Discussion
Although most dental treatments are performed in the office without the
need for sedation or general anesthesia, some adult patients with
inadequate cooperation due to intellectual disabilities or those with
high levels of fear may require general anesthesia. Anesthesia for
outpatient dental treatments should be followed with a quick and safe
recovery with minimum post anesthesia complications. Therefore, choosing
the right anesthetic drug is of paramount importance. As most of the
adult patients who are candidate for dental treatment under general
anesthesia are intellectually disabled, it is vital to study the effects
of anesthesia on these patients. [11] The main concerning
complications of general anesthesia in these patients include
cardiovascular problems. A wide range of cardiovascular problems
including extreme alterations in heart rate, cardiac output, myocardial
functioning as well as arrhythmias can complicate the anesthesia and
treatment procedures. In addition to complete pre-operative medical
history taking and perioperative monitoring of blood pressure, ECG,
pulse oximetry and management of anxiety both pre-operation and
post-operation is vital to decrease cardiovascular complications.
Dexmedetomidine is a highly specific alpha-two receptor agonist with
sedative, analgesic, and anxiolytic properties. Considerable attention
has been given to this drug in recent years because, unlike other
sedatives, it does not cause respiratory depression. [12] The
mechanism of action of this drug is related to its binding to central
and peripheral alpha-two adrenoreceptors. When binding to the
adrenoreceptors located in the pons, sedative and anxiolytic properties
are seen. This binding inhibits adenyl cyclase enzyme and, consequently,
reduces the production of cAMP. It also promotes changes in ion
channels, which ultimately inhibit the release of norepinephrine. This
drug is used effectively both before the induction of anesthesia as a
prodrug and during anesthesia to control pain throughout and after the
procedure. It is also used to reduce the activity of the sympathetic
system during the induction of anesthesia and to maintain a stable
hemodynamic profile. Moreover, it has also been shown that
dexmedetomidine can reduce the maximum heart rate by 18%. By increasing
the effectiveness of anesthetic drugs, dexmedetomidine can reduce the
need for anesthetic drug sodium thiopental by 17-30%. [13]
The results of current study showed that stable systolic and diastolic
blood pressures in patients during general anesthesia can be achieved by
using dexmedetomidine. Side effects of dexmedetomidine are usually in
the form of hemodynamic alterations. However, no significant bradycardia
or hypotension requiring intervention was observed due to the
dexmedetomidine infusion used in the current study. In fact, a more
stable systolic blood pressure was observed in the intervention group.
This finding is consistent with previous studies that showed established
dexmedetomidine, given by infusion, attenuated hemodynamic stress
response in surgical procedures. [14-17] In a study that compared
hemodynamics in patients undergoing general anesthesia for laryngeal
microsurgery with dexmedetomidine or remifentanil, comparable results
were obtained for the two groups. [18] Another study comparing
dexmedetomidine and fentanyl for laparoscopic cholecystectomy favored
dexmedetomidine for hemodynamic stability. [19] In another study
using perilesional infiltration of dexmedetomidine for maxillofacial
surgeries under general anesthesia, stable hemodynamics was maintained
both during and after operation, whereas the patients in placebo group
experienced tachycardia and hypertension frequently. [20] Similarly,
in another study investigating intra-cranial operations, the
dexmedetomidine group had a considerably more stable hemodynamics than
patients receiving placebo. [21]
A biphasic hemodynamic response following the intravenous bolus
administration of dexmedetomidine has been reported in the literature.
The bolus administration causes a peak concentration of the drug in the
plasma which acts on alpha-two receptors in vascular smooth muscles,
increasing vascular resistance and causing peripheral vasoconstriction
and hypertension. This is followed by baroreceptor reflex bradycardia.
With the decrease in plasma concentration of the drug, vasodilation due
to activation of alpha-two receptors in vascular endothelial cells
begins. The combination of catecholamine release inhibition, increased
vagal activity and vasodilation initiates the hypotensive phase. This
phenomenon is not as marked with infusion administration of
dexmedetomidine. [5] Although no previous study was found on
hemodynamics with dexmedetomidine in dental treatments, it seems that
dexmedetomidine, if administered properly, can be used without causing
hemodynamic instability in different clinical scenarios.
As for the recovery time, the use of dexmedetomidine did not
statistically significantly increase the patients’ stay. A meta-analysis
on the use of dexmedetomidine with sevoflurane in children undergoing
general anesthesia demonstrated a shorter period of stay in
post-anesthesia care unit (PACU) with use of dexmedetomidine. [22] A
retrospective cohort study suggested that there was a dose-dependent
association between the use of dexmedetomidine and the longer stays in
PACU. This finding was explained with respect to long acting time of
dexmedetomidine which is of importance only in short procedures.
[23] Dexmedetomidine activates central alpha-two receptors (both
pre-synaptic and post-synaptic) located in locus coeruleus. This
activation induces a level of unconsciousness similar to that observed
in natural sleep, which may contribute to delayed emergence in patients.
[5] A high inter-individual variability has been observed in
pharmacokinetics of this drug for distribution volume and hepatic
clearance. [5] This variability can explain the inconsistency
present in the literature. The results of the current study suggest that
the factors influencing the recovery time for intellectually disabled
patients are complicated, and the sole use of dexmedetomidine does not
statistically significantly elongate the recovery duration.
Dexmedetomidine has been shown to be effective in reducing the incidence
of emergence delirium in children. [12] It has also been effective
at reducing agitation in patients who were experiencing symptoms of
pre-operative anxiety. [24] According to a systematic review
dexmedetomidine relieves postoperative pain and prevents emergence
agitation. [25] In the current study, dexmedetomidine had a positive
effect on the agitation levels of patients 15 and 30 minutes after
entering the recovery. The agitation levels after 45 minutes onward were
comparable in both study groups. This finding suggests that the benefit
of using dexmedetomidine to control agitation is most prominent during
the first 30 minutes of recovery, which is actually the interval that
patients are susceptible to experience post-anesthesia agitation the
most. In a recent meta-analysis about the effect of dexmedetomidine on
the quality of recovery, it was concluded that the anxiolytic and
analgesic effects of dexmedetomidine along with its inhibition of stress
and inflammation of the surgical trauma lead to higher scores for
quality of recovery in adult patients. [6]
An important aspect in conducting clinical trials is to avoid
confounding factors as much as possible via randomization. The strength
of our study was complete adherence to protocols needed to avoid
introduction of any biases or confounders into the study. The
demographic profile of patients, duration of treatment and types of
dental treatments were not statistically different between the two
groups, minimizing the need to adjustments in data analysis. Known
factors impacting on dexmedetomidine pharmacokinetics are obesity,
hepatic impairment and possibly cardiac disorders, all of which were
avoided in the recruitment process. [5]
One of the limitations of the current study was the unfeasibility of
using a Visual Analogue Scales to quantitatively measure the severity of
pain in the recovery due to the intellectual disability of the patients.
Furthermore, progressive postoperative forgetfulness is suggested to be
one of the side effects of using dexmedetomidine. However, it was not
assessed in the current study either due to the intellectual conditions
of the participants. Nevertheless, more comprehensive studies on use of
dexmedetomidine in patients with intellectual and physical problems will
provide better understanding of different uses of this drug.