- Email: [email protected]
Intrathecal morphine compared with diamorphine for postoperative analgesia following unilateral knee arthroplasty
Acute Pain 4 (2002) 5–8
Intrathecal morphine compared with diamorphine for postoperative analgesia following unilateral knee arthroplasty Tamer Riad, MBChB FRCA, Brian Williams, MBChB FRCA, Jamie Musson, MBChB FKCA, Bob Wheatley, MBChB FRCA∗ Acute Pain Management Unit, York District Hospital, Wigginton Road, York YO3 7HE, UK
Abstract Objectives: To compare the efficacy and side effects of low dose intrathecal morphine and diamorphine for postoperative analgesia after total knee arthroplasty. Methods: Sixty-four patients were included in a prospective, randomised, double-blind study. Following a standardised general anaesthetic technique, patients received either 0.3 mg of intrathecal morphine or diamorphine with 2–2.5 ml of 0.5% heavy spinal bupivacaine. Supplementary analgesia was provided postoperatively by regular eight hourly diclofenac and patient controlled IV morphine (bolus 1 mg, lockout 5 min, no background infusion). Results: Patients in the morphine group had significantly lower median numerical rating score (NRS) for pain on movement at 4 h [0 versus 3.5] (P = 0.0008) and 8 h [0 versus 4] (P = 0.0083). In addition, median PCA morphine consumption was significantly reduced at 4 h [0 versus 1] (P = 0.0005), 8 h [0.5 versus 6] (P = 0.0063) and 12 h [3 versus 8.5] (P = 0.0426) in the morphine group. There was no significant difference in the total morphine consumption or NRS for pain at 24 h between the two groups. There was no significant difference in the incidence of side effects between the two groups. Conclusion: In the doses used in this study, morphine produced more effective analgesia than diamorphine in the early postoperative period with comparable side effects [Acute Pain 4 (1) (2001) 7]. © 2002 Published by Elsevier Science B.V. Keywords: Spinal analgesia; Opioids; Knee arthroplasty
1. Introduction The wide variety of analgesic techniques (IV PCA, continuous nerve blocks epidural and spinal analgesia, cryotherapy) described, following total knee arthroplasty highlights the clinical problem of providing effective analgesia whilst allowing early rehabilitation following this type of surgery. Although intrathecal opioids have previously been studied following major orthopaedic surgery [1–9], there is little agreement on the optimal choice or dose of opioids. The results of a recent systematic review of spinal opioids following caesarean section would suggest that the highly lipid soluble agents such as fentanyl and sufentanil would be too short acting for major orthopaedic surgery [10]. Although a survey of European practice showed that morphine was the most widely used intrathecal opioid [11] its use has been limited by concerns about dose-dependent opioid side effects. However, in the UK diamorphine is the most ∗ Corresponding
author. Tel.: +44-1539-488981. E-mail address: [email protected] (B. Wheatley).
1366-0071/02/$ – see front matter © 2002 Published by Elsevier Science B.V. PII: S 1 3 6 6 - 0 0 7 1 ( 0 2 ) 0 0 0 0 3 - 7
commonly used spinal opioid. This lipid soluble pro-drug of morphine is deacetylated to morphine within neural tissue [12] and has the potential advantage of rapid onset of action, intermediate duration with a shorter half-life in the CSF and a reduced risk of centrally mediated side effects. In a study of patients undergoing caesarean section, 0.2 mg of intrathecal diamorphine was shown to be as effective as the same dose of intrathecal morphine with reduced drowsiness and pruritus [13]. The aim of this study was to compare the efficacy and side effects of low dose (0.3 mg) intrathecal morphine and diamorphine for postoperative analgesia after total knee arthroplasty.
2. Methods The Hospital Ethical Committee approved the prospective, randomised, double-blind study. Following discussion of the study aims, informed consent was obtained from 64 ASA I or II patients scheduled for unilateral knee arthroplasty.
