Key words
regional anesthesia - obstetrics - pain therapy
Schlüsselwörter
Regionalanästhesie - Geburtsanalgesie - Geburtshilfe - Schmerztherapie
Introduction
One of the biggest challenges in routine anesthesiology and obstetric practice is
achieving pain relief during delivery which is both satisfactory and safe. The most
common methods used for pain relief during delivery are regional anesthesia (RA) using
a spinal or epidural analgesic and parenteral opioid therapy, in particular pethidine
and meptazinol [1]. The opioids have been criticized because of their limited analgesic efficacy, the
associated side effects such as nausea, fatigue, and the potential for maternal and
neonatal respiratory depression [2], [3]. The analgesic superiority of regional analgesia over parenteral opioid therapy
has been sufficiently documented elsewhere in randomized studies [4], [5]. Higher levels of maternal satisfaction with pain management are usually reported
for RA [6], [7], although a recent meta-analysis found that results for RA were comparable to those
for opioids [8]. It has been suggested that the administration of RA results in prolonged labor
and higher numbers of surgical vaginal deliveries [8]. The secondary cesarean section rate is not affected by RA [8], [9].
Pethidine is the most commonly used opioid in the obstetric setting [1]. It acts mainly through the µ1 and µ2 opioid receptors. The active metabolite norpethidine
crosses the placenta and is excreted into breast milk. The recommended method of administration
is through intramuscular administration [10]. The individual dose for adults is 25–150 mg when administered intramuscularly (IM)
and 50 mg with intravenous (IV) administration [11]. It reaches its maximum effect after 30–40 minutes and can be re-administered after
3–6 hours [12]. Its elimination half-life in neonates is around 23 hours because of the neonateʼs
immature elimination pathways, while in adults the elimination half-life of pethidine
is only 3 hours [13].
The opioid analgesic meptazinol is increasingly being used in obstetrics. It acts
through the µ1 opioid receptor and central cholinergic neurotransmission and can be
administered either intramuscularly or intravenously, reaching its maximum effect
after 30–60 min. The standard individual dose for an adult is IM 75–100 mg and IV
50–100 mg. Repeat administration is possible after 2–4 h [11]. The elimination half-life is around 3.5 hours in neonates and 2 hours in adults
[12], [14].
In the literature the analgesic effect of both opioids is usually classified as equivalent
and as generally low, although sometimes meptazinol is judged to have a better side
effects profile with less neonatal respiratory depression [15], [16]. Very few studies have looked at maternal satisfaction with parenteral opioid therapy
and, on investigation, the opioids are generally found to be comparable [17].
A comprehensive evaluation of pain management therapies should include the effects
of therapy on maternal birth experience, as it does not necessarily depend on the
extent of pain relief [18]. In a parallel study, a cooperating study group therefore examined the impact of
systemic opioid therapy and regional analgesia on womenʼs birth experiences in the
same observational period [19].
The purpose of this study was to compare the opioid analgesics pethidine and meptazinol
in clinical practice in a level-1 perinatal center with regard to administration,
pain relief, side effects profile and maternal satisfaction with therapy in an observational
study. The rates for additional administration of analgesics, in particular, the rates
for secondary regional neuraxial analgesics administered following administration
of one of the opioids served as an additional quality criterion for the respective
opioid therapy.
Materials and Method
Study design
This study was a prospective, single-center, non-interventional, observational study.
After receiving the approval of the local ethics committee (AZ036-12-23012012) on
February 7th, 2012, the twelve monthsʼ observation period was started on March 1st,
2012 in the Department of Obstetrics of Leipzig University Hospital. In the first
six months, only pethidine was used for peripartum opioid therapy; in the last six
months meptazinol was exclusively used for peripartum opioid therapy. Administration
of neuraxial RA was always possible at any time over the entire study period.
Inclusion and exclusion criteria
Adult women who had delivered spontaneously or had a surgical vaginal delivery in
the ≥ 37th week of gestation and who received pethidine or meptazinol and/or RA were
included in the study. Patients who did not consent and patients who required secondary
cesarean section were excluded from the study. In accordance with the standards used
in non-interventional observational studies, the individual decisions for therapy
were based on established medical practice and on a consensus between the physician
or midwife and the informed patient.
