Remifentanil pharmacodynamics during conscious sedation using algometry: a more clinically relevant pharmacodynamical...

Area of Science:

• Anesthesiology and Pharmacology
• Pharmacokinetics and Pharmacodynamics
• Pain Management

Background:

• The Minto remifentanil pharmacokinetic/pharmacodynamic (PK/PD) model is integral to target-controlled infusion (TCI) devices.
• The model's k_e0 parameter, crucial for predicting drug effect timing, is derived from electroencephalogram (EEG) data, which are only sensitive at high remifentanil concentrations.
• This study investigates the temporal accuracy of the Minto model's effect-site concentration predictions against pressure pain thresholds at clinically relevant, lower remifentanil concentrations.

Purpose of the Study:

• To evaluate the temporal agreement between effect-site concentrations predicted by the Minto PK/PD model and actual analgesic effects measured by pressure pain thresholds.
• To assess the Minto model's performance at low, clinically relevant remifentanil concentrations during conscious sedation.
• To determine if algometry data can improve opioid PK/PD modeling.

Main Methods:

• One hundred patients undergoing gynecological surgery were divided into three groups: remifentanil infusion alone, remifentanil with midazolam, and saline control.
• Remifentanil infusions were targeted at 1.5 ng/mL effect-site concentration.
• Pressure pain thresholds were measured using algometry at various time points, alongside vital signs.

Main Results:

• The Minto model predicted rapid stabilization of effect-site concentrations (within 1.5 minutes).
• While hemodynamics stabilized quickly, pressure pain thresholds showed a delayed analgesic effect, increasing significantly for up to 15 minutes in remifentanil groups.
• Midazolam did not influence the pressure pain threshold, and a new PD model incorporating algometry and the Minto PK model was developed.

Conclusions:

• The Minto PK/PD model exhibits limitations at low remifentanil concentrations, showing a temporal discrepancy between EEG-based predictions and analgesic effects measured by pressure pain thresholds.
• Clinicians should be aware that the onset of remifentanil's analgesic effects may be slower than predicted by the Minto model at lower concentrations.
• Algometry data should be considered for future opioid PK/PD modeling studies to enhance accuracy at clinically relevant concentrations.