Thiopentone Sodium
NOTE The name thiobarbital has been applied to thiopentone
and has also been used to describe a barbiturate of different
composition.
Some include thiopentone sodium with. some without, anhy-
drous sodium carbonate; some only include a sterile mixture
for injection.
A white lo yellowish-while hygroscopic crystalline powder.
or pale greenish hygroscopic powder with a characteristic al-
liaceous odour.
Thiopental Sodium and Sodium Carbonate (Ph. Eur.) con-
tains 84 to 87% thiopentone and 10.2 to 11.2% sodium. Its
solubilities are; freely soluble in water: partly soluble in de-
hydraled alcohol: practically insoluble in ether. Thiopental
Sodium (USP 23) solubilities are: soluble in water and in al-
cohol: insoluble in ether and in petroleum spirit. Solutions of
thiopenlone sodium are incompatible with acidic and oxidis-
ing substances so that, amongst other drugs, a number of an-
tibiotics, muscle relaxants and analgesics should not be
mixed with it. Compounds commonly listed as incompatible
include amikacin sulphate, benzyl penicillin salts, cefapirin
sodium, codeine phosphate, ephedrine sulphate, fentanyl cit-
rate. glycopyrronium bromide, morphine sulphate, pentazoc-
ine lactate. prochlorperazine edisylale, suxamethonium sails.
and tubocurarine chloride. Solutions decompose on standing
and precipitation occurs on boiling. Store in airtight contain-
ers. Protect from light.
Loss of thiopentone in polyvinyl chloride and cellulose pro-
pionate delivery systems has been reported, but in another
study no loss of potency was noted.
Adverse Effects and Treatment
As for phenobarbitone.
Excitatory phenomena such as coughing, hiccupping
sneezing, and muscle twitching or jerking may oc
cur with any of the barbiturate anaesthetics, particu
larly during induction, but they occur more
frequently with methohexitone than with thiopen
tone. Laryngeal spasm or bronchospasm may also
occur during induction. The intravenous injection of
concentrated solutions of thiopentone sodium such
as 5% may result in thrombophlebitis. Extravasation
of barbiturate anaesthetics may cause tissue necro
sis. Intra-arterial injection causes severe arterial
spasm with burning pain and may cause prolong
blanching of the forearm and hand and gangrene of
digits. Hypersensitivity reactions have been report
ed. Barbiturate anaesthetics can cause respiratory
depression. They depress cardiac output and often
cause an initial fall in blood pressure, and overdos-
age may result in circulatory failure. Postoperative
vomiting is infrequent but shivering may occur and
ibere may be persistent drowsiness. confusion, and
amnesia. Headache has also been reported.
Hypersensitivity. Anaphylactic reactions to thiopentone
have been reported, although such reactions are rare. There
has also been a report of haemolytic anaemia and renal failure
in association with the development of an anti-thiopentone
antibody in a patient who had undergone general anaesthesia
induced by thiopentone.
Intra-arterial injection. Accidental intra-arterial injection
of thiopentone sodium produces severe arterial spasm with
intense burning pain. Anaesthesia, paresis, paralysis, and gan-
grene may occur. Therapy has concentrated on dilution of in-
jected thiopentone, prevention and treatment of arterial
spasm, prophylaxis of thrombosis, thrombectomy and other
measures to sustain good blood flow. There has been a report'
of the successful use of urokinase intra-arterially in the man-
agement of one patient accidentally given thiopentone intra-
arterially.
Precautions
Barbiturate anaesthetics are contra-indicated when
there is dyspnoea or respiratory obstruction such as
in acute severe asthma or when maintenance of an
airway cannot be guaranteed. They are also contra-
indicated in porphyria.
Barbiturate anaesthetics should be used with caution
in shock and dehydration, hypovolaemia. severe
anaemia, hyperkalaemia, toxaemia, myasthenia
gravis, myxaedema and other metabolic disorders,
or in severe renal disease. Caution is also required in
patients with cardiovascular disease, muscubr dys-
trophies, adrenocortical insufficiency, or with in-
creased intracranial pressure. Reduced doses are
required in the elderly and in severe hepatic disease.
