Characterization of the temporal profile of the antinociceptive effects of an intravenous bolus of ketamine using the analgesia nociception index in no-anesthetized adult patients
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View abstract on PubMed
Summary
This summary is machine-generated.This study developed a pharmacokinetic-pharmacodynamic model for ketamine
Area Of Science
- Pharmacology
- Anesthesiology
- Pharmacometrics
Background
- Precise titration of intravenous analgesics requires effect-site target-controlled infusion (TCI).
- The analgesia nociception index (ANI) monitors the balance between analgesia and nociception during general anesthesia.
- Understanding ketamine's antinociceptive effects is crucial for optimizing its use in anesthesia.
Purpose Of The Study
- To derive a pharmacokinetic-pharmacodynamic (PKPD) model for ketamine's antinociceptive effect.
- To characterize the time lag between ketamine plasma concentrations and ANI response using the Domino PK parameter set.
- To establish parameters for potential effect-site TCI of ketamine for analgesia.
Main Methods
- Twenty awake adult patients received a single intravenous bolus of ketamine (0.1 mg·kg⁻¹).
- ANI values were recorded, and a PKPD model incorporating the Domino PK parameter set and an effect compartment was used.
- Model parameters were estimated using NONMEM® 7.5, with Ke0 characterizing the effect-site time lag.
Main Results
- Ketamine administration increased basal ANI values from 38.5 ± 4.95 to a maximum of 53.5 ± 4.95.
- The time-to-peak effect was observed at 1.83 ± 0.74 min.
- A Ke0 value of 0.238 min⁻¹ (95% CI 0.20-0.28) was estimated, characterizing the hysteresis between plasma concentrations and ANI response.
Conclusions
- The developed PKPD model adequately characterized the temporal profile of ketamine's antinociceptive effect.
- The estimated model parameters support the feasibility of effect-site TCI for ketamine analgesia.
- This model provides a foundation for more precise ketamine administration in clinical settings.
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