Dosages of intrapartum medication
There were no fixed dosages for peripartum medications. Depending on the individual
decisions of the clinicians, pethidine was usually administered at a dose of 100 mg
IM (84.6 %), followed by 10–15 mg IV (8.3 %), and 50 mg IM (5.3 %). In most cases
meptazinol was administered at a dose of 100 mg IV (44.5 %). Other common dosages
were meptazinol 50 mg IV (27.7 %), 100 mg IM (13.4 %) and 25–40 mg IV (9.9 %). Other
doses were only administered in isolated cases.
In 83.9 % of cases, RA consisted of combined spinal-epidural anesthesia (CSE) and
in 16.1 % of cases of peridural anesthesia (PDA), with intermittent bolus administration
of the respective medication. Adrenalin and lidocaine were generally administered
in test doses (99.4 and 97.6 %). 82.1 % of patients who received RA were given sufentanil,
initially administered intrathecally at a dose of 5–10 µg; in 7.7 % of cases, the
same dose was administered by epidural injection. 19.7 % of patients who received
RA were given an initial epidural dose of ropivacaine 5–20 mg. 17.9 % of RA patients
received subsequent epidural injections of sufentanil 5–20 µg and 35.7 % of RA patients
had subsequent injections of ropivacaine 10–20 mg.
Data collection
Data collection was done in three steps. During the birth, the midwife asked the parturient
patient when administering the opioid about the intensity of the pain she was experiencing
prior to the therapeutic intervention and at 30 and 60 minutes after the intervention
using an eleven point numerical rating scale (NRS0, 30 and 60; values ranged from
0 = “no pain” to 10 = “strongest imaginable pain”). If a neuraxial RA block was placed,
the anesthesia nurse similarly asked the parturient patient about the intensity of
the pain she was experiencing prior to the therapeutic intervention and at 30 and
60 minutes after the intervention using the same numerical rating scale described
above. Maternal, neonatal and obstetric data were obtained from patient records, the
protocol of the birth and the hospitalʼs own electronic documentation programs. Data
recorded included the administration and doses of any analgesics, birth complications,
any administration of oxytocin for the induction or stimulation of labor, the rate
of surgical vaginal deliveries, the duration of the birth, i.e., the duration from
the start of the early stage of labor until complete delivery of the placenta, and
the duration of analgesia from the first anesthetic intervention till the birth. The
neonatal outcome was assessed using the parameters “Apgar score” (at one, five and
ten minutes postnatally), umbilical cord arterial pH, postnatal monitoring, and respiratory
assistance. After the birth, patients were given a questionnaire which they were requested
to complete within 24–72 hours post partum. The questionnaire recorded maternal satisfaction
with the therapeutic intervention using a 7-point scale (from 1 = “not satisfied at
all” to 7 = “entirely satisfied”). The women were also asked about nausea and emesis
during the birth, their success in breastfeeding up to that point, their preparations
for the birth, and their subjective attitude to the pain of giving birth. Postpartum
data collection was also done in those cases where the intrapartum assessment of the
pain was partially or entirely lacking, for example because of staff shortages or
because the birth had ended within the one-hour observation period.
Statistical analysis
Patients were divided into groups according to the analgesia method used and the aspect
being investigated. Data were analyzed descriptively with standard univariate testing.
The level of significance was 5 %. χ2-test, Fisherʼs exact test and t-test for independent or paired samples were used,
depending on the type of sample and on the aspect being investigated. Non-normally
distributed samples of n < 30 were analyzed using Mann-Whitney U-test and Wilcoxon
signed rank test. Pain relief obtained by different therapeutic methods over time
and in comparison were analyzed using multivariate analysis of variance with repeated
measures. Various patient characteristics were also analyzed using binary logistic
regression to determine how much they increased the probability or risk of the patient
requiring RA. To do this, the total study population was analyzed using χ2-test to determine the factors which were found to be present significantly more often
with RA patients. All of these factors were subsequently included in the multivariate
regression analysis.
Results
A total of 449 patients were included in the observational study. 157 women were given
pethidine (35 %), 162 women received meptazinol (36 %), and 168 women had regional
analgesia (37 %). The last group was subdivided into 130 patients who only had RA
(primary RA, 29 %), and 38 patients who had regional analgesia after receiving opioid
therapy previously (secondary RA, 8 %). [Table 1] shows the comparison between groups with regard to medical history, demographic
factors and clinical parameters.
