Systems and methods for controlled delivery of analgesic and hypnotic agents
Inventors
DUMONT, Guy • Van Heusden, Klaske • Ansermino, Mark
Assignees
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Publication Number
US-12377214-B2
Publication Date
2025-08-05
Expiration Date
Abstract
The invention involves the administration of clinical anesthesia. Particular embodiments provide systems and methods for controlled delivery of a combination of an analgesic agent and a hypnotic agent. More specifically, the invention involves closed-loop control systems/methods for automatically controlling the administration of a combination of a hypnotic agent and an analgesic agent in a clinical anesthesia setting which incorporate feedback based on one or more indirect measures/indicia of analgesia. The invention further includes such control systems/methods that account for limitations of such indirect measures/indicia of analgesia.
Core Innovation
The invention provides a computer-implemented method for controlling a first rate of infusion of a hypnotic agent uP and a second rate of infusion of an analgesic agent uR into a subject. A measure representative of a depth of hypnosis (DOH) is selected from a group of indices consisting of a WAVCNS index or a BIS index, and this DOH measure is used by a computer processor to determine control signals. The control signals are output to a hypnotic agent administration actuator and an analgesic agent administration actuator to inject the agents at respective infusion rates.
The method determines the first control signal for each of a first series of time steps and the second control signal for each of a second series of time steps, wherein determining both control signals is based on the same measure representative of the depth of hypnosis. The first series of time steps is the same as the second series of time steps, and the hypnotic agent control and the analgesic agent control are coordinated using a shared DOH measure.
The invention adds a robust stability design objective for implementing robust stability of the measure representative of depth of hypnosis (DOH) despite non-linear interaction between the hypnotic and analgesic agents. It also includes frequency-domain dominance and amplification criteria that define how the controller response to a hypnotic-agent control signal based on the DOH error is dominant at lower frequencies than the controller response to an analgesic-agent control signal based on the same DOH error.
The frequency-domain partitioning is expressed using low and high frequency ranges of interest and amplification integrals or amplification integral ratio thresholds tied to power spectral densities of control signals and DOH error. The method is directed toward controlled DOH behavior under inter-patient variability and nonlinear drug interaction, while using the DOH index measure as the key feedback basis for both hypnotic and analgesic infusion control.
Claims Coverage
The independent claim is clm-00001. The claim coverage centers on DOH-index-based simultaneous computation of hypnotic and analgesic control signals at the same time steps, and it is further refined in dependents by frequency-domain dominance and amplification and robust-stability requirements, including non-linear interaction robustness.
Doh index-based dual-actuator infusion control at same time steps
Receiving a measure representative of a depth of hypnosis (DOH) of the subject selected from a group of indices consisting of a WAVCNS index or a BIS index, determining a first control signal for each of a first series of time steps to control a first rate of infusion of a hypnotic agent uP and determining a second control signal for each of a second series of time steps to control a second rate of infusion of an analgesic agent uR, wherein determining both control signals are both based on the measure representative of the depth of hypnosis, outputting the first control signal to a hypnotic agent administration actuator at each of the first series of time steps, and outputting the second control signal to an analgesic agent administration actuator at each of the second series of time steps, wherein the first series of time steps is the same as the second series of time steps.
Frequency-domain dominance of hypnotic vs analgesic control responses
Defining that a controller’s response to a hypnotic-agent control signal based on a DOH error is dominant at lower frequencies than the controller’s response to an analgesic-agent control signal based on the same DOH error.
Analgesic amplification threshold using amplification integral ratio
Defining low and high frequency ranges for calculating analgesic-agent amplification where the ratio of an amplification integral over the high-frequency range to the amplification integral over the low-frequency range is at least 20, and defining analgesic-agent amplification AR(ω) based on power spectral density of a second control signal over power spectral density of the DOH error.
Hypnotic amplification constraint using low-frequency amplification integral
Defining low- and high-frequency interest ranges and requiring that an amplification integral of hypnotic-agent amplification over the low-frequency range be greater than or equal to 0.2, where the hypnotic-agent amplification is defined as the ratio of power spectral density of a first hypnotic-agent control signal to power spectral density of the DOH error.
Robust stability of DOH measure despite nonlinear drug interaction
Determining first and second control signals that, when output to a hypnotic-agent administration actuator and an analgesic-agent administration actuator, cause infusion at a first hypnotic infusion rate uP and a second analgesic infusion rate uR to implement robust stability of the measure representative of depth of hypnosis (DOH) despite non-linear interaction between the hypnotic and analgesic agents.
Across the independent claim and indicated refinements, the core coverage is a computer-based method that uses a selected DOH index (WAVCNS or BIS) to determine coordinated hypnotic and analgesic actuator control signals at the same time steps, with additional dependents specifying robust stability against nonlinear interaction and frequency-domain dominance and amplification constraints for hypnotic versus analgesic control responses.
Stated Advantages
Implement robust stability of the measure representative of depth of hypnosis (DOH) despite non-linear interaction between the hypnotic and analgesic agents.
Achieve a frequency-domain dominance relationship where hypnotic-agent control response is dominant at lower frequencies and analgesic-agent control response is dominant at higher frequencies.
Documented Applications
Closed-loop clinical anesthesia control for infusing a hypnotic agent uP and an analgesic agent uR based on a depth of hypnosis (DOH) measure selected from a WAVCNS index or a BIS index.
Controlling infusion behavior to maintain or implement robust stability of the DOH measure despite nonlinear interaction between the hypnotic and analgesic agents.
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