and enhance arousability and the patient’s
ability to communicate with caregivers.
Dexmedetomidine may reduce delirium after
long-term sedation as compared with
midazolam, 50 and also reduce the overall
neurocognitive adverse events of sedation, such
as agitation, anxiety, and delirium, compared
with propofol. 51
However, safety and efficacy of this drug have
not been evaluated in some ICU patient groups,
such as patients with acute neurologic disorder
(for example, stroke and head trauma). 2
Newer alternatives
Inhalative sedation in the ICU is starting to spread
all over Europe and has been recommended as an
alternative in a German consensus guideline. 52
The device used is called AnaConDa (Anaesthetic
Conserving Device), which makes possible the
administration of anaesthetic agents (isoflurane
and sevoflurane) in any ventilator commonly
found in the ICU. 53–55
Isoflurane, sevoflurane and desflurane have
shown some benefits compared with intravenous
sedation. They have a low metabolism and, due
to their low solubility, are eliminated quickly
and offes shorter and more predictable wake-up
times than intravenous agents. 54-58 They can also
prevent the development of bronchospam, 53,55
have cardioprotective effects 54 and are
haemodynamically more stable than intravenous
drugs. 55
Some volatile anesthetics abolish cerebral
autoregulation at high doses; it has been reported
that at 1.0 MAC sevoflurane, the autoregulation of
cerebral blood flow remained intact, but that this
was impaired at 2.0 MAC. They also have a direct
neuroprotective effect in periods of in vitro 59 and
in vivo 60 ischaemia or administered prior to it
(anaesthetic conditioning). 61 Preconditioning has
been described in in vitro 62 and in vivo 63 models of
cerebral ischaemia. Sevorane also has a role in
post-conditioning; its application could be of
interest once cerebral ischaemia has occurred.
Lee et al 64 found that isoflurane post-conditioning
reduced brain injury due to ischaemia in rats.
However, at 0.5 MAC, adequate neuroprotection
is not obtained, which means that the effect of
sevoflurane post-conditioning in focal ischaemic
lessions is dose-dependent. 65
In a prospective study of sevoflurane sedation
in patients with acute stroke or subarachnoid
haemorrhage, sufficient sedation levels without
clinically relevant ICP increases were achieved in
68% of patients. 66 However, serious adverse events
observed in the remaining 32% raise considerable
safety concerns. Mean arterial pressure (MAP)
had to be stabilised actively to maintain CPP.
Based on these observations, it was concluded
that that the alleged neuroprotective potential of
sevoflurane do not outweighs the risk of adverse
events and sevoflurane sedation should probably
not be used in this specific patient population. 66
Volatile sedation has historically been
considered unsafe in neurocritical care units
around the world. However, as previously
mentioned and suggested in several studies, the
potential neuroprotective benefit of inhalative
sedation has to be more studied.
As well as inhalative sedatives, the use of
ketamine has also been debated because of the
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concern raised by early studies that it was
associated with increased ICP. 67 In studies
examining the cerebral haemodynamic effects
of ketamine after acute brain injury, ICP was
reduced and CPP remained stable or increased,
without significant changes in cerebral
haemodynamics. 68 A systematic review concluded
that ketamine was not associated with an
increased risk of ICP elevation, as said
previously. 69
Ketamine is a short-acting NMDA receptor
antagonist with a rapid onset of action. It does
not alter systemic haemodynamics or respiratory
drive, therefore it can be used in non-intubated
patients. At doses of 1–5mg/kg/hour, it can be
used as an adjunct to other sedatives to improve
their effects and thus limit drug requirements.
Conclusions
Sedation and analgesia is frequently used in
the management of critically ill patients and is
related to a longer hospital stay and more
difficult weaning from mechanical ventilation.
However, in neurointensive care units, it is also
a therapeutic strategy. Therefore studies have
been developed to achieve efficient sedation and
avoid the adverse effects as much as possible.
Midazolam and propofol are the most
frequently used first-line sedatives; however,
use of benzodiazepines is less common because
of their deleterious effects, such as prolonging
mechanical ventilation time and increasing
awakening times.
New trends, such as inhalative sedation or
ketamine, are beginning to garner more
attention, but more studies are required to fully
confirm their use.