An alternative to dextrose as the osmotic agent in the dialysate solution is
icodextrin, a starch-derived, water-soluble, non-dextrose polymer that is
approximately 40% absorbed and subsequently metabolized to maltose
oligosaccharides. Icodextrin is approved for use in the United States in patients
having CAPD or APD during the long-dwell period. Unlike glucose, icodextrin does
not readily diffuse across the peritoneal membrane, but it is slowly removed from the
peritoneal cavity via convective uptake into the peritoneal lymphatics.
to dextrose solutions for ultrafiltration.
Icodextrin has been shown to have less
glucose absorption, carbohydrate exposure, fat accumulation, and weight gain than
A number of factors need to be considered when icodextrin is used. Insulin
requirements may decrease when icodextrin is substituted for dextrose solutions
during the long dwell. On the other hand, a more worrisome concern is that
insulin and other medications used to manage hyperglycemia may be increased
unnecessarily, resulting in iatrogenic hypoglycemia. A pharmacovigilance report
identified three cases of iatrogenic hypoglycemia in patients undergoing peritoneal
dialysis with icodextrin, with two of these patients in the ICU for severe
66 Other undesirable effects of icodextrin include skin rash, mild
hyponatremia, sterile peritonitis, and false reductions of serum amylase
concentrations which can complicate the diagnosis of pancreatits.
and administration for M.J.’s infection.
The most significant complication among patients undergoing PD is peritonitis.
The patient usually presents with abdominal pain, nausea and vomiting, and fever
with or without a cloudy effluent. The effluent should be inspected and sent to the
laboratory for cell count with differential, Gram stain, and culture, with antibiotic
therapy initiated in the interim. Bacterial peritonitis generally is accompanied by an
elevated dialysate WBC count greater than 100/μL with greater than 50%
neutrophils. Specific consensus recommendations of the International Society for
Peritoneal Dialysis Ad Hoc Advisory Committee on Peritoneal Dialysis-Related
Infections are located at http://www.ispd.org.
Empiric antibiotics must cover both gram-positive and gram-negative organisms.
The increasing prevalence of vancomycin-resistant organisms has resulted in a shift
in empiric therapy away from vancomycin, toward first-generation cephalosporins
(cefazolin or cephalothin). Without a Gram stain, therapy should be initiated with a
combination of cefazolin or cephalothin (to cover gram-positive organisms) and
ceftazidime (to cover gram-negative organisms), coadministered by the
intraperitoneal route (IP) in the same dialysate solution at a dose of 15 mg/kg
(rounded to the nearest 500 mg) for both drugs, once daily.
therefore a 1 g dose cefazolin and ceftazidime IP is appropriate. Both antibiotics are
available as 1 g vials. To prepare the doses for IP administration, each sterile
antibiotic powder is reconstituted with 3 to 10 mL of Sterile Water for Injection and
shaken well. The contents are withdrawn into separate syringes and injected into the
peritoneal dialysis bag. Separate syringes must be used to add the antibiotics to
dialysis solutions. An aminoglycoside can be used in place of ceftazidime. While
aminoglycosides were not found to adversely affect residual renal function,
absorption and prolonged half-life of gentamicin was found in patients with
peritonitis, which can lead to drug accumulation.
69 Short-term use appears to be safe
and effective, but there is a potential risk of toxicity, such as oto- and/or vestibular
toxicity, with prolonged therapy. Gentamicin, tobramycin, or netilmicin are given at
doses of 0.6 mg/kg/bag, once daily, and for amikacin, 2 mg/kg/bag once daily.
Antibiotics should be allowed to dwell for at least 6 hours, and the minimum
duration of therapy is 2 weeks.
67 M.J. should receive the antibiotics in the overnight
bag, since it has the longest dwell time. Subsequent antibiotic therapy should be
based on culture and sensitivity results, incorporating specific dosage regimens
based on the treatment guidelines.
