Spontaneous ventilation with remifentanil
in children
J MARK ANSERMINO MBBCh , MMed , MSc , FFA(SA) , PETER
BROOKS MBChB , FRCA, DAVID ROSEN MD, FRCPC,
CHRISTINE A VANDEBEEK BBA, MBA AND CLAYTON
REICHERT BSc , MD, FRCPC
Department of Anesthesia, British Columbia Children’s Hospital, University of British
Columbia, BC, Canada
Summary
Background: Remifentanil is a short-acting drug that allows us to study
the specific respiratory effects of potent opioid analgesics. The
purpose of this study is to describe the effects of a remifentanil
infusion during spontaneous ventilation in children. Pharmacokinetic
studies provide useful information on the time course of opioid blood
concentrations; however, they cannot be easily translated into infusion
administration guidelines for pediatric clinical practice.
Methods: A total of 32 children, aged 2–7 years, undergoing restorat-
ive dentistry, spontaneously breathing under sevoflurane anesthesia
were enrolled in the study. After an initial bolus dose of remifentanil,
an infusion was administered in ascending logarithmic increments
at 10 min intervals. Increments were discontinued when endtidal
carbon dioxide exceeded 9 kPa (70 mmHg), desaturation occurred
(SpO2 < 94%) or with the onset of apnea (>5 s). The maximum
tolerated dose was determined for each subject. Endtidal carbon
dioxide, minute ventilation and respiratory rate were continuously
recorded.
Results: The median tolerated dose of remifentanil was 0.127
lgÆkg)1Æmin)1 (range: 0.053–0.3 lgÆkg)1Æmin)1). When comparing the
last four incremental increases in each subject, 35% change in
respiratory rate occurred in the last 10 min period while changes in
endtidal carbon dioxide and minute ventilation were gradual and of
less magnitude. There was no correlation between age and respiratory
rate.
Conclusions: There is a large variation in the dose of remifentanil
tolerated by children while breathing spontaneously under anes-
thesia. A respiratory rate of <10 bÆmin)1 appears to be the best
predictor of the maximum tolerated dose.
Keywords: remifentanil; ventilation; anesthetic techniques;
respiration; children
Correspondence to: J.M. Ansermino, Department of Pediatric Anesthesia, British Columbia Children’s Hospital, University of British
Columbia, 4480 Oak Street, Room 1L7, Vancouver, BC, Canada V6H 3V4 (email: anserminos@yahoo.ca).
Pediatric Anesthesia 2005 15: 115–121 doi:10.1111/j.1460-9592.2004.01397.x

2004 Blackwell Publishing Ltd 115

Introduction
Remifentanil is a potent, ultra short-acting opioid
analgesic. The rapid plasma clearance by plasma
esterases produces an elimination that is independ-
ent of rate or duration of infusion (1). The pharma-
cokinetics of remifentanil in children has indicated a
half-life of 3–6 min with an increased clearance in
neonates and infants (2). These controlled studies
provide useful information on the time course of
opioid blood concentrations but are not useful in
determining the optimum dose of remifentanil that
maintains spontaneous breathing children in the
clinical setting.
In practice, the respiratory depressant effects of
administered opioid analgesics are commonly used
to determine variability in response among patients
under anesthesia. In addition, ventilatory depres-
sion, as a marker of opioid effect, has been used to
compare the potencies of opioid analgesics (3).
Doses of remifentanil in the range of 0.02–0.05
lgÆkg)1Æmin)1 have been shown to be compatible
with spontaneous ventilation when combined with
propofol anesthesia in adults (4,5).
Short-acting drugs allow an improved titration of
effect, permitting rapid changes in concentration in
response to changes in surgical stimulation. A
common clinical example in pediatric practice
would be the maintenance of spontaneous respir-
ation (without intubation) during diagnostic laryng-
oscopy and bronchoscopy, thus avoiding the need
for tracheal intubation or jet ventilation. This tech-
nique produces an undistorted view of the larynx
and removes the risk of fire due to ignition of a
tracheal tube during laser surgery. Deep inhalation
anesthesia has traditionally been used to facilitate
airway endoscopy. We have increasingly been
employing an intravenous infusion of remifentanil
for the following purposes: (1) to act as a supple-
ment to the inhaled anesthetic, or (2) when com-
bined with an intravenous agent (e.g. propofol), to
avoid the volatile anesthetic agents completely. The
advantage of this technique is that it provides a
titratable degree of analgesia during these stimula-
ting procedures and reduces the amount of inhaled
anesthetic agent required, reducing environmental
pollution.
Short-acting drugs, such as remifentanil, allow
better titration of effect compared with long-acting
drugs such as fentanyl and alfentanil. Maximizing
the synergistic anesthetic effects while preventing
respiratory depression in the face of varying surgical
stimulus can only be achieved with ultra-short-
acting drugs, such as remifentanil. In this study, we
have described the effect of remifentanil in sponta-
neously breathing children during anesthesia.
Methods
With approval from the institutional review board,
written informed parental consent was obtained for
32 children, aged 2–7 years, scheduled for dental
restoration under anesthesia, where tracheal intuba-
tion was indicated. Exclusion criteria included a
history of or clinical signs of respiratory disease, a
documented history of allergy to opioids, or expo-
sure to opioids within the previous 30 days. Patients
were also excluded if intubation was expected to be
difficult.
Paracetamol 20 mgÆkg)1 was orally administered
preoperatively. On arrival in the operating room, an
intravenous cannula was inserted. Anaesthesia was
induced with a bolus of propofol (3–5 mgÆkg)1),
remifentanil (4 lgÆkg)1) and lidocaine (0.5 mgÆkg)1).
Tracheal intubation was performed with an
uncuffed nasal RAE tracheal tube. No airway filter
was employed. Anesthesia was maintained with
60% nitrous oxide in oxygen and 1% endtidal
sevoflurane. Routine monitoring included ECG,
pulse oximetery (SpO2), noninvasive blood pressure
and temperature. Spirometry and gas monitoring
was performed using the Pedi-Lite (Datex-Ohmeda,
Helsinki, Finland). The spirometry module was
calibrated daily. Assisted ventilation was gradually
reduced to allow spontaneous ventilation.
A PC serial interface cable connected the monitor
to a laptop computer for recording trends automat-
ically using the S5 COLLECT data collection software
(S/5 Collect, Datex-Ohmeda, Helsinki, Finland).
Recording included 5-s trend data for anesthetic
agent, respiratory rate (RR), minute ventilation
(MV), endtidal carbon dioxide (PECO2), nitrous
oxide, SpO2, oxygen and blood pressure.
Remifentanil infusion was started at 0.03 lgÆkg)1Æ
min)1, using an infusion pump (Medfusion 2010;
Medex, Duluth, CA, USA) once spontaneous respir-
ation had returned. The infusion was connected as
close to the intravenous catheter as possible with a
116 J.M. ANSERMINO ET AL.

2004 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 115–121