Pediatrics 1995 Mar;95(3):335-339
Department of Pediatrics, Saint Francis Hospital and
Medical Center, Hartford, CT 06105.
OBJECTIVE. To investigate the efficacy and safety of oral
transmucosal fentanyl (OTFC) in providing analgesia and
sedation for painful diagnostic procedures in children.
DESIGN. Randomized, placebo-controlled clinical trial.
METHOD. Forty-eight children referred to the University
Connecticut Division of Pediatric Hematology/Oncology for
bone marrow aspiration or lumbar puncture were randomized to
receive either OTFC (15 to 20 micrograms/kg) or a placebo
lollipop. Thirty minutes after administration, the procedure
was begun. An anesthesiologist monitored the child's heart
rate, blood pressure, and oxygen saturation every 10 minutes.
At the conclusion of the procedure, the nurse, the child's
parent, and all children over 8 years of age were asked to
rate the pain associated with the procedure using a 1 to 10
visual analogue scale. Young children (less than 8) used a
modified scale, the Oucher, yielding a 0 to 5 score. RESULTS.
Significant differences in pain ratings between the OTFC and
placebo groups were noted on the pain scores of the parents
(P = .005), nurses (P = .001), younger children (P = .006),
and older children (P = .013), and median pain scores in the
OTFC group were reduced to tolerable levels. Vomiting (P =
.003) and itching (P = .001) were more common in the OTFC
group, but no clinically significant vital sign deviations
occurred. CONCLUSION. OTFC is safe and effective for use in
relieving the pain of pediatric procedures, but frequency of
vomiting may restrict its clinical usefulness.
Anesth Analg 1996 Dec;83(6):1200-1205
Department of Anesthesiology, Jefferson Medical College,
Philadelphia, Pennsylvania 19107, USA.
Oral transmucosal fentanyl citrate (OTFC) is a labeled
preoperative pediatric sedative. Doses greater than 15
micrograms/kg are associated with a high incidence of
post-operative nausea and vomiting and occasional respiratory
depression. We studied the safety and efficacy of OTFC in
children 6 yr old and younger at a dose of 15 micrograms/kg.
Nineteen patients undergoing surgery associated with
postoperative pain were randomized to receive
OTFC/intravenous (IV) saline or placebo lozenge/IV fentanyl.
After 45 min, patients receiving OTFC became more sedated
than the placebo group, but there were no differences in
cooperation, apprehension, parental separation, or induction
cooperation scores. Preoperatively, neither respiratory
depression nor oxygen desaturation occurred. Nine of 10 OTFC
patients developed mild pruritus, and three of 10 OTFC
patients vomited preoperatively; neither complication
occurred in the placebo group. (The high incidence of
preoperative vomiting led to the termination of the protocol
before the anticipated enrollment of 40 patients.) General
anesthesia was induced via a mask, followed by a propofol
infusion. Spo2 and respiratory rate were monitored, and
sedation, apprehension, cooperation, ease of parental
separation, and induction cooperation were scored. One OTFC
patient developed rigidity during induction. Emergence and
recovery were not delayed by OTFC despite a 50% incidence of
postoperative vomiting. We do not recommend the use of OTFC
in a 15 micrograms/kg dose as a routine preoperative sedative
in children 6 yr old and younger.
Pain 1991 May;45(2):149-153
Department of Anesthesiology, University of Utah Health
Sciences Center, Salt Lake City 84132.
Ten patients with advanced cancer and breakthrough pain
between the ages of 39 and 78 received oral transmucosal
fentanyl citrate (10-15 micrograms/kg) 4 or 5 times each over
2 days (42 total administrations) in an open study. Baseline
vital sign and rating scale results did not vary over
administrations, except for heart rate which showed an 8
beats/min decrease over 4 administrations. Heart rate and
oxygen saturation did not vary significantly over 120 min of
evaluation, and minimal changes in blood pressure and
respiration rate were found. Significant reduction in pain
scores as measured by a pain descriptive scale, the
McGill-Melzack scale, and a numeric (VAS) scale were seen at
all evaluations from 5 to 120 min. Average time to onset of
pain relief was 9.5 min after administration. Wellbeing was
significantly increased at all evaluations. Activity level as
recorded by the investigator was significantly reduced from
10 to 30 min after administration, however, activity level as
reported by the patient was significantly increased at 5 min
and from 60 to 120 min after OTFC administration. There were
no significant adverse effects.
