Review Br. J . Surg. 1992, Vol. 79, August, 735-741

A. R . Naylor, P. R . F. Bell and C. V. Ruckley* Departments of Surgery, Leicester Royal Infirmary, Leicester and *The Royal Infirmary, Edinburgh, UK Correspondence to: Mr A. R. Naylor, Department of Surgery, Leicester Royal Infirmary,

Leicester LE2 7LX. UK

Monitoring and cerebral protection during carotid enda rterectomy Two recently published multicentre trials have confirmed the overall benefit of carotid endarterectomy in symptomatic patients with severe carotid artery disease. The key to improving further the long-term advantages of carotid endarterectomy, however, remains the continued reduction of the initial operative risk, While the principal responsibility f o r this continues to be borne by the surgeon, specifically in reducing technical error, the time is perhaps approaching when he or she might also be able to apply some of the recent advances in cerebrovascular research to reduce operative morbidity still further in the future. This article summarizes the aetiology and pathophysiology of operationrelated neurological deficits and reviews current approaches towards intraoperative monitoring, cerebral protection and assessment of quality control.

‘The discussion of ways to prevent neurologic complications cannot be limited to the pros and cons of a temporary shunt.’ Alain Branchereau’

The European and North American trials have shown that carotid endarterectomy offers a better long-term prognosis than medical therapy in symptomatic patients with a severe ( > 70 per cent) stenosis of the internal carotid artery (ICA)’13. These results have important implications. First, referral practice and investigation will have to change so that appropriate patients can be considered for surgery or medical therapy; it will no longer be acceptable simply to start patients on aspirin without further investigation. Second, operative risks must be reduced, particularly if a greater proportion of higher risk patients are referred. This entails more than just careful patient selection and meticulous technique. Recent advances in knowledge of the pathophysiology of cerebral ischaemia (which often fail to reach the general or vascular surgical literature) have important implications for the development and application of cerebral cytoprotective agents and, by inference, for the attitude of surgeons towards intraoperative monitoring.

Pathophysiology of operation-related neurological deficits The risk of death and/or major stroke after carotid endarterectomy2x3is 2-4 per cent, although the morbidity rate is significantly higher if all minor neurological deficits are included4, possibly increasing to 12 per cent if silent infarcts seen on computed tomography ( C T ) are considered5. Two-thirds of operative strokes occur during surgery, of which 20 per cent are probably haemodynamic in origin6. While embolization remains the principal cause of morbidity, a higher proportion of intraoperative strokes are caused by haemodynamic failure than is observed in the natural history of spontaneous stroke, of which perhaps 1-2 per cent arise in this way7. Particulate embolization is invariably associated with technical error (Table 1 ). Air embolization may occur in up to 90 per cent of patients, particularly following shunt insertion

ooO7-1323/92/08073547

8 1992 Butterworth-Heinernann

Ltd

and final restoration of f l o ~ ~and , ~ although , its significance remains controversial, it is clearly undesirable and merits further study. Apart from cross-clamping, a haemodynamic stroke may follow a critical reduction in boundary zone perfusion pressure secondary to intracranial occlusive disease or may occur as a consequence of shunt complications (occlusion, kinking, malpositioning, spasm). In the absence of transcranial Doppler ultrasonography ( T C D ) or other in-line monitoring methods, one might incorrectly attribute any ensuing neurological morbidity to shunt-induced embolism rather than to a haemodynamic cause. After operation strokes tend to be thrombotic, although embolization and intracerebral haemorrhage may also occur. Early thrombosis may affect 2 per cent of patients”, and may even start during the operation owing to an enhanced rate of platelet deposition”.”. Thrombosis may be associated with technical error such as an arterial kink, intimal corrugation or flap formation, but may also result from a systemic cause such as hypotension or a heparin-mediated platelet membrane antibodyI3. Certain patients appear to be at higher risk of operative stroke, including those with a history of crescendo transient ischaemic attacks or recent stroket4, evidence from CT of infarction’ ’, a residual neurological deficit before operation4, and complex ulcerated lesions at the carotid bifurcation4.“. The latter condition has not been well studied. Although embolization by relatively large particles or thrombi is the principal cause of intraoperative stroke, insufficient attention has been paid to the vulnerability of the haemodynamically compromised brain to minor embolization or an apparently innocuous reduction in cerebral perfusion pressure4. Impaired cerebral vascular reserve (arterioles with a reduced capacity to vasodilate in response to a declining cerebral blood flow) and cerebral embolization are not mutually exclusive and may explain why certain patients are more at risk during surgery4, particularly as it has been shown that the normal brain is better able to withstand periods of ischaemia than is a brain that has previously suffered ischaemic damageI7. In other words, patients with cerebral infarction, a residual neurological deficit, and partial or total haemodynamic compromise are less capable of adapting to reduced perfusion or minor emboli, so the margin for technical error is reduced or possibly non-existent.

