EXTRADURAL MORPHINE FOR PAIN AFTER SURGERY

Br. J. Anaesth. (1981), 53, 921

EXTRADURAL MORPHINE FOR PAIN AFTER SURGERY W. A. CHAMBERS, C. J. SINCLAIR AND D. B. SCOTT SUMMARY

In spite of numerous reports of opiates administered to the extradural space in the treatment of acute and chronic pain (Behar et al., 1979; Bromage, Camporesi and Chestnut, 1980; Chayen, Rudick and Borvine, 1980; Magora et al., 1980; Torda et al., 1980) there have been few controlled studies. In a previous report of the effects of extradural saline 10 ml, either alone or with morphine sulphate 2 or 5mg added, in 30 patients studied on the day after major gynaecological surgery involving laparotomy (McClure et al., 1980) there was no difference between the groups with regard to the mean reduction in pain score at 20 min after injection. Although the patients who had received the placebo required analgesia sooner than those who had received morphine, this would have occurred regardless of its route of administration. We conducted the following studies to compare the effects of morphine sulphate lOmg administered either extradurally or i.m. One study involved morphine injections before the occurrence of pain (just before surgery) and the other 24 h after operation when pain was present. In this way it was hoped to assess the efficacy of extradural morphine both in preventing and in treating pain after operation.

major gynaecological surgery involving laparotomy and inforrried consent was obtained.

Study I Premedication was diazeparn lOmg orally and atropine 0.6 mg i.m. 1 h before anaesthesia. Extradural block was performed using a catheter inserted through L1/T12 interspace. Injection of 20ml of 0.5% bupivacaine was made with the patient lying supine and, 2-3 min later, general anaesthesia was induced with thiopentone 500 mg and maintained with 0.5% halothane in 66% nitrous oxide in oxygen from a circle system using a face-mask. Operating conditions were entirely satisfactory in all cases. Bupivacaine was chosen as we wished to have the patients awake and co-operative before the onset of pain after operation. Morphine lOmg was given to all patients either by adding it to the bupivacaine (10 patients) or by i.m. injection (10). Because i.m. morphine is sometimes painful, it was not given until immediately after thiopentone administration. Those given morphine extradurally were given an i.m. injection of saline immediately after the thiopentone. The person administrating the morphine did so by reference to a randomized list just before METHODS the extradural injection was given. He took no part Two studies, each involving two groups of 10 in the assessment of pain after operation. Assessment of pain after operation. All patients patients had the approval of the local ethics committee. The patients were about to undergo were seen 2.5, 3, 4, 6 and 8h after the extradural injection by the same nurse observer who was unaware of the route of administration of the W. A. CHAMBERS, M.B., CH.B., F.F.A.R.C.S.; C. J. SINCLAIR, M.B., CH.B., F.F.A.R.C.S.; D . B. SCOTT, M.D., F.R.C.P., F.F.A.R.C.S.; morphine and had not been present in the anaesthetic or operating room. The patients were asked Department of Anaesthetics, Royal Infirmary, Edinburgh. 0007-0912/81/090921-05 801.00

© Macmillan Publishers Ltd 1981

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The effects of lOmg of morphine sulphate given either extradurally or i.m. for the relief of pain after operation were compared in two randomized double-blind trials in patients undergoing major gynaecological idrgery. In the first trial when morphine was given with the local anaesthetic before surgery, extradural administration resulted in significantly longer lasting analgesia: mean 707 min compared with 371 min (i.m.). In the second trial in patients complaining of pain after operation, extradural morphine had a slower onset of action, but longer duration of action compared With i.m. morphine, although the differences were not statistically significant, in this group extradural morphine often failed to provide useful. analgesia. The extradural group received Significantly less additional morphine (6.75mg) than did the i.m. group (18.75mg) in the following 24h.

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to assess their pain on a visual analogue scale—an unmarked 10-cm line the opposite ends of which were labelled NO PAIN and SEVERE PAIN—which had been explained to them before the operation. Heart rate, arterial pressure and respiratory rate were recorded together with the upper dermatomal level (as judged by loss of pinprick) of the remaining extradural blockade. Analgesics were given by the nursing staff using their normal clinical criteria.

