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TREATMENT OF HD ACCESS PUNCTURE SITE BLEEDING
Treatment of Dialysis Access
Puncture Wound Bleeding with
Chitosan Dressings
Nathan Bachtell, MD; Teresa Goodell, RN, CNS, PhD; Gary Grunkemeier, PhD; Ruyun Jin, MD; Kenton Gregory, MD
Drs. Bachtell, Grunkemeier, and Jin are with Providence Health System; T. Goodell is with Oregon Health & Science Center School
of Nursing; and Dr. Gregory is with Oregon Medical Laser Center, Portland, Oregon.
Background. Bleeding from coagulopathic hemodialysis puncture sites can contribute to anemia in dialysis patients, and current
compressive dressings may contribute to graft thrombosis. We studied the safety and efficacy of a new chitosan-based bandage
with an active clotting surface and compared its time to hemostasis and compression strap usage in dialysis access puncture
wounds with that of conventional gauze dressings.
Methods. Fifty patients received both the chitosan-based and conventional gauze dressings in random order on 2 successive
visits. Time to hemostasis and compression strap usage were compared between the visits. Time to hemostasis was analyzed
using the binary response variable at 2 and 4 minutes. A compression strap was used if dressing application was unsuccessful at
4 minutes. Covariates included coagulation state as measured by laboratory analysis and anticoagulation therapy.
Results. Hemostasis was achieved by 2 minutes in 30% of the chitosan-based and 38% of the conventional dressings (p ¼ 0.608)
and by 4 minutes in 86% of the chitosan-based and 72% of the conventional dressings (p ¼ 0.040). Compression strap usage was
reduced by 50% in the chitosan-based group compared to the conventional group (7 vs. 14 patients; p ¼ 0.052). No adverse events
were reported with either dressing.
Conclusions. The chitosan-based bandage from HemCon is a safe and effective hemostatic agent to reduce prolonged post-
hemodialysis puncture site bleeding and may reduce the use of occlusive compression straps.
B
leeding at dialysis puncture post-dialysis bleeding, compression Improved hemostasis dressings
sites is a source of chronic devices are frequently used that with active clotting surfaces and
blood loss that can contribute are effective but may create trauma components have been recently
to the chronic anemia seen in hemo- or stasis and subsequent graft reported in trauma and other litera-
dialysis-dependent patients with thrombosis. ture to accelerate hemostasis in
renal failure. Hemodialysis patients Stenosis and thrombosis of the moderate to severe bleeding.4,5 We
have coagulopathies associated arteriovenous fistulas are the most investigated the safety and efficacy of
with chronic renal failure and iatro- frequent complications of vascular a chitosan-based dressing (HemCon
genic coagulopathy as a result of access1 accounting for 20% of hospi- Bandage, HemCon, Portland, Ore.) to
systemic heparinization and the tal admissions of dialysis patients.2 improve hemostasis at dialysis site
common use of oral anticoagulant The cost of access procedures and punctures and to reduce the need for
drugs to treat comorbid conditions. complications has been estimated at compressive devices.
These factors can contribute to occa- $1 billion annually, the single greatest Chitosan is a naturally occurring
sional difficulties achieving prompt categorical expense for dialysis pa- substance whose molecular makeup
hemodialysis-site hemostasis, which tient care.2 Although repeated access and preparation have been discussed
contributes to further blood loss to these sites with catheters is consid- previously.6 Chitosan hemorrhage
and consumes valuable staff time ered the most common traumatic in- control dressings have been shown
treating and monitoring these sult, occlusive pressure dressings and to be effective in animal models
patients. In patients with prolonged compression devices also contribute.3 of severe hemorrhage.4 Preclinical
studies in swine surgical spleen
trauma, carotid lacerations, liver
Financial disclosure: Dr. Gregory is an equity holder in HemCon. Dr. Goodell,
lacerations, and aortic perforation
Grunkemeier, and Jin were paid an hourly stipend by HemCon.
