Amnesia reduces the likelihood of any unpleasant mem- Sedative and analgesic
15.1.4 Amnesia reduces the likelihood of any unpleasant mem- Sedative and analgesic
ories of the procedure (although benzodiazepines, par-
peri-operative drugs
ticularly when used for more profound sedation, can sometimes induce sexual fantasies). Benzodiazepines
15.1.4.1 Anxiolytics and neuroleptics
are also used in intensive care units for sedation, parti-
15.1.4.2 cularly in those receiving assisted ventilation. Non-opioid analgesics
15.1.4.3 Opioid analgesics
Benzodiazepines may occasionally cause marked resp- iratory depression and facilities for its treatment are essential; flumazenil (section 15.1.7) is used to antag-
Premedication These drugs are given to allay fear and onise the effects of benzodiazepines. They are best anxiety in the pre-operative period (including the night
avoided in myasthenia gravis, especially peri-opera- before an operation), to relieve pain and discomfort
tively.
when present, and to augment the action of subsequent Diazepam is used to produce mild sedation with amne- anaesthetic agents. A number of the drugs used also
sia. It is a long-acting drug with active metabolites and a provide some degree of pre-operative amnesia. The
second period of drowsiness can occur several hours choice will vary with the individual patient, the nature
after its administration. Peri-operative use of diazepam of the operative procedure, the anaesthetic to be used,
in children is not generally recommended; its effect and and other prevailing circumstances such as outpatients,
timing of response are unreliable and paradoxical obstetrics, and recovery facilities. The choice also varies
effects may occur.
between elective and emergency operations. Diazepam is relatively insoluble in water and prepara- Premedication in children Oral administration is tions formulated in organic solvents are painful on preferred where possible but it is not altogether satis-
intravenous injection and give rise to a high incidence factory; the rectal route should only be used in excep-
of venous thrombosis (which may not be noticed for tional circumstances. For further details consult BNF for
several days after the injection). Intramuscular injection Children .
of diazepam is painful and absorption is erratic. An emulsion formulated for intravenous injection is less
Application of a local anaesthetic (section 15.2) to the irritant and reduces the risk of venous thrombosis; it is injection site can help to prevent pain.
not suitable for intramuscular injection. Diazepam is also available as a rectal solution but this preparation
Dental procedures Anxiolytics diminish tension, is not used for premedication or sedation. anxiety and panic, and may benefit anxious patients. However, their use is no substitute for sympathy and
Temazepam is given by mouth and has a shorter reassurance.
duration of action and a more rapid onset than diaze- pam given by mouth. It has been used as a premedicant
Diazepam and temazepam are effective anxiolytics for in inpatient and day-case surgery; anxiolytic and seda- dental treatment in adults, but they are less suitable for
tive effects last about 90 minutes although there may be children. Diazepam has a longer duration of action than
residual drowsiness.
temazepam. When given at night diazepam is asso- ciated with more residual effects the following day;
Lorazepam produces more prolonged sedation than patients should be very carefully warned not to drive
temazepam and it has marked amnesic effects. It is (important: for general advice on anaesthesia and driv-
used as a premedicant the night before major surgery; ing see p. 687). For further information on hypnotics
a further, smaller dose may be required the following and anxiolytics, see section 4.1. For further information
morning if any delay in starting surgery is anticipated. on hypnotics used for dental procedures, see section
Alternatively the first dose may be given early in the
4.1.1. morning on the day of operation. Midazolam is a water-soluble benzodiazepine which is
Anaesthesia and driving See section 15.1. often used in preference to intravenous diazepam; recovery is faster than from diazepam. Midazolam is associated with profound sedation when high doses are given intravenously or when used with certain other
15.1.4.1 Anxiolytics and neuroleptics
drugs.
Anaesthesia
Anxiolytic benzodiazepines are widely used for pre- There have been reports of overdosage when high medication; neuroleptics such as chlorpromazine are
strength midazolam has been used for conscious rarely used.
sedation. The use of high strength midazolam (5 mg/mL in 2 mL and 10 mL ampoules, or 2 mg/ mL in 5 mL ampoules) should be restricted to gen-
Benzodiazepines
eral anaesthesia, intensive care, palliative care, or other situations where the risk has been assessed. It
Benzodiazepines possess useful properties for premedi- is advised that flumazenil (section 15.1.7) is available cation including relief of anxiety, sedation, and amnesia;
where midazolam is used, to reverse the effects if short-acting benzodiazepines taken by mouth are the
necessary.
most common premedicants. They have no analgesic effect so an opioid analgesic may sometimes be required for pain.