The results were assessed using either the Student's t test or Wilcoxon's rank sum test as appropriate, P<0.05 being taken to indicate a significant difference. RESULTS

The mean age of the 40 patients was 38.1 yr, the mean weight 61 kg and the mean height 160 cm. The mean duration of surgery was 110 min. There were no statistically significant differences between the different groups of patients with regard to these variables. Study I While the local anaesthetic effect of bupivacaine was still effective, all pain scores were low. There was no obvious difference between the two groups with regard to duration of spinal nerve block, regression to Tl2 occurring after about 6 h. All the patients who had received i.m. morphine required analgesia as the sensory block regressed below T12. In contrast only three of those who had received extradural morphine required analgesia at this time and the other seven remained comfortable. The mean time to the first administration of analgesia after the preoperative injection was 371±SEM 25.9 min in the i.m. group compared with 707+ 92.5 min in the extradural group. This difference was highly significant (P<0.01). Individual times are shown in figure 1. One patient in each group received cyclizine because of nausea. Three patients who had received extradural morphine complained of an itchy face, although this was not particularly troublesome, and two of these were those who obtained the longest duration of pain relief. One patient who had received extradural morphine had a delayed recovery from anaesthesia and 30 min after surgery had been completed, she had not regained consciousness. She had pin-point pupils and her respiratory rate was 10b.p.m. Following the administration of naloxone 0.2mg i.v. she regained consciousness and was free of pain. She had no further episodes of depression of consciousness or respiration over the ensuing 24 h. Study II No patient required further analgesia before 1 h. The mean pain scores up to that time are shown in figure 2. There was no significant difference between the mean pain scores before injection and, although the patients in the i.m. group tended to

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Study II In this study all observations on pain were made on the day after operation. In view of this, the routine practice was used in premedication and in the local anaesthetic agents used. Premedication consisted of diamorphine 5 mg and atropine 0.6 mg given 1 h before operation. Extradural block was obtained by injecting 20 ml of 2% lignocaine via a catheter. This was followed by light general anaesthesia as in study I. Pain relief after operation was obtained in most cases with a continuous extradural infusion of 0.25% bupivacaine 8-lOmlh" 1 . However, this method was not available on four occasions (two patients in each group). These patients received a single injection of morphine 5mg in 10 ml of normal saline extradurally when they required analgesia on the day of operation. The bupivacaine infusions were stopped at 6 a.m. on the following day and patients were accepted into the trial if and when they required further analgesia during the morning. Assessment of pain was made using a visual analogue scale. Two injections were then given, one i.m. and one extradural, the patients being told that they were receiving a pain-killing drug. In one group of 10 patients morphine lOmg was given extradurally in 10 ml of saline, together with an i.m. injection of 1 ml of saline. The other 10 patients received morphine lOmg i.m. and 10ml of saline extradurally. Thus all patients received lOmg of morphine, 10 extradurally and the other 10 i.m. The order was randomized and the person making up the two injections for each patient took no part in assessing the effects. Analogue scale assessments were made at 20,40, 60, 120, 240, 360 and 480 min after the morphine administration, provided no further analgesia had been given. The ward staff were free to give opiate analgesics at any time and if this was done the study was terminated at that point.

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EXTRADURAL MORPHINE FUR POSTOPERATIVE PAIN

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8-

20

7-

18

V

6-

16

K

o

'Extradural

I 3'

12

PIM

2-

0

8

20

40

60

Time (mm)

FIG. 2. Mean pain scores in patients in study II who had received morphine lOmg by i.m. or extradural injection.

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was 18.7 mg in the i.m. group and 6.7mg in the extradural group; this difference was statistically significant. DISCUSSION IM Extradural

IM Extradural

Study I

Study II

FIG. 1. Times (h) from extradural and i.m. injection until next administration of analgesic in patients who had received morphine extradurally and others who had received morphine i.m. in the two studies. * Three patients in study II required no further analgesic.

have a greater reduction in pain score at 1 h, this was not statistically significant (table I, fig. 2). Three patients who had received extradural morphine did not receive any further analgesia, but the difference between the groups was not statistically significant. The actual times to further analgesia are shown in figure 1, alongside those from study I. The mean total dose of morphine given over the 24 h following the extradural and i.m. injections

Since the first descriptions of intrathecal (Wang, Nauss and Thomas, 1979) and extradural (Behar, et al., 1979) morphine for pain relief, many reports have been published and the great majority have been favourable. However, few properly controlled studies have been carried out and quite frequently it is not possible to determine if the opiate gave analgesia as a direct effect on the spinal cord or by a central effect following systemic absorption. There has been a trend also towards larger and larger dosage, particularly with extradural administration, presumably because the small doses originally recommended were found to be ineffective. Thus the 2 mg of morphine first described by Behar is now seldom used and 10 mg appears to be the dose most commonly used.

