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Fluid and pharmacological agents for adhesion prevention after

gynaecological surgery (Review)

Ahmad G, Thompson M, Kim K, Agarwal P, Mackie FL, Dias S, Metwally M, Watson A

Ahmad G, Thompson M, Kim K, Agarwal P, Mackie FL, Dias S, Metwally M, Watson A.

Fluid and pharmacological agents for adhesion prevention after gynaecological surgery.
Cochrane Database of Systematic Reviews 2020, Issue 7. Art. No.: CD001298.
DOI: 10.1002/14651858.CD001298.pub5.

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Fluid and pharmacological agents for adhesion prevention after gynaecological surgery (Review)
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Informed decisions.
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[Intervention Review]

Fluid and pharmacological agents for adhesion prevention after

gynaecological surgery

Gaity Ahmad1, Matthew Thompson2, Kyungmin Kim2, Priya Agarwal2, Fiona L Mackie3, Sofia Dias4, Mostafa Metwally5, Andrew Watson6

1Department of Obstetrics and Gynaecology, Pennine Acute Hospitals NHS Trust, Manchester, UK. 2Pennine Acute Hospitals NHS
Trust, Manchester, UK. 3Obstetrics & Gynaecology, Pennine Acute NHS Trust, Manchester, UK. 4Centre for Reviews and Dissemination,
University of York, York, UK. 5The Jessop Wing and Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK. 6Department
of Obstetrics and Gynaecology, Tameside & Glossop Acute Services NHS Trust, Ashton-Under-Lyne, UK

Contact address: Gaity Ahmad, gaity.ahmad@pat.nhs.uk, gaityahmad@hotmail.com.

Editorial group: Cochrane Gynaecology and Fertility Group.

Publication status and date: Edited (no change to conclusions), published in Issue 10, 2020.

Citation: Ahmad G, Thompson M, Kim K, Agarwal P, Mackie FL, Dias S, Metwally M, Watson A. Fluid and pharmacological agents for
adhesion prevention after gynaecological surgery. Cochrane Database of Systematic Reviews 2020, Issue 7. Art. No.: CD001298. DOI:
10.1002/14651858.CD001298.pub5.

Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT

Background
Adhesions are fibrin bands that are a common consequence of gynaecological surgery. They are caused by conditions that include pelvic
inflammatory disease and endometriosis. Adhesions are associated with comorbidities, including pelvic pain, subfertility, and small bowel
obstruction. Adhesions also increase the likelihood of further surgery, causing distress and unnecessary expenses. Strategies to prevent
adhesion formation include the use of fluid (also called hydroflotation) and gel agents, which aim to prevent healing tissues from touching
one another, or drugs, aimed to change an aspect of the healing process, to make adhesions less likely to form.

Objectives
To evaluate the effectiveness and safety of fluid and pharmacological agents on rates of pain, live births, and adhesion prevention in women
undergoing gynaecological surgery.

Search methods
We searched: the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and Epistemonikos to
22 August 2019. We also checked the reference lists of relevant papers and contacted experts in the field.

Selection criteria
Randomised controlled trials investigating the use of fluid (including gel) and pharmacological agents to prevent adhesions after
gynaecological surgery.

Data collection and analysis

We used standard methodological procedures recommended by Cochrane. We assessed the overall quality of the evidence using GRADE
methods. Outcomes of interest were pelvic pain; live birth rates; incidence of, mean, and changes in adhesion scores at second look-
laparoscopy (SLL); clinical pregnancy, miscarriage, and ectopic pregnancy rates; quality of life at SLL; and adverse events.

Main results
We included 32 trials (3492 women), and excluded 11.

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We were unable to include data from nine studies in the statistical analyses, but the findings of these studies were broadly in keeping with
the findings of the meta-analyses.