have been successfully treated with
NOVEMBER 2006 DIALYSIS & TRANSPLANTATION 1
TREATMENT OF HD ACCESS PUNCTURE SITE BLEEDING
the HemCon Bandage.4 The HemCon All aspects of the research, includ- trauma throughout the graft. The
Bandage is a lyophilized chitosan- ing patient consent forms, were distance between the 2 catheter sites
acetate–based hemostatic dressing. approved by the Providence Health during any visit typically varied from
U.S. military personnel in the con- System IRB committee. All patients 1 to 3 inches. Simply by convention,
flicts in Iraq and Afghanistan have were given a copy of the consent form the first catheter removed was
successfully used the HemCon Ban- to review both before and after labeled catheter A and the second
dage to stop severe hemorrhage not consent was obtained. Once written removed was labeled catheter B.
controlled by conventional bandages consent was obtained, each patient The pressure differential across
in more than 64 patients without was assigned a unique identifying the access site was considered negli-
adverse effects.7 The HemCon number used in all paperwork related gible despite each site having both
Bandage is also an FDA-cleared to the study in order to maximize arterial and venous anatomic origins.
hemostatic dressing suitable for use confidentiality. Given the proximity of the sites to
in hemodialysis-associated bleeding. each other, bleeding from one site
Clinical characteristics and efficacy, Dressings could influence interpretation of
though, have not yet been studied Sterilized pieces of HemCon Bandage bleeding from the next. That is,
in randomized fashion in this 20 mm in diameter and 5.5 mm thick any attempt to look at the sites
population. were used. The control dressing was individually was considered difficult
The treatment of post-hemodialy- standard surgical 20 Â20 gauze (Ken- in practice, compromising the inde-
sis bleeding at our center uses regular dall Versalon by Tyco; Mansfield, pendence of the observations.
gauze with manual pressure or com- Mass.) folded twice to make a 10 Â10 Because of this, the final analysis
pression straps, with most vascular gauze dressing (the standard of care combined data from sites A and B,
access sites being occluded for 8– at this dialysis center). with the longer of the 2 times (2, 4,
12 minutes. For refractory bleeding, All patients had either an arterio- or > 4 minutes) recorded as the bleed-
Gelfoam (RxMed, Louisville, KY.) is venous fistula or nylon graft as access ing time for a visit. Accordingly, if a
often used, with repeated vascular on an upper extremity. Hemodialysis compression strap was needed for
access occlusion using a strap. If was initiated after the nurse placed either puncture site during a visit,
bleeding is still not achieved, transfer both needle-based catheters into then bleeding control during that
to the emergency department for the access site. Blood flowed out one visit was designated as requiring a
more definitive treatment may be catheter to the hemodialysis device compression strap.
required. A more effective hemo- and back to the patient through
static agent in this setting may the other (Figure 1). The placement Procedure
decrease time to hemostasis, as well of these catheters within the access Patient data were collected on 3
as reduce the need for occlusive site was random and varied from visit consecutive hemodialysis visits.
compression devices. We studied the to visit in order to distribute the Patients were randomized to receive
time to hemostasis and usage of
compression devices in 50 patients
using both routine treatment and the
HemCon Bandage.
Patients and Methods
Patients
Patients who underwent routine
outpatient hemodialysis at the
Providence Outpatient Kidney
Dialysis Center between July 18
and October 15, 2005, were consid-
ered for inclusion in the study.
Exclusion criteria were: cognitive
inability to provide informed con-
sent; participation in another IRB-
confirmed clinical trial; allergy to
shellfish, shrimp, chitin, or chitosan;
and central line–based hemodialy- Figure 1. Vascular access site of hemodialysis.
sis access.
2 DIALYSIS & TRANSPLANTATION NOVEMBER 2006
TREATMENT OF HD ACCESS PUNCTURE SITE BLEEDING
either the HemCon Bandage or a tape was placed over the dressing patient was asked about any side
routine gauze dressing during visit 1 simply to keep it in place. If bleeding effects observed outside the dialysis
and to get the treatment not received was again observed, the dressing was center since the last visit, including
the first time at visit 2. They were replaced once more, and a compres- evidence of a rash or delayed bleed-
interviewed about side effects at sion strap was positioned over the ing (this was the only intervention
visits 2 and 3. Patient demographic site. Every 4 minutes for the next during visit 3).
