Onset is slow and the duration of action prolonged so that
ventilatory support is required post-operatively. Addition of a
small dose of volatile anaesthetic, benzodiazepine or propofol
is required to avoid awareness during anaesthesia. High-dose
opioids can cause chest wall rigidity interfering with mechan-
ical ventilation. This can be prevented by muscle relaxants.
FENTANYL
Fentanylis a synthetic opioid and is the most commonly
employed analgesic supplement during anaesthesia. It is very
lipid soluble and has an onset time of one to two minutes. It
has approximately 100 times the analgesic activity of mor-
phine.Fentanylis rapidly and extensively metabolized, the
t1/2being two to four hours, the short duration of action (the
peak effect lasts only 20–30 minutes) being explained by redis-
tribution from brain to tissues. Particular care should be taken
after multiple injections because of saturation of tissue stores.
Depression of ventilation can occur for several minutes.
Fentanyland the other potent opioids must not be used in situ-
ations where ventilation cannot be controlled. Fentanylhas
little cardiovascular effect, but bradycardia may occur.
Neuroleptanalgesia is produced by a combination of a
butyrophenone (droperidol) and an opioid (fentanyl). It is a
state of inactivity and reduced response to external stimuli,
sometimes used for complex diagnostic procedures.
ALFENTANIL
Alfentanilis a highly lipid-soluble derivative of fentanylthat
acts in one arm–brain circulation time. It has a short duration
of action of five to ten minutes, and is often used as an infusion,
but causes marked respiratory depression for some minutes.
REMIFENTANIL
Remifentanilis a μ agonist with a rapid onset and short dur-
ation. It has an ester linkage, making it susceptible to rapid
hydrolysis by a number of non-specific esterases in blood and
tissues. It is administered as an infusion and does not accumu-
late even after a three-hour infusion. Its t1/2is five to seven
minutes. It is a useful adjunct to anaesthetics, particularly in
patients with renal or hepatic impairment.
α 2 -ADRENOCEPTOR AGONISTS
Clonidinehas analgesic, anxiolytic and sedative properties. It
potentiates inhalational and intravenous anaesthetics. The
reduction of MAC of anaesthetics is more marked with the
more specific α 2 -adrenoceptor agonist dexmetomidine, but
this is not currently available in the UK. Adverse effects
include hypotension and bradycardia.
SEDATION IN THE INTENSIVE CARE UNIT
Patients in the intensive care unit frequently require sedative/
analgesic drugs to facilitate controlled ventilation, to provide
sedation and analgesia during painful procedures, to allay
anxiety and psychological stress and to manage confusional
states. The choice of agent(s) used is tailored to meet the needs
150 ANAESTHETICS AND MUSCLE RELAXANTS
of the individual patient and must be frequently reviewed.
Most sedative and analgesic drugs are given by continuous
intravenous infusion both for convenience of administration
and for control. Opioids are often used to provide analgesia.
They also suppress the cough reflex and are respiratory
depressants, which is useful in ventilated patients. Morphine
andfentanylhave been used for long-term sedation. Alfentanil
has a short half-life and is given by infusion. Opioids are often
combined with benzodiazepines (e.g. midazolam). Monitoring
the level of sedation is particularly important in cases where
long-acting opioids or benzodiazepines are being used whose
action may be prolonged due to accumulation of drug and
active metabolites. Propofolis increasingly used where short-
term sedation or regular assessment is required, because its
lack of accumulation results in rapid recovery. It is not recom-
mended in children. Etomidatewas used for intensive care
sedation before it was shown to increase mortality by adreno-
cortical suppression. Inhalational agents, such as isoflurane,
have also been successfully used to provide sedation.
Occasionally, muscle relaxants are indicated in critically ill
patients to facilitate ventilation. Atracuriumis then the drug
of choice and sedation must be adequate to avoid awareness.PREMEDICATION FOR ANAESTHESIA
Premedication was originally introduced to facilitate induc-
tion of anaesthesia with agents, such as chloroform and ether,
that are irritant and produce copious amounts of secretions.
Modern induction methods are simple and not unpleasant,
and the chief aim of premedication is now to allay anxiety in
the patient awaiting surgery. Oral temazepamis often the
only premedication used before routine surgery. Adequate
premedication leads to the administration of smaller doses
of anaesthetic than would otherwise have been required,
thereby resulting in fewer side effects and improved recovery.
Intravenousmidazolam, which causes anxiolysis and amnesia,
can be used. Opioids such as morphine, phenothiazines and
muscarinic receptor antagonists (e.g. hyoscine) are also used.
Gastric prokinetic agents, anti-emetics and H 2 -receptor antag-
onists are used to enhance gastric emptying, decrease the inci-
dence of nausea and vomiting, and reduce gastric acidity and
volume in certain situations.MUSCLE RELAXANTS
Muscle relaxants are neuromuscular blocking drugs which
cause reversible muscle paralysis (Figure 24.3). They are grouped
as follows:- non-depolarizing agents (competitive blockers), such as
vecuroniumandatracurium, which bind reversibly to the
post-synaptic nicotinic acetylcholine receptors on the motor
end-plate, competing with acetylcholine and thereby
preventing end-plate depolarization and blocking
neuromuscular transmission; - suxamethonium, a depolarizing agent which also binds
acetylcholine receptors at the neuromuscular junction,