Anaesthesia, 1990, Volume 45, pages 1020-1023

Obstetric epidural analgesia with mixtures of bupivacaine, adrenaline and fentanyl

G. YAU, M. A. GREGORY, T. GIN

AND

T. E. OH

Summary We performed a double-blind comparison of six solutions for epidural analgesia in 90 healthy Chinese women with uncomplicated pregnancies. Patients were randomly allocated to receive I 0 ml bupivacaine 0.125% or 0.25% plain, bupivacaine 0.125% with adrenaline 1.25 pglml, bupivacaine 0.25% with adrenaline 2.5 pgLglml or the latter two solutions with added fentanyl 50 pg. Analgesia was unsatisfactory in 30% of the bupivacaine 0.125% groups without fentanyl. The addition of adrenaline, compared with bupivacaine 0.25% plain, gave faster onset and longer duration of analgesia ( p < 0.05) which was similar to that found in both fentanyl groups. There were no diyerences in method of delivery or neonatal Apgar scores among groups. The least concentrated mixture that gave the best analgesia was the combination of bupivacaine 0.125% with adrenaline 1.25 pg/ml and fentanyl50 pg.

Key words Anaesthesia; obstetric. Analgesics; fentanyl.

Epidural opioids have been used for obstetric analgesia since the discovery of opioid receptors in the brain and spinal cord,' but with limited success on their own., Several groups demonstrated that the addition of opioids such as fentanyl to bupivacaine produced significantly longer duration and better quality of analgesia compared with either agent on its OW^.^,^ However, there were conflicting results at different concentrations of bupivacaine, and some studies used adrenaline-containing solutions. Adrenaline is often added to local anaesthetics in an effort to improve the duration and quality of analge~ia.~ The addition of both fentanyl and adrenaline may further enhance the analgesic effects of the local anaesthetic through their combined effects at spinal opioid receptors and spinal alpha adrenoceptors. Most previous studies compare only two or three study solutions and it is difficult to form an overall picture when different researchers have used different control groups, volumes of local anaesthetic, dose of fentanyl and adrenaline concentration. The aim of this study was to examine the effects of adding fentanyl and adrenaline to low concentrations of bupivacaine for epidural analgesia in labour.

Method The study was approved by the Chinese University Ethics Committee, and informed consent was obtained from each patient. Ninety ASA 1 Chinese women with uncomplicated pregnancies of at least 37 weeks' gestation and single fetal cephalic presentation were studied in a double-blind manner. Patients were in established labour and had requested epidural analgesia before reaching 6-cm cervical dilatation. The women were assigned at random to receive one of the following study solutions prepared by diluting commercially available (Astra Pharmaceuticals) bupivacaine 0.5% or bupivacaine 0.5% and adrenaline 5 pg/ml (1:200 000) with physiological saline to a final volume of 10 ml: bupivacaine 0.125% plain; bupivacaine 0.125% with adrenaline 1.25 pg/ml; bupivacaine 0.125% with adrenaline 1.25 pg/ml and fentanyl 50 pg; bupivacaine 0.25% plain; bupivacaine 0.25% with adrenaline 2.5 pg/ml; bupivacaine 0.25% with adrenaline 2.5 pg/ml and fentanyl 50 pg. The epidural technique was standardised and performed with the patient in the left lateral position. A 16-gauge Tuohy needle was used and the epidural space at L, or L,

,

G. Yau, MB, BS, FFARCS, T. Gin, MB, ChB, BSc, FFARCS, FFARACS, Lecturers, T.E. Oh, MB, BS, FFARCS, FFARACS, FFARACS(1nt Care), Professor, Department of Anaesthesia and Intensive Care, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, M.A. Gregory, MB, BS, FFARCS, Consultant, Royal Oldham Hospital, Rochdale Road, Oldham OL1 2JH. Accepted 8 May 1990. 0003-2409/90/121020 +04 $03.00/0

@ 1990 The Association of Anaesthetists of Gt Britain and Ireland

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Obstetric epidural analgesia with bupivacaine, adrenaline and fentanyl