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Carotid endarterectomy: A. R. Naylor et al. Table 1 Factors associated wifh development

of an

intraoperative neurological deficit

Embolic

Thrombotic

Haemodynamic

Atheromatous plaque Carotid dissection or mobilization Shunt insertion

Perioperative hypotension

Carotid clamping Shunt occlusion or kinking

Uncorrected internal carotid artery kink or loop

lntimal flaps Clamp induced Residual Shunt induced

Platelet-fibrin thrombus Idiopathic Heparin dependent Wall irregularity Intimal flap

Incomplete endarterectomy

Hypoplastic internal carotid artery

Suture stenosis Distal arteriotomy closure Toe of patch angioplasty

Perishunt thrombosis

Shunt malpositioning or malfunction Shunt-induced spasm Intracranial disease or thrombosis

Air embolism Shunt insertion Inadequate backventing of arteriotomy

Pathophysiology of cerebral ischaemia A perfusion of 40-60 ml per 100 g brain per min provides a plentiful supply of oxygen and metabolic substrates for aerobic respiration to maintain high-energy phosphate stores, half of which are used to maintain the sodium-potassium ionic pump'' and a resting neuronal membrane potential d i f f e r e n ~ e ' ~ of -70 mV. As the pressure gradient across an extracranial carotid stenosis increases, there is first a compensatory increase in cerebral blood volume (in order to maintain cerebral blood flow) followed by an increase in oxygen extraction fraction, before the true haemodynamic reserve is exhausted and cerebral blood flow declines2'. Below 12-15 ml per 100 g brain per min the electroencephalogram (EEG ) becomes flat or isoelectric and evoked potentials disappear; this perfusion level is termed the flow threshold for failure of neuronal electrical function". Below this level, metabolism switches to anaerobic glycolysis but residual perfusion is still sufficient to maintain near-normal adenosine 5'-triphosphate ( A T P ) levels'', i.e. there exists a narrow range of perfusion (perhaps 5-7 ml per 100 g brain per min) in which there is loss of cerebral electrical activity, but sufficient blood flow to maintain high-energy phosphate stores and hence cell viability. Below 10 ml per 100 g brain per min a complex sequence of events occurs which if not arrested will lead to neuronal death; this perfusion level is termed the flow threshold for failure of energy metabolism and ion pumping". Declining high-energy phosphate stores cause rapid failure of ionic pumps with a net efflux of potassium ions and influx of sodium and chloride ions and water,', ultimately causing cellular oedema and anoxic membrane depolarization22.Lactic acid accumulation reduces cellular p H and may cause damage in its own right23, while the presence of hyperglycaemia at the time of ischaemic injury may increase the ensuing volume of cerebral i n f a r ~ t i o n , ~ . Within a short time, there is a significant increase in the extracellular concentration of the excitatory neurotransmitter glutamate'' resulting from the combination of depolarization and failure of glutamate reuptake mechanisms26. Moreover, this spreading wave of depolarization can extend into adjacent non-ischaemic tissues and further potentiate the accumulation of glutamate. The combination of membrane depolarization and glutamate accumulation repeatedly activates the N-methylD-aspartate ( N M D A ) receptor complex. This receptor complex is linked to an ion channel that controls calcium entry into the cell2' and, once the channel is open, there is a rapid influx of calcium ions. The presence of raised intracellular calcium ion concentrations (augmented by increased calcium release from impaired mitochondria and the endoplasmic reticulum) triggers a cascade of events that culminates in neuronal death from the release of proteases and lipases, free radical and superoxide formation, and the activation of phospholipase A,, causing

