ANAESTHETICS, GENERAL › VOLATILE LIQUID
Should only be administered by, or under the direct
supervision of, personnel experienced in their use, with
adequate training in anaesthesia and airway
management, and when resuscitation equipment is
l CONTRA-INDICATIONS Susceptibility to malignant
l CAUTIONS Can trigger malignant hyperthermia .raised
intracranial pressure (can increase cerebrospinal pressure)
l ALLERGY AND CROSS-SENSITIVITY Can cause
hepatotoxicity in those sensitised to halogenated
l DIRECTIONS FOR ADMINISTRATION Volatile liquid
anaesthetics are administered using calibrated vaporisers,
using air, oxygen, or nitrous oxide-oxygen mixtures as the
carrier gas. To prevent hypoxia, the inspired gas mixture
should contain a minimum of 25% oxygen at all times.
Driving and skilled tasks Patients given sedatives and
analgesics during minor outpatient procedures should be
very carefully warned about the risks of driving or
undertaking skilled tasks afterwards. For a short general
anaesthetic, the risk extends to at least 24 hours after
administration. Responsible persons should be available to
take patients home. The dangers of taking alcohol should
Induction of anaesthesia (but not recommended)
▶ Adult: 4–11 %, to be inhaled through specifically
Maintenance of anaesthesia (in nitrous oxide–oxygen)
▶ Adult: 2–6 %, to be inhaled through a specifically
Maintenance of anaesthesia (in oxygen or oxygenenriched air)
▶ Adult: 2.5–8.5 %, to be inhaled through a specifically
l INTERACTIONS → Appendix 1: volatile halogenated
▶ Common or very common Coagulation disorder. conjunctivitis
▶ Uncommon Myalgia . myocardial infarction . myocardial
▶ Frequency not known Abdominal pain . asthenia . heart
dysfunction . visual acuity decreased
l PREGNANCY May depress neonatal respiration if used
l BREAST FEEDING Breast-feeding can be resumed as soon
as mother has recovered sufficiently from anaesthesia.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Desflurane (Non-proprietary)
Desflurane 1 ml per 1 ml Desflurane volatile liquid | 240 ml P s
Induction of anaesthesia (in oxygen or nitrous oxideoxygen)
▶ Adult: Initially 0.5 %, increased to 3 %, adjusted
according to response, administered using specifically
Maintenance of anaesthesia (in nitrous oxide–oxygen)
▶ Adult: 1–2.5 %, to be administered using specifically
calibrated vaporiser; an additional 0.5–1% may be
required when given with oxygen alone
Maintenance of anaesthesia in caesarean section (in
▶ Adult: 0.5–0.75 %, to be administered using specifically
l INTERACTIONS → Appendix 1: volatile halogenated
l SIDE-EFFECTS Carboxyhaemoglobinaemia . chest
l PREGNANCY May depress neonatal respiration if used
l BREAST FEEDING Breast-feeding can be resumed as soon
as mother has recovered sufficiently from anaesthesia.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Isoflurane (Non-proprietary)
Isoflurane 1 ml per 1 ml Isoflurane inhalation vapour | 250 ml P £35.29 (Hospital only)
▶ AErrane (Baxter Healthcare Ltd)
Isoflurane 1 ml per 1 ml AErrane volatile liquid | 250 ml P s
Maintenance of anaesthesia in conjunction with other
▶ Adult: 50–66 %, to be administered using suitable
anaesthetic apparatus in oxygen
1332 General anaesthesia BNF 78
▶ Adult: Up to 50 %, to be administered using suitable
anaesthetic apparatus in oxygen, adjusted according to
Nitrous oxide should only be administered by, or under
the direct supervision of, personnel experienced in its
use, with adequate training in anaesthesia and airway
management, and when resuscitation equipment is
injury .recent intra-ocular gas injection
CAUTIONS, FURTHER INFORMATION Nitrous oxide may have
such a space with a resulting increase in pressure. This
effect may be dangerous in conditions such as
pneumothorax, which may enlarge to compromise
respiration, or in the presence of intracranial air after head
injury, entrapped air following recent underwater dive, or
recent intra-ocular gas injection.
l INTERACTIONS → Appendix 1: nitrous oxide
membrane perforation . vomiting
SIDE-EFFECTS, FURTHER INFORMATION Exposure of
patients to nitrous oxide for prolonged periods, either by
continuous or by intermittent administration, may result
in megaloblastic anaemia owing to interference with the
action of vitamin B12; neurological toxic effects can occur
without preceding overt haematological changes.
