A Textbook of Clinical Pharmacology and Therapeutics

SUPPLEMENTARYDRUGS 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 lidocainemixed with
  propofol.


• Involuntary movements and convulsions (which can be
  delayed).

KETAMINE

Use and pharmacokinetics

Ketamineis 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 stimu-
lant. 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 anaes-
thetists. 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 intra-
venous 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 dura-
tion 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.

SUPPLEMENTARY DRUGS

BENZODIAZEPINES

See Chapters 18 and Chapter 22.

Midazolamis a water-soluble benzodiazepine and useful

intravenous sedative. It has a more rapid onset of action than

diazepamand 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 induc-

tion of anaesthesia is usually confined to slow induction of

poor-risk patients. Prior administration of a small dose of

midazolamdecreases 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.

Diazepamis used for premedication (oral), sedation (by

slow intravenous injection) and as an anticonvulsant (intra-

venously). A preparation formulated as an emulsion in soya-

bean 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 fentanylprovide cardiac stability.

Key points

• Intravenous anaesthetics may cause apnoea and
  hypotension.


• Adequate resuscitation facilities must be available.

OTHER AGENTS

Etomidatehas 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 phe-
nomena 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 propofolgradually

replacingthiopentalin 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
  thanpropofolandthiopental, 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).