Prof. Dr. med. C. Schmitz, Komm. Direktor, Klinikum Großhadern, Marchioninistr. 15, D-81377 München
CAMP US GROS SHADERN HERZCHIRURGISCHE K LINIK UND P OL IKL INIK
Munich, September 20th, 2011
Comparison of Topical Hemostatic Agents:
Starch powder, Gelatin sponge or Gelatin matrix and Oxidized
regenerated Cellulose
Review of Adverse Events
Dr. H. Mair
Department of Cardiac Surgery, University of Munich
(Head of Department: Prof. Dr. med. C. Schmitz)
Abstract: There are a variety of absorbable hemostats locally placed during surgery commercially available. Proper
handling is essential to control bleeding and only the required amount should be used, even though the
hemostat is expected to dissolve promptly. By using local hemostats, it is possible to improve the
condition of the patient, reduce complications, and lower direct and indirect costs.
In this article we describe side effects of textile (or woven fabric) based hemostats. Gelatin sponge,
Gelatin matrix or oxidized cellulose are currently in widespread use. Unfortunately there are product
related adverse events like inflammation, foreign body reactions, Granuloma formation or blockade of
healing when these devices were used. Even more compression and damage of tissue, e.g. nerves with
consecutive palsy is described. One reason for this damaging effect is the late swelling of the textiles.
Mimicking of structures in medical imaging, e.g. radiology or ultrasound diagnostics is as well frequently
reported. Deleterious migration of the textile-based hemostats is as well described as cause of severe
adverse events. A well-known complication of hemostats is the promotion of painful adhesions, especially
in abdominal or gynecological procedures.
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In contrast there are starch based hemostat powders with broad range of application and good hemostatic
effect. To date, there are no serious product related adverse events known. Even more, there is evidence
that starch powder might prevent adhesions.
Introduction: Local hemostats are applied as adjuncts for bleeding control when pressure, ligature, cautery or other
conventional hemostatic methods are not beneficial or not applicable. Historical normal cotton gauze and
pressure was used for bleeding control. But there was always need for improvements in action and
performance. In 1943 Frantz presented oxidized cellulose [1] as one of the first topical hemostats with
improved performance. Another hemostat is the absorbable gelatin foam or sponge which developed was
and introduced in 1945 [2]. However, the hemostatic action obtained by these local hemostatic agents was
somehow limited, side effects and adverse events were reported and therefore as a logical consequence
further developments were invented. One was e.g. Floseal, a gelatin matrix combined with Thrombin.
Floseal has bovine components. The hemostatic effect was improved, but there are still concerns regarding
adverse events.
In the late 1990th Carboxymethyl-starch products were invented for bleeding control in surgery. To date
there are no major product related adverse events reported.
In the following report we review the biodegradability, absorption and adverse events of oxidized
cellulose, gelatin sponge, gelatin matrix combined with Thrombin and Carboxymethyl-starch products
when used for bleeding control in surgery reported in the literature.
OXIDIZED REGENERATED CELLULOSE:
It is said that oxidized cellulose dissolves promptly in various sites. In an animal experiment it was
reported that complete dissolution is within 6 weeks [1]. In another experiment, Surgicel (Johnson and
Johnson, New Brunswick, NJ, USA) was implanted subcutaneously in rats and residue was recognized in
a few animals at 30 days with infection [3].
Dissolution does not always mean disappearance of hemostat from the implanted area. Even though the
material dissolves in a short period, absorption of the residue and wound healing of the implanted site are
two different processes. Several case reports have indicated that residue of oxidized cellulose can be
recognized at reoperation. Oxidized cellulose fibers were detected histologically near a coronary bypass
graft anastomosis after 5 years and 9 months [4]. Even more the patient experienced graft stenosis because
of the hemostat.
