Department of Anaesthesiology, Vall d'Hebron University Hospital, Barcelona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain.
Functional Imaging Laboratory, German Primate Center (DPZ), Goettingen, Germany.
Br J Anaesth. 2022 Dec;129(6):868-878. doi: 10.1016/j.bja.2022.08.026. Epub 2022 Oct 4.
The Minto remifentanil pharmacokinetic/pharmacodynamic (PK/PD) model is used in target-controlled infusion (TCI) devices. The endpoint used to calculate the PD parameters, including the k, was the electroencephalogram (EEG), which only changes at high remifentanil concentrations. As the k should adequately predict the time course of drug effects at clinically relevant concentrations, we evaluated the temporal agreement between effect-site concentrations estimated with the Minto model and pressure pain thresholds during conscious sedation.
We enrolled 100 patients scheduled for gynaecological surgery. The first group (35 subjects) received an effect site targeted remifentanil infusion (target 1.5 ng ml); the second group (35 subjects) received the same infusion and a 1 mg bolus of midazolam to evaluate anxiolytic effects; the control group (30 subjects) received a saline infusion. Algometry and vital signs were measured at different time points.
The Minto model predicted stable effect-site concentrations within 1.5 min of starting the infusion. Haemodynamic variables stabilised within 5 min, whereas there was a significant increase in pressure pain threshold for up to 15 min in both remifentanil groups. Midazolam had no effect on pressure pain threshold. A PD model based on algometry and Minto PK model was developed.
Our results demonstrate the limitation of the Minto PD model at low target remifentanil concentrations, with a discrepancy in the time course between EEG and pressure pain threshold changes. Clinicians should be aware that the time course of onset of analgesic effects is slower than the estimates of the Minto model. Investigators should consider using algometry data in future opioid PD modelling studies.
Minto 瑞芬太尼药代动力学/药效学（PK/PD）模型用于靶控输注（TCI）装置。用于计算 PD 参数（包括 k）的终点是脑电图（EEG），它仅在高瑞芬太尼浓度下才会发生变化。由于 k 应该能够充分预测在临床相关浓度下药物作用的时间过程，因此我们评估了 Minto 模型估算的效应部位浓度与清醒镇静期间的压力疼痛阈值之间的时间一致性。
我们招募了 100 名计划接受妇科手术的患者。第一组（35 名受试者）接受了靶向效应部位的瑞芬太尼输注（目标 1.5ng/ml）；第二组（35 名受试者）接受了相同的输注和 1mg 咪达唑仑推注，以评估抗焦虑作用；对照组（30 名受试者）接受了生理盐水输注。在不同时间点测量了压痛和生命体征。
Minto 模型在输注开始后 1.5 分钟内预测了稳定的效应部位浓度。血流动力学变量在 5 分钟内稳定下来，而在两个瑞芬太尼组中，压力疼痛阈值在长达 15 分钟的时间内显著增加。咪达唑仑对压力疼痛阈值没有影响。开发了基于压痛和 Minto PK 模型的 PD 模型。
我们的结果表明，在低目标瑞芬太尼浓度下，Minto PD 模型存在局限性，EEG 和压力疼痛阈值变化之间的时间过程存在差异。临床医生应该意识到，镇痛作用的起始时间比 Minto 模型的估计要慢。研究人员在未来的阿片类药物 PD 建模研究中应考虑使用压痛数据。
