Chronic Peritoneal Dialysis Access
Jose A. Diaz-Buxo, Series Editor
Peritoneal Dialysis Catheter Exit Site Infections:
Prevention, Diagnosis, Treatment,
and Future Directions
Zbylut J. Twardowski
From the Division of Nephrology, Department of Medicine, University of Missouri-
Columbia School of Medicine and Harry S Truman Veterans Administration Hospital,
Dalton Research Center, Columbia, Missouri
One of the most important components of the
peritoneal dialysis system is a permanent and trouble
free access to the peritoneal cavity. The three pre-
vious articles in this series described relationships
between catheter design, materials, implantation
technique, and acute postimplantation care for
mostly noninfectious complications of peritoneal
catheters (1-3).
Catheter exit site and tunnel infections are fre-
quent in continuous ambulatory peritoneal dialysis
(CAPD) patients leading to morbidity, prolonged
treatment, recurrent peritonitis, and catheter failure.
According to the final report of the National CAPD
Registry, depending on catheter type, 3-year catheter
survival varies from 6 to 36%; 8-39% of catheters
are removed because of exit/tunnel infection (4).
With the reduced incidence of peritonitis since the
introduction and widespread acceptance of the Y-
connector, the problem of exit site and tunnel infec-
tions has become the primary infectious complica-
tion of peritoneal dialysis (5-7). The following review
will concentrate on factors influencing exit and tun-
nel infections.
Glossary
As mentioned in previous articles of this series
there are numerous catheter designs and implanta-
tion techniques. To avoid confusion I will briefly
review terminology pertinent to the infectious com-
plications of the peritoneal catheter (8). The catheter
is composed of the catheter body (or tubing) and
cuff(s), attached to the catheter, for its fixation. Most
cuffs are made of fabric to facilitate fibrous tissue
Address correspondence to: Zbylut J. Twardowski, MD, Di-
vision of Nephrology. MA 436 Health Sciences Center, Uni-
versity of Missouri, Columbia, MO 65212.
Seminars in Dialysis-Vol 5, No 4 (Oct-Dec) 1992 pp 305-
315
305
ingrowth. The intramural catheter segment is the
part of the catheter contained within the tunnel.
The peritoneal catheter tunnel is the passageway
through the abdominal wall within which the peri-
toneal catheter is contained. The tunnel may be
straight or curved. The tunnel has two exits: the
internal exit is the inlet of the tunnel into the peri-
toneal cavity; the external or skin exit is the skin
outlet of the tunnel. The epiperitoneal (inner, deep,
or internal) cuff is located close to the endoabdom-
inal fascia; the subcutaneous (outer, superficial, or
external) cuff is located close to the skin. The sinus
tract is the part of the tunnel between the skin exit
and the outer cuff. The exit site includes the most
external part of the sinus tract and the surrounding
skin. The tissue ingrown into the cuff (even if the
cuff is located less than 1 cm beneath the exit)
belongs not to the exit site but to the tunnel proper.
The peritoneal tunnel recess is a peritoneal pocket
covered with the mesothelium extending from the
internal tunnel exit to the mesothelial interface with
the collagen of the inner (deep, epiperitoneal) cuff.
The tunnel proper includes the fibrous sheath be-
tween the cuffs together with the fibrous tissue in-
grown into the cuff(s). With double-cuff catheters
the tunnel proper includes both cuffs; with single-
cuff catheters only the cuff constitutes the tunnel
proper.
Catheter Tunnel Healing
Initial Tissue Reaction to a Skin-Penetrating
Foreign Body
The tissue reaction begins immediately after a
break in the integument occurs. Bleeding from cap-
illaries and body fluids form a coagulum of a hydro-
philic fibrin-fibronectin gel and cellular debris. Var-
ious cytokines coordinate the subsequent entry of
inflammatory cells and fibroblasts and the formation
306 Twardowski
of new blood vessels (9). Polymorphonuclear leuko-
cytes phagocytize local bacteria and participate in
the formation of a scab, which is a dried-out com-
bination of coagulum, pus, and serum. Healing of
the wound starts with transformation of the coag-
ulum into granulation tissue, composed mostly of
new vessels and fibroblasts. Upon this tissue, there
is a peripheral ingrowth of new epithelial cells.
Mechanical Factors, Hypoxia, Perfusion
The coagulum and necrotic tissue are gradually
removed from the tunnel. Part of the necrotic tissue
is absorbed, part is drained out of the tunnel. The
tunnel should not be too tight, to allow free drainage
of necrotic tissue and to prevent tissue edema: these
decrease local perfusion and O2 tension, which are
critical for the wound healing process (10). On the
other hand, too large an incision prolongs healing by
the sheer volume of needed repair and the movement
of loose tubing in the tunnel. Mechanical stress slows
the healing process (1 1); thus, the catheter should be
relatively tightly anchored in the tunnel and well
immobilized outside the tunnel, especially during
the break-in period. Also, constricting sutures can
cause pressure necrosis with skin sloughing and must
not be used.
Sinus Epithelialization
Epidermal cells spread over the granulation tissue
beneath the scab. Based on animal experiments it
has been widely accepted that epithelial cells spread
over granulation tissue until they meet epithelial cells
from the opposite “shore” or until they encounter
dense collagen fibers ( 1 1- 19). Winter ( 19) postulated
that in naturally occurring percutaneous organs such
as teeth, the inhibition of epithelial migration is
achieved by a periodontal membrane which consists
of bundles of collagen fibers embedded in the ce-
mentum of the tooth. In his view other situations
where epidermal cell migration is inhibited include
macroporous implants and skin autographs. Finally
he assumed that the basement membrane, a collag-
enous structure, also inhibits basal cell invasion of
the dermis.