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release of arachidonic acid and prostaglandins which predispose towards vasoconstriction and platelet aggregati~n'~-~'.

Reducing the operative risk A commitment to reducing the operative risk should include not only an attempt to ensure adequate perfusion, but should also exploit the recent advances in cerebrovascular and metabolic research and improve quality control through a combination of personal audit, reduction of technical error and careful intraoperative assessment. General considerations A heightened awareness of the need for meticulous technique is the key to reducing operative risk because most of the factors associated with operation-related morbidity are secondary to technical error (Table 1 ). Carotid dissection before clamping should be minimal to reduce the risk of embolization; in many centres the carotid bifurcation is not dissected until the distal ICA has been clamped'. It is essential t o leave the endarterectomy surface free of intimal flaps and debris, and this can be made easier by the use of operating loupes or by argon laser radiation3' which also welds the endarterectomy endpoints. The arteriotomy site should be carefully backvented and flushed, although one should be aware that preliminary venting up the external carotid artery (before releasing the ICA clamp) may also lead to cerebral embolization via reversed flow in the ipsilateral ophthalmic artery'. The toe of the vein patch or the most distal aspect of the arteriotomy is prone to suture-induced stenosis. This can be prevented by the use of interrupted sutures around the apex or using a stent to aid closure. One should also be aware of the potential for kinking and corrugation of the carotid bifurcation and, if necessary, correct for this. The role of the shunt in carotid surgery is controversial, primarily because it has never been clearly proven to be of benefit. Despite its attractive logic, there are a number of negative features which include difficulty of insertion in the small-calibre carotid, problems visualizing the plaque endpoint, risk of atheromatous or air embolism, intimal dissection or plaque elevation, occlusion, malpositioning or malfunction, kinking and perishunt thrombosis. With care, however, all these problems may be avoided and shunt patency can be monitored using TCD~. Surgeons rely on anaesthetists to maintain a stable cardiovascular environment during carotid endarterectomy. General anaesthesia reduces cerebral metabolism and hence oxygen consumption; isoflurane in particular is associated with fewer EEG changes during carotid clamping than ha1othane3,. Most centres advocate a policy of maintaining blood pressure as close to the preoperative level as possible, although this may

