SPICE III (original research)
Trial question
What is the role of early sedation with dexmedetomidine among patients undergoing mechanical ventilation in the ICU?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
38.0% female
62.0% male
N = 3918
3918 patients (1503 female, 2415 male).
Inclusion criteria: critically ill adult patients who had been undergoing ventilation for < 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day.
Key exclusion criteria: age under 18 years, invasive ventilation in the ICU for > 12 hours before enrollment, and suspected or proven acute primary brain injury or spinal cord injury.
Interventions
N=1954 dexmedetomidine (starting intravenous dose of 1 mcg/kg of body weight per hour with a maximum dose of 1.5 mcg/kg/hr to achieve a RASS score in the target range).
N=1964 usual care (propofol, midazolam, or other sedatives, excluding dexmedetomidine, as directed by the treating physician).
Primary outcome
Death from any cause at 90 days
29.1%
29.1%
29.1 %
21.8 %
14.6 %
7.3 %
0.0 %
Dexmedetomidine
Usual
care
No significant
difference ↔
No significant difference in death from any cause at 90 days (29.1% vs. 29.1%; OR 1, 95% CI 0.87 to 1.15).
Secondary outcomes
No significant difference in death at 180 days (31.5% vs. 31.3%; OR 1.01, 95% CI 0.88 to 1.16).
No significant difference in institutional dependency at 180 days (6.7% vs. 7%; OR 0.96, 96% CI 0.73 to 1.27).
Significant increase in mean score on short informant questionnaire on cognitive decline in the elderly at 180 days (3.14 points vs. 3.08 points; AD 0.06 points, 95% CI 0.02 to 0.11).
Safety outcomes
No significant differences in coma or delirium free days, mean score on the European QoL 5-Dimension 3-Level questionnaire.
Significant differences in serious adverse events of bradycardia (0.7% vs. 0.05%), hypotension (0.5% vs. 0.05%), prolonged sinus arrest (0.7% vs. 0.1%).
Conclusion
In critically ill adult patients who had been undergoing ventilation for < 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day, dexmedetomidine was not superior to usual care with respect to death from any cause at 90 days.
Reference
Yahya Shehabi, Belinda D Howe, Rinaldo Bellomo et al. Early Sedation with Dexmedetomidine in Critically Ill Patients. N Engl J Med. 2019 Jun 27;380(26):2506-2517.
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