The hypothesis that collagen fibers play a para-
mount role in inhibiting epithelial cell spreading led
to the development of several devices of porous
material to encourage dermal ingrowth and to pre-
vent epithelial sinus tract formation (“marsupializa-
tion”) (13-15, 20). It has been suggested that the
epithelium adjacent to a silicone catheter tends to
migrate toward and beyond the subcutaneous cuff,
creating a sinus between the tubing and the skin that
is prone to bacterial colonization with subsequent
infection ( 15).
The development of an epithelialized tract seemed
well supported in animal models (1 3, 14,20), and in
our previous reviews we cited these data as relevant
to human peritoneal catheter sinus tracts (2 1-23).
However, our recent study of catheter tunnels re-
moved from patients showed that in almost all hu-
man peritoneal catheter tunnels the epithelium does
not reach to the cuff but stops a few millimeters
from the exit in the sinus tract (24). These observa-
tions lead us to believe that granulation tissue per se
can also inhibit epidermal cell spreading. This obser-
vation also has an important influence on catheter
design and implantation, particularly the material
for the superficial cuff and its distance from the exit.
In humans, unlike animals, the spreading of epi-
dermis is slow. This discrepancy should not be sur-
prising, because the epidermal turnover rate in ani-
mals is about six to seven times faster than in humans
(25). We found that in fast-healing catheter exits in
humans the epidermis starts entering into the sinus
after 2-3 weeks; in slow-healing exits the epidermis
starts entering into the sinus after 4-6 weeks (26).
The healing process is complete after about 4-8
weeks, when the epidermis covers approximately
one-half of a visible sinus tract, with the remaining
half covered by plain granulation tissue (26).
Microorganisms
Infection is the major cause of impaired healing
(27). Antibiotic penetration into the coagulum is
poor; therefore, antibiotics should be present in suf-
ficient concentration in blood and tissue fluids before
the coagulum is formed. This may be achieved if
antibiotics are given prior to implantation,
The humoral tissue reaction to the foreign im-
plants is to coat them with various proteins, such as
fibronectin, laminin, fibrin, collagen, and immuno-
globulins. Some of these substances serve as receptors
for colonizing organisms. A receptor site for binding
Staphylococcus aureus has been identified within the
27-kilodalton amino-terminal fragment of fibronec-
tin (28). S. aureus was found to have several receptor
sites for soluble and solid-phase fibronectin (29, 30).
Binding to fibronectin seems to be less extensive
with Staphylococcus epidermidis than with S. aureus
(31). Receptors similar to laminin were found in S.
aureus but not in S. epidermidis (32). Type IV
collagen, vitronectin (S protein), and fibrin may also
participate in bacterial adherence, but their role in
foreign body colonization has not been clarified (33,
34).
Bacteria themselves, even without participation of
specific protein receptors, may adhere to the foreign
body by electrostatic attachment or by London-van
der Waals’ forces (35). Adhered bacteria synthesize
and excrete a variety of complex polysaccharides
(biofilm) which serve to protect them from host
mechanisms (36, 37). It is not surprising that almost
all peritoneal catheter exits and sinus tracts, even
without signs of infection, are colonized by bacteria.
Systemic Factors Influencing Wound Healing
During the healing process part of the granulation
tissue is gradually resorbed and replaced by fibrous
tissue. The fibrous tissue and part of the granulation
 PERITONEAL DIALYSIS CATHETER EXIT SITE INFECTIONS
tissue are covered with epidermis (24). Impaired
nutrition, diabetes mellitus, uremia, and corticoste-
roids are all known factors that decrease wound
healing by decreasing fibrosis (38). It is prudent to
avoid catheter implantation while the patient is se-
verely uremic, malnourished, or taking glucocorti-
coids.
In Asia, an extract of Ceiitella asiatica, asiatic
acid, has been used for the treatment of skin wounds.
The active ingredient of this extract (which also has
mineralocorticoid properties) increases both collagen
synthesis in cultured fibroblasts of human skin and
the tensile strength of skin wounds (39, 40). Miner-
alocorticoids may also promote wound healing by
increasing fibrosis, although controlled studies on
wound healing acceleration in humans have not yet
been performed.
Infection Preventive Factors in Healed
Catheter Tunnel
Several elements in catheter design, implantation
technique, and postimplantation care are important
in preventing exit/tunnel infection. In this part of
the review these elements will be discussed; however,
to understand their relevance, a brief description of
tunnel morphology is needed.
Morphology
A detailed description of peritoneal catheter tunnel
morphology has been published elsewhere (24). In
uninfected peritoneal dialysis catheter tunnels the
epithelium covers only the external part of the sinus
tract, while the deeper part is covered with granula-
tion tissue. The epithelium may reach the cuff lo-
cated less than 15 mm from the exit. The outer cuff
limits the spread of granulation tissue and/or epithe-
lium beyond the cuff. In the deeper part of some
sinus tracts, a fibrous sheath replaces the granulation
tissue. Dense capsule surrounds the cuff. Giant
multinucleated cells and mature collagen fibers sur-
round polyester fibers of the cuff in well-healed
catheters. Only islands of mononuclear infiltrates are
seen in the cuff.
The intercuff tunnel segment resembles a tendon
sheath with a dense fibrous capsule and a surface
covered with amorphous, mucinous substance on
top of a modified layer of fibroblasts forming pseudo-
synovium. Giant cells form as a reaction to polyester
fibers and bacterial colonization. Silicon rubber per
se does not induce giant cell formation.
During the healing period, only the part of the cuff
adjacent to the tissue is invaded by fibroblasts and
macrophages coalescing into giant cells. Immature
collagen fibers are also deposited. The part of the
cuff adjacent to the tubing is filled with a clot.
Gradually the clot is reabsorbed, giant cells surround
polyester fibers, and mature collagen fibers become
intertwined with polyester fibers.
