A comparison between dosages and plasma concentrations of dexmedetomidine in clinically ill patients: a prospective, observational, cohort study in Japan

Fujita, Yoshihito; Inoue, Kōichi; Sakamoto, Tasuku; Yoshizawa, Saya; Tomita, Maiko; Maeda, Yoshie; Taka, Hitomi; Muramatsu, Ai; Hattori, Youichiro; Hirate, Hiroyuki; Toyo’oka, Toshimasa; Sobue, Kazuya

doi:10.1186/2052-0492-1-15

Cited by 21 publications

(17 citation statements)

References 9 publications

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“…The clinically recommended intravenous infusions of dexmedetomidine are in the range of 0.2 – 0.7 μg/kg/h to achieve plasma concentrations of 0.3–2.5 ng/ml [37]. 2.5 ng/ml corresponds to approximately 12 nM.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine’s inhibitory effects on acetylcholine release from cholinergic nerves in guinea pig trachea: a mechanism that accounts for its clinical benefit during airway irritation

et al. 2017

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BackgroundAirway instrumentation can evoke upper airway reflexes including bronchoconstriction and cough which can cause serious complications including airway trauma, laryngospasm or bronchospasm which may in turn lead to difficulty with ventilation and hypoxemia. These airway events are mediated in part by irritant-induced neuronal modulation of airway tone and cough responses. We investigated whether the commonly used anesthetic agents dexmedetomidine, lidocaine or remifentanil attenuated neuronal and airway smooth muscle responses in the upper airways of guinea pigs.MethodsThe ability of dexmedetomidine, lidocaine or remifentanil to attenuate direct cholinergic nerve stimulation, C-fiber stimulation or direct smooth muscle contraction were studied using isolated tracheal rings from male guinea pigs under four paradigms; (1) the magnitude of contractile force elicited by cholinergic electrical field stimulation (EFS); (2) the amount of acetylcholine released during cholinergic EFS; (3) the direct airway smooth muscle relaxation of a sustained acetylcholine-induced contraction and (4) the magnitude of C-fiber mediated contraction.ResultsDexmedetomidine (1–100 μM) and lidocaine (1 mM) attenuated cholinergic 30Hz EFS-induced tracheal ring contraction while remifentanil (10 μM) had no effect. Dexmedetomidine at 10 μM (p = 0.0047) and 100 μM (p = 0.01) reduced cholinergic EFS-induced acetylcholine release while lidocaine (10 μM-1 mM) and remifentanil (0.1–10 μM) did not. Tracheal ring muscle force induced by the exogenous addition of the contractile agonist acetylcholine or by a prototypical C-fiber analogue of capsaicin were also attenuated by 100 μM dexmedetomidine (p = 0.0061 and p = 0.01, respectively). The actual tracheal tissue concentrations of dexmedetomidine achieved (0.54–26 nM) following buffer application of 1–100 μM of dexmedetomidine were within the range of clinically achieved plasma concentrations (12 nM).ConclusionsThe α2 adrenoceptor agonist dexmedetomidine reduced cholinergic EFS-induced contractions and acetylcholine release consistent with the presence of inhibitory α2 adrenoceptors on the prejunctional side of the postganglionic cholinergic nerve-smooth muscle junction. Dexmedetomidine also attenuated both exogenous acetylcholine-induced contraction and C-fiber mediated contraction, suggesting a direct airway smooth muscle effect and an underlying mechanism for cough suppression, respectively.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine’s inhibitory effects on acetylcholine release from cholinergic nerves in guinea pig trachea: a mechanism that accounts for its clinical benefit during airway irritation

et al. 2017

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“…Furthermore, plasma dexmedetomidine concentrations are moderately correlated with the dose administered 19 .…”

Section: Discussionmentioning

confidence: 98%

Combined Neuroprotective Effects of Propofol and Dexmedetomidine on Endoplasmic Reticulum Stress-mediated Apoptosis in SH-SY5Y Cells

