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1.  Reduced morphine consumption and pain intensity with local infiltration analgesia (LIA) following total knee arthroplasty 
Acta Orthopaedica  2010;81(3):354-360.
Background and purpose
Postoperative pain is often severe after total knee arthroplasty (TKA). We investigated the efficacy of the local infiltration analgesia (LIA) technique, both intraoperatively and postoperatively.
Methods
48 patients undergoing TKA were randomized into 2 groups in a double-blind study. In group A, 400 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine were infiltrated periarticularly during operation. In group P, no injections were given. 21 h postoperatively, 200 mg ropivacaine, 30 mg ketorolac, and 0.1 mg epinephrine were injected intraarticularly in group A, and the same volume of saline was injected in group P. All patients were followed up for 3 months.
Results
Median morphine consumption was lower in group A during the first 48 h: 18 (1–74) mg vs. 87 (36–160) mg in group P. Postoperative pain was lower at rest in group A during the first 27 h, and on movement during the first 48 h, except at 21 h. Time to fulfillment of discharge criteria was shorter in group A than in group P: 3 (1–7) vs. 5 (2–8) days. Patient satisfaction was higher in group A than in group P on days 1 and 7. The unbound venous blood concentration of ropivacaine was below systemic toxic blood concentrations.
Interpretation
The local infiltration analgesia (LIA) technique provides excellent pain relief and lower morphine consumption following TKA, resulting in shorter time to home readiness and higher patient satisfaction. There were few side effects and systemic LA concentrations were low.
doi:10.3109/17453674.2010.487241
PMCID: PMC2876839  PMID: 20450425
2.  Pain control after total knee arthroplasty: a randomized trial comparing local infiltration anesthesia and continuous femoral block 
Acta Orthopaedica  2011;82(4):441-447.
Background and purpose
Pain after total knee arthroplasty (TKA) is usually severe, and epidural analgesia or femoral nerve block has been considered to be an effective pain treatment. Recently, local infiltration analgesia (LIA) has become increasingly popular but the outcome of this method regarding the analgesic effect has not been fully evaluated. We compared local infiltration analgesia and femoral block with regard to analgesia and morphine demand during the first 24 h after TKA.
Methods
40 patients undergoing TKA under spinal anesthesia were randomized to receive femoral nerve block (group F) or peri- and intraarticular infiltration analgesia (group LIA) with a mixture containing ropivacaine, ketorolac, and epinephrine. All patients had access to intravenous patient-controlled analgesia (PCA) with morphine postoperatively. Pain intensity at rest and upon movement was assessed on a numeric rating scale (0–10) on an hourly basis over 24 h if the patients were awake.
Results
The average pain at rest was marginally lower with LIA (1.6) than with femoral block (2.2). Total morphine consumption per kg was similar between the 2 groups. Ancillary analysis revealed that 1 of 20 patients in the LIA group reported a pain intensity of > 7 upon movement, as compared to 7 out of 19 in the femoral block group (p = 0.04).
Interpretation
Both LIA and femoral block provide good analgesia after TKA. LIA may be considered to be superior to femoral block since it is cheaper and easier to perform.
doi:10.3109/17453674.2011.581264
PMCID: PMC3237035  PMID: 21561303
3.  Intraarticular vs. extraarticular ropivacaine infusion following high-dose local infiltration analgesia after total knee arthroplasty 
Acta Orthopaedica  2011;82(6):692-698.
Background and purpose
Ropivacaine infusion following high-volume local infiltration analgesia has been shown to be effective after total knee arthroplasty, but the optimum site of administration of ropivacaine has not been evaluated. We compared the effects of intraarticular and extraarticular adminstration of the local anesthetic for postoperative supplementation of high-volume local infiltration analgesia.
Patients and methods
In this double-blind study, 36 rheumatic patients aged 51–78 years with physical status ASA 2–3 who were scheduled for total knee arthroplasty were randomized into 2 groups. All patients received wound infiltration at the end of surgery with 300 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine (total volume 156 mL). A tunneled catheter was randomly placed either extraarticularly or intraarticularly. Continuous infusion of ropivacain (0.5%, 2 mL/h) was started immediately and was maintained during the next 48 h. Pain intensity at rest, on movement, and with mobilization was estimated by the patients and the physiotherapist; rescue morphine consumption was recorded.
Results
As estimated by the patients, ropivacaine administered intraarticularly did not improve analgesia relative to extraarticular infusion, but improved the first mobilization. The incidence of high intensity of pain (VAS 7–10) was less in the group with intraarticular infusion. Analgesic requirements were similar in the 2 groups (47 mg and 49 mg morphine). No complications of postoperative wound healing were seen and there were no toxic side effects.
Interpretation
Continuous infusion of ropivacaine intraarticulary did not improve postoperative analgesia at rest relative to extraarticular administration, but it appeared to reduce the incidence of high pain intensity during first exercises, and could therefore be expected to improve mobilization up to 24 h after total knee arthroplasty.
doi:10.3109/17453674.2011.625535
PMCID: PMC3247887  PMID: 22026413
4.  Pain Management for Total Knee Arthroplasty: Single-Injection Femoral Nerve Block versus Local Infiltration Analgesia 
Background:
Pain is one of the major concerns of patients underwent Total Knee Arthroplasty (TKA); appropriate pain management is a key factor in patient's early physical fitness to move, physiotherapy, and most importantly, patient satisfaction.
Objectives:
In this study the analgesic effect of single injection femoral nerve block (SFNB) was compared with local infiltration analgesia (LIA).
Patients and Methods:
Forty patients who underwent TKA under spinal anesthesia were randomized to receive single femoral nerve block (group F) or intra-periarticular infiltration (group I). Group F received single injection 20cc ropivacaine (10mg/cc) and in group I, a combination of 300mg ropivacaine, 30mg ketorolac and 0.5mg epinephrine diluted to a volume of 150cc and locally injected in and around the knee joint in 3 stages. Postoperative pain intensity measured by Visual Analog Scale (VAS). Morphine consumption, mobilization time and patients’ satisfaction evaluated as well.
