The local infiltration of analgesia following total knee replacement

INSTRUCTIONAL REVIEW: KNEE The local infiltration of analgesia following total knee replacement A REVIEW OF CURRENT LITERATURE D. M. R. Gibbs, T. P. Green, C. N. Esler From Leicester General Hospital, Leicester, United Kingdom D. M. R. Gibbs, MA, MRCS, Specialty Registrar in Trauma and Orthopaedic Surgery T. P. Green, FRCS (Tr & Orth), Consultant Trauma and Orthopaedic Surgeon C. N. Esler, FRCS (Tr & Orth), Consultant Trauma and Orthopaedic Surgeon Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. Correspondence should be sent to Mr D. M. R. Gibbs; e-mail: dmrgibbs@yahoo.co.uk 2012 British Editorial Society of Bone and Joint Surgery doi:10.1302/0301-620x.94b9. 28611 $2.00 J Bone Joint Surg Br 2012;94-B:1154 9. Controversy remains regarding the optimal post-operative analgesic regimen following total knee replacement. A delicate balance is required between the provision of adequate pain relief and early mobilisation. By reviewing 29 randomised trials we sought to establish whether local infiltration of analgesia directly into the knee during surgery provides better pain relief and a more rapid rehabilitation. Although we were able to conclude that local infiltration can provide improved post-operative pain relief, and to suggest the most promising technique of administration, there is no evidence that it reduces hospital stay. A recent systematic review supported the use of either general anaesthesia combined with a femoral nerve block, or spinal anaesthesia, to provide both operative anaesthesia and postoperative pain relief following total knee replacement (TKR). 1 Severe complications are rare following peripheral nerve blocks 2 or spinal anaesthesia, 3 but many patients remain in significant pain following surgery despite their use, 4 and this may increase the incidence of chronic pain. 5 Local infiltration of analgesic agents (LIA) into soft tissues following TKR may provide effective pain relief while permitting accelerated rehabilitation. Andersen et al 6 described local infiltration as the systematic of high volumes of analgesic agents with into all tissues exposed, instrumented or incised during surgery, including the capsule, ligaments and other soft tissues, as well as the subcutaneous layers. A wide range of local infiltration techniques have been described, using various agents and methods of administration. Agents used in combination with local anaesthetic include steroids, 7 magnesium sulphate, 8 morphine 9 and nonsteroidal anti-inflammatory drugs. 10 Methods of administration include intra-articular, 11 infiltration of all instrumented tissues 6 and intraarticular. 12 There is currently no consensus on the effectiveness of local infiltration compared with peripheral nerve blocks or placebo, or what effect they may have on hospital stay. Our aim was to review the literature pertaining to the use of local infiltration in providing pain relief following TKR. We sought to establish whether it offers effective safe analgesia and a shorter hospital stay, with a view to identifying the most promising techniques. Patients and Methods We searched the National Institutes of Health PubMed database for English-language articles using the phrases intra-articular analgesia following TKR and TKR analgesia. This produced 11 and 386 matches, respectively. Articles relating to the local administration of analgesia were selected. Non-randomised controlled trials, and those including surgery other than TKR, were excluded, leaving a total of 29 studies to review. The studies were divided into three categories (Tables I to III): those comparing a single local administration of analgesia with a control group (13 studies) 7-9,11,13-21 ; those comparing a continuous, or multiple administrations of analgesia to the knee, with a control group (11 studies) 10,12,22-30 ; and those evaluating different local infiltration techniques (five studies). 6,31-34 Outcome measures The primary endpoints used in the studies included pain at rest and/or during exercise, typically measured using a visual analogue score; and opiate consumption. In general, opiate consumption and pain during exercise were more sensitive outcome measures than pain at rest. Other endpoints included patient satisfaction, discharge readiness, and length of inpatient stay. Results Studies including a control group and single administration of analgesic agents to the knee. Of the 13 studies identified, seven concluded that the technique was beneficial in providing analgesia, 7,8,11,13-16 and six concluded that it was of no benefit. 9,17-21 However, none 1154 THE JOURNAL OF BONE AND JOINT SURGERY

