1. What is the clinical effectiveness of femoral nerve blocks in adult patients undergoing total knee and anterior cruciate ligament reconstruction?

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1 TITLE: Femoral Nerve Block for Total Knee and Anterior Cruciate Ligament Reconstruction: Review of Clinical Effectiveness, Cost Effectiveness, and Guidelines DATE: 27 September 2010 CONTEXT AND POLICY ISSUES: Total knee arthroplasty (TKA) and anterior cruciate ligament (ACL) reconstruction are painful surgical procedures requiring effective analgesia in the post-operative period to enhance functional recovery, and minimize post-operative morbidity. 1,2 Peripheral block of the femoral nerve is an option for analgesia, which may be combined with other pain control measures such as opioids, non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular (IA) injection of local anesthetics or opioids, or epidural analgesia. 1,3 To induce a femoral block, local anesthetics, such as bupivacaine, ropivacaine, mepivacaine, or levobupivacaine, are injected into the perineural sheath. 4,5 A single dose of local anesthetic may be injected, or continuous infusion initiated to provide sensory blockade to the front of the knee. 6 The addition of a sciatic nerve block provides sensory blockade to the back of the knee. 6 This report will review the clinical effectiveness, safety, and cost-effectiveness literature to provide information to clinicians on the use of femoral nerve blocks in adults undergoing major knee surgery. RESEARCH QUESTIONS: 1. What is the clinical effectiveness of femoral nerve blocks in adult patients undergoing total knee and anterior cruciate ligament reconstruction? 2. What is the cost effectiveness of femoral nerve blocks in adult patients undergoing total knee and anterior cruciate ligament reconstruction? 3. What are the risks associated with femoral nerve blocks in adult patients undergoing total knee and anterior cruciate ligament reconstruction? Disclaimer: The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing health care in Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources and a summary of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. HTIS responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material. It may be copied and used for non-commercial purposes, provided that attribution is given to CADTH. Links: This report may contain links to other information available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners own terms and conditions.

2 4. What are the recommendations from evidence-based guidelines regarding the use of femoral nerve blocks in adult patients undergoing total knee and anterior cruciate ligament reconstruction? METHODS: A limited literature search was conducted on key health technology assessment resources, including Ovid MEDLINE, Ovid EMBASE, PubMed, The Cochrane Library (Issue 8, 2010), University of York Centre for Reviews and Dissemination (CRD) databases, ECRI (Health Devices Gold), EuroScan, international health technology agencies, and a focused Internet search. The search was limited to English language articles published between January 1, 2000, and August 27, No filters were applied to limit the retrieval by study type. In order to be included, studies had to meet the selection criteria listed in Table 1. Table 1: Study Selection Criteria Dimension Criteria Population Adult patients undergoing TKA or ACL reconstruction Interventions Femoral block with bupivacaine or ropivacaine, with or without epinephrine Comparators No femoral block, or femoral block with a different blocking agent Outcomes Pain, functional outcomes, adverse events, cost, cost-effectiveness Study designs Systematic review or meta-analysis, RCTs, economic analyses, evidence based guidelines* Exclusions Studies that compared two types of femoral block (e.g., single dose versus continuous block, or femoral block compared to femoral and sciatic block), or those that assessed different doses of the same blocking agent were excluded. ACL: anterior cruciate ligament; TKA: Total knee arthroplasty; RCT: Randomized controlled trials *Due to the volume of higher quality evidence identified, non-randomized trials were excluded from the report The Jadad score was used to evaluate the methodologic quality of the included RCTs. 7 The Jadad score includes an assessment of randomization (0 to 2 points), double blinding (0 to 2 points) and completeness of follow-up (1 point). Scores can range from 0 to 5 and studies with Jadad scores of 3 to 5 are considered higher quality. HTIS reports are organized so that the higher quality evidence is presented first. Therefore, systematic reviews and meta-analyses are presented first, followed by RCTs. SUMMARY OF FINDINGS: Three systematic reviews 1-3 and 20 reports from 18 unique RCTs met the inclusion criteria. 4,6,8-25 An additional 20 RCTs were identified that met the inclusion criteria, but these studies were included in one or more of the three systematic reviews 1-3 and, therefore, were not individually summarized in this report. No relevant economic studies or evidence-based guidelines were identified. Femoral Nerve Block for Total Knee and ACL Reconstruction 2

