Obstetrical
analgesia with tramadol ?
Joseph Eldor, MD
csen_international@csen.com
Bitsch et al. (1) used in 1980 parenteral
analgesia with Tramal in 23 normal deliveries. The results
were compared with a group of normal deliveries in which analgesia was achieved
with pethidine. Both medications exerted an identical
analgetic efficiency. No adverse side effects were
observed with Tramal concerning the follow-up of labour or the newborn.
Long
and Yue (2)
evaluated the safety and analgesic efficacy of patient controlled
intravenous analgesia (PCIA) with tramadol, and
compared its benefits and risks with combined spinal-epidural analgesia (CSEA)+
patient controlled epidural analgesia (PCEA). Eighty American Society of
Anesthesiologist (ASA) I-II at term parturients in
active labor were randomly divided into 3 groups: the control group (n = 30)
received no analgesia; group A (n = 30) received spinal administration with ropivacaine 2.5 mg and fentanyl 5
microg, then with PCEA; group B (n = 20) received 1
mg/kg tramadol loading dose i.v.
PCIA with 0.75% tramadol and it included: PCA dose 2
ml, lockout time 10 minutes, background infusion 2 ml/h, total dose no more
than 400 mg. The intensity of pain was evaluated using Visual Analogue Scale
(VAS). Both group A and B showed good pain relief. VAS pain scores were
significantly decreased in group A and B compared with those in the control
group (P < 0.01). In comparison with group B, the VAS pain scores decreased
in group A (P < 0.05). The onset times of analgesia in group A were shorter
than those in group B (P < 0.05). Apgar scores in
group B were lower than those in group A (P < 0.05). The periods of second
stage of labor in group A were longer than those in the control group and group
B (P < 0.05). The cesarean delivery rate was significantly higher in the
control group (16.7%) than in group A (3.3%) and group B (5.0%), but it did not
differ between group A and B. There were no significant differences in vital
signs, fetal heart rate, degree of motor block, and uterine contractions among
the 3 groups. PCIA with tramadol is now a useful
alternative when patients are not candidates for CSEA for labor, or do not want
to have a neuraxial block anesthesia. However,
sometimes it may not provide satisfactory analgesic effect.
Jain
et al. (3) compared analgesic efficacy of intramuscular opioids:
meperidine and tramadol
with epidural analgesia. One hundred and twenty-eight term nulliparous
women with singleton pregnancy and vertex presentation were randomized to
receive either epidural (n=43), meperidine (n=39) or tramadol (n=44). A visual analog scale (VAS) was used to
assess the severity of pain. The parameters analyzed were analgesic efficacy, effect
on labor, other maternal side effects, perinatal
outcome and maternal satisfaction. Median VAS scores following first dose were
0 (0-5), 5 (3-8) and 5 (3-8) in epidural, meperidine
and tramadol groups, respectively. Ninety percent of
women rated analgesia as good to excellent in the epidural group as compared
with 72% of women in the meperidine group and 65% in tramadol group. However, epidural caused a significant
prolongation of first (P<0.05) and second (P<0.01) stage of labor with an
increased number of operative deliveries (27% in the epidural, 7.6% in the meperidine, and 11.4% in the tramadol
groups, P<0.05). In the epidural group 40% women had urinary retention and
16% had motor weakness, whereas sedation was the only side effect seen in the meperidine (41%) and tramadol
groups (9%). Respiratory depression was noted among three neonates in the meperidine group, two in the tramadol
group and none in the epidural group. The analgesic efficacy and maternal
satisfaction is better with epidural analgesia than with opioids.
Analgesia provided by meperidine and tramadol is comparable and approximately 50% of women rated
the analgesia as good. Meperidine is better in the
second stage than tramadol. Hence in developing
nations where availability of facilities is the main limiting factor,
intramuscular opioids can be considered suitable
alternatives.
Keskin
et al. (4) evaluated and compared the
analgesic efficacy and adverse effects of tramadol
and pethidine in labor. Fifty-nine full term parturients were randomly assigned to one of two groups in
active labor. Group 1 received 100 mg pethidine;
group 2, 100 mg tramadol, intramuscularly. Analgesic
efficacy, maternal side effects, changes in the blood pressure, heart rate, and
duration of labor were assessed. At 30 and 60 min after drug administration,
pain relief was greater in the pethidine group than
in tramadol group. The incidence of nausea and
fatigue was higher in the tramadol group. Following
drug administration the decrease in systolic and diastolic blood pressure and
the increase in heart rate were statistically significant in both groups. No
significant difference was found between the groups when compared for duration
of labor and Apgar scores. None of the neonates
developed respiratory depression. Pethidine seems to
be a better alternative than tramadol in obstetric
analgesia because of its superiority in analgesic efficacy and low incidence of
maternal side effects.
