Anesth Analg 2005;100:866-872
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000143952.75985.8F
REGIONAL ANESTHESIA
Adding Clonidine to the Induction Bolus and Postoperative Infusion During Continuous Femoral Nerve Block Delays Recovery of Motor Function After Total Knee Arthroplasty
Andrea Casati, MD*,
Federico Vinciguerra, MD
,
Gianluca Cappelleri, MD,
Giorgio Aldegheri, MD,
Guido Fanelli, MD*,
Marta Putzu, MD*, and
Jacques E. Chelly, MD
*Department of Anesthesiology, University of Parma, Parma, Italy; Department of Anesthesiology, Vita-Salute University of Milano, Milano, Italy; and Department of Anesthesiology, University School of Medicine, Pittsburgh, Pennsylvania
Address correspondence and reprint requests to Andrea Casati, MD, Department of Anesthesiology, Policlinico Di Parma, Via Gramsci 14-43100, Parma, Italy. Address e-mail to acasati.{at}ao.pr.it.
 |
Abstract
|
|---|
We evaluated the effects of adding clonidine for continuous peripheral nerve infusions. Sixty patients undergoing total knee arthroplasty under combined single-injection sciatic block and continuous femoral infusion were randomly allocated to three groups: block induction with 0.75% ropivacaine followed by 0.2% ropivacaine (group control; n = 20); block induction with 0.75% ropivacaine and 1 µg/kg clonidine followed by 0.2% ropivacaine (group cloni-bolus; n = 20), and block induction with 0.75% ropivacaine and 1 µg/kg clonidine followed by 0.2% ropivacaine with 1 µg/mL clonidine (group cloni-infusion; n = 20). After surgery, continuous femoral infusion was provided with a patient-controlled infusion pump (basal infusion rate, 6 mL/h; incremental dose, 2 mL; lockout time, 15 min). The median (range) onset time of surgical block was 15 min (5–30 min) in group control, 10 min (5–35 min) in group cloni-bolus, and 10 min (5–30 min) in group cloni-infusion (P = 0.07). No differences were reported among groups in the degree of pain measured with the visual analog scale. The total consumption of local anesthetic solution after a 24-h infusion was 170 mL (144–220 mL) in group control, 169 mL (144–260 mL) in group cloni-bolus, and 164 mL (144–248 mL) in group cloni-infusion (P = 0.51); after the second day of infusion, total consumption was 168 mL (144–200 mL) in group control, 156 mL (144–288 mL) in group cloni-bolus, and 150 mL (144–210 mL) in group cloni-infusion (P = 0.48). Hemodynamic profiles and sedation were similar in the three groups. Motor function impairment after 48 h of infusion was observed in 27% of cloni-infusion patients but in only 6% of both the control and cloni-bolus groups (P = 0.05). We conclude that adding clonidine 1 µg/mL to local anesthetic for continuous femoral nerve block does not improve the quality of pain relief but has the potential for delaying recovery of motor function.
|
Introduction
|
|---|
Interest in continuous peripheral nerve blocks has greatly increased in the last few years both because of their effectiveness in providing postoperative analgesia, especially in patients undergoing total knee arthroplasty (TKA) (1–3), and because of increasing concerns about the extensive use of central nerve blocks in patients receiving antithrombotic prophylaxis (4). The use of these techniques also facilitates functional recovery and reduces opioid consumption and related side effects, thus increasing patient satisfaction (1–3).
Long-acting local anesthetic solutions, such as bupivacaine, ropivacaine, or levobupivacaine, are mostly used to maintain postoperative analgesia (1,3,5,6). The addition of clonidine, an 
2-adrenoceptor agonist, to the local anesthetic solution enhances peripheral nerve blocks (1,2,7,8). Ilfeld et al. (9) recently reported that the addition of clonidine 1 µg/mL to 0.2% ropivacaine for maintenance of a continuous infraclavicular brachial plexus block in outpatients modestly decreased the volume of local anesthetic consumed during the first 24 h of infusion; however, this type of surgery is associated with mild to moderate postoperative pain and is appropriate only for limited needs for postoperative physical therapy. In contrast, TKA is associated with moderate to severe pain and requires more intense physical therapy. We therefore conducted a prospective, randomized, double-blind study to test the hypothesis that adding clonidine 1 µg/kg to the initial bolus or 1 µg/kg to the initial bolus and 1 µg/mL to the infusion solution reduces the consumption of 0.2% ropivacaine during the first 2 days of continuous femoral nerve block for TKA.