Table 1 Comparison of groups with respect to demographic data, patient history and clinical
parameters (t-test for independent samples, χ2-test and Fisherʼs exact test).
|
Pethidine (n = 157)
|
Meptazinol (n = 162)
|
Opioid monotherapy (n = 281)
|
Primary RA (n = 130)
|
Secondary RA (n = 38)
|
|
1 High-risk pregnancy according to the criteria of the German Maternity Guidelines,
2 Oxytocin, misoprostol or Prepidil gel, 3 Premature rupture of membranes, nuchal cord, green amniotic fluid, pathological CTG,
uterine atony, other complications.
|
|
Age in years (M ± SD)
|
29.2 ± 5.2
|
29.4 ± 5.4
|
29.5 ± 5.3
|
28.9 ± 5.3
|
27.8 ± 5.1
|
|
Height in m (M ± SD)
|
1.67 ± 0.06
|
1.67 ± 0.06
|
1.67 ± 0.06
|
1.68 ± 0.07
|
1.67 ± 0.05
|
|
BMI prior to pregnancy (M ± SD)
|
23 ± 4
|
23 ± 5
|
23 ± 4
|
23 ± 4
|
26 ± 7
|
|
BMI at birth (M ± SD)
|
28 ± 4
|
28 ± 5
|
28 ± 4 ← p = 0.009 →
|
29 ± 5
|
31 ± 7
|
|
Week of gestation (M ± SD)
|
40.0 ± 1.0 ← p = 0.02 →
|
39.7 ± 1.1
|
39.8 ± 1.1
|
39.9 ± 1.2
|
40.2 ± 1
|
|
Primipara (%)
|
64
|
63
|
61 ← p = 0.003 →
|
76
|
79
|
|
High-risk pregnancy1 (%)
|
75
|
81
|
77
|
84
|
92
|
|
Specific pregnancy risks (%)
|
|
|
|
|
|
|
|
8 ← p = 0.003 →
|
1
|
5
|
8
|
5
|
|
|
1
|
1
|
1 ← p = 0.03 →
|
5
|
0
|
|
Birth (%)
|
|
|
|
|
|
|
89
|
92
|
89
|
93
|
97
|
|
|
11
|
8
|
11
|
7
|
3
|
|
Induced birth2 (%)
|
34 ← p = 0.04 →
|
24
|
26 ← p < 0.001 →
|
59
|
53
|
|
Birth complications3 (%)
|
65
|
70
|
68
|
73
|
66
|
Clinical administration of pethidine and meptazinol
Pethidine was usually administered as an intramuscular injection (94 %) and meptazinol
usually as an intravenous injection (83 %) (p < 0.001). The mean total opioid dose
for a single birth was comparable for pethidine and meptazinol, with a mean dose of
99.8 mg for pethidine and a mean dose of 95.3 mg for meptazinol (p = 0.194). Meptazinol
was administered repeatedly (≥ two times) in 27 % of cases, while pethidine was only
administered repeatedly in 6 % of cases (p < 0.001). The final dose of meptazinol
was administered at a significantly shorter interval to the birth (1.9 ± 2.7 h) compared
to the final dose of pethidine, which was administered 2.6 ± 2.8 hours prior to the
birth (p < 0.05). If an opioid was administered repeatedly, the mean interval between
two opioid doses was 5.2 ± 3.7 hours for pethidine compared to 1.6 ± 1.4 hours for
meptazinol (p < 0.001).
Pain relief with pethidine and meptazinol
On the 11-point rating scale, the mean severity of pain experienced immediately before
receiving the initial opioid dose (NRS0) for all patients given opioid therapy was
8.2 ± 1.3 prior to receiving pethidine and 8.5 ± 1.2 prior to receiving meptazinol.
[Tables 2] and [3] show the pain relief obtained with the two opioids over time and compare the two.
Only patients who provided information about the intensity of pain experienced at
each of the three time points were included in the analysis. The number of cases is
therefore lower in this analysis compared to the total number of samples.