Infection causes formation of granulocytic infiltra-
tion, which propagates through the tunnel along the
307
catheter and is usually confined within the fibrous
capsule. The tissue ingrown into the cuff does not
seem to constitute per se a critical barrier for spread-
ing infection.
Bacterial Colonization of the Sinus
Almost all healed catheter sinuses are colonized
by bacteria.* It has been well established in the
surgical literature that wound infection is the result
of a major disturbance in the balance between host
defense and bacteria (27). The number of bacteria as
a critical factor in wound infection was already rec-
ognized in World War I (4 1). Elek (42) demonstrated
that it requires 7.5 x lo6 staphylococcal organisms
to produce a pustule in normal human skin, but the
number of bacteria necessary to cause infection was
reduced 10,000-fold in the presence of a single su-
ture. Bacterial virulence is also important; S. aureus
or Pseudomonas aeruginosa are more likely to in-
duce an inflammatory response than is s. epidermi-
dis.
It appears that there is a constant struggle between
the colonizing bacteria and defense mechanisms of
the sinus tract. The part of the sinus tract covered
with epidermis seems to respond to bacteria in the
same way as the rest of the body integument, but the
part covered with granulation tissue appears to re-
spond by constant exudation of serum with white
blood cells to suppress bacterial proliferation and
curb their penetration deeper into the sinus. If the
number of bacteria increases, then the amount of
exudate increases and granulation tissue proliferates
and becomes more vascularized. The number of
bacteria entering deeper into the sinus depends on
the number and species of bacteria at the exit site,
exit direction, as well as sinus tract length; the latter
is an important contributing factor in the amplitude
of catheter movement in the sinus. Defense mecha-
nisms, after the sinus is healed, are best in undam-
aged epidermis and granulation tissue; trauma to
these structures may tilt the balance toward attacking
microorganisms and allow their rapid multiplication.
S. uufeus Nasal Carriage
The importance of S. uiirezis as an etiologic agent
of peritoneal catheter exit site infection has been well
established (43,44). Nasal carriage status of S. azirezis
is reported to be common in patients undergoing
hemodialysis (45) and peritoneal dialysis (46, 47). A
recent multicenter study found an increased inci-
dence of exit site infections in nasal carriers of S.
az~~ezis: in 85% of these infections the strain from
the nares and the strain causing the infection were
similar in phage type and antibiotic profile (48).
However, in our study we found that, by antibiotic
profile, the strain causing exit infection and the strain
cultured from nares are different (49). Judging by
Twardowski ZJ, Prowant BF, Nolph KD, Khanna R, Everett
ED, Moore HL, unpublished observations.
308 Twardowski
our study, there is an increased probability of S.
aureus exit infection in patients who carry S. aureus
in nares, but the strain is not the same. A multicenter
study currently under way in Europe will, it is hoped,
settle the controversy. In this randomized, placebo-
controlled study the influence of intranasal mupiro-
cin ointment on nasal camage and incidence of exit
site infection is to be assessed.
Exit Direction
Little attention has been paid to exit direction
since Tenckhoff s original recommendation of a
downward-pointing exit (50). In our retrospective
analysis we found that exits directed downward
tended to be infected less frequently and, once in-
fected, were significantly less resistant to treatment
(51). This should not be surprising since upward-
directed tunnels facilitate exit contamination by
downward-flowing sweat, water, and dirt. Once the
exit is infected it is resistant to treatment because of
poor external drainage; rather, the pus tends to pen-
etrate deeper into the tunnel. Also, downward drain-
age of necrotic tissue immediately postimplantation
is easier than drainage against gravity.
The advantage of caudal exit direction in prevent-
ing and treating infections has support in several
other clinical conditions. Periodontitis, which may
be considered as a naturally occurring “foreign” body
exit site infection, afflicts most frequently the lower
incisors (“exits”directed upward) (52). The influence
of exit position on the frequency and tenacity of
paranasal sinus infections was postulated by Zuck-
erkandl in the nineteenth century. The relatively
frequent infections of the maxillary sinus are be-
lieved to be due to unfavorable conditions for dis-
charge because the ostium maxillare (in the upright
position of the body) is located at the highest point
of the cavity; the cavity must be completely filled
with secretions before the discharge may escape (53).
All of the other cavities are more favorably con-
structed for drainage and less likely to be infected
(53). Exit infections of long-term jugular and/or
subclavian catheters are less frequent than those of
peritoneal catheters. Using catheterswith downward-
directed tunnels, So et al. (54) reported 1 exit infec-
tion per 998 catheter days; Raaf ( 5 5 ) reported 16
exit site infections with 698 catheters in cancer pa-
tients.
Sinus Tract Length
The epidermis covering the sinus tract undergoes
a turnover probably similar to the normal epidermis
with cell maturation and desquamation. Desqua-
mated cells, if not expelled, create a conducive milieu
for bacterial growth. With a long sinus tract the
chances of infection are higher ( 1 1-14); therefore,
the sinus tract should be as short as possible. Tenck-
hoff recommended that “the subcutaneous Dacron
felt cuff should be located immediately beneath the
skin exit” (56). Such a localization of the cuff, how-
ever, predisposes to its extrusion. Indeed, in some
centers the rate of extrusion reaches 100% (57). In
other centers the rate, although lower, was high
enough to question the wisdom of using the super-
ficial cuff.
Cuff Extrusion
There are at least two forces favoring extrusion of
the CUR( a ) the pushing force of catheter resilience
and ( b ) pulling and tugging on the catheter. In our
previous reviews (2 1-23) we also accepted a “vector
force” of epidermal cells as postulated by Hall et al.
( 12). In experiments on canines, goats, and pigs they
found that maturing epidermal basal cells attached
to the velor create a vector force toward the exterior,
tending to extrude implants. The rate of implant
migration has been calculated at I mm/month.
