title: Protocolized sedation vs usual care in pediatric patients mechanically ventilated for acute respiratory failure: a randomized clinical trial.
abstract: OBJECTIVE
  Protocolized sedation improves clinical outcomes in critically ill adults, but its effect in children is unknown.
  
  
  OBJECTIVE
  To determine whether critically ill children managed with a nurse-implemented, goal-directed sedation protocol experience fewer days of mechanical ventilation than patients receiving usual care.
  
  
  METHODS
  Cluster randomized trial conducted in 31 US pediatric intensive care units (PICUs). A total of 2449 children (mean age, 4.7 years; range, 2 weeks to 17 years) mechanically ventilated for acute respiratory failure were enrolled in 2009-2013 and followed up until 72 hours after opioids were discontinued, 28 days, or hospital discharge.
  
  
  METHODS
  Intervention PICUs (17 sites; n = 1225 patients) used a protocol that included targeted sedation, arousal assessments, extubation readiness testing, sedation adjustment every 8 hours, and sedation weaning. Control PICUs (14 sites; n = 1224 patients) managed sedation per usual care.
  
  
  METHODS
  The primary outcome was duration of mechanical ventilation. Secondary outcomes included time to recovery from acute respiratory failure, duration of weaning from mechanical ventilation, neurological testing, PICU and hospital lengths of stay, in-hospital mortality, sedation-related adverse events, measures of sedative exposure (wakefulness, pain, and agitation), and occurrence of iatrogenic withdrawal.
  
  
  RESULTS
  Duration of mechanical ventilation was not different between the 2 groups (intervention: median, 6.5 [IQR, 4.1-11.2] days; control: median, 6.5 [IQR, 3.7-12.1] days). Sedation-related adverse events including inadequate pain and sedation management, clinically significant iatrogenic withdrawal, and unplanned endotracheal tube/invasive line removal were not significantly different between the 2 groups. Intervention patients experienced more postextubation stridor (7% vs 4%; P = .03) and fewer stage 2 or worse immobility-related pressure ulcers (<1% vs 2%; P = .001). In exploratory analyses, intervention patients had fewer days of opioid administration (median, 9 [IQR, 5-15] days vs 10 [IQR, 4-21] days; P = .01), were exposed to fewer sedative classes (median, 2 [IQR, 2-3] classes vs 3 [IQR, 2-4] classes; P < .001), and were more often awake and calm while intubated (median, 86% [IQR, 67%-100%] of days vs 75% [IQR, 50%-100%] of days; P = .004) than control patients, respectively; however, intervention patients had more days with any report of a pain score ≥ 4 (median, 50% [IQR, 27%-67%] of days vs 23% [IQR, 0%-46%] of days; P < .001) and any report of agitation (median, 60% [IQR, 33%-80%] vs 40% [IQR, 13%-67%]; P = .003), respectively.
  
  
  CONCLUSIONS
  Among children undergoing mechanical ventilation for acute respiratory failure, the use of a sedation protocol compared with usual care did not reduce the duration of mechanical ventilation. Exploratory analyses of secondary outcomes suggest a complex relationship among wakefulness, pain, and agitation.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00814099.
authors.affiliation: School of Nursing and Perelman School of Medicine, University of Pennsylvania, Philadelphia2Critical Care and Cardiovascular Program, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Martha A Q
authors.initials: MA
authors.lastname: Curley
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts4Department of Pediatrics, Harvard Medical School, Boston, Massachusetts5Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: David
authors.initials: D
authors.lastname: Wypij
authors.affiliation: Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, Washington7Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Pittsburgh, Pennsylvania.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Watson
authors.affiliation: Pediatric Critical Care, Primary Children's Hospital, Salt Lake City, Utah.
authors.forename: Mary Jo C
authors.initials: MJ
authors.lastname: Grant
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Asaro
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: Ira M
authors.initials: IM
authors.lastname: Cheifetz
authors.affiliation: Department of Pharmacy, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Dodson
authors.affiliation: University of California at San Francisco School of Nursing, San Francisco.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Franck
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee.
authors.forename: Rainer G
authors.initials: RG
authors.lastname: Gedeit
authors.affiliation: Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Pittsburgh, Pennsylvania.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Angus
authors.affiliation: University of California at San Francisco School of Medicine, San Francisco.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
mesh_terms: D060666:Airway Extubation; D000701:Analgesics, Opioid / Q000008:administration & dosage; D001143:Arousal; D002648:Child; D002675:Child, Preschool; D016292:Procedural Sedation / Q000379:methods*; D016638:Critical Illness; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D015278:Intensive Care Units, Pediatric; D009732:Nursing Care / Q000592:standards; D010146:Pain; D011595:Psychomotor Agitation; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000451:nursing / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives