Author: Thomas Rosenthal
Dexmedetomidine offers several important advantages for weaning patients off mechanical ventilation in the ICU. But whether the drug is a clear-cut front-runner for these patients—particularly the 15% who prove resistant to such weaning—needs further study, Gilles L. Fraser, PharmD, MCCM, noted during the 2018 annual congress of the Society of Critical Care Medicine (SCCM).
Dexmedetomidine offers theoretical advantages in this setting, said Dr. Fraser, a critical care pharmacist at the Maine Medical Center, in Portland. For example, it “offers anxiolysis, some morphine-sparing properties, and it does not interfere with respiratory drive.”
But dex also has disadvantages, Dr. Fraser explained, such as hemodynamic derangement, and what he called “econotoxicity”—that is, a much higher cost than the other two frequently used choices, benzodiazepines and propofol. The daily acquisition cost is $40 for a benzodiazepine, $120 for propofol and $500 for dexmedetomidine, he noted.
“Dex costs a lot of money,” Dr. Fraser stressed. However, that cost is offset by a savings of $5,000 per day achieved by a reduction in the time patients are mechanically ventilated and in the ICU compared with when benzodiazepines are used, he noted. In addition, he said data indicate that dexmedetomidine is cost-effective compared with midazolam. But “we do not know if the same applies to propofol. I suggest not, since clinical outcomes are similar with dex and propofol.”
7 Years of Data
Some clues into how all of the various drugs for facilitating extubation stack up can be gleaned from a seven-year study of 9,603 episodes of mechanical ventilation lasting longer than two days, presented at SCCM’s 2015 congress and published in Chest (2016;149:1373-1379). The study found that “propofol and dexmedetomidine were associated with less time to extubation compared with benzodiazepines, but dexmedetomidine was also associated with less time to extubation versus propofol,” Dr. Fraser said. The study also found that benzodiazepines and propofol were associated with increased ventilator-associated risks whereas dexmedetomidine was not. However, Dr. Fraser said only 12% of the patients in the study received dexmedetomidine, and most of them had undergone cardiac surgery.
Given those caveats, “is dexmedetomidine the silver bullet to facilitate extubation? It’s absolutely not clear,” Dr. Fraser said. “We use it all the time, but we don’t have any firm data.”
The research gap led Dr. Fraser to only one recommendation: “There is no black and white in the ICU. Everything is gray, and all clinical decisions should be made within the context of the patient at the bedside.”
Nicholas Watson, MD, an anesthesiologist in Grand Rapids associated with Michigan State University College of Human Medicine, agreed that cost needs to be factored into the dexmedetomidine debate. “When caring for a mechanically ventilated patient, it is appropriate to argue that a less costly sedative is optimal,” he commented. “Dr. Fraser broadens this perspective when he reminds us that the cost of ICU care is also affected by the number of days in an ICU and the duration of mechanical ventilation.”
Dr. Watson also agreed with Dr. Fraser’s contention that there are no absolutes in the ICU. “While the literature is sparse, some patients may have shorter duration of mechanical ventilation when sedated with dexmedetomidine. Agitated patients, in particular, should—theoretically—benefit from dexmedetomidine sedation. Until we have additional evidence to help us identify which, if any, patients benefit most from dexmedetomidine, we should be considering patient-specific factors, cumulative cost over ICU duration and theoretical pharmacologic benefits when deciding if dexmedetomidine will best serve a mechanically ventilated patient.”
Dexmedetomidine, while relatively new compared with the two other sedatives, has been around for 20 years. The FDA approved it in 1999 as a short-term (<24 hours) sedative and analgesic for critically ill or injured patients in the ICU. In 2008, the FDA expanded its indication to nonintubatedpatients needing sedation for surgical and nonsurgical procedures.
Where There Is Some Clarity
Although no clear winner has emerged in the search for an optimal drug to facilitate extubation in the ICU, there is a strong consensus on the need for such weaning. CHEST/ATS guidelines on the practice support extubating high-risk patients and then transitioning them to noninvasive mechanical ventilation (Chest 2017;151:160-165). The guidelines also stress the need to minimize the use of sedation for patients who are acutely ill and who have been ventilated for more than 24 hours.