6
T. Riad et al. / Acute Pain 4 (2002) 5–8
Exclusion criteria were: patients weighing less than 50 kg or more than 110 kg, patients aged more than 80 years or patients in whom amide local anaesthetic drugs, spinal anaesthesia or NSAIDs were contraindicated. All patients received a standardised perioperative technique. General anaesthesia was induced in unpremedicated patients with propofol (1–3 mg kg−1 ) and fentanyl 50 g. Anaesthesia was maintained with oxygen, nitrous oxide and enflurane while spontaneously breathing through a laryngeal mask. Spinal anaesthesia was performed with 2–2.5 ml of heavy bupivacaine plus a pharmacy prepared solution of preservative free morphine 0.3 mg in 0.3 ml or diamorphine 0.3 mg in 0.3 ml, which was allocated on a doubleblind, randomised basis using computer generated random numbers. Patients received 50 mg of diclofenac diluted in 500 ml normal saline intravenously at the end of surgery and 50 mg orally eight hourly in the postoperative period. Supplementary analgesia was provided by self-administration of IV morphine by a PCA device (Graseby 9300) in 1 mg boli with a 5 min lockout period. Metoclopramide was routinely prescribed for postoperative nausea and vomiting. All patients received oxygen via nasal cannulae at 2 l min−1 during the course of the study. The use of a numerical rating score (NRS) from 0 to 10 was described at the preoperative visit. The score was used to measure pain at rest, pain on movement, nausea and itching at 1, 4, 8, 12, 16 and 24 h. Patients also gave a verbal rating score (VRS) at 24 h for the quality of analgesia (poor, fair, good, excellent). Time to first PCA demand and PCA morphine consumption were also recorded. The patient’s ability to straight-leg-raise on the affected side was noted at 24 and 48 h. Respiratory rate, blood pressure, pulse rate, oxygen saturation and sedation score were measured at four hourly intervals but were omitted at night if the patients were sleeping. The sedation score used was: 0 (none, patient alert); 1 (mild, occasionally drowsy, easy to arouse); 2 (moderate, frequently drowsy, easy to arouse); 3 (severe, somnolent, difficult to arouse). Data were analysed using the Minitab Statistics Program (Version 13) on Windows 98. Mann–Whitney and χ 2 -tests were used for the non-parametric data and a two sample Student’s t-test for the patient characteristics. A value of P < 0.05 was regarded as statistically significant. With regard to the time to first PCA demand, a time of 1440 min (24 h) was assigned to those patients who did not use PCA. Graphs were processed using SPSS Statistics Package, Version 10. The sample size of 64 patients was determined by a priori power analysis, using Minitab, to detect a 50% difference in 24 h PCA morphine consumption (0.05% significance level, 80% power). This calculation was based on previously published data [9] which showed that patients receiving 0.3 mg intrathecal morphine for knee arthroplasty had a mean 24 h morphine consumption of 21 mg (S.D. 14.8).
Table 1 Patient characteristics mean (S.D.)
Age (years) Weight (kg) Male:female a
Morphine group (n = 32)
Diamorphine group (n = 32)
70.3 (7.3) 80.1 (13.4) 15:17
71.4 (9.6) 79.8 (15.5) 9:23a
χ 2 , P = 0.121.
3. Results Sixty-six patients were recruited into the study. Two patients were excluded from the study because spinal anaesthesia could not be performed for technical reasons. Two patients from the diamorphine group were not included in the analysis for itching as they had preoperative pruritus. There were no significant differences between the groups in terms of patient characteristics (Table 1). Patients in the intrathecal morphine group had significantly lower NRS pain scores on movement during the first 8 h after surgery (Fig. 1) and used significantly lower doses of PCA morphine in the first 12 h (Fig. 2). The time to first PCA demand was not significantly different in the two groups. Mean (S.D.) is 660 (448) and 581 (447), for morphine and diamorphine, respectively. Four patients in the morphine group and five patients in the diamorphine group did not use the PCA device. The ability to straight-leg-raise was not significantly different between the groups at 24 and 48 h (morphine group 18/30 at 24 h and 25/29 at 48 h; diamorphine group 20/32 at 24 h and 28/32 at 48 h). There was no significant difference in the NRS for nausea and itching or in the incidence of nausea, vomiting, itching, urinary retention or catheterisation, between the two groups.
Fig. 1. Box plot of i.v. PCA morphine consumption at 4, 8, 12, 16 and 24 h postsurgery. Boxes represent interquartile range: horizontal lines in the boxes represent median values. There is a significant difference between both groups P values (0.001, 0.007, 0.043 at 4, 8, 12 h respectively).
