1. Funding: Health Foundation, ESVS The GALA Trial General versus Local Anaesthesia for Carotid Endarterectomy Michael J Gough on behalf of the GALA Trial Collaborators Discussants: Michael Gough, Michael Horrocks

2. Funding: Health Foundation, ESVS Local Versus General Anaesthesia in Carotid Endarterectomy: a Systematic Review of the Evidence C. Tangkanakul, C. E. Counsell, C. P. Warlow Eur J Vasc Endovasc Surg 1997, 13: 491-499 The Differing Effects of Regional and General Anaesthesia on Cerebral Metabolism During Carotid Endarterectomy A.J. McCleary, N. M. Dearden, D. H. Dickson, A. Watson, M. J. Gough Eur J Vasc Endovasc Surg 1996, 12: 173-181 Introduction

3. Funding: Health Foundation, ESVS Methods Eligibility 15 CEAs/surgeon/year + 10 LA symptomatic or asymptomatic uncertainty re: best method co-operate with awake testing no other surgery randomise only once Randomisation Stratified by centre Telephone, Fax, Web Surgery GA: follow normal practice LA: shunt only on basis awake test testing Monitoring, GA shunts, patch endarterectomy, as per normal Follow-up Post-discharge/death form: 7 days 1 month: examination by “blind” independent neurologist 12 month FU: telephone, questionnaire, face-face

4. Funding: Health Foundation, ESVS Primary end points: Stroke (retinal infarct) MI (fatal or non-fatal) Death Analysis intention-to-treat

5. Funding: Health Foundation, ESVS 3526 randomised (95 centres, 24 countries) GA 1753 allocated: 1628  GA 31 no anaesthesia - 92 cross- over 2 unknown 1752 for primary outcome 21 incomplete FU 19 no 1m physician form LA 1773 allocated: 1655  LA 41 no anaesthesia - 75 cross- over 2 unknown 1771 for primary outcome 21 incomplete FU 19 no 1m physician form 99.9% FU

6. Funding: Health Foundation, ESVS Baseline Data GeneralLocal Age70 (sd 9)69 (sd 9) Male1232 (70%)1256 (71%) Asymptomatic stenosis685 (39%)677 (38%) Mean % stenosis81 (sd 11) Contralateral ICA occlusion150 (9%)160 (9%) Smoking, PAD, CAD, AF, DM all equal

7. Funding: Health Foundation, ESVS Compliance – No anaesthesia Reasons: General (n=31) Local (n=41) Stroke/Death before operation22 Carotid artery occlusion88 Too ill (unrelated)76 Stenosis/symptoms too mild411 Patient refused913 Carotid stent instead11 Consent early – Randomise late

8. Funding: Health Foundation, ESVS Compliance – Cross-overs Reasons: General (n=92) Local (n=75) Medical decision4120 Administrative issues159 Patient’s decision2944 Reason unknown72

9. Funding: Health Foundation, ESVS Conversions Reasons:Local (n=69) After start of anaesthesia, pre-surgery Patient’s decision6 Problem with position on table etc3 Patient deteriorated after local block8 After start of surgery Pain at operative site9 Discomfort, anxiety, claustrophobia25 Physiological instability5 Protracted or difficult surgery6 Neurological deterioration on cross-clamping7

10. Funding: Health Foundation, ESVS Primary outcome events 70 66 4 9 5 10 0% 1% 2% 3% 4% 5% General 84/1752 (4.8%) Local 80/1771 (4.5%) Other deaths MI (fatal or non-fatal) Stroke (fatal or non-fatal)

11. Funding: Health Foundation, ESVS Primary outcome events Stroke3(-10 to +16) MI-4(-8 to +2) Death (any cause)4(-3 to +12) Stroke or death4(-9 to +18) Stroke, MI or death3(-11 to +17) Favours GeneralFavours Local Events prevented/1000 (95% CI) -20-1001020

12. Funding: Health Foundation, ESVS Other Complications GeneralLocal Cranial nerve injuries184 (11%)213 (12%) Wound haematoma146 (8%)150 (8%) Wound haematoma requiring reoperation 45 (3%)40 (2%)

13. Funding: Health Foundation, ESVS Survival analysis

14. Funding: Health Foundation, ESVS Subgroups (primary outcome)

15. Funding: Health Foundation, ESVS Implications of GALA Stroke & Death Favours LocalFavours General Meta-analysis of 7 earlier trials GALA Meta-analysis including GALA OR (95% CI) 0.62 (0.24 to 1.59) 0.88 (0.64 to 1.23) 0.85 (0.63 to 1.16)

16. Funding: Health Foundation, ESVS Implications of GALA Death Favours LocalFavours General Meta-analysis of 7 earlier trials GALA Meta-analysis including GALA OR (95% CI) 0.23 (0.05 - 1.01) 0.72 (0.40 - 1.30) 0.62 (0.36 – 1.07)

17. Funding: Health Foundation, ESVS Primary outcome events (according to anaesthetic received) 79/1621 4.9% 64/1575 4.1% 8 events prevented/1000 (95% CI: -6 to +23)

18. Funding: Health Foundation, ESVS Confounding Factors P<0.001 BP manipulated up P<0.001 Patch angioplasty

19. Funding: Health Foundation, ESVS Conclusions Primary outcomes: no reason to prefer LA or GA Secondary outcomes: no influence on length of stay or QOL Sub-groups: trend favouring LA for contralateral occlusion Trends favouring LA: Peri-operative death Event free survival to 1 year Implications:Offer both LA & GA for patient preference or medical reasons