Intrathecal infusion of bupivacaine with or without morphine for postoperative analgesia after hip and knee arthroplasty

Transcription

1 British Journal of Anaesthesia 1997; 78: Intrathecal infusion of bupivacaine with or without morphine for postoperative analgesia after hip and knee arthroplasty M. BACHMANN, E. LAAKSO, L. NIEMI, P. H. ROSENBERG AND M. PITKÄNEN Summary Postoperative pain after major orthopaedic operations can be controlled by continuous intrathecal administration of opioids or local anaesthetics. Effective intrathecal analgesia can be achieved through synergism of low doses of the two analgesic drugs and, possibly, less drug-related adverse effects. Therefore, we have evaluated the usefulness of a combined low-dose bupivacaine and morphine infusion in patients undergoing hip and knee arthroplasty. Spinal anaesthesia was induced in 55 ASA I III patients with 0.5% bupivacaine 2 ml via a 28-gauge spinal catheter (L3 4 interspace) and 0.5-ml increments were given if needed. Intrathecal 24-h infusions consisted of bupivacaine alone (n 18), bupivacaine alone (n 18) or bupivacaine combined with morphine 8 g h 1 (n 19). The interview after 3,6,12 and 24 h included assessment of pain at rest and on movement (VAS scale), occurrence of sensory and motor block and nausea/vomiting. combined with an infusion of morphine provided as good postoperative analgesia as bupivacaine 2 mg h 1, but motor block disappeared earlier (P 0.01). Patients in the bupivacaine 1-mg h 1 group required more supplementary doses of oxycodone i.m. than the other groups (P 0.04). Time to first oxycodone dose from the start of intrathecal infusion did not differ between groups. The frequency of nausea and vomiting was similar in all groups. In spite of this, antiemetic medication was required more often in the bupivacaine 1-mg h 1 group (possible because of opioid rescue medication). On the ward, one patient in the bupivacaine 2-mg h 1 group experienced a new increase in sensory block with concomitant hypotension. One patient in the same group had minor decubitus on the heel of the operated leg, probably because of prolonged motor block. We conclude that intrathecal infusion of a combination of bupivacaine and morphine 8 g h 1 produced adequate postoperative analgesia. Unfortunately, postoperative nausea and vomiting was a frequent disturbing adverse effect. (Br. J. Anaesth. 1997; 78: ). Key words Anaesthetic techniques, subarachnoid. Pain, postoperative. Anaesthetics local, bupivacaine. Analgesics opioid, morphine. Surgery, orthopaedic. Continuous spinal anaesthesia and analgesia have been achieved effectively by administration of local anaesthetics for surgery and opioids for postoperative pain. 1 4 Opioids are generally given intrathecally for analgesia 3 5 either as a single bolus or as a continuous infusion. 2 5 Treatment of postoperative nausea and vomiting (PONV) after intrathecal opioids has not yet been mastered. 7 8 Recently, the usefulness of continuous administration of intrathecal bupivacaine for postoperative analgesia has been evaluated. 4 9 We showed that continuous infusion of bupivacaine produced adequate analgesia after hip and knee arthroplasty but the reappearance of spinal block and concomitant haemodynamic instability in some patients suggested that it was risky in terms of the benefits of this analgesia regimen. 4 The synergism between local anaesthetics and opioids in extradural analgesia is a well established phenomenon. 10 This effect may be useful also in continuous intrathecal analgesia and thus the occurrence of adverse effects of both components should be reduced. Therefore, we have combined 0.25% bupivacaine and 0.002% morphine for low-dose continuous intrathecal infusion and evaluated its efficacy in the control of postoperative pain in comparison with infusion of bupivacaine alone. Patients and methods The study was approved by the Ethics Committee of the hospital and informed consent was obtained from each patient. We studied 60 ASA I III patients, aged yr, undergoing elective hip or knee arthroplasty. On the day of surgery, oral diazepam 5 15 mg was given as premedication. Subarachnoid puncture was performed in the midline at the L3 4 interspace, with the patient in the lateral position. A 28-gauge spinal catheter (CoSPAN Kendall, Basingstoke, UK) was inserted via a 22-gauge spinal needle. The catheters were advanced 3 cm past the needle tip into the subarachnoid space. Plain 0.5% bupivacaine 2 ml was injected via the catheter for induction of M. BACHMANN, MD, PHD, E. LAAKSO, MD, L. NIEMI, MD, PHD, P. H. ROSENBERG, MD, PHD, M. PITKÄNEN, MD, PHD, Department of Anaesthesia, Töölö Hospital, Helsinki University Central Hospital, Topeliuksenkatu 5, FIN Helsinki, Finland. Accepted for publication: February 17, 1997.