102 1

Table 1. First epidural dose, n = 15 in each group. The number of patients with unsatisfactory analgesia and median pain score values at 15 minutes, time to achieve lowest pain score, duration of analgesia and maximum percentage reduction in pain score. P, plain; A, adrenaline; F, fentanyl 50 pg. *p < 0.05, t p < 0.01 compared with corresponding P group; t p < 0.01 compared with corresponding A group. Bupivacaine 0.125%

Failure of analgesia Pain score at 15 minutes Time to lowest pain score; minutes Analgesic duration; minutes Maximum YOreduction in pain score

FA

Bupivacaine 0.25%

P

A

P

5 30

4 22

0

1 39

15

0 *O

28 75

22 90

15 ti120

38 90

15 *135

*15 *I20

94

85

ti100

100

100

100

1

A

FA 1

Demographic and other parametric data were compared using one-way analysis o f variance, while pain scores, analgesic duration and Apgar scores were compared using the Kruskal-Wallis test. Categorical data were compared using contingency table analysis with pooling of some groups. Differences were accepted as significant when p I 0.05.

identified with a loss of resistance to air technique. Three to five cm of catheter were left in the space. The study solution was administered slowly in divided doses after preloading the circulation with compound sodium lactate solution 500 ml. Pain was assessed with a 10-cm visual analogue scale before the epidural was established. Pain scores were recorded after the first four uterine contractions and at 15minute intervals after the study solution had been given. Maternal arterial blood pressure, heart rate and fetal heart rate were recorded at 5-minute intervals for 30 minutes. Failure of satisfactory epidural analgesia was defined as failure to achieve 50% reduction in initial pain score, o r a request for further analgesia within 30 minutes of the first dose. Onset of analgesia was assessed by several indices: the time taken to achieve 50% reduction in initial pain score, the time to maximum analgesia and the pain score at 15 minutes. Quality of analgesia was calculated as the maximum percentage reduction in pain score. Duration of analgesia was taken as the time from administration of the first dose to the time when the patient requested further analgesia. The incidence of side effects such as nausea, vomiting, drowsiness, pruritus, shivering and urinary retention were recorded. Hypotension was defined as a systolic arterial pressure less than 100 mmHg. Ten millilitres of the study solution was given when additional analgesia was requested, and if satisfactory then this solution was continued until delivery. Assessment of analgesia was repeated for the second epidural dose. The study solution was abandoned and bupivacaine 0.25% or 0.375% given instead, if pain relief was found to be inadequate after the second dose. The outcome of labour, neonatal birth weight and Apgar scores at 1 and 5 minutes were recorded.

Results

There were no demographic differences among the six groups. Overall, the mean (SD) age was 27.4 (4.5) years, height 156 (5.9) cm, weight 65.2 (8.0) kg and gestation 40 (1.3) weeks. There were no differences in parity among the groups with a total of 78 primiparae. Epidural analgesia was performed at a similar stage of labour among groups; the mean (SD) cervical dilatation was 2.7 (1.2) cm at that time. The course of labour appeared to be similar among groups with no differences in the number o f induced labours o r the number of cases that required augmentation with oxytocin. There were differences in onset, quality and duration of analgesia among the groups. Analysis of results after the second epidural dose agree with findings from the initial dose (Tables 1 and 2). EfSect of concentration. There was a higher incidence of unsatisfactory analgesia in the bupivacaine 0.125% groups with and without adrenaline, compared with the bupivacaine 0.25% groups with and without adrenaline (p < 0.05). There were no differences between bupivacaine 0.125% with fentanyl and adrenaline, and bupivacaine 0.25% with fentanyl and adrenaline. Effect of adrenaline. There were no differences between bupivacaine 0.125% and bupivacaine 0.125% with adrena-

Table 2. Second epidural dose. The number of patients with unsatisfactory analgesia and median values for time to achieve lowest pain score, and duration of analgesia. P, plain; A, adrenaline; F, fentanyl 50 pg. *p < 0.05 compared with corresponding P group; t p < 0.05 compared with corresponding A group. Bupivacaine 0.125%

Number of patients Failure of analgesia Time to lowest pain score; minutes Analgesic duration; minutes

FA

Bupivacaine 0.25%

P

A

13 2

11 0

12 0

13 1

13 0

8 0

45 90

30 90

15 *?I65

30 75

10 105

15 *I28

P

A

FA

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G. Yuu et al. Table 3. Incidence of side effects and method of delivery with 15 patients in each group. P, plain; A, adrenaline; F, fentanyl 50 p g .

