University of Groningen
New measures to prevent inguinal infections in vascular surgery
Vierhout, Bastiaan Pieter
DOI:
10.33612/diss.97720548
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Vierhout, B. P. (2019). New measures to prevent inguinal infections in vascular surgery. Rijksuniversiteit Groningen. https://doi.org/10.33612/diss.97720548
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3
New measures to prevent inguinal
infections in vascular surgery
Bastiaan P. Vierhout
“New measures to prevent inguinal infections in vascular surgery”
PhD thesis, University Medical Center Groningen, with summary in Dutch. ISBN (Printed book): 978-94-034-1977-0
ISBN (Ebook): 978-94-034-1978-7
Copyright © B.P. Vierhout, 2019 Groningen, The Netherlands
All rights are reserved. No part of this book may be reproduced or transmitted in any form or by any means, without prior written permission of the author.
Cover design: B.P. Vierhout Lay-out: B.P. Vierhout Printed by: pro-ontwerp.nl
The printing of this thesis was financially supported by the following gratefully acknowledged sponsors: Abbott Vascular, W.L. Gore & Associates, Vascutek, Noord Negentig, LeMaitre vascular.
New measures to prevent inguinal
infections in vascular surgery
Proefschrift
ter verkrijging van de graad van doctor aan de
Rijksuniversiteit Groningen
op gezag van de
rector magnificus prof. dr. C. Wijmenga
en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op
woensdag 23 oktober 2019 om 11.00 uur
door
Bastiaan Pieter Vierhout
geboren op 16 april 1972
7
Promotor
Prof. dr. C.J.A.M. Zeebregts
Copromotores
Dr. R.A. Pol Dr. A. Ott
Beoordelingscommissie
Prof. dr. R.H. Geelkerken Prof. dr. A.W. Friedrich Prof. dr. M. Reijnen
Table of contents
Chapter 1 General introduction and thesis outline
Chapter 2 Cyanoacrylate skin microsealant for preventing surgical site infection after vascular surgery: A discontinued randomized clinical trial. Vierhout BP, Ott A, Reijnen MMPJ, Oskam J, van den Dungen JAM, Zeebregts CJ
(published in Surg Infect. 2014;15(4):425-430)
Chapter 3 First application of an absorbable skin stapler in peripheral vascular surgical procedures. Vierhout BP, de Korte JD, de Vos B, Bottema JT, Zeebregts CJ (published in J Aesth Reconstr Surg. 2017;3(1):1-7)
Chapter 4 Editor’s choice - Arteriotomy closure devices in EVAR, TEVAR, and TAVR: A systematic review and meta-analysis of randomized clinical trials and cohort studies. Vierhout BP, Pol RA, El Moumni M, Zeebregts CJ (published in Eur J Vasc Endovasc Surg. 2017;54(1):104-115)
Chapter 5 A comparison of percutaneous femoral access in endovascular repair versus open femoral access (PiERO): study protocol for a randomized controlled trial. Vierhout BP, Saleem BR, Ott A, van Dijl JM, de Kempenaer TD, Pierie ME, Bottema JT, Zeebregts CJ (published in Trials. 2015;16:1-7) Chapter 6 Randomized multicenter trial on percutaneous versus open access in
endovascular aneurysm repair (PiERO). Vierhout BP, Pol RA, Ott A, Pierie MEN, van Andringa de Kempenaer TMG, Hissink RJ, Wikkeling ORM, Bottema JT, El Moumni ME, Zeebregts CJ (published in J Vasc Surg. 2019;69:1429-1436).
Chapter 7 Inguinal microbiome in patients undergoing an endovascular aneurysm repair: Application of next-generation sequencing of the 16S-23S regions. Vierhout BP, Ott A, Kruithof I, Wisselink G, van Zanten E,
Kooistra-Smid AMD, Zeebregts CJ, Pol RA (published in Med Hypotheses. 2019;132:109358)
Chapter 8 Thesis summary & future perspectives Chapter 9
Chapter 10 Chapter 11 Chapter 12
Summary in Dutch / Nederlandse samenvatting Acknowledgements / Dankwoord
Bibliography Curriculum Vitae
Appendices Covering of an exposed vascular graft in the groin with an external oblique muscle rotational flap. Vierhout BP, Smit JM, Zeebregts CJ (published in J Surg Case Rep. 2017)
Tracking down the cause of necrotizing fasciitis in a patient with negative cultures. Vierhout BP, van Zanten E, Wisselink G, Kooistra-Smid AMD, Ott A (published in Clinics Surg 2018;3:1-2)
Chapter 1
General introduction and thesis outline
Surgical site infections (SSIs) are the third most common nosocomial infections, accounting for 38% of all infections after surgical interventions (1). In the year 2012, globally 312.9 million (95%CI 266.2 – 359.5 million) surgical interventions were performed (2). In the USA, a rate of SSIs of 2% to 5% of all surgeries was reported, but its’ estimated range varied widely between 1.5% and 20% (3-5). The median excess costs associated with SSI during a first hospitalization were calculated at $2,047 to $3,089 (6, 7) (equals €1,790 to €2,700) and may be generalized in the proximity of $2,500 (€2,186) with variations attributable to the procedure as well as the country of origin (3). Age and methicillin resistant Staphylococcus aureus (MRSA) status also cause large variation in costs (5). In total, with an average SSI rate of 3.5%, an additional expense of approximately $27 billion per year can be expected. And still these costs have been argued to be underestimated when related to patients with SSIs blocking in hospital beds and requiring help from related care givers, thus interfering with other productive activities (6)(Figure 1).
Surgical site infection costs: SSI hospital impact: SSI social impact: SSI caregiver impact:
14 15
A long time ago, surgery developed without anesthetics. These painful procedures were performed quickly and without sterilization. Joseph Lister was one of the last surgeons to witness such an un-anesthetized major amputation in his early medical studies in London. After the introduction of the anesthetics, he saw the infectious complications increase, due to the increasing duration of the surgical procedures. Pain during the operation was relieved and this enabled surgeons to operate longer. It took Lister three decades in the second half of the 19th century to reduce the risk of sepsis and related death after an anesthetized procedure. He eventually
developed the use of carbolic acid (8).
Only after the discovery of penicillin in the early 20st century, hospitals gradually became a safer place. One decade later, surgery evolved into its current practice, but still, local infection and generalized sepsis are feared complications of open surgery. Nowadays, we discern the value of disinfection and work with two teams in the operating room, including a sterile team and a ‘circulating’, non-sterile team. In this thesis, as well as in national guidelines, the definition of SSI is used as formulated by the Centers for Disease Control and Prevention (CDC). The definition comprises signs of redness, swelling, heat and pain or tenderness, in combination with an open wound or a positive culture (1). This definition is accepted throughout most parts of the world among which by the RIVM (Rijksinstituut voor
Volksgezondheid en Milieu = National Institute for Public Health and the Environment) in the Netherlands (9).
Different parts of the body have different SSI incidences. Although the definition remains the same for all body parts, variation exists in relation to skin
characteristics and SSI risk. Head wounds are known to cause few wound
infections, probably due to excellent vascularization. Instead, the groin is known to cause more wound problems. The groin accommodates a heavy load of microbial flora in the proximity of rectum and genitals and an abundance of lymphatic ves-sels (10-13). Comparable to the axilla, the groin is positioned at the “nipple line”, on which many sebaceous glands are known to be located (14). All of these
characteristics may explain high infection rates of up to 20% in peripheral vascular bypass surgery on the groin (15).
Apart from body localization, host characteristics play a role. The ASA classification of physical status is a strong predictor of the occurrence of SSI (16). Optimizing the general condition of the patient is advised (17). Patients with diabetes mellitus or on immunosuppressive agents have a higher rate of SSIs, and also female sex,
smoking habits and hemodialysis are identified as risk factors (12, 18).
