Description of the condition
Around 20% of patients presenting with transient ischaemic attack or non-disabling ischaemic stroke have a significant stenosis with unstable atheromatous plaque at or around the bifurcation of the ipsilateral carotid artery. This plaque gives rise to the embolus. Carotid endarterectomy is an operation to remove this stenosis together with unstable plaque and, therefore, decrease the risk of stroke.
Description of the intervention
Carotid endarterectomy has been shown in large, well-conducted randomised controlled trials (RCTs) to reduce the risk of stroke in patients with recently symptomatic, severe (greater than 70%) internal carotid artery stenosis (ECST 1991; NASCET 1991). In a pooled analysis of data from these RCTs of endarterectomy versus medical treatment, surgery was of marginal benefit in terms of the five-year risk of ipsilateral ischaemic stroke in those with 50% to 69% stenosis, and was highly beneficial in those with 70% stenosis or greater without near occlusion (Rothwell 2003; Rerkasem 2011). These benefits were seen despite the significant perioperative risks associated with carotid endarterectomy. The risk of stroke or death within 30 days of the operation was between 5% and 7% in the trials. If the risk of perioperative stroke could be reduced, the benefits from carotid endarterectomy would be greater. Thus it is important to make the operation as safe as possible.
Some perioperative strokes occur during the operative procedure and may relate to reduced blood flow during carotid artery clamping. If the onset of such strokes could be recognised early, it may be possible to reverse the ischaemia by placing a shunt across the clamped artery, thereby increasing blood flow. In patients operated on under general anaesthetic, the development of a new stroke is only recognised after recovery from the anaesthetic. In order to minimise the operative risk of stroke, several different approaches to shunting have been adopted when the procedure is performed under general anaesthetic: namely the placement of a shunt in all patients (Javid 1979; Thompson 1979; Gumerlock 1988); the placement of a shunt in some patients thought to be at risk of an operative stroke (Ricotta 1983; Sundt 1986; Buche 1988; Schweiger 1988; Steiger 1989); or avoiding a shunt altogether (Prioleau 1977; Ott 1980; Reddy 1987). The avoidance of a shunt is based on the fact that only a small minority of patients do not tolerate arterial clamping without a shunt. Shunting may be associated with risks such as intimal damage promoting early postoperative thrombosis and late restenosis, which cause stroke. Thus, to many people, the selective method appears to be the most appropriate because it implies that only those patients who are at risk of having a stroke during carotid clamping are exposed to the risks of shunt placement. However, there is little consensus about the best way of identifying those patients who are at risk of stroke during the procedure. Several methods have been used to identify patients at risk of stroke including preoperative assessment (e.g. a history of recent stroke or occlusion of the contralateral artery), and a variety of techniques designed to directly or indirectly monitor cerebral blood flow during surgery. Techniques for monitoring blood flow during surgery include electroencephalographic monitoring, somatosensory evoked potential monitoring, transcranial Doppler monitoring, and measurement of the internal carotid artery back pressure (Rerkasem 2010). However, these methods are not reliable for detecting intraoperative stroke (Bass 1989; Gnanadev 1989; Kresowik 1991; Kearse 1992).
How the intervention might work
Performing carotid endarterectomy in awake patients under local anaesthetic offers the advantage of accurate assessment of the clinical state of the patient during surgery and during the early postoperative period (Benjamin 1993). Any neurological change, either during test clamping or during surgery itself, can be detected early and therefore allow more appropriate use of selective shunting in these patients. In addition, the cardiac and pulmonary morbidity of general anaesthetic may be avoided (Corson 1987; Becquemin 1991). There is also the suggestion that operation under local anaesthetic may be associated with an overall shorter hospital stay, and lower costs (Godin 1989; McCarthy 2001; Gurer 2003).
However, carotid endarterectomy under local anaesthetic may be associated with certain problems. The operation may be technically more difficult, which may increase the risk of a poor result from surgery. Patients may also undergo undue stress and pain during the operation, which may result in an increased risk of myocardial ischaemia. Finally, some surgeons may find performing the operation under local anaesthetic stressful. It is also possible that there may be certain advantages to operating under general anaesthetic. For example, there is some evidence that general anaesthetics reduce cerebral metabolic rate and may have a neuroprotective effect in the presence of ischaemia (Wells 1963; Michenfelder 1975; Markowitz 1984).
Why it is important to do this review
Carotid surgery is one of the most common types of vascular surgery. To date, there is no clear evidence that carotid endarterectomy performed under local anaesthesia is associated with reduced mortality. This issue is particularly important in older patients who comprise the majority of patients who need this type of surgery. The only reliable way to assess the relative risks and benefits of carotid endarterectomy under local anaesthetic versus general anaesthetic is by direct comparison in RCTs. We therefore undertook a systematic review of all such trials. This systematic review is an update of a Cochrane Review first published in 1996 and previously updated in 2004 and 2008 (Tangkanakul 1996; Rerkasem 2004; Rerkasem 2008).
