Coordinated semi‐adaptive closed‐loop control for infusion of two interacting medications

Abstract

SummaryThis paper presents a coordinated and semi-adaptive closed-loop control approach to the infusion of 2 interacting medications. The proposed approach consists of an upper-level coordination controller and a lower-level semiadaptive controller. The coordination controller recursively adjusts the reference targets based on the estimated dose-response relationship of a patient to ensure that they can be achieved by the patient. The semi-adaptive controller drives the patient outputs to the reference targets while estimating the patient's dose-response relationship online. In this way, the controller is resilient to unachievable caregiver-specified reference targets and responsive to the medication needs of individual patients. To establish the proposed approach, we developed the following: (1) a linear two-input-two-output dose-response model; (2) a two-input-two-output semi-adaptive controller to regulate the patient outputs while adapting high-sensitivity parameters in the patient model; and (3) a coordination controller to adjust the reference targets that reconcile caregiver inputs and medication use. The proposed approach was applied to an example scenario in which cardiac output and respiratory rate are regulated via infusion of propofol and remifentanil in an in silico simulation setting. The results show that the coordinated semi-adaptive control could (1) track achievable reference targets with consistent transient and steady-state performance and (2) resiliently adjust the unachievable reference targets to achievable ones.

Real-time Projected Gradient-based Nonlinear Model Predictive Control with an Application to Anesthesia Control

“…Time varying input constraints are required for anesthesia as drug infusion during induction (first 10 minutes) is much higher than during maintenance. The following parameters are used here [37]:…”

Credibility Evidence for Computational Patient Models Used in the Development of Physiological Closed-Loop Controlled Devices for Critical Care Medicine

“…Computational physiological models have been widely used to design and evaluate closed-loop anesthetic delivery systems. The systems control level of consciousness (Elkfafi et al, 1998; Bibian et al, 2006a,b; Dumont et al, 2009; Hahn et al, 2012; Kharisov et al, 2012; Merigo et al, 2017), analgesia (Gentilini et al, 2002; Ionescu et al, 2014), neuromuscular blockade (Zhusubaliyev et al, 2014; Almeida et al, 2017) or combinations of these goals (Fang et al, 2014; Silva et al, 2014; Jin et al, 2018). Additionally a series of studies designed closed-loop propofol delivery with the specific aim of inducing and maintaining pharmacologic burst suppression based on processed EEG signal (Liberman et al, 2013; Westover et al, 2015).…”

“…PCLC devices intended for control of hypnosis delivered propofol and used feedback variables such as bispectral index (BIS) (Kharisov et al, 2012; Merigo et al, 2017), WAVcns (Dumont et al, 2009; Hahn et al, 2012), or auditory evoked response (Elkfafi et al, 1998) to titrate anesthetic agents including propofol and isoflurane. Some studies combined the closed-loop delivery of hypnosis with analgesia leading to closed-loop co-administration of propofol and remifentanil (Ionescu et al, 2014; Jin et al, 2018). Neuromuscular blockade agents such as rocuronium and atracurium were used and controlled using feedback variables based on muscle movement (Silva et al, 2015; Almeida et al, 2017) and in some studies combined with closed-loop hypnosis delivery (Linkens and Mahfouf, 1992; Fang et al, 2014; Silva et al, 2014).…”

“…The authors used such models to build controllers robust to parametric variability and disturbances. Minto et al (2000) and Jin et al (2018) continued the work done by Hahn et al (2012) and designed a coordination controller that recursively adjusts the reference targets based on the estimated dose–response relationship of a patient using a classical PK/PD model of propofol and remifentanil.…”

Physiological closed-loop control in critical care: opportunities for innovations

“…Most prior PCLC systems have been developed with the rather unrealistic assumption that a single PCLC system is recruited in an isolated fashion for patient care, and subsequently, these isolated and independent PCLC systems have been recruited together without much careful account for their interactions [18,21,44,45,47]. In contrast, existing efforts on the development of PCLC systems capable of co-administering multiple treatments simultaneously with explicit account for possible loop-to-loop interactions are relatively rare [62]. More fundamentally, potential adverse events and safety risks associated with the interferences among multiple PCLC systems acting on a patient have been largely neglected, and naturally, innovations to reconcile and harmonize conflicts in therapeutic objectives that can occur during the co-management of multiple PCLC systems (e.g.…”