Somei

Inagaki

Oguchi

et al. 2016

Showa Univ J Med Sci

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: Propofol is a short-acting intravenous anesthetic agent. Dexmedetomidine, a highly selective 2 -adrenergic receptor agonist, has a well-known sedative effect. Both agents exhibit cytoprotective effects in the nervous system under ischemic conditions. Recently, the combination of propofol plus dexmedetomidine was used for the sedation of mechanically ventilated patients in an intensive care unit, but there are few experimental reports of the protective effects of the propofol plus dexmedetomidine combination in cells. Meanwhile, intraoperative brain ischemia-reperfusion induces endoplasmic reticulum ER stress-mediated apoptosis. The aim of the present study was to clarify molecular details underlying the neuroprotection afforded by the combination of propofol plus dexmedetomidine against thapsigargin TG -induced ER stress in human neuroblastoma SH-SY5Y cells, and whether the combination provided more ef cient neuroprotection. TG was used to generate ER stress in SH-SY5Y cells. Cells were pretreated with propofol or dexmedetomidine, individually or in combination, for 1 h before cotreatment with TG for 20 h. There was a signi cant increase in Ca 2 i , caspase activation, and the expression of ER stress biomarkers in TG-induced apoptotic cells. The increase in Ca 2 i and the induction of ER stress by TG were suppressed by pretreatment with propofol, dexmedetomidine, and their combination. The dexmedetomidineinduced reduction in caspase activity and ER stress biomarkers was inhibited by pretreatment with an 2 -adrenergic receptor antagonist, but was enhanced by pretreatment with a cAMP inhibitor. Treatment with the propofol plus dexmedetomidine combination exhibited the strongest protection against TG-induced apoptosis. These results demonstrate that the combination of propofol plus dexmedetomidine at clinically relevant concentrations suppresses ER stress-induced apoptosis in neuroblastoma SH-SY5Y cells. The ndings suggest that the combination of propofol plus dexmedetomidine within a clinically relevant concentration range may be used safely in patients.

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“…[66][67][68][69][70][71][72][73][74][75][76][77][78][79][80] However, the sensitive determination of negatively charged molecules, such as carboxylic acids, is not always promising even though MS detection is highly sensitives. 81,82) In such a case, the derivatization technique, which is generally used positively-charged reagents, is adopted for increasing the detection sensitivity and separation efficiency of reversed-phase chromatography.…”

Section: Derivatization Reagents For Amines and Carboxyls In Lc-ms/msmentioning

confidence: 99%

Diagnostic Approach to Disease Using Non-invasive Samples Based on Derivatization and LC-ESI-MS/MS

Toyo’oka

2016

Biological & Pharmaceutical Bulletin

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The determination of biologically-active molecules is very important in order to understand biological functions. A novel approach for the highly sensitive and specific determination seems to be essential for this purpose. Based on this consideration, we synthesized various types of fluorogenic and fluorescent reagents for the derivatization of chiral and achiral molecules. The fluorescence analysis is excellent for the analysis of target molecules and generally provides good expected results. However, the trace analysis of the bioactive molecules in complex matrices, such as plasma and urine, is not always satisfactory even using high-performance fluorometry. In such a situation, mass spectrometry (MS) is another technique for the selective and sensitive determination of biological components. Therefore, various derivatization reagents for MS/MS detection were developed and used for the determination of amines and carboxyls including chiral molecules. These newly developed reagents were also adopted for the biomarker detection related to diseases using non-invasive samples (i.e., saliva, nail, hair). Although the determination of the targeted chiral molecules is relatively easy, it is very difficult to identify and/or determine the enantiomeric biomarker in real samples. To solve this difficulty, we proposed the strategy called "chiral metabolomics," which means the total analysis of the enantiomers of various chiral metabolites in complex matrices. This review paper focused on the development of various new derivatization reagents for amines and carboxyls by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and the detection of the biomarker candidates related to several diseases in non-invasive samples (i.e., hair, nail, saliva) using these reagents.

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A comparison between dosages and plasma concentrations of dexmedetomidine in clinically ill patients: a prospective, observational, cohort study in Japan

Cited by 21 publications

References 9 publications

Dexmedetomidine’s inhibitory effects on acetylcholine release from cholinergic nerves in guinea pig trachea: a mechanism that accounts for its clinical benefit during airway irritation

Dexmedetomidine’s inhibitory effects on acetylcholine release from cholinergic nerves in guinea pig trachea: a mechanism that accounts for its clinical benefit during airway irritation

Combined Neuroprotective Effects of Propofol and Dexmedetomidine on Endoplasmic Reticulum Stress-mediated Apoptosis in SH-SY5Y Cells

Diagnostic Approach to Disease Using Non-invasive Samples Based on Derivatization and LC-ESI-MS/MS

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