cannot be used because of the absence of a proper bone window for ultrasounds.
Venous TCD
Venous TCD is an evolving technique which has been extensively used for diagnosis and follow-up of patients with cerebral venous thrombosis, stroke and head trauma (75, 76).
A case report studied the relationship between venous blood flow (BFV) and raised ICP, finding a good correlation (77).
A few years later the same authors investigated this relationship in 30 control volunteers and 25 patients with raised ICP. They performed serial venous TCD studies of the basal vein of Rosenthal and the straight sinus and calculated the relationship between ICP and gPI derived from venous flow velocities (maximal BFV - minimal BFV) / mean BFV). A linear relationship between mean ICP and maximal venous BFV in the basal vein of Rosenthal (r = 0.645; p = 0.002) and in the straight sinus was found (r = 0.928; p =0.0003)(77).
According to the Monroe-Kellie doctrine, cerebral compliance strongly depends on the compressibility of the low-pressure venous or capacitance segment of the vascular bed, which
46
is the first compensatory mechanism in case of increased ICP.
However, the insonation of the basal vein of Rosenthal is possible in 88% of and the straight sinus in 72% of the patients, reflecting anatomical variations in cerebral veins and transcranial insonation difficulties (78, 79).
EYE BALL Ophtalmic artery
Ragauskas et al. (80, 81) described a new method for nICP measurement based on a two- depth high-resolution transcranial Doppler insonation of the ophthalmic artery, which does not need calibration.
The intracranial segment of the ophthalmic artery is compressed by ICP, and the extracranial segment can be compressed by pressure applied from external (eP), which is transferred into orbit without pressure gradient as the orbital tissues are incompressible (figure 4).
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Figure 2.4. Non-invasive two-depth TCD device for absolute ICP measurements.
A: Anatomy of the ophthalmic artery (OA). OA is the first major branch of the internal carotid artery (ICA). The entire course of the ophthalmic artery can be divided into three parts: intracranial, intracanalicular, and intraorbital. Intracranial part starts where it branches off from the ICA siphon (curved part of the internal carotid artery) and extends to the area of the “A”. Intracanalicular part of the OA extends from the area of the “A” to the apex of the orbit. The intracranial and intracanalicular course of the artery is divided into the following parts:
short limb, angle “a”, long limb, angle “b”, and the distal part up to the apex of the orbit.
B: Method for non-invasive estimation. Intracranial segment of OA is located in intracranial compartment and it is affected by ICP. Extracranial segment is located in orbit, and it is influenced by external pressure. The ultrasound transducer of the Doppler subsystem is surrounded by an externally applied pressure chamber with a controlled external pressure (Pe) source and measurement. Blood flow parameters are measured simultaneously in both segments of the ophthalmic artery using TCD. The point when differences of relative parameters of blood flow become lowest is determined. (with permission from Ragauskas et al. 2012).
TCD can simultaneously measure flow velocities both in the intra- and in the extra-cranial segments of the ophthalmic artery during application of a series of small pressure steps to the tissues surrounding the eyeball. When the PI of FV in intracranial and extra-cranial segments are approximately the same, eP equals ICP.
Studies on healthy volunteers in different body positions vertical, supine, and three head down tilt positions were carried out in order to find out the transfer function of non-invasive
48
absolute ICP value measurement system. Linear regression equation was found of non- invasive absolute ICP value measurements in a range of ICP values from 0 to 40 mmHg with a slope and intercept of the regression line of 0.892 and 0.006, respectively and a strong linear correlation (R = 0.996).
In 2012 Ragauskas et al. (81) compared this method with invasive CSF pressure measurement, through lumbar puncture, demonstrating good accuracy and a low mean systematic error and high precision (SD ±2.19 mm Hg) for this method.
However, the use of this technique in clinical practice is limited because of specific location of the intracranial and extracranial segments of the ophthalmic artery. Even if many doctors believe that the ophthalmic artery is not so difficult to find, this technique requires highly skilled transcranial Doppler specialist and anatomical knowledge.
METABOLIC ALTERATIONS
NIRS
Near Infrared Spectroscopy (NIRS) is an optical monitoring based on infrared light, detected by optodes transversing biologic tissues and its absorption at specific wavelengths correlates with the presence of biologic chromo-phores (deoxyhemoglobine and oxyhemoglobine).
Thus, this method can detect intra-cerebral oxygen saturation and subsequently cerebral blood flow, volume and oxygenation (82). The ratio of oxygenated to total hemoglobin, with its percentage value, is expressed as the Tissue Oxygenation Index (TOI), which can be regarded as a surrogate measure of local CBF changes.