Migration of textile based hemostat can be another cause of adverse events. Dutton presented a case of
optic nerve compression by migration of Surgicel 48h after surgery [5]. (In an unpublished case we had
similar experience in our institute. After use of Surgicel for bleeding control on the heart we left the
Surgicel on the bleeding area, because removal of the material caused again bleeding from the right
KLINIKUM DER UNIVERSITÄT MÜNCHEN SEITE 3 VON 11
ventricle. Five hours later the patient needed an emergency reoperation due to occlusion of the venous
bypass graft to the right coronary. This was caused from Surgicel which was moving under the venous
bypass, swelling and therefore kinking the bypass-graft.) Nevertheless, manufacturers of these hemostats,
e.g. Surgicel and Gelfoam, recommend the removal of the material once hemostasis is achieved. But as
mentioned, removal results most times in recurent bleeding and therefore most surgeons tend to leave it in
place.
Another case demonstrating late- or non-resorption of oxidized cellulose: A yellowish ocher tumor was
macroscopically observed 2 years and 7 months after valve replacement and it was granulomatous tissue
from oxidized cellulose [6]. One year after aortic root replacement with a graft and resuspension of the
aortic valve commissures, thick cheesy material was macroscopically observed at reoperation and found to
be retained non-absorbed Surgicel [7].
Textilomas may present with neuroimaging features that mimic recurrent tumor (Figure 1, Surgicel was
found 6 months after first operation; Figure 2, Gelfoam was not resorbed and still present after 3 months)
and giving trouble in postoperative diagnostics, e.g. mimicking tumors [8]. These hemostats (here
Surgicel, Oxycel, Avitene and Gelfoam; [8]) may produce significant space-occupying mass lesions
appropriately termed textilomas that are clinically and/or radiologically apparent. These reports reveal
earlier reports of persistence of Surgicel at sites of implantation. When local hemostats are used and left in
place of the operation side, depending on different environmental factors, the material is not resorbed in
time.
Fig. 1: Residual material of Surgicel was found in the reoperation, 6 months after primarily opration of a
Glioma. This residual material was mimicking the recurrency of the tumor [8].
One of most deleterious adverse events caused by hemostats is palsy. Main reason is compression of
nerves or brain-structures because the products were used in cavities, left in place during surgery and start
Arch Pathol Lab Med—Vol 128, July 2004 Textiloma Mimicking Recurrent Intracranial Tumor—Ribalta et al 751
Figure 2. Case 3. Surgicel textiloma and residual tumor. A, A postcontrast axial T1-weighted magnetic resonance image shows enhancement ofthe textiloma (blue asterisk). Residual gliosarcoma is present adjacent to the textiloma (yellow arrowheads). B, A hematoxylin-eosin–stained tissuesection shows the characteristic appearance of degenerating Surgicel fibers, which appear as empty ‘‘ghost’’ fibers cut in longitudinal section andcross-section (hematoxylin-eosin, original magnification !100).
Surgicel (Figure 1, D through F). Surgicel (Ethicon) isan oxidized cellulose polymer (the functional unit is po-lyanhydroglucuronic acid) that is believed to act as a tem-plate for coagulation of bleeding vessels. The polymer wasintroduced into clinical practice more than 50 years ago37
and is formed by dissolving pure "-cellulose in an alkalinesolution. It is then regenerated into continuous fiber, knit-ted into gauze, and oxidized. Oxycel (Becton Dickinson,Franklin Lakes, NJ; Figure 1, G through I) is another ox-idized cellulose polymer product that is similar to Surgi-cel. Although both are composed of meshes of cellulosepolymer fibers, under microscopic examination in teasedfiber preparations (Figure 1, F and I) Surgicel and Oxycelcan be distinguished; Surgicel is composed of solid fiberswith irregular contours on cross-section, whereas Oxycelis composed of hollow ‘‘twisted tubule’’ fibers. Surgiceland Oxycel stain weakly eosinophilic or occasionally lightpurple with H&E and show no birefringence. Surgicel ismore commonly used in current surgical practice. Themost characteristic microscopic feature of Surgicel is in-terlacing bundles of fibers cut in alternating cross-sectionsand longitudinal sections. Although the fibers are solid inthe native state (Figure 1, F), in surgical specimens theyoften appear as hollow ‘‘ghost’’ fibers surrounded byblood breakdown products and inflammatory reaction(see Figures 2, B and 3, B).
