Multicenter clinical trial confirms safety of deep general anesthesia

General anesthesia allows millions of patients each year to undergo life-saving operations while remaining unconscious and pain-free. However, this medical method, which has been used for 176 years, involves the use of powerful drugs that raise concerns about their effects on the brain, especially when used in high doses.

The new findings, published in the Journal of the American Medical Association (JAMA), confirm previous research, indicating that anesthesia is no more harmful to the brain when higher doses than low doses, according to the researchers.

The new study presents results from a multidisciplinary clinical trial involving more than 1,000 elderly patients undergoing cardiac surgery at four Canadian hospitals. Researchers from these hospitals, in collaboration with colleagues from 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 post-operative cognitive impairment are one of the main reasons older people avoid or delay quality of life procedures,” said Dr. Michael S Avidan, professor of anesthesiology and chairman of the department of anesthesiology at the University of Washington.

“Our new study adds to other compelling evidence that high doses of general anesthesia are not toxic to the brain. Dispelling the erroneous and common belief that general anesthesia causes cognitive impairment will have a significant societal impact in helping older adults make smart decisions about necessary surgeries, which will help them maintain healthier lives."

The dose of anesthesia administered has traditionally been a carefully calculated balance between too little and too much. Administering an insufficient dose puts patients at risk for intraprocedural awareness. Despite advances in anesthetic care, around one in 1,000 people still experience unintentional awakening during surgery, unable to move or express their pain or stress. 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, senior author of the study.

“Anesthesiologists can now confidently administer a sufficient dose of general anesthesia, ensuring a safe level of unconsciousness, without fear of damaging their patients' brains. Practice in general anesthesia 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 approximately 25% of older patients after major surgery, can be a cause of concern 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 effects 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.

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

To expand on the results of its 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 multidisciplinary trial involving patients at four Canadian hospitals—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. Approximately half of the patients received brain activity-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, length of hospital stay, incidence of medical complications, and 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 group that received the lower dose of anesthesia experienced unwanted movements during surgery, which could negatively affect the progress of the operations.

“Deep general anesthesia was thought to excessively suppress electrical activity in the brain and cause postoperative delirium,” Avidan said.

“Taken together, our two clinical trials involving nearly 2,400 high-risk elderly surgical patients at five hospitals in the US and Canada debunk 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 explore other ways to prevent postoperative delirium. But we can now 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 brain."