15.1.1 Intravenous anaesthetics
15.1.2 Inhalational anaesthetics
15.1.3 Antimuscarinic
drugs
15.1.4 Sedative and analgesic perioperative
drugs
15.1.4.1 Anxiolytics
and neuroleptics
15.1.4.2 Non-opioid
analgesics
15.1.4.3 Opioid analgesics
15.1.5.1 Non-depolarising muscle relaxants
15.1.5.2 Depolarising muscle relaxants
15.1.6 Drugs for the reversal of neuromuscular blockade
15.1.7 Antagonists for central and respiratory
depression
15.1.8 Malignant hyperthermia
15.2 Local anaesthesia
15.3 Anaphylaxis under general anaesthesia
15.4
Prophylaxis of acid aspiration
15.1 General anaesthesia
15.1.1 Intravenous
anaesthetics
Thiopental, an ultra-short acting barbiturate, is the benchmark agent
for induction of anaesthesia but it causes cardiovascular depression. Etomidate also has a short half-life and causes
little cardiovascular depression. Propofol is
ultra-short acting with rapid redistribution and may be given by infusion for
maintenance of anaesthesia. Cardiovascular depression is equivalent to thiopental.
Its use is restricted in children. Ketamine, a
dissociative anaesthetic, may be given im, it does
not cause cardiovascular depression and it is analgesic at low dose. It may
cause sympathetic stimulation, dysphoria and
hallucinations.
For expert use:
Etomidate injection: 20mg in 10ml
[£1.38] Dose: for adults 300microgram/kg slow iv injection.
Ketamine injection: 200mg in 20ml
[£5.06]; 500mg in 10ml [£8.77]; 1000mg in 10ml [£16.10]. Dose: for
adults 1-4.5mg/kg iv injection over at least 60 secs (2mg/kg usually produces 5-10mins of surgical
anaesthesia); 6.5-13mg/kg im injection (10mg/kg
usually produces 12-25 minutes of surgical anaesthesia).
Propofol 1% injection: 200mg in 20ml
amp [75p]; 500mg in 50ml vial [£1.85]; 500mg in 50ml syringe [£4.32]. Dose:
induction of anaesthesia in adults
1.5-2.5mg/kg iv at a rate of 20-40mg every 10 secs until response; maintenance
of anaesthesia by iv infusion in adults 4-12mg/kg/hour.
Propofol 2% injection: 1000mg in 50ml
vial [£3.35].
Thiopental sodium injection: (BAN = thiopentone
sodium) 0.5g in 20ml [£3.38].
15.1.2 Inhalational
anaesthetics
Nitrous oxide used in combination with other anaesthetic agents, is
also available premixed with an equal quantity of oxygen (Entonox)
for analgesia in labour and after trauma. Halothane causes some
cardiovascular depression and is rarely used because of its association with
severe hepatotoxicity. particularly
after repeated exposure. Isoflurane has
no adverse effect on the liver or kidneys but it does cause slight
cardiovascular depression. Recovery from anaesthetic is more rapid than with halothane. Sevoflurane
gives faster induction and recovery than isoflurane.
Its pleasant smell makes it useful for gas induction of small children. Desflurane is a rapid acting anaesthetic. Early postoperative pain relief may be
required because of emergence and recovery are
particularly rapid.
For expert use:
Nitrous oxide:
Nitrous oxide 50% & oxygen 50% (Entonox):
Desflurane: via vaporiser [240ml
£61.41].
Isoflurane: via vaporiser [250ml £8.33].
Sevoflurane: via vaporiser [250ml
£84.87].
15.1.3 Antimuscarinic drugs
Anticholinergic drugs are used mainly to reduce
salivary and bronchial secretions and to prevent bradycardia
during anaesthesia and surgery. Atropine may cause tachycardia, a rise
in temperature, particularly in children, and it may be sedative in the
elderly. Hyoscine is mildly sedative
and anti-emetic and may cause amnesia or confusion, especially in the elderly. Glycopyrronium causes less tachycardia than atropine
and is less sedative in the elderly.