Results:
Group I had significantly lower morphine consumption in the first postoperative day (10 vs. 12.5mg, P-value < 0.05). Within 6 hours postoperatively, VAS score was statistically lower in group I compared to group F (3 vs. 4, P-value < 0.05). However, within 12 hours it was statistically higher in group I than group F (6 vs. 5, P-value < 0.05). Other parameters were not statistically different in two groups.
Conclusions:
Both methods LIA and SFNB provided excellent pain relief and lower morphine consumption following TKA. LIA is a surgeon-controlled analgesic technique, which can be used to enhance patients’ satisfaction and reduce the pain in the very early postoperative period by surgeon independently.
doi:10.5812/ircmj.13247
PMCID: PMC3964426  PMID: 24719708
Femoral Nerve Block; Analgesia; Morphine; Local Infiltration Analgesia
5.  No evidence of a clinically important effect of adding local infusion analgesia administrated through a catheter in pain treatment after total hip arthroplasty 
Acta Orthopaedica  2011;82(3):315-320.
Background and purpose
Postoperative analgesia after primary total hip arthroplasty (THA) using opioids is associated with troublesome side effects such as nausea and dizziness, and epidural analgesic means delayed mobilization. Thus, local infiltration analgesia (LIA) during surgery prolonged with local infusion analgesia (LINFA) into the soft tissue in the hip region through a catheter in the first postoperative days has gained major interest in THA fast-track settings within a short period of time. LIA at the time of surgery is a validated treatment. We investigated the additional effect of giving postoperative LINFA after THA in patients already having LIA during surgery.
Patients and methods
60 consecutive patients undergoing non-cemented THA were randomized into two groups in a double-blind and controlled study. During surgery, all patients received standardized pain treatment with LIA. Postoperatively, they were treated either with a solution of Ropivacain, Ketorolac, and Adrenaline (LINFA group) or placebo (placebo group) administered through a catheter to the hip 10 and 22 h after surgery. Pain score, opioid consumption, and length of stay (LOS) were evaluated.
Results
After adjustment for multiple testing, there was no statistically significant postoperative difference between the LINFA group and the placebo group regarding pain and tiredness. We found some evidence of a short-term effect on nausea and vomiting. Opioid consumption and length of stay were similar in the two groups.
Interpretation
We found some evidence of a short-term effect of LINFA on nausea and vomiting, but no evidence of an effect on postoperative pain and tiredness. Thus, LINFA cannot be recommended as a standard pain treatment in patients with THA.
doi:10.3109/17453674.2011.570671
PMCID: PMC3235309  PMID: 21619503
6.  Is peri-articular multimodal drug infiltration in knee arthroplasty safe when used in conjunction with autologous retransfusion drains? 
INTRODUCTION
Adequate peri-operative analgesia following total knee arthroplasty (TKA) promotes earlier rehabilitation but remains problematic because of the drug side-effects. Peri-articular multimodal drug infiltration (PMDI) has been developed as an alternative strategy to avoid such complications. Autologous retransfusion drains reduce the need for peri-operative allogenic blood transfusions and the consequent risk. There is a theoretical risk of local anaesthesia toxicity when these systems are used concurrently. We performed a review of current practice to quantify this risk.
PATIENTS AND METHODS
A series of 10 patients undergoing TKA by the senior author (CAB) had drain fluid analysed for the concentration of ropivacaine. At the same time, the patients completed a questionnaire to establish the presence of ropiva-caine-induced side-effects.
RESULTS
The ropivacaine level in the retransfusion blood was less than 10 mg in all patients. This concentration was a factor of 6 below the published safe level. Three patients had minor neurological disturbances which recovered spontaneously and quickly. There were no cases of significant cardiovascular compromise.
CONCLUSIONS
The theoretical risk of local anaesthesia toxicity when these systems are used together is negligible and we conclude that peri-articular multimodal drug infiltration is safe in conjunction with the use of autotransfusion drains.
doi:10.1308/003588410X12628812459733
PMCID: PMC3025216  PMID: 20501020
Arthroplasty; Knee; Analgesia; Drain
7.  A Randomized Controlled Trial of Intraarticular Ropivacaine for Pain Management Immediately Following Total Knee Arthroplasty 
HSS Journal  2010;6(2):155-159.
Total knee arthroplasty (TKA) is a commonly performed procedure for the treatment of end-stage arthritis of the knee. Pain control following TKA is difficult to manage in some patients. We examined the use of a postoperative intraarticular injection of 100 mL of 0.2% (200 mg) ropivacaine in a double-blind, prospective, placebo-controlled pilot study to evaluate its use as a pain control modality. All patients received general anesthesia. Postoperatively, patients were placed on intravenous patient-controlled analgesia with morphine. The ropivacaine group showed an early trend in lower visual analog scale (VAS) scores when compared with the placebo group. Patients receiving ropivacaine used a similar amount of narcotics compared with the placebo group. Intraarticular ropivacaine used for pain control after TKA demonstrated no statistically significant difference in lowering VAS scores or narcotic usage; therefore, intraarticular ropivacaine as a single modality is not recommended for effective pain management.
doi:10.1007/s11420-010-9155-2
PMCID: PMC2926371  PMID: 21886529
total knee arthroplasty; ropivacaine; intraarticular injection; pain control; randomized controlled trial
8.  Local anesthetic wound infiltration for pain management after periacetabular osteotomy 
Acta Orthopaedica  2014;85(2):141-146.
Background and purpose
To our knowledge, there is no evidence to support the use of local infiltration analgesia (LIA) for postoperative pain relief after periacetabular osteotomy (PAO). We investigated the effect of wound infiltration with a long-acting local anesthetic (ropivacaine) for postoperative analgesia after PAO.
Patients and methods
We performed a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov: NCT00815503) in 53 patients undergoing PAO to evaluate the effect of local anesthetic infiltration on postoperative pain and on postoperative opioid consumption. All subjects received intraoperative infiltration followed by 5 postoperative injections in 10-hour intervals through a multi-holed catheter placed at the surgical site. 26 patients received ropivacaine and 27 received saline. The intervention period was 2 days and the observational period was 4 days. All subjects received patient-controlled opioid analgesia without any restrictions on the total daily dose. Pain was assessed at specific postoperative time points and the daily opioid usage was registered.