THE LOCAL INFILTRATION OF ANALGESIA FOLLOWING TOTAL KNEE REPLACEMENT 1155 Table I. Effect of single-administration of local infiltration of anaesthetic agents (LIA) on post-operative pain relief Authors Patients (n) Groups * method Administration Cocktail Paracetamol/ Drain/blocks/ anaesthesia Findings of LIA Badner et al 11 82 1. Pre-op Intra-articular 150 mg bupivacaine, 0.15 mg 2. Post-op 3. Saline Tanaka et al 13 69 1. RA synovectomy + saline Intra-articular 75 mg bupivacaine, 0.15 mg, 5 mg morphine 2. RA synovectomy + local 3. OA + saline 4. OA + local Busch et al 14 64 1. LIA 400 mg ropivacaine,, 5 mg epimorphine, 0.6 mg 2. No LIA?nerve block. Reduced morphine consumption in group All GA 2 for 24 h. No difference in pain All had drains.?nerve block. in groups 2+4 for 48 h. Reduced pain at rest groups 2+4 for 24 h?nerve block. for 24 h. Mix of GA & spinal Reduced pain for 4 h Fu et al 15 80 1. Treatment 30 mg bupivacaine, 5 mg morphine, 1 mg betamethasone 2. Saline?para. All had celecoxib?nerve block. Reduced morphine consumption for 36 h. Reduced pain for 36 h Chen et al 8 80 1. Treatment Intra-articular 190 mg ropivacaine, magnesium sulphate 2. Saline?nerve block. Reduced morphine consumption for 24 h. Reduced pain for 24 h Fu et al 7 100 1. Treatment, tramadol and celecoxib 2. Saline, placebo Koh et al 16 55 (110 knees) 1. Injection Systematic infiltration IPC 2. No 150 mg ropivacaine, 0.5 mg, 1 ml betamethasone 300 mg ropivacaine, 10 mg morphine, 0.3 mg?para. Group 1 received tramadol & Para/S controlled?nerve block. Reduced morphine consumption for 7 days. Reduction in pain for 7 days? Spinal then epidural for up to 3 days Reduction in pain for 24 h Ritter et al 9 437 1. Morphine Intra-articular 10 mg morphine, 25 mg bupivacaine?para. Ketorolac use varied 2. Bupivacaine 3. Saline 4. Morphine + bupivacaine Klasen et al 17 30 1. Epidural Intra-articular 1 mg morphine 2. Injection 3. Control Browne et al 18 60 1. Treatment Intra-articular 100 mg bupivacaine 2. Saline No drains. Mix of spinal & epidural?blocks. Spinal?drain.?nerve blocks.?ga/spinal Groups 1+3 required more opiate. No difference in pain No difference in morphine consumption. No difference in pain No significant difference in opioid requirement or pain for 24 h Han et al 19 90 1. LA,, morphine SLIA EPC 300 mg ropivacaine, 1.25 mcg, 5 mg morphine 2. LA, 3. Saline Drains used.?nerve block. Spinal + epidural pca 24 h No difference in opiate consumption. No difference in pain Mauerhan et al 20 105 1. Saline Injection via drain 50 mg bupivacaine, 5 mg morphine 2. Morphine 3. LA 4. Morphine + LA Drains used.?nerve block. No difference in opioid consumption. Reduced pain for 4 h Badner et al 21 75 1. LA + Intra-articular 150 mg bupivacaine, 1.5 mg, 1 mg morphine Drains used.?nerve block. All GA No difference in morphine consumption. No difference in pain 2. LA, + morphine 3. Adrenaline + morphine * RA, rheumatoid arthritis; OA, osteoarthritis; LA, local anaesthetic /EPC, systematic infiltration including/excluding posterior capsule para, paracetamol;, non-steroidal anti-inflammatory drug;?, use or absence not described GA, general anaesthesia; pca, patient-controlled analgesia described the use of peripheral nerve blocks. The single study in this group that adequately controlled oral analgesic use found that local infiltration provided additional analgesia even against the background of an epidural. 16 Failure of the other studies to demonstrate analgesic efficacy may be explained by the lack of systematic infiltration 17-21 or the use of subtherapeutic doses. 9,17,20 The only study to include data on length of hospital stay found that local infiltration had no effect. 9 Studies including or multiple administration of analgesic agents to the knee. Of the 11 randomised controlled studies identified, seven used multiple administrations of analgesia to the knee following TKR, 10,22-26,29 and four used continuous. 12,27,28,30 Of the former, only four controlled for usage of both paracetamol and non-steroidal anti-inflammatory drugs, 10,23,25,29 and five studies reported local infiltration to be effective in providing analgesia. 10,22-24,26 Three of the studies employing a VOL. 94-B, No. 9, SEPTEMBER 2012

