Full text of DOI:10.1007/BF03019815

54
REGIO N AL AN EST H ESIA A N D P AI N
Epidural naloxone
reduces intestinal hypo-
motility but not analge-
Jaemin Lee MD, Jae Y. Shim MD,
Jeong H . Choi MD , Eun S. Kim MD,
Ou K. Kwon MD, Dong E. Moon MD ,
sia of epidural morphine Jong H . Choi MD, Michael J. Bishop MD*
Purpose: Epidural morphine is associated with decreased bowel motility and increased transit time. Low doses
of intravenous naloxone reduce morphine-induced pruritus without reversing analgesia, but the effect of epidur-
al naloxone on bowel motility has not been studied. Therefore we evaluated bowel motility and analgesia when
naloxone was co-administered with morphine into the epidural space.
Methods: Forty-three patients having combined thoracic epidural and general anesthesia for subtotal gastrecto -
my were randomly assigned to one of two study groups. All received a bolus dose of 3 mg epidural morphine at
the beginning of surgery, followed by a continuous epidural infusion containing 3 mg morphine in 100 ml bupiva-
caine 0.125% with either no naloxone (control group, n= 18) or a calculated dose of 0.208 µg·kg–1·hr–1 of nalox-
one (experimental group, n= 25) for 48 hr. We measured the time to the first postoperative passage of flatus and
feces to evaluate the restoration of bowel function, and visual analog scales (VAS) for pain during rest and move-
ment. Scores were assessed at 2, 4, 8, 16, 24, 36 and 48 hr postoperatively.
Results: The experimental group had a shorter time to the first postoperative passage of flatus (51.9 ± 16.6 hr
vs 87.0 ± 19.5 hr, P < 0.001) and feces (95.3 ± 25.0 hr vs 132.9 ± 29.4 hr, P < 0.001). No differences were
found in either resting or active VAS between the two groups.
Conclusion: Epidural naloxone reduces epidural morphine-induced intestinal hypomotility without reversing its
analgesic effects.
Objectif : L’administration péridurale de morphine est associée à une baisse de la motilité intestinale et à une
augmentation de la durée du transit. De faibles doses de naloxone intraveineuse réduisent le prurit induit par la
morphine sans renverser l’analgésie, mais l’effet de l’administration péridurale de naloxone sur la motilité intesti-
nale n’a pas encore été étudié. C’est pourquoi nous avons évalué cette action et l’analgésie de la naloxone admi-
nistrée avec de la morphine dans l’espace péridural.
Méthode : Quarante-trois patients qui recevaient une anesthésie péridurale thoracique et générale combinée,
pour une gastrectomie partielle, ont été répartis au hasard en deux groupes. Tous ont reçu un bolus de 3 mg de
morphine péridurale au début de l’intervention, suivi d’une perfusion péridurale continue de 3 mg de morphine
dans 100 ml de bupivacaïne à 0,125 % sans naloxone (groupe témoin, n= 18) ou avec une dose calculée de
–1
0,208 µg·kg ·h–1 de naloxone (groupe expérimental, n= 25) pendant 48 h. Nous avons mesuré le temps écoulé
avant la première expulsion des gaz intestinaux et des selles afin d’évaluer la restauration de la fonction intestinale
et mesuré les scores de douleur à l’aide de l’échelle visuelle analogique (EVA), au repos et pendant le mouve-
ment. Les scores postopératoires ont été relevés à 2, 4, 8, 16, 24, 36 et à 48 h.
Résultats : Dans le groupe expérimental, le temps précédant le premier passage postopératoire des gaz (51,9
± 16,6 h vs 87,0 ± 19,5 h, P < 0,001) et des selles (95,3 ± 25,0 h) a été plus court comparé au groupe témoin
(132,9 ± 29,4 h, P < 0,001). Aucune différence intergroupe n’a été observée aux scores de l’EVA obtenus au
repos ou pendant le mouvement.