data, including age, sex, access type, 12 minutes the site was evaluated for
and anticoagulation status, were evidence of rebleeding. Statistical Analysis
recorded at visit 1 (anticoagulation Once bleeding had stopped at The 2 primary efficacy variables
status was rechecked at visit 2 catheter puncture site A, the catheter considered were compression time
in order to document any new at site B was removed, and the type of required for hemostasis and use of a
medications). dressing used at site A was applied strap compression device. The sec-
The study protocols employed in immediately at site B. If site A had not ondary efficacy variables were cross-
visits 1 and 2 were identical for all required a compression strap, site B over rate and evidence of short-term
patients, except for the dressing used. was treated identically and also did (within 48 hours) thrombosis of the
On arrival at the dialysis unit, the not get a strap. However, if catheter vascular access site (observed at the
patients had blood drawn for both a site A had required a compression following hemodialysis run).
complete blood count and an inter- strap, then site B automatically Compression times (<2 minutes,
national normalized ratio (INR). received one as well. There were 3 2–4 minutes, >4 minutes) were
During the last 15 minutes of each reasons for this: compared using the Stuart-Maxwell
hemodialysis run, blood was drawn test,8,9 which tested the marginal
1. A significant change in pressure to
to determine the activated clotting homogeneity of all 3 categories
the access site occurred at that
time (ACT). simultaneously, taking the pairing
time;
Following dialysis, blood pressure between observations into account.
2. A visit was categorized as having
was measured and recorded. One The use of strap compression (yes/
more than 4 minutes of bleeding if
catheter (catheter A) was removed no) in the 2 groups (HemCon vs.
a strap had been used at either
from each patient, immediately fol- control) was compared using the
site, regardless of there being 2
lowed by placement of the appro- McNemar test10 in order to ensure
sites; and
priate dressing. A hemodialysis staff proper pairing.
3. This would reduce the impact on
member manually applied pressure Covariates included systolic and
staff and patient time.
at the site for 2 minutes. (Because in- diastolic blood pressure, coagulation
consistently applying pressure could If either site started to bleed after state of the patient as measured by
have confounded the results, the placement of the tape (4–12 minutes ACT, INR, and platelet count, as
performance of this procedure was after removal of the catheter), the well as anticoagulation state with
standardized by having all participat- dressing was replaced, and a com- heparin, Coumadin, or platelet inhi-
ing staff undergo training in which pression strap was used to hold bitors (aspirin, Plavix, Aggrenox).
they repeatedly practiced generating pressure on the site. If rebleeding The paired t test was used to com-
approximately 500 mmHg of force as was noted after placement of a strap, pare the means of the continuous
measured on a standard pressure the dressing was removed and the variables, and the Wilcoxon signed-
gauge.) patient was crossed over to the other rank test was used to compare
After 2 minutes, pressure was dressing, with a strap used immedi- the medians of the continuous
removed to look for evidence of ately to maintain adequate pressure. variables.
bleeding around the dressing. If no During either visit, once complete
bleeding was noted, a 4-inch piece hemostasis had been achieved for at Results
of paper tape was placed over least 12 minutes, each dressing was Fifty patients were enrolled in the
the dressing. If any bleeding was gently removed and replaced with study, 26 men and 24 women, aged
observed, a new dressing was placed 20 Â20 piece of gauze that was taped in 24–85. Among them, 34 patients
over the catheter site, which on place (a routine practice at our had an arteriovenous fistula and
average took less than 3 seconds, center). This was done so patients 16 patients had a nylon graft. All
and pressure was applied at the site would leave with the standard-of- patients were heparinized; most
for another 2 minutes. Then pressure care treatment of their access sites. were on heparin only, and the others
was again released and bleeding At the beginning of visits 2 and 3, were also on Coumadin, Aggrenox,
assessed. If no evidence of bleeding each access site was assessed for Plavix, or ASA (Figure 2). There were
was observed, a 4-inch piece of paper evidence of thrombosis, and each no significant differences between
NOVEMBER 2006 DIALYSIS & TRANSPLANTATION 3
TREATMENT OF HD ACCESS PUNCTURE SITE BLEEDING
Discussion
Many factors contribute to the high
morbidity and mortality associated
with end-stage renal disease, includ-
ing complications from hemodial-
ysis. These complications include
chronic anemia, vascular access-
site thrombosis and failure, and life-
threatening bacteremia. Although
the exact causes of these complica-
tions are not always well understood,
anything that would minimize their
frequency should be considered.
