Prolonged anesthesia significantly alters the synaptic architecture of the brain regardless of age, according to new research. Prolonged anesthesia, also known as medically induced coma, is a life-saving procedure carried out across the globe on millions of patients in intensive medical care units every year.

Unfortunately, after this type of coma, which takes the brain to a state of unconsciousness deeper than short-term anesthesia for surgical procedures, it is common for family members to report that after hospital discharge their loved ones were not quite the same.

It is long known that ICU survivors suffer lasting cognitive impairment, such as confusion and memory loss, that can languish for months and, in some cases, years,

said Michael Wenzel, MD, lead author of the study1.

Covid Patients Will Up Prevalence

Wenzel, a former postdoctoral researcher at Columbia University with experience as a physician in neuro-intensive care in Germany, said reports of post-hospital cognitive dysfunction will likely become even more prevalent because of the significant number of coronavirus patients dependent on ventilators who have taken days or weeks to awake from medically induced comas.

Until now, despite the body of evidence that supports the association between prolonged anesthesia and cognition, the direct effects on neural connections have not been studied, said Rafael Yuste, a professor of Biological Sciences at Columbia and senior author of the paper.

This is because it is difficult to examine the brains of patients at a resolution high enough to monitor connections between individual neurons,

Yuste said.

Miniature ICU

To circumvent the problem, Yuste and Wenzel developed an experimental platform in mice to investigate the connections between neurons, or synapses, and related cognitive effects of prolonged anesthesia.

Inspired by Wenzel’s experience in neuro-intensive care, the researchers established a miniature ICU-like platform for mice. They performed continuous anesthesia for up to 40 hours, many times longer than the longest animal study to date (only six hours).

The researchers performed in vivo two-photon microscopy, a type of neuroimaging that can render live brain structures at micrometer resolution. The technique enabled them to monitor cortical synapses in the sensory cortex, the area of the brain responsible for processing bodily sensations, an approach they combined with repeated assessment of behavior in the cortex.

The results should sound an alarm in the medical community, since they show a physical link between cognitive impairment and prolonged medically induced coma, Wenzel said.

This study is only a pilot in mice, so further study is needed, the researchers said. They added that it will be important to test different, widely used anesthetics, as well as the combination of anesthetics administered to patients. Currently, anesthetics are not individually tailored to patients in a systematic fashion.

We are well aware that anesthesia is a life-saving procedure. Refining treatment plans for patients and developing supportive therapies that keep the brain in shape during prolonged anesthesia would substantially improve clinical outcomes for those whose lives are saved, but whose quality of life has been compromised,

Wenzel said.


  1. Michael Wenzel, Alexander Leunig, Shuting Han, Darcy S. Peterka, Rafael Yuste. Prolonged anesthesia alters brain synaptic architecture. Proceedings of the National Academy of Sciences Feb 2021, 118 (7) e2023676118; DOI:10.1073/pnas.2023676118 ↩︎


For future updates, subscribe via Newsletter here or Twitter