Anesthesiologists could achieve better results with less medication if they had a precise method for managing dosages. This would enable them to maintain the perfect level of unconsciousness while minimizing post-surgery cognitive issues, particularly in vulnerable populations like older adults. However, given their multitude of tasks, such as keeping patients both stable and deeply unconscious, anesthesiologists can't accomplish this without technological help. To tackle this challenge, scientists have created a closed-loop system that uses brain state monitoring to automatically adjust the doses of the anesthesia drug propofol at 20-second intervals.

The advanced closed-loop anesthesia delivery (CLAD) system developed by researchers at MIT (Cambridge, MA, USA) and Massachusetts General Hospital (Boston, MA, USA) tailors propofol dosages by monitoring the brain state of the individual, with the objective of achieving the specific level of unconsciousness required while reducing postoperative side effects. The CLAD system employs real-time feedback from brain state metrics to continuously adjust the administered dose.

The uniqueness of the CLAD system lies in its use of direct, physiologically based brain state indicators to measure unconsciousness. In the operating room, anesthesiologists usually depend on indirect signs like heart rate, blood pressure, and physical immobility. Instead, this research team established a brain-based indicator by recording shifts in neural spiking activity during unconscious states, along with the larger scale rhythms they generate, known as Local Field Potentials (LFPs). By correlating LFP power with these spiking-based measures in animal subjects, they identified that the total LFP power between 20 and 30 Hz serves as a reliable unconsciousness marker.

Additionally, the researchers integrated a physiologically principled model into the system that determines the pharmacokinetics (PK) and pharmacodynamics (PD) of propofol into their system. The model helps to determine both the speed and dosage of the drug needed to change the state of consciousness. The system adjusts the infusion rate every 20 seconds based on the difference between the measured LFP power and the targeted level set by the anesthesiologist, using this PK/PD model to close the gap. Initially, the team conducted computer simulations of the CLAD system under real-world conditions. Then, they carried out nine experiments, each lasting 125 minutes, with two animal subjects. In each case, the system had to maintain the animals at a specific unconsciousness level for various durations. It successfully kept the unconsciousness marker extremely close to the targeted levels during the entire experiment.

However, the researchers admit that more work is required to make the system suitable for human application. One necessary step is shifting the system's foundation to EEGs, which can be measured non-invasively from the scalp. Alongside this, a reliable marker for unconsciousness based on human EEGs must be identified. Additionally, they aim to enhance the system to not only sustain unconsciousness but also to help initiate it and aid in bringing the patient back to consciousness.

“One of the ways to improve anesthesia care is to give just the right amount of drug that’s needed,” said Emery N. Brown, Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience at MIT and an anesthesiologist at MGH. “This opens up the opportunity to do that in a really controlled way.” 

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