Avitene (Figure 1, J through L). Avitene (MedChemProducts, Woburn, Mass), often referred to generically asmicrofibrillar collagen, is a partially water-insoluble acidsalt of purified bovine corium collagen that is processedinto microcrystals of submicron size. Microfibrillar colla-gen is available in a ‘‘flour form’’ and also in a nonwovenweb form that is produced by compression of the flour
form.38 In addition to its hemostatic properties, Avitene isalso used for embolization of vascular malformations. Mi-croscopically, eosinophilic acellular coarse fibers or amor-phous material can be seen. Avitene fibers exhibit thecharacteristic birefringence of collagen under polarizedlight, but this physical property is gradually lost duringbiodegradation and resorption in vivo. By electron mi-croscopy, the ultrastructural appearance of Avitene isunique and distinctive compared to that of all the otherhemostatic agents: the collagen microfibers show a char-acteristic banding periodicity (see Figure 4, I and J).
Nonresorbable AgentsCottonoids and Kites. Cottonoids and kites are syn-
thetic strips and pledgets composed of rayon fibers thatcontain a filament or strip impregnated with radio-opaquebarium sulfate, which is visible on plain radiographic ex-amination.
Muslin. Muslin is a cotton fabric that is used to pro-vide reinforcement of an aneurysmal wall in unclippableor partially clippable intracranial aneurysms.10,12,14,15,17,18
Muslin fibers are generally inconspicuous on routine H&Esections because they appear essentially transparent, butthey become strikingly apparent under polarized light.
A wide variety of other synthetic materials may be leftin place during intracranial procedures. For example, sil-icone-coated synthetic sheets (Silastic) are used as a duramater substitute for the repair of dural defects.22 Of his-torical interest, Mills and Lininger23 reported a case of in-tracranial ‘‘myospherulosis’’ after instillation of antibioticointment into a posttraumatic brain abscess. Microscopicremnants of cotton gauze of no clinical consequence areoften inadvertently left in the surgical field and subse-
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swelling after the operation was finished. Quite a notable amount of reports with paraplegia after
thoracotomy and lumbar laminectomy have been published. Some exemplary publications: Most
paraplegic complications occurred within 24 hours after the operation [9, 10]. An article published by
Brodbelt [11] presented three more cases with delayed paraplegia between 12h and 2 days after
thoracotomy. They found that Surgicel had passed through the intervertebral foramen causing spinal cord
compression. Iwabuchi et colleagues [12] described a case of paraplegia which occurred on day one after
thoracotomy. It was caused by spinal cord compression due to use of Surgicel.
Surgicel and other foreign substances that are deliberately introduced in the surgical site may induce an
excessive inflammatory reaction, which produces clinically symptomatic and/or imiging apparent mass
lesion as long as the material is not resorbed. When Surgicel left in place the acidic nature may be
responsible for a mild to strong inflammatory reaction. However, in most cases mild reactions remain
asymptomatic. Chronic inflammation, strong foreign body reactions, and infections after local use of the
hemostats may result in granuloma formation. Surgicel granulomas have been reported in numerous cases
including surrounding of a coronary bypass graft [4], the intra-cranial space [13] and after valve surgery
[14]. However, an untamable inflammation targeting against the foreign material might produce space-
occupying masses and large granulomas with clinical relevance.
It is also a well known and multiple described side effect of hemostats that they might promote adhesions.
Especially when used in the abdominal cavity or in gynecological procedures for bleeding control they can
cause long lasting pain. Not for use in closed spaces because. Another worning is: Do not use oxidized
cellulose in bone fracture.
GELATIN BASED HEMOSTATS:
Gelatin based hemostats like e.g. GELFOAM (Pharmacia and Upjohn Company, Michigan USA) is
prepared from purified porcine skin. Thus far, there are no transmissible diseases with porcine material
reported. However, raw material from medical devices based from animal origin always bears this risk.