This is M.J.’s first episode of peritonitis. The most likely pathogen, a
Staphylococcus species, is consistent with the positive Gram stain. Her treatment
should consist of monotherapy with cefazolin (or cephalothin) 15 mg/kg IP daily as
ordered. Ceftazadime should be discontinued. Vancomycin should not be used for
empiric therapy. Instead, it should be reserved for methicillin-resistant S. aureus
infections or methicillin-resistant S. epidermidis if M.J. does not respond to empiric
CASE 30-3, QUESTION 3: A new order is written to add heparin to M.J.’s dialysate fluid. What is the
In addition to antibiotics, heparin 500 units/L should be added to each exchange to
prevent fibrin clots from forming, obstructing outflow from the peritoneal cavity, and
67 M.J.’s blood glucose should be monitored, because infection
causes insulin resistance and peritonitis will increase glucose and insulin absorption.
Inability to control the blood glucose concentration may require temporary
discontinuation of the intraperitoneal (IP) insulin and administration by another route.
Also see Case 30-2, Question 7, for other considerations regarding insulin dosing.
CASE 30-3, QUESTION 4: If M.J. was receiving APD instead of CAPD, would the treatment of her
Cycler machines automatically cycle dialysate into and out of the peritoneal cavity
in APD. Patients having CCPD will generally need three to five exchanges, each
lasting approximately 2 hours, using a cycler while the patient sleeps. During the
daytime hours, the patient maintains a reservoir of dialysate in the peritoneal cavity,
resulting in a long dwell. The cycler process repeats at night. Six to eight exchanges
are performed every night for patients having NIPD. The peritoneum is left dry, and
patients do not continue dialysis during the day. Nightly dwell times are generally 1
to 2 hours for each exchange, resulting in a higher clearance for small molecules
because of the increased dialysate flow rate.
For patients having APD, the choice of first-line antibiotics is the same as for
CAPD because the likely organisms are similar. Drug dosage regimens, however,
can differ because patients having CCPD or NIPD undergo PD only during the
nighttime hours, and those having NIPD do not have residual peritoneal fluid during
the day. The rapid exchanges in APD may lead to inadequate time to achieve
therapeutic drug concentrations. The dose of cefazolin in APD is 20 mg/kg (rounded
to the nearest 500 mg) every day, in the long day dwell.
cefazolin 1,500 mg IP in the long day dwell. A concern is that patients given a single
dose of a cephalosporin during the long day dwell may have IP levels at night that are
below the MIC of most organisms allowing biofilm-associated organisms to survive,
resulting in relapsing peritonitis.
67 A safer approach would be to add the
cephalosporin to each exchange in APD. Because of the lack of clinical trials with
other antibiotics in patients having APD, extrapolation from the CAPD literature may
be necessary. A review addresses the current knowledge and issues surrounding the
pharmacokinetics of antibiotics in patients with peritonitis undergoing APD.
EXIT-SITE INFECTION: PROPHYLAXIS
What information should be provided to educate M.J. in daily catheter care? Recommend an appropriate
antimicrobial cream for M.J. to administer around the catheter exit site.
Prevention of catheter exit-site infections (and thus peritonitis) is the primary goal
of exit-site care. Several preventative measures are important: adequate catheter
placement, dedicated postoperative catheter care, and routine daily care of the exit
site. Dressing changes of a newly placed catheter are done by a dialysis nurse using
sterile technique until the exit site is well healed, which can take up to 2 weeks. Once
the exit site is well healed, M.J. can be educated and trained to do routine exit-site
care, including thorough hand cleansing before touching the exit site by rubbing both
hands for at least 15 seconds using antiseptics that contain at least 70% alcohol or
71 The exit site is then washed daily with antibacterial soap,
although use of an antiseptic (e.g., povidone iodine or chlorhexidine) is a reasonable
option as long as concentrations are non-cytotoxic.
72 Hydrogen peroxide should be
avoided as a routine antiseptic because it causes drying. After daily cleansing, M.J.
can be instructed to apply antimicrobial creams (e.g., mupirocin, gentamicin) around
the catheter exit site using a cotton swab. Mupirocin ointment, not the cream, can
cause structural damage to polyurethane catheters and should be avoided in patients
Catheter exit-site infections are most often caused by S. aureus and Pseudomonas
In a randomized, double-blind trial, gentamicin sulfate 0.1% cream was
found to be as effective as mupirocin 2% cream in preventing S. aureus infections.
