Dexmedetomidine is a recently introduced drug in India, which has gained immense popularity
among the anaesthesiologists. The sedation and analgesic activity without producing
respiratory depression has been considered as the greatest advantage of the drug when
compared with benzodiazepines and opioids, and this property is also responsible for
its popularity. It has been originally introduced in the United States and approved
for use in the intensive care as a sedative agent in the critically ill patients requiring
mechanical ventilation to be administered as intravenous infusion by the Food and
Drug Administration in 1998.[1] Dexmedetomidine has found its ways from intensive care unit to various places including
the operation rooms, catheterization laboratories, radiological suite, etc., and its
route of administration also widened from the intravenous route to inclusion in regional
blocks as adjuvants, as an oral premedication agent, etc. Dexmedetomidine use has
also expanded to various surgical specialties including cardiac surgical, pediatric
surgical, regional anaesthesia, and neurosurgical practice. Its use has been found
to reduce the needs for opioids and anaesthetics intraoperatively.
It has a potent sedative, anxiolytic, and analgesic activity, and it is a selective
α-2 agonist agent. α-2 receptors are present in large concentrations in the arousal
areas of the brain as well as vascular smooth vessels. In the central nervous system
(CNS), activation of α-2 receptors reduces norepinephrine release, reduced sympathetic
activity and sedation. In the cortical blood vessels activation of presynaptic α-2-adrenoreceptors
decrease norepinephrine release, whereas postsynaptic α-2- adrenoreceptors may directly
increase vascular smooth muscle tone. Hence, infusions of dexmedetomidine may have
both direct (i.e. α-2 agonist-mediated increases in calcium flux, triggering vascular
smooth muscle constriction) and α-2 indirect (changes in central sympathetic activity
and decreased cerebral metabolic rate) effects on cerebral blood flow (CBF).[2]
In the peripheral blood vessels, effects of dexmedetomidine depends on the balance
between central and peripheral mechanisms. By central mechanisms, it reduces sympathetic
outflow and causes hypotension, whereas peripheral direct action of vasoconstriction
may lead to hypertension. Thus, loading dose of dexmedetomidine usually cause systemic
hypertension, followed by hypotension. The degree of haemodynamic effects depends
on the dose and fluid status of the patient.
Though the drug has been used in the critical care setting in the medical patients,
its use in neuroanaesthesia practice is limited. Hence, it is imperative to understand
the CNS effects of dexmedetomidine in neurological patients. The basic principles
of neuroanaesthesia are prevent cerebral ischaemia, control of increased intracranial
pressure (ICP), haemodynamic stability during surgery and rapid awakening at the end
of surgery.[3] In addition intraoperative neuroprotection is also a necessity. Prevention of cerebral
ischaemia is achieved by optimizing the cerebral perfusion pressure, cerebral oxygenation
and control of intraoperative ICP is achieved by preventing cerebral vasodilation,
cerebral oedema, and brain swelling. Modern neurosurgery lays lot of emphasis on the
functional preservation and minimally invasive surgery. The goals in managing these
patients addition to the above basic necessities are awakening of patients during
surgery, monitoring of electrocorticogram (ECoG), intraoperative evoked potential
monitoring, etc. Hence, an anaesthetic agent must be satisfying the above needs of
the neuroanaesthetist and should not be detrimental to the outcome.
Infusion of dexmedetomidine was found not to increase the ICPs measured via lumbar
catheter in spinal subarachnoid space following pituitary surgery. All these patients
had normal cerebrospinal fluid pressure.[4] However, its effects on patients with raised ICP have not been evaluated well. In
a small series of 12 patients with head injury, dexmedetomidine infusion did not result
in increased ICP. However, all of them had ICP of <20 mmHg.[5] It needs to be seen that the drug is safe in patients with moderate or severely
raised ICP.
The effects of dexmedetomidine on the CBF have been well established in many studies.
Both the low and high dose of the drug has been found to reduce the global as well
as regional CBF in cortical and subcortical areas.[6] This reduction in CBF cannot be explained by the modest reduction in heart rate
and blood pressure the drug causes by acting on the systemic vasculature. This reduction
was thought to be direct cerebral vasoconstriction mediated by α-2 receptor activation.