Tenckhoff challenged Hall’s hypothesis, citing his
experience with peritoneal catheters (60), which
lasted for many years without cuff extrusion. Our
recent study confirms Tenckhoff’s premise, since in
the majority of patients epidermal cells do not attach
to the cuff (24).
The resilience of the straight catheter implanted
in an arcuate tunnel plays the most important role
in cuff extrusion (51). Experience with swan neck
catheters confirms this hypothesis (59-6 1). Pulling
and tugging on the catheter with frequent CAPD
exchanges probably contributes to this complication.
There is a possibility that the high pressure in the
abdomen due to the constant presence of fluid in the
peritoneal cavity while the patient is ambulatory also
tends to push the external cuff. Finally, the cuff may
be extruded as a result of infection with consequent
tissue contraction due to scarring after the infection
is cured (6 1).
At present we think that the cuff should be im-
planted approximately 1-2 cm beneath the skin as a
compromise; sinus tract should be short enough to
prevent infection but not too short to prevent cuff
extrusion. Also, resilience forces should be elimi-
nated and tugging on the catheter should be avoided.
It is extremely important to avoid resilience forces
pushing on the cuff if implanting it relatively close
to the skin exit.
Double- or Single-Cuff Catheter
Single (only external) cuff catheters were used by
Tenckhoff for acute renal failure. This type of cath-
eters used in patients undergoing chronic intermit-
tent peritoneal dialysis yielded results similar to those
of the double-cuff catheter; however, with continu-
ous ambulatory peritoneal dialysis, double-cuff cath-
eter survival was better than that of single-cuff cath-
eters (62). The major complication of these single-
cuff catheters was the development of pseudoherniae
due to high intraabdominal pressure from the con-
stant presence of fluid in the peritoneal cavity.
 PERITONEAL DIALYSIS CATHETER EXIT SITE INFECTIONS
Another type of single-cuff catheter is provided
with only a deep cuff. This type of catheter has been
used because of problems with external cuff extru-
sion and the questionable value of this cuff. Exit site
infections were found to be similar, with single- and
double-cuff catheters in some reports (63); however,
in a retrospective survey of catheter results in 395
patients, tunnel infections were almost 3 times more
frequent with single cuffs than with double cuffs
(57). Also, in our institution we found that exit
infections tended to be more frequent and were
significantly more resistant to treatment with single-
cuff catheters compared to double-cuff ones (5 1).
The discrepancy in the results may be due to the
varying length of the sinus tract with different im-
plantation techniques. Usually, but not always, a
longer sinus tract is created with a single cuff catheter
than with a double cuff catheter. If a short sinus tract
is present the results regarding exit infections should
be similar irrespective of which cuff limits the depth
of the sinus tract.
Material for the External Cuff and Tubing in
the Sinus
It has been postulated that the external cuff should
provide a strong attachment of collagen fibers to
limit epidermal cell spreading (12). As an example
of a perfect arrangement, the anatomy of the tooth/
gingival interface was cited ( 15). The periodontal
ligament attaches to the cementum, creating an ex-
tremely strong bond. The cementum is composed of
hydroxyapatite crystals, collagen fibers, proteogly-
cans, and mucopolysaccharides (66). Such a living
material is unlikely to be used for the external cuff.
Dasse et al. (1 5) and Poirier et al. (20) evaluated
collagen attachment to various materials on their
elaborate external seal for the percutaneous energy
transmission systems. The seal is composed of a
semi-rigid polyurethane skirt positioned at the sub-
dermal level and a hollow collar protruding through
the skin. The polyurethane is covered with sintered
titanium spheres, porous polytetrafluoroethylene,
and Dacron velour. In experiments on miniature
pigs the Dacron velour, especially wetted with saline
before implantation, provided the strongest collagen
attachment with an excellent inhibition of epidermal
downgrowth. Preliminary experience with this device
in CAPD patients was encouraging (15); however,
long-term experience has not yet been published.
Others have had very poor results, with all catheters
ultimately removed due to exit/tunnel infection.$
Favorable experience gained with alumina ce-
ramic in orthopedic surgery, otorhinolaryngology,
and dentistry inspired Amano et al. (65) to use
alumina ceramic for a peritoneal catheter. In this
catheter, the part of the silicon tubing designated to
be contained within the sinus tract is replaced with
a rigid alumina ceramic connector. Dog experiments
with this material revealed only minimal skin down-
§ Oreopoulos DG, personal communication.
309
growth. Preliminary human experience was encour-
aging.
Ogden et al. (66) found a very high rate of chronic
exit site infections with right-angle Gore-Tex cathe-
ters. These catheters were provided with a subcuta-
neous flange covered with expanded polytetrafluor-
oethylene and a cuff of the same material. Ten of 17
catheters developed chronic exit site infection, and
seven of them had to be removed when antibiotics
failed to eradicate infections.
As mentioned previously, the tissue ingrown into
the cuff does not seem to constitute, per se, a critical
barrier to the spread of infection (24). It seems that
the basic benefit of the external cuff in infection
prevention is gained by anchoring the catheter, re-
sulting in restriction of its pistonlike movements,
thus decreasing transport of bacteria into the sinus.
Favorable results with a “wing” instead of a cuff
appear to give clinical support to this hypothesis
(67). This “wing,” however, does not seem to anchor
the catheter as well as the cuff. More supportive data
are needed to accept a substitute for polyester fabric
(Dacron velour) as a material for the external cuff.
The consistently poor results with cuffs implanted
very close to the exit and the results of our study on
catheter tunnel morphology (24) lead me to believe
that it is not desirable to have epidermis attached to
the cuff. The whole premise of the paramount im-
portance of epidermal downgrowth inhibition to pre-
vent exit/tunnel infection with transcutaneous de-
vices based on animal experiments does not seem to
be relevant to transcutaneous devices in humans.
