Ibuprofen and other NSAIDs may reduce the risk of postoperative delirium

Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, may help reduce patients’ risk of postoperative delirium, according to a study presented at the ANESTHESIOLOGY® 2024 annual meeting.

“Postoperative delirium is a serious complication associated with a risk for health problems and even death after surgery,” said Steven M. Frank, M.D., co-author of the study and a professor in the Department of Anesthesiology and Critical Care Medicine at Johns Hopkins University, Baltimore. “Anesthesiologists use several methods to try to prevent this complication, and our research shows that a simple intervention such as giving patients an NSAID could be another very effective option.”

Postoperative delirium is a change in mental function that can cause confusion and occurs in up to 15% of surgical patients. In certain high-risk patients, such as those with hip fractures, the incidence can be even higher. It is a significant complication in older adults. Pain, age, stress, anxiety and insomnia are known to contribute to the risk for postoperative delirium.

In the study, researchers analyzed a large medical records database to identify patients who had surgery with anesthesia between 2014 and 2023. The researchers grouped patients by age (18-64 and 65 or older) and the medications they received — acetaminophen only, salicylate NSAIDs (e.g., aspirin) only, and non-salicylate NSAIDs (e.g., ibuprofen, ketorolac or celecoxib) only — and compared their rates of delirium over a seven-day period after surgery. Patients received the medications either orally or intravenously on the day of surgery, before or during the procedure. For both age groups, non-salicylate NSAIDs lowered the risk of delirium when compared to acetaminophen and salicylate NSAIDs.

For patients aged 18 to 64:

  • The non-salicylate NSAIDs vs. acetaminophen comparison included a total of 210,678 patients, with 105,339 patients in each group. Overall, patients in this age group who were given non-salicylate NSAIDs had a 22% lower risk for postoperative delirium than those given acetaminophen.
  • The non-salicylate NSAIDs vs. salicylate NSAIDs comparison included a total of 32,538 patients, with 16,269 patients in each group. Overall, patients in this age group who were given non-salicylate NSAIDs had a 70% lower risk for postoperative delirium than those given salicylate NSAIDs.

For patients aged 65 or older:

  • The non-salicylate NSAIDs vs. acetaminophen comparison included a total of 72,130 patients, with 36,065 patients in each group. Overall, patients in this age group who were given non-salicylate NSAIDs had a 33% lower risk for postoperative delirium than those given acetaminophen.
  • The non-salicylate NSAIDs vs. salicylate NSAIDs comparison included a total of 24,960 patients, with 12,480 patients in each group. Overall, patients in this age group who were given non-salicylate NSAIDs had a 45% lower risk for postoperative delirium than those given salicylate NSAIDs.

“Recent studies show acetaminophen helps reduce the risk of postoperative delirium, but our study is the largest to show non-salicylate NSAIDs like ibuprofen could be even better at reducing this risk,” said Dr. Frank. “Our findings suggest that using a non-salicylate NSAID may make surgical procedures safer by reducing postoperative delirium, possibly by using fewer opioids. Although additional research should be done on this topic, our findings are promising.”

Dr. Frank added that all NSAIDs can have side effects, including nausea and vomiting, impaired kidney function, and an increased risk of bleeding or excessive clotting during surgery, which may outweigh the benefit for those at the lowest risk for postoperative delirium, such as younger patients. It’s important to assess a patient’s overall health and risk factors before using NSAIDs to reduce postoperative delirium, he said.

Postoperative delirium can significantly impact recovery by increasing the cost of care, length of hospital stay and risk of more serious outcomes, such as cognitive decline, dementia, decline in physical function, placement in a long-term care facility and death. To reduce these risks, anesthesiologists use various methods, including performing an assessment before surgery to identify those at risk and adjusting their anesthesia plan as needed. During surgery, anesthesiologists monitor anesthesia levels to ensure appropriate sedation and use non-opioid pain medication when possible. After surgery, they monitor patients closely and ensure they are up and walking as soon as possible. Additionally, they talk with the family about how to help prevent their loved one from becoming disoriented by being present by their bedside and ensuring they have any needed hearing aids or eyeglasses.


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