Atropine sulphate injection: 600microgram in 1ml [12p]. Dose: for
adults 600microgram im or iv.
Hyoscine hydrobromide
injection: 400microgram in 1ml [67p]. Dose: for adult
400microgram im or iv.
Hyoscine hydrobromide
tabs: 300microgram [14p]. Dose: see 4.6.1.
Glycopyrronium bromide injection:
200microgram in 1ml [28p]; 600microgram in 3ml [50p]. Dose: for
adults 200-400microgram iv.
15.1.4 Sedative and analgesic perioperative drugs
15.1.4.1 Anxiolytics
and neuroleptics
|
Link to NICE guidance |
Sedation in children and young people. Clinical Guideline No. 112 |
Oral benzodiazepines are used for premedication, notably diazepam,
lorazepam and the shorter acting temazepam. Injected benzodiazepines may cause
respiratory depression, especially if given by rapid iv
injection in large doses. Diazepam solution for injection is rarely
used. Given im its absorption is erratic; given iv it is irritant, causing pain (unless infused into a large
vein) and venous thrombosis, which may be delayed. Diazepam emulsion (Diazemuls) is preferred. It is less irritant given iv, it does not cause pain or venous thrombosis but it
should not be given im. Midazolam,
a water soluble benzodiazepine, is about twice as potent as diazepam. It
is less irritant on iv injection but it may cause
severe hypotension if given rapidly in high dose, especially in the elderly and
debilitated.
Diazepam and midazolam in subanaesthetic
doses produce sedation and amnesia. They do not possess analgesic properties
but are given with local or opioid analgesia for
painful procedures. Care is needed because of a combined effect on respiratory
depression. Also see 4.1.1.
Diazepam tabs: 2mg [28 tabs 71p]; 5mg [28 tabs 72p]; 10mg [28 tabs 77p].
Lorazepam tabs: 1mg [28 tabs
£3.35]; 2.5mg [28 tabs £5.04].
Temazepam tabs: 10mg [28 tabs
£2.31]; 20mg [28 tabs £1.65] (CD).
Temazepam oral solution: 10mg in 5ml
[300ml £42.90] (CD).
Alimemazine strong syrup: (BAN =
trimeprazine) 30mg in 5ml [100ml £10.57].
Diazepam solution for injection: 10mg in 2ml [45p].
Diazepam emulsion for injection: (Diazemuls®)
10mg in 2ml [91p].
Midazolam injection: 10mg in 2ml
[23p]; 10mg in 5ml [27p]; 5mg in 5ml [19p].
15.1.4.2 Non-opioid analgesics
NSAIDs are used perioperatively.
They give adequate analgesia for minor surgery and reduce the need for opioids in major surgery. They can be given orally,
rectally or parenterally, the first dose can be given
preoperatively and they are particularly good for musculoskeletal pain. Some
have antiplatelet effects so there is the possibility
of increased surgical bleeding. See
10.1.1 and see 4.7.1.
Preferred oral preparation
Piroxicam orodispersible
20mg tablets [26p] which can be taken by placing on the tongue or by
swallowing.
Preferred parenteral preparation
Diclofenac 75mg (Dyloject®)
[£4.80]. Dose: acute
postoperative pain 75mg by iv injection repeated after four to six hours if
necessary, max 150mg in 24 hours for 2 days; prevention of postoperative pain
25-50mg by iv injection repeated after four to six hours if necessary, max
150mg in 24 hours for 2 days.
15.1.4.3 Opioid analgesics
Alfentanil and fentanyl
are very potent short acting opioids used to
supplement anaesthesia or to provide analgesia and sedation in ICU. They can
cause marked respiratory depression which can be reversed by naloxone (see 15.1.7).
Remifentanil is a new ultra short
acting, very potent opioid. It is normally given by infusion
and is useful where cardiovascular stability is essential.
