Hermann
Mellinghoff, MD
Department
of Anaesthesiology, University Hospital, D-50924 KOELN, Germany
The choice of anaesthetics
with a rapid and predictable recovery is essential for a rapid turnover of
patients in the operating theatre. "Fast-tracking“ after surgery is an
attempt to decrease the time from the end of surgery to the extubation of the
trachea. A muscle relaxant well suited for "fast-tracking" should
produce a rapid onset and a short duration of action and its offset period
should allow equally rapid recovery from neuromuscular block.
Decreased neuromuscular blocking
potency as well as a rapid clearance seem to be responsible for a more rapid
onset of action of muscle relaxants. Onset after the injection of muscle
relaxants decreases with increasing molar potency. Consistent with these
findings, rapacuronium (ED95 of 1.0 mg/kg active moiety) has a more rapid
onset of action than any of the other nondepolarizing muscle relaxants and,
when injected in doses of 1.5-2.5mg/kg, appears to have an onset of action
compatible with that of succinylcholine. Muscle relaxants are injected during
induction of anaesthesia to facilitate tracheal intubation. A rapid onset of action
has become expected at least in part due to the rapid onset of neuromuscular
block of succinylcholine. However, is well accepted, that the time from
injection of a muscle relaxant to its maximum effect is in the order of less
than one minute (succinylcholine) to up to three minutes (cisatracurium). This
implies that, even when the choice of the muscle relaxant for
"fast-tracking" is based on a rapid onset of action, the time saved
is minimal. Furthermore, it was shown, that onset of neuromuscular block produced
by muscle relaxants is faster at the laryngeal muscles than at the adductor
pollicis muscles, and that therefore the clinician is not forced to wait for
complete abolition of the peripheral twitch response.
With muscle relaxants of ultra-short
(succinylcholine), short (mivacurium), intermediate (atracurium, vecuronium,
cisatracurium and rocuronium) and long duration of action (pancuronium) the anaesthesiologist
has a wide array of drugs at his disposal. It is obvious, that the choice of a
muscle relaxant depends on the estimated duration of the surgical procedure.
Preference should be given to muscle relaxants with a short or intermediate
duration of action because they can easily be adapted to a varying duration of
surgery.
Recovery from neuromuscular block is
assumed to be complete when any effect of a muscle relaxant has disappeared. As
more than 70% of the acetylcholine receptors may be occupied by muscle
relaxants before any reduction of the twitch response to nerve stimulation is detectable,
these drugs may not have disappeared from the organism even when no effect of
the twitch response to nerve stimulation can be measured. For a long time, a
train-of-four (TOF) fade ratio of >0.70 following nerve stimulation has been
regarded as a reliable indicator of acceptable clinical recovery. Once that
ratio was greater than 0.70, muscle strength was assumed to have returned to a
near-normal state, as indicated by sensitive clinical tests, such as head-lift.
In 1997, Kopman presented results that indicated that a TOF-ratio of 0.70 can
no longer be regarded as an indicator for adequate neuromuscular function. He
reports, that even at TOF-ratios of 0.90 after mivacurium, visual disturbances
were present in all subjects. Diplopia and inability to follow moving objects
even persisted when the TOF-ratio had fully recovered. Also, when the TOF-ratio
was <0.75, "all subjects were uncomfortable".
The use of long-acting muscle relaxants
like pancuronium has been shown to be associated with a prolonged postoperative
recovery. Even after the administration of mivacurium, a high incidence of
residual block was demonstrated in one study when the neuromuscular block had
not been antagonized at the end of surgery. Consequently, even after
short-acting muscle relaxants spontaneous recovery can be slow enough to make
residual block visible in the recovery room. Accordingly, pharmacologic
reversal of neuromuscular block should be based on the findings of
neuromuscular monitoring and considered whenever necessary, possibly even after
the use of a short-acting relaxant. On the other hand the choice of a short- or
intermediate-acting muscle relaxant for fast-tracking anaesthesia concepts is
underlined by those findings.
In the context of fast-tracking
anaesthesia, the administration of long-acting muscle relaxants is not appropriate.
Therefore, only intermediate and short-acting muscle relaxants will be
presented. These drugs can be classified into two chemical groups:
aminosteroidal muscle relaxants (rocuronium, rapacuronium) and those of the
benzylisoquinolinium type (mivacurium, cisatracurium). Rocuronium (ED95
0.30 mg/kg) has a time course of action similar to that of vecuronium, with the
exception that its onset of action is faster. After 1.5mg/kg rapacuronium,
the onset of action is almost as rapid as that of succinylcholine, although
with a greater variation. The duration of action of 1.5mg/kg rapacuronium has
been reported to be 14 min. In another study, spontaneous recovery after repeat
doses of rapacuronium was 70 minutes. Its 3-desacetyl metabolite (Org9488) has
neuromuscular blocking activity and a clearance lower than the parent compound
and thus gradually prolongs the recovery from neuromuscular block after
increasing doses of rapacuronium. Mivacurium is a short-acting non-depolarizing muscle
relaxant (ED95 0.08 mg/kg). The rapid hydrolysis by plasma cholinesterase is
responsible for its short duration of action. A study on the time course
characteristics of neuromuscular block of up to 10 consecutive repeat doses of
mivacurium confirmed the recovery after mivacurium to be rapid and predictable.
Cisatracurium (ED95 0.05 mg/kg) is the cis-cis isomer of atracurium.
Following intubation doses, onset of action is attained at ca 3 min. The
recovery profile of cisatracurium is independent of the administered dose or
organ dysfunction. Cisatracurium does not induce dose-dependent histamine
release and even after 8*ED95 displays a haemodynamically stable profile.
The different pharmacology of the two
groups of muscle relaxants is reflected in different pharmacodynamic profiles:
the aminosteroidal muscle relaxants rocuronium and rapacuronium have a low
potency providing a fast onset of action. The benzylisoquinolinium muscle
relaxants mivacurium and cisatracurium are rapidly metabolized into inactive compounds
providing reliable and fast recovery characteristics, even after repeated bolus
dose administration or continuous infusion.
Recent studies suggest the importance
of an almost complete recovery of neuromuscular transmission to achieve full
neuromuscular function after the administration of muscle relaxants. This is
particularly important when muscle relaxants are used in the context of new
fast-tracking anaesthesia concepts. Discharge of patients from the recovery
area is only possible when no effect of a muscle relaxants impairs any muscle
function of the patient. These rules almost exclude the use of a long-acting
muscle relaxant for fast-tracking anaesthesia, and even influences the choice
among the intermediate- and short-acting muscle relaxants. In general, the
anaesthesiologist should know in detail the pharmacologic properties of a
chosen muscle relaxant, and restrict this choice to the muscle relaxant with a
sufficiently short duration of action and a rapid and predictable recovery
profile for fast-tracking anaesthesia.