Simple measures can reduce post-operative cognitive dysfunction in older patients

Brazilian study published in PLoS One shows benefits of administering anti-inflammatory drug dexamethasone before surgery.

By Karina Toledo  |  Agência FAPESP – Post-operative cognitive dysfunction (POCD), a condition mostly observed in older patients following surgery under general anesthesia, is characterized by impaired memory and concentration. The impairment may be temporary or permanent and incapacitating.

The problem has become more frequent as the population ages and also as a growing number of older adults undergo surgical procedures made possible by more advanced medical technology. Data from the scientific literature suggest a rise in mortality from POCD in the first year after surgery under general anesthesia.

The good news, according to a study published on May 6 by the journal PLoS One, is that two relatively simple measures can help to reduce the incidence of POCD: administering a small dose of the anti-inflammatory drug dexamethasone immediately before an operation and avoiding profound anesthesia during the operation.

Opinions on the adequate depth of anesthesia and the risks of very profound anesthesia currently diverge. Excessively superficial anesthesia is known to incur a risk of patient recall of the procedure, which is undesirable.

“Our findings confirm recent evidence that the deeper the anesthesia-induced hypnosis, the higher the incidence of POCD. The literature points to a link with the systemic inflammatory response induced by surgical trauma, damaging the central nervous system. If so, the use of an anti-inflammatory drug may have a protective effect,” said Maria José Carvalho Carmona, a professor of anesthesiology at the University of São Paulo’s Medical School (FM-USP) and principal investigator for the study.

The study was conducted with FAPESP’s support during the PhD research of Lívia Valentin, the first author of the article.

The researchers evaluated 140 patients aged between 60 and 87 who underwent surgery under propofol-induced general anesthesia at the Central Institute of Hospital das Clínicas, FM-USP’s teaching hospital, in most cases for removal of gallstones.

“We excluded cases of heart and orthopedic surgery, two of the procedures most frequently associated with POCD and hence the most explored in previous research,” Carmona said.

Pre-operative assessment included a battery of tests to measure mental and cognitive status. Patients who failed to achieve a cutoff score were excluded. The remaining subjects were divided randomly into four groups. In the operating room, deep anesthesia typical of major surgical procedures was induced in the first and third groups, and more superficial anesthesia in the second and fourth. Only the third and fourth groups received dexamethasone.

The depth of anesthesia was monitored using bispectral index (BIS) technology, which processes electroencephalogram signals to measure drug-induced unconsciousness. The researchers classified a BIS of 35-45 as deep anesthesia and a BIS of 46-55 as superficial anesthesia.

In the first group (deep anesthesia without dexamethasone), the incidence of POCD on the third day after surgery was 68%, and 25.3% of individuals still displayed impaired cognitive functions after six months.

In the second group (superficial anesthesia without dexamethasone), only 27.2% displayed post-operative POCD, although six months later the proportion had hardly changed (21.7%).

In the third group (deep anesthesia with dexamethasone), the incidence of POCD was 25.2% immediately after surgery but fell to only 3.1% after six months.

In the fourth group (superficial anesthesia with dexamethasone), the incidence of POCD was 15.3% immediately after surgery, but after six months the pre-operative cognitive status was restored in all patients.

“The results reinforce recent evidence of the importance of avoiding deep anesthesia,” Carmona said. “With regard to the use of dexamethasone, more research is needed to confirm our finding, preferably in multicenter trials, but there are strong indications that it can be beneficial in many cases.”

Improving diagnosis

The earliest trials with patients who developed POCD were performed after the 1950s, according to Carmona. Before that, older patients were rarely subjected to major surgery, and significant research in this field has only been conducted for approximately 15-20 years.

“The causes of and risk factors for POCD are still being discussed,” she said. “Little is said about rehabilitation or ways of helping patients recover pre-operative cognitive function.”

One of the obstacles to reliable diagnosis and rehabilitation is a lack of practical and secure instruments for pre- and post-operative cognitive assessment. “The tests available today are either too time consuming or quick but unreliable,” Carmona said. “This makes it hard to follow up on patients.”

According to Valentin, conventional neuropsychological tests are hard to apply and are used exclusively by psychologists who specialize in neuropsychology. “This hinders pre- and post-operative cognitive assessment, especially for multidisciplinary teams that don’t include a neuropsychologist,” she said.

Since she earned her PhD, Valentin has focused on bridging this gap by developing a computer game called MentalPlus in partnership with Izotonic Studios. The game assesses cognitive functions in 25 minutes, whereas a battery of conventional neuropsychological tests can take more than two hours.

In addition to FM-USP, the project involves nine institutions in other countries, including Harvard Medical School (USA), the University of Copenhagen (Denmark), the Sorbonne (France) and Oxford University (UK). The method is being validated by Valentin’s laboratory at FM-USP.

“The game is being validated for use by the general public as a state-of-the-art tool for cognitive assessment,” Valentin said. “It can also help users reorganize impaired cognitive functions. The idea is to put it in the public domain, rather than confining its use to psychologists or neuropsychologists.”