Benzodiazepines can alleviate anxiety at doses that do not necessarily cause excessive sedation and they are of
DIAZEPAM
particular value during short procedures or during Indications premedication; sedation with amnesia, operations under local anaesthesia (including dentistry).
and in conjunction with local anaesthesia; other indi-
15.1.4 Sedative and analgesic peri-operative drugs BNF 57 cations (section 4.1.2, section 4.8.2, and section
Side-effects see notes above; gastro-intestinal distur- 10.2.2)
bances, increased appetite, jaundice; hypotension, Cautions see notes above, section 4.1.2, and section
cardiac arrest, heart rate changes, anaphylaxis,
4.8.2 thrombosis; laryngospasm, bronchospasm, respir- Contra-indications see notes above and section 4.1.2
atory depression and respiratory arrest (particularly Side-effects see notes above and section 4.1.2
with high doses or on rapid injection); drowsiness, Dose
confusion, ataxia, amnesia, headache, euphoria, hal- lucinations, convulsions (more common in neonates),
. By mouth , 5 mg on night before minor or dental surgery then 5 mg 2 hours before procedure; dizziness, vertigo, involuntary movements, paradox-
(or debilitated), half adult dose ical excitement and aggression (especially in children and elderly), dysarthria; urinary retention, incont- . By intravenous injection into a large vein, sedative
ELDERLY
inence, changes in libido; blood disorders; muscle cover for minor surgical and medical procedures,
weakness; visual disturbances; salivation changes; ADULT over 18 years, 10–20 mg over 2–4 minutes,
skin reactions; injection-site reactions immediately before procedure; premedication 100–
200 micrograms/kg, Dose CHILD under 18 years see BNF for Children
. Conscious sedation, by slow intravenous injection .
(approx. 2 mg/minute) 5–10 minutes before proce- By rectum , CHILD 1–18 years, see BNF for Children
dure, initially 2–2.5 mg ( ELDERLY 0.5–1 mg), increased if necessary in steps of 1 mg ( ELDERLY 0.5–
Preparations
1 mg); usual total dose 3.5–5 mg (max. 7.5 mg), Section 4.1.2
ELDERLY max. 3.5 mg; CHILD by intravenous injection over 2–3 minutes, 6 months–5 years initially 50– 100 micrograms/kg, dose increased if necessary in
small steps (max. total dose 6 mg), 6–12 years Indications sedation with amnesia; premedication;
LORAZEPAM
initially 25–50 micrograms/kg, dose increased if other indications (section 4.1.2 and section 4.8.2)
necessary in small steps (max. total dose 10 mg) Cautions see notes above and section 4.1.2; interac-
By intramuscular injection , CHILD 1–15 years 50– tions: Appendix 1 (anxiolytics and hypnotics)
150 micrograms/kg; max. 10 mg Contra-indications see notes above and under
6 months–18 years, see BNF for Diazepam (section 4.1.2)
By rectum , CHILD
Children
Side-effects see notes above and under Diazepam . Sedative in combined anaesthesia, by intravenous (section 4.1.2)
injection , 30–100 micrograms/kg repeated as Dose
required or by continuous intravenous infusion , 30– . By mouth , 2–3 mg the night before operation; 2–
100 micrograms/kg/hour ( ELDERLY lower doses
4 mg 1–2 hours before operation needed); CHILD not recommended .
. By slow intravenous injection Premedication, , preferably diluted by deep intramuscular injection , 70– with an equal volume of sodium chloride intra-
100 micrograms/kg ( ELDERLY and debilitated 25– venous infusion 0.9% or water for injections,
50 micrograms/kg) 20–60 minutes before induc-
50 micrograms/kg 30–45 minutes before operation CHILD tion; 1–15 years 80–200 micrograms/kg . By intramuscular injection , diluted as above,
By intravenous injection , 1–2 mg repeated as
50 micrograms/kg 60–90 minutes before operation required ( ELDERLY and debilitated 0.5 mg, repeat dose slowly as required)
Preparations By rectum , CHILD
6 months–12 years, see BNF for Section 4.1.2
Children
thesia
. Induction (but rarely used), by slow intravenous injection , 150–200 micrograms/kg ( ELDERLY and
Anaes MIDAZOLAM
debilitated 50–150 micrograms/kg) given in divided Indications sedation with amnesia; sedation in inten-
doses (max. 5 mg) at intervals of 2 minutes; max.
