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Epidural combination of ropivacaine with sufentanil for postoperative analgesia after total knee replacement: a pilot study

Kampe, S.*; Diefenbach, C.*; Kanis, B.*; Auweiler, M.*; Kiencke, P.; Cranfield, K.

European Journal of Anaesthesiology: September 2002 - Volume 19 - Issue 9 - p 666-671
Original Article

Background and objective: We assessed the analgesic efficacy of postoperative epidural infusions of ropivacaine 0.1 and 0.2% combined with sufentanil 1 μg mL−1 in a prospective, randomized, double-blinded study.

Methods: Twenty-two ASA I-III patients undergoing elective total-knee replacement were included. Lumbar epidural blockade using ropivacaine 0.75% was combined with either propofol sedation or general anaesthesia for surgery. After surgery, the epidural infusion was commenced. Eleven patients in each group received either an epidural infusion of ropivacaine 0.1% with 1 μg mL−1 sufentanil (Group 1) or ropivacaine 0.2% with 1 μg mL−1 sufentanil (Group 2) at a rate of 5-9 mL h−1. All patients had access to intravenous pirinatrimide (piritramide) via a patient-controlled analgesia (PCA) device.

Results: Motor block was negligible for the study duration in both groups. There was no significant difference with the 100 mm visual analogue scale (VAS) scores, with the consumption of rescue analgesia or with patient satisfaction. Patients in Group 1 experienced significantly less nausea (P < 0.05) than those in Group 2. Both treatment regimens provided effective postoperative analgesia with only a minimal use of supplemental opioid PCA.

Conclusions: We recommend the use of ropivacaine 0.1% with 1 μg mL−1 sufentanil for postoperative analgesia after total knee replacement as it provides efficient pain relief with no motor block of the lower limbs. In addition, compared with 0.2% ropivacaine with sufentanil, the mixture reduces local anaesthetic consumption without compromise in patient satisfaction or VAS scores. Patients even experience less nausea.

University of Cologne, Departments of *Anaesthesiology and Intensive Care Medicine andMedical Statistics, Cologne, Germany;Aberdeen Royal Infirmary, Department of Anaesthesiology, Aberdeen, UK

Correspondence to: Sandra Kampe, Department of Anaesthesiology and Intensive Care Medicine, University of Cologne, Joseph-Stelzmann-Str. 9, D-50931 Cologne, Germany. E-mail:; Tel: +49 221 478 4807, Fax: +49 221 478 6093

Accepted for publication April 2001 EJA 575

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After total knee replacement, the early ability to mobilize the knee joint and intensive physical therapy are of great importance for ultimate functional outcome [1,2]. Therefore, postoperative pain therapy is a major concern. Singelyn and colleagues [3] demonstrated that a continuous three-in-one block and a continuous epidural infusion with bupivacaine 0.125%, sufentanil 0.1 μg mL−1 and clonidine 1 μg mL−1 provided better pain relief than intravenous (i.v.) patient-controlled analgesia (PCA) with morphine after total knee replacement.

It was shown [4] that an epidural infusion of ropivacaine 0.1% with sufentanil 1 μg mL−1 was highly effective in preventing pain after total hip replacement with the specific aim of avoiding motor block of the lower limbs. No data were available on the epidural combination of ropivacaine with an opioid for postoperative epidural analgesia after total knee replacement. The aim of the present study was to investigate the clinical efficacy of the continuous epidural infusion of low-dose ropivacaine/sufentanil mixtures for postoperative analgesia after total knee replacement.

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After obtaining institutional Ethics Committee approval and written informed consent, 23 patients were enrolled in the study. Eligible patients were those scheduled for elective total knee replacement, aged 30-75 yr, ASA I-III, weighing 50-100 kg and 150-190 cm height, and who could operate an i.v. PCA device. Exclusion criteria were any contraindications to epidural anaesthesia, an allergy to local anaesthetics or opioids, a history of opioid dependency, postoperative care in an intensive care unit, or communication difficulties that would prevent reliable postoperative assessment. Patients were randomly allocated to two groups. Midazolam 7.5-15 mg by mouth was given 1 h before operation. At least 500 mL isotonic saline (0.9% NaCl) solution over 15 min was given i.v. Then an epidural catheter was inserted 3-5 cm into the epidural space at L3-5 via an 18-G Touhy needle, with cephalad direction of the needle curvature and the patient in the lateral position. With the catheter secured and the patient in the supine position, a 3 mL test dose of ropivacaine 0.75% was given over 15 s through the catheter after aspiration for cerebrospinal fluid or blood proved negative [5,6]. Five minutes later, a further 12 mL ropivacaine 0.75% was administered over 5 min. If sensory block to pinprick did not reach T10 within 30 min after injection, an additional 5 mL top-up dose of ropivacaine 0.75% was administered. Patients were sedated with propofol or, if the patient desired, general anaesthesia was induced with thiopental, cizatracurium, isoflurane and oxygen in nitrous oxide and a maximal dose of fentanyl 100 μg. Additional doses (3-5 mL) of 0.75% ropivacaine were injected epidurally every 2 h during surgery. No additional doses of fentanyl were allowed. If the epidural block was inadequate (e.g. requirement of additional doses of fentanyl), patients were excluded from the study.