Alfentanil injection: 500microgram/ml:
[2ml 63p; 10ml [£2.90]; 5mg in 1ml [£2.32]. (CD)
Fentanyl injection: 50microgram/ml:
[2ml 11p; 10ml 21p]. (CD)
Remifentanil injection: 1mg
[£5.12]; 2mg [£10.23]; 5mg [£25.58]. (CD)
15.1.5.1 Non-depolarising
(competitive) muscle relaxants
The effects of competitive muscle relaxants tend to be terminated by renal
excretion. Their action is therefore prolonged by renal failure and also by
hypothermia, hypokalaemia, acidosis and interaction
with aminoglycoside antibiotics.
Vecuronium has an action of about 20mins, the
onset of block is rapid and it is easily reversed.
Atracurium undergoes non-enzymatic metabolism
which is independent of liver and kidney function, thus allowing its use in
patients with hepatic or renal impairment.
Mivacurium is short acting (10-15mins),
rapidly metabolised by plasma cholinesterase, and does not need to be reversed.
Rocuronium exerts an effect within 2
minutes and has the most rapid onset of any of the competitive muscle
relaxants.
For expert use:
Atracurium besylate
injection: 25mg in 2.5ml [44p]; 50mg in 5ml [75p]; 250mg in 25ml [£4.75]. Dose:
surgery or intubation in adults, by iv
injection, initially 300 - 600 microgram/kg; maintenance 100 - 200
microgram/kg as required;
or by iv infusion
5 - 10 microgram/kg/min.
Mivacurium injection: 2mg/ml [5ml
£2.79, 10ml £4.51]. Dose: by iv
injection for adults 70-250microgram/kg initially; maintenance
100microgram/kg every 15min.
Rocuronium bromide injection: 10mg/ml
[5ml £2.89]. Dose: for adult intubation 600 micrograms/kg; maintenance
150 micrograms/kg.
Vecuronium bromide injection: 10mg
reconstituted with water [£3.37]. Dose: for adult intubation initially
80-100microgram/kg; maintenance 20-30 micrograms/kg.
15.1.5.2 Depolarising muscle
relaxants
Suxamethonium has a very short
action of up to 5mins which terminates spontaneously. The initial block is
usually preceded by muscle fasciculation which may cause pain. Successive doses
may cause bradycardia and prolonged muscular
blockade.
For expert use:
Suxamethonium chloride injection: 100mg in 2ml
[40p]; 100mg in 2ml prefilled syringe [£8.45]. Dose: by iv injection
for adults initially 1mg/kg.
15.1.6 Drugs for the
reversal of neuromuscular blockade
Drugs which inhibit cholinesterase at the neuromuscular junction increase
the concent-ration of acetylcholine at the motor end
plate and antagonise competitive neuromuscular blockade. They prolong the
action of suxamethonium. Side effects due to anticholinesterase action at muscarinic
receptors, including salivation, bradycardia, bronchoconstriction and increased bowel motility, may be
prevented by atropine or glycopyrronium.
Edrophonium injection: 10mg in 1ml
[£7.70].
Neostigmine injection: 2.5mg in
1ml [40p].
Neostigmine 2.5mg with glycopyrronium
500microgram /ml injection: [50p].
Sugammadex is used for the reversal of neuromuscular
blockade induced by rocuronium or vecuronium.
For specialist use only
Sugammadex injection: 500mg in 5ml [£149.10].
15.1.7 Antagonists for
central and respiratory depression
Doxapram is a respiratory stimulant and
also has a nonspecific effect on arousal. Flumazenil
reverses the sedative and also potentially the anticonvulsant effects of
benzodiazepines. It has a short duration of action so sedation may return. Naloxone, a specific opioid
antagonist reverses the respiratory depression of opioids
but also their analgesic effects and it may cause tachycardia and nausea. Its
action is short so it may need to be given repeatedly..
Doxapram injection: 100mg in 5ml
[£2.24], 1000mg in 500ml [£23.46]. Dose: postoperative respiratory
depression in adults, by iv injection
over at least 30 secs, 1-1.5mg/kg repeated if
necessary after intervals of one hour or alternatively by iv infusion 2-3mg/min adjusted according to response.
