COMPARISON OF MORPHINE AND SUBLINGUAL BUPRENORPHINE FOLLOEING ABDOMINAL SURGERY

Br. J. Anaesth. (1984), 56, 855

COMPARISON OF MORPHINE AND SUBLINGUAL BUPRENORPHINE FOLLOWING ABDOMINAL SURGERY R. J. CUSCHIERI, C. G. MORRAN AND C. S. McARDLE SUMMARY

Most HiniHans recognize that the intermittent administration of morphine i.m. provides unsatisfactory control of pain following abdominal surgery (Leading Article, 1978; Leading Article, 1980; Dodson, 1982; Tammisto and Tigerstedt, 1982). Although alternative methods of providing superior pain relief, including the infusion of opiates i.v. (Church, 1979; Fry, 1979a), patient-operated ondemand techniques (Chakravarty et al., 1979; Harmer et al., 1983), and extradural analgesia (Bromage, 1967; Spence and Smith, 1970) have been advocated, the administration of opiates by intermittent i.m. injection remains the most widely used method of providing analgesia in the period after operation (Dodson, 1982; Cuschieri, Morran and McArdle, 1983). Buprenorphine is a potent analgesic drug with a high affinity for opiate receptors. The slow dissociation of the drug—receptor complex results in a prolonged duration of action, despite low plasma concentrations (Bullingham et al., 1980). Buprenorphine 0.3 mg i.m. has been shown to provide a degree of pain relief similar to that given by morphine 10mg i.m (Tigerstedt and Tammisto, 1980), and buprenorphine 0.4mg sublingualry to produce analgesia equivalent to morphine 10 mg i.m. (Edge, Cooper and Morgan, 1979). The relative potency of sublingual buprenorphine and the ability to provide R. J. CusanERi, F.R.C.S.; C. G. MORRAN, F.R_OS.; C. S. MCAR-

DLE, M.D., F.R.CS.; University Department of Surgery, Royal Infirmary, Glasgow G4 OSF. Correspondence to C. S. McA.

regular analgesia with ease of administration, suggest that the sublingual administration of buprenorphine may be of value in the management of pain after operation. The aim of the present study was to assess the role of sublingual buprenorphine in the management of postoperative pain following abdominal surgery. PATIENTS AND METHODS

Consecutive patients undergoing elective abdominal surgery, without evidence of hepatic, renal or severe cardiorespiratory dysfunction, were considered eligible for the study. All patients received a standard opiate and atropine premedication. Following the induction of anaesthesia with thiopentone, intermittent positive pressure ventilation was instituted. Anaesthesia was maintained with volatile inhalation agents supplemented with narcotic analgesics i.v. or narcotics alone, at the discretion of the anaesthetist. Following surgery, the patients were allocated randomly to receive either morphine 10 mg i.m. on demand or a single injection of buprenorphine 0.3 mg i.m. followed by sublingual buprenorphine 0.4 mg every 6h for 3 days. Patients in the buprenorphine group who had inadequate pain relief were allowed additional morphine 10 mg i.m., if required. Pain was assessed by a 100-mm linear analogue scale where zero represented no pain and 100 mm the mavimal conceivable pain (Huskisson, 1974). This technique has been shown to be a reliable and reproducible method of assessing pain (Revill et al., 1976). Assessments were carried out before the © The Macmillan Press Ltd 1984

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In a prospective Jtudy, patients undergoing abdominal surgery were allocated randomly to receive intermittent morphine lOmgi.m. (n —41) or a lingle injection of buprenorphine 0.3 mgi.m. followed by sublingual buprenorphine 0.4 mg every 6h (n= 39) for 3 days following operation. Patients receiving buprenorphine were allowed additional morphine, if required. Pain (cores (linear analogue scale) in those patients receiving regular sublinguftl buprenorphine were consistently less than in those receiving intermittent morphine i.m. Half the patients receiving buprenorphine required no additional analgesia; only 15% required additional armigi-nin after the first day following operation. Arterial blood-gas analyses showed m'gnrfirant hypozaemU and significantly greater carbon dioxide tensions in those receiving buprenorphine. These results suggest that a regimen based on the use of sublingual buprenorphine provides pain relief comparable to that provided by intermittent opiates i.m.

