4. Suxamethonium Flashcards
Structure:
in common with all muscle relaxants, suxamethonium is a quaternary
amine, which is the dicholine ester of succinic acid. This compound is almost
identical to two molecules of acetylcholine (ACh).
It is bisquaternary, and each of its ammonium radicals, N+(CH3)3, bind to the α units of the ACh receptor
Actions
: suxamethonium is the only currently available depolarizing muscle relaxant.
It acts as an agonist at the ACh receptor, but, unlike acetylcholine, once having induced
the conformational change that allows the ionophore to open (and then revert to a
closed, inactivated conformation), it remains bound to the receptor for some minutes.
Indications
: it is an ultra-short-acting agent whose prime use is to allow rapid
tracheal intubation in patients who are at risk of pulmonary aspiration of gastric
contents.
A typical intubating dose is 1.0–1.5 mg kg–1.
It can be used intermittently
(with the purported problems of bradycardia with subsequent doses,
although this is not always seen) and also by infusion. T
he maximum quoted total dose is 10 mg kg−1,
although it is likely that phase II block can be induced at lower doses.
Metabolism and elimination:
the primary metabolic route is ester hydrolysis in the presence of plasma cholinesterase.
A small amount is hydrolyzed by non-specific
plasma esterases, and 10% is excreted unchanged through the kidney.
Does Suxamethonium Have a Future in Clinical Practice
The search for a ‘clean’ alternative to suxamethonium has lasted decades, so far
without success. The drug provides the quickest means of achieving tracheal intubation.
In severe laryngospasm in a patient without intravenous access, it can also be
given intramuscularly or intra-lingually (in a dose of 4 mg kg−1). At least one metaanalysis
has asserted that, despite its many adverse effects, it is still the first-line agent
in rapid sequence induction.
Vs Rocuronium
Rocuronium has a much more benign side effect profile, and in a high dose of 0.9–1.0
mg kg–1 it can provide intubating conditions equivalent to those provided by
suxamethonium, although up to 35 seconds slower. The problem of prolonged
paralysis has been negated by the introduction of sugammadex, which can reverse
the effect of rocuronium from any depth of neuromuscular block
Suxamethonium – problems with its use
- Myalgia
- Bradyarrhythmias
- Muscle fasciculation and masseter spasm
- Hyperkalaemia
- Prolonged action owing to decreased enzyme activity
- Prolonged action owing to abnormal enzymes:
- Malignant hyperpyrexia and anaphylaxis
- Phase II block
Bradyarrhythmias
Bradyarrhythmias: stimulation of muscarinic receptors in the sinoatrial node
may lead to bradycardia, although the immediate administration of suxamethonium
is frequently associated with transient tachycardia which often goes
unnoticed or is attributed to the stress of laryngoscopy
Myalgia
Myalgia: this should not be underestimated, as it can be very severe. Because it
affects intercostal muscle and the diaphragm, it can have visceral characteristics
which can even mimic symptoms of cardiac ischaemia. The mechanism is unclear;
although suxamethonium causes fasciculations and an increase in muscle creatine
phosphokinase (CPK), neither of these is directly related to post-administration
pain
Early ambulation, female gender,
middle age and, it is said, lack of muscular fitness are all associated with a higher
incidence, as are rapid injection and repeated smaller doses
Muscle fasciculation and masseter spasm
. These are characteristics of the
drug rather than specific problems, although both can be disconcerting. The
phenomena are believed to be due to the prejunctional stimulation of acetylcholine
receptors on the motor nerve, with transiently repetitive firing and ACh
release.
Hyperkalaemia:
serum potassium may rise about 0.5 mmol l−1 in the normal
patient, but this increase can be dangerously high in patients in whom muscle cells
are damaged or in whom muscles are denervated. Damaged muscle leaks potassium,
while denervated muscle demonstrates an increase in extrajunctional ACh
receptors. Conditions in which suxamethonium should be avoided, therefore,
include renal failure, burns, spinal cord damage, polyneuropathies and crush
injury. Dangerous rises can also occur in the critically ill, and the drug must be
used with caution in intensive care patients.
Prolonged action owing to decreased enzyme activity
: suxamethonium undergoes ester hydrolysis in a reaction that is catalysed by plasma cholinesterase
Qualitative and quantitative changes in this enzyme have a substantial effect on
the drug’s duration of action.
Enzyme activity is reduced by decreased enzyme
synthesis due to liver disease, starvation, carcinomatosis, pregnancy, renal disease
and myxoedema (hypothyroidism).
Such reduction may increase by several times
its normal duration of action of 3–5 minutes
Prolonged action owing to abnormal enzymes:
qualitative differences result from inherited deficiencies of plasma cholinesterase.
Its synthesis is controlled by autosomal recessive genes,
of which 14 different mutations have so far been
identified.
The normal gene is characterized as Eu,
and the commonest atypical gene as Ea
(others include the fluoride gene, Ef, and the silent gene, Es).
The action of suxamethonium in a heterozygote, EuEa,
will be prolonged by around 30 minutes,
whereas in a homozygote, EaEa, this will extend to several hours
Testing using
inhibition by dibucaine and fluoride has been superseded by direct assay of
cholinesterase activity
Malignant hyperpyrexia and anaphylaxis
: it is a trigger for malignant hyperpyrexia,
and, although allergic reactions are rare, anaphylaxis is more commonly seen
with suxamethonium than with any other muscle relaxant, accounting for almost
50% of reactions.
Phase II block
repeated doses or prolonged infusions of suxamethonium (as was
once a routine technique for caesarean sections under general anaesthesia) can
result in the development of a Phase II block, which has all the characteristics of a
non-depolarizing competitive block. A nerve stimulator will therefore show the
typical fade of the train-of-four response, tetanic fade and post-tetanic potentiation.
(Phase I describes the initial depolarizing block.) The mechanism has not
been clearly elaborated, but theories include post-junctional receptor desensitization
and pre-synaptic inhibition of acetylcholine synthesis and release. Phase II
block is potentiated by inhalational anaesthetic agents. Although it can be
reversed with standard anticholinesterases, the response is unpredictable.
