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Anesth Analg 2003;97:706-712
© 2003 International Anesthesia Research Society

AMBULATORY ANESTHESIA

Continuous Infraclavicular Perineural Infusion with Clonidine and Ropivacaine Compared with Ropivacaine Alone: A Randomized, Double-Blinded, Controlled Study

Brian M. Ilfeld, MD*, Timothy E. Morey, MD*, and F. Kayser Enneking, MD*,{dagger}

Departments of *Anesthesiology and {dagger}Orthopedics and Rehabilitation, University of Florida College of Medicine, Gainesville, Florida

Address correspondence and reprint requests to F. Kayser Enneking, MD, Department of Anesthesiology, PO Box 100254, Gainesville, FL 32610-0254. Address e-mail to enneking{at}ufl.edu


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Appendix 1. Nightly...
 References
 
Although clonidine has been shown to increase the duration of local anesthetic action and prolong postoperative analgesia when included in single-injection nerve blocks, a controlled investigation of the efficacy of this practice to improve analgesia for continuous perineural local anesthetic infusion has not been reported. In this study, ambulatory patients (n = 34) undergoing moderately painful upper extremity orthopedic surgery received an infraclavicular brachial plexus block (mepivacaine 1.5%, epinephrine 2.5 µg/mL, and bicarbonate 0.1 mEq/mL) and a perineural catheter before surgery. After surgery, patients were discharged home with a portable infusion pump delivering either ropivacaine 0.2% or ropivacaine 0.2% plus clonidine 1 µg/mL via the catheter for 3 days (basal, 8 mL/h; patient-controlled bolus, 2 mL every 20 min). Investigators and patients were blinded to random group assignment. Daily end-points included pain scores, patient-controlled bolus doses, oral analgesic use, sleep quality, and symptoms of catheter- or infusion-related complications. Adding clonidine to ropivacaine resulted in a statistically significant decrease in the number of self-administered 2-mL bolus doses on postoperative Days 0 and 1 (P < 0.02), but this decreased actual local anesthetic consumption by an average of only 2–7 mL/d (P < 0.02). There were no statistically significant differences between the two groups for any of the other variables investigated, including sleep quality or oral analgesic requirements. We conclude that adding 1 µg/mL of clonidine to a ropivacaine infraclavicular perineural infusion does not provide clinically relevant improvements in analgesia, sleep quality, or oral analgesic requirements for ambulatory patients having moderately painful upper extremity surgery.

IMPLICATIONS: Clonidine is often added to long-acting local anesthetic perineural infusions in an effort to improve postoperative analgesia. This randomized, double-blinded, controlled study did not find evidence of clinically relevant benefits from adding clonidine to ropivacaine infraclavicular brachial plexus perineural infusions in ambulatory patients after moderately painful upper extremity surgery.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Appendix 1. Nightly...
 References
 
Local anesthetic infused via a perineural catheter provides potent analgesia (1), decreases narcotic use (2) and related side effects (3) and, in some cases, decreases convalescence duration (4,5). Clonidine, an {alpha}2-adrenoceptor agonist, increases the duration of local anesthetic action when included in single-injection nerve blocks (6–11). In an effort to further improve postoperative analgesia, clonidine is often added to a long-acting local anesthetic for continuous perineural femoral (4), anterior lumbar plexus (5,12,13), interscalene (14), and popliteal (15) infusions. However, a controlled investigation of the efficacy of this practice to improve analgesia has not been reported.

For ambulatory perineural infusion in which there is a limited local anesthetic reservoir volume, minimizing local anesthetic consumption allows for increased infusion duration and, therefore, prolonged analgesia (16). It is currently unknown whether the addition of clonidine to a perineural infusion will provide equivalent analgesia at a smaller rate of anesthetic consumption and thus extend postoperative analgesia. Therefore, the primary objectives of this study were to determine whether the addition of clonidine to a local anesthetic perineural infusion improves postoperative analgesia at an equivalent basal infusion rate and, if so, whether this allows for a decreased basal infusion rate while providing equivalent analgesia.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Appendix 1. Nightly...
 References
 