Bupivacaine 0.125%

Bupivacaine 0.25%

P

A

FA

P

A

FA

Pruritus

0

0

1 1

0 3

0 3 7 2 6

4 0 3 8 4

2 2 2 3 3 3 8

0 1 0 4 4 6 4 5

0 0 0 2 0 6 4

2

Drowsiness Nausea or vomiting Shivering Hypotension Spontaneous vaginal Ventouse or forceps Caesarean section

1 6 4

5

5

line 1.25 pg/ml. Bupivacaine 0.25% with adrenaline 2.5 pg/ ml gave longer duration and faster onset of analgesia than bupivacaine 0.25% plain (p < 0.05). Efect of adrenaline and fentanyl. The addition of fentanyl 50 p g and adrenaline to bupivacaine 0.125% gave longer duration and better quality of analgesia compared with plain bupivacaine 0.125% or bupivacaine 0.125% with adrenaline ( p < 0.01). Bupivacaine 0.25% with fentanyl 50 pg and adrenaline gave longer duration and more rapid onset of analgesia than plain bupivacaine 0.25% (p < 0.05). There were no differences between bupivacaine 0.25% with fentanyl and adrenaline and bupivacaine 0.25% with adrenaline alone. There were no differences among the six groups when individual side effects were compared. However, the total number of side effects was greater in the groups that contained fentanyl (p < 0.05), particularly pruritus, which appeared only in the fentanyl groups (Table 3). The addition of fentanyl did not reduce the incidence of shivering. Urinary retention was difficult to assess since urinary catheterisation was routinely performed before all operative deliveries. Hypotension was rare and easily treated with intravenous fluid and left uterine displacement. There was no difference in the outcome of labour among groups, with a total of 31 spontaneous vaginal deliveries, 30 instrumental deliveries and 29 Caesarean sections (Table 3). The median duration of the first and second stages of labour were 8.8 hours and 45 minutes respectively. There were no differences among groups in fetal heart rate after epidural injection, Apgar scores at delivery o r birth weight.

Discussion

Epidural opioids appeared to be ideal for pain relief in labour because they selectively affect pain perception while sparing the autonomic and motor pathways. Epidural morphine alone in clinical practice was relatively ineffectivc6 However, epidural fentanyl 150-200 pg was effective only during the early part of labour,’ while other workers showed that epidural fentanyl 80-100 pg was effective for perineal a n a l g e ~ i a .Nevertheless, ~.~ the addition of fentanyl to low concentration bupivacaine has produced satisfactory analgesia for labour.’O The use of low concentrations of local anaesthetic may decrease the patient’s motor block which in turn may prevent an increased incidence of operative deliveries.”,” The reduced local anaesthetic requirement may decrease the incidence of potentially life