To determine whether carotid endarterectomy under local anaesthetic: (1) reduces the risk of perioperative stroke and death compared with general anaesthetic; (2) reduces the complication rate (other than stroke) following carotid endarterectomy; and (3) is acceptable to patients and surgeons.
Criteria for considering studies for this review
Types of studies
All randomised and quasi-randomised trials that compared local with general anaesthetic for carotid endarterectomy and that measured clinically relevant outcomes were eligible for inclusion.
Types of participants
We considered trials that included any type of patient undergoing unilateral or bilateral carotid endarterectomy to be eligible for inclusion, whether the initial indication was symptomatic or asymptomatic carotid disease.
Types of interventions
We sought to identify all trials comparing carotid endarterectomy under general anaesthetic of any type with carotid endarterectomy under local anaesthetic of any type, including both epidural and skin or deep infiltration.
Types of outcome measures
The primary outcome was the proportion of patients who had a stroke of any kind (i.e. fatal or non-fatal, contralateral or ipsilateral or brainstem, haemorrhage or infarction) within 30 days of surgery, and during long-term follow-up.
Secondary outcomes included the following.
- Stroke ipsilateral to the operated artery within 30 days of operation and during long-term follow-up.
- Deaths from all causes within 30 days of surgery. We tried to classify each death as stroke-related, related to other vascular disease (cardiac disease, pulmonary embolism, haemorrhage or other vascular disease) or non-vascular.
- The proportion of patients who had a stroke or died within 30 days of surgery.
- Any myocardial infarction (fatal or non-fatal) within 30 days of surgery.
- Other significant complications related to surgery (e.g. local haemorrhage from the artery or neck wound, pulmonary complications including pneumonia, pulmonary embolism, atelectasis, prolonged intubation and pulmonary oedema, and cranial nerve palsies).
- The numbers of participants with raised or lower blood pressure (hypertension or hypotension) during or after surgery.
- The percentage of participants in whom a shunt was used during surgery.
- The total duration of hospital and intensive care unit stay.
- The overall satisfaction and preference of participants with each type of procedure. We hoped this would indirectly assess outcomes such as pain and anxiety during and after the procedure.
- The overall satisfaction and preference of surgeons.
- The feasibility of carrying out carotid endarterectomy under local anaesthetic. This was assessed by calculating the percentage of participants allocated to have the surgery under local anaesthetic but who had crossed over to general anaesthetic. We tried to divide further into those patients who had their choice of anaesthetic changed before the procedure was started and those who converted from local to general anaesthesia once the procedure had started.
Search methods for identification of studies
See the 'Specialized register' section in the Cochrane Stroke Group module. No language restriction was used in the searches and we arranged for translation of all possibly relevant non-English language publications.
We searched the Cochrane Stroke Group Trials Register in September 2013. In addition we searched the following electronic bibliographic databases from inception to 30 September 2013: the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013 Issue 8, Appendix 1), MEDLINE (Ovid, Appendix 2), and EMBASE (Ovid, Appendix 3). We developed the search strategies with the help of the Cochrane Stroke Group Trials Search Co-ordinator.
We also systematically searched the conference proceedings database Index to Scientific and Technical Proceedings (ISTP) (BIDS) (1980 to September 2013) using the terms 'carotid' and 'trial or random*'.
Searching other resources
- We handsearched the following journals:
- Annals of Surgery (1981 to September 2013);
- Annals of Vascular Surgery (1995 to September 2013);
- Vascular (previously Cardiovascular Surgery) (1995 to September 2013);
- European Journal of Vascular and Endovascular Surgery (previously European Journal of Vascular Surgery) (1988 to September 2013);
- Journal of Vascular Surgery (1995 to September 2013); and
- Stroke (1995 to September 2013).
- We reviewed the reference lists of all relevant studies.
- For a previous version of the review we advertised the review in Vascular News, a newspaper for European vascular specialists (August 2001) and handsearched the following journals:
- British Journal of Surgery (1985 to 2002);
- International Journal of Angiology (1995 to 2002);
- Journal of Cardiovascular Surgery (1995 to 2002);
- Neurology (1995 to 2002);
- Neurosurgery (1995 to 2002);
- Surgical Neurology (1995 to 2002); and
- World Journal of Surgery (1978 to 2002).
Data collection and analysis
Three authors (TV, WC, KR) independently collected data, including details of methods, participants, setting, context, interventions, outcomes, results, publications and investigators. We performed meta-analysis using RevMan 5.2 (RevMan 2012).
Selection of studies
Three authors (TV, WC, KR) independently read the titles and abstracts of the records obtained from the searches and excluded obviously irrelevant studies. We obtained the full-text articles of potentially relevant studies and the same authors independently selected studies for inclusion based on the predefined criteria. We resolved any disagreements through discussion.
