Pa g e 77 A similar correlation has been found between SEP amplitude and cerebral blood flow. SEP monitoring can be easier to maintain as monitoring SEP amplitude produces only a single number which is more easily interpreted than the complex waveform seen with EEG. Metaanalysis of a number of series of SEP monitoring during surgery shows that SEP has a sensitivity of about 96%. 33 A number of centres monitor some index of cerebral blood flow as opposed to neurophysiological monitoring. Two of the more commonly applied methods are carotid stump pressure and transcranial Doppler. There are no controlled trials directly comparing outcome between neurophysiological monitoring and transcranial Doppler. EEG would appear to be at least as sensitive though possibly less specific than transcranial Doppler. 34 Comparison of stump pressure monitoring with EEG in the same patients would suggest that stump pressure monitoring is possibly more sensitive with similar specificity. 31 S pinal Surgery Operations which compromise the spinal cord or its blood flow can also be monitored using evoked potentials. Examples of such surgery include removal of spinal cord tumours and vascular malformations. There is also a small but significant risk of spinal cord damage associated with the surgical management of scoliosis. This occurs particularly with sublaminar wiring. The integrity of the spinal cord can be assessed by continuous monitoring of the SEP throughout the surgery. This can be done by recording the cortical SEP or spinal SEP with epidural electrodes. Monitoring of the spinal SEP has the advantage of being more robust and resistant to changes in anaesthetic concentration and blood pressure. There is no direct evidence from controlled clinical trials that monitoring reduces the incidence of complications. However, the occurrence and degree of preoperative changes correlate with the postoperative deficit and the risk of postoperative deficit is reduced if the electrophysiological changes can be reversed. 35,33 A multicentre survey has shown a lower incidence of complications in those centres where scoliosis surgery is performed with spinal monitoring performed by experienced staff. 36 Other Procedures In many neurosurgical procedures neurophysiological monitoring may be useful in minimizing the surgical morbidity. In pituitary gland surgery VEPs may be useful in monitoring for optic chiasm damage. 37 SEP and BAEP are useful means of monitoring brainstem function during surgery in posterior cranial fossa. 38,39 SEP and EEG monitoring allow detection of developing cerebral ischaemia in aneurysm surgery. 40,41 Electro p h y siolo g ical Monitorin g in the Intensive Care Unit The techniques of neurophysiology provide a useful extension of clinical examination in the assessment of patients in the intensive care unit. In particular, there are four areas where neurophysiological methods are beneficial: 1. making specific diagnoses; 2. continuous EEG or evoked potential monitoring of critically ill patients; 3. management of status epilepticus; 4. using EEG and evoked potentials to predict outcome. EEG and S p ecific Dia g noses While many neurological conditions are associated with changes on the EEG, the number of conditions with specific diagnostic EEG changes is limited. 42 Examples of these include herpes simplex encephalitis, post measles encephalitis and Creutzfeldt-Jakob disease (Fig. 5.9). There is also a subgroup of patients who may not be able to have an MRI scan for clinical reasons, in whom the EEG may p oint towards lateralized pathology such as ischaemia or space-occupying lesions before changes appear on CT scanning. Continuous Monitorin g The possibility of continuous EEG monitoring is very attractive. The goal of such monitoring would be to allow the clinician to detect cerebral dysfunction before it has become irreversible. In particular, the EEG demonstrates cerebral ischaemia, which may not be immediately obvious in the sedated patient, and subclinical seizures 43 . While the EEG reflects changes in intracranial pressure, this may not be relevant in centres with continuous intracranial pressure monitoring. However, there are considerable difficulties involved in establishing continuous EEG monitoring in the ICU setting. First, it is technically difficult to maintain a continuous low-noise, low-impedance connection between the patient and the EEG machine. To maintain a continuous connection therefore requires Pa g e 78 Figure 5.9 EEG in generalized status epilepticus. The EEG shows continuous high-amplitude