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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.  Local infiltration analgesia is not improved by postoperative intra-articular bolus injections for pain after total hip arthroplasty 
Acta Orthopaedica  2015;86(6):647-653.
Background and purpose — The effect of postoperative intra-articular bolus injections after total hip arthroplasty (THA) remains unclear. We tested the hypothesis that intra-articular bolus injections administered every 6 hours after surgery during the first 24 hours would significantly improve analgesia after THA.
Patients and methods — 80 patients undergoing THA received high-volume local infiltration analgesia (LIA; 200 mg ropivacaine and 30 mg ketorolac) followed by 4 intra-articular injections with either ropivacaine (100 mg) and ketorolac (15 mg) (the treatment group) or saline (the control group). The intra-articular injections were combined with 4 intravenous injections of either saline (treatment group) or 15 mg ketorolac (control group). All patients received morphine as patient-controlled analgesia (PCA). The primary outcome was consumption of intravenous morphine PCA and secondary outcomes were consumption of oral morphine, pain intensity, side effects, readiness for hospital discharge, length of hospital stay, and postoperative consumption of analgesics at 3, 6, and 12 weeks after surgery.
Results — There were no statistically significant differences between the 2 groups regarding postoperative consumption of intravenous morphine PCA. Postoperative pain scores during walking were higher in the treatment group from 24–72 hours after surgery, but other pain scores were similar between groups. Time to readiness for hospital discharge was longer in the treatment group. Other secondary outcomes were similar between groups.
Interpretation — Postoperative intra-articular bolus injections of ropivacaine and ketorolac cannot be recommended as analgesic method after THA.
doi:10.3109/17453674.2015.1081340
PMCID: PMC4750761  PMID: 26312445
3.  Femoral nerve block-sciatic nerve block vs. femoral nerve block-local infiltration analgesia for total knee arthroplasty: a randomized controlled trial 
BMC Anesthesiology  2015;15:182.
Background
The use of femoral nerve block (FNB) combined with sciatic nerve block (SNB) after total knee arthroplasty (TKA) has recently become controversial. Local infiltration analgesia (LIA) has been reported to be effective for postoperative TKA pain control. We aimed to assess whether LIA with continuous FNB is as effective as SNB combined with continuous FNB.
Methods
This was a prospective, randomized, single-center, observer-blinded, parallel group comparison trial of 34 American Society of Anesthesiologists (ASA) physical status 1–3 patients who underwent TKA and fulfilled the inclusion and exclusion criteria. Patients were randomized into two groups: a periarticular LIA and FNB group (group L, n = 17), and an SNB and FNB group (group S, n = 17). In both groups, participants received FNB with 20 mL of 0.375 % ropivacaine, and 5 mL h−1 of 0.2 % ropivacaine after surgery. In group L, participants received 100-ml injections of 0.2 % ropivacaine and 0.5 mg epinephrine to the surgical region. In group S, participants received SNB with 20 ml of 0.375 % ropivacaine.
After TKA, Numeric Rating Scale (NRS) scores for the first 24 h post-operation were compared via repeated-measures analysis of variance (ANOVA) as the primary outcome. Other outcome measures included NRS score changes within groups, area under the curve for the NRS scores, total analgesic dose, change in knee flexion and extension, pain control satisfaction, nausea and vomiting, and hospital stay duration.
Results
NRS score changes were greater in group L than in group S (P < 0.01, ANOVA) and greater in group L than in group S at three postoperative time points: 3 h (P < 0.01), 6 h (P < 0.01), and 12 h (P = 0.013; Mann–Whitney U test). Changes in the mean NRS score were observed in each group (P < 0.01, Friedman test). No significant differences were detected in the other outcome measures (Mann–Whitney U, Wilcoxon signed-rank, and chi-squared tests).
Conclusions
Sciatic nerve block with femoral nerve block is superior to local anesthetic infiltration with femoral nerve block for postoperative pain control within 3–12 h of total knee arthroplasty.