1156 D. M. R. GIBBS, T. P. GREEN, C. N. ESLER Table II. The effect of multiple administrations of analgesia on post-operative pain Author/s Patients (n) Groups * method Administration Cocktail used in initial infiltration Subsequent Drains/nerve block/ administrations Paracetamol/ Findings of LIA anaesthesia Kazak Bengisun et al 22 60 1. Bupivacaine + 2. Levobupivacaine + 1. 200 mg bupivacaine, 0.5 mg 1. 120 mg bupivacaine at 10 h and 22 h 2. 200 mg levobupivacaine, 0.5 mg adrena- + 0.5 mg at 10 h 2. 120 mg levobupivacaine line and 22 h 3. Saline 3. Saline 3. - Vendittoli et al 10 42 1. LIA 1. 275 mg ropivacaine, 0.5 mg 2. Control No / Andersen et al 23 12 (24 knees) 1. LIA 1. 340 mg ropivacaine, 1.7 mg 2. Control 2. Saline Essving et al 24 48 1. LIA 1. 400 mg ropivacaine, 0.5 mg, 2. No 2. Saline Carli et al 25 40 1. LIA. Solution A infiltrated in posterior capsule. Solution B used for LIA in remainder of knee. A: 100 mg ropivacaine, 0.25 mg, 15 mg ketorolac B: 200 mg ropivacaine,, 0.5 mg LIA 2. Continuous Infiltration of posterior capsule Solution A femoral nerve block for 48 h with infiltration of only the posterior capsule 1. 150 mg ropivacaine after 16 to 24 h, intra-articular via catheter 1. At 8 h, 40 mg ropivacaine + 0.2 mg intraarticular. At 24 h, 100 mg ropivacaine + 0.5 mg into joint with catheter pull?para. Diclofenac as rescue 1. At 21 h, 200 mg ropivacaine All para.? + + 0.1 mg intraarticular 1. 250 mg ropivacaine30 mg ketorolac, 0.25 mg at 24 h in joint 2. Ropivacaine via femoral nerve catheter blocks. blocks. blocks. No drains. No blocks. All GA and pain in groups 1 and 2 for 48 h for 48 h. Reduced pain for 48 h Reduced pain for 24 h for 48 h. Reduced pain for 27 h No drains. Femoral Greater morphine consumption. No difference in block. pain Spreng et al 26 99 1. Epidural 48 h 1. - 1. - All para.?s No drains.?blocks. Reduced morphine consumption in group 2 over 3 days. Reduced pain groups 2+3 on days 2 and 3 2. LIA 2. 150 mg ropivacaine, 2. At 24 h, intra-articular catheter 332.5 mg ropivacaine, 0.5 mg, 5 mg morphine, 30 mg LIA ketorolac LIA 3. LIA + ketorolac i.v. Gómez-Cardero and 50 1. LA SLIA EPC 1. Ropivacaine 10 mg/ Rodríguez-Merchán 27 hour for 60 hours 3. 150 mg ropivacaine, 3. At 24 h, intra-articular catheter 332.5 mg ropivacaine, i.v. 0.5 mg, 5 mg morphine LIA, 30 mg ketorolac i.v. 2. Saline 2. - 2. - 1. - All para. & ketorolac blocks. and pain for 3 days Andersen et al 28 40 1. LIA + intra articular 2. Epidural + i.v. ketorolac Ong et al 12 54 1. Control. 1.Morphine iv PCA only 1. - 2. Continuous intraarticular for 48 h 3. intra articular + 48 hr 300 mg ropivacaine, 1. of ropivacaine All para. & ketorolac, 0.5 mg 8 mg/h + 1.25 mg/h ketorolac for 48 h 2. 240 mg/day bupivacaine 3. 240 mg/day bupivacaine, and, 10 mg morphine and 100 mg bupivacaine 2. Epidural 8 mg/h ropivacaine for 48 h & i.v. ketorolac 2. - blocks. 3. - All para. & etoricoxib Drains used.?blocks. Spinal & GA Toftdahl et al 29 77 1. Femoral nerve 1. Femoral nerve block 1. Continuous femoral nerve All para. & ibuprofen block and femoral block for 48 h 2. LIA and delayed Nechleba et al 30 30 1. Bupivacaine Intra-articular 2. 300 mg ropivacaine, 2. At 12 & 24h, 200 mg ropivacaine,,, 0.5 mg 0.5 mg via intraarticular catheter 2. Saline 2. Saline * LIA, local infiltration of anaesthetic agent; i.v., intravenous; LA, local anaesthetic /EPC, systematic infiltration including/excluding posterior capsule para, paracetamol;, non-steroidal anti-inflammatory drug;?, use or absence not described all statements imply statistical significance achieved. Pain refers to pain at rest measured by VAS unless stated otherwise Drains used. Blocks as described Reduced morphine consumption for 2 days. Reduced pain for 3 days Reduced morphine consumption in groups 2+3 for 2 days. Reduced pain in groups 2+3 for 2 days in group 1 for 24 h. No difference in pain 1. 100 mg bupivacaine 1. 10.25 mg/h bupivacaine?para Drain used No difference in opioid consumption. No difference in pain continuous reported analgesic efficacy. 12,27,28 Spreng et al 26 found local application of ketorolac to be more effective than systemic administration. Carli et al 25 and Toftdahl et al 29 demonstrated that local infiltration provided less effective analgesia than a continuous femoral nerve block. None of these studies reported an increase in infection with the use of local infiltration. However, only Essving et al 24 THE JOURNAL OF BONE AND JOINT SURGERY

