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.

62

It is superior

to dextrose solutions for ultrafiltration.

63

Icodextrin has been shown to have less

glucose absorption, carbohydrate exposure, fat accumulation, and weight gain than

glucose-containing PD fluids.

64

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

icodextrin can cause false elevations in glucose concentrations with certain glucosemonitoring devices unable to distinguish glucose from maltose.

65

In this situation,

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

hypoglycemia.

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.

65

PERITONITIS

CASE 30-3, QUESTION 2: M.J. now presents to the dialysis clinic with complaints of abdominal tenderness

and cloudy effluent. Examination of the dialysate reveals a white blood cell (WBC) count of 330 cells/μL with

62% neutrophils. Gram stain is positive for gram-positive cocci. Her diabetes has been controlled by the addition

of 10 units of regular insulin to each daytime bag and 15 units to the overnight bag. While awaiting cultures, dual

therapy with cefazolin and ceftazidime is ordered. Is this treatment coverage appropriate? Provide the dosages

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.

67

Empiric antibiotics must cover both gram-positive and gram-negative organisms.

67

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.

67 M.J. weighs 65 kg,

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,

68 high

systemic

p. 661

p. 662

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

therapy.

CASE 30-3, QUESTION 3: A new order is written to add heparin to M.J.’s dialysate fluid. What is the

reason for this? She is also receiving insulin intraperitoneally. Is this appropriate or should she be switched to

subcutaneous insulin?

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

occluding the catheter.

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

infection be different?

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.

58

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.

67 M.J. should receive

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.

70

EXIT-SITE INFECTION: PROPHYLAXIS

CASE 30-3, QUESTION 5: Catheter exit-site infections are a significant risk factor for developing peritonitis.

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

antibacterial soap.

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

with these catheters.

72

Catheter exit-site infections are most often caused by S. aureus and Pseudomonas

species.

67

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.

73

Gentamicin cream was also highly effective in reducing Pseudomonas aeruginosa and

other gram-negative catheter infections, whereas mupirocin cream was not. A longer

time to first catheter infection and a reduction in peritonitis, particularly gramnegative organisms, was also seen with gentamicin use. For these reasons, daily

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

CASE 30-3, QUESTION 6: If M.J. were to exhibit an exit-site infection despite appropriate catheter care,

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.

67 Local

erythema alone can be treated with topical agents, whereas purulent drainage

indicates more significant infection and the need for systemic antibiotics. Grampositive organisms are treated with first-generation oral cephalosporins, or with oral

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

potential drug interactions.

p. 662

p. 663

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

orally twice daily.

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

normal.

WEIGHT GAIN

CASE 30-3, QUESTION 7: M.J. is noted to have gained weight since starting peritoneal dialysis. Besides

fluid retention, what other possible cause is there for the weight gain? How might this affect her insulin

requirements?

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

dosing.

KEY REFERENCES AND WEBSITES

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

after the reference.

Key References

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Wolters Kluwer Health; 2015:59. (8)

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Blake PG. Adequacy of peritoneal dialysis and chronic peritoneal dialysis prescription. In: Daugirdas JT et al, eds.

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The National Kidney Foundation–Kidney Disease Outcomes Quality Initiative. NKF-K/DOQI clinical practice

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(1)

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The National Kidney Foundation–Kidney Disease Outcomes Quality Initiative. NKF-K/DOQI clinical practice

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The National Kidney Foundation–Kidney Disease Outcomes Quality Initiative. NKF-K/DOQI clinical practice

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Ward RA et al. Dialysis water and dialysate. In: Daugirdas JT et al, eds. Handbook of Dialysis. Philadelphia, PA:

Wolters Kluwer Health; 2015:89. (12)

Key Websites

NFK KDOQI Guidelines. https://www.kidney.org/professionals/guidelines/guidelines_commentaries.

COMPLETE REFERENCES CHAPTER 30 RENAL DIALYSIS

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