But there are several reports regarding allergic reactions and anaphylactic shock reaction to the porcine
material of Gelfoam [15-18]. Even in the IFU of e.g. GELFOAM PLUS (Gelfoam matrix plus human
Thrombin) toxic shock syndrome has been reported in association with the use of GELFOAM Sterile
Sponge in nasal surgery [19]. Continuing with IFU of GELFOAM PLUS: it is written, that it contains
Thrombin made from human plasma and is not possible to remove completely all viral infectivity from
derivatives of human plasma. E.g. parvovirus B19, are particularly difficult to remove or inactivate at this
time. Some viruses, such as parvovirus B19 are most seriously affecting pregnant women, or immune-
compromised individuals. Symptoms include fever, drowsiness, chills and runny nose followed about two
weeks later by a rash and joint pain.
GELFOAM Sterile Sponge may serve as a nidus for infection and abscess formation and has been
reported to potentiate bacterial growth [19; 30]. When Gelfoam was used in laminectomy operations,
multiple neurologic events were reported, including but not limited to cauda equina syndrome, spinal
KLINIKUM DER UNIVERSITÄT MÜNCHEN SEITE 5 VON 11
stenosis, meningitis, arachnoiditis, headaches, paresthesias, pain, bladder and bowel dysfunction, and
impotence [20]. Even in an enclosed space, Gelfoam also expanded and compromised the spinal cord [21-
24].
In the manufacturers IFU is stated, that it is usually absorbed completely within four to six weeks. But as
previously described residual hemostatic material might not be resorbed in the time given from
manufacturer (Figure 2, Gelfoam was not resorbed and still present after 3 months) and giving trouble in
postoperative diagnostics, e.g. mimicking tumors [8]. As described above these hemostats (here Surgicel,
Oxycel, Avitene and Gelfoam; [8]) may produce significant space-occupying mass lesions appropriately
termed textilomas that are clinically and/or radiologically apparent. Textilomas may present with
neuroimaging features that mimic recurrent tumor.
Notable: In 2004 the FDA released notification to users about Gelfoam® and its swelling and use in
neurosurgical procedures because of the potential for paralysis.
Fig. 2: A Gelfoam textiloma (A = MRI and B = microscopic examination of explanted material) was
responsible for the soft tissue density observed on MRI 3 months after primarily operation [8].
Giant cell granuloma has been reported at the implantation site of absorbable gelatin product in the brain
[21], as has compression of the brain and spinal cord resulting from the accumulation of sterile fluid [25].
Foreign body reactions, “encapsulation” of fluid and hematoma have also been reported [19, 27]. The
ability of Gelfoam of fluid absorbtion and late swelling when left in place as a hemostatic cover in a resection
field it causes it might cause severe adverse events. Gelfoam was the active agent in the case below (Fig. 3)
[27]. This is consistent with many reports on granulomas caused by that material. Excessive fibrosis and
prolonged fixation of a tendon have been reported when absorbable gelatin products were used in severed
tendon repair. Fever, failure of absorption, and hearing loss have been reported in association with the use
of GELFOAM sponge during tympanoplasty [19].
752 Arch Pathol Lab Med—Vol 128, July 2004 Textiloma Mimicking Recurrent Intracranial Tumor—Ribalta et al
Figure 3. Case 5. Gelfoam textiloma with mixed cottonoid/kite rayon fibers. A, A coronal postcontrast T1-weighted magnetic resonance imageshows soft tissue density along the inferolateral portion of the sella (yellow arrows). B, Microscopic examination of the mass reveals the charac-teristic morphology of Gelfoam (hematoxylin-eosin, original magnification !200). C and D, Scattered birefringent rayon fibers from a cottonoidor kite were also present in the surgical specimen (hematoxylin-eosin, original magnification !400 [C]; polarized light, original magnification!400 [D]). E and F, Electron microscopic examination shows the characteristic bland, amorphous ultrastructural appearance of Gelfoam with amoth-eaten pattern seen in degenerating fibers (F, inset) (transmission electron microscopy, original magnifications !1000 [E], !20 000 [F], and!20 000 [F, inset]).