The
need for analgesia to overcome pain in labour is
highly requested by women today. Various ways either non pharmachologic
e.g. Emotional sustain, psycho-prophylactic preparation, yoga and hypnosis or pharmachologic such as epidural blockade or parenteral are used. Therefore in Fieni
et al. (5) evaluated the efficacy and tolerability of the two opioids usually used today in parenteral
analgesia to reduce pain during labour: Tramadol and Meperidine. They
studied two groups of patients each made up of 20 women in labour,
all at term and with a physiologic course of pregnancy. 75 mg i.m. of Meperidine were
administered in the first group while in the second group 100 mg i.m. of tramadol were
administered. Various maternal, fetal and neonatal parameters were then
monitored demonstrating--A moderate maternal analgesic effect in both drugs (evaluated
through the analogic grading of pain). In the group
to whom Meperidine was given, sedative effects on the
mother were observed associated with respiratory depression in the newborn (the
latter evaluated through the Apgar index at 1st and
5th minute of life and pH of the blood obtained at the umbilical cord). Tramadol gave an analogous analgesic effect, with better
tolerability for the absence of collateral effects on the mother, fetus and
newborn.
The
pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage and
administration of tramadol were reviewed (6). Tramadol
is a synthetic analogue of codeine that binds to mu
opiate receptors and inhibits norepinephrine and
serotonin reuptake. It is rapidly and extensively absorbed after oral doses and
is metabolized in the liver. Analgesia begins within one hour and starts to
peak in two hours. In patients with moderate postoperative pain, i.v. or i.m. tramadol
is roughly equal in efficacy to meperidine or
morphine; for severe acute pain, tramadol is less
effective than morphine. Oral tramadol can also be
effective after certain types of surgery. Tramadol
and meperidine are equally effective in postoperative
patient-controlled analgesia. In epidural administration for pain after
abdominal surgery, tramadol is more effective than bupivacaine but less effective than morphine. In patients
with ureteral calculi, both dipyrone
and butylscopolamine are more effective than tramadol. For labor pain, i.m. tramadol works as well as meperidine
and is less likely to cause neonatal respiratory depression. Oral tramadol is as effective as codeine for acute dental pain.
In several types of severe or refractory cancer pain, tramadol
is effective, but less so than morphine; for other types of chronic pain, such
as low-back pain, oral tramadol works as well as
acetaminophen-codeine. Common adverse effects of tramadol
include dizziness, nausea, dry mouth, and sedation. The abuse potential seems
low. The recommended oral dosage is 50-100 mg every four to six hours. Tramadol is an effective, if expensive, alternative to
other analgesics in some clinical situations.
Tramadol is a cyclohexanol derivative with mu-agonist activity. It has been used as an analgesic for
postoperative or chronic pain since the late 1970s, and became one of the most
popular analgesics of its class in
Ninety
primigravide were randomly allocated into three
groups at the beginning of active phase of labor (8). Dihydroetorphine
hydrochloride (DHE) was administered to group A (n = 30), tramadol
to group B (n = 30), and group C (n = 30) was a blank control. Various
parameters about analgesia effects, progress of labour
and fetal and neonatal well-being were investigated and also umbilical artery
and vein blood gases analyzing were carried out in all cases. As a result, the
effective rate of pain relief in group A was 67% and in group B 63% (P >
0.05). The average time of onset of action in DHE group was 16.5 +/- 2.9
minutes which was significantly shorter than 26.1 +/- 5.4 minutes in tramadol group (P = 0.0001). There were higher rate (36.7%)
of operative intervention (forceps and vaginally or cesarean section) and a
higher average amount of postpartum hemorrhage in group A, as compared with the
control group, but no significant difference was shown between group B and
group C. No difference was found in other parameters (among the three groups -
duration of labour, Apgar
scores of neonates, cord blood gases, etc.). The conclusion is that, both DHE
and tramadol may have a good effect on pain relief in
labour. The time of onset of action in DHE group is
significantly shorter than that in tramadol group.
