incidence and mechanism of post carotid endarterectomy hypertension

307 Pages·2014·3.9 MB·English

INCIDENCE AND MECHANISM OF
POST CAROTID ENDARTERECTOMY
HYPERTENSION

Thesis submitted for the degree of
Doctor of Medicine
at the University of Leicester

by
Mr Jeremy Edward Newman MBBS BSc MRCS (Eng)

Department of Cardiovascular Sciences
University of Leicester

January 2014
Incidence and Mechanism of Post Carotid
Endarterectomy Hypertension
Jeremy Edward Newman MBBS BSc MRCS (Eng)
Post-endarterectomy hypertension (PEH) is associated with intracranial haemorrhage
(ICH), hyperperfusion syndrome stroke and cardiac complications. Whilst well
recognised, its pathophysiology is poorly understood.
It was hypothesised that pre-operative poorly controlled blood pressure, baroreceptor
dysfunction and impairment of cerebral autoregulation might be associated with PEH.
Our aim was to investigate these and other pre-operative clinical variables which may
be predictive of those who suffer PEH.
106 patients undergoing carotid endarterectomy (CEA) underwent investigations to
evaluate the pathophysiology of PEH including; 24-hour ambulatory BP, central aortic
BP, baroreceptor sensitivity (BRS), cerebral autoregulation and transcranial Doppler
(TCD) measurement of middle cerebral artery blood flow velocity (MCAV); Clinical
details, BP readings from the ward, induction of anaesthesia and during surgery, mode
of anaesthesia, vasoactive medications and MCAV changes following flow restoration.
Patients with PEH (defined as systolic pressure (SBP)>170mmHg + no symptoms or
>160mmHg with headache/seizure/deficit) were treated according to Unit guidelines.
40/106 required treatment for PEH (26 in recovery, 27 on the ward), while 7 had
surges in SBP>200mmHg on the ward. PEH (recovery/ward) was not associated with
pre-operative patient characteristics or TCD variables and was not associated with
impaired autoregulation (autoregulation was better preserved in PEH patients (ARI 4.3
+/-1.4 vs. ARI 3.5 +/-1.6 (p=0.03)). PEH was significantly associated with; (i) higher pre-
operative BP (peak SBP>170mmHg = 59% prevalence); (ii) peak SBP>170mmHg before
induction of anaesthesia (61% prevalence) and (iii) impaired BRS (3.4 +/- 1.7ms/mmHg
vs. 5.3 +/-2.8ms/mmHg, p=0.001). Length of stay was significantly increased in PEH
patients (p<0.001), while three patients with temporary headache/seizure/deficit and
one with delayed ICH required treatment for PEH (p=0.02).
PEH was associated with pre-operative poorly controlled BP and impairment of
baroreceptor sensitivity. Cerebral autoregulation was better preserved in those who
suffered PEH. Within the time constraints of carrying out surgery in the hyper acute
period, it is neither achievable nor advisable to aggressively optimise blood pressure
prior to surgery. For now the optimal management remains an uncompromising
approach to treating PEH.
i
Acknowledgements
Professor A Ross Naylor for his boundless enthusiasm and encouragement as my
supervisor, for the late nights with the red pen and his unwavering support whilst
carrying out this research.

Professor Rob Sayers for giving me the opportunity to carry out my research at the
Department of Cardiovascular Sciences. For his support, guidance and
encouragement from start to finish.

Professors Tom Robinson (Stroke Medicine), Jonathan Thompson (Anaesthetics) and
Bryan Williams (Hypertensive Medicine) for co-supervising this research and providing
expertise in their respective fields.

Professor Ronney Panerai (Medical Physics), Dr Nazia Saeed and Mrs Angela Salinet,
for all their patient tuition on the investigation of baroreceptor function and cerebral
autoregulation.

Mr Matt Bown for his support and guidance during my research and his patient and
invaluable assistance in the statistical analysis of my results.

Dr Peter Lacy for his knowledge and advice in all aspects of measuring blood pressure.

To the Department of Vascular Surgery; the Surgeons, Anaesthetists, Nursing and
Theatre Staff and particularly the Vascular Scientists who supported me unreservedly
in carrying out this research.

To all the patients who despite the stress of surgery agreed to participate, without
whom this research would not have been possible.