NIRS is highly suitable for long-term monitoring, and has shown several clinical applications as monitoring device, in particular in neurovascular diseases (83). However, the utility of NIRS in neurocritical care and in the estimation of ICP is less developed. This technique could provide information about ICP just indirectly, as it has been demonstrated that patients with high ICP present significant alterations in NIRS signals (84, 85), in particular during ICP slow waves (86) as consequence of the decrease in CPP and in oxygen supply. Moreover, many neurocritical care diseases (TBI) are heterogeneous diseases and a major limitation of
49
NIRS is that it does not take into account these regional differences in physiology. For example, a patient with frontal contusions will have significant alterations in CBF, thereby making any deductions of the global intracranial physiology invalid with NIRS.
At present, despite the potential benefits of a non-invasive and continuous monitoring for oxygen metabolism, NIRS does not allow a correct absolute measurement of ICP, neither the evaluation of changes in ICP (87).
NEUROPHYSIOLOGICAL REGISTRATIONS OF FUNCTIONAL ACTIVITY EEG
Since raised ICP alters cerebral perfusion, this is also reflected on brain metabolism and lately on neuronal activity (88). Several studies demonstrated that EEG changes and therefore entropy and Bispectral Index (BIS) values also correlate with CPP (89), and thus also with ICP.
Moreover, EEG patterns are correlated with CBF (89). In particular, EEG burst duration correlates with ICP changes (90).
In 2012, a new technique based on EEG power spectrum was proposed by Chen et al. as a noninvasive method for ICP monitoring (91). The authors calculated a pressure index (PI) from the EEG analysis in brain injured patients detecting a significant negative correlation between PI and ICP (r = -0.849, p < 0.01).
EEG is not an immediately available technique and thus it is not suited for the emergency setting (92). In addition, this technique still needs further studies to be applied in clinical practice.
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Visual evoked potentials
Visual-evoked potentials (VEP) accurately detect alterations of the visual pathways.
Therefore, any disorder affecting the physiological function of visual pathways, including elevated ICP, can be detected as VEP alterations.
A flashing light elicits electrical brain activity, which is recorded with occipital EEG electrodes. ICP is estimated from either the latency of the second negative going wave (N2) of the VEP (93) or from the latency of the third positive-going wave (P3) of VEP (94).
Several authors found good correlations between ICP and N2 wave latencies in adults (95, 96) and children (93), suggesting that the VEP based method can detect ICP with accuracy, and is safe and easy to perform, with only a minimal risk of complications.
Despite these optimistic results, Andersson et al. (97) demonstrated that this method has a wide variability in terms of range of latency, amplitude and waveform in healthy subjects. In addition, a large proportion of subjects also had a high intra-individual variability over time.
This variability makes the technique unreliable as a marker for intracranial pressure.
Otoacustic emission
ICP is known to affect the phases and levels of lower-frequency distortion-product otoacoustic emissions (DPOAE) (98, 99) and can give characteristic alterations suggestive of an increase in the stiffness of the stapes system, probably in relation to an increased intracochlear pressure (100).
In patients with increased ICP, significant phase-shift changes on DPOAEs were found for low frequencies (99, 101) with a significant correlation between invasive ICP and DPOAE phase shift was demonstrated (102).
DPOAE seems to be able to detect ICP changes associated with postural changes in healthy volunteers (101) and it represents a good method to monitor ICP at extreme altitudes (103).
This method potentially could be a valuable tool for monitoring ICP non-invasively (99, 104), but it presents several limitations: it cannot be applied on patients with sensorineural or
51
conductive hearing deficits (105), it provides a good detection of ICP changes, rather than absolute ICP values, with a large inter-subject variability that requires an individual baseline measurement (106).
Time of flight
Ultrasonic time-of-flight for non-invasive volume and ICP assessment was introduced by Ragauskas et al.(107). The method is based on the different acoustic properties of intracranial components (cerebral tissue, blood, CSF) such as ultrasound speed, and frequency dependent attenuation, measuring the acoustic properties of the intracranial media (IM). A change of the content of intracranial components inside the acoustic path influences the total acoustic characteristics of the IM and the monitored parameters of the ultrasonic signal as well (108, 109).
Petkus et al. (108) calculated nICP in an experimental study using the linear functions after the real-time and in situ compensation of the skull bone/external tissue influence on the measured time-of-flight data, demonstrating that changes of US velocity are linearly dependent on ICP changes (R=0.99 p=0.001).
