Practicalities of Total Intravenous Anesthesia and Target-controlled Infusion in Children

Brian J. Anderson, Ph.D., F.A.N.Z.C.A., F.C.I.C.M.; Oliver Bagshaw, M.B.Ch.B., F.R.C.A.


Anesthesiology. 2019;131(1):164-185. 

In This Article

Abstract and Introduction


Propofol administered in conjunction with an opioid such as remifentanil is used to provide total intravenous anesthesia for children. Drugs can be given as infusion controlled manually by the physician or as automated target-controlled infusion that targets plasma or effect site. Smart pumps programmed with pharmacokinetic parameter estimates administer drugs to a preset plasma concentration. A linking rate constant parameter (keo) allows estimation of effect site concentration. There are two parameter sets, named after the first author describing them, that are commonly used in pediatric target-controlled infusion for propofol (Absalom and Kataria) and one for remifentanil (Minto). Propofol validation studies suggest that these parameter estimates are satisfactory for the majority of children. Recommended target concentrations for both propofol and remifentanil depend on the type of surgery, the degree of surgical stimulation, the use of local anesthetic blocks, and the ventilatory status of the patient. The use of processed electroencephalographic monitoring is helpful in pediatric total intravenous anesthesia and target-controlled infusion anesthesia, particularly in the presence of neuromuscular blockade.


Total intravenous anesthesia has been widely practiced in adult anesthesia since the introduction of propofol into routine clinical practice in 1982. Although there were reports of the use of total intravenous anesthesia in children as early as 1989, it is only in recent years that the practice in children has become more common, attributable to the publication of pediatric pharmacokinetic parameter estimates for propofol. Propofol parameter estimates for neonates and infants younger than 1 yr are less published.

These propofol pharmacokinetic parameter estimates for children were used to determine drug delivery rates given by pump that would achieve a plasma target concentration associated with anesthesia. Drug delivery rates (mass infusion rates) require frequent manual changes by the clinician to maintain the target concentration. The incorporation of parameter estimates into target-controlled infusion (or "smart") pumps removed operator dependence. A target-controlled infusion is accomplished by a computer within the pump that performs rapid sequential calculations every 8 to 10 s to estimate the infusion rate required to produce a user-defined drug concentration in either the plasma or at the effect site of action of the drug in the brain in an open-loop system. Open-loop systems require the physician to alter the target concentration depending on the observed effect, e.g., clinical signs of depth of anesthesia and/or a processed electroencephalographic signal. When effect measures are automatically used by the device to control infusion rate (a feedback method) the system is known as closed-loop. Open-loop rather than closed-loop target-controlled infusion is the routine in pediatric anesthesia, although closed-loop systems have been described.[1,2]

Pharmacokinetic parameter estimates and effect measures are associated with variability,[3] similar to that observed with inhalational vapors.[4] Consequently, the anesthesiologist should use both smart pumps and mass infusion pumps as a basis for initiating a total intravenous anesthesia technique but must also use skill, knowledge, and experience to titrate the intravenous agents to effect and to avoid awareness, pain, and other adverse effects.

The aim of this article is to provide some background pharmacokinetic information essential for undertaking total intravenous anesthesia and target-controlled infusion in children of all ages and some practical advice on how this might be successfully achieved. The article concentrates on total intravenous anesthesia using propofol and remifentanil because these two drugs are commonly used in pediatric total intravenous anesthesia practice.[5]