1Department of Anaesthesia, Southmead Hospital, Westbury-on-Trym, Bristol, UK. 2Department of Anaesthesia, Royal Bournemouth Hospital, UK. 3Department of Anaesthesia, Frenchay Hospital, Frenchay Park Road, Bristol, UK*Corresponding author: Department of Anaesthesia, Taunton and Somerset Hospital, Musgrove Park, Taunton TA1 5DA, UK
Accepted for publication: November 9, 2001
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Abstract |
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Methods. In an open pilot study, 36 women requesting meperidine for analgesia were recruited early in labour and randomized to receive either meperidine i.m. or remifentanil given as patient-controlled analgesia (PCA). Pain severity, sedation and anxiety were assessed with visual analogue scales and overall effective analgesia was assessed by the woman and midwife.
Results. The pain scores were lower in the remifentanil group: median pain score at 60 min was 72 mm for meperidine and 48 mm for remifentanil (P=0.004) and median maximum pain score during the first 2 h was 82.5 mm for the meperidine group and 66.5 mm for the remifentanil group (P=0.009). Both the midwives and the womens assessments of overall effective analgesia were higher in the remifentanil group [Likert scale (5 = excellent to 1 = poor): 2=12.10, P=0.002 for mothers assessment;
2=12.80, P=0.002 for midwives assessment].
Conclusion. In this pilot study, remifentanil by PCA gave better pain relief to mothers in labour than intramuscular meperidine. However, remifentanil is a potent respiratory depressant and adequate continuous monitoring is necessary.
Br J Anaesth 2002; 88: 3748
Keywords: analgesics opioid, meperidine; analgesics opioid, remifentanil; analgesia, obstetric
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Introduction |
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Remifentanils rapid onset and offset of effect3 4 should make it an ideal drug for the intermittent painful contractions of labour. It has been used as an i.v. infusion during non-urgent Caesarean section as an adjunct to epidural anaesthesia. It does cross the placenta (mean uterine vein:maternal artery ratio=0.88) but is rapidly metabolized, redistributed or both (mean uterine artery:uterine vein ratio=0.29), with no clinically adverse effects on the neonate.5
Patient-controlled analgesia (PCA) techniques are not new to obstetrics: PCA is the standard delivery system for Entonox. Meperidine,6 butorphanol tartrate,7 tramadol,8 nalbuphine9 and fentanyl10 11 have all been given by PCA in labour. Remifentanil may have an advantage compared with these because of its rapid onset time and rate of hydrolysis. There are case reports of remifentanil PCA in labour in parturients with known platelet abnormalities.12 13 Intravenous PCA should be better than intermittent i.m. injections because it avoids the pain of injection and allows better matching of analgesic delivery to the pain.
We conducted an open randomized pilot study to compare the analgesic effect of remifentanil given as PCA with i.m. meperidine during labour.
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Methods |
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Pain was assessed with a continuous visual analogue scale (VAS; 100 mm, marked no pain to worse pain imaginable). Women were asked to mark on the line the worst pain they had felt during their last contraction after it had finished. Sedation and anxiety were assessed similarly, using the terms wide awake to very sleepy for sedation, and very calm to very anxious for anxiety. Nausea scores and the physiological variables of blood pressure, pulse rate, ventilatory rate and oxygen saturation by pulse oximetry were also measured.
Baseline recordings were made and then measurements were taken every 30 min after analgesia was started. Although measurements were recorded every 30 min, all women were observed throughout by their attending midwife, and one of the investigators was available in the delivery suite at all times during the study. All patients were monitored by continuous pulse oximetry.
If the assigned analgesia was inadequate for the patient at any time, an alternative was offered and further study recordings were discontinued.
The foetus was monitored by continuous cardiotocography and Apgar scores were noted at delivery. All women had access to Entonox at all times.
The overall effective analgesia was rated after delivery by the mother and attending midwife within 2 h of delivery on a five-point verbal scale ranging from excellent to poor (Likert scale: 5=excellent, 4=very good, 3=good, 2=fair, 1=poor).
A power calculation was performed at the design stage of the study. We estimated that the probability of a woman who was receiving remifentanil reporting a lower pain score than a woman receiving meperidine was 0.85. Assuming that the pain scores would be compared using a Wilcoxon rank sum test, for a two-sided 5% level of statistical significance and 90% power we estimated that we needed to recruit 30 patients in total, 15 in each group.