Depression of white cell formation may also occur.
l PREGNANCY May depress neonatal respiration if used
l BREAST FEEDING Breast-feeding can be resumed as soon
as mother has recovered sufficiently from anaesthesia.
▶ Assessment of plasma-vitamin B12 concentration should
be considered in those at risk of deficiency, including the
elderly, those who have a poor, vegetarian, or vegan diet,
and those with a history of anaemia.
▶ Nitrous oxide should not be given continuously for longer
than 24 hours or more frequently than every 4 days
without close supervision and haematological monitoring.
l DIRECTIONS FOR ADMINISTRATION For analgesia (without
loss of consciousness), a mixture of nitrous oxide and
oxygen containing 50% of each gas (Entonox ®, Equanox ®)
l HANDLING AND STORAGE Exposure of theatre staff to
nitrous oxide should be minimised (risk of serious sideeffects).
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Nitrous oxide (Non-proprietary)
Nitrous oxide 1 ml per 1 ml Nitrous oxide cylinders size E | 1800 litre p s
Medical Nitrous Oxide cylinders size D | 900 litre p s
Medical Nitrous Oxide cylinders size G | 9000 litre p s
Nitrous oxide cylinders size F | 3600 litre p s
Nitrous oxide cylinders size J | 18000 litre p s
Nitrous oxide cylinders size G | 9000 litre p s
Medical Nitrous Oxide cylinders size F | 3600 litre p s
Nitrous oxide cylinders size D | 900 litre p s
Medical Nitrous Oxide cylinders size E | 1800 litre p s
Induction of anaesthesia (in oxygen or nitrous oxide–
▶ Adult: Initially 0.5–1 %, then increased to up to 8 %,
increased gradually, according to response, to be
administered using specifically calibrated vaporiser
Maintenance of anaesthesia (in oxygen or nitrous oxide–
▶ Adult: 0.5–3 %, adjusted according to response, to be
administered using specifically calibrated vaporiser
l CAUTIONS Susceptibility to QT-interval prolongation
l INTERACTIONS → Appendix 1: volatile halogenated
▶ Common or very common Drowsiness . fever. hypothermia
▶ Uncommon Asthma . atrioventricular block . confusion
▶ Frequency not known Dystonia . intracranial pressure
increased . muscle rigidity . nephritis tubulointerstitial . oedema . pancreatitis
l PREGNANCY May depress neonatal respiration if used
l BREAST FEEDING Breast-feeding can be resumed as soon
as mother has recovered sufficiently from anaesthesia.
l RENAL IMPAIRMENT Use with caution.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Sevoflurane (Non-proprietary)
Sevoflurane 1 ml per 1 ml Sevoflurane volatile liquid | 250 ml P £123.00 (Hospital only)
Pre-medication and peri-operative
Regurgitation and aspiration of gastric contents
(Mendelson’s syndrome) can be an important complication
of general anaesthesia, particularly in obstetrics and during
emergency surgery, and requires prophylaxis against acid
gastric emptying may be delayed.
A H2-receptor antagonist can be used before surgery to
increase the pH and reduce the volume of gastric fluid. It
does not affect the pH of fluid already in the stomach and
this limits its value in emergency procedures; an oral H2-
receptor antagonist can be given 1–2 hours before the
procedure. Antacids are frequently used to neutralise the
Antimuscarinic drugs are used (less commonly nowadays) as
premedicants to dry bronchial and salivary secretions which
are increased by intubation, upper airway surgery, or some
BNF 78 Anaesthesia adjuvants 1333
inhalational anaesthetics. They are also used before or with
neostigmine p. 1125 to prevent bradycardia, excessive
salivation, and other muscarinic actions of neostigmine.
They also prevent bradycardia and hypotension associated
with drugs such as propofol p. 1330 and suxamethonium
Atropine sulfate p. 1334 is now rarely used for
premedication but still has an emergency role in the
treatment of vagotonic side-effects. Atropine sulfate may
have a role in acute arrhythmias after myocardial infarction.
Hyoscine hydrobromide p. 439 reduces secretions and also
provides a degree of amnesia, sedation, and anti-emesis.
Unlike atropine sulfate it may produce bradycardia rather
Glycopyrronium bromide p. 1335 reduces salivary
secretions. When given intravenously it produces less
tachycardia than atropine sulfate. It is widely used with
neostigmine for reversal of non-depolarising neuromuscular
Phenothiazines do not effectively reduce secretions when
Fear and anxiety before a procedure (including the night
before) can be minimised by using a sedative drug, usually a
benzodiazepine. Premedication may also augment the
individual, the nature of the procedure, the anaesthetic to be
used, and other prevailing circumstances such as
outpatients, obstetrics, and availability of recovery facilities.