|
Methods
|
|---|
After we obtained the approval of the San Raffaele Hospital’s Ethical Committee and obtained written informed consent from all patients, 60 ASA physical status II/III inpatients undergoing TKA during combined sciatic/femoral nerve block were prospectively studied. Patients receiving chronic opioid therapy and those with contraindications to regional anesthesia, severe cardiopulmonary disease (ASA physical status 
IV), thyroid disease, diabetes, or central or peripheral neuropathies were excluded.
Patients were premedicated with IV midazolam (0.05 mg/kg) 10 min before the blocks were placed. Standard monitoring was used throughout the procedure, including noninvasive arterial blood pressure, electrocardiograph (lead II), heart rate, and oxygen saturation. Continuous femoral and single sciatic nerve blocks were used to provide intraoperative surgical anesthesia and postoperative analgesia (10). Nerve blocks were performed with the aid of a nerve stimulator (Plexygon; Vygon, France) by using an 18-gauge Teflon-coated insulated Tuohy needle with a 20-gauge catheter (Plexolong; Pajunk, Germany) for the continuous femoral block and a 20-gauge short-beveled insulated needle (Locoplex; Vygon) for the sciatic nerve block. The stimulation frequency was set at 2 Hz and the pulse duration at 0.15 ms, and the stimulating intensity, initially set at 1 mA, was progressively decreased to 
0.5 mA after the appropriate muscular response was elicited. For the continuous femoral nerve block, after the proper contraction of the quadriceps muscle was observed with an intensity 0.5 mA, the catheter was advanced through the introducer Tuohy needle. The Tuohy needle was then removed, and the catheter was secured in place with a locking system (Lockit; Portex, Italy) and covered with a transparent TegadermTM dressing, which allowed direct visualization of the insertion site and the catheter.
By use of a computer-generated sequence of numbers, patients were randomly allocated to one of three groups according to the solution to induce and maintain the continuous femoral nerve block. In the first group, the nerve block was induced with 25 mL of 0.75% ropivacaine and maintained with 0.2% ropivacaine (group control; n = 20); in the second group, the nerve block was induced with 25 mL of 0.75% ropivacaine with 1 µg/kg clonidine and maintained with 0.2% ropivacaine alone (group cloni-bolus; n = 20); and in the third group, the nerve block was induced with 25 mL of 0.75% ropivacaine with 1 µg/kg clonidine and maintained with 0.2% ropivacaine with 1 µg/mL clonidine (group cloni-infusion; n = 20). The local anesthetic solutions required to induce and maintain the block after surgery were prepared in a double-blind fashion by one of the authors not taking part in patient management. The anesthesiologists and pain nurses managing the patients both during and after surgery were blinded to the anesthetic solution used. The patient-controlled analgesia (PCA) infusion was started 4 h after the induction bolus at a basal infusion rate of 6 mL/h, an incremental dose of 2 mL, a lockout time of 15 min, and a maximum of three incremental doses per hour (allowing a maximum hourly volume of 12 mL/h).
A single-shot subgluteal sciatic nerve block was also placed with 15 mL of 0.75% ropivacaine equally divided between the tibialis and common peronealis stimulation. After completion of block placement, sensory and motor blocks on the operated limb were evaluated every 5 min after the injection of the anesthetic solution by an independent blinded observer, who was not present during block placement, until achievement of adequate sensory (loss of pinprick sensation on both the sciatic and femoral nerve distributions) and motor (inability to extend the leg with the hip passively flexed) blocks. A hemostatic tourniquet was always placed around the thigh and inflated 100 mm Hg more than the systolic arterial blood pressure. Supplemental sedation during the procedure was provided, if requested by the patient, by a target-controlled infusion (Diprifusor; AstraZeneca, Italy) of propofol (target concentrations ranged from 1.5 to 2 µg/mL). In case of pain (especially before proximal drilling of the femur to place the femoral shaft of the prosthesis), supplemental analgesia with IV fentanyl (100 µg) was provided.