quently identified incidentally on microscopic examina-
tion of a specimen obtained at repeat surgery. Other iat-
rogenically introduced foreign materials that may be en-
countered in neurosurgical specimens include copolymer
chemotherapy wafers (Gliadel wafers) and several types
of agents used for embolization of highly vascular tumors
(in addition to Gelfoam and Avitene, as mentioned above),
such as polyvinyl alcohol particles and tris-acryl gelatin
microspheres (Embospheres). Finally, a number of addi-
tional materials of diverse nature may elicit an inflam-
matory foreign body reaction in the central nervous sys-
tem.28,33
In the general surgical literature, the incidence of texti-
loma is highest following abdominal surgery, followed by
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Fig. 3: MR image revealed a ring-enhancing structure (arrow) that was believed to be recurrent tumor leading
to reoperation 2 months after first operation. A glasslike mass with the macroscopic appearance of Gelfoam
was resected (arrow) [27].
In 1999 a new agent was introduced called Floseal™ which basically consists of thrombin plus cross-
linked gelatin granules mixed together. Bovine based devices bears the risk of transmissible diseases. So
the way it works is your bovine thrombin directly activates fibrinogen and converts it into fibrin
monomers. Of note, Floseal™ do cause more inflammatory reactions than the others. Floseal™ does
require two to five minute prep time, you combine the thrombin with calcium and combine that to the
gelatin granules. The completely mixed product has to be used within 2 hours. Floseal™ should not be
used in combination with blood salvage or cardiopulmonary bypass systems. Floseal™ is much more
expensive than the others.
CARBOXYMETHYL STARCH PRODUCTS:
Starsil Hemostat is a Carboxymethyl-Starch powder that will be CE-marked in 2012. It is a second
generation starch based product with more water-absorption capacity and more efficiacy regarding the
hemostatic effect, when compared to the starch powders of the first generation like Arista MPH.
Starch based hemostat powders have a broad range of application and good hemostatic effect. To date,
there are no serious product related adverse events known. Even more, there is evidence that starch
powder might prevent adhesions [28]. Hoffmann and coworkers [28] proved in a rat cecal model that
Carboxymethyl starch particles do not enhance inflammation. They tested six agents: Starch particles,
glutaraldehyde activated collagen, thrombin coated collagen microspheres, thrombin activated fibrin
polymer, polyethylene glycol polymer and oxidized cellulose. In the histopathological examination of rat
caecum the Starch particles and polyethylene glycol polymer demonstrated significantly lower adhesion
formation than controls and others and some even aggravates inflammation and foreign body reaction.
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There are numerous articles published which are dealing with starch based hemostatic powders. All
hemostatic products like Surgicel, Gelfoam, Floseal or even Starch based powders have an ability for
adverse events like granuloma formation, inflammation, foreign body reactions or blockade of healing.
But these reactions are less distinct with starch powders [29]. The degradation process of Starch particles
is enzymatically performed by Amylase and Pyrase. Thus, there is only mild or no foreign body reaction
[28]. Another study demonstrates that Starch powders do not enhance abdominal infection like various
Gelatin products [30]. In the animal study of Ereth and coworkers an animal infection model demonstrates
this (Fig. 4+5).
Fig. 4+5: Starch powders like Starsil (here MPH) do not enhance abdominal infection, but gelfoam does. When
Gelfoam was used in presence of E.coli the colonization rate “exploded” significantly after 72 hrs.
