Anaesthesia, 1991, Volume 46, pages 169-173
Epidural infusion of diamorphine with bupivacaine in labour A comparison with fentanyl and bupivacaine
G. R. ENEVER, H. A. NOBLE, D. KOLDITZ, S. VALENTINE
AND
T. A. THOMAS
Summary
We have compared the analgesic effects of three epidural infusions in a randomised, double-blind study of 61 mothers in labour. An initial dose of bupivacaine 0.5% 8 ml was followed by either bupivacaine 0.125%, bupivacaine 0.125% with diamorphine 0.0025% or bupivacaine 0.125% with fentanyl 0.0002%. All infusions were run at a rate of 7.5 mllhour. Analgesia was significantly better in both the groups receiving opioids. Diamorphine was shown to be the more effective supplement to bupivacaine. The 5% incidence of pruritis in the opioid groups was less than that reported by earlier authors. Key words
Anaesthetic techniques, regional; epidural. Analgesics; diamorphine, fentanyl.
The epidural administration of opioids to women in labour has been widely investigated in recent years,' either as an alternative or as a supplement to local anaesthetic agents. Morphine has been found to be unsuitable* and pethidine requires large doses to be effe~tive.~ Fentanyl has become although early work indicated that analgesic quality might not be sustained into late labour.4 Alfentanil, sufentanil and butorphanol are currently under investigation) in the continued search for the ideal agent. Unfortunately, epidural opioids have side effect^.^ Nausea, pruritis and sedation are common, with respiratory depression a rare but serious complication. Problems are more likely if large doses are given, as when opioids are used alone. In order to reduce opioid dosage, combination with a local anaesthetic agent, such as bupivacaine, is employed. The quality of analgesia is generally thought to be better with these mixtures than with either drug alone. However, side effects, especially pruritis, are still noted in many reports. The most suitable combination and dose of opioid and local anaesthetic is yet to be identified. Diamorphine has been popular for many years for postoperative analgesia via the epidural route.1° It is highly lipophilic, a property shared with fentanyl, but it has a longer duration of action. The only study of its use during labour to date reports the effects of a 5 mg bolus of diamorphine, where good analgesia was noted but also a 70% incidence of pruritis." The paucity of published research is perhaps because most of the studies using epidural opioids in labour have come from countries where
diamorphine is not freely available, especially the United States. In this study it was our intention to investigate the efficacy of diamorphine, combined with bupivacaine infused epidurally during labour. Groups receiving plain bupivacaine or a combination with fentanyl were included for comparison. We used smaller doses of both local anaesthetic and opioid agents than previously reported, to observe the effects on analgesia and the incidence of side effects. Infusions rather than an intermittant technique were used because we believe they are safer and more effective.lz.13 Methods
The study was approved by the District Ethics Committee, and written informed consent was obtained from all participants. Healthy mothers with uncomplicated singleton pregnancies were included in the study, provided they had not received any systemic opioid before requesting an epidural for analgesia. Women with a cervical dilatation of 6 cm or more at their previous vaginal examination, less than 150 cm tall or who weighed more than 100 kg at their last visit to clinic were not studied. A large-bore intravenous cannula was inserted before performing the epidural and the circulation preloaded with 1000 ml compound sodium lactate solution. A baseline pain score was obtained at the peak of a contraction using a 20-cm visual analogue scale, a method validatedL4and
G.R. Enever,* MA, MB, BS, FCAnaes, Clinical Research Fellow, H.A. Noble, BM, FCAnaes, Senior Registrar, D. Kolditz, MB, BCh, FCAnaes, Locum Senior Registrar, S. Valentine,? MB, ChB, FCAnaes, Registrar, T.A. Thomas, MB, ChB, FCAnaes, Consultant, Department of Anaesthesia, Bristol Maternity Hospital, Southwell Street, Bristol BS2 8EG. * Present appointment: Senior Registrar, Royal Victoria Infirmary, Newcastle-upon-Tyne. t Present appointment: Senior Registrar, Queen Alexandra Hospital, Portsmouth. Accepted 8 August 1990. 0003-2409/91/030169 +05 $03.00/0
@ 1991 The Association of Anaesthetists of Gt Britain and Ireland
169
170
G.R. Enever et. al.