Hydroflotation agents versus no hydroflotation agents (10 RCTs)

We are uncertain whether hydroflotation agents affected pelvic pain (odds ratio (OR) 1.05, 95% confidence interval (CI) 0.52 to 2.09; one
study, 226 women; very low-quality evidence).

It is unclear whether hydroflotation agents affected live birth rates (OR 0.67, 95% CI 0.29 to 1.58; two studies, 208 women; low-quality
evidence) compared with no treatment.

Hydroflotation agents reduced the incidence of adhesions at SLL when compared with no treatment (OR 0.34, 95% CI 0.22 to 0.55, four
studies, 566 women; high-quality evidence). The evidence suggests that in women with an 84% chance of having adhesions at SLL with no
treatment, using hydroflotation agents would result in 54% to 75% having adhesions.

Hydroflotation agents probably made little or no difference to mean adhesion score at SLL (standardised mean difference (SMD) -0.06, 95%
CI -0.20 to 0.09; four studies, 722 women; moderate-quality evidence).

It is unclear whether hydroflotation agents affected clinical pregnancy rate (OR 0.64, 95% CI 0.36 to 1.14; three studies, 310 women;
moderate-quality evidence) compared with no treatment. This suggests that in women with a 26% chance of clinical pregnancy with no
treatment, using hydroflotation agents would result in a clinical pregnancy rate of 11% to 28%.

No studies reported any adverse events attributable to the intervention.

Gel agents versus no treatment (12 RCTs)

No studies in this comparison reported pelvic pain or live birth rate. (SMD -0.24, 95% CI -0.55 to 0.08)

Gel agents reduced the incidence of adhesions at SLL compared with no treatment (OR 0.26, 95% CI 0.12 to 0.57; five studies, 147 women;
high-quality evidence). This suggests that in women with an 84% chance of having adhesions at SLL with no treatment, the use of gel
agents would result in 39% to 75% having adhesions.

It is unclear whether gel agents affected mean adhesion scores at SLL (SMD -0.24, 95% CI -0.55 to 0.08; four studies, 159 women; moderate-
quality evidence), or clinical pregnancy rate (OR 0.20, 95% CI 0.02 to 2.02; one study, 30 women; low-quality evidence).

No studies in this comparison reported on adverse events attributable to the intervention.

Gel agents versus hydroflotation agents when used as an instillant (3 RCTs)

No studies in this comparison reported pelvic pain, live birth rate or clinical pregnancy rate.

Gel agents probably reduce the incidence of adhesions at SLL when compared with hydroflotation agents (OR 0.50, 95% CI 0.31 to 0.83;
three studies, 538 women; moderate-quality evidence). This suggests that in women with a 46% chance of having adhesions at SLL with a
hydroflotation agent, the use of gel agents would result in 21% to 41% having adhesions.

We are uncertain whether gel agents improved mean adhesion scores at SLL when compared with hydroflotation agents (MD -0.79, 95%
CI -0.82 to -0.76; one study, 77 women; very low-quality evidence).

No studies in this comparison reported on adverse events attributable to the intervention.

Steroids (any route) versus no steroids (4 RCTs)

No studies in this comparison reported pelvic pain, incidence of adhesions at SLL or mean adhesion score at SLL.

It is unclear whether steroids affected live birth rates compared with no steroids (OR 0.65, 95% CI 0.26 to 1.62; two studies, 223 women;
low-quality evidence), or clinical pregnancy rates (OR 1.01, 95% CI 0.66 to 1.55; three studies, 410 women; low-quality evidence).

No studies in this comparison reported on adverse events attributable to the intervention.

Authors' conclusions
Gels and hydroflotation agents appear to be effective adhesion prevention agents for use during gynaecological surgery, but we found no
evidence indicating that they improve fertility outcomes or pelvic pain, and further research is required in this area. It is also worth noting
that for some comparisons, wide confidence intervals crossing the line of no effect meant that clinical harm as a result of interventions
could not be excluded. Future studies should measure outcomes in a uniform manner, using the modified American Fertility Society score.
Statistical findings should be reported in full. No studies reported any adverse events attributable to intervention.