Results
Infiltration with 75 mL (150 mg) of ropivacaine did not reduce postoperative pain or opioid requirements during the first 4 days.
Interpretation
The clinical importance of ropivacaine as single component in postoperative treatment of pain is questionable, and we are planning further studies to explore the potential of LIA in larger volume—and also a multimodal regimen—to treat pain in this category of patients.
doi:10.3109/17453674.2014.899840
PMCID: PMC3967255  PMID: 24650022
9.  High-volume infiltration analgesia in bilateral hip arthroplasty 
Acta Orthopaedica  2011;82(4):423-426.
Background and purpose
High-volume infiltration analgesia may be effective in postoperative pain management after hip arthroplasty but methodological problems prevent exact interpretation of previous studies.
Methods
In a randomized, double-blind placebo-controlled trial in 12 patients undergoing bilateral total hip arthroplasty (THA) in a fast-track setting, saline or high-volume (170 mL) ropivacaine (0.2%) with epinephrine (1:100,000) was administered to the wound intraoperatively along with supplementary postoperative injections via an intraarticular epidural catheter. Oral analgesia was instituted preoperatively with a multimodal regimen (gabapentin, celecoxib, and acetaminophen). Pain was assessed repeatedly for 48 hours postoperatively, at rest and with 45° hip flexion.
Results
Pain scores were low and similar between ropivacaine and saline administration. Median hospital stay was 4 (range 2–7) days.
Interpretation
Intraoperative high-volume infiltration with 0.2% ropivacaine with repeated intraarticular injections postoperatively may not give a clinically relevant analgesic effect in THA when combined with a multimodal oral analgesic regimen with gabapentin, celecoxib, and acetaminophen.
doi:10.3109/17453674.2011.596063
PMCID: PMC3237031  PMID: 21751861
10.  A randomized, controlled trial comparing local infiltration analgesia with epidural infusion for total knee arthroplasty 
Acta Orthopaedica  2010;81(5):606-610.
Background
There have been few studies describing wound infiltration with additional intraarticular administration of multimodal analgesia for total knee arthroplasty (TKA). In this study, we assessed the efficacy of wound infiltration combined with intraarticular regional analgesia with epidural infusion on analgesic requirements and postoperative pain after TKA.
Methods
40 consecutive patients undergoing elective, primary TKA were randomized into 2 groups to receive either (1) intraoperative wound infiltration with 150 mL ropivacaine (2 mg/mL), 1 mL ketorolac (30 mg/mL), and 0.5 mL epinephrine (1 mg/mL) (total volume 152 mL) combined with intraarticular infusion (4 mL/h) of 190 mL ropivacaine (2 mg/mL) plus 2 mL ketorolac (30 mg/mL) (group A), or (2) epidural infusion (4 mL/h) of 192 mL ropivacaine (2 mg/mL) combined with 6 intravenous administrations of 0.5 mL ketorolac (30 mg/mL) for 48 h postoperatively (group E). For rescue analgesia, intravenous patient-controlled-analgesia (PCA) morphine was used.
Morphine consumption, intensity of knee pain (0–100 mm visual analog scale), and side effects were recorded. Length of stay and corrected length of stay were also recorded (the day-patients fulfilled discharge criteria).
Results
The median cumulated morphine consumption, pain scores at rest, and pain scores during mobilization were reduced in group A compared to group E. Corrected length of stay was reduced by 25% in group A compared to group E.
Interpretation
Peri- and intraarticular analgesia with multimodal drugs provided superior pain relief and reduced morphine consumption compared with continuous epidural infusion with ropivacaine combined with intravenous ketorolac after TKA.
doi:10.3109/17453674.2010.519165
PMCID: PMC3214751  PMID: 20860447
11.  The Effects of Local Anesthetic Concentration and Dose on Continuous Infraclavicular Nerve Blocks: A Multicenter, Randomized, Observer-Masked, Controlled Study 
Anesthesia and analgesia  2009;108(1):345-350.
BACKGROUND
It remains unclear whether local anesthetic concentration or total drug dose is the primary determinant of continuous peripheral nerve block effects. The only previous investigation, involving continuous popliteal-sciatic nerve blocks, specifically addressing this issue reported that insensate limbs were far more common with higher volumes of relatively dilute ropivacaine compared with lower volumes of relatively concentrated ropivacaine. However, it remains unknown if this relationship is specific to the sciatic nerve in the popliteal fossa or whether it varies depending on anatomic location. We therefore tested the null hypothesis that providing ropivacaine at different concentrations and rates, but at an equal total basal dose, produces comparable effects when used in a continuous infraclavicular brachial plexus block.
METHODS
Preoperatively, an infraclavicular catheter was inserted using the coracoid approach in patients undergoing moderately painful orthopedic surgery distal to the elbow. Patients were randomly assigned to receive a postoperative perineural ropivacaine infusion of either 0.2% (basal 8 mL/h, bolus 4 mL) or 0.4% (basal 4 mL/h, bolus 2 mL) through the second postoperative day. Both groups, therefore, received 16 mg of ropivacaine each hour with a possible addition of 8 mg every 30 min via a patient-controlled bolus dose. Our primary end point was the incidence of an insensate limb during the 24-h period beginning the morning after surgery. Secondary end points included analgesia and patient satisfaction.
RESULTS
Patients given 0.4% ropivacaine (n = 27) experienced an insensate limb, a mean (sd) of 1.8 (1.6) times, compared with 0.6 (0.9) times for subjects receiving 0.2% ropivacaine (n = 23; estimated difference = 1.2 episodes, 95% confidence interval, 0.5–1.9 episodes; P = 0.001). Satisfaction with postoperative analgesia (scale 0–10, 10 = highest) was scored a median (25th–75th percentiles) of 10.0 (8.0–10.0) in Group 0.2% and 7.0 (5.3–8.9) in Group 0.4% (P = 0.018). Analgesia was similar in each group.