BRITISH JOURNAL OF ANAESTHESIA

856

TABLE I. Comparison of groups (m*an±SD) Morphine

Buprenorphine

41 17:24

ft

M:F Age(yr) Height (cm) Weight (kg) Upper abdominal Lower abdominal Anaesthesia Inhalation + narcotic Narcotic Duration (min)

39

52 ±15 161 ±11 63 ±10

23:16 58±14 164± 8 63 ±13

30 11

30 9

34 7

32 7

113±45

106 ±42

RESULTS

Of 89 patients eligible for entry to the study, six were unable to record their pain on the linear analogue scale and three died, leaving 41 patients in the morphine and 39 in the buprenorphine groups. The physical characteristics, surgical procedures and duration of anaesthesia were similar in both groups (table I). There were no differences in the number of patients in each group receiving narcotics during the surgical procedure, or in the total amount of narcotic used. There was no significant difference in the severity of pain measured by the linear analogue scales before the initial dose of analgesia (table II). The severity of pain was consistently less in the buprenorphine group throughout the 3 days of the study, reaching significance on the 2nd day after operation in patients undergoing upper abdominal surgery. Nineteen patients in the buprenorphine group required supplementary morphine; although only six required additional analgesia after the 1st day after operation. Patients in the buprenorphine group required an average of morphine 7 mg within

1 day and 13 mg within 3 days of surgery compared with patients in the morphine group who received a mean of 50 mg and 80 mg morphine within 1 and 3 days of surgery, respectively. Arterial oxygen and carbon dioxide tensions were similar in both groups before surgery (table III). Arterial oxygen tensions were less in the buprenorphine group, the differences reaching significance on the 3rd and 4th days after operation. Arterial carbon dioxide tensions were significantly greater in the buprenorphine group throughout the period of study. One patient developed a respiratory rate of 4b.p.m. following buprenorphine i.m., but spontaneous recovery occurred. Drowsiness occurred in two patients in the morphine group and in 10 of those receiving buprenorphine (P<0.05). Six patients in the morphine group and five in the buprenorphine group complained of persistent nausea; one patient in each group had persistent vomiting. Postoperative chest infections developed in 15 patients in the morphine group and in 14 in the buprenorphine group.

TABLE n. Untar analogue pain scores (mm) (mean ± SEM). *P < 0.05 Dayl Pretreatmcnt Upper abdominal incision Morphine Buprenorphine Lower abdominal JTv*i«inn Morphine Buprenorphine

Day 3

Day 2 p.m.

p.m.

p.m.

67 ± 4 60 ± 4

47±5

37±4

39±4

35±4*

28±4

26±4

37±5

33±3

28±3

25±3*

22±3

22±3

63 ± 6 58 ± 9

46±9 39±7

41±9 30±7

42±10 38±8

44±10 24±8

42±10 28±8

44±10 28±6

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administration of the first dose of analgesic and, thereafter, twice daily for 3 days, patients being asked to record their average pain over the previous 12 h. All assessments were supervised by a single observer. Arterial blood-gas analyses were performed before operation, and on the morning of the first 4 days after operation. The frequency of postoperative chest infection was recorded and the occurrence of drowsiness, nausea and vomiting noted. Pain scores were compared using a Mann-Whitney U test. The results of blood-gas analyses were analysed using an unpaired t test. Chi-squared test with Yates' correction was used to assess qualitative differences between groups.

