Muscle Relaxants (see Chapter
13
)
Nondepolarizing Relaxants
The only recognized effect of nondepolarizing relaxants on the
cerebral vasculature occurs through the release of histamine. Histamine can result
in a reduction in CPP because of the simultaneous increase in ICP (caused by cerebral
vasodilation) and decrease in MAP.[374]
It is not
entirely clear, when the BBB is intact, whether histamine directly causes cerebral
vasodilation or whether it is a secondary (autoregulatory) response to a reduction
in MAP. d-Tubocurarine is the most potent histamine
releaser among the available muscle relaxants. Metocurine, atracurium, and mivacurium
also release histamine in lesser quantities.[375]
[376]
This effect is likely to be clinically inconsequential
[377]
unless these agents are administered in the
large doses necessary to achieve intubating conditions rapidly. Of this group of
drugs, cisatracurium has the least histamine-releasing effect. No evidence of histamine
release was seen after the administration of 0.15 mg/kg (three times the dose effective
in 95% [ED95
] for twitch depression) of cisatracurium in neurosurgical
ICU patients.[378]
Vecuronium, in relatively large doses of 0.1 to 0.14 mg/kg, had
no significant effect on cerebral physiology in patients with brain tumors.[379]
[380]
Pipecuronium and rocuronium have not been
studied but should similarly be without direct effect, and no adverse events have
been reported.
The indirect actions of relaxants may also have effects on cerebral
physiology. Pancuronium given as a large bolus dose can cause an abrupt increase
in arterial pressure. This increased arterial pressure might elevate ICP in the
setting of impaired intracranial compliance and defective autoregulation; however,
no significant clinical event has ever been reported. Muscle relaxation may reduce
ICP because coughing and straining are prevented, and this results in lowering of
central venous pressure with a concomitant reduction in cerebral venous outflow impedance.
[381]
A metabolite of atracurium, laudanosine, may be epileptogenic.
However, although large doses of atracurium caused an EEG arousal pattern in dogs,
CBF, CMR, and ICP were unaltered.[382]
In cats,
the seizure threshold for lidocaine-induced seizures was not different during paralysis
with atracurium, vecuronium, or pancuronium.[383]
In rabbits, administration of laudanosine did not increase the severity of the epileptoid
activity caused by direct application of cephalosporin to the cortical surface.[384]
It appears highly unlikely that epileptogenesis will occur in humans with atracurium.
[385]
[386]
In summary, vecuronium, pipecuronium, rocuronium, atracurium,
mivacurium, cisatracurium, metocurine, and pancuronium (if acute elevation in MAP
is prevented with the latter) are all reasonable drugs for use in patients with or
at risk for intracranial hypertension. Doses of metocurine, atracurium, and mivacurium
should be limited to ranges not associated with hypotension. Curare (for the diehards)
is best administered slowly and in small divided doses to avoid substantial histamine
release.
Succinylcholine
Succinylcholine can produce an increase in ICP in lightly anesthetized
humans. Minton and colleagues[387]
studied
patients with intracranial tumors. Their subjects received morphine, 0.1 mg/kg,
1 hour before induction of anesthesia with thiopental, 6 mg/kg. The patients were
ventilated by mask with 70% N2
O to maintain normocapnia and then received
succinylcholine, 1 mg/kg. ICP increased from 15 ± 1 (SE)
to a maximum of 20 ± 2 mm Hg after 1 to 3 minutes and
returned to baseline in 8 to 10 minutes. The effect appears to be the result of
cerebral activation (as evidenced by EEG changes and increases in CBF) caused by
afferent activity from the muscle spindle apparatus.[388]
[389]
[390]
Note,
however, that correlation between the occurrence of visible muscle fasciculations
and an increase in ICP is poor. As might be expected with what appears to be an
arousal phenomenon, deep anesthesia has been observed to prevent succinylcholine-induced
ICP increases in the dog.[388]
In humans, the increase
in ICP is also blocked by paralysis with vecuronium[387]
and by "defasciculation" with metocurine, 0.03 mg/kg.[391]
The efficacy of other defasciculating agents has not been examined in humans. However,
defasciculation with pancuronium did not prevent increases in ICP in the dog.[389]
Although succinylcholine can produce increases in ICP, it need
not be viewed as contraindicated in circumstances in which its use for rapid attainment
of paralysis is otherwise seen as appropriate. Kovarik and coworkers observed no
ICP change after the administration of succinylcholine, 1 mg/kg, to nonparalyzed,
ventilated neurosurgical ICU patients, 6 of 10 of whom had sustained head injury.
[392]
Their observations are very relevant because
it is in precisely this population of patients that the issue of the use of succinylcholine
arises most frequently. Given that the ICP effect of succinylcholine may be an arousal
phenomenon caused by increased afferent traffic from muscle spindles,[390]
it is not unreasonable that disease processes that substantially blunt the level
of consciousness might similarly blunt this response. As with many drugs, the concern
should be not whether it is used but how it is used. If administered with proper
attention to the control of carbon dioxide tension, blood pressure, and depth of
anesthesia and after defasciculation, preferably with metocurine pending additional
information, little hazard should attend its use.
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