epileptiform activity. special training of the nursing staff and several daily visits by the technician. Monitoring is also impeded by multiple generators of artefact in the ICU setting. High-frequency electrical noise is generated by other computerized equipment in the ICU. Mechanical ventilators generate both mechanical and electrical rhythmical artefact. Nursing procedures and chest physiotherapy can generate a large amount of mechanical artefact that is in the frequency range of the EEG. 44 Because of the large amount of data generated by continuous monitoring, the EEG is often supplemented by some form of automated EEG processing (Lifescan, CFAM or compressed spectral array). Given the considerable investment of time and resources required for continuous EEG monitoring in the ICU, it is pertinent to question the benefits of continuous monitoring. One study of patients with a variety of different neurological diagnoses showed that the EEG had a significant impact on patient management in 50% of cases. 45 In a study of 18 patients with carotid stenosis the EEG showed alteration when the patients were subjected to hypotensive or hypertensive stress and this information was a factor in considering patients for surgery. 46 Recent studies in acute stroke have shown that certain EEG patterns are predictive of a poor outcome and allow diagnosis of cerebral infarction before changes are seen on CT scanning. 47 Further, continuous monitoring allows detection of cerebral ischaemia and vasospasm in patients with subarachnoid haemorrhage, allowing treatment to begin earlier. 48 In one study alterations in the processed EEG predicted vasospasm before transcranial Doppler in 70% of cases. 49 In severe head trauma and postneurosurgical patients continuous EEG monitoring allows the immediate diagnosis and treatment of non-convulsive status epilepticus. Unfortunately, there are no controlled trials assessing the objective benefit to morbidity and mortality of continuous EEG. The indirect evidence that continuous EEG monitoring allows the detection of subclinical seizures and ischaemia suggests that when available, EEG monitoring is a useful adjunct to other forms of CNS monitoring in the management of the unconscious patient. Pa g e 79 The EEG in Status E p ile p ticus The EEG is an important tool in the management of both convulsive status epilepticus and non-convulsive status epilepticus (Fig. 5.10). While status epilepticus is a medical emergency and treatment should not be delayed if an EEG is not available, clinical examination alone may result in misdiagnosis of status epilepticus for two reasons. First psychogenic status is a common cause of diagnostic confusion. In one study 20% of patients presenting to an accident and emergency department of a tertiary referral centre with intractable convulsive movements had psychogenic seizures. 49 Second non-convulsive status is underrecognized and patients with non-convulsive status are often mislabelled as being confused or postictal. 43 Once treatment for convulsive status is established, the role for the EEG is not clear. Certainly in sedated patients treated with general anaesthesia, continuous EEG monitoring allows immediate recognition and treatment of seizures. Seizure activity increases cerebral metabolic rate of oxygen and causes excitotoxic cell damage. 50,51 Continuous EEG monitoring facilitates adequate seizure control without overtreatment in status epilepticus and reduces this risk of excitotoxic cell damage. While there are no controlled trials to support this conclusion, there is some indirect evidence. Mortality in status epilepticus increases with the duration of seizures. 52 It is therefore reasonable to assume that early detection of subclinical seizures in the ICU reduces mortality and mortality. Where continuous EEG monitoring is not available it is reasonable to obtain an EEG daily while the patient remains unconscious and to consider performing an Figure 5.10 EEG in Creutzfeldt–Jakob disease. The EEG shows a characteristic p attern of p eriodic p ositive shar p wave com p lexes. θ δ δ θ α δ Pa g e 81 Table 5.1 Prognostic validity of Synek's grading system 63 EEG pattern Survive d Die d Benign 15.9% 1.6% Uncertain 14.3% 13.2% Malignant 0 55% mately half of the 'uncertain' group died. Since about 30% of patients fell into this category, the grading system fails to fulfil the criteria of being a universally applicable prognostic test. In essence, it only provides prognostic information for 70% of the patient group studied. A convenient model for studying non-traumatic coma is that of coma following cardiac arrest in hospital. In this patient group the onset of coma is clearly documented and the timing of the EEG can be easily controlled. Four recently published studies adopting this model are summarized in Table 5.2. 