Tissue adhesives for closure of surgical incisions

Jo C Dumville; Paul Coulthard; Helen V Worthington; Philip Riley; Neil Patel; James Darcey; Marco Esposito; Maarten van der Elst; Oscar J F van Waes

doi:10.1002/14651858.CD004287.pub4

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Figure 1

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

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Analysis 1.1

Comparison 1 Adhesive versus suture, Outcome 1 Dehiscence: all studies.

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Analysis 1.2

Comparison 1 Adhesive versus suture, Outcome 2 Dehiscence: sensitivity analysis.

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Analysis 1.3

Comparison 1 Adhesive versus suture, Outcome 3 Infection: all studies.

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Analysis 1.4

Comparison 1 Adhesive versus suture, Outcome 4 Infection: sensitivity analysis.

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Analysis 1.5

Comparison 1 Adhesive versus suture, Outcome 5 Cosmetic appearance rated by patient.

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Analysis 1.6

Comparison 1 Adhesive versus suture, Outcome 6 Cosmetic appearance rated by surgeon.

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Analysis 1.7

Comparison 1 Adhesive versus suture, Outcome 7 Patient/parent satisfaction (% satisfied).

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Analysis 1.8

Comparison 1 Adhesive versus suture, Outcome 8 Patient/parent satisfaction (VAS Scale 0 to 100).

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Analysis 1.9

Comparison 1 Adhesive versus suture, Outcome 9 Surgeon satisfaction (% satisfied).

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Analysis 1.10

Comparison 1 Adhesive versus suture, Outcome 10 Time taken for wound closure.

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Analysis 2.1

Comparison 2 Adhesive versus adhesive tape, Outcome 1 Dehiscence.

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Analysis 2.2

Comparison 2 Adhesive versus adhesive tape, Outcome 2 Infection.

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Analysis 2.3

Comparison 2 Adhesive versus adhesive tape, Outcome 3 Cosmetic appearance rated by patient (VAS).

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Analysis 2.4

Comparison 2 Adhesive versus adhesive tape, Outcome 4 Cosmetic appearance rated by patient (% satisfied).

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Analysis 2.5

Comparison 2 Adhesive versus adhesive tape, Outcome 5 Cosmetic appearance rated by surgeon (VAS).

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Analysis 2.6

Comparison 2 Adhesive versus adhesive tape, Outcome 6 Patient satisfaction.

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Analysis 2.7

Comparison 2 Adhesive versus adhesive tape, Outcome 7 Surgeon satisfaction.

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Analysis 2.8

Comparison 2 Adhesive versus adhesive tape, Outcome 8 Time taken for wound closure.

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Analysis 3.1

Comparison 3 Adhesive versus staples, Outcome 1 Dehiscence.

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Analysis 3.2

Comparison 3 Adhesive versus staples, Outcome 2 Infection.

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Analysis 3.3

Comparison 3 Adhesive versus staples, Outcome 3 Cosmetic appearance rated by patient (scar scale).

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Analysis 3.4

Comparison 3 Adhesive versus staples, Outcome 4 Cosmetic appearance by plastic surgeons (VAS).

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Analysis 3.5

Comparison 3 Adhesive versus staples, Outcome 5 Patient satisfaction.

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Analysis 3.6

Comparison 3 Adhesive versus staples, Outcome 6 Time taken for wound closure.

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Analysis 4.1

Comparison 4 Adhesive versus other method, Outcome 1 Dehiscence.

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Analysis 4.2

Comparison 4 Adhesive versus other method, Outcome 2 Infection.

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Analysis 4.3

Comparison 4 Adhesive versus other method, Outcome 3 Patient satisfaction.

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Analysis 4.4

Comparison 4 Adhesive versus other method, Outcome 4 Clinician satisfaction.

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Analysis 4.5

Comparison 4 Adhesive versus other method, Outcome 5 Time taken for wound closure.

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Analysis 5.1

Comparison 5 Adhesive versus adhesive: High viscosity versus low viscosity, Outcome 1 Dehiscence.

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Analysis 5.2

Comparison 5 Adhesive versus adhesive: High viscosity versus low viscosity, Outcome 2 Infection.