The local IRB approved the study protocol. We prospectively enrolled patients scheduled for moderately painful ambulatory unilateral orthopedic surgery of the upper extremity involving, or distal to, the elbow. Inclusion criteria included 1) ASA physical status I or II, 2) age 18 yr or older, 3) ability to provide informed consent, and 4) understanding of the possible local anesthetic-related complications, the study protocol, and care of the catheter and infusion pump system. In addition, patients were required to have a caretaker who would remain with them during the local anesthetic infusion and be available and capable of removing the catheter. Exclusion criteria included any contraindication to infraclavicular nerve block, history of opioid dependence or allergy or contraindication to study medications, current chronic analgesic therapy (use more than twice a week), known hepatic or renal insufficiency, peripheral neuropathy, hypertension, and patient refusal. Enrollment began August 2001 and concluded 14 mo later.

After written, informed consent, an IV cannula was placed. Patients were placed in the supine position with their head turned slightly away from the operative side. Standard noninvasive monitors were applied, and oxygen (8–10 L/min) was administered via a face mask. IV midazolam and fentanyl were titrated for patient comfort in divided doses, ensuring that patients remained responsive to verbal cues throughout the procedure. All infraclavicular blocks and catheters were placed by one of the authors (B.M.I.). The area that would be subsequently covered by the catheter dressing was prepared with chlorhexidine gluconate and isopropyl alcohol (ChloraPrep One-Step; Medi-Flex Hospital Products, Inc., Overland Park, KS) and then shaved with a surgical safety razor, if necessary.

After sterile preparation (with additional chlorhexidine gluconate) and draping, a nerve stimulator (Stimuplex-DIG; B. Braun Medical, Bethlehem, PA) and a 102-mm, 18-gauge insulated stimulating needle (Contiplex; B. Braun Medical) were used to place an infraclavicular brachial plexus block by using the landmarks previously described by Wilson et al. (17). A skin wheal was raised 2 cm medial and 2 cm caudad to the center of the coracoid process. The needle was inserted through the skin wheal with the bevel pointed toward the patient’s head and the long axis of the needle perpendicular to the gurney in all planes. With continuous aspiration and the nerve stimulator initially set at 1.2 mA and 2 Hz, the needle was advanced directly posterior. If the brachial plexus was not identified after 5–8 cm of insertion, depending on patient habitus, the needle was withdrawn to the skin and redirected either cephalad or caudad in the paramedian sagittal plane until discrete, stimulated motion occurred in any digit with a current between 0.30 and 0.50 mA. Directing the needle tip out of the paramedian sagittal plane was strictly prohibited—neither medially toward the lung nor laterally toward the terminal nerves of the brachial plexus. Flexion or extension at the elbow or wrist that resulted in motion of the fingers, without intrinsic hand/digit motion, was rejected.

For the surgical block, 50 mL of anesthetic solution was injected in divided doses via the needle, with gentle aspiration every 3 mL. The injectate contained mepivacaine 1.5%, sodium bicarbonate 5 mEq, and epinephrine 125 µg. A 20-gauge multiport polyamide catheter (B. Braun Medical) was then inserted to the tip of the needle but was not advanced past the tip, to avoid axillary artery puncture (3). The catheter was held securely in place while the needle was withdrawn over the catheter. This technique left the catheter tip at the original location of the tip of the needle. After being withdrawn roughly halfway to the skin, the needle was held in place and the catheter was advanced 5 cm. Subsequently, the needle was completely withdrawn over the remaining catheter, leaving 5 cm of catheter "slack" between the skin and brachial plexus.

After negative aspiration, the catheter was injected with 1 mL of sterile preservative-free saline 0.9% to ensure its patency. The catheter was then secured with sterile liquid adhesive (Mastisol; Ferndale Laboratory, Ferndale, MI) and sterile tape (Steri-Strips; 3M Corp., St. Paul, MN). An occlusive dressing (Tegaderm; 3M Corp.) was placed over the site to retain sterility, and the catheter was further secured to the top of the original dressing with a second dressing. Patients were withdrawn from the study if a sensory block failed to develop at 15 min or if the catheter was placed in a vessel. Block failure was defined as a lack of major sensory changes to touch from baseline in the forearm or hand. Specific nerve distributions and degree of sensory blockade were not formally evaluated for the purposes of this study.

