4.1.1. Dexmedetomidine

In this study we analyzed quantitative effects of DEX on MER following two different PSA protocols. In the first protocol PSA agents (DEX alone or DEX and REMI) were discontinued approximately 20 min before the start of MER. It can be speculated that the effects on MER in the discontinued group are solely DEX effects, since REMI has a very short context-sensitive half-time of 3–4 min. In these patients, MUA was significantly suppressed while, SU activity showed a trend towards a lower firing rate but no change in CV. Interestingly, an earlier study by Mathews et al., in which a similar PSA protocol was used (discontinuation of PSA agents before the MER), reported no difference in firing rate, but showed a significant decrease in CV [14]. Their protocol was not identical to ours. Patients received either REMI in bolus (the control group in that study), or DEX and REMI in bolus prior to MER. Moreover, the dose of DEX was higher in their study (0.1–1.0 μg kg−<sup>1</sup> h−<sup>1</sup> versus 0.2–0.5 μg kg−<sup>1</sup> <sup>h</sup>−1). In another case series by Kwon et al., patients received a loading dose of DEX 0.9 μg kg−<sup>1</sup> followed by a maintenance dose of 0.5 μg kg−<sup>1</sup> h−<sup>1</sup> combined with REMI at 0.05 μg kg−<sup>1</sup> min−<sup>1</sup> and propofol was administered in small boluses. Using this protocol, the depth of sedation was maintained at a level of slight sedation (Bispectral index (BIS) of 80). All PSA agents were discontinued 20 min before MER. In that study, firing rates of STN neurons were significantly reduced compared to the control group who received no sedatives [15]. The suppression of firing rates in this protocol (that included

higher DEX dose in addition to the high loading does) is in line with our finding of a dose-dependent suppression, although it is challenging to compare previous studies in which DEX was discontinued before MER with our findings, due to di fferent dose regimens. Taken together, the previous literature and our data sugges<sup>t</sup> that DEX still has an e ffect on MER after 20 min of discontinuation.

In our study, a second group of patients received continuous DEX infusions, alone or in combination with REMI during MER. Firing rates were not significantly altered, but there was a trend to lowering. Both CV and MUA were significantly a ffected whereby CV was increased and MUA decreased. Correlation analysis showed that these e ffects were dose-dependent, including lowering of the firing rate. A small case series reported a suppression of neuronal activity in patients who received DEX sedation throughout the full procedure (range 0.1–0.4 μg kg−<sup>1</sup> <sup>h</sup>−1) in comparison to patients in which DEX was discontinued before recordings [12]. In another study, patients received a bolus DEX of 0.5–1.0 μg kg−<sup>1</sup> followed by a maintenance infusion of 0.1–1.0 μg kg−<sup>1</sup> h−1. They reported a slight increase in firing rate and a significant decrease in burst index (decreased number of spikes within a burst) compared to patients who received no sedation [13]. Thus, these findings appear contradictory to our findings as well as with previous literature. A possible explanation for the di fferences with our findings is the dose they used, which included a bolus followed by a relatively high maintenance dose.

To summarize our results, dexmedetomidine caused a trend toward decreased firing rates, significantly suppressed MUA and increased CV. These e ffects were present even at low dose and even after discontinuation of DEX. However, direct comparison of our findings with previous studies is challenging, because of the variability of the sedation protocols, patients groups and methodology.
