Full text of DOI:10.1007/BF03017327

384
Obstetrical and Pediatric Anesthesia
Intravenous tenoxicam reduces uterine cramps
after Cesarean delivery
[Le ténoxicam intraveineux réduit les crampes utérines à la suite d’une césarienne]
Yu-Chen Huang MD,* Shen-Kou Tsai PhD,* Chi-Hsiang Huang MD,* Mao-Hsien Wang MD,† Pei-Lin Lin MD,*
Li-Kuei Chen MD,* Chen-Jung Lin MD,* Wei-Zen Sun MD*
Purpose: Postpartum uterine contraction pain is a common phe-
nomenon after Cesarean delivery. We investigated the effectiveness
of tenoxicam in reducing uterine contraction pain.
celles du Groupe II 40 mg iv de ténoxicam après le clampage du cor-
don ombilical. L’échelle verbale analogique a servi à enregistrer la
douleur postopératoire liée à l’incision et aux contractions utérines à
deux, quatre, huit, 16 et 24 h.
Methods: We enrolled 120 consecutive non-breastfeeding
women who were scheduled for elective Cesarean delivery. After
the administration of spinal anesthesia with bupivacaine and
intrathecal morphine 0.15 mg injection, the patients were random-
ly divided into two groups. Group I received placebo (normal
saline) iv injection, and Group II received tenoxicam 40 mg iv injec-
tion after clamping the umbilical cord. Verbal analogue scale of
wound pain and uterine contraction pain were recorded at two,
four, eight,16, and 24 hr after Cesarean delivery.
Résultats : Les scores de douleurs liées à l’incision n’ont pas différé
d’un groupe à l’autre (tous les scores ont été # 3). Par ailleurs, dans
le groupe ténoxicam, les scores liées aux contractions utérines ont été
plus bas et les demandes d’analgésie supplémentaire avec mépéridine
moins importantes que dans le groupe placebo (8,5 % vs 41,4 %, P
< 0,05). Nausées, vomissements, prurit ou saignements n’ont pas
présenté de différence intergroupe significative.
Conclusion : Une dose intraveineuse de 40 mg de ténoxicam a
réduit significativement l’intensité des crampes utérines sans causer
d’effets secondaires à la suite d’une césarienne.
Results: There was no significant difference in wound pain scores
between the two groups (all scores #3). However, the tenoxicam
group had significant lower uterine contraction pain scores and
required less supplemental meperidine medication than did the
placebo group (8.5% vs 41.4%, P <0.05). The incidences of nau-
sea or vomiting, pruritus, and bleeding were not significantly differ-
ent between groups.
OSTPARTUM uterine contraction pain is a
very common problem and can evoke a gen-
eralized neuroendocrinal stress response
Conclusion: Intravenous tenoxicam 40 mg significantly reduced
the intensity of uterine cramps in patients undergoing Cesarean
delivery without increasing side effects.
1
P
producing widespread physiological effects.
Intrathecal injection of morphine is well established
for the management of postoperative pain,2 but it has
limited effect in relieving uterine cramps.3 However,
nonsteroidal anti-inflammatory drugs (NSAIDs) can-
not only provide postoperative analgesia4–6 but also
relieve the discomfort of uterine cramps after vaginal
delivery.7–10
Objectif : La douleur des contractions utérines du postpartum est un
phénomène fréquent après la césarienne. Nous avons vérifié l’effica-
cité du ténoxicam à réduire ces douleurs.
Méthode : Nous avons recruté 120 femmes qui devaient subir une
césarienne non urgente et qui ne devaient pas allaiter leur bébé. Après
la rachianesthésie avec de la bupivacaïne et une injection intrathécale
de 0,15 mg de morphine, nous avons formé deux groupes. Les
patientes du Groupe I ont reçu un placebo (soluté physiologique) iv et
Tenoxicam (Tilcotil®; Roche), a long-acting
NSAID, is commonly used for the treatment of
rheumatoid arthritis,11 osteoarthritis,12,13 acute gout,14
From the Departments of Anesthesiology, National Taiwan University Hospital, College of Medicine and Hospital,* and the En-Chu-
Kong Hospital,† Taipei, Taiwan.
Address correspondence to: Dr. Li-Kuei Chen, Department of Anesthesiology, National Taiwan University Hospital, No. 7, Chung-Shan
South Rd., Taipei, Taiwan. Phone: 886-2-2312-3456 ext. 5516; Fax: 886-2-2341-5736; E-mail: clk0619@ane1.mc.ntu.edu.tw
Accepted for publication October 25, 2001.