3 Systematic reviews and meta-analyses In a systematic review by Mall et al. 2010, 3 the effectiveness of femoral nerve block to control post-operative pain was assessed in patients undergoing ACL reconstruction surgery. The authors searched PubMed, EMBASE and the Cochrane databases for English language clinical trials in patients undergoing ACL reconstruction surgery. Studies were included if they compared the effect of femoral nerve block on pain relief or narcotic medication use to a control group. Two authors screened and appraised articles according to a checklist of necessary elements from the Consolidated Standards of Reporting Trials (CONSORT) statement. The review included 13 RCTs or controlled clinical trials that compared single dose or continuous infusion femoral nerve block to placebo or sham block, no block, ketorolac, or IA injection of local anesthetic or opioid. The femoral nerve block or control interventions were administered in addition to multimodal pain control measures such as oral or parenteral opioids, and NSAIDS. In ten of the studies, bupivacaine was used for the nerve block, ropivacaine was used in two studies, and levobupivacaine was used in one study. The studies enrolled between 20 and 233 patients (median 56 patients). Eight of the RCTs were rated as lower quality studies by the authors of the review with the potential for selection, observer, co-intervention or attrition biases. Five the studies were rated as higher quality. When a femoral nerve block was compared to placebo or a no block group (eight studies), no difference was detected on the amount of pain medication consumed in six studies and in two studies no difference was detected between groups on pain scores. Two studies reported lower pain scores or analgesic use in the nerve block than in the placebo groups, and these differences reached statistical significance. In five studies pain scores were similar between IA injection of local anesthetic and femoral nerve block. In three studies use of pain medication was similar between IA injection of local anesthetic and femoral nerve block. In one study, no difference in pain control was detected between patients treated with intravenous (IV) ketorolac compared to femoral nerve block. For all studies but one that reported on adverse events, the incidence was similar between the femoral block and control groups. In one study the incidence of nausea and vomiting was higher in patients who received IA injection compared to femoral block. The review authors commented that most of the included studies had methodologic limitations, small sample sizes, and that the clinical importance of any differences on the measures used to assess pain control was not clear. The follow-up time was limited to a few days post-op. The authors concluded that there is no benefit to femoral nerve block in the majority of patients undergoing ACL reconstruction. 3 Fischer et al. (2008) published a systematic review and meta-analysis of studies evaluating analgesic, anesthetic or surgical interventions to minimize pain following TKA. 2,26 The authors searched MEDLINE and EMBASE (1966 to 2005) for English language RCTs in adults undergoing TKA. Studies were included if they assessed postoperative pain scores using a visual analog scale (VAS), a verbal rating scale or numerical rating scale. Methods for screening were not reported. The quality of articles were assessed according to the Jadad criteria, completeness of follow-up >80%, allocation concealment, and compliance with the CONSORT statement. Where data were available and study populations, interventions, and designs were similar, meta-analyses were conducted. In some cases, data suitable for meta-analysis were only available for a subset of relevant RCTs. Femoral Nerve Block for Total Knee and ACL Reconstruction 3

4 A total of 112 RCTs were included in the report and of these, 16 assessed the use of femoral or femoral and sciatic nerve block. 2,26 Of these included studies, 15 were rated by the review authors as higher quality and one was rated lower quality. The median sample size was 47 patients. Bupivacaine was the local anesthetic used in treatment arms in 14 studies and ropivacaine was used in four studies. In six of eight studies, single dose femoral nerve block was associated with lower pain scores compared to placebo, no treatment or systemic analgesics (piritramide plus diclofenac). The weighted mean difference (WMD) in visual analog scale (VAS) pain scores were statistically significantly lower during motion in the block versus sham block groups at 24 hours and at 48 hours following surgery (Table 2). The difference in pain scores at rest was not statistically significant between treatments. Four of seven RCTs reported that the consumption of morphine was statistically significantly lower in the block versus control groups. Three of these studies were suitable for pooling. Meta-analysis showed the block group consumed 25.9 mg less of morphine (95% CI to -2.2, p=0.03) than the control group, 0 to 48 hours after surgery. Two of three studies reported improved functional outcomes in the block versus placebo or no treatment groups. No difference in the incidence of nausea and vomiting was detected in seven of eight RCTs. The incidence of respiratory depression, pruritus, dizziness and urinary retention was similar in the block and control groups in four of four studies. There was no statistically significant difference in the length of hospital stay in three of four studies that assessed this outcome. 2,26 Table 2. Summary of pooled data from Fischer et al. 2 Comparison Outcome Number of studies, patients Single dose VAS pain scores (mm) during 3 studies femoral block vs. motion/physical therapy at 24 h N=76 sham block VAS pain scores (mm) during 3 studies motion/physical therapy at 48 h N=76 VAS pain scores (mm) at rest at 3 studies 24 h N=76 VAS pain scores (mm) at rest at 3 studies 48 h N=76 Use of supplemental analgesia 3 studies (morphine in mg) from 0 to 48 h Continuous VAS pain scores (mm) during femoral block vs. motion/physical therapy at 24 h sham block/no VAS pain scores (mm) during treatment motion/physical therapy at 48 h VAS pain scores (mm) at rest at 24 h VAS pain scores (mm) at rest at 48 h mm=millimeter; VAS=visual analog scale; WMD=weighted mean difference * Negative values favor the block group. N=70 3 studies N=94 3 studies N=94 4 studies N=129 3 studies N=92 WMD (95% CI)* P value (-24.7 to -5.4) P= (-20.3 to -3.1) P= (-26.3 to 5.7) P= (-13.0 to 2.6) P= (-49.7 to -2.2) P= (-18.4 to -3.0) P= (-22.2 to -8.5) P< (-25.6 to -4.9) P= (-12.2 to -1.3) P=0.01 Femoral Nerve Block for Total Knee and ACL Reconstruction 4

