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REMIFENTANIL FOR THE TREATMENT OF PAIN IN EXTERNAL
Henar Muñoz Hernández 1, MD
Amanda López-Picado 2, MPH
Sandra Guerra Merino 3, MD
Pilar Pérez Vaquero 1, MD
Cesar Valero Martínez 1, MD
Felipe Aizpuru 2, MD, MPH
Department of Anaesthesiology and Resuscitation, Txagorritxu University Hospital
Álava Research Unit, Txagorritxu University Hospital (Vitoria-Gasteiz)2
Department of Gynaecology and Obstetrics, Txagorritxu University Hospital (Vitoria-
Address: Henar Muñoz Hernández
Calle José Atxotegi, s/n, VITORIA-GASTEIZ; SPAIN
Keywords: Remifentanil, external cephalic version, pain, obstetrics, anaesthesia,
External cephalic version (ECV) is a process used for changing a breech to a cephalic
presentation. Its success rate ranges from 40 to 74%, leading to a decrease in the
number of caesareans and reducing the risk for mother and her child. Despite being a
recommended procedure, it is not performed in many centres due its association with
levels of pain between 4.5 and 8 on the visual analogue scale (VAS).
We report 44 women on which ECV was carried out administrating them remifentanil 0.1mg/kg/min by continuous infusion with rescue boluses of 0.1 mg/kg.
The percentage of success was of 43.2%. Pain (VAS) was 3.18 ±2.05: 2.47 ±1.87 and 3.72± 2.06 in successful and unsuccessful cases, respectively (p=0.045). Continuous infusion of remifentanil with rescue boluses might be a good analgesic alternative for ECV, with no observed increase in adverse effects or complications for the mother or foetus.
In 3-4% of pregnancies that reach term the baby is in breech presentation (1,2). External
cephalic version (ECV), also known as external version, is a procedure used to turn the
foetus from a breech to a cephalic presentation, wich is more favourable for delivery. The procedure of external version is simple and entails little risk if the indications are followed. Three stages can be identified: moving the foetus up away from the mother´s pelvic bones, whole rotation and bringing the head down again into the pelvis in order to allow the patient to have a vaginal delivery with the baby in cephalic presentation.
The use of this procedure is successful in 40 to 74% of cases (3-6), making it possible to
significantly reduce, by between 9 and 16%, the number of breechbuttock presentations
and caesareans (7-9). This is a simple, effective and safe method that would avoid the need for many caesareans (7-12). For this reason, several prestigious international societies recommend the use of this technique (13,14).
It has to be emphasized that in order to achieve success with this procedure it
should not be painful and it is important that the patient remains relaxed. Indeed, the
version cannot be carried out against the will of the patient or if she resists the
Despite the immense amount scientific evidence that supports external version as a
manoeuvre to favour vaginal delivery, its use is not generalised for two main reasons:
the need for an expert gynaecologist to perform it and, above all, the difficulty of
finding a suitable analgesic to alleviate the pain that the process entails. Studies using
the VAS to assess the pain experienced by patients indicate values ranging between 4.6
and 8.5 out of 10 (4,5,15). For this reason, between 18 and 76% of pregnant women
refuse the procedure (16-18).
Although several options have been evaluated, such as intradural and epidural analgesia,
the results have not been very conclusive (19-21) and so it is necessary to continue to
search for an effective analgesic.
Given that, in recent years, remifentanil has emerged as a new option for analgesia and
sedation in obstetrics.
Remifentanil is a pure agonist for opioid receptors that has great analgesic effect, with
unique pharmacokinetics, including a rapid onset of action (in approximately 1 minute),
which enables more effective titration of the dose, and fast degradation by plasma and
tissue esterases to inactive metabolytes with a constant half-life of approximately 3
minutes (22,23). Consequently, this drug has a good safety profile, both for pregnant
woman and for foetuses (24,25). In particular, it does not accumulate, regardless of the
dose administered (25,26).
