Goal-Directed Sedation in Mechanically Ventilated Infants and Children
Maximizing Efficacy of Goal-Directed Sedation to Reduce Neurological Dysfunction in Mechanically Ventilated Infants and Children Study
Vanderbilt University Medical Center
372 participants
May 10, 2021
INTERVENTIONAL
Conditions
Summary
Ventilated pediatric patients are frequently over-sedated and the majority suffer from delirium, a form of acute brain dysfunction that is an independent predictor of increased risk of dying, length of stay, and costs. Universally prescribed sedative medications-the GABA-ergic benzodiazepines-worsen this brain organ dysfunction and independently prolong duration of ventilation and ICU stay, and the available alternative sedation regimen using dexmedetomidine, an alpha-2 agonist, has been shown to be superior to benzodiazepines in adults, and may mechanistically impact outcomes through positive effects on innate immunity, bacterial clearance, apoptosis, cognition and delirium. The mini-MENDS trial will compare dexmedetomidine and midazolam, and determine the best sedative medication to reduce delirium and improve duration of ventilation, and functional, psychiatric, and cognitive recovery in our most vulnerable patients-survivors of pediatric critical illness.
Eligibility
Inclusion Criteria7
- Patients will be eligible for enrollment if they are 1) aged 44 weeks post-menstrual age and up to 11 years, 2) planned admission to the pediatric ICU at Monroe Carell Jr. Children's Hospital at Vanderbilt (MCJCHV), and 3) requiring mechanical ventilation (MV) and sedation. Pre-pubescent children (\<11 years) are typically different from older children who often behave physiologically more similar to adults. Pre-pubescent children are more likely to be admitted to the PICU and are undergoing a steeper curve of neurocognitive maturation. Therefore, these patients may be at greatest risk for worse brain dysfunction.
- Attending physician refusal
- hour period of eligibility was exceeded before the patient was enrolled
- Legal Authorized Decision Maker (e.g. legal guardian/power of attorney) refusal
- Legal Authorized Decision Maker (e.g. legal guardian/power of attorney) unavailable
- Legal Authorized Decision Maker (e.g. legal guardian/power of attorney) is non-English speaking and available research staff is not proficient and/or translation services are not available in that particular language.
- Adjusted dosing weight is \> 50 kg at time of screening.
Exclusion Criteria12
- Receiving continuous sedation for \> 72 hours prior to screening.
- Rapidly resolving respiratory failure at screening, with planned immediate liberation from MV.
- Severe developmental delay at baseline defined as a score of ≥ 4 (severe disability) on the Pediatric Cerebral Performance Category (PCPC) Scale, referencing cognitive status prior to critical illness.
- Clinically significant 2nd or 3rd degree heart block or bradycardia \< 60 beats per minute.
- Benzodiazepine dependency with ongoing medical requirement of continuous benzodiazepine (infusion).
- Inability to co-enroll with another study.
- Expected death or care plan for withdrawal of support measures within 24 hours of enrollment.
- Bilateral vision loss.
- Deafness that will preclude delirium evaluation.
- Inability to understand English that will preclude delirium evaluation. The inability to understand English in verbal participants will not result in exclusion when the research staff is proficient and/or translation services are actively available in that particular language.
- Documented allergy to either dexmedetomidine or midazolam.
- Medical requirement of continuous (infusion) neuromuscular blockade administration that is planned ongoing for at least 48 hours at time of screening.
Interventions
For patients in the dexmedetomidine group, dose will range from 0.2-2.0 mcg/kg/hr. For example, a 10 kg patient on an infusion of 1 mcg/kg/hr of dexmedetomidine would receive 10 mcg of study drug per hour. This dose range have been selected after literature review and discussions with critical care practitioners, investigational pharmacists, and the mini-MENDS study steering committee.
For patients in the midazolam group, dose will range from 0.025-0.25 mg/kg/hr. For example, a 10 kg patient on an infusion of 0.15 mg/kg/hr of midazolam would receive 1.5 mg of midazolam per hour. This dose range have been selected after literature review and discussions with critical care practitioners, investigational pharmacists, and the mini-MENDS study steering committee.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT04801589