5 All five RCTs comparing continuous infusion femoral block to placebo or no treatment reported lower pain scores in the block groups. 2,26 Pooled data showed statistically significant differences favoring the block groups on VAS pain scores at rest, and with movement, 24 hours and 48 hours after surgery (Table 2). The need for supplemental analgesics was statistically significantly lower in the block groups versus placebo or no treatment, in three of five studies (data not reported). The incidence of nausea and vomiting was similar between groups in three of four RCTs. One study reported higher rates of nausea and vomiting in the block versus control group (p value and rates not reported). 2,26 Two RCTs compared femoral block with ropivacaine to bupivacaine and found no statistically significant difference in pain scores or analgesic consumption between groups (Table 3). 2,26 Motor block occurred more frequently with ropivacaine in one study, but this did not prevent patients from ambulating. Pain scores and supplemental analgesic use were similar in patients who received femoral block and those who received spinal morphine in one RCT (Table 3). The incidence of nausea, vomiting and pruritus was statistically significantly lower in the block than the spinal morphine group. Three RCTs compared femoral or femoral and sciatic nerve block to epidural analgesia. These studies have been included in the systematic review by Fowler et al. 1 and so have not been described here. Table 3. Summary of RCTs comparing femoral block to active control 2,26 Interventions, Pain control outcomes Other outcomes number of patients Femoral block with bupivacaine vs. femoral block with ropivacaine N=48 Pain scores (with movement and at rest) and morphine consumption over 48 h NS different between ropivacaine and bupivacaine groups. SD femoral & sciatic block with ropivacaine vs. SD femoral & sciatic block with bupivacaine vs. no block N=74 SD Femoral block vs. spinal morphine N=40 Morphine use lower in bupivacaine (8 h to 48 h p<0.05) and ropivacaine (4 h to 24 h, p<0.05) vs. no block groups. Pain scores and morphine consumption over 48 h NS different between ropivacaine and bupivacaine groups. Pain scores and morphine consumption over 24 h NS different between groups. H=hour; NS=not statistically significant; post-op=post-operative; SD=single dose NS difference between groups on length of hospital stay, or incidence of nausea, vomiting, pruritus, or sedation. Emesis score lower in bupivacaine vs. no block at 8 h (p<0.05), NS difference between ropivacaine and no block. NS difference on sedation score between block groups and no block group. Emesis and sedations scores similar between ropivacaine and bupivacaine groups. Motor block greater in ropivacaine (but not bupivacaine) vs. no block group in first 24 h (p<0.05) but did not prevent mobilization. Incidence of nausea, vomiting and pruritus lower in block versus spinal morphine group (p<0.05 all cases). Femoral Nerve Block for Total Knee and ACL Reconstruction 5

6 The authors recommended femoral nerve block for patients undergoing TKA based on evidence showing reduced pain and reduced need for supplemental analgesics. Because of lack of data, they drew no conclusions on the comparative benefits of single versus continuous femoral block techniques. Heterogeneity between studies and the number of studies available limited the systematic review. The review authors also stated that additional information is needed on adverse events, and the impact of pain management on length of hospital stay and ability to attain rehabilitation goals. In 2008, Fowler et al. 1 published a systematic review and meta-analysis of studies in patients undergoing major knee surgery. The authors searched MEDLINE, EMBASE, PubMed, CINAHL, Bandolier and Cochrane databases (until April 2007) for RCTs comparing epidural analgesia with local anesthetic agents to peripheral nerve block in adults undergoing major knee surgery. The search for studies was not limited by language. The reports were screened and appraised by two authors. Quality was assessed according to the Jadad scale. Outcomes of interest were pain scores, adverse effects, patient satisfaction, and rehabilitation indices. Meta-analysis was conducted where sufficient data were available from three or more studies. 1 The report included eight studies, none of which were double blinded. The Jadad scores for the included RCTs ranged from one to three. Of the 510 patients enrolled in the trials (median 60 patients per study), 91% had undergone TKA and 6% had ACL reconstructions. A femoral nerve block was used in five studies, a femoral and sciatic nerve block was used in two studies, and lumbar plexus/sciatic block was used in one RCT. Bupivacaine, ropivacaine and lidocaine were the local anesthetic agents used for the peripheral nerve block in five, two and one study, respectively. 1 When the data were combined, there was no statistically significant difference in the VAS pain scores between comparators for the first 12 hours after surgery, and between 12 and 24 hours after surgery (Table 4). The mean pain scores in the epidural groups were statistically significantly lower compared to the peripheral nerve block group at 24 to 48 hours after surgery. Subgroup analyses for femoral and sciatic block, and femoral block alone, produced similar results. 1 Table 4. Summary of pooled data from Fowler et al. 1 Comparison Outcome Number of studies, patients Femoral block vs. epidural VAS pain scores 0 to 6 studies (all studies) 12 h N=310 VAS pain scores 12 h 7 studies to 24 h N=413 VAS pain scores 24 h 6 studies to 28 h Use of supplemental analgesia (morphine in mg) from 0 to 24 h Hypotension N=354 3 studies N=NR 4 studies N=235 WMD (95% CI)* P value 0.22 (-0.36 to 0.81) p= (-0.91 to 0.91) p= (-0.69 to -0.02) p= ( to 5.86) p value NR OR 0.19 (0.08 to 0.45) P< Femoral Nerve Block for Total Knee and ACL Reconstruction 6