In many efforts to reduce the number of SSIs, preoperative protocols have been adapted over the years; repeated hand washing and scrubbing of the operation site with antibacterial soaps and brushes have proven ineffective and have been abandoned in the Netherlands (19). However, a recent update of the Guideline for Prevention of SSI, from the American Medical Association, advised a shower or bath with soap on the night before the operative day (20). Cloth drapes have been replaced by disposable drapes and shaving is replaced by removal of unwanted hair with clippers, preferably performed in the operating theatre. Small series
reported an increase in SSI after shaving with a razor instead of using a clipper (21). The most effective preoperative prophylaxis is the antibiotic medication given to the patient 15 to 60 minutes before incision (11). The operating team, with scrub nurses and operating surgeon, perform one washing session at the beginning of the day, after which disinfection of hands for 1.5 minute is sufficient, provided that one does not leave the operating theatre complex. Rings and jewelry are prohibited in the operating department, and body hair should be covered with clothing or caps. During the operation, sterile draping, gloves, and laminar down flow, in combination with sterilized instruments, should prevent contamination of the wound from
outside (22). Recently, a meta-analysis concluded that laminar airflow does not protect against infections (23). True sterilization of the surgical site can never be realized (24), as bacteria are even found intradermally and may even survive intracellularly after having taken all of these measures (25). Disciplinary measures, such as the use of face masks do not lower the number of infections, but are
thought to intensify team concentration and effort (26-28). Similarly, the minimization of the number of door openings intensifies team concentration, and this does seem related to reduced SSI incidence (29). Many factors, however, may be of importance in this relation; e.g. poor preparation of the operation and complexity of the proce-dures performed (29). The development of an SSI is multifactorial and it may be concluded that various measures are still under debate.
Towards the end of the operation, subcutaneous tissue is closed and various skin-closure techniques are available. Non-absorbable sutures and metallic staples are often used but intra-cutaneous sutures have the advantage of solubility. The wound may be left open in contaminated procedures such as contaminated bowel surgery and drainage of abscesses (30).
After the operation, despite working in a clean environment and meticulously fol-lowing antiseptic rules, various bacterial species have the ability to initiate an SSI (8). Since the introduction of routine culture of bacteria on agar plates it has been discovered that Staphylococcus aureus (SA) causes most SSI (3, 13).
Eradication of SA would be a logical step towards further prevention of SSI, as was shown in orthopedic procedures (31). Ideally, the exact origin of the causative pathogen should be identified in advance of the operation, but studies showed it to be difficult to identify these pathogens in advance (32, 33).
Despite the above named preventive measures, the Centers for Disease Control warns for increased costs from infections due to more severe comorbidity and antimicrobial resistance (20). The resistance of the bacterial species is a troublesome development. Some countries report 50% MRSA in SA infected wounds, with increasing difficulty of treatment (26). In vascular surgery SSI
precedes a major part of infected prosthetic grafts and these infections may lead to limb amputation or even a life-threatening septicemia (10, 13, 16). Major challenges giving rise to explore novel techniques and devices invented to prevent the
occurrence of SSI, which forms the basis of this thesis.
Where do bacteria causing SSIs come from and can we completely sterilize the groin? While disinfection is the process of eliminating or reducing harmful
microorganisms from objects and surfaces, sterilization is the process of killing all microorganisms. After disinfection, remaining bacteria are probably dormant inside the skin, mostly adjacent to hair follicles, sweat glands and sebaceous glands (Figure 2), ready to recolonize the skin around the surgical wound (34).It seems logical to try to fix or glue these bacteria down to the skin in an attempt to inhibit them from activation and spreading, especially when they are concealing in the deeper layers of the skin (25). In cardiac cardiac surgery the benefit of InteguSeal®
has been reported (35), but similar results have not been shown after vascular interventions at the level of the groin. The pre-sternal skin is smooth and without folds, but the inguinal skin has folds and
multiple glands, able to contain many microorganisms.
In Chapter 2 we investigated the effects of a
relatively new skin sealant device in a cohort of patients who underwent a vascular procedure through the groin.
Besides gluing bacteria down to the skin, suturing the skin in a different way could prevent infections as well. Metal staples and non-absorbable sutures have the disadvantage of creating a connection from the outer skin into the subcutaneous space. Absorbable materials do not create this connection, and have been available since the use of catgut (8). Modern
absorbable sutures consist of an absorbable
polymer. Despite the absence of connection through the skin, a disadvantage of an absorbable suture is caused by its running properties, thus sealing the skin airtight. This prevents wound fluid from evacuating through the skin. Consequently,
collections of wound fluid and lymphatic fluid may form under the incision site, with formation of hematomas or seromas, an ideal prerequisite for bacterial growth (15). Absorbable staples could solve the problem of both closure techniques; no
connection through the skin and fluid evacuation between staples. A cohort study to compare a running absorbable suture with absorbable staples was designed for patients treated with a femoropopliteal bypass, as described in Chapter 3.
Attention was paid also to methods of surgical access. Does a percutaneous technique cause less SSI compared to the open surgical access of the common femoral artery (CFA)? To answer this question we focused on a procedure routinely performed in the vascular field, i.e. the abdominal aortic aneurysm (AAA) repair.
Figure 2: Skin adnexa storing
18 19
There are currently two ways to access such an aneurysm: the classical open surgical approach and the endovascular approach. The endovascular aneurysm repair (EVAR) has dramatically changed the vascular surgeons practice, as well asthe patient’s outcome. Although the long-term mortality does not improve, surgical complications of the open abdominal access are forestalled. Comparatively, it is anticipated that percutaneous approach of the CFA might be advantageous compared to surgical cut down, by further reduction of the invasiveness of the procedure. On the other hand, the percutaneous method might be sensed as “less controlled”, which would lead, therefore, to reduced safety (36). The invasive surgical technique may lead to more inguinal SSIs compared to the
percutaneous access of the CFA. Many studies were published reporting
advantages of this percutaneous EVAR (36), but a thorough systematic review, to bolster the body of evidence was still lacking. Therefore, we investigated available literature on patients treated for an aneurysm of the abdominal or thoracic aorta or percutaneous aortic valve implantation with either the use of an arteriotomy closure device (ACD) or surgical cut down (SCD). A comparison between ACD and SCD was made in terms of effectiveness and applicability, complications and duration of treatment in patients indicated for an endovascular procedure. A systematic review was performed and a meta-analysis of the available data is presented in Chapter 4.
The two methods ACD and SCD were also investigated in a multicenter prospective randomized controlled trial carried out in the vascular units of six hospitals in the Northern part of the Netherlands. The objective was to investigate whether
percutaneous access of the CFA with an ACD would decrease the number of SSIs compared to open surgical access of the CFA in EVAR. This trial is described in
Chapter 5 and its outcome in Chapter 6.
In a final effort to explain the source of a surgical site infection, microorganisms located at the incision site were analyzed. A technique for culture-free identification of microorganisms was applied to our patients of the PiERO trial and the results are described in Chapter 7. Earlier studies used these molecular methods analyzing
DNA of microorganisms in tissue (37). Probably, the presence of bacteria in skin tissue may contribute to the initiation of an SSI. We used several techniques to detect the presence of skin bacteria. Nasal and groin swabs were taken for SA
culture, and skin biopsies, taken just before the surgical procedure and were investigated with conventional histology and 16S-23S next generation sequencing (NGS) of any bacterial DNA. These techniques were used in a selection of patients suffering from SSIs and in patients without SSIs.
References
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3. Leaper DJ, van Goor H, Reilly J, Petrosillo N, Geiss HK, Torres AJ, Berger A. Surgical site infection — a European perspective of incidence and economic
burden. Int Wound J. 2004;1:247-73.
4. Martone WJ, Nichols RL. Recognition, prevention, surveillance, and management of surgical site infections: Introduction to the promblem and symposium overview. Clin Infect Dis. 2001;33:S67-S8.
