Assessment of graded changes in the Central Nervous System, during general anaesthesia and ...

200 Pages·2011·8.69 MB·English

Assessment in the Central Nervous System,
of graded changes
during in the
general anaesthesia and surgery man, using
auditory evoked response
A thesis submitted to the University of London for the degree of
Doctor Philosophy
of
Christine Thornton
Institute Neurology, University London
of of
Clinical Research Centre,
Northwick Park Hospital,
Harrow,
Middlesex.
2
ACKNOWLEDGEMENTS
The experimental work of the thesis was carried out at the Medical
Research Council Division Anaesthesia, Clinical Reasearch
of
Centre, Northwick Park Hospital, Harrow. I indebted to the
am
in the Division I the
anaesthetists with whom worked on project and
I am grateful to the staff of the John Squire Medical library who
provided reference I like to thank
material. would particularly
Professor Gareth Jones Dr P Rudge for their invaluable
and
Dr JF Nunn, Dr DEF Newton, Dr DC White, Mrs CJ
supervision and
Dore Mr C Jordan for discussion
and their
and support.
3
ABSTRACT
(AER)
the
The thesis the use of auditory evoked response
examines
'depth
to of anaesthesia'.
measure
The historical background to general anaesthesia is reviewed.
Developments in recording the evoked responses with particular
factors
to the the which
reference auditory evoked response and
influence this described.
are
The effects of increasing concentrations of six general
(halothane, isoflurane,
etomidate,
anaesthetic agents enflurane,
Althesin the brainstem and early cortical
and propofol) on
by
auditory evoked responses and the modification of these effects
indicator
The AER
investigated. as an
surgical stimulation were
'awareness'
of was also assessed.
These produced
studies showed that all six general anaesthetics
the
qualitatively in the early cortical section of
similar changes
AER. These in of
increases in latency and reductions amplitude
were
the waves Pa Nb increasing of anaesthetics.
concentrations
and with
The during
amplitude surgery.
changes were partially reversed
Only (halothane,
the inhalation and
enflurane
anaesthetics
isoflurane) The
produced changes in the brainstem response.
latencies of waves III and V and their interpeak intervals
increased increasing These
with anaesthetic concentrations. changes
during
were not reversed surgery.
Nb,
The latency of the early cortical wave emerged as a
indicator of 'awareness' in that, in a group of patients
possible
to
anaesthetised with nitrous oxide and oxygen prior general
latencies below 44.5 ms were associated with a positive
surgery,
the isolated forearm technique. In a second study,
response using
4
during Caesarian latencies below 44.5
section surgery, ms occurred
frequently following delivery in in
more patients whom anaesthesia
was maintained with nitrous oxide-opiate anaesthesia only, compared
to those to whom an enflurane supplement was given.
These, findings their theoretical implications
and are examined
in the light the literature. The the
of practical application of
depth is discussed.
technique
as a clinical monitor of anaesthetic
5
CONTENTS
Acknowledgements 2
Abstract 3
Contents 5
Index Abbreviations 9'
of
Index Tables 10
of
Index Figures 11
of
CHAPTER 1 INTRODUCTION 14
SECTION A LITERATURE REVIEW 20
CHAPTER 2 HISTORICAL DEVELOPMENTS IN ANAESTHESIA
2.1. Early 21
anaesthesia
2.2. Modern Anaesthesia 22
2.3. Tracheal intubation 22
2.4. Neuromuscular blockers 23
2.5. Intravenous 24
agents
2.6. Clinical 'depth 25
signs of of anaesthesia'
2.7. 29
Electroencephalographic indices
of
'depth
of anaesthesia'
CHAPTER
3 HISTORICAL BACKGROUND TO THE AUDITORY EVOKED RESPONSE
3.1. The first 33
electronic averager
3.2.
The late 33
cortical response
3.3.
The 33
early cortical response
3.3.1.
Is 35
the
response myogenic or neurogenic?
3.3.2.
Are Na Pa 39
and separately generated?
3.3.3.
What the Na Pa? 41
are generators of and
3.4. The brainstem 43
response
CHAPTER 4 FACTORS AFFECTING THE AUDITORY EVOKED RESPONSE
4.1. Introduction 46
4.2. Technical factors 46
4.2.1. Recording 46
system
4.2.2. Stimulus 53
6
4.3. Subject factors 57
related
4.3.1. Temperature 57
4.3.2. Age Gender 57
and
4.3.3. Level 59
of arousal
4.3.4. Neurological factors 63
4.4. Pharmacological factors 63
4.4.1. General 63
anaesthetic agents
4.4.2. Opiates 65
analgesics
-
4.4.3. Sedatives 65
SECTION B METHODS 67
CHAPTER 5 STUDY DESIGN AND ANAESTHETIC PROTOCOL
5.1. Introduction 68
5.2. Standard 69
anaesthetic protocol
5.3. Effect 69
the AER
of general anaesthetics on
5.4. Effect the AER 71
of surgical stimulation on
5.5. An AER indicator 'awareness' 71
of
5.5.1. Assessment 'awareness' 71
of
72
5.5.2. Investigations to
prior general surgery
72
5.5.3. Investigations during Caesarian
section
CHAPTER 6 ESTIMATION OF ANAESTHETIC CONCENTRATIONS
74
6.1.
Gases
74
6.1.1.