7 Comparison Outcome Number of studies, patients Nausea or vomiting 5 studies WMD (95% CI)* P value OR 0.66 (0.28 to 1.55) P= (-0.32 to 0.82) p= (-1.91 to 1.79) p= (-1.19 to 2.06) p= (-1.08 to 1.03) p=0.96 N=218 Femoral block (with sciatic VAS pain scores 0 to 3 studies block) vs. epidural 12 h N=168 VAS pain scores 12 h 3 studies to 24 h N=168 Femoral block (without VAS pain scores 0 to 3 studies sciatic block) vs. epidural 12 h N=142 VAS pain scores 12 h 4 studies to 24 h N=245 H=hours; NR=not reported; OR=odds ratio; VAS=visual analog scale; WMD=weighted mean difference * data presented as WMD unless otherwise stated; Negative values favor the block group. There was no difference in morphine consumption, the rate of nausea and vomiting, pruritis or sedation between the femoral block and epidural groups (Table 4). 1 Urinary retention and hypotension occurred more frequently in the epidural treated patients (p<0.001). There was no difference between groups in the range of knee movement six months after surgery. Block failure was reported in four RCTs and occurred in 7.7% and 3.0% of patients in the epidural and peripheral block groups respectively. One major neurological complication was reported. One patient, who had received an epidural, experienced foot drop and sphincteric disturbance after surgery. No neurological complications were reported among patients who received a femoral block. The systematic review was limited by the number of patients and lack of blinding in the included RCTs. There was also variation in the type of peripheral nerve block used in the studies. The review authors concluded that peripheral nerve block provides comparable postoperative analgesia to epidurals with a better side-effect profile. 1 Randomized controlled trials A total of 18 RCTs met the inclusion criteria and are summarized in the Appendix. Of these, 14 studies (16 reports) enrolled patients undergoing TKA surgery, 4,6,8-15,17,18,20,22 three studies enrolled patients undergoing ACL reconstruction surgery and one study included TKA and ACL reconstruction patients. 16 The study sample size ranged from 23 to 280 patients (median 59 patients). Eight studies were rated as lower quality based on a Jadad score of 2 or less. 4,6,11,12,15,22,24,25 Most studies were not double blinded. 4,6,9,11,12,14-16,20,22-25 Nine studies compared femoral block to a placebo, sham block or no block group. 4,6,15-18,20,22,23 Active comparator groups included opioid patient controlled analgesia (2 studies), 11,14 IA infiltration (3 studies), 8,12,25 intrathecal morphine (1 study), 9 epidural analgesia (2 studies), 14,25 ketoprofen (1 study), 24 or another type of peripheral nerve block (8 studies). 4,6,10,13,16,18,22,23 In nine studies, 6,9,13,16-18,20,22,23 a single dose of local anesthetic (with or without other agents) was administered to achieve the femoral block, and in nine studies, 4,8,10-12,14,15,24,25 a continuous infusion of local anesthetic was used. Ropivacaine was the local anesthetic used in 13 studies, 4,8-16,20,23,25 bupivacaine in eight studies, 6,13,16-18,22-24 and levobupivacaine in one study. 10 In five studies a combined femoral and sciatic block was evaluated. 6,10,11,13,14 In most studies, patients received multi-modal pain control measures, such as NSAIDs, acetaminophen, and parenteral opioids, in addition to the experimental intervention. Femoral Nerve Block for Total Knee and ACL Reconstruction 7

8 Total knee arthroplasty Compared to placebo, sham block, or no block treatment, patients who received a femoral block reported statistically significantly lower post-operative pain scores in six of eight studies. 6,15,16,18,20,22 In two studies where patients received a single dose femoral block, pain scores were significantly lower than control on the day of surgery, but did not differ 10 hours to 48 hours after surgery. 16,20 Two studies found no difference in pain scores 4,17 or opioid use 18,22 between the block and no block groups. Consumption of opioids was statistically significantly lower in the block versus control groups in six RCTs. 4,6,15-17,20 Functional outcomes, such as ability to ambulate, or length of hospital stay, were similar in the block and no block groups in five of six RCTs reporting these measures. 4,15,17,18,22 The incidence of adverse events was similar between groups except for nausea, which occurred more frequently in the control group in three studies. 15,16,20 it should be noted that in all three of these studies, the control group consumed higher quantities of morphine. No serious block-related complications were reported in any of the studies. In two RCTs, a continuous femoral block (ropivacaine) was compared to IA injection of ropivacaine and ketorolac as a single dose 8 or multiple doses. 12 The differences in pain scores did not reach statistical significance in either study with one exception of one time point in one study. In the repeat dose IA study group, 12 pain scores were significantly lower with movement on day 1 post-op (p=0.001) compared to the femoral block group. The block group used significantly less morphine than the single dose IA group on post-op days 1 and 2. 8 The consumption of opioids was similar between groups in the second RCT. 12 Functional outcomes were similar in the groups up to six weeks after surgery. 8 Some early ambulation goals were reached by more patients in the IA group than the block group in one report. 12 One patient in the IA group developed deep infection, and two patients developed bullae on the wound, one of which became necrotic. 12 Intrathecal morphine was compared to a single dose femoral block (ropivacaine) in one RCT. 9 In this study, the intrathecal group reported statistically significantly lower pain scores six to 72 hours after surgery. Differences in the amount of morphine consumed did not reach statistical significance. Patient satisfaction, nausea, vomiting and itching were similar in both groups. 9 In a second trial that compared epidural analgesia (bupivacaine and fentanyl infusion) to continuous femoral and sciatic block (ropivacaine), no statistically significant differences were detected on pain scores or functional outcomes between the groups. 14 Compared to patient controlled analgesia (PCA) with morphine, a combined femoral and sciatic nerve block showed statistically significantly lower post-operative pain scores. 11,14 One RCT reported lower morphine use in the block versus the PCA group on day 1 (p<0.001) but not on days 2 or Functional recovery was similar between groups in both studies. 11,14 Neither study reported on adverse events. Three studies compared peripheral blocks using different local anesthetic agents. 10,13,16 No differences were detected between ropivacaine and levobupivacaine administered as a PCA femoral block infusion. 10 One patient who received levobupivacaine was unable to ambulate due to motor block. 10 In the two studies that compared bupivacaine to ropivacaine, differences between groups on pain scores, morphine use, or adverse effects were not statistically Femoral Nerve Block for Total Knee and ACL Reconstruction 8