Data extraction and management
We extracted details of the method of randomisation, the blinding of outcome assessments, losses to follow-up, cross-overs and exclusions after randomisation from the publications. We also compared patient characteristics (age, sex, vascular risk factors, and indication for surgery) and details of the operation (type of cerebral monitoring, use of carotid patching, use of shunts, use of perioperative antiplatelet therapy) between the treatment groups in each trial. Also, although asymptomatic patients were included in some studies, the data were not available in sufficient detail to allow separate analysis of the outcomes of carotid endarterectomy in symptomatic and asymptomatic patients. However, it is unlikely that the relative effect of local versus general anaesthesia will vary qualitatively with symptom status.
Assessment of risk of bias in included studies
Three authors (TV WC KR) independently assessed the methodological quality of the included trials using the Cochrane risk of bias tool (Higgins 2011). We resolved disagreements in the methodological assessment by reaching consensus through discussion. If an item was assessed as unclear, we contacted trialists for clarification and to request missing information.
Measures of treatment effect
We estimated treatment effect for the following outcomes within 30 days of surgery: stroke, death, stroke or death, myocardial infarction, local haemorrhage, cranial nerve injuries, and shunted arteries. Peto odds ratios (OR) and corresponding 95% confidence intervals were calculated for each outcome.
Unit of analysis issues
An event is the onset of an adverse outcome. We extracted the outcome events reported for each study. Some studies included patients who had bilateral operations, but only reported the number of patients, and not arteries, in each group. However, since bilateral carotid endarterectomy was unusual, we used the number of patients as the number of operations in such studies. Where possible we used the number of patients, not the number of arteries in the analysis.
Dealing with missing data
When data were missing, we contacted the corresponding author or a co-author to request missing information. When missing data could not be obtained, we analysed only the available data.
Assessment of heterogeneity
We assessed heterogeneity between study results using the I² statistic (Higgins 2003). This measure describes the percentage of total variation across studies due to heterogeneity rather than chance. An I² value over 75% was considered to indicate a high level of heterogeneity.
- 0% to 40%: might not be important;
- 30% to 60%: may represent moderate heterogeneity;
- 50% to 90%: may represent substantial heterogeneity; and
- 75% to 100%: considerable heterogeneity.
Assessment of reporting biases
In an effort to minimize the impact of reporting biases we sought to identify all relevant trials, including unpublished studies, by searching not only MEDLINE and EMBASE, but also the Cochrane Stroke Group Trials Register. In addition, we handsearched relevant journals and reviewed the reference lists of all relevant studies. In the previous version of this review we advertised the review in Vascular News, a newspaper for European vascular specialists. We did not impose any language restriction in the searches and we arranged translation of all relevant non-English language papers. Given a sufficient number of studies, publication bias was to be assessed by constructing funnel plots.
We calculated proportional risk reductions based on a weighted estimate of the odds ratio using the Peto method (APT 1994). We calculated a pooled Peto OR and 95% CI for the following outcomes that occurred within 30 days of surgery: stroke, death, stroke or death, myocardial infarction, local haemorrhage, cranial nerve injuries, and shunted arteries.
Subgroup analysis and investigation of heterogeneity
Where there was considerable heterogeneity, we investigated the explanation for such interactions.
When the decisions for the process undertaken in this systematic review were arbitrary or unclear, we applied sensitivity analyses. For example, both fixed-effect and random-effects meta-analyses were performed to evaluate the consistency of the results, or pooled estimates of all studies' results compared with the results with studies of poorer quality excluded.
Description of studies
Results of the search
For this review we updated our previous searches of the Cochrane Stroke Group Trials Register, MEDLINE, EMBASE and ISTP. We also searched CENTRAL. We reviewed a total of 2392 references from the searches and obtained the full paper copy of 43 trial reports. We identified 14 RCTs.
We included 14 RCTs, involving 4596 operations, which compared local and general anaesthetic for carotid endarterectomy. Most studies were small except the GALA trial, which reported on 3526 operations (GALA 2008). All studies were published in English except four, which were translated from French (Pluskwa 1989), German (Binder 1999), Serbian (Sindelic 2004), and Czech (Mrozek 2007) into English. There were two reports from one trial (McCarthy 2004). Initially the first report was published in 2002 with 67 participants and then, in 2004, another article was published including data from another hospital with a total of 176 participants (McCarthy 2004).
Since publication of the previous version of this review (Rerkasem 2008), we identified five new studies that appeared to meet the inclusion criteria (Mrozek 2007; Ebner 2008; Luchetti 2008; Mazul-Sunko 2010; Moritz 2010). Two studies were published in 2008, but they were not included in the previous version due to delayed publication (Ebner 2008; Luchetti 2008). One Czech paper was published in 2007, but this was missed because the journal was not included in MEDLINE or EMBASE (Mrozek 2007). This paper was retrieved from the Cochrane Stroke Group Trials Register. Another article was published in 2010 and was retrieved from the Cochrane Stroke Group Trials Register (Mazul-Sunko 2010). One trial was subsequently excluded (Ebner 2008), leaving four new studies for inclusion in the review (Luchetti 2008; Mrozek 2007; Moritz 2010; Mazul-Sunko 2010). We found no ongoing studies.