COMPARISON OF MORPHINE AND BUPRENORPHINE

857

TABLE HI. Blood-gas anatytts (kPa) (mtan± SEM) *P < 0.05; **P < 0.001

Day after operation Before

operation

1

2

3

4

Arterial O2 tension Morphine Buprenorphine

11.7±0.1 11.7±0.1

9.5±0.3 9.1 ±0.3

9.3±0.3 8.8±0.3

10.0±0.3* 9.3±0.3*

10.5±0.3* 9.8±0.3*

Morphine Buprenorphine

4.5±0.1 4.6±0.1

4.6±0.1* 4.9±0.1*

4.5±0.1* 4.8±0.1*

4.3±0.1* 4.6±0.1*

anaesthesia. In patients in the buprenorphine group with inadequate pain relief, we felt that it would be unjustified not to provide alternative analgesia if required. It was considered that supplementary buprenorphine i.m. was inappropriate in a general ward in view of its known potential for respiratory depression. Supplementary morphine i.m. as opposed to buprenorphine was chosen because of ease of reversal should respiratory depression occur. Despite the theoretical hazard of interaction between buprenorphine and morphine, we found that the addition of morphine provided adequate pain relief in most patients. In one patient the respiratory rate decreased markedly (with no increase in arterial carbon dioxide tension) after buprenorphine i.m., emphasizing the need for continuous supervision in the period immediately after operation. There was no clinical evidence of respiratory insufficiency associated with the use of sublingual buprenorphine. However, arterial oxygen tensions were less and carbon dioxide tensions greater in the buprenorphine group. The frequency of chest infection after operation was similar in both groups. This study has demonstrated that a regimen based on the use of sublingual buprenorphine has a role in the management of postoperative pain. Ellis and colleagues (1982) demonstrated that the regular sublingual administration of buprenorphine alone produced pain relief comparable to that from morphine i.m. in patients undergoing cholecystectomy. In contrast, approximately half the patients in the buprenorphine group in our study required supplementary analgesia within the first 24 h, although only 15% required additional analgesia after the 1st day following operation. Adequate control of pain in the early period after operation remains a significant problem and further studies are necessary to assess alternative methods

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DISCUSSION

Numerous studies support the inadequacies of traditional intermittent on-demand i.m. analgesia (Keeri-Szanto and Heaman, 1972; Utting and Smith, 1979; Rutter, Murphy and Dudley, 1980). Failure to recognize the extent of pain and fear of precipitating respiratory depression along with the regulations governing the use of a controlled drug may lead to analgesia being withheld from the patient. This results in irregular administration of opiate drugs, fluctuating plasma concentrations and inadequate relief of pain. Regular administration of analgesia provides superior pain relief. In a prospective randomized trial, patients receiving regular morphine i.m. had significantly lower pain scores than patients allocated to receive intermittent morphine i.m. (Rutter, Murphy and Dudley, 1980). Although the concept of regular analgesia is attractive, the administration of a controlled drug requires the supervision of senior nursing staff. Early reports of sublingual buprenorphine suggested that it provided adequate analgesia combined with ease of administration (Edge, Cooper and Morgan, 1979; Fry, 1979b). In this study on patients undergoing abdominal surgery, we compared a policy of a single i.m. injection of buprenorphine followed by the regular sublingual administration of buprenorphine (plus supplementary morphine, if required) with our standard ward policy of intermittent morphine i.m. The results show that these two regimens provided comparable pain relief. The pain scores in those patients receiving regular sublingual buprenorphine were consistently less than those receiving intermittent morphine i.m., and were significantly less on the 2nd day after operation. To assess the value of sublingual buprenorphine in the context of conventional anaesthetic practice, no attempt was made to standardize the technique of

4.3±0.1** 4.9±0.1**

BRITISH JOURNAL OF ANAESTHESIA

858 of pain relief. Sublingual buprenorphine provides satisfactory analgesia in most patients after the 1st postoperative day. There are obvious advantages in the ease of administration, and the use of a drug which is outwith the regulations governing controlled drugs. ACKNOWLEDGEMENTS

REFERENCES

Bromage, P. R. (1967). Eztradural analgesia for pain relief. Br. J. AfuwrtA.,39,721. Bullingham, R. E. S., McQuay, J. H., Moore, R. A., and Bennett, M. R. D. (1980). The pharmacokinetics of buprenorphine in man. Clin. Pharmacol. Thtr., 28,667. Chakravany, K., Tucker, W., Rosen, M., and Vickers, M. D. (1979). Comparison of buprenorphine and pethidine given intravenously on HrmanH to relieve postoperative pain. Br.

