Implementation of a piritramide based patient-controlled
analgesia (PCA) as a standard of care is not effective for pain control
in late abortion induction: a prospective cohort study from a patient
perspective
Tascón Padrón L.1, Emrich NLA.1,
Strizek B. 1, Gass A.2, Link C.2 Hilbert T. 2 Klaschik
S.2, Meissner W.3, Gembruch U.1, Jiménez Cruz J. 1
1 Department of Obstetrics and Prenatal Medicine,
University Hospital Bonn, Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
2 Department of Anesthesiology and Intensive Care
Medicine, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn,
Germany
3 Department for Anesthesiology and Intensive Care
Medicine/ Department of Palliative Care, University Hospital of
Jena,07740 Jena, Germany.
RUNNING HEAD
PCA is inefficient reducing pain in late abortion
ABSTRACT
Objective To assess whether the implementation of
patient-controlled analgesia (PCA) with piritramide using an automatic
pump system under routine conditions is effective to reduce pain in late
abortion inductions
Design Prospective observational cohort study
Setting Patients requiring medically indicated abortion
induction from 14 weeks of pregnancy onwards between July 2019 and July
2020 at the department of Obstetrics and Prenatal Medicine of the Bonn
University Hospital in Germany.
Methods Evaluation of pain management after implementation of a
PCA system compared with previous nurse-controlled tramadol-based
standard under routine conditions. Patients answered a validated pain
questionnaire and requirement of rescue analgesics was assessed. Pain
intensity and satisfaction were measured on a ten-point numeric rating
scale.
Main Outcome Measure Maximal pain intensity
Results Forty patients were included. Patients using
Piritramide-PCA complained of higher pain sores than those in the
standard group (6.90 (± 2.34) vs. 4.83 (± 2.87), (p < 0.05)).
In both groups the level of satisfaction with the analgesia received was
comparable (8.00 (± 2.45) vs 7.67 (± 2.62), (p = 0.7)). Patients in the
PCA group suffered more nausea (63.2% vs 30% respectively, OR 4.0,
95% CI 1.05-15.20, p<0.05) and expressed more the desire for
more analgesic support compared to the control group (OR 5.7 (1-33.25),
p = 0.05).
Conclusion Women with abortion induction after 14 weeks of
gestation suffer from relevant severe pain, which requires adequate
therapy. However, addition of PCA does not seem to bring any advantage
in patients undergoing this procedure.
Tweetable
abstract
Patient-controlled analgesia is not effective as a form of analgesia in
medically induction of abortion.
INTRODUCTION
Medically-indicated termination of pregnancy (TOP) is one of the most
commonly performed procedures in obstetrics. It is estimated that of the
99,948 TOPs performed in Germany in 2020, almost 3,900 were due to
health conditions and a total of 2,874 were performed after the
12th week of pregnancy The standard approach for TOP
in the second and third trimester of gestation in Germany is usually
medical rather than surgical. This means induction of labour with
prostaglandins often after application of mifepristone.
During second or third trimester abortion induction, notably more
complications can be expected. In addition to heavy bleeding, nausea and
pain, patients may experience higher levels of psychological stress due
to longer exposure to pregnancy. It is well established that
psychological mechanisms like catastrophizing, resilience and levels of
psychological distress play a relevant role in pain modulation. As TOP
is an exceptional emotional situation, it is conceivable that this
procedure could lead to a higher pain experience in these patients.
Some studies have assessed pain experience and analgetic management in
termination of pregnancy in the first trimester . Although little is
known about pain management in the later trimesters, it has been shown
that suffering pain during birth has a significant long term influence
on the physical and psychological wellbeing of mothers even many years
after delivery . Being affected by highly intensive pain during delivery
has also been correlated with a higher risk of developing postpartum
depression Opioid-based patient-controlled analgesia (PCA) is an
established technique for postoperative analgesia, has been demonstrated
to be an effective method for postoperative pain management and is
recommended by evidence-based guidelines worldwide. Patient-controlled
remifentanil has been used effectively in the past There is currently no
data available for this type of analgesia in medical TOP after the first
trimester.
The aim of the present study was to evaluate the introduction of an
opioid-based intravenous PCA technique into routine care for pain
control during medically induced 2nd or
3rd trimester TOP with the primary outcome measure
being maximal pain intensity. Secondary aims were the evaluation of pain
management from a patient perspective and evaluation of risk factors for
higher pain intensity.