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Mode of action of Starsil® Hemostat:
The hydrophilic polysaccharide spheres are synthesized by cross-linking purified plant starch and do not
contain any human or animal components. The carboxymethyl starch (CMS) particles functions as
molecular filters by separating serum from the cellular constituents such as platelets and erythrocytes. The
CMS particles are a fine white and sterilized powder which is filled in a 1 to 5 g bellow bottle. If
necessary an applicator is attached to access difficult to reach wound areas. This gives more credit to
starch powders when used for minimal-invasive surgery, because it is much easier to reach. The
application of some hemostatic or products that prevent adhesion formation is often difficult. Especially
fleeces, textile based products or membranes are difficult to apply through the laparoscopic channel and
they are often difficult to handle [30]. Starch powders like Starsil are easy to apply through a scope using
an applicator. They are not limited to any region. Other products like e.g. Seprafilm, Gelatin fleezes are
not very easy to handle, and experience is needed to apply the product as intended. E.g. dislocation of the
membrane or fleezes might be possible after application, and this may diminish the anti-adhesive effect
[32]. Even more, dislocation might cause delirious adverse events as earlier described! Devices that would
be easier to handle would probably be more effective. Especially in laprascopic surgery the Starch powder
dominates with easy and fast application.
The Starch particles absorb much of the water portion of the blood and expands multiple times of its dry
volume. This process acts to concentrate blood solids that are excluded, which then form a gel matrix. The
gel matrix slows blood flow and serves to enhance clotting. The mesh of carboxymethyl starch particles
and blood particles form a plug which acts as an temporary mechanical barrier. It is enzymatically
absorbed within 72 h by degradation from alpha-amylase and pyrase. These particles are biocompatible,
non-pyrogenic.
Even more compression and damage of tissue, e.g. nerves with consecutive palsy is not described with
Carboxymethyl Starch powders. Starch particles acts within seconds and after its use in surgery and
closure of the wounds, there is no late swelling like it is described with Gelatins sponges or Oxidized
cellulose.
Conclusion:
Starch powders like Starsil are a further development of medical devices for hemostasis in surgery. It can
be used in all kind of surgical procedures (only ocular surgery with open chamber or open vitreous body is
excluded). To date, no major product related adverse events were reported. In contrast there exist already a
large number of trials or case reports which demonstrates negative effects of other hemostatic devices like
oxidized cellulose or Gelatin based sponges and matrix (with or without Thrombin). This limits the use of
these devices for some surgical indications.
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Literature:
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[3] Alpaslan C, Alpaslan GH, Oygur T. Tissue reaction to three subcutaneously implanted local
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[30] Ereth MH1, Dong Y, Schrader LM, Henderson NA, Agarwal S, Oliver WC, Nuttall GA.
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[31] Al-Musawi, D. and Thompson, J. N. (2001), Adhesion prevention: state of the art. Gynaecological
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[32] Wietske W. Vrijland, Larissa N. L. Tseng, Heert J. M. Eijkman, Wim C. J. Hop, Jack J. Jakimowicz,
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Munich, September 20th, 2011
Dr. med. Helmut Mair
AMENDMENT TO THE ARTICLE FROM SEPTEMBER 20TH, 2011:
“Comparison of Topical Hemostatic Agents: Starch powder, Gelatin
sponge or Gelatin matrix and Oxidized regenerated Cellulose
Review of Adverse Events” Author: Dr. med. Helmut Mair
Department of Cardiac Surgery, Rinecker Clinic, Teaching Hospital of the University of
Munich
Date: 5.1.2016
STARSIL Hemostat is a Carboxymethyl-Starch powder that was CE-marked in 2012. It is a second
generation starch based product with more water-absorption capacity and more efficiacy regarding the
hemostatic effect, when compared to the starch powders of the first generation like Arista MPH. The
device is ready to use and needs no preparation and has a broad range of use in surgical procedures (Fig.
1). There are studies published or submitted for publication demonstrating the efficiacy and safety of
STARSIL Hemostat in open surgery or minimal invasive laparoscopic surgery [1-4].