used in previous s t ~ d i e s . ' ~The , ' ~ epidural catheter was inserted at the second or third lumbar interspace with the mother in the lateral position. Loss of resistance was detected with air and approximately 3 cm of catheter was inserted into the epidural space. All patients then received a test dose of 3 ml 0.5% bupivacaine followed by 5 ml to establish analgesia, with further increments of 3 ml given if necessary. If adequate analgesia was not obtained, the catheter was resited and the patient removed from the study. A pain score and the extent of sensory and motor blockade were assessed and recorded before starting the infusions. Loss of temperature sensation to ethyl chloride spray was used to define the upper limit of sensory blockade, and motor blockade was assessed using the Bromage scale.'' Epidural infusions were commenced once adequate pain relief was established, with one of three randomly allocated solutions. Group P received plain 0.125% bupivacaine, Group D 0.125% bupivacaine with 0.0025% diamorphine and Group F 0.125% bupivacaine with 0.0002% fentanyl. All infusions were run at a rate of 7.5 ml/hour. They were prepared by the anaesthetist performing the epidural using 30 ml 0.25% bupivacaine diluted in a syringe to a final volume of 60 ml using 0.9% saline, after the addition of diamorphine 1.5 mg or fentanyl 120 pg. The infusions were given via a bacterial filter (Portex) using a syringe driver wickers Treonic IP4) and were continued until delivery was completed. After starting the study infusions, specially trained midwives18 carried out all observations, unaware of which solution the mother received. Assessment of motor blockade, height of blockade and pain scores were repeated every hour. Arterial blood pressure, pulse rate, respiratory rate and fetal heart rate were recorded every 30 minutes. Posture of the mothers during the study was not controlled, as long as the position adopted avoided aortocaval compression. Respiratory rate was monitored for a further 8 hours after delivery.
If any mother complained of inadequate analgesia, additional top-up doses of 0.25% bupivacaine 8 ml were given. The number of doses was recorded, as was the time to first top-up. The top-up interval (being the infusion time divided by the sum of the top-up doses plus the initial dose)19 was obtained for each patient and the mean calculated for each group. The incidence of pruritis, nausea or vomiting was elicted by direct questioning during and after the period of infusion. Details of the mode of delivery and the condition of the infant, as assessed by the Apgar score, were recorded. The mothers were interviewed the next day to assess any urinary problems, and the general quality and acceptability of the epidural analgesia they had received. Statistical analyses were performed using the Chi-squared test and analysis of variance (ANOVA) as appropriate.
Results Sixty-one women were included in this study, of whom 21 received bupivacaine alone (group P), 19 bupivacaine with diamorphine (group D) and 21 bupivacaine with fentanyl (group F). There were no statistical differences in the demographic data of the three groups (Table 1). Seven mothers in each group required no additional topups, while only four patients in the study needed more than three (Table 2). The times (SD) to either first top-up or delivery in the three groups were 21 1 (106) minutes (group P), 252 (139) minutes (group D) and 260 (152) minutes (group F). There was no statistical difference between the three groups. There was no statistical difference in the mean top-up interval between the three groups, the values being 192 (SD103) minutes (group P), 213 (SD144) minutes (group D) and 233 (SD142) minutes (group F). The mean duration (SD) of infusion for the three groups was 327 (148) minutes (group P), 393 (204) minutes (group
Table 1. Demographic data on entering study; mean (SD). There were no significant differences between the three groups ( p i 0.05). Bupivacaine (n = 21)
Bupivacaine/ diamorphine (n = 19)
Bupivacaine/ fentanyl (n = 21)
Age; years Height; cm Weight; kg Primiparous; % Cervical dilatation; cm
27.1 (6.8) 161(7) 74.0(12.0) 66.7 3.2 (1.3)
24.3 (6.5) 160(6) 67.0(10.3) 68.4 3.6 (1.6)
23.7 (3.9) 162(5) 74.4(13.8) 80.9 3.2 (1.4)
Median pain Score (Range)
