148 ANAESTHETICS AND MUSCLE RELAXANTS
infants among female operating department staff. Although
much of the evidence is controversial, scavenging of expired
or excessive anaesthetic gases is now standard practice.
INTRAVENOUS ANAESTHETICS
UPTAKE AND DISTRIBUTIONThere is a rapid increase in plasma concentration after admin-
istration of a bolus dose of an intravenous anaesthetic agent; this
is followed by a slower decline. Anaesthetic action depends on
the production of sufficient brain concentration of anaesthetic.
The drug has to diffuse across the blood–brain barrier from arte-
rial blood, and this depends on a number of factors, including
protein binding of the agent, blood flow to the brain, degree of
ionization and lipid solubility of the drug, and the rate and vol-
ume of injection. Redistribution from blood to viscera is the main
factor influencing recovery from anaesthesia following a single
bolus dose of an intravenous anaesthetic. Drug diffuses from the
brain along the concentration gradient into the blood. Metabolism
is generally hepatic and elimination may take many hours.
THIOPENTAL
Use and pharmacokinetics
Thiopentalis a potent general anaesthetic induction agent
with a narrow therapeutic index which is devoid of analgesic
properties. Recovery of consciousness occurs within five to
ten minutes after an intravenous bolus injection. The alkaline
solution is extremely irritant. The plasma t1/2βof the drug is
six hours, but the rapid course of action is explained by its
high lipid solubility coupled with the rich cerebral blood flow
which ensures rapid penetration into the brain. The short-
lived anaesthesia results from the rapid fall (αphase) of the
blood concentration (short t1/2α), which occurs due to the dis-
tribution of drug into other tissues. When the blood concen-
tration falls, the drug diffuses rapidly out of the brain. The
main early transfer is into the muscle. In shock, this transfer is
reduced and sustained high concentrations in the brain and
heart produce prolonged depression of these organs.
Relatively little of the drug enters fat initially because of its
poor blood supply, but 30 minutes after injection the thiopen-
talconcentration continues to rise in this tissue. Maintainance
of anaesthesia with thiopentalis therefore unsafe, and its use
is in induction.
Metabolism occurs in the liver, muscles and kidneys. The
metabolites are excreted via the kidneys. Reduced doses are
used in the presence of impaired liver or renal function.
Thiopentalhas anticonvulsant properties and may be used in
refractory status epilepticus (see Chapter 22).
Adverse effects
- Central nervous system– many central functions are
depressed, including respiratory and cardiovascular centres.
The sympathetic system is depressed to a greater extent
than the parasympathetic system, and this can result in
bradycardia. Thiopentalis not analgesic and at
subanaesthetic doses it actually reduces the pain threshold.
Cerebral blood flow, metabolism and intracranial pressure
are reduced (this is turned to advantage when thiopental
is used in neuroanaesthesia).- Cardiovascular system– cardiac depression: cardiac output
is reduced. There is dilatation of capacitance vessels.
Severe hypotension can occur if the drug is administered
in excessive dose or too rapidly, especially in hypovolaemic
patients in whom cardiac arrest may occur. - Respiratory system– respiratory depression and a short
period of apnoea is common. There is an increased tendency
to laryngeal spasm if anaesthesia is light and there is
increased bronchial tone. - Miscellaneous adverse effects– urticaria or anaphylactic shock
due to histamine release. Local tissue necrosis and
peripheral nerve injury can occur due to accidental
extravascular administration. Accidental arterial injection
causes severe burning pain due to arterial constriction, and
can lead to ischaemia and gangrene. Post-operative
restlessness and nausea are common. - Thiopentalshould be avoided or the dose reduced in
patients with hypovolaemia, uraemia, hepatic disease,
asthma and cardiac disease. In patients with porphyria,
thiopental(like other barbiturates) can precipitate
paralysis and cardiovascular collapse.
PROPOFOL
Uses
Propofolhas superseded thiopentalas an intravenous induc-
tion agent in many centres, owing to its short duration of
action, anti-emetic effect and the rapid clear-headed recovery.
It is formulated as a white emulsion in soya-bean oil and egg
phosphatide. It is rapidly metabolized in the liver and extra-
hepatic sites, and has no active metabolites. Its uses include:- Intravenous induction–propofolis the drug of choice for
insertion of a laryngeal mask, because it suppresses
laryngeal reflexes. - Maintenance of anaesthesia–propofoladministered as an
infusion can provide total intravenous anaesthesia (TIVA).
It is often used in conjunction with oxygen or oxygen-
enriched air, opioids and muscle relaxants. Although
recovery is slower than that following a single dose,
accumulation is not a problem. It is particularly useful in
middle-ear surgery (where nitrous oxide is best avoided)
and in patients with raised intracranial pressure (in whom
volatile anaesthetics should be avoided). - Sedation– for example, in intensive care, during
investigative procedures or regional anaesthesia.
Adverse effects- Cardiovascular system–propofolcauses arterial
hypotension, mainly due to vasodilation although there is
some myocardial depression. It should be administered
particularly slowly and cautiously in patients with
hypovolaemia or cardiovascular compromise. It can also
cause bradycardia, responsive to a muscarinic antagonist.