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      The efficacy of preoperative administration of gabapentin/pregabalin in improving pain after total hip arthroplasty: a meta-analysis

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          Abstract

          Background

          The purpose of this systematic review and meta-analysis of randomised controlled trials (RCTs) was to evaluate the pain control by gabapentin or pregabalin administration versus placebo after total hip arthroplasty (THA).

          Methods

          In January 2016, a systematic computer-based search was conducted in the Medline, Embase, PubMed, CENTRAL (Cochrane Controlled Trials Register), Web of Science and Google databases. This systematic review and meta-analysis were performed according to the PRISMA statement criteria. The primary endpoint was the cumulative morphine consumption and visual analogue scale (VAS) scores at 24 and 48 h with rest or mobilisation. The complications of vomiting, nausea, dizziness and pruritus were also compiled to assess the safety of gabapentin and pregabalin. Stata 12.0 software was used for the meta-analysis. After testing for publication bias and heterogeneity across studies, the data were aggregated for random-effects modelling when necessary.

          Results

          Seven studies involving 769 patients met the inclusion criteria. The meta-analysis revealed that treatment with gabapentin or pregabalin can decrease the cumulative morphine consumption at 24 h (mean difference (MD) = −7.82; 95 % CI −0.95 to −0.52; P < 0.001) and 48 h (MD = −6.90; 95 % CI −0.95 to −0.57; P = 0.118). Gabapentin or pregabalin produced no better outcome than placebo in terms of VAS score with rest at 24 h (SMD = 0.15; 95 % CI −0.17 to −0.48; P = 0.360) and with rest at 48 h (SMD = 0.22; 95 % CI −0.25 to 0.69; P = 0.363). There was no statistically significant difference between the groups with respect to the VAS score at 24 h postoperatively (SMD = 0.46; 95 % CI −0.19 to 1.11; P = 0.164) and at 48 h postoperatively (SMD = 1.15; 95 % CI −0.58 to 2.89; P = 0.193). Gabapentin decreased the occurrence of nausea (relative risk (RR), 0.49; 95 % CI 0.27–0.92, P = 0.025), but there was no significant difference in the incidence of vomiting, dizziness and pruritus.

          Conclusions

          On the basis of the current meta-analysis, gabapentin or pregabalin can decrease the cumulative morphine consumption and decrease the occurrence of nausea; however, further trials are needed to assess the efficacy of pain control by gabapentin or pregabalin.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12891-016-1231-4) contains supplementary material, which is available to authorized users.

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          Most cited references24

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          Pregabalin for acute and chronic pain in adults.

          Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions. To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain. We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified from the reference lists of retrieved papers and on-line clinical trial databases. Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome. Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals. There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic nociceptive pain, like arthritis.Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose. The best (lowest) NNT for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia.With 600 mg pregabalin daily somnolence typically occurred in 15% to 25% and dizziness occurred in 27% to 46%. Treatment was discontinued due to adverse events in 18 to 28%. The proportion of participants reporting at least one adverse event was not affected by dose, nor was the number with a serious adverse event, which was not more than with placebo.Higher rates of substantial benefit were found in postherpetic neuralgia and painful diabetic neuropathy than in central neuropathic pain and fibromyalgia. For moderate and substantial benefit on any outcome NNTs for the former were generally six and below for 300 mg and 600 mg daily; for fibromyalgia NNTs were much higher, and generally seven and above. Pregabalin has proven efficacy in neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events. Individualisation of treatment is needed to maximise pain relief and minimise adverse events. There is no evidence to support the use of pregabalin in acute pain scenarios.
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            Postoperative pain treatment after total hip arthroplasty: a systematic review.

