One of the main adverse events faced by elderly patients undergoing surgery is postoperative cognitive dysfunction (POCD). Yet, according to researchers at the University of Sao Paulo, in Brazil, the incidence of POCD appears to be manageable with the addition of dexamethasone to a general anesthetic regimen, especially one that uses light anesthesia.
As reported by Livia S. Valentin, PhD, POCD occurs most commonly in elderly patients, making it a very real issue, given the increasing frequency with which elderly patients are undergoing surgery based on current demographics. To help determine the effect of dexamethasone and depth of anesthesia on POCD after noncardiac surgery, the researchers enrolled 170 patients, aged 60 to 87 years, with American Society of Anesthesiologists performance status I-II, into the prospective, randomized double-blind trial.
The patients underwent general anesthesia that was either deep or light according to the Bispectral Index (35-45 vs. 46-60, respectively). Of these, half received IV dexamethasone 8 mg and the remaining patients did not. Neuropsychological tests were administered preoperatively as well as on days 3, 7, 21, 90 and 180 after surgery; these data were then compared with normative data using Z-score analysis for POCD definition.
“We observed that the group with the highest incidence of cognitive impairment was those receiving the deep anesthesia without dexamethasone,” Dr. Valentin reported at the 2014 annual meeting of the American Society of Anesthesiologists (abstract A2045). Global cognitive function assessments performed on postoperative day 3 revealed that POCD occurred in 68.2% of patients undergoing deep anesthesia and 27.2% of those in the light-anesthesia group. By comparison, 25.2% of deep-anesthesia patients receiving dexamethasone, and 15.3% of those undergoing light anesthesia and receiving dexamethasone experienced POCD (P<0.0001).
“Not surprisingly, the incidence of postoperative cognitive dysfunction decreased during the evaluation period for all groups,” Dr. Valentin said. “Moreover, no patient in the dexamethasone–light anesthesia group presented with postoperative cognitive dysfunction six months after surgery [P<0.0001]. Neuropsychological testing also revealed that dexamethasone with light anesthesia was particularly effective in preserving long-term memory, attention and executive function.
“We conclude that dexamethasone can reduce the incidence of postoperative cognitive dysfunction in noncardiac surgical patients undergoing general anesthesia, especially if the depth of anesthesia is light and the patients are elderly,” Dr. Valentin said. “It remains to be seen why this association exists, and further research is certainly warranted.”
According to Roderic G. Eckenhoff, MD, the Austin Lamont Professor and vice chair for research at the Perelman School of Medicine, at the University of Pennsylvania, in Philadelphia, the rationale for dexamethasone’s ability to mitigate POCD is clear and logical. “It is known that surgery induces peripheral inflammation, and that in many patients this stimulates neuroinflammation as well, causing well-described ‘sickness behavior,’” he said. “This may be ‘early’ POCD, which resolves in most people, but could turn into ‘durable’ POCD in certain subpopulations.
“But if it all starts from inflammation, then a strong anti-inflammatory drug like dexamethasone should block it. The Valentin study supports this idea, but extends it by also implicating anesthesia depth, which has variously been also implicated by other studies. The anesthetic itself could also be important, as some have suggested that certain drugs, such as isoflurane, are worse than others. Unfortunately, single clinical studies are rarely definitive.”
Indeed, as Dr. Eckenhoff pointed out, at least two other trials of dexamethasone were published in 2014, neither of which demonstrated a beneficial effect of the drug on POCD (J Neurosurg Anesthesiol 2014;26:220-225; Anesthesiology 2014;121:492-500). “The bottom line,” he said, “is that sufficient evidence to change practice does not yet exist, and that more research on this important topic is needed.”