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PLAIN LANGUAGE SUMMARY

Use of fluids and pharmacological agents (medicinal drugs) to prevent the formation of adhesions (scar tissue) after surgery of the
female pelvis

Review question: This Cochrane Review evaluated the use of fluid and pharmacological agents that aim to prevent adhesion formation
after gynaecological surgery (we defined gels as fluid agents).

Background: Adhesions are a type of scar tissue, which can cause two normally separate surfaces within the body to stick together.
Adhesions often form within the pelvis following surgery, infection, or due to endometriosis. Adhesions caused by gynaecological surgery
can cause pain and reduced fertility. Women with adhesions often require further surgery. Strategies to prevent adhesion formation include
the use of fluid and gel agents, which aim to prevent healing tissues from touching one another, or drugs, aimed to change an aspect of
the healing process, to make adhesions less likely to form.

Study characteristics: We included 32 randomised controlled trials (3492 women). We pooled the results of 23 trials (2796 women). We
were unable to pool the results from the remaining nine trials, because investigators either measured adhesions in a way that would not
allow us to pool the findings with other data, or did not report important statistical information. We searched all evidence up to August 2019.

Key results:

Fluids and gels appear to be effective in reducing adhesions, but more information is needed to determine whether they affect pelvic pain
or live birth rates. Large, high-quality studies should be conducted in which investigators use the standardised way of measuring adhesions,
developed by the American Fertility Society (the modified AFS score).

For the outcome of pain: one study reported uncertain results of the effect of a fluid agent (4% icodextrin, a glucose polymer) on pelvic
pain. No studies reported pelvic pain outcomes with any other interventions.

For the outcome of fertility: the pooled results of two studies of fluid agents (dextran, another glucose polymer) found uncertain effects
on live birth rates. The data suggest that in women with a 13% chance of giving birth with no treatment, 4% to 19% would give birth if
treated with fluid agents. The pooled results of two studies of steroids found uncertain effects on live birth rates. The data suggest that
in women with a 13% chance of giving birth with no treatment, 4% to 19% would give birth if treated with steroids. No studies reported
live birth rate with any other interventions.

We are uncertain whether fluid agents, gel agents, or steroids affect clinical pregnancy rates compared with no treatment. No studies
comparing the effect of fluid agents with gel agents reported clinical pregnancy rates.

For the outcome of adhesions at SLL: four studies found that fluid agents reduced the incidence of adhesions at second-look laparoscopy
(SLL) compared with no treatment (high-quality evidence). This suggests that in women with an 84% chance of having adhesions at SLL
with no treatment, the use of fluid agents would result in 54% to 75% having adhesions. Five studies found that gel agents reduced the
incidence of adhesions at SLL compared with no treatment (high-quality evidence). This suggests that in women with an 84% chance of
having adhesions at SLL with no treatment, using gel agents would result in 39% to 75% having adhesions. Three studies found that gel
agents probably reduced the incidence of adhesions at SLL compared with fluid agents (moderate-quality evidence). This suggests that in
women with a 46% chance of having adhesions at SLL with a fluid agent, using gel agents would result in 21% to 41% having adhesions.

Eight studies examined the effect of gel agents or fluid agents on mean adhesion score. We are uncertain if they have an effect when
compared with no treatment, or with each other.

No studies reported the effect of steroids on adhesion incidence or mean adhesion scores at SLL.

For the outcome of adverse events: no studies reported any adverse events caused by the intervention being investigated.

Quality of the evidence: The quality of the evidence ranged from very-low to high. The main reasons for downgrading evidence were
imprecision (small sample sizes and wide confidence intervals that crossed the line of no effect), and poor reporting of methods.

Fluid and pharmacological agents for adhesion prevention after gynaecological surgery (Review) 3
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.