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We previously provided evidence that extending an overnight continuous femoral nerve block to 4 days after tricompartment knee arthroplasty (TKA) provides clear benefits during the perineural infusion in the immediate postoperative period. However, it remains unknown if the extended infusion improves subsequent health-related quality of life between 7 days and 12 months.
Patients undergoing TKA received a femoral perineural infusion of ropivacaine 0.2% from surgery until the following morning, at which time patients were randomized to either continue perineural ropivacaine (n=25) or normal saline (n=25) in a double-masked fashion. Patients were discharged with their catheter and a portable infusion pump, and catheters were removed on postoperative day 4. Health-related quality of life was measured using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index preoperatively and then at 7 days, as well as 1, 2, 3, 6, and 12 months after surgery. The WOMAC evaluates 3 dimensions of health-related quality of life: pain, stiffness and physical functional disability. For inclusion in the analysis, we required a minimum of 4 of the 6 time points, including day 7 and at least 2 of months 3, 6 and 12.
The 2 treatment groups had similar WOMAC scores for the mean area under the curve calculations (point estimate for the difference in mean area under the curve for the 2 groups [overnight infusion group − extended infusion group]=1.2, 95% confidence interval: −5.6 to +8.0; p=0.72) and at all individual time points (p>0.05).
We found no evidence that extending an overnight continuous femoral nerve block to 4 days improves (or worsens) subsequent health-related quality of life between 7 days and 12 months after TKA. (ClinicalTrials.gov number, NCT00135889.)
While knee arthroplasty reduces chronic joint pain and improves patients’ functional status, the prostheses rarely completely abolish pain and restore functional performance to a normal level.1–4 Improved surgical outcomes, such as knee range-of-motion, are associated with improved analgesia and physical therapy in the immediate postoperative period.5;6 Furthermore, improving postoperative analgesia may decrease the incidence of chronic pain,7 and increasing joint motion may optimize subsequent functioning by decreasing the effects of immobilization on muscles and synovial joints.8 Thus, there is indirect evidence that maximizing analgesia in the immediate postoperative period may lead to decreased long-term pain, joint stiffness and functional disability.
One intervention that has been shown to improve analgesia after tricompartment total knee arthroplasty (TKA) is a continuous femoral nerve block.9–11 Unlike traditional IV opioid administration or epidural infusion, a continuous femoral nerve block may be continued after discharge using a portable infusion pump, providing extended-duration treatment without requiring prolonged hospitalization.12 Therefore, an extended-duration continuous femoral nerve block after TKA offers the theoretical possibility of “long-term benefits from a short-term intervention.”13
Indeed, a continuous femoral nerve block for only 48–72 hours after TKA is associated with accelerated passive knee flexion for up to 6 weeks after catheter removal.10;11 However, the most important outcomes for patients are measures of functional status and well-being.14 These measures reflect the dimensions of health as they are conceptualized and valued by patients themselves.15 Although health-related quality of life is a subjective concept, various instruments are available that convert health status into quantifiable values.15;16 The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is an instrument specifically designed to evaluate clinically important, patient-relevant changes in health-related quality of life after treatment interventions in patients with osteoarthritis of the knee.17;18 The WOMAC evaluates 3 dimensions of health-related quality of life: pain, stiffness and physical functional disability. Whether accelerated recovery in passive knee flexion that results from a continuous femoral nerve block translates into increased health-related quality of life remains unknown.10;11
Therefore, we completed this prospective follow-up study of a previously reported, randomized, controlled clinical trial.9 We hypothesized that, as measured using the WOMAC instrument, the improvement in pain, stiffness and functional ability would be greater not only at 1 week, but also at 1, 2, 3, 6, and 12 months after TKA in patients who received a 4-day continuous femoral nerve block, compared with an overnight continuous femoral nerve block in the immediate postoperative period.
The IRB approved all study procedures and all subjects provided written, informed consent. Details of the study methods have been published previously.9 In brief, patients offered enrollment included adults (18–80 years) with osteoarthritis scheduled for primary, unilateral, tricompartment, cemented TKA via a 12–18 cm midline skin incision and parapatellar approach, and who desired a continuous femoral nerve block for postoperative analgesia.
Subjects received a femoral nerve block and perineural catheter (StimuCath, Arrow International, Reading, PA) followed by a perineural ropivacaine, 0.2%, infusion (8 mL/h basal; 4 mL patient-controlled bolus; 30-min lockout) from surgery until the following morning, at which time patients were randomized to either continue perineural ropivacaine (“extended infusion,” n=25) or switched to normal saline (“overnight infusion,” n=25). Randomization was performed in a triple-masked fashion (patients, investigators, statisticians) with stratification according to clinical site. Additional analgesics included 1 week of oral acetaminophen (975 mg every 6 h), a sustained-release oral opioid (Oxycontin, 10 mg every 12 h), and either oral aspirin (650 mg daily) or celecoxib (200 mg every 12 h). Patients were provided oral (oxycodone 5 mg tablets) and/or IV opioids (morphine sulfate 2–4 mg) for breakthrough pain.
