title: Continuous infusion of clonidine in ventilated newborns and infants: a randomized controlled trial.
abstract: OBJECTIVE
  To assess the influence of an infusion of clonidine 1 μg/kg/hr on fentanyl and midazolam requirement in ventilated newborns and infants.
  
  
  METHODS
  Prospective, double-blind, randomized controlled multicenter trial. Controlled trials.com/ISRCTN77772144.
  
  
  METHODS
  Twenty-eight level 3 German PICUs/neonatal ICUs.
  
  
  METHODS
  Ventilated newborns and infants: stratum I (1-28 d), stratum II, (29-120 d), and stratum III (121 d to 2 yr).
  
  
  METHODS
  Patients received clonidine 1 μg/kg/hr or placebo on day 4 after intubation. Fentanyl and midazolam were adjusted to achieve a defined level of analgesia and sedation according to Hartwig score.
  
  
  RESULTS
  Two hundred nineteen infants were randomized; 212 received study medication, 69.7% were ventilated in the postoperative care and 30.3% for other reasons. Primary endpoint: consumption of fentanyl and midazolam in the 72 hours following the onset of study medication (main observation period) in the overall study population. The confirmatory analysis of the overall population showed no difference in the consumption of fentanyl and midazolam. Explorative age-stratified analysis demonstrated that in stratum I (n = 112) the clonidine group had a significantly lower consumption of fentanyl (clonidine: 2.1 ± 1.8 μg/kg/hr, placebo: 3.2 ± 3.1 μg/kg/hr; p = 0.032) and midazolam (clonidine: 113.0 ± 100.1 μg/kg/hr, placebo: 180.2 ± 204.0 μg/kg/hr; p = 0.030). Strata II (n = 43) and III (n = 46) showed no statistical difference. Sedation and withdrawal-scores were significantly lower in the clonidine group of stratum I (p < 0.001). Frequency of severe adverse events did not differ between groups.
  
  
  CONCLUSIONS
  Clonidine 1 μg/kg/hr in ventilated newborns reduced fentanyl and midazolam demand with deeper levels of analgesia and sedation without substantial side effects. This was not demonstrated in older infants, possibly due to lower clonidine serum levels.
authors.affiliation: 1Department of Neonatology and Pediatric Intensive Care, University of Cologne, Children's Hospital, Köln, Germany. 2Department of Pediatric Cardiology and Congenital Heart Disease, German Heart Center Munich, TUM, München, Germany. 3Department of Pediatric Anesthesia, DRK Children's Hospital, Siegen, Germany. 4Department of Anaesthesiology and Postoperative Intensive Care Medicine, University of Cologne, Köln, Germany. 5Department of Neonatology, University Hospital Halle, Halle, Germany. 6Department of Pediatric Intensive Care, Children's Hospital of the University of Essen, Essen, Germany. 7Department of Pediatrics, Hospital of the University of Leipzig, Leipzig, Germany. 8Department of Pediatrics III, University of Göttingen, Göttingen, Germany. 9Department of Pediatric Anaesthesia, Children's Hospital of the City of Cologne, Köln, Germany. 10Department of Pediatrics, Neonatology and Intensive Care, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany. 11Department of Pediatric Cardiology, German Heart Center of Berlin, Berlin, Germany. 12Department of Pediatrics, Hospital of the University of Freiburg, Freiburg, Germany. 13Department of Pediatrics, Intensive Care, University of Mainz, Mainz, Germany. 14Department of Neonatology, University Hospital of Bonn, Bonn, Germany. 15Department of Therapeutic Drug Monitoring, Institute of Pharmacology, University of Cologne, Köln, Germany. 16Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Köln, Germany. 17Center of Clinical Studies, University of Cologne, Köln, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hünseler
authors.forename: Gunter
authors.initials: G
authors.lastname: Balling
authors.forename: Christoph
authors.initials: C
authors.lastname: Röhlig
authors.forename: Rainer
authors.initials: R
authors.lastname: Blickheuser
authors.forename: Uwe
authors.initials: U
authors.lastname: Trieschmann
authors.forename: Ulla
authors.initials: U
authors.lastname: Lieser
authors.forename: Christian
authors.initials: C
authors.lastname: Dohna-Schwake
authors.forename: Corinna
authors.initials: C
authors.lastname: Gebauer
authors.forename: Oliver
authors.initials: O
authors.lastname: Möller
authors.forename: Fritz
authors.initials: F
authors.lastname: Hering
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoehn
authors.forename: Stephan
authors.initials: S
authors.lastname: Schubert
authors.forename: Roland
authors.initials: R
authors.lastname: Hentschel
authors.forename: Ralf G
authors.initials: RG
authors.lastname: Huth
authors.forename: Andreas
authors.initials: A
authors.lastname: Müller
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller
authors.forename: Gernot
authors.initials: G
authors.lastname: Wassmer
authors.forename: Moritz
authors.initials: M
authors.lastname: Hahn
authors.forename: Urs
authors.initials: U
authors.lastname: Harnischmacher
authors.forename: Julie
authors.initials: J
authors.lastname: Behr
authors.forename: Bernhard
authors.initials: B
authors.lastname: Roth
mesh_terms: D000367:Age Factors; D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D003000:Clonidine / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D012121:Respiration, Artificial / Q000379:methods*; D013375:Substance Withdrawal Syndrome / Q000209:etiology
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D003000:Clonidine; D008874:Midazolam; D005283:Fentanyl