5. Yasunaga H, Ide H, Imamura T, Ohe K. Accuracy of economic studies on surgical site infection. J Hosp Infect. 2007;65:102-7.
6. Graves N, Halton K, Doidge S, Clements A, Lairson D, Whitby M. Who bears the cost of healthcare-acquired surgical site infection? J Hosp Infect.
2008;69:274-82.
7. Kirkland KB, Briggs JP, Trivette SL, Wilkinson WE, Sexton DJ. The impact of surgical-site infections in the 1990s: Attributable mortality, excess length of
hospitalization, and extra costs. Inf Contr Hosp Epidem. 1999;20:725-30. 8. Fitzharris L. The butchering art: Scientific American; 2017.
9. Rijksinstituut voor Volksgezondheid en Milieu RIVM. Referentiecijfers 2012/2013 Postoperatieve wondinfecties. 2015 [Table 3]. Available from:
http://www.rivm.nl/dsresource?type=pdf&disposition=inline&objectid=rivmp:270084& versionid=&subobjectname=.
10. Szilagyi ED, Smith RG, Elliott JP, Vrandecic MP. Infection in arterial reconstruction with synthetic grafts. Ann Surg. 1972;176:321-33.
11. Jamieson GG, DeWeese JA, Rob CG. Infected arterial grafts. Ann Surg. 1975;181:850-2.
12. Shermak MA, Yee K, Wong L, Jones CE, Wong J. Surgical management of groin lymphatic complications after arterial bypass surgery. Plast Reconstr Surg. 2005;115(7):1954-62.
13. Antonios VS, Noel AA, Steckelberg JM, Wilson WR, Mandrekar JN,
Harmsen WS, Baddour LM. Prosthetic vascular graft infection: A risk factor analysis using a case–control study. J Infect. 2006;53:49-55.
14. Pieh-Holder KL. Lactationl ectopic breast tissue of the vulva: Case report and brief historical review. Breastfeed Med. 2013;8:223-5.
15. Reifsnyder T, Bandyk D, Seabrook G, Kinney E, Towne JB. Wound complications of the in situ saphenous vein bypass technique. J Vasc Surg. 1992;15:843-50.
16. Woodfield JC, Beshay NMY, Pettigrew RA, Plank LD and Van Rij AM.
American Society of Anesthesiologists classification of physical status as a predictor of wound infection. ANZ J Surg. 2007;77(738-741):738.
17. van Laar C, Timman ST, Noyez L. Decreased physical activity is a predictor for a complicated recovery post cardiac surgery. Health Qual Life Outcomes. 2017;15:5.
18. McPhee JT, Nguyen LL, Ho KJ, Ozaki CK, Conte MS, Belkin M. Risk
prediction of 30-day readmission after infrainguinal bypass for critical limb ischemia. J Vasc Surg. 2013;57:1481-8.
19. Earnshaw JJ, Berridge DC, Slack RCB, Makin GS, Hopkinson BR. Do preoperative chlorhexidine baths reduce the risk of infection after vascular reconstruction? Eur J Vasc Surg. 1989;3:323-6.
20. Berríos-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, Reinke CE, Morgan S, Solomkin JS, Mazuski JE, Dellinger P, Itani KMF, Berbari EF, Segreti J, Parvizi J, Blanchard J, Allen G, Kluytmans AJW, Donlan R, Schecter WP; for the Healthcare Infection Control Practices Advisory Committee. Centers for disease Control and Prevention guideline for the prevention of surgical site infection, 2017. JAMA Surg. 2017;152:784-91.
21. Tanner J, Norrie P, Melen K. Preoperative hair removal to reduce surgical site infection. Cochrane Database of Systematic Reviews. 2011;11:CD004122.
22 23
22. Perez P, Holloway J, Ehrenfeld L, Cohen S, Cunningham L, Miley GB, Hollenbeck BL. Door openings in the operating room are associated with increased environmental contamination. Am J Infec Control. 2018;46:954-6.
23. Bischoff P, Kubilay NZ, Allegranzi B, Egger M, Gastmeier P. Effect of laminar airflow ventilation on surgical site infections: a systematic review and meta-analysis. Lancet Infect Dis. 2017;17:553-61.
24. Kelsey JC. The myth of surgical sterility. The Lancet. 1972;2(7790):1301-3. 25. Kubica M, GUzik K, Koziel J, Zarebski M, Richter W, Gajkowska B, Golda A, Maciag-Gudowska A, Brix K, Shaw L, Foster T, Potempa J. A potential new pathway for Staphylococcus aureus dissemination: the silent survival of S. aureus
phagocytosed by human monocyte-derived macrophages. PLoS ONE. 2008;3:e1409.
26. Young PY, Khadaroo RG. Surgical Site Infections. Surg Clin North Am. 2014;94:1245-64.
27. Specialisten FM. Richtlijnendatabase 2011 [Infectiepreventie peroperatief]. 28. Vincent M, Edwards P. Disposable surgical face masks for preventing surgical wound infection in clean surgery. Cochrane Database of Systematic Reviews. 2016:CD002929.
29. Roth JA, Juchler F, Dangel M, Eckstein FS, Battegay M, Widmer AF. Frequent door openings during cardiac surgery are associated with increased risk for surgical site infection: A prospective observational study. Clin Infect Dis. 2018;DOI: 10.1093/cid/ciy879.
30. Watanabe M, Suzuki H, Nomura S, Maejima K, Chihara N, Komine O, Mizutani S, Yoshino M, Uchida E. Risk factors for surgical site infection in
emergency colorectal surgery: A retrospective analysis. Surg Inf. 2014;15:256-61. 31. Rao N, Cannella BA, Crossett LS, Yates Jr AJ, McGough RL, Hamilton CW. Preoperative screening/decolonization for Staphylococcus aureus to prevent orthopedic surgical site infection. J Arthroplasty. 2011;26:1501-7.
32. Roe CC, Horn KS, Driebe EM, Bowers J, Terriquez JA, Keim P, Engelthaler DM. Whole genome SNP typing to investigate methicillin-resistant Staphylococcus aureus carriage in a health-care provider as the source of multiple surgical site infections. Hereditas. 2016;153:1-7.
33. Whyte W, Hambraeus A, Leurell G, Hoborn J. The relative importance of routes and sources of wound contamination during general surgery. J Hosp Infect. 1991;18:93-107.
34. Wistrand C, Söderquist B, Falk-Brynhildsen K, Nilsson U. Exploring bacterial growth and recolonization after preoperative hand disinfection and surgery between operating room nurses and non-health care workers: a pilot study. BMC Infect Dis. 2018;18:466.
35. Dohmen PM, Gabbieri D, Weymann A, Linneweber J, Konertz W. Reduction in surgical site infection in patients treated with microbial sealant prior to coronary artery bypass graft surgery: a case control study. J Hosp Infect. 2009;72:119-26. 36. Bernardi FL, Gomes WF, de Brito Jr FS, Mangione JA, Sarmento-Leite R, Siqueira D, Carvalho LA, Tumelero R, Guerios EE, Lemos PA. Surgical cutdown versus percutaneous access in transfemoral transcatheter aortic valve implantation: Insights from the Brazilian TAVI registry. Cath Cardiovasc Intervent. 2015;86:501-5. 37. Iriz E, Cirak MY, Zor MH, Engin D, Oktar L, Unal Y. Differential identification of atypical pneumonia pathogens in aorta and internal mammary artery related to ankle brachial index and walking distance. J Surg Res. 2013;183:537-43.
27
Chapter 2
Cyanoacrylate skin microsealant for preventing surgical site
infection after vascular surgery: a discontinued randomized
clinical trial.