Interactions
Difficulty may be experienced in producing anaes-
thesia with the usual dose of barbiturate anaesthetics
in patients accustomed to taking alcohol or other
CNS depressants: additional anaesthetics may be
necessary. Care is required when anaesthetizing pa-
tients being treated with phenothiazines antipsychot-
ics since there may be increased hypotension. Some
phenothiazines, especially promethazine, may in-
crease the incidence of excitatory phenomena pro-
duced by barbiturate anaesthetics; cyclizine may
possibly have a similar effect. Opioid analgesics car
potentiate the respiratory depressant effect of barbit-
urate anaesthetics and the dose of the anaesthetic
may need to be reduced. Concomitant administra-
tion of nitrous oxide greatly reduces the dose of bar-
biturate anaesthetics required for anaesthesia
Reduced doses of thiopentone may be required in
patients receiving sulphafurazole.
Antidepressants. Potentiation of barbiturate anaesthesia
may be expected in patients receiving tricyclic antidepres
sants or MAOls .
Aspirin. Pretreatment with aspirin, a highly protein-bound
drug, has been shown to potentiate thiopentone anaesthesia.
Probenecid. Pretreatment with probenecid. a highly pro
tein-bound drug, has been shown to potentiate thiopenton
anaesthesia.
Pharmacokinetics
Thiopentone is highly lipid soluble and when it is
administered intravenously as the sodium salt. con-
centrations sufficient lo produce unconsciousness
are achieved in the brain within 30 seconds. Onset of
action occurs within 8 to 10 minutes when thiopen-
tone sodium is given rectally but absorption may be
unpredictable if a suspension rather than a solution
is used. Recovery from anaesthesia is also rapid due
to redistribution to other tissues, particularly fat.
About 80% of thiopentone may be bound to plasma
proteins, although reports show a wide range of fig-
ures. Thiopentone is metabolised almost entirely in
the liver, but as it is only released slowly from lipid
stores this occurs at a very slow rate.
It is mostly metabolised to inactive metabolites but
a small amount is desulphurated to pentobarbitone
Repeated or continuous administration can lead to
accumulation of thiopentone in fatty tissue and this
can result in prolonged anaesthesia and respiratory
and cardiovascular depression. Elimination of thio-
pentone following bolus injection can be described
by a triexponential curve. The terminal elimination
half-life has been reported to be 10 to 12 hours in
adults and about 6 hours in children. However, val-
ues of 26 to 28 hours have been reported in obese
patients and pregnant patients at term. Thiopenione
readily diffuses across the placenta and is distributed
into breast milk.
Uses and Administration
Thiopentone is a short-acting barbiturate anaesthet-
ic. It is usually given for the induction of general an-
aesthesia but may be used as the sole
anaesthetic to maintain anaesthesia for short proce-
dures with minimal painful stimuli. It is also used in
anaesthesia as a supplement lo other anaesthetics, as
a hypnotic in balanced anaesthesia, and for basal an-
aesthesia or basal narcosis. Thiopentone sodium
may also be used in the control of refractory tonic-
clonic status epilepticus and in neurosurgical pa-
tients to reduce increased intracranial pressure.
Thiopentone does not usually produce excitation
and induction of anaesthesia is usually smooth. It
has poor muscle relaxant properties and a muscle re-
laxant must be administered before intubation is at-
tempted. Thiopentone also has poor analgesic
properties and small doses may even lower the pain
threshold. Recovery from an induction dose may oc
cur within 10 to 30 minutes although drowsiness
may persist for some time.
