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.