When the patients arrived in the recovery room, an epidural infusion with either 0.1% ropivacaine and 1 μg mL−1 sufentanil (Group 1) or 0.2% ropivacaine and 1 μg mL−1 sufentanil (Group 2) was commenced at a rate calculated as follows [4]: EQUATION

All patients had access to an i.v. PCA device (Abbott Lifecare PCA Infusor®; Abbott Laboratories, North Chicago, IL, USA) delivering pirinitramide (piritramide), a commonly used opioid in Europe [7] with approximately 0.7 of the potency of morphine, in 1.5 mg bolus doses, with a 6 min lockout time and a 45 mg dose limit over 4 h.

Wound pain at rest and on movement was assessed by using a 100 mm visual analogue scale (VAS) ranging from 0 (no pain) to 100 (worst pain imaginable). Sensory block was assessed bilaterally by using analgesia to pinprick with a short-bevelled 27-G needle, and motor block was assessed according to a modified Bromage scale (0: no motor block; 1: inability to flex the hip; 2: inability to flex the knee; 3: inability to flex the ankle). All postoperative assessments at 4, 8, 20, 32 and 44 h were performed by the same blinded anaesthesiologist. The quality of pain management was judged by the patients and recorded at the last assessment on a four-point scale (1: poor; 2: fair; 3: good; 4: excellent). Monitoring included non-invasive arterial pressure, heart rate (HR) and respiratory rate.

Hypotension was defined as systolic arterial pressure <80 mmHg or >30% decrease compared with baseline; hypertension was defined as arterial pressure >180 mmHg systolic or 110 mmHg diastolic; bradycardia was defined as HR < 50 bpm; and tachycardia was defined as HR > 120 beats min−1[8,9]. Bradypnoea was defined as a respiratory rate <12 breaths min−1 and tachypnoea was defined as a respiratory rate >20 breaths min−1. Sedation was recorded on a four-point scale (0: no signs of sedation; 1: mild sedation; 2: moderate sedation; 3: severe sedation). The incidence of nausea and vomiting was recorded. Patients who experienced nausea received i.v. metoclopramide, and those who vomited received i.v. ondansetron. Hypotension was treated with 500 mL crystalloid infusion i.v.

Statistical analysis was performed by using the SPSS 9.0® statistical package (SPSS, Inc., Chicago, IL, USA). The study was designed as a pilot study with low-dose ropivacaine/sufentanil mixtures after total knee replacement. Therefore, the standard deviation (SD) of relevant variables was not available and thus sample size could not be calculated. Ten patients per group were selected as it was thought that clinical differences could be detected with this sample size, especially as one group received twice as much local anaesthetic as the other group. Post hoc power analysis was performed using Statistical Power Analysis 5.5® (Stat Soft, Tulsa, OK, USA) (power 0.8, α = 0.05). PCA pirinitramide consumption was the primary efficacy measure and was compared in a pairwise manner using the two-tailed Wilcoxon signed rank sum test. Patients' characteristics, procedure duration and the time from the end of surgery until the start of epidural infusion, and the i.v. PCA device were analysed using the U-test, pain scores and patient satisfaction using a parametric t-test. Adverse events were analysed using Fisher's z-test. Significance was determined at P < 0.05. Unless indicated, data are means ±SD.

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Twenty-three patients were enrolled. One patient was withdrawn because the epidural catheter could not be placed. The data of 22 patients were eligible for statistical analysis, 11 in each group. Population data are presented in Table 1. No difference was noted among the groups. Both groups had a minimal, but constant pirinitramide use over the study (Fig. 1). Group 1 consumed 34.8 ± 25 mg pirinitramide in the first 44 h after operation; Group 2 consumed 26.4 ± 23 mg (P = 0.75). Post hoc power analysis indicated that 67.5 patients per group would have been necessary to detect a 10% difference in pirinitramide consumption. Means ± SE for pain scores (VAS) at rest and on movement are shown in Figures 2 and 3 after 4, 8, 20, 32 and 44 h of infusion. Pain scores at rest and upon movement were lower in Group 2 than in Group 1, but the difference was not significant. Two patients (one male, one female; 18.2%) of Group 1 and seven patients (all females; 63.6%) of Group 2 experienced nausea over the 44 h study period (P = 0.042). Two females of Group 1 (18.2%) and four of Group 2 (36.4%) vomited (P = 0.35). Sedation was of a mild nature in both studies groups, except for one patient in Group 1 who experienced moderate sedation at one assessment after 32 h of postoperative analgesia. One patient in each group at three different assessment points experienced hypotension. Over the study, the total number of patients with adverse events declined successively (36.4% after 4 h, 31.8% after 8 h, 27.3% after 20 h and 13.6% after 44 h of epidural infusion) (Table 2). All patients rated the quality of pain management as excellent or good (P = 0.82). In both groups, motor block and sensory block resolved rapidly. Only two patients had a Bromage Grade 1 motor block after 8 h in Group 1. In Group 2, two patients experienced a Grade 1 motor block up to 32 h postoperatively and a sensory block still at L4-5.