Trial registration
UMIN-CTRID:000013364R:000015591
doi:10.1186/s12871-015-0160-3
PMCID: PMC4681154  PMID: 26669859
Postoperative pain; Knee arthroplasty; Nerve block; Femoral nerve; Sciatic nerve; Local anesthesia
4.  Doubtful effect of continuous intraarticular analgesia after total knee arthroplasty 
Acta Orthopaedica  2015;86(3):373-377.
Background and purpose
Local infiltration analgesia (LIA) is well established for effective postoperative pain relief in total knee arthroplasty (TKA). To prolong the effect of LIA, infusion pumps with local intraarticular analgesia can be used. We evaluated the effect of such an infusion pump for the first 48 h postoperatively regarding pain, knee function, length of stay (LOS) in hospital, and complications.
Patients and methods
200 patients received peroperative LIA and a continuous intraarticular elastomeric infusion pump set at 2 mL/h. The patients were randomized either to ropivacaine (7.5 mg/mL) or to NaCl (9 mg/mL) in the pump. Visual analog scale (VAS) pain (0–100 mm), analgesic consumption, side effects of medicine, range of motion (ROM), leg-raising ability, LOS, and complications during the first 3 months were recorded.
Results
On the first postoperative day, the ropivacaine group had lower VAS pain (33 vs. 40 at 12 noon and 36 vs. 43 at 8 p.m.; p = 0.02 and 0.03, respectively), but after that all recorded variables were similar between the groups. During the first 3 months, the ropivacaine group had a greater number of superficial and deep surgical wound infections (11 patients vs. 2 patients, p = 0.02). There were no other statistically significant differences between the groups.
Interpretation
Continuous intraarticular analgesia (CIAA) with ropivacaine after TKA has no relevant clinical effect on VAS pain and does not affect LOS, analgesic consumption, ROM, or leg-raising ability. There may, however, be a higher risk of wound-healing complications including deep infections.
doi:10.3109/17453674.2014.991629
PMCID: PMC4443449  PMID: 25428755
5.  Single-injection or Continuous Femoral Nerve Block for Total Knee Arthroplasty? 
Background
The ideal local anesthetic regime for femoral nerve block that balances analgesia with mobility after total knee arthroplasty (TKA) remains undefined.
Questions/purposes
We compared two volumes and concentrations of a fixed dose of ropivacaine for continuous femoral nerve block after TKA to a single injection femoral nerve block with ropivacaine to determine (1) time to discharge readiness; (2) early pain scores and analgesic consumption; and (3) functional outcomes, including range of motion and WOMAC scores at the time of recovery.
Methods
Ninety-nine patients were allocated to one of three continuous femoral nerve block groups for this randomized, placebo-controlled, double-blind trial: a high concentration group (ropivacaine 0.2% infusion), a low concentration group (ropivacaine 0.1% infusion), or a placebo infusion group (saline 0.9% infusion). Infusions were discontinued on postoperative Day (POD) 2. The primary outcome was time to discharge readiness. Secondary outcomes included opioid consumption, pain, and functional outcomes. Ninety-three patients completed the study protocol; the study was halted early because of unanticipated changes to pain protocols at the host institution, by which time only 61% of the required number of patients had been enrolled.
Results
With the numbers available, the mean time to discharge readiness was not different between groups (high concentration group, 62 hours [95% confidence interval [CI], 51–72 hours]; low concentration group, 73 hours [95% CI, 63–83 hours]; placebo infusion group 65 hours [95% CI, 56–75 hours]; p = 0.27). Patients in the low concentration group consumed significantly less morphine during the period of infusion (POD 1, high concentration group, 56 mg [95% CI, 42–70 mg]; low concentration group, 35 mg [95% CI, 27–43 mg]; placebo infusion group, 48 mg [95% CI, 38–59 mg], p = 0.02; POD 2, high concentration group, 50 mg [95% CI, 41–60 mg]; low concentration group, 33 mg [95% CI, 24–42 mg]; placebo infusion group, 39 mg [95% CI, 30–48 mg], p = 0.04); however, there were no important differences in pain scores or opioid-related side effects with the numbers available. Likewise, there were no important differences in functional outcomes between groups.