The clinical investigations of this new technology showed the similarity between the invasively recorded ICP and non-invasively recorded intracranial blood volume, pulse waves, slow waves and slow trends in neurocritical care patients, with good correlation (R > 0.9) (109), between invasively and non-invasively recorded intracranial slow waves.
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DISCUSSION
ICP monitoring is crucial for managing neurocritical patients at risk of increased intracranial pressure. Invasive measurement of ICP remains the gold standard and should be performed when indicated (4). Among the invasive devices, EVD is considered the gold standard, despite some risks of infection and hemorrhage (110, 111).
When invasive monitoring is contraindicated or unavailable, an accurate noninvasive method could be desirable. Moreover, there are many “borderline” situations in which the insertion of an invasive monitoring is questioned, but a non-invasive ICP measurement could be useful (112-116), in particular in children (117).
The ideal non-invasive monitoring device should be low cost, easily available and also suitable in emergency settings, free of risks, reliable in terms of not operator dependent, accurate and precise. Non-invasive methods have a very low risk of complications, if no risks at all and low costs (table 2.2). They require only the single expense of purchasing the device, and then the devices can be used multiple times without further costs. Moreover, most of the non-invasive techniques have to option to monitor ICP (or related parameters) bilaterally, in particular TCD (118).
All the non-invasive methods have the common disadvantage of not being sufficiently accurate to replace the traditional invasive techniques.
Most of the non-invasive techniques are affected by different operator-dependent factors and in some cases they cannot be applied in clinical practice (a measurement with TMD method is not possible in 60% (63) of cases).
According to our revision of available methods, each noninvasive ICP monitoring strategy has its own advantages and limits, and thus does not satisfy alone all the above requirements (table 2.2).
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Table 2.2. Characteristics of the nICP methods.
CT imaging, for instance, are easily available and not operator dependent, but they are not predictive (PPV 0-88%, table 3) for increased ICP neither at short, nor at long term (table 2);
further, CT scan does not allow a continuous monitoring.
ONSD has shown a good correlation with ICP increases and its measure is highly reproducible (table 1). Among the morphological tools to measure ONSD, ultrasound has proved to be the less expensive, more easily available and repeatable if compared to CT or MRI, showing good correlation coefficents and good specificity and sensitivity in most of cases (table 1). Moreover, ONSD findings obtained with ultrasound can indicate when more complex imaging, such as MRI or even CT, is indicated.
All the described methods proved to have a better accuracy in detecting ICP changes of the individual patient, rather than absolute ICP values. Thus, a continuous monitoring offers a better and more timely detection of ICP variations.
Arterial TCD has been extensively studied and allows a continuous monitoring, but it is Method
Availability Operator
dependency Temporal
resolution Suitable in
Emergency Risk of Infections/
haemorrage
Cost
Radiological findings CT High No poor Yes None Medium
MRI Medium No poor No None High
ONSD US High Yes good Yes None Low
ONSD CT High No poor Yes None Low
ONSD MRI Medium No poor No None High
TMD High Yes poor No None Low
Fundoscopy High Yes poor No None Low
Arterial TCD High Yes good Yes None Low
Venous TCD High Yes poor Yes None Low
Ophtalmic artery Low Yes poor Yes None Low
NIRS Medium Yes good No None Low
EEG Low Yes good No None Low
VEP Low Yes good No None Low
EOAEs Low Yes poor No None Low
Time of flight Low Yes poor No None Low
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operator dependent and still under study as concerns the identification of the most appropriate formula for ICP estimation. Venous TCD is a promising technique, as described by Schoser et al. (77), but further studies need to confirm its role in the estimation of ICP.
Also, EEG (including VEP) offers a continuous monitoring, but its interpretation requires a neurophysiological training and it is not available in emergency situations. At the present, NIRS cannot be considered reliable enough to be used to assess ICP.
There are several techniques which are less commonly considered and still probably used in clinical research settings, with only very small series published, though maybe promising in the near future, such as MRI method by Alperin, eye-ball ophthalmic artery method, fundoscopy, tympanic membrane displacement, otoacustic emission and TOF.
We noted that data on sensitivity and specificity is not systematically available in most of the revised literature, and most of the studies include a small number of patients, making a quantitative comparison truly difficult.
Most of the authors demonstrated good correlation with invasive for many of these methods;
in particular, eye ball OA method, MR method by Alperin and TMD method demonstrated good ICP with good sensitivity and specificity (table 3). However, most of these techniques are not easily available and in clinical practice.