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be complicated by the hypotensive nature of many anaesthetic agents and barbiturates. Others have recommended a blood pressure approximately 10-20 per cent above Intraoperative hypertension (whether therapeutically induced with phenylephrine or catecholamine-driven as with local or regional a n a e s t h e ~ i amay ~ ~ )be associated with a higher risk of myocardial i ~ c h a e m i a ~The ~ . benefits of slight to moderate hypertension must be balanced against the cost in terms of morbidity, remembering that in some studies myocardial events have been the leading cause of postoperative death35. The rationale behind maintenance of systemic arterial blood pressure (SABP) is its close relationship to ICA stump pressure and cerebral perfusion pressure, and hence to the delivery of oxygen and glucose to the brain. This is particularly relevant during carotid clamping because cerebral autoregulation may be impaired. ICA stump pressure and cerebral blood flow may be manipulated by increasing SABP36 and this alone may reverse electrophysiological abnormalities associated with carotid clamping37.In patients with unilateral carotid disease, a 3-mmHg increase in SABP (after carotid clamping) produces a 1-mmHg rise in stump pressure, whereas in patients with significant bilateral ICA disease a 7-mmHg increase in SABP is required to raise the stump pressure38 by 1 mmHg. The normally occurring reduction in cerebral perfusion pressure in the boundary zones between the principal vascular territories must also be c o n ~ i d e r e dThese ~ ~ . areas become more vulnerable to an intraoperative drop in blood pressure if there are any associated intracerebral occlusions or stenoses, or areas of infarction surrounded by an already compromised penumbra". Moreover, this vulnerability may be aggravated by factors that impair cerebral autoregulation such as the use of volatile anaesthetic agents4' and in hypertensive patients (whose autoregulatory curve is shifted to the right) and those with any other condition that may be associated with pial arterial vasodilatation. Potential role of cerebral protective agents The traditional approach to the development of ischaemia is early restoration of cerebral blood flow. This is illustrated by the tendency of many surgeons to re-explore the operated ICA to exclude thrombosis as soon as possible after discovering a postoperative neurological deficit. This will not, however, help in the case of focal, intracerebral embolic events, and restoration of blood flow alone may not reverse an ischaemic deficit4'. With advancing knowledge of the pathophysiology of cerebral ischaemia, attention is now being directed towards cytoprotection (in addition to improving blood flow). Advances relate primarily to reversing the effects of calcium ion-induced neurotoxicity, preventing free radical release and avoiding hyperglycaemia. One of the most promising avenues of research is an attempt to intercept the cascade of events mediated by calcium ion influx. This might be achieved by agents that block the NMDA receptor directly, via its linked ion channel, or by calcium antagonists that do not appear to be receptor mediated4'. There is an increasing body of in vitro and in vivo evidence that competitive and non-competitive NMDA antagonists may reduce ischaemic neuronal injury following transient global ischaemia (e.g. after a cardiac arrest) and following focal ischaemic events (e.g. embolism)27. Overall, the results for global ischaemia are not as promising as those for focal injuriesz7 but, as cytoprotection from the latter would be the principal aim in carotid surgery, NMDA antagonists may yet prove promising for intervention or prophylaxis. The apparent discrepancy between global and focal injuries is thought to be because NMDA antagonists may be maximally cytoprotective only in situations where there is still some remaining cellular energy production (e.g. in the ischaemic penumbra), thus enabling some residual capacity for ATP-driven calcium ion extrusionz7.The most consistent finding in animal models of focal ischaemia has been a reduction in the ensuing volume of cerebral infarction when NMDA antagonists are administered

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before, and even after, the onset of ischaemiaz7. Other agents currently under assessment are the non-receptor-mediated calcium antagonists, such as flunarizine4'. Although the exact mechanism of action is unknown, evidence suggests that a delay is caused in the onset of anoxia-induced depolarization and that there is a reduction in calcium ion influx41. Flunarizine has few significant side-effects and because it has already been used in humans for the treatment of vertigo, migraine and epilepsy, may be one of the first agents to be used in controlled trials4'.

Rationale for intraoperative monitoring A number of monitoring methods were developed and subsequently rejected, usually because they failed to influence neurological morbidity. This problem is highlighted by current attitudes towards the use of a temporary indwelling shunt which is inserted routinely or selectively to maintain adequate cerebral perfusion during carotid clamping. As noted above, there is no convincing evidence that shunting reduces the operative risk. Now that carotid endarterectomy has found an established place, it is clearly time to embark on carefully designed, randomized trials to evaluate the role of the shunt and, more importantly, the correct criteria for its deployment. If a policy of selective shunting is to be employed, the risk-benefit analysis is dependent on restricting the use of the shunt to those patients at risk of critical clamp-induced i ~ c h a e m i areliable ~ ~ ; methods are required to identify patients who are in the threshold area between electrical and neuronal failure. Experience suggests that shunting alone is not the answer'. The design of future trials must now be considered to evaluate the role of glutamate and calcium antagonists, free-radical scavengers and the avoidance of hyperglycaemia in the reduction of operative risk. These agents should not, however, be expected to confer immunity against developing a neurological deficit. Nevertheless, it is possible that some might prevent extension of ischaemia from the central core of infarction (where there is no residual energy production) towards the periphery, where impaired but functionally viable neurones have some capacity for ATP production, and so reduce the extent of the ensuing neurological deficit. Ideally, a safe agent that could be given on the induction of anaesthesia is needed. If this were possible, monitoring might become less necessary, but because some glutamate antagonists may be associated with hypotension4' or cognitive impairment43 a rationale for intraoperative monitoring must be developed that allows identification of impending ischaemia which is not resolved by first-line methods (control of blood pressure, shunt insertion). No single monitoring method is infallible, partly because of the heterogeneity of the causes of cerebral ischaemia, the complex and often unpredictable sequelae of cellular events and the variable location of the ischaemic insult (i.e. lacunar as opposed to cortical). Monitoring is expensive, particularly when technical support is required, but the avoidance of catastrophic complications is so important that proper evaluation of available methods is essential.