Thirteen studies used a cervical block and one study (Pluskwa 1989) used an epidural block to provide local anaesthesia. All studies used standard medication in the general anaesthetic group. Ten trials reported the indication for shunting (Forssell 1989; Binder 1999; Sbarigia 1999; McCarthy 2004; Kasprzak 2006; Mrozek 2007; Luchetti 2008; GALA 2008; Moritz 2010; Mazul-Sunko 2010). One trial used intraluminal shunting in all patients (Binder 1999). One trial aimed to follow patients up to one year (GALA 2008). Four trials indicated the period of follow-up as follows: 30 postoperative days (Sbarigia 1999; Kasprzak 2006), two postoperative days (Binder 1999), and the time of hospital discharge (Forssell 1989). In the other trials, the period of follow-up was not stated but appeared to be up to the time of hospital discharge.
In most studies important outcomes were not assessed. Only the GALA trial determined whether the strokes were ipsilateral to the operated artery (GALA 2008). However, most strokes will have been ipsilateral. The GALA trial was the only study that reported the cause of death and the severity of stroke in terms of disability (GALA 2008). Patient satisfaction was formally assessed in only one trial (McCarthy 2004). Surgeon satisfaction was not formally assessed.
We excluded one trial because the randomised allocation was based on the rotation of the two anaesthetists who could perform cervical plexus block (Ebner 2008).
Risk of bias in included studies
One of the 14 RCTs was published as an abstract (Gimenez 2004). For this study, only data from the abstract and oral presentation were available. In general, reporting of methodology was poor. The overall results of the risk of bias analysis are summarized in Figure 1.
|Figure 1. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.|
In all studies, allocation by randomisation was reported. However, only six papers indicated the method of randomisation. This included block randomisation (Binder 1999; GALA 2008), computer randomisation (Kasprzak 2006; Luchetti 2008; Moritz 2010), and date of birth (Mrozek 2007). The methods used for randomisation in the remaining trials were unclear.
All studies were unable to blind patients and surgical teams to randomised treatment allocation. In most trials, the blinding of outcome assessment was unclear. In three trials outcomes were assessed by neurologists who were blind to the type of anaesthesia used (Sbarigia 1999; Kasprzak 2006; GALA 2008).
Incomplete outcome data
Most studies did not report how incomplete outcome data was handled. However, six studies did report this information (Sbarigia 1999; McCarthy 2004; Sindelic 2004; Kasprzak 2006; GALA 2008; Moritz 2010). In six studies, some patients who were randomised to have surgery under local anaesthesia actually had surgery under general anaesthesia (Forssell 1989; Binder 1999; Sbarigia 1999; Kasprzak 2006; GALA 2008; Moritz 2010). Apart from two RCTs (GALA 2008; Moritz 2010), the reasons for the change were usually unclear, and these patients were excluded from the analysis in five trial reports (Forssell 1989; Binder 1999; Sbarigia 1999; GALA 2008; Moritz 2010). In one trial (Forssell 1989), 11 (11%) patients underwent staged bilateral endarterectomies and were randomised twice. Some of these patients may have had one operation under general anaesthesia and the other under local anaesthesia.
Most studies did not indicate prespecified outcomes or report all prespecified outcomes. Only six studies reported all expected outcomes that were prespecified (Binder 1999; GALA 2008; Kasprzak 2006; Mazul-Sunko 2010; Moritz 2010; Mrozek 2007).
Other potential sources of bias
Regarding allocation concealment, two trials used sequentially numbered sealed envelopes but it was not stated if these were opaque (Forssell 1989; Sbarigia 1999). The GALA 2008 study utilised central allocation, while in 11 trials the method of concealment of allocation was unclear.
We were able to assess other bias, including measurement bias and funding bias in one study (GALA 2008).
Only the GALA trial clearly reported on the major differences in baseline prognostic factors between the two groups of patients (GALA 2008), although some studies provided limited data. Only four trials commented on the use of patching: two trials used a selective patch approach (Sbarigia 1999; Kasprzak 2006), one used patching in all patients (Binder 1999) and one study used various patching approaches (GALA 2008). Only the GALA trial reported on perioperative antiplatelet therapy (GALA 2008).
Effects of interventions
We included data from 14 randomised trials (4596 operations) in this review. We only assessed outcomes within 30 days of surgery, because none of the included studies reported long-term results.