CHILD sive care; premedication, induction of anaesthesia;
total dose 600 micrograms/kg; 7–18 years status epilepticus [unlicensed use], section 4.8.2
initially 150 micrograms/kg (max. 7.5 mg) given in Cautions see notes above; cardiac disease; respiratory
steps of 50 micrograms/kg (max. 2.5 mg) over 2–5 disease; myasthenia gravis; neonates; children (parti-
minutes; wait for 2–5 minutes then give additional cularly if cardiovascular impairment); risk of airways
doses of 50 micrograms/kg (max. 2.5 mg) every 2 obstruction and hypoventilation in children under 6
minutes if necessary; max. total dose 500 micr- ograms/kg (not exceeding 25 mg)
months (monitor respiratory rate and oxygen satura- tion); history of drug or alcohol abuse; reduce dose in
. Sedation of patients receiving intensive care, by slow elderly and debilitated; avoid prolonged use (and
intravenous injection , initially 30–300 micrograms/ abrupt withdrawal thereafter); concentration of mid-
kg given in steps of 1–2.5 mg every 2 minutes, then azolam in children under 15 kg not to exceed 1 mg/
by slow intravenous injection or by continuous mL; hepatic impairment (Appendix 2); renal impair-
intravenous infusion , 30–200 micrograms/kg/hour; ment (Appendix 3); pregnancy (Appendix 4) and
reduce dose (or reduce or omit initial dose) in breast-feeding (Appendix 5); interactions: Appendix
hypovolaemia, vasoconstriction, or hypothermia;
1 (anxiolytics and hypnotics) lower doses may be adequate if opioid analgesic
Contra-indications also used; NEONATE under 32 weeks gestational age
marked neuromuscular respir- by continuous intravenous infusion , 30 micr- atory weakness including unstable myasthenia gravis;
ograms/kg/hour, NEONATE over 32 weeks gesta- severe respiratory depression; acute pulmonary
tional age and CHILD under 6 months 60 micr- insufficiency
BNF 57
15.1.4 Sedative and analgesic peri-operative drugs 695
ograms/kg/hour, CHILD over 6 months by slow Suppositories of diclofenac and ketoprofen may be intravenous injection , initially 50–200 micrograms/
effective alternatives to the parenteral use of these kg, then by continuous intravenous infusion , 60–
drugs. Flurbiprofen is also available as suppositories. 120 micrograms/kg/hour, adjusted according to response
Midazolam (Non-proprietary) C KETOROLAC TROMETAMOL
Injection , midazolam (as hydrochloride) 1 mg/mL, Indications short-term management of moderate to net price 2-mL amp = 50p, 5-mL amp = 60p, 50-mL
severe acute postoperative pain only vial = £7.87; 2 mg/mL, 5-mL amp = 65p; 5 mg/mL, 2-
Cautions section 10.1.1; avoid in acute porphyria mL amp = 58p, 10-mL amp = £2.50
(section 9.8.2); interactions: Appendix 1 (NSAIDs) Hypnovel c (Roche)
C Contra-indications section 10.1.1; also complete or Injection , midazolam (as hydrochloride) 2 mg/mL,
partial syndrome of nasal polyps; haemorrhagic dia- net price 5-mL amp = 75p; 5 mg/mL, 2-mL amp =
theses (including coagulation disorders) and following 90p
operations with high risk of haemorrhage or incom- plete haemostasis; confirmed or suspected cerebro- vascular bleeding; hypovolaemia or dehydration
TEMAZEPAM
Side-effects section 10.1.1; also gastro-intestinal dis- turbances; flushing, bradycardia, palpitation, chest
Indications premedication before surgery; anxiety pain; dyspnoea, asthma; malaise, euphoria, psychosis, before investigatory procedures; hypnotic (section
paraesthesia, convulsions, abnormal dreams, hyper- 4.1.1)
kinesia; urinary frequency, thirst; hyponatraemia, Cautions see notes above and under Diazepam (sec-
hyperkalaemia, myalgia; visual disturbances (includ- tion 4.1.2; interactions: Appendix 1 (anxiolytics and
ing optic neuritis); pallor, purpura, pain at injection hypnotics)
site
Contra-indications see notes above and under
Dose
Diazepam (section 4.1.2) . ADULT and CHILD over 16 years, by mouth , 10 mg Side-effects see notes above and under Diazepam
every 4–6 hours ( ELDERLY every 6–8 hours) as (section 4.1.2)
required; max. 40 mg daily; max. duration of treat- Dose
ment 7 days
. By mouth , premedication, 20–40 mg (elderly, 10– . ADULT and CHILD over 16 years, by intramuscular
injection or by intravenous injection over at least 15 (max. 30 mg)
20 mg) 1 hour before operation; CHILD
1 mg/kg
seconds, initially 10 mg, then 10–30 mg every 4–6 hours as required (up to every 2 hours during initial
Preparations postoperative period); max. 90 mg daily ( ELDERLY and Section 4.1.1
patients weighing less than 50 kg max. 60 mg daily); max. duration of treatment 2 days Note When converting from parenteral to oral administra- tion, total combined dose on the day of converting should
not exceed 90 mg (60 mg in the elderly and patients weighing
15.1.4.2 less than 50 kg) of which the oral component should not Non-opioid analgesics
exceed 40 mg
Since non-steroidal anti-inflammatory drugs (NSAIDs)
