Delay and stability of central venous administration of norepinephrine in children: a bench study

Eur J Pediatr. 2014 Jan;173(1):69-73. doi: 10.1007/s00431-013-2121-5. Epub 2013 Aug 11.


In children, because of the dead volume of the central venous catheter (CVC) and the low flow rate of norepinephrine (NE) infusion, the delay between start-up and effective administration can be adversely long. A theoretical calculation enables to estimate the delay and variations of effective administration. However, numerous factors can hinder this theoretical approach. Herein, we measured via bench testing the actual delay and stability of NE administration kinetics. Using an assembly reproducing our currently-implemented catecholamine administration protocol, diluted NE (200 μg ml(-1)) was infused at an initial rate of 2 ml h(-1) (theoretically 6.67 μg min(-1)) for a period of 24 h. An assay measuring the amount of NE (μg) exiting the CVC was conducted by high-pressure liquid chromatography with colorimetric detection. The theoretical calculation of the delay in administered NE, taking into account a CVC dead volume of 0.3 ml, was 9 min. The measured percentage of the administered dose as a function of time in minutes (M) was M0-M3 (0 %), M3-M6 (0 %), M6-M9 (13 %), M9-M12 (28 %), M12-M15 (70 %), and M15-M18 (100 %) The amount of NE (μg) at fixed rate (2 ml h(-1)) was established at 6.9 ± 0.4 μg min(-1) during the 24 h.

Conclusion: Continuous NE infusion via a CVC at low rate is stable. In children, because of CVC dead volume and low flow rate infusion, the delay in achieving intended dose delivery is significantly longer than that estimated by theoretical calculation. New modalities of initiation of catecholamine infusion adapted to the child are warranted.

MeSH terms

  • Adrenergic alpha-Agonists / administration & dosage*
  • Adrenergic alpha-Agonists / pharmacokinetics
  • Catheterization, Central Venous
  • Child
  • Humans
  • Infusions, Intravenous / methods*
  • Norepinephrine / administration & dosage*
  • Norepinephrine / pharmacokinetics


  • Adrenergic alpha-Agonists
  • Norepinephrine