Dexmedetomidine pharmacokinetic–pharmacodynamic modelling in healthy volunteers: 1. Influence of arousal on bispectral index and sedation

Colin, Pieter; Hannivoort, Laura N.; Eleveld, Douglas J.; Reyntjens, Koen; Absalom, Anthony; Vereecke, Hugo; Struys, Michel

doi:10.1093/bja/aex085

Cited by 61 publications

(62 citation statements)

References 21 publications

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“…In the present study, the Ce 50 values of MOAA/S ≤ 4, 3 and 2 were 0.57, 0.89 and 1.19 ng/mL, respectively, using a naïve pooled data approach for PD modelling. 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 .…”

Section: Discussionsupporting

confidence: 91%

“…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.…”

Section: Discussionmentioning

confidence: 55%

“…TCI can maintain the drug concentration in a steady state, enabling physicians to objectively estimate changes in concentration‐dependent effects and titrate drug infusion more precisely over the entire therapeutic range. 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 .…”

Section: Discussionmentioning

confidence: 99%

“…After confirming the block level, sedation was induced with TCI of dexmedetomidine (100 µg/mL; Precedex, Hospira Inc) using a syringe pump (Pion pump, Bionet) controlled using Asan pump software (version 2.1.5, http://www.fit4nm.org; last accessed: June 2014) programmed with the PKPD model reported by Colin et al The plasma effect‐site equilibration rate constant ( k e0 ) for MOAA/S was used, whose value is 0.0428 (min −1 ) . Dexmedetomidine was diluted in 0.9% sodium chloride solution to achieve a concentration of 4 µg/mL prior to administration.…”

Section: Methodsmentioning

confidence: 99%

“…Obara et al evaluated the predictive ability of nine PK models of dexmedetomidine and found that the model of Hannivoort et al most accurately predicted the dexmedetomidine plasma concentration in patients undergoing spinal anaesthesia. Recently, Colin et al reported a pharmacokinetic‐pharmacodynamic (PKPD) model for sedation scale and bispectral index (BIS) that was developed in the same subjects used in Hannivoort's PK model . This PKPD model enables prediction of the dexmedetomidine effect‐site concentration (Ce) and target‐controlled infusion (TCI).…”

Section: What Is Known and Objectivementioning

confidence: 99%

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

et al. 2019

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What is known and objective Dexmedetomidine has been a preferred sedative for patients undergoing regional anaesthesia and is mostly administered via conventional zero‐order infusion. Recently, a pharmacokinetic‐pharmacodynamic (PKPD) model of dexmedetomidine has been published, but no external validation has been reported in clinical trials. We aimed to administer target‐controlled infusion (TCI) of dexmedetomidine at the effect‐site concentration (Ce) to patients undergoing spinal anaesthesia and investigate the relationship between dexmedetomidine Ce and the sedative effects. Methods Forty‐five patients scheduled for orthopaedic surgery received spinal anaesthesia with 0.5% bupivacaine. After confirmation of sensory block level, we initiated effect‐site TCI of dexmedetomidine using Colin's model and assessed sedation levels using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale and bispectral index (BIS) with each stepwise increase in the dexmedetomidine Ce. We used a non‐linear mixed‐effects model to determine the PD relationships between the dexmedetomidine Ce and sedation level. Results The dexmedetomidine Ce associated with 50% probability (Ce50) of the MOAA/S scale ≤4, 3 and 2 was 0.57, 0.89 and 1.19 ng/mL, respectively. Mean dexmedetomidine Ce when BIS decreased ≤70 was 0.99 ± 0.15 ng/mL. As dexmedetomidine Ce increased, the MOAA/S scale decreased significantly (correlation coefficient [r] = −.832, P < .0001). BIS decreased significantly with increasing dexmedetomidine Ce (r = −.811, P < .0001) and decreasing MOAA/S scale (r = .838, P < .0001). The most common side effects were hypertension (26.67%) and bradycardia (20%). What is new and conclusion We applied effect‐site TCI of dexmedetomidine in patients undergoing spinal anaesthesia for the first time. Dexmedetomidine Ce correlated significantly with MOAA/S scale and BIS, and was 0.89 and 1.19 ng/mL for moderate and deep sedation, respectively.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: What Is Known and Objectivementioning

confidence: 99%

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

et al. 2019

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Dexmedetomidine versus propofol at different sedation depths during drug‐induced sleep endoscopy: A randomized trial

et al. 2019

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Objectives/Hypothesis: The aim of this study was to compare the effect of dexmedetomidine and propofol on airway dynamics, cardiorespiratory system, and emergence following drug-induced sleep endoscopy (DISE).Study Design: Prospective, randomized, single-blinded study. Methods: Sixty patients age 18 to 65 years in American Society of Anesthesiologists physical status groups 1 and 2 scheduled to undergo DISE were randomly allocated to either Group P (N = 30; receiving propofol infusion at 50-150 μg/kg/min) or Group D (N = 30; receiving dexmedetomidine bolus of 1 μg/kg followed by infusion at 0.5-1.0 μg/kg/hr). DISE was done at light sleep and deep sleep. Airway obstruction at tongue base was recorded as primary outcome. Airway obstruction at velum, oropharyngeal lateral wall, and epiglottis level during light and deep sedation, hemodynamic and respiratory parameters, time to attain sufficient sedation, time for emergence from sedation, and any adverse events during DISE with the two study drugs were recorded as secondary outcomes.Results: There was a greater degree of obstruction at the tongue base level (P = 0.001) and Oropharynx level (P = 0.017) in Group P compared with Group D during deep sedation. Increase in airway obstruction from light to deep sleep was seen with propofol at the oropharynx (P = 0.0185) and tongue base (P = 0.0108) levels. Two patients (6.6%) in Group D and 10 patients (33.3%) in Group P showed oxygen saturation below the minimum oxygen saturation recorded during polysomnography. Time to open eyes to call after stopping sedation was significantly less in Group P (P = 0.005).Conclusions: Dexmedetomidine shows a lesser degree of airway collapse and higher oxygen saturation levels at greater sedation depth during DISE. Propofol has a faster onset and emergence from sedation.

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Neuromonitoring and Sedation; Is There a Role?

Seth

2021

Pediatric Sedation Outside of the Operating Room

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Dexmedetomidine pharmacokinetic–pharmacodynamic modelling in healthy volunteers: 1. Influence of arousal on bispectral index and sedation

Abstract: NCT01879865.

Cited by 61 publications

References 21 publications

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

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

Dexmedetomidine versus propofol at different sedation depths during drug‐induced sleep endoscopy: A randomized trial

Neuromonitoring and Sedation; Is There a Role?

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