Toradol c (Roche) A
do not depress respiration, do not impair gastro-intes- Tablets , ivory, f/c, ketorolac trometamol 10 mg, net tinal motility, and do not cause dependence, they may
price 20-tab pack = £5.79. Label: 17, 21
be useful alternatives (or adjuncts) to the use of opioids Injection , ketorolac trometamol 10 mg/mL, net price for the relief of postoperative pain. NSAIDs may be
1-mL amp = 94p; 30 mg/mL, 1-mL amp = £1.14 inadequate for the relief of severe pain. Acemetacin, diclofenac, flurbiprofen, ibuprofen,
PARECOXIB
ketoprofen, (section 10.1.1), paracetamol (section 4.7.1), parecoxib, and ketorolac are licensed for post-
Indications short-term management of acute post-
Anaesthesia
operative use. Diclofenac, ketoprofen, ketorolac, and
operative pain
paracetamol can be given by injection as well as by Cautions section 10.1.1; dehydration; following cor- mouth. Intramuscular injections of diclofenac and keto-
onary artery bypass graft surgery; interactions: profen are given deep into the gluteal muscle to mini-
Appendix 1 (NSAIDs) mise pain and tissue damage; diclofenac can also be
Contra-indications section 10.1.1; also history of given by intravenous infusion for the treatment or pre-
allergic drug reactions including sulphonamide vention of postoperative pain. Ketorolac is less irritant
hypersensitivity; inflammatory bowel disease on intramuscular injection but pain has been reported; it
can also be given by intravenous injection. Side-effects section 10.1.1; also flatulence; hyper- tension, hypotension, peripheral oedema; pharyngitis, Parecoxib (a selective inhibitor of cyclo-oxygenase-2)
respiratory insufficiency; hypoaesthesia; alveolar can be given by intramuscular or intravenous injection
osteitis; oliguria; postoperative anaemia, hypokal- (but see also NSAIDs and Cardiovascular Events, sec-
aemia; back pain; pruritus; less commonly bradycardia, tion 10.1.1). The Scottish Medicines Consortium has
cardiovascular events, increased blood urea nitrogen, advised (January 2003) that parecoxib should not be
ecchymosis, thrombocytopenia, rarely vomiting, used because there is no evidence of a reduction in
tachycardia, rash (discontinue—risk of serious reac- postoperative haemorrhagic or gastro-intestinal compli-
tions including Stevens-Johnson syndrome and toxic cations compared with non-selective NSAIDs.
epidermal necrolysis), anaphylaxis
15.1.4 Sedative and analgesic peri-operative drugs BNF 57 Dose
arrhythmias, cough, hiccup, laryngospasm, visual . By deep intramuscular injection or by intravenous
disturbances
injection , initially 40 mg, then 20–40 mg every 6–12
Dose
hours when required; max. 80 mg daily; ELDERLY weighing less than 50 kg, initially 20 mg, then max.
To avoid excessive dosage in obese patients, dose may
40 mg daily; need to be calculated on the basis of ideal body-weight CHILD and ADOLESCENT under 18 years, not recommended
. By intravenous injection , spontaneous respiration, Dynastat c (Pharmacia) TA
ADULT , initially up to 500 micrograms over 30 sec- Injection , powder for reconstitution, parecoxib (as
onds; supplemental, 250 micrograms sodium salt), net price 40-mg vial = £4.96, 40-mg vial
With assisted ventilation, ADULT over 18 years, initially (with solvent) = £5.67
30–50 micrograms/kg; supplemental, 15 micr- ograms/kg; CHILD
1 month–18 years, initially 10–
20 micrograms/kg; supplemental doses up to
15.1.4.3 Opioid analgesics
10 micrograms/kg . By intravenous infusion , with assisted ventilation,
Opioid analgesics are now rarely used as premedicants; ADULT and CHILD , initially 50–100 micrograms/kg they are more likely to be administered at induction.
over 10 minutes or as a bolus, followed by main- Pre-operative use of opioid analgesics is generally lim-
tenance of 0.5–1 micrograms/kg/minute ited to those patients who require control of existing
Analgesia and suppression of respiratory activity pain. The main side-effects of opioid analgesics are
during intensive care, with assisted ventilation, by respiratory depression, cardiovascular depression,
intravenous infusion , initially 2 mg/hour subse- nausea, and vomiting; for general notes on opioid anal-
quently adjusted according to response (usual range gesics and their use in postoperative pain, see section
0.5–10 mg/hour); more rapid initial control may be
4.7.2. obtained with an intravenous dose of 5 mg given in For the management of opioid-induced respiratory
divided portions over 10 minutes (slowing if hypo- depression, see section 15.1.7.
tension or bradycardia occur); additional doses of 0.5–1 mg may be given by intravenous injection
Intra-operative analgesia Opioid analgesics given in during short painful procedures small doses before or with induction reduce the dose
Rapifen c (Janssen-Cilag) C requirement of some drugs used during anaesthesia.
