Peritonitis with continuous ambulatory peritoneal dialysis and continuous cycling peritoneal dialysis

Peritonitis with continuous ambulatory peritoneal dialysis and continuous cycling peritoneal dialysis The frequency and cause of peritonitis in 18 children receiving continuous ambulatory peritoneal dialysis (CAPD) and nine children receiving continuous cycling peritoneal dialysis (CCPD) are described. Cumulative CAPD and CCPD experience demonstrated 58 episodes of peritonitis in 294 patient treatment months (one case per 5.1 patient treatment months). Total hospitalization for the treatment of peritonitis was 0.18 days per patient treatment month. Life table analysis revealed no significant difference in the peritonitis-free "survival" between the two modalities. Gram-negative organisms accounted for a significantly increased percentage of the peritonitis in CAPD compared with CCPD (65% vs 17%) (P < 0.001). Thirty-seven percent of the gram-negative infections in the CAPD population were in children with nephrostomies. Factors predisposing to peritonitis were identified in 76% of cases Occurring with CAPD. Peritonitis remains the major contributor to the morbidity associated with peritoneal dialysis, regardless of the technique. The resultant frequency of hospitalization is not prohibitive. Attention to the "high-risk'" pediatric patient and education directed at several well-recognized predisposing factors may yield improved results. (J PEDIATR 105:726, 1984)

Bradley A. Warady, M.D., Sally F. Campoy, M.S.N., Susan P. Gross, B.S.N., Aileen B. Sedman, M.D., and Gary M. Lum, M.D. Denver, Colorado

CONTINUOUS AMBULATORY PERITONEAL DIALYS(S

and continuous cycling peritoneal dialysis are two modalities used to treat end-stage renal disease. Both methods have been shown to be applicab!e in the pediatric population.t' 2 The most common complication of these techniques is peritonitis? Several authors hav e published their experience ~with peritonitis as a complication of CAPD in a pediatric population, ~,4-7 but only one report has been presented concerning peritonitis With the use of CCPD in children? Over the past 3 years our pediatric renal division had the opportunity to observe and compare the clinical course of 18 children with end-stage renal disease receiving CAPD and nine children receiving CCPD. We report our experience with the complication of peritonitis in these two patient populations. From the Department of Pediatrics, University of Colorado Health Sciences Center. Submitted for publication Feb. 13, 1984; accepted May 11, 1984. Reprint requests: Bradley A. Warady. M.D., Department of Pediatric Nephrotogy, Children's Mercy Hospital, 24th at Gill ham Rd., Kansas City, MO 64108.

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TheJournalofPEDIATR1CS

METHODS

Patient population and dialysis technique. Twenty-two children ranging in age from 0.8 to 19 years (mean age 8.8 years) comprised the pediatric CAPD and CCPD populations. All patients were part of the University of Colorado Home Dialysis Program between November 1980 and November 1983. Of the 22 patients, 13 underwent CAPD alone, four CCPD alone, and five CAPD and CCPD (four See related'article, p. 721. CAPD CCPD

Continuousambulatory peritoneal dialysis Continuouscycling peritoneal dialysis

[

I

of these five patients received CCPD initially, then CAPD). The total patient treatment months with both groups Combined, was 294 months (CAPD 176 months, CCPD 118 months). The dialysis regimen varied according to each child's clinical status and creatinine clearance (combined renal and peritoneal). In all patients total creatinine clearance ranged from 6 to 10 ml/min/1.73 m 2. Patients receiving

