1.1 Neuromuscular blockade 1336
1.2 Neuromuscular blockade reversal 1339
1.3 Peri-operative analgesia 1340
1.4 Peri-operative sedation page 1345
Several different types of drug are given together during
general anaesthesia. Anaesthesia is induced with either a
volatile drug given by inhalation or with an intravenously
administered drug; anaesthesia is maintained with an
intravenous or inhalational anaesthetic. Analgesics, usually
short-acting opioids, are also used. The use of
neuromuscular blocking drugs necessitates intermittent
positive-pressure ventilation. Following surgery,
anticholinesterases can be given to reverse the effects of
neuromuscular blocking drugs; specific antagonists can be
used to reverse central and respiratory depression caused by
some drugs used in surgery. A local topical anaesthetic can
be used to reduce pain at the injection site.
Individual requirements vary considerably and the
recommended doses are only a guide. Smaller doses are
indicated in ill, shocked, or debilitated patients and in
significant hepatic impairment, while robust individuals may
require larger doses. The required dose of induction agent
may be less if the patient has been premedicated with a
sedative agent or if an opioid analgesic has been used.
Intravenous anaesthetics may be used either to induce
anaesthesia or for maintenance of anaesthesia throughout
surgery. Intravenous anaesthetics nearly all produce their
effect in one arm-brain circulation time. Extreme care is
required in surgery of the mouth, pharynx, or larynx where
the airway may be difficult to maintain (e.g. in the presence
of a tumour in the pharynx or larynx).
To facilitate tracheal intubation, induction is usually
followed by a neuromuscular blocking drug or a short-acting
The doses of all intravenous anaesthetic drugs should be
titrated to effect (except when using ‘rapid sequence
induction’); lower doses may be required in premedicated
This is a technique in which major surgery is carried out with
all drugs given intravenously. Respiration can be
spontaneous, or controlled with oxygen-enriched air.
Neuromuscular blocking drugs can be used to provide
relaxation and prevent reflex muscle movements. The main
problem to be overcome is the assessment of depth of
anaesthesia. Target Controlled Infusion (TCI) systems can be
used to titrate intravenous anaesthetic infusions to
predicted plasma-drug concentrations in ventilated adult
Drugs used for intravenous anaesthesia
Propofol p. 1330, the most widely used intravenous
anaesthetic, can be used for induction or maintenance of
anaesthesia in adults and children, but it is not commonly
used in neonates. Propofol is associated with rapid recovery
and less hangover effect than other intravenous
anaesthetics. Propofol can also be used for sedation during
diagnostic procedures and sedation in adults in intensive
Thiopental sodium p. 338 is a barbiturate that is used for
induction of anaesthesia, but has no analgesic properties.
Induction is generally smooth and rapid, but dose-related
cardiovascular and respiratory depression can occur.
Awakening from a moderate dose of thiopental sodium is
rapid because the drug redistributes into other tissues,
particularly fat. However, metabolism is slow and sedative
effects can persist for 24 hours. Repeated doses have a
cumulative effect and recovery is much slower.
Etomidate p. 1330 is an intravenous agent associated with
rapid recovery without a hangover effect. Etomidate causes
less hypotension than thiopental sodium and propofol
during induction. It produces a high incidence of extraneous
muscle movements, which can be minimised by an opioid
analgesic or a short-acting benzodiazepine given just before
Ketamine p. 1345 is used rarely. Ketamine causes less
hypotension than thiopental sodium and propofol during
induction. It is used mainly for paediatric anaesthesia,
particularly when repeated administration is required (such
as for serial burns dressings); recovery is relatively slow and
there is a high incidence of extraneous muscle movements.
The main disadvantage of ketamine is the high incidence of
hallucinations, nightmares, and other transient psychotic
effects; these can be reduced by a benzodiazepine such as
diazepam p. 343 or midazolam p. 340.
Inhalational anaesthetics include gases and volatile liquids.