Flumazenil injection: 500microgram
in 5ml [£1.46]. Dose: for adults 200 micrograms over 15 secs, then 100 micrograms at 60 sec intervals if required;
usual dose range 300-600 microgram; maximum total dose 1mg (2mg in ICU);
question aetiology if no response to repeated doses.
Naloxone injection: 40microgram in
2ml (for neonatal use) [£4.60]; 400microgram in 1ml [52p]. Dose: for
adults up to 800microgram in divided doses preferably by iv
injection, but if iv route not available may be given by im
or sc injection.
Malignant hyperthermia may be triggered by halothane, other volatile
anaesthetics and suxamethonium in
susceptible people. It has a mortality of 80% and dantrolene
is the only specific treatment. Supplies are held in the Pharmacy and main
theatres at NDDH, and at
Dantrolene sodium injection: 20mg vial
[£51.00]. Dose: 1mg/kg iv without delay then 1mg/kg every 5-10mins; max
may exceed 10mg/kg in 24hrs.
If malignant hyperthermia is suspected:
1. All inhalational anaesthetics should be stopped immediately. If essential,
anaesthesia may be continued for a short period with intravenous agents such as
propofol and fentanyl but
surgery should be terminated as soon as possible. Suxamethonium
should not be given.
2. The lungs should be hyperventilated with 100% oxygen.
3. Dantrolene sodium should be given as soon as
possible at an initial dose of 1mg/kg iv. A response usually occurs within
minutes. Further doses may be given every 5-10mins, titrated against
temperature, muscle rigidity and heart rate. Doses of about 2.5mg/kg are
usually effective but doses above 10mg/kg in 24hrs may be needed. Side effects
such as myocardial depression are not seen at these doses. The Pharmacy should
be notified to ensure supplies of dantrolene.
4. Heart rate, ECG, core temperature, arterial blood pressure, urine output and
central venous pressure should all be monitored.
5. Sodium bicarbonate at an initial dose of 100mmol may be given to an adult
and more may be given according to arterial blood gases.
6. The patient should be transferred to ICU and remain there until at least
24hrs after resolution because of risk of relapse.
7. Temperature reduction should be achieved by various means such as surface
cooling by cold circulating mattress, cold peritoneal or gastric lavage, cold peritoneal dialysis or extracorporeal blood
cooling. Cold sodium chloride solution 0.9% may be infused iv but Hartmann's
solution should be avoided because of its lactate content.
8. Urine output should be maintained with iv fluids and mannitol
1g/kg iv if needed, but diuretic induced dehydration should be avoided.
9. Hyperkalaemia may be treated with intravenous
insulin and glucose.
10. Cardiac dysrhythmias resulting from acidosis and hyperkalaemia usually respond to correction of pH and
electrolytes but beta blockade may also be needed.
11. Dantrolene should be continued for 48hrs at a
dose of 4mg/kg/day.
12. Hypothermia should be avoided as the condition resolves.
13. The patient should be counselled, and so should relatives who may also need
to be investigated for this autosomal dominant
condition.
Local anaesthetics cause a reversible block to nerve conduction, smallest
fibres being affected first. They do not work in inflamed tissues but systemic
absorption is increased due to hyperaemia. Adrenaline, a vasoconstrictor
mixed with some local anaesthetics, reduces local blood flow and systemic
absorption, thus increasing the maximum safe dose and prolonging the effect. It
should not be used in the digits where there is risk of ischaemic
necrosis.
Systemic absorption of local anaesthetics is determined by the type of anaesthetic,
the dose and duration of the injection, the vascularity
of the site and the use of vasoconstrictor agents. Maximum plasma levels and
any adverse reactions tend to occur after 10-30mins. Toxic effects include CNS
excitation such as nervousness, nausea, restlessness and convulsions followed
by depression and, later, cardiovascular depression.
Lidocaine has a rapid onset and short
duration of action which is prolonged to 1.5hrs if given with adrenaline. It is
absorbed via mucous membranes and useful for surface anaesthesia in strengths
of 2-4%. The maximum recommended dose is 3mg/kg without or 7mg/kg with
adrenaline (equivalent to 20ml lidocaine 1% or 50ml lidocaine 1% with adrenaline for a 70kg adult).