Conclusions
Based on this study, which was terminated prematurely before the desired sample size could be achieved, we were unable to demonstrate that varying the concentration and volume of a fixed-dose ropivacaine infusion for continuous femoral nerve block influences time to discharge readiness when compared with a conventional single-injection femoral nerve block after TKA. A low concentration of ropivacaine infusion can reduce postoperative opioid consumption but without any important differences in pain scores, side effects, or functional outcomes. These pilot data may be used to inform the statistical power of future randomized trials.
Level of Evidence
Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-013-3192-3
PMCID: PMC3971237  PMID: 23928707
6.  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
7.  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
8.  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
9.  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
10.  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
11.  Perioperative local infiltration anesthesia with ropivacaine has no effect on postoperative pain after total hip arthroplasty 
Acta Orthopaedica  2015;86(6):654-658.
Background and purpose — The local infiltration analgesia (LIA) technique has been widely used to reduce opioid requirements and to improve postoperative mobilization following total hip arthroplasty (THA). However, the evidence for the efficacy of LIA in THA is not yet clear. We determined whether single-shot LIA in addition to a multimodal analgesic regimen would reduce acute postoperative pain and opioid requirements after THA.
Patients and methods — 116 patients undergoing primary THA under spinal anesthesia were included in this randomized, double-blind, placebo-controlled trial. All patients received oral opioid-sparing multimodal analgesia: etoricoxib, acetaminophen, and glucocorticoid. The patients were randomized to receive either 150 mL ropivacaine (2 mg/mL) and 0.5 mL epinephrine (1 mg/mL) or 150 mL 0.9% saline. Rescue analgesic consisted of morphine and oxycodone as needed. The primary endpoint was pain during mobilization in the recovery unit. Secondary endpoints were pain during mobilization on the day after surgery and total postoperative opioid requirements on the first postoperative day.
Results — The levels of pain during mobilization—both in the recovery unit and on the day after surgery—and consumption of opioids on the first postoperative day were similar in the 2 groups.
Interpretation — LIA did not provide any extra analgesic effect after THA over and above that from the multimodal analgesic regimen used in this study.
doi:10.3109/17453674.2015.1053775
PMCID: PMC4750762  PMID: 25997827
12.  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
13.  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
14.  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
15.  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
16.  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
17.  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
18.  Epinephrine Affects Pharmacokinetics of Ropivacaine Infiltrated Into Palate 
Anesthesia Progress  2016;63(2):71-79.
Pulpal anesthesia success rates for ropivacaine following maxillary infiltration anesthesia seem to be low. We investigated the hypothesis that the addition of epinephrine would affect the pharmacokinetics of ropivacaine by retaining ropivacaine in the mucosa of the injected area through the time-dependent distribution of ropivacaine in the rat maxilla and serum following maxillary infiltration anesthesia using 3H-labeled ropivacaine. We then examined the vasoactivity of ropivacaine with or without epinephrine on local peripheral blood flow. The addition of epinephrine to ropivacaine increased ropivacaine concentrations in the palatal mucosa and adjacent maxilla by more than 3 times that of plain ropivacaine at 20 minutes. By observing the autoradiogram of 3H-ropivacaine, plain ropivacaine in the maxilla was remarkably reduced 20 minutes after injection. However, it was definitely retained in the palatal mucosa, hard palate, adjacent maxilla, and maxillary nerve after the administration with epinephrine. Ropivacaine with epinephrine significantly decreased labial blood flow. This study suggests that 10 μg/mL epinephrine added to 0.5% ropivacaine could improve anesthetic efficacy and duration for maxillary infiltration anesthesia over plain ropivacaine.
doi:10.2344/0003-3006-63.2.71
PMCID: PMC4896045  PMID: 27269664
Ropivacaine; Infiltration anesthesia; Epinephrine
19.  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
20.  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
21.  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
22.  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
23.  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
24.  Comparison of patient outcomes in periarticular and intraarticular local anaesthetic infiltration techniques in total knee arthroplasty 
Background
The use of local infiltration analgesia in the setting of knee arthroplasty is well established. There are no studies to date which have directly compared differences in infiltration techniques. The purpose of this study is to establish if a difference in patient outcomes exists when the infiltrate is injected into the periarticular tissues or directly into the joint.