T. Riad et al. / Acute Pain 4 (2002) 5–8
Fig. 2. Box plots of numerical rating scores of pain on movement (NRSm). Boxes represent interquartile range: horizontal lines in boxes represent median values. The NRSm scores were significantly reduced at 4 h (P = 0.0046) and 8 h (P = 0.0083) in the intrethecal morphine group.
Table 2 Incidence of side effects and patient impression (VRS for pain relief) during the first 24 h [Number of patients (%)]
Nausea Emesis Antiemetic given Pruritus Retention Catherisation Patient VRS (Good/excellent)
Morphine group (n = 32)
Diamorphine group (n = 32)
p value
26 21 20 14 8 4 22
19 17 22 11 4 4 23
0.44 0.31 0.59 0.57 0.2 0.72 0.95
(69) (66) (63) (44) (25) (12.5) (69)
(60) (53) (69) (37) n = 30 (12.5) (12.5) (72)
There was no difference in the number of patients rating their pain relief as good or excellent between the two groups (Table 2). No patient had a respiratory rate below 10 min−1 , or oxygen saturation below 92%.
4. Discussion This study was prompted by the difficulty in clinical practice of choosing an appropriate intrathecal opioid drug to provide long lasting analgesia without an unacceptably high incidence of side effects. Highly lipid soluble opioids such as fentanyl have a rapid onset, but their short duration of action limits their use following surgery [10]. The most widely used and studied drug is morphine. The poor lipid solubility of morphine results in high CSF levels (5–10,000 times higher than the mean plasma levels 5 min postinjection) [14] which on the one hand provides long lasting analgesia, but on the other, lead to the rostral spread of the
7
drug and the development of potentially serious opioid side effects. Although doses of 0.5–2.5 mg of morphine have been used following orthopaedic surgery [2–15,16], these doses are significantly higher than the calculated optimal dose of 0.25 mg [17]. The clinical efficacy of morphine in lower doses has been confirmed by Bengtsson who used 0.3 mg morphine following hip surgery [5] and in a recent dose-finding study, 0.1 mg of intrathecal morphine provided effective analgesia with minimal side effects following hip surgery [3]. Although this approach is likely to limit opioid side effects, respiratory depression has been described following doses of intrathecal morphine as low as 0.3 mg [9,18]. An alternative approach for UK anaesthetists has been to use diamorphine intrathecally This opioid drug has higher lipid solubility than morphine, which facilitates entry of the drug into neural tissue where it is deacetylated to morphine. Doses of diamorphine between 0.75 and 2.5 mg have been shown to be as effective as similar doses of morphine [15,16]. In a dose–response study looking at doses from 0 to 2.5 mg, Jacobson et al. [7] found that the optimal dose of intrathecal diamorphine following knee surgery was 0.75 mg. However, they did not recommend the routine use of this dose of diamorphine because the analgesic effects were unpredictable and associated with a high incidence of opioid side effects. In contrast, Reay et al. [8] demonstrated that 0.25 mg of diamorphine was as effective as 0.5 mg in providing analgesia after major orthopaedic surgery. The conflicting results in the literature can in part be explained by the design of the studies. Although knee replacement is associated with more severe pain and increased analgesic demands [19], in some studies hip and knee replacement patients have been regarded as a homogenous group. Furthermore, in earlier studies NSAIDs were not used as part of a balanced analgesic technique and analgesic efficacy was measured at rest. The two main areas of concern with regard to the design of this study are the choice of opioid dose and the gender distribution of the patients in the two groups. The dose of 0.3 mg morphine was based on an earlier dose–response study [20]. The use of 0.1 mg morphine for hip surgery was not described until this study was near completion [3]. Although patients were randomly allocated to the two treatment groups, there was a higher proportion of women in the diamorphine group. Whilst this difference did not reach statistical significance, women have been shown to present for knee replacement surgery with more severe functional impairment [21] and use less PCA morphine than men following major surgery [22]. In summary, in contrast to a previous study of patients following caesarean section [13], this study has shown that 0.3 mg of intrathecal morphine provides more effective analgesia following knee arthroplasty than the same dose of diamorphine given intrathecally. This improvement in analgesia is associated with lower PCA morphine consumption and no significant increase in side effects.
