1. Craigavon
Area
Hospital
CT1
Educa.on
Series
(Intro)
Intravenous
Anaesthe.cs
Dr.
Andrew
Ferguson
2. Overview
• Mechanisms
of
ac.on
• Pharmacological
principles
• Individual
agent
overviews
• Pharmacokine.cs
• Induc.on
characteris.cs
• Organ
effects
Dr.
Andrew
Ferguson
3. How
do
they
work?
• Major
inhibitory
neuro-‐transmiMer
in
the
CNS
=
GABA
• Ac.ve
GABA
receptor
=>
Cl-‐
influx
=>
hyperpolarisa.on
• Propofol
&
barbiturates
slow
GABA/receptor
dissocia.on
• Benzodiazepines
increase
GABA
to
receptor
coupling
• Ketamine
acts
at
NMDA
receptor
• These
effects
lead
to
seda.ve
&
hypno.c
effects
Dr.
Andrew
Ferguson
4. Pharmacodynamics
• Increasing
dose
=>
seda.on
=>
hypnosis
• All
iv
anaesthe.cs
affect
other
organ
systems
– Poten.al
for
respiratory
depression
– Poten.al
for
CVS
depression
– Poten.al
for
altered
CBF/ICP
• Hypovolaemia
=>
severe
haemodynamic
effects
seen
due
to
decreased
blood
pool
– Use
lower
doses!
Dr.
Andrew
Ferguson
7. Context-‐sensi.ve
Half-‐Time
• Time
required
for
central
compartment
blood
concentra.on
to
fall
by
half
as
a
func.on
of
the
dura.on
of
an
infusion
(of
variable
rate
designed
to
maintain
steady
state)
Dr.
Andrew
Ferguson
8. Schema
for
Discussing
Drugs
• Chemistry
• Structure
&
structure-‐ac.vity
rela.onship
• Physical
proper.es
• Mode
of
ac.on
• Organ
effects
• CVS
• RS
• CNS
• GIT
etc.
• Pharmacokine.cs
• Distribu.on
• Metabolism
• Elimina.on
• Side-‐effects
• Clinical
Use
Dr.
Andrew
Ferguson
9. Propofol
• Very
widespread
use...know
inside
out!
• 2,6-‐diisopropylphenol
• Emulsion
with
10%
soybean
oil,
2.25%
glycerol
and
1.2%
lecithin
(egg
yolk
phospha.de
-‐
?
allergen)
• Injec.on
pain
(up
to
65%)
decreased
by
lidocaine
• Induc.on
dose
higher
in
kids,
lower
in
elderly
• Metabolised
in
liver
&
?
lungs
• Wake-‐up
due
to
redistribu.on,
not
metabolism
• Significant
vasodilata.on
&
baroreceptor
inhibitor
• An.eme.c
• Suppresses
laryngeal
reflexes
Dr.
Andrew
Ferguson
10. Etomidate
• Imidazole
deriva.ve,
D-‐(+)
isomer
• Poorly
soluble
in
H2O
=>
propylene
glycol
used
• Wake-‐up
due
to
redistribu.on
• Metabolised
by
ester
hydrolysis
to
inac.ves
• Minimal
haemodynamic
effects,
short
half-‐life
• High
incidence
of
PONV
(35-‐40%)
• May
ac.vate
seizure
foci,
myoclonus
in
50%
• Adrenocor.cal
suppression
• dose-‐dependent
11
β-‐hydroxylase
inhibi.on
• lasts
4-‐12
hrs
aier
single
dose
(much
longer
in
cri.cally
ill)
Dr.
Andrew
Ferguson
11. Ketamine
• Phencyclidine
deriva.ve
• Racemic
mixture:
S-‐isomer
fewer
adverse
effects
• Effects
– Significant
analgesia
at
sub-‐anaesthe.c
doses
– “Dissocia.ve
anaesthesia”
-‐
catalep.c
state
– Blocks
NMDA
receptor
(NOT
GABAA
ac.ve)
– Vivid
dreams
or
hallucina.ons
during
recovery
– EEG
changes
cannot
be
used
to
gauge
depth
– More
stable
haemodynamics
in
unstable
pa.ents
– Less
diminu.on
of
airway
reflexes
(less,
not
none!!)
Dr.
Andrew
Ferguson
12. Benzodiazepines
• iv
prep:
midazolam,
diazepam,
lorazepam
• Midazolam
has
imidazole
ring
• ring
protonated
=>
water
soluble
at
acid
pH
• In
body,
ring
unprotonated
=>
lipid
soluble
• solubility
NOT
due
to
opening
of
benzo
ring
at
low
pH
• At
pH
4
only
9%
of
MDZ
rings
are
open
(75%
at
pH
2)
• Bind
specific
site
between
α
+
γ
subunits
of
GABAA
receptor
• Hepa.c
metabolism
• Vasodilata.on
with
MDZ
>
Diazepam
Dr.
Andrew
Ferguson
13. Thiopental
• Thiobarbiturate
• Sodium
salt
+
anhdrous
NaHCO3
=>
pH
10-‐11
• Precipitates
with
acidic
drugs
e.g.
NMBs
• Extravascular
injec.on
=>
pain
+
.ssue
injury
• Intra-‐arterial
injec.on
=>
crystals
+
ischaemia
• Dose
dependent
CNS
depression
• Decrease
CBF,
ICP,
CMRO2,
seizure
ac.vity
• Less
BP
fall
at
induc.on
than
propofol
• Compensatory
heart
rate
increase
offsets
vasodilata.on
effects
• Cau.on
in
hypovolaemia,
tamponade,
IHD,
heart
failure
• Wake-‐up
due
to
redistribu.on
Dr.
Andrew
Ferguson
14. Management
of
intra-‐arterial
injec1on
of
Thiopental
Stop
injec1on
but
leave
needle
or
cannula
in
place
Dilute
with
immediate
injec.on
of
saline
Give
intra-‐arterial
LA
+
vasodilator
Lidocaine
50mg
(5
ml
of
1%
solu.on)
Phenoxybenzamine
(α
blocker)
0.5
mg
bolus
or
50-‐200
µg/minute
infusion
Consider
systemic
papaverine
40-‐80
mg
Consider
sympathe.c
blockade
(stellate
ganglion
or
brachial
plexus
block)
Start
iv
heparin
infusion
Consider
intra-‐arterial
hydrocor.sone
Postpone
non-‐urgent
surgery
Liaise
with
vascular
surgeon
Dr.
Andrew
Ferguson