February 20, 2019
By Will Boggs MD
NEW YORK (Reuters Health) - Intravenous acetaminophen combined with dexmedetomidine or propofol reduces in-hospital delirium after cardiac surgery in older patients, according to results from the DEXACET trial.
"Effective pain management with nonopioid techniques can decrease postoperative delirium, a common and devastating complication seen in the postoperative period in patients 60 and older undergoing cardiac surgery with cardiopulmonary bypass," Dr. Balachundhar Subramaniam from Beth Israel Deaconess Medical Center, Harvard Medical School, in Boston, told Reuters Health by email.
Opioid-based analgesia and perioperative sedation are potential risk factors for delirium, which affects as many as 50% of cardiac surgical patients and is associated with morbidity, mortality and long-term cognitive decline.
Dr. Subramaniam and colleagues investigated the effect of IV acetaminophen versus placebo, combined with IV dexmedetomidine or propofol on the incidence of postoperative delirium in their randomized controlled trial of 120 patients aged 60 years or older undergoing coronary-artery-bypass graft surgery with or without valve replacement requiring cardiopulmonary bypass.
Patients assigned to acetaminophen had a significantly lower incidence of in-hospital delirium, compared with patients assigned to placebo (10% vs. 28%, P=0.01), the researchers report in the February 19 issue of JAMA.
There was no significant difference in the incidence of delirium between patients assigned to dexmedetomidine (17%) and those assigned to propofol (21%).
Patients who received acetaminophen experienced a significantly shorter duration of delirium, a shorter stay at the intensive-care unit and a lower opioid dose in the first 48 hours postoperatively, compared with patients who received placebo.
Duration of delirium and length of the ICU stay did not differ between the dexmedetomidine and propofol groups, but patients who received propofol had a larger total morphine equivalent dose in the first 48 hours postoperatively than did patients who received dexmedetomidine.
Postoperative cognition did not differ between the acetaminophen and placebo groups or between the dexmedetomidine and propofol groups.
In an exploratory analysis, the acetaminophen-dexmedetomidine group had 83% lower odds of developing in-hospital delirium, whereas the acetaminophen-propofol group and the placebo-dexmedetomidine group did not differ significantly in the odds of developing in-hospital delirium.
Adverse events and clinical outcomes did not differ significantly when stratified by randomization group.
"The next step is to duplicate these results in a larger multicenter trial," Dr. Subramaniam said. "Even before that, significant attention will be given to the adequate postoperative pain management following cardiac surgery with minimal opioid use."
Dr. Charles Brown from Johns Hopkins University School of Medicine, in Baltimore, Maryland, who has studied various aspects of postoperative delirium, said the effect size was for acetaminophen was "large and was somewhat surprising."
"Additionally, there have been several studies showing differing results for dexmedetomidine with respect to delirium. The finding of no difference in delirium by sedation strategy is important," he told Reuters Health by email.
"Patients may benefit from postoperative standing acetaminophen for both opioid-sparing effects and for reduction in delirium," said Dr. Brown, who was not involved in the new work. "In this study, they used IV acetaminophen. It is unclear whether IV offers substantial benefit to non-IV administration, which certainly is less costly."
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