In conclusion, there is no a non-invasive technique accurate and established enough to substitute invasive ICP method. However, based on the above considerations, we propose a flow chart for a strategic use of a selection of available tools for ICP monitoring aimed at selecting the best timepoint where CT scan might become a necessity and possible aggressive management of ICP. The flowchart merges the possibility of a continuous monitoring such as that provided by TCD with the accuracy and availability of ONSD measurement by ultrasound methods (Figure 2.5).
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Figure 2.5. Flowchart. Proposal of for invasive or non-invasive monitoring of ICP in traumatic brain injured patients at arrival in Emergency Department. Beside clinical assessment and brain CT we propose a possible use of a combination of the non-invasive techniques to screen patients where there is doubt on the need for invasive ICP/CPP methods to monitoring patients, when the indications for an invasive method are not completely met or when an invasive method is contraindicated or not available.
*GCS ≤ 8 and abnormal brain CT Head
GCS ≤ 8age and normal brain CT but: under 40 years, or if systolic blood pressure is ≤ 90 mmHg, or flexion or extension motor response to pain at clinical evaluation
**Coagulopathy, piastrinopenia
This flowchart can be useful to screen patients where there is doubt on the need for invasive ICP monitoring, such as patients with high energy traumas where the indications for an invasive monitoring are not completely met, or when clinical assessment is difficult (or taking too much time), or when there are contraindications for the insertion of non-invasive devices, as previously described for TCD (119).
Further studies will be necessary to compare different non-invasive techniques with the gold standard to clarify the performance of each method.
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Chapter 3 . Doppler non-invasive monitoring of ICP in an animal model of acute intracranial hypertension.
Chiara Robba, Joseph Donnelly, Rita Bertuetti, Danilo Cardim, Mypinder S Sekhon, Marcel Aries, Peter Smielewski, Hugh Richards and Marek Czosnyka
Neurocrit Care. 2015 Dec;23(3):419-26
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ABSTRACT
Introduction: In many neurological diseases, intracranial pressure (ICP) is elevated and needs to be actively managed. ICP is typically measured with an invasive transducer, which c arries risks. Non-invasive techniques for monitoring ICP (nICP) have been developed. The aim of this study was to compare three different methods of Transcranial Doppler (TCD) assessment of nICP in an animal model of acute intracranial hypertension.
Methods: In 28 rabbits ICP was increased to 70–80 mmHg by infusion of Hartmann’s solution into the lumbar subarachnoid space. Doppler flow velocity in the basilar artery was recorded. nICP was assessed through 3 different methods: Gosling’s pulsatility index PI (gPI), Aaslid’s method (AaICP), and a method based on diastolic blood flow velocity (FVdICP).
Results: We found a significant correlation between nICP and ICP when all infusion experiments were combined (FVdICP: r = 0.77, AaICP: r = 0.53, gPI: r = 0.54). The ability to distinguish between raised and ‘normal’ values of ICP was greatest for FVdICP (AUC 0.90 at ICP > 40 mm Hg). When infusion experiments were considered independently, FVdICP demonstrated again the strongest correlation between changes in ICP and changes in nICP (mean r = 0.85).
Conclusion: TCD based methods of nICP monitoring are better at detecting changes of ICP occurring in time, rather than absolute prediction of ICP as a number. Of the studied methods of nICP, the method based on FVd is best to discriminate between raised and ‘normal’ ICP and to monitor relative changes of ICP.
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INTRODUCTION
Elevated intracranial pressure (ICP) is an important secondary brain injury because it can cause both brain ischaemia and mechanical compression of vital brain structures.
Unsurprisingly, intracranial hypertension is associated with a poor outcome (1). Its evaluation is crucial in many neurological diseases (2,3)as clinical signs of elevated ICP (such as altered consciousness, headache, vomiting) are not always reliable predictors of this condition (4).
Invasive measurement of ICP through an intraventricular or intraparechymal catheter are considered the gold standard (5).
However, these methods can cause complications such as infection, haemorrhage, or soft tissue scarring (6-9). Non-invasive monitoring of ICP could be valuable in the management of many neurological patients. Several techniques have been proposed for the non-invasive measurement of ICP (10-12), but none of these seem to be accurate enough to be used as a replacement for invasive ICP measurement.
Transcranial Doppler Ultrasonography (TCD) is one possible tool to assess non-invasive ICP (nICP) and Cerebral Perfusion Pressure (CPP). Increased ICP produces specific changes in cerebral blood flow velocity (FV) measured by TCD, with diastolic FV being particularly sensitive (13). Gosling Pulsatility Index (gPI) was one of the first measures derived from the TCD waveform that has been studied in relation to ICP (14-16). However, its clinical utility is questionable due to its poor precision (17,18).