Postoperative analgesia consisted of 100 mg of ketoprofen IV every 8 h and a continuous femoral nerve block maintained with a PCA infusion pump. Rescue analgesia was provided with 5 mg of subcutaneous morphine if required despite the use of all PCA boluses to maintain a visual analog score (VAS) score 4 cm.
The degree of pain was assessed both at rest and during active mobilization of the operated limb by using a 10-cm VAS. Assessments were performed when the PCA femoral infusion started, every 8 h for the first 24 h of infusion, and, finally, after 48 h of infusion. At the same times, the degree of motor block and sedation was also evaluated. Motor blockade was evaluated with a two-point scale: 0 = persistent motor block (the patient was unable to raise the operated limb and maintain the leg extended); 1 = recovery of motor function (the patient was able to raise the operated limb and maintain the leg extended). The degree of sedation was assessed with the Observer’s Assessment of Alertness and Sedation Scale (11) (Appendix 1).
The total consumption of the local anesthetic solution during the 2 days of infusion, the number of incremental doses requested and given by the PCA pump, the need for rescue morphine, and the occurrence of untoward effects during the study period were recorded. On the second postoperative day, the catheter was removed and the insertion site examined. The orthopedic surgeon then evaluated complete recovery of neurological function before patient discharge from the orthopedic ward.
To calculate the required study size, we considered the results of a previous pilot study (12) that evaluated the consumption of local anesthetic solution during the first 24 h of infusion in patients receiving or not receiving clonidine with 0.2% ropivacaine (data of the pilot study were not included in the final analysis). A total of 20 patients per group allowed detection of a 25-mL reduction in the volume of local anesthetic solution required to provide effective pain relief during the first 24 h of infusion in patients receiving clonidine, with a two-tailed error of 5% and a ß error of 10% (13).
Statistical analysis was performed with Systat 7.0 (SPSS Inc., Chicago, IL). Normal distribution of the collected data was first verified with the Kolmogorov-Smirnov test. Continuous variables were analyzed with analysis of variance or the Kruskal-Wallis test according to data distribution. Post hoc comparisons were performed with the unpaired Student’s t-test or the Mann-Whitney U-test and Bonferroni’s correction, as indicated. Categorical variables were analyzed by using contingency table analysis and the 
2 test with the appropriate corrections. A value of P 0.05 was considered significant. Continuous variables are presented as mean ± sd or median (range) according to data distribution, and categorical variables are presented as n (%).
|
Results
|
|---|
No differences in age, sex, weight, height, or ASA physical status were observed among the three groups (Table 1). The median (range) onset time of surgical block was 15 min (5–30 min) in group control, 10 min (5–35 min) in group cloni-bolus, and 10 min (5–30 min) in group cloni-infusion (P = 0.07). Comparing patients who received clonidine in the initial bolus (groups cloni-bolus and cloni-infusion) with those who did not have clonidine in the block solution used for induction (group control), the mean difference in onset time was 4.2 min (95% confidence interval [CI], –0.9 to +7.3 min; P = 0.12). Surgery was successfully completed in all studied patients. Supplemental fentanyl analgesia was provided to 14 patients (70%) not receiving clonidine in the block solution (group control) and 19 patients (47%) receiving clonidine in the induction bolus (P = 0.09) (9 of them were in group cloni-bolus [45%], and 10 were in group cloni-infusion [50%]).
One patient of group control (5%) and one patient of group cloni-infusion (5%) had a technical failure of postoperative analgesia that was due to accidental removal/dislodgment of the catheter before the first 24 h of infusion was completed (P = not significant), and they were withdrawn from final data analysis. Postoperative analgesia was adequate in all three groups, and there were no differences among the groups. (Figure 1 shows the evolution of the VAS in the three groups both at rest and during motion.
