The role of pharmacokinetics and pharmacodynamics in clinical anaesthesia practice

Hannivoort, Laura N.; Absalom, Anthony; Struys, Michel

doi:10.1097/aco.0000000000000881

Cited by 13 publications

(13 citation statements)

References 63 publications

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“…This was thought to activation of ɑ2-receptor in the vascular smooth muscles, leading peripheral vasoconstriction and consequently hypertension. After a few minutes, the vasodilatation, presynaptic a2-adrenoreceptors inhibiting sympathetic release of catecholamines and the increased vagal activity, causing a hypotensive phase [29]. Although the systolic blood pressure increased over 200 mmHg in 2 patients, the maximum changes in hemodynamics were all less than 30% of the baseline, which is generally considered acceptable.…”

Section: Discussionmentioning

confidence: 99%

Median Effective Dose of Dexmedetomidine Inducing Bradycardia in Elderly Patients Determined by Up-and-Down Sequential Allocation Method

Yang¹,

Fu²,

Deng³

et al. 2022

Int. J. Med. Sci.

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Purpose: When dexmedetomidine is used in elderly patients, high incidence of bradycardia is reported. Given age-related physiological changes in this population, it is necessary to know the safety margin between the loading dose of dexmedetomidine and bradycardia. Therefore, we conducted this study to investigate the median effective dose (ED50) of dexmedetomidine causing bradycardia in elderly patients. Methods: Thirty patients with ages over 65 years undergoing elective general surgery were enrolled. The Dixon and Massay sequential method were applied to determine the loading dose of dexmedetomidine, starting from 1.0 µg/kg. The dose for the follow-up subjects increased or decreased according to the geometric sequence with the common ratio 1.2, based on the 'negative' or 'positive' response of the previous subject. Positive mean that the subject developed bradycardia during the test. Hemodynamic data including heart rate and systolic blood pressure were recorded. The level of sedation was assessed with the Observer Assessment of Alertness and Sedation Scale (OAA/S). Results: Bradycardia occurred in 13 patients (43.3%). The ED50 of dexmedetomidine causing bradycardia was 1.97 µg/kg (95% CI, 1.53-2.53 µg/kg). OAA/S scores at 10 min after the beginning of the dexmedetomidine infusion and 10 min after the termination of dexmedetomidine administration showed no significant differences between the positive and negative groups (P > 0.05). Conclusion:The ED50 of dexmedetomidine causing bradycardia in our cohort was higher than clinical recommended dose. A higher loading dose appears acceptable for a faster onset of sedation under careful hemodynamic monitoring. Trial registration: ChiCTR 15006368.

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Section: Discussionmentioning

confidence: 99%

Median Effective Dose of Dexmedetomidine Inducing Bradycardia in Elderly Patients Determined by Up-and-Down Sequential Allocation Method

Yang¹,

Fu²,

Deng³

et al. 2022

Int. J. Med. Sci.

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“…The state change during ROR back to consciousness may include the task of overcoming the orexinergic blockade and hence emergence may even be deemed an active process [ 36 ]. Hence, the substance-specific differences in the EEG towards ROR may be caused by the different modes of action [ 37 , 38 ] and the basic pharmacokinetic properties of the administered anesthetics [ 39 ]. Although both anesthetics seem to modulated the activity in the thalamocortical loop [ 37 ], the impact of propofol and sevoflurane on these structures may be different [ 38 ] as it may be for isoflurane as well [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Anesthetic Specific EEG Dynamics during State Transitions between Loss and Return of Responsiveness

et al. 2021

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Purpose: electroencephalographic (EEG) information is used to monitor the level of cortical depression of a patient undergoing surgical intervention under general anesthesia. The dynamic state transitions into and out of anesthetic-induced loss and return of responsiveness (LOR, ROR) present a possibility to evaluate the dynamics of the EEG induced by different substances. We evaluated changes in the EEG power spectrum during anesthesia emergence for three different anesthetic regimens. We also assessed the possible impact of these changes on processed EEG parameters such as the permutation entropy (PeEn) and the cerebral state index (CSI). Methods: we analyzed the EEG from 45 patients, equally assigned to three groups. All patients were induced with propofol and the groups differed by the maintenance anesthetic regimen, i.e., sevoflurane, isoflurane, or propofol. We evaluated the EEG and parameter dynamics during LOR and ROR. For the emergence period, we focused on possible differences in the EEG dynamics in the different groups. Results: depending on the substance, the EEG emergence patterns showed significant differences that led to a substance-specific early activation of higher frequencies as indicated by the “wake” CSI values that occurred minutes before ROR in the inhalational anesthetic groups. Conclusion: our results highlight substance-specific differences in the emergence from anesthesia that can influence the EEG-based monitoring that probably have to be considered in order to improve neuromonitoring during general anesthesia.

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“…The accuracy of intravenous drug administration can be improved by the use of target controlled infusion (TCI) systems [ 59 ]. TCI systems use computer driven infusion pumps with pharmacological models incorporated into the software to reach and maintain a user-defined plasma or effect site concentrations.…”

Section: New Pk-pd Models For Existing Anaesthetic Drugs For Tci Appl...mentioning

confidence: 99%

What’s New in Intravenous Anaesthesia? New Hypnotics, New Models and New Applications

Vellinga

Valk

Absalom

et al. 2022

JCM

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New anaesthetic drugs and new methods to administer anaesthetic drugs are continually becoming available, and the development of new PK-PD models furthers the possibilities of using arget controlled infusion (TCI) for anaesthesia. Additionally, new applications of existing anaesthetic drugs are being investigated. This review describes the current situation of anaesthetic drug development and methods of administration, and what can be expected in the near future.

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The role of pharmacokinetics and pharmacodynamics in clinical anaesthesia practice

Cited by 13 publications

References 63 publications

Median Effective Dose of Dexmedetomidine Inducing Bradycardia in Elderly Patients Determined by Up-and-Down Sequential Allocation Method

Median Effective Dose of Dexmedetomidine Inducing Bradycardia in Elderly Patients Determined by Up-and-Down Sequential Allocation Method

Evaluation of Anesthetic Specific EEG Dynamics during State Transitions between Loss and Return of Responsiveness

What’s New in Intravenous Anaesthesia? New Hypnotics, New Models and New Applications

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