The overall effective analgesia rating (Likert scale) was analysed using the 2 test. Fishers exact test was applied to the nausea and vomiting scores and epidural conversion rates. The combined influence of drug treatment and other postrandomization events was assessed by analysis of variance. All other non-parametric data were compared using the Wilcoxon rank sum test. Parametric data were analysed with the t-test. Analysis was performed using Stata for Windows (Stata Corporation, Texas, USA) and Microsoft Excel for Windows.
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Results |
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There was no difference between the two groups in the pain scores at 1 h or maximum pain score over the first 2 h in relation to artificial rupture of membranes (P=0.86, P=0.31) or Syntocinon usage (P=0.77, P=0.35).The midwives and mothers assessments of overall effective analgesia were both higher in the remifentanil group (P=0.002) (Figs 1 and 2). There were no other significant differences between the two groups.
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There was no significant difference in the recorded minimum ventilatory rate between the two groups (P=0.60), although rates less than 8 between contractions were recorded for three patients receiving remifentanil; these responded quickly to verbal stimulation.
All women receiving meperidine were given an antiemetic at the same time (promethazine 25 mg or prochlorperazine 12.5 mg). No antiemetic was given to women receiving remifentanil unless indicated clinically. Ten women receiving meperidine and five receiving remifentanil experienced nausea and vomiting (P=0.06). Three women receiving remifentanil went on to receive an antiemetic (either promethazine 25 mg or prochlorperazine 12.5 mg).
Three women receiving meperidine later received an epidural, while seven receiving remifentanil required additional analgesia and later an epidural (P>0.05).
There were more non-spontaneous vaginal deliveries in the remifentanil group (P=0.04). The three Caesarean sections in the women receiving remifentanil were not related in time to the use of remifentanil and all three women needed epidural analgesia because of inadequate pain relief. The time to section after the epidural was sited was between 2 and 8 h. Three of the four ventouse deliveries in the women receiving remifentanil were not related in time to the use of remifentanil and all three women needed epidural analgesia because of inadequate pain relief. The time to ventouse delivery after the epidural was sited was between 3 and 7 h. If this information is taken into account, there would be one non-spontaneous vaginal delivery in each group. The results of ventouse deliveries and Caesarean sections are summarized in Table 2.
There were no differences in Apgar scores between the two groups (epidural conversions excluded).
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Discussion |
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This pilot study compared two different pharmacological regimes of analgesic administration, and this may limit the usefulness of its clinical findings. Using a PCA device can improve satisfaction scores in the clinical setting and itself affect the severity of pain. When visited the following day, almost all women who had received remifentanil commented spontaneously on the controllability of the PCA, which they considered to be an advantage. PCA meperidine and remifentanil have recently been compared in labour, but poor Apgar scores in the meperidine group terminated the study prematurely.14
Seven women receiving remifentanil went on to have an epidural compared with three women receiving meperidine. This was an unexpected finding as pain scores were significantly lower in the remifentanil group. The difference in epidural conversion rate between the two groups was not significant, but our sample size was small. Meperidine is a sedative. This may have some influence on women requesting an epidural. In our pilot study, a fixed bolus dose of remifentanil was used. Ideally, the dose should be tailored to the individual patient and adjustments made as necessary with the progression of labour, especially as acute tolerance can develop with prolonged use of remifentanil.15
More women using remifentanil had lower haemoglobin oxygen saturations and some women had low ventilatory rates. Remifentanil is a potent opioid with potentially serious side-effects. It has a rapid onset, with a time to peak effect of 6080 s.3 From clinical observations, we suggest that the mothers must be encouraged to make a demand at the start of contractions rather than when the contractions become painful. If pressed too late, the maximum analgesic effect will occur after the peak of the contraction, along with the side-effects. It is then that ventilatory depression, if it does occur, is more likely. There must be close communication between mother, attending midwife and anaesthetist to ensure proper use of the PCA for best effect with least side-effects.
Remifentanil may be an acceptable alternative to meperidine when epidural analgesia is unsuitable. However, it is a potent respiratory depressant and adequate continuous monitoring is advisable.
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References |
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