One of the important differences between animals
and humans is the fact that the epidermis in humans
enters only a few millimeters into the sinus tract.
Catheter Exit Care Recommendations
Catheter exit care and treatment recommenda-
tions are based on our 14 years of experience with
peritoneal catheters (21-23, 49, 51, 59, 61, 68-70),
particularly that acquired during the last 3 years of
exit study (26).*
Implantation
Prior to implantation, depending on the size and
shape of the abdomen and presence of previous scars,
and taking into account patient preference, the exit
should be marked in such a way that the catheter
would not be subjected to excessive motion with the
patient’s activities, and there will be no pressure
exerted on the tunnel by a belt or a tight garment or
when the patient bends forward. Prophylactic anti-
biotics should be given (preferably 1 g of vancomy-
cin), in slow intravenous infusion. This will provide
a good antibiotic level in the coagulum and decrease
the bacterial load in the wound. General anesthesia
should be avoided, if possible, because it predisposes
to vomiting and constipation and requires voluntary
coughing during the postoperative period as a part
310 Twardowski
of pulmonary atelectasis prevention; coughing, vom-
iting, and straining markedly increase intra-abdom-
inal pressures and predispose to abdominal leaks
(68).
A meticulously sterile surgical technique of im-
plantation is mandatory. A perfect hemostasis, pref-
erably by cauterization, is required because, in our
experience, a wound hematoma inevitably leads to
early exit infection. Postimplantation the catheter is
covered with several layers of gauze and anchored
with air-permeable tape; the dressing is left in place
for a week. Peritoneal dialysis exchanges are per-
formed to check the patency of the catheter and
remove residual blood from the peritoneal cavity, if
present. The exchanges are continued until the dialy-
sate is clear.
Postimplantation Care
Pericatheter dialysate leak interferes with fibrous
tissue ingrowth into the cuff and should be avoided.
Therefore, ambulatory peritoneal dialysis is delayed
for at least 10 days after the implantation, but peri-
toneal dialysis in the strict supine position may be
started immediately after “in and out” exchanges are
completed. One-liter volumes of dialysis solutions
are used for the first supine peritoneal dialysis.
To delay bacterial colonization of the exit site and
minimize trauma, the dressing should not be
changed frequently. The surgical dressing is gently
removed after 1 week. Hydrogen peroxide is used to
help gauze removal if it is attached to the scab. If the
scab is forcibly removed the epidermal layer is bro-
ken, a new scab has to be made, and the epidermi-
zation is prolonged. Care is taken to avoid catheter
pulling or twisting. The exit and skin surrounding
the catheter are cleansed with liquid soap containing
a weak disinfectant, rinsed with sterile water, patted
dry with sterile gauze, covered with several layers of
gauze dressings, and secured with air-permeable tape.
The dressing is changed after another week. Weekly
dressing changes are continued until the healing
process is completed, which takes 4-8 weeks. The
patient may shower only before the dressing change
and, at other times, must take sponge baths and
avoid exit wetting.
Protecting the catheter from mechanical stress
seems to be extremely important, especially during
break-in. Catheters should be anchored in such a
way that the patient’s movements are only minimally
transmitted to the exit. The method of catheter
immobilization is individualized, depending on exit
location and shape of the abdomen. I believe that
better exit protection prevents infections in most
patients.
The exit should be carefully evaluated every week
for quality of healing. Unless a large hematoma in
the wound is present, all exits look the same a week
after implantation. The exit is painless or minimally
tender with light pink color of less than 13 mm in
diameter from border to border (including the width
of the catheter). Blood clot or serosanguinous drain-
age is visible in the sinus. No epidermis is visible in
the sinus, and the granulation tissue is white and
plain. Signs of good healing include a decrease in
color saturation and diameter around the exit,
change of drainage to serous, decreased drainage
amount, decreased tenderness, and progression of
epidermis into the sinus. An increase in color di-
ameter or saturation around the exit, change of
drainage to yellow, change of granulation tissue color
to mottled, pink or red, and change of granulation
tissue texture into slightly exuberant or exuberant
are signs of poor healing. Our exit study (26) revealed
two categories of healing exits: fast (or well) and slow
(or poorly) healing.
In fast healing exits, tenderness of the exit abates,
pink color around the exit remains the same, gran-
ulation tissue in the sinus remains white and plain,
and the sinus becomes damp or dry 2 weeks after
implantation. Epidermis starts to enter into the sinus
within 2-4 weeks. Four to six weeks after implanta-
tion the epidermis covers at least half of the visible
sinus, achieving features of a healed, good exit. In
slow healing exits, the tenderness and serous drainage
persist longer than 1 week, pen-exit color diameter
and saturation increase, and granulation tissue in
the sinus becomes mottled, red, or frankly exuberant.
Epidermis does not enter into the sinus until 5-6
weeks postimplantation. Drainage changes from ser-
ous to yellow and purulent. A slow healing exit is
tantamount to an early, acutely infected exit and
requires the use of systemic antibiotics.
Late care, after the healing process is completed,
seems to be easier. The results of a prospective study
indicate that cleaning with soap and water is the least
expensive and tends to prevent infections better than
povidone-iodine painting and hydrogen peroxide
cleaning (69). It is worth realizing that the cleansing
agent should not only decrease the number of bac-
teria but also be harmless to the body defenses.
Povidone-iodine is cytotoxic to mammalian cells in
bacteriocidal concentrations (7 1) and is harmful to
granulation tissue if it enters the sinus. After cleans-
ing, the exit has to be patted dry with sterile gauze,
dried out additionally with a hot air blower for about
30 seconds, and well immobilized. Most of my pa-
tients use a dressing cover for 6-12 months after
implantation. One year after implantation patients
are allowed to omit the cover dressing, if desired. I
could not find any reason why in some patients an
uncovered exit seems to do better, in others worse.