Current intraoperative monitoring methods There are a number of methods for monitoring cerebral function and outcome during carotid endarterectomy (Table 2). A few, notably measurement of jugular venous oxygen saturation or transconjunctival oxygen tension, and supraorbital photoplethysmography, have not been accepted because of their failure to correlate with other monitoring methods and clinical outcome. Neurological testing in the awake patient It is generally accepted that neurological testing while the patient is awake (during regional anaesthesia provided by a combination of deep and superficial cervical plexus blockade) is one of the most sensitive monitors of cerebral function44.

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Carotid endarterectorny: A. R. Naylor et al.

Table 2 Current intraoperative monitoring methods Assessment of adequacy of cerebral perfusion during clamping Neurological testing in the awake patient

Electroencephalography Somatosensory evoked potentials Cerebral perfusion measurement Transcranial Doppler ultrasonography Internal carotid artery stump pressure Internal carotid artery backflow Jugular venous oxygen saturation Transconjunctival oxygen tension Supraorbital photoplethysmography Identification of intraoperative embolization Transcranial Doppler ultrasonography Verification of shunt integrity and function Transcranial Doppler ultrasonography In-line Doppler ultrasonography flow probes Assessment of complete endarterectomy Intraoperative angiography Intraoperative ultrasonography Intraoperative angioscopy

Following carotid clamping, up t o 21 per cent of patients may develop aphasia, contralateral paresis, changes in mental status or loss of consciousness45 which can usually be reversed by raising the blood pressure or insertion of a shunt. The majority develop symptoms within 2 min of clamping46 but, because symptoms may occur later at 10-20 min after clamping47, the anaesthetist should continue to test the patient throughout the procedure. This form of testing can identify patients at high risk even when sensitive EEG monitoring remains normal48, possibly because the ischaemic insult is located within the deeper structures of the brain and internal capsule. Moreover, assessment while awake may be of particular benefit for patients with a previous stroke or infarct as new electrophysiological abnormalities may be difficult to identify when superimposed on pre-existing abnormalities4’. Despite these many advantages, most surgeons and anaesthetists prefer to use general anaesthesia. The principal problems of operating on the awake patient include a variety of cardiovascular effects, especially h y p e r t e n ~ i o n ~which ~ , increases myocardial oxygen demand and the risk of myocardial infarction. This is particularly relevant in patients with a history of ischaemic heart disease who may represent 57 per cent of the population undergoing carotid surgery4’. Further problems include patient compliance and discomfort, movement during dissection, and maintenance of the airway; cerebral metabolic requirements are at their greatest during awake testing. Electroencephalography and evoked potentials The EEG represents the summation of spontaneous electrical activity arising from postsynaptic potentials (primarily from the superficial layers of the cerebral cortex) which may be excitatory (depolarizing) o r inhibitory (hyperpolarizing)”. The amplitude of the EEG (pV) and power (pV2) are indicators of the ‘amount of EEG activity’ present5’, while the frequency component is reflected as the relative distribution of frequencies (6, 8, CI,B). The rationale for using an EEG is that as perfusion falls below 18ml per 1OOg brain per min there is loss of high-frequency activity and lower amplitude wave?’, while below 15ml per 1OOg brain per min the EEG becomes isoelectric, i.e. early focal changes appear. The latter is seen in 10-29 per cent of patients after carotid clamping5’ and is assumed to represent a higher risk of developing ischaemia; it warns the anaesthetist that the threshold for loss of electrical activity is approaching. Appropriate intervention may be undertaken to improve the circulation, or a shunt may be inserted. The development of EEG abnormalities does not necessarily represent the presence of a neurological deficit as the threshold for cellular ischaemia is lower, which may explain the discrepancy between the incidence of EEG changes and