Methods
One hundred and forty-two consecutive patients waitlisted for primary total knee arthroplasty were enrolled after primary exclusion criteria were applied. These included the following: allergy to study drugs, inability to receive spinal anaesthesia, and planned bilateral surgery. Patients were divided into two groups, a periarticular infiltration group (group A) and an intraarticular infiltration group (group B). Secondary exclusion criteria of regular opioid use, psychiatric illness, and serious medical comorbidity left a total of 47 patients in group A and 54 patients in group B. Both groups received a combination of 30 mg ketorolac, 500 μg of adrenaline, and 300 mg of ropivacaine, and normal saline. This was either injected into the periarticular tissues during surgery (group A) or intraarticularly after closure of the wound (group B).
Primary outcome measures included opioid consumption during the first 24 h postoperatively and over the total admission, and visual analogue scales (VAS) on postoperative day 1 and at discharge. Secondary measures included Oxford Knee Score, knee flexion, length of stay, haemoglobin drop, and transfusion requirement.
Ethics approval was granted by the hospital review board. The trial is registered in the Australian New Zealand Clinical Trials Registry, registration ACTRN12615000488505.
Results
No statistically significant differences in postoperative analgesic use were observed between the two groups. However, there was a trend toward decreased postoperative patient-controlled analgesia use in the periarticular group (mean 53.1 vs 68.3 mg morphine equivalents; p = 0.093), as well as a statistically significant reduction in postoperative visual analogue pain scores. No statistically significant differences were observed for haemoglobin drop, range of motion, or pre- to 6-week postoperative Oxford Score difference.
Conclusions
Our study is the first we are aware of to directly compare a periarticular to intraarticular injection technique when using local infiltration analgesia for total knee arthroplasty. Our results show no clear statistically significant benefit with either technique. The periarticular group showed a statistically significant reduction in postoperative VAS pain scores alongside a trend in that group toward reduced overall opioid use.
doi:10.1186/s13018-015-0249-x
PMCID: PMC4521462  PMID: 26227482
Local infiltration analgesia; Local anaesthetic; Total knee arthroplasty; Total knee replacement
25.  Comparison of local infiltration and epidural analgesia for postoperative pain control in total knee arthroplasty and total hip arthroplasty: A systematic review and meta-analysis 
Pain management after total knee arthroplasty (TKA) and total hip arthroplasty should permit early mobilization with minimal pain. Local infiltration analgesia (LIA) is a new popular method for decreasing postoperative pain. The goal of this meta-analysis is to evaluate the efficacy of LIA in comparison with epidural analgesia. A literature search was performed in PubMed, EMBASE, the OVID database, Web of Science, and the Cochrane Library databases. The risk of bias was assessed using the Cochrane collaboration tool. Outcomes of interest included visual analog scale score, range of flexion, length of stay, and complications. Nine trials involving 537 patients met the inclusion criteria. LIA provides better pain relief and larger range of motion in TKA patients compared to epidural analgesia at the late postoperative period. No significant difference was observed in regard to the length of stay and complications. The current evidence shows that the use of local infiltration is effective for postoperative pain management in TKA patients. More high-quality randomized controlled trials with long-term follow-up are required for examining the long-term efficacy and safety of local infiltration.
doi:10.17305/bjbms.2016.1072
PMCID: PMC5136758  PMID: 27209072
Total knee arthroplasty; total hip arthroplasty; local infiltration; epidural analgesia; meta-analysis

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