Table 2 Pain relief obtained with the respective opioid therapy over time; comparison of
pethidine with meptazinol (multivariate analysis of variance with repeated measures).
|
Pethidine, 1st dose
|
Relative decrease in pain scores
|
Meptazinol, 1st dose
|
Relative decrease in pain scores
|
Comparison between groups
|
|
n
|
M ± SD
|
Effect over time
|
n
|
M ± SD
|
Effect over time
|
|
NRS0
|
46
|
8.3 ± 1.2
|
|
|
64
|
8.2 ± 1.4
|
|
|
p = 0.577
|
|
NRS30
|
46
|
6.7 ± 2.1
|
p < 0.001
|
19 %
|
64
|
6.0 ± 2.0
|
p < 0.001
|
27 %
|
|
|
NRS60
|
46
|
6.9 ± 2.6
|
|
− 3 %
|
64
|
7.3 ± 2.1
|
|
− 22 %
|
|
Table 3 Pain relief obtained with the therapy over time; comparison of opioid monotherapies
with regional anesthesia (multivariate analysis of variance with repeated measures).
|
Opioid monotherapy, 1st dose
|
Relative decrease in pain scores
|
Primary RA
|
Relative decrease in pain scores
|
Comparison between groups
|
|
n
|
M ± SD
|
Effect over time
|
n
|
M ± SD
|
Effect over time
|
|
NRS0
|
97
|
8.2 ± 1.3
|
|
|
94
|
8.7 ± 1.3
|
|
|
p < 0.001
|
|
NRS30
|
97
|
6.2 ± 2.1
|
p < 0.001
|
24 %
|
94
|
1.9 ± 2.3
|
p < 0.001
|
78 %
|
|
|
NRS30
|
97
|
7.1 ± 2.3
|
|
− 15 %
|
94
|
2.7 ± 2.6
|
|
− 42 %
|
|
The tables show that both opioids achieved statistically comparable decreases in the
intensity of pain (p = 0.577). However, pain relief over time differed significantly
between the two opioids (p < 0.001). In the first 30 minutes after administration
pethidine reduced pain by an average of 1.6 points on the scale (19 %); meptazinol
reduced pain by an average of 2.2 points (27 %). Over a period of 30 to 60 minutes
the pain increased again by 0.2 points (3 %) in women taking pethidine and by 1.3
points (22 %) in women taking meptazinol. Analysis using paired t-test showed that
pain increased significantly more with meptazinol over this period (p < 0.01).
Maternal and neonatal outcomes after pethidine and meptazinol
[Table 4] compares the two opioids with regard to duration of the birth, side effects, neonatal
outcomes and maternal satisfaction with pain relief therapy. Postnatal umbilical cord
arterial pH was significantly lower (p < 0.01) in children born to women who had received
pethidine compared to children whose mothers had received meptazinol. All other parameters
were comparable for the two opioids.
Table 4 Maternal and neonatal outcomes following pethidine and meptazinol monotherapy; n.s.
= not significant.
|
Pethidine monotherapy (n = 132)
|
Meptazinol monotherapy (n = 149)
|
Comparison (χ2- und t-test)
|
|
1 If an opioid was administered several times during parturition, the time of administering
the first dose was taken as the starting point.
|
|
Duration of the birth in h (M ± SD)
|
5.6 ± 2.6
|
5.7 ± 2.5
|
n.s.
|
|
Interval between administration of pain relief1 and birth in h (M ± SD)
|
2.9 ± 3.2
|
2.2 ± 2.8
|
n.s.
|
|
Side effects
|
|
|
|
|
|
59
|
50
|
n.s.
|
|
|
24
|
21
|
n.s.
|
|
|
15
|
13
|
n.s.
|
|
|
11
|
8
|
n.s.
|
|
|
43
|
37
|
n.s.
|
|
Neonatal outcome
|
|
|
|
|
|
8.6 ± 1.0
|
8.6 ± 1.1
|
n.s.
|
|
|
9.3 ± 0.8
|
9.5 ± 0.8
|
n.s.
|
|
|
9.7 ± 0.6
|
9.8 ± 0.4
|
n.s.
|
|
|
7.23 ± 0.09
|
7.26 ± 0.08
|
p = 0.02
|
|
|
14
|
9
|
n.s.
|
|
|
11
|
6
|
n.s.
|
|
|
95
|
93
|
n.s.
|
|
Maternal satisfaction with pain relief therapy using a 7-point scale (M ± SD)
|
4.9 ± 1.6
|
4.8 ± 1.7
|
n.s.