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Analysis 5.3

Comparison 5 Adhesive versus adhesive: High viscosity versus low viscosity, Outcome 3 Patient satisfaction.

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Analysis 5.4

Comparison 5 Adhesive versus adhesive: High viscosity versus low viscosity, Outcome 4 Clinician satisfaction.

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Analysis 5.5

Comparison 5 Adhesive versus adhesive: High viscosity versus low viscosity, Outcome 5 Time taken for wound closure.

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Analysis 6.1

Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 1 Dehiscence.

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Analysis 6.2

Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 2 Infection.

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Analysis 6.3

Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 3 Cosmetic assessment rated by patient (VAS).

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Analysis 6.4

Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 4 Cosmetic assessment rated by surgeon (VAS).

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Analysis 6.5

Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 5 Surgeon satisfaction (with device).

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Analysis 6.6

Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 6 Surgeon satisfaction (with closure).

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Analysis 6.7

Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 7 Time taken for wound closure.

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Summary of findings for the main comparison. Tissue adhesive compared to sutures for surgical incisions

Tissue adhesive compared to sutures for surgical incisions
Patient or population: People with surgical incisions Settings: Intervention: Tissue adhesive Comparison: Sutures
Outcomes	*Illustrative comparative risks⁴ (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Sutures	Tissue adhesive
Wound dehiscence	Study population		RR 3.35 (1.53 to 7.32)	736 (10 studies)	⊕⊕⊝⊝ low^1,2
	13 per 1000	45 per 1000 (21 to 99)
	Moderate

Wound infection	Study population		RR 1.72 (0.92 to 3.16)	744 10 studies	⊕⊝⊝⊝ very low^2,3
	38 per 1000	76 per 1000 (14 to 397)
	Moderate

The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) CI: Confidence interval; RR: Risk ratio
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: we are very uncertain about the estimate
¹ Possible unit of analyses issues. A sensitivity analysis changes a statistically significant difference to a non‐statistically significant difference ² Study 95% CIs are wide ³ Possible unit of analysis issues ⁴ Median control (suture) group risk across studies

Summary of findings for the main comparison. Tissue adhesive compared to sutures for surgical incisions

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Summary of findings 2. Tissue adhesive compared to adhesive tape for surgical incisions

Tissue adhesive compared to adhesive tape for surgical incisions
Patient or population: people with surgical incisions Settings: Intervention: tissue adhesive Comparison: adhesive tape
Outcomes	*Illustrative comparative risks³ (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Adhesive tape	Tissue adhesive
Wound dehiscence	Study population		RR 0.96 (0.06 to 14.55)	50 (1 study)	⊕⊕⊝⊝ low¹
	42 per 1000	40 per 1000 (2 to 606)
	Moderate

Wound infection	Study population		RR 1.37 (0.39 to 4.81)	190 (3 studies)	⊕⊕⊝⊝ low^1,2
	43 per 1000	60 per 1000 (17 to 209)
	Moderate

The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) CI: Confidence interval; RR: Risk ratio
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: we are very uncertain about the estimate
¹ Study 95% CIs are very wide ² Evidence of inconsistency in point estimates. With the point estimate from one study lying outside the 95% CIs of another ³ Control (tape) group risk in included study

Summary of findings 2. Tissue adhesive compared to adhesive tape for surgical incisions

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Summary of findings 3. Tissue adhesive compared to staples for surgical incisions

Tissue adhesive compared to staples for surgical incisions
Patient or population: people with surgical incisions Settings: Intervention: tissue adhesive Comparison: staples
Outcomes	*Illustrative comparative risks³ (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Staples	Tissue adhesive
Wound dehiscence	Study population		RR 0.53 (0.05 to 5.33)	37 (1 study)	⊕⊕⊝⊝ low¹
	105 per 1000	56 per 1000 (5 to 561)
	Moderate

Wound infection	Study population		RR 1.39 (0.3 to 6.54)	250 (3 studies)	⊕⊝⊝⊝ very low^1,2
	71 per 1000	99 per 1000 (21 to 463)
	Moderate

The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Study 95% CIs are very wide. ² Evidence of point estimates lying in opposite directions with the estimate for one study lying outside the 95% CI of another. ³ Control (staples ) group risk for included study.