To my wife Sophie, without whose encouragement and support throughout, this
would not have been achievable.

ii
Papers and Presentations
Papers
Newman J E, Ali M, Sharpe R, Bown M J, Sayers R D, Naylor A R Changes in middle
cerebral artery velocity after carotid endarterectomy do not identify patients at high-
risk of suffering intracranial haemorrhage or stroke due to hyperperfusion syndrome.
Eur J Vasc Endovasc Surg, 2013. 45(6): p 562-71

Presentations
JE Newman, MJ Bown, RD Sayers, JP Thompson, TG Robinson, B Williams, RB Panerai,
PS Lacy, AR Naylor. Poorly controlled Blood Pressure and impaired baroreceptor
function (but not impaired autoregulation) are associated with a significantly higher
prevalence of post-carotid endarterectomy hypertension. - Oral presentation at the
Vascular Society AGM, Manchester – November 2012 (Sol Cohen Prize Session)

JE Newman, M Ali, R Sharpe, M Bown, R Sayers, A R Naylor. Significant Increases in
Mean Middle Cerebral Artery Velocity after Carotid Endarterectomy Do Not Identify
Patients at Higher Risk of Suffering Intracranial Haemorrhage or Stroke due to
Hyperperfusion Syndrome. - Poster presentation (awarded prize) at West Midlands
Society meeting – November 2012

JE Newman, M Ali, R Sharpe, M Bown, R Sayers, A R Naylor. Significant Increases in
Mean Middle Cerebral Artery Velocity after Carotid Endarterectomy Do Not Identify
Patients at Higher Risk of Suffering Intracranial Haemorrhage or Stroke due to
Hyperperfusion Syndrome. - Oral presentation at the European Society of Vascular
Surgery meeting, Bologna - September 2012 (Prize Session)