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T. Riad et al. / Acute Pain 4 (2002) 5–8
Acknowledgements We thank Mrs. F. McManus, senior pharmacist at York District Hospital. References [1] P. Grattidge, Nausea and vomiting after major arthroplasty with spinal anaesthesia including morphine: a randomised trial of subhypnotic propofol infusion as prophylaxis, Acta Anaesthesiol. Scand. 42 (1998) 124–127. [2] M.K. Drakeford, K.A. Pettine, L. Brookshire, et al., Spinal narcotics for postoperative analgesia in total joint arthroplasty. A prospective study, J. Bone Joint Surg. AM 73 (1991) 424–428. [3] R. Slappendel, E.W. Weber, R. Dirksen, et al., Optimisation of the dose of intrathecal morphine in total hip surgery: a dose-finding study, Anesth. Analg. 88 (1999) 822–826. [4] K.R. Milligan, D.J. Fogarty, The characteristics of analgesic requirements following subarachnoid diamorphine in patients undergoing total hip replacement, Reg. Anesth. 18 (1993) 114–117. [5] M. Bengtsson, J.B. Lofstrom, H. Merits, Postoperative pain relief with intrathecal morphine after major hip surgery, Reg. Anesth. 8 (1983) 139–143. [6] D.W. Barron, J.E. Strong, Postoperative analgesia in major orthopaedic surgery, Anaesthesia 36 (1981) 937–941. [7] L. Jacobson, M.S. Kokri, A.K. Pridie, Intrathecal diamorphine: a dose-response study, Ann. R. Coll. Surg. Eng. 71 (1989) 289–292. [8] B.A. Reay, A.J. Semple, W.A. Macrae, et al., Low-dose intrathecal diamorphine analgesia following major orthopaedic surgery, Br. J. Anaesth. 62 (1989) 248–252. [9] P.J. Cole, D.A. Craske, R.G. Wheatley, Efficacy and respiratory effects of low-dose spinal morphine for postoperative analgesia following knee arthroplasty, Br. J. Anaesth. 85 (2000) 233–237. [10] J.B. Dahl, I.S. Jeppesen, H. Jorgensen, et al., Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing caesarean section with spinal anesthesia:
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a qualitative and quantitative systematic review of randomised controlled trials, Anesthesiology 91 (1999) 1919–1927. N. Rawal, R. Allvin, J. Neumark, et al., Epidural and intrathecal opioids for postoperative pain management in Europe—A 17-nation questionnaire study of selected hospitals, Med. Sci. Monitor 3 (1997) 57–63. H.I. Kotob, C.W. Hand, R.A. Moore, Intrathecal morphine heroin in humans. Six hour drug levels in fluid and plasma, Anesth. Analg. 39 (1986) 718–722. S.W. Husaini, I.F. Russell, Intrathecal diamorphine compared with morphine for postoperative analgesia after caesarean section under spinal anaesthesia, Br. J. Anaesth. 81 (1998) 135–139. S. Sjostrom, A. Tamsen, M.P. Persson, et al., Pharmacokinetics of intrathecal morphine and meperidine in humans, Anesthesiology 67 (1987) 889–895. D.J. Fogarty, K.R. Milligan, Postoperative analgesia following total hip replacement: a comparison of intrathecal morphine and diamorphine, J. R. Soc. Med. 88 (1995) 70–72. G.M. Paterson, H.J. McQuay, R.E. Bullingham, et al., Intradural morphine and diamorphine. Dose response studies, Anaesthesia 39 (1984) 113–117. G. Nordberg, T. Hedner, T. Mellstrand, et al., Pharmacokinetic aspects of intrathecal morphine analgesia, Anesthesiology 60 (1984) 448– 454. N. Rawal, S. Amer, L.L. Gustafsson, et al., Present state of extradural and intrathecal opioid analgesia in Sweden, Br. J. Anaesth. 59 (1987) 791–799. L. Preble, D. Paige, R.S. Sinatra, Varying narcotic requirements among orthopaedic patients, Anesthesiology 73 (1990) A813. V.J. Sarma, U.V. Bostrom, Intrathecal morphine for the relief of post hysterectomy pain—a double-blind dose response study, Acta Anaesthesiol. Scand. 37 (1993) 223–227. J.N. Katz, E.A. Wright, E. Guadagnoli, et al., Differences between men and women undergoing major orthopaedic surgery for degenerative arthritis, Arthritis Rheum. 37 (1994) 687–694. J.W. Burns, N.B. Hodsman, T.T. McLintock, The influence of patient characteristics on the requirements for postoperative analgesia, Anaesthesia 44 (1989) 2–6.
