Postoperative pain treatment after total knee arthroplasty: A systematic review

<div><p>Introduction</p><p>The aim of this systematic review was to document efficacy, safety and quality of evidence of analgesic interventions after total knee arthroplasty (TKA).</p><p>Methods</p><p>This PRISMA-compliant and PROSPERO-registered review includes all-language randomized controlled trials of medication-based analgesic interventions after TKA. Bias was evaluated according to Cochrane methodology. Outcomes were opioid consumption (primary), pain scores at rest and during mobilization, adverse events, and length of stay. Interventions investigated in three or more trials were meta-analysed. Outcomes were evaluated using forest plots, Grading of Recommendations Assessment, Development and Evaluation (GRADE), L’Abbe Plots and trial sequential analysis.</p><p>Results</p><p>The included 113 trials, investigating 37 different analgesic interventions, were characterized by unclear/high risk of bias, low assay sensitivity and considerable differences in pain assessment tools, basic analgesic regimens, and reporting of adverse events. In meta-analyses single and continuous femoral nerve block (FNB), intrathecal morphine, local infiltration analgesia, intraarticular injection of local anaesthetics, non-steroidal anti-inflammatory drugs, and gabapentinoids demonstrated significant analgesic effects. The 24-hour morphine-sparing effects ranged from 4.2 mg (CI: 1.3, 7.2; intraarticular local anaesthetics), to 16.6 mg (CI: 11.2, 22; single FNB). Pain relieving effects at rest at 6 hours ranged from 4 mm (CI: -10, 2; gabapentinoids), to 19 mm (CI: 8, 31; single FNB), and at 24 hours from 3 mm (CI: -2, 8; gabapentinoids), to 16 mm (CI: 8, 23; continuous FNB). GRADE-rated quality of evidence was generally low.</p><p>Conclusion</p><p>A low quality of evidence, small sample sizes and heterogeneity of trial designs prohibit designation of an optimal procedure-specific analgesic regimen after TKA.</p></div

Flow chart of trial selection.

<p><i>From</i>: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). <i>P</i>referred <i>R</i>eporting <i>I</i>tems for <i>S</i>ystematic Reviews and <i>M</i>eta-<i>A</i>nalyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:<a href="http://dx.doi.org/10.1371/journal.pmed1000097" target="_blank">10.1371/journal.pmed1000097</a>. For more information, visit <a href="http://www.prisma-statement.org" target="_blank">www.prisma-statement.org</a>.</p

Study information.

<p>Study information.</p

0–24 hour morphine consumption.

<p>Forest plot displaying mean difference in 0–24 hour morphine consumption for each meta-analyzed intervention. Green squares with horizontal lines represent mean differences and 95% confidence intervals for each trial. Black tiles represent the mean difference of each intervention.</p

Summarized outcomes in Grading of Recommendations Assessment, Development and Evaluation (GRADE) for each major intervention.

<p>Summarized outcomes in Grading of Recommendations Assessment, Development and Evaluation (GRADE) for each major intervention.</p

Qualitative analysis of other interventions.

<p>Treatment effects and adverse events are presented as results in control group → intervention group. FNB: femoral nerve block. PCA: patient controlled analgesia. LIA: local infiltration analgesia. PACU: postoperative care unit.</p

Risk of bias in included studies.

<p>Green plus is low risk, yellow question mark is unclear risk, and red minus is high risk of bias. Slanted lines indicate that the trial is part of both surrounding subgroups. * Indicates that information regarding the bias domain has been reevaluated after obtaining an elaboration from the corresponding author of the trial.</p

Efficacy, quality of evidence and risk of bias.

<p>A summary of each meta-analyzed intervention regarding the effect on each outcome (opioid sparing effect in i.v. morphine equivalents mg, pain scores, and side effects), the GRADE-rated quality of evidence for each outcome and the estimated risk of bias of the included trials. The bold numbers are mean reductions for the relevant outcome, below each bold number is the 95% confidence interval, the p-value and the quality of evidence. Below each intervention the number of trials investigating the specific intervention is depicted. The colored bars to the right depict the distribution of summarized risk of bias for the included trials. Not all trials investigated all relevant outcomes. GRADE: The Grading of Recommandations Assessment, Development and Evaluation.</p

Summarized outcomes in Grading of Recommendations Assessment, Development and Evaluation (GRADE) for each major intervention.

<p>Summarized outcomes in Grading of Recommendations Assessment, Development and Evaluation (GRADE) for each major intervention.</p

24 hours pain scores.

<p>Forest plot displaying mean difference in pain scores 24 hours postoperative at rest for each meta-analyzed intervention. Green squares with horizontal lines represent mean differences and 95% confidence intervals for each trial. Black tiles represent the mean difference of each intervention.</p