METHODS
This prospective observational study was performed between July 2019 and
July 2020 at the department of Obstetrics and Prenatal Medicine of the
Bonn University Hospital in Germany. An approval of the local ethics
committee was provided
(Registration Number: 208/18).
Inclusion criteria were age over 18 years, pregnancy with a gestational
age over 14 weeks and medical indication for termination of pregnancy
according to the current German regulations. Women with a medical
history of opiate abuse or any contraindications for opiate use were
excluded from the study.
The procedure of TOP was performed according to standards of the Bonn
University Hospital. This consists of taking 600 mg of mifepristone
starting in the afternoon on the day of admission, followed by
misoprostol the following day at 10:00 pm administered every 4 hours
after being informed about off label use of misoprostol for this
indication. The dose of misoprostol depends on gestational age and
obstetrical history. Patients with a gestational age between 12+0 and
27+6 weeks and without previous uterine operations received a first dose
of 200mg orally followed by 400 mg administered vaginally every 4 hours.
If the gestational age was over 28+0 weeks, first dose of misoprostol
was 100 mg administered orally, increasing to 200 mg of misoprostol
every 4 hours vaginally. Patients with a history of uterine surgery
prior to abortion induction (such as previous cesarean section) were
given a different drug regimen, after being counseled about the
potentially increased risk of complications such as uterine rupture. In
these cases, patients between 12+0 to 22+6 weeks of gestation received a
first dose of 100 mg of misoprostol orally, followed by 100 mg vaginally
every 4 hours and patients between 23+0 to 29+6 weeks of gestation were
administered 75 mg of misoprostol orally every 4 hours. For those
patients receiving TOP later than 31st week of
pregnancy after uterine surgery induction of labour was performed by
cervical ripening with a Foley-balloon catheter on the same the day as
mifespristone administration. The catheter remained in the uterine
cavity for 24 hours. If no contractions were achieved after 24 h,
oxytocin was administered in the delivery room on the following day
after removing the balloon catheter. In cases of more than two previous
uterine operations or cesarean sections, or in cases of uterine
longitudinal- or T-shaped uterotomy in their medical history, a
pharmacological plan for individual abortion induction was prepared.
If TOP was indicated after 20 weeks of gestation, feticide was performed
by percutaneous ultrasound-guided injection of potassium chloride into
the umbilical vein before administration of mifepristone.
The analgesic management consisted of nurse-controlled administration of
ibuprofen 600 mg, paracetamol (acetaminophen) 1 g, metamizole 1 g,
tramadol 100 mg or a combination of meptazinol 100 mg and hyoscine
butylbromide 40 mg as short infusion on demand depending on patient’s
pain. In analogy to analgesic medication for labour in this center no
basic analgesia was provided and drug administration was performed
depending on pain intensity: nonsteroidal anti-inflammatory drugs
(NSAID) for mild pain, tramadol for moderate pain and meptazinol
combined with hyoscine butylbromide for severe pain allowing combination
in a three-step strategy. For comparison of opioid consumption dosage of
the drugs was converted to equivalents of oral morphine using standard
literature. According to this it was assumed, that 100 mg meptazinol are
equivalent to 12 mg of oral morphine and 15 mg piritramide are
equivalent to 30 mg oral morphine.
On April 1st, 2020, an additional form of analgesia was implemented as
standard care in our center for women undergoing this procedure. This
consisted of intravenous administration of piritramide via PCA pump. A
dose of 2 mg of piritramide bolus was given, triggered by the patient as
needed. The bolus could be repeated every ten minutes with a maximum
dosage of 30 mg in 4 hours. If higher doses were needed, consultation
with a specialist from the pain unit was additionally initiated to
reevaluate pain management. Otherwise, the patient was seen by a member
of the pain unit twice a day. Pump records were evaluated (times and
intervals of the applications) and the regime was adjusted as needed.
Application of ibuprofen, paracetamol or metamizole was also allowed.
The study group consisted of patients treated after the introduction of
the new pain management protocol. The control group was composed of all
patients who underwent abortion induction with standard analgesia before
the introduction of the PCA pump.
