Tang et al. Journal of Orthopaedic Surgery and Research (2017) 12:125 DOI 10.1186/s13018-017-0621-0 RESEARCHARTICLE Open Access Intrathecal morphine versus femoral nerve block for pain control after total knee arthroplasty: a meta-analysis Yi Tang, Xu Tang, Qinghua Wei and Hui Zhang* Abstract Background: This meta-analysis aims to illustrate the efficacy and safety of intrathecal morphine (ITM) versus femoral nerve block (FNB) for pain control after total knee arthroplasty (TKA). Methods: In April 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, Cami Info. Inc., Casalini databases, EBSCO databases, Verlag database and Google database. Data on patients prepared for TKA surgery in studies that compared ITM versus FNB for pain control after TKA were collected. The main outcomes were the visual analogue scale (VAS) at 6, 12, 24, 48 and 72 and total morphine consumption at 12, 24 and 48 h. The secondary outcomes were complications that included postoperative nausea and vomiting (PONV) and itching. Stata 12.0 was used for pooling the data. Results: Five clinical studies with a total of 225 patients (ITM group = 114, FNB group = 111) were ultimately included in the meta-analysis. The results revealed that the ITM group was associated with a reduction of VAS at 6, 12, 24, 48 and 72 h and total morphine consumption at 12, 24 and 48 h. There was no significant difference between the occurrences of PONV. However, the ITM group was associated with an increased occurrence of itching after TKA. Conclusions: Some immediate analgesic efficacy and opioid-sparing effects were obtained with the administration of ITM when compared with FNB. The complications of itching in the ITM group were greater than in the FNB group. The sample size and the quality of the included studies were limited. A multi-centre RCT is needed to identify the optimal method for reaching maximum pain control after TKA. Keywords: Intrathecal morphine, Total knee arthroplasty, Femoral nerve block, Meta-analysis Background recommendation by the PROSPECT working group [6], Total knee arthroplasty (TKA) leads to considerable post- FNB and ITM have become two common methods for operative pain [1, 2]. Ineffective pain control after TKA postoperative analgesia management following TKA. can cause many side effects [3]. Optimal pain control can Regarding the efficacy and safety of ITM and FNB for not only decrease complications but also facilitate fast re- pain control after TKA, there has yet to be a consensus. covery during the immediate postoperative period [4]. Recently, Li et al. [7] conducted a meta-analysis for this Currently, a multimodal technique, a new concept, is topic. However, several disadvantages existed in that accepted by most surgeons. Multimodal analgesia includes meta-analysis. First it ignored important randomized regional techniques, systemic opioids and preoperative ad- controlled trials (RCTs), which may have had an import- ministration gabapentin. Thus, femoral nerve block (FNB) ant influence on the final results [8]. Furthermore, and intrathecal morphine (ITM) are seldom used alone continuous FNB and single-shot FNB were not com- for the management of postoperative pain, though they pared in a subgroup analysis. Thus, the purpose of this are known to provide excellent analgesia [5]. Since the meta-analysis is to compare the efficacy and safety of ITM and FNB for pain control after TKA (Table 1). * Correspondence: [email protected] Department of Orthopedics, People’s Hospital of JianYang, No. 180, Yiyuan Road, Jiancheng zhen, Jianyang, Sichuan Province, China © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Tang et al. Journal of Orthopaedic Surgery and Research (2017) 12:125 Page 2 of 8 Table 1 The general characteristic of the included studies. Study Country FNB Group Surgery ITM Group Outcomes Follow- up No. of Method Drug No. of Dose Concomitant pain patients patients management Frassanito Italy 26 SFNB Ropivacaine TKA 26 Hyperbaric Paracetamol 1 g i.v. 1, 2, 3, 4 48 h 2010 0.75% 25 ml bupivacaine four times daily and 15 mg plus intravenous. Ketorolac 0.1 mg of 30 mg 2 times every morphine 24 h sulphate Mohamed Egypt 20 SFNB Hyperbaric bupivacaine TKA 20 0.2 mg PCA with morphine 1, 2, 3, 4 3 month 2016 15 mg morphine Olive Australia 27 CFNB 20 ml bottle of TKA 28 0.5% 0.5% bupivacaine 1, 2, 3, 4 1 year 2015 0.5% bupivacaine bupivacaine 3.5 mL 3.5 ml plus 0.175 mg morphine Sites 2004 USA 20 SFNB 40 mL of 0.5% TKA 20 0.25 mg 30 mg ketorolac IV 1, 2, 3, 4 48 h ropivacaine with 75 mg morphine every 6 h of clonidine and 5 mg/mL and 15 mg of epinephrine hyperbaric