View larger version (25K):
[in this window]
[in a new window]
|
Figure 1. Degree of pain measured at rest (A) and during motion (B) by using a 10-cm visual analog scale (VAS). Group control (n = 20) received a continuous femoral nerve block with 0.2% ropivacaine alone. Group cloni-bolus (n = 20) received 0.2% ropivacaine alone after 1 µg/kg clonidine was added to the initial bolus. Group cloni-infusion (n = 20) received 0.2% ropivacaine with 1 µg/mL clonidine after 1 µg/kg clonidine was added to the initial bolus.
|
|
The median (range) consumption of local anesthetic solution during the first postoperative day was 170 mL (144–220 mL; 95% CI, 160–181 mL) in group control, 169 mL (144–260 mL; 95% CI, 163–194 mL) in group cloni-bolus, and 164 mL (144–248 mL; 95% CI, 154–184 mL) in group cloni-infusion (P = 0.51). Median (range) consumption during the second postoperative day was 168 mL (144–200 mL; 95% CI, 161–177 mL) in group control, 156 mL (144–288 mL; 95% CI, 151–188 mL) in group cloni-bolus, and 150 mL (144–210 mL; 95% CI, 150–175 mL) in group cloni-infusion (P = 0.48).
No differences in hemodynamic variables were reported among the three groups throughout the study (Fig. 2). In no case was an Observer’s Assessment of Alertness and Sedation Scale score <4 reported in any group, and no differences in the degree of sedation were reported at any observation time among the three groups. Analgesia supplementation with morphine was required in six patients of group control (31%), three patients of group cloni-bolus (15%), and three patients of group cloni-infusion (16%) (P = 0.36). The median (range) consumption of morphine was 0 mg (0–20 mg) in group control, 0 mg (0–20 mg) in group cloni-bolus, and 0 mg (0–15 mg) in group cloni-infusion (P = 0.45).
View larger version (23K):
[in this window]
[in a new window]
|
Figure 2. Changes in systolic and diastolic blood pressure and heart rate during the 2-day postoperative infusion. Group control (n = 20) received a continuous femoral nerve block with 0.2% ropivacaine alone; group cloni-bolus (n = 20) received 0.2% ropivacaine alone after 1 µg/kg clonidine was added to the initial bolus; group cloni-infusion (n = 20) received 0.2% ropivacaine with 1 µg/mL clonidine after 1 µg/kg clonidine was added to the initial bolus.
|
|
(Figure 3 shows the proportion of patients with complete recovery of motor function on the operated limb during the study period. A larger proportion of patients receiving the infusion of 0.2% ropivacaine with the addition of 1 µg/mL clonidine showed the persistence of motor block from the 16th to the 48th hour of infusion as compared with the other two groups (P < 0.05).
View larger version (22K):
[in this window]
[in a new window]
|
Figure 3. Percentage of patients with complete recovery of motor function during the study. Group control (n = 20) received a continuous femoral nerve block with 0.2% ropivacaine alone; group cloni-bolus (n = 20) received 0.2% ropivacaine alone after 1 µg/kg clonidine was added to the initial bolus; group cloni-infusion (n = 20) received 0.2% ropivacaine with 1 µg/mL clonidine after 1 µg/kg clonidine was added to the initial bolus.
|
|
Postoperative nausea and vomiting during the study period was reported in four patients of group control (21%), six patients of group cloni-bolus (30%), and five patients of group cloni-infusion (26%) (P = 0.71). Recovery of normal neurological function was complete in all studied patients, and no postoperative complications were reported in any group.
|
Discussion
|
|---|
The results of this prospective, randomized, double-blind study showed that the addition of clonidine 1 µg/mL to 0.2% ropivacaine does not provide any clinically relevant advantage to patients receiving a continuous femoral nerve block for the postoperative management of pain after TKA, but it can potentially delay the recovery of motor function. When considering the effects of adding 1 µg/kg clonidine to the initial 25-mL bolus of 0.75% ropivacaine, we found a trend toward a reduction in the onset time of surgical block. Increasing the sample size of the study population might have resulted in achieving statistical significance; however, the observed difference in the onset time was clinically insignificant. Similar effects of clonidine on the onset time of peripheral nerve blocks have been reported by other investigators, who evaluated the addition of 30–300 µg of clonidine to short-acting local anesthetics (7,14). However, other investigations failed to demonstrate a significant reduction in the onset time of nerve block when combining clonidine with long-acting drugs, such as ropivacaine (8,14).
