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Preliminary Communication
Caring for the Critically Ill Patient
February 19, 2019

Effect of Intravenous Acetaminophen vs Placebo Combined With Propofol or Dexmedetomidine on Postoperative Delirium Among Older Patients Following Cardiac Surgery: The DEXACET Randomized Clinical Trial

Author Affiliations
  • 1Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
  • 2Department of Medicine, Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
JAMA. 2019;321(7):686-696. doi:10.1001/jama.2019.0234
Key Points

Question  Does postoperative use of scheduled intravenous acetaminophen (paracetamol), combined with intravenous propofol or dexmedetomidine, reduce the risk of postoperative delirium among older patients undergoing cardiac surgery?

Findings  In this randomized clinical trial that included 120 patients undergoing cardiac surgery, scheduled intravenous acetaminophen administered postoperatively for 48 hours, combined with intravenous propofol or dexmedetomidine as a sedative, significantly reduced in-hospital delirium compared with placebo (10% vs 28%, respectively).

Meaning  In older patients undergoing cardiac surgery, postoperative use of scheduled intravenous acetaminophen, combined with intravenous propofol or dexmedetomidine, may be considered to reduce the incidence of postoperative delirium, although additional research is needed.


Importance  Postoperative delirium is common following cardiac surgery and may be affected by choice of analgesic and sedative.

Objective  To evaluate the effect of postoperative intravenous (IV) acetaminophen (paracetamol) vs placebo combined with IV propofol vs dexmedetomidine on postoperative delirium among older patients undergoing cardiac surgery.

Design, Setting, and Participants  Randomized, placebo-controlled, factorial clinical trial among 120 patients aged 60 years or older undergoing on-pump coronary artery bypass graft (CABG) surgery or combined CABG/valve surgeries at a US center. Enrollment was September 2015 to April 2018, with follow-up ending in April 2019.

Interventions  Patients were randomized to 1 of 4 groups receiving postoperative analgesia with IV acetaminophen or placebo every 6 hours for 48 hours and postoperative sedation with dexmedetomidine or propofol starting at chest closure and continued for up to 6 hours (acetaminophen and dexmedetomidine: n = 29; placebo and dexmedetomidine: n = 30; acetaminophen and propofol: n = 31; placebo and propofol: n = 30).

Main Outcomes and Measures  The primary outcome was incidence of postoperative in-hospital delirium by the Confusion Assessment Method. Secondary outcomes included delirium duration, cognitive decline, breakthrough analgesia within the first 48 hours, and ICU and hospital length of stay.

Results  Among 121 patients randomized (median age, 69 years; 19 women [15.8%]), 120 completed the trial. Patients treated with IV acetaminophen had a significant reduction in delirium (10% vs 28% placebo; difference, −18% [95% CI, −32% to −5%]; P = .01; HR, 2.8 [95% CI, 1.1-7.8]). Patients receiving dexmedetomidine vs propofol had no significant difference in delirium (17% vs 21%; difference, −4% [95% CI, −18% to 10%]; P = .54; HR, 0.8 [95% CI, 0.4-1.9]). There were significant differences favoring acetaminophen vs placebo for 3 prespecified secondary outcomes: delirium duration (median, 1 vs 2 days; difference, −1 [95% CI, −2 to 0]), ICU length of stay (median, 29.5 vs 46.7 hours; difference, −16.7 [95% CI, −20.3 to −0.8]), and breakthrough analgesia (median, 322.5 vs 405.3 µg morphine equivalents; difference, −83 [95% CI, −154 to −14]). For dexmedetomidine vs propofol, only breakthrough analgesia was significantly different (median, 328.8 vs 397.5 µg; difference, −69 [95% CI, −155 to −4]; P = .04). Fourteen patients in both the placebo-dexmedetomidine and acetaminophen-propofol groups (46% and 45%) and 7 in the acetaminophen-dexmedetomidine and placebo-propofol groups (24% and 23%) had hypotension.

Conclusions and Relevance  Among older patients undergoing cardiac surgery, postoperative scheduled IV acetaminophen, combined with IV propofol or dexmedetomidine, reduced in-hospital delirium vs placebo. Additional research, including comparison of IV vs oral acetaminophen and other potentially opioid-sparing analgesics, on the incidence of postoperative delirium is warranted.

Trial Registration  ClinicalTrials.gov Identifier: NCT02546765