Although to date there have been no reports of its use for the treatment of pain produced
by ECV, there have been publications concerning its usefulness in obstetrics
which have reported very satisfactory results (27-31) due to its predictable pharmacokinetics and easy administration.
Given all of this, it was decided to undertake a pilot study with the objective of
evaluating the effect and safety of remifentanil as an analgesic for ECV.
MATERIAL AND METHODS:
Patients were recluted for a 1 year period ( from September 2008 to September 2009) at Txagorroitxu Hospital (Vitoria-Gasteiz, Spain). The study was approved by the Txagorritxu Hospital Ethics Research Committee. All the participants gave informed consent.
The administration of remifentanil on a compassionate use basis was carried out by the anesthetist according to the Txagorroitxu Hospital protocol.
The infusion pump (B Braun Medical ® Ltd, Sheffield, UK) was set up and programmed to supply the medication according to the patient’s weight. A combination of 100 ml of saline 0.9%, 1 mg of remifentanil (ULTIVA 1mg. GSK®), was used for continuous infusion at a rate of 0.1 mcg/kg/min with rescue boluses of 0.1 mcg/kg infused over one minute.
Infusion was started before beginning the ECV manoeuvre. As many boluses as needed were administered as long as the woman remained alert and able to respond to tactile stimuli, haemodynamically stable and did not feel pain.
The procedures was considered to be successful when ultrasound showed the cephalic
pole to be in line with the pelvis of the mother, and it was considered unsuccessful when
this was not achieved or if there was any complication causing the procedure to be
halted. The procedure was interrupted when this was requested by the woman, for any
reason, or when the gynaecologist or anaesthesiologist considered appropriate.
Forty-four pregnant women had pregnancies with no complications and fulfilled the
inclusion criteria (Table Ib).
Table I: External cephalic version (ECV) inclusion and exclusion criteria
- Inclusion criteria:
? Foetus between week 36 and 41 of gestation confirmed by
ultrasound to be in non-cephalic presentation
? ASA I-II pregnant women
? Informed consent form signed by the pregnant woman or by her legal representative.
- Exclusion criteria:
? Foetal abnormalities
? Severe hypertension
? Allergy to any drug or material used in the procedure
? Amniotic fluid index < 8 cm
? Abnormal contraction stress test
? Contraindications for vaginal delivery
? Abnormalities of the uterus and clotting disorders
? Placenta praevia
? Rh sensitization
? Multiple gestation
? Rupture of membranes
? Premature abruption of normally inserted placenta
? History of substance abuse
? Heart or cerebrovascular disease
A total of 44 women participated in the study (mean age 33.98±3.24 years) of whom
86% were nulliparous, and only one of them had previously undergone a caesarean. None of the patients who were offered to participate in the study declined.
The mean stage of pregnancy was 36 ± 1.10 weeks and the mean weight of the foetuses was 2806 ± 301 g.
The technique was successful in 19 cases (43,2%). No one successful ECV was reverted to breech. With regards to adverse events, 1 cases of dizziness (2,22%) were registered among the women, while there were 4 instances of mild fetal bradycardia (8,89%), but in no case the procedure was aborted ( mild fetal bradycardia was defined as fetal cardiac frecuency lower than 100 beats/minute for less than 10 seconds).
The average pain score, on the VAS, was 3.18 ± 2.05. Successful procedures showed
VAS scores of 2.47 ±1.87 while unsuccessful procedures 3.72± 2.06. The difference
between the two groups was stadistically significant (p=0.045).
The mean number of remifentanil boluses used was 4.18 ± 3.44. Successful and
unsuccessful cases had mean values of 3.32 ± 2.34 and 4.84 ± 4.01, respectively, but no
significant difference was found between the groups.
There were 14 vaginally delivered out of 19 successful ECV. The remaining 5 cases underwent a caesarean surgery, however the reasons why patients recived caesarean procedure there were no related to previous ECV. There were no successful ECV that reverted to breech.
