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Early dexmedetomidine did not reduce 90-day mortality in ICU patients on mechanical ventilation



Dexmedetomidine fell short for reducing 90-day mortality as the primary sedative for patients on mechanical ventilation, according to results of the randomized, controlled, open-label SPICE III trial, which was presented at the annual meeting of the American Thoracic Society and simultaneously published in the New England Journal of Medicine.

“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,” Yahya Shehabi, PhD, of Monash University in Clayton, Australia, and colleagues wrote.

The study was conducted in 74 ICUs in eight countries. Researchers randomly assigned 4,000 patients who were critically ill, had received ventilation for less than 12 hours, and were likely to require mechanical ventilation for at least the next day to either dexmedetomidine or usual care (propofol, midazolam, or another sedative). The sedation goal was a Richmond Agitation and Sedation Scale (RASS) score of –2 (lightly sedated) to +1 (restless), and was assessed every 4 hours. Intravenous dexmedetomidine was administered at 1 mcg/kg of body weight per hour without a loading dose and adjusted to a maximum dose of 1.5 mcg/kg per hour to achieve a RASS score in the target range. Use was continued as clinically required for up to 28 days.

The modified intention-to-treat analysis included 3,904 patients. The 90-day mortality rate was 29.1% (556 of 1,948 patients) for patients who received dexmedetomidine and 29.1% (569 of 1,956 patients) for those who received usual care. There was no significant difference for patients with suspected or proven sepsis at randomization and those without sepsis. Mortality did not vary based on country, cause of death, or discharge destination.

Dr. Shehabi and colleagues noted that, for 2 days after randomization, patients who received dexmedetomidine were also given propofol (64% of patients), midazolam (3%), or both (7%) as supplemental sedation. In the control group, 60% of the patients received propofol, 12% received midazolam, and 20% received both. About 80% of patients in both groups received fentanyl. The use of multiple agents may reflect sedation requirements during the acute phase of critical illness.

With regard to adverse events, the patients receiving dexmedetomidine more commonly experienced bradycardia and hypotension than the usual-care group.

SPICE III was funded in part by a grant from the National Health and Medical Research Council of Australia and the National Heart Institute of Malaysia. Dr. Shehabi reports grants from the National Health and Medical Research Council of Australia, nonfinancial and other support from Pfizer, and nonfinancial and other support from Orion Pharma.

SOURCE: Shehabi Y et al. N Eng J Med. 2019 May 19. doi: 10.1056/NEJMoa1904710.

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