The infraclavicular block was intended to provide surgical anesthesia for all patients. Intraoperative sedation was provided with IV propofol (0–50 µg · kg-1 · min-1, titrated for patient comfort). Alternatively, nitrous oxide via a laryngeal mask airway and larger doses of IV propofol were used at the attending anesthesiologists’ discretion. Whether block inadequacy or simply patient/physician preference resulted in a general anesthetic was not evaluated. No anesthetic or analgesic medication besides propofol and nitrous oxide was administered after infraclavicular block placement.

After successful block and catheter placement, patients were randomly assigned to receive 1 of 2 possible postoperative catheter infusions: ropivacaine 0.2% or ropivacaine 0.2% combined with preservative-free clonidine 1 µg/mL. An investigational pharmacist using a computer-generated randomization table performed group assignment and provided the investigational injectate. Assignment was not revealed to the patients or any clinical personnel. Likewise, clinical investigators were blinded to patient assignment until the conclusion of the study.

After surgery, when patients met standard ambulatory home-discharge criteria, the catheter was tested for intravascular positioning with gentle aspiration followed by a 10-mL incremental bolus of study fluid into which 30 µg of fresh epinephrine had been added. Subsequently, a portable, programmable, battery-powered mechanical infusion pump (Microject PCA Pump; Sorenson Medical, West Jordan, UT) was attached to the catheter with a reservoir containing 550 mL of study solution. A continuous infusion of 8 mL/h was begun with a 2-mL patient-controlled bolus available every 20 min.

The patient and caretaker were given standard postoperative outpatient instructions. In addition, verbal and written instructions on the use of the pump and catheter were given. Specific attention was given to signs and symptoms of hypotension, local anesthetic toxicity, catheter site infection, and catheter migration. Telephone and pager numbers for physicians available at all times were given to each patient. Patients were instructed not to drive motorized vehicles during the study period. They were instructed to keep their operative limb well protected in a sling during the infusion period, unless instructed otherwise by their surgeon or physical therapist. The following supplies were given to patients: a medication log, a prescription for an oral analgesic (oxycodone 5 mg, combined with acetaminophen 500 mg), a prescription for an oral nonsteroidal antiinflammatory drug (ketorolac 10 mg taken three or four times per day, depending on patient age, for 4 days), 2 additional occlusive dressings, a pair of nonsterile gloves, and a hospital-addressed and stamped padded envelope for return of the pump. In the event of "breakthrough" pain, patients were instructed to first use the bolus function of the infusion pump. If the pain had not resolved after 20 min, patients were instructed to take an oxycodone/acetaminophen tablet and to record this use in their medication log. This regimen of oxycodone/acetaminophen and ketorolac is identical to analgesic prescriptions routinely supplied to patients who receive similar operative procedures at our institution but who did not participate in the study.

Patients could contact a physician by telephone at any time during the study period. Patients were contacted by telephone beginning the night of surgery and continuing each evening thereafter through the night after catheter removal. Information obtained included patient-controlled boluses delivered, pain scores, and sleep quality (see Appendix 1 for questionnaire). To determine boluses delivered, the infusion pump memory was interrogated by the patient or caretaker by using instructions given by the physician. Patients were also questioned about gross sensory and motor functions, symptoms of local anesthetic toxicity, vertigo, and the appearance of the catheter site. On the evening of postoperative day (POD) 0, patients were instructed to contact the physician if they awoke the next morning without any feeling in their arm or hand. If this occurred at any time on or after the morning of POD 1, patients were instructed to 1) decrease the basal infusion rate by 2 mL/h by using instructions provided by the physician by telephone, 2) pause their infusion, and 3) restart the infusion when they regained feeling in the extremity.

In the evening of POD 1, if indicated depending on multiple variables (Fig. 1), patients reprogrammed their infusion pumps, by using instructions given by the physician, to either increase or decrease their basal infusion rate. In the evening of POD 2, patients’ caretakers were instructed on removal of the catheter by using the pair of nonsterile gloves, with the physician in telephone contact throughout. The presence of a blue catheter tip confirmed complete removal. Residual study fluid was disposed of in a sink or toilet. In the evening of POD 3, patients were instructed to return their medication log and infusion pump to the surgical center in the preaddressed/stamped envelope the following morning.