9 significant. 13,16 Three patients experienced paresthesia while the anesthetist was performing the block that was resolved by redirecting the needle. 13 Anterior cruciate ligament reconstruction Among patients undergoing arthroscopic ACL reconstruction surgery, one study compared single dose femoral block with either ropivacaine 0.25%, ropivacaine 0.75% or bupivacaine 0.25%, to a placebo femoral block (saline injection). 23 This study enrolled 280 patients with a mean age of 30 to 33 per treatment group. Patients in the femoral block groups had statistically significantly lower pain scores and lower use of other pain medications in the first 24 hours post-op than the placebo group. No differences were detected between block groups on pain control, and no block related complications were reported. 23 A second RCT compared a continuous femoral block with bupivacaine plus clonidine to IV ketoprofen (n=60, mean age 24 ). 24 Patients in the ketoprofen group reported significantly higher pain scores and required on average of 21 more mg of morphine over 48 hours than the femoral block group (p<0.001). More patients in the ketoprofen group experienced nausea and vomiting (p<0.01) and had lower satisfaction scores (p<0.05) than the block group. 24 A third RCT compared continuous post-operative femoral block to an epidural block or IA infiltration of ropivacaine and sufentanil solution. 25 Sixty patients were enrolled with a mean age varying from 28 to 33 per treatment group. No significant difference was detected on pain scores between the epidural and femoral block groups. The IA group reported higher pain scores than the other two groups however these differences reached statistical significance compared to the epidural group at one time point only. Urinary retention was reported more frequently among patients who received an epidural, but the incidence of other adverse effects was similar between groups. 25 None of the studies of patients undergoing ACL reconstruction met the Jadad criteria for adequate double blinding. In one study, the anesthesia that patients received during surgery was not the same for all groups. 25 Two groups were given an epidural, and the third group received a lumbar plexus and sciatic block. 25 Limitations This rapid review is limited by the literature search methods which were not as comprehensive as those used for a systematic review. Most of the included studies did not clearly indicate if the patient or proxy (e.g., health-care provider) assessed the patient s level of pain. This, combined with the lack of adequate blinding in most of the studies, can potentially lead to observer bias. This is of particular concern for subjective outcomes such as pain. Although numerous RCTs were identified in the search, most enrolled a limited number of patients with inadequate numbers to capture uncommon adverse events. In the individual RCTs, withdrawals generally did not exceed 10%, however considering the limited number of patients enrolled in many of the studies, this could bias the findings. The intervention and control treatments varied across studies, making comparison between studies difficult. In addition, co-interventions were not always the same within treatment arms of the same study and between different studies. The follow-up of patients was, in almost all studies, limited to a few days following surgery which limits the ability to make any conclusions about longer-term outcomes. The authors of one of the Femoral Nerve Block for Total Knee and ACL Reconstruction 9

10 systematic reviews commented that the clinical significance of differences in scores on the instruments used to assess pain were not clear. 3 CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING: Evidence from one systematic review and eight individual RCTs suggests that for patients undergoing TKA, femoral nerve block reduces pain scores and analgesic use when compared to placebo, sham block, or no block. These benefits, however, were not consistent across studies. Femoral block appears to offer similar pain control as epidural analgesia based on one systematic review of eight trials and one additional RCT. Based on data from four RCTs, ropivacaine and bupivacaine appear equally effective in controlling post-operative pain. The evidence to support the use of femoral block in patients undergoing ACL reconstruction is less clear. Although some individual studies demonstrated a benefit in pain control with the femoral block, authors of one systematic review concluded there was no benefit for the majority of patients. Few studies reported on functional outcomes or length of hospital stay, so no conclusion can be made about these outcomes. No conclusions can be drawn regarding the safety of femoral nerve block due to poor reporting of adverse events and the small sample size of studies. No evidence was found regarding the cost-effectiveness, or guidelines for use of femoral nerve block, thus no conclusions can be made. PREPARED BY: Health Technology Inquiry Service htis@cadth.ca Tel: Femoral Nerve Block for Total Knee and ACL Reconstruction 10

11 REFERENCES: 1. Fowler SJ, Symons J, Sabato S, Myles PS. Epidural analgesia compared with peripheral nerve blockade after major knee surgery: a systematic review and meta-analysis of randomized trials. Br J Anaesth [Internet] Feb [cited 2010 Aug 27];100(2): Available from: 2. Fischer HB, Simanski CJ, Sharp C, Bonnet F, Camu F, Neugebauer EA, et al. A procedure-specific systematic review and consensus recommendations for postoperative analgesia following total knee arthroplasty. Anaesthesia Oct;63(10): Mall NA, Wright RW. Femoral nerve block use in anterior cruciate ligament reconstruction surgery. Arthroscopy Mar;26(3): Seet E, Leong WL, Yeo AS, Fook-Chong S. Effectiveness of 3-in-1 continuous femoral block of differing concentrations compared to patient controlled intravenous morphine for post total knee arthroplasty analgesia and knee rehabilitation. Anaesth Intensive Care Feb;34(1): Jeng CL, Rosenblatt MA. Overview of peripheral nerve blocks May [cited 2010 Aug 27]. In: UpToDate [Internet]. Version Waltham (MA): UpToDate; c Available from: Subscription required. 6. Hunt KJ, Bourne MH, Mariani EM. Single-injection femoral and sciatic nerve blocks for pain control after total knee arthroplasty. J Arthroplasty Jun;24(4): Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials [Internet] [cited 2010 Aug 19];17(1):1-12. Available from: 8. Carli F, Clemente A, Asenjo JF, Kim DJ, Mistraletti G, Gomarasca M, et al. Analgesia and functional outcome after total knee arthroplasty: periarticular infiltration vs continuous femoral nerve block. Br J Anaesth Aug;105(2): Frassanito L, Vergari A, Zanghi F, Messina A, Bitondo M, Antonelli M. Post-operative analgesia following total knee arthroplasty: comparison of low-dose intrathecal morphine and single-shot ultrasound-guided femoral nerve block: a randomized, single blinded, controlled study. Eur Rev Med Pharmacol Sci Jul;14(7): Heid F, Muller N, Piepho T, Bares M, Giesa M, Drees P, et al. Postoperative analgesic efficacy of peripheral levobupivacaine and ropivacaine: a prospective, randomized doubleblind trial in patients after total knee arthroplasty. Anesth Analg [Internet] May [cited 2010 Aug 27];106(5): Available from: Fletcher D, Martin F, Martinez V, Mazoit JX, Bouhassira D, Cherif K, et al. Antiinflammatory effect of peripheral nerve blocks after knee surgery: Clinical and biologic Femoral Nerve Block for Total Knee and ACL Reconstruction 11