Bastiaan P. Vierhout1; Alewijn Ott2; Michel M.P.J. Reijnen3; Jacques Oskam4;
Jan J.A.M. van den Dungen5; Clark J. Zeebregts5
1. Department of Surgery, Wilhelmina Hospital, Assen 2. Department of Microbiology, Wilhelmina Hospital, Assen 3. Department of Surgery, Rijnstate Hospital, Arnhem
4. Department of Surgery, Division of Vascular Surgery, Isala Hospital, Zwolle 5. Department of Surgery, Division of Vascular Surgery, University Medical Centre Groningen, University of Groningen, Groningen
Abstract
Background: Surgical site infections (SSI) after vascular surgery are related to
substantial morbidity. Restriction of bacterial access to the site of surgery with cyanoacrylate sealant is a new concept. We performed a randomized clinical trial to assess the effect of the sealing of skin with a cyanoacrylate at the site of surgery on the incidence of SSI’s after arterial reconstruction.
Methods: Patients scheduled for vascular reconstruction in or distal to the groin
were randomized into a treatment and control group. Standard measures for preventing contamination of the surgical field were taken in the control group,
whereas cyanoacrylate was used as a skin sealant at the surgical site in the patients in the treatment group. We hypothesized that the incidence of SSI with the use of cyanoacrylate would be two-thirds (67%) lower than that with standard preparation of the surgical site, and performed an interim analysis of 50 patients to assess this.
Results: Risk factors among the 50 patients in the study included smoking (28%),
hypertension (77%), diabetes mellitus (36%), and hypercholesterolemia (74%). Indications for surgery were invalidating claudication (Fontaine IIb), pain at rest or tissue necrosis. The overall SSI-incidence was 3/47 (6%), without differences between groups; 9% SSIs in the control group versus 4% SSIs in the intervention group.
Conclusion: We could not confirm a reduction in the incidence of SSI after inguinal
vascular surgery with the use of a cyanoacrylate skin sealant as compared with conventional means for preparing the surgical site.
Introduction
The incidence of surgical site infections (SSI’s) shows wide variation, depending on patient-, surgeon- and hospital-related factors. In inguinal vascular procedures, incidences of SSI of 7% - 44% have been described (1, 2). Although surgical techniques have evolved considerably in recent decades, the incidence of SSI after vascular surgery, and its consequences, have not changed. In this context, groin infection in relation to the infection of prosthetic grafts in vascular surgery (3, 4) is responsible for a high rate of limb-loss and death(5).
Possible reasons for the relatively high incidence of infections in the groin in relation to the use of prosthetic vascular grafting to the femoral artery include the close proximity of the groin to the perineum, the relatively superficial position of these grafts, and the presence of lymphatic tissue ventral to the common femoral artery (6). More than 50% of all SSIs are caused by endogenous bacteria (7). The elimination of these micro-organisms could reduce the risk of groin infection after vascular surgery. A recent review and cost analysis found that replacement of iodine antisepsis by antisepsis with chlorhexidin was associated with statistically
significantly fewer SSI (adjusted risk ratio 0.64, 95% confidence interval [CI] 0.51-0.80)(8). However, the use of iodine draping did not cause a significant decrease in the incidence of SSIs (risk ratio 1.03, 95% CI 0.064-1.66)(9).
Cyanoacrylate sealant is a film-forming liquid provided in a ready-to-use applicator that has been developed to bond to the skin surface. Cyanoacrylate was cleared in September 2006 (by the European Medicines Agency, London, United Kingdom) as a surgical drape accessory; it bonds to the skin upon application and immobilizes the bacteria that survive the application of antimicrobial products for surgical preparation of the patient’s skin. The cyanoacrylate remains on the skin after the completion of the surgical procedure and may prevent contamination of the surgical incision during the first few days post-operatively. Dohmen et al. studied the effect of cyanoacrylate on the incidence of SSI after coronary artery bypass grafting (CABG) (10). They found that superficial or deep sternal SSI developed in seven patients (7.8%) in a control group (n= 545) as compared with only one patient (1.1%) in a group (n= 131) whose surgical site was applied with cyanoacrylate (OR 7.5, p=0.062). Iyer et al. recently reported a significant reduction of SSI in the harvesting of portions of the greater saphenous vein when using a
30 31
group treated with sealant, whereas the incidence of SSI in the control group was 25.5% (n=12, p=0.001).
In the present study we tested the hypothesis that the additional attention given to the specific issue of SSI in a clinical study of its occurrence and the use of a cyanoacrylate skin sealant at the site of surgery could more than halve the incidence of SSI in the groin region after vascular procedures, as compared with standard preventive measures. The study and the present report were done according to the guidelines of the Consolidated Standards of Reporting Trials (CONSORT) Statement (12).
Patients and methods
Study design
We conducted a randomized, single-blind, clinical trial to evaluate the effect of a cyanoacrylate sealant on the incidence of groin infections after vascular surgery on the femoral artery. In the treatment arm of the trial a ready-to-use applicator
(InteguSeal® IS200, Kimberly-Clark, Roswell, GA) was used to apply the sealant to the incision site. Wounds were evaluated with the Southampton Wound
Assessment-score (SWA-score) (13). In case of fluid evacuation from the wound bacterial cultures were taken.
During a pre-operative outpatient clinical visit, all consecutive adults over 18 y of age who had an indication for infrainguinal vascular reconstruction were informed about the study, and written informed consent was obtained from those who agreed to participate. The surgical procedures done on the patients in the study included common femoral reconstruction, popliteal, crural, and femoro-femoral crossover bypass graft implantation; excluded were thrombectomies done through an inguinal incision, patients younger than 18 y of age, and those with a previous groin incision or vascular reconstruction done cranially to the site of
incision in the present study (e.g., endovascular aneurysm repair procedures). After signing an informed consent agreement, patients were randomly assigned in a 1:1 ratio to one of the two groups, with randomization accomplished by the drawing of a sealed envelope in the operation room one-half hour before surgery by the surgeon performing the operation. Ethical approval for the study was granted by the
Committee on Research involving Human Subjects, Arnhem-Nijmegen, The Netherlands (reference NL25592.091.08).
Procedure
All patients received prophylactic cephazolin (Kefzol®, Lilly, Houten, The
Netherlands) 2 g IV prophylactically from 15-60 min before the incision for surgery was made. Patients were prepared in the routine manner for surgery, involving removal of hair with a clipper immediately before the procedure, disinfection with chlorhexidine 0.5% in 70% isopropyl alcohol, and sterile draping with disposable drapes (Secu-Drape®, Sengewald, Germany). In the treatment group cyanoacry-late was applied to the site of surgical incision after regular disinfection but before incision, by pressing the foam tip of the applicator gently against the skin (Fig. 1). All patients underwent a wound evaluation at 2 d,
14 d, and 6 wk after operation. The wound evaluation was done at 2 wk and 6 wk post-operatively by a researcher who was blinded to the randomization done in the study, using the Southampton Wound Assessment (SWA) score (13) and
maximizing correct definition through the additional use of wound culture results. A blinded wound evaluation at 2 d post-operatively was not possible. If a patient presented with a wound infection before the next scheduled wound evaluation, the infection was registered under the most recent previous evaluation. An efficacy interim analysis of the data was planned after inclusion of the first 50 patients.
Outcome measures
The primary endpoint was the incidence of SSI within the first two postoperative weeks, defined as a SWA score of grade III or higher, in combination with a positive fluid result of culture of a fluid specimen obtained aseptically from a primarily closed surgical site (14). Criteria for SWA scores are given in Table 1 (13).