Table 1

Table 1

Figure 1

Figure 1

Figure 2

Figure 2

Figure 3

Figure 3

Table 2

Table 2

Problems with urinary retention could not be assessed as all patients had received a urinary catheter as part of the surgical management.

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After total knee replacement, poorly managed analgesia may inhibit early mobilization of the knee joint, which may result in capsular contracture and adhesions, and consequently a delay or an impaired ultimate functional outcome [1]. Postoperative pain relief can be achieved by a variety of techniques after total knee replacement, but pain control during the immediate postoperative period still remains difficult [10,11]. A combination of i.v. PCA opioid and non-steroidal anti-inflammatory analgesics represents the current optimal systemic analgesic therapy after total-knee replacement [12]. Studies examining the use of peripheral nerve blocks as analgesic adjuncts to systemic opioids have produced conflicting results [12-15]. It has been shown that i.v. PCA with morphine is less effective in preventing pain after total knee replacement than continuous epidural analgesia, a continuous three-in-one block and a femoral block, respectively [3,16]. Compared with i.v. PCA with opioids, postoperative epidural analgesia is associated with an improved early rehabilitation [16], a better ultimate outcome [2] and a shorter hospital stay [2]. Dickenson [17] and Dickenson and Sullivan [18] postulated the theoretical advantages for adding lipophilic drugs to epidural local anaesthetics.

We showed [4] that the epidural combination of ropivacaine 0.1% with 1 μg mL−1 sufentanil was highly effective in preventing pain after total hip replacement, causing no motor weakness of the legs. Total knee replacement with continuous passive motion for postoperative rehabilitation may cause more severe pain and thus may require a higher local anaesthetic concentration than that required for pain due to rehabilitation after total hip replacement. To our knowledge, there are no data available on the epidural combination of ropivacaine with sufentanil after total knee replacement.

The study was designed as a pilot study of low-dose ropivacaine/sufentanil mixtures for preventing pain after total knee replacement, a problem very difficult to manage in clinical practice. In accord with previous studies, pirinitramide consumption via the i.v. PCA device was the primary efficacy measure [4,8,9]. There was no significant difference in pirinitramide consumption between the two groups. Both concentrations of ropivacaine combined with sufentanil provided effective pain relief (VAS at rest <25, <40 mm on movement) with a minimal pirinitramide consumption and minimal adverse events. It was only 8 h after operation that patients in both groups were unable to achieve sufficient pain relief at rest and on movement. In this context, it is surprising that patients did not use the PCA device more frequently, even though all had free access to unrestricted i.v. pirinitramide via the PCA device. This finding is in accordance with Schug and colleagues [8] who reported that patients receiving ropivacaine 0.3% used some morphine, despite the high quality of analgesia at all times. This may compromise the often-recommended use of i.v. PCA as an 'objective' pain measurement device.

Hypotension is a common local anaesthetic-related side-effect. Capdevila and colleagues [16] described a significantly increased incidence of hypotension during continuous epidural infusion of lidocaine 1%. Ropivacaine causes hypotension in a dose-dependent manner in the same way as bupivacaine [8]. Whereas Schug and colleagues [8] described hypotension occurring more frequently with ropivacaine 0.2% than with ropivacaine 0.1%, hypotension was negligible in both our study groups. This absence of hypotension is most likely due to the lower epidural infusion rate used.

There were no patients in the ropivacaine 0.1% with sufentanil group who demonstrated motor blockade, thus confirming previous results [4,8,9]. An epidural infusion of ropivacaine 0.2% after abdominal surgery caused both sensory and motor blockade [8,9]. In our study, two patients experienced a Grade 1 motor block up to 32 h postoperatively and a sensory block still at L4-5 in the 0.2% ropivacaine with sufentanil group.

One aspect of our study design deserves comment. The sample size per group was small, but both groups were homogenous. The study was unusual in that the patients were observed for 44 h [8,9]. The incidence of nausea reached statistical significance, although both groups had the same opioid consumption. However, postoperative nausea and vomiting is complex and dependent on a variety of factors, including age, obesity, a history of motion sickness and/or previous postoperative nausea and vomiting, menstruation, surgical procedure, anaesthetic technique, and postoperative pain [19]. With regard to these risk factors, we found no difference between the groups. These results are from a pilot study. Therefore, the question remains whether the difference in incidence of nausea is of clinical significance.