How long it takes and the technique
used to stop post-hemodialysis
bleeding are areas worthy of such
consideration.
The current standard of care at our
center is to use regular gauze, manual
pressure, and a plastic compression
device to control hemorrhage. For
Figure 2. Anticoagulation therapy. prolonged bleeding, Gelfoam is used
with direct pressure, and if neces-
sary, the patient is transferred to
treatment groups in platelet count, who had a HemCon dressing and the emergency department for more
INR, ACT, and systolic and diastolic 38% of the patients who had a definitive treatment. Although it is
blood pressures (Table I). No throm- control dressing (p ¼ 0.608), and by unusual for vascular access puncture
bosis or other vascular access site 4 minutes in 86% of those with sites to bleed severely enough for
complications were reported in either HemCon and 72% of those with a transfusion to be required and no one
treatment arm. Rebleeding 6 hours the control (p ¼ 0.040). Compression has died at our center, we investi-
post-hemodialysis while at home straps were used in 14 of 50 patients gated an alternative mechanism for
was reported by 1 patient after use (28%) in the control group and 7 of achieving hemostasis.
of the HemCon Bandage. This 50 patients (14%) in the HemCon In animal studies, chitosan dres-
stopped spontaneously. group (p ¼ 0.052; Figure 3). An insig- sings were found to be effective in
The comparison of time to hemo- nificant number of patients required controlling major arterial bleeding.11
stasis is depicted in a 3Â3 table crossover to stop bleeding beyond Recent data have also demonstrated
(Table II). Hemostasis was achieved 4 minutes (2 gauze, 4 HemCon: that chitosan is bactericidal.13
by 2 minutes in 30% of the patients p > 0.05). Prospective, randomized clinical
research in hemorrhage control is
challenging because of the variability
in patient characteristics and presen-
tation. In fact, no prospective, rando-
Table I. Coagulation status by group. mized human studies in which a
chitosan dressing was used have
Variable HemCon Control p Value* been done. The HemCon Bandage
platelet count (mean Æ SD) 244 Æ 77 243 Æ 79 0.773 is a chitosan-based hemorrhage-
control dressing already approved
activated clotting time (mean Æ SD) 175 Æ 36 168 Æ 33 0.138
for use in the hemodialysis setting.
systolic blood pressure (mean Æ SD) 138 Æ 26 134 Æ 24 0.248 Therefore, we developed a prospec-
diastolic blood pressure (mean Æ SD) 68 Æ 16 68 Æ 14 0.946 tive, randomized study to evaluate
international normalized ratio (INR) 1.1 (median) 1.1 (median) 0.129 whether or not the HemCon Bandage
improved post-hemodialysis hemor-
*p Value for paired t test for all variables except INR, for which Wilcoxon signed-rank test was rhage control and reduced excessive
performed.
compression.
4 DIALYSIS & TRANSPLANTATION NOVEMBER 2006
TREATMENT OF HD ACCESS PUNCTURE SITE BLEEDING
Table II. Time to hemostasis and usage of strap by group.
Control Group
<2 minutes/strapÀ 2–4 minutes/strapÀ >4 minutes/strapþ Total
HemCon Group
<2 minutes/strapÀ 12 2 1 15
2–4 minutes/strapÀ 6 13 9 28
>4 minutes/strapþ 1 2 4 7
Total 19 17 14 50
The dressings used to control face is in contact with blood. Our time to hemostasis if the results of
vascular access bleeding vary from protocol called for pressure to be this informal survey were, in fact,
center to center, as do the techn- applied immediately after removal of accurate. The effectiveness of gauze
iques used to augment this control. the catheter, which may have limited alone at 2 and 4 minutes was surpris-
The HemCon Bandage used in this the amount of blood available for ing, knowledge of which may pro-
study was small enough to facilitate contact below the dressing site. mote improvements in the standard
easy manipulation within the vasc- This may have contributed to the of care. Regardless, the HemCon
ular access site yet large enough to observed lower efficacy of the Hem- Bandage was shown to be as effective
ensure adequate coverage of the Con Bandage after 2 minutes of at 2 minutes and more effective at
puncture site. The size and thick- applied pressure. 4 minutes (p ¼ 0.04). There were
ness of the HemCon Bandage made According to the results of an no significant adverse reactions
its use by the staff simple and informal survey prior to the study, reported in either group. Further-
straightforward after only minimal time to hemostasis in our patient more, these results were obtained
training. population averaged 8–15 minutes. from patients anticoagulated with
Previous clinical results showed The results reported for patients who heparin, some of them with ad-
that the HemCon Bandage works received the regular gauze would ditional anticoagulants, a finding
most effectively if the chitosan sur- demonstrate a profound reduction in not previously reported in human
subjects.