I recommend that my patients use only a shower
and avoid submersion in water, particularly in a
jacuzzi, hot tube, or public pool, unless water-tight
exit protection can be implemented. Prolonged sub-
mersion in water containing high concentrations of
bacteria frequently leads to severe infection with
consequent catheter loss. Swimming in the ocean
and well-sterilized private pools is less dangerous.
Exit care must be performed immediately after a
shower or water submersion, with particular atten-
tion to obtaining a well-dried exit.
 PERITONEAL DIALYSIS CATHETER EXIT SITE INFECTIONS
Diagnosis and Treatment of Exit Site Infection
Definition of Exit Site Infection
There is no single definition of exit site infection
that has achieved universal approval. The most
widely accepted is that published by Pierratos in
1984 (72), which was agreed upon by the vast ma-
jority of Peritoneal Dialysis Bulletin editorial board
members. Pierratos defined exit site infection as:
“Redness or skin induration or purulent discharge
from the exit site. Formation of a crust around the
exit may not indicate infection. Positive cultures
from the exit site in the absence of inflammation do
not indicate infection.” The definition implies the
presence of infection in the instances where labora-
tory cultures are negative and rejects the existence
of infection based on a positive culture without
inflammation.
Several recent publications used similar criteria
(73-75). This definition, however, is not sufficiently
precise to delineate infected from noninfected exits
in many instances. Many other definitions used in
the literature were recently reviewed (26). It is in-
ferred that an exit without signs of infection is
healthy; thus only two categories (infected or not
infected) are assumed. I am aware of only one paper
describing a normal exit site and various degrees of
infection (76). The rates of exit infections and the
outcome of treatment are astonishingly discrepant
in the literature. Rates as low as 0.05 or 0. l/patient/
year (77, 78) or as high as 1.02/patient/year (74)
have been reported. It is likely that this discrepancy
in infection rates does not reveal a real variation but
reflects disagreement regarding the definition of exit
site infection (76).
There is no difficulty in the diagnosis of peritonitis;
dialysate contains either a small number of cells
when uninfected or a large number of cells, mostly
granulocytes, when infected. Normal dialysate does
not contain microorganisms; a correctly performed
culture is usually positive in peritonitis. Bacterial
peritonitis cannot be cured without antibiotics. At-
tempts to classify exit appearance into two categories
(infected and noninfected) is difficult, if not impos-
sible, because infected and noninfected exit appear-
ances overlap. This overlap is due to the peculiarity
of tissue reaction to the foreign body penetrating the
skin and stems from the delicate balance between
bacteria in the sinus and host defenses as described
above. The presence of a small amount of exudate
causing crust formation does not indicate infection,
but if the bacterial attack is more severe then the
amount of exudate increases; granulation tissue pro-
liferates and becomes more vascularized, epithelium
regresses, and signs of infection become obvious.
Low-grade exit infection may abate without systemic
antibiotics.
Classification of Exit Site Appearance
For the last 3 years we have been evaluating exit
site appearance in the immediate postimplantation
31 1
period and later, after the exit is healed (26).* The
classification is based on the cardinal signs of inflam-
mation as proposed by Aulus Cornelius Celsus in his
treatise, De Medicina, written in the first century AD.
These are well known: calor (heat), rubor (redness),
turgor (swelling), and dolor (pain). Additional fea-
tures, specific for an exit of any skin-penetrating
foreign body, are drainage, regression of epidermis,
and exuberance (profuse overgrowth) of granulation
tissue (“proud flesh”). Granulation tissue is defined
as exuberant if it is significantly elevated above the
epidermis level. Culture results did not influence exit
classification. Positive cultures in exits not inflamed
indicate colonization, not infection. Cultures were
commonly negative from infected exits on antibiotic
therapy. However, inflammation in almost all cases
is caused by infection, regardless of culture results.
Inflammatory response to tubing itself or local irri-
tants is rare.
Improvement or deterioration of inflammation is
associated with respective decreases or increases of
pain, induration, drainage, and/or exuberant gran-
ulation tissue, and/or regression or progression of
epithelium in the sinus. Increased lightness (pink,
pale pink) or darkness (deep black, brown) and de-
creased color diameter indicate improvement; in-
creased red color saturation and diameter indicate
deterioration. Ultimately, five categories of exit ap-
pearances have been established: acutely inflamed,
chronically inflamed, equivocal, good, and perfect.
An acutely inflamed exit has the following features
in various combinations: pain, induration, redness
with a diameter (border to border, including the
width of the catheter) 2 13 mm, liquid external drain-
age, exuberant granulation tissue around the exit
and/or in the sinus, and a duration of inflammation
of less than 4 weeks.
In a chronically inflamed exit the following fea-
tures are typically present: liquid external drainage,
exuberant granulation tissue around the exit and/or
in the sinus, and a duration of inflammation of more
than 4 weeks. The following features are typically
absent: pain, induration, and redness.
In an equivocal exit the following features are
commonly present: liquid drainage in the sinus only
and slightly exuberant granulation tissue around the
exit and/or in the sinus. External drainage is thick,
if present; crust forms daily, or dried exudate is seen
on the dressing. The following features are com-
monly absent: pain, induration, redness with a di-
ameter L 13 mm, and distinctly exuberant granula-
tion tissue,
A good exit is characterized by the presence of
plain (not exuberant) granulation tissue in the sinus
with visible epithelium in the sinus at least partly
mucosal (fragile, not keratinized) and thick drainage
or dampness in the sinus. Crust forms no more
frequently than every 2 days; specks of crust (but not
dried exudate) may be seen on the dressing. The
following features are absent: pain, induration, red-
ness (any diameter), any external drainage, liquid
drainage in the sinus, and exuberant (even slight)
granulation tissue. The exit may be pale pink.