64–67 In essence, they confirm the trend seen in the retrospective studies: an EEG pattern regarded as 'malignant' is a useful predictor of poor outcome but patterns regarded as 'benign' or 'uncertain' do not appear to predict a good outcome. Furthermore, a prospective study in traumatic coma, 68 although difficult to compare with the findings in non-traumatic coma (the data are presented as a correlation between EEG score and Glasgow Outcome Score), found a correlation between EEG score and outcome. However, the EEG did not add any further information to that provided by clinical assessment alone. The EEG is therefore a useful extension of clinical examination and is particularly helpful when clinical assessment is impeded. However, it is not always p ossible to make an accurate prediction of outcome on the basis of the EEG alone. The Somatosensory Evoked Potential (SEP) The SEP has several advantages over the EEG in assessing outcome. In the EEG there are many patterns which have to be subjectively graded whereas the SEP is either present or absent, delayed or not delayed, with a normal or abnormal waveform. Many studies have looked at using the SEP to predict outcome in both traumatic and hypoxic coma. These are summarized in Table 5.3. 64– 66,69–74 To compare studies, we divided SEP findings into three groups: 1. normal SEP where the latency and the waveform of the SEP were within acceptable limits; 2. unilaterally abnormal SEP where the SEP is either delayed, absent from one hemisphere or has an abnormal waveform; 3. bilaterally absent SEP. As with the EEG, the SEP accurately identifies a group of patients who do badly. Patients with bilaterally absent SEP will invariably have a bad outcome. These findings are supported by a systematic review of prediction of poor outcome in anoxic ischaemic coma. Pooled data from 11 studies showed that a bilaterally absent SEP is the most accurate predictor of a poor outcome. 75 However, if the SEP is present patients may still do badly, so in this group of patients the SEP does not provide any additional prognostic information. Unlike the EEG, which is generated by the brain alone, the SEP may be influenced by injuries Table 5.2 Summary of four prospective studies looking at EEG grade and outcome in hypoxic/ischaemic coma (from references 64–67 ) Authors No. of patients No. with benign, uncertain or grades I–III No. with good outcome (GOS 3–5) No. with malignant or grades IV or V No. with bad outcome Death or PVS Chen et al 34 12 5 22 20 Rothstein et al 40 29 14 11 11 Scollo et al 26 12 5 14 12 Bassetti et al 60 40 12 20 20 Total 160 93 36 66 61 Pa g e 82 Table 5.3 Using SEP to predict outcome in coma (from references 64–66,69–74 ) Author No. of patients Normal SEP No. with good outcome Abnormal SEP No. with good outcome Absent SEP No. with good outcome Cant et al 40(T) 21 17 5 3 14 2 Judson et al 100(T) 38 33 26 19 36 3 Bassetti et al 60(H) 20 10 12 1 23 0 Brunko et al 50(H) 20 5 Not given Not given 30 0 Chen et al 34(H) 16 7 6 2 12 0 Goldie et al 36(T) 16 9 8 2 12 6 Rothstein et al 40(H) 14 11 7 3 19 0 Goldberg 24(H+T) 4 4 15 9 5 0 Goodwin 37(H+T) 8 6 2 0 29 0 H = hypoxic/ischaemic coma T = traumatic coma elsewhere in the nervous system, including the peripheral nerves and spinal cord. There are a number of studies where the SEP grade or central conduction time is correlated with final outcome or disability score, in all of which the SEP was more effective than clinical examination alone. 58,76,77 B rainstem Auditor y Evoked Potential (BAEP) The BAEP has a number of theoretical advantages over the SEP for assessing prognosis. It is less likely to be influenced by injury elsewhere in the nervous system. It would appear logical to assume that the brainstem is the most critical point in determining survival so assessing brainstem function should give a good guide as to prognosis. Again, the value of BAEP in assessing prognosis has been investigated in a number of studies. 60,78,79 Some of these are reviewed in Table 5.4. A significant relationship between interpeak latency and mortality has also been shown. 