TABLE I. Patients in study II: Mean (± SEM) pain scores before injection and at 20, 40 and 60 min after injection in the two groups of patients

Extradural

Before injection

20 min

40 min

60 min

7.10±0.68 7.25±0.61

4.15±0.54 5.15±0.75

2.85 ±0.47 4.90 ±1.06

2.80±1.40 3.85 ±0.92

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mg) doses of morphine extradurally is almost totally useless and the dose must be increased to that commonly used for i.m. injection (10mg). This also holds for other drugs such as fentanyl, of which, in one study reporting favourably (Nalda, Camp and Burzaco, 1981), a mean dose of 0.25 mg was used. As the dose of opiate is increased there can be no doubt that a substantial part of the effect will be attributable to systemic absorption, the extradural space presenting little in the way of a barrier to this process. As experience with intraspinal opiates increases so do the number of reported side-effects. These include respiratory depression, nausea and vomiting, intractable pruritis and coma. Subarachnoid injection seems to be particularly liable to cause respiratory depression, but extradural injection also does so on occasion. One of our patients receiving extradural morphine before operation could not be roused after operation until naloxone had been given. The present practice of intraspinal opiate administration requires elucidation and this can only be realized with properly controlled studies. Thus, we need data on the degree and duration of analgesia compared with the more usual routes of administration, the effect of dosage and, above all, the nature and frequency of side-effects.

REFERENCES

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In a previous controlled study (McClure et al., 1980) morphine 2 mg and 5 mg given extradurally were compared with a placebo injection in patients suffering from postoperative pain similar to those in the present two studies. It was found that 5mg gave better results than 2mg, which itself was better than placebo. However, the same result might have been obtained with i.m. injection. Both doses of morphine frequently failed to provide any significant or long-lasting analgesia. Placebo reactors were also common, one patient requiring no pain relief for 8 h after the injection of saline. At 20 min after injection, the placebo group as a whole had a statistically significant reduction in the mean pain score. In the present studies we were impressed by the much better results we obtained in regard to pain relief when the morphine was given before the onset of pain—in study I when mixed with the local anaesthetic drug before operation. In seven of 10 patients it took from 11 to 19 h before further analgesia was required. This compares with a mean of 6h for those given morphine lOmg i.m. just before operation, a figure we found surprisingly large and probably because of the long duration of analgesia found with a dose of 20 ml of 0.5% bupivacaine. If pain was present before giving morphine, as was the case in study II, the results, although still favouring the extradural route, were less impressive. Minor and short-lived analgesia occurred in four of 10 patients in the extradural group. Indeed, the degree of analgesia during the 1st hour was better in the i.m. group. The impression gained was that extradural morphine frequently failed in the patient with pain because the onset of analgesia was so prolonged. This statement must be contrasted with the frequent reports that analgesia (almost always total) appears within a few minutes, lasts many hours and all this in 100% of patients. Such assertions are both unrealistic and liable to bring the method into disrepute. The exact mechanism by which intraspinal opiates work is not clear, although the theoretical reasons why it should mimic naturally occurring endorphins are cogent. That this explanation does not meet all aspects of the problem is also becoming clear. Pain is a multifactorial phenomenon and the pain of labour, for example, cannot be compared to chronic pain or even the acute pain of the period after operation. Clinically it has been shown that the relief of labour pain using small (2-

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Behar, M., Magora, F., Olshwang, D., and Davidson, J. T. (1979). EpiduraJ morphine in treatment of pain. Lancet, 1, 527. Bromage, P. R., Camporesi, E., and Chestnut, D. (1980). Epidural narcotics for post-operative analgesia. Anesih. Analg. (Cleve.), 59, 473. Chayen, M. S., Rudick, V., and Borvine, A. (1980). Pain control with epidural injection of morphine. Anesthesiology, 53, 338. McClure, J. H., Chambers, W. A., Moore, E., and Scott, D. B. (1980). Epidural morphine for postoperative pain. Lancet, 1, 975. Magora, F., Olshwang, D., Eimerl, D., Shorr, J., Katzenelson, R., Cotev, S., and Davidson, J. T. (1980). Observations in extradural morphine analgesia in various pain conditions. Br. J. Anaesth., 52, 247. Naldo, M. A., Campo, F., and Burzaco, I. (1981). Obstetric analgesia with fentanyl administered by the extradural route. Br. J. Anaesih., 53, 113. Torda, T. A., Pybus, D. A., Liberman, H., Clark, M., and Crawford, M. (1980). Experimental comparison of extradural and i.m. morphine. Br. J. Anaesth., 52, 939. Wang, J. K., Nauss, L. A., and Thomas, J. E. (1979). Pain relief by intrathecally applied morphine in man. Anesthesiology, 50, 149.