Despite these findings, the study
had several methodological limita-
tions. Sample size was restricted by
limited patient availability because of
the small size of our center and by
patient inclusion in other studies.
Many staff members were trained
and subsequently participated in the
study, certainly contributing to varia-
bility in technique and possibly in
outcomes. The time taken to remove
failed dressings was considered
negligible yet may have influenced
placement and adhesion of the next
bandage. Substituting unsuccessful
dressings with fresh replacements
at the 2-minute interval may have
disrupted clot formation, whereas
continuing pressure with the same
dressing may have more effectively
reduced hemorrhage in both groups.
Future studies, which may answer
Figure 3. Time to hemostasis and usage of strap by group.
these and other questions, are
NOVEMBER 2006 DIALYSIS & TRANSPLANTATION 5
TREATMENT OF HD ACCESS PUNCTURE SITE BLEEDING
needed. Any impact on the develop- Acknowledgements 6. Evans EE, Kent SP. The use of basic
ment of access malfunction, includ- We would like to acknowledge polysaccharides in histochemistry and
HemCon, the U.S. Department of cytochemistry: IV—precipitation and ag-
ing thrombosis, would require a
glutination of biological materials by
larger study population and longer- Defense, Providence Kidney Dialysis aspergillus polysaccharide and deacetyl-
term follow-up. Other clinical appli- Center, Margo Clark, RN, and Staci A. ated chitin. J Histochem Cytochem. 1962;
cations related to needle puncture McAdams in the preparation of this 10;24–28.
bleeding should also be considered manuscript. 7. Wedmore I, McManus JG, Pusateri AE,
for study given the risks associated Holcomb JB. A special report on the
References chitosan-based hemostatic dressing: ex-
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Conclusions surgeon’s point of view. Nephrol Dial 8. Stuart AA. A test for homogeneity of the
The HemCon Bandage is currently Transplant. 2004;19:309–311. marginal distributions in a two-way clas-
FDA cleared for use in hemodialysis. 2. Saran R, Pisoni RL, Weitzel WF. Epide- sification. Biometrika. 1955;42:412–416.
Prolonged bleeding and excessive miology of vascular access for hemodia- 9. Maxwell AE. Comparing the classification
lysis and related practice patterns. Contrib of subjects by two independent judges. Br
compression at vascular access
Nephrol. 2004;142:14–28. J Psychiatry. 1970;116:651–655.
sites may contribute to unnecessary 3. Feldman HI, Kobrin S, Wasserstein 10. McNemar Q. Note on the sampling error of
morbidity, including anemia and A. Hemodialysis vascular access morb- the difference between correlated pro-
thrombosis of the access site. We idity. J Am Soc Nephrol. 1996;7:523–535. portions or percentages. Psychometrika.
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Effect of a chitosan-based hemostatic 11. Gustafson S, et al. Control of severe
Bandage was effective in hemorrhage
dressing on blood loss and survival in a femoral artery bleeding in a swine model
control, did not cause adverse model of severe venous hemorrhage and using a novel chitosan based hemostatic
events, and may reduce the use hepatic injury in swine. J Trauma 2003;54: dressing. Prehospital Emerg Care, sub-
of compression straps in anticoagu- 177–182. mitted.
lated patients. The limitations of 5. Fischer TH, Connolly R, Thatte HS, 12. Burkatovskaya M, Tegos GP, Swietlik E,
Schwaitzberg SS. Comparison of structural Demidova TN, Castano AP, Hamblin MR.
this study warrant further study
and hemostatic properties of the poly-N- Use of chitosan bandage to prevent fatal
of the use of chitosan-based dres- acetyl glucosamine Syvek Patch with infections developing from highly con-
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6 DIALYSIS & TRANSPLANTATION NOVEMBER 2006
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