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Meta-analysis
ACE Report #9228

Opioid-sparing effect, but limited analgesic efficacy, with preop gabapentinoids in THA


Study Type:Meta analysis
OE Level Evidence:2
Journal Level of Evidence:N/A

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

BMC Musculoskelet Disord. 2016 Aug 30;17(1):373

Contributing Authors: Y Mao L Wu W Ding

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Synopsis

Seven randomized controlled trials were included in this meta-analysis evaluating the efficacy and safety of preoperative gabapentin and pregabalin for postoperative analgesia following total hip arthroplasty. In all studies, gabapentin and/or pregabalin were compared to either placebo or no intervention. Pooled results demonstrated significantly lower cumulative morphine consumption with gabapentin compared to control up to 24 hours after surgery, and with pregabalin compared to control up to 48 hours after surgery. In contrast, pooled pain scores at rest or on mobilization did not demonstrate significantly lower scores with either gabapentin or pregabalin compared to control. In fact, pain scores during mobilization after 48 hours were significantly higher among gabapentin groups compared to control groups.

Publication Funding Details +
Funding:
Not Reported
Conflicts:
None disclosed

Risk of Bias

5.5/10

Reporting Criteria

16/20

Fragility Index

N/A

Were the search methods used to find evidence (original research) on the primary question or questions stated?

Was the search for evidence reasonably comprehensive?

Were the criteria used for deciding which studies to include in the overview reported?

Was the bias in the selection of studies avoided?

Were the criteria used for assessing the validity of the included studies reported?

Was the validity of all of the studies referred to in the text assessed with use of appropriate criteria (either in selecting the studies for inclusion or in analyzing the studies that were cited)?

Were the methods used to combine the findings of the relevant studies (to reach a conclusion) reported?

Were the findings of the relevant studies combined appropriately relative to the primary question that the overview addresses?

Were the conclusions made by the author or authors supported by the data and or analysis reported in the overview?

How would you rate the scientific quality of this evidence?

Yes = 1

Uncertain = 0.5

Not Relevant = 0

No = 0

The Reporting Criteria Assessment evaluates the transparency with which authors report the methodological and trial characteristics of the trial within the publication. The assessment is divided into five categories which are presented below.

4/4

Introduction

4/4

Accessing Data

3/4

Analysing Data

4/4

Results

1/4

Discussion

Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. J Clin Epidemiol. 1992;45:255-65

The Fragility Index is a tool that aids in the interpretation of significant findings, providing a measure of strength for a result. The Fragility Index represents the number of consecutive events that need to be added to a dichotomous outcome to make the finding no longer significant. A small number represents a weaker finding and a large number represents a stronger finding.

Why was this study needed now?

One of the most important areas of research regarding perioperative treatment of patients undergoing total hip arthroplasty is postoperative analgesia. Patient-controlled analgesia with opioids remains a standard method of analgesia, although the undesirable side-effects of opioids have led to an emphasis on trying to limit their administration to only rescue analgesia and improve primary treatment. Gabapentinoids, such as gabapentin and pregabalin, have been suggested as medications with possible analgesic efficacy in these patients.

What was the principal research question?

What are the efficacy and safety profiles of preoperative gabapentin and pregabalin, compared to control, for analgesia following total hip arthroplasty?

Study Characteristics -
Data Source:
MEDLINE, EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, Web of Science, and Google were searched for relevant articles published up to January 2016. Reference lists of identified articles were also hand search for any additional studies possibly missed by the electronic search.
Index Terms:
Search terms included: "gabapentin", "pregabalin", "pain control", "total hip arthroplasty", "total hip replacement", "THA" and "THR".
Study Selection:
Eligibility criteria included: a randomized controlled trial design; patients were scheduled for total hip arthroplasty; patients were allocated to an intervention group, consisting of treatment with either preoperative gabapentin or pregabalin, and a control group, consisting of either placebo treatment or no treatment; and reported at least one of the following outcomes: visual analog scale for pain, morphine consumption, or incidence of either pruritus, dizziness, or nausea. Study search and selection was performed independently by two reviewers, with disagreements resolved through discussion with a third reviewer. A total of 7 RCTs, with data sampled from 769 patients, were selected for final inclusion.
Data Extraction:
Data extraction was performed independently by two reviewers, with disagreement resolved by discussion and consensus.
Data Synthesis:
Statistical analyses were performed using Stata software (Stata 12.0). Continuous outcomes were expressed as mean differences (MD), and dichotomous outcomes as relative risks (RR), both with 95% confidence intervals. Heterogeneity was assessed using the I-squared (I^2) statistic, with values >50% considered indicative of significant statistical heterogeneity.

What were the important findings?

  • Pooled cumulative morphine consumption was significantly lower among gabapentin groups compared to control after 24h (MD -2.65 [95%CI -3.67, -1.63]; p<0.001) but not 48h (MD 0.00 [95%CI -7.69, 7.69]; p=1.000), while it was significantly lower for pregabalin compared to control after both 24 (MD -19.42 [95%CI -11.72, -3.93]; p<0.001) and 48h (MD -33.02 [95%CI -45.86, -20.19]; p<0.001).
  • VAS pain at rest and at 24h did not significantly differ between gabapentin and control (MD 0.32 [95%CI -0.03, 0.67]; p=0.076), and pregabalin and control (MD -3.05 [95%CI -11.63, 5.53]; p=0.486). VAS pain at rest was significantly higher with gabapentin compared to control after 48h (MD 0.41 [95%CI 0.00-0.81]; p=0.049).
  • VAS pain with mobilization between gabapentin and control did not significantly differ after 24h (MD 0.72 [95%CI -0.23, 1.66]), and was significantly higher among gabapentin groups after 48h (MD 1.90 [95%CI 0.04-3.75]; p=0.045). No significant difference in VAS pain with mobilization between pregabalin and control was observed after 24h (MD -0.78 [95%CI -6.91, 5.35]; p=0.803).
  • No significant difference between gabapentin/pregabalin groups overall and control groups was observed in the incidences of vomiting (RR 0.95 [95%CI 0.47-1.92]), dizziness (RR 0.82 [95%CI 0.51-1.33]), or pruritus (RR 0.89 [95%CI 0.57-1.39]). A significantly lower incidence of nausea was observed with gabapentin/pregabalin groups compared to control (RR 0.49 [95%CI 0.27-0.92]).

What should I remember most?

In total hip arthroplasty, an opioid-sparing effect was observed with preoperative gabapentin up to 24 hours after surgery, and with preoperative pregabalin up to 48 hours after surgery. However, neither treatment provided a significant benefit compared to the control group for pain at rest or on movement. In contrast, pooled pain scores during movement were actually higher in gabapentin groups compared to control groups after 48 hours.

How will this affect the care of my patients?

While there may be a short-term reduction in opioid requirement with the use of either gabapentin or pregabalin following total hip arthroplasty, these interventions do not appear to significantly reduce short-term pain scores in patients. Therefore, their role in postoperative analgesia following total hip arthroplasty should be scrutinized based on the currently available data. It is important to note limitations of the available body of evidence, as only 2-3 studies were available to separately assess the efficacy and safety of gabapentin and pregabalin each indicating the need to further large randomized controlled trials.

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