Mtd.J.,2, 895. Church, J. J. (1979). Continuous narcotic infusion for relief of postoperative pain. Br. Mtd. / . , 1,977. Cuschieri, R. J., Morran, C. G., and McArdle, C. S. (1983). Methods of postoperative pain relief. Ann.R. Coll. Surg. Engl., 65,136. Dodson, M. (1982). A review of methods for relief of postoperative pain. Ann. R. Coll. Surg. Engl., 64, 324. Edge, W. G., Cooper, G. M., and Morgan, M. (1979). Analgesic effects of sublingual buprenorphine. Anatsthtsia, 34,463. Ellis, R., Haines, D., Shah, R., Cotton, B. R., and Smith, G. (1982). A comparison of i.m. morphine, sublingual buprenorphine and self-administered i.v. pethidine. Br. J. Anatsth., 54, 421. Fry, E. N. S. (1979a). Postoperative analgesia using continuous infiimnn of papaveretum. Aim. R. Coll. Surg. Engl., 61, 371. (1979b). Relief of pain after surgery. Anatsthtsia, 34, 549. Harmer, M., Slattery, P. J., Rosen, M., and Vickers, M. D. (1983). Intramuscular on demand analgesia: double-blind controlled trial of pethidine, buprenorphine, morphine and meptazinoL Br. Mtd. J., 286,680. Huskisson, E. C. (1974). Measurement of pain. Lancet,!, 1127. Reeri-Szanto, M., and Heaman, S. (1972). Postoperative demand analgesia. Surg. Gynatcol. Obsut., 134,647. trading Article (1978). Postoperative pain. Br. Mtd. / . , 2, 517. (1980). Patient controlled analgesia. Lanctt, 1,289. Revill, S. I., Robinson, J. D . , Rosen, M., and Hogg, M. I. J. (1976). The reliability of a linear analogue for evaluating pain.

Anaathtsia, 31, 1191. Rutter, P. C , Murphy, F., and Dudley, H. A. F. (1980). Morphine: controlled trial of different methods of administration for postoperative pain. Br. Mtd. J., 280,12. Spence, A. A., and Smith, G. (1971). Postoperative analgesia and lung function: a comparison of morphine with eztradural block. Br. J. Anatsth., 43,144. Tammisto, T., and Tigerstedt, I. (1982). Analgesics in postoperative pain relief in adults. Acta Anattthtsiol. Scand., (Suppl.),74,161. Tigerstedt, I., and Tammisto, T. (1980). Double-blind mutiple-

COMPARAISON ENTRE MORPHINE ET BUPRENORPHINE SUBLINGUALE APRES CHIRURGIE ABDOMINALE RESUME

Au cours d'une etude prospective, des patients devant etre operes de rabdomen ont eti repartis de facon aleatoire dans deux groupes qui devaient recevoir soit des injections i.m. icpctees de 10 mg de morphine ( n - 4 1 ) , soit une injection unique de buprenorphine 0,3 mg i.m. ruivie de l'administration de 0,4 mg de buprenorphine par voie sublinguale, toutes les 6h (n = 39) pendant les trois premiers jours post-operatoires. Les patients qui recevaient de la buprenorphine pouvaient avoir en plus de la morphine, si necessaire. Les algometries (echelle lineaire analogue) des patients qui recevaient regulierement de la buprenorphine par voie sublinguale etaient nettement plus basses que • celles de ceuz qui recevaient de la morphine i.m. discontinue. La mcdtie des patients qui recevaient de la buprenorphine n'ont pas eu bcsoin d'analgesie complementaire; seuls 15% d'entre euz ont reclamf une telle nnalgiw apris les premieres 24 h postoperatoires. L'analyse des gaz du sang a mis en evidence une hypox£mie significative et des pressions de gaz carbonique significativement plus elevens chez les patients qui recevaient de la buprenorphine. Ces resvutats suggerent qu'un protocole d'analgesie bas£ sur l'utilisation de buprenorphine ffyhiingiial^ procure une analgesic comparable a celle obtenue par l'utilisation intermittente des opiaces i.m.

