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Meta-Analysis
. 2022 May 19;17(5):e0268178.
doi: 10.1371/journal.pone.0268178. eCollection 2022.

Effect of methylene blue on experimental postoperative adhesion: A systematic review and meta-analysis

Su Hyun Seo  1 , Geun Joo Choi  1 , Oh Haeng Lee  1 , Hyun Kang  1
Affiliations
Meta-Analysis

Effect of methylene blue on experimental postoperative adhesion: A systematic review and meta-analysis

Su Hyun Seo et al. PLoS One. .

Abstract

Adhesion is a primary challenge following surgery, and the anti-adhesive effect of methylene blue (MB) has been investigated. This systematic review and meta-analysis aimed to evaluate the effect of MB on postoperative adhesions in experimental studies. We initially searched OVID-MEDLINE, EMBASE, and Google Scholar in February 2021, and then in May 2021. The anti-adhesive efficacy of MB was compared with that of the control (either placebo or nothing) after the surgical procedure. The primary and secondary outcomes were the macroscopic and microscopic adhesion scores, respectively. Traditional meta-analysis, meta-regression, and trial sequential analysis (TSA) were performed to analyze the retrieved outcomes. We included 13 experimental studies of 367 rats (200 rats received MB and 167 rats received placebo or nothing). The macroscopic adhesion scores were significantly lower in the MB-administered group than in the control group (standardized mean difference, 2.313; 95% confidence interval, 1.104 to3.523; I2 = 94.0%, Tau = 2.059). Meta-regression analysis showed that macroscopic adhesion tended to decrease with an increase in MB dose. TSA demonstrated that the cumulative Z curve crossed both the conventional test and trial sequential monitoring boundary for the macroscopic adhesion score. MB had a beneficial effect on intraperitoneal adhesion following laparotomy, and adhesions decreased with increase in dose.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow diagram showing the number of abstracts and articles identified and evaluated during the review.
Fig 2
Fig 2. Forest plot showing an overall effect of macroscopic adhesion score compared with the combined results of using saline and nothing as control.
The figure depicts individual trials as filled squares with relative sample size and the 95% confidence interval (CI) of the difference as a solid line. The diamond shape indicates the pooled estimate and uncertainty for the combined effect.
Fig 3
Fig 3. Forest plot showing sensitivity analysis performed by removing one study at a time for an overall effect of macroscopic adhesion score, compared with combined results of using saline and nothing as control.
The figure depicts individual trials as filled squares with relative sample size and the 95% confidence interval (CI) of the difference as a solid line. The diamond shape indicates the pooled estimate and uncertainty for the combined effect.
Fig 4
Fig 4. Forest plot showing an overall effect of macroscopic adhesion score compared with results of using saline as control.
The figure depicts individual trials as filled squares with relative sample size and the 95% confidence interval (CI) of the difference as a solid line. The diamond shape indicates the pooled estimate and uncertainty for the combined effect.
Fig 5
Fig 5. Forest plot showing sensitivity analysis performed by removing one study at a time for an overall effect of macroscopic adhesion score, compared with results of using saline as control.
The figure depicts individual trials as filled squares with relative sample size and the 95% confidence interval (CI) of the difference as a solid line. The diamond shape indicates the pooled estimate and uncertainty for the combined effect.
Fig 6
Fig 6. Forest plot showing an overall effect of macroscopic adhesion score compared with results of using nothing as control.
The figure depicts individual trials as filled squares with relative sample size and the 95% confidence interval (CI) of the difference as a solid line. The diamond shape indicates the pooled estimate and uncertainty for the combined effect.
Fig 7
Fig 7. Forest plot showing sensitivity analysis performed by removing one study at a time for an overall effect of macroscopic adhesion score, compared with results of using nothing as control.
The figure depicts individual trials as filled squares with relative sample size and the 95% confidence interval (CI) of the difference as a solid line. The diamond shape indicates the pooled estimate and uncertainty for the combined effect.
Fig 8
Fig 8. Meta-regression of mean macroscopic adhesion score by a dose of methylene blue.
The X-axis represents the dose of methylene blue and Y-axis represents the macroscopic adhesion score. The size of the data marker is proportional to the weight in the meta regression.
Fig 9
Fig 9. Funnel plot of comparison: Methylene blue compared with combined results of using saline and nothing as control; outcome—macroscopic adhesion score.
White circles: included comparisons. Black circles: imputed comparisons using the trim-and-fill method. White diamond: pooled observed log risk ratio. Black diamond: pooled imputed log risk ratio.
Fig 10
Fig 10. Funnel plot of comparison: Methylene blue compared with saline used as control; outcome—macroscopic adhesion score.
White circles: included comparisons. Black circles: imputed comparisons using the trim-and-fill method. White diamond: pooled observed log risk ratio. Black diamond: pooled imputed log risk ratio.
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