At 18:00 on postoperative day (POD) 2 (36 h after randomization), a portable infusion pump (Pain Pump 2 Blockaid, Stryker Instruments, Kalamazoo, MI) containing 400 mL of the same study solution (basal 5 mL/h; bolus 4 mL; lock-out 60 min) replaced the previous infusion pump. Patients were discharged with their pump and perineural catheter in situ as early as 10:00 on POD 3. In the evening of POD 4, patients’ caretakers removed the femoral catheters with physician instructions provided by telephone.
The current study was a planned secondary analysis of prospectively collected health-related quality-of-life data, as measured with the WOMAC questionnaire. This instrument evaluates 3 dimensions: pain, stiffness and physical functional disability with 5, 2, and 17 questions, respectively. An ordinal Likert scale from 0 to 4 is used for each question, with lower scores indicating lower levels of symptoms or physical disability.17 Each subscale is summated to a maximum score of 20, 8, and 68, respectively. The individual dimensions are always analyzed separately, and investigators have often added a “global” score, which is calculated by summating the scores for the 3 subscales.20;21 The questionnaire may be self-administered or administered via telephone and takes 5–10 minutes to complete.22–24 Because it is a proprietary instrument, the questionnaire itself may not be published and is therefore not included in an appendix.
Since its inception 2 decades ago, the WOMAC has been translated into 60 languages and used in several hundred published clinical trials.25 It has been rigorously examined, demonstrating excellent construct validity, responsiveness, and test-retest reliability in patients after total knee replacement;17;20;22;23;26–31 it is therefore recommended in the Osteoarthritis International Research Society’s guidelines for clinical trials.25;28;30–36
Therefore, to investigate the relationship between postoperative analgesic technique and subsequent health-related quality of life, a baseline WOMAC was administered prior to surgery (POD 0), and again at 7 days as well as 1, 2, 3, 6, and 12 months after surgery. The baseline measurement was a self-administered written questionnaire, whereas subsequent measurements after hospital discharge were administered via the telephone. Scores from self-administered and telephone-administered WOMAC instruments have a demonstrated error rate of 0.9–2.6%.24
The study was powered for the 2 previously published primary end-points (1) time to attain 3 discharge criteria (adequate analgesia, independence from IV analgesics and ambulation of at least 30 m), and (2) ambulatory distance in 6 minutes the afternoon after surgery.9 To analyze the WOMAC scores, the WOMAC responses were joined by straight lines between timepoints from POD 7 (t=0.25 months) to t=12 months. The personal progress estimated mean area under the curve was defined as the integral of this curve from 0.25 to 12, divided by 11.75 months. The WOMAC hypotheses asked the question of whether overall personal means over a continuum for 12 months of the WOMAC scores (mean area under the curve) differ between treatment groups.
The mean area under the curve measurements were compared by a 2-sided Z-test with non-pooled variance estimates, as the primary question of the null hypothesis that the 2 groups have the same WOMAC profile over time. To be included in this specific analysis, we required a minimum of 4 of the 4 time points, including day 7 and at least 2 of months 3, 6, and 12. The trapezoidal rule, above, effectively imputes missing values by linear interpolation between the values on either side of the one missing or in the case of month 12, linear extrapolation from the values of months 3 and 6. If the extrapolated value was below zero, a value of zero was used as month 12. Note that the point and interval estimates did not require the stringent inclusion criteria described for the mean area under the curve calculation, and they presume a missing at random assumption. However, under the null hypothesis that the treatments are equivalent with respect to the WOMAC, the method does provide a valid approximation to the permutational t-test and hence a valid p-value.37 Additional analysis involved timepoint by timepoint comparisons followed by 2-sided Z-tests.
Details of the study results for the immediate postoperative period have been published previously.9 For the mean area under the curve calculations, follow-up WOMAC data meeting our stringent inclusion criteria (a minimum of 4 of the 6 timepoints, including day 7 and at least 2 of months 3, 6, and 12) were available from 17 subjects (68%) from the extended infusion and 15 (60%) subjects from the overnight infusion groups. The 2 treatment groups had similar WOMAC scores for the mean area under the curve calculations (point estimate for the difference in mean area under the curve for the 2 groups [overnight infusion group − extended infusion group]=1.2, 95% confidence interval: −5.6 to +8.0; p=0.72). For the remaining analyses, only 1 subject from each treatment group was completely lost to follow-up, and 3 subjects randomized to the extended infusions withdrew from the study, resulting in available data for 45 subjects (90%). However, the 2 treatment groups had similar WOMAC scores at all individual time points in terms of both raw scores and changes from baseline (p>0.05; Fig. 1 and and2,2, and Tables 1 and and22).
From the ropivacaine group, 2 subjects requested study withdrawal on POD 0 prior to any study intervention, and an additional subject requested withdrawal on POD 1 after experiencing a myocardial infarction. Data were not collected on these subjects subsequent to study withdrawal as mandated by United States ethical guidelines.39 A 56-year-old subject from the ropivacaine group suffered a pulmonary embolism on POD 3, but was discharged without sequelae after aggressive anticoagulation. One 74-year-old subject from the ropivacaine group fell walking into his house for the first time after being discharged the morning of POD 3. No injury occurred, but he was readmitted to the hospital for overnight observation. For purposes of analysis, each of these subjects was retained in their respective treatment group per the intention-to-treat principle.