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schwerer gynakologischer Chirurgie unterzogen. Als beim ersten Versuch Morphin zur gleichen Zeit wie die ortliche Betaubung vor der Chirurgie verabreicht wurde, fuhrte die extradurale Verabreichung zu einer bedeutend langer anhaltenden Analgesie—im Durchschnitt 707 min im Vergleich zu 371 min bei intramuskularer Verabreichung. Beim zweiten RESUME Versuch mit Patienten, die sich nach der Operation uber Nous avons compare, au cours d'etudes a double inconnue Schmerzen beklagten, setzte die Wirkung von extraduralem effectuees au hasard, les effets de lOmg de sulfate de morphine Morphin langsamer ein, hielt aber langer als bei intramusadministres soit par voie extraduralc, soit par voie mtramus- kularem Morphin an, obwohl die Unterschiede statistisch culaire afin de soulager les douleurs postoperatoires ressenties unbedeutenden waren. Bei dieser Gruppe hatte extradurales par dcs patientes ayant subi des operations gynecologiques Morphin oft keine brauchbare Wirkung. Die Gruppe von majeures. Au cours de la premiere etude, la morphine a etc Patienten, die Morphin extradural bekamen, erhielt bedeutend administree en meme temps que l'agent anesthesiant local avant weniger zusarzliches Morphin (6,75 mg) in den nachfolgenden l'intervention, et 1'adininistration extradurale a eu pour effct de 24 Srunden als die Gruppe, die Morphin intramuskular bekam produire une analgesie d'une duree nenemment plus longue: (18,75 mg). moyenne 707 min contre 371 min avec l'injecnon lntramusculairc. Lors de la seconde etude, effectuee sur des patientes se plaignant de douleurs postoperatoires, la morphine adminiMORFINA EXTRADURAL PARA EL DOLOR stree par voie extradurale a demande plus de temps avant POSOPERATORIO d'agir, mais sa duree d'action a ete plus longue qu'avec l'administration de morphine par voie intramusculaire, bien SUMARIO que les ecarts n'aient pas eu une bien grande importance Los efectos de lOmg de sulfato de morfina, administrados statistique. Dans ce groupe, la morphine administree par voie extradurale n'a pas toujours entraine d'analgesie utile. Le extradural o intramuscularmente, para el alivio del dolor groupe auquel la morphine avait ete administree par voie posoperatorio, se compararon en dos pruebas aleatorizadas de extradurale a recu nettement moins de morphine supplement- doble anonimato, en pacientes sometidos a operaciones quiriiraire (6,75 mg) au cours des 24 h suivantes que le groupe jicas de importancia. En la primera preuba, en la que la morfina se administro junto con la anestesia local antes de la operacion, recevant la morphine par voie intramusculaire (18,75mg). la administration extradural tuvo como resultado una anestesia cuya duration fue signincativamente mucho mas large: Media de 707 min en comparacion con los 371 min (intramuscular). En EXTRADURALES MORPHIN ZUR la segunda prueba y en pacientes aquejados de dolor posoperaSCHMERZENSLINDERUNG NACH DER torio, la morfina extradural tuvo un inicio de actividad mas CHIRURGIE lento pero una actividad mas duradera, en comparacion con la morfina intramuscular, aunque la diferencia no era relevante ZUSAMMENFASSUNG desde el punto de vista estadistico. En lo tocante a este grupo, la Die Auswirkungen von lOmg Morphinsulfat, entweder extra- morfina extradural no proveyo una analgesia iitil. El grupo dural oder intramuskular verabreicht zur Schmerzens- extradural recibio, de forma significativa, menos cantidad de linderung nach der Operation, wurden in zwei randomisienen morfina complemcntaria (6,75 mg) que el grupo de administraDoppelblindversuchen mit Parienten verglichen, die sich cion intramuscular (18,75 mg) durante las 24horas siguientes. MORPHINE ADMINISTREE PAR VOIE EXTRADURALE POUR LE SOULAGEMENT DE LA DOULEUR APRES UNE INTERVENTION CHIRURGICALE

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