Sample size calculation
The mean incidence of vascular SSI as reported in the literature is 12% (1, 2, 6, 14, 15). The assumption had been made that the use of a cyanoacrylate sealant would reduce the incidence of SSI by two-thirds of this reported value, from 12% to 4% (10, 11), as compared with standard preventive measures. For a trial demonstrating a superiority of cyanoaclylate with an effect size of 90% and a margin of 10%, 180 patients per group were needed (alpha 5%, power 80%) to provide a significant difference, as calculated in a power analysis. We performed a power analysis with the following formula (16): n = 8 x (P1(1 – P1) + P2(1 – P2))/(P1 – P2)2, on the basis of an intention-to-treat principle. Significance was tested with the Fisher Exact test. A value of p< 0.05 was considered significant.
Results
The study included 50 patients and was conducted from January 2010 to April 2011 at the Wilhelmina Hospital, Assen, The Netherlands. All patients approved their participation in the study. Three patients were excluded from analysis of the study
Clinical description
Grade 0 Normal wound healing
Grade I Wound healing with mild bruising or erythema
A Some bruising
B Considerable bruising
C Mild erythema
Grade II Erythema plus other signs of inflammation
A At one point
B Around sutures
C Along the wound
D Around the wound
Grade III Clear or haemoserous discharge
A At one point only (< 2cm)
B Along the wound (> 2cm)
C Large volume
D Prolonged (> 3d)
Grade IV Pus
A At one point only (< 2cm)
B Along the wound (> 2cm)
Table 1. Southampton wound assessment
data because of early post-operative death. Two of these three patients died from cardiac complications in the immediate postoperative period and the third died from bowel ischemia one week after vascular reconstruction in the groin (Fig. 2). As a result, a total of 47 groin incisions were available for analyses.
Figure 2. Details of the screening and randomization procedures used in the study.
Patients included in the analyses had a mean age of 71+10 y, and 28 patients were male (60%). Co-morbidity included a history of smoking in 28% (n= 13) of the patients, hypertension in 74% (n= 36), diabetes mellitus in 36% (n= 17), and
hypercholesterolemia in 72% (n= 34). In 68% (n= 32) only a vascular reconstruction of the common femoral artery and its branches was performed. The remaining operations included 10 femoro-popliteal bypass procedures, one femoro-tibial bypass, two femoro-femoral cross-overs, and two endarteriectomies of the common femoral artery in combination with a percutaneous transluminal angioplasty (PTA) of the superficial femoral artery. The group in which the cyanoacrylate was used and the group given standard surgical preparation were comparable with regard to the types of procedures and risk factors in each group (Table 2).
34 35
The overall incidence of SSI’s was 6% (3 patients)(Table 3). At all measured time points, the difference in incidence of SSI in the treatment and control groups was smaller than expected (in the control group, two infections were diagnosed, on post-operative days 6 and 18, respectively, and in the treatment group, one infection was diagnosed, on post-operative day 22)(Figure 3).
Group 1 (n=22) Without CA Group 2 (n=25) With CA Gender (male) 14 (64%) 14 (56%) Smoking 7 (32%) 6 (24%) Hypertension 19 (86%) 17 (68%) Dyslipidemia 17 (77%) 17 (68%) Diabetes mellitus 9 (41%) 8 (32%) BMI (SD) 27 (4.6) 28 (4.5) Age < 50 y 1 (5%) 1 (4%) 51-60 y 2 (9%) 5 (2%) 61-70 y 7 (32%) 9 (36%) 71-80 y 7 (32%) 4 (16%) > 80 y 5 (23%) 6 (24%) Fontaine IIa 4 2 Fontaine IIb 9 12 Fontaine III 6 8 Fontaine IV 3 3 Common femoral reconstr. 16 (73%) 16 (64%) Femoro-popliteal bypass 3 (14%) 7 (28%) Femoro-crural bypass 1 (5%) 0 Crossover bypass 0 2 (8%) Other 2 (9%) 0 Mean operating time, min (SD) 132 (41.4) 151 (48.0)
Table 2. Procedures and risk factors in study groups. BMI= body mass index; CA= cyanoacrylate.
No SSI SSI
Cyanoacrylate (-) 20 (91%) 2 (9%) Cyanoacrylate (+) 24 (96%) 1 (4%)
Table 3. Number of SSIs in study groups. SSI= surgical site infection
The two infections in the control group were caused by Staphylococcus aureus and
Pseudomonas aeruginosa. The patient with SSI in the group treated with
cyanoacrylate, took a bit longer to develop symptoms and had only Staphylococcus
aureus in its culture.
The two patients in the control group who developed infections underwent endarterectomy of the common femoral artery with venous patching. They were empirically treated with oral antibiotics (amoxicillin/clavulanic acid 625mg 3dd), and their wounds were opened and rinsed with water twice a day until closure. Both healed without further complications. A re-operation at 22 days after initial surgery was required in the patient in the cyanoacrylate group who developed a SSI because of an infected polytetrafluoroethylene femoro-femoral crossover bypass.
Figure 3. Kaplan-Meier curve of 25 patients treated with cyanoacrylate skin sealant before surgery
(treatment group) and 22 patients prepared for surgery without cyanoacrylate (control group).
Lymphatic complications occurred in two patients each, in the cyanoacrylate and control group. All of these patients had sterile fluid draining from their surgical incisions, as confirmed by negative cultures in all four cases.
Discussion
the results of the present study. Various factors may explain the difference. First, the study conducted by Dohmen et al. had a selection bias (10). Patients treated with the cyanoacrylate sealant in their study underwent surgery by one surgeon,
whereas other surgeons treated patients in the control group. Second, the operations done both by Iyer et al. and done by Dohmen et al. (10, 11) were
performed in clean areas of the body, whereas the groin is usually considered to be clean-contaminated. A higher overall incidence of SSI could therefore have been expected. The skin of the groin is known to contain more sweat glands, and develops folds in a seated patient, thereby creating an environment for microbial contamination (19). Moreover, these folds increase the flexibility of the skin in the groin, thereby causing multiple cracks to develop in the sealant and counteracting its mechanism of action. A recent trial confirmed our conclusion in showing no significant decline in the incidence of SSI in 496 incisions treated with the same cyanoacrylate as used in our study (18). A better surgical site for research on the use of cyanoacrylate would be the area of the carotid artery, but because SSI in this area is rare, larger study groups would be needed to provide statistical power in a comparison of cyanoacrylate with other preparative techniques for carotid surgery. The present study has several limitations. First, the study was a randomized, single site trial, and may therefore have been susceptible for patient selection. Second, the preponderance in the study of non-smokers and patients without CLI was
surprisingly high (72% and 87%, respectively), which may well have affected the incidence of SSIs. Unfortunately, screening for colonization with S. aureus was not performed pre-operatively. All cultures of the infected incisions contained S. aureus, and they could possibly could have been prevented had preoperative eradication been performed (20). Additionally, most of the surgical procedures done in the study consisted solely of a reconstruction of the common femoral artery, and the
performing surgeon was informed about the allocation of the patient, thereby creating the risk of bias in the conduct of the surgeon. All of the foregoing factors may have attributed to the relatively low incidence of infections in the present study. In conclusion, we could not show a reduction in the incidence of SSI in the groin after vascular surgery following the use of cyanoacrylate skin sealant. The number of patients needed to treat to reach clinical significance was considered too great for clinical relevance of the findings in the present study. A multi-center trial, preferably including older patients with CLI, might show significance with a lower
number-needed-to-treat of patient for such a finding.
References
1. Reifsnyder T, Bandyk D, Seabrook G, Kinney E, Towne JB. Wound
complications of the in situ saphenous vein bypass technique. J Vasc Surg. 1992;15:843-50.
2. Donaldson MC, Whittemore AD, Mannick JA. Further experience with an all-autogenous tissue policy for infrainguinal reconstruction. J Vasc Surg. 1993;18:41-8.
3. Jamieson GG, DeWeese JA, Rob CG. Infected arterial grafts. Ann Surg. 1975;181:850-2.
4. Antonios VS, Noel AA, Steckelberg JM, Wilson WR, Mandrekar JN,
Harmsen WS, Baddour LM. Prosthetic vascular graft infection: A risk factor analysis using a case–control study. J Infect. 2006;53:49-55.
