CONCLUSIONS:
Barriers to prevent the formation of PPAs are heterogeneous with respect
to composition and effectiveness. The present systematic review of the
literature identified a total of 13 barriers, including two barrier
product combinations. These models were analyzed with respect to their
safety and efficacy in the clinical setting for the cardiac surgery
patient.
The safety of adhesion barriers varies considerably with respect to
rates of infection, bleeding events, and mortality. No barrier had
reported rates of 0.00% for all three variables; however, Seprafilm
demonstrated the lowest combined rates (infection 0.00% vs control
0.00%; bleeding event 0.00% vs control 0.00%; mortality 0.57% vs
control 1.22%). Cova CARD, Porcine and Polyester Gelatin Sheet, and
PTFE + Seprafilm also demonstrated rates of 0.00% for at least two
categories with no reported data on the third. The heterogeneity in
reporting was found to be prevalent, as few barriers had reported
control data. Only four of the 13 barriers had reported data for all
three safety variables. PTFE and COSEAL were two of these barriers, and
they also demonstrated relevant safety concerns. PTFE had the second
greatest mortality rate (4.89% vs control 1.22%), third greatest
infection rate (1.14% vs control 4.88%), and third greatest bleeding
event rate (0.75% vs control 1.22%). Although less than the control
population, PTFE may influence infection and bleeding because it
requires both sutures for placement as well as re-operation for removal.
Another explanation for these findings is that PTFE was assessed in the
greatest number of studies with some dating back to over three decades
ago; general surgical techniques have likely improved considerably since
that point in time. Silcone rubber had the second greatest bleeding
event rate (6.86%); however, it also was assessed in the earliest study
identified (1981).13
COSEAL had the greatest infection rate (6.58%) and bleeding event rate
(10.53%). COSEAL is a sprayable synthetic polymeric hydrogel that is
bioresorbable. No possible reasons for the infection or bleeding event
rates have been proposed; however, infection and bleeding were also
among the greatest adverse events in a randomized control trial of
COSEAL in vascular surgery.14 REPEL-CV also
demonstrated significant safety concerns with not only the greatest
mortality rate (17.05%; control 13.04%) but also the second greatest
infection rate (4.55%; control 1.45%). The primary study of REPEL-CV
was in infants undergoing initial sternotomy for eventual staged
palliative cardiac operations with no significant difference identified
in mortality rates between the barrier and control group
(p=0.6405).15 The immune system function of these
infants was likely limited as well and may have influenced the response
to a foreign body, resulting in increased infection rates relative to
the control group. Overall, the ability to draw comparisons between the
safety of the adhesion barriers is limited due to the heterogeneity with
respect to study design and reporting bias. As noted, many studies did
not provide control groups for comparion. The varied procedures
performed in differing patient populations suggest further limit the
ability to draw definitive conclusions between the groups. No major
studies have also identified the overall rates of infection, bleeding
event, and mortality in cardiac surgery without adhesion barriers. A
detalied understanding of these topics would be of great value for those
attempting to weigh the risks and benefits of adhesion barrier use in
cardiac surgery.
The efficacy of adhesion barriers in preventing PPA formation and
limiting tenacity scores varied as well. Unlike the safety data, most
barriers did have reported data for both efficacy variables. Only one
barrier had an adhesion formation rate of 0.00% with a TSS of 0.00:
Polyisoprene Blue Band Strips. The study regarding Polyisoprene Blue
Band Strips did not identify a control group for comparison though and
only had nine patients in the barrier group with a mean placement time
of 31 days.16 The strips were applied to the major
vessels surrounding the heart and were not used to cover the heart
itself. Excluding Polyisoprene Blude Band Strips, PTFE demonstrated the
lowest adhesion formation rate (37.31% vs control 100.00%) and the
third-lowest TSS (26.50 vs control 80.26%). PTFE was the most
frequently used barrier among all studies (67% of patients) with the
widest range of years (1988-2012). PTFE has historically been effective
because it is physiologically inert, has low adhesiveness with
cells/tissues, separates damaged surfaces without degradation, and is
biocompatible.3 PTFE is commonly used in cardiac
surgery today due to its demonstrated effectiveness in reducing
adhesions; however, the safety concerns discussed previously should be
considered. Applying PTFE in combination with other barriers is a
particular area of interest that may address these concerns, as PTFE +
Seprafilm resulted in limited infections and bleeding
events.17
Cova CARD was also among the most effective barriers with the third
lowest adhesion formation rate (78.95%) and the second lowest TSS
(15.00). Cova CARD is a relatively new barrier that acts as a
resorbable, malleable porcine collagen membrane, promoting tissue
regeneration.3, 18 While the human data is limited,
collagen sheets have been shown to resemble native pericardial membranes
at 24 weeks after operation in animal models.3, 19 The
adhesion formation rate may be greater relative to PTFE; however, the
improved TSS suggests that this barrier may provide easier dissection
than PTFE. Easier dissection may also explain the improved safety
identified regarding infection and bleeding events relative to PTFE.
