Browse through our Medical Journals...

REMIFENTANIL FOR THE TREATMENT OF PAIN IN EXTERNAL

CEPHALIC VERSION

Authors:

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

(Vitoria-Gasteiz)¹

Álava Research Unit, Txagorritxu University Hospital (Vitoria-Gasteiz)²

Department of Gynaecology and Obstetrics, Txagorritxu University Hospital (Vitoria-

Gasteiz)³

Corresponding author:

Address: Henar Muñoz Hernández

Hospital Txagorritxu

Calle José Atxotegi, s/n, VITORIA-GASTEIZ; SPAIN

Tel: 34-945-007413

Fax: 34-945-007336

Keywords: Remifentanil, external cephalic version, pain, obstetrics, anaesthesia,

delivery

ABSTRACT:

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.

INTRODUCTION.

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

manoeuvre.

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.

RESULTS:

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.

DISCUSSION:

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

(19-21).

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

sections.

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.

REFERENCES:

Hutton EK, Kaufman K, Hodnett E, Amankwah K, Hewson SA, McKay D, et al. External cephalic versión beginning al 34 weeks gestation versus 37 weeks gestation: a randomized multicenter trial. Am J Obstet Gynecol. 2003;89: 245-254
Hickok DE, Gordon DC, Milberg JA, Williams MA, Daling JR. The frequency of breech presentation by gestational age at birth: a large population-based study. Am J Obstet Gynecol. 1992;166:851-852.
Mahomed K, Seereas R, Coulson R. External caphalic version at term: A randomized controlled trail using tocolysis. Br J Obstet Gynaecol 1991; 8-13.
Nagy J, Nyklová E. Is fear of external cephalic version well-founded?. Ceska Gynekol. 2008;73:254-260.
Sela HY, Fiegenberg T, Ben-Meir A, Elchalal U, Ezra Y. Safety and efficacy of external cephalic version for women with a previous cesarean delivery. Eur J Obstet Gynecol Reprod Biol. 2009;142:111-114.
Kok M, Bais JM, van Lith JM, Papatsonis DM, Kleiverda G, Hanny D,et al. Nifedipine as a uterine relaxant for external cephalic version: a randomized controlled trial. Obstet Gynecol. 2008;112:271-276.
Hofmeyr GJ, Kulier R. External cephalic version for breech presentation at term. Cochrane Database Syst Rev 2000:CD000083.
Tasnim N, Mahmud G, Khurshid M. External cephalic version with salbutamol - success rate and predictors of success. Coll Physicians Surg Pak. 2009;19:91-94.
Collaris RJ, Oei SG. External cephalic version: a safe procedure? A systematic review of version-related risks. Acta Obstet Gynecol Scand 2004;83:511–518.
Subtil D, Vaast P, Dufour P, Depret-Mosser S, Codaccioni X, Puech F. Conséuqences maternelles de césarienne par rapport à la voie basee. J Gynecol Obstet Biol Reprod. 2000;29; Suppl 2 :10-16
Kok M, Cnossen J, Gravendeel L, van der Post J, Opmeer B, Mol BW. Clinical factors to predict the outcome of external cephalic version: a metaanalysis. Am J Obstet Gynecol. 2008;199:630.1-7
Collaris RJ, Oei SG. External cephalic version: A safe procedure? A systematic review of version-related risks. Acta Obstet Gynecol Scand 2004;83:511-518.
American College of Obstetricians and Gynecologists Committee Opinion No. 340. Mode of term singleton breech delivery. Obstet Gynecol 2006;108:235-7.
De Miguel JR, De Cabrillo E, Carrasco S, Ezqurdia M, Martínez J, Melchor JC, et al. Documentos de consenso. SEGO. Meditex: Madrid; 2001:9-48.
Burgos J, Melchor JC, Cobos P, Eguiguren N, Centeno Mª, Fernandez-Llebrez, et al. Análisis del dolor en la versión externa. Prog Obstet Ginecol. 2009;52:557-561
Leung TY, Lau TK, Lo KW, Rogers MS. A survey of pregnant women’s attitude towards breech delivery and external cephalic version. Aust N Z J Obstet Gynaecol 2000;40:253-259.
Raynes-Greenow CH, Roberts CL, Barratt A, Brodrick B, Peat B. Pregnant women’s preferences and knowledge of term breech management in an Australian setting. Midwifery 2004;20:181-187.
Yogev Y, Horowitz E, Ben-Haroush A, Chen R, Kaplan B. Changing attitudes toward mode of delivery and external cephalic version in breech presentations. Int J Gynaecol Obstet 2002;79:221-224.
Weiniger CF, Ginosar Y, Elchalal U, Sharon E, Nokrian M, Ezra Y External cephalic version for breech presentation with or without spinal analgesia in nulliparous women at term: a randomized controlled trial. Obstet Gynecol. 2007;110:1343-1350.
Sullivan JT, Grobman WA, Bauchat JR, Scavone BM, Grouper S, McCarthy RJ,et al Int J Obstet Anesth. 2009;18:328-334.
Hofmeryr GJ, Gyte G. Interventions to help external cephalic version for breech presentation at term. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD000184.
Leppa M, Korvenoja A, Carlson S et al. Acute opioid effects on human brain as revealed by functional magnetic resonance imaging. Neuroimage 2006; 31: 661–669.
Kapila A, Glass PS, Jacobs JR et al. Measured contextsensitive half-times of remifentanil and alfentanil. Anesthesiology 1995; 83: 968–975.
Macarthur AJ, Gagnon S, Tureanu LM, Downey KN. Anesthesia facilitation of external cephalic version: a meta-analysis. Am J Obstet Gynecol. 2004;191:1219-1224.
Davis PJ, Stiller RL, Wilson AS, et al. In-vitro remifentanil metabolism: the effects of whole blood constituents and plasma butyrylcholinesterase. Anesth Analg 2002; 95:1305–1307.
CrankshawDP,Chan C, Leslie K, et al.Remifentanilconcentration during targetcontrolled infusion of propofol. Anaesth Intens Care 2002; 30:578–583.
Evron S, Ezri T. Options for systemic labor analgesia. Current Opinion in Anaesthesiology 2007, 20:181–185
Hill D. Remifentanil in obstetrics. Current opinion in anaesthesiology 2008: 21: 270-274
Kan RE, Hughes SC, Rosen MA, et al. Intravenous remifentanil: placental transfer, maternal and neonatal effects. Anesthesiology 1998; 88:1467–1474.
Volikas I, Butwick A, Wilkinson C, et al. Maternal and neonatal side-effects of remifentanil patient-controlled analgesia in labour. Br J Anaesth 2005;95:504–509.
Blair JM, Hill DA, Fee JP. Patient-controlled analgesia for labour using remifentanil: a feasibility study. Br J Anaesth 2001; 87:415–420.
Nassar N, Roberts CL, Barratt A, Bell JC, Olive EC, Peat B. Systematic review of adverse outcomes of external cephalic version and persisting breech presentation at term.Paediatr Perinat Epidemiol. 2006;20:163-171.
Leung TY, Sahota DS, Fok WY, Chan LW, Lau TK. Quantification of contact surface pressure exerted during external cephalic version. Acta Obstet Gynecol Scand. 2003; 82:1017-1023