Results for mechanically ventilated adults with sepsis receiving mild sedation were the same regardless of whether they received dexmedetomidine or propofol, according to data from a randomized, double-blind, placebo-controlled study published on- line today in the New England Journal of Medicine.
Dexmedetomidine (alpha2 receptor agonist) and propofol (gamma-aminobutyric acid [GABA] receptor agonist) have similar safety profiles.
The results from the trial Increasing the Efficacy of Sedation and Reducing Neurology Disorders and Mortality in Septic Patients with Severe Respiratory Failure (MENDS2) were published on an accelerated schedule to coincide with the Society for Critical Care Medicine (SCCM) 2021 Critical Care Transport.
Christopher Hughes
Lead author Christopher G. Hughes, MD, head of anesthesiology in emergency care medicine at Vanderbilt University Medical Center in Nashville, Tennessee, said. Medscape Medical News that previous experiments have shown that dexmedetomidine appears to be superior to benzodiazepines, especially in the development of delirium, coma, and airway obstruction. Until this test, the performance of dexmedetomidine in head-to-head comparisons with propofol – the standard care-producing agent – was unclear.
The researchers found that, “despite the theoretical benefits of dexmedetomidine, this did not translate into the clinical field when patients were receiving up-to-date sedation care,” he said..
Current guidelines recommend both drugs when light is needed for adults on ventilators. The drugs differ in the way they affect arousability, immunity, and inflammation, but a comparison of outcomes in adults with sepsis – in terms of living days without brain dysfunction – has never been performed. in a randomized, controlled trial.
In this trial, 422 patients were randomly assigned to receive either dexmedetomidine (0.15 – 1.5 μg per kilogram of body weight per hour) or propofol (5 – 50 μg per kilogram per minute). Doses were adjusted by bedside nurses (who were unrelated) to achieve specific sedation goals.
The main outcome was live days without delirium or coma in the 14 days of intervention. The researchers found no difference between the two groups (modified average, 10.7 vs. 10.8 days; odds ratio [OR], 0.96; 95% CI, 0.74 – 1.26).
There was also little difference in three secondary outcomes: unventilated days (median, 23.7 vs. 24.0 days; OR, 0.98); death at 90 days (38% vs. 39%; risk ratio, 1.06); or the Telephone Interview for Cognitive Status (TICS) Total score measuring global experience at 6 months (modified mean score, 40.9 vs. 41.4; OR, 0.94).
Hughes said the researchers “were particularly associated with a high incidence of disease that would be likely to be affected.”
He said the drugs have different side effects profiles, so a clinician can consider those in deciding between the two, but that either should be good at her. baseline.
The researchers note that at least 20 million patients each year develop sepsis with severe organ failure, and more than 20% receive mechanical ventilation.
Confirmation of current Guidance
Sandra Kane-Gill
Sandra Kane-Gill, PharmD, president of SCCM, said Medscape Medical News she is impressed by the design of the study and said the findings provide definitive confirmation of current guidance.
“The design of the rigorous study is different from previous comparative efficacy tests on the drugs in this group of patients,” she said.
Regarding what clinicians think when choosing one over the other, Kane-Gill said, with dexmedetomidine, there may be more concern about bradycardia, but propofol may be associated with concerns about high triglycerides.
“There may be more comfort in using propofol,” and dexmedetomidine can be more expensive than propofol, she said, so that could be factors in decision-making. also.
Hughes said this study offers a strong insight into post-ICU psychology, which is receiving more and more attention.
“We had a much broader mental battery that we did on patients than in previous studies,” Hughes said, “and it’s important that we didn’t find a difference in the second main experience or in the other mental scores between the two representatives. . “
Registration was completed prior to the pandemic, but he said the results are relevant for COVID-19 patients because those who are ventilated in the ICU are in a sick, septic-shock cohort.
“COVID patients are the type of patients we enrolled in this study,” he said, “with the severity of the illness and disease as well as airway obstruction. We know sedation regimens have been challenging in COVID patients. “
Hughes and Kane-Gill did not disclose any material financial relationships.
Society for Critical Care Medicine (SCCM) 2021 Critical Care Medicine. Presented February 2, 2021.
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News and Nurse.com and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Louis. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.
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