Gaseous anaesthetics require suitable equipment for storage
and 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. Higher concentrations
of oxygen (greater than 30%) are usually required during
inhalational anaesthesia when nitrous oxide p. 1332 is being
Volatile liquid anaesthetics can be used for induction and
maintenance of anaesthesia, and following induction with
Isoflurane p. 1332 is a volatile liquid anaesthetic. Heart
rhythm is generally stable during isoflurane anaesthesia, but
heart-rate can rise, particularly in younger patients.
Systemic arterial pressure and cardiac output can fall, owing
to a decrease in systemic vascular resistance. Muscle
relaxation occurs and the effects of muscle relaxant drugs
are potentiated. Isoflurane is the preferred inhalational
anaesthetic for use in obstetrics.
Desflurane p. 1332 is a rapid acting volatile liquid
anaesthetic; it is reported to have about one-fifth the
potency of isoflurane. Emergence and recovery from
anaesthesia are particularly rapid because of its low
solubility. Desflurane is not recommended for induction of
anaesthesia as it is irritant to the upper respiratory tract.
Sevoflurane p. 1333 is a rapid acting volatile liquid
anaesthetic and is more potent than desflurane. Emergence
and recovery are particularly rapid, but slower than
desflurane. Sevoflurane is non-irritant and is therefore often
used for inhalational induction of anaesthesia; it has little
effect on heart rhythm compared with other volatile liquid
Nitrous oxide is used for maintenance of anaesthesia and, in
sub-anaesthetic concentrations, for analgesia. For
anaesthesia, nitrous oxide is commonly used in a
concentration of 50 to 66% in oxygen as part of a balanced
technique in association with other inhalational or
intravenous agents. Nitrous oxide is unsatisfactory as a sole
anaesthetic owing to lack of potency, but is useful as part of
a combination of drugs since it allows a significant reduction
For analgesia (without loss of consciousness), a mixture of
nitrous oxide and oxygen containing 50% of each gas
(Entonox ®, Equanox ®) is used. Self-administration using a
demand valve is popular in obstetric practice, for changing
painful dressings, as an aid to postoperative physiotherapy,
Nitrous oxide may have a deleterious effect if used in
patients with an air-containing closed space since nitrous
oxide diffuses into 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.
Malignant hyperthermia is a rare but potentially lethal
complication of anaesthesia. It is characterised by a rapid
rise in temperature, increased muscle rigidity, tachycardia,
and acidosis. The most common triggers of malignant
hyperthermia are the volatile anaesthetics. Suxamethonium
chloride p. 1337 has also been implicated, but malignant
hyperthermia is more likely if it is given following a volatile
anaesthetic. Volatile anaesthetics and suxamethonium
chloride should be avoided during anaesthesia in patients at
high risk of malignant hyperthermia.
Dantrolene sodium p. 1346 is used in the treatment of
resuscitation in dental practice
Sedation for dental procedures should be limited to
conscious sedation. Diazepam p. 343 and temazepam p. 488
are effective anxiolytics for dental treatment in adults.
For details of sedation, anaesthesia, and resuscitation in
dental practice see A Conscious Decision: A review of the use of
general anaesthesia and conscious sedation in primary dental
care; report by a group chaired by the Chief Medical Officer
and Chief Dental Officer, July 2000 and associated
documents. Further details can also be found in Standards for
Conscious Sedation in the Provision of Dental Care; report of
an Intercollegiate Advisory Committee for Sedation in
Surgery and long-term medication
The risk of losing disease control on stopping long-term
medication before surgery is often greater than the risk
posed by continuing it during surgery. It is vital that the
anaesthetist knows about all drugs that a patient is (or has
Patients with adrenal atrophy resulting from long-term
corticosteroid use may suffer a precipitous fall in blood
pressure unless corticosteroid cover is provided during
anaesthesia and in the immediate postoperative period.
Anaesthetists must therefore know whether a patient is, or
has been, receiving corticosteroids (including high-dose
Other drugs that should normally not be stopped before
surgery include antiepileptics, antiparkinsonian drugs,
antipsychotics, anxiolytics, bronchodilators, cardiovascular
antagonists), glaucoma drugs, immunosuppressants, drugs
of dependence, and thyroid or antithyroid drugs. Expert
advice is required for patients receiving antivirals for HIV
infection. See general advice on surgery in diabetic patients
in Diabetes, surgery and medical illness p. 689.