Volume 105 Number 5 CAPD required 3 to 5 exchange s per day with commercially available dialysate in bags (Dianeal, Travenol Laboratories, Deerfield, Ill.). Each exchange necessitated a break in the dialysis tubing system. Each evening children receiving CCPD were connected to an automatic peritoneal cycler (America n Medical Products Corporation, Fairfield, N.J.), on which four to six air-vented 2 L bottles of dialysis fluid (Peritoneal Dialysis Solution, American McGaw, Irvine, Calif.) were hung and attached to a dialysis tubing set. Four to five cycles of dialysis fluid were provided throughout the night, and the patient was disconnected from the cycler in the morning, with the final pass retained throughout the day: Pass size ranged from 250 ml to 2 L, at all times providing 35 to 50 ml/kg body weight. Various dialysate glucose concentrations (1.5%, 2.5%, 4.25%) were used based on each child's requirement to maintain a euvolemic state. Dialysate electrolyte and lactate content was essentially the same for either product. The training for CAPD and CCPD lasted 2 to 3 weeks and included instructions as to actions taken by the patient or responsible parties (in most cases, a parent) when peritonitis was suspected. Because of our program's wide geographic area and the importance Of prompt recognition in the treatment of peritonitis, patients and parents were instructed to presume that peritonitis existed if any of the following signs and symptoms were present: cloudy outflow (most predictive ols peritonitis), abdominal pain, fever, and nausea or vomiting. If any of these presumptive findings were noted, the parent(s) obtained a sample of peritoneal effluent for Gram stain, cell c0unt'with differential, and culture. The sample was taken to the nearest laboratory, which had received prior instructions concerning the University of Colorado Health Sciences Center peritonitis treatment Protocol (see below) and the appropriate method of processing the sample of dialysate. The results of the analysis were communicated by the Home Dialysis Unit to the patient's private physician. Once the specimen was obtained, treatment was begun on an outpatient basis if symptoms were reported as mild or if an examination by the local physician revealed mild symptoms. Five rapid exchanges were instituted with dialysate containing cephalothin 250 mg/L and hepar!n 250 U/L. Heparin was added to inhibit fibrin formation. If the child responded to the initial treatment with improvement in symptoms, the routine CAPD or CCPD schedule was resumed with the addition of the same medication. If the child's condition did not improve immediately; tobramycin was added to the drug regimen, using 1.7 mg/kg body weight as a loading dose and 6 mg/L dialysate as a maintenance dose. 6 Any child who did not demonstrate improvement within the initial 24 hours of therapy or whose course worsened at any time during the early phases of therapy was hospitalized. All children remained onthe

Peritonitis with peritoneal dialysis

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4 6 8 10 12 14 Months on CAPD/CCPD

16

Figure. Life table for time to initial episode of peritonitis.

above-noted intraperitoneal antibiotic therapy until sensitivities were known, and then were given the most appropriate antibiotic (intraperitoneal) to complete a 10- to 14-day treatment course. Although not routinely obtained, tobramycin blood levels were >2 #g/ml and <5 ~zg/ml in every case so evaluated. Throughout each peritonitis episode the home dialysis staff remained in close phone contact with the patient and local physician. The nurse was responsible for collecting data, such as signs and symptoms of peritonitis, laboratory results, and treatment, and factors or details that may have had bearing on the development of peritonitis. The latter information was more completely documented in patients receiving CAPD because this form of data collection began in January 1982, when no patients were receiving CCPD. Definition of peritonitis. Our criteria for the diagnosis of peritonitis during our 3-year observation period, based on our experiences as well as the recommendations of others, 9 were (1) cloudy dialysate outflow with abdominal pain, (2) white blood cell count in dialysate effluent o f >100 cells :per milliliter, and (3) dialysate effluent neutrophil count more than 50% of total WBC count. A positive Gram stain or culture was not a requirement for diagnosis; however, as often as possible these data were obtained and evaluated. RESULTS Incidence of peritonitis. The cumulative CAPD and CCPD experience demonstrated 58 episodes of peritonitis in 294 patient treatment months (one case per 5.1 patient treatment months). Twenty-nine episodes of peritonitis

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Warady et al.

The Journal of Pediatrics November 1984

Table. Bacteriology of peritonitis CA PD Organisms

n

%

Gram positive Gram negative Culture negative

9 19 1

31 65 4

I

[ [

CCPD n

%

P*

19 5 5

66 17 17

<0.01 <0.001 NS

*Chi-square analysis.

occurred in 176 patient treatment months with CAPD (one case per 6.1 patient treatment months), and 29 occurred in 118 patient treatment months with CCPD (one case per 4.1 patient treatment months). Five (28%) patients receiving CAPD had 18 (62%) of the episodes of peritonitis, and 4 (44%) patients receiving CCPD had 20 (69%). When the peritonitis incidence data for each dialysis technique were compared, with the use of life table analysis and using the first episode of peritonitis as