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  		Figure 1. Protocol for changes made to the basal infusion on the evening after surgery. The fastest rate indicated took precedence. For example, with an average pain score of 1 (indicating a decrease in rate), if the number of opioid tablets or boluses delivered was 4, then the infusion would not be decreased. If either the number of opioid tablets or boluses delivered was >4 or >5, respectively, then the infusion would be increased regardless of pain score. The infusion was never increased or decreased >2 or >1.9 mL/h, respectively; *9.9 mL/h was the maximal infusion pump continuous basal rate.

 
Sample size calculations were centered around our primary hypothesis that the addition of clonidine to ropivacaine infused via an infraclavicular perineural catheter decreases postoperative pain compared with ropivacaine alone. We chose the outcome variable "worst pain" on POD 1 to estimate a probable sample size and considered a 50% reduction in the pain score to be clinically relevant. On the basis of our experience with previous patients receiving plain ropivacaine (3), we expected patients to have a mean "worst pain" score of 4 on a scale of 0 to 10 (0 = no pain; 10 = worst imaginable pain). Assuming a standard deviation in each group of 2, a 2-sided Type I error protection of 0.05, and a power of 0.80, approximately 17 patients in each group were required to reveal a 50% reduction in this pain score with the addition of clonidine (StatMate 1.01; GraphPad Software, San Diego, CA).

Normality of distribution was determined by using the Kolmogorov-Smirnov test with the Lilliefors correction (Sigma Stat 2.03; SPSS, Inc., Chicago, IL). Continuous parametric data are reported as mean ± SD. Nonparametric data are reported as median with 25th–75th and/or 10th–90th percentiles, as indicated in table and figure legends. For normally distributed data, single comparisons were tested with Student’s t-test, whereas multiple comparisons were made with repeated-measures analysis of variance, with Tukey’s post hoc pairwise testing when appropriate. For nonparametric data, the Mann-Whitney ranked sum test or repeated-measures analysis of variance for ranks was used. Categorical data were analyzed with Fisher’s exact test. P < 0.05 was considered significant. For the purposes of analysis, data after an infusion discontinuation secondary to pump failure or catheter dislodgement were not included.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Appendix 1. Nightly...
 References
 
Of 77 patients evaluated, 40 (52%) were excluded after medical history review or patient interview, mostly because of chronic analgesic therapy. One patient declined enrollment. Of the 36 patients enrolled, no intravascular catheters were placed, but 2 (6%) block failures occurred. The remaining 34 subjects were randomized to receive either ropivacaine (n = 17) or ropivacaine plus clonidine (n = 17). There were no statistically significant differences between these groups in demographics, IV sedation for block placement, surgical duration, or surgical procedures (Tables 1 and 2).


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  		Table 1. Population Data for the Two Study Groups
 

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  		Table 2. Surgical Procedures for Each Study Group
 
Patients receiving clonidine/ropivacaine had a statistically significant decrease in the number of self-administered 2-mL bolus doses on POD 0 and 1 (Fig. 2), but this decreased the actual local anesthetic consumption by an average of only 2–7 mL/d (P < 0.02). There were no statistically significant differences between the two groups for any of the other variables investigated (Table 3, Fig. 3). One patient from each group retained a complete lack of sensation in the surgical extremity on the morning of POD 1 that resolved after a 2-h discontinuation of local anesthetic infusion (both had their infusions decreased that evening per the protocol defined in Fig. 1).



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  		Figure 2. Effects of clonidine (1 µg/mL) addition to ropivacaine on patient-administered 2-mL bolus doses after moderately painful upper extremity surgery. Data are expressed as median with boxes (25th–75th percentiles) and whiskers (10th–90th percentiles) for patients randomly assigned to receive either clonidine/ropivacaine (n = 17) or ropivacaine only (n = 17). *P < 0.05 for clonidine/ropivacaine compared with ropivacaine only for a given day.

 

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  		Table 3. Outcome Variables
 


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  		Figure 3. Effects of clonidine (1 µg/mL) addition to ropivacaine infusion on average pain at rest (A) and worst pain overall (B) after moderately painful upper extremity surgery (scale of 0–10). The infusion was discontinued after postoperative Day 2, as indicated by the horizontal line. Data are expressed as median (horizontal bar) with 25th–75th (box) and 10th–90th (whiskers) percentiles for patients randomly assigned to receive either clonidine/ropivacaine (n = 17) or ropivacaine alone (n = 17). For tightly clustered data (e.g., Panel A, postoperative Day 0, clonidine/ropivacaine group), the median approximated the 10th and 25th percentile values. In this case, the median is 0, and only the 75th and 90th percentiles are clearly noted. Differences between the two study groups for each day were not statistically significant.

