title: An analysis of drug delivery dynamics via a pediatric central venous infusion system: quantification of delays in achieving intended doses.
abstract: BACKGROUND
  Pediatric patients frequently receive continuous infusions of drugs via central venous catheters in the intensive care unit and the operating room. This study characterized drug delivery profiles in a quantitative laboratory model of a standard pediatric central venous infusion system.
  
  
  METHODS
  We evaluated drug delivery via a standard pediatric 8-cm, 4-F double-lumen catheter. One syringe pump infused normal saline as the carrier fluid through a limb of a Y-piece connected to the catheter's 22-gauge distal lumen. Through the other limb of the Y-piece, a second syringe pump infused methylene blue, the model drug, at a constant rate of 0.5 mL/h. The volume delivered was collected every minute for quantitative analysis. We compared 2 mL/h and 12 mL/h total flow rates to mimic volume delivery to a 3-kg infant, and priming of the Y-piece with the model drug, to mimic resumption of a stopped drug infusion, versus no priming, to mimic a new infusion. Drug pump system start-up performance was measured to estimate this factor's contribution to infusion onset profiles.
  
  
  RESULTS
  When initiating a new infusion of the model drug, the time to steady-state delivery at the catheter's end varied significantly among the studied scenarios as measured by the time to reach half of the targeted dose (t(50)). Onset of delivery with a low total flow was much slower (t(50) = 23.5 +/- 2.1 min) than with the high flow rate (t(50) = 15.7 +/- 2.9 min). Priming the drug limb of the connecting Y-piece with methylene blue substantially shortened the time to steady state (low flow t(50) = 12.7 +/- 0.6 min, high flow t(50) = 5.2 +/- 0.8 min). Time to cessation of drug delivery to the end of the catheter after stopping the drug pump was substantially shorter using the high carrier flow rate (t(50) = 3 +/- 0.5 min) compared with the low carrier flow rate (t(50) = 11.6 +/- 0.8 min). Drug pump system start-up performance contributed to onset delay.
  
  
  CONCLUSIONS
  Current infusion techniques in the pediatric care setting can result in significant, unrecognized, and potentially hazardous delays in achieving delivery of intended drug doses to the patient. Total flow rate, priming of the infusion system, the dead volume of the fluid path, and the start-up performance of the infusion pump system contribute to delays in achieving targeted rates of drug delivery.
authors.affiliation: Department of Anesthesia and Critical Care, Massachusetts General Hospital, Jackson 439, 55 Fruit St., Boston, MA 02114, USA.
authors.forename: Karsten
authors.initials: K
authors.lastname: Bartels
authors.forename: David R
authors.initials: DR
authors.lastname: Moss
authors.forename: Robert A
authors.initials: RA
authors.lastname: Peterfreund
mesh_terms: D002405:Catheterization, Central Venous / Q000295:instrumentation; D016503:Drug Delivery Systems / Q000295:instrumentation; D004867:Equipment Design; D006801:Humans; D007231:Infant, Newborn; D007260:Infusion Pumps; D007262:Infusions, Intravenous / Q000295:instrumentation; D008751:Methylene Blue / Q000008:administration & dosage / Q000493:pharmacokinetics; D008954:Models, Biological; D013053:Spectrophotometry; D013594:Syringes
chemical_list: D008751:Methylene Blue