312 Twardowski
In a perfect exit the following features are usually
present: the exit is mature, 6 months or older; strong,
mature epithelium is present in the sinus; the sinus
tract is usually dry but may be damp or may contain
thick drainage; a crust forms no more frequently
than every 7 days, and specks of crust may be seen
on the dressing; the exit color is natural or dark; a
pale pink color occasionally may be present. The
following features are absent: pain, induration, a
pink or red color around the exit, any external
drainage, liquid drainage in the sinus, and any visible
granulation tissue.
Exit trauma is an important cause of exit site
infection. Features of a traumatized exit depend on
the intensity of trauma and time of examination.
Common features of trauma are pain, bleeding, for-
mation of a scab, and a deterioration of the exit’s
appearance: a perfect exit may transform to a good,
equivocal, or acutely infected one.
Care and Treatment Recommendations
Acutely lnflumed Exif. Systemic antibiotics for
Gram-positive organisms should be started before
culture results are available. Excessive crust should
be removed with hydrogen peroxide. Liquid soap
should be continued around the exit. Dressing
changes are to be performed twice or once daily
depending on the amount of drainage. Catheter im-
mobilization and protection from trauma (if not
already implemented) are essential. Antibiotics
should be adjusted as indicated by sensitivity tests
when available, but antibiotics have to be changed if
there is no improvement, regardless of culture re-
sults. Treatment is to be continued for 7 days after
criteria for a good exit are fulfilled. The catheter is
to be removed in cases of accompanying refractory
peritonitis. Surgical intervention, such as sinus de-
roofing and/or cuff shaving in tunnel infections, is
to be considered. Our recent experience indicates
that such procedures prolong catheter life only mod-
erately. Only if the patient is not supposed to stay
on peritoneal dialysis for a long time is it prudent to
use these procedures; otherwise it is better to remove
the catheter.
Exuberant granulation tissue (“proud flesh”)
should be cauterized with a silver nitrate stick. In
my experience such cauterization markedly expe-
dites treatment and facilitates epithelialization. It is
important to apply silver nitrate only to the granu-
lation tissue and avoid touching epithelium; thus
only a physician or nurse, not a patient, should apply
cautery. I use a 4.5 x magnifying loupe to facilitate
precise application of silver nitrate. Surgical excision
of the “proud flesh” is usually not needed.
Excision and/or cauterization of exuberant gran-
ulation tissue in wound care have been used for
centuries. It was mentioned, probably for the first
time, by Paul of Aegina (Paulus Aegineta, 625 BC,
d.c. 690, Alexandrian physician and surgeon) in
Epitomes latrikes biblio hepta (Medical Compen-
dium in Seven Books), which contained nearly
everything known about medical arts in that time. It
was adopted by Western medicine through Persian
master physician ar-Rlzi (Rhazes) in Kitdb al-Man-
sari (Book to al-Mans%) and Abii al-08sim (Albu-
cask) one of Islam’s foremost surgeons in at-Tayif
(The Method). Now this method is widely used in
surgical practice, both human and veterinary (79).
Chronically lnflumed Exit. Treatment is similar
to that for acute inflammation; however, whereas
one cauterization is usually sufficient in acute in-
flammation, several cauterizations once or twice
weekly may be needed in chronic inflammation. The
species of bacteria flora or antibiotic sensitivity usu-
ally changes during the course of therapy, and anti-
biotics have to be changed accordingly. Features of
a good exit may not be obtained for a long time; if
features of an equivocal exit persist for several weeks,
systemic antibiotics may be stopped and local anti-
biotics may be used.
Equivocal Exit. Treatment of an equivocal exit
stems from two observations: ( a ) an equivocal exit
if untreated is likely to become explicitly inflamed;
and ( b ) systemic antibiotics usually prevent devel-
opment of acute infection. Cauterization of slightly
exuberant granulation tissue may be sufficient. Local
therapy with mupirocin (Bactroban) ointment (for
Gram-positive organisms) or Neosporin cream, oint-
ment, or ophthalmic solution for a variety of orga-
nisms including S. aureus and Pseudomonas may be
successful.
Good and Perfect Exit. Catheter immobiliza-
tion, protection from trauma, use of liquid soap and
water for daily care, and use of hydrogen peroxide
to remove large, irritating crust are appropriate
measures to prevent infection. In my experience a
perfect exit is unlikely to become infected unless it
is severely traumatized or grossly contaminated after
submersion in water loaded with bacteria.
Truumutized Exit, For severe trauma prophylac-
tic antibiotics should be used. Mild trauma of a
perfect exit with a change of appearance to good
ones does not require antibiotics. If the exit assumes
an equivocal or acutely inflamed appearance, the
treatment is the same as described above. It is pru-
dent to administer systemic antibiotics if the pa-
tient’s exit cannot be evaluated within 2 or 3 days
after trauma.
Local and Systemic Use of Antibiotics for
Prophyluxis and Treutment of Exit Infection.
Antibiotics used for prophylaxis in good or perfect
exits may only be harmful, not beneficial. An excep-
tion may be a rare case with frequent recurrence of
acute infection. Local antibiotics in acute or chronic
infection are of little value because they cannot
achieve proper local concentrations before being
washed away with large amounts of drainage; anti-
biotics administered systemically can provide thera-
peutic concentrations locally by being excreted into
the drainage. Local antibiotics can achieve high con-
centrations in the sinus in equivocal, good, or perfect
exits but are useful only in equivocal exits.