80 An abnormal BAEP does not always imply a poor outcome and in three of the four studies reviewed, a significant number of survivors had an abnormal BAEP. BAEP would appear to be less useful than the SEP in prediction of outcome. E ven t -Related Potentials These are scalp potentials produced in response to a simple discrimination task and are probably the electrophysiological representation of cognitive processing. They are probably generated by subcortical/cortical and cortico/cortical circuits and therefore have a potential theoretical application in predicting coma outcome since they depend on an extensive network of connections. One such potential, the P300, was used to predict outcome in a group of 20 patients 81 in non-traumatic coma. The relationship to outcome in this study is summarized in Table 5.5. The P300 is useful to identify a subgroup of patients who will improve but unfortunately does not identify those patients who will do badly. Another auditory event-related potential is the mismatch negativity (MMN) in oddball paradigms of AEP recording. The relationship of MMN to outcome was examined in a group of hea d -injured patients 82 and is summarized in Table 5.6. The other interesting finding in this study was the role of MMN in predicting awakening. They found a subgroup of 13 patients in whom the MMN was initially absent but later returned. The return of the MMN always preceded clinical awakening (by 24 h to 21 days). R ole of Functional Imagin g Functional imaging techniques such as positron emission tomography (PET), single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI) allow an accurate determination of regional cerebral blood flow and metabolism. Studies with SPECT in acutely brain-injured patients can potentially be used to estimate the severity of brain injury and to predict clinical outcome. 83,84,85 In addition, early studies have shown a strong correlation between alteration in the EEG and changes in cerebral blood flow elucidated with PET. 86 Pa g e 83 Table 5.4 Summary of studies looking at outcome and BAEP (from references 60,78,79 ) Author No. of patients No. with normal BAEP No.of survivors No. with abnormal BAEP No. of dead or PVS Cant et al 40 32 19 8 7 Karnaze et al 26 19 17 7 4 Karnaze et al 45 29 28 16 8 Goldberg 32 16 16 16 5 Studies which combine functional imaging with EEG and evoked potentials will allow a greater insight into the changes in cerebral blood flow and metabolism which underlie the changes which are seen on the EEG in acute brain injury. This knowledge may allow EEG to be even more widely applied in determining the severity of brain injury and predicting clinical outcome. Conclusion There are significant correlations between parameters measured by many of the neurophysiological techniques and outcome. However, none of the techniques listed above is sufficiently accurate to predict outcome in all cases. Can the accuracy of these neurophysiological techniques be improved? A number of studies have examined the predictive value of combinations of either EEG and SEP 63,65 or SEP and BAEP. 87 As the EEG or BAEP is less effective at predicting outcome than SEP, the combinations are not much more effective than SEP alone. However, a combination of bilateral SEP and EEG is easily obtained and interpreted. The EEG may give other useful information such as the detection of epileptiform activity or burst suppression. Using these techniques, a group of patients in whom there is a high probability of a bad outcome can be identified. More specialized techniques such as event-related potentials may have a role in patients with prolonged coma, particularly in predicting awakening. In the future it is predicted that functional imaging in combination with neurophysiology will widen the scope for the clinical assessment of brain-injured patients. Table 5.5 P300 and outcome in non-traumatic coma (from reference 81 ) Awake No awakening P300 present 5 1 P300 absent 4 10 Summar y EEG, nerve conduction studies and evoked potentials provide a safe and inexpensive means of monitoring brain function in the operating theatre and the intensive care unit. We hope that the newer techniques will shed light on the causes of the evolution in the EEG that occurs in anaesthesia and cerebral injury. An increasing understanding of the alterations in cerebral physiology which underlie electrophysiological changes in unconscious patients is likely to improve our ability to draw firm clinical conclusions based on the EEG. Acknowled g ements We would like to thank Mr Nicholas Carvill, Dr Julian Ray and Mr Martin Coleman for their assistance in the preparation of this manuscript. Table 5.6 MMN and outcome in traumatic coma (from reference 82 ) Alive Dead MMN present 35 1 MMN absent 4 14 References 1. Creutzfeldt OD, Watanabe S, Lux HD. Relations between EEG phenomena and potentials of single cortical cells. Spontaneous and convulsoid activity. Electroencephalogr Clin Neurophysiol 1966; 20: 19 – 37. 