CONCLUSIONS
For continuous infraclavicular nerve blocks, local anesthetic concentration and volume influence perineural infusion effects in addition to the total mass of local anesthetic administered. Insensate limbs were far more common with smaller volumes of relatively concentrated ropivacaine. This is the opposite of the relationship previously reported for continuous popliteal-sciatic nerve blocks. The interaction between local anesthetic concentration and volume is thus complex and varies among catheter locations.
doi:10.1213/ane.0b013e31818c7da5
PMCID: PMC2745828  PMID: 19095871
12.  General Anaesthesia With Multimodal Principles Versus Intrathecal Analgesia With Conventional Principles in Total Knee Arthroplasty: A Consecutive, Randomized Study 
Background
Postoperative outcomes following major surgery are influenced by surgical and anaesthesiological factors. While techniques of minimal invasive surgery have been associated with improved outcome, the techniques of minimal invasive, multimodal anaesthesia have not been adequately investigated. The aim of this study was to compare intrathecally based anaesthesia (ITA) including standardized, traditional intraoperative and postoperative care, with, general anaesthesia (GA) combined with intraoperative glucocorticoids, exclusion of intraoperative tourniquet and indwelling urethral catheter, and, an accelerated postoperative care regime. Outcome variables in the study were pain, requirement of analgesics, global satisfaction score and length-of-hospital stay.
Methods
Sixty patients were included and randomized to the ITA or the GA group. The ITA group received intrathecal bupivacaine (12.5 - 15.0 mg)/morphine (0.1 mg)/clonidine (0.03 mg), a standard surgical procedure, local infiltration analgesia (LIA) with ropivacaine (110 mg) /epinephrine (0.5 mg)/morphine (10 mg), an indwelling urethral catheter and mobilization with start Day 1 after the surgery. The GA group received a target-controlled infusion of propofol/remifentanil, betamethasone 4 mg i.v. intraoperatively, surgery was performed without a tourniquet, an indwelling urethral catheter was not used, LIA was with ropivacaine (250 mg)/epinephrine (0.3 mg) and mobilization was planned with start ≤ 2 hrs. after end of surgery. Outcomes were followed daily for the first 96 hrs. and at visits 3 months and 12 months postoperatively.
Results
Requirement of analgesics was decreased in the ITA group in the immediate postoperative period (P < 0.05). Pain scores were significantly lower in the ITA group (P < 0.01) between 0 - 12 hrs and in the GA group (P < 0.05) between 12 - 24 hrs after surgery. Fifteen of the patients in the GA group had to be intermittent catheterized due to bladder volumes > 400 mL. The LOS in the ITA group was significantly longer compared to the GA group (P < 0.01). There was no difference in global satisfaction score.
Conclusion
General anaesthesia combined with intraoperative glucocorticoids and accelerated postoperative care, compared with, intrathecal blockade and traditional postoperative care, seems to generate the same overall pain ratings and a decrease in length-of-hospital stay, in patients undergoing elective total knee arthroplasty.
doi:10.4021/jocmr1210e
PMCID: PMC3564567  PMID: 23390475
General anaesthesia; Glucocorticoids; Intrathecal analgesia; Length of hospital stay; Postoperative recovery; Total knee arthroplasty; Urinary catheter
13.  The Effects of Varying Local Anesthetic Concentration and Volume on Continuous Popliteal Sciatic Nerve Blocks 
Anesthesia and analgesia  2008;107(2):701-707.
BACKGROUND
It remains unknown whether local anesthetic concentration, or simply total drug dose, is the primary determinant of continuous peripheral nerve block effects. We therefore tested the null hypothesis that providing different concentrations and rates of ropivacaine, but at equal total doses, produces comparable effects when used in a continuous sciatic nerve block in the popliteal fossa.
METHODS
Preoperatively, a perineural catheter was inserted adjacent to the sciatic nerve using a posterior popliteal approach in patients undergoing moderately painful orthopedic surgery at or distal to the ankle. Postoperatively, patients were randomly assigned to receive a perineural ropivacaine infusion of either 0.2% (basal 8 mL/h, bolus 4 mL) or 0.4% (basal 4 mL/h, bolus 2 mL) through the second postoperative day. Therefore, both groups received 16 mg of ropivacaine each hour with a possible addition of 8 mg every 30 min via a patient-controlled bolus dose. The primary end point was the incidence of an insensate limb, considered undesirable, during the 24-h period beginning the morning after surgery. Secondary end points included analgesia and patient satisfaction.
RESULTS
Patients given 0.2% ropivacaine (n = 25) experienced an insensate limb with a mean (sd) of 1.8 (1.8) times, compared with 0.6 (1.1) times for subjects receiving 0.4% ropivacaine (n = 25; estimated difference = 1.2 episodes, 95% confidence interval, 0.3–2.0 episodes; P = 0.009). In contrast, analgesia and satisfaction were similar in each group.
CONCLUSIONS
For continuous popliteal-sciatic nerve blocks, local anesthetic concentration and volume influence block characteristics. Insensate limbs were far more common with larger volumes of relatively dilute ropivacaine. During continuous sciatic nerve block in the popliteal fossa, a relatively concentrated solution in smaller volume thus appears preferable.
doi:10.1213/ane.0b013e3181770eda
PMCID: PMC2585804  PMID: 18633055
14.  Minimally invasive surgery did not improve outcome compared to conventional surgery following unicompartmental knee arthroplasty using local infiltration analgesia 
Acta Orthopaedica  2012;83(6):634-641.
Background and purpose
There has recently been interest in the advantages of minimally invasive surgery (MIS) over conventional surgery, and on local infiltration analgesia (LIA) during knee arthroplasty. In this randomized controlled trial, we investigated whether MIS would result in earlier home-readiness and reduced postoperative pain compared to conventional unicompartmental knee arthroplasty (UKA) where both groups received LIA.