VERGLEICH ZWISCHEN MORPHIUM UND SUBLINGUALEM BUPRENORPHIN NACH ABDOMINALEINGRIFFEN ZUSAMMENFASSUNG

In einer prospektiven Studie wurden Patienten, die Baucheingriffen unterzogen wurden, auf zwei Gruppen zufallsverteilt, von denen die cine 10 mg Morphium i.m. intermittierend (n —41), die andere eine einzelne Injektion 0,3 mg Buprenorphin und dnnarh 6stundlich 0,4 mg Buprenorphin sublingual (n -= 39) wShrend der ersten drei postoperativen Tage erhiek. Die Patienten dcr Buprenorphin-Gruppc bekamen auf Bedarf zusfitzlich Morphium. Die Schmerzpunkte (Unear-analoge Skala) waren bei den Patienten mit regelmafiiger sublingualer BuprenorphinGabe durchweg niedriger als bei denen mit intermittierender Morphium-Gabe. Die HSlfte der Patienten mit Buprenorphin brauchte keine zusatzlkhe Analgesie; nur 15% brauchten zusfitzliche Analgesie nach dem emen postoperativen Tag. Die Analysen der arteriellen Blutgase zeigten bei den Patienten mit Buprenorphin eine signifikante Hypoxfimie und signifikant grofiere CC*2-Spannungen. Die Ergebnisse deutcn darauf bin, dafi n-gflmafiigr Gabe von sublingualem intramuskulare Opiatgabe erlekhtcrt.

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We thank our surgical and anaesthetic colleagues for their cooperation in this study. This work was supported by a grant from the Scottish Hospital Endowments Research Trust.

dose comparison of buprenorphine and morphine in postoperative pain. Acta. Anatsthtsiol. Scand., 24, 462. Utting, J. E., and Smith, J. M. (1979). Postoperative analgesia. Anatsthtsia, 34, 320.

COMPARISON OF

3UPRENQRPHJNE

CXJMPARAQON DE LA MORFINA Y DE LA BUPRENORFINA SUBLINGUAL DESPUES DE CIRUJIA ABDOMINAL SUMARIO

En tin estudio prospecdro, te distribuyo al azar a los pacientes sometidos a drujia abdominal para la administracion de 10 mgde mnrfina i.m. (n •= 41) o de una inyecaon unica de buprenorfina de 0,4 mg cada 6horas (n = 39) durante 3 dias despues de la operadon. Si fuese necesario, los pacientes que reobian buprenorfina podian recibir tnmbicn morfina adirional. Las marcas al dolor (escala analoga linear) en los pacientes

859 __

con buprenorfina sublingual adminittrada con r constantemente menores de las de los pacientes a los cuales se administraba morfina iTnii de manera intennitente^ Lamitad de los pacientes con buprenorfina necesitaron ningiina analgesia complementana; un 15% lolamente ezigid una analgesia adicional despues del primer dia Siguientc a la operacion. Los fln^linin sangre-gas de las arterias indicaron una hipaxemia significativa y tensiones dc anhidxido carbonico mayores ^n los quc rccibian buprenorfina. Dichos resultados sugieren que un regimen basado en el uso de buprenorfina sublingual provee un alivio del dolor comparable al que facilitan los opiatos i.m. intermitentes. Downloaded from http://bja.oxfordjournals.org/ at University of California, San Fransisco on April 24, 2015