2. Thatcher R, John ER. Foundations of cognitive processes. 1977, Wiley, NewYork. Pa g e 84 3. Creutzfeldt OD. The neural generation of the EEG. In: Redmond A (ed) ECN handbook, vol. 2, part C, 1974, Elsevier, Amsterdam. 4. Li CL, Jasper HH. Microelectrode studies of the cerebral cortex of the cat. J Physiol 1953; 121: 117 – 140. 5. Burns BD. Some properties of the cat's isolated cortex. J Physiol 1950; 111: 50 – 68. 6. Jasper H. 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Sensitivity of rCBF to focal lesions Stroke 1981; 12: 631 – 635 23 Donley RF, Sundt TM Jr, Anderson RE et al Blood flow measurements and the 'look-through' artifact in focal cerebral ischemia Stroke 1975; 6: 121– 131 24 Obrist WD, Wilkinson WE Regional cerebral blood flow measurements in humans by Xenon- 133 Cerebrovasc Brain Metab Rev 1990; 2: 2 83 32 7 25 Obrist WD, Thompson HK, King CH et al Determination of regional... Localizing and prognostic value of auditory evoked responses in coma after closed head injury Neurology 1982; 32 (3) : 299 30 2 80 Facco E, Martini A, Zuccarello M, Agnoletto M, Giron GP Is the auditory brain stem response effective in the assessment of post traumatic coma? Electroencephalogr Clin Neurophysiol 1985; 62: 33 2 33 7 81 De Giorgio CM, Rabinowicz AL, Gott PS Predictive value of P300 event related... Rec 1 934 ; 54: 419–426 33 Stocchetti N, Paparella A, Bridelli F et al Cerebral venous oxygen saturation studied with bilateral samples in the internal jugular veins Neurosurgery 1994; 34 : 38 –44 34 Andrews PJD, Dearden NM, Miller JD Jugular bulb cannulation: description of a cannulation technique and validation of a new continuous monitor Br J Anaesth 1991; 67: 5 53 558 35 Cruz J Contamination of jugular... 1948; 27: 476–4 83 7 Kety SS, Harmel MH, Brommell HT et al The solubility of nitrous oxide in blood and brain J Biol Chem 1948; 1 73: 487–496 8 Mapleson WW, Evans DE, Flook V The variability of partition coefficients for nitrous oxide and cyclopropane in the rabbit Br J Anaesth 1970; 42: 1 033 –1041 9 Kozam RL, Landau SM, Cubina JM, Lukas DS Solubility of nitrous oxide in biologic fluid and myocardium J... myocardium J Appl Physiol 1970; 29: 5 93 597 10 Sharples PM, Stuart AG, Aynsley-Green A et al A practical method of serial bedside measurements of cerebral blood flow and metabolism during neurointensive care Arch Dis Child 1991; 66: 132 6– 133 2 11 Gibbs EL, Lennox WG, Gibbs FA Bilateral internal jugular blood Comparison of A-V differences, oxygendextrose ratios and respiratory quotients Am J Psychiatry... Figure 6 .3 Compartmental analysis of CBF using a semilogarithmic plot The curve shows flow through grey and white matter or fast and slow components respectively The inert gas clearance techniques have been modified over the years to reduce the disadvantages and enhance their applicability in the bedside measurement of CBF The radioactive isotope commonly used is 133 Xe because of its short half-life and. .. content between the left and right jugular bulb blood have been demonstrated in head-injured patients .33 Other factors that can affect the accuracy of CBF estimation using jugular bulb oximetry include contamination of jugular bulb blood with extracerebral blood, malpositioning of the catheter tip, speed of blood withdrawal from the catheter and the position of the patient's head .34 ,39 Therefore, for best... and Vi the volumes (ml) of blood and indicator, λb and λi the specific heat of blood and indicator, and ρb and ρi the density of blood and indicator If time is brought into the equation, the volumes become flows and: Figure 6.4 (Top trace) Diagrammatic representation of a thermodilution catheter using two thermistors which can be inserted in the jugular bulb for the measurement of CBF (Bottom trace) . indicator respectively, Vb and Vi the volumes (ml) of blood and indicator, λ b and λi the specific heat of blood and indicator, and ρ b and ρi the density of blood and indicator. If time is. Anaesth Analg 19 83; 62: 186 – 192. 30 . Ballotta E, Dagiau G, Saladini M et al. Results of electroencephalographic monitoring of 36 9 revascularisations. Eur Neurol 1997; 37 : 43 – 47. 31 . McCarthy. Neurophysiol 1985; 62: 33 2 – 33 7. 81. De Giorgio CM, Rabinowicz AL, Gott PS. Predictive value of P300 event related potentials compared with EEG and somatosensory evoked potentials in non-traumatic coma.