The choice also varies between elective and emergency
Premedicants can be given the night before major surgery;
a further, smaller dose may be required before surgery.
Alternatively, the first dose may be given on the day of the
Benzodiazepines possess useful properties for premedication
common premedicants. Benzodiazepines are also used in
intensive care units for sedation, particularly in those
receiving assisted ventilation. Flumazenil p. 1368 is used to
antagonise the effects of benzodiazepines.
Diazepam p. 343 is used to produce mild sedation with
amnesia. It is a long-acting drug with active metabolites and
a second period of drowsiness can occur several hours after
its administration. Peri-operative use of diazepam in
children is not recommended; its effect and timing of
response are unreliable and paradoxical effects may occur.
Diazepam is relatively insoluble in water and preparations
formulated in organic solvents are painful on intravenous
injection and give rise to a high incidence of venous
thrombosis (which may not be noticed for several days after
the injection). Intramuscular injection of diazepam is painful
and absorption is erratic. An emulsion formulated for
intravenous injection is less irritant and reduces the risk of
venous thrombosis; it is not suitable for intramuscular
Temazepam p. 488 is given by mouth for premedication
and has a shorter duration of action and a more rapid onset
than oral diazepam; anxiolytic and sedative effects last
about 90 minutes although there may be residual
Lorazepam p. 339 produces more prolonged sedation than
temazepam and it has marked amnesic effects.
Midazolam p. 340 is a water-soluble benzodiazepine that is
often used in preference to intravenous diazepam; recovery
is faster than from diazepam, but may be significantly longer
in the elderly, in patients with a low cardiac output, or after
repeated dosing. Midazolam is associated with profound
sedation when high doses are given intravenously or when it
is used with certain other drugs.
Dexmedetomidine p. 1346 and clonidine hydrochloride
p. 145 are alpha2-adrenergic agonists with sedative
properties. Dexmedetomidine is licensed for the sedation of
patients receiving intensive care who need to remain
responsive to verbal stimulation. Clonidine hydrochloride
[unlicensed indication] can be used by mouth or by
intravenous injection as a sedative agent when adequate
sedation cannot be achieved with standard treatment.
Antagonists for central and respiratory depression
Respiratory depression is a major concern with opioid
analgesics and it may be treated by artificial ventilation or be
reversed by naloxone hydrochloride p. 1369. Naloxone
hydrochloride will immediately reverse opioid-induced
respiratory depression but the dose may have to be repeated
because of the short duration of action of naloxone
hydrochloride; however, naloxone hydrochloride will also
antagonise the analgesic effect.
Flumazenil is a benzodiazepine antagonist for the reversal
of the central sedative effects of benzodiazepines after
anaesthetic and similar procedures. Flumazenil has a shorter
half-life and duration of action than diazepam or midazolam
so patients may become resedated.
Doxapram hydrochloride p. 299 is a central and respiratory
stimulant but is of limited value in anaesthesia.
Bradycardia due to acute massive overdosage of betablockers
▶ Child: 40 micrograms/kg (max. per dose 3 mg)
Treatment of poisoning by organophosphorus insecticide
or nerve agent (in combination with pralidoxime
▶ Child: 20 micrograms/kg every 5–10 minutes (max. per
dose 2 mg) until the skin becomes flushed and dry, the
pupils dilate, and bradycardia is abolished, frequency
of administration dependent on the severity of
▶ Adult: 2 mg every 5–10 minutes until the skin becomes
flushed and dry, the pupils dilate, and bradycardia is
abolished, frequency of administration dependent on
Symptomatic relief of gastro-intestinal disorders
characterised by smooth muscle spasm
▶ Adult: 0.6–1.2 mg daily, dose to be taken at night
▶ Child 12–17 years: 300–600 micrograms, to be
administered immediately before induction of
▶ Adult: 300–600 micrograms, to be administered
immediately before induction of anaesthesia
▶ BY SUBCUTANEOUS INJECTION, OR BY INTRAMUSCULAR
▶ Child 12–17 years: 300–600 micrograms, to be
administered 30–60 minutes before induction of
▶ Adult: 300–600 micrograms, to be administered
30–60 minutes before induction of anaesthesia
1334 Anaesthesia adjuvants BNF 78
▶ Child 12–17 years: 300–600 micrograms, larger doses
▶ Adult: 300–600 micrograms, larger doses may be used
Control of muscarinic side-effects of neostigmine in
reversal of competitive neuromuscular block
▶ Child 12–17 years: 0.6–1.2 mg
Excessive bradycardia associated with beta-blocker use
▶ Adult: 0.6–2.4 mg in divided doses (max. per dose
Bradycardia following myocardial infarction (particularly
if complicated by hypotension)
▶ Adult: 500 micrograms every 3–5 minutes; maximum
Antimuscarinic drugs used for premedication to general
anaesthesia should only be administered by, or under
the direct supervision of, personnel experienced in their
l INTERACTIONS → Appendix 1: atropine
▶ With intravenous use Psychotic disorder
▶ With intravenous use Angina pectoris . hypertensive crisis . seizure
▶ With intravenous use Insomnia
l PREGNANCY Not known to be harmful; manufacturer
l BREAST FEEDING May suppress lactation; small amount
present in milk—manufacturer advises caution.
