Key points:
- The development of an advanced closed-loop anesthesia delivery system that monitors brain state to tailor propofol dose could reduce post-op side effects.
- In experiments, the system enabled more than 18 hours of fine-grained consciousness control over the course of nine anesthesia sessions with two animal subjects.
- Researchers are now looking into how to ready the system for possible human use.
Researchers at MIT and Massachusetts General Hospital have invented a closed-loop system based on brain state monitoring that accurately controls unconsciousness by automating doses of the anesthetic drug propofol every 20 seconds.
In the operating room, the practice of maintaining dose rather than consciousness level is common because most anesthesiologists are not trained to track brain states and often don’t have the time to precisely manage dosing. This is where a closed-loop anesthesia delivery (CLAD) system can help.
A foundation of the CLAD technology is that it employs a physiologically principled readout of unconsciousness from the brain (in the OR, anesthesiologists typically rely on indirect markers such as heart rate, blood pressure and immobility). The researchers established their brain-based marker by measuring changes in neural spiking activity amid unconsciousness in the animals and the larger scale rhythms that spiking produces, called local field potentials (LFPs). By closely associating LFP power with spiking-based measures of unconsciousness in the animal subjects, they were able to determine that the total power of LFPs between 20 and 30 Hz is a reliable marker.
The researchers also built into the system a physiologically principled model of the pharmacokinetics (PK) and pharmacodynamics (PD) of propofol, which determines how much drug is needed to alter consciousness and how fast a given dose will have that effect. In the study they show that by coupling the model with the unconsciousness marker they could quickly tune the model for each subject.
To manage propofol dosing, every 20 seconds a “linear quadratic integral” controller determines the difference between the measured 20-30 Hz LFP power and the desired brain state (set by the anesthesiologist) and uses the PK/PD model to adjust the infusion of medicine to close the gap.
In their paper, published in PNAS Nexus, the team demonstrates that the system enabled more than 18 hours of fine-grained consciousness control over the course of nine anesthesia sessions with two animal subjects. In each case the CLAD had to bring the animals to a precise state of unconsciousness for 45 minutes, change to a different level for another 40 minutes, and then bring them back to the original level for 40 more minutes. In every session the system kept the marker very close to the goal levels throughout the duration of the testing.
Next, to ready the system for possible human use, the researchers intend to base the system on EEGs, as well as determine a marker of unconsciousness based on EEG measurements of human brain rhythms, rather than animal LFPs. The team also wants to extend the system’s capabilities so that it not only maintains unconsciousness, but also helps induce it and helps bring patients back to wakefulness.