Summary of findings 3. Tissue adhesive compared to staples for surgical incisions

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Summary of findings 4. Tissue adhesive compared to other methods for surgical incisions

Tissue adhesive compared to other methods for surgical incisions
Patient or population: people with surgical incisions Settings: Intervention: tissue adhesive Comparison: other methods
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Other methods	Tissue adhesive
Wound dehiscence	Study population		RR 0.55 (0.13 to 2.38)	209 (1 study)	⊕⊕⊝⊝ low^1,2
	49 per 1000	27 per 1000 (6 to 117)
	Moderate

Wound infection	Study population		RR 0.41 (0.11 to 1.6)	209 (1 study)	⊕⊕⊝⊝ low^1,2
	66 per 1000	27 per 1000 (7 to 105)
	Moderate

The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) CI: Confidence interval; RR: Risk ratio
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: we are very uncertain about the estimate
¹ Study 95% CIs are very wide ² Single study with low event rate

Summary of findings 4. Tissue adhesive compared to other methods for surgical incisions

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Summary of findings 5. High viscosity tissue adhesive compared to low viscosity tissue adhesive for surgical incisions

High viscosity tissue adhesive compared to low viscosity tissue adhesive for surgical incisions
Patient or population: people with surgical incisions Settings: Intervention: high viscosity tissue adhesive Comparison: low viscosity tissue adhesive
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Low viscosity tissue adhesive	High viscosity tissue adhesive
Wound dehiscence	Study population		RR 3.74 (0.21 to 67.93)	148 (1 study)	⊕⊝⊝⊝ very low^1,2
	Could not be calculated	Could not be calculated


Wound infection	Study population		RR 0.82 (0.16 to 4.31)	148 (1 study)	⊕⊝⊝⊝ very low^1,2
	47 per 1000	38 per 1000 (7 to 200)
	Moderate

The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) CI: Confidence interval; RR: Risk ratio
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: we are very uncertain about the estimate
¹ Study 95% CIs are very wide ² Single study with low event rate

Summary of findings 5. High viscosity tissue adhesive compared to low viscosity tissue adhesive for surgical incisions

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Summary of findings 6. Octylcyanoacrylate compared to butylcyanoacrylate for surgical incisions

Octylcyanoacrylate compared to butylcyanoacrylate for surgical incisions
Patient or population: people with surgical incisions Settings: Intervention: octylcyanoacrylate Comparison: butylcyanoacrylate
Outcomes	*Illustrative comparative risks² (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Butylcyanoacrylate	Octylcyanoacrylate
Wound dehiscence	26 per 1000	38 per 1000 (5 to 297)	RR 1.46 (0.19 to 11)	80 (2 studies)	⊕⊕⊝⊝ low¹
Wound infection	Study population		RR 0.63 (0.21 to 1.88)	37 (1 study)	⊕⊕⊝⊝ low¹
	333 per 1000	210 per 1000 (70 to 627)
	Moderate

The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) CI: Confidence interval; RR: Risk ratio
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: we are very uncertain about the estimate
¹ The 95% CI estimate around the RR of 1.46 is very wide ² Median control group risk across studies

Summary of findings 6. Octylcyanoacrylate compared to butylcyanoacrylate for surgical incisions

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Table 1. Summary of study comparisons

Tissue adhesive vs tissue adhesive

(Comp 5)

Mixed control

(Comp 4)

Butyl‐2‐

cyanoacrylate

vs staples

(Comp 3)

2‐octyl

cyanoacrylate

vs staples

(Comp 3)

2‐octyl

cyanoacrylate

vs tape

(Comp 2)

Butyl‐2‐

cyanoacrylate

vs sutures

(Comp 1)

2‐octyl

cyanoacrylate

vs sutures

(Comp1)

Trial ID

2‐octyl

cyanoacrylate

Butyl‐2‐

cyanoacrylate

Sutures

Staples

Adhesive tape/strips

Mixed sutures and staples

All non‐tissue adhesive closure methods

Other viscosity 2‐octyl

cyanoacrylate

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

✓

Abbreviation

Comp = comparison

Table 1. Summary of study comparisons

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Comparison 1. Adhesive versus suture

