1. In this randomized controlled trial, post-operative scheduled intravenous (IV) acetaminophen combined with propofol or dexmedetomidine reduced risk of post-operative delirium in older patients undergoing cardiac surgery compared to placebo.
2. The combination with IV acetaminophen also significantly reduced delirium duration, ICU length of stay, and breakthrough analgesia compared with placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Delirium is common after cardiac surgery in older patients and is associated with increased length of ICU stay, morbidity, mortality, and long-term cognitive dysfunction. As pain management is an important part of delirium prevention, understanding the effects of different analgesic regimens is essential. In this randomized controlled trial, elderly patients who received IV acetaminophen combined with propofol or dexmedetomidine after cardiac surgery had a significant reduction in delirium compared to those who received placebo. There were no differences between patients receiving dexmedetomidine or propofol. Among the secondary outcomes, acetaminophen use was associated with a significant reduction in delirium duration, ICU length of stay, and breakthrough analgesia. Reduced need for breakthrough analgesia was also found with dexmedetomidine.
Overall, this study suggests that among older patients undergoing cardiac surgery, use of IV acetaminophen combined with dexmedetomidine or propofol is associated with a significant reduction in post-operative delirium. However, this study is limited by its small sample size. Further research will be helpful evaluate the use of IV vs oral acetaminophen as well as other opioid-sparing analgesics in reducing post-operative delirium.
Relevant Reading: Postoperative Delirium: Acute Change with Long-Term Implications
In-Depth [randomized controlled trial]: This study was a randomized, placebo-controlled, factorial clinical trial that was conducted at the Beth Israel Deaconess Medical Center in Boston, Massachusetts, from September 2015 to April 2018. Patients were eligible for inclusion if aged 60 years or older undergoing coronary artery bypass graft surgery with or without aortic and/or mitral valve replacement requiring cardiopulmonary bypass. Computer generated block randomization resulted in 4 cohort combinations for the total 120 patients: acetaminophen and propofol, acetaminophen and dexmedetomidine, placebo and propofol, and placebo and dexmedetomidine. Acetaminophen and placebo were administered within 1 hour of ICU admission and then every 6 hours for 8 doses. During these 48 hours, both groups received opioids and other analgesics per standard of care practices. Dexmedetomidine doses included 0.5 to 1 ug/kg during chest closure, and 0.1 to 1.4 ug/kg per hour for maintenance infusion. Propofol group received maintenance dose of 20 to 100 ug/kg per minute. Primary outcome was incidence of postoperative in-hospital delirium at any time during the hospital stay. Delirium was assessed via Confusion Assessment Method (CAM) or CAM-ICU for intubated patients. Secondary outcomes included duration of delirium, postoperative cognition at discharge, 48-hour breakthrough analgesic requirements, and ICU and hospital lengths of stay. Patients treated with acetaminophen had a significant reduction in delirium (10% vs 28%; p = 0.01). There was no difference between the dexmedetomidine and propofol groups (17% vs 21%; p = 0.54). Significant differences were found for 3 secondary outcomes including delirium duration (median 1 vs 2 days), ICU length of stay (median 29.5 vs 46.7 hours), and breakthrough analgesia (median 322.5 vs 405.3 ug). The dexmedetomidine group was associated with significantly reduced breakthrough analgesia (median 328.8 vs 397.5 ug).
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