The evaluation was performed according to the QUIPS project (quality
improvement in postoperative pain management [23],
www.quips-projekt.de, last visited 28th of November 2021) and data
collection was performed in a highly standardized manner as described in
a previous study. QUIPS is a national multicenter interdisciplinary
project for the evaluation of acute pain management using patient
reported outcomes (PROs). This is the biggest database for acute
postoperative pain worldwide with more than 500,000 patient records in
Germany. The pain questionnaire was handed out to the patient at
admission. Patients were instructed to fill out the questionnaire
anonymously at the time of discharge. Demographical, clinical and
outcome data were sampled on the day of discharge. The questionnaire
consisted of fifteen questions divided into three thematic groups: pain
intensity, impairment due to pain and pain medication and satisfaction
with therapy (Table 1). Patients were asked to use a numeric rating
scale (NRS) from 0 (no pain) to 10 (most unbearable pain) for questions
regarding pain intensity. The NRS was also used for the evaluation of
satisfaction with the prescribed analgesia, here being 0 absolutely
unsatisfied and 10 very satisfied. The personnel performing the
questionnaires and data collection were specifically trained and
provided with written guidelines to ensure standardized data collection.
Once the questionnaire was filled out by the participants, the data were
entered in the central electronic database of the QUIPS project. QUIPS
is included in the german registry for clinical trials (DRKS-ID:
DRKS00006153)
Pain levels of seven or more were considered severe for the analysis of
risk factors for severe pain.
STATISTICAL ANALYSIS
A two-point reduction on the NRS was defined as clinically relevant for
the sample size calculation. Based on earlier publications a mean pain
score for maximal pain of 4.6 with standard variation of 2.2 was used
and nineteen patients were needed in each arm to see a reduction of two
points on the NRS with 80 % power and assuming a 5 % type 1 error.
The Mann-Whitney-U-test was used for the analysis of the ordinal
variables (NRS for pain intensity and satisfaction) since no normal
distribution was observed. The Student’s t-test was performed for
continuous variables (dosage of rescue medication, time to first rescue
medication). Descriptive categorical variables were analyzed using
X2 or Fischer’s exact test as appropriate. Results are
expressed as mean, plus / minus standard deviation (SD) for continuous
variables and as percentage or odd ratio with 95& confidence interval
for categorical variables. Statistical analysis was performed using SPSS
version 19.0 (SPSS inc. Chicago, IL).
RESULTS
Forty patients were included in the study. Both the study group and the
control group consisted of twenty women each. No statistical differences
could be found between both groups concerning demographic data and
baseline characteristics (Table 2).
Women in the study group reported higher maximum NRS pain levels (6.90
(± 2.34) vs. 4.83 (± 2.87), (p < 0.05)). Minimal pain and pain
related to movement were similar. Satisfaction levels with pain
management were similar in both groups (8.00 (± 2.45) vs. 7.67 (± 2.62),
(p = 0.7)) (figure 1). The occurrence of nausea was significantly more
frequent in patients with piritramide PCA (63.2 % vs 30.0 %
respectively, OR 4.0 (95 % CI 1.05 - 15.20) p<0.05). Women in
the study group were also more often awake at night due to pain (75 %
vs. 20 %, p = 0.048, OR 4.8 (95 % CI 4.2 - 19.9)). No differences
between the two groups were observed for dizziness, fatigue or other
items of the questionnaire including wanting more analgesia (table 3).
Regarding the use of analgesic drugs, non-opioids were rarely used in
both groups (two women received paracetamol in the control group and one
woman in the PCA group) except hyoscine butylbromide, since this was
administrated in a fixed combination with meptazinol in the control
group. Opioid consumption was similar in both groups. Sixteen patients
(80 %) in the control group received opioids for analgesia while
nineteen women (95 %) used the piritramide pump in the study group (p =
0.34). The analysis of the cumulated dosage of opioid drugs
administrated thorough the whole procedure did not significantly differ
between the control and PCA group (15 mg (± 13.5) vs. 20 mg (± 20.6) of
equivalent oral morphine respectively, p = 0.37).