153 (65-200)
I58 ( 105-200)
145 (88-20)
~
Table 2. Requirements for top-up injections of bupivacaine during infusion; number of patients (YO). There were no significant differences between the three groups (p 6 hours
21 (0-170) 3 (0-12)
21 0 (0-195) 4 0 (0-30)
19 5
38 (0-165) 21 103*(16-165) 6
* p 20%) Nausea only Nausea with vomiting Pruritis Apgar < 8 at 1 minute Apgar < 8 at 5 miKutes Sensory level
Spontaneous vaginal Forceps Ventouse Caesarean section
delivery was very low, with only one patient in each group requiring short periods of catheterisation. No symptoms associated with systemic toxicity of bupivacaine were noted during this study. In group D the dose rate of diamorphine was 0.163 mg/hour and the mean total dose per patient was 1.05 mg. In group F the dose rate of fentanyl was 15 pg/hour and the mean total dose per patient was 117 pg. No evidence of respiratory depression, as judged by respiratory rate changes, was noted in any mother. No sedation was noted in any patient, apart from that normally seen when pain is relieved during labour. The incidence of other side effects are shown in Table 5. There was only one woman in each of group D and group F who experienced pruritis. There was no significant difference in the condition of infants at one or five minutes, and no infants required naloxone or resuscitation other than normal bag and mask oxygen. The mode of delivery is also shown in Table 5. There was no statistically significant difference between the three groups, although there were more spontaneous vaginal deliveries in group D (0.1 > p > 0.05). Discussion
In this study, we have demonstrated that the addition of only small amounts of opioids to epidural solutions improved the quality of analgesia. This was not unexpected with the fentanyl group because we had the results of previous studies for c o m p a r i s ~ n .However, ~~~ it was interesting to find that analgesia in the diamorphine group was as good as, or better than, the fentanyl group. In fact, the women receiving diamorphine had more hourly pain scores of zero than the other two groups, and this was achieved with a dose of only 0.163 mg/hour. The need for top-ups was not increased by our low infusion rates when compared to other fixed-rate Our mean top-up interval is similar to that found by other investigators who used larger doses of bupivacaine.I9The interval exceeded 3 hours for all three groups. For an infusion regimen to offer benefits to the mother in labour, we believe that it is important for it to be effective into the second stage and during delivery. For this reason we continued our infusion until the third stage of labour was completed and continued our observations until delivery was imminent. By doing so we noted a tendency for pain scores to increase in patients receiving fentanyl when labour lasted over 6 hours. Although only 15 patients out
*
Bupivacaine/
Bupivacainel
Bupivacaine (n = 21)
diamorphine (n = 19)
fentanyl (n = 21)
4(19.2) 2 (9.5)
S(26.3)
S(23.8)
0
0
2 (9.5) 0 S(23.8) 2 (9.5)
4(21.1) 1 (5.3) 4(21.1)
T9 6(28.6) 6(28.6) b(28.6) 3(14.2)
T9 lO(52.6) S(26.3) 4(21.1)
3(14.3) 1 (4.6) 4(19.2) 3(14.3) T9 6(28.6)
1 (5.3)
0
S(23.8)
7133.3) 3(14.3)
of the 61 had long labours (Table 3), this difference achieved statistical significance at p = 0.01. This finding was in keeping with some previous research: where inadequate analgesia was seen with repeated bolus doses of fentanyl. Whether the pattern we saw was a result of our dose of fentanyl being inadequate to compensate for the increasing pain of late labour, or that we were observing tachyphylaxis we are not sure. The fact that the group receiving no opioids at all had lower pain scores than the fentanyl group in late labour leads us to surmise that the latter may be true. The diamorphine group, however, maintained a consistant quality of analgesia in the majority of patients receiving it. This phenomenon deserves further investigation. There was a low incidence of pruritis in this study, with only one woman in each of the diamorphine and fentanyl groups reporting it. This is an improvement on previous investigations using either epidural f e n t a n ~ 1 , 4 ~ .where ~&~~ the incidence ranged between 17 and 75%, or epidural diamorphine, where it was 72% after a single bolus