Internal jugular veins are the major cerebral venous outflow pathway in supine humans. In upright humans the positioning of these veins above heart level causes them to collapse. An alternative cerebral outflow pathway is the vertebral venous plexus. We set out to determine the effect of posture and central venous pressure (

One of the difficulties in the development of a reliable artificial pancreas for people with type 1 diabetes mellitus (T1DM) is the lack of accurate models of an individual's response to insulin. Most control algorithms proposed to control the glucose level in subjects with T1DM are model-based. Avoiding postprandial hypoglycemia ( 60 mg/dl) while minimizing prandial hyperglycemia ( > 180 mg/dl) has shown to be difficult in a closed-loop setting due to the patient-model mismatch. In this paper, control-relevant models are developed for T1DM, as opposed to models that minimize a prediction error. The parameters of these models are chosen conservatively to minimize the likelihood of hypoglycemia events. To limit the conservatism due to large intersubject variability, the models are personalized using a priori patient characteristics. The models are implemented in a zone model predictive control algorithm. The robustness of these controllers is evaluated in silico, where hypoglycemia is completely avoided even after large meal disturbances. The proposed control approach is simple and the controller can be set up by a physician without the need for control expertise.

SUMMARYThis paper presents a data-driven controller tuning method that includes a set of constraints for ensuring closed-loop stability. The approach requires a single experiment and can also be applied to nonminimum-phase and unstable systems. The tuning scheme generates an estimate of the closedloop output error that is used to minimize an approximation of the model reference control problem. The correlation approach is used to deal with the influence of measurement noise. For linearly parameterized controllers, this leads to a convex optimization problem. A sufficient condition for closed-loop stability is introduced, which can be included in the optimization problem for control design. As the data length tends to infinity, closed-loop stability is guaranteed. The quality of the estimated controller is analyzed for finite data length. The effectiveness of the proposed method is demonstrated in simulation as well as experimentally on a laboratory-scale mechanical setup.

Data-driven controller tuning for model reference control problem is investigated. A new controller tuning scheme for linear time-invariant single-input single-output systems is proposed. The method, which is based on the correlation approach, uses a single set of input/output data from openloop or closed-loop operation. A specific choice of instrumental variables makes the correlation criterion an approximation of the model reference control criterion. The controller parameters and the correlation criterion are asymptotically not affected by noise. In addition, based on the small gain theorem, a sufficient condition for the stability of the closed-loop system is given in terms of the infinity norm of a transfer function. An unbiased estimate of this infinity norm can be obtained as the solution to a convex optimization problem using an infinite number of noise-free data. It is also shown that, for noisy data, the use of the correlation approach can improve significantly the estimate. The effectiveness of the proposed method is illustrated via a simulation example.

This paper describes the design of a robust proportional-integral derivative (PID) controller for propofol infusion in children and presents the results of clinical evaluation of this closed-loop system during endoscopic investigations in children age 6-17. The controller design is based on a set of models that describes the interpatient variability in the response to propofol infusion in the study population. The PID controller is tuned to achieve sufficient robustness margins for the identified uncertainty. 108 children were enrolled in this study, and anesthesia was closed-loop controlled in 102 of these cases. Clinical evaluation of the system shows that closed-loop control of both induction and maintenance of anesthesia in children based on the WAV CNS index as a measure of clinical effect is feasible. A robustly tuned PID controller can accommodate the interpatient variability in children and spontaneous breathing can be maintained in most subjects.

A robust closed-loop system can provide effective propofol administration during induction and maintenance of anesthesia in children. Wide variation in the calculated Ce highlights the limitation of open-loop regimes based on pharmacokinetic/pharmacodynamic models.

A dip in blood pressure (BP) in response to head-up tilt (HUT) or active standing might be due to rapid pooling in the veins below the heart (preload) or muscle activation-induced drop in systemic vascular resistance (afterload). We hypothesized that, in the cardiovascular response to passive HUT, where, in contrast to active standing, little BP dip is observed, features affecting the preload play a key role. We developed a baroreflex model combined with a lumped-parameter model of the circulation, including viscoelastic stress-relaxation of the systemic veins. Cardiac contraction is modeled using the varying-elastance concept. Gravity affects not only the systemic, but also the pulmonary, circulation. In accordance with the experimental results, model simulations do not show a BP dip on HUT; the tilt-back response is also realistic. If it is assumed that venous capacities are steady-state values, the introduction of stress-relaxation initially reduces venous pooling. The resulting time course of venous pooling is comparable to measured impedance changes. When venous pressure-volume dynamics are neglected, rapid (completed within 30 s) venous pooling leads to a drop in BP. The direct effect of gravity on the pulmonary circulation influences the BP response in the first ϳ5 s after HUT and tilt back. In conclusion, the initial BP response to HUT is mainly determined by the response of the venous system. The time course of lower body pooling is essential in understanding the response to passive HUT. baroreflex; cardiovascular system; modeling; tilt table A MODELING APPROACH to the study of the blood circulation and its response to postural changes can provide insight into the underlying physiology. Existing models approximate certain aspects of the circulation and its response to orthostatic stress, but the transients seen on passive head-up tilt (HUT) have proven difficult to capture.Transient response of the cardiovascular system to active standing and passive HUT has been the focus of various studies (3,34,45,47,51,59). The steady-state response to active standing and HUT is usually comparable, but there is a difference in the blood pressure (BP) and heart rate (HR) responses in the first 30 s (Fig. 1). On passive HUT, Rossberg and Martinez (34) found initial increases in HR comparable to the response to active standing. In later studies, however, a BP dip on active standing was reduced (3, 47) or absent (45,51,59) in passive HUT responses. The initial BP dip on standing is thought to be due to a decrease in peripheral resistance resulting from the active part of the maneuver (45). Sprangers et al. (45) point out two mechanisms: 1) the central (autonomic) command that accompanies active muscle contraction and 2) the displacement of large amounts of venous blood to the right atrium by the massive muscle action induced by active standing, eliciting a cardiopulmonary (CP) reflex effect on the systemic circulation. In passive tilt, if abrupt muscle contraction in response to sudden tilt maneuvers is avoided, perip...

Closed-loop control of anesthesia is expected to decrease drug dosage and wake up time while increasing patient safety and decreasing the work load of the anesthesiologist. The potential of closed-loop control in anesthesia has been demonstrated in several clinical studies. One of the challenges in the development of a closed-loop system that can be widely accepted by clinicians and regulatory authorities is the effect of interpatient variability in drug sensitivity. This system uncertainty may lead to unacceptable performance, or even instability of the closed-loop system for some individuals. The development of reliable models of the effect of anesthetic drugs and characterization of the uncertainty is, therefore, an important step in the development of a closed-loop system. Model identification from clinical data is challenging due to limited excitation and the lack of validation data. In this paper, approximate models are validated for controller design by evaluating the predictive accuracy of the closed-loop behavior. A set of 47 validated models that describe the interpatient variability in the response to propofol in children is presented. This model set can be used for robust linear controller design provided that the experimental conditions are similar to the conditions during data collection.