5. Szilagyi ED, Smith RG, Elliott JP, Vrandecic MP. Infection in arterial reconstruction with synthetic grafts. Ann Surg. 1972;176:321-33.
6. Giovannacci L, Renggli JC, Eugster T, Stierli P, Hess P, Gürke L. Reduction of groin lymphatic complications by application of fibrin glue: preliminary results of a randomized study. Ann Vasc Surg. 2001;15:182-5.
7. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Am J Infec Control.
1999;27:97-132.
8. Lee WA, Brown MP, Nelson PR, Huber TS, Seeger JM. Midterm outcomes of femoral arteries after percutaneous endovascular aortic repair using the Preclose technique. J Vasc Surg. 2008;47:919-23.
9. Webster J, Alghamdi A. Use of plastic adhesive drapes during surgery for preventing surgical site infection. Cochrane database of systematic reviews. 2013;CD006353(1).
10. Dohmen PM, Gabbieri D, Weymann A, Linneweber J, Konertz W.
Reduction in surgical site infection in patients treated with microbial sealant prior to coronary artery bypass graft surgery: a case control study. J Hosp Infect. 2009;72:119-26.
11. Iyer A, Gilfillan I, Thakur S, Sharman S. Reduction of surgical site
infection using a microbial sealant: A randomized trial. J Thorac Cardiovasc Surg. 2011;142:438-42.
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12. Schulz KF, Altman DG, Moher D, Schulz K. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:698-702.
13. Bailey IS, Karran SE, Toyn K, Brough P, Ranaboldo C, Karran SJ. Community surveillance of complications after hernia surgery. BMJ. 1992;304:469-71.
14. Rijksinstituut voor Volksgezondheid en Milieu RIVM. Referentiecijfers 2012/2013 Postoperatieve wondinfecties. 2015 [Table 3].
Available from: http://www.rivm.nl/dsresource?type=pdf&disposition=inline&o bjectid=rivmp:270084&versionid=&subobjectname=.
15. Ploeg AJ, Lardenoye JWP, Vrancken Peeters MPFM, Hamming JF, Breslau PJ. Wound complications at the groin after peripheral arterial surgery sparing the lymphatic tissue:
a double-blind randomized clinical trial. Am J Surg. 2009;197:747-51. 16. Campbell MJ, Swinscow TDV. Statistics at square one. 11th ed. West
Sussex: Wiley-Blackwell; 2009.
17. Woodfield JC, Beshay NMY, Pettigrew RA, Plank LD and Van Rij AM. American Society of Anesthesiologists classification of physical status as a predictor of wound infection. ANZ J Surg. 2007;77(738-741):738.
18. Waldow T, Szlapka M, Hensel J, Plötze K, Matschke K, Jatzwauk L. Skin sealant InteguSeal has no impact on prevention of postoperative
mediastinitis after cardiac surgery. J Hosp Infect. 2012;81:278-82.
19. Perng CK, Yeh FL, Ma H, Lin JT, Hwang CH, Shen BH, Chen CH, Fang RH. Is the treatment of axillary osmidrosis with liposurction better than open surgery? Plast Reconstr Surg. 2004;114:93-7.
20. Rao N, Cannella BA, Crossett LS, Yates Jr AJ, McGough RL, Hamilton CW. Preoperative screening/decolonization for Staphylococcus aureus to prevent orthopedic surgical site infection. J Arthroplasty. 2011;26:1501-7.
43
Chapter 3
First application of an absorbable skin stapler in peripheral
vascular surgical procedures
Vierhout BP1, De Korte JD1, De Vos B1, Bottema JT2 and Zeebregts CJ2
1. Department of Surgery, Wilhelmina Hospital, Assen, Netherlands
2. Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Abstract
Objective: Appropriate skin closure is essential and several techniques are
available such as dermal sutures and metal staples. Absorbable staples have promising qualities. Our aim was to lower the surgical site infection (SSI) rate with the use of subcuticular absorbable skin (Insorb™) staples.
Design and Patients: A long-term (IDEAL) phase 4 historical comparative
effectiveness trial was performed during a 2-year period from December 2012 to December 2014 in patients undergoing an infra-inguinal femoro-popliteal bypass operation. We compared closure of the skin by means of an absorbable stapler with a cohort of patients treated with intracutaneous sutures. Primary outcome: number of SSI’s. Secondary outcome: other complications, duration of surgery and hospital length of stay.
Results: 44 patients were enrolled in the study; 6 patients underwent skin closure
with the absorbable staples. 4 of them had an SSI. Of 38 patients treated with intracutaneous sutures 7 had an SSI (risk difference: 0.48, 95% CI 0.09-0.88). Duration of surgery (p= 0.84) and length of stay (p= 0.15) were similar.
Conclusion: Due to a large proportion of SSI’s in the absorbable stapler group the
use of these subcuticular absorbable staples was discontinued in our facility. We consider the absorbable staples not strong enough for wound closure in peripheral vascular surgery.
Introduction
Appropriate surgical incision closure plays a key role in the overall outcome of each surgical procedure. Several techniques and materials have been described to achieve closure of the skin. Widely adopted are transcutaneous non-absorbable sutures, absorbable sutures and metal staples. Since 2005, a new technique was developed using subcuticular absorbable staples of polylactic/polyglycolic
copolymer (comparable with braided absorbable threads such as Vicryl™), named Insorb™ Absorbable Skin Stapler (Incisive Surgical Inc., Plymouth, MN, USA)(1). Reducing the number of SSI’s is of large interest for patients and surgeons, based both on the reduction of morbidity and costs. An increasing number of publications are available concerning wound closure with absorbable sutures. These reports show positive results regarding pain, cosmetics, and absorptivity in wound closure after caesarean sections and in plastic surgery (2-4). In vascular bypass surgery wounds are a major challenge for the surgeon; besides limb salvage and distal wound healing, wound healing of the inflicted incisions must be reached. It was anticipated that for this reason, the application of the new absorbable Insorb™ staples could positively attribute to a better wound healing.
Because of these possible advantages, we decided to test Insorb™ Staples in cardiovascular compromised patients who were indicated for infra-inguinal bypass surgery in our facility. We expected the rapidly applicable absorbable staples to reduce the SSI-rate in femoro-popliteal bypass surgery. A comparison was made with a cohort of patients undergoing an infra-inguinal bypass in the preceding two years. Special attention was paid to the incidence of infection and wound healing.
Methods
Study design
The surgical procedures were performed during a 2-year period from December 2012 to December 2014 at Wilhelmina Hospital Assen, the Netherlands. The design was consistent with a phase 4 study as described in the IDEAL framework (5). A comparison was made of absorbable skin staples with a prospectively maintained database of patients treated with intracutaneous suture. Retrospectively, these data were reviewed for patient characteristics. Patients’ data were analyzed anonymously.
46 47
Ethical considerations
Institutional Review Board approval for the introduction of this skin closure technique was obtained. Informed consent was received for the patients
prospectively included. We had no plans for publication, but because of the rare outcome this seemed mandatory post-hoc (5). As a consequence, besides the Institutional Review Board, the Medical Ethical Commission was not informed. Study information for the patients was provided in advance during their preoperative visit. They were informed about the procedure and required compliance. All patients were given one-week time to make their decision regarding participation in the study and all gave informed consent (absorbable stapler group).
In the intracutaneous sutures group retrospective patient file research was not in the scope of the Dutch Human Bound Research and ethical approval was not required.