Intrathecal morphine compared with diamorphine for postoperative analgesia following unilateral knee arthroplasty Tamer Riad, MBChB FRCA, Brian Williams, MBChB FRCA, Jamie Musson, MBChB FKCA, Bob Wheatley, MBChB FRCA∗ Acute Pain Management Unit, York District Hospital, Wigginton Road, York YO3 7HE, UK
Abstract Objectives: To compare the efficacy and side effects of low dose intrathecal morphine and diamorphine for postoperative analgesia after total knee arthroplasty. Methods: Sixty-four patients were included in a prospective, randomised, double-blind study. Following a standardised general anaesthetic technique, patients received either 0.3 mg of intrathecal morphine or diamorphine with 2–2.5 ml of 0.5% heavy spinal bupivacaine. Supplementary analgesia was provided postoperatively by regular eight hourly diclofenac and patient controlled IV morphine (bolus 1 mg, lockout 5 min, no background infusion). Results: Patients in the morphine group had significantly lower median numerical rating score (NRS) for pain on movement at 4 h [0 versus 3.5] (P = 0.0008) and 8 h [0 versus 4] (P = 0.0083). In addition, median PCA morphine consumption was significantly reduced at 4 h [0 versus 1] (P = 0.0005), 8 h [0.5 versus 6] (P = 0.0063) and 12 h [3 versus 8.5] (P = 0.0426) in the morphine group. There was no significant difference in the total morphine consumption or NRS for pain at 24 h between the two groups. There was no significant difference in the incidence of side effects between the two groups. Conclusion: In the doses used in this study, morphine produced more effective analgesia than diamorphine in the early postoperative period with comparable side effects [Acute Pain 4 (1) (2001) 7]. © 2002 Published by Elsevier Science B.V. Keywords: Spinal analgesia; Opioids; Knee arthroplasty
1. Introduction The wide variety of analgesic techniques (IV PCA, continuous nerve blocks epidural and spinal analgesia, cryotherapy) described, following total knee arthroplasty highlights the clinical problem of providing effective analgesia whilst allowing early rehabilitation following this type of surgery. Although intrathecal opioids have previously been studied following major orthopaedic surgery [1–9], there is little agreement on the optimal choice or dose of opioids. The results of a recent systematic review of spinal opioids following caesarean section would suggest that the highly lipid soluble agents such as fentanyl and sufentanil would be too short acting for major orthopaedic surgery [10]. Although a survey of European practice showed that morphine was the most widely used intrathecal opioid [11] its use has been limited by concerns about dose-dependent opioid side effects. However, in the UK diamorphine is the most ∗ Corresponding
author. Tel.: +44-1539-488981. E-mail address: [email protected] (B. Wheatley).
1366-0071/02/$ – see front matter © 2002 Published by Elsevier Science B.V. PII: S 1 3 6 6 - 0 0 7 1 ( 0 2 ) 0 0 0 0 3 - 7
commonly used spinal opioid. This lipid soluble pro-drug of morphine is deacetylated to morphine within neural tissue [12] and has the potential advantage of rapid onset of action, intermediate duration with a shorter half-life in the CSF and a reduced risk of centrally mediated side effects. In a study of patients undergoing caesarean section, 0.2 mg of intrathecal diamorphine was shown to be as effective as the same dose of intrathecal morphine with reduced drowsiness and pruritus [13]. The aim of this study was to compare the efficacy and side effects of low dose (0.3 mg) intrathecal morphine and diamorphine for postoperative analgesia after total knee arthroplasty.
2. Methods The Hospital Ethical Committee approved the prospective, randomised, double-blind study. Following discussion of the study aims, informed consent was obtained from 64 ASA I or II patients scheduled for unilateral knee arthroplasty.