Any stroke within 30 days of operation
There were 149 reported strokes of any type within 30 days of surgery. There was no statistically significant difference in the incidence of stroke between the local anaesthesia group and the general anaesthesia group. The incidence of strokes in the local anaesthesia group was 3.2% compared to 3.5% in the general anaesthesia group (Peto OR 0.92, 95% CI 0.67 to 1.28, Analysis 1.1). Only the GALA trial data allowed a comparison between ipsilateral and contralateral stroke (GALA 2008), and reported the rate of ipsilateral stroke as 57/1771 (3.2%) in local anaesthesia and 54/1752 (3.1%) in general anaesthesia.
Death within 30 days of operation
There were 52 deaths: 16 due to coronary artery diseases, 27 due to stroke and 9 due to other causes. There were 20 deaths (0.9%) in the local anaesthesia group compared to 32 deaths in the general anaesthesia group (1.5%). There was no statistically significant difference in death rates (Peto OR 0.62, 95% CI 0.36 to 1.07, Analysis 1.2).
Stroke or death within 30 days of operation
The rate of stroke or death in the local anaesthesia group was 3.6% compared with 4.2% in the general anaesthesia group. There was no statistically significant difference in the rate of stroke or death (Peto OR 0.85, 95% CI 0.63 to 1.16, Analysis 1.3).
Myocardial infarction within 30 days of operation
Twenty-three patients suffered a myocardial infarction within 30 days of surgery. Fourteen patients (0.6%) in the local anaesthesia group had a myocardial infarction compared with nine patients (0.4%) in the general anaesthesia group). There was no statistically significant difference between the groups in the rate of myocardial infarction (Peto OR 1.53, 95% CI 0.67 to 3.47, Analysis 1.4). The 95% CI was wide.
Other operative complications
Five studies reported the rate of haemorrhage from the wound. There were 314 haemorrhages. Haemorrhage was reported in 7.7% of patients in the local anaesthesia group compared with 8.1% of patients in the general anaesthesia group. There was no statistically significant difference between the groups (Peto OR 0.95, 95% CI 0.75 to 1.19, Analysis 1.5). There was no indication of the severity of these bleeds.
Cranial nerve injuries
Four trials reported cranial nerve palsies. Eleven per cent of patients in the local anaesthesia group had cranial nerve injuries compared with 9.7% of general anaesthesia patients. There was no statistically significant difference between the groups (Peto OR 1.17, 95% CI 0.95 to 1.44, Analysis 1.6).
One trial reported on pulmonary complications (Kasprzak 2006), and found no statistically significant difference in the rate of pneumonia under local anaesthesia compared with general anaesthesia. The GALA trial reported on pulmonary embolism as an outcome and reported no events in either treatment group (GALA 2008).
Twelve trials recorded blood pressure during and after surgery. However, the studies did not consistently report the number of patients with significant hypotension or hypertension or mean arterial pressure during and after surgery. Furthermore, the definitions of hypertension and hypotension varied between trials. We have therefore simply described the results.
Six reported that blood pressure dropped in the general anaesthesia group after induction of anaesthesia (Forssell 1989; Pluskwa 1989; Prough 1989; McCarthy 2004; Sindelic 2004; GALA 2008). In one trial, more patients in the general anaesthesia group had significant hypotension during or after surgery compared with the local anaesthesia group (25% versus 7%) (Forssell 1989). However, this was not confirmed in another trial (Pluskwa 1989). The GALA trial reported on the manipulation of blood pressure (GALA 2008). More general anaesthesia than local anaesthesia patients had their blood pressure manipulated up (43% compared with 17%), and more local anaesthesia patients had their blood pressure manipulated down or not manipulated at all (74% compared with 41%) during or after surgery. The difference in blood pressure manipulation between the two trial arms was statistically significant (GALA 2008).
Five trials showed that blood pressure tended to increase during clamping of the carotid artery in the local anaesthesia group compared with the general anaesthesia group (Forssell 1989; Pluskwa 1989; Prough 1989; Gimenez 2004; Luchetti 2008) but this was not found in another trial (McCarthy 2004). In two trials, there were significantly more patients with hypertension in the local anaesthesia group during surgery than in the general anaesthesia group (Forssell 1989: 36% versus 0%; Pluskwa 1989: 80% versus 20%). Three trials reported that during surgery the mean arterial pressure in the local anaesthesia group was higher than in the general anaesthesia group (Mrozek 2007; Luchetti 2008; Moritz 2010). Two studies suggested that hypotension was more common in the postoperative period with local anaesthesia than with general anaesthesia (Pluskwa 1989; Prough 1989). Two trials found that patients operated on under general anaesthesia had more postoperative (within day one) hypertension than those operated on under local anaesthesia (Gimenez 2004; Kasprzak 2006).
Eight studies reported the number of arteries shunted. The use of local anaesthetic was associated with significantly fewer shunts than general anaesthetic. Fifteen per cent of patients in the local anaesthesia group had their arteries shunted compared with 42% of of patients in the general anaesthesia group. As there was significant heterogeneity between studies (I² = 91%), we used the random-effects model to pool the results (OR 0.24, 95% CI 0.08 to 0.73, Analysis 1.7).
