Conference Coverage

Dexmedetomidine: ‘Silver bullet’ for ventilator liberation?


 

EXPERT ANALYSIS FROM CCC47

– Among medications to facilitate extubation, dexmedetomidine offers favorable attributes, but whether it’s the best choice for patients who have difficulty being liberated from the ventilator remains to be proven, said Gilles L. Fraser, BS Pharm, PharmD.

The current CHEST/ATS guidelines on liberation from mechanical ventilation in critically ill adults strongly suggest extubation to noninvasive mechanical ventilation in high-risk patients (Chest. 2017 Jan;151[1]:160-5. doi: 10.1016/j.chest.2016.10.037). Guideline authors also suggested protocols attempting to minimize sedation for acutely hospitalized patients ventilated for more than 24 hours, based on some evidence showing a trend toward shorter ventilation time and ICU stay, as well as lower short-term mortality.

“Is dexmedetomidine the silver bullet to facilitate extubation? It’s absolutely not clear,” said Dr. Fraser, one of the coauthors of the guidelines, during his presentation at the Critical Care Congress sponsored by the Society for Critical Care Medicine.

“I’ll leave you up to your own devices,” he told attendees at a session on conundrums in critical care that are not addressed in current guidelines. “We use it all the time, frankly, but I don’t have any firm data to support that contention.”

Despite best practices, extubation attempts are not always successful: “If you follow the rules of the road, success is going to occur about 85% of the time,” said Dr. Fraser, who is a clinical pharmacist at Maine Medical Center, Portland, and professor of medicine at Tufts University, Boston. “That means that about 15% of our patients have difficulties in being liberated from the ventilator.”

In terms of medications to facilitate ventilator liberation, benzodiazepines, dexmedetomidine, and propofol all have roles to play, according to Dr. Fraser. Clinicians have to consider agent-specific side effects, pharmacokinetics and dynamics, and “econotoxicity,” or the cost of care, he added.

Although there are few comparative data available to guide choice of medication, Dr. Fraser and his colleagues have published a systematic review and meta-analysis of randomized trials of benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adult patients (Crit Care Med. 2013 Sep;41[9 Suppl 1]:S30-8. doi: 10.1097/CCM.0b013e3182a16898).

They found that dexmedetomidine- or propofol-based sedation regimens appeared to reduce mechanical ventilation duration and length of ICU stay versus benzodiazepine-based sedation, but they stated that larger controlled studies would be needed to further define outcomes in this setting.

More recently, other investigators reported an evaluation of 9,603 consecutive mechanical ventilation episodes (Chest. 2016 Jun;149[6]:1373-9. doi: 10.1378/chest.15-1389). In this large, real-world experience, propofol and dexmedetomidine were both associated with less time to extubation versus benzodiazepines, and dexmedetomidine was associated with less time to extubation versus propofol.

Relatively few patients (about 12%), however, received dexmedetomidine in that large series, and that was mostly in the setting of cardiac surgery, Dr. Fraser noted. Moreover, the investigators reported finding no differences between any two agents in hospital discharge or mortality hazard ratio.

“We’re not suggesting the benzodiazepines as routine sedative agents in our patient populations,” Dr. Fraser said in his presentation. “The primary reason is that they result in a longer time on the vent, typically between 1 and 2 days.”

But this doesn’t mean that the benzodiazepines are the “devil’s handiwork,” he added, noting that they may be useful in patients with anxiety related to ventilator weaning and those recovering from hemodynamic instability or at risk for GABA-agonist withdrawal.

Dexmedetomidine is opioid sparing and has a minimal effect on respiratory drive, among other advantages; however, some potential drawbacks include its hemodynamic effects and its cost, according to Dr. Fraser.

Dr. Fraser said that his institution’s daily acquisition cost for dexmedetomidine is $500, compared with $120 for propofol and $40 for benzodiazepines, but some pharmacoeconomic evaluations suggest use of dexmedetomidine may actually save between $3,000 and $9,000 per ICU admission. “At least in our place, one day in the ICU costs about $5,000, so that all makes sense … and I can argue fairly effectively that dexmedetomidine really isn’t that expensive compared to midazolam,” he said.

Dr. Fraser said that he had no disclosures related to his presentation.

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