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Contents
Acknowledgements .......................................................................................................... ii
Papers and Presentations ................................................................................................ iii
Contents .......................................................................................................................... iv
1. The Pathogenesis of Stroke ........................................................................................ 1
1.1 Stroke ................................................................................................................. 1
1.2 Types of Stroke .................................................................................................. 3
1.3 Atherosclerosis .................................................................................................. 4
1.4 Plaque instability and rupture ........................................................................... 7
2 Carotid Endarterectomy ............................................................................................. 9
2.1 Extra-cranial Cerebrovascular Disease .............................................................. 9
2.2 Carotid Endarterectomy .................................................................................. 11
2.2.1 The Benefits of Carotid Endarterectomy - Randomised Trials of Carotid
Surgery 12
2.2.2 Asymptomatic Carotid Surgery ................................................................ 26
2.3 Technical Considerations for Carotid Endarterectomy ................................... 34
2.3.1 Imaging ..................................................................................................... 35
2.3.2 Primary closure vs. patch closure ............................................................. 38
2.3.3 Shunting .................................................................................................... 39
2.3.4 Local vs. general anaesthetic .................................................................... 40
2.4 Complications of Carotid Surgery .................................................................... 41
2.4.1 Perioperative stroke ................................................................................. 41
2.4.2 Cardiac complications............................................................................... 42
2.4.3 Cranial nerve injuries & wound complications ........................................ 42
3 A local Perspective to Reducing the Risk of Carotid Surgery ...................................... 44
3.1 Monitoring & Quality Control .......................................................................... 44
3.1.1 Transcranial Doppler ................................................................................ 44
3.1.2 Angioscopy ............................................................................................... 47
3.2 Postoperative stroke ........................................................................................ 51
3.2.1 Prevention of thrombotic stroke after CEA: the role of TCD [95] ............ 51
3.2.2 Patients thromboembolic potential between bilateral carotid
endarterectomies remains stable over time [98] ................................................... 54
3.2.3 Patients’ thromboembolic potential following endothelial disruption is
related to the platelets’ sensitivity to ADP [99] ...................................................... 55
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3.2.4 Beneficial effects of clopidogrel with aspirin in reducing cerebral emboli
in patients undergoing carotid endarterectomy [100] ........................................... 57
3.3 A new direction ................................................................................................ 60
4 Post Carotid Endarterectomy Hypertension .............................................................. 61
4.1 Hypertension after carotid endarterectomy: a review of the literature......... 61
4.1.1 Post-CEA blood pressure variability ......................................................... 61
4.1.2 Pre and perioperative factors associated with post CEA hypertension ... 65
4.1.3 Complications associated with post-CEA hypertension ........................... 69
4.2 Intracerebral haemorrhage after CEA, cerebral hyperperfusion syndrome or
hypertensive encephalopathy .................................................................................... 73
4.2.1 Cerebral hyperperfusion syndrome or hypertensive encephalopathy .... 74
4.3 Cerebral Autoregulation .................................................................................. 76
4.3.1 Static vs. dynamic cerebral autoregulation .............................................. 77
4.3.2 Measurement of cerebral autoregulation ............................................... 78
4.4 Baroreceptor reflex and control of blood pressure ......................................... 82
4.4.1 Baroreceptor Anatomy and physiology.................................................... 82
4.4.2 Baroreceptor dysfunction ........................................................................ 84
4.4.3 Baroreceptor sensitivity in patients with carotid artery disease ............. 86
4.4.4 Baroreceptor sensitivity after carotid endarterectomy ........................... 89
4.5 Measurement of baroreceptor function ....................................................... 103
4.5.1 Non-invasive measurement of BRS ........................................................ 104
Experimental Work ....................................................................................................... 106
5 Methods Overview ................................................................................................ 107
5.1 Patient Selection ............................................................................................ 107
5.2 Individual patient study timeline ................................................................... 108
5.3 Pre-operative assessment ............................................................................. 109
5.3.1 Patient characteristics and information ................................................. 109
5.3.2 Blood pressure recordings ...................................................................... 110
5.3.3 Transcranial Doppler, cerebral autoregulation and baroreceptor function
110
5.4 Operation and peri-operative assessment .................................................... 112
5.4.1 Post-operative assessment..................................................................... 112
5.5 Post-operative hypertension management ................................................... 113
5.6 24-hour ambulatory blood pressure monitoring .......................................... 114
5.6.1 Healthstats BPRo® Radial Pulse Wave Acquisition Device ..................... 114
5.6.2 SpaceLabs 90207 ambulatory blood pressure monitor ......................... 116
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5.6.3 BPro reliability ........................................................................................ 118
6 Can Pre-operative Patient Variables Predict Patients Who Develop Post-CEA
Hypertension? .............................................................................................................. 121
6.1 Introduction ................................................................................................... 121
6.2 Aim ................................................................................................................. 122
6.3 Recruitment and data collection ................................................................... 122
6.4 Treatment of PEH........................................................................................... 125
6.5 Statistical methods ........................................................................................ 125
6.6 Results ............................................................................................................ 126
6.6.1 Pre-operative patient characteristics ..................................................... 126
6.6.2 Pre-operative blood pressure recordings............................................... 140
6.6.3 Pre-operative systolic blood pressure thresholds .................................. 145
6.6.4 Comparison of blood pressure recordings between devices ................. 157
6.7 Discussion ...................................................................................................... 160
6.7.1 Pre-operative patient demographics and clinical variables ................... 160
6.7.2 Pre-operative blood pressure ................................................................. 162
7 Is Pre-operative Impairment of Baroreceptor Sensitivity Associated with Post-
CEA Hypertension? ....................................................................................................... 170
7.1 Introduction ................................................................................................... 170
7.2 Aims ............................................................................................................... 171
7.3 Methods of data collection and analysis for baroreceptor sensitivity and
cerebral autoregulation ............................................................................................ 171
7.3.1 Data Collection ....................................................................................... 172
7.3.2 Data editing and analysis ........................................................................ 175
7.4 Patient recruitment ....................................................................................... 179
7.5 Statistical analysis .......................................................................................... 180
7.6 Results ............................................................................................................ 181
7.6.1 Baroreceptor sensitivity in patients experiencing PEH in PACU ............ 183
7.6.2 Baroreceptor sensitivity in patients experiencing PEH on the ward ..... 185
7.6.3 Baroreceptor sensitivity in patients with SBP >200mmHg on the ward 187
7.6.4 Baroreceptor sensitivity in relation to pre-operative blood pressure ... 190
7.6.5 Baroreceptor sensitivity in relation to carotid stenosis, patient sex, age
and history of diabetes ......................................................................................... 191
7.7 Discussion ...................................................................................................... 194
8 Is Pre-operative Impairment of Cerebral Autoregulation Associated with Post-
CEA Hypertension? ....................................................................................................... 200
8.1 Introduction ................................................................................................... 200
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8.2 Aims ............................................................................................................... 201
8.3 Recruitment and data collection ................................................................... 201
8.4 Statistical analysis .......................................................................................... 202
8.5 Results ............................................................................................................ 204
8.5.1 Cerebral autoregulation in patients experiencing PEH in PACU ............ 205
8.5.2 Cerebral autoregulation in patients experiencing PEH on the ward ..... 206
8.5.3 Cerebral autoregulation in patients experiencing SBP>200mmHg ........ 208
8.5.4 Cerebral autoregulation and patient characteristics ............................. 210
8.6 Discussion ...................................................................................................... 216
9 Can Peri-Operative Patient Variables Predict Those who Receive Treatment for
Post-CEA Hypertension? ............................................................................................... 222
9.1 Introduction ................................................................................................... 222
9.2 Aims ............................................................................................................... 222
9.3 Recruitment and data collection ................................................................... 223
9.4 TCD measurements and timeframes ............................................................. 224
9.5 Statistical methods ........................................................................................ 227
9.6 Results ............................................................................................................ 228
9.6.1 Perioperative patient variables .............................................................. 228
9.6.2 Peri-operative blood pressure recordings .............................................. 233
9.6.3 Pre-induction of anaesthesia systolic blood pressure thresholds ......... 236
9.6.4 Intra-operative changes in middle cerebral artery velocity ................... 242
9.7 Discussion ...................................................................................................... 244
Chapter 10: Is post-CEA hypertension associated with increased risk of peri-
operative complications? .............................................................................................. 249
10.1 Introduction ................................................................................................... 249
10.2 Aim ................................................................................................................. 249
10.3 Recruitment and data collection ................................................................... 249
10.4 Statistical methods ........................................................................................ 251
10.5 Results ............................................................................................................ 252
10.5.1 Post-CEA complications .......................................................................... 252
10.5.2 Post-CEA length of stay .......................................................................... 255
10.6 Discussion ...................................................................................................... 256
Chapter 11: Summary .................................................................................................. 259
Appendix 1 ................................................................................................................... 265
Appendix 2 ................................................................................................................... 269
References.................................................................................................................... 270
vii
The Pathogenesis of Stroke
The Pathogenesis of Stroke