Patients taking antiplatelet medication or an oral
anticoagulant present an increased risk for surgery. In these
circumstances, the anaesthetist and surgeon should assess
the relative risks and decide jointly whether the antiplatelet
or the anticoagulant drug should be stopped or replaced with
heparin (unfractionated) p. 133 or low molecular weight
heparin therapy.g In patients with stable angina,
perioperative aspirin p. 121 should be only continued where
there is a high thrombotic risk (e.g. patients with a recent
acute coronary syndrome, coronary artery stents, or an
Drugs that should be stopped before surgery include
combined oral contraceptives, see Contraceptives, hormonal
p. 791; for advice on hormone replacement therapy, see Sex
hormones p. 750. MAOIs can have important interactions
with some drugs used during surgery, such as pethidine
hydrochloride p. 470. Tricyclic antidepressants need not be
stopped, but there may be an increased risk of arrhythmias
and hypotension (and dangerous interactions with
vasopressor drugs); therefore, the anaesthetist should be
informed if they are not stopped. Lithium should be stopped
24 hours before major surgery but the normal dose can be
continued for minor surgery (with careful monitoring of
fluids and electrolytes). Potassium-sparing diuretics may
need to be withheld on the morning of surgery because
hyperkalaemia may develop if renal perfusion is impaired or
BNF 78 General anaesthesia 1329
if there is tissue damage. Angiotensin-converting enzyme
(ACE) inhibitors and angiotensin-II receptor antagonists can
be associated with severe hypotension after induction of
anaesthesia; these drugs may need to be discontinued
24 hours before surgery. Herbal medicines may be associated
with adverse effects when given with anaesthetic drugs and
consideration should be given to stopping them before
ANAESTHETICS, GENERAL › INTRAVENOUS
▶ BY SLOW INTRAVENOUS INJECTION
▶ Adult: 150–300 micrograms/kg (max. per dose 60 mg),
to be administered over 30-60 seconds (60 seconds in
patients in whom hypotension might be hazardous)
▶ Elderly: 150–200 micrograms/kg (max. per dose 60 mg),
to be administered over 30-60 seconds (60 seconds in
patients in whom hypotension might be hazardous)
Etomidate 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
l CAUTIONS Acute circulatory failure (shock) . adrenal
▶ Adrenal insufficiency Etomidate suppresses adrenocortical
function, particularly during continuous administration,
and it should not be used for maintenance of anaesthesia.
It should be used with caution in patients with underlying
adrenal insufficiency, for example, those with sepsis.
l INTERACTIONS → Appendix 1: etomidate
reactions . vascular pain . vomiting
dysfunction . nystagmus . procedural complications
▶ Frequency not known Adrenal insufficiency . atrioventricular block . cardiac arrest. embolism and
thrombosis . seizures . shock . Stevens-Johnson syndrome . trismus
SIDE-EFFECTS, FURTHER INFORMATION Pain on injection
Can be reduced by injecting into a larger vein or by giving
an opioid analgesic just before induction.
Extraneous muscle movements Extraneous muscle
movements can be minimised by an opioid analgesic or a
short-acting benzodiazepine given just before induction.
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.
Dose adjustments Manufacturer advises reduce dose in
l DIRECTIONS FOR ADMINISTRATION To be administered
over 30–60 seconds (60 seconds in patients in whom
hypotension might be hazardous).