THE LOCAL INFILTRATION OF ANALGESIA FOLLOWING TOTAL KNEE REPLACEMENT 1157 Table III. Studies comparing different local infiltration of anaesthetic (LIA) techniques with no control group Author/s Patients (n) Groups Administration method * Cocktail in initial Drain/block/ infiltration Subsequent administrations Paracetamol/ anaesthesia Findings Andersen et al 6 48 1. LIA + bandage Both groups: 340 mg Both groups: At 6 and 12 h, ropivacaine, 1 mg ; at 24 h, 40 mg ropivacaine, 0.2 mg 100 mg ropivacaine 2. LIA Less pain at 8 h with bandage Andersen et al 31 43 1. LIA Both groups: 300 mg ropivacaine, 1 mg 1. At 6 and 24 h intra-articular 20 ml 0.5% ropivacaine 2. LIA 2. At 6 and 24 h intra-articular 10 ml 1% ropivacaine No difference Andersen et al 34 16 (32 knees) 1. LIA 1. 200 mg ropivacaine, 1 mg, and 100 mg ropivacaine to superficial layers 2. LIA (excl. superficial layers) 2. 200 mg ropivacaine, 2. Saline 1 mg, and saline to superficial layers 1. 100 mg ropivacaine subcutaneously at 24 h Group 1, less pain for 6 hours. No difference at 24 h Andersen et al 32 60 1. LIA + delayed extra-articular 2. LIA + delayed intra-articular Both groups: 300 mg ropivacaine, 1 mg 1. At 6 and 24 h, 100 mg intracapsular extra-articular 2. At 6 and 24 h, 100 mg intracapsular intra-articular No difference between groups Andersen et al 33 32 1. LIA + 3 delayed s and extra-articular local anaesthetic 2. LIA + 3 delayed s Both groups: 340 mg ropivacaine, 1.2 mg 1. At 6 h, 12 h and 24 h, 40 mg ropivacaine + 0.2 mg intra-articular. Additional 60 mg ropivacaine + 0.3 mg on drain retraction 2. At 6 h, 12 h and 24 h, 40 mg ropivacaine + 0.2 mg intra-articular. Saline on drain retraction No difference between groups *, systemic infiltration including posterior capsule para, paracetamol;, non-steroidal anti-inflammatory drug all results stated imply statistical significance was achieved Table IV. Effect of delayed administrations of local anaesthetic on post-operative pain at rest Interval Authors Delivery route Six hours Eight hours 12 hours 21 hours 24 hours Effect on pain at rest * Andersen et al 23 Intra-articular 40 mg ropivacaine + 0.2 mg Essving et al 24 Intra-articular 200 mg ropivacaine, + 0.1 mg Andersen et al 6 Intra-capsular 40 mg ropivacaine + 0.2 mg 40 mg ropivacaine + 0.2 mg 100 mg ropivacaine + 0.5 mg 100 mg ropivacaine + 0.5 mg At 8 h: none. At 24 h: 9 mm decrease on an 10 mm visual analogue scale Decrease At 6 h: none. No data for 12 h and 24 h Andersen et al 31 Intra-capsular 100 mg ropivacaine 100 mg ropivacaine At 6 h: none. At 24 h decrease Andersen et al 32 Intra-/extra-articular 100 mg ropivacaine 100 mg ropivacaine At 6 h and 24 h: decrease Andersen et al 33 Intra-articular 40 mg ropivacaine + 0.2 mg 40 mg ropivacaine + 0.2 mg 100 mg ropivacaine No data for 6 h and 12 h. At 24 h: no decrease Andersen et al 34 Subcutaneous tissues 100 mg ropivacaine No decrease * all statements imply statistical significance was reached unless otherwise stated followed the patients for more than six weeks. They found that three catheter tips grew Staphylococcus when sent for culture. 24 In this study the catheters had remained in situ for 21 hours post-operatively. Essving et al 24 and Andersen et al 23 demonstrated a decrease in pain both at rest and during movement following an given 24 hours after surgery. The results of the effect of delayed s from these studies, and those from studies comparing different LIA techniques, are summarised in Table IV. A total of nine studies measured length of hospital stay 12,22,24-28,30,31 : six found that local infiltration failed to demonstrate a significant reduction in length of stay. 12,24,25,28-30 Two of these 24,28 reported that local infiltration reduced the time taken for patients to be ready for discharge, without achieving a significant reduction in length of hospital stay. Spreng et al, 26 Gómez-Cardero and Rodrígues-Merchán 27 and Kazak Bengisun et al 22 all reported a shorter hospital stay with local infiltration. Studies comparing different local infiltration techniques. Andersen et al 6,31-34 conducted five randomised controlled studies investigating the efficacy of a variety of local infiltration techniques, in which the administration of oral analgesics were controlled. All used the same initial infiltration of ropivacaine and of all instrumented tissues. Following this, groups received slight variations in volume/concentration of analgesia, 31 use of VOL. 94-B, No. 9, SEPTEMBER 2012