|
Rate of secondary regional anesthesia
The rate of secondary RA administration after prior administration of pethidine was
16 % (n = 25) and thus higher compared to the rate of secondary RA after meptazinol
which was 8 % (n = 13) (p = 0.029). [Table 5] shows the results of multivariate regression analysis of all relevant RA-promoting
factors identified in our pool of data using χ2-test. The odds ratio reflects the increased likelihood or increased risk for RA administration
depending on specific parameters and indicates the existing probability for RA. With
pethidine therapy, the risk for RA was more than twice as high (OR = 2.4) compared
to meptazinol therapy (p = 0.046). A birth of more > 7 hours was associated with a
9.9-fold higher risk for RA (p < 0.001), while medical induction of labor increased
the risk 5.4-fold (p < 0.001). Factors which were found to be less relevant for RA
administration were “high maternal BMI (> 29) at the time of birth”, “primiparity”,
“the belief of the parturient woman that painless birth was desirable”, and “attending
antenatal classes”.
Table 5 Risk factors for increased administration of regional anesthetic; univariate and
multivariate analysis of factors (χ2-test and binary logistic regression).
|
RA risk factor
|
Univariate comparison (χ2)
|
Odds ratio
|
95 %-CI for odds ratio
|
Multivariate comparison (Wald)
|
|
1 Dichotomized mean value for a scale ranging from 1–7, with 1 = “painless birth is
entirely desirable” and 7 = “painless birth is not at all desirable”, mean: 3.6; 2 continuous variation of features in BMI groups (< 21, 22–24, 25–29, 30–34, 35–39,
≥ 40).
|
|
Pethidine vs. meptazinol (ref)
|
0.029
|
2.412
|
1.017–5.723
|
0.046
|
|
Primiparity vs. multiparity (ref)
|
0.001
|
1.766
|
0.634–4.915
|
0.276
|
|
Induced birth, yes vs. no (ref)
|
< 0.001
|
5.434
|
2.169–13.615
|
< 0.001
|
|
Duration of birth > 7 h vs. ≤ 7 h (ref)
|
< 0.001
|
9.901
|
3.916–25.031
|
< 0.001
|
|
Antenatal classes yes vs. no (ref)
|
0.03
|
0.345
|
0.110–1.082
|
0.068
|
|
Painless birth is desirable,1 yes vs. no (ref)
|
0.001
|
1.686
|
0.737–3.856
|
0.216
|
|
BMI at the time of delivery in groups2
|
0.001
|
1.849
|
1.217–2.809
|
0.004
|
Pain relief with opioid monotherapy and regional analgesia
Administration of regional analgesia was the primary pain relief therapy in 77 % of
cases and the secondary pain relief therapy in 23 %. The intrapartum pain prior to
therapy (NRS0) was comparable for opioid monotherapy (pethidine or meptazinol without
secondary RA; n = 281) and primary RA, with pain evaluated as 8.4 ± 1.2 prior to opioid
monotherapy and 8.6 ± 1.3 prior to RA on the 11-point numerical rating scale. [Tables 2] and [3] show the results for pain intensity experienced with the respective therapies over
time and in comparison. This analysis again only included patients who had provided
information on the intensity of pain experienced at each of the three measurement
time points.
Results of variance analysis showed that pain relief was significantly stronger following
primary RA compared to opioid monotherapy (p < 0.001), although pain was significantly
reduced over time with both treatment methods (p < 0.001). Analyzed individually,
opioid therapy reduced pain in the first 30 minutes by 2.0 points on the scale (24 %)
while primary RA reduced pain by 6.8 points (78 %). In the interval between 30 and
60 minutes after administration, pain increased again by 0.9 points (15 %) for patients
receiving opioid therapy and by 0.8 points (42 %) for patients receiving primary RA.
The pain relief achieved with secondary RA was reported as 6.4 points in the first
30 minutes and 6.5 points at 60 minutes, which was comparable with the pain relief
obtained with primary RA (p > 0.05 respectively).