2 Postoperative intrathecal bupivacaine morphine infusion 667 spinal anaesthesia. Patients undergoing knee arthroplasty were turned gently to the supine horizontal position and patients undergoing hip arthroplasty remained in t he lat eral recumbent posit ion. Cephalad spread of analgesia was assessed by pinprick. After a period of 15 min, incremental doses of bupivacaine 0.5 ml were administered when necessary with the aim of reaching a spinal block level of T10. A double-blind study design was used with patients allocated randomly to one of three groups, each comprising 20 patients. Patients received a coded solution for spinal infusion containing plain 0.5% bupivacaine 0.4 ml h 1 ( ), plain 0.25% bupivacaine 0.4 ml h 1 ( ) or 0.25% bupivacaine combined with morphine 20 g ml 1 (192 g of morphine in 24 h). The infusion (JMS Syringe pump SP-100, JMS Company, Ltd, Hirosima, Japan) was started 60 min after induction of spinal anaesthesia if the level of spinal block was below T6. If not, the infusion was started after the sensory analgesia level had decreased below T6 and haemodynamic variables were stable. All patients had a urinary catheter during the study. During operation, small doses of sedatives or fentanyl were given as required. I.v. fluids, including packed red cells, were given according to the clinical requirements of each patient. Arterial pressure and heart rate were recorded at 5-min intervals during surgery and at 10-min intervals in the postanaesthesia care unit. ECG and peripheral oxygen saturation were monitored continuously. Patients were transferred to the ward 3 5 h after surgery when they were haemodynamically stable (changes in heart rate or arterial pressure 15% compared with preoperative values). For postoperative pain, paracetamol 1 g was given three times a day. If adequate analgesia was not achieved (at the operation site) oxycodone 0.14 mg kg 1 i.m. was administered at request. Metoclopramide 10 mg i.v. was given for PONV when needed. Patients were interviewed by one of the investigators 3, 6, 12 and 24 h after the intrathecal infusion was started. Each interview included an assessment of the intensity of pain at rest and on movement of t he operat ed leg using a visual analogue scale (VAS) (0 10). Cephalad extension of analgesia was assessed by pinprick and the degree of motor block (scale 0 3, 0 no block, 3 complete motor block) of the lower extremities was recorded using the criteria described by Bromage. 11 Heart rate, arterial pressure and the occurrence of nausea and vomiting were also recorded. The spinal catheters were removed by one of the investigators on the first postoperative day. For removal, the patient was placed in the same flexed recumbent position as during the puncture. STATISTICAL ANALYSIS Statistical analysis of patient data and single efficacy end-points (VAS values) was performed using oneway analysis of variance; Bonferroni corrections were used in pairwise comparisons. Frequency data were compared using the chi-square test. Motor and sensory block and doses of analgesics and antiemetic drugs needed were analysed with non-parametric Kruskal Wallis one-way analysis of variance using the Bonferroni-corrected Mann Whitney test for pairwise comparisons. P 0.05 was considered statistically significant. Results The study was discontinued in five patients; two were excluded because of accidental disconnection of the hub of the catheter and one patient in the bupivacaine 2-mg h 1 group and one patient in the bupivacaine morphine group wanted the infusion interrupted because of disturbing reappearance of sensory (T6 and T9 dermatomes, respectively) and motor block. The patient in the bupivacaine Table 1 Patient characteristics (means (SD or range) or number) Morphine 8 g h 1 No of patients Age (yr) 67 (44 88) 66 (45 82) 70 (48 84) Weight (kg) 78 (11) 73 (11) 71 (10) Height (cm) 169 (9) 167 (8) 165 (7) Sex (F/M) 10/8 11/7 15/4 Surgery: hip/knee (No.) 11/7 13/5 13/6 Cephalad extension of spinal analgesia at 60 min (median (range)) Th 7 (T2 T12) Th 7 (T2 L1) Th 8 (T3 L1) Table 2 Postoperative 24-h requirements for oxycodone. **P 0.01 (chi-square), bupivacaine compared with bupivacaine and bupivacaine morphine; P 0.05 (Kruskal Wallis), bupivacaine compared with bupivacaine-morphine Morphine 8 g h 1 No. of patients % Patients needing oxycodone 39 78** 31 Oxycodone doses/group Oxycodone doses/patient (mean, range) 1.8 (0 7) 3.0 (0 11) 1.6 (0 13) Time to first dose of oxycodone (min) (mean (SD)) 214 (79) 306 (211) 451 (389)

