Monograph: |
Methohexitone Sodium
Methohexitone Sodium for Injection (BP 1993) is a sterile
mixture of 100 parts by weight of the a-form of methohexi-
tone sodium and 6 parts by weight of dried sodium carbonate
included as a buffer. It may also contain auxiliary substances.
A 5% solution in water has a pH of 10.6 to 11.6.
Methohexital Sodium for Injection (USP 23) is a similar
freeze-dried sterile mixture prepared from an aqueous solu-
tion of methohexitone. sodium hydroxide, and sodium car-
bonate. It is a white to off-white hygroscopic powder. A 5%
solution in water has a pH of 10.6 to 11.6 .
Solutions of methohexitone sodium are incompatible with
acidic substances so that amongst other drugs, a number of
antibiotics, neuroleptics, muscle relaxants, antimuscarinics,
and analgesics should not be mixed with it. Compounds com-
monly listed as incompatible include atropine sulphate, pethi-
dine hydrochloride, metocurine iodide, fentanyl citrate.
morphine sulphate, pentazocine lactate, silicones. suxame-
thonium chloride, tubocurarine chloride, and compound sodi-
um lactate injection. Only preservative-free diluents should
be used to reconstitute methohexitone sodium: precipitation
may occur if a diluent containing a bacteriostatic agent is
used.
Solutions in Water for Injections are stable for at least 6
weeks at room temperature: however reconstituted solutions
should be stored no longer than 24 hours as they contain no
bacteriostalic agent. Solutions in glucose or sodium chloride
injections are stable only for about 24 hours.
Adverse Effects and Precautions
As for Thiopentone Sodium.
Excitatory phenomena are more common and in-
duction less smooth with methohexitone than with
thiopentone. Methohexitone should be used with
caution, if at all. in patients with a history of epilep-
sy.
See also Adverse Effects and Precautions for Gener-
al Anaesthetics, like halothane.
In a study of 4379 administrations of methohexitone in den-
tistry to 2722 patients using the minimal incremental tech-
nft]ue the total dose ranged from 20 mg to 560 mg with a
mean of 151 mg. the mean duration of treatment ranged from
8 to 32 minutes. The most frequent complication was rest-
lessness and occurred in 292 administrations; a supplement of
diazepam 5 mg did not prevent restlessness. Respiratory com-
plications occurred in 214 administrations and uncontrollable
crying during recovery after 73 administrations. Pain along
the vein was recorded in 45 cases, with 5 patients developing
thrombophlebitis. In 22 administrations jactitations were ob-
served and allergic reaction occurred in 10 administrations.
Effects on the nervous system. Two case reports of sei-
zures induced by methohexitone in children with seizure dis-
orders. Seizures are considered a rare adverse effect of
methohexitone. In 48 000 patients given methohexitone, only
3 developed clonic-type seizures.
A case of a tonic-clonic seizure possibly due to an interaction
between paroxetine and methohexitone is discussed below.
Pain on injection. Methohexitone is associated with severe
pain particularly if veins on the back of the hands are used.
The incidence of pain on injection may be reduced by using a
forearm vein or by pre-injection with lignocaine.
Rebound anaesthesia. Rebound of anaesthesia with aboli-
tion of reflexes and depression of respiration occurred in a 6-
year-old boy 100 minutes after anorectal induction with
27.6 mg per kg body-weight methohexitone.
Interactions
As for Thiopentone Sodium.
Antidepressants. A 42-year-old woman' suffered a gener-
alised tonic-clonic seizure immediately after being anaesthe-
tised with methohexitone for the last in a series of six
electroconvulsive therapies. She had been receiving paroxet-
ine throughout the series. A previous course, without concur-
rent paroxetine had been uneventful.
Pharmacokinetics
Methohexitone is less lipid soluble than thiopentone
but when administered intravenously as the sodium
salt concentrations sufficient to produce anaesthesia
are attained in the brain within 30 seconds. Metho-
hexitone is also absorbed when given rectally. pro-
ducing an effect within about 5 to 11 minutes.
Recovery from anaesthesia occurs quickly as a re-
sult of rapid metabolism and redistribution into oth-
er body tissues. Methohexitone does not appear to
concentrate in fatty tissues to the same extent as oth-
er barbiturate anaesthetics. Protein binding has been
reported to be about 73%. Methohexitone is rapidly
metabolised in the liver through Demethylation and
oxidation. The terminal half-life ranges from 1.5 to
6 hours. Methohexitone diffuses across the placenta
and has been detected in breast milk.
Uses and Administration
Methohexitone is a short-acting barbiturate anaes-
thetic which has actions similar to those of thiopen-
tone but it is about 2 to 3 times more potent.
It is administered as the sodium salt and has similar
uses to thiopentone in anaesthesia. Induction of an-
aesthesia is less smooth than with thiopentone and
there may be excitatory phenomena. It has a shorter
duration of action than thiopentone and recovery af-
ter an induction dose occurs within 5 to 7 minutes
although drowsiness may persist for some time.
As with other barbiturate anaesthetics the dose of
methohexitone required varies greatly according to
the state of the patient and the nature of other drugs
being used concurrently. Methohexitone so-
dium is usually given intravenously as a 1%
solution. Higher concentrations may markedly in-
crease the incidence of adverse effects. A typical
dose for induction of anaesthesia is 50 to 120 mg ad-
ministered at a rate of approximately 10 mg (I mL
of a 1% solution) every 5 seconds. Doses in children
range from I to 2 mg per kg body-weight. For the
maintenance of general anaesthesia methohexitone
sodium may be given in doses of 20 to 40 mg every
4 to 7 minutes as required or it may be administered
as a 0.2% solution by continuous intravenous infusion.
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 methohexitone sodium 0.5% at a
rate of 25 mg per minute induced anaesthesia in a mean of
83.8 seconds and required a mean dose of 0.56 mg per kg
body-weight. Corresponding values for an administration rate
of 100 mg per minute were 43.6 seconds and 1.00 mg per kg
respectively.
Dental sedation. Some anaesthetics are used as sedatives in
denial procedures . Methohexitone has been tried
for patient-controlled sedation in oral surgery under local an-
aesthesia. In a group of 42 patients, results with 2.5 mg ol
methohexitone compared favorably with those obtained ir
patients receiving 5 mg of propofol on demand, although pa-
tients in the methohexitone group experienced a greater de-
gree of postoperative drowsiness.
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