Conclusion : La naloxone péridurale réduit l’hypomotilité intestinale induite par la morphine péridurale sans
renverser ses effets analgésiques.
From the Department of Anesthesiology, Kangnam Saint Mary’s Hospital, 505 Banpo-dong, Seocho-gu, Seoul, Korea. 137-040, and
Puget Sound Veterans Affairs Medical Center* and the University of Washington School of Medicine, Seattle, Washington.
Address correspondence to: Dr. Jong H. Choi; Phone: 82-2-590-1545; Fax: 82-2-537-1951; E-mail: jchoi@cmc.cuk.ac.kr
Accepted for publication September 22, 2000.

Lee et al.: EPID U RAL N ALO XO N E
55
ume of 10 ml·kg–1, I:E ratio at 1:2, and respiratory
rate of 8/ min ~ 12/ min.
O-ADMINISTRATION of epidural mor-
phine and bupivacaine is an effective
method of postoperative pain control that
maintains analgesia while reducing the side
Ten minutes after induction of general anesthesia, 3
mg morphine were administered via the epidural
catheter. Patients then received 5 ml bupivacaine
0.33% at one hour intervals until the end of surgery.
When the surgeons closed the peritoneum, a continu-
ous infusor (Baxter®, USA) was attached to the
epidural catheter for 48 hr postoperative pain control.
Patients were randomly assigned to one of two
groups by flipping a coin; naloxone was added to the
continuous infusor in the treatment group, but not in
the control group. The control group (n=18) received
3 mg morphine in 100 ml bupivacaine 0.125% at 2
ml·hr–1 for two days via the infusor. The treatment
group (n=25) received the same mixture, but with the
addition of 0.208 µg·kg–1·hr– 1 naloxone using the
same method.
We used Visual Analog Scales (VAS; 10 cm) to
assess postoperative pain at 2, 4, 8, 16, 24, 36, and 48
hr, both at rest and after coughing. In order to evalu-
ate the recovery of intestinal motility, the times to the
first postoperative passage of flatus and feces were
measured as well. All assessments were carried out by
anesthesiologists who had not taken part in the exper-
iment and were blinded to the group assignment.
Pain scales were analyzed to identify inter-group
differences using the Mann-Whitney U test. The inde-
pendent t test carried out for difference in intestinal
motility times were analyzed using Student’s t test for
independent data.
C
effects when compared with epidural morphine
alone.1 Postoperative gastric emptying is delayed after
epidural analgesia with morphine compared with
epidural bupivacaine2 , 3 and, for this reason, some sur-
geons are not inclined to use an epidural for postop-
erative pain control.
Choi et al.4 found in a recent report that epidural
naloxone preserves analgesia while minimizing the
side effects of itching and nausea. Animal experiments
have shown that an opioid antagonist such as nalox-
one reverses the morphine-induced decline in intesti-
nal motility,5 and clinical experiments have also
documented that intravenous or subcutaneous injec-
tion of naloxone can antagonize opioid-related intesti-
nal hypomotility.6,7
The effect of epidural naloxone on human intesti-
nal hypomotility has not been studied. We hypothe-
sized that co-administration of naloxone would
preserve both analgesia and intestinal motility when
epidural bupivacaine and morphine are used for pain
control after gastrectomy.
Methods
The experiment was carried out on 43 ASA 1-2
patients with stomach cancer, without any pre-existing
cardio-pulmonary, endocrine, hepatic, or renal dis-
ease. The protocol was approved by the H uman
Subjects Review Board of Catholic Medical Center’s
Kangnam Saint Mary’s H ospital and all the patients
provided written consent for the study. Patients
weighed 60~70 kg and had a height of 160~170 cm.
In order to eliminate interference from different sur-
gical techniques, the experiment was undertaken in
patients of a single surgeon performing subtotal gas-
trectomy and Billroth II anastomosis.
After identification of the epidural space between
the 8th and 9th thoracic vertebrae using the loss of
resistance technique, a 20 gauge epidural catheter was
placed three centimeters cephalad into the epidural
space with patients in a left lateral decubitus position.
