The results of this study showed that in obese adults, anesthetized with sevoflurane undergoing nasal surgery, intraoperative dexmedetomidine 0.5 μg/kg/h infusion till extubation was as equally effective as magnesium sulfate infusion 20 mg/kg/h till extubation, in reducing the incidence of emergence agitation compared to placebo (5.6%, 8.5%, and 54.4, respectively, p = 0.001). Published data, addressing emergence agitation in adults, reported conflicting array of incidences, ranging from as low as 20% up to 60% (Patel et al., 2010). Indeed, there are factors associated with increased risk of developing emergence agitation: male gender, BMI > 30, benzodiazepine premedication, sevoflurane inhalational anesthetics, tracheal tubes, and ear, nose, and throat surgery (Radtke et al., 2010).
In our clinical trial, we anticipated high incidence of emergence agitation as our inclusion criteria included patients who were obese BMI > 30; nasal surgery with nasal packing; endotracheal tubes were used; sevoflurane inhalational anesthesia was given. As anticipated, the incidence of emergence agitation in the control group in our study was 54.2% which was in consistent with other previous reports (Kang et al., 2020).
Dexmedetomidine, a selective central α2 adrenergic agonist effect, has sympatholytic, anxiolytic, sedative, and analgesic action without respiratory depression. In comparison to other sedatives, Dex is associated with less neurocognitive dysfunction and least delirium (Hauber et al., 2015; Shukry et al., 2010). Therefore, it is potentially good candidate to prevent emergence delirium in high-risk adults. In this trial, Dex reduced the incidence of emergence agitation by 48.6% which is consistent with reports from other researches (Kim et al., 2013; Patel et al., 2010; Radtke et al., 2010; Kang et al., 2020).
Magnesium sulfate is the 4th most abundant blood cation and has pivotal roles in key physiological pathways in humans (Taheri et al., 2015). Recently, it has been a focus of interests in literatures for its antinociceptive, anticonvulsant, and cellular membrane-stabilizing properties (Gallagher et al., 2015). It antagonizes N-methyl d-aspartate receptor in non-competitively and inhibits Ca-ATPase gated and Na-K-ATPase gated ion exchange channels, leading to cell membrane stabilization (Ryu et al., 2008). In addition, it inhibits angiotensin-converting enzyme activity and stimulates prostacyclin synthesis resulting in vasodilation (Ryu et al., 2009). Moreover, magnesium sulfate has analgesic action and it decrease post-operative pain scores and opioid requirements (Song et al., 2011). Owing to its calcium channel blocking action, magnesium reduces acetylcholine release at the presynaptic clefts, which decreases muscle fibers excitability and diminishes the amplitude of action potential, leading to augmentation muscles relaxation (Teymourian et al., 2015). It might be worth mentioning that magnesium sulfate minimize non-depolarizing muscle relaxants requirements and enhances their onset in patients’ under general anesthesia (Borazan et al., 2012). In our study, magnesium sulfate infusion resulted in significantly decreasing the incidence of emergence agitation by 51.7%, when compared to control group. However, the incidence was not significant between Dex and magnesium groups.
Pain is a key factor to the development of EA although, a direct relationship has not been found, yet. In our trial, both Dex and magnesium sulfate groups, showed statistically significant lower pain scores in the post-operative period compared to control group. This is reflected on the consumption of the total amount of rescue analgesics. Patients in D and M groups needed les analgesics compared to patients in the control group, in the post-operative PACU period. Indeed, we can stipulate that the pain modulating effect of either Dex or magnesium sulfate might have contributed to the observed low EA incidence in both groups. This in consistence with other data claiming that adequate analgesia may reduce the incidence of EA (Borazan et al., 2012). Nevertheless, concerning the analgesic efficacy, none of the tested drugs (Dex vs magnesium sulfate) was superior to the other.
In this study, the extubation time was prolonged in patients in Dex group compared to other groups. This in accordance to other published data (Kim et al., 2013; Patel et al., 2010) and it could be due to its analgesic and sedative action. However, other studies claimed that Dex shortens extubation time (Mason, 2017; Lepouse et al., 2006). The reason for these conflicting reports could be attributed to the dose and duration of Dex administration. In our study, Dex .7 μg/kg/h kept running throughout the whole operation, and was turned off just when we stopped administrating general anesthesia. This dose is relatively higher than the usual infusion dose of 5 μg/kg/h and it might contribute to residual sedation and delayed extubation time. This residual sedation was continued in the PACU, and the PACU time was significantly delayed in patients received Dex compared to patients in magnesium and placebo groups. Although, the duration of magnesium sulfate infusion was similar to the duration of Dex infusion, patients in magnesium sulfate group did not show delayed extubation time or stayed longer in the PACU.
Comparing Dex and magnesium sulfate, it is hard to explain why magnesium did not affect the extubation and PACU times, while have comparable results with Dex in reducing the incidence of EA. This is could not be attributed solely to the dose we used in our protocol (20 mg/kg/h infusion, no loading dose), as other studies, used higher dose 30 mg/kg/h infusion and others used bolus doses with infusion without delay. It could be that magnesium is cleared out of the N-methyl-D-aspartate (NMDA) receptors to the extracellular fluid quickly, or may have decreased agitation by its calcium antagonistic effect and brain protective neuromodulation, rather than sedative effect.
Both dexmedetomidine and magnesium sulfate result in hemodynamic changes. Dex has biphasic effect on blood pressure, transient hypertension followed by hypotension and magnesium sulfate has hypotensive effect that makes him a useful adjuvant for hypotensive anesthesia. In our clinical trial, MAP and HR during anesthesia till discharge from PACU showed lower values in group D compared with group M and group C; however, there were no significant differences between the groups. Indeed, 4 patients in the D group suffered from bradycardia but it was transient and did not require atropine rescue.
Our study has limitations to be addressed. First, sample size was based on the incidence of emergence agitation in adults reported in previous publications. These reported incidences were varied and inconsistent. We cannot exclude confounding factors that might have attributed to reported incidences. Second, there is no consensus on the definition of emergence. We chose to define emergence as 5 min after extubation as most agitation occurred during this time (Kim et al., 2013). However, different definition would have resulted in different outcome. Third, the outcomes were evaluated based on subjective measuring scale (RASS and NRS). Nevertheless, our rationale was that these subjective scales were validated and used widely in clinical settings.