Mechanism-based pharmacodynamic model for propofol haemodynamic effects in healthy volunteers☆

Su, Hong; Eleveld, Douglas J.; Struys, Michel; Colin, Pieter

doi:10.1016/j.bja.2022.01.022

Cited by 17 publications

(8 citation statements)

References 46 publications

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“…Previous examples dealt with controlling two interacting agents, each having different PK/PD properties. However, recent studies 9,31 pointed out the need to consider different effects with their dynamics even for single drugs. Particularly, for opioids, Abad et al described that current remifentanil PD models, based on Electroencephalogram (EEG), might reflect more the sedative aspects than the analgesic ones.…”

Section: Resultsmentioning

confidence: 99%

Multi-drug interaction target-controlled infusion from simultaneous optimization of pharmacometric models

Martinez-Vazquez,

Abad-Torrent

2024

Preprint

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Background Accurately controlling drug delivery is crucial for safe anesthesia. Target-controlled infusion (TCI) systems use pharmacokinetic and pharmacodynamic (PK/PD) models to administer intravenous agents to reach target concentrations. However, TCI's operation is restricted to a single-drug and a linear PK/PD model, not accounting for drug interactions. Dose-response interaction (DRI) models quantify such interactions by representing shared effects as a function of agents' concentrations. For example, the co-administration of an analgesic and a hypnotic with TCI leads to an uncontrolled synergy. Methods We introduce a new administering methodology for multi-drug infusions, interaction target-controlled infusion (iTCI), that combines the PK/PD models of the co-administered drugs and their interactions into a single optimal non-linear dynamic control problem with terminal constraints. Results Incorporating DRI and PK/PD models allows novel administration procedures. Simulations of iTCI in different clinical scenarios under propofol and remifentanil co-administrations are presented. These show that: (1) iTCI requires lower administered volumes than TCI to reach simultaneously the same target concentrations. (2) It offers optimal interdependent administrations that address not only concentration targets but also effect targets. (3) iTCI comes with additional constraints on the administration, including controlled titrations along iso-effect conditions (isoboles) or (5) directly limiting plasma concentration levels. (6) Unlike TCI, iTCI can include different exerted effects (ke0) per drug, particularly relevant for opioids. Conclusion The iTCI is a versatile multi-drug infusion paradigm where effects and interactions play a relevant role - providing better delivery profiles than current TCI while opening the door for using non-linear PK/PD descriptions in anesthesia.

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Section: Resultsmentioning

confidence: 99%

Multi-drug interaction target-controlled infusion from simultaneous optimization of pharmacometric models

Martinez-Vazquez,

Abad-Torrent

2024

Preprint

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“…TCI requires a lower dose of propofol to achieve loss of consciousness than manual infusion [ 17 – 19 ]. Remimazolam and propofol decrease blood pressure in a dose-dependent manner [ 22 – 25 ]. The Food and Drug Administration recommends a 1.5 mg/kg maximum dose of propofol for inducing anesthesia in elderly patients [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of hemodynamics during induction of general anesthesia with remimazolam and target-controlled propofol in middle-aged and elderly patients: a single-center, randomized, controlled trial

et al. 2023

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Background Remimazolam confers a lower risk of hypotension than propofol. However, no studies have compared the efficacy of remimazolam and propofol administered using target-controlled infusion (TCI). This study aimed to investigate hemodynamic effects of remimazolam and target-controlled propofol in middle-aged and elderly patients during the induction of anesthesia. Methods Forty adults aged 45–80 years with the American Society of Anesthesiologists Physical Status 1–2 were randomly assigned to remimazolam or propofol group (n = 20 each). Patients received either remimazolam (12 mg/kg/h) or propofol (3 μg/mL, TCI), along with remifentanil for inducing anesthesia. We recorded the blood pressure, heart rate (HR), and estimated continuous cardiac output (esCCO) using the pulse wave transit time. The primary outcome was the maximum change in mean arterial pressure (MAP) after induction. Secondary outcomes included changes in HR, cardiac output (CO), and stroke volume (SV). Results MAP decreased after induction of anesthesia in both groups, without significant differences between the groups (− 41.1 [16.4] mmHg and − 42.8 [10.8] mmHg in remimazolam and propofol groups, respectively; mean difference: 1.7 [95% confidence interval: − 8.2 to 4.9]; p = 0.613). Furthermore, HR, CO, and SV decreased after induction in both groups, without significant differences between the groups. Remimazolam group had significantly shorter time until loss of consciousness than propofol group (1.7 [0.7] min and 3.5 [1.7] min, respectively; p < 0.001). However, MAP, HR, CO, and SV were not significantly different between the groups despite adjusting time until loss of consciousness as a covariate. Seven (35%) and 11 (55%) patients in the remimazolam and propofol groups, respectively, experienced hypotension (MAP < 65 mmHg over 2.5 min), without significant differences between the groups (p = 0.341). Conclusions Hemodynamics were not significantly different between remimazolam and target-controlled propofol groups during induction of anesthesia. Thus, not only the choice but also the dose and usage of anesthetics are important for hemodynamic stability while inducing anesthesia. Clinicians should monitor hypotension while inducing anesthesia with remimazolam as well as propofol. Trial registration UMIN-CTR (UMIN000045612).