Injection , alfentanil (as hydrochloride) 500 micr- Alfentanil, fentanyl, and remifentanil are particularly
ograms/mL, net price 2-mL amp = 67p; 10-mL amp = useful because they act within 1–2 minutes and have
short durations of action. The initial doses of alfentanil Intensive care injection , alfentanil (as hydrochloride) or fentanyl are followed either by successive intra-
5 mg/mL. To be diluted before use. Net price 1-mL venous injections or by an intravenous infusion; pro-
amp = £2.46
longed infusions increase the duration of effect. Repeated intra-operative doses of alfentanil or fentanyl should be given with care since the resulting respiratory
FENTANYL
depression can persist postoperatively and occasionally Indications analgesia during operation, enhancement it may become apparent for the first time postopera-
of anaesthesia; respiratory depressant in assisted tively when monitoring of the patient might be less
respiration; analgesia in other situations (section intensive. Alfentanil, fentanyl, and remifentanil can
cause muscle rigidity, particularly of the chest wall or Cautions section 4.7.2 and notes above jaw; this can be managed by the use of neuromuscular
thesia Contra-indications section 4.7.2 blocking drugs.
Side-effects section 4.7.2 and notes above; also In contrast to other opioids which are metabolised in the
myoclonic movements; less commonly laryngospasm; Anaes liver, remifentanil undergoes rapid metabolism by non-
rarely asystole, insomnia specific blood and tissue esterases; its short duration of
Dose
15 action allows prolonged administration at high dosage, without accumulation, and with little risk of residual
To avoid excessive dosage in obese patients, dose may postoperative respiratory depression. Remifentanil
need to be calculated on the basis of ideal body-weight should not be given by intravenous injection intra-
. By slow intravenous injection , with spontaneous operatively, but it is well suited to continuous infusion;
respiration, ADULT and CHILD over 12 years, initially
a supplementary analgesic is given before stopping the 50–100 micrograms (max. 200 micrograms on spe- infusion of remifentanil.
cialist advice), then 50 micrograms as required; CHILD 2–12 years, initially 2–3 micrograms/kg, then
1 microgram/kg as required Indications
ALFENTANIL
ADULT and CHILD over 12 years, initially 0.3–3.5 mg, then 100–200 micrograms tive procedure and outpatient surgery; enhancement
With assisted ventilation, analgesia especially during short opera-
2–12 years, initially 2–3 micr- of anaesthesia; analgesia and suppression of respir-
CHILD ograms/kg, then 1 microgram/kg as required atory activity in patients receiving intensive care, with
as required;
assisted ventilation, for up to 4 days By intravenous infusion , with spontaneous respira-
Cautions tion, ADULT , 50–80 nanograms/kg/minute adjusted
section 4.7.2 and notes above according to response Contra-indications section 4.7.2
With assisted ventilation, ADULT , initially 10 micr- Side-effects section 4.7.2 and notes above; also
ograms/kg over 10 minutes then 100 nanograms/kg/ hypertension, myoclonic movements; less commonly
minute adjusted according to response; may require
BNF 57
15.1.5 Neuromuscular blocking drugs 697
up to 3 micrograms/kg/minute during cardiac sur- infusion rate of at least 100 nanograms/kg/minute gery
for at least 5 minutes before procedure and adjust Fentanyl (Non-proprietary) C every 2–5 minutes according to requirements, usual
Injection , fentanyl (as citrate) 50 micrograms/mL, net range 250–750 nanograms/kg/minute price 2-mL amp = 54p, 10-mL amp = £1.65
. Cardiac surgery, consult product literature
c Note Sublimaze Remifentanil doses in BNF may differ from those in (Janssen-Cilag) C product literature Injection , fentanyl (as citrate) 50 micrograms/mL, net
Ultiva price 2-mL amp = 22p, 10-mL amp = £1.11 c (GSK) C Injection , powder for reconstitution, remifentanil (as hydrochloride), net price 1-mg vial = £5.12; 2-mg vial
= £10.23; 5-mg vial = £25.58 Indications supplementation of general anaesthesia
REMIFENTANIL
during induction and analgesia during maintenance of anaesthesia (consult product literature for use in patients undergoing cardiac surgery); analgesia and sedation in ventilated, intensive care patients
15.1.5 Neuromuscular blocking
Cautions section 4.7.2 (but no dose adjustment
necessary in renal impairment) and notes above
drugs
Contra-indications section 4.7.2 and notes above; left ventricular dysfunction Side-effects
Neuromuscular blocking drugs used in anaesthesia are section 4.7.2 and notes above; also