This prospective investigation found no evidence that extending an overnight continuous femoral nerve block to 4 days improves subsequent health-related quality of life between 7 days and 12 months following TKA. The lack of treatment effect after perineural catheter removal contrasts with the clear benefits provided during the infusion, as demonstrated in multiple randomized, controlled trials.9–11;19 Therefore, a lack of long-term effect for an extended-duration femoral perineural infusion is disappointing as there are both theoretical reasons and clinical data suggesting that improving analgesia in the immediate postoperative period may decrease long-term pain, reduce joint stiffness and improve functional status.5–8 However, extending the continuous femoral nerve block to 4 days also resulted in no apparent outcome detriments, and therefore the previously reported continuous femoral nerve block benefits in the immediate postoperative period are not negated by this WOMAC follow-up data.9
Two previous studies found that, after TKA or knee arthrolysis, using a 48- or 72-hour hospital-based continuous femoral nerve block compared with opioids alone resulted in subsequent increased passive knee flexion for up to 6 postoperative weeks.10;11 Whether this acceleration in range-of-motion was associated with increased health-related quality of life is unknown, as this dimension of health was not studied. It is therefore noteworthy that subjects of the current study randomized to the 4 days of perineural ropivacaine infusion demonstrated increased passive knee flexion in a range similar to that of previous studies during the infusion (approximately 10–15°),9 as it is probable that the post-infusion flexion increases were similar to those reported in the prior studies. Given the lack of improvement in post-infusion stiffness and physical functioning found in the current study, the value of accelerated passive knee flexion provided by a continuous femoral nerve block requires further investigation. This relationship may be analogous to continuous passive motion after TKA: short-term benefits, such as increased range-of-motion and decreased hospitalization duration, have not been matched with subsequent long-term benefits.38
The WOMAC scores were secondary outcomes for the original study and thus do not have the statistical strength of primary outcomes. In addition, the individual means, variances and covariances at and between specific timepoints provided by this study may be used as planning variables for future investigations. Lastly, the intervention protocol used in this investigation reflected our clinical practice during the study period. However, little data are available to define the optimal post-TKA infusion protocol. Importantly, 10 subjects (43%) of the ropivacaine group had their basal ropivacaine infusion halved the day after surgery because of quadriceps weakness verses 3 subjects (12%) of the placebo group.9 One of the 10 subjects in the ropivacaine group required a second halving of her basal rate because of continued quadriceps weakness9 It is possible that an alternative infusion protocol would result in different findings than the current study.
Future studies should consider the probable difficulties in contacting subjects over the course of a full year: of 50 subjects randomized in the current study, only 32 (64%) provided a minimum of 4 of the 6 WOMACs, including day 7 and at least 2 of months 3, 6, and 12. Simple subject retention is far easier; in our study, we had only 1 subject in each treatment arm lost to follow-up, but collecting a nearly complete sample at all timepoints proved to be more challenging.
The authors gratefully acknowledge the invaluable assistance of Marina Nekhendzy, Research Coordinator, Department of Anesthesiology, University of California San Diego (San Diego, California); Jennifer Woodard, BS, Research Coordinator, Department of Anesthesiology, University of Florida (Gainesville, Florida); and the entire staff of the University of Florida General Clinical Research Center (Gainesville, Florida).
Financial Suport:Funding for this project provided by the National Institutes of Health grant GM077026 from the National Institute of General Medical Sciences (Bethesda, Maryland, United States); the Foundation of Anesthesia Education and Research (Rochester, Minnesota, United States); NIH grants RR00082 and RR000827 from the National Center for Research Resources (Bethesda, Maryland, United States); the Departments of Anesthesiology, University of California San Diego (San Diego, California, United States) and University of Florida (Gainesville, Florida, United States); Stryker Instruments (Kalamazoo, Michigan, United States); and Arrow International (Reading, PA, United States). Dr. Sessler is supported by the Joseph Drown Foundation (Los Angeles, California, United States). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of these entities.
Abbreviated, preliminary results of this investigation were submitted as an abstract for the Annual Meeting of the American Society of Anesthesiologists, Orlando, Florida, United States, October 18–22, 2008.
Conflict of Interest: Arrow International (Reading, Pennsylvania, United States) and Stryker Instruments (Kalamazoo, Michigan, United States) provided funding and donated portable infusion pumps and perineural catheters for the original investigation. These two companies had absolutely no input into any aspect of study conceptualization, design, and implementation; data collection, analysis and interpretation; or manuscript preparation of the previous or current studies. Drs. Mariano and Enneking conduct continuous peripheral nerve block workshops for Stryker Instruments (Kalamazoo, Michigan, United States). None of the other authors has any personal financial interest in this research.
Implications statement: Previously, we provided evidence that extending an overnight continuous femoral nerve block to 4 days after tricompartment knee arthroplasty provides clear benefits in the immediate postoperative period. But, in this investigation, we found no evidence that the extended perineural infusion improves subsequent health-related quality of life between 7 days and 12 months.