Revision accepted December 17, 2001.
CAN J ANESTH 2002 / 49: 4 / pp 384–387

Huang et al.: TENOXICAM AND UTERINE CRAMPS
385
and other extra-articular diseases. The potentially bene-
ficial effect of iv tenoxicam on uterine cramps after
Cesarean delivery remains unknown. Therefore, we
studied 120 women undergoing elective Cesarean
delivery. The effectiveness of pain relief, reduction of
cramps and the incidence of side effects of iv tenoxicam
were recorded.
TABLE I Clinical characteristics of patients
Placebo group Tenoxicam group
(n=59) (n=58)
Age (yr)
31 30
5
6
Body height (cm)
Body weight (kg)
Parity: nulliparous/multiparous 16/43
158.2 6.5
68.6 2.4
159.3 5.7
70.7 2.0
21/37
Methods
A prospective, double-blinded, randomized, placebo-
controlled study was designed and approval was
obtained from the hospital Ethical Committee.
Informed consent was obtained from all patients
before the study. One hundred twenty ASA I/II con-
secutive non-breastfeeding women who were sched-
uled for elective Cesarean section were studied.
Patients with impaired liver or renal function, gastritis,
gastric or duodenal ulcers, abnormal bleeding tenden-
cy, and known history of allergy to salicylates or
NSAIDs were excluded from the study.
All patients received an infusion of Ringer’s solu-
tion 1000 mL before induction of spinal anesthesia.
After placement of standard monitors (electrocardio-
graph, automated arterial blood pressure, and pulse
oximetry), spinal anesthesia was performed with a 27-
gauge Whitacre needle via the L2–3 or L3–4 inter-
space. All patients received 1.8 mL to 2.2 mL of 0.5%
hyperbaric bupivacaine (dosage adjusted according to
body height) for spinal anesthesia and preservative-
free morphine 0.15 mg for postoperative pain control.
Sensory anesthesia (determined by pinprick) extend-
ing to the T–4 dermatome was achieved.
The patients were randomly divided into two
groups. After the umbilical cord was clamped, iv
ergonovine 0.2 mg was given. Group I received an
infusion of oxytocin 10 units and placebo (normal
saline) in 500 mL of Lactate Ringer’s solution, and
Group II received an infusion of oxytocin 10 units and
tenoxicam 40 mg15 in 500 mL of Lactate Ringer’s
solution. An anesthesiologist, blinded to the treat-
ment groups, was responsible for visiting the patients
to record pain scores at two, four, eight, 16 and 24 hr
after Cesarean section. Patients were asked to rate the
intensity of wound pain and uterine contraction pain
on a 10-cm analogue scale, which ranged from 0 for
no pain to 10 for the worst pain imaginable. Wound
pain was defined as continuous abdominal pain, and
uterine contraction pain was defined as intermittent,
short lasting, cramping pain which might be unrelat-
ed to the surgical side. The postoperative supplemen-
tal analgesic regimen was standardized. IM
meperidine 50 mg every four hours at the patient’s
request was prescribed. Side effects such as nausea or
vomiting or both, and pruritus were managed with
diphenhydramine (30 mg im). The surgeon evaluated
uterine relaxation and decided if repeated doses of
oxytocin were needed. We recorded the incidence of
bleeding and bleeding was regarded as abnormal
when the obstetrician decided to use additional oxy-
tocin to increase uterine tone. Vaginal blood loss, esti-
mated from nursing inspection of the perineal pad,
was graded as small, moderate, or large.
Data are presented as mean SD. The P2 test was
used to test associations among dichotomous parame-
ters, and Yate’s correction was used when necessary.
Analysis of variance was used to compare continuous
variables between groups. A P value < 0.05 was con-
sidered statistically significant.
Results
There were no significant differences between the two
groups with regard to age, weight, height, and parity
(Table I). Three patients (one in the placebo group and
two in the tenoxicam group) were excluded because
they could not make the difference between uterine
contraction pain and wound pain. The results showed
that the mean wound pain scores at two, four, eight, 16
and 24 hr in the tenoxicam group were not significant-
ly different from those in the placebo group (all scores
#3; Figure 1). However, the mean uterine contraction
pain scores of the tenoxicam group at two, four, eight,
16, and 24 hr were significantly lower than those of the
placebo group (Figure 2). In the 24-hr postoperative
period, 8.5% of patients (5/58) in the tenoxicam group
and 41.4% of patients (24/59) in the placebo group
required meperidine treatment (P < 0.05).