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dehiscence: all studies Show forest plot	17	1225	Risk Ratio (M‐H, Random, 95% CI)	3.35 [1.53, 7.33]

2 Dehiscence: sensitivity analysis Show forest plot	13	935	Risk Ratio (M‐H, Random, 95% CI)	2.70 [0.95, 7.68]

3 Infection: all studies Show forest plot	18	1239	Risk Ratio (M‐H, Random, 95% CI)	1.72 [0.94, 3.16]

4 Infection: sensitivity analysis Show forest plot	15	977	Risk Ratio (M‐H, Random, 95% CI)	2.03 [0.80, 5.12]

5 Cosmetic appearance rated by patient Show forest plot	2	199	Mean Difference (IV, Random, 95% CI)	‐2.12 [‐7.20, 2.95]

5.1 VAS 0 to 100	2	199	Mean Difference (IV, Random, 95% CI)	‐2.12 [‐7.20, 2.95]
6 Cosmetic appearance rated by surgeon Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

6.1 VAS scale 0 to 100	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Scar assessment (0 to 5 scale)	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Patient/parent satisfaction (% satisfied) Show forest plot	2	206	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.96, 1.07]

8 Patient/parent satisfaction (VAS Scale 0 to 100) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

9 Surgeon satisfaction (% satisfied) Show forest plot	2	150	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.58, 2.19]

10 Time taken for wound closure Show forest plot	5		Mean Difference (IV, Random, 95% CI)	Subtotals only

Comparison 1. Adhesive versus suture

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Comparison 2. Adhesive versus adhesive tape

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dehiscence Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2 Infection Show forest plot	3	190	Risk Ratio (M‐H, Random, 95% CI)	1.37 [0.39, 4.81]

3 Cosmetic appearance rated by patient (VAS) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4 Cosmetic appearance rated by patient (% satisfied) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5 Cosmetic appearance rated by surgeon (VAS) Show forest plot	2	139	Mean Difference (IV, Random, 95% CI)	9.56 [4.74, 14.37]

6 Patient satisfaction Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7 Surgeon satisfaction Show forest plot	2	141	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.63, 1.19]

8 Time taken for wound closure Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

Comparison 2. Adhesive versus adhesive tape

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Comparison 3. Adhesive versus staples

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dehiscence Show forest plot	2	107	Risk Ratio (M‐H, Random, 95% CI)	0.53 [0.05, 5.33]

2 Infection Show forest plot	4	320	Risk Ratio (M‐H, Random, 95% CI)	1.39 [0.30, 6.54]

3 Cosmetic appearance rated by patient (scar scale) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4 Cosmetic appearance by plastic surgeons (VAS) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5 Patient satisfaction Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

6 Time taken for wound closure Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

Comparison 3. Adhesive versus staples

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Comparison 4. Adhesive versus other method

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dehiscence Show forest plot	2	249	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.13, 2.38]

2 Infection Show forest plot	2	249	Risk Ratio (M‐H, Random, 95% CI)	0.41 [0.11, 1.60]

3 Patient satisfaction Show forest plot	1	187	Mean Difference (IV, Fixed, 95% CI)	0.40 [0.10, 0.70]

4 Clinician satisfaction Show forest plot	1	209	Mean Difference (IV, Fixed, 95% CI)	0.53 [0.29, 0.77]

5 Time taken for wound closure Show forest plot	1	209	Mean Difference (IV, Fixed, 95% CI)	‐1.05 [‐1.79, ‐0.31]

Comparison 4. Adhesive versus other method

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Comparison 5. Adhesive versus adhesive: High viscosity versus low viscosity

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dehiscence Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2 Infection Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3 Patient satisfaction Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4 Clinician satisfaction Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5 Time taken for wound closure Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

Comparison 5. Adhesive versus adhesive: High viscosity versus low viscosity

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Comparison 6. Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Dehiscence Show forest plot	2	80	Risk Ratio (M‐H, Random, 95% CI)	1.46 [0.19, 11.30]

2 Infection Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3 Cosmetic assessment rated by patient (VAS) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4 Cosmetic assessment rated by surgeon (VAS) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5 Surgeon satisfaction (with device) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

6 Surgeon satisfaction (with closure) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

7 Time taken for wound closure Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

Comparison 6. Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate

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