Dexmedetomidine helpful but inadequate alone for sedation (SPICE III)

In a new randomized trial, use of dexmedetomidine (Precedex) as the primary sedative in mechanically ventilated patients in the ICU resulted in no reduction in 90 day mortality. Dexmedetomidine resulted in a small improvement in delirium and ventilator days, but was almost never adequate to sedate patients on its own, and brought a small increase in serious adverse events The findings were reported at a major specialty society conference.

In the SPICE III trial, investigators randomized 4,000 critically ill patients at 74 ICUs in eight countries (not including the U.S.) to receive either dexmedetomidine or usual care (which could include any reasonable sedative, most often propofol). Patients in the "dex" arm were allowed get low-dose propofol early on to achieve initial sedation.

Patients in both groups had 29% all-cause mortality after 90 days of follow-up. Patients receiving dex had slightly less coma/delirium and were off the ventilator one day sooner on average, compared to the usual care group.

Almost the entire dexmedetomidine arm required additional drugs (usually propofol) to reach the goal sedation level of RASS -2 to +1.

Patients receiving dexmedetomidine also had more serious adverse events (2.7% vs. 0.4%): hypotension, bradycardia, and prolonged sinus pause (asystole) occurred at rates 5-10x the control arm (but still less than 1% each).

In a subgroup analysis, younger patients receiving dexmedetomidine had greater mortality than those receiving usual sedation, while older patients on dexmedetomidine had reduced mortality compared to usual sedation; these effects persisted after adjustment for multiple confounders.

Authors concluded,

Dexmedetomidine was insufficient alone or as the primary agent to achieve clinically desired target sedation levels and was associated with more reported adverse events than usual care."

The trial aligned well with results in an earlier phase II trial showing dexmedetomidine prevented ICU delirium in a large proportion of patients, compared to placebo.

Dexmedetomidine has entered wide use because of its lower side effects overall when compared to benzodiazepine infusions, which it has largely replaced at many centers. That success makes it important to understand dexmedetomidine’s limitations and risks, as well.

Source: NEJM