Relationship between age and spontaneous
ventilation during intravenous anesthesia
in children
NIGEL BARKER MB ChB FRCA, JOANNE LIM MASc,
ERICA AMARI BA, STEPHAN MALHERBE MB ChB M Med FRCPC
AND J. MARK ANSERMINO MBBCh M Med MSc FRCPC
Department of Anesthesiology, Pharmacology & Therapeutics, The University of British
Columbia, Vancouver, BC, Canada
Summary
Background: Maintaining spontaneous ventilation in children, using
total intravenous anesthesia (TIVA), is often desirable, particularly for
airway endoscopy. The aim of this study was to evaluate the effect of
age on the dose of remifentanil tolerated during spontaneous
ventilation under anesthesia maintained with infusions of propofol
and remifentanil and to provide guidelines for the administration of
remifentanil and propofol to maintain spontaneous ventilation in
children.
Methods: Forty-five children scheduled for strabismus surgery were
divided by age into three groups (group I: 6 months–3 years, group II:
3 years–6 years, and group III: 6 years–9 years). The propofol infusion
was titrated using State Entropy as a pharmacodynamic endpoint and
remifentanil infused, using a modified up-and-down method, with
respiratory rate depression as a pharmacodynamic endpoint. A
respiratory rate of just greater than 10, stable for 10 min, determined
the final remifentanil infusion rate. The group mean was estimated
from the final remifentanil infusion rate tolerated (RD50).
Results: The RD50 of groups I, II, and III were 0.192 (0.08), 0.095 (0.04),
and 0.075 (0.03) lgÆkg)1Æmin)1 respectively. Pair-wise comparisons
between the groups for the rate of remifentanil tolerated revealed a
statistically significant increase in the RD50 in children less than
3 years of age compared with older children in groups II and III
(P < 0.001). The relationship between remifentanil dose and age,
weight or height was not linear.
Conclusions: Younger children, especially those aged less than 3 years,
tolerate a higher dose of remifentanil while still maintaining
spontaneous respiration. TIVA with spontaneous ventilation is readily
achieved in younger children and infants.
Keywords: ventilation; TIVA; propofol; remifentanil; anesthesia;
children
Correspondence to: J. Mark Ansermino, Room 1L7, Department of Pediatric Anesthesia, British Columbia Children’s Hospital, 4480 Oak
Street, Vancouver, V6H 3 V4, BC, Canada (email: anserminos@yahoo.ca).
Pediatric Anesthesia 2007 17: 948–955 doi:10.1111/j.1460-9592.2007.02301.x
 2007 The Authors
948 Journal compilation  2007 Blackwell Publishing Ltd

Introduction
Total intravenous anesthesia (TIVA) is an effective
technique for themaintenance of anesthesia, owing to
the introduction of short-acting drugs. The pharma-
cokinetic properties of propofol and remifentanil,
such as a rapid onset of action, ease of titration and
rapid clearance by redistribution andmetabolism, are
particularly advantageous for TIVA.
The advantages of propofol and remifentanil,
delivered intravenously, over conventional volatile
anesthetic agents used in children are quicker
recovery (1), reduced nausea and vomiting (2),
decreased postoperative delirium (3) and less
environmental pollution (4). Organ specific effects,
such as reduced airway reactivity, improved post-
operative ciliary function (5), maintained cerebral
vascular reactivity (6), and preserved middle ear
pressure (7) are significant advantages in specific
clinical situations.
Despite these advantages TIVA is not widely used
in children. The pharmacokinetics and pharmaco-
dynamics of propofol in children are distinctly
different from adults (8). Concern about the poten-
tial for toxicity following prolonged infusions in
children in the intensive care unit (9) has created a
reluctance to use propofol infusions in children and
highlights drug response differences between adults
and children.
The advantages of intravenous anesthesia can be
illustrated in a clinical example; deep inhalational
anesthesia has been the traditional method to faci-
litate airway endoscopy. We have increasingly
employed an intravenous infusion of remifentanil
and propofol for these procedures, even in infants.
Contrary to our expectations, spontaneous ventila-
tion has been easier to maintain in infants than in
older children. The advantage of this technique is
that it provides a titratable degree of hypnosis and
analgesia, avoids the need for tracheal intubation
and reduces the environmental pollution with
inhaled anesthetic agents. This technique produces
an undistorted view of the larynx and removes the
risk of fire from ignition of a tracheal tube during
laser surgery.
Respiratory depression may limit the use of
opioids during spontaneous ventilation. Intravenous
delivery of propofol and remifentanil has been used
in spontaneously breathing adults (10,11). The
incidence of respiratory depression increased when
the rate of remifentanil exceeded 0.05 lgÆkg)1Æmin)1.
Propofol and remifentanil have been administered
to spontaneously breathing children, however, the
procedures were relatively noninvasive and the
studies did not yield specific age-related infusion
guidelines (12–14). We have previously investigated
spontaneous ventilation with remifentanil and a
volatile anesthetic (sevoflurane) in children. We
found that the maximum dose tolerated by children
varied widely between 0.05 and 0.3 lgÆkg)1Æmin)1
and that a reduction in respiratory rate (<10 brÆ
min)1) appeared to be the best predictor of imminent
apnea (15).
We conducted this prospective observational
study to provide further clinical evidence for the
use of propofol and remifentanil in children. Using
respiratory rate depression as a pharmacodynamic
endpoint, we studied the relationship between age
and spontaneous ventilation in a group of children
undergoing strabismus surgery with infusions of
propofol and remifentanil anesthesia administered
intravenously.
Methods
We obtained approval for our study from two
institutional ethics review boards and the Health
Canada Therapeutic Products Directorate. We ob-
tained written informed consent from parents or
legal guardians, and patient assent where appropri-
ate, for 45 children, ages 6 months–9 years, sched-
uled for strabismus surgery. Exclusion criteria
included ASA classes 3 and 4, patients with a
history of or clinical signs of respiratory disease, a
history of allergy to opioids, or exposure to opioids
within the previous 30 days. Patients were also
excluded if they had a history of gastrooesophageal
reflux since the technique employed spontaneous
ventilation using a laryngeal mask airway (LMA).
Patients were stratified by age into three groups:
group I (6 months–3 years), group II (3–6 years),
group III (6–9 years). There were 15 patients in each
group.
Preoperatively we administered acetaminophen
20 mgÆkg)1 orally. Lidocaine and prilocaine cream
(EMLA) was applied to the skin of upper or lower
extremity sites to facilitate placement of an intra-
venous cannula. When the patient arrived in the
INTRAVENOUS ANESTHESIA AND SPONTANEOUS VENTILATION 949
 2007 The Authors
Journal compilation  2007 Blackwell Publishing Ltd, Pediatric Anesthesia, 17, 948–955