Introduction
Acquired neuromuscular diseases or congenital disorders either
affect the neuromuscular transmission or the muscle itself. When
the neuromuscular transmission is involved, two pathophysiological
mechanisms must be distinguished: the abnormality of the nicotinic
receptor at the endplate (myasthenia gravis, upregulation of the
receptor) and the abnormality of acetylcholine release (Lambert-Eaton
myasthenic syndrome, iatrogenic myasthenic syndrome). In both
situations pharmacodynamic properties of neuromuscular blocking
agents (NMBA) are profoundly affected.
Myasthenia gravis
Myasthenia gravis is an autoimmune disorder of neuromuscular transmission.
Antibodies against the acetylcholine receptor at the neuromuscular
junction result in a reduction of the number of the functional
receptors with a decreased safety margin of neuromuscular transmission.
Major symptoms are muscle weakness and fatiguability, relieved
by rest. Anticholinesterase drugs provide symptomatic improvement
in most patients. Myasthenia gravis is frequently associated with
abnormalities of the thymus, so thymectomy is the main surgical
procedure offered to these patients [4]. Anticholinesterase drugs
should be stopped a few days before surgery if the clinical status
of the patient allows it, because they could increase the effect
of succinylcholine and inhibit the effect of non depolarising
NMBAs. Muscle relaxants are not contraindicated in myasthenia
gravis but adequate understanding of the response of the myasthenic
patient to NMBAs is necessary for their safe administration. Concerning
depolarising NMBAs a resistance (decreased potency) is observed
because the number of available receptors at the endplate is reduced
[1, 6]. High doses of succinylcholine may be required for rapid
sequence tracheal intubation but phase II block is frequent even
after a single dose [8]. The sensitivity to, and the duration
of action of nondepolarising NMBAs are increased, reducing the
intraoperative needs. A reduction of 50 to 75% of the usual doses
is common [7, 11]. Nondepolarising NMBAs of intermediate duration
of action must be chosen [3]. Administration of reduced doses
and the use of neuromuscular monitoring allow early extubation
in most cases. All the risk factors which predispose to neuromuscular
function impairment must be controlled (i.e. hypothermia, hypokalemia,
acidosis). The need for anticholinesterase drugs is decreased
in the first 48 postoperative hours. These drugs must be restarted
carefully and titrated to avoid the risk of cholinergic crisis.
Myasthenic syndrome
The Lambert-Eaton myasthenic syndrome is characterised by a proximal
fatiguability, relieved by exercise. It is mainly associated with
malignant tumours (pulmonary). The production of anti-calcium
voltage dependent channel antibodies implies a presynaptic neuromuscular
blockade with abnormal acetylcholine release [12]. Symptoms disappear
with treatment of the underlying disease in 50 to 70 % of cases.
Their reappearance often precedes a recurrence of the malignant
process. Symptomatic treatment is provided by 3,4 diaminopyridine
which promotes release of acetylcholine at the endplate. The response
to succinylcholine seems to be normal but the sensitivity to nondepolarising
NMBAs is increased [17]. If muscle relaxants are required, titration
beginning with the tenth of the usual dose and careful monitoring
of neuromuscular blockade are necessary. Pyridostigmine is not
effective and calcium antagonists are contraindicated.
Muscle disorders
Duchenne muscular dystrophy or pseudohypertrophic dystrophy
Duchenne muscular dystrophy (DMD) is the most common of childhood
muscular dystrophy (3 per 10 000 births). The disease is caused
by an X-linked recessive gene and is often undiagnosed until the
age of 3 to 5 years. The initial symptoms involve the proximal
muscle groups of the pelvis. Kyphoscoliosis may develop and skeletal
muscle atrophy predisposes to long bone fractures. Elevated plasma
creatinine kinase concentrations results from muscle fibre necrosis.
Pulmonary complications and congestive heart failure are the main
causes of death which occurs between the ages of 15 and 25 years
[9]. Anaesthesia is required for scoliosis correction, tendon
releases for contractures or exploratory laparotomy for ileus.
These procedures improve the quality of life and must be carried
out early in order to limit the operative risk. Anaesthesiologists
must consider impaired cardiac function and the risk of life-threatening
cardiac dysrythmia and avoid depression of cardiac contractility
[5]. Pulmonary and cardiac function have to be evaluated preoperatively
(respiratory function tests, echocardiography, Holter) because
impaired muscle function limits symptomatology [10, 14]. Succinylcholine
is formally contraindicated because of a the risk of lethal hyperkalemia
than can simulate malignant hyperthermia. Therefore, all malignant
hyperthermia triggering agents must be avoided. Sensitivity to
nondepolarising NMBAs is increased. A recent study demonstrated
a significant increase in sensitivity to vecuronium for both maximal
effect and duration of action [15]. Most postoperative complications
are respiratory.
Myotonic dystrophy
Myotonic dystrophy designates a group of hereditary degenerative
diseases of skeletal muscles characterised by persistent contracture
of skeletal muscles after their stimulation, resulting from abnormal
calcium metabolism. Steinert's disease is the most common and
serious form of this group (3 to 5 per 100 000 population). It
seen in adults. Cardiac dysrythmia and conduction defect with
pulmonary aspiration are the main causes of death [2, 13]. Like
in DMD succinylcholine is formally contraindicated because of
the risk of lethal hyperkalemia. A myotonic crisis can be triggered
by succinylcholine, hypothermia, surgical manipulations, electrocautery
or drugs (clofibrate, propanolol, neostigmine, potassium) [16].
Nondepolarising NMBAs are not effective in these crisies. The
use of nondepolarising NMBAs, if they are needed, requires monitoring
the neuromuscular blockade. Reversal agents can precipitate skeletal
muscle contraction by facilitating depolarisation of the endplate.
Up-regulation of skeletal muscle acetylcholine receptor
Clinical conditions in which the neuromuscular responses simulate
an increased receptor number include denervation, disuse muscle
atrophy, thermal and direct muscle trauma, infection, and chronic
treatment with antagonists of neuromuscular transmission [8].
In these conditions the new acetylcholine receptor (or immature)
differs from the normal (or mature) with the substitution of the
e subunit for the g subunit. The pharmacological effects of NMBAs
are profoundly modified. The increased sensitivity to agonists
such as succinylcholine may induce a lethal hyperkalemic response.
Therefore, succinylcholine is formally contraindicated from 48
hours after injury and until symptoms disappear. The sensitivity
to non depolarising NMBAs is decreased because the number of receptors
in the extra-junctional area is increased [8].
Conclusion
Neuromuscular diseases represent an entity including very various
pathologies with different patterns. The perioperative complications
(cardiac and respiratory) are serious and potentially lifethreatening.
Preoperatively, an evaluation of the pulmonary and cardiac systems,
which are often involved in these diseases must be performed.
Some anaesthetic agents may lead to specific complications. If
muscle relaxants are needed careful monitoring of neuromuscular
blockade is necessary. Succinylcholine is formally contradicated
in muscle disorders and in conditions with up-regulation acetylcholine
receptor.
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