The duration of hospital stay was reported in three trials (Binder 1999; McCarthy 2004; GALA 2008). The average time in hospital was not significantly different between the local and general anaesthesia groups.
Patient satisfaction was formally assessed in one study (McCarthy 2004). There was no statistically significant difference in satisfaction between anaesthetic techniques. In Forssell 1989, of the three patients who had repeat carotid endarterectomies (having had a local anaesthetic for the first operation) none refused repeat randomisation (Forssell 1989). Forssell 1989 reported that one patient in the local anaesthesia group became extremely agitated during the procedure. Another trial evaluated patient satisfaction by a questionnaire (Binder 1999). They found that both types of anaesthesia were equally acceptable but the publication did not describe the questionnaire in detail. All patients preferred the same type of anaesthesia if they needed a second operation, except one patient in the local anaesthesia group (total 27 patients) who wished to have general anaesthesia for any further surgery. Mrozek 2007 asked patients about any unpleasant sensations after surgery and during the postoperative period. A minimum amount of unpleasant sensation was reported for both types of anaesthetic after surgery and during the postoperative period (Mrozek 2007).
The satisfaction or preference of the surgeon was not assessed in any of the trials.
Feasibility of performing operation under local anaesthetic
One trial recorded the number of patients randomised to have surgery under local anaesthesia, but who had surgery under general anaesthesia (Forssell 1989). Eight patients crossed over from local to general anaesthesia whilst none switched from general to local anaesthesia. The most common reasons for cross-over were that the patient changed his or her consent or that the patient had unstable cardiac disease. Seven out of eight patients had their anaesthetic changed before the procedure was started. In another trial, six patients were switched from local to general anaesthesia due to severe agitation (three patients), insufficient anaesthesia under local anaesthesia (two patients), and intravascular injection during application of local anaesthetic agent (one patient) (Kasprzak 2006). Three out of six patients had their anaesthetic changed before the procedure was started. No general anaesthesia cases were switched to local anaesthesia in this study (Kasprzak 2006). In the GALA trial, 167 patients were crossed over before initiation of anaesthesia: 75 patients crossed over from local to general anaesthesia whilst 92 switched from general to local anaesthesia (GALA 2008). Patients allocated to general anaesthesia were more likely to cross over due to a medical decision, whereas patients allocated local anaesthesia were more likely to cross over due to the patient's preference. Sixty-nine out of 1771 (3.9%) local anaesthesia patients were switched to general anaesthesia after initiation of anaesthesia, 17 before and 52 after the start of surgery. In one trial, two patients switched from local to general anaesthesia (Moritz 2010) and in another trial, no patients switched from local anaesthesia to general anaesthesia (Mrozek 2007).
Summary of main results
We identified 14 studies comparing adverse outcomes for carotid endarterectomy performed under local anaesthesia with adverse outcomes for carotid endarterectomy performed under general anaesthesia. Meta-analysis of the randomised studies showed that there was no statistically significant difference between the anaesthesia groups in the proportion of patients who had a stroke, or died or a myocardial infarction within 30 days of surgery.
Overall completeness and applicability of evidence
The pooled analyses showed no statistically differences in the rate of stroke or death between the two types of anaesthetic technique used during carotid endarterectomy. There was a non-significant trend towards lower operative mortality with local anaesthesia (Peto OR 0.62, 95% CI 0.36 to 1.07), but neither the GALA 2008 study nor the pooled analysis were adequately powered to reliably detect an effect on mortality. It is unlikely that a sufficiently large (about 20,000 patients) randomised trial will be performed in the foreseeable future to confirm or refute this possible effect on mortality.
Twelve trials recorded blood pressure during and after surgery, but these data were difficult to interpret. It is interesting to note that two studies suggested that hypotension was more common in the postoperative period with local anaesthesia (Pluskwa 1989; Prough 1989). This is may be due to the high rate of blood pressure being manipulated down, but we could not find any hard evidence to support this at the present time.
The choice of anaesthetic technique will therefore depend on the clinical situation and the preferences of individual patients and their surgeon. In some patients the operation may be technically more difficult under local anaesthesia (e.g. in patients with short, wide necks). Some patients, perhaps as many as 10%, will refuse to have the operation under local anaesthesia (Forssell 1989), and some surgeons may feel more comfortable performing the operation under general anaesthesia.
GALA 2008 was also designed to determine whether the type of anaesthesia influenced the cost of endarterectomy. These data showed that the expected costs of carotid endarterectomy under local anaesthesia are less than those under general anaesthesia (mean difference GBP 178) (Gomes 2010). This difference was mainly due to the longer length of stay in an intensive care unit and the use of consumables such as shunts and patches. A post hoc subgroup analysis (40 patients) from the GALA 2008 study investigated the influence of local versus general anaesthesia on postoperative neurocognitive function. This study showed that local anaesthesia beneficially influenced early postoperative neurocognitive functions. Mazul-Sunko 2010 found shunting to be the only parameter associated with neurocognitive decline on the first day after carotid endarterectomy. Local anaesthesia was hypothesised to offer an indirect benefit due to the reduced rate of shunting (Mazul-Sunko 2010). However, given the small size of these studies, early postoperative neurocognitive function requires further investigation (Weber 2009).
