Simulated mid-ranging control of propofol and remifentanil using EEG-measured hypnotic depth of anesthesia

Abstract

Abstract-This paper suggests an extension of an existing, clinically evaluated, closed-loop drug delivery system for hypnotic depth control using propofol. The extension introduces closed-loop administration of the analgesic drug remifentanil, thus forming a multiple input-single output (MISO) control system. Remifentanil acts and is metabolized at a significantly faster time scale than propofol. Direct control of analgesia is hindered by the current absence of a reliable real-time nociception monitor. However, several hypnotic depth monitors respond to nociception. Sudden changes in the measured hypnotic depth are frequently caused by changes in noxious stimulation. The novelty of this work lies in increasing the disturbance rejection bandwidth of the control system for hypnotic depth by directing the high frequency content of its control error to a remifentanil controller. Such a mid-ranging control system was implemented and tuned based on 23 patient models obtained from a previous clinical study and its performance is demonstrated through a simulation study.

Modeling and control of pharmacodynamics

“…Multi-drug regimens can be directly incorporated into these underlying model structures when used for control synthesis. Future efforts for additional modeling and control of anesthesia response, suggested by our results and those of our peers thus include continued construction of multi-drug MIMO models, which could be completed using identification-based techniques, as discussed in this paper; design of multi-objective control strategies such as that considered in [76], for example, feedback control strategies aimed at optimizing dosing and administration of anesthetic agents affecting sedation while simultaneously regulating hemodynamic functions, and further incorporating robustness analysis and design objectives. Additional studies to determine whether central models exist for patient groups, such as specific population groups, is suggested based on our preliminary cross-validation results and some of the anesthetic pharmacodynamics literature [47,71,65,19,54].…”

“…Mortier et al also considered control of sedation level via BIS monitoring in [57], where PK-PD model-based adaptive control of propofol was proposed for surgical settings, and Morley et al investigated the performance of PID based controllers designed based on PK-PD models to control the delivery of both intravenous anesthetics, and volatile anesthetics [56]. Soltesz, van Heusden and colleagues considered robust PID designs to control sedation level and manage pain via the delivery of proposal and remifentanil [76,82]. In an intensive care setting, adaptive and neural network based control designs for the regulation of unconciousness under administration of propofol was considered by Haddad et al in [31].…”

Hybrid Approach for Automatic Drug Dispensing and Control

“…This feedback is known as control variable. To measure depth of anesthesia EEG is often used by anesthetist [8] and [11]. Therefore, a vital sign monitor is used to view the control variable is always required to assist the clinician [4].…”

Controlling the depth of anesthesia by a novel positive control strategy

“…These systems have gained increasing attention in the control literature during the last decades. See for example Farina and Rinaldi [1], Haddad et al [2], Roszak and Davison [3], Roszak and Davison [4],Kaczorek [5], Willems [6], Soltesz et al [7]. In this latter reference, a controller by integral action together with a positivity constraint was proposed, showing that the input is positive provided that the integral gain ' > 0 is chosen su ciently small.…”

“…For instance, the work developed in Soltesz et al [7] presents two controllers in parallel for the DoA of a patient based on a PID controller for the administration of propofol and a proportional controller for the input of remifentanil. Here, we present one single multi-output feedback controller for both drugs.…”