Nitrous
oxide and oxygen
74
6.1.2. Carbon dioxide
76
6.1.3.
Halothane
and enflurane
77
6.1.4.
Enflurane Isoflurane
and
6.2.
Intravenous 78
agents
6.2.1. 78
Etomidate
6.2.2. 78
Althesin
6.2.3. 79
Propofol
CHAPTER 7 AER RECORDING AND ANALYSIS
7.1. Electrode 80
placements
7.2. Amplifiers 80
7.3. Stimulus 83
7.3.1. Production the 83
of click stimulus
7.3.2. Effect 84
of stimulus presentation
(constant
time
rate/number period)
7
7.4. Extraction AER 87
of variables
7.5. Statistical 89
analyses
7.5.1. Effect 89
of general anaesthetics
7.5.2. Effect 90
of surgical stipulation
7.5.3. An AER indicator 'awareness' 90
of
SECTION C RESULTS 92
CHAPTER 8 EFFECT OF GENERAL ANAESTHETICS ON THE AER
8.1. Introduction 93
8.2. Brainstem 93
response
8.2.1. Description 93
of changes
8.2.2. Statistical 96
analyses
8.3. Early 107
cortical changes
.
8.3.1.
Description 107
of changes
8.3.2. Statistical 111
analyses
8.4. Arterial deep body 117
temperature
pressure and
CHAPTER 9 EFFECT OF SURGICAL STIMULATION ON THE AER
9.1. Introduction 119
9.2. Effect 120
of surgery
120
9.2.1. Description data
of
120
9.2.2.
Statistical
analyses
9.3. Autonomic 126
responders versus non-responders
9.3.1. Description data 126
of
9.3.2. 127
Statistical
analyses
CHAPTER 10
AN AER INDICATOR OF AWARENESS
10.1.
Introduction 128
10.2.
Extraction 131
to
of mathematical criteria
distinguish
'three 'two AERs
wave' and wave'
10.3. Nb latency in 'awareness' 134
to
relation
10.3.1.
Investigations 134
to
prior general surgery
10.3.2. Investigations during Caesarian 136
section
SECTION D DISCUSSION 142
CHAPTER 11 THE FINDINGS OF THE THESIS
11.1. Introduction 143
8
143
11.2. Graded increasing
changes with concentrations
of general anaesthetics
143
11.2.1. Brainstem
response
148
11.2.2. Early
cortical response
151
11.3. Changes by surgical stimulation
reversed
'awareness' 152
11.4. An AER indicator
of
OF THE FINDINGS
CHAPTER 12 'SIGNIFICANCE
154
12.1. Introduction
154
12.2. Graded'changes with general anaesthetics
154
12.2.1. Brainstem
response
154
12.2.2. Early
cortical response
155
12.2.3. Effects AER in
on of anaesthetics
relation to their anaesthetic potency
158
12.3. Reversal
of general anaesthetic effects
by
surgical stimulation
159
'awareness'
12.4. An AER indicator
of
159
'awareness'
12.4.1. AER
variables and
159
'awareness'
12.4.2. Definitions
of and
'anaesthesia'
161
during
12.4.3. 'Two-store' theory
of memory
anaesthesia
164
findings
12.4.4. Interpretation of the of
in to the
the thesis relation
'two-store'
memory model
166
12.5. Clinical the thesis
of
contribution
169
12.6. Future
work
171
REF ENS
200
APPENDIX
200
from
Publications the thesis
9
INDEX OF ABBREVIATIONS
AER
auditory evoked response
cv coefficient of variation
dB decibels
( )
dose for 50% 12.2.3.
ED50 of patients see
effective
EEG
electroencephalogram
EOG
electrooculogram
frequency
FM
modulated
liquid
GLC
gas chromatography
high liquid
HPLC performance chromatography
i. intravenous
v. -
(see )
2.6.
MAC
minimum alveolar concentration
S. D. deviation
standard
SER
somatosensory evoked response
10
INDEX OF TABLES
68
5.1. Summary
of studies
85
7.1. Effect
rate/number
of stimulus presentation
(constant
time period) on the early cortical
response
87
7.2. Effect of stimulus presentation rate/number
(constant brainstem
the
time period) on response
for latencies 89
7.3. Pre-anaesthetic values of waves
data
III, V, Pa, Nb the
compared with of
(1974)
Picton
et al.
8.1. Brainstem latencies interpeak intervals 101
and
time
regressions against
-
102
8.2. Brainstem time
amplitudes regressions against
-
8.3. Brainstem latencies interpeak intervals 105
and
regressions
- against'concentration
106
8.4. Brainstem
amplitudes - regressions against
concentration
115
8.5. Early latencies
cortical and amplitudes
time
- regressions against
116
8.6. Early latencies
cortical and amplitudes
- regressions against concentration
118
8.7. Changes in systolic arterial pressure with the
various test agents
119
9.1.
Patient for
information the'surgery
study
120
9.2. Mean for`the
following
changes surgery, eleven
patients, for AER latencies and amplitudes. '
124
9.3. Trends, before during in AER
and surgery,
latencies
and amplitudes
9.4. Autonomic 126
responses to surgical stimulation
of the patients who took part in the study
132
10.1. Changes
in the AER following induction
pattern
low
of anaesthesia the
and addition of
concentrations of anaesthetics