 
One patient from each group reported minor vertigo, unassociated with frequent boluses or standing, that resolved within 30 min. One patient from the ropivacaine-only group had her catheter inadvertently dislodged 2 h before its scheduled removal on POD 2 (circumstances were unclear). One infusion pump malfunctioned after 36 h and was returned to the manufacturer for evaluation (ropivacaine-only group; report pending). Other than these cases, there were no apparent local anesthetic-, pump-, or catheter-related complications during infusion, and patients used and reprogrammed the portable infusion pumps with little difficulty. Likewise, patients’ caretakers were able to safely remove all of the perineural catheters at home.

The main complaint consistently noted by patients (roughly 60%) was leakage of clear fluid from under the occlusive dressing. Approximately 40% of patients had at least one nonscheduled contact with the on-call physician during the course of their infusion. All infusion pumps were returned to the surgical center via the postal service.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Appendix 1. Nightly...
 References
 
This randomized, double-blinded, controlled study demonstrates that the addition of clonidine to a perineural infusion of ropivacaine via an infraclavicular perineural catheter does not provide a clinically relevant improvement in analgesia after moderately painful hand or arm surgery. Furthermore, the addition of clonidine did not allow for a slower infusion rate while still providing adequate analgesia by using the algorithm of this investigation (Fig. 1). Satisfaction with postoperative analgesia was also not improved with the addition of clonidine. On the basis of these data, we reject our initial hypothesis that the addition of clonidine to ropivacaine infused via an infraclavicular perineural catheter decreases postoperative pain compared with ropivacaine alone.

Studies have demonstrated that small doses of clonidine prolong surgical anesthesia and postoperative analgesia when added to lidocaine (8–10) and mepivacaine (6,7) single-injection peripheral nerve blocks. However, a much smaller improvement or no improvement has been found when clonidine is added to longer-acting ropivacaine (11) and bupivacaine (18) single-injection blocks. Of note, in this study there was a trend toward lower pain scores and opioid tablet ingestion in the clonidine/ropivacaine group on POD 0 (Table 3, Fig. 3). It is possible that the 10 µg of clonidine in the catheter test dose delivered immediately after surgery prolonged the effects of the initial surgical block of mepivacaine. However, this assertion requires confirmation with a prospective, controlled trial.

Multiple investigations have included clonidine added to either ropivacaine or bupivacaine for continuous perineural infusions (4,5,12–15). Unpublished data demonstrating improved analgesia with the addition of clonidine to bupivacaine are often cited (12–14). The results of our study contradict this assertion for clonidine/ropivacaine combinations, although it is possible that combined with bupivacaine, clonidine may prove beneficial.

This study demonstrates the basal infusion rate variability necessary to provide adequate analgesia among patients with an infraclavicular perineural catheter. Regardless of whether clonidine was added to the ropivacaine infusion, the initial basal infusion rate of 8 mL/h was optimal for roughly 21% of patients. With the algorithm of this study (Fig. 1), 53% required a faster rate and 26% required a slower rate. We have not found an accurate method to predict individual patients’ basal rate requirements, and we assume that this variability is influenced by patients’ sensitivity to local anesthetics, the surgical procedure, and the accuracy of perineural catheter tip placement. Patients’ highly variable and unpredictable basal requirements demonstrate the potential benefits of a reprogrammable infusion pump.

Although at-home perineural local anesthetic infusion offers significant improvements in pain control after many ambulatory procedures, there are several potential inherent risks involving infraclavicular catheters, including catheter site infection, catheter migration (19), and local anesthetic toxicity (20). In this investigation, there were no major medical complications attributable to the initial regional block, catheter placement, or local anesthetic infusion. However, the small number of patients does not permit us to draw definite conclusions about its relative safety. To maximize safety with this technique, patients were given extensive written and verbal instruction regarding the signs and symptoms of possible catheter- and local anesthetic-related complications. Patients had the ability to contact a physician at all times and were contacted by telephone at least once a day and specifically asked about these symptoms. Because not all patients desire, or are capable of accepting, the extra responsibility that comes with the catheter and pump system, appropriate patient selection is crucial for safe ambulatory local anesthetic infusion.