 PERITONEAL DIALYSIS CATHETER EXIT SITE INFECTIONS
New Advances
Humoral Factors
Recent advances in bioengineering may dramati-
cally improve the healing process of the catheter
tunnel. Growth factors are being used to improve
healing of chronic cutaneous ulcers and burns. Epi-
dermal growth factor, a peptide initially isolated
from murine salivary glands, is now produced by
recombinant DNA procedures (80, 8 1). This factor
accelerates epidermal regeneration, stimulates colla-
gen and glycosaminoglycandeposition, and activates
angiogenesis. Growth factor a and platelet-derived
growth factor have been successfully used to accel-
erate wound healing (82, 83). None of these factors
has been tried to improve healing of the peritoneal
catheter tunnel.
New Exit Location
As mentioned above, a major cause of exit site
infection is trauma at the site where superficial cuff
binds with the surrounding tissue. This may be
caused by catheter pulling or tugging, twisting, pres-
sure on the exit by a tight garment, or movement of
the patient’s abdominal wall, transmitting mechani-
cal stress to the exit. Avoidance of mechanical stress
and good immobilization are extremely important
for good healing and prevention of exit site infection,
especially during break-in; however, all efforts to
immobilize the catheter using various devices have
been only partially successful because the abdomen
is very mobile. Any change of the body position
results in abdominal wall motion. This motion is
transmitted to the catheter, causes pistonlike move-
ment within the sinus tract, traumatizes the exit and
sinus, and brings about bacterial penetration deep
into the sinus. Damage to the epidermis and/or
granulation tissue within the sinus combined with
the deep bacterial penetration results in infection.
Downward-directed exits of catheters implanted
into jugular and/or subclavian veins are less prone
to infection than those of peritoneal catheters (54,
55). It is possible that the major reason for low
infection rates with these catheters is their location
on the chest. The chest is a very solid structure, with
minimal wall motions, especially of the upper chest
and over the sternum. A catheter exit located on the
chest wall is subjected to only minimal movement.
Decreased pistonlike movement of the catheter
within the sinus reduces inward transfer of outer
sinus tract flora. Moreover, a tight garment is usually
not worn on the chest and thus there is less pressure
on the exit.
Based on this rationale a new catheter was de-
signed, the swan neck presternal catheter. It is com-
posed of two flexible tubes joined with a titanium
connector in the subcutaneous tunnel at the time of
implantation: ( a ) the distal tubing, consisting of the
intraperitoneal segment with a deep cuff which is
identical to the swan neck Missouri coiled catheter,
and ( b ) the proximal tubing, which comprises the
313
remaining intramural segment with two cuffs and
the external catheter segment. A long subcutaneous
tunnel extending from the abdominal wall to the
presternal area is created during implantation. Two
such catheters have been implanted so far. The heal-
ing process of the exit was excellent in these two
patients. I feel that the idea is worth pursuing.
Summary
There are three fundamental prerequisites for exit
site infection prevention: catheter design, implanta-
tion technique, and postimplantation care. Silicon
rubber tubing with double polyester cuffs still is the
best design. A permanent bend between cuffs seems
to offer an advantage because it allows implantation
of the catheter in an unstressed condition in an
arcuate tunnel with both internal and external exits
directed downward. The exit should be located in a
place only minimally subjected to pressure and
movement. Prophylactic antibiotic prior to implan-
tation and a meticulous, sterile surgical technique
with perfect hemostasis prevent early infection. Heal-
ing of the exit lasts 4-8 weeks. During this time a
non-occlusive (air-permeable) dressing changed
weekly is recommended. After the exit is healed the
simplest and best method of care is protection from
trauma, cleaning with water and liquid soap contain-
ing mild disinfectant, and avoidance of gross exit
contamination. Early antibiotics with mild infection
prevent severe infection leading to catheter loss.
Unfortunately, with the best available designs and
care, exit site infections are still frequent. New hu-
moral factors capable of accelerating healing and use
of a new exit location on the chest, instead of the
abdomen, may improve the results.
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Double Trouble: Leaky Twin Coils

In the early years of dialysis, researchers in large medical centers designed and built a
variety of experimental dialysis systems. In the 1950s, Willem Kolff, who was then at the
Cleveland Clinic, developed a "twin-coil" artificial dialyzer. Two cellophane tubes, at-
tached at both ends to a blood port, were mounted side by side on a mesh screen, which
was then wound around a cental core (the prototype used an orange juice can). Dialysate
flowed around and between the coils of the dialyzer, which was about the size of a
cooking pot. In 1956 Travenol Laboratories marketed the device, together with the 100-
liter dialysate tank, in which the dialyzer was submerged (the prototype was a clothes-
washing machine). This was the first mass-produced and disposable dialysis system. Each
coil cost about $60, a considerable expense for chronic dialysis patients; coils were primed
with banked blood.
One particularly troublesome problem with these coils was the inevitable leakage of
blood from the pressurized blood column within the cellophane tubing into the dialysate.
Frequently, these leaks were of no hemodynamic significance to the patient. Dialysis bath
water contained the usual microorganisms found in the water supply, but an intact coil
was impermeable to bacteria. After a blood leak, the usual practice was to halt dialysis
and discard the coil (together with a considerable volume of the patient's blood) in order
to prevent bactermia and shunt infection. A new coil was primed and dialysis resumed. In
1969, microbiologist Philip Tierno and chief technician Ruben Aboody at the Bronx Veterans
Hospital in New York studied 58 leaks in 1200 dialyses. In each case, the blood within the
coil remained sterile. No patient developed bacteremia. The authors concluded that
dialysis could continue after a small blood leak, thus saving nursing time, the considerable
expense of a new coil, and additional exposure of the patient to banked blood.
McBride P: Genesis of the Artificial Kidney. Travenol Laboratories, 1979
Tierno PM, Aboody R: Risk of bacterial infection resulting from a blood leak during hemodialysis. Nephron
6:110-114, 1969