Patients and methods
40 patients scheduled for UKA were randomized to a MIS group or a conventional surgery (CON) group. Both groups received LIA with a mixture of ropivacaine, ketorolac, and epinephrine given intra- and postoperatively. The primary endpoint was home-readiness (time to fulfillment of discharge criteria). The patients were followed for 6 months.
Results
We found no statistically significant difference in home-readiness between the MIS group (median (range) 24 (21–71) hours) and the CON group (24 (21–46) hours). No statistically significant differences between the groups were found in the secondary endpoints pain intensity, morphine consumption, knee function, hospital stay, patient satisfaction, Oxford knee score, and EQ-5D. The side effects were also similar in the two groups, except for a higher incidence of nausea on the second postoperative day in the MIS group.
Interpretation
Minimally invasive surgery did not improve outcome after unicompartmental knee arthroplasty compared to conventional surgery, when both groups received local infiltration analgesia. The surgical approach (MIS or conventional surgery) should be selected according to the surgeon’s preferences and local hospital policies.
ClinicalTrials.gov. (Identifier NCT00991445).
doi:10.3109/17453674.2012.736169
PMCID: PMC3555459  PMID: 23043272
15.  Intra-synovial Ropivacaine and Morphine for Pain Relief after Total Knee Arthroplasty -A Prospective, Randomized, Double Blind Study- 
Yonsei Medical Journal  2007;48(2):295-300.
Purpose
Several analgesic techniques are available for pain management after a major operation.
Materials and Methods
From December 2005 to February 2006, a prospective, double-blind study was performed involving 90 patients who had undergone a total knee arthroplasty. Patients were randomly divided into three equal groups (n = 30). Demographic data, including age, height, weight, knee score, visual analogue scale (VAS), and range of flexion were evaluated preoperatively. Before wound closure, patients were given intra-synovial injections of the following solutions: patients in group I received 40 mL of 300 mg ropivacaine with 1 : 200,000 epinephrine and 5 mg morphine; patients in Group II received 40 mL of 300 mg ropivacaine with epinephrine; and patients in Group III received 50 mL normal saline as a control. All patients received an epidural patient-controlled analgesia (PCA) for 24 postoperative hours. Analgesic efficacy was evaluated using the VAS at intervals of 2, 4, 6, 12, 24, 32, 40, and 48 hours postoperatively. During this period, the side effects, the dosage of rescue analgesia required, and the range of knee flexion were recorded for each group.
Results
There were no significant differences among the three groups with regards to the VAS and the required dose of rescue analgesia (p > 0.05). None of the groups demonstrated significant differences in the range of knee flexion and the incidence of postoperative nausea and emesis (p > 0.05).
Conclusion
Therefore, we found that ropivacaine, alone or with morphine, injected into the synovial tissue, along with an epidural PCA has no additional benefits in pain control after a total knee arthroplasty.
doi:10.3349/ymj.2007.48.2.295
PMCID: PMC2628113  PMID: 17461530
Total knee arthroplasty; intra-synovial; ropivacaine; morphine
16.  Patient-controlled epidural analgesia after Caesarean section: levobupivacaine 0.15% versus ropivacaine 0.15% alone or combined with fentanyl 2 µg/ml: a comparative study 
Introduction
The aim of this study was to compare the postoperative analgesic efficacy of epidural ropivacaine 0.15%, levobupivacaine 0.15% and ropivacaine 0.15% plus fentanyl 2 µg/ml, used with a patient-controlled epidural analgesia (PCEA) device after Caesarean section.
Material and methods
Sixty women undergoing elective Caesarean section under combined spinal-epidural anaesthesia were enrolled. Postoperatively, patients received PCEA with either ropivacaine or levobupivacaine 0.15% (basal rate 6 ml/h, bolus 5 ml/20 min), or ropivacaine 0.15% plus fentanyl 2 µg/ml (basal rate 6 ml/h, bolus 4 ml/20 min). Sympathetic and sensory level of analgesia, motor ability (Bromage 0-3), and pain scores at rest, movement and cough (VAS 0-10), haemodynamic parameters, oxygenation, side effects and total doses of local anaesthetic were documented every 6 h for 24 h. Patient satisfaction was assessed using a descriptive scale.
Results
No significant difference was observed in pain scores at all time intervals. A significantly higher sympathetic and sensory blockade occurred with levobupivacaine and ropivacaine 0.15% compared to ropivacaine 0.15% plus fentanyl, with no significant difference in total local analgesic consumption at 24 h (p = 0.08). Rescue analgesic requirements did not differ between the groups (p = 0.8) while patients’ satisfaction was significantly higher in the ropivacaine 0.15% plus fentanyl group (p = 0.02). Haemodynamics, oxygenation, nausea, pruritus and numbness did not differ between the groups.
Conclusions
Dilute local anaesthetic solutions provided satisfactory postoperative analgesia after Caesarean section when used with a PCEA device. The combination of ropivacaine 0.15% with fentanyl 2 µg/ml appeared superior, since it provided higher patient satisfaction with statistically equal pain scores and local anaesthetic consumption.
doi:10.5114/aoms.2011.24140
PMCID: PMC3258763  PMID: 22291806
postoperative epidural analgesia; local anaesthetics; opioids; postoperative pain management
17.  A Multicenter, Randomized, Triple-Masked, Placebo-Controlled Trial of The Effect of Ambulatory Continuous Femoral Nerve Blocks on Discharge-Readiness Following Total Knee Arthroplasty In Patients on General Orthopaedic Wards 
Pain  2010;150(3):477-484.