4

1

2 4

threatening complications from local anaesthetic toxicity and inadvertent intravascular or subarachnoid injection. Adrenaline has been added to epidural local anaesthetic solutions t o decrease systemic absorption of local anaesthetic and improve onset and prolong duration of analgesia. We preferred to dilute existing commercially available solutions than add adrenaline separately but this decreases the concentration of adrenaline with increasing dilution. We believe that this method is more practical and safer than adding adrenaline separately, although it was suggested that freshly added adrenaline provides a superior b10ck.I~ There are many factors which complicate the interpretation of results from studies of analgesia in labour. Patients are generally an homogeneous group, but their response to pain and the course of labour can be very different. Labours that are induced o r augmented may produce more painful contractions. One often forgotten factor is the change in p H of the resultant mixture when bupivacaine solutions are diluted. The p H of the study solutions ranged from 4.29 in the bupivacaine 0.25% with adrenaline mixture to 5.72 in the bupivacaine 0.125% plain mixture. An increase in p H may quicken the onset of analgesia but the effects of this have not been explored in the context of this and other similar studies. We found that adrenaline 1.25 pg/ml was not effective in potentiating bupivacaine 0.125%, and 30% of patients had inadequate analgesia. Bleyaert et a1.I4 found that bupivacaine 0.125% with adrenaline 1.25 pg/ml gave satisfactory analgesia in more than 90% of their patients, but the total volume administered to each patient initially, including the test dose of the same solution, was at least 15 ml, while our patients received only 10 ml. The addition of adrenaline 2.5 pg/ml to bupivacaine 0.25% in our study caused faster onset and longer duration of analgesia compared with the plain solution. Similar results have been reportedS and the addition of adrenaline 3.33 pg/ml to bupivacaine 0.5% also reduced and delayed the incidence of hypotension.Is However, the addition of adrenaline to bupivacaine 0.5% during labour did not prolong analgesia and only slightly reduced systemic absorption of bupivacaine.I6 Concern was expressed over the use of adrenaline in parturients because of possible adverse effects on uterine blood flow,” but epidural adrenaline 26 pg did not cause any adverse neonatal effects.15 The addition of fentanyl 50 pg to bupivacaine 0.125% with adrenaline resulted in better and longer lasting analgesia than the plain o r adrenaline-containing solution.

Obstetric epidural analgesia with bupivacaine, adrenaline and fentanyl Bupivacaine 0.25% with adrenaline 2.5 pg/ml on its own provides good analgesia in most patients and it was difficult to demonstrate any significant benefit from the addition of fentanyl 50 pg. It was reported that the addition of both fentanyl and adrenaline to bupivacaine 0.25% provided longer duration of analgesia than the addition of either agent alone.'8 We did not compare the fentanyl and bupivacaine groups with and without adrenaline in this study, but we have previously investigated the effects of fentanyl and bupivacaine mixtures in a study with similar methodology.IY The bupivacaine, fentanyl and adrenaline groups in that study had longer duration of analgesia than the corresponding groups without adrenaline. Pruritus is a recognised side effect after epidural opioids, but this symptom was elicited only on direct questioning and the patients in this study thought itching was only mild. We did not show that epidural fentanyl decreased the incidence of shivering, but this has been reported previously.*" Motor block was not evaluated and although the method of delivery was similar among groups, we cannot make any further conclusions, since some patients in the lower concentration groups received bupivacaine 0.25% or 0.375% after analgesia was assessed to be inadequate. Pain increases as labour progresses and it is not unusual to increase the frequency or dose of epidural solution. Our study groups are too small and not controlled sufficiently to correlate total epidural drug requirement with method of delivery. There were no adverse neonatal effects in the fentanyl groups and fentanyl 50 pg appears to be a safe lumbar epidural dose to administer. Epidural fentanyl 150 to 200 pg gave mean maternal arterial fentanyl levels of 0.3 ng/ml and umbilical arterial fentanyl of 0.18 ng/ml without any respiratory depression to mother or neonate.' Analgesia was best with the bupivacaine 0.25% with adrenaline 2.5 pg/ml and the two fentanyl mixtures. We see no advantage in using the more concentrated mixture since the two fentanyl groups were similar. We conclude that the combination of bupivacaine 0.125% with adrenaline 1.25 pg/ml and fentanyl 50 pg gives good pain relief and is a suitable choice for obstetric epidural analgesia. References I . SNYDERSH. Opiate receptors in the brain. New England Journal qf Medicine 1977; 296 266-7 I . 2. HUSEMEYER RP, OCONNORMC, DAVENPORT HT. Failure of epidural morphine to relieve pain in labour. Anaesthesia 1980; 3 5 161-3.