dose." Our low incidence may well be related to the small doses of opioids given in this study. We avoided the use of opioids in the initial bolus dose, and used very low concentrations in our infusions. This may indicate that pruritis after epidural opioids is dose related. The incidence of nausea and vomiting was similar to previous investigations, occurring in approximately 20% of women irrespective of their group. It is interesting to note that the incidence of nausea in women without epidurals is appreciable during labour,24often related to delayed gastric emptying and the use of oxytocic drugs. No woman in this study developed a respiratory rate of less than 10 breaths/minute, as would be expected from previous s t u d i e ~ . ~ ~However, . " . ~ ~ a recent report using longterm oximetry to monitor nonobstetric postoperative patients has indicated that respiratory depression can occur with epidural diamorphine,z6 although much larger doses were used than in our study. Oximetry, and perhaps even capnography, may play a role in future investigations of epidural opioids in the perinatal period, since the limitations of observing only respiratory rates are well known. We saw no drowsiness in the women receiving diamorphine in labour compared to the other reported use of it in a similar situation." We presume that, as we have seen analgesic effects but little or no evidence of side effects, that the opioids we are giving are acting only locally. This is in keeping with the marked lipophilicity combined with low
Epidural infusion of diamorphine with bupivacaine in labour doses of both fentanyl and diamorphine. However, we cannot rule out the possibility that the opioids given were having some systemic action. The groups receiving opioids in their epidurals in this study had longer infusion times. The fentanyl a nd diamorphine groups have identical mean times, when just the primiparous patients are compared, 88 minutes longer than the plain group. Variability causes this difference to not achieve statistical significance, but it is an interesting trend. It differs from a previous report’ in which women receiving epidural fentanyl had shorter labours than those who received plain local anaesthetic. It is possible that epidural opioids may be acting to alter the neurohumoral control of uterine activity. Evidence to support this theory is meagre, although plasma oxytocin levels a t delivery have been shown to be reduced by local anaesthetics,*’ presumably by neural blockade, while recent work has indicated that epidural fentanyl may affect uterine activity.28 This study has indicated that it is possible to obtain adequate epidural analgesia by using low dose solutions of combined local anaesthetic and opioids infused at a low rate. We believe this combination improves safety and reduces the incidence of some side effects. We have also investigated the use of low doses of diamorphine during labour and have found it to be effective as a supplement to bupivacaine.
Acknowledgments We thank the Midwifery staff working on the Central Delivery Suite, Bristol Maternity Hospital, for all their efforts and support during this study.
References 1. REYNOLDS F. Extradural opioids in labour. British Journal of Anaesthesia 1989; 6 3 251-3.
2. HUSEMEYER RP, O’CONNOR MC, DAVENPORT HT. Failure of epidural morphine to relieve pain in labour. Anaesthesia 1980; 35 161-3. 3. PERISSBW. Epidural pethidine in labour. A study of dose requirements. Anaesthesia 1980; 3 5 380-2. LES, OSULLIVAN GM, SEEGOBIN R. Epidural fentanyl 4. CARRIE in labour. Anaesthesia 1981; 3 6 965-9. F. A 5. JUSTINSDM, FRANCISD, HOULTONPG, REYNOLDS controlled trial of extradural fentanyl in labour. British Journal of Anaesthesia 1982; 54: 409-14. P, EASTWOOD D, PATELH, BHATIAR, COWAN 6. YOUNCSTROM R, SUTHEIMER C. Epidural fentanyl and bupivacaine in labor: double-blind study. Anesthesiology 1984; 61: A414. I. COHENES, TAN S, ALBRIGHTGA, HALPERNJ. Epidural fentanyl/bupivacaine mixtures for obstetric analgesia. Anesthesiology 1987; 67: 403-7. DH, OWENCL, BATES JN, OSTMAN LG, CHOIWW, 8. CHESTNUT GEIGERMW. Continuous infusion epidural analgesia during labor: a randomized, double-blind comparison of 0.0625% bupivacaine/0.0002% fentanyl versus 0.125% bupivacaine. Anesthesiology 1988; 68:754-9.