The incidences and severity of nausea or vomiting,
and pruritus were not higher in the tenoxicam group
than in the placebo group at 24 hr after operation
(Table II). Assessment of blood loss or the need for
oxytocics either intra- or postoperatively was not dif-
ferent in patients receiving tenoxicam. The surgeon’s
assessment of uterine relaxation also indicated that
there was no difference between the two groups.

386
CANADIAN JOURNAL OF ANESTHESIA
TABLE II Analgesic requirements and side-effects
Placebo group Tenoxicam group
(n=59)
(n=58)
Percentage that required
meperidine (%)
Nausea/vomiting
Pruritus
41.4 (24/59)*
10/59 (16.9%)
50/59 (84.7%)
0
8.5 (5/58)
12/58 (20.7%)
47/58 (79.7%)
0
Bleeding
*P < 0.05 placebo group vs tenoxicam group.
Cesarean delivery.17–19 However, wound pain and uter-
ine contraction pain are qualitatively different. Our study
demonstrates that the analgesic effect of iv tenoxicam
can reduce the intensity of postpartum uterine contrac-
tion pain. Theoretically, tenoxicam can also reduce
wound pain, but this was not the case since mean wound
pain scores were not different between groups. This was
probably due to the profound analgesic efficacy of
intrathecal morphine (0.15 mg) in relieving incisional
pain (all pain scores # 3).
FIGURE 1 Wound pain scores in the two groups. No differ-
ences were found between tenoxicam and placebo.
Tenoxicam, a NSAID, has a marked analgesic effect
directed selectively against pain induced by inflamma-
tory or traumatic processes.20 It is less ulcerogenic,
lacks tinnitus, dizziness, or gastro-intestinal side-
effects and is tolerated better than aspirin.20,21 Reports
have shown the analgesic effect of iv ketoprofen and
diclofenac for the treatment of pain after Cesarean
delivery.17 However, the half-life of ketoprofen is five
to six hours and that of diclofenac is 1.5 hr,22 indicat-
ing that repeated doses may be needed. Tenoxicam
specifically inhibits prostaglandin synthetase and has a
long plasma half-life (75 hr) allowing once daily
dosage.21 Furthermore, tenoxicam can be adminis-
tered parenterally. This route is preferred to im and
rectal routes. Oral administration may be unsuitable in
the early postoperative period. In addition to inhibi-
tion of platelet aggregation and thromboxane produc-
tion, NSAIDs may increase postpartum uterine
bleeding23 but no evidence of increased postoperative
blood loss was found in our study.
FIGURE 2 Uterine contraction pain scores in the two groups.
*P < 0.05 tenoxicam group vs placebo group.
Discussion
In conclusion, tenoxicam (40 mg iv), a long acting
NSAID that induces analgesia by inhibiting peripher-
al prostaglandin synthesis, reduced postpartum uter-
ine contraction pain without adverse effects. Further
studies should evaluate analgesic effects vs side effects
of iv tenoxicam as a function of dosage.
In the management of postCesarean analgesia, intrathe-
cal morphine has remarkable efficacy in relieving inci-
sional pain, but is ineffective for pure uterine contraction
pain. This may be due to the fact that uterine contraction
pain involves several chemical nociceptive mediators such
as bradykinins, leukotrienes, prostaglandins, serotonin,
lactic acid and substance P.1 Its mechanism might be
mediated by a second messenger-prostaglandin system16
that can be inhibited by aspirin-type anti-inflammatory
analgesics. Studies have shown that the analgesic efficacy
of NSAIDs could reduce opioid consumption after
References
1 Brownridge P. The nature and consequence of child-
birth pain. Eur J Obstet Gynecol Reprod Biol 1995;
59(Suppl): S9–15.

Huang et al.: TENOXICAM AND UTERINE CRAMPS
387
16 Moghissi KS. Prostaglandins in reproduction. Obstet
2 Cousins MJ, Mather LE. Intrathecal and epidural
administration of opioids. Anesthesiology 1984; 61:
276–310.
3 Bloomfield SS, Cissell GB, Mitchell J, Barden TP.
Codeine and aspirin analgesia in postpartum uterine
cramps: qualitative aspects of quantitative assessments.