Maternal and neonatal outcomes after opioid therapy or regional analgesia
[Table 6] shows duration of the birth, side effects, maternal satisfaction with pain relief
therapy and neonatal outcomes following primary RA and opioid monotherapy. The mean
duration of the birth and the interval from the time of administering the first dose
of analgesia to delivery was longer for women who had primary RA compared to women
given opioid therapy (p < 0.001). The duration of the birth was even longer for women
who had secondary RA (9.3 ± 4.0 h; p < 0.05 compared with primary RA), with primary
and secondary RA administered at statistically comparable intervals prior to delivery
(4.6 ± 3.8 h vs. 4.0 ± 2.5 h; p > 0.05). The rate of oxytocin administration prior
to delivery was higher for women with primary RA (p < 0.001). There were no statistical
differences with regard to any of the other side effects. Mean maternal satisfaction
with pain relief therapy was significantly higher after primary RA than after opioid
monotherapy (p < 0.001). Maternal satisfaction with pain relief therapy was 5.1 ± 1.7
after secondary RA and thus significantly lower than after primary RA (p < 0.01).
Neonatal outcomes were comparable between the different pain relief treatment groups.
Table 6 Maternal and neonatal outcomes following opioid monotherapy or primary regional anesthesia;
n.s. = not significant.
|
Opioid monotherapy (n = 281)
|
Primary RA (n = 130)
|
Comparison (χ2- and t-test)
|
|
1 If an opioid was administered several times during parturition, the time when the
first dose was administered was taken as the starting point.
|
|
Duration of the birth in h (M ± SD)
|
5.7 ± 2.5
|
7.6 ± 2.5
|
< 0.001
|
|
Interval between administration of pain relief1 and birth in h (M ± SD)
|
1.9 ± 2.2
|
4.6 ± 3.8
|
< 0.001
|
|
Side effects
|
|
|
|
|
|
53
|
59
|
n.s.
|
|
|
22
|
30
|
n.s.
|
|
|
14
|
13
|
n.s.
|
|
|
9
|
7
|
n.s.
|
|
|
40
|
70
|
< 0.001
|
|
|
11
|
7
|
n.s.
|
|
Neonatal outcome
|
|
|
|
|
|
8.6 ± 1.1
|
8.7 ± 0.9
|
n.s.
|
|
|
9.4 ± 0.8
|
9.5 ± 0.7
|
n.s.
|
|
|
9.8 ± 0.5
|
9.8 ± 0.5
|
n.s.
|
|
|
7.25 ± 0.09
|
7.24 ± 0.08
|
n.s.
|
|
|
11
|
12
|
n.s.
|
|
|
9
|
9
|
n.s.
|
|
|
94
|
94
|
n.s.
|
|
Maternal satisfaction with pain relief therapy using a 7-point scale (M ± SD)
|
4.8 ± 1.6
|
6.1 ± 1.2
|
< 0.001
|
Discussion
This study shows the differences in parenteral administration of the opioids pethidine
and meptazinol in routine clinical practice and demonstrates that these can affect
the need for additional regional analgesia.
In accordance with the rules of observational studies, there were no prior specifications
governing the administration or the dosages of the opioids, and the clinicians decided
when to administer the opioid and chose the dosage based on the standard rules used
in clinical practice. This makes it difficult to compare the opioids from a strictly
pharmacological point of view, and it is not clear whether a study with pre-determined
rules of administration would have also resulted in the same differences between opioid
preparations. The advantage of an observational study, however, is that its results
are realistic and clinically relevant. The results should therefore be taken into
account in the routine administration of these preparations.
The classification described in the “Initiative on Methods, Measurement and Pain Assessment
in Clinical Trials” (IMMPACT) was used to assess the pain relief obtained by the various
therapies. According to this classification, a decrease in NRS values by 10–20 % corresponds
to rather limited pain relief, a decrease of ≥ 30 % corresponds to moderate relief
and a decrease by ≥ 50 % amounts to substantial pain relief [20]. While this classification refers to chronic pain, it is largely consistent with
studies measuring acute pain [21].
The relative pain relief was 19 % following the administration of pethidine and 27 %
after meptazinol in the first 30 minutes, and 17 % after pethidine and 11 % with meptazinol
one hour after administration. Although statistical analysis showed a significant
reduction in pain for both opioids, neither of the opioids achieved a moderate level
of pain relief as defined in the IMMPACT. The renewed increase in pain between 30
and 60 minutes after administration was around 3 % with pethidine and 22 % with meptazinol.
