title: Quantitative analysis of continuous intravenous infusions in pediatric anesthesia: safety implications of dead volume, flow rates, and fluid delivery.
abstract: OBJECTIVE
  Quantitative characterization of continuous pediatric drug infusions.
  
  
  BACKGROUND
  The dynamics of drug delivery by continuous infusion to pediatric patients have not been systematically examined. This study extends previously described analytic models to propofol and remifentanil delivery, focusing on infants and toddlers. We postulated that infusion system dead volume, and drug and carrier flow rates, significantly influence drug delivery.
  
  
  METHODS
  We studied effects of patient weight, infusion system dead volume, drug and carrier flow rates, along with drug stock concentration and dose, on propofol and remifentanil delivery to the circulation. We calculated the drug mass available for inadvertent bolus in the dead volume, the volume of fluid supplied by drug infusions, and model-based estimates of the range of lag times to achieve a targeted steady-state rate of drug delivery.
  
  
  RESULTS
  The drug mass in the dead volume at steady state increased with dead volume size and drug dose. For infants, this drug mass could exceed 100% of commonly used loading doses. Predicted lag times to steady state depend on patient size, fluid flow rates, and the mixing behavior of the drug entering the main fluid pathway. Neonates have the longest lag times to achieve steady state. Fluid quantities delivered by drug infusions increase with drug flow rate and can represent a large fraction of estimated maintenance fluid requirements. Fluid delivery increases if stock drug concentrations are diluted. These relationships were qualitatively similar for propofol and remifentanil.
  
  
  CONCLUSIONS
  Traditional studies focus on drug disposition once a drug enters the circulation. Our analysis shows the potential importance of factors influencing drug delivery to the patient's circulation, focusing on propofol and remifentanil administration to small patients. The drug mass available for inadvertent bolus residing in the reservoir of the dead volume at steady state may be large and clinically relevant. Lag times to achieve steady-state delivery are long, depending on the infusion system's architecture and fluid flow rates. By themselves, drug infusions can deliver significant fluid loads to children. These observations have practical and perhaps safety implications for infusions of drugs commonly administered to infants and children.
authors.affiliation: Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Haobo
authors.initials: H
authors.lastname: Ma
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lovich
authors.forename: Robert A
authors.initials: RA
authors.lastname: Peterfreund
mesh_terms: D000465:Algorithms; D000771:Anesthesia, Intravenous / Q000009:adverse effects; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous / Q000009:adverse effects* / Q000379:methods*; D010880:Piperidines / Q000008:administration & dosage; D015742:Propofol / Q000008:administration & dosage; D000077208:Remifentanil
chemical_list: D018686:Anesthetics, Intravenous; D010880:Piperidines; D000077208:Remifentanil; D015742:Propofol