DOSE Trial of Opioid Sparing Effect

Exclusion Criteria

• •1. Previous participation in this study.
• •2. Severe traumatic brain injury as the underlying etiology for critical illness requiring mechanical ventilation or baseline pediatric cerebral performance category (PCPC) \>3.
• •3. Planned receipt of sedatives other than fentanyl or dexmedetomidine.
• •4. Anticipated receipt of neuromuscular blockade for \>48 consecutive hours during the study period.
• •5. Receipt of fentanyl or dexmedetomidine via continuous infusion for \>12 hours in the 24 hours prior to enrollment.
• •6. Extracorporeal life support (including renal replacement therapy, extracorporeal membrane oxygenation, ventricular assist device, etc.) at the time of enrollment.
• •7. Chronic use of or recent overdose of serotonergic agents (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase (MAO) inhibitors, cyclic antidepressants)
• •8. Known pregnancy
• •9. Known liver dysfunction, defined as: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2x the upper limit of normal for age
• •10. Known or impending renal failure defined as: anuria \> or equal to 12 hours prior to enrollment or requiring renal replacement therapy
• •11. High risk children, define as: a. known heart block b. known bradyarrythmia including clinically significant bradycardia (defined as requiring chronotropic agents or cardiac pacing to treat)
• •12. Receipt of mechanical ventilation during an admission for cardiac surgery
• •Note: receipt of drugs other than fentanyl or dexmedetomidine for intubation, and receipt of neuromuscular blockage for intubation, will not be considered exclusionary criteria.