Monograph: |
Mivacurium Chloride
Adverse Effects, Treatment, and Precautions
As for competitive neuromuscular blockers in gen-
eral (see Atracurium). Mivacurium chloride
has no significant vagal or ganglion blocking activi-
ty at recommended doses.. It may induce histamine
release especially when given in large doses rapidly.
Mivacurium should be used with caution, if at all. in
patients with plasma cholinesterase deficiency,
since its duration of action will be prolonged in such
patients.
Burns. In common with other competitive muscle relaxants
patients with burns may develop resistance to mivacurium
and require increased doses (see under Atracurium ).
However, as these patients may also have reduced plasma
cholinesterase activity dosage requirements could also be re-
duced. The manufacturer recommends that such patients
should be given a lest dose of 150 to 200 ng per kg body-
weight with subsequent dosage adjustments being guided by
monitoring of the block.
Hepatic and renal Impairment. The pharmacokinetics of
mivacurium have been studied in patients with kidney or
liver impairment. Compared with healthy subjects, the du-
ration of relaxation produced by mivacurium was approxi-
mately 1.5 times greater than normal in patients with kidney
disease and up to about 3 times greater than normal in patients
with liver impairment. The reduced plasma-cholinesterase ac-
tivity in the patients with liver impairment may have played
an important part in this effect. Although an anticholineste-
rase such as neostigmine hastens recovery by only a few min-
utes in healthy subjects its use may be indicated in patients in
whom recovery is delayed.
Neuromuscular disorders. Neuromuscular blockade was
successfully achieved with mivacurium in an obese elderly
patient with myasthenia gravis requiring surgery. Only about
half the usual dose was required and even then recovery was
delayed. See Atracurium, for a discussion of the use
of competitive neuromuscular blockers in patients with neu-
romuscular disorders.
Plasma cholinesterase deficiency. There have been re-
ports of prolonged neuromuscular block produced by mivacu-
rium in patients with plasma cholinesterase deficiency.
Time to full recovery had varied; one patient required up to 8
hours.
Tourniquets. It has been suggested that mivacurium might
be unsuitable for neuromuscular blockade of a limb which
has been isolated with a tourniquet in order to provide a
bloodless field for surgery. Mivacurium is largely inactivated
by the enzymatic action of plasma cholinesterase and would
therefore continue to degrade locally leading to a loss of
blockade in the limb and this could not be corrected by further
doses unless the tourniquet was deflated. However, Torrance
et all- found that, as for other competitive neuromuscular
blockers. the use of mivacurium to supplement regional an-
aesthesia produced prolonged muscle weakness well beyond
cuff deflation. This suggests that mivacurium is not broken
down in the ischaemic limb and that recovery is not depend-
ent on plasma concentrations of mivacurium.
Interactions
For interactions associated with competitive neu-
romuscular blockers, see Atracurium.
Pharmacokinetics
Mivacurium is administered as a mixture of 3 stere-
oisomers, 2 of which (cis-trans and trans-lrans) are
considered to account for most of the neuromuscular
blocking effect. All 3 isomers are inactivated by
plasma cholinesterase. Renal and hepatic mecha-
nisms are involved in their elimination with excre-
tion in urine and bile.
Uses and Administration
Mivacurium chloride is a benzylisoquinolinium
competitive neuromuscular blocker (see Atracuri-
um).
Following intravenous injection muscle relaxation
occurs within 2 to 2.5 minutes with a duration of ac-
tion of about 10 to 20 minutes. It is used for endotra-
cheal intubation and to provide muscle relaxation in
general anaesthesia for surgical procedures ,and to aid
controlled ventilation
Doses are expressed in terms of mivacurium base.
The initial dose by intravenous injection is 70 to
250 mcg per kg body-weight. Doses up to 150 mcg per
kg may be administered over 5 to 15 seconds but
higher doses should be given over 30 seconds. In pa-
tients with asthma or cardiovascular disease, or
those who are sensitive to falls in arterial blood pres-
sure, administration should be over 60 seconds. A
suggested method for administration of a dose of
250 mcg per kg for tracheal intubation is to give one
injection of 150 mcg per kg followed 30 seconds later
by an injection of 100 mcg per kg. Maintenance doses
of 100 mcg per kg may be given at intervals of 15 min-
utes. In children aged 2 to 6 months an initial dose
of 150 mcg per kg has been given; in children aged 7
months to 12 years, an initial dose of 200 mcg per kg
has been given. A maintenance dose of 100 mcg per
kg may be given every 6 to 9 minutes for children
aged 2 months to 12 years. Reduced doses may be
required in elderly patients. For obese patients
weighing more than 30% over their ideal body-
weight the manufacturer recommends that the initial
dose should be based upon their ideal body-weight
and not actual body-weight. Mivacurium chloride
may also be administered by continuous intravenous
infusion for maintenance of block. For adults the in-
itial rate is 8 to 10 mcg per kg per minute adjusted
every 3 minutes if necessary by increments of 1 mcg
per kg per minute to a usual dose of 6 to 7 ng per kg
per minute, in children aged 2 months to 12 years
the usual dose is 11 to 14 mcg per kg per minute.
Reviews.
Action. Mivacurium has a shorter duration of action than
most other competitive neuromuscular blockers. Studies
suggest that it is a useful alternative to suxamethonium for the
production of neuromuscular block of short duration and has
the advantage that its block can be reversed with an anti-
cholinesterase. For a discussion of the choice of anti-
cholinesterase for reversal of neuromuscular block produced
by short-acting blockers such as mivacurium. see under Ne-
ostigmine. Although its onset of action may be accel-
erated by giving a priming dose, mivacurium has a slower
onset than suxamethonium and so may not be a suitable
alterncrtiveJ when rapid intubation is required.
Administration in the elderly. In a study comparing the
effects of mivacurium in elderly and young adults the dura-
tion of neuromuscular effects was prolonged in elderly pa-
tients by about 30%. The mean infusion requirement in
elderly patients was 3.67 mcg per kg body-weight per minute
compared with 5.5 mcg per kg per minute in young adults.
|