A bolus of clonidine may precipitate hypotension and sedation when introduced by one of a number of possible routes (21), including perineural injection as part of a peripheral nerve block (18). However, these 2 complications have not been reported with a perineural infusion of clonidine of <=10 µg/h (5,12–15) or with an epidural infusion of 40 µg/h (21). In patients receiving an epidural bolus of clonidine 4 µg/kg followed by a 2 µg · kg-1 · h-1 infusion, plasma clonidine concentrations decreased over 24 hours (22). These data provide evidence that the protocol used for this study posed minimal risk to ambulatory subjects. For this investigation, patients with hypertension were excluded because blood pressure often decreases more in these patients after systemic or epidural clonidine (23). It is not our intention to suggest that inclusion of these patients is an unsafe practice; we simply prefer cautious application of this technique until additional investigation of hospitalized, medically supervised patients documents its safety.

Infraclavicular catheters were used in this study. It is possible that clonidine would improve analgesia if infused in another anatomic location, at a larger dose, with an initial loading dose in the initial surgical block, or it could allow for a smaller concentration of ropivacaine to be used. Additionally, clonidine may interact differently with long-acting local anesthetics other than ropivacaine used for continuous perineural infusion, although we believe that this is unlikely on the basis of the results of one investigation involving single-injection interscalene blocks with bupivacaine (18).

In conclusion, this study did not find evidence of clinically relevant benefits to adding clonidine 1 µg/mL to a ropivacaine infraclavicular perineural infusion after moderately painful upper extremity surgery.


   Appendix 1. Nightly Questionnaire
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1. Nightly...
References
 
Pain Scores (POD 0–3)
"Please answer the following questions regarding your surgical pain since the last time we spoke using a scale of 0 to 10, 0 being no pain at all and 10 being the worst pain you can imagine."

"What was the worst pain you have felt?"

"While you were resting, what was the average pain you have felt?"

Sleep Quality (POD 1–3)
"Did you awaken last night because of pain (no = 0)?" If "yes," then: "How many times did you awaken last night because of pain (if >= 4 awakenings, score = 4)?"

Satisfaction (POD 2)
"How satisfied are you with your pain control following your operation on a scale of 0–10, 0 being very dissatisfied and 10 being very satisfied?"


   Acknowledgments
 
Supported by the University of Florida Department of Anesthesiology, Gainesville, FL. Sorenson Medical (West Jordan, UT) donated the infusion pumps used in this investigation.

The authors thank Paul C. Dell, MD, Professor of Orthopedics and Rehabilitation, University of Florida College of Medicine, for his assistance in conducting this study.


   Footnotes
 
Presented in part at the annual meeting of the American Society of Regional Anesthesia and Pain Medicine, April 4, 2003, San Diego, CA.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1. Nightly...
 References
 

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Accepted for publication April 23, 2003.




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P. F. White
The Changing Role of Non-Opioid Analgesic Techniques in the Management of Postoperative Pain
Anesth. Analg., November 1, 2005; 101(5S_Suppl): S5 - 22.
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B. M. Ilfeld and F. K. Enneking
Continuous Peripheral Nerve Blocks at Home: A Review
Anesth. Analg., June 1, 2005; 100(6): 1822 - 1833.
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B. M. Ilfeld, T. E. Morey, L. J. Thannikary, T. W. Wright, and F. K. Enneking
Clonidine Added to a Continuous Interscalene Ropivacaine Perineural Infusion to Improve Postoperative Analgesia: A Randomized, Double-Blind, Controlled Study
Anesth. Analg., April 1, 2005; 100(4): 1172 - 1178.
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A. Casati, F. Vinciguerra, G. Cappelleri, G. Aldegheri, G. Fanelli, M. Putzu, and J. E. Chelly
Adding Clonidine to the Induction Bolus and Postoperative Infusion During Continuous Femoral Nerve Block Delays Recovery of Motor Function After Total Knee Arthroplasty
Anesth. Analg., March 1, 2005; 100(3): 866 - 872.
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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press