6
T. Riad et al. / Acute Pain 4 (2002) 5–8
Exclusion criteria were: patients weighing less than 50 kg or more than 110 kg, patients aged more than 80 years or patients in whom amide local anaesthetic drugs, spinal anaesthesia or NSAIDs were contraindicated. All patients received a standardised perioperative technique. General anaesthesia was induced in unpremedicated patients with propofol (1–3 mg kg−1 ) and fentanyl 50 g. Anaesthesia was maintained with oxygen, nitrous oxide and enflurane while spontaneously breathing through a laryngeal mask. Spinal anaesthesia was performed with 2–2.5 ml of heavy bupivacaine plus a pharmacy prepared solution of preservative free morphine 0.3 mg in 0.3 ml or diamorphine 0.3 mg in 0.3 ml, which was allocated on a doubleblind, randomised basis using computer generated random numbers. Patients received 50 mg of diclofenac diluted in 500 ml normal saline intravenously at the end of surgery and 50 mg orally eight hourly in the postoperative period. Supplementary analgesia was provided by self-administration of IV morphine by a PCA device (Graseby 9300) in 1 mg boli with a 5 min lockout period. Metoclopramide was routinely prescribed for postoperative nausea and vomiting. All patients received oxygen via nasal cannulae at 2 l min−1 during the course of the study. The use of a numerical rating score (NRS) from 0 to 10 was described at the preoperative visit. The score was used to measure pain at rest, pain on movement, nausea and itching at 1, 4, 8, 12, 16 and 24 h. Patients also gave a verbal rating score (VRS) at 24 h for the quality of analgesia (poor, fair, good, excellent). Time to first PCA demand and PCA morphine consumption were also recorded. The patient’s ability to straight-leg-raise on the affected side was noted at 24 and 48 h. Respiratory rate, blood pressure, pulse rate, oxygen saturation and sedation score were measured at four hourly intervals but were omitted at night if the patients were sleeping. The sedation score used was: 0 (none, patient alert); 1 (mild, occasionally drowsy, easy to arouse); 2 (moderate, frequently drowsy, easy to arouse); 3 (severe, somnolent, difficult to arouse). Data were analysed using the Minitab Statistics Program (Version 13) on Windows 98. Mann–Whitney and χ 2 -tests were used for the non-parametric data and a two sample Student’s t-test for the patient characteristics. A value of P < 0.05 was regarded as statistically significant. With regard to the time to first PCA demand, a time of 1440 min (24 h) was assigned to those patients who did not use PCA. Graphs were processed using SPSS Statistics Package, Version 10. The sample size of 64 patients was determined by a priori power analysis, using Minitab, to detect a 50% difference in 24 h PCA morphine consumption (0.05% significance level, 80% power). This calculation was based on previously published data [9] which showed that patients receiving 0.3 mg intrathecal morphine for knee arthroplasty had a mean 24 h morphine consumption of 21 mg (S.D. 14.8).
Table 1 Patient characteristics mean (S.D.)
Age (years) Weight (kg) Male:female a
Morphine group (n = 32)
Diamorphine group (n = 32)
70.3 (7.3) 80.1 (13.4) 15:17
71.4 (9.6) 79.8 (15.5) 9:23a
χ 2 , P = 0.121.
3. Results Sixty-six patients were recruited into the study. Two patients were excluded from the study because spinal anaesthesia could not be performed for technical reasons. Two patients from the diamorphine group were not included in the analysis for itching as they had preoperative pruritus. There were no significant differences between the groups in terms of patient characteristics (Table 1). Patients in the intrathecal morphine group had significantly lower NRS pain scores on movement during the first 8 h after surgery (Fig. 1) and used significantly lower doses of PCA morphine in the first 12 h (Fig. 2). The time to first PCA demand was not significantly different in the two groups. Mean (S.D.) is 660 (448) and 581 (447), for morphine and diamorphine, respectively. Four patients in the morphine group and five patients in the diamorphine group did not use the PCA device. The ability to straight-leg-raise was not significantly different between the groups at 24 and 48 h (morphine group 18/30 at 24 h and 25/29 at 48 h; diamorphine group 20/32 at 24 h and 28/32 at 48 h). There was no significant difference in the NRS for nausea and itching or in the incidence of nausea, vomiting, itching, urinary retention or catheterisation, between the two groups.
Fig. 1. Box plot of i.v. PCA morphine consumption at 4, 8, 12, 16 and 24 h postsurgery. Boxes represent interquartile range: horizontal lines in the boxes represent median values. There is a significant difference between both groups P values (0.001, 0.007, 0.043 at 4, 8, 12 h respectively).
