title: A randomized controlled trial of daily sedation interruption in critically ill children.
abstract: OBJECTIVE
  To compare daily sedation interruption plus protocolized sedation (DSI + PS) to protocolized sedation only (PS) in critically ill children.
  
  
  METHODS
  In this multicenter randomized controlled trial in three pediatric intensive care units in the Netherlands, mechanically ventilated critically ill children with need for sedative drugs were included. They were randomly assigned to either DSI + PS or PS only. Children in both study arms received sedation adjusted on the basis of validated sedation scores. Provided a safety screen was passed, children in the DSI + PS group received daily blinded infusions of saline; children in the PS group received blinded infusions of the previous sedatives/analgesics. If a patient's sedation score indicated distress, the blinded infusions were discontinued, a bolus dose of midazolam was given and the 'open' infusions were resumed: DSI + PS at half of infusion rate, PS at previous infusion rate. The primary endpoint was the number of ventilator-free days at day 28. Data were analyzed by intention to treat.
  
  
  RESULTS
  From October 2009 to August 2014, 129 children were randomly assigned to DSI + PS (n = 66) or PS (n = 63). The study was terminated prematurely due to slow recruitment rates. Median number of ventilator-free days did not differ: DSI + PS 24.0 days (IQR 21.6-25.8) versus PS 24.0 days (IQR 20.6-26.0); median difference 0.02 days (95 % CI -0.91 to 1.09), p = 0.90. Median ICU and hospital length of stay were similar in both groups: DSI + PS 6.9 days (IQR 5.2-11.0) versus PS 7.4 days (IQR 5.3-12.8), p = 0.47, and DSI + PS 13.3 days (IQR 8.6-26.7) versus PS 15.7 days (IQR 9.3-33.2), p = 0.19, respectively. Mortality at 30 days was higher in the DSI + PS group than in the PS group (6/66 versus 0/63, p = 0.03), though no causal relationship to the intervention could be established. Median cumulative midazolam dose did not differ: DSI + PS 14.1 mg/kg (IQR 7.6-22.6) versus PS 17.0 mg/kg (IQR 8.2-39.8), p = 0.11.
  
  
  CONCLUSIONS
  In critically ill children, daily sedation interruption in addition to protocolized sedation did not improve clinical outcome and was associated with increased mortality compared with protocolized sedation only.
authors.affiliation: Intensive Care, Erasmus MC - Sophia Children's Hospital, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands. n.vet@erasmusmc.nl.|Department of Pediatrics, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands. n.vet@erasmusmc.nl.
authors.forename: Nienke J
authors.initials: NJ
authors.lastname: Vet
authors.affiliation: Intensive Care, Erasmus MC - Sophia Children's Hospital, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.|Department of Pediatric Surgery, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Saskia N
authors.initials: SN
authors.lastname: de Wildt
authors.affiliation: Intensive Care, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Carin W M
authors.initials: CW
authors.lastname: Verlaat
authors.affiliation: Divison of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands.|Clinical Pharmacy, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Catherijne A J
authors.initials: CA
authors.lastname: Knibbe
authors.affiliation: Intensive Care, Erasmus MC - Sophia Children's Hospital, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.|Department of Pediatric Surgery, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Miriam G
authors.initials: MG
authors.lastname: Mooij
authors.affiliation: Intensive Care, AMC, Emma Children's Hospital, Amsterdam, The Netherlands.
authors.forename: Job B M
authors.initials: JB
authors.lastname: van Woensel
authors.affiliation: Department of Biostatistics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: van Rosmalen
authors.affiliation: Intensive Care, Erasmus MC - Sophia Children's Hospital, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.|Department of Pediatric Surgery, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.affiliation: Intensive Care, Erasmus MC - Sophia Children's Hospital, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: de Hoog
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003422:Critical Care / Q000379:methods*; D016638:Critical Illness; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D007223:Infant; D007231:Infant, Newborn; D015278:Intensive Care Units, Pediatric; D008297:Male; D008874:Midazolam / Q000008:administration & dosage*; D009426:Netherlands; D013997:Time Factors
chemical_list: D006993:Hypnotics and Sedatives; D008874:Midazolam
keywords: Clinical pharmacology; Critical illness; Interruption; Pediatrics; Sedation