6/29/23, 11:45 PM SPICE III Pathway Feedback Search Clinical Topics Home Studies SPICE III SPICE III 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 38.8% female N = 4000 61.2% male 4000 patients (1503 female, 2415 male) Inclusion criteria: critically ill adults 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 g/kg of body weight per hour with a maximum dose of 1.5 g per/kg/hour to achieve a Richmond Agitation Sedation Scale 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 % https://web.pathway.md/studies/receTqmAW4SmrZvDj 1/2 6/29/23, 11:45 PM SPICE III Pathway 14.6 % 7.3 % No significant difference 0.0 % Dexmedetomidine Usual care 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 vs. 3.08; AD 0.06, 95% CI 0.02 to 0.11) Safety outcomes No significant differences in coma or delirium free days, mean score on the European Quality of Life 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 adults 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. Open reference URL https://web.pathway.md/studies/receTqmAW4SmrZvDj 2/2