A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

SUPPLEMENTARY DRUGS 149
• Respiratory system – apnoea following injection may require
assisted ventilation. If opioids are also administered, as with
other agents, the respiratory depression is more marked.
• Pain on injection – this is common, and the incidence is
reduced if a larger vein is used or lidocaine mixed with
propofol.
• Involuntary movements and convulsions (which can be
delayed).
KETAMINE
Use and pharmacokinetics
Ketamine is chemically related to phencyclidine (still used as
an animal tranquillizer, but no longer for therapeutic use in
humans because of its psychogenic effects and potential for
abuse), and produces dissociative anaesthesia, amnesia and
profound analgesia. It is a relatively safe anaesthetic from the
viewpoint of acute cardiorespiratory effects since, unlike other
intravenous anaesthetics, it is a respiratory and cardiac stimulant.
A patent airway is maintained and it is a bronchodilator.
Because of its ease of administration and safety, its use is
widespread in countries where there are few skilled anaesthetists.
It has been used for management of mass casualties or
for anaesthesia of trapped patients to carry out amputations,
etc. It is used in shocked patients, because unlike other intravenous
anaesthetics it raises rather than lowers blood pressure.
An intravenous dose produces anaesthesia within 30–60
seconds, which lasts for 10–15 minutes. An intramuscular
dose is effective within three to four minutes, and has a duration
of action of 15–25 minutes. There is a high incidence of
hallucinations, nightmares and transient psychotic effects.
Children cannot articulate such symptoms and it is disturbing
that it is still used particularly in this age group.
Adverse effects
• Psychosis and hallucinations are common.
• Intracranial pressure is increased by ketamine.
• Blood pressure and heart rate are increased.
• Salivation and muscle tone are increased.
• Recovery is relatively slow.
Key points
• Intravenous anaesthetics may cause apnoea and
hypotension.
• Adequate resuscitation facilities must be available.
OTHER AGENTS
Etomidate has a rapid onset and duration of action and has
been used for induction. Its use has declined because it causes
pain on injection, nausea and vomiting, and excitatory phenomena
including extraneous muscle movements. Etomidate
can suppress synthesis of cortisol (see below) and it should
not be used for maintenance of anaesthesia.
Key points
Intravenous induction agents
All have a rapid onset of action, with propofol gradually
replacing thiopental in the UK as the usual agent of choice.
• Propofol – rapid recovery, pain on injection, bradycardia
which may be avoided by use of an antimuscarinic agent,
rarely anaphylaxic and causing convulsions.
• Thiopental – smooth induction but narrow therapeutic
index, cardiorespiratory depression, awakening usually
rapid due to redistribution, but metabolism slow and
sedative effects prolonged, very irritant injection.
• Methohexitone – barbiturate similar to thiopental, less
smooth induction, less irritant, may cause hiccup, tremor
and involuntary movements.
• Etomidate – rapid recovery and less hypotensive effect
than propofol and thiopental, but painful on injection.
Extraneous muscle movements and repeated doses cause
adrenocortical suppression.
• Ketamine – good analgesic, increases cardiac output
and muscle tone. Due to unpleasant psychological effects
(e.g. nightmares and hallucinations) it is restricted to
high-risk patients. Useful in children (in whom central
nervous system (CNS) effects are less problematic),
particularly when repeated doses may be required, and in
mass disasters (relatively wide therapeutic index, may be
used intramuscularly, slow recovery, safer than other
agents in less experienced hands).
SUPPLEMENTARY DRUGS
BENZODIAZEPINES
See Chapters 18 and Chapter 22.
Midazolam is a water-soluble benzodiazepine and useful
intravenous sedative. It has a more rapid onset of action than
diazepam and a shorter duration of action, with a plasma
half-life of 1.5–2.5 hours. Dose is titrated to effect. Midazolam
causes amnesia, which is useful for procedures such as
endoscopy or dentistry. The use of benzodiazepines for induction
of anaesthesia is usually confined to slow induction of
poor-risk patients. Prior administration of a small dose of
midazolam decreases the dose of intravenous anaesthetic
required for induction. Large doses can cause cardiovascular
and respiratory depression. Repeated doses of midazolam
accumulate and recovery is prolonged.
Diazepam is used for premedication (oral), sedation (by
slow intravenous injection) and as an anticonvulsant (intravenously).
A preparation formulated as an emulsion in soyabean
oil has reduced thrombophlebitis from intravenous
diazepam.
OPIOIDS
High-dose opioids (see Chapter 25) are used to induce and
maintain anaesthesia in poor-risk patients undergoing major
surgery. Opioids such as fentanyl provide cardiac stability.