Quality of the evidence
There were significant problems in the quality of the randomised trials. The method used for allocation concealment was inadequately reported in most of the included studies. The duration of follow-up was short in all included studies. It was also unclear in most of the studies whether the outcomes had been assessed blind to treatment allocation. It is well known that studies that have neurologists as assessors are associated with higher stroke and death rates (Rothwell 1996; Rerkasem 2009). Only two studies reported that they had neurologists as blinded assessors (Kasprzak 2006; GALA 2008). At least five of the trials excluded some randomised patients from the analysis, especially patients who crossed over anaesthetic type (Forssell 1989; Binder 1999; Sbarigia 1999; GALA 2008; Moritz 2010). If excluded patients differed from those patients who remained in the analysis, the results may be biased.
Potential biases in the review process
Many studies reported the number of arteries rather than the number of patients. Also, it was not clear how many of the strokes were ipsilateral, and how many were disabling. Few trials assessed patients' or surgeons' satisfaction or preference, or the duration of intensive care and overall hospital stay.
There was marked heterogeneity between studies in the use of shunts with both types of anaesthesia. This in part may be reflected by the different policies in shunting between studies. For example, in the Binder 1999 study all patients were shunted irrespective of treatment allocation. All patients in the local anaesthetic group were shunted despite the fact that surgeons preferred local anaesthetic due to the low rate of shunting. Apart from this trial, the remaining seven RCTs in the pooled analysis used selective shunting. For six RCTs, although the indication of shunting in the local anaesthesia group was not markedly different, the indication for shunting in the general anaesthesia group varied considerably. One study used stump pressure measurement and clinical judgment (Forssell 1989), while another study used a mix of transcranial Doppler, stump pressure measurement, EEG, and clinical judgment (GALA 2008). Although another two studies used somatosensory evoked potentials, the indication was not identical (Kasprzak 2006; Moritz 2010). One trial carried out shunting routinely, but the actual rate of shunting was 82% because of expected technical difficulties with shunt insertion in 18% of the cases in the general anaesthetic group (Mazul-Sunko 2010).The remaining three RCTs did not report the indication for shunting in the general anaesthesia group (Sbarigia 1999; Mrozek 2007; Moritz 2010). All of these differences may explain the considerable heterogeneity in the use of shunts.
Agreements and disagreements with other studies or reviews
It is also interesting to note that in our previous review, the non-randomised studies showed consistently lower risks of operative stroke and death when carotid endarterectomy was done under local anaesthesia (Rerkasem 2008). With the addition of GALA 2008 study the meta-analyses show that these apparent differences were probably due to biases in the non-randomised comparisons, illustrating the importance of adequately powered randomised controlled trials (Collins 2001).
Implications for practice
The proportion of patients who had a stroke or died within 30 days of surgery did not differ significantly between the two types of anaesthetic techniques used during carotid endarterectomy. This systematic review provides evidence to suggest that patients and surgeons can choose either anaesthetic technique, depending on the clinical situation and their own preferences.
Implications for research
There was a non-significant trend towards lower operative mortality with local anaesthesia. However, our pooled analysis was not adequately powered to reliably detect an effect on mortality. More randomised controlled trials comparing local anaesthesia with general anaesthesia are needed to assess the potential beneficial effect on mortality.
We would like to thank Dr Chanpong Tangkanakul, Dr Carl Counsell, Professor Charles Warlow, Mr Richard Bond and Professor Peter Rothwell for their contribution to previous versions of this review; Hazel Fraser for providing us with references to relevant trials from the Cochrane Stroke Group's Trials Register; Professor Graeme Hankey, Ms Brenda Thomas, Dr Paul Nederkoorn, Mr Brian Stafford and Ms Ann Fonfa for commenting on the manuscript and Dr Branka Mazul-Sunko for providing unpublished data for a trial. Professor Kittipan Rerkasem was funded by The Thailand Research Fund (RSA5580008) and Faculty of Medicine, Chiang Mai University.
If anyone is aware of any randomised trials that we have omitted please contact Professor Kittipan Rerkasem.