            Treatment of postoperative pain should rely on results from randomized controlled trials and meta-analyses of high scientific quality. The efficacy of a particular intervention may depend on the type of surgical procedure, which supports the reporting of "procedure-specific" interventions. The aim of this systematic review was to document the procedure-specific evidence for analgesic interventions after total hip arthroplasty (THA). This PRISMA-compliant and PROSPERO-registered review includes randomized placebo-controlled trials (RCTs) of medication-based analgesic interventions after THA. Endpoints were postoperative opioid consumption, pain scores (rest and during mobilization), adverse events, and length of hospital stay. Fifty-eight trials with 19 different interventions were retrieved. High risk of bias, substantial differences in assessment-tools and criteria for pain, irregular reporting of adverse events, considerable differences in supplemental analgesic consumption, and basic analgesic regimens generally characterized trials. Meta-analyses of non-steroidal anti-inflammatory drugs, local infiltration analgesia, intrathecal opioids, and lumbar plexus block provided a 24-hour intravenous morphine-sparing effect of 14.1 (95 % confidence interval: 8.0-20.2) mg, 7.5 (3.7-11.3) mg, 19.8 (14.9-24.7) mg, and 11.9 (6.4-17.3) mg, respectively. Non-steroidal anti-inflammatory drugs and lumbar plexus block were demonstrated to provide reductions in postoperative pain scores. Intrathecal opioids increased pruritus, and lumbar plexus block reduced nausea and pruritus. The GRADE-rated quality of evidence ranged from low to very low throughout the analyses. This review demonstrated, that some analgesic interventions may have the capacity to reduce mean opioid requirements and/or mean pain intensity compared with controls, but the available randomized placebo-controlled trials does not allow a designation of a "best proven intervention" for THA.
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              Pregabalin and dexamethasone for postoperative pain control: a randomized controlled study in hip arthroplasty.

              Optimal pain treatment with minimal side-effects is essential for early mobility and recovery in patients undergoing total hip arthroplasty. We investigated the analgesic effect of pregabalin and dexamethasone in this surgical procedure. One hundred and twenty patients were randomly allocated to either Group A (placebo), Group B (pregabalin 300 mg), or Group C (pregabalin 300 mg+dexamethasone 8 mg). The medication and acetaminophen 1 g were given before operation. Spinal anaesthesia was performed. Postoperative pain treatment was with acetaminophen 1 g three times daily and patient-controlled i.v morphine, 2.5 mg bolus. Nausea was treated with ondansetron. Morphine consumption, pain intensity at rest and during mobilization, nausea and vomiting, sedation, dizziness, and consumption of ondansetron were recorded 2, 4, and 24 h after operation. P<0.05 was considered statistically significant. Twenty-four hour morphine consumption was significantly reduced in Groups B [mean (SD) 24 (14) mg] and C [25 (19) mg] compared with Group A [47 (28) mg]. Vomiting was reduced in Group C compared with Group B (P=0.03). Sedation was significantly increased in Group B compared with the other groups. Pregabalin resulted in a 50% reduction in 24 h postoperative morphine requirements. This was not associated with a reduced incidence of nausea or vomiting. Pregabalin resulted in increased levels of sedation. Combining pregabalin and dexamethasone provided no additional effects on pain or opioid requirements.
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                Author and article information

                Contributors
                maodeyinglong@163.com
                guoliangtougao@sina.com
                dingweiguotougao@sina.com
                Journal
                BMC Musculoskelet Disord
                BMC Musculoskelet Disord
                BMC Musculoskeletal Disorders
                BioMed Central (London )
                1471-2474
                30 August 2016
                30 August 2016
                2016
                : 17
                : 1
                : 373
                Affiliations
                [1 ]Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang Chinese Medical University, 318 Chaowang Road, Hangzhou, Zhejiang 310005 People’s Republic of China
                [2 ]Department of Orthopaedics, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou, Zhejiang 310012 People’s Republic of China
                Article
                1231
                10.1186/s12891-016-1231-4
                5004259
                99ebcfc3-7229-423c-96ce-f545b7468ded
                © The Author(s). 2016

                Open AccessThis 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.

                History
                : 1 April 2016
                : 23 August 2016
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2016

                Orthopedics
                gabapentin,pregabalin,total hip replacement,meta-analysis
                Orthopedics
                gabapentin, pregabalin, total hip replacement, meta-analysis

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