▶ Control of muscarinic side-effects of neostigmine in reversal of
competitive neuromuscular block Since atropine has a shorter
duration of action than neostigmine, late unopposed
bradycardia may result; close monitoring of the patient is
l LESS SUITABLE FOR PRESCRIBING Atropine tablets less
l EXCEPTIONS TO LEGAL CATEGORY Prescription only
medicine restriction does not apply where administration
is for saving life in emergency.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension, oral
solution, solution for injection, solution for infusion
▶ Atropine sulfate (Non-proprietary)
Atropine sulfate 600 microgram Atropine 600microgram tablets | 28 tablet P £52.92 DT = £52.92
▶ Atropine sulfate (Non-proprietary)
Atropine sulfate 100 microgram per 1 ml Atropine
Atropine sulfate 200 microgram per 1 ml Atropine 1mg/5ml
solution for injection pre-filled syringes | 1 pre-filled disposable
injection P £7.29–£13.00 | 10 pre-filled disposable
Atropine sulfate 300 microgram per 1 ml Atropine 3mg/10ml
solution for injection pre-filled syringes | 1 pre-filled disposable
injection P £7.29–£13.00 DT = £7.29 | 10 pre-filled disposable
Atropine sulfate 400 microgram per 1 ml Atropine
400micrograms/1ml solution for injection ampoules | 10 ampoule P £102.26 DT = £102.26
Atropine sulfate 600 microgram per 1 ml Atropine
600micrograms/1ml solution for injection ampoules | 10 ampoule P £11.71 DT = £11.71
Atropine 600micrograms/1ml solution for injection pre-filled syringes
| 1 pre-filled disposable injection P £7.29
Atropine sulfate 1 mg per 1 ml Atropine 1mg/1ml solution for
injection ampoules | 10 ampoule P £94.68 DT = £94.68
Glycopyrronium bromide 13-Sep-2017
▶ BY INTRAMUSCULAR INJECTION, OR BY INTRAVENOUS
▶ Adult: 200–400 micrograms, alternatively
4–5 micrograms/kg (max. per dose 400 micrograms)
▶ Adult: 200–400 micrograms, alternatively
4–5 micrograms/kg (max. per dose 400 micrograms),
Control of muscarinic side-effects of neostigmine in
reversal of non-depolarising neuromuscular block
▶ Adult: 10–15 micrograms/kg, alternatively,
200 micrograms per 1 mg of neostigmine to be
Bowel colic in palliative care | Excessive respiratory
▶ Adult: 200 micrograms every 4 hours and when
required, hourly use is occasionally necessary,
particularly in excessive respiratory secretions
Antimuscarinic drugs used for premedication to general
anaesthesia should only be administered by, or under
the direct supervision of, personnel experienced in their
l INTERACTIONS → Appendix 1: glycopyrronium
l SIDE-EFFECTS Anhidrosis . bronchial secretion decreased . mydriasis
l PRESCRIBING AND DISPENSING INFORMATION
Palliative care For further information on the use of
glycopyrronium bromide in palliative care, see
www.medicinescomplete.com/#/content/palliative/
BNF 78 Anaesthesia adjuvants 1335
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Glycopyrronium bromide (Non-proprietary)
Glycopyrronium bromide 200 microgram per 1 ml
Glycopyrronium bromide 200micrograms/1ml solution for injection
ampoules | 10 ampoule P £5.72–£14.00 DT = £9.99
Glycopyrronium bromide 600micrograms/3ml solution for injection
ampoules | 3 ampoule P £8.00 | 10 ampoule P £14.86 DT =
Neuromuscular blocking drugs used in anaesthesia are also
known as muscle relaxants. By specific blockade of the
neuromuscular junction they enable light anaesthesia to be
used with adequate relaxation of the muscles of the
abdomen and diaphragm. They also relax the vocal cords and
allow the passage of a tracheal tube. Their action differs from
the muscle relaxants used in musculoskeletal disorders that
act on the spinal cord or brain.