In summary, both treatment regimens provided sufficient postoperative analgesia with only a minimal use of rescue medication after total knee replacement. Repivacaine 0.1% produced similar patient satisfaction and VAS with less motor block when compared with the 0.2% concentration. More studies with a much larger number of patients will be necessary to evaluate whether low-dose ropivacaine/ sufentanil mixtures are as favourable for pain treatment after total knee replacement as they proved to be after total hip replacement, and whether this combination of analgesia and no motor block may lead to improved patient outcome and earlier hospital discharge.

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The authors thank Professor W. Buzello for his critical reading of the manuscript, and Cornelia Hünermann and Dr Gabriele Randebrock for help and support.

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1. Akeson W, Amiel D, Abel M, Garfin SR, Woo SL. Effects of immobilization on joints. Clin Orthop 1987; 219: 28-37.
2. Williams-Russo P, Sharrock N, Haas S, et al. Randomized trial of epidural versus general anesthesia: outcomes after primary total knee replacement. Clin Orthop 1996; 331: 199-208.
3. Singelyn FJ, Deyaert M, Joris D, Pendeville E, Gouverneur JM. Effects of intravenous patient-controlled analgesia with morphine, continuous epidural analgesia, and continuous three-in-one block after unilateral total knee arthroplasty. Anesth Analg 1998; 87: 88-92.
4. Kampe S, Weigand C, Kaufmann J, Klimek M, Konig DP, Lynch J. Postoperative analgesia with no motor block by the continuous epidural infusion of ropivacaine 0.1% and sufentanil after total hip replacement. Anesth Analg 1999; 89: 395-398.
5. Concepion M, Arthur GR, Steele SM, Bader AM, Covino BG. A new local anesthetic, ropivacaine. Its epidural effects in humans. Anesth Analg 1990; 70: 80-85.
6. Kerkkamp HEM, Gielen MJM. Cardiovascular effects of epidural local anaesthetics. Comparison of 0.75% bupivacaine and 0.75% ropivacaine, both with adrenaline. Anaesthesia 1991; 46: 361-366.
7. Stehr-Zirngibl S, Zirngibl H, Angster R, Taeger K. Patient-controlled analgesia (PCA) in the general ward: experience gained. Anaesth Intensivmed 1995; 36: 128-134.
8. Schug SA, Scott DA, Payne J, Mooney PH, Hagglof B. Postoperative analgesia by continuous extradural infusion of ropivacaine after upper abdominal surgery. Br J Anaesth 1996; 76: 487-491.
9. Scott DA, Chamley DM, Mooney PH, Deam RK, Mark AH, Hagglof B. Epidural ropivacaine infusion for postoperative analgesia after major abdominal surgery - a dose finding study. Anesth Analg 1995; 81: 982-986.
10. Etches RC, Warriner CB, Badner N, et al. Continuous intravenous administration of ketorolac reduces pain and morphine consumption after total hip or knee arthroplasty. Anesth Analg 1995; 81: 1175-1180.
11. Fragen RJ, Stulberg SD, Wixson R, Glisson S, Librojo E. Effect of ketorolac tromethamine on bleeding and on requirements after total knee arthroplasty. J Bone Joint Surg Am 1995; 77: 998-1002.
12. Allen HW, Liu SS, Ware PD, Nairn CS, Owens BD. Peripheral nerve blocks improve analgesia after total knee replacement surgery. Anesth Analg 1998; 87: 93-97.
13. Hirst GC, Lang SA, Dust WN, Cassidy JD, Yip RW. Femoral nerve block. Single injection versus continuous infusion for total knee arthroplasty. Reg Anesth 1996; 21: 292-297.
14. Serpell MG, Millar FA, Thomson MF. Comparison of lumbar plexus block versus conventional opioid analgesia after total knee replacement. Anaesthesia 1991; 46: 275-277.
15. Edwards ND, Wright EM. Continuous low-dose 3-in-1 nerve blockade for postoperative pain relief after total knee replacement. Anesth Analg 1992; 75: 265-267.
16. Capdevila X, Barthelet Y, Biboulet P, Ryckwaert Y, Rubenovitch J, d'Athis F. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 1999; 91: 8-15.
17. Dickenson AH. Spinal cord pharmacology of pain. Br J Anaesth 1995; 75: 193-200.
18. Dickenson AH, Sullivan AF. Combination therapy in analgesia; seeking synergism. Curr Opin Anaesthesiol 1993; 6: 861-865.
19. Watcha MF, White PF. Postoperative nausea and vomiting: its etiology, treatment, and prevention. Anesthesiology 1992; 77: 162-184.


© 2002 European Academy of Anaesthesiology