The stronger increase with meptazinol is because this opioid is usually administered
intravenously which results in a shorter duration of action. Intravenous administration
also results in a faster onset of action, making intravenous analgesia easier to control
compared to intramuscular administration, and allowing repeat doses of the opioid
to be administered at shorter intervals without running the risk of overdosing. This
means that meptazinol is more likely to be administered more often, that the interval
between two administrations of meptazinol is shorter than with pethidine and that
the last dose of meptazinol can be administered much closer to the time when the baby
is delivered than the last dose of pethidine. Some patients received meptazinol until
just before giving birth. Nevertheless, the overall dosages of the two opioids per
birth were similar, as the individual doses of meptazinol were lower on average than
the doses of pethidine. It is common knowledge that labor pain varies considerably
in patients and does not always increase linearly [22]. Intravenously administered meptazinol with its faster onset to action and potential
for repeated administration to mitigate against peaks of acute pain appears to be
better adapted to delivery than pethidine which is administered by intramuscular injection.
The potential to give repeated doses of meptazinol allows parturient women to receive
pain relief up until the time of delivery. This may also explain the significantly
lower rate of additional regional analgesia needed by women receiving meptazinol.
A possible reason for the cautious intravenous administration of pethidine in clinical
practice could be the risk described in the literature of vasodilation, hypotension
and reflectory tachycardia following rapid IV injection of this opioid [10]. No such risk has been described for meptazinol.
The data comparing different parental opioids with respect to maternal satisfaction
with therapy is generally unsatisfactory [17]. Our study showed that maternal satisfaction with pethidine therapy was comparable
with satisfaction with meptazinol therapy in clinical practice. Satisfaction with
both opioids was in the top one third of the 7-point satisfaction rating scale, which
is surprising given the limited analgesic efficacy of the opioids. It appears that
the degree of analgesia achieved is not the sole determinant for patientsʼ satisfaction
with treatment. It is conceivable that other factors such as simple and rapid administration,
low invasiveness and few side effects or even just the attention and care given to
the patient have a positive impact on the patientʼs satisfaction with the treatment
she received. The differences in the administration of the opioids do not appear to
have had any relevant impact on patient satisfaction with treatment.
In this study, the side effects of the opioids on mother and child were largely comparable
for both opioids. The differences between pethidine and meptazinol postulated in other
studies with regard to postnatal Apgar scores [16], maternal nausea and emesis [23] and inhibitory effect on oxytocin secretion [24], [25] were not found in our study. Only postnatal umbilical cord arterial pH was found
to be lower following pethidine therapy, although the averages for both opioids were
within normal ranges and the difference was therefore not clinically relevant. Our
results however partly support the findings of other studies which reported a stronger
respiratory depression effect following pethidine administration [15], [16]. This difference is caused by the different receptor affinities of the two opioids
– as pethidine binds more strongly to µ2 opioid receptors binding this is assumed
to result in respiratory depression – and the longer elimination half-time of pethidine
in neonates [13], [14].
Another difference between the two opioids was the significantly higher rate of secondary
RA following pethidine therapy. This effect has not been previously described in the
literature and confirms the hypothesis of better pain relief with meptazinol. Multivariate
tests using binary logistic regression showed that the risk of RA following pethidine
treatment was more than double compared to that for meptazinol therapy. Regression
analysis found that other significant peripartum predictors for RA were longer duration
of birth and induction of labor. But it is not clear whether the longer duration of
birth was a side effect of RA [26], or whether complicated and prolonged births led to an increased need for RA [27]. The increased risk for RA after labor was induced is probably due to the fact that
induction of labor can result in more painful and less effective uterine contractions
compared to spontaneous induction of labor [28] and therefore requires more pain relief.
While random sampling of all pethidine and meptazinol patients (n = 319) showed significant
differences with regard to factors promoting RA such as induction of labor and S/P
cesarean section (cf. [Table 1]), when all patients who received opioid treatment followed by secondary RA (n = 38)
were analyzed with regard to all tested RA predictors, no differences were found except
for the choice of opioid (p > 0.05 respectively). This confirms the supposition that
pethidine therapy itself was decisive for the increased demand for RA.