Sensory block at least to the dermatome of the 6th
thoracic vertebra in the supine position was confirmed
in each case. Patients underwent anesthetic induction
and tracheal intubation after 4 mg·kg–1 thiopental and
1 mg·kg–1 succinylcholine. Muscle relaxation was
induced by 0.08 mg·kg– 1 pancuronium, and general
anesthesia was maintained with 3 L·min– 1 N2O and 2
L·min–1 O2 using a semi-closed circle system.
Controlled ventilation was conducted with a tidal vol-
Results
There were no differences between the two groups in
age, weight or height. (Table)
Evaluation of postoperative pain control
At rest, the highest VAS scores were recorded at two
hours after surgery and the scores decreased steadily
thereafter. The average VAS score was below 3.2 at all
points of evaluation for both groups, indicating satis-
factory levels of pain control. Comparison of the two
groups at each evaluation point showed no significant
inter-group differences. (Figure 1)
T ABLE Demographic data
Age(yr)
BW(kg)
Height(cm)
Control Group
Experimental Group
52.5 ± 11.2 64.2 ± 6.9 164.4 ± 8.5
53.4 ± 10.8 63.6 ± 6.4 162.0 ± 6.7
Values are mean ± SD
No significant difference between groups

56
C AN AD I AN JO U RN AL O F AN ESTH ESIA
FIGU RE 1 Postoperative resting VAS(visual analog scale) scores
at 2, 4, 8, 16, 24, 36 and 48 hr after the surgery. Values are mean
± SD. No significance could be found between two groups.
FIGU RE 3 Time to postoperative first flatus and first feces of
the two groups. Values are mean ± SD. FFL: first flatus, FFE: first
feces. *P < 0.001 compared with control group.
Discussion
Co-administration of morphine and bupivacaine is
widely used as an effective method of postoperative
pain control. Despite its benefits, morphine-induced
side-effects including respiratory depression, nausea,
and vomiting restrict its use in some cases. H owever,
Choi et al.4 reported that naloxone co-administered
with morphine via the epidural route reduced nausea,
vomiting and itching while not reversing analgesia and
that, at certain doses, naloxone improved the analgesic
effect. In our assessment of VAS scores, the dose and
the method of administration for morphine and bupi-
vacaine were found to be safe and effective for post-
gastrectomy pain control. The experimental group
that received naloxone in addition also showed good
results for postoperative pain control, confirming that
naloxone used in appropriate quantities will not antag-
onize the analgesic effect of morphine.
FIGU RE 2 Postoperative movement VAS(visual analog scale)
scores at 2, 4, 8, 16, 24, 36 and 48 hr after the surgery. Values are
mean ± SD. No significance could be found between two groups.
During coughing, VAS scores were again highest at
two hours after the end of surgery and showed a
decline afterwards. At all evaluation points with the
exception of two and four hours, the average VAS
score was < 3.6. Comparison of the two groups at
each evaluation point again showed no significant
inter-group differences. (Figure 2)
Assessment of recovery in intestinal motility
The VAS during coughing was 1 or 2 points high-
er than at rest until four hours postoperatively, but was
not different thereafter. This difference probably
occurs because afferent sensory transmission from the
surgical wound differs during rest and movement and,
as a result, a qualitatively different evaluation is made.8
Since intestinal motility has a high correlation with
The time to the first postoperative passage of flatus
was 87.0 ± 19.5 hr for the control group (mean ±
SD), and 51.9 ± 16.6 hr for the experimental group (P
< 0.001). The time to the first feces was 132.9 ± 29.4
hr for the control group and 95.3 ± 25.0 hr for the
experimental group (P < 0.001). (Figure 3)

Lee et al.: EPID U RAL N ALO XO N E
57
postoperative ambulation, it is essential to carry out an
inter-group comparison of analgesia during move-
ment as well as at rest.
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