3 668 British Journal of Anaesthesia Table 3 Data on postoperative patient interviews at fixed times during the 24-h follow-up. Patients estimated pain on a VAS (0 10) (mean (SD)). Cephalad extension of sensory block (dermatome) was assessed by pinprick and motor block by the Bromage score 11 (% of patients having motor block degree 2 3). There was more pain on movement than at rest: *P<0.05 (ANOVA), bupivacaine and bupivacaine-morphine compared with bupivacaine ; P 0.01 (Kruskal Wallis), bupivacaine compared with the other groups; P 0.05 (Kruskal Wallis), bupivacaine morphine compared with other groups; P 0.05 (Kruskal Wallis), bupivacaine 2 mg h 1 compared with other groups morphine 8 g h 1 3 h VAS (rest) 1.0 (1.9) 1.3 (2.2) 0.6 (1.3) VAS (motion) 1.3 (2.6) 1.4 (2.5) 0.6 (1.3) Sensory block L1 L1 L1 Motor block (%) 72% 74% 72% 6 h VAS (rest) 1.1 (1.9) 1.4 (2.1) 0.9 (1.2) VAS (motion) 1.4 (2.3) 1.7 (2.5) 1.3 (2.0) Sensory block L1 L1 L3 Motor block (%) 44% 42% 32% 12 h VAS (rest) 1.6 (2.5) 2.4 (2.7) 1.3 (1.7) VAS (motion) 2.1 (2.7) 3.3 (3.1) 2.2 (2.6) Sensory block T12 L4 L3 Motor block (%) 33% 11% 32% 24 h VAS (rest) 1.5 (2.3) 1.5 (1.8) 1.0 (1.7) VAS (motion) 2.0 (2.6) 3.5 (2.6)* 2.4 (2.6)* Sensory block L2 0 0 Motor block (%) 28% 0 5% Table 4 Postoperative nausea and vomiting. *P 0.05 (Kruskal Wallis), bupivacaine compared with other groups morphine 8 g h 1 No. of patients Nausea (No.) Vomiting (No.) Requiring antiemetics (No.) 1 5* 0 2-mg h 1 group also developed transient hypotension 10 h after surgery and required extra i.v. infusion of Ringer s acetate. One patient had an acute myocardial infarction and was therefore excluded from the study. Data from the remaining 55 patients were analysed. Patient groups were comparable in age, weight, height, sex, arterial pressure and heart rate values obtained before operation, and type of surgery (table 1). Similarly, there were no differences in median cephalad dermatome level of sensory block 60 min after induction of spinal anaesthesia. Doses of sedatives, amount of intraoperative fluids and blood products did not differ between groups. We found that 78% (14/18) of patients in the bupivacaine 1-mg h 1 group needed supplementary opioid medication compared with 39% and 31% in the two other groups (P 0.01) during the 24-h postoperative period (table 2). The number of supplementary oxycodone doses differed between groups (P 0.04), being higher in the bupivacaine 1-mg h 1 group than in the other groups (table 2). Mean time from induction of anaesthesia to administration of i.m. opioid was comparable in all groups. VAS scores at 3, 6, 12 and 24 h at rest and on movement did not differ between groups. VAS scores were relatively low also during movement (table 3), and as a rule patients reported higher pain scores on movement than at rest (ns). At 24 h, patients who received either bupivacaine 1 mg h 1 or bupivacaine morphine experienced significantly more pain on movement of the operated leg than at rest compared with patients in the bupivacaine 2-mg h 1 group (P 0.03) (table 3). During the 24-h postoperative follow-up period, extension of sensory analgesia level and the intensity of motor block decreased in all groups. However, compared with the other groups, the bupivacaine 2-mg h 1 group had significantly more extensive sensory block at 12 h (P 0.02) and at 24 h (P 0.05) than the other groups (table 3). Motor block was comparable in all groups at 3, 6 and 12 h. At 24 h after the start of infusion, partial motor block was observed in the bupivacaine 2-mg h 1 group, and no motor block in the two other groups (P 0.01) (table 3). On the ward all patients in the bupivacaine 2-mg h 1 group, except the one mentioned above, were haemodynamically stable. There was no difference in the incidence of PONV between groups. Patients in the bupivacaine 1-mg h 1 group were given more antiemetics than patients in the two other groups (P 0.02) (table 4). One patient in the bupivacaine 2-mg h 1 group developed a minor decubitus on the heel of the operated extremity during the first week after surgery. This patient had second degree