The study also shows that, based on clinical observation, regional analgesia also
offers effective, satisfactory and safe pain relief peripartum. Compared with parenteral
opioid therapy, the efficacy of pain relief obtained with RA was found to be significantly
higher. While opioids did not achieve even moderate pain relief as measured by IMMPACT
as they only reduced pain by 24 % in the first 30 minutes and by 13 % over a one hour
observation period, RA achieved a substantial pain reduction of 78 % after 30 minutes
and 69 % over 60 minutes. The results are consistent with those in the current literature
[8]. Maternal satisfaction with pain therapy was highest following primary RA, followed
by secondary RA and finally after opioid monotherapy. That use of RA as the analgesia
method is associated with higher levels of patient satisfaction with treatment has
been noted previously in the literature [6], [7]. That secondary RA resulted in a lower patient satisfaction compared to primary
RA has not been previously described and the reason for this is probably that the
prior, less effective opioid therapy contributed to the poorer assessment of secondary
RA.
Typical side effects of RA reported in the literature are prolonged delivery, higher
rates of surgical vaginal deliveries, and intrapartum oxytocin administration [8], [29]. All of these could be due to lower uterine performance. Our results also showed
longer delivery times with RA compared to opioid treatment. But it is debatable whether
RA is the reason for the prolonged birth or whether women with prolonged delivery
times per se demand more RA in consequence. That fact that the period from analgesic
intervention to birth is significantly longer for RA compared to opioid treatment
would appear to indicate that RA prolongs delivery. The longest births were those
where women initially received opioid therapy and secondary RA, although in these
cases opioid administration always preceded RA administration. It is therefore also
conceivable that these births were prolonged beyond the sole impact caused by RA.
After all, they did provide enough time for several different treatment methods to
be used. Alternative explanations for prolonged delivery include cervical dystocia
or cephalopelvic disproportion [30]. In our study, the rate of oxytocin administrations peripartum was also increased
after RA. The number of surgical-vaginal deliveries was comparable for RA and opioid
treatment. The rate of cesarean sections for the respective treatments was not analyzed,
as patients who required secondary cesarean section were excluded from the study.
This was necessary to avoid differences in samples to the detriment of the RA group,
as early RA is indicated particularly in women who have more risk factors for secondary
cesarean section [31]. Randomized studies have already confirmed that RA does not increase the rate of
cesarean sections [8], [9].
This study was an observational study. In contrast to a randomized double-blind study,
the advantage of an observational study is that it offers the opportunity to investigate
treatments carried out in a real environment with decisions taken based on routine
clinical considerations. At the same time, the study design can be a source of error.
It is important to be aware of differences between the groups ([Table 1]). Overall, the patients who had pethidine therapy had more factors which could result
in greater severity of pain during labor. On the one hand, the higher number of patients
requiring induction of labor in this group could also increase overall pain levels
[28]. On the other hand, this group also included a significantly higher number of women
with a history of previous cesarean section. This means that the percentage of women
giving birth to their second child for whom this was the first vaginal delivery, was
significantly higher (p < 0.01). In the pain analysis these women were evaluated in
the same way as primipara, who in turn regularly described the birth as more painful
than multipara did [32]. A comparison of the groups receiving opioid monotherapy with the group of women
who had primary RA showed that the RA group had more pain-enhancing factors such as
primiparity and induction of labor [28], [32]. There are also indications that strong weight gain in and high maternal and fetal
weight at birth result in stronger labor pains [22]. The higher maternal BMI in the RA group therefore may also have resulted in greater
severity of pain. The rate of women with breech presentation was also higher in the
RA group, but stronger pain in women with breech presentation has not been described
in the literature. However, the initial NRS pain prior to any intervention was comparable
between groups. The unequal distribution in factors associated with higher affinity
to pain did not appear to have any effect in our patients.
Conclusion for Clinical Practice
Conclusion for Clinical Practice
The clinical evaluation of parenteral opioids showed an advantage for intravenously
administered meptazinol. Meptazinol administration resulted in pain relief and patient
satisfaction with pain therapy which was comparable to that for pethidine; however,
meptazinol administration was associated with a lower need to escalate analgesia though
secondary regional anesthesia. Overall, the analgesic efficacy of parenteral opioid
administration lagged far behind that of regional analgesics. The group with the highest
satisfaction rate regarding pain relief therapy consisted of those women who had primary
RA.
