Pharm-02A11: Briefly outline the effects of thiopentone and ketamine not mediated via the central nervous system.
77%
Pharm-99B14: Briefly outline the actions of intravenous induction agents not mediated via the central nervous system. 24%
Thiopentone
CVS effects
HR Compensatory increase (due to
intact BRR and SNS output)
CO - Dose-dependent fall (20%) due
to direct myocardial depression
(–ve inotrope)
- At induction doses, fall in CO
is MINIMAL due to SNS
outflow from an intact BRR.
This effect is lost at higher doses
BP - Dose-dependent fall mainly due
to drop in SVR (and also a fall in
CO at higher doses only)
- At induction doses, the fall in
BP is only mild and transient as
CO is minimally affected (due to
masking of –ve inotropy by an
intact BRR)
- At higher doses, BP fall
significant due to loss of BRR
and unmasking of –ve intropic
effects
SVR Dose-dependent fall due to
peripheral vasodilation
Haemodynamic - Mild fall in BP does not blunt
sequelae of AW the haemodynamic sequelae of
instrumentation AW instrumentation
- Fall in BP can be reversed by
hypetensive effects of AW
instrumentation
Propofol
- Generally unchanged (due to
depression of BRR and SNS
outflow)
- Significant bradycardia and
asystole can occur
Dose-dependent decrease by
up to 20% (direct –ve inotropy
and myocardial depression)
- Dose-dependent decrease by
15-25% due to fall in SVR and
C.O.
Dose-dependent decrease (due
to vasodilation)
- Fall in BP can be reversed by
hypertensive sequelae of AW
instrumentation
- Fall in BP can blunt the
hypertensive response to AW
instrumentation
Etomidate
Minimal change at induction
doses (compensatory
increase in HR occurs at
higher doses due to BRR)
Minimal change at induction
doses (-ve inotropic effects
and fall in CO occur at
higher doses
- Dose-dependent decrease
mainly due to fall in SVR
(and at higher doses, fall in
CO contributes to fall in BP)
- At induction doses, BP
falls by 15% (less prominent
cf. other IV agents)
Decreased due to peripheral
vasodilation
Hypertensive response to
AW instrumentation cannot
be blunted by the fall in BP
caused by etomidate – Thus,
opioids must be given
concurrently
Ketamine Midazolam
- Ketamine has indirect Dose-dependent increase in
effects on the CVS via – (i) HR (up to 20%) due to
direct central (CNS) activation of BRR with the fall
stimulation of SNS outflow, in BP
and (ii) inhibition of NAd
reuptake Unchanged
- This leads to:
- Increased HR (as
BRR is maintained)
- Increased CO
- Increased BP
- Increased CMRO2
(and also increased Dose-dependent fall in MAP
coronary blood (up to 5%) due to decreases in
flow) SVR
- Nb. SVR is
unchanged despite
increased SNS
activity
- Nb. There are no
arrhythmogenic
effects (even with
the use of Adr)
- Ketamine is a –ve inotrope
as it has direct myocardial Dose-dependent decrease (15-
depressive effects (esp R- 30%) due to peripheral
isomer) – This produces a vasodilation
fall in CO and BP when SNS - Hypertensive response to
outflow is exhausted (Eg. AW instrumentation
end-stage shock) or inhibited CANNOT be blunted by the
(Eg. SAB, use of volatile fall in BP caused by
agents, opioids, midazolam
benzodiazepines) - Hypotensive effects of
- Ketamine (only the R- midazolam can be prevented
isomer) inhibits ischaemic by the hypertensive response

Arrhythmogenicity Nil. Also QTC not prolonged
Coronary BF and
CMRO2
Respiratory effects
Minute ventilation - Dose-dependent ventilatory
and resting PaCO2 depression (decreased TV and
RR). Usually causes apnoea when
used with other CNS depressants
- Increased resting PaCO2
Ventilatory response Decreased ventilatory response
to PaCO2 and PaO2 with increased apnoeic threshold
Effect on AW - Depresses UAW reflexes
ONLY at high doses
- Laryngospasm and
bronchospasm occur in response
to AW instrumentation or
presence of secretions as UAW
reflex may be inadequately
depressed at induction doses
Pulmonary Hypoxic pulmonary
vasculature vasoconstriction intact
GI, GU, metabolic - Reduced HBF (but normal
and other effects LFTs)
- Reduced GFR, RBF and U/O
due to fall in CO and increased
Nil. Also QTC not prolonged
Decreased myocardial O2
consumption and myocardial
perfusion, BUT myocardial
ischaemia can occur due to
regional mismatch in
myocardial O2 supply and
demand
- Dose-dependent ventilatory
depression (decreased TV and
RR), which can lead to apnoea
- Increased resting PaCO2
- Decreased
- Increased apnoeic threshold
- Bronchodilation (although
sodium metabisulfite can cause
bronchoconstriction!)