A continuous femoral nerve block (cFNB) involves the percutaneous insertion of a catheter adjacent to the femoral nerve, followed by a local anesthetic infusion, improving analgesia following total knee arthroplasty (TKA). Portable infusion pumps allow infusion continuation following hospital discharge, raising the possibility of decreasing hospitalization duration. We therefore used a multicenter, randomized, triple-masked, placebo-controlled study design to test the primary hypothesis that a four-day ambulatory cFNB decreases the time until each of three predefined readiness-for-discharge criteria (adequate analgesia, independence from intravenous opioids, and ambulation ≥ 30 meters) are met following TKA compared with an overnight inpatient-only cFNB. Preoperatively, all patients received a cFNB with perineural ropivacaine 0.2% from surgery until the following morning, at which time they were randomized to either continue perineural ropivacaine (n=39) or switch to normal saline (n=38). Patients were discharged with their cFNB and portable infusion pump as early as postoperative day three. Patients given four days of perineural ropivacaine attained all three criteria in a median (25th–75th percentiles) of 47 (29–69) hours, compared with 62 (45–79) hours for those of the control group (Estimated ratio=0.80, 95% confidence interval: 0.66–1.00; p=0.028). Compared with controls, patients randomized to ropivacaine met the discharge criterion for analgesia in 20 (0–38) vs. 38 (15–64) hours (p=0.009), and intravenous opioid independence in 21 (0–37) vs. 33 (11–50) hours (p=0.061). We conclude that a four-day ambulatory cFNB decreases the time to reach three important discharge criteria by an estimated 20% following TKA compared with an overnight cFNB, primarily by improving analgesia.
doi:10.1016/j.pain.2010.05.028
PMCID: PMC2921457  PMID: 20573448
18.  Continuous Interscalene Brachial Plexus Block via an Ultrasound-Guided Posterior Approach: A Randomized, Triple-Masked, Placebo-Controlled Study 
Anesthesia and analgesia  2009;108(5):1688-1694.
BACKGROUND
The posterior approach for placing continuous interscalene catheters has not been studied in a controlled investigation. In this randomized, triple-masked, placebo-controlled study, we tested the hypothesis that an ultrasound-guided continuous posterior interscalene block provides superior postoperative analgesia compared to a single-injection ropivacaine interscalene block after moderately painful shoulder surgery.
METHODS
Preoperatively, subjects received a stimulating interscalene catheter using an ultrasound-guided, in-plane posterior approach. All subjects received an initial bolus of ropivacaine. Postoperatively, subjects were discharged with oral analgesics and a portable infusion device containing either ropivacaine 0.2% or normal saline programmed to deliver a perineural infusion over 2 days. The primary outcome was average pain on postoperative day (POD) 1 (scale: 0–10). Secondary outcomes included least and worst pain scores, oral opioid requirements, sleep disturbances, patient satisfaction, and incidence of complications.
RESULTS
Of the 32 subjects enrolled, 30 perineural catheters were placed per protocol. Continuous ropivacaine perineural infusion (n = 15) produced a statistically and clinically significant reduction in average pain (median [10th–90th percentile]) on POD 1 compared with saline infusion (n = 15) after initial ropivacaine bolus (0.0 [0.0–5.0] versus 3.0 [0.0–6.0], respectively; P < 0.001). Median oral opioid consumption (oxycodone) was lower in the ropivacaine group than in the placebo group on POD 1 (P = 0.002) and POD 2 (P = 0.002). Subjects who received a ropivacaine infusion suffered fewer sleep disturbances than those in the placebo group (P = 0.005 on POD 0 and 1 nights) and rated their satisfaction with analgesia higher than subjects who received normal saline (P < 0.001).
CONCLUSIONS
Compared to a single-injection interscalene block, a 2-day continuous posterior interscalene block provides greater pain relief, minimizes supplemental opioid requirements, greatly improves sleep quality, and increases patient satisfaction after moderate-to-severe painful outpatient shoulder surgery.
doi:10.1213/ane.0b013e318199dc86
PMCID: PMC2745838  PMID: 19372355
19.  Reduced hospital stay, morphine consumption, and pain intensity with local infiltration analgesia after unicompartmental knee arthroplasty 
Acta Orthopaedica  2009;80(2):213-219.
Background and purpose The degree of postoperative pain is usually moderate to severe following knee arthroplasty. We investigated the efficacy of local administration of analgesics into the operating area, both intraoperatively and postoperatively.
Methods 40 patients undergoing unicompartmental knee arthroplasty (UKA) were randomized into 2 groups in a double–blind study (ClinicalTrials.gov identifier: NCT00653926). In group A (active), 200 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine (total volume 106 mL) were infiltrated intraoperatively into the soft tissue, while in group P (placebo), no injections were given. 21 hours postoperatively, 150 mg ropivacain, 30 mg ketorolac, and 0.1 mg epinephrine were injected intraarticularly via a catheter in group A, whereas patients in group P were injected with the same volume of saline (22 mL).
Results Median hospital stay was shorter in group A than in group P: 1 (1–6) days as opposed to 3 (1–6) days (p < 0.001). Postoperative pain in group A was statistically significantly lower at rest after 6 h and 27 h and on movement after 6, 12, 22, and 27 h. Morphine consumption was statistically significantly lower in group A for the first 48 h, resulting in a lower frequency of nausea, pruritus, and sedation. Postoperatively, there were improved functional scores (Oxford knee score and EQ–5D) in both groups relative to the corresponding preoperative values.
Interpretation Local injection of analgesics periarticularly at the end of the operation and intraarticularly at 21 h postoperatively provided excellent pain relief and earlier home discharge following UKA. There was a high degree of patient satisfaction in both groups after 6 months (Clinical Trials.gov: NCT 00653926).
doi:10.3109/17453670902930008
PMCID: PMC2823175  PMID: 19404806
20.  The Efficacy of Periarticular Multimodal Drug Infiltration in Total Hip Arthroplasty 
Background
Patient-controlled analgesia is a widely used and effective method of controlling pain after THA. This method is associated with substantial undesirable side effects. Local infiltration has been introduced in an attempt to reduce opioid requirements postoperatively, but its ability to reduce pain without complications is still questioned.
Questions/Purposes
We evaluated patient-controlled analgesia use, pain and satisfaction scores, complication rates, and ropivacaine levels associated with the use of periarticular multimodal drug infiltration in THA.
Patients and Methods
We randomized 64 patients undergoing THA to receive a periarticular intraoperative multimodal drug injection or to receive no injection. All patients received patient-controlled analgesia for 24 hours after surgery. The final assessment was at 6 weeks.
