C H A P T E R 2 7
General and local anaesthetic agents
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sedation and produces a state of mental detachment.
It also has antiemetic effects, reducing the incidence of
nausea and vomiting in surgical and diagnostic proced
ures. Ketamine has been associated with a bizarre
state of unconsciousness in which the person appears
to be awake but is unconscious and cannot feel pain.
This drug, which causes sympathetic stimulation with
increase in blood pressure and heart rate, may be helpful
in situations when cardiac depression is dangerous.
Propofol is often used for short procedures because it
has a very rapid clearance and produces much less of a
hangover effect and allows for quick recovery. It is also
used to maintain people on mechanical ventilation.
Pharmacokinetics
Midazolam has a rapid onset but does not reach peak
effectiveness for 30 to 60 minutes. Droperidol has an
onset of action within 3 minutes and an ultra-short
recovery period. Ketamine has an onset of action within
30 seconds and a very slow recovery period (45 minutes).
Propofol is a very short-acting anaesthetic with a rapid
onset of action of 30 to 60 seconds.
Contraindications and cautions
Midazolam is more likely to cause nausea and vomiting
than are some of the other anaesthetics, and so it should
be used with caution in any person who could be com-
promised by vomiting. It has been associated with
respiratory depression and respiratory arrest, and so life
support equipment should be readily available whenever
it is used. Droperidol should be used with caution in
individuals with renal or hepatic failure and should be
used with extreme care in people with prolonged QT
intervals or who are at risk for prolonged QT intervals.
Adverse effects
People receiving any general anaesthetic are at risk for
skin breakdown because they will not be able to move.
Care must be taken to prevent decubitus ulcer forma-
tion. People receiving midazolam should be monitored
for respiratory depression and CNS suppression. During
the recovery period, droperidol may cause hypoten-
sion, chills, hallucinations and drowsiness. It may also
cause QT prolongation, which puts the person at risk
for serious cardiac arrhythmias. Ketamine crosses
the blood–brain barrier and can cause hallucinations,
dreams and psychotic episodes. Propofol often causes
local burning on injection. It can cause bradycardia,
hypotension and, in extreme cases, pulmonary oedema.
Clinically important drug–drug interactions
If ketamine and isoflurane are used in combination,
severe cardiac depression with hypotension and brady-
cardia may occur. If these agents must be used together,
the person should be monitored closely. Droperidol
should not be used with other drugs that prolong the
QT interval. If this combination is necessary, the person
should be monitored continuously. Ketamine may also
potentiate the muscular blocking of NMJ blockers, and
the person may require prolonged periods of respira-
tory support. Midazolam is associated with increased
toxicity and length of recovery when used in combina-
tion with inhaled anaesthetics, other CNS depressants,
opioids, propofol or thiopentone. If any of these agents
are used in combination, careful balancing of drug doses
is necessary.
Prototype summary: Midazolam
Indications:
Sedation, anxiolysis and amnesia before
diagnostic, therapeutic or endoscopic procedures;
induction of anaesthesia; continuous sedation of
intubated people.
Actions:
Acts mainly at the limbic system and RAS;
potentiates the effects of GABA; has little effect on
cortical function; exact mechanism of action is not
understood.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
30–60 mins 12 hours
2–6 hours
IM 15 mins
30 mins
2–6 hours
IV 3–5 mins
<30 mins
2–6 hours
T
1/2
:
1.8 to 6.8 hours; metabolised in the liver,
excreted in the urine.
Adverse effects:
Transient drowsiness, sedation,
drowsiness, lethargy, apathy, fatigue,
disorientation, restlessness, constipation, diarrhoea,
incontinence, urinary retention, bradycardia,
tachycardia, phlebitis at IV injection site.
A
naesthetic gases
Like all inhaled drugs, anaesthetic gases enter the
bronchi and alveoli, rapidly pass into the capillary system
(because gases flow from areas of higher concentration
to areas of lower concentration) and are transported
to the heart to be pumped throughout the body. These
gases have a very high affinity for fatty tissue, and they
are lipophilic, including the lipid membrane of the
nerves in the CNS. The gases pass quickly into the brain
and cause severe CNS depression. Once the person is
in stage 3 of anaesthesia, the anaesthetist regulates the
amount of gas that is delivered to ensure that it is suffi-
cient to keep the person unconscious but not enough to
cause severe CNS depression. This is done by decreas-
ing the concentration of the gas that is flowing into the
bronchi, creating a concentration gradient that results
