You are taking care of a 75-year-old female patient scheduled to undergo an elective mitral valve replacement. She has been reading in the news that older patients have a higher risk of delirium. You inform her that your hospital has an enhanced recovery after cardiac surgery (ERACS) pathway that may help reduce the risk of delirium. According to a recent study, which of the following common ERACS pathway medications is MOST likely to decrease the rate of postoperative delirium?

  • (A) Dexmedetomidine
  • (B) Acetaminophen
  • (C) Gabapentin

Postoperative delirium can result in substantial morbidity, including functional decline, cognitive impairment, and mortality. The risk is particularly high among those undergoing cardiac surgery – at a rate ranging from 26%-52% – though much of the current research focuses on patients undergoing noncardiac surgery. A recent study investigated the rate of postoperative delirium in patients undergoing cardiac surgery and whether it decreased with the ERACS pathway.

Enhanced recovery after surgery (ERAS) pathways generally aim to reduce opioid exposure because opioids, along with benzodiazepines, have been associated with postoperative delirium. ERAS pathways use nonopioid analgesics, including acetaminophen and dexmedetomidine, both of which have been previously associated with a reduction in postoperative delirium in noncardiac surgery but have not been extensively studied in the cardiac surgery population.

This single-center study included adult patients undergoing elective cardiac surgery between November 2, 2017, and February 2, 2021, and excluded those undergoing emergency surgery, heart transplants, ventricular assist device placement, placement or removal of mechanical circulatory support devices, and pulmonary endarterectomy, as well as patients who either died or were not admitted to the intensive care unit (ICU) postoperatively. The ERACS pathway involved use of one or more opioid-sparing analgesics, including oral acetaminophen and gabapentin and intraoperative intravenous infusions of ketamine, lidocaine, and dexmedetomidine in any combination deemed appropriate by the anesthesia team. The primary outcome was postoperative delirium determined by the Confusion Assessment Method for the ICU (CAM-ICU), the gold-standard assessment for ICU postoperative delirium. Secondary outcomes were opioids received after surgery in morphine milligram equivalents, rates of acute kidney injury and atrial fibrillation, postoperative ventilation-free days, in-hospital mortality, and ICU and hospital lengths of stay.

Of 1,000 patients who received ERACS medications, 122 (12.2%) experienced postoperative delirium. Of 675 patients who did not receive ERACS medications, 98 (14.5%) experienced postoperative delirium. Although no difference in development of postoperative delirium was shown between the two groups, in analyzing the various medications individually, acetaminophen was found to be associated with decreased postoperative delirium (odds ratio [OR], 0.60; 95% CI, 0.37-0.95). No association was found between delirium reduction and any other individual ERACS medication (gabapentin: OR, 1.36; 95% CI, 0.97-2.21; ketamine: OR, 1.15; 95% CI, 0.72-1.83; lidocaine: OR, 0.86; 95% CI, 0.53-1.37; dexmedetomidine: OR, 0.79; 95% CI, 0.46-1.31).

Associations were found between the use of ERACS medications and hospital length of stay, ICU length of stay, postoperative opioid administration, and postoperative intubation duration, but these associations, per the authors, were not clinically relevant.

In summary, as a whole, the ERACS pathway did not result in a clinically important reduction in the rate of postoperative delirium. However, in analyzing individual medications, acetaminophen was found to have a substantial association with decreased postoperative delirium while oral gabapentin and intraoperative infusions of ketamine, lidocaine, and dexmedetomidine were found to have no association. An association between acetaminophen and reduced postoperative delirium was also present in a 2019 randomized controlled trial (the DEXACET study) that analyzed dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium following cardiac surgery.

Answer: B