Other formulae and mathematical approaches that incorporate the arterial blood pressure as well as the cerebral blood flow velocity waveform have been proposed. Aaslid et al. (19,20) presented a formula for the estimation of CPP, based on spectral pulsatility index (SPI) and the first harmonic component of the Arterial Blood Pressure (ABP) which demonstrated to be quite sensitive to the variation of CPP, but it has a limited accuracy (21). Czosnyka, Matta et al. proposed a similar but modified formula for non-invasive estimation of CPP (nCPP), and therefore of ICP, which showed a low estimation error compared to real CPP (22).The authors reinforced these preliminary results in a prospective study demonstrating that the absolute difference between real CPP and nCPP was less than 10 mm Hg in 89% of
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measurements and less than 13 mm Hg in 92% of measurements with a confidence range for predictors that was no wider than ±12 mm Hg (23). Whether these formulae for estimating CPP can be used to assess ICP non-invasively by simple mathematical rearrangement (i.e.
nICP= ABP – nCPP), is unclear.
The aim of this study was to compare the ability of these three non-invasive methods (20,22,28) to monitor experimental raise in ICP.
METHODS
All the animal experiments performed in this study were carried out in 1995 under UK Home Office license, with permission from the Institutional Animal Care and Use Committee at Cambridge University and in accordance with the standards set by the UK Animals Scientific Procedures Act of 1986. Recordings from 28 experiments of male New Zealand White rabbits (weighing from 2.7 to 3.7 kg) were analysed retrospectively, including high-resolution sampling of ABP, ICP, and basilar artery FV. The experimental protocols have been previously presented (24-26) and briefly described here.
A tracheostomy was performed and a jugular vein was cannulated. A femoral artery was cannulated and the catheter advanced to lie high in the dorsal aorta to monitor arterial blood pressure (GaelTec, Dunvegan, UK) and for blood gas analysis. The animals were placed on a padded warming blanket and the rectal temperature was monitored. A general anesthesia was induced using intravenous alphaxalone/alphadalone (Saffan, Pitman-Moore, Uxbridge, UK, 0.2mL/kg). Halothane at 1.5% in 3:1 nitrous oxide/oxygen was maintained. FV was monitored with an 8 MHz pulsed Doppler ultra- sound probe (PcDop 842, SciMed, Bristol, UK) positioned over the basilar artery. To access the artery, a posterior frontal burr hole (7 mm diameter) at the bregma to the left of the midline was made and the Doppler ultrasound probe was positioned over the exposed dura and adjusted to obtain the best Doppler spectra from the basilar artery. 2 weeks before experiment both carotid arteries of the rabbits were ligated (on different days), to make cerebral blood flow dependent on basilar artery flow. A second burr hole of diameter 1.5 mm was made over the contralateral cerebral hemisphere
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close to the bregma, and a Laser Doppler probe of 1 mm in diameter (Moor Instruments, Axbridge, Devon, UK) was placed epidurally. ICP was monitored through a third burr hole 1.5 mm in diameter, after insertion of an intraparenchymal microsensor (Codman and Shurtleff, Raynham, MA, USA).
Ventilation was controlled and PaCO2 monitored and stabilized adjusting the ventilator tidal volume (confirmed by blood-gas analysis) to normocapnia. Parameters were compared at baseline ICP and ABP. A laminectomy was performed in all the rabbits and a catheter was inserted into the lumbar subarachnoid space. After recovery from surgery and stabilization of PaCO2, ABP, ICP, basilar artery FV and Laser Doppler Flowmetry LDF values were recorded to establish a baseline before experimental manouvers.
ICP was increased by infusion of Hartmann’s solution into the lumbar catheter in the subarachnoid space at an increasing the rate from 0.1 to 2 mL/min to produce a controlled and marked rise in ICP. ABP, CPP and FV were continuously recorded, converted into digital samples using an analog-to-digital converter fitted into an IBM-compatible personal computer (27) and saved on hard disk in digital form, with sampling frequency 50Hz.
Data acquisition and analysis
The recorded signals were analyzed using our own software for clinical data processing (ICM+; http://www.neurosurg.cam.ac.uk/icmplus). The maximal and minimal values of ABP and FV from consecutive 2 s epochs were derived and then averaged over 10 s to give ABPs, ABPd, FVs and FVd, respectively. Fundamental amplitudes of FV and ABP pulse waveforms were calculated using spectral analysis. Heart rate was calculated using position of the spectral peak associated with the first harmonic of ABP. Mean values of ABP, ICP, FV, and CPP (and non-invasive indicators of ICP described below) were calculated in 30 second epochs by ICM plus.