1158 D. M. R. GIBBS, T. P. GREEN, C. N. ESLER bandaging, 6 catheter site placement 32,33 and additional subcutaneous administrations of analgesia. 33 None of the minor variations in technique demonstrated any convincing superiority in efficacy. All of the studies permitted additional doses of local analgesia at various times following the initial infiltration. Of these studies, three found no efficacy in reducing pain, 6,33,34 whereas two did find efficacy in pain relief. 31,32 A summary of data on pain following delayed administrations of analgesia is shown in Table IV. Discussion There is evidence that local infiltration is safe and can reduce post-operative pain following TKR. The most effective technique involves the infiltration of a mixture of high-dose ropivacaine with and ketorolac. There is less strong evidence that local infiltration can reduce hospital stay. Many studies were poorly controlled, with no standardisation of oral analgesics, 7-9,11,13-15,17-22,24,26,30 whereas in some studies where this factor was standardised there was no control group. 6,31-34 In eight studies 10,12,16,23,25,27-29 representing 437 TKRs, standardised analgesia was used and a control group was included. Of these, six 10,12,16,23,27,28 found local infiltration to reduce post-operative pain. Carli et al 25 and Toftdahl et al 29 found local infiltration to be less effective than a continuous femoral nerve block. From these reports we would recommend that local infiltration be used as an adjunct to, rather than in place of, a femoral nerve block. All of the six trials with standardised oral analgesia and a control group that found local infiltration to be effective 10,12,16,23,27,28 used a cocktail of high-dose local anaesthetic (usually ropivacaine). Five used, and all used non-steroidal anti-inflammatory drugs either orally or in the infiltrate. It is noteworthy that ketorolac, an, has been shown to provide greater effect when given locally than systemically. 26 Despite previous concerns regarding the risk of haemorrhage following the use of ketorolac post-operatively, 35 no such complication was recorded in any of the studies. Of the 12 studies employing systematic infiltration of all tissues exposed in the operative field, including the posterior capsule, eleven found local infiltration to be effective. 7,10,14-16,23,24,26,27,29,30 Carli et al 25 did not find it to be effective. Of the 12 studies that did not employ systematic infiltration, 8,9,11-13,17-21,27,30 only five found local infiltration to be effective. 8,11,13,18,20 Accordingly we advocate the use of a cocktail of high-dose ropivacaine, and ketorolac delivered by systematic infiltration of all exposed tissues, including the posterior capsule. No cardiac side effects or convulsions were reported in any of these studies, nor was there any increase in infection associated with indwelling catheters. However, in many studies the follow-up period may not have been of sufficient duration to detect infection. 36 Of the seven studies that provided some data on the efficacy of delayed administrations 6,23,24,31-34 only three showed any therapeutic benefit (Table IV). 23,24,31 Given the possibility of infection, and the disappointing result of delayed doses of local analgesia, we would suggest the use of a single intra-operative administration of anaesthetic cocktail. Of the ten studies that investigated the effect of local infiltration on hospital stay, 9,12,22,24-30 seven found it to make no significant difference. 9,12,24,25,28-30 Length of stay following TKR is dependent on many factors, including pre-operative haemoglobin, age, American Society of Anesthesiologists grading 37 and gender. 38 At present there is no conclusive evidence that local infiltration reduces hospital stay. Acute post-operative pain, when poorly managed, is a predictive factor in the development of chronic pain. 5 Therefore, by reducing acute post-operative pain local infiltration might be expected to reduce the occurrence of chronic postoperative pain. Although data are currently lacking, an investigation is under way to provide the answer. 39 In conclusion, although we advocate the use of local infiltration as an adjunct to a femoral nerve block to provide additional analgesia, there is no definitive evidence that it reduces the length of hospital stay. 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