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neurological deficits during awake testing52 and overall operative morbidity rate53. It also explains why reliance on EEG criteria for shunting increases the rate of shunt usage compared with that used during awake testing54. There is also no association between extent of change in the EEG and severity of ensuing neurological More importantly, because the EEG reflects changes principally in the most superficial layers of the cerebral cortex, there may be no apparent EEG abnormality in the presence of significant subcortical or internal capsular i ~ c h a e m i a ~ Moreover, ~. the EEG may be influenced by diathermy54, the type of general anaesthesia used56,arterial partial pressure of carbon dioxide ( Paco2),h y p o t e n ~ i o nand ~~ clinical presentation. Patients with a previous stroke or infarction are significantly more likely to have pre-existing EEG abnormalities, which may make subsequent interpretation of new and subtle changes more d i f f i ~ u l t ’ ~such ; patients are precisely those a t highest risk of suffering an intraoperative neurological deficit. Also, vulnerable cerebral tissue in the ischaemic penumbra surrounding an infarct may be electrically silent5’. As a consequence, accurate interpretation of EEG changes requires highly sensitive multichannel equipment and an experienced technician with access to either a neurophysiologist or neurologist. Because many centres have staffing or financial limitations, and because many consider the EEG to be o v e r ~ e n s i t i v e attention ~~, has been directed away from the unprocessed ‘raw’ EEG (multiple channels displaying voltage as a function of time) to processed EEG systems. Here the raw EEG data are analysed, condensed and presented in a more easily interpreted way by filter processing, power spectrum analysis, period-amplitude analysis and waveform analysis. A number of such systems are now available for evaluation in trials. One uses period-amplitude analysis, which enables zero-crossing rates, integrated amplitude values and interhemispheric asymmetry ratios to be calculated and presented as easily interpreted graphical displays, in association with on-line recording of basic patient data such as blood pressure, drug administration, anaesthetic regimen, etc. Transient interhemispheric asymmetry (responding to manipulation of blood pressure or shunting) has never been associated with an intraoperative stroke but 50 per cent of patients with persisting asymmetry have been shown to develop major neurological morbidity57.Such a system could be used in trials of cerebroprotective agents. The potential value of somatosensory evoked potentials (SEPs) in carotid surgery was first evaluated by Markand et ~ 1 in . 1984. ~ Unlike ~ the EEG, which is oversensitive to the superficial layers of the cortex, SEPs reflect the integrity of the afferent pathways from the peripheral nerves to the somatosensory cortex, including the internal capsule. Following stimulation of the median nerve at the wrist, an ascending volley of potentials is generated which travels up the afferent sensory nervous system to the somatosensory cortex via the spinal cord and brain stem”. The SEPs, recorded by scalp electrodes, are time-averaged (the mean of a large number of artefact-free responses) in order that relatively low-voltage potentials can be demonstrated with minimum extraneous noise”. They are displayed graphically to permit calculation of the central conduction time (the time taken by the afferent stimulus to pass from the dorsal column nuclei to the sensory cortex) and the amplitude of the primary cortical potential. Evidence suggests that these parameters may be better indicators of impending cerebral ischaemia than changes in latency5’, and that they correlate better with cerebral blood flow6’ and are perhaps more sensitive than the EEG6’. A number of criteria for shunting have now been advocated, the most common being a 50 per cent reduction in the amplitude of the primary cortical wave and prolongation of the central conduction time by 1 ms. Appropriate use of these criteria6’ may reduce the rate of shunt usage to about 11 per cent. The principal advantage of SEP monitoring is its ability to evaluate the deeper structures of the brain, but it requires a finite time for data to be acquired, averaged, filtered and displayed. An experjenced operator is essential to exclude artefacts, as is access to a neurophysiologist