Patients who have received a neuromuscular blocking drug
should always have their respiration assisted or controlled
until the drug has been inactivated or antagonised. They
should also receive sufficient concomitant inhalational or
intravenous anaesthetic or sedative drugs to prevent
Non-depolarising neuromuscular blocking drugs
Non-depolarising neuromuscular blocking drugs (also
known as competitive muscle relaxants) compete with
acetylcholine for receptor sites at the neuromuscular
junction and their action can be reversed with
into the aminosteroid group, comprising pancuronium
bromide p. 1339, rocuronium bromide p. 1339, and
vecuronium bromide, and the benzylisoquinolinium group,
comprising atracurium besilate p. 1337, cisatracurium
p. 1338, and mivacurium p. 1338.
Non-depolarising neuromuscular blocking drugs have a
slower onset of action than suxamethonium chloride
p. 1337. These drugs can be classified by their duration of
action as short-acting (15–30 minutes), intermediate-acting
(30–40 minutes), and long-acting (60–120 minutes),
although duration of action is dose-dependent. Drugs with a
shorter or intermediate duration of action, such as
atracurium besilate and vecuronium bromide, are more
widely used than those with a longer duration of action, such
Non-depolarising neuromuscular blocking drugs have no
sedative or analgesic effects and are not considered to trigger
For patients receiving intensive care and who require
may facilitate intubation. Atracurium besilate or
cisatracurium may be suitable for long-term neuromuscular
blockade since their duration of action is not dependent on
elimination by the liver or the kidneys.
Atracurium besilate, a mixture of 10 isomers, is a
benzylisoquinolinium neuromuscular blocking drug with an
intermediate duration of action. It undergoes non-enzymatic
metabolism which is independent of liver and kidney
function, thus allowing its use in patients with hepatic or
renal impairment. Cardiovascular effects are associated with
significant histamine release; histamine release can be
minimised by administering slowly or in divided doses over
Cisatracurium is a single isomer of atracurium besilate. It
is more potent and has a slightly longer duration of action
than atracurium besilate and provides greater cardiovascular
stability because cisatracurium lacks histamine-releasing
Mivacurium, a benzylisoquinolinium neuromuscular
blocking drug, has a short duration of action. It is
metabolised by plasma cholinesterase and muscle paralysis
is prolonged in individuals deficient in this enzyme. It is not
associated with vagolytic activity or ganglionic blockade
although histamine release can occur, particularly with rapid
Pancuronium bromide, an aminosteroid neuromuscular
blocking drug, has a long duration of action and is often used
in patients receiving long-term mechanical ventilation in
intensive care units. It lacks a histamine-releasing effect, but
vagolytic and sympathomimetic effects can cause
Rocuronium bromide exerts an effect within 2 minutes and
has the most rapid onset of any of the non-depolarising
neuromuscular blocking drugs. It is an aminosteroid
neuromuscular blocking drug with an intermediate duration
of action. It is reported to have minimal cardiovascular
effects; high doses produce mild vagolytic activity.
Vecuronium bromide, an aminosteroid neuromuscular
blocking drug, has an intermediate duration of action. It
does not generally produce histamine release and lacks
Depolarising neuromuscular blocking drugs
Suxamethonium chloride has the most rapid onset of action
of any of the neuromuscular blocking drugs and is ideal if
fast onset and brief duration of action are required, e.g. with
tracheal intubation. Unlike the non-depolarising
neuromuscular blocking drugs, its action cannot be reversed
and recovery is spontaneous; anticholinesterases such as
neostigmine potentiate the neuromuscular block.
Suxamethonium chloride should be given after anaesthetic
induction because paralysis is usually preceded by painful
muscle fasciculations. While tachycardia occurs with single
use, bradycardia may occur with repeated doses in adults and
with the first dose in children. Premedication with atropine
reduces bradycardia as well as the excessive salivation
associated with suxamethonium chloride use.
Prolonged paralysis may occur in dual block, which occurs
with high or repeated doses of suxamethonium chloride and
is caused by the development of a non-depolarising block
following the initial depolarising block. Individuals with
myasthenia gravis are resistant to suxamethonium chloride
but can develop dual block resulting in delayed recovery.
Prolonged paralysis may also occur in those with low or
atypical plasma cholinesterase. Assisted ventilation should
be continued until muscle function is restored.
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