The reduction can be considered harmful in patients who depend on the CBF like acute
stroke as well as cerebral vasospasm whereas it can be beneficial in states like vasogenic
cerebral oedema. Dexmedetomidine sedation has been found to reduce cerebral metabolic
rate of oxygen. This can also be a contributing factor for reduction in CBF. Though
the action of the drug causes concern of cerebral ischaemia in neurosurgical patients,
a small study in acute brain injury has shown that lactate/pyruvate ratio was comparable
with propofol infusion well maintained favoring its use.[7] There are certain areas of cerebral haemodynamic where limited knowledge is available
with dexmedetomidine use. The most important of these is carbon-dioxide (CO2) reactivity and cerebral autoregulation. Even though the CO2 reactivity is maintained in volunteers, the effects on impaired auto regulation need
to be determined. There is limited data on this aspect.
Haemodynamic stability is one of the important goals of neuroanaesthesia. Intraoperative
use of dexmedetomidine infusion during a neurosurgical procedure has been found to
maintain the haemodynamics better despite the feared hypotension, reduces the requirement
of opioids and anaesthetic agents.[8] Our experience also showed dexmedetomidine infusion prevents haemodynamic response
to skull pin insertions as well as reduced requirement of opioids and anti hypertensives
during transphenoidal pituitary resection surgery. There are two major disadvantages
of dexmedetomidine; hypotension and severe bradycardia and can induce sinus arrest.[9] In patients with raised ICP with bradycardia as well as patients on b-blockers,
administration of dexmedetomidine can precipitate sinus arrest. Hypotension is usually
caused by the loading dose of the drug especially in hypovolemic patients. Neurosurgical
patients can be dehydrated in the preoperative period especially those on diuretics.
Hypotension can be avoided by giving only the maintenance dose of the drug, skipping
the loading dose and adequately hydrating the patient.
The greatest advantage of dexmedetomidine is its conscious sedation with rapid recovery
with analgesic action and ability to test neurological intactness in patients undergoing
neurosurgery. Dexmedetomidine use is widespread during functional neurosurgery like
deep brain stimulation as it maintains the abnormal movements, neuronavigational procedures
and awake craniotomy for tumor and epilepsy surgery.[10] It has also been found to be useful in coiling of aneurysms in neuroradiological
suite.[11] There are limited randomized data available in comparison with propofol/remifentanyl
combination. Dexmedetomidine has been found effective for sedation in both adults
and pediatric patients undergoing magnetic resonant imaging.[12]
Intraoperative ECoG and evoked potential monitoring are few specialized procedures
that are usually affected by the administration of anaesthetic drugs. Dexmedetomidine
infusion did not affect the quality of ECoG as it produces electroencephalography
like normal sleep pattern.[12] Moreover, experience during scoliosis surgery has shown that dexmedetomidine preserved
the somatosensory and motor evoked potentials.[13]
More often than not neuroanaesthesiologist encounters difficult intubations especially
in diseases of the cervical spine such as cervical trauma and atlantoaxial dislocation.
Awake fiberoptic intubation as well as awake positioning may be required in these
cases. Dexmedetomidine infusion during the procedure has been found to be safe with
better patient comfort, oxygen saturation without the fear of loss of airway.[14]
As with many intravenous and inhalational anaesthetic drugs, dexmedetomine has also
been found to have neuroprotective properties in animal studies. It helps in preventing
schema reperfusion injury, apoptosis.[15] The clinical utility of neuroprotection has not been studied so far.
Patients in neurocritical care are different from other intensive care in that they
may require good sedation for control of the raised ICP. In addition, they need to
be monitored neurologically with pupillary changes as well as neurological testing.
High dose opioids with benzodiazepines are usually the practice in many neurointensive
care units. They can cause haemodynamic instability, interferes with the pupillary
assessment and prolonged use may cause withdrawal features. Dexmedetomidine can counter
the effects of high dose of these drugs. It helps in neurological assessment and does
not interfere in the pupillary assessment. It is helpful in weaning the patients who
are at risk of opioid withdrawal syndrome.[16] The duration of infusion of dexmedetomidine is not clearly defined. Even though,
it is recommended for short term (<24 h), reports of prolonged infusion without adverse
event exists in the literature.
In conclusion, dexmedetomidine is a very useful drug, especially in functional neurosurgery,
awake craniotomies, sedation for radiological procedures and short term use in neurocritical
care. However, it should be borne in mind its haemodynamic adverse effects like hypotension
and bradycardia when choosing this drug for neurologically ill. At present, there
are limited studies related to the use of dexmedetomidine in Neuroanaesthesia and
neurocritical care and many of them are case series. There are no definitive guideline
that exist favoring any strong recommendation for the use this drug in Neuroanaesthesia
practice.