Results
Patients receiving the periarticular injection used less patient-controlled analgesia 6 hours postoperatively. The 24-hour patient-controlled analgesia requirement postsurgery also was less. The visual analog scale score for pain on activity in the postanesthetic care unit was less for patients who received an injection. The visual analog scale satisfaction score was similar in the two groups throughout the followup period. Recorded unbound ropivacaine levels were 2.5 times lower than toxic levels.
Conclusions
Periarticular intraoperative injection with multimodal drugs can reduce postoperative patient-controlled analgesia requirements and pain on activity in patients undergoing THA with no apparent increase in risk.
Level of Evidence
Level I, therapeutic study. See the guidelines online for a complete description of level of evidence.
doi:10.1007/s11999-009-1198-7
PMCID: PMC2895844  PMID: 20020333
21.  Adductor Canal Block for Postoperative Pain Treatment after Revision Knee Arthroplasty: A Blinded, Randomized, Placebo-Controlled Study 
PLoS ONE  2014;9(11):e111951.
Background
Revision knee arthroplasty is assumed to be even more painful than primary knee arthroplasty and predominantly performed in chronic pain patients, which challenges postoperative pain treatment. We hypothesized that the adductor canal block, effective for pain relief after primary total knee arthroplasty, may reduce pain during knee flexion (primary endpoint: at 4 h) compared with placebo after revision total knee arthroplasty. Secondary endpoints were pain at rest, morphine consumption and morphine-related side effects.
Methods
We included patients scheduled for revision knee arthroplasty in general anesthesia into this blinded, placebo-controlled, randomized trial. Patients were allocated to an adductor canal block via a catheter with either ropivacaine or placebo; bolus of 0.75% ropivacaine/saline, followed by infusion of 0.2% ropivacaine/saline. Clinicaltrials.gov ID: NCT01191593.
Results
We enrolled 36 patients, of which 30 were analyzed. Mean pain scores during knee flexion at 4 h (primary endpoint) were: 52±22 versus 71±25 mm (mean difference 19, 95% CI: 1 to 37, P = 0.04), ropivacaine and placebo group respectively. When calculated as area under the curve (1–8 h/7 h) pain scores were 55±21 versus 69±21 mm during knee flexion (P = 0.11) and 39±18 versus 45±23 mm at rest (P = 0.43), ropivacaine and placebo group respectively. Groups were similar regarding morphine consumption and morphine-related side effects (P>0.05).
Conclusions
The only statistically significant difference found between groups was in the primary endpoint: pain during knee flexion at 4 h. However, due to a larger than anticipated dropout rate and heterogeneous study population, the study was underpowered.
Trial Registration
Clinicaltrials.gov NCT01191593
doi:10.1371/journal.pone.0111951
PMCID: PMC4227669  PMID: 25386752
22.  Continuous Femoral Versus Posterior Lumbar Plexus Nerve Blocks for Analgesia After Hip Arthroplasty: A Randomized, Controlled Study 
Anesthesia and analgesia  2011;113(4):897-903.
BACKGROUND
Hip arthroplasty frequently requires potent postoperative analgesia, often provided with an epidural or posterior lumbar plexus local anesthetic infusion. However, American Society of Regional Anesthesia guidelines now recommend against epidural and continuous posterior lumbar plexus blocks during administration of various perioperative anticoagulants often administered after hip arthroplasty. A continuous femoral nerve block is a possible analgesic alternative, but whether it provides comparable analgesia to a continuous posterior lumbar plexus block after hip arthroplasty remains unclear. We therefore tested the hypothesis that differing the catheter insertion site (femoral versus posterior lumbar plexus) after hip arthroplasty has no impact on postoperative analgesia.
METHODS
Preoperatively, subjects undergoing hip arthroplasty were randomly assigned to receive either a femoral or posterior lumbar plexus stimulating catheter inserted 5 to 15 cm or 0 to 1 cm past the needletip, respectively. Postoperatively, patients received perineural ropivacaine, 0.2% (basal 6 mL/hour, bolus 4 mL, 30 min lockout) for at least two days. The primary end point was the average daily pain scores as measured with a numeric rating scale (0–10) recorded in the 24-h period beginning at 07:30 the morning after surgery, excluding twice-daily physical therapy sessions. Secondary end points included pain during physical therapy, ambulatory distance, and supplemental analgesic requirements during the same 24-h period, as well as satisfaction with analgesia during hospitalization.
RESULTS
The mean (SD) pain scores for subjects receiving a femoral infusion (n = 25) were 3.6 (1.8) versus 3.5 (1.8) for patients receiving a posterior lumbar plexus infusion (n = 22) resulting in a group difference of 0.1 (95% confidence interval −0.9 to 1.2; P = 0.78). Because the confidence interval was within a prespecified −1.6 to 1.6 range, we conclude that the effect of the two analgesic techniques on postoperative pain was equivalent. Similarly, we detected no differences between the two treatments with respect to the secondary end points, with one exception: subjects with a femoral catheter ambulated a median (10th–90th percentiles) 2 (0–17) m the morning after surgery, compared with 11 (0–31) m for subjects with a posterior lumbar plexus catheter (data nonparametric; P = 0.02).
CONCLUSIONS
After hip arthroplasty, a continuous femoral nerve block is an acceptable analgesic alternative to a continuous posterior lumbar plexus block when using a stimulating perineural catheter. However, early ambulatory ability suffers with a femoral infusion.
doi:10.1213/ANE.0b013e318212495b
PMCID: PMC3132825  PMID: 21467563
23.  Effects of Local Anesthetic Concentration and Dose on Continuous Interscalene Nerve Blocks: A Dual-Center, Randomized, Observer-Masked, Controlled Study 
Background and Objectives:
It is currently unknown if the primary determinant of continuous peripheral nerve block effects is simply total drug dose, or whether local anesthetic concentration and/or volume have an influence. We therefore tested the null hypothesis that providing ropivacaine at different concentrations and rates—but at an equal total basal dose—produces similar effects when used in a continuous interscalene nerve block.