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9. CousiNs MJ, MATHER LE. Intrathecal and epidural administration of opioids. Anesthesiology 1984; 61: 276-3 10. FF. Epidural diamorphine and 10. HOULTONPG, REYNOLDS fentanyl for postoperative pain. Anaesthesia 1981; 3 6 1144-5. DK, DAVIS AG. Epidural 11. MCGRADYEM, BROWNHILL diamorphine and bupivacaine in labour. Anaesthesia 1989; 4 4 400-3. 12. LI DF, REESGAD, ROSENM. Continuous extradural infusion of 0.0625% or 0.125% bupivacaine for pain relief in primigravid labour. British Journal of Anaesthesia 1985; 57: 264-70. A, 13. EWEN A. MCLEOD DD, MACLEODDM, CAMPBELL TUNSTALL ME. Continuous infusion epidural analgesia in obstetrics. A comparison of 0.08% and 0.25% pubivacaine. Anaesthesisa 1986; 41: 143-7. TA, GRIFFITHS MJ. A pain slide rule. Anaesthesia 14. THOMAS 1982; 37: 960-1. TA, FLETCHER JE, HILLRG. Influence of medication, 15. THOMAS pain and progress in labour on plasma 8-endorphin-like immunoreactivity. British Journal of Anaesthesia 1982; 5 4 401-8. MJ, THOMAS TA. A comparison of the analgesic 16. GRIFFITHS effects of meptazinol and pentazocine following removal of impacted third molars. British Dental Journal 1985; 158 19-21. 17. BROMAGEPR. Epidural analgesia. Philadelphia: W.B.. Saunders, 1983. 18. JONESMJT, BOGOD DG, REESGAD, ROSENM. Midwives’ assessment of the upper sensory level after epidural blockade. Anaesthesia 1988; 4 3 557-9. 19. BOCODDG, ROSENM, REES GAD. Extradural infusion of 0.125% bupivacaine at I0 ml h-’ to women during labour. British Journal of Anaesthesia 1987; 5 9 325-30. 20. JONESG , PAULDL, ELTONRA, MCLUREJH. Comparison of bupivacaine and bupivacaine with fentanyl in continuous extradural analgesia during labour. British Journal of Anaesthesia 1989; 63: 254-9. 21. JUSTINS DM, KNOTTC, LUTHMAN J, REYNOLDS F. Epidural versus intramuscular fentanyl. Analgesia and pharmacokinetics in labour. Anaesthesia 1983; 3 8 937-42. 22. VELLALM, WILLATTS DG, KNOTTC, LINTIN DJ, JUSTINS DM, REYNOLDS F. Epidural fentanyl in labour. An evaluation of the systemic contribution to analgesia. Anaesthesia 1985; 40: 741-7. 23. REYNOLDS F, O’SULLIVAN G. Epidural fentanyl and perineal pain in labour. Anaesthesia 1989; 44: 341-4. 24. MCDONALDR. Infusion epidurals for pain relief in labour. Frontiers in Pain 1989; 1: 1-3. 25. MALINSAF, GOODMAN NW, COOPERGM, PRYS-ROBERTS C, BAIRDRN. Ventilatory effects of pre- and postoperative diamorphine. A comparison of extradural with intramuscular administration. Anaesthesia 1984; 3 9 118-25. 26. WHEATLEY RG, SOMERVILLE ID, SAPSFORD DJ, JONESJG. Postoperative hypoxaemia: comparison of extradural, i.m. and patient-controlled opioid analgesia. British Journal of Anaesthesia 1990; 64: 267-75. CF, HULL MGR, SWAABDF, DOCTEROM J, 21. GOODFELLOW BUIJS RM.. Oxytocin deficiency at delivery with epidural analgesia. British Journal of Obstetrics and Gynecology 1983; 90: 214-9. CM, LE BOUEDEC G, 28. BAZINJE, DISSAITV, MONTEILLARD TROLESE JF, SCHOEFFLER PF. Variations in uterine activity related to epidural fentanyl during labour. Anesthesiology 1989; 71: A849.
Epidural infusion of diamorphine with bupivacaine in labour A comparison with fentanyl and bupivacaine
G. R. ENEVER, H. A. NOBLE, D. KOLDITZ, S. VALENTINE
AND
T. A. THOMAS
Summary
We have compared the analgesic effects of three epidural infusions in a randomised, double-blind study of 61 mothers in labour. An initial dose of bupivacaine 0.5% 8 ml was followed by either bupivacaine 0.125%, bupivacaine 0.125% with diamorphine 0.0025% or bupivacaine 0.125% with fentanyl 0.0002%. All infusions were run at a rate of 7.5 mllhour. Analgesia was significantly better in both the groups receiving opioids. Diamorphine was shown to be the more effective supplement to bupivacaine. The 5% incidence of pruritis in the opioid groups was less than that reported by earlier authors. Key words
Anaesthetic techniques, regional; epidural. Analgesics; diamorphine, fentanyl.