- Depresses UAW reflexes
(good for AW instrumentation
but risk of aspiration and AW
obstruction)
Hypoxic pulmonary
vasoconstriction intact
- Does not adversely impact
renal/hepatic function
- Anti-emetic effect
- Anti-pruritic effect
Nil. QTc not prolonged
Cardiac MRO2 and O2
delivery stable as –ve
inotropic effects minimal at
induction doses
- Dose-dependent
ventilatory depression
(decreased TV and RR),
which can lead to apnoea at
high doses
- At induction doses,
significant respiratory
depression and apnoea are
unlikely if given alone
- Mildly increased resting
PaCO2
- Mild depression of
ventilatory response
- Slight increase in apnoeic
threshold
- No effect on AW smooth
muscle
- Depresses UAW reflexes
(good for AW
instrumentation but risk of
aspiration and AW
obstruction)
Hypoxic pulmonary
vasoconstriction intact
- No effect on hepatic or
renal function
preconditioning as it inhibits
the KATP channel
- Minimal effect on MV,
BUT decreased RR and
apnoea can occur with rapid
IV bolus or concurrent
opioids/benzodiazepines
- Resting PaCO2 unchanged
Maintained. No increase in
apnoeic threshold
- Potent bronchodilator
(good for bronchospasm)
- UAW reflex maintained
- Increased UAW gland
secretions
Hypoxic pulmonary
vasoconstriction intact
- No hepatic/renal effects
- Increased salivation
- Increased PONV
- Increased uterine tone
to AW instrumentation
Nil. Does not prolong QTc
Decreased O2 metabolism and
increased O2 delivery (due to
coronary vasodilation)
- Dose-dependent decrease in
MV (TV decreases but RR
increases)
- Increased resting PaCO2
Impaired
- No bronchodilatory effects
- Depresses UAW reflexes
(risk of aspiration and AW
obstruction)
Hypoxic pulmonary
vasoconstriction intact
- Decreased HBF
- Decreased GFR, RBF and
U/O
- Decreased PONV
 ADH release
- No effects on the uterus
- Does not trigger MH
Issues with - Pain on injection (esp if 5%
injection STP)
- Extravascular injection very
painful (serious tissue necrosis)
- Intra-arterial injection causes
severe pain and tissue ischaemia
due to precipitation of crystals
- Venous thrombosis can occur
due to precipitation of crystals
Relevant adverse - Risk of acute porphyric crisis
or undesired - Allergic reactions (anaphylaxis
effects and anaphylactoid reactions –
1:20,000-30,000)
- Minimal histamine release
- Tolerance occurs
- Abusive potential (dependence
and withdrawal occur with
prolonged barbiturate use)
- Immunosuppression (with
long-term high doses)
CNS effects
General effects - Sedative-hypnotic effect to full
general anaesthesia – Smooth
and rapid induction with rapid
recovery, BUT with residual
CNS effects lasting hours
(“hangover”)
- Antanalgesic at low doses
CBF Decreased due to cerebral
vasoconstriction from decreased
metabolism
ICP (and IOP and - ICP falls due to decreased CBF
CPP) - CPP increased because the fall
- Does not trigger MH
- Does not trigger acute
porphyric crisis
- Pain on injection (30%) -
Venous thrombosis and
phlebitis (< 1%)
- Intra-arterial injection causes
severe pain only
- Low risk of allergic reactions
and anaphylaxis
- Propofol infusion syndrome