also known as muscle relaxants. By specific blockade hypertension, hypoxia; very rarely asystole and
of the neuromuscular junction they enable light anaes- anaphylaxis
thesia to be used with adequate relaxation of the mus- Dose
cles of the abdomen and diaphragm. They also relax the To avoid excessive dosage in obese patients, dose
vocal cords and allow the passage of a tracheal tube. should be calculated on the basis of ideal body-weight
Their action differs from the muscle relaxants used in musculoskeletal disorders (section 10.2.2) that act on
. Induction of anaesthesia, ADULT and CHILD over 12 the spinal cord or brain. years, by intravenous infusion , 0.5–1 micrograms/
Patients who have received a neuromuscular blocking kg/minute, with or without an initial dose by intra-
drug should always have their respiration assisted or venous injection of 0.25–1 microgram/kg over at
controlled until the drug has been inactivated or antag- least 30 seconds
onised (section 15.1.6). They should also receive suffi- Note If patient to be intubated more than 8 minutes after
cient concomitant inhalational or intravenous anaes- start of intravenous infusion, initial intravenous injection dose is not necessary
thetic or sedative drugs to prevent awareness. . Maintenance of anaesthesia in ventilated patients,
ADULT and CHILD over 12 years, by intravenous infu- sion , 0.05–2 micrograms/kg/minute (with or without
Non-depolarising neuromuscular
an initial dose by intravenous injection of 0.25–
blocking drugs
1 micrograms/kg over at least 30 seconds) accord- ing to anaesthetic technique and adjusted according Non-depolarising neuromuscular blocking drugs (also to response; in light anaesthesia supplemental doses known as competitive muscle relaxants) compete with
by intravenous injection every 2–5 minutes acetylcholine for receptor sites at the neuromuscular junction and their action can be reversed with anti-
. Maintenance of anaesthesia with spontaneous cholinesterases such as neostigmine (section 15.1.6). respiration, ADULT and CHILD over 12 years, by intra-
venous infusion Non-depolarising neuromuscular blocking drugs can , initially 40 nanograms/kg/minute
be divided into the aminosteroid group, comprising adjusted according to response, usual range 25–
pancuronium, rocuronium, and vecuronium, and the 100 nanograms/kg/minute
benzylisoquinolinium group, comprising atracurium,
. Maintenance of anaesthesia, CHILD 1–12 years, by cisatracurium, and mivacurium. intravenous infusion , 0.05–1.3 micrograms/kg/
Anaesthesia
slower onset of action than suxamethonium. These least 30 seconds) according to anaesthetic techni-
minute (with or without an initial dose by intra- venous injection of 0.1–1 microgram/kg over at
Non-depolarising neuromuscular blocking drugs have a
drugs can be classified by their duration of action as que and adjusted according to response
short-acting (15–30 minutes), intermediate-acting (30– . Analgesia and sedation in ventilated, intensive-care
40 minutes), and long-acting (60–120 minutes), patients,
by intravenous infusion although duration of action is dose-dependent. Drugs ,
years, initially 100–150 nanograms/kg/minute with a shorter or intermediate duration of action, such adjusted according to response in steps of 25 nan- as atracurium and vecuronium, are more widely used ograms/kg/minute (allow at least 5 minutes than those with a longer duration of action, such as between dose adjustments); usual range 6– pancuronium.
ADULT over 18
740 nanograms/kg/minute; if an infusion rate of Non-depolarising neuromuscular blocking drugs have 200 nanograms/kg/minute does not produce ade-
no sedative or analgesic effects and are not considered quate sedation add another sedative (consult pro-
to trigger malignant hyperthermia. duct literature for details)
For patients receiving intensive care and who require . Additional analgesia during stimulating or painful
tracheal intubation and mechanical ventilation, a non- procedures in ventilated, intensive-care patients, by
depolarising neuromuscular blocking drug is chosen intravenous infusion , ADULT over 18 years, maintain
according to its onset of effect, duration of action, and
15.1.5 Neuromuscular blocking drugs BNF 57 side-effects. Rocuronium, with a rapid onset of effect,
ATRACURIUM BESILATE
may facilitate intubation. Atracurium or cisatracurium
may be suitable for long-term neuromuscular blockade (Atracurium besylate)
since their duration of action is not dependent on Indications neuromuscular blockade (short to inter- elimination by the liver or the kidneys.