The epidural administration of opioids to women in labour has been widely investigated in recent years,' either as an alternative or as a supplement to local anaesthetic agents. Morphine has been found to be unsuitable* and pethidine requires large doses to be effe~tive.~ Fentanyl has become although early work indicated that analgesic quality might not be sustained into late labour.4 Alfentanil, sufentanil and butorphanol are currently under investigation) in the continued search for the ideal agent. Unfortunately, epidural opioids have side effect^.^ Nausea, pruritis and sedation are common, with respiratory depression a rare but serious complication. Problems are more likely if large doses are given, as when opioids are used alone. In order to reduce opioid dosage, combination with a local anaesthetic agent, such as bupivacaine, is employed. The quality of analgesia is generally thought to be better with these mixtures than with either drug alone. However, side effects, especially pruritis, are still noted in many reports. The most suitable combination and dose of opioid and local anaesthetic is yet to be identified. Diamorphine has been popular for many years for postoperative analgesia via the epidural route.1° It is highly lipophilic, a property shared with fentanyl, but it has a longer duration of action. The only study of its use during labour to date reports the effects of a 5 mg bolus of diamorphine, where good analgesia was noted but also a 70% incidence of pruritis." The paucity of published research is perhaps because most of the studies using epidural opioids in labour have come from countries where
diamorphine is not freely available, especially the United States. In this study it was our intention to investigate the efficacy of diamorphine, combined with bupivacaine infused epidurally during labour. Groups receiving plain bupivacaine or a combination with fentanyl were included for comparison. We used smaller doses of both local anaesthetic and opioid agents than previously reported, to observe the effects on analgesia and the incidence of side effects. Infusions rather than an intermittant technique were used because we believe they are safer and more effective.lz.13 Methods
The study was approved by the District Ethics Committee, and written informed consent was obtained from all participants. Healthy mothers with uncomplicated singleton pregnancies were included in the study, provided they had not received any systemic opioid before requesting an epidural for analgesia. Women with a cervical dilatation of 6 cm or more at their previous vaginal examination, less than 150 cm tall or who weighed more than 100 kg at their last visit to clinic were not studied. A large-bore intravenous cannula was inserted before performing the epidural and the circulation preloaded with 1000 ml compound sodium lactate solution. A baseline pain score was obtained at the peak of a contraction using a 20-cm visual analogue scale, a method validatedL4and
G.R. Enever,* MA, MB, BS, FCAnaes, Clinical Research Fellow, H.A. Noble, BM, FCAnaes, Senior Registrar, D. Kolditz, MB, BCh, FCAnaes, Locum Senior Registrar, S. Valentine,? MB, ChB, FCAnaes, Registrar, T.A. Thomas, MB, ChB, FCAnaes, Consultant, Department of Anaesthesia, Bristol Maternity Hospital, Southwell Street, Bristol BS2 8EG. * Present appointment: Senior Registrar, Royal Victoria Infirmary, Newcastle-upon-Tyne. t Present appointment: Senior Registrar, Queen Alexandra Hospital, Portsmouth. Accepted 8 August 1990. 0003-2409/91/030169 +05 $03.00/0
@ 1991 The Association of Anaesthetists of Gt Britain and Ireland
169
170
G.R. Enever et. al.
used in previous s t ~ d i e s . ' ~The , ' ~ epidural catheter was inserted at the second or third lumbar interspace with the mother in the lateral position. Loss of resistance was detected with air and approximately 3 cm of catheter was inserted into the epidural space. All patients then received a test dose of 3 ml 0.5% bupivacaine followed by 5 ml to establish analgesia, with further increments of 3 ml given if necessary. If adequate analgesia was not obtained, the catheter was resited and the patient removed from the study. A pain score and the extent of sensory and motor blockade were assessed and recorded before starting the infusions. Loss of temperature sensation to ethyl chloride spray was used to define the upper limit of sensory blockade, and motor blockade was assessed using the Bromage scale.'' Epidural infusions were commenced once adequate pain relief was established, with one of three randomly allocated solutions. Group P received plain 0.125% bupivacaine, Group D 0.125% bupivacaine with 0.0025% diamorphine and Group F 0.125% bupivacaine with 0.0002% fentanyl. All infusions were run at a rate of 7.5 ml/hour. They were prepared by the anaesthetist performing the epidural using 30 ml 0.25% bupivacaine diluted in a syringe to a final volume of 60 ml using 0.9% saline, after the addition of diamorphine 1.5 mg or fentanyl 120 pg. The infusions were given via a bacterial filter (Portex) using a syringe driver wickers Treonic IP4) and were continued until delivery was completed. After starting the study infusions, specially trained midwives18 carried out all observations, unaware of which solution the mother received. Assessment of motor blockade, height of blockade and pain scores were repeated every hour. Arterial blood pressure, pulse rate, respiratory rate and fetal heart rate were recorded every 30 minutes. Posture of the mothers during the study was not controlled, as long as the position adopted avoided aortocaval compression. Respiratory rate was monitored for a further 8 hours after delivery.