Neither analgesics cause circulation and respiratory depression in the mother
and neonates, but DHE may have influence on uterine contraction.
Lehmann
(9) reviewed the use of tramadol in the management of
acute pain. Tramadol is a weak opioid
analgesic with a potency comparable to that of pethidine.
While it is not recommended as a supplement to general anesthesia because of
its insufficient sedative activity, tramadol has been
successful in the treatment of postoperative pain. Several studies have
demonstrated its analgesic efficacy after intramuscular and intravenous
application, both in adults and children. Moreover, negligible respiratory
depressant activity and only minor side effects have consistently been shown.
Patient-controlled analgesia with tramadol has been
frequently employed and was well accepted by the patients. There have been only
a few studies of oral or spinal application of tramadol
in acute pain states. Tramadol has also been used for
the control of pain associated with labour and acute
myocardial infarction, as well as for the management of trauma pain. In
summary, tramadol can be recommended as a basic
analgesic for the treatment of patients with moderate to severe pain.
The
analgesic efficacy and safety of tramadol 50 mg, 100
mg and pethidine 75 mg, administered intramuscularly
were compared in a randomized, double-blind clinical trial in 90 pregnant women
with labour pain (10). Pain relief was measured by a
4-point verbal rating scale 10, 20, 30, 45 and 60 min after the administration
of study drugs. The average total pain relief score within the first hour was
0.9 with tramadol 50 mg, 1.7 with tramadol
100 mg and 1.7 with pethidine 75 mg. In comparison to
both tramadol doses the administration of pethidine was associated with a significantly higher
frequency of adverse events and a significantly lower respiratory rate in the
neonates. The results indicate that tramadol 100 mg
is as effective as pethidine 75 mg but has a superior
safety profile.
Kainz
et al. (11) examined in a prospective, randomised,
blind study the analgesic potency and tolerance of intramuscular Tramadol compared to a standard obstetric analgesia with Pethidine. Triflupromazine was
administrated in combination with the two tested analgesics in order to study
its efficacy in alleviating the emetic side effects of the tested analgesics.
66 parturients were randomly assigned to three
groups: group A: 100 mg Tramadol (Tramal),
group B: 100 mg Tramadol (Tramal)
and 10 mg Triflupromazine (Psyquil),
group C: 50 mg Pethidine (Alodan)
and 10 mg Triflupromazine (Psyquil).
No significant differences concerning duration of labour,
FHR-alterations, umbilical cord blood gases, respiration pattern and Apgar Scores of the neonate occurred. In all three groups
the analgesic effect was equally good. Combination of the analgesic with the antiemetic showed no reduction of the incidence and
severity of side effects.
Because
tramadol does not exhibit a depressive effect on ventilatory activity it is often be used in the obstetrical
analgesia, at most in the form of an intramuscular injection. In a prospective
study on 49 women under labour the clinical effect of
the noninvasive rectal application of Tramadol, Pethidin, and Denaverin has been
compared (12). The first dosage was 100 mg of all substances. Around half of
the women said that analgetic effect was good or very
good. The effect was the same in all treatment groups. Because of a low
incidence of maternal side effects, the absence of side effects on the newborn,
and near the same results on the analgetic effect of parenteral application in other studies, tramadol suppositories can be recommended for obstetrical
analgesia.
Morphine
derivatives are the most frequently used analgetic
substances in obstetrics today. Nevertheless, nausea, vomiting, weariness, and
somnolence are common side effects of these drugs. Moreover opiates exhibit a
depressive effect on ventilatory activity. As many
studies have demonstrated tramadol does not show a
depressive effect to such a high degree. Husslein et
al. (13) in a prospective randomized trial
compared the efficacy as well as the safety of 100 mg tramadol and 100 mg pethidine in
40 women asking for pain relief during labour. The
duration of labour was slightly but not statistical
significantly shorter in the pethidine group. An analgetic effect could be observed in the pethidine as well as the tramadol
group by both the pregnant women and the attending physician about 10 min after
application lasting for about 2 hours. Concerning the side effects tramadol highly contrasted with pethidine.
There were less cases of weariness and somnolence and the ventilatory
frequency of the newborn babies tended to be higher than in the pethidine group. The serum levels of tramadol
in umbilical and maternal veins demonstrated values of 0.83 +/- 0.15 (mean +/-
SEM; quotient). The results of this study seem to establish an analgetic effect of tramadol
similar to pethidine but with less side effects.
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