Irrespective of the effects of clonidine on the onset time of peripheral nerve blocks, most studies report a prolongation of the duration of both anesthesia and analgesia when clonidine 0.5–1 µg/kg is added to the local anesthetic for peripheral nerve blocks (8,14,15). Nonetheless, this investigation failed to demonstrate significant effects on postoperative pain relief or local anesthetic consumption in patients who received clonidine only with the initial bolus. The effects of clonidine on the prolongation of nerve blockade are clearly dose-dependent (7,16), and using larger doses of clonidine for the initial bolus could result in more significant sparing effects after surgery. However, it has been demonstrated that clonidine-related side effects, such as bradycardia, hypotension, and sedation, are also dose-dependent (7). For this reason, we used the minimum dose of clonidine that has been demonstrated to have a clinical effect on the profile of peripheral nerve blocks (7,16), thus decreasing the risk for clonidine-related side effects. Another possible explanation for the lack of difference among the three regimens could be that continuous femoral block alone is not sufficient to provide complete analgesia after TKA; thus, the excessive use of PCA infusion through the femoral catheter after sciatic nerve block wore off could have obscured the effects of such a small dose of clonidine on the consumption of ropivacaine.
The addition of clonidine to 0.2% ropivacaine during postoperative infusion slowed the recovery of motor function in the femoral nerve distribution as compared with patients not receiving clonidine or receiving clonidine only with the initial bolus. The enhancement of the effects of the local anesthetic on nerve function produced by clonidine can easily explain this finding. In fact, other authors have demonstrated that combining clonidine with local anesthetic solutions reduces the concentration of local anesthetic required to produce the block (17) or that it results in deeper motor block if the concentration of the local anesthetic is not reduced accordingly (18). However, it must be noted that reducing the proportion of patients with complete recovery of motor function can be considered undesirable for orthopedic patients, in whom early mobilization is important to improve postoperative rehabilitation.
Further studies evaluating the possibility of reducing the ropivacaine concentration when adding small concentrations of clonidine for peripheral nerve blocks should be performed to better evaluate the theoretical advantages of the enhancement of nerve block induced by 2-adrenoceptor agonists; however, results of this prospective, randomized, double-blind study suggest that adding clonidine 1 µg/kg in the initial bolus followed by clonidine 1 µg/mL in the postoperative infusion solution does not provide clinically relevant advantages in terms of improved postoperative analgesia or reduced volumes of 0.2% ropivacaine required to maintain an adequate analgesia, but it has the potential for delaying the recovery of motor function.
|
Appendix 1.