If any mother complained of inadequate analgesia, additional top-up doses of 0.25% bupivacaine 8 ml were given. The number of doses was recorded, as was the time to first top-up. The top-up interval (being the infusion time divided by the sum of the top-up doses plus the initial dose)19 was obtained for each patient and the mean calculated for each group. The incidence of pruritis, nausea or vomiting was elicted by direct questioning during and after the period of infusion. Details of the mode of delivery and the condition of the infant, as assessed by the Apgar score, were recorded. The mothers were interviewed the next day to assess any urinary problems, and the general quality and acceptability of the epidural analgesia they had received. Statistical analyses were performed using the Chi-squared test and analysis of variance (ANOVA) as appropriate.
Results Sixty-one women were included in this study, of whom 21 received bupivacaine alone (group P), 19 bupivacaine with diamorphine (group D) and 21 bupivacaine with fentanyl (group F). There were no statistical differences in the demographic data of the three groups (Table 1). Seven mothers in each group required no additional topups, while only four patients in the study needed more than three (Table 2). The times (SD) to either first top-up or delivery in the three groups were 21 1 (106) minutes (group P), 252 (139) minutes (group D) and 260 (152) minutes (group F). There was no statistical difference between the three groups. There was no statistical difference in the mean top-up interval between the three groups, the values being 192 (SD103) minutes (group P), 213 (SD144) minutes (group D) and 233 (SD142) minutes (group F). The mean duration (SD) of infusion for the three groups was 327 (148) minutes (group P), 393 (204) minutes (group
Table 1. Demographic data on entering study; mean (SD). There were no significant differences between the three groups ( p i 0.05). Bupivacaine (n = 21)
Bupivacaine/ diamorphine (n = 19)
Bupivacaine/ fentanyl (n = 21)
Age; years Height; cm Weight; kg Primiparous; % Cervical dilatation; cm
27.1 (6.8) 161(7) 74.0(12.0) 66.7 3.2 (1.3)
24.3 (6.5) 160(6) 67.0(10.3) 68.4 3.6 (1.6)
23.7 (3.9) 162(5) 74.4(13.8) 80.9 3.2 (1.4)
Median pain Score (Range)
153 (65-200)
I58 ( 105-200)
145 (88-20)
~
Table 2. Requirements for top-up injections of bupivacaine during infusion; number of patients (YO). There were no significant differences between the three groups (p 6 hours
21 (0-170) 3 (0-12)
21 0 (0-195) 4 0 (0-30)
19 5
38 (0-165) 21 103*(16-165) 6
* p 20%) Nausea only Nausea with vomiting Pruritis Apgar < 8 at 1 minute Apgar < 8 at 5 miKutes Sensory level
Spontaneous vaginal Forceps Ventouse Caesarean section
delivery was very low, with only one patient in each group requiring short periods of catheterisation. No symptoms associated with systemic toxicity of bupivacaine were noted during this study. In group D the dose rate of diamorphine was 0.163 mg/hour and the mean total dose per patient was 1.05 mg. In group F the dose rate of fentanyl was 15 pg/hour and the mean total dose per patient was 117 pg. No evidence of respiratory depression, as judged by respiratory rate changes, was noted in any mother. No sedation was noted in any patient, apart from that normally seen when pain is relieved during labour. The incidence of other side effects are shown in Table 5. There was only one woman in each of group D and group F who experienced pruritis. There was no significant difference in the condition of infants at one or five minutes, and no infants required naloxone or resuscitation other than normal bag and mask oxygen. The mode of delivery is also shown in Table 5. There was no statistically significant difference between the three groups, although there were more spontaneous vaginal deliveries in group D (0.1 > p > 0.05). Discussion
In this study, we have demonstrated that the addition of only small amounts of opioids to epidural solutions improved the quality of analgesia. This was not unexpected with the fentanyl group because we had the results of previous studies for c o m p a r i s ~ n .However, ~~~ it was interesting to find that analgesia in the diamorphine group was as good as, or better than, the fentanyl group. In fact, the women receiving diamorphine had more hourly pain scores of zero than the other two groups, and this was achieved with a dose of only 0.163 mg/hour. The need for top-ups was not increased by our low infusion rates when compared to other fixed-rate Our mean top-up interval is similar to that found by other investigators who used larger doses of bupivacaine.I9The interval exceeded 3 hours for all three groups. For an infusion regimen to offer benefits to the mother in labour, we believe that it is important for it to be effective into the second stage and during delivery. For this reason we continued our infusion until the third stage of labour was completed and continued our observations until delivery was imminent. By doing so we noted a tendency for pain scores to increase in patients receiving fentanyl when labour lasted over 6 hours. Although only 15 patients out