To date, over 40 000 units of Starsil were sold. There are no serious product related adverse events
reported. In contrast, there are many more articles in the literature presenting adverse events and side
effects with the use of oxidized cellulose or Gelatin-based products as shown above (Review from
September 20th, 2011) or demonstrated below (Fig. 2 and 3) [5-8]. As previously published, we did not
observe any severe adverse events resulting from Granuloma formation, inflammation, foreign body
reaction enhancement of infection, compression of nerval structures or brain resulting in palsy or
paraplegia, occlusion of vessels or bypass-grafts. With use of Starsil in minimal invasive laparoscopical
gynecological procedures the surgeons were very satisfied with bleeding control [2]. With the applicator
the powder was very easy to apply and in addition an adhesion preventive effect is assumed. Same
satisfying observation was as well found in all kinds of surgery, like neurological-, orthopedic-,
abdominal-, cardiac surgery [1]. In abdominal surgery a study was performed to demonstrate good to very
good effect of bleeding control and in addition adhesion prevention with STARSIL [3]. An interesting
observation was made in plastic and reconstructive surgery, where skin transplantation after heavy burns
was found to improve attachment and healing [4]. All surgeons were very pleased with the easy
application and good to very good bleeding control even under difficult conditions.
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Fig. 1: Some examples for the use of Starsil Hemostat in different surgical settings ranging from cardiac
surgery, general surgery, abdominal surgery, trauma surgery, orthopedic surgery, plastic and
reconstructive surgery or gynecological and laparoscopic surgery
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Fig. 3: Persistence of combined use of three “absorbable” hemostatic agents (“package” of Surgicel,
Floseal and Tissel; arrow) applied during laparoscopic nephron-sparing surgery for renal cell carcinoma
(A= CT-scan 3 months postop). Follow up CT-scan (B) 1,5 years later shows still presence of the
“hemostat-pack” (arrow) [5].
Fig. 4: Surgicel applied during laparoscopic cholecystectomy. A= CT-scan on postop day 4 with some air
bubbles (white arrows). CT-scan 5 days later demonstrates increase in size of the region compatible with
development of an abscess (white arrows) [5].
Munich, January 5th, 2016
Dr. med. Helmut Mair
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Literatur: [1] Schmitz C, Sodian R. Use of a plant-based polysaccharide hemostat for the treatment of sternal
bleeding after median sternotomy. J Cardiothorac Surg. 2015; 10: 59. Published online 2015 April 24.
doi: 10.1186/s13019-015-0263-4
[2] Krichbaum M. How to do it - Prevention of Adhesion Formation After Laparoscopical Gynecological
Surgery Using Carboxymethyl Starch Powder. Submitted to Case Reports in Obstetrics and Gynecology
[3] Mitrović M. Prevention of Adhesion Formation After Abdominal Operations Using a New Plant Based
Polysaccharide Powder. Submitted to International Surgery
[4] Certic B. Starsil Hemostat in Heavy Burned Wounds. Submitted to the Journal of Plastic,
Reconstructive & Aesthetic Surgery
[5] Iatrogenic Conditions of the Chest, Abdomen, and Pelvis (Radiologic Clinics of North America)– 9.
September 2014 by Gabriela Gayer und Katz, Douglas S., M.D.; Chapter: Gayer G, Lubner MG, Bhalla S,
Pickhardt PJ. Imaging of Abdominal and Pelvic Surgical and postprocedural Foreign Bodies; page 1003
[6] Ji J, Barrett EJ. Suspected Intraoperative Anaphylaxis to Gelatin Absorbable Hemostatic Sponge.
Anesth Prog 2015; 62:22–24
[7] Spencer HT, Hsu JT, McDonald DR, Karlin LI. Intraoperative anaphylaxis to gelatin in topical
hemostatic agents during anterior spinal fusion: a case report. Spine J. 2012;12:e1–e6
[8] Khoriaty E, McClain CD, Permaul P, Smith ER, Rachid R. Intraoperative anaphylaxis induced by the
gelatin component of thrombin-soaked gelfoam in a pediatric patient. Ann Allergy Asthma Immunol.
2012;108:209–210