12 evaluation. Anesthesiology [Internet] [cited 2010 Aug 27];109(3): Available from: eripheral_nerve_blocks.19.aspx 12. Toftdahl K, Nikolajsen L, Haraldsted V, Madsen F, Tønnesen EK, Søballe K. Comparison of peri- and intraarticular analgesia with femoral nerve block after total knee arthroplasty: a randomized clinical trial. Acta Orthop [Internet] Apr [cited 2010 Aug 27];78(2): Available from: Beaulieu P, Babin D, Hemmerling T. The pharmacodynamics of ropivacaine and bupivacaine in combined sciatic and femoral nerve blocks for total knee arthroplasty. Anesth Analg [Internet] Sep [cited 2010 Aug 27];103(3): Available from: Mistraletti G, De La Cuadra-Fontaine JC, Asenjo FJ, Donatelli F, Wykes L, Schricker T, et al. Comparison of analgesic methods for total knee arthroplasty: metabolic effect of exogenous glucose. Reg Anesth Pain Med May;31(3): Kadic L, Boonstra MC, DE Waal Malefijt MC, Lako SJ, VAN Egmond J, Driessen JJ. Continuous femoral nerve block after total knee arthroplasty? Acta Anaesthesiol Scand Aug;53(7): de Lima E Souza, Correa CH, Henriques MD, de Oliveira CB, Nunes TA, Gomez RS. Single-injection femoral nerve block with 0.25% ropivacaine or 0.25% bupivacaine for postoperative analgesia after total knee replacement or anterior cruciate ligament reconstruction. J Clin Anesth Nov;20(7): Good RP, Snedden MH, Schieber FC, Polachek A. Effects of a preoperative femoral nerve block on pain management and rehabilitation after total knee arthroplasty. Am J Orthop Oct;36(10): Kardash K, Hickey D, Tessler MJ, Payne S, Zukor D, Velly AM. Obturator versus femoral nerve block for analgesia after total knee arthroplasty. Anesth Analg [Internet] Sep [cited 2010 Aug 27];105(3): Available from: Bergeron SG, Kardash KJ, Huk OL, Zukor DJ, Antoniou J. Functional outcome of femoral versus obturator nerve block after total knee arthroplasty. Clin Orthop [Internet] Jun [cited 2010 Aug 27];467(6): Available from: Özen M, Inan N, Tümer F, Uyar A, Baltaci B. The effect of 3-in-1 femoral nerve block with ropivacaine 0.375% on postoperative morphine consumption in elderly patients after total knee replacement surgery. Agri derg [Internet] Oct [cited 2010 Aug 27];18(4): Available from: Femoral Nerve Block for Total Knee and ACL Reconstruction 12

13 21. Shum CF, Lo NN, Yeo SJ, Yang KY, Chong HC, Yeo SN. Continuous femoral nerve block in total knee arthroplasty: immediate and two-year outcomes. J Arthroplasty Feb;24(2): Tugay N, Saricaoglu F, Satilmis T, Alpar U, Akarcali I, Citaker S, et al. Single-injection femoral nerve block. Effects on the independence level in functional activities in the early postoperative period in patients with total knee arthroplasty. Neurosciences. 2006;11(3): Wulf H, Löwe J, Gnutzmann KH, Steinfeldt T. Femoral nerve block with ropivacaine or bupivacaine in day case anterior crucial ligament reconstruction. Acta Anaesthesiol Scand Apr;54(4): Contreras-Domínguez VA, Carbonell-Bellolio PE, Ojeda-Greciet AC, Sanzana ES. Extended three-in-one block versus intravenous analgesia for postoperative pain management after reconstruction of anterior cruciate ligament of the knee. Revista Brasileira de Anestesiologia. 2007;57(3): Dauri M, Polzoni M, Fabbi E, Sidiropoulou T, Servetti S, Coniglione F, et al. Comparison of epidural, continuous femoral block and intraarticular analgesia after anterior cruciate ligament reconstruction. Acta Anaesthesiol Scand Jan;47(1): Prospects: procedures specific postoperative pain management [Homepage]. Geneva: European Society of Regional Anaesthesia and Pain Therapy. Procedures specific postoperative pain management; 2010 Jan 20 [cited 2010 Aug 27]. Available from: Femoral Nerve Block for Total Knee and ACL Reconstruction 13