Gentamicin cream was also highly effective in reducing Pseudomonas aeruginosa and
other gram-negative catheter infections, whereas mupirocin cream was not. A longer
gentamicin cream at the exit site is considered to be the prophylaxis of choice in
patients having PD and would be the preferred treatment for M.J. Finally, the catheter
should be immobilized with a small gauze dressing and tape to prevent pulling and
trauma to the exit site, which may lead to infection.
EXIT-SITE INFECTION: TREATMENT
could oral therapy be used or is intraperitoneal therapy required?
Empiric therapy for exit-site infections may be started immediately and should
always cover S. aureus. Oral antibiotic therapy has been shown to be as effective as
IP therapy with the exception of methicillin-resistant S. aureus infections.
erythema alone can be treated with topical agents, whereas purulent drainage
penicillinase-resistant penicillins. Rifampin may be added at 600 mg/day orally (in
single or split dose) for slowly resolving infections. It should not be used as
monotherapy, or in areas where tuberculosis is endemic. Rifampin is an inducer of
drug-metabolizing enzymes and concurrent medications should be evaluated for
Oral quinolone antibiotics are recommended as first-line agents in the treatment of
P. aeruginosa exit-site infections. Monotherapy is not recommended because
resistance develops rapidly, and P. aeruginosa infections are difficult to treat often
requiring prolonged therapy with two antibiotics. If the infection is slow to resolve
or if in cases of a recurrence, a second antipseudomonal drug can be added (e.g.,
ceftazidime IP). Gram-negative organisms can be treated with ciprofloxacin 500 mg
74 Scheduling of the quinolone dose is important, so that
coadministration with foods or other drug therapies that may chelate the quinolone in
the gut is avoided. Potentially chelating agents include calcium products, iron,
multivitamins, antacids, zinc, sucralfate, and dairy products. Antibiotic therapy
should be continued for a minimum of 2 weeks until the exit site appears entirely
Dextrose is present in dialysate solutions primarily to serve as an osmotic agent
for the removal of fluid during each exchange. Higher concentrations are expected to
result in greater fluid removal. Approximately 500 to 1,000 kcal/day are absorbed as
glucose from PD solutions, which can lead to weight gain in patients. Some patients
may require modification of oral caloric intake to avoid excessive weight gain.
Insulin requirements generally are increased in patients with diabetes as a result of
the additional calories and, when administered IP, usually are 2 to 3 times the normal
subcutaneous dose because of their reduced bioavailability of 20% to 50% by this
route. Also see Case 30-3, Question 3, for other considerations regarding insulin
A full list of references for this chapter can be found at
http://thepoint.lww.com/AT11e. Below are the key references and websites for this
chapter, with the corresponding reference number in this chapter found in parentheses
Wolters Kluwer Health; 2015:59. (8)
Kidney Int Suppl. 2013;3(1):1. (2)
Handbook of Dialysis. Philadelphia, PA: Wolters Kluwer Health; 2015:464. (59)
update. Perit Dial Int. 2010;30(4):393. (67)
guidelines for hemodialysis adequacy: update 2006. Am J Kidney Dis. 2006;48(Suppl 1):S2. (4)
guidelines for peritoneal dialysis adequacy: update 2006. Am J Kidney Dis. 2006;48(Suppl 1):S91. (5)
guidelines for vascular access. Am J Kidney Dis. 2006;48(Suppl 1):S176. (6)
Wolters Kluwer Health; 2015:89. (12)
NFK KDOQI Guidelines. https://www.kidney.org/professionals/guidelines/guidelines_commentaries.
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Kidney Int Suppl. 2013;3(1):1.
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Wolters Kluwer Health; 2015:66.
Daugirdas JT et al. A nomogram approach to hemodialysis urea modeling. Am J Kidney Dis. 1994;23:33.
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