bupivacaine Tarkkila India 18 CFNB 0.25% bupivacaine at a TKA 20 0.3 mg Oxycodone 0.1– 1, 2, 3, 4 48 h 1998 rate of 0.1 mL kg 1 h 1 morphine 0.14 mg/kg mixed with bupivacaine FNB femoral nerve block, ITM intrathecal morphine, TKA total knee arthroplasty Methods Inclusion criteria and study selection This systematic review was reported according to the Patients: patients prepared for primary unilateral TKA; preferred reporting items for systematic reviews and Intervention: use ITM as an intervention group; Com- meta-analyses (PRISMA) guidelines [9]. parison: use FNB as a comparison group; Outcomes: VAS at 6, 12, 24, 48 and 72 h, total morphine consump- tion at 12, 24 and 48, and related complications (postop- Search strategies erative nausea and vomiting (PONV) and itching); Study The following databases were searched in September design: RCTs (Fig. 1). 2016 without restrictions on location or publication Two independent reviewers screened the title and types: PubMed (1950–April 2017), EMBASE (1974– abstracts of the identified studies after removing the du- April 2017), the Cochrane Library (April 2017, Issue 4), plicates from the search results. Any disagreements Cami info. Lnc (1950–April 2017), Casalini databases about the inclusion or exclusion of a study were solved (1950–April 2017), EBSCO databases (1950–April 2017), through discussion or consultation with an expert Verlag database (1950–April 2017) and Google database (skilled in pain control and TKA). The reliability of the (1950–April 2017). The Mesh terms and their combina- study selection was determined by Cohen’s kappa test, tions used in the search were as follows: “analgesia” OR and the acceptable threshold value was set at 0.61 [6, 7]. “pain management” OR “anaesthetic agents” OR “total knee arthroplasty” OR “total knee replacement” OR “TKA” OR “TKR” OR ““Arthroplasty, Replacement, Data abstraction and quality assessment Knee”[Mesh]” AND “intrathecal morphine” OR “femoral A specific extraction was conducted to collect data in a nerve block”. The reference lists of related reviews and pre-generated standard Microsoft® Excel (Microsoft Cor- original articles were searched for any relevant studies, poration, Redmond, Washington, USA) file. The items ex- including RCTs involving adult humans. There was no tracted from relevant studies were as follows: first author language restriction for this meta-analysis. When mul- and publication year, country, sample size of the interven- tiple reports describing the same sample were published, tion and control groups, preoperative and postoperative the most recent or complete report was used. This doses, timing and frequency and the total dose of gaba- meta-analysis gathered data from published articles, and pentin per number of days and follow-ups. Abstracted and thus, no ethics approval was necessary for this article. recorded in the spreadsheet were outcomes such as the Tang et al. Journal of Orthopaedic Surgery and Research (2017) 12:125 Page 3 of 8 Fig. 1 Flowchart of study search and inclusion criteria VAS at 6, 12, 24, 48 and 72 h; total morphine consump- Outcome measures and statistical analysis tion at 12, 24 and 48 h; and related complications (PONV Continuous outcomes (VAS at 6, 12, 24, 48 and 72 h and and itching). Postoperative pain intensity was measured total morphine consumption at 12, 24 and 48 h) were using a 110-point VAS (0 = no pain and 100 = extreme expressed as weighted mean differences (WMD) with 95% pain). When the numerical rating scale (NRS) was CI. Dichotomous outcomes (the occurrence of PONV and reported, it was converted to a VAS. Additionally, a 10- itching) were expressed as a risk ratio (RR) with 95% CI. point VAS was converted to a 100-point VAS [10]. Data in Statistical significance was set at P <0.05tosummarize other forms (i.e. median, interquartile range, and mean ± 95% the findings across the trials. Variables in the meta- confidence interval (CI)) were converted to the mean ± stand- analysis were calculated using Stata software, version 12.0 ard deviation (SD) according to the Cochrane Handbook (Stata Corp., College Station, TX). Statistical heterogeneity [11]. If the data were not reported numerically, we extracted was evaluated using the chi-square test and the I2 statistic. these data using the “GetData Graph Digitizer” software When there was no statistical evidence of heterogeneity from the published figures. All the data were extracted by (I2 <50%,P > 0.1), a fixed-effects model was adopted; two independent reviewers, and disagreements were re- otherwise, a random-effects model was chosen.