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or neurologist. In common with the EEG, SEPs are affected by a number of anaesthetic, analgesic and sedative drugs and by changes in blood pressure, all of which must be taken into account when interpreting the finding^'^,^^. Measurement of cerebral perfusion A few centres have operating table headrests that incorporate external scintillation detectors to enable measurement of cerebral perfusion after carotid clamping using the xenon washout t e ~ h n i q u e ' ~This . method requires a steady physiological state and is not very practicable. The inert gas washout method is oversensitive to the superficial layers of the cerebral cortex to the exclusion of the deeper regions of the brain; it may ignore ischaemic zones and record emissions from overlying normal tissues63. This may explain the discrepancy between cerebral perfusion and TCD findingP4, EEG a b n ~ r m a l i t i e s shunt ~ ~ , requirements (27 per cent for a critical level of 18 ml per 100 g brain per and neurological outcome66.In general, EEG changes are not usually seen with a perfusion in excess of 30 ml per 100 g brain per min, while major changes become apparent below 18 ml per 100 g brain per min; these thresholds may vary with different anaesthetic agentP. Internal carotid artery stump pressure and backjow The ICA stump pressure is the arterial pressure in the ICA distal to the clamp and represents the contribution of the vertebrobasilar and contralateral carotid inflows to the collateral c i r c ~ l a t i o n Its ~ ~ .use as an index of the collateral circulation during carotid clamping was proposed by Moore and Hall6' in 1969 and a range of thresholds (25-70 mmHg) have been recommended as criteria for shunt insertion. Although a single stump pressure measurement and subjective assessment of ICA backflow are probably the easiest and most accessible methods for assessing collateral flow, they do not reflect subsequent changes in perfusion during the entire period of clamping and may be dangerously misleading in the presence of significant middle cerebral artery (MCA) mainstem disease. Stump pressure is affected by a large number of factors36 including anaesthetic agents, systemic blood pressure, cerebral venous pressure, intracranial pressure, Ppco2and arterial partial pressure of oxygen; errors of between 5 and 50 mmHg may be present in up to 13 per cent of calculation^^^, usually because of problems with instrument calibration. Few authors actually state whether it is the systolic or mean pressure that is being measured. Overall, there is a tendency for a low stump pressure to correlate with an increased operative risk69, but one must accept that a reliance on stump pressure criteria will increase the rate of shunt usage5'. There may be an unreliable correlation with EEG data7', awake testing7', cerebral p e r f ~ s i o and n ~ ~clinical outcome73,particularly in patients with a previous history of stroke74. As with all monitoring techniques, however, its benefits must be balanced against its limitations; a high stump pressure will not protect a patient against embolization secondary to technical error. Transcranial Doppler ultrasonoyraphy By directing a low-frequency ultrasound beam through the relatively thin temporal bone, it is possible to measure blood flow velocity in the basal cerebral arteries75. The most important of these (with respect to carotid surgery) is the MCA and by using a fixed-head probe system it is possible to monitor mainstem velocity in this artery continuously throughout the operation'. This makes it more practical than cerebral perfusion methods but it is essential to remember that blood flow velocity is not synonymous with absolute blood flow; according to the Hagen-Pouiseille law, the latter is proportional to the fourth power of the vessel radius while velocity is proportional to the radius squared. This might explain some of the apparent discrepancies observed between MCA velocity and cerebral perfusion measurement^^^, particularly as the latter are more sensitive to the superficial regions of the cerebral cortex while

