Control of Drug Administration During Monitored Anesthesia Care

Autom. Control Lab., ETH Zurich, Zurich
IEEE Transactions on Automation Science and Engineering (Impact Factor: 2.43). 05/2009; 6(2):256 - 264. DOI: 10.1109/TASE.2008.2009088
Source: IEEE Xplore


Monitored anesthesia care (MAC) is increasingly used to provide patient comfort for diagnostic and minor surgical procedures. The drugs used in this setting can cause profound respiratory depression even in the therapeutic concentration range. Titration to effect suffers from the difficulty to predict adequate analgesia prior to application of a stimulus, making titration to a continuously measurable side effect an attractive alternative. Exploiting the fact that respiratory depression and analgesia occur at similar drug concentrations, we suggest to administer opioids and propofol during MAC using a feedback control system with transcutaneously measured partial pressures of CO2(PtcCO2) as the controlled variable. To investigate this dosing paradigm, we developed a comprehensive model of human metabolism and cardiorespiratory regulation, including a compartmental pharmacokinetic and a pharmacodynamic model for the fast acting opioid remifentanil. Model simulations are in good agreement with ventilatory experimental data, both in presence and absence of drug. Closed-loop simulations show that the controller maintains a predefined CO2 target in the face of surgical stimulation and variable patient sensitivity. It prevents dangerous hypoventilation and delivers concentrations associated with analgosedation. The proposed control system for MAC could improve clinical practice titrating drug administration to a surrogate endpoint and actively limiting the occurrence of hypercapnia/hypoxia.

Download full-text


Available from: Antonello Caruso, May 12, 2014
18 Reads
  • Source
    • "In general, feedback control technologies, and MPC in particular, have started to gain significant attention in the biomedical area [26], [27]. Typical biomedical applications of control methods include the glucose–insulin system in diabetics [28]–[32], anesthesia [26], [33]–[35], anticoagulant administration [36], [37], and HIV [12]–[14], [38]–[40]. In general, any kind of (linear or nonlinear) model, cost function and constraints can be used, although it is often desirable to use linear models, linear constraints, and quadratic (or linear) cost functions. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In this paper, model predictive control (MPC) strategies are applied to the control of human immunodeficiency virus infection, with the final goal of implementing an optimal structured treatment interruptions protocol. The MPC algorithms proposed in this paper use a dynamic model recently developed in order to mimic both transient responses and ultimate behavior, and to describe accordingly the different effect of commonly used drugs in highly active antiretroviral therapy (HAART). Simulation studies show that the proposed methods achieve the goal of reducing the drug consumption (thus minimizing the severe side effects of HAART drugs) while respecting the desired constraints on CD4+ cells and free virions concentration. Such promising results are obtained with realistic assumptions of infrequent (possibly noisy) measurements of a subset of model state variables. Furthermore, the control objectives are achieved even in the presence of mismatch between the dynamics of true patients and that of the MPC model.
    IEEE Transactions on Biomedical Engineering 06/2010; 57(5-57):1040 - 1050. DOI:10.1109/TBME.2009.2039571 · 2.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The ability of anesthetic agents to provide adequate analgesia and sedation is limited by the ventilatory depression associated with overdosing in spontaneously breathing patients. Therefore, quantitation of drug induced ventilatory depression is a pharmacokinetic-pharmacodynamic problem relevant to the practice of anesthesia. Although several studies describe the effect of respiratory depressant drugs on isolated endpoints, an integrated description of drug induced respiratory depression with parameters identifiable from clinically available data is not available. This study proposes a physiological model of CO2 disposition, ventilatory regulation, and the effects of anesthetic agents on the control of breathing. The predictive performance of the model is evaluated through simulations aimed at reproducing experimental observations of drug induced hypercarbia and hypoventilation associated with intravenous administration of a fast-onset, highly potent anesthetic mu agonist (including previously unpublished experimental data determined after administration of 1 mg alfentanil bolus). The proposed model structure has substantial descriptive capability and can provide clinically relevant predictions of respiratory inhibition in the non-steady-state to enhance safety of drug delivery in the anesthetic practice.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 02/2008; 2008:5564-8. DOI:10.1109/IEMBS.2008.4650475
  • [Show abstract] [Hide abstract]
    ABSTRACT: Because propofol is the sedative preferred by gastroenterologists, we focus this review on gastroenterologist-directed propofol sedation, provide simulations of the respiratory depressant effect of different dosing protocols and give a perspective on future developments in computer-assisted sedation techniques. Propofol use by nonanesthesiologists remains a contraindication in the package insert of propofol in most countries. Sedation guidelines produced by the American Society of Gastroenterology partially contradict those produced by the American Society of Anesthesiologists for sedation by nonanesthesiologists, whereas the German guidelines were developed with anesthesiologists involved. The use of fospropofol, recently approved by the US Food and Drug Administration for sedation, is considered an alternative to propofol by some gastroenterologists. Methodological errors in earlier pharmacological studies have to be solved before widespread use of fospropofol is justified, however. Our simulations show that dosing protocols with small boluses administered at reasonable intervals induce less respiratory depression than large boluses. Interindividual variability of propofol-induced respiratory depression is illustrated by different pharmacokinetic and dynamic parameter sets used in the simulation. Two computer-assisted propofol infusion systems are currently being investigated. They not only incorporate the target effect but also the side effects, which may limit respiratory depression. Propofol use by gastroenterologists may be well tolerated if appropriate patient selection, staff training, monitoring and low-dose sedation protocols are applied.
    Current opinion in anaesthesiology 07/2009; 22(4):524-31. DOI:10.1097/ACO.0b013e32832dbb7c · 1.98 Impact Factor
Show more