4 Postoperative intrathecal bupivacaine morphine infusion 669 motor block 24 h after surgery, that is until the end of the intrathecal infusion. The skin healed with conservative therapy. Discussion Our data indicated that continuous low-dose infusion of morphine 8 g h 1 combined with continuous infusion of bupivacaine provided as good postoperative analgesia as bupivacaine 2 mg h 1 without opioid. This analgesic effect, as measured by requirements for supplementary opioids, was significantly better than the effect of bupivacaine alone. In addition to analgesia via spinal cord opioid receptors, intrathecal morphine suppresses selectively ascending A-delta and C-fibre activity evoked by stimulation of primary nociceptive afferents. 12 In animal models it has been shown that spinally administered morphine potentiates the analgesic effects of bupivacaine. 13 This concept has been used successfully in extradural analgesia for many years It is suggested that bupivacaine induces conformational change in the spinal opioid receptor thus facilitating synergism. 13 This synergistic effect has been demonstrated previously using single bolus doses in the clinical setting. 16 In addition to good analgesia, the bupivacaine morphine combination caused less motor block than the higher dose of bupivacaine alone. This might be clinically important even in patients who are not allowed to move in the first 24 h after surgery, because patients are encouraged to exercise their legs as early as possible in order to maintain good perfusion of the extremities, even during bed rest. The bed sore on the heel of one of our patient may be blamed on postoperative analgesia. Therefore, when higher doses of continuous intrathecal local anaesthetics are used it is important that the patient s position must be changed during the postoperative period if they are not able to move their legs voluntarily. The use of spinal morphine, especially in higher doses, is associated with adverse effects such as respiratory depression, urinary retention, pruritus, and nausea and vomiting. 17 Higher peak concentrations of opioids observed after single boluses may increase the incidence and severity of side effects. 18 In our study we did not notice any difference in the incidence of nausea and vomiting between the groups, perhaps because the dose of morphine was relatively small. Interestingly, requirements for antiemetic medication were highest in the bupivacaine 1-mg h 1 group. One explanation might be that patients in this group needed more systemically administered supplementary opioids which possibly induced greater intensity of nausea and therefore a greater demand for antiemetics. Intrathecally administered plain bupivacaine is unpredictable regarding the final cephalad spread of the block. 19 In our study only one patient (in the bupivacaine 2-mg h 1 group) suffered transient hypotension on the ward. This was related to the reappearance of the spinal block to T6. Also, in our previous study with intrathecal infusion of plain bupivacaine, reappearance of spinal block occurred relatively late during the first postoperative day. 4 Previously we have demonstrated changes in the level of bupivacaine spinal anaesthesia by changing the patient s posture min after induction of anaesthesia. 20 Such a sudden change is probably caused by bulk displacement of CSF and movement of local anaesthetic which has not yet been bound or absorbed. On the other hand, the slowly progressing extension of the block on the ward, with patients in the horizontal position, resembles the slower diffusional type of drug distribution. Regional anaesthetic and analgesic techniques are becoming popular for postoperative analgesia. 21 Extradural opioids are frequently combined with local anaesthetics for postoperative extradural analgesia because of their synergistic effects. For instance, combinations of morphine and bupivacaine, 22 fentanyl and bupivacaine 23 or sufentanil and bupivacaine 24 for extradural postoperative analgesia have been found to be superior to bupivacaine alone. Most importantly, the synergistic combination of an opioid and bupivacaine appears to be effective for pain during movement. 22 Also, in this study enhanced intrathecal analgesia tended to be more pronounced with movement but was also present at rest. It should be emphasized that the intensity of pain experienced by our patients remained low also at movement and therefore the tests we used may not be sensitive enough to detect a significant additive or synergistic analgesic effect of drug combinations. 