|
|---|
|
References
|
|---|
- Singelyn F, Deyaert M, Pendeville E, et al. Effects of intravenous patient-controlled analgesia with morphine, continuous epidural analgesia, and continuous three-in-one block on postoperative pain and knee rehabilitation after unilateral total knee arthroplasty. Anesth Analg 1998;87:88–92.[Abstract/Free Full Text]
- Capdevila X, Barthelet Y, Biboulet P, et al. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 1999;91:8–15.[Web of Science][Medline]
- Chelly JE, Greger J, Gebhard R, et al. Continuous femoral nerve blocks improve recovery and outcome of patients undergoing total knee arthroplasty. J Arthroplasty 2001;16:436–45.[Web of Science][Medline]
- Horlocker TT, Wedel DJ, Benzon H, et al. Regional anesthesia in the anticoagulated patient: defining the risks (the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Reg Anesth Pain Med 2003;28:172–97.[Web of Science][Medline]
- Ilfeld BM, Morey TE, Wang RD, Enneking FK. Continuous popliteal sciatic nerve block for postoperative pain control at home: a randomized, double-blinded, placebo controlled study. Anesthesiology 2002;97:959–65.[Web of Science][Medline]
- Casati A, Vinciguerra F, Scarioni M, et al. Lidocaine versus ropivacaine for continuous interscalene brachial plexus block after open shoulder surgery. Acta Anaesthesiol Scand 2003;47:355–60.[Web of Science][Medline]
- Bernard JM, Macarie P. Dose-range effects of clonidine added to lidocaine for brachial plexus block. Anesthesiology 1997;87:277–84.[Web of Science][Medline]
- Casati A, Magistris L, Fanelli G, et al. Small-dose clonidine prolongs postoperative analgesia after sciatic-femoral nerve block with 0.75% ropivacaine for foot surgery. Anesth Analg 2000;91:388–92.[Abstract/Free Full Text]
- Ilfeld BM, Morey TE, Enneking FK. Continuous infraclavicular perineural infusion with clonidine and ropivacaine compared with ropivacaine alone: a randomized, double-blinded, controlled study. Anesth Analg 2003;97:706–12.[Abstract/Free Full Text]
- Chelly JE, Casati A, Fanelli G, eds. Continuous peripheral nerve block techniques. Segrate, Italy: Mosby, 2001:59–80.
- Chernik DA, Gilling SD, Laine H, et al. Validity and reliability of the Observer’s Assessment of Alertness/Sedation scale: study with intravenous midazolam. J Clin Psycopharmacol 1990;10:244–51.[Web of Science][Medline]
- Casati A, Manzoni P, Mamo D, et al. A preliminary evaluation of the effects of adding clonidine to 0.2% ropivacaine for continuous femoral nerve block after major knee surgery [abstract]. Anesthesiology 2003;99:A1016.
- Browner WS, Black D, Newman B, Hulley SB. Estimating sample size and power. In: Hulley SB, Cummings SR, eds. Designing clinical research: an epidemiologic approach. Baltimore: Williams & Wilkins, 1988:139–50.
- Erlacher W, Schuschnig C, Koinig H, et al. Clonidine as adjuvant for mepivacaine, ropivacaine and bupivacaine in axillary, perivascular brachial plexus block. Can J Anaesth 2001;48:522–5.[Web of Science][Medline]
- Casati A, Magistris L, Beccaria P, et al. Improving postoperative analgesia after axillary brachial plexus anesthesia with 0.75% ropivacaine: a double-blind evaluation of adding clonidine. Minerva Anestesiol 2001;67:407–12.[Medline]
- Singelyn FJ, Gouverneur JM, Robert A. A minimum dose of clonidine added to mepivacaine prolongs the duration of anesthesia and analgesia after axillary brachial plexus block. Anesth Analg 1996;83:1046–50.[Abstract]
- Aveline C, El Metaoua S, Masmoudi A, et al. The effect of clonidine on the minimum local analgesic concentration of epidural ropivacaine during labor. Anesth Analg 2002;95:735–40.[Abstract/Free Full Text]
- Landau R, Schiffer E, Morales M, et al. The dose-sparing effect of clonidine added to ropivacaine for labor epidural analgesia. Anesth Analg 2002;95:728–34.[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
Y.-S. Huang, L.-C. Lin, B. K. Huh, M. J. Sheen, C.-C. Yeh, C.-S. Wong, and C.-T. Wu
Epidural Clonidine for Postoperative Pain After Total Knee Arthroplasty: A Dose-Response Study
Anesth. Analg.,
May 1, 2007;
104(5):
1230 - 1235.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Tran, T. J. Ganley, L. Wells, A. Ganesh, K. I. Minger, and G. Cucchiaro
Intraarticular Bupivacaine-Clonidine-Morphine Versus Femoral-Sciatic Nerve Block in Pediatric Patients Undergoing Anterior Cruciate Ligament Reconstruction
Anesth. Analg.,
November 1, 2005;
101(5):
1304 - 1310.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