Study population
Table 1 shows the in- and exclusion criteria for enrollment in this study. The
absorbable stapler group (group A) consisted of a group of prospectively screened patients that underwent infra-inguinal bypass surgery with absorbable skin staples. The staples were deployed capturing the dermal layer of both sides of the incision. The stapler contains 20 individual, horseshoe-shaped staples, 5 mm long x 3.5 mm wide x 0.7 mm thick. Closures were accomplished by having an assistant
approximate and elevate the skin edges into the stapler device, using 2 forceps, while the surgeon fired the stapler (Figs. 1 and 2). All involved vascular surgeons and surgical assistants were trained on the use of the dermal stapler. All had the opportunity to use the stapler in a testing setting.
Group A; absorbable staples (prospective) Group B; control cohort (retrospective) Inclusion criteria • Age > 18 years
• Suitable for peripheral bypass surgery • Adequate popliteal landing zone
Exclusion criteria • Incapacity (mentally disabled or legal disqualification)
• Severe concomitant illness that drastically shortens life expectancy or increases risk of therapeutic interventions
Table 1: Inclusion and exclusion criteria.
Figure 1. InsorbTM stapler and its use in the operating theater.
Group B, which served as a control group, consisted of a prospectively maintained database with retrospectively recorded characteristics treated with intracutaneous sutures. They underwent surgery in the time period December 2012 to July 2014, with closure of the wound using a running absorbable suture (Caprosyn™ 3-0 monofilament absorbable suture, Covidien, Mansfield, MA, USA).
Patients in both groups underwent surgery with closure of the subcutaneous tissue with a running 3-0 braided polygalactin suture (Polysorb; US Surgical, Norwalk, CT, USA).
Figure 2. A patient from group A treated with subcuticular staples. Although initial wound closure
seems adequate, the staples were not strong enough to retain the revascularization edema, resulting in an open wound (Figure 3).
Data collection and outcomes
Data recorded included age, sex, Fontaine classification, risk factors (smoking habits, diabetes mellitus, hypertension, hypercholesterolemia, familial
predisposition), side of the operation, duration of surgery, supra- or infragenual landing zone of the bypass, autologous vein or PTFE (either heparin coated or not) and hospital length of stay. Post-procedure complications were recorded, as well as the need for redo surgery. Primary, primary assisted, and secondary patencies of the bypass were calculated.
The primary outcome was the rate of surgical site infections (SSI’s). Secondary outcomes were the numbers of seroma formations and rebleeding necessitating reoperation. Also the duration of operation and the hospital length of stay were evaluated, as were the patency of the bypass and the necessity of an additional amputation.
The definition of a SSI was purulent drainage from the incision, organisms isolated from an aseptically obtained culture in case the wound opened spontaneously, or an incision that was deliberately opened by a surgeon for reasons of suspicion for infection, and its culture positive or not cultured. The patient had at least one of the following signs or symptoms: pain or tenderness, localized swelling, erythema, or heat, as mentioned in the CDC-guidelines (6).
In patients treated with the absorbable stapler (group A) and patients from group B, hospital-location and treating vascular surgeons and assistants were unchanged.
Statistics
In 2015, the incidence of reported SSI’s in infra-inguinal bypass surgery was 15% in the Netherlands (7). We hoped to reach a reduction of our infection rate from 18% (our own historical data) to 9%. A power-analysis with an effect size of 90% and a margin of 10% in the formula; n= 8 x (p1(1-p1) + p2(1-p2))/(p1-p2) (8), calculated 227 patients in each group necessary to avoid a type II error (alpha 5%, power of 80%) (8).
The proportion of patients complicated with an SSI was calculated with risk differences (RD) and their corresponding 95% confidence intervals (CI)(Standard Error (SE)= √ [pA(1-pA)/nA + pB(1-pB)/nB]). When this CI includes zero, the H0 is accepted, meaning no significant difference between the proportions. The same method was used for the risk factors of the participants in each group and their secondary outcomes. Differences between continuous variables, such as age,
duration of surgery, hospital length of stay and duration of follow up, were calculated using the Students t-test. Normal distribution was tested with Kolmogorov-Smirnov test and in case of skewness a log- or inverse-transformation was performed. Significance was set at p<0.05.
Results
Demographics
A total of 6 subjects with an indication for infra-inguinal bypass surgery were identified and gave permission for inclusion in the absorbable stapler group, coded as group A. Patient demographics and operative parameters are shown in Table 2. The retrospective study cohort ICS consisted of 38 consecutive patients, who had been treated with a running intradermal suture: group B. Patient risk factors were not significantly different between the two groups, except for familial predisposition and the number of patients with Fontaine grade III classification; they were more common in group B. The latter group also enclosed patients treated for popliteal aneurysms, two with minor symptoms of distal ischemia (Table 2).
Group A Group B Insorb™ stapler Intracutaneous
sutures Number of subjects 6 38
Mean age in years (range) 72 (53-85) 68 (46-90) 68.5 (63.1-81.3) n pption n pption RD(95%-CI) Male gender 4 0.67 22 0.58 0.09 (-0.32-0.5) Risk factors Smoking habits 2 0.33 16 0.42 0.09 (-0.32-0.5) Diabetes mellitus 2 0.33 15 0.4 0.06 (-0.35-0.47) Hypertension 4 0.67 29 0.76 0.10 (-0.3-0.5) Hypercholesterolemia 4 0.67 27 0.71 0.04 (-0.36-0.45) Familial predisposition 0 0.0 13 0.34 0.34 (0.19-0.49) Fontaine classification* I 0 0.0 1† 0.03 0.03 (-0.02-0.08) IIa 0 0.0 2† 0.05 0.05 (-0.02-0.12) IIb 2 0.33 14 0.37 0.04 (-0.37-0.44) III 0 0.0 13 0.34 0.34 (0.19-0.49) IV 4 0.67 12 0.32 0.35 (-0.05-0.76) Chronic distal wounds present 4 0.67 12 0.32 0.35 (-0.05-0.76) Affected right leg 3 0.5 20 0.53 0.03 (-0.4-0.46) Mean DOS in minutes (range) 183 (156-215) 178 (162-195) 179 (164-194) Venous bypass 6 1.0 25 0.66 0.34 (0.19-0.49) Anastomosis below the knee 4 0.67 21 0.55 0.11 (-0.29-0.52) DSA at the end of the operation 6 1.0 32 0.84 0.15 (0.04-0.27)
Table 2. Demographics and risk factors. pption= proportion, RD= risk difference, FU= follow up.
50 51
A
B
A completion angiogram was routinely performed since the beginning of 2013. As a consequence, not all patients of group B had an angiographic evaluation at the end of the operation (16%).
Primary outcome
A total of 4 wounds of group A (n= 6) were complicated with an SSI (67%). Three wounds opened spontaneously, due to traction on the skin. Staples were removed, but the wound was not cultured. The fourth patient had a positive culture for
Pseudomonas aeruginosa. Due to extensive edema after revascularization, the
staples seemed unable to contain continuity of the skin (Figures 3 and 4).
Figure 3. Postoperative edema provokes dehiscence of the wound. Wounds of a patient shown three days postoperatively (A) and 3 weeks postoperatively (B)
In control group B (n=38) 7 patients (18%) had a surgical site infection (SSI). The risk difference (RD) between group A and B was 0.48 in favor of group B
(95%-CI 0.09-0.88). Four of these 7 patients of group B needed a second operation due to this infection (Table 3). Two patients had cultures positive for Staphylococcus
aureus, one contained Bacteroides fragilis, and the 4th was infected with Escherichia coli and Enterococcus faecalis. The other 3 had a minor SSI with
dehiscence of the wound. One wound was cultured and showed growth of
Staphylococcus aureus, the remaining 2 were not cultured.
Figure 4. Normal wound healing after debridement and negative pressure therapy after 6 weeks (A). Three months postoperatively the wound is almost closed (B).
Secondary outcomes
Postoperative seroma formation was only seen in group B (7/38= 18%)(RD 0.18, 95%CI 0.06-0.31). One of these 7 patients had a subsequent wound infection, but
A
no organisms were identified from the cultured wound fluid. The remaining 6
wounds with a seroma healed without further complications. One patient from group A had profuse lymph leakage. The seroma drained through the staples.