mediate duration) for surgery or during intensive care Cautions see notes above; pregnancy (Appendix 4);
Cautions Allergic cross-reactivity between neuro- breast-feeding (Appendix 5) muscular blocking drugs has been reported; caution is
Side-effects see notes above; seizures also reported advised in cases of hypersensitivity to these drugs. Their
Dose
activity is prolonged in patients with myasthenia gravis and in hypothermia, and lower doses are required. Non-
To avoid excessive dosage in obese patients, dose should be calculated on the basis of ideal body-weight
depolarising neuromuscular blocking drugs should be used with great care in those with other neuromuscular
CHILD bances, as response is unpredictable. Resistance can
. Surgery or intubation, ADULT and over 1 month, disorders and those with fluid and electrolyte distur-
by intravenous injection , initially 300–600 micr- develop in patients with burns, who may require
ograms/kg; maintenance, by intravenous injection , increased doses; low plasma cholinesterase activity in
100–200 micrograms/kg as required or by intra- these patients requires dose titration for mivacurium.
venous infusion , 5–10 micrograms/kg/minute Interactions: Appendix 1 (muscle relaxants).
(300–600 micrograms/kg/hour) . Intensive care, ADULT and CHILD over 1 month, by intravenous injection , initially 300–600 micr- Side-effects Benzylisoquinolinium non-depolarising
ograms/kg (optional) then by intravenous infusion neuromuscular blocking drugs (except cisatracurium)
4.5–29.5 micrograms/kg/minute (usual dose 11– are associated with histamine release, which can
13 micrograms/kg/minute) cause skin flushing, hypotension, tachycardia, broncho- spasm, and very rarely anaphylactoid reactions. Most
Atracurium (Non-proprietary) A aminosteroid neuromuscular blocking drugs produce
Injection , atracurium besilate 10 mg/mL, net price minimal histamine release. Drugs with vagolytic activity
2.5-mL amp = £1.85; 5-mL amp = £3.37; 25-mL amp can counteract any bradycardia that occurs during
surgery. Acute myopathy has also been reported after Tracrium prolonged use in intensive care. c (GSK) A Injection , atracurium besilate 10 mg/mL, net price Atracurium, a mixture of 10 isomers, is a benzylisoqui-
2.5-mL amp = £1.66; 5-mL amp = £3.00; 25-mL amp nolinium neuromuscular blocking drug with an inter-
mediate 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.
CISATRACURIUM
Cisatracurium is a single isomer of atracurium. It is Indications neuromuscular blockade (intermediate more potent and has a slightly longer duration of action
duration) for surgery or during intensive care than atracurium and provides greater cardiovascular
Cautions see notes above; pregnancy (Appendix 4); stability because cisatracurium lacks histamine-releas-
breast-feeding
ing effects. Side-effects see notes above Mivacurium, a benzylisoquinolinium neuromuscular
Dose
thesia blocking drug, has a short duration of action. It is To avoid excessive dosage in obese patients, dose metabolised by plasma cholinesterase and muscle
should be calculated on the basis of ideal body-weight Anaes paralysis is prolonged in individuals deficient in this enzyme. It is not associated with vagolytic activity or . Intubation, by intravenous injection , ADULT and CHILD
15 ganglionic blockade although histamine release can over 1 month, initially 150 micrograms/kg; main-
occur, particularly with rapid injection. tenance, by intravenous injection , 30 micrograms/ Pancuronium, an aminosteroid neuromuscular block-
kg approx. every 20 minutes; CHILD 2–12 years, ing drug, has a long duration of action and is often used
20 micrograms/kg approx. every 9 minutes; or in patients receiving long-term mechanical ventilation
maintenance, by intravenous infusion , ADULT and in intensive care units. It lacks a histamine-releasing
CHILD over 2 years, initially, 3 micrograms/kg/min- effect, but vagolytic and sympathomimetic effects can
ute, then after stabilisation, 1–2 micrograms/kg/ cause tachycardia and hypertension.
minute; dose reduced by up to 40% if used with Rocuronium exerts an effect within 2 minutes and has
isoflurane
the most rapid onset of any of the non-depolarising . Intensive care, by intravenous infusion , ADULT 0.5– neuromuscular blocking drugs. It is an aminosteroid
10.2 micrograms/kg/minute (usual dose 3 micr- neuromuscular blocking drug with an intermediate
ograms/kg/minute) duration of action. It is reported to have minimal cardi-
Note Lower doses can be used for children over 2 years ovascular effects; high doses produce mild vagolytic
when not for intubation activity.