Driving and skilled tasks Patients given sedatives and
analgesics during minor outpatient procedures should be
very carefully warned about the risk 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
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
EXCIPIENTS: May contain Propylene glycol
▶ Hypnomidate (Piramal Critical Care Ltd)
Etomidate 2 mg per 1 ml Hypnomidate 20mg/10ml solution for
injection ampoules | 5 ampoule P £6.90
▶ Etomidate-Lipuro (B.Braun Medical Ltd)
Etomidate 2 mg per 1 ml Etomidate-Lipuro 20mg/10ml emulsion for
injection ampoules | 10 ampoule P £16.09
Induction of anaesthesia using 0.5% or 1% injection
▶ BY SLOW INTRAVENOUS INJECTION, OR BY INTRAVENOUS
▶ Adult 18–54 years: Usual dose 1.5–2.5 mg/kg, to be
administered at a rate of 20–40 mg every 10 seconds
until response, for debilitated patients use dose for
▶ Adult 55 years and over: Usual dose 1–1.5 mg/kg, to be
administered at a rate of 20 mg every 10 seconds until
Induction of anaesthesia using 2% injection
▶ Adult 18–54 years: Usual dose 1.5–2.5 mg/kg, to be
administered at a rate of 20–40 mg every 10 seconds
until response. For debilitated patients use dose for
▶ Adult 55 years and over: Usual dose 1–1.5 mg/kg, to be
administered at a rate of 20 mg every 10 seconds until
Maintenance of anaesthesia using 1% injection
▶ INITIALLY BY INTRAVENOUS INFUSION
▶ Adult: Usual dose 4–12 mg/kg/hour, alternatively (by
slow intravenous injection) 25–50 mg, dose may be
repeated according to response, for debilitated patients
▶ Elderly: Usual dose 3–6 mg/kg/hour, alternatively (by
slow intravenous injection) 25–50 mg, dose may be
repeated according to response
Maintenance of anaesthesia using 2% injection
▶ Adult: Usual dose 4–12 mg/kg/hour, for debilitated
▶ Elderly: Usual dose 3–6 mg/kg/hour
Sedation of ventilated patients in intensive care using 1%
▶ BY CONTINUOUS INTRAVENOUS INFUSION
▶ Adult: Usual dose 0.3–4 mg/kg/hour, adjusted
Induction of sedation for surgical and diagnostic
procedures using 0.5% or 1% injection
▶ BY SLOW INTRAVENOUS INJECTION
▶ Adult: Initially 0.5–1 mg/kg, to be administered over
1–5 minutes, dose and rate of administration adjusted
according to desired level of sedation and response
1330 General anaesthesia BNF 78
Maintenance of sedation for surgical and diagnostic
procedures using 0.5% injection
▶ INITIALLY BY INTRAVENOUS INFUSION
▶ Adult: Initially 1.5–4.5 mg/kg/hour, dose and rate of
administration adjusted according to desired level of
sedation and response, followed by (by slow
intravenous injection) 10–20 mg, (if rapid increase in
sedation required), patients over 55 years or debilitated
may require lower initial dose and rate of
Maintenance of sedation for surgical and diagnostic
▶ INITIALLY BY INTRAVENOUS INFUSION
▶ Adult: Initially 1.5–4.5 mg/kg/hour, dose and rate of
administration adjusted according to desired level of
sedation and response, followed by (by slow
intravenous injection) 10–20 mg, (if rapid increase in
sedation required), patients over 55 years or debilitated
may require lower initial dose and rate of
Maintenance of sedation for surgical and diagnostic
▶ INITIALLY BY INTRAVENOUS INFUSION
▶ Adult: Initially 1.5–4.5 mg/kg/hour, dose and rate of
administration adjusted according to desired level of
sedation and response, followed by (by slow
intravenous injection) 10–20 mg, using 0.5% or 1%
injection (if rapid increase in sedation required),
patients over 55 years or debilitated may require lower
initial dose and rate of administration
Propofol 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
l CAUTIONS Acute circulatory failure (shock). cardiac
intracranial pressure .respiratory impairment
l INTERACTIONS → Appendix 1: propofol
oedema . sexual disinhibition . soft tissue necrosis . urine
SIDE-EFFECTS, FURTHER INFORMATION Bradycardia
Bradycardia may be profound and may be treated with
intravenous administration of an antimuscarinic drug.
