title: Robust closed-loop control of induction and maintenance of propofol anesthesia in children.
abstract: BACKGROUND
  During closed-loop control, a drug infusion is continually adjusted according to a measure of clinical effect (e.g., an electroencephalographic depth of hypnosis (DoH) index). Inconsistency in population-derived pediatric pharmacokinetic/pharmacodynamic models and the large interpatient variability observed in children suggest a role for closed-loop control in optimizing the administration of intravenous anesthesia.
  
  
  OBJECTIVE
  To clinically evaluate a robustly tuned system for closed-loop control of the induction and maintenance of propofol anesthesia in children undergoing gastrointestinal endoscopy.
  
  
  METHODS
  One hundred and eight children, aged 6-17, ASA I-II, were enrolled. Prior to induction of anesthesia, NeuroSENSE™ sensors were applied to obtain the WAVCNS DoH index. An intravenous cannula was inserted and lidocaine (0.5 mg·kg(-1) ) administered. Remifentanil was administered as a bolus (0.5 μg·kg(-1) ), followed by continuous infusion (0.03 μg·kg(-1) ·min(-1) ). The propofol infusion was closed-loop controlled throughout induction and maintenance of anesthesia, using WAVCNS as feedback.
  
  
  RESULTS
  Anesthesia was closed-loop controlled in 102 cases. The system achieved and maintained an adequate DoH without manual adjustment in 87/102 (85%) cases. Induction of anesthesia (to WAVCNS  ≤ 60) was completed in median 3.8 min (interquartile range (IQR) 3.1-5.0), culminating in a propofol effect-site concentration (Ce ) of median 3.5 μg·ml(-1) (IQR 2.7-4.5). During maintenance of anesthesia, WAVCNS was measured within 10 units of the target for median 89% (IQR 79-96) of the time. Spontaneous breathing required no manual intervention in 91/102 (89%) cases.
  
  
  CONCLUSIONS
  A robust closed-loop system can provide effective propofol administration during induction and maintenance of anesthesia in children. Wide variation in the calculated Ce highlights the limitation of open-loop regimes based on pharmacokinetic/pharmacodynamic models.
authors.affiliation: Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: West
authors.forename: Guy A
authors.initials: GA
authors.lastname: Dumont
authors.forename: Klaske
authors.initials: K
authors.lastname: van Heusden
authors.forename: Christian L
authors.initials: CL
authors.lastname: Petersen
authors.forename: Sara
authors.initials: S
authors.lastname: Khosravi
authors.forename: Kristian
authors.initials: K
authors.lastname: Soltesz
authors.forename: Aryannah
authors.initials: A
authors.lastname: Umedaly
authors.forename: Eleanor
authors.initials: E
authors.lastname: Reimer
authors.forename: J Mark
authors.initials: JM
authors.lastname: Ansermino
mesh_terms: D000293:Adolescent; D000465:Algorithms; D000762:Anesthesia Recovery Period; D000769:Anesthesia, Inhalation; D000771:Anesthesia, Intravenous / Q000295:instrumentation* / Q000379:methods*; D018686:Anesthetics, Intravenous / Q000097:blood / Q000493:pharmacokinetics; D002648:Child; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D004569:Electroencephalography; D004724:Endoscopy; D004867:Equipment Design; D005260:Female; D006801:Humans; D007267:Injections / Q000009:adverse effects; D008297:Male; D016343:Monitoring, Intraoperative / Q000295:instrumentation / Q000379:methods; D010146:Pain / Q000209:etiology / Q000517:prevention & control; D015742:Propofol / Q000097:blood / Q000493:pharmacokinetics; D015656:Respiratory Mechanics / Q000502:physiology; D016896:Treatment Outcome; D014584:User-Computer Interface
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol
keywords: anesthetics; automation; drug delivery systems/methods; electroencephalography/drug effects; intravenous/administration & dosage; propofol/administration & dosage; software