Data and analyses
- Top of page
- Authors' conclusions
- Data and analyses
- What's new
- Contributions of authors
- Declarations of interest
- Sources of support
- Differences between protocol and review
- Index terms
Appendix 1. Cochrane Central Register of Controlled Trials (CENTRAL) search strategy
#1 [mh ^“endarterectomy, carotid”]
#2 [mh “carotid arteries”/SU]
#3 [mh “carotid artery diseases”/SU]
#4 [mh “carotid arteries”]
#5 [mh “carotid artery diseases”]
#7 #4 or #5 or #6
#8 [mh ^endarterectomy]
#9 (endarterectom* or surg*):ti,ab
#10 #8 or #9
#11 #7 and #10
#12 #1 or #2 or #3 or #11
#13 [mh anesthesia]
#14 [mh anesthetics]
#15 (anesthe* or anaesthe*):ti,ab
#16 [mh ^”cervical plexus”]
#17 (cervical NEXT block):ti,ab
#18 (bupivacaine or lidocaine or lignocaine or prilocaine or ropivacaine or mepivacaine or alfentanil or propofol or fentanyl or ketamine or midazolam or sevoflurane or desflurane or etomidate or isoflurane):ti,ab
#19 #13 or #14 or #15 or #16 or #17 or #18
#20 #12 and #19
Appendix 2. MEDLINE searcg strategy (OVID)
1 Endarterectomy, carotid/
2 exp carotid arteries/su
3 exp carotid artery diseases/su
4 exp carotid arteries/
5 exp carotid artery diseases/
7 4 or 5 or 6
9 (endarterectom$ or surg$).tw.
10 8 or 9
11 7 and 10
12 1 or 2 or 3 or 11
13 exp anesthesia/
14 exp anesthetics/
15 (anesthe$ or anaesthe$).tw.
16 cervical plexus/
17 cervical block.tw.
18 (bupivacaine or lidocaine or lignocaine or prilocaine or ropivacaine or mepivacaine or alfentanil or propofol or fentanyl or ketamine or midazolam or sevoflurane or desflurane or etomidate or isoflurane).tw.
20 12 and 19
21 exp animals/ not humans.sh
22. 20 not 21.
Appendix 3. EMBASE search strategy (OVID)
1. carotid artery surgery/ or carotid endarterectomy/
2. exp carotid artery/su [Surgery]
3. exp carotid artery disease/su [Surgery]
4. exp carotid artery/
5. exp carotid artery disease/
7. 4 or 5 or 6
9. (endarterectom$ or surg$).tw.
10. 8 or 9
11. 7 and 10
12. 1 or 2 or 3 or 11
13. exp anesthesia/
14. exp anesthetic agent/
15. exp local anesthetic agent/
16. (anesthe$ or anaesthe$).tw.
17. cervical plexus/
18. cervical block.tw.
19. (bupivacaine or lidocaine or lignocaine or prilocaine or ropivacaine or mepivacaine or alfentanil or propofol or fentanyl or ketamine or midazolam or sevoflurane or desflurane or etomidate or isoflurane).tw.
20. 13 or 14 or 15 or 16 or 17 or 18 or 19
21. 12 and 20
22. Randomized Controlled Trial/
24. Controlled Study/
25. control group/
26. clinical trial/ or phase 1 clinical trial/ or phase 2 clinical trial/ or phase 3 clinical trial/ or phase 4 clinical trial/ or controlled clinical trial/
27. Double Blind Procedure/
28. Single Blind Procedure/ or triple blind procedure/
29. drug comparison/ or drug dose comparison/
30. "types of study"/
32. (controlled adj5 (trial$ or stud$)).tw.
33. (clinical$ adj5 trial$).tw.
34. ((control or treatment or experiment$ or intervention) adj5 (group$ or subject$ or patient$)).tw.
35. (quasi-random$ or quasi random$ or pseudo-random$ or pseudo random$).tw.
36. ((control or experiment$ or conservative) adj5 (treatment or therapy or procedure or manage$)).tw.
37. ((singl$ or doubl$ or tripl$ or trebl$) adj5 (blind$ or mask$)).tw.
39. (assign$ or allocat$).tw.
41. trial.ti. or (RCT or RCTs).tw.
43. 21 and 42
44. (exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/) not (human/ or normal human/ or human cell/)
45. 43 not 44
Last assessed as up-to-date: 30 September 2013.
Review first published: Issue 1, 1996
Contributions of authors
Tanat Vaniyapong, Wilaiwan Chongruksut, Kittipan Rerkasem: designed the protocol, performed searches, selected studies for inclusion or exclusion, extracted data and updated the review.
Declarations of interest
Sources of support
- Faculty of Medicine, Chiang Mai University, Thailand.
- Center for Applied Science, Research Institute of Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
- The Thailand Research Fund, Thailand.
- Stroke Prevention Research Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, England, UK.
Differences between protocol and review
The non-randomised studies, which are prone to bias and which were previously included in the review, have been removed.
Medical Subject Headings (MeSH)
*Anesthesia, General; *Anesthesia, Local; Endarterectomy, Carotid [*adverse effects; methods]; Incidence; Myocardial Infarction [epidemiology; etiology]; Randomized Controlled Trials as Topic; Stroke [epidemiology; *etiology]
MeSH check words
* Indicates the major publication for the study