Many medical interventions associated with obstetrics are accompanied by intense pain
for the patient. This has led to search intensification for analgesic therapies, that are
useful for these procedures, and safe both for pregnant women and foetuses.
Specifically, the ECV procedure, although painful, may mean a significant
decrease of the number of caesarean sections.
The rate of ECV success achieved in our study falls within the wide range reported in the literature (21). Taking into account that in our study 86.4% of participants were
nulliparous, and their ECV success rate are lower (21,32), we can consider our outcomes to be satisfactory.
One of the possible explanations for these results may be the use of remifentanil as an
analgesic drug. The fact that the patient is more relaxed and pain free, allows the
gynaecologist to work more freely and safely. It also makes it easier to consider repeating the procedure, if needed, thus increasing the chances of success.
The method of administration selected in this study was continuous infusion with rescue
boluses. This was despite remifentanil having been shown to be more effective as
patient-controlled analgesia (PCA) than by continuous infusion (30,31) in obstetric
analgesia for labour. However, in our case, the pain is continuous, ongoing throughout
the time taken to carry out the manoeuvre and, for this reason, continuous infusion with
rescue boluses for moments when infusion was inadequate, seemed likely to be much
more effective than PCA-on-demand. In this way, the level of analgesia required by
each patient is administered individually, not only improving pain control, but also
reducing as much as possible adverse effects.
This does not imply that we should not act with extreme caution while performing this
technique, given that though few, important complications have been reported in
association with the procedure (21,32), such as rupture of membranes, vaginal bleeding,
placental abruption, and sustained foetal bradycardias. In some cases, it has even been
necessary to carry out emergency caesarean sections due to suspicion of risk of loss of
foetal well-being (21,32). However in our study, there were no severe adverse events associated with the procedure.
With regards to adverse reactions caused by remifentanil, there was only 1 case (2.22%)
among the women and there were 4 (8.89%) among the foetuses. In the case of the
pregnant woman, the adverse effects were attributable to remifentanil: mild desaturation
that eased off with brief stimulation and a feeling of queasiness and drowsiness that
disappeared once the administration of the drug was stopped, without it being necessary
to take further measures. These are similar or equivalent to effects caused by
remifentanil in other non-pregnant patients (27-29).
Bradycardias were the only adverse effect detected in the foetuses, which disappeared
when the procedure was temporarily suspended. And in no cases the procedure was finally aborted. Moreover, as indicated by other studies, remifentanil is a safe drug (27-
29) and it is not unusual for mild and transient bradycardias to occur during this
procedure whether analgesia is used (5,6,32).
Despite ECV being an evidently painful procedure, the results of our study are very positive, with a mean VAS score of 3.18. Other studies investigating this
procedure without analgesia have reported VAS values ranging between 4.5 and 8.6.
Our findings showed that the mean pain VAS was 3.18 while other alternatives such as spinal analgesia (20) has been reported to yield VAS of 3.6 (20) and up to 8.5 when analgesia was not given . Therefore, remifentanil administred in continuous infusion with rescue boluses, might be a good analgesic alternative for the ECV procedure without increasing adverse effects or complications.
To date, regional anaesthesia, either spinal or epidural, has been studied in several trials
with contradictory results, from which it has not been possible to recommend their use
It has been found that pain is the main objection to this procedure (16-18), so finding a
technique that can achieve pain relief may lead to an increase in the number of pregnant
women who accept the procedure and hence a decrease in the number of caesarean
The greatest limitation of the study lies in the fact that the sample size is small and that
There were no control group; with the methodological deficiencies that this represents, the results, although relevant for some parameters such as subjective pain, should be
interpreted with caution.
In conclusion, this is the first study carried out using remifentanil for EVC procedures. Our results hav showned that there is a new avenue for the treatment of pain caused by the ECV procedure and a potential corresponding improvement in the outcome, which ultimately may help to decrease the number of caesarean sections, with benefits in terms of cost savings and safety for mother and child.
However it is necessary to continue and carry out further studies to confirm this results.
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