14 Appendix 1: Summary of Included Randomized Controlled Trials Study, Jadad score Population total N, age, sex Intervention groups, Other pain medications Pain control TKA Active comparator Carli Primary unilateral TKA R: 2 B: 1 Jadad total: 4 Frassanito R: 2 Jadad total: 3 N= 40 Mean age: 71 Male: 28% Elective unilateral TKA N=52 Mean age: 68 Male: 63% + placebo IA infiltration (ropivacaine infusion 48 h) 2. IA infiltration + placebo femoral block (ropivacaine + epi + ketorolac) Spinal anesthesthesia, morphine PCA, oxycodone, celecoxib, acetaminophen (SD ropivacaine) 2. IT morphine Spinal anesthesia, PCA morphine, ketorolac, acetaminophen Differences in pain scores did not reach statistical significance. Block group used less morphine than the IA group in first 2 days postop (mean difference day 1: 11.5 mg, day 2: 10.5 mg, p=0.02 between groups). IT group had significantly lower pain scores from 6 h to 72 h post-op vs. femoral block group (p<0.05). IT group used less PCA morphine than femoral block group but the difference was not statistically significant. Functional & other outcomes There was no difference between groups on the distance travelled in the 2 min walk test in the first 72 h postop, or in the 6 min walk test at 6 weeks. Patient satisfaction was similar in both groups. Adverse events Incidence of nausea was higher in the block than in the IA group on day 2 (p=0.04) but not on day 1. No hospital readmissions in first 30 days post-op. Incidence of nausea, vomiting, and itching was not significantly different between groups. No incidents of respiratory depression occurred. Femoral Nerve Block for Total Knee and ACL Reconstruction 14

15 Study, Jadad score Heid R: 2 B: 1 Jadad total: 4 Martin R: 1 Jadad total: 2 Population total N, age, sex TKA N=60 Mean age: 70 Male: 32% TKA N=40 Mean age: 68 Male: 25% Intervention groups, Other pain medications 1. SD sciatic + 72 h femoral block (ropivacaine PCA) 2. SD sciatic + 72 h femoral block (levobupivacaine PCA) General anesthesia, acetaminophen, piritramid (opioid) 1. SD sciatic + 48 h femoral block (ropivacaine infusion) 2. morphine PCA General anesthesia, morphine PCA, acetaminophen, Pain control The volume of local anesthetic and number of PCA doses was similar in the groups. Pain intensity and need for opioid was similar in both groups. Pain scores at rest and with movement were lower in block vs. PCA group on day 1 to 7 (p=0.005). No difference between groups on pain scores after 1 or 3 months. Functional & other outcomes Patient satisfaction with pain management did not differ between groups. There was no difference between groups in functional recovery after 3 months. Adverse events One patient in levobupivacaine unable to ambulate due to motor block NR Morphine use was significantly lower in block vs. PCA group on day 0 and 1 (p<0.001). Differences were not statistically significant on day 2 or 3 post-op. Femoral Nerve Block for Total Knee and ACL Reconstruction 15

16 Study, Jadad score Toftdahl R: 1 Jadad total:2 Beaulieu R: 2 B: 2 Jadad total: 5 Population total N, age, sex Primary TKA N=80 Mean age: 71 Male: 39% Unilateral TKA N=50 Mean age: 66 Male: 39% Intervention groups, Other pain medications (ropivacaine infusion 48 h) + IA infiltration (SD morphine + bupivacaine) 2. IA infiltration + placebo femoral block (3 doses every 12 h of ropivacaine + epi + ketorolac) Spinal anesthesia, acetaminophen, ibuprofen, oxycodone, rescue IV morphine 1. femoral + sciatic block (SD bupivacaine) 2. femoral + sciatic block (SD ropivacaine) General anesthesia, morphine PCA, acetaminophen Pain control Pain scores at rest were similar in both groups. With movement, the IA group reported a lower pain score on day 1 (p=0.001) but not day 2 (p=0.7) compared to the block group. Consumption of opioids was similar in the groups over the first 4 days postop. Pain scores at rest and with movement were not significantly different between groups at 12 of 16 time points in the first 48 h. Total morphine use was similar in the groups. Functional & other outcomes Significantly more patients were able to walk >3 m on day 1 and day 2 in the IA group compared to the block group (p<0.05). Median length of stay was not significantly different between the groups. NR Adverse events The incidence of nausea, vomiting, dizziness, itching or constipation was similar in the groups. In the IA group one patient developed deep infection and two patients developed bullae on their wound. No long-term complications related to the nerve block were reported. Three patients experienced paresthesia while performing the block that was resolved by redirecting the needle. Femoral Nerve Block for Total Knee and ACL Reconstruction 16