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the former perhaps reflects flow to the basal arteries. Thus, because the MCA diameter is unknown, overinterpretation of minor velocity changes should be avoided. In practice, however, provided end-tidal Pace, remains stable, it has become conventional to use relative changes in middle cerebral artery velocity (MCAV) as an index of change in associated blood Preliminary experience with TCD indicates that the technique shows the predictable changes associated with carotid clamping and shunt in~ertion'.~and that there is a good correlation between MCAV and ICA stump pressure'. A systolic ICA stump pressure of 50 mmHg corresponds to a peak velocity of 42 cm s - l and a mean velocity' of 30cm s-'. Few studies have correlated TCD with the EEG and SEP. These should be undertaken but it is inevitable that discrepancies will occur as the EEG and SEP reflect the functional state of the brain while TCD measures some parameter of blood flow. The introduction of TCD, however, often heightens awareness of potentially dangerous occurrences during carotid endarterectomy. These include excessive manipulation of the carotid bifurcation (as manifest by its resultant effect on the MCA waveform)8, shunt kinking and malfunction8, and air or particulate embolization (differentiation is at present not possible with TCD)839s77. TCD may also be helpful in differentiating between intraoperative haemodynamic or embolic neurological and can usually diagnose postoperative ICA thrombosis on the basis of directional flow changes in the circle of Willis. Overall, TCD shows considerable promise as a monitoring and quality-control technique, but is most likely to find its optimal role in conjunction with an electrophysiologicalmethod such as EEG or SEP measurement. Intraoperative assessment of carotid endarterectomy It is perhaps surprising, given the fact that the integrity of many other types of vascular reconstruction is verified by some form of on-table assessment, that similar consideration is so seldom applied to carotid endarterectomy. This is despite the fact that technical error is the most significant contributor to operationrelated morbidity, that the resultant effect may be catastrophic in severity, and that the 'time window' for intervention is probably very Perhaps some surgeons are reluctant to concede that, despite their very best efforts, some technical error may have escaped their attention. However, significant intraluminal abnormalities may be present that are not evident to either inspection or palpation78. In 1967, Blaisdell et al." demonstrated that up to 26 per cent of patients may have a technically unsatisfactory result following endarterectomy, including a 5 per cent on-table ICA occlusion rate. This experience has subsequently been verified by others using on-table a n g i ~ g r a p h yultrasonography ~~, (pulsed Doppler and spectral analysis78,B-mode imaging", duplex" or continuous wavea2) and occasionally angioscopys3. Angiography is limited by the need for clear biplanar views or fluoroscopic screening, while most duplex probes are too large to image the upper limit of the endarterectomy. However, using angiographic criteria of residual stenosis > 30 per cent, intimal flap > 3 mm, kinking or occlusion84, or flow disturbance detected by analysis of the back-scattered Doppler signal79, 2- 10 per cent of endarterectomy sites require r e - e x p l o r a t i ~ n ' ~.- Unfortunately, ~~,~~ on their own neither angiography nor ultrasonography is at present reliably accurate"; there is perhaps a tendency to screen with ultrasonography and to proceed to angiography when there are abnormal findings. In general, however, a normal laminar flow pattern or mild flow disturbance correlates with normal a n g i ~ g r a p h y ~Evidence ~. suggests that a policy of intraoperative assessment helps surgeons to improve their operative techniquea5and may start to reduce the incidence of operation-related morbidity".

Conclusion Carotid endarterectomy now has a justified place in the management of symptomatic cerebrovascular disease. However,

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Carotid endarterectomy: A. R. Naylor et al. despite almost 40 years of experience ( a n d more t h a n 1 000 000 endarterectomies ) certain questions still require answers. Monitoring equipment a n d technical staff are very expensive and, while many of the techniques are clinically useful, none has proven t o be clearly superior. But there are grounds for optimism. A commitment t o meticulous operative technique must be renewed which, with quality control and close collaboration with neurological, neurophysiological an d research colleagues, should lead t o safer surgery for patients in the years t o come.

References 1.

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Paper accepted 16 March 1992

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Monitoring and cerebral protection during carotid endarterectomy.

Two recently published multicentre trials have confirmed the overall benefit of carotid endarterectomy in symptomatic patients with severe carotid art...
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