*
Bupivacaine/
Bupivacainel
Bupivacaine (n = 21)
diamorphine (n = 19)
fentanyl (n = 21)
4(19.2) 2 (9.5)
S(26.3)
S(23.8)
0
0
2 (9.5) 0 S(23.8) 2 (9.5)
4(21.1) 1 (5.3) 4(21.1)
T9 6(28.6) 6(28.6) b(28.6) 3(14.2)
T9 lO(52.6) S(26.3) 4(21.1)
3(14.3) 1 (4.6) 4(19.2) 3(14.3) T9 6(28.6)
1 (5.3)
0
S(23.8)
7133.3) 3(14.3)
of the 61 had long labours (Table 3), this difference achieved statistical significance at p = 0.01. This finding was in keeping with some previous research: where inadequate analgesia was seen with repeated bolus doses of fentanyl. Whether the pattern we saw was a result of our dose of fentanyl being inadequate to compensate for the increasing pain of late labour, or that we were observing tachyphylaxis we are not sure. The fact that the group receiving no opioids at all had lower pain scores than the fentanyl group in late labour leads us to surmise that the latter may be true. The diamorphine group, however, maintained a consistant quality of analgesia in the majority of patients receiving it. This phenomenon deserves further investigation. There was a low incidence of pruritis in this study, with only one woman in each of the diamorphine and fentanyl groups reporting it. This is an improvement on previous investigations using either epidural f e n t a n ~ 1 , 4 ~ .where ~&~~ the incidence ranged between 17 and 75%, or epidural diamorphine, where it was 72% after a single bolus dose." Our low incidence may well be related to the small doses of opioids given in this study. We avoided the use of opioids in the initial bolus dose, and used very low concentrations in our infusions. This may indicate that pruritis after epidural opioids is dose related. The incidence of nausea and vomiting was similar to previous investigations, occurring in approximately 20% of women irrespective of their group. It is interesting to note that the incidence of nausea in women without epidurals is appreciable during labour,24often related to delayed gastric emptying and the use of oxytocic drugs. No woman in this study developed a respiratory rate of less than 10 breaths/minute, as would be expected from previous s t u d i e ~ . ~ ~However, . " . ~ ~ a recent report using longterm oximetry to monitor nonobstetric postoperative patients has indicated that respiratory depression can occur with epidural diamorphine,z6 although much larger doses were used than in our study. Oximetry, and perhaps even capnography, may play a role in future investigations of epidural opioids in the perinatal period, since the limitations of observing only respiratory rates are well known. We saw no drowsiness in the women receiving diamorphine in labour compared to the other reported use of it in a similar situation." We presume that, as we have seen analgesic effects but little or no evidence of side effects, that the opioids we are giving are acting only locally. This is in keeping with the marked lipophilicity combined with low
Epidural infusion of diamorphine with bupivacaine in labour doses of both fentanyl and diamorphine. However, we cannot rule out the possibility that the opioids given were having some systemic action. The groups receiving opioids in their epidurals in this study had longer infusion times. The fentanyl a nd diamorphine groups have identical mean times, when just the primiparous patients are compared, 88 minutes longer than the plain group. Variability causes this difference to not achieve statistical significance, but it is an interesting trend. It differs from a previous report’ in which women receiving epidural fentanyl had shorter labours than those who received plain local anaesthetic. It is possible that epidural opioids may be acting to alter the neurohumoral control of uterine activity. Evidence to support this theory is meagre, although plasma oxytocin levels a t delivery have been shown to be reduced by local anaesthetics,*’ presumably by neural blockade, while recent work has indicated that epidural fentanyl may affect uterine activity.28 This study has indicated that it is possible to obtain adequate epidural analgesia by using low dose solutions of combined local anaesthetic and opioids infused at a low rate. We believe this combination improves safety and reduces the incidence of some side effects. We have also investigated the use of low doses of diamorphine during labour and have found it to be effective as a supplement to bupivacaine.
Acknowledgments We thank the Midwifery staff working on the Central Delivery Suite, Bristol Maternity Hospital, for all their efforts and support during this study.
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