INHALATIONAL ANAESTHETIC AGENTS FOR NEUROANESTHESIA

Erwin Kresnoadi
Departement Of Anesthesiology and Reanimation Faculty Of Medicine Mataram University

ABSTRAK
Semua obat anestesi inhalasi jenis fluorine memiliki efek pada aliran darah serebral,
volume darah serebral, dan ukuran oksigen metabolik serebral. Aliran darah serebral meningkat
pada pemakaian obat anestesi inhalasi oleh karena efek intrinsik langsung dengan cara
mengurangi ketegangan dinding arteri serta menyebabkan vasodilatasi serebral. Besarnya
peningkatan aliran darah serebral tergantung pada keseimbangan antara tindakan vasodilatasi
intrinsik dan penurunan aliran darah sekunder terhadap penurunan ukuran oksigen metabolik
serebral.
Kata kunci : obat anestesi inhalasi, vasodilatasi serebral, aliran darah serebral, volume darah
serebral, ukuran oksigen metabolik serebral

INTRODUCTION
All the fluorinated agents have effects on. cerebral blood flow (CBF), cerebral blood
volume (CBV), cerebral metabolic rate oxygen (CMRO2). CBF increases with all agents by a
direct intrinsic effect which reduces arterial wall tension and results in cerebral vasodilatation.
The magnitude of the increase in CBF depends on the balance between this intrinsic vasodilatory
action and the reduction in blood flow secondary to a doserelated decrease in CMRO2. The order
of rise in CBF is approximately halothane > enflurane > isoflurane sevoflurane. Desflurane has
similar effects to isoflurane. CBV increases as a consequence of vasodilatation, which in turn
increases brain volume and possibly ICP.1
The gradient of the flow metabolism coupling relationship increases in clinically used
doses. These changes are attenuated by hypocapnia. CO 2 reduction attenuates the increase in
CBF. The normal CO2 vs CBF curve is shifted to the left. Hypercapnia causes a more rapid
increase in CBF with these agents. Autoregulation of CBF is impaired in a dose dependent
manner until CBF becomes dependent on mean arterial pressure. Progressive slowing of the EEG
at concentrations > 1 MAC.2

ISOFLURANE
1

Isoflurane produces less cerebral vasodilatation than the other agents except possibly
sevoflurane.3 Global CMRO2 and CBF decreases in low doses and there is greater cortical
metabolic suppression than halothane.4 At higher concentrations ( 2 MAC), an isoelectric EEG
is achieved with a 50% decrease in CMRO 2. Autoregulation is disrupted 1.5 MAC and a
dosedependent rise in CBF and ICP occurs. These effects can be attenuated by hypocapnia
commenced when isoflurane is introduced or modified by baseline physiology and other
pharmacological agents. Isoflurane may decrease CSF production and decreases its resistance to
absorption.3

Figure 1. Changes in gradient of flow-metabolism coupling in an animal model exposed to 1 and 2 MAC isoflurane.
CMRGlu = cerebral metabolic rate of glucose reflecting metabolic rate, CBF = cerebral blood flow. (Adapted from
Todd MM, Warner DS. Neuroanesthesia. In: Principles and practice of anesthesia, 1993.)

SEVOFLURANE
Although similar to isoflurane in its cerebral vascular effects in animals, there is some
evidence to suggest that it produces less intrinsic vasodilation of cerebral vessels and allows
cerebral autoregulation to occur at higher anaesthetic concentrations compared with other agents.
Up to 1.5 MAC sevoflurane anaesthesia causes little increase in ICP.5 The responsiveness of CBF
to changes in PaCO2 is also maintained. The lower blood:gas solubility coefficient (0.6) allows a
rapid induction and recovery from anaesthesia and this combined with lower airway irritability
has favoured its use for inhalation induction especially in children. The EEG is activated in some
animal models and decreased in others.5,6
2

HALOTHANE
Halothane has a potent vasodilatory action and produces a dose-related decrease in
CMRO2. However, the effect on CMRO2 is less than with other agents and global CBF increases
more than with equipotent concentrations of other inhalational agents. Unlike isoflurane, this rise
in CBF can only be attenuated by hypocapnia if induced before addition of halothane. In
concentrations above 2.5% there is evidence that it may be directly toxic on oxidative
phosphorylation.4
DESFLURANE
Cerebral effects are similar to isoflurane with a dosedependent decrease in CMRO 2, CBF
and loss of cerebral autoregulation. Under conditions of maximal metabolic suppression (high
dose), intrinsic vasodilatation is also similar to isoflurane. Again these changes can be attenuated
by hypocapnia induced at the time desflurane is commenced. During prolonged desflurane
administration a slow increase in ICP is observed, possibly due to an increase in CSF production.
EEG burst suppression is attenuated over time in some animal models.1
ENFLURANE
Low concentrations decrease CMRO2, CBF and cerebral autoregulation. Concentrations
> 1.5 MAC produce spike and wave EEG appearances especially with concomitant hypocapnia
(< 4.0 kPa). The rate of production and resistance to reabsorption of CSF are also increased by
enflurane, thereby exacerbating any increase in ICP.1
NITROUS OXIDE
N2O alone causes an increase in CBF without a decrease in CMRO 2. This increase is
unaffected by hypocapnia alone but is modified when hypocapnia is combined with other
inhalational agents or barbiturates. This may be of concern in cerebral ischaemia and should be
used with care if ICP is raised. Work in humans has shown N 2O to cause a significant increase in
cerebral blood flow acting synergistically with inhalational agents. More importantly, the
increase in CBF due to a combination of isoflurane and N2O is greater than equipotent
concentrations of the inhalational agent alone. Increases in ICP have been demonstrated when

N2O is used for patients with intracranial tumours. 7 However one study addressing short-term
outcome found no difference when N2O was used.
SUMMARY
All inhalational anaesthetic agents cause cerebral vasodilatation. All agents effect
cerebral autoregulation. All agents decrease CMRO2. These effects are dose dependent and
modified by hypocapnia. Flow metabolism coupling is maintained in low doses.

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