In anaesthesia, the dosage of thiopentone varies
greatly according to the state of the patient and the
nature of other drugs being used concurrently (see
under Precautions above and Interactions above for
further details). Thiopentone is usually administered
intravenously as the sodium salt as a 2.5% solution
but a 5% solution is occasionally used. A typical
dose for inducing anaesthesia is 100 to 150 mg in
jected over 10 to 15 seconds, repeated after 30 to 60
seconds according to response. Some prefer to initi
ate induction with a test dose of 25 to 75 mg. The
UK manufacturer recommends that the total dosage
used in pregnant patients should not exceed 250 mg
' Children's doses range from 2 to 7 mg per kg body
weight. When thiopentone is used as the sole anaes
thetic, anaesthesia can be maintained by repeat do
es as needed or by continuous intravenous infusion
of a 0.2 or 0.4% solution. Thiopentone sodium may
be given rectally for basal anaesthesia or basal nar-
cosis.
A suggested dose in refractory tonic-clonic status
epilepticus is 50 to 125 mg intravenously given as
soon as possible after convulsions begin; up to
250 mg may be required over 10 minutes (sec also
under Status Epilepticus, below).
Recovery is usually rapid after moderate doses, but
the patient may remain sleepy or confused for sever-
al hours. Large doses, repeated smaller doses, or
continuous administration may markedly delay re-
covery.
Administration in the elderly. It is usually recommended
that the dosage of barbiturate anaesthetics is reduced in the
elderly. One study' in elderly patients has demonstrated that
although reducing the rate of intravenous administration re-
duces the speed of induction, the dosage required is also re-
duced. Administration of thiopentone sodium 2.5% solution
at a rate of 125 mg per minute induced anaesthesia in a mean
of 90.8 seconds and required a mean dose of 2.8 mg per kg
body-weight. Corresponding values for an administration rate
of 500 mg per minute were 40.8 seconds and 5 mg per kg re-
spectively.
Anaesthesia Some of the adverse effects of the neuromus-
cular blocker suxamethonium may be reduced when thiopen-
tone is used as part of the anaesthetic regimen. For a
suggestion that thiopentone may help to counteract the rise in
intra-ocular pressure associated with the use of suxamethoni-
um for intubation. For reports
that thiopentone reduces the adverse effects of suxamethoni-
um on muscles, see under Effects on the Muscles in the Ad-
verse Effects of Suxamethonium.
Cerebrovascular disorders. Barbiturates are considered
to be suitable anaesthetics for use in patients with or at risk of
raised intracranial pressure. Barbiturate-induced coma (com-
monly with pentobarbitone or thiopentone) has been used.
both therapeutically and prophylactically, to protect the brain
from ischaemia resulting from all kinds of neurological in-
sults including head injury, stroke, Reye's syndrome, and he-
patic encephalopathy. Rationale includes the ability of
barbiturates to reduce intracranial pressure and to reduce met-
abolic demands of cerebral tissues. While Nussmeicr et al.
showed that thiopentone could protect patients against the
neuropsychiatric complications of cardiopulmonary bypass,
the Brain Resuscitation Clinical Trial I Study GroupS found
no cerebral benefit from thiopentone in comatose survivors of
cardiac arrest. Nor did Eyre and Wilkinson" observe any ben-
efit from thiopentone-induced coma in infants with severe
birth asphyxia. It is considered that there is no convincing ev-
idence of improvement in neurological outcome to justify the
risks of (he procedure in conditions causing global ischaemia,
although administration of barbiturates without necessarily
inducing coma may have a limited role in reduction of raised
intracranial pressure refractory to other therapy. Use of bar-
biturates in the setting of regional cerebral ischaemia. includ-
ing use during cardiopulmonary bypass to prevent focal
neurological complications, remains controversial.
Status epilepticus. Anaesthesia in conjunction with assist-
ed ventilation may be instituted to control refractory tonic-
clonic status epilepticus. A short-acting barbiturate
such as thiopentone is usually used. A loading dose of 5 mg
tier kg body-weight liven intravenously has been suggested.
This may be followed after 30 minutes by an infusion given
at a rate of I to 3 mg per kg per hour adjusted to maintain a
maximum blood concentration of 60 to 100 micro gm per mL. It has
been recommended that administration should be continued
for at least 12 hours after seizure activity has ceased and then
slowly discontinued.