1.1 Stroke
Stroke/Cerebrovascular Accident (CVA): Is defined by the World Health Organisation
(WHO) as ‘rapidly developing clinical signs of focal (at times global) disturbance of
cerebral function, lasting more than 24 hours or leading to death with no apparent
cause other than that of vascular origin’ [1]. It is of significant and increasing socio-
economic importance, affecting approximately 15 million people a year worldwide [2],
accounting for 5.4 million deaths [3] and being one of the largest causes of complex
disability in adulthood [4].

Incidence in high-income countries has declined 42% between 1970 and 2008, whilst
low-middle income countries have seen a rise of more than 100% in that time [5]. This
divergence is not fully understood, but is likely to be due to improved risk factor
modification and stroke prevention in developed countries and ‘health transition’,
with death from infectious diseases making way to degenerative diseases in
developing countries [6]. Even with this declining incidence in high income countries,
the WHO still predicts that the number of stroke events in Europe is likely to increase
from 1.1 million per year in 2000 to 1.5 million per year in 2025 due to aging
populations [7]. European population projections predict a rise from 14.8% to 26.9%
in the over 65’s and from 3% to 9.3% in the over 80’s between 2000 and 2050, with
the median age in Europe increasing from 37.6 years to 45.7 years during that time
[8]. With increasing age being an important risk factor, 80% of strokes occurring in the
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The Pathogenesis of Stroke
over 65’s and people aged over 75 having a nine-fold increase in the risk of a first ever
stroke compared to people aged 45-64 years [9], this poses a significant health
problem.

In England and Wales it is estimated that 133,700 people will suffer a stroke each year,
87,700 people will suffer their first ever stroke, 53,700 a recurrent stroke. After one
year, approximately 40,000 will have died and 33,000 will have a significant disability
requiring on going care [9]. It is estimated that 900,000 people are living in England
with the effects of stroke, half of these requiring help with everyday activities [10].
The cost to the NHS is estimated to be around £2.8 billion [11].

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