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“…TCI requires a lower dose of propofol to achieve loss of consciousness than manual infusion [17][18][19]. Remimazolam and propofol decrease blood pressure in a dose-dependent manner [21][22][23][24]. The Food and Drug Administration (FDA) recommends a 1.5 mg/kg maximum dose of propofol for inducing anesthesia in elderly patients [25].…”

Section: Discussionmentioning

confidence: 99%

Comparison of hemodynamics during induction of general anesthesia with remimazolam and target-controlled propofol in middle-aged and elderly patients: A single-center, randomized, controlled trial

Sekiguchi

Kinoshita

Kawanishi

et al. 2022

Preprint

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Background Remimazolam confers a lower risk of hypotension than propofol. However, no studies have compared efficacy of remimazolam and propofol administered using target-controlled infusion (TCI). This study aimed to investigate hemodynamic effects of remimazolam and target-controlled propofol in middle-aged and elderly patients during the induction of anesthesia. Methods Forty adults aged 45–80 years with the American Society of Anesthesiologists Physical Status 1–2 were randomly assigned to remimazolam or propofol group (n = 20 each). Patients received either remimazolam (12 mg/kg/h) or propofol (3 µg/mL, TCI), along with remifentanil for inducing anesthesia. We recorded the blood pressure, heart rate (HR), and estimated continuous cardiac output (esCCO) using the pulse wave transit time. The primary outcome was the maximum change in mean arterial pressure (MAP) after induction. Secondary outcomes included changes in HR, cardiac output (CO), and stroke volume (SV). Results MAP tended to decrease after induction of anesthesia in both the groups, without significant differences between the groups (-41.1 [16.4] mmHg and − 42.8 [10.8] mmHg in remimazolam and propofol groups, respectively; mean difference: 1.7 [95% confidence interval: -8.2 to 4.9]; p = 0.613). Furthermore, HR, CO, and SV decreased after induction in both groups, without significant differences between the groups. Remimazolam group had significantly shorter time until loss of consciousness than propofol group (1.7 [0.7] min and 3.5 [1.7] min, respectively; p < 0.001). However, MAP, HR, CO, and SV were not significantly different between the groups despite adjusting time until loss of consciousness as a covariate. Remimazolam group tended to have a lower frequency of hypotension (MAP < 65 mmHg) than propofol group (7 [35%] and 11 [55%] cases, respectively; p = 0.341). Conclusions Hemodynamics were not significantly different between remimazolam and target-controlled propofol groups during induction of anesthesia. Thus, the choice, dose, and usage of anesthetics are important for hemodynamic stability while inducing anesthesia. Clinicians should monitor hypotension while inducing anesthesia with remimazolam as well as propofol. Trial registration: UMIN-CTR (UMIN000045612).

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Mechanism-based pharmacodynamic model for propofol haemodynamic effects in healthy volunteers☆

Cited by 17 publications

References 46 publications

Multi-drug interaction target-controlled infusion from simultaneous optimization of pharmacometric models

Multi-drug interaction target-controlled infusion from simultaneous optimization of pharmacometric models

Comparison of hemodynamics during induction of general anesthesia with remimazolam and target-controlled propofol in middle-aged and elderly patients: a single-center, randomized, controlled trial

Comparison of hemodynamics during induction of general anesthesia with remimazolam and target-controlled propofol in middle-aged and elderly patients: A single-center, randomized, controlled trial

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