Bupivacaine has a slower onset of
action than lidocaine, up to 30mins for full effect,
but a longer duration of action up to 8hrs although this is not prolonged
further by the addition of adrenaline. It has greater myocardial toxicity than lidocaine or prilocaine and is
contra-indicated for intravenous regional anaesthesia (Bier's blocks). The
maximum recommended dose is 2mg/kg.
Prilocaine is similar to lidocaine.
It is the drug of choice for intravenous regional anaesthesia (Bier's block).
The maximum recommended dose is 5mg/kg or 8mg/kg if mixed with adrenaline. At
high dose it may cause methaemoglobinaemia which can
be treated with intravenous methylene blue 1mg/kg.
NB for lidocaine, BAN = lignocaine
Lidocaine injection: 0.5% [20ml vial
£3.28].
Lidocaine injection: 1% [5ml amp
18p; 20ml amp 60p].
Lidocaine injection: 2% [5ml amp
19p].
Lidocaine 1% with adrenaline 1 in 200,000: [20ml
£1.29].
Lidocaine 2% with adrenaline 1 in 200,000: [20ml
£1.36].
Lidocaine 2% with adrenaline 1 in 80,000: cartridge
[2ml 32p].
Lidocaine gel 2% with chlorhexidine:
[6ml £1.24; 11ml £1.30].
Lidocaine ointment 5%: [15g £3.68].
Lidocaine topical solution: 4% [30ml
£3.68].
Lidocaine aerosol spray: 10% [50ml
£4.37].
NB: 1ml of a 1% of lidocaine solution
contains 10mg; 1ml of a 1 in 200,000 solution of adrenaline contains 5microgram.
Levobupivacaine injection: 0.25% [10ml
£1.41]; 0.5% [10ml £1.62].
Levobupivacaine injection(sterile
overwrapped): 0.25% [10ml £1.41]; 0.5%
[10ml £1.62].
Bupivacaine heavy injection: 5mg/ml for
spinal anaesthesia [4ml £1.21].
Bupivacaine 0.25% with adrenaline 1 in
200,000: [10ml £1.40].
Bupivacaine 0.5% with adrenaline 1 in
200,000: [10ml £1.30].
Prilocaine 1% injection: [50ml £3.52].
Also:
Tetracaine gel: 4% (Ametop®
gel) (BAN = amethocaine): [1.5g £1.08].
For expert use (ENT):
Cocaine solution: 10% [2ml nasal spray £8.77; 5ml £15.93; 25ml £43.05]. CD
Cocaine paste: 10% [4g £17.24]. CD
Lidocaine 5% with phenylephrine
0.5% spray: [2.5ml nasal spray £8.98].
15.3 Anaphylaxis under general anaesthesia
If major anaphylaxis occurs under general anaesthesia:
1. Suspect drugs should be stopped.
2. Surgery and anaesthesia should be discontinued if feasible.
3. Oxygen 100% should be given; tracheal intubation and assisted ventilation
should be considered.
4. Resuscitation should proceed as in 3.4.3.
15.4 Prophylaxis of acid
aspiration
Regurgitation and
aspiration of gastric contents (Mendelson’s syndrome)
is an important complication of general anaesthesia,
particularly in obstetrics and emergency surgery, and requires prophylaxis
against acid aspiration. Prophylaxis is also needed in those with gastro-oesophageal reflux disease and in circumstances where
gastric emptying may be delayed.
An H2-receptor antagonist
or a proton pump inhibitor such
as omeprazole may be used before surgery to increase
the pH and reduce the volume of gastric fluid. They do not affect the pH of
fluid already in the stomach and this limits their value in emergency
procedures; oral H2-receptor antagonists can be given 1–2 hours
before the procedure but omeprazole must be given at
least 12 hours earlier. Antacids are frequently used to neutralise
the acidity of the fluid already in the stomach; ‘clear’ (non-particulate)
antacids such as sodium citrate are preferred.
Sodium citrate 0.3M oral solution:
30ml [£2.73].