Differentiating Drug-related and State-related Effects of Dexmedetomidine and Propofol on the Electroencephalogram

Abstract

Background Differentiating drug-related changes and state-related changes on the electroencephalogram during anesthetic-induced unconsciousness has remained a challenge. To distinguish these, we designed a rigorous experimental protocol with two drugs known to have distinct molecular mechanisms of action. We hypothesized that drug- and state-related changes can be separated. Methods Forty-seven healthy participants were randomized to receive dexmedetomidine (n = 23) or propofol (n = 24) as target-controlled infusions until loss of responsiveness. Then, an attempt was made to arouse the participant to regain responsiveness while keeping the drug infusion constant. Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness. We conducted statistical comparisons between the drugs and different states of consciousness for spectral bandwidths, and observed how drug-induced electroencephalogram patterns reversed upon awakening. Cross-frequency coupling was also analyzed between slow-wave phase and alpha power. Results Eighteen (78%) and 10 (42%) subjects were arousable during the constant drug infusion in the dexmedetomidine and propofol groups, respectively (P = 0.011 between the drugs). Corresponding with deepening anesthetic level, slow-wave power increased, and a state-dependent alpha anteriorization was detected with both drugs, especially with propofol. The slow-wave and frontal alpha activities were momentarily disrupted as the subjects regained responsiveness at awakening. Negative phase-amplitude coupling before and during loss of responsiveness frontally and positive coupling during the highest drug concentration posteriorly were observed in the propofol but not in the dexmedetomidine group. Conclusions Electroencephalogram effects of dexmedetomidine and propofol are strongly drug- and state-dependent. Changes in slow-wave and alpha activity seemed to best detect different states of consciousness.

Target‐controlled infusion of dexmedetomidine effect‐site concentration for sedation in patients undergoing spinal anaesthesia

“…These dexmedetomidine Ce values were similar to those reported by Colin et al, which were 0.43, 0.79 and 1.34 ng/mL at MOAA/S ≤ 4, 3 and 2, respectively, in volunteers in a silent environment. Although the estimated Ce 50 values of sedation scales in patients have not been reported yet, other studies have shown comparable ranges of dexmedetomidine plasma concentration . Scheinin et al documented the deep sedative concentration of dexmedetomidine as 1.36 ng/mL in plasma.…”

“…Although the estimated Ce 50 values of sedation scales in patients have not been reported yet, other studies have shown comparable ranges of dexmedetomidine plasma concentration . Scheinin et al documented the deep sedative concentration of dexmedetomidine as 1.36 ng/mL in plasma. In the present study, a higher dexmedetomidine Ce was required for light‐to‐moderate sedation (MOAA/S 3‐4), whereas a lower value than that used in the previous volunteer studies was required for deep sedation (MOAA/S ≤ 2) .…”

“…Currently, there is only one PKPD model of the sedative effect of dexmedetomidine; thus, before this model was established, the TCI for its plasma concentration was performed . However, PK models for dexmedetomidine do not account for the haemodynamic or sedative effects; therefore, it is difficult to control the sedative effects directly based on the plasma concentration and overshooting could occur . Effect‐site TCI facilitates maintenance and prediction of the desired effect.…”

“…Scheinin et al documented the deep sedative concentration of dexmedetomidine as 1.36 ng/mL in plasma. In the present study, a higher dexmedetomidine Ce was required for light‐to‐moderate sedation (MOAA/S 3‐4), whereas a lower value than that used in the previous volunteer studies was required for deep sedation (MOAA/S ≤ 2) . This may have been because most patients were nervous before surgery; thus, a higher dexmedetomidine Ce was required to induce sedation, but after initiation, lower values were required to retain the profound sedative effect under regional anaesthesia.…”

“…The present study investigated the relationship between dexme- However, PK models for dexmedetomidine do not account for the haemodynamic or sedative effects; therefore, it is difficult to control the sedative effects directly based on the plasma concentration and overshooting could occur. 10 Effect-site TCI facilitates maintenance and prediction of the desired effect. However, there has only been one case report of the use of effect-site TCI for sedation with dexmedetomidine in the clinical setting.…”