No SSI occurred.
Re-operation for persistent bleeding was performed in two patients from group B (RD: 0.05, 95% CI -0.02-0.12). Duration of surgery was similar in both groups: the mean of group A was 183 min (95% CI 156-215 minutes) versus a mean of group B 178 min (95%CI 162-195 min)(p= 0.84, normality after log-transformation). Mean hospital length of stay for group A was 6.7 days (95%CI 4.6-12.1) and for group B 4.7 days (95%CI 4.1-5.5)(p= 0.15), with an overall mean hospital length of stay of 4.9 days (95%CI 4.2-5.7days)(normal distribution after inverse transformation).
Group A Group B Insorb™ Stapler Intracutaneous
sutures Number of subjects 6 38
n pption n pption RD (95%-CI) Surgical site infection (SSI) 4 0.67 7 0.18 0.48 (0.09-0.88) - SSI requiring re-operation 0 0.0 4 0.11 0.11 (0.01-0.2) - Bleeding req. re-operation 0 0.0 2 0.05 0.05 (-0.02-0.12) Seroma 0 0.0 7 0.18 0.18 (0.06-0.31) Toe amputation 1 0.17 0 0.0 0.17 (-0.13-0.46) Forefoot amputation 0 0.0 2 0.05 0.05 (-0.02-0.12) Leg amputation 0 0.0 3 0.08 0.08 (-0.01-0.16) Death of congestive heart failure 0 0.0 2 0.05 0.05 (-0.02-0.12) Mean HLOS in days (range) 6.7 (4.6-12.1) 4.7 (4.1-5.5) 4.8 (4.3-5.7) Mean follow up in months (range) 7 (3-11) 15 (0-30) 14.5 (12.7-16.3)
Primary patency bypass 5 83% 22 49% Primary assisted patency 5 83% 25 70% Secondary patency 6 100% 27 80% Lost to FU 0 0% 1 3%
Died during follow up 0 0% 4 10%
Table 3. Postoperative complications after infra-inguinal bypass surgery. Patencies are calculated at the time of follow up (mean 7 months for group A and mean 15 months for group B). HLOS= hospital length of stay.
One patient from group A had a toe amputation due to persisting ischemia. Five patients of group B were treated with an additional amputation (forefoot-, below
knee amputation, and through knee amputation). Two patients (5%) died within 30 days post-surgery, due to congestive heart failure after surgery (Table 3).
After a mean follow up of 6.8 months all conduits were patent for group A. One patient of this group was re-operated for closure of a persisting arteriovenous fistula following an in-situ venous femoro-tibial bypass (Table 3). The mean follow up with duplex ultrasound examination of group B was 15 months and available for 31 patients (82%); 2 patients had died in the first days postoperatively (5%), 4 patients (11%) expired during follow up from conditions unrelated to infra-inguinal vascu-lar disease, and 1 patient was lost to follow up (3%). During follow up 6 bypasses (16%) failed due to thrombosis. This occurred after a mean time of 12 months (2, 4, 10, 13, 22, and 23 months) after initial operation. The occluded bypasses were above the knee with vein in 1 and below the knee with vein in 2 patients. PTFE was used in 1 patient above the knee and 2 below the knee. One graft was successfully recanalized with intra-arterial mediated thrombolysis and additional stenting of the distal anastomosis. One patient was treated with a second open surgical bypass below the knee. Two patients were not suitable for redo surgery and an amputation was performed. The remaining 2 patients had healed wounds without complaints. During follow up 3 other bypasses showed a proximal, or in-bypass stenosis. These patients underwent an additional percutaneous intervention, one patient in the common iliac artery and 2 patients in the bypass.
The primary patency, primary assisted patency, and secondary patencies for group A were 83%, 83%, and 100%, respectively. For the control group (group B) these numbers were 49%, 70%, and 80%, respectively.
Discussion
This study shows that subcuticular absorbable skin staples in peripheral vascular surgery do not decrease the number of wound complications. The technique has positive aspects such as fast applicability and easy evacuation of wound fluids, but more dehiscence was seen in the intervention group. Postoperative swelling and edema seem to contribute in these problems. Absorbable staples are not strong enough, resulting in a higher infection-rate than the average 15% (7).
Endovascular surgery becomes increasingly popular. It enhances convalescence in peripheral arterial disease. Favorable outcomes are seen with a lower number of
54 55
SSI’s (9). However, there still is a necessity for open surgery in selected cases. In our cohort, severe signs of ischemia were seen. The majority of our patients (57%) needed a bypass below the knee joint (TASC C and D lesions) not suitable for endovascular techniques. And the average age of the patients was 70 years, with skin thinning.
In these vulnerable patients, we hoped to reduce wound complications with the relatively new technique. These supposed advantages are highlighted hereunder: 1. The applicability seems to be more rapid compared to dermal sutures
(3, 10-12). Despite training of our vascular team, we did not find a shorter OR-duration in our intervention group. But, these were 6 venous bypasses, necessitating harvesting of the greater saphenous vein, which may explain the lack of time reduction.
2. Evacuation of excessive fluids would be an advantage of the new staples thus evacuating the postoperative seroma. One patient suffered from excessive drainage of fluids after using absorbable staples. Formation of a huge seroma was prevented. This would not have been possible in case of intracutaneous running sutures, closing the wound airtight. In the outcome, more seroma formation was seen in the control intracutaneous sutures group.
3. Metal staples require an open connection between the subcutaneous tissue and the dressings, draped upon the skin. They give more erythema and drainage (13). Metal staples cause skin irritation and require removal (12, 14). The puncture holes result in scarring, as well (1). Although absorbable staples seem to cause some short-term patient discomfort they also proved to have advantages over metal staples (14).
When these rapid absorbable staples do evacuate excessive wound fluid, and do not increase inflammation, we could hypothesize that only the strength of the staples was insufficient. Research shows them unsupportive after 3 weeks (<0.3 lbf*)(13). Especially patients with skin thinning, such as elderly, are inappropriate candidates (10). The strength was a problem larger than the drainage of fluids. Stress on the wound edges was mentioned before to cause problems (3, 11). Additional subcutaneous sutures may prevent disruption (11), and one study even mentioned oversewing absorbable staples with extra sutures (14). When looking at our outcomes, the number of SSI’s was higher in the ASS group compared to the
ICS group (respectively 67% versus 18%). All wounds opened were classified as infected, but the number of reoperations was significantly lower than in the ICS group (57% of the infected wounds). These surgical sites were infected in a deeper layer. At skin-level the absorbable staples do not increase the amount of fibroblast proliferation, inflammation, or collagen deposition compared to dermal sutures (10). SSI’s were not caused by the absorbable staples, but infection followed the
dehiscence of the wound.
Limitations to the present study are numerous. The design is not randomized; numbers are small; a historic cohort was compared to a small number of
prospective participants. Not all wounds were cultured when opened and duration of follow up was different between the two groups. But disappointing results urged us to warn fellow surgeons (15).
In peripheral vascular surgery wounds have a high stress on skin edges and regarding our results, we would advise against the absorbable staples in peripheral vascular surgery. Wounds in other parts of the body, e.g. in breast surgery,
transplantation surgery, and facial surgery may have different characteristics and therefore less dehiscence.
* lbf= pound-force (1 lbf= 0.45kg x 9.8m/s2= 4.4 Newton)
Conclusion
Although this study is underpowered, we describe the first application of an absorbable skin closure technique in major peripheral vascular procedures.
Absorbable staples were compared to standard closure with running intracutaneous absorbable sutures. Because of insufficient strength of the staples and
postoperative edema in peripheral vascular surgery, we advise against absorbable staples in peripheral vascular surgery.
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