Anesth Analg 1993 Feb;76(2):377-381
Oral transmucosal fentanyl citrate (OTFC) has been used in
a variety of clinical situations. This study was designed to
determine if OTFC could provide analgesia to patients with
acute pain after major surgery. Following written informed
consent, 38 ASA Physical Status I-III patients undergoing
either a total hip replacement or total knee arthroplasty
were studied prospectively. The patients were randomly
allocated to receive either OTFC (7-10 micrograms/kg) or a
placebo identical in appearance to an OTFC unit. General
anesthesia was administered for surgery, and
patient-controlled analgesia (PCA) with morphine was
initiated in all patients. The PCA interval dose was adjusted
to provide adequate analgesia as determined by the patient
and physician; the PCA lock-out time was not changed. On the
morning after surgery, the most recent 12 h of PCA data
(milligrams per hour of morphine and PCA attempts per hour)
were recorded. OTFC or placebo units were administered at
times 0, 4, and 8 h during a 12-h study, resulting in three
identical units being completely consumed. PCA data, as well
as incidence and severity of any adverse side effects, were
recorded during the study and for the next 12 h. Treatment
groups were compared for similarity, and study variables were
analyzed. Twenty-eight patients completed the study, 13 in
the control group and 15 in the OTFC group. There were no
significant differences between the study groups as to
patients' age, gender, ASA classification, or surgical
procedure. In addition, there were no differences between the
groups in the number of PCA attempts or delivered dose of
morphine during the prestudy or poststudy periods.
Anesthesiology 1991 Aug;75(2):223-229
Department of Anesthesiology, University of Utah School of
Medicine, Salt Lake City 84132.
Oral transmucosal fentanyl citrate (OTFC) is a novel,
noninvasive dosage form of fentanyl used to provide children
and adults with sedation, anxiolysis, and analgesia. In order
to determine the bioavailability and absorption of fentanyl
from OTFC, 12 volunteers were given intravenous fentanyl
citrate or OTFC 15 micrograms/kg on each of two occasions. On
a third occasion, the authors assessed oral administration
(gastrointestinal absorption) by giving eight of the same
volunteers the same dose of a solution of fentanyl citrate to
swallow. In each study, arterial blood samples were taken
over 24 h for analysis of plasma fentanyl. After intravenous
(iv) administration of fentanyl, clearance (mean +/- standard
deviation) was 0.67 +/- 0.15 l/min; volume of distribution at
steady state was 287 +/- 79 l; and the terminal elimination
half-life was 425 +/- 102 min. Peak plasma concentrations of
fentanyl were higher (3.0 +/- 1.0 vs. 1.6 +/- 0.6 ng/ml, P =
0.01) and occurred sooner (22 +/- 2.5 vs. 101 +/- 48.8 min, P
= 0.003) after OTFC than after oral solution administration.
Plasma concentrations of fentanyl after OTFC decreased
rapidly, to less than 1.0 ng/ml within 75-135 min after the
beginning of administration. Peak absorption rate was greater
(11.1 +/- 4.3 vs. 3.6 +/- 2.1 micrograms/min, P = 0.004) and
occurred much sooner after OTFC than after oral solution
administration (19 +/- 2.6 vs. 87.5 +/- 38.1 min, P = 0.001).
Systemic bioavailability was greater after OTFC
administration than after the oral solution (0.52 +/- 0.1 vs.
0.32 +/- 0.1, P = 0.01).