25 Continuous spinal anaesthesia with local anaesthetics produces profound intraoperative analgesia and motor block and the duration of analgesia can be adjusted to the duration of surgery. In spite of technical problems, 8 26 when a spinal microcatheter has been placed for intraoperative analgesia, it may be used after operation also. We have demonstrated that the combination of a low dose of morphine (8 g h 1 ) and bupivacaine ( ) produced as good postoperative analgesia as twice the dose (2 mg h 1 ) of bupivacaine alone, but with less motor block. References 1. Sutter PA, Gamulin Z, Foster A. Comparison of continuous spinal and continuous epidural anaesthesia for low limb surgery in elderly patients. A retrospective study. Anaesthesia 1989; 44: Guinard J-P, Chiolero R, Mavrocordatos P, Carpenter RL. Prolonged intrathecal fentanyl analgesia via 32-gauge catheters after thoracotomy. Anesthesia and Analgesia 1993; 77: Reuben SS, Dunn SM, Duprat KM, O Sullivan P. An intrathecal fentanyl dose response study in lower extremity revascularisation procedures: Anesthesiology 1994; 81: Niemi L, Pitkänen M, Laakso E, Dunkel P, Rosenberg PH. Evaluation of the usefulness of intrathecal bupivacaine infusion for analgesia after hip and knee artroplasty. British Journal of Anaesthesia 1996; 77: Niemi L, Pitkänen M, Tuominen M, Rosenberg PH. Comparison of intrathecal fentanyl infusion with morphine infusion or bolus for postoperative pain relief after hip arthroplasty. Anesthesia and Analgesia 1993; 77: Nordberg G, Hedner T, Mellstrand T, Dahlström B. Pharmacokinetic aspects of intrathecal morphine analgesia. Anesthesiology 1984; 60:

5 670 British Journal of Anaesthesia 7. Pitkänen M, Niemi L, Tuominen M, Rosenberg P. Effect of tropisetron, a 5-HT 3 receptor antagonist, on analgesia and nausea after intrathecal morphine. British Journal of Anaesthesia 1993; 71: Niemi L, Pitkänen M, Tuominen M, Rosenberg P. Technical problems and side effects associated with continuous intrathecal or epidural postoperative analgesia in patients undergoing hip artroplasty. European Journal of Anaesthesiology 1994; 11: Standl T, Eckert S, Schulte am Esch J. Microcatheter continuous spinal anaesthesia in the post-operative period: a prospective study of its effectiveness and complications. European Journal of Anaesthesiology 1995; 12: Chrubasik S, Chrubasik J. Postoperative regional anaesthesia and analgesia. Current Opinion in Anesthesiology 1995; 8: Bromage PR. A comparison of the hydrochloride and carbon dioxide salts of lidocaine and prilocaine epidural anaesthesia. Acta Anaesthesiologica Scandinavica 1965; 16: Doi T, Jurna I. Analgesic effects of intrathecal morphine demonstrated in ascending nociceptive activity in the rat spinal cord and ineffectiveness of caerulein and cholecystokinin octapeptide. Brain Research 1982; 234: Tejwani GA, Rattan AK, McDonald JS. Role of spinal opioid receptors in the antinociceptive interactions between intrathecal morphine and bupivacaine. Anesthesia and Analgesia 1992; 74: Asantila R, Eklund P, Rosenberg PH. Continuous epidural infusion of bupivacaine and morphine for postoperative analgesia after hysterectomy. Acta Anaesthesiologica Scandinavica 1991; 35: Breivik H. Epidural opioids: current use. Current Opinion in Anesthesiology 1992; 5: Kalso E. Effects of intrathecal morphine, injected with bupivacaine, on pain after orthopaedic surgery. British Journal of Anaesthesia 1983; 55: Gustafsson LL, Schildt B, Jacobsen KJ. Adverse effects of extradural and intrathecal opiates: report of a nationwide survey in Sweden. British Journal of Anaesthesia 1982; 54: Cousins MJ. Comparative pharmacokinetics of spinal opioids in humans: A step toward relative safety. Anesthesiology 1987; 67: Tuominen M. spinal anaesthesia. Acta Anaesthesiologica Scandinavica 1991; 35: Niemi L, Pitkänen M, Tuominen M, Rosenberg PH. Effects of late posture change on the level of spinal anaesthesia with plain bupivacaine. British Journal of Anaesthesia 1993; 71: Kehlet H. General versus regional anaesthesia. In: Rogers M, Tinker J, Covino B, Longecker DE, eds. Principles and Practice of Anesthesiology. St Louis: CV Mosby, 1993; Dahl J, Rosenberg J, Hansen B, Hjortsø N, Kehlet H. Differential analgesic effects of low-dose epidural morphine and morphine bupivacaine at rest and during mobilization after major abdominal surgery. Anesthesia and Analgesia 1992; 74: George K, Wright P, Chisakuta A. Continuous thoracic epidural fentanyl for post-thoracotomy pain relief: with or without bupivacaine. Anaesthesia 1991; 46: Mourisse J, Hasenbons M, Gielen M, Moll J, Crohmeecke G. Epidural bupivacaine, sufentanil or the combination for postthoracotomy pain. Acta Anaesthesiologica Scandinavica 1992; 36: Bjune K, Stubhaug A, Dodgson MS, Breivik H. Additive analgesic effect of codeine and paracetamol can be detected in strong, but not moderate, pain after Caeserean section. Acta Anaesthesiologica Scandinavica 1996; 40: Silvanto M, Pitkänen M, Tuominen M, Rosenberg PH. Technical problems associated with the use of 32-gauge and 22-gauge spinal catheters. Acta Anaesthesiologica Scandinavica 1992; 36: