Peter G. Katona

Apnea of Prematurity: Comparative Therapeutic Effects of Cutaneous Stimulation and Nasal Continuous Positive Airway Pressure.

It has been suggested that idiopathic apnea of prematurity is related to hypoxia from pulmonary instability or an immaturity of central respiratory control mechanisms. To explore these hypotheses, 18 preterm infants were studied to examine the therapeutic effects of prophylactic cutaneous stimulation (6) and continuous positive airway pressure(12). The frequency of apnea using each procedure was reduced by 35 and 69 percent, respectively. These findings constitute the basis for new therapeutic measures for treatment of idiopathic neonatal apnea.

Adaptive Multivarable Drug Delivery: Control of Artenal Pressure and Cardiac Output in Anesthetized Dogs

An adaptive algorithm (CAMAC, control advance moving average controller) to control multiinput/multioutput physiological systems has been implemented and tested. The algorithm is a self-tuning controller that determines the input on the basis of the expected difference between the output and desired output at a time interval equal to or greater than the system dead time. The algorithm was used to simultaneously control mean arterial pressure and cardiac output in anesthetized dogs by the simultaneous computer-controlled infusion of sodium nitroprusside and dobutamine. The results demonstrate the feasibility of using CAMAC for multivariable drug delivery, but they indicate the need for further work before clinical applications are attempted.

Maturation of cardiac control in full-term and preterm infants during sleep

ECG and respiration were recorded from 13 full-term and 8 preterm infants at 2-5 week intervals during sleep at home in the first year of life. Average pulse interval in both quiet and active sleep was minimum at postnatal ages between 4 and 10 weeks, with the minimum during quiet sleep being significantly smaller for preterm (409 +/- 22 (SE) msec) than for full-term (445 +/- 9 msec) infants. The minimum average pulse interval of preterm infants was smaller than the pulse interval of full-term infants at any post-conceptional age, and a smaller average pulse interval and smaller variations in pulse interval in preterm infants during quiet sleep persisted until a postnatal age of 7 months. The pulse interval variations attributable to respiration varied substantially with age. The results indicate that developmental changes in cardiac rate control are functions of both postnatal and post-conceptional age, with the post-conceptional age at birth setting the mean level of pulse interval, a level which is then altered by development linked to postnatal age.

The self-tuning controller: comparison with human performance in the control of arterial pressure

A self-tuning controller was implemented for the automated infusion of sodium nitroprusside to lower mean arterial pressure in anesthetized dogs. The system incorporated a recursive least-squares parameter identifier and a modified minimumvariance controller. The onset delay was estimated on-line, the performance criterion included the cost of control, and requested step-changes were automatically translated into five successive smaller steps to reduce overshoot. The performance of the system in lowering mean arterial pressure was quantitatively compared with that of a well-trained anesthesiologist. In 10 runs in four animals, the automated system performed as well as the physician who devoted 100% of his attention to the task. Since the stability of the self-tuning controller cannot be guaranteed, such a system should be operated only in the presence of appropriate supervisory algorithms.

Cardiorespiratory responses to glutamatergic antagonists in the caudal ventrolateral medulla of rats.

The role of caudal ventrolateral medullary (CVLM) depressor neurons in influencing arterial pressure and ventilation as well as the baroreflex control of arterial pressure was investigated, and the part played by excitatory N-methyl-D-aspartate (NMDA) and non-NMDA receptors in mediating the responses was determined. In urethane-anesthetized, spontaneously breathing rats unilateral microinjections into the caudal depressor area of the broad-band glutamatergic antagonist kynurenic acid (KYN, 5 nmol or 1.58 nmol), or NMDA antagonist 2-amino-5-phosphonovaleric acid (2-APV, 2.7 nmol), or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 0.257 nmol) caused a respiratory arrest within 4 min and the animals had to be artificially ventilated. Respiratory frequency increased on injecting KYN and CNQX while it did not change significantly with 2-APV. Apnea resulted from progressive decrease in tidal volume. During the apnea ventilation with 5% CO2 did not revive breathing. Mean arterial pressure (MAP) increased significantly with KYN and 2-APV injections but not with CNQX. The baroreflex decrease of MAP, elicited by left or right aortic depressor nerve stimulation, was significantly reduced or abolished after bilateral microinjections of all 3 antagonists. Ventilation as well as the baroreflex usually recovered after 1-1.5 h. Microinjections of the same doses of antagonists into the facial nucleus, as well as application of KYN (25 nmol) to the ventral medullary surface above the hypoglossal rootlets, had no significant effect. The results support previous findings that the CVLM neurons of the rat inhibit sympathetic neurons providing the vasomotor tone, and that an intact CVLM is obligatory for mediating the baroreflex decrease of arterial pressure. The results also indicate that: (1) the CVLM is essential for sustaining ventilation in the rat; (2) only NMDA receptors are involved in maintaining baseline blood pressure while both NMDA and non-NMDA receptors mediate the baroreceptor depressor reflex; and (3) both NMDA and non-NMDA receptor activation is necessary to sustain ventilation.