The analysis of the effect of relevant pain levels shows that patients
reporting pain levels of seven or more were more likely to suffer nausea
or vomiting (OR 8.5, 95 % CI 1.96 - 36.79, p = 0.004) and dizziness (OR
6.6 (95 % CI 1.62 - 26.87) p = 0.009) and felt more impaired in their
mobility (OR 6.79 (95 % CI 1.60 - 28.86) p = 0.009). These patients
stated significantly more often that they wanted more analgesics during
the whole procedure (OR 5.73 (95 % CI 1.0-33.25), p = 0.05). Feticide
performed prior to induction of labour and fetal weight over 350 g
showed a significant correlation with the development of severe pain
with their distribution being similar. Eleven (64.7 %) patients who had
a fetus weighing more than 350g complained about severe pain levels,
while only six women (30.4 %) with a fetus of less than 350 g reported
maximum pain levels of seven or more. Feticide was also performed in
eleven (64.7 %) vs. six (30.4 %) pregnancies. The OR was the same for
both variables: feticide and fetal weight over 350 g; 4.19 (95 % CI
1.1-15.9) p = 0.03). No correlation was found between pain intensity
higher than seven and any other study variable such as need of
curettage, maternal age, induction time, etc.
DISCUSSION
Main findings and Interpretation
In the present study, patients reported high periinterventional pain
scores during late medically indicated TOP, even when using
patient-controlled analgesia with an automatic intravenous PCA device.
To the best of the authors’ knowledge, this is the first study
evaluating the use of opioid based PCA for analgesia during TOP in the
second and third trimester under standardized conditions. Unfortunately,
not much is known about pain, pain management and consequences of pain
in patients undergoing medical TOP after the first trimester. The
available evidence shows unexpectedly high levels of pain intensity
related to this procedure. Therefore, this study group was unable to
find any noteworthy evidence, written guidelines or recommendations
regarding pain management for women undergoing late medical abortion.
Although the TOP procedure itself is subject of heterogeneous
regulations in each country and different medical societies have issued
different guidelines, pain management is not part of these guidelines.
By introducing PCA as a new standard of care for pain management, the
authors expected to observe a reduction of pain levels and an increased
satisfaction with pain therapy. However, patients treated with the new
standard complained about significantly higher pain levels and these
pain levels were related with wish for more analgesia. Other studies
came to a similar conclusion when opioids were added to standard pain
management in early TOP. Colwill et al. observed that adding oxycodone
to standard therapy does not reduce the pain intensity for medical
abortion in early pregnancy . In addition, the use of nitrous oxide
failed to improve pain management in surgical TOP before 16 weeks of
gestation
Several studies have shown that administering opioids as analgesics not
only does not reduce pain satisfactorily after surgical TOP but also
causes relevant side effects, such as nausea or vomiting. This implies
increased discomfort during this stressful process and further
medicalization of women who require abortion induction as they need
additional antiemetic.
Opioid consumption was over 80 % in both groups, but equivalent
cumulative dosages seem to be rather low with 15 mg and 20 mg
respectively. However, we have to admit that there is no clear
equivalent conversion factor for intravenous meptazinol, since it is an
uncommonly used opioid drug outside of obstetrics and currently accepted
standard conversion values are based on old studies describing
equivalence between intramuscular meptazinol and morphine.
Considering that administration of non-opioid was almost inexistent in
both groups, sufficiency of analgesic treatment in both groups can be
questioned and considered a plausible explanation for the high levels of
pain described in the present study. Since hyoscine butylbromide was
always administrated in a fixed combination with meptazinol in the
control group, an additional effect of this drug on the observed
difference between groups cannot be clearly excluded in this study.
Although the analgesic effect of this drug it is not clear, it has been
demonstrated, that hyoscine butylbromide reduces the duration of labor,
and this could have an effect on the whole pain experience
Nonpharmacological interventions for pain management have been evaluated
in other studies. Dufresne et al. studied whether hypnosis before and
during TOP had a positive influence on pain management. They showed that
patients who were under hypnosis required less intravenous analgesia
although they reported similar pain levels compared to women who
underwent the standard pain management . The pain questionnaire used for
the present study also included one question about the use of
non-pharmacological interventions, but patients used these strategies
very rarely. For example, relaxation techniques were the most used
nonpharmacological method for pain relief, but these were used only by
five patients. Although no patients using relaxation techniques reported
high severe pain levels, this difference was not statistically
significant. Other methods (massage, respiration techniques, local
warmth etc.) were used by only one or two patients.