Clin Pharmacol Ther 1983; 34: 488–95.
4 Hodsman NBA, Burns J, Blyth A, et al. The morphine
sparing effects of diclofenac sodium following abdomi-
nal surgery. Anaesthesia 1987; 42: 1005–8.
5 Gillies GWA, Kenny GNC, Bullingham RES, McArdle
CS. The morphine sparing effect of ketorolac
tromethamine. A study of a new, parenteral non-
steroidal anti-inflammatory agent after abdominal
surgery. Anaesthesia 1987; 42: 727–31.
Gynecol Annu 1972; 1: 297–337.
17 Rorarius MGF, Suominen P, Baer GA, Romppanen O,
Tuimala R. Diclofenac and ketoprofen for pain treat-
ment after elective caesarean section. Br J Anaesth
1993; 70: 293–7.
18 Elhakim M, Nafie M. I.v. tenoxicam for analgesia dur-
ing Caesarean section. Br J Anaesth 1995; 74: 643–6.
19 Belzarena SD. Evaluation of intravenous tenoxicam for
postoperative cesarean delivery pain relief. Preliminary
report. Reg Anesth 1994; 19: 408–11.
20 Bird HA, Bamford L, Pickup ME, et al. A comparison
between gastro-intestinal blood loss caused by tilcotil
(Ro 12-0068) and aspirin in normal volunteers. Curr
Med Res Opin 1982; 8: 9–13.
6 Carlborg L, Lindoff C, Hellman A. Diclofenac versus
pethidine in the treatment of pain after hysterectomy.
Eur J Anaesthesiol 1987: 4: 241–7.
7 Bloomfield SS, Mitchell J, Cissell G, Barden TP.
Analgesic sensitivity of two post-partum pain models.
Pain 1986; 27: 171–9.
8 Bloomfield SS, Barden TP, Mitchell J. Naproxen, aspirin,
and codeine in postpartum uterine pain. Clin
Pharmacol Ther 1977; 21: 414–21.
9 Sunshine A, Zighelboim I, Olson NZ, De Sarrazin C,
Laska E. A comparative oral analgesic study of indo-
profen, aspirin, and placebo in postpartum pain. J Clin
Pharmacol 1985; 25: 374–80.
21 Bird HA, Pickup ME, Taylor P, et al. Gastro-intestinal
blood loss with high dose tilcotil (Ro 12-0068) and
aspirin: an open crossover clinical trial and pharmacoki-
netic assessment in normal volunteers. Curr Med Res
Opin 1983; 8: 412–6.
22 Small RE. Diclofenac sodium. Clin Pharm 1989; 8:
545–58.
23 Diemunsch P, Alt M, Diemunsch A-M, Treisser A. Post
cesarean analgesia with ketorolac tromethamine and
uterine atonia. Eur J Obstet Gynecol Reprod Biol
1997; 72: 205–6.
10 Sun H-L, Wu C-C, Lin M-S, Chang C-F. Effects of
epidural morphine and intramuscular diclofenac combi-
nation in postcesarean analgesia: a dose-range study.
Anesth Analg 1993; 76: 284–8.
11 Bird HA, Hill J, Lowe JR, Wright V. A double-blind
comparison of tenoxicam (Tilcotil, Mobiflex) at two
doses against ibuprofen in rheumatoid arthritis. Eur J
Rheumatol Inflamm 1984; 7: 28–32.
12 Lund B, Andersen RB, Fossgreen J, et al. A long-term
randomised trial on tenoxicam and piroxicam in
osteoarthritis of the hip or knee: a 24-month interim
report focusing on the 12-24 month interval. Eur J
Rheumatol Inflamm 1987; 9: 58–67.
13 Bird HA, Hill J, Dixon JS, Looi D, Wright V. A double-
blind parallel study of tenoxicam and piroxicam in
patients with osteoarthrosis. Eur J Rheumatol Inflamm
1985; 8: 53–9.
14 Waterworth RF, Waterworth SM. An open assessment
of tenoxicam (Tilcotil) in the treatment of acute gout
in general practice. N Z Med J 1987; 100: 744–5.
15 Vandermeulen EP, Van Aken H, Scholtes JL, Singelyn F,
Buelens A, Haagen L. Intravenous administration of
tenoxicam 40 mg for post-operative analgesia: a dou-
ble-blind, placebo-controlled multicentre study. Eur J
Anaesth 1997; 14: 250–7.