Self-tuning controller for drug delivery systems

A new adaptive control algorithm, the Control Advance Moving Average Controller (CAMAC), was implemented in a drug delivery system to control mean arterial pressure by the infusion of sodium nitroprusside. The CAMAC, which is designed to control non-minimum-phase systems with unknown or varying dead times, is presented here. The control law minimizes a cost function at a time advance which is equal to or greater than the dead time, based upon an assumption that is made on future inputs. By properly tuning the control advance and implementing an estimator with an extended B parameter matrix, the CAMAC can effectively control non-minimum-phase systems with unknown or varying deadtimes. By allowing the control advance to be selected separately (though not independently) for each output in a multivariable system, the CAMAC can decrease the output error for systems where the deadtime for individual input-output pairs may differ. In animal experiments the controller effectively lowered the mean arterial pressur...

Closed Loop Control

In this chapter the use of “closed loop” or “feedback” automated control systems in two areas of clinical medicine is examined: drug delivery systems and functional electrical stimulation of paralysed muscle. These two applications are areas of intense current research in the use of computers in clinical medicine.

Regarding self-tuning controllers for nonminimum phase plants

Abstract This correspondence is in response to the recent excellent survey of Clarke (1984, Automatica , 20, 501–517), which points out that minimum variance self-tuning controllers fail in the control of nonminimum-phase plants. It is also in response to recent algorithms of Ydstie (1984, Preprints 9th IFAC World Congress, Budapest) which have application in the control of such systems. A new control algorithm, designed to control nonminimum-phase plants, is described here. This “Control Advance Moving Average Controller” (CAMAC) determines the input that minimizes the variance between the output and the setpoint at a time advance equal to or greater than the input-output (I/O) transport delay, based upon an assumption made on future inputs. The CAMAC algorithm is tuned by determining the appropriate control time advance. This approach is similar to that of Ydstie (1984, Preprints 9th IFAC World Congress, Budapest), but uses a different assumption on future inputs which yields substantially different controller performance. Its performance (in simulation) compares very favorably with that of self-tuning control algorithms reviewed in Clarke (1984, Automatica 20, 501–517) and those described in Ydstie (1984, Preprints 9th IFAC World Congress, Budapest) in the control of nonminimum-phase plants. Since it is not restricted to controlling the plant at the assumed I/O transport delay, it is also suitable for plants with unknown or time-varying dead times. The CAMAC algorithm has been successfully implemented in the control of mean arterial pressure in anesthetized animals.

Parameter Identification and Adaptive Control for Blood Pressure

Abstract The on-line identification of the defining parameters and the closed-loop adaptive control of the blood pressure response of anesthetized dogs to the infusion rate of a vasoactive drug is considered. The response of mean arterial pressure to the infusion rate of sodium nitroprusside is modelled as a single-input single-output ARMAX process with known delay. Recursive least squares and maximum likelihood techniques are employed for parameter estimation and closed loop control is provided by a minimum variance algorithm. Simulation results and animal experiments indicate that the behavior of the various adaptive controllers is predicted well by theoretical considerations and that the closed loop performance is excellent.

Continuous real-time computation and display of systolic time intervals from surgical patients.

Abstract The noninvasive measurement of systolic time intervals (STI) during surgery is expected to provide a useful index of the status of the patients heart. A PDP-11 based system has been developed to continuously measure and report these intervals in real time. The software has been designed to allow easy implementation of a variety of monitoring tasks, in addition to STI. To accomplish this, a general purpose control program was developed which maintains a multipatient environment and performs all operations which are task independent. Applications modules, specific to the parameters being measured, are called from the control program. For STI, these modules operate on samples of the ECG, carotid pulse, and heart sounds to obtain the onsets of the QRS, systolic upstroke, dicrotic notch, and second heart sound. Every 15 sec, other modules derive mean and standard deviation of the preejection period (PEP), left-ventricular ejection time (LVET), and heart rate. Trend graphs of these parameters are displayed in the operating room. The accuracy of computer-determined STI was evaluated by comparing manual and machine measurements of 250 randomly selected heartbeats. The mean difference between the measurements was less than 1.5 ± 7 (SD) msec.