(with long-term IV infusion)
- “Excitatory phenomenon”
- Addictive and abusive
potential
- Bacterial growth and risk of
sepsis
- Excretion of green urine and
production of green hair with
prolonged infusions
- Conscious sedation to full
general anaesthesia
- Smooth and rapid induction
with clear and rapid recovery
- Amnesic effect
- No analgesia
Decreased due to cerebral
vasoconstriction from
decreased metabolism
- ICP falls due to fall in CBF
- CPP may decrease – Due to
- Pain on injection (only with None
propylene glycol; not with
lipid solution)
- Risk of venous thrombosis
- No issues with intra-arterial
injection
- Adrenocortical suppression
- Risk of inducing porphyric
crisis
- Increased PONV
- Excitatory phenomenon
and proconvulsant activity
- Histamine release and
allergic reactions rare
- Conscious sedation and
amnesia to full general
anaesthesia
- Smooth and rapid
induction with rapid
recovery (however, mild
psychomotor dysfunction)
- No analgesia
Decreased due to cerebral
vasoconstriction from
decreased metabolism
- Decreased ICP due to fall
in CBF
- Does not trigger MH
- Does not trigger acute
porphyric crisis
- Does not cause histamine
release or allergic reactions
- Lower potential for abuse as
less tolerance (cf. other
benzodiazepines), BUT
dependence and withdrawal
symptoms still occur
- Delayed awakening
- Emergence delirium
- Addictive and subject to
abuse
- Tolerance with
infusion/repeated doses (esp
to analgesia)
- Hypertonia and myoclonic
seizure-like activity
- Dissociative anaesthesia - Anxiolysis
- Analgesia (at - Sedation/hypnosis
subanaesthetic doses) - Skeletal muscle relaxation
- Amnesia - Anterograde amnesia
- Absence of analgesic effects
Increased due to cerebral Decreased due to cerebral
vasodilation vasoconstriction from
decreased metabolism
- Increased ICP due to rise - No rise in ICP for patients
in CBF with IC pathology
 in ICP is generally greater than
the fall in MAP
- Decreased IOP
CMRO2 Dose-dependent fall (max fall of
55% with isoelectric EEG)
EEG and seizure - Dose-related decrease in EEG
activity activity – Gradual progression
from awake α pattern (high
frequency, low voltage) to δ- and
θ-waves (slow frequency, high
voltage), then burst suppression,
and f silent (isoelectric) EEG
- Anticonvulsant effect
significant hypotensive effects
of propofol
- Decreased IOP
Decreased
- Dose-related decrease in
EEG activity (similar to STP)
- Anticonvulsant effects
- Reduces seizure duration
during ECT
- CPP maintained due to
minimal fall in MAP
- Decreased IOP
Decreased
- Dose-related decrease in
EEG activity (similar to
STP)
- Anticonvulsant effects
- Ideal for ECT as it has
minimal effects on duration
of seizures
- Raised IOP
Increased
- Dose-related decrease in
cortical EEG activity
- Excitatory EEG activity is
seen ONLY at the thalamic
and limbic systems
- Used as an anticonvulsant
- Increase in ICP if severe
head trauma with ICP < 18
mmHg or if given rapidly
- Does not prevent rise in ICP
caused by AW instrumentation
Dose-dependent decrease
- Dose-related decrease in
EEG activity (similar to STP)
- Potent anticonvulsant