The pain levels reported in this manuscript were unexpectedly high and
should be of concern. As a comparison, similar NRS pain levels (6.98 SD
+/- 0.27) have been reported after cesarean sections in a recent
publication . This is relevant since cesarean section can be considered
one of the most painful surgeries compared with non gynaecological
procedures and the most painful surgical procedure in the gynaecological
spectrum .
Pain scores for operative TOP in the first trimester are not as high as
for later medical abortion induction . This can probably be explained by
the controlled conditions under which surgical procedures are performed,
the use of anesthesia during the process, but also the availability of
clear guidelines and recommendations. Patients might also suffer lower
mental stress levels due to the shorter duration of pregnancy and
different indications for TOP.
In the case of surgical TOP in the first trimester, being married, lower
expectations for bleeding and being unafraid of prior pelvic exploration
have been related to lower pain scores. In contrast to these data, the
present study shows that only fetal weight above 350 g and performance
of feticide have a significant correlation with severe pain. Since
feticide is only performed in pregnancies after the 20th week of
gestation and fetal weigh in these cases is expected to be higher, it is
not possible to evaluate the size effect of each variable separately.
Other factors such as need of curettage, maternal age or prior obstetric
history, did not play a relevant role in this study. However, marital
status and patient expectations were not subject of research in the
study.
Since medical abortion induces psychological stress and pain modulation
is also affected by psychological factors, it could be assumed that
these women have a higher perception of pain. This has been already
described for catastrophizing and anxiety regarding other medical
procedures. Pur et al. for example showed that patients with higher
scores for anxiety in the STAI (State-Trait-Anxiety Inventory)
questionnaire tended to report higher pain levels after first trimester
termination of pregnancy .
Insufficient pain control during abortion procedures is also related
with a worse whole health care experience. The present data are in line
with these findings since patients who reported high pain scores were
less satisfied with the whole management. This has been described for
other gynaecological procedures such as cesarean section or gynaecologic
laparoscopy .
Recommendations for pain management for second trimester medical
abortion have been described as poor and heterogeneous by other groups.
Due to the lack of qualitative evidence for analgesic strategies in
these patients, each center tends to use local guidelines which are
inconsistent and not well evaluated.
Strengths and Limitations
To our knowledge, this is the first study evaluating different pain
management modalities in patients undergoing medically induced
termination of pregnancy after the first trimester. The strength of this
prospective study is the use of a validated high standardized tool for
evaluation of acute pain management using patient reported outcomes.
Since the purpose of this study was to evaluate the introduction of a
PCA pump as a standard of care in daily standard hospital conditions,
randomization or blinding was not performed, so selection bias cannot be
excluded. In order to address this issue, the following measures were
taken: no member of the obstetric team was involved in the data
collection as patients filled out the questionnaire alone and external
assessors were responsible for data input. Patients were informed about
the use of a PCA pump by the anesthesiology team, but they were not
aware of the different interventions being evaluated.
The present study has certain limitations. The first of which is the
small sample size calculated for the primary outcome. Only nineteen
patients per group were needed for each arm to detect a relevant pain
reduction with 80 % power. Consequently, this could mean that the
evaluation of secondary outcomes is statistically underpowered. Another
limitation of this study is the change of setting within the study
period. The prenatal unit moved to another building within the hospital
nearly four weeks after introducing PCA pumps. The influence of this
issue is uncertain, since the personnel and the rest of the standards
were unchanged. The study center is a high-volume reference center for
prenatal diagnosis and thus no significant fluctuations in the reference
population were expected. This could be shown since no significant
difference between the groups could be found for demographical
characteristics. The study did not evaluate the stress or anxiety levels
of the women undergoing TOP. The effect of these factors has been
described in other studies, so it is not possible for the authors to
rule out the influence of these aspects on the results of the present
study.
Conclusion
TOP in the late trimester is associated with high pain intensity. Using
piritramide PCA for this procedure was associated with higher pain
intensity, nausea and vomiting than the previous standard pain
medication on demand. Higher fetal weight and feticide seem to be
associated with higher pain levels. Since very little is known about
appropriate pain management in these women, more studies are needed to
improve patient care.