Multicenter clinical trial confirms safety of deep general anesthesia

General anesthesia allows millions of patients to undergo life-saving surgery each year while remaining unconscious and pain-free. But the 176-year-old medical technique involves the use of powerful drugs that raise concerns about their effects on the brain, especially when used in high doses.

New findings published in the Journal of the American Medical Association (JAMA) support previous research, suggesting that anesthesia is no more dangerous to the brain at high doses than at low doses, according to the researchers.

The new study presents the results of a multi-site clinical trial involving more than 1,000 older patients undergoing cardiac surgery at four hospitals in Canada. Researchers at these hospitals, in collaboration with colleagues at Washington University School of Medicine in St. Louis, found that the amount of anesthesia used during surgery did not affect the risk of postoperative delirium, a condition that can contribute to long-term cognitive decline.

“Concerns that general anesthesia is harmful to the brain and causes both early and long-term postoperative cognitive impairment are one of the leading reasons why older adults avoid or delay procedures that improve quality of life,” said Dr. Michael S. Avidan, professor of anesthesiology and chief of the department of anesthesiology at the University of Washington.

"Our new study confirms other compelling evidence that high doses of general anaesthesia are not toxic to the brain. Dispelling the misconception that general anaesthesia causes cognitive impairment would have significant societal implications by helping older people make informed decisions about necessary surgeries, leading to healthier lives."

The dose of anesthesia administered has traditionally been a carefully calculated balance between too little and too much. Giving too little puts patients at risk of intraprocedural awareness. Despite advances in anesthesia care, about one in 1,000 people still experience an involuntary awakening during surgery, unable to move or express their pain or distress. This can lead to suffering and lifelong emotional trauma.

"The good news is that the threatening complication of intraprocedural awareness can be more reliably prevented," said Avidan, the study's senior author.

"Anaesthetists can now confidently administer a sufficient dose of general anaesthesia to achieve a safe level of unconsciousness without fear of damaging their patients' brains. General anaesthetic practice must change based on accumulating encouraging evidence."

Previous small studies have suggested that too much anesthesia may be a cause of postoperative delirium, a neurological problem that includes confusion, altered attention, paranoia, memory loss, hallucinations, and delusions, among other symptoms. This common postoperative complication, affecting about 25% of older patients after major surgery, can be distressing for patients and their families. It is usually temporary, but is associated with longer intensive care unit and hospital stays, other medical complications, permanent cognitive decline, and an increased risk of death.

To study the impact of minimizing anesthesia on postoperative delirium, Avidan and colleagues previously conducted a similar clinical trial involving more than 1,200 elderly surgical patients at Barnes-Jewish Hospital in St. Louis.

The researchers used an electroencephalogram (EEG) to monitor patients' electrical brain activity during major surgeries and adjusted anesthesia levels to prevent suppression of brain activity, which is considered a sign of too much anesthesia. They found that minimizing anesthesia administration did not prevent postoperative delirium.

To expand on the results of his single-hospital clinical trial, Avidan collaborated with Alain Deschamps, MD, professor of anesthesiology at the Université de Montréal in Montreal, and a team of Canadian clinical researchers to conduct a multi-site trial involving patients at four hospitals in Canada—in Montreal, Kingston, Winnipeg and Toronto.

This randomized clinical trial included 1,140 patients undergoing cardiac surgery, which is a high-risk procedure with a high rate of postoperative complications. About half of the patients received brain-based anesthesia, while the other group of patients received conventional treatment without EEG monitoring.

The first group received almost 20% less anesthesia than the second group and also had 66% less time with suppressed electrical activity in the brain, but in both groups, 18% of patients experienced delirium in the first five days after surgery. Moreover, the length of hospital stay, the incidence of medical complications, and the risk of death up to one year after surgery did not differ between patients in the two study groups.

However, nearly 60% more patients in the lower-dose anesthesia group experienced unwanted movements during surgery, which could have negatively impacted the progress of the surgery.

"It was thought that deep general anesthesia overly suppressed the electrical activity of the brain and caused postoperative delirium," Avidan said.

"Taken together, our two clinical trials, involving nearly 2,400 high-risk elderly surgical patients at five hospitals in the U.S. and Canada, dispel concerns that higher doses of general anesthesia carry a neurotoxic risk. Delirium is likely caused by factors other than general anesthesia, such as pain and inflammation associated with surgery.

"Future research should look at other ways to prevent postoperative delirium. But now we can confidently reassure our patients that they can expect to be unconscious, motionless and pain-free during surgical procedures without worrying about general anesthesia damaging their brains."