Nimbex c (GSK) A Vecuronium, an aminosteroid neuromuscular blocking
Injection , cisatracurium (as besilate) 2 mg/mL, net drug, has an intermediate duration of action. It does not
price 10-mL amp = £7.55 generally produce histamine release and lacks cardio-
Forte injection , cisatracurium (as besilate) 5 mg/mL, vascular effects.
net price 30-mL vial = £31.09
BNF 57
15.1.5 Neuromuscular blocking drugs 699
MIVACURIUM
Dose
Indications neuromuscular blockade (short duration) To avoid excessive dosage in obese patients, dose for surgery
should be calculated on the basis of ideal body-weight Cautions see notes above; low plasma cholinesterase activity; elderly; hepatic impairment (Appendix 2);
. Intubation, ADULT and CHILD over 1 month, by intra- renal impairment (Appendix 3); pregnancy (Appendix
venous injection , initially 600 micrograms/kg; 4)
maintenance by intravenous injection , 150 micr- Side-effects see notes above
ograms/kg ( ELDERLY 75–100 micrograms/kg) or Dose
maintenance by intravenous infusion , 300– 600 micrograms/kg/hour ( ELDERLY up to 400 micr-
To avoid excessive dosage in obese patients, dose ograms/kg/hour) adjusted according to response should be calculated on the basis of ideal body-weight
. Intensive care, by intravenous injection , ADULT initi- ally 600 micrograms/kg; maintenance by intra- . By intravenous injection , 70–250 micrograms/kg;
venous infusion , 300–600 micrograms/kg/hour for maintenance 100 micrograms/kg every 15 minutes;
first hour, then adjusted according to response CHILD 2–6 months initially 150 micrograms/kg, 7
Esmeron months–12 years initially 200 micrograms/kg; c (Organon) A maintenance ( CHILD
2 months–12 years) 100 micr- Injection , rocuronium bromide 10 mg/mL, net price ograms/kg every 6–9 minutes
5-mL vial = £3.01, 10-mL vial = £6.01 Note Doses up to 150 micrograms/kg may be given over 5–
15 seconds, higher doses should be given over 30 seconds. In patients with asthma, cardiovascular disease or those who
VECURONIUM BROMIDE
Indications neuromuscular blockade (intermediate . By intravenous infusion , maintenance of block, 8–
are sensitive to falls in arterial blood pressure give over 60 seconds
duration) for surgery
10 micrograms/kg/minute, adjusted if necessary Cautions see notes above; pregnancy (Appendix 4) every 3 minutes by 1 microgram/kg/minute to
Side-effects see notes above usual dose of 6–7 micrograms/kg/minute; CHILD 2 Dose
months–12 years, usual dose 11–14 micrograms/ kg/minute
To avoid excessive dosage in obese patients, dose
c Mivacron should be calculated on the basis of ideal body-weight (GSK) A Injection , mivacurium (as chloride) 2 mg/mL, net
. By intravenous injection , intubation, ADULT and CHILD price 5-mL amp = £2.79; 10-mL amp = £4.51
over 5 months, 80–100 micrograms/kg ( CHILD under
1 year, onset more rapid and high intubation dose
may not be required); maintenance 20–30 micr- Indications
PANCURONIUM BROMIDE
ograms/kg adjusted according to response; NEONATE neuromuscular blockade (long duration)
and CHILD up to 4 months, initial test dose 10– for surgery or during intensive care
20 micrograms/kg then incremental doses to Cautions see notes above; hepatic impairment
achieve response
(Appendix 2); renal impairment (Appendix 3); . By intravenous infusion , 0.8–1.4 micrograms/kg/ pregnancy (Appendix 4) and breast-feeding (Appen-
minute (after initial intravenous injection of 40– dix 5)
100 micrograms/kg) Side-effects see notes above Dose c Norcuron (Organon) A
Injection , powder for reconstitution, vecuronium To avoid excessive dosage in obese patients, dose
bromide, net price 10-mg vial = £3.95 (with water for should be calculated on the basis of ideal body-weight
injections)
. Intubation, by intravenous injection , initially 50– 100 micrograms/kg then 10–20 micrograms/kg as
Depolarising neuromuscular blocking
required; CHILD initially 60–100 micrograms/kg,
then 10–20 micrograms/kg, NEONATE 30–40 micr-
drugs
Anaesthesia
ograms/kg initially then 10–20 micrograms/kg Suxamethonium has the most rapid onset of action of . Intensive care, by intravenous injection , 60 micr-
any of the neuromuscular blocking drugs and is ideal if ograms/kg every 60–90 minutes
fast onset and brief duration of action are required e.g. Pancuronium (Non-proprietary) A with tracheal intubation. Its duration of action is about 2
Injection , pancuronium bromide 2 mg/mL, net price to 6 minutes after intravenous doses of about 1 mg/kg; 2-mL amp = £1.20
repeated doses can be used for longer procedures. Suxamethonium acts by mimicking acetylcholine at the