17 Study, Jadad score Mistraletti R: 2 Jadad total: 3 Population total N, age, sex Primary unilateral TKA N=27 Mean age: 64 to 70 Male: 33% TKA Placebo control Kadic Primary TKA R: 1 Jadad total: 2 Hunt R: 0 W: 0 Jadad total: 0 N=58 Mean age: 67 Male: 26% TKA N=88 Mean age: 69 Male: 30% Intervention groups, Other pain medications 1. femoral + sciatic block (SD lidocaine+epi, ropivacaine 48 h infusion) 2. epidural (bupivacaine + fentanyl infusion) 3. morphine PCA Spinal anesthesia, naproxen, acetaminophen, rescue opioids (ropivacaine infusion 48 h) 2. no block Spinal anesthesia, diclofenac, acetaminophen, rescue morphine PCA (SD bupivacaine) 2. femoral +sciatic block (SD bupivacaine) 2. placebo block (SD saline) General anesthesia, morphine PCA Pain control Pain scores were statistically significantly lower in the femoral block vs. the PCA group at rest and with movement in the first 48 h post-op. No difference on pain scores was detected between the epidural and femoral block groups. Femoral block group had significantly lower pain scores, and lower morphine use vs. no block group for first 48 hours (p<0.01). Patients in the block groups reported lower pain scores up to post-op day 2 (p<0.05) and lower morphine for first 36 hours post-op (p<0.05) vs. sham block group. Functional & other outcomes Time out of bed, time to walk, and length of stay were similar between groups. Knee flexion and function scores were similar between groups at 3 months. Femoral block patients reported greater satisfaction with pain control in first 48 hours than control patients (p=0.001). NR Adverse events NR More patients in the control group reported nausea (p=0.001). No paraesthesia, nerve damage, or other nerve block related complications were reported. NR Femoral Nerve Block for Total Knee and ACL Reconstruction 17

18 Study, Jadad score De Lima esouza R: 2 Jadad total: 3 Population total N, age, sex TKA or ACL reconstruction N=96 Mean age 54 to 61 Male 42% ACL: 31% TKA: 69% Intervention groups, Other pain medications (SD bupivacaine+epi) 2. femoral block (SD ropivacaine) 3. no block Spinal anesthesia, codeine/acetaminophen, tenoxican, morphine IV Pain control Up to 10 hours post-op, patients in block groups had lower pain scores at rest and with movement than those in control group (p<0.05) No difference detected from 10 to 24 hours post-op. No difference in pain scores between bupivacaine and ropivacaine groups in first 24 hours. Functional & other outcomes More patients in the block groups were satisfied with pain management than in the control group (80% vs. 46%, p<0.05). Adverse events Incidence of vomiting, sedation, pruritus and urinary retention similar between groups. Incidence of nausea was higher in control group than the block groups (p=0.001). Good R: 1 B: 2 W: 0 Jadad total: 3 TKA N=42 Mean age: 70 Male: 62% (SD bupivacaine+epi) 2. placebo block (saline) Anesthesia type NR, morphine PCA Use of morphine lower in block groups vs. control but not statistically significant for all time points. No difference between groups on pain scores for first 72 hours. Block group used significantly less morphine than control group (mean difference 12.0 mg p=0.016) over 4 days. Ambulation distances were similar in each group. Incidence of adverse events was similar between groups. Femoral Nerve Block for Total Knee and ACL Reconstruction 18

19 Study, Jadad score Kardash ,19 R: 1 B: 1 Jadad total:3 Ozen R: 2 Jadad total: 3 Population total N, age, sex Elective unilateral TKA N=60 Mean age: 65 to 72 Male: 22% Unilateral TKA N=34 Mean age: 64 y ears Male: 30% Intervention groups, Other pain medications (SD bupivacaine+epi) 2. obturator block (SD bupivacaine+epi) 2. sham block Spinal anesthesia, PCA fentanyl, celecoxib, acetominophen (SD ropivacaine) 2. no block General anesthesia, morphine PCA Pain control Pain at rest or with movement similar between groups on day 1 or day 2 post-op. Pain score change from baseline significantly better in femoral vs. sham group (p=0.02) Fentanyl or other pain medication use was similar between groups. Pain scores were significantly lower in the block group vs. the control group for the first 8 h post-op. Pain scores were similar 10 h to 48 h post-op. Morphine consumption in first 48 h significantly lower in the block group vs. control (mean difference 45.2 mg, p<0.001) Functional & other outcomes No difference detected between groups for time in recovery room, knee flexion, or total hospital stay. HSS knee score similar between groups 6 weeks and 1 year post-op NR Adverse events One patient with persistent numbness in femoral block group, which resolved after 5 days. No difference in incidence of urinary retention, nausea, pruritus, or sedation. No block related complications were reported. More patients in the control group reported nausea or vomiting than the block group (p value not reported). Femoral Nerve Block for Total Knee and ACL Reconstruction 19

20 Study, Jadad score Seet ,21 R: 1 Jadad total: 2 Tugay R: 1 W: 0 Jadad total: 1 ACL Reconstruction Population total N, age, sex Elective unilateral TKA N=60 Mean age: 66 Male: 20% Elective TKA N=23 Mean age: 66 Male: 13% Intervention groups, Other pain medications (ropivacaine 0.15% infusion for 48 h) 2. femoral block (ropivacaine 0.2% infusion for 48 h) 3. no block Spinal anesthesia, morphine PCA, acetaminophen, rofecoxib (SD bupivacaine post-op) 2. femoral block (SD bupivacaine pre-op) 3. no block General anesthesia, morphine PCA Pain control Pain scores at rest and with movement were not significantly different between groups in first 72 h post-op. The control group consumed more morphine than either block group (p<0.05). There was no difference between block groups on morphine use. Pain scores in first 48 h were significantly higher in the control than in the block groups (p<0.02). No difference was detected between preand post-op block groups. Total morphine use was similar among groups. Functional & other outcomes Median day of first ambulation and duration of hospital stay were similar between groups. Functional outcomes 2 after surgery were similar in the block and control groups. No significant differences were detected between groups on functional scores, ambulation velocity or length of stay. Adverse events No difference in incidence of nausea and vomiting, pruritus, urinary retention, hypotension, giddiness, or sedation. No block related complications occurred. NR Femoral Nerve Block for Total Knee and ACL Reconstruction 20