Even after being taken off sedation, many Covid-19 patients who had been receiving treatment with mechanical breathing for weeks or months have had trouble regaining consciousness.
New research published in the Proceedings of the National Academy of Sciences proposes that this unusual response could be the result of the brain inducing a hibernation-like condition to protect cells from harm when oxygen is scarce.
A very similar state, characterized by the same signature change in brain rhythms, is observed not only in cardiac arrest patients treated by lowering their body temperature, a method known as “hypothermia,” but also in the painted turtle, which has evolved a form of self-sedation to deal with long periods of oxygen deprivation, or “anoxia,” when it overwinters underwater
According to authors Nicholas D. Schiff and Emery N. Brown, “hypoxia combined with certain therapeutic maneuvers may initiative an as yet unrecognized protective down-regulated state (PDS) in humans that results in prolonged recovery of consciousness in severe COVID-19 patients following cessation of mechanical ventilation and in post-cardiac arrest patients treated with hypothermia.”
In severe Covid-19 patients, they hypothesize that “the specific combination of intermittent hypoxia, severe metabolic stress and GABA-mediated sedation may provide a trigger for the PDS.”
The fact that “burst suppression”—a brain rhythm pattern that is shared by the hibernating painted turtle, Covid-19 patients with extended wakeups following sedation and breathing, and cardiac arrest patients treated with hypothermia—is a motivating observation for the duo’s concept.
In the same journal a decade ago, ShiNung Ching, Brown, and co-authors published a model indicating that burst suppression is an activity pattern indicating that the brain is limiting its energy use when insufficient supplies are available. By doing so, the brain prevents neurons from suffering the harm they could otherwise sustain from striving to function at maximum capacity.
“Biophysical modeling has shown that burst suppression is likely a signature of a neurometabolic state that preserves basic cellular function during states of lowered energy availability,” the authors wrote.
Hours after oxygen becomes limited, the turtles appear to reach this state by rapidly increasing the production of GABA, a neurotransmitter chemical known to decrease neuronal activity in the brain. The energy requirement of brain cells is decreased by this GABA release, also referred to as the “endogenous anesthesia for the anoxic turtle brain’.” The authors see a direct parallel in the fact that GABA-based sedatives are often given to people with Covid.
According to Brown and Schiff, if their theories are true, there may be a two-part, principled method for better bringing Covid patients back from the dead if ventilation is cut off.
The first step is to give Szeto-Schiller peptides, which are small pieces of proteins that are known to help neurons make more of the molecule ATP, which is needed for energy metabolism. This could help the brain cells get back to a more active state and start making energy again.
In the second part, two drugs are needed to restore neural activity and communication by making the neurotransmitters glutamate and acetylcholine more active. This is basically the opposite of what GABA does, which is to slow down neural activity and metabolism.
The findings of the study predict “the existence of a human form of PDS that may underlie prolonged recovery of consciousness following treatment for severe Covid-19 or treatment for post-cardiac arrest treated with hypothermia,” according to the authors. “The possible existence of human PDS suggests many testable hypotheses for further investigation and the possibility of developing novel therapeutic strategies.”
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