Pain on injection Pain on injection can be reduced by
Propofol infusion syndrome Prolonged infusion of
propofol doses exceeding 4mg/kg/hour may result in
potentially fatal effects, including metabolic acidosis,
arrhythmias, cardiac failure, rhabdomyolysis,
hyperlipidaemia, hyperkalaemia, hepatomegaly, and renal
l PREGNANCY May depress neonatal respiration if used
Dose adjustments Max. dose for maintenance of
l BREAST FEEDING Breast-feeding can be resumed as soon
as mother has recovered sufficiently from anaesthesia.
l HEPATIC IMPAIRMENT Manufacturer advises caution.
l RENAL IMPAIRMENT Use with caution.
l MONITORING REQUIREMENTS Monitor blood-lipid
concentration if risk of fat overload or if sedation longer
l DIRECTIONS FOR ADMINISTRATION Shake before use;
microbiological filter not recommended; may be
0.5% emulsion for injection or intermittent infusion; may
be administered undiluted, or diluted with Glucose 5% or
Sodium chloride 0.9%; dilute to a concentration not less
than 1 mg/mL. 1% emulsion for injection or infusion; may
be administered undiluted, or diluted with Glucose 5%
(Diprivan ®) or (Propofol-Lipuro ®) or Sodium chloride 0.9%
(Propofol-Lipuro ® only); dilute to a concentration not less
than 2 mg/mL; use within 6 hours of preparation. 2%
emulsion for infusion; do not dilute.
Driving and skilled tasks Patients given sedatives and
analgesics during minor outpatient procedures should be
very carefully warned about the risk 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
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Propofol 10 mg per 1 ml Propofol 500mg/50ml emulsion for
infusion vials | 1 vial P £15.00 (Hospital only)
Propofol-Lipuro 1% emulsion for infusion 50ml vials | 10 vial P £97.56 (Hospital only)
Propofol 1g/100ml emulsion for infusion vials | 1 vial P £15.00
Propofol-Lipuro 1% emulsion for infusion 100ml vials | 10 vial P £186.66 (Hospital only)
Propofol 20 mg per 1 ml Propofol 1g/50ml emulsion for infusion
vials | 1 vial P £15.00 (Hospital only)
Propofol-Lipuro 2% emulsion for infusion 50ml vials | 10 vial P £186.64 (Hospital only)
▶ Diprivan (Aspen Pharma Trading Ltd)
Propofol 10 mg per 1 ml Diprivan 1% emulsion for infusion 50ml
pre-filled syringes | 1 pre-filled disposable injection P £10.68
Propofol 20 mg per 1 ml Diprivan 2% emulsion for infusion 50ml
pre-filled syringes | 1 pre-filled disposable injection P £15.16
▶ Propoven (Fresenius Kabi Ltd)
Propofol 10 mg per 1 ml Propoven 1% emulsion for infusion 50ml
vials | 10 vial P £120.60 (Hospital only)
Propoven 1% emulsion for infusion 100ml vials | 10 vial P £241.50 (Hospital only)
Propofol 20 mg per 1 ml Propoven 2% emulsion for infusion 50ml
vials | 10 vial P £241.50 (Hospital only)
Propofol 10 mg per 1 ml Propofol 200mg/20ml emulsion for
injection vials | 5 vial P £20.00 (Hospital only)
Propofol-Lipuro 1% emulsion for injection 20ml ampoules | 5 ampoule P £20.16 (Hospital only)
▶ Diprivan (Aspen Pharma Trading Ltd)
Propofol 10 mg per 1 ml Diprivan 1% emulsion for injection 20ml
ampoules | 5 ampoule P £15.36 (Hospital only)
▶ Propofol-Lipuro (B.Braun Melsungen AG)
Propofol 5 mg per 1 ml Propofol-Lipuro 0.5% emulsion for injection
20ml ampoules | 5 ampoule P £15.15
▶ Propoven (Fresenius Kabi Ltd)
Propofol 10 mg per 1 ml Propoven 1% emulsion for injection 20ml
ampoules | 5 ampoule P £23.90 (Hospital only)
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