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3. CELLENO D, CAPOCNAG . Epidural fentanyl plus bupivacaine 0.125 per cent for labour: analgesic effects. Cunadiun Journui of' Anaesthesia 1988; 35: 375-8. 4. COHENSE, TAN S, ALBRIGHT G A , HALPERNJ . Epidural fentanyl/bupivacaine mixtures for obstetric analgesia. Anesthesiology 1987; 67: 403-7. 5. EISENACH JC, GRICESC, DEWAND M . Epinephrine enhances analgesia produced by epidural bupivacaine during labor. Anesthesia and Analgesia 1987; 66: 417-5 I , 6. BOOKERPD, WILKES RG, BKYSONTHL, BEDDARD J . Obstetric pain relief using epidural morphine. Anarsrhesiu 1980; 3 5 371-9. 7. CARRIE LES, O'SULLIVAN G M , SEEWBINR. Epidural fentanyl in labour. Anaesthesia 1981; 3 6 965-9. 8. JUSTINS D M , FRANCISD, HOULTONPG, REYNOLDSF. A controlled trial of extradural fentanyl in labour. Briti.rh Journal of Anaesthesia 1982: 5 4 409-1 4. 9. REYNOLDS F, O'SULLIVAN G. Epidural fentanyl and perineal pain in labour. Anaesthesia 1989; 44: 3 4 1 4 . 10. VELLALM, WILLATTS D G , KNOTTC, LINTINDJ, JIJSTINSD M , REYNOLDS F. Epidural fentanyl in labour. An evaluation of the systemic contribution to analgesia. Anuesthrsia 1985; 4 0 141-1. 1 1 . VANZUNDERT A , VANDEKAA PP, VANIER DONCK A , MEEUWIS H, VAESL. Motor blockade expulsion times and instrumental deliveries associated with epidural analgesia for vaginal delivery. Obstetric Anesthesia Digest 1984; 4 152-6. 12. NAULTYJS, SMITHR, Ross R. Effect of changes in labor analgesic practice on labor outcome. Ane.sthesiology 19x8; 6 9 A660. S, DUKSZTMAN M, TUKNDOKFH . Local 13. RAMANATHAN anesthetics with freshly added epinephrine produce longer obstetrical analgesia. Anesthesiology 1985; 63: A452. 14. BLEYAERT A, SOETENS M , VAESL, VAN STEENBEKGE AL, VAN DER DONCKA . Bupivacaine 0.125%. in obstetric epidural analgesia. Evidence in three thousand cases. Anc~sthc,.viology 1979; 51: 435-8. 15. ABBOUI)TK, SHEIKH-OL-ESLAM A , YANAGIT, M ~ J K A K AKW, A COSTANDIJ, ZAKARIAN M, HOFFMAND, HAROUTUNIAN S. Safety and efficacy of epinephrine added to bupivacaine for lumbar epidural analgesia in obstetrics. Anrsthe.viu und Analgesia 1985; 64: 585-91. 16. REYNOLDSF, TAYLOR G. Plasma concentrations of bupivacaine during continuous epidural analgesia in labour: the effect of adrenaline. Briti.sh Journal qf Anac~sthesiaI97 I ; 4 9 43640. 17. SKJOLDEBRAND A , EKLUNDJ, LUNELLN - 0 , NYLIINI) L, S A R B Y B, THORNSTROM S. The effect on uteroplacental blood flow of epidural anaesthesia containing adrenaline for caesarean section. Acta Anaesthe.siologica Scandinuvicu 1990; 34: X5-9. 18. GRICESC, EISENACH JC, DEWAN D M , WEINEKJ . Effect of epinephrine on the duration of analgesia with epidural bupivacaine and fentanyl. Anesthesiolo,gy 1986; 67: A440. 19. YAU G, GREGORYMA, G I N T, B m o o D G . OH TE. The addition of fentanyl to epidural bupivacaine in first stage labour. Labour and Intensive Care 1990 (in press). 20. SHEHABI Y, GATTS, BUCKMAN T , ISERT P. EfTect of adrenaline. fentanyl and warming of injectate on shivering following extradural analgesia in labour. Anaesthesia and Intensive Care 1990; 18: 31-7.

Obstetric epidural analgesia with mixtures of bupivacaine, adrenaline and fentanyl.

We performed a double-blind comparison of six solutions for epidural analgesia in 90 healthy Chinese women with uncomplicated pregnancies. Patients we...
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