T. Riad et al. / Acute Pain 4 (2002) 5–8
Fig. 2. Box plots of numerical rating scores of pain on movement (NRSm). Boxes represent interquartile range: horizontal lines in boxes represent median values. The NRSm scores were significantly reduced at 4 h (P = 0.0046) and 8 h (P = 0.0083) in the intrethecal morphine group.
Table 2 Incidence of side effects and patient impression (VRS for pain relief) during the first 24 h [Number of patients (%)]
Nausea Emesis Antiemetic given Pruritus Retention Catherisation Patient VRS (Good/excellent)
Morphine group (n = 32)
Diamorphine group (n = 32)
p value
26 21 20 14 8 4 22
19 17 22 11 4 4 23
0.44 0.31 0.59 0.57 0.2 0.72 0.95
(69) (66) (63) (44) (25) (12.5) (69)
(60) (53) (69) (37) n = 30 (12.5) (12.5) (72)
There was no difference in the number of patients rating their pain relief as good or excellent between the two groups (Table 2). No patient had a respiratory rate below 10 min−1 , or oxygen saturation below 92%.
4. Discussion This study was prompted by the difficulty in clinical practice of choosing an appropriate intrathecal opioid drug to provide long lasting analgesia without an unacceptably high incidence of side effects. Highly lipid soluble opioids such as fentanyl have a rapid onset, but their short duration of action limits their use following surgery [10]. The most widely used and studied drug is morphine. The poor lipid solubility of morphine results in high CSF levels (5–10,000 times higher than the mean plasma levels 5 min postinjection) [14] which on the one hand provides long lasting analgesia, but on the other, lead to the rostral spread of the
7
drug and the development of potentially serious opioid side effects. Although doses of 0.5–2.5 mg of morphine have been used following orthopaedic surgery [2–15,16], these doses are significantly higher than the calculated optimal dose of 0.25 mg [17]. The clinical efficacy of morphine in lower doses has been confirmed by Bengtsson who used 0.3 mg morphine following hip surgery [5] and in a recent dose-finding study, 0.1 mg of intrathecal morphine provided effective analgesia with minimal side effects following hip surgery [3]. Although this approach is likely to limit opioid side effects, respiratory depression has been described following doses of intrathecal morphine as low as 0.3 mg [9,18]. An alternative approach for UK anaesthetists has been to use diamorphine intrathecally This opioid drug has higher lipid solubility than morphine, which facilitates entry of the drug into neural tissue where it is deacetylated to morphine. Doses of diamorphine between 0.75 and 2.5 mg have been shown to be as effective as similar doses of morphine [15,16]. In a dose–response study looking at doses from 0 to 2.5 mg, Jacobson et al. [7] found that the optimal dose of intrathecal diamorphine following knee surgery was 0.75 mg. However, they did not recommend the routine use of this dose of diamorphine because the analgesic effects were unpredictable and associated with a high incidence of opioid side effects. In contrast, Reay et al. [8] demonstrated that 0.25 mg of diamorphine was as effective as 0.5 mg in providing analgesia after major orthopaedic surgery. The conflicting results in the literature can in part be explained by the design of the studies. Although knee replacement is associated with more severe pain and increased analgesic demands [19], in some studies hip and knee replacement patients have been regarded as a homogenous group. Furthermore, in earlier studies NSAIDs were not used as part of a balanced analgesic technique and analgesic efficacy was measured at rest. The two main areas of concern with regard to the design of this study are the choice of opioid dose and the gender distribution of the patients in the two groups. The dose of 0.3 mg morphine was based on an earlier dose–response study [20]. The use of 0.1 mg morphine for hip surgery was not described until this study was near completion [3]. Although patients were randomly allocated to the two treatment groups, there was a higher proportion of women in the diamorphine group. Whilst this difference did not reach statistical significance, women have been shown to present for knee replacement surgery with more severe functional impairment [21] and use less PCA morphine than men following major surgery [22]. In summary, in contrast to a previous study of patients following caesarean section [13], this study has shown that 0.3 mg of intrathecal morphine provides more effective analgesia following knee arthroplasty than the same dose of diamorphine given intrathecally. This improvement in analgesia is associated with lower PCA morphine consumption and no significant increase in side effects.
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