Methods:
Preoperatively, an interscalene perineural catheter was inserted using the anteriolateral approach in patients undergoing moderately painful shoulder surgery. Subjects were randomly assigned to receive a postoperative perineural infusion of either 0.2% ropivacaine (basal 8 mL/h, bolus 4 mL) or 0.4% ropivacaine (basal 4 mL/h, bolus 2 mL) through the second postoperative day. Our primary end point was the incidence of an insensate hand/finger during the 24-hours beginning the morning following surgery.
Results:
The incidence of an insensate hand/finger did not differ between the treatment groups (n=50) to a statistically significant degree (0.2% ropivacaine mean [SD] of 0.8 [1.3] times; 0.4% ropivacaine mean 0.3 [0.6] times; estimated difference=0.5 episodes, 95% confidence interval, −0.1 to 1.1 episodes; p=0.080). However, this is statistically inconclusive given the confidence interval. In contrast, pain (p=0.020) and dissatisfaction (p=0.011) were greater in patients given 0.4% ropivacaine.
Conclusions:
For continuous interscalene nerve blocks, the 95% confidence interval (plausible differences in the incidence of an insensate hand/finger) contains values ranging from a clinically important disadvantage (1.1) to a clinically unimportant advantage (−0.1) for the lower concentration. Given the statistically inconclusive results and design limitations of the current study, further research on this issue is warranted. In contrast, providing a lower concentration of local anesthetic at a higher basal rate provided superior analgesia. These relationships are different than previously reported for continuous popliteal-sciatic nerve blocks. The interaction between local anesthetic concentration and volume is thus complex and varies among catheter locations.
PMCID: PMC2711692  PMID: 19258966
anesthesia; continuous peripheral nerve block; continuous interscalene nerve block; patient-controlled regional analgesia; perineural local anesthetic infusion
24.  The efficacy of 0.75% levobupivacaine versus 0.75% ropivacaine for peribulbar anesthesia in vitreoretinal surgery 
Saudi Journal of Anaesthesia  2012;6(1):22-26.
Background:
We evaluated the anesthetic efficacy and the postoperative analgesic effects of 0.75% levobupivacaine versus 0.75% ropivacaine for peribulbar anesthesia in patients undergoing primary vitreoretinal surgery.
Methods:
We investigated 120 patients subjected to vitreoretinal surgery under peribulbar anesthesia. They were randomized into two equal groups according to the local anesthetic (LA) used, namely, 0.75% levobupivacaine or 0.75% ropivacaine, both with the addition of hyaluronidase. Nerve block was carried out by injection of 5–7 mL of the LA using single injection percutaneous peribulbar anesthesia with a short needle.
Results:
When compared with 0.75% ropivacaine, 0.75% levobupivacaine provided more successful akinesia at 10 min after block (P=0.026), fewer supplementary injections (P=0.026), and less volume (mL) was used (P=0.031). Also, levobupivacaine provided significantly longer motor block duration (342±27 min versus 206±40 min, P=0.001) and significantly longer sensory block duration (513±24 min versus 394±11 min, P=0.001) when compared with ropivacaine. In the postoperative period, the patients in the levobupivacaine group achieved lower values of verbal numeric rating scale of pain compared with patients in the ropivacaine group among the period from 4 to 12 h. Also, there were significantly (P=0.001) lower diclofenac consumption (mg) and the percentage of patients who required tramadol rescue medication were significantly less (P=0.034) in the levobupivacaine group compared with the ropivacaine group.
Conclusion:
We are concluding that, at equipotent doses and concentrations, 0.75% levobupivacaine provides more effective peribulbar anesthesia and more effective postoperative analgesia for vitreoretinal surgery compared with 0.75% ropivacaine.
doi:10.4103/1658-354X.93050
PMCID: PMC3299109  PMID: 22412772
Levobupivacaine; peribulbar anesthesia; ropivacaine
25.  Continuous paravertebral infusion of ropivacaine with or without fentanyl for pain relief in unilateral multiple fractured ribs 
Indian Journal of Anaesthesia  2013;57(6):555-561.
Background:
Continuous thoracic paravertebral block (TPVB) provides effective analgesia for unilateral multiple fractured ribs (MFR). However, prolonged infusion of local anaesthetic (LA) in high doses can predispose to risk of LA toxicity, which may be reduced by using safer drugs or drug combinations. This study was conducted to assess efficacy and safety of paravertebral infusion of ropivacaine and adrenaline with or without fentanyl to provide analgesia to patients with unilateral MFR.
Methods:
Thirty adults, having ≥3 unilateral MFR, with no significant trauma outside chest wall, were studied. All received bolus of 0.5% ropivacaine 0.3 ml/kg through paravertebral catheter, followed by either 0.1-0.2 ml/kg/hr infusion of ropivacaine 0.375% with adrenaline 5 μg/ml in group RA or ropivacaine 0.2% with adrenaline 5 μg/ml and fentanyl 2 μg/ml in group RAF. Rescue analgesia was provided by IV morphine.
Results:
Statistical analysis was performed using unpaired Student t-test, Chi-square test and repeated measures ANOVA. After TPVB, VAS scores, respiratory rate and PEFR improved in both groups with no significant inter-group differences. Duration of ropivacaine infusion, morphine requirements, length of ICU and hospital stay, incidence of pulmonary complications and opioid-related side-effects were similar in both groups. Ropivacaine requirement was higher in group RA than group RAF. No patient showed signs of LA toxicity.
Conclusion:
Continuous paravertebral infusion of ropivacaine 0.375% with adrenaline 5 μg/ml at 0.1-0.2 ml/kg/hr provided effective and safe analgesia to patients with unilateral MFR. Addition of fentanyl 2 μg/ml allowed reduction of ropivacaine concentration to 0.2% without decreasing efficacy or increasing opioid-related side-effects.
doi:10.4103/0019-5049.123327
PMCID: PMC3883389  PMID: 24403614
Fentanyl; local anaesthetic toxicity; rib fractures; ropivacaine; thoracic paravertebral block

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