In this episode, I’ll discuss an article about using dexmedetomidine in critically ill patients. This trial turned out to be a negative trial which can sometimes be as instructive as a positive one. In this case, it turned out to be a study in how not to use dexmedetomidine.
Lead author: Yahya Shehabi
Published in New England Journal of Medicine May 2019
Dexmedetomidine is an alpha-2 agonist sedative agent. Recent SCCM guidelines give an equal weighting towards recommending either propofol or dexmedetomidine as first-line sedation for critically ill patients. Like propofol, dexmedetomidine is known to cause bradycardia and hypotension. Unlike propofol, dexmedetomidine provides sedative effects without respiratory depression. As the use of dexmedetomidine as the sole or primary sedative agent in mechanically ventilated patients has not been extensively studied, the authors sought to add to the body of knowledge on this topic.
The study was an open-label, randomized trial. Critically ill patients needed to have been ventilated for less than 12 hours with an expected need for ventilation to be beyond the next calendar day to be included in the study. Patients received either dexmedetomidine as the sole or primary sedative or usual care which included propofol, midazolam, or other sedatives.
A target RASS of -2 to +1 was used in the study and the primary outcome was all-cause mortality at 90 days.
A total of 4000 patients were enrolled evenly between the 2 groups, but a modified intent to treat analysis was performed because 96 patients withdrew consent or were lost to follow-up.
The primary outcome occurred in 29.1% in both groups.
To achieve the intended level of sedation of RASS -2 to +1, 74% of the patients in the dexmedetomidine group needed either propofol, midazolam, or both at some point in the first 2 days after being randomized.
The usual care group received propofol alone 60% of the time, midazolam alone 12% of the time, and both propofol and midazolam 20% of the time.
Bradycardia and hypotension were found to be more common in the dexmedetomidine group.
The authors concluded:
Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group.
In my practice, it has always been apparent that dexmedetomidine alone cannot be counted on as the sole agent for many critically ill patients. This study reinforces this notion, as almost three-quarters of patients who got dexmedetomidine needed another sedative.
This is not to say that dexmedetomidine does not deserve its first-line ranking in the SCCM sedation guidelines. Rather, I take this study as confirmation that when dexmedetomidine is ordered, additional plans for sedatives should be made so that the nurse has the tools needed to maintain adequate sedation for the patient. This may include a significant dose of fentanyl, possibly as a continuous infusion given with dexmedetomidine, or as needed doses of midazolam.
The most disappointing part of this study for me was the lack of detail regarding adverse effects presented in the main article. I had to go into the supplemental appendix to find the exact incidence rates of bradycardia and hypotension for each group. Bradycardia occurred in 5.1% vs 0.5% of patients in the dexmedetomidine vs usual care groups, and hypotension occurred in 2.7% vs 0.5% of patients in the dexmedetomidine vs usual care groups.
Members of my Hospital Pharmacy Academy have access to in-depth, practical training on the use of dexmedetomidine and other sedatives including propofol, ketamine, benzodiazepines and opioids in the ICU. To get immediate access to these and other resources go to pharmacyjoe.com/academy.
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