Control of Drug Administration During Monitored Anesthesia Care

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(P_tcCO2) 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.