Adhesion formation occurred with almost every patient when using
Seprafilm (95.83% vs control 94.12%), COSEAL (100.00%), REPEL-CV
(100.00%; control 100.00%), Silicone Rubber (100.00%), Polyglycolic
Acid Mesh (100.00% vs control 100.00%), and Porcine and Polyester
Gelatin Sheet (100.00%). The study assessing Polyglycolic Acid Mesh
should be discussed though, as it used computerized tomography (CT)
imaging instead of re-operation to identify adhesion
formation.20 Polyglycolic Acid Mesh was compared
against PTFE and a no barrier control group that both had adhesion
formation rates of 100.00% as well. The increased rate of adhesions for
PTFE in this study relative to its overall adhesion formation rate
(37.31%) suggests that CT imaging may allow for more detailed
identification of adhesions that may not necessarily be clinically
relevant in the re-operation setting. Nevertheless, the study did note
that PTFE was a more effective substitute than Polyglycolic Acid Mesh
with respect to the reported “total adhesion scores” (p <
0.001). While the adhesion formation rate was high for nearly all
barriers, the TSS demonstrated noteworthy variance. The similar TSS
scores in the control groups also suggest that comparison may be
appropriate among the barriers’ TSS scores. Nevertheless, the wide
variance in reported values for safety and efficacy likely relates to
the subjective approach used to report these variables and suggests a
need for standardization moving forward.
This study has limitations given its study design as a systematic
review. These limitations relate to the evidence included in the review
as well as the review process itself. With respect to the evidence
included, not all studies reported the same safety and efficacy
variables. Some of the relevant variables discussed in this review were
not mentioned in some studies; furthermore, other variables included in
a few studies were not assessed here to ensure appropriate comparisons.
Statistical analyses comparing the barriers was also limited due to the
heterogeneity of data reported. A major contributor was the variance in
study design and presence of control groups, which contributed to the
risk of bias in the studies. Future adhesion barrier studies should
address these limitations by providing detailed safety and efficacy data
that includes the variables discussed here for both the intervention and
comparison cohorts. Other potentially valuable variables include
structural injuries, visibility, dissection duration, and ease of use.
With respect to the review process, the search strategies were unable to
assess all publications to date on adhesion barriers in the clinical
setting of cardiac surgery. Although the search strategies used were
broad and included two separate databases, other relevant articles may
have not been identified. Publication bias likely influenced the results
as well in that only published studies were used in this systematic
review. Future systematic reviews should be mindful of these limitations
and pursue a more inclusive approach as additional PPA barrier studies
are published.
In conclusion, this is the first systematic review of adhesion barrier
safety and efficacy in cardiac surgery. The findings suggest that no
ideal adhesion barrier currently exists for preventing PPAs. While the
barriers assessed in this study are commonly used in other forms of
surgery, future barrier development must focus on the requirements
unique to operating in and around the heart during cardiac surgery. PTFE
has historically been used, but the relevant safety and efficacy
concerns identified here suggest areas for improvement. Recent adhesion
barriers have been developed that demonstrate improvements in infection
rates, bleeding event rates, mortality, adhesion formation, and tenacity
scores. In particular, Cova CARD may provide better outcomes.
Combinations of adhesion barriers, such as PTFE + SprayGel and PTFE +
Seprafilm, may also provide synergistic improvements in safety and
efficacy. However, further validation is required before drawing any
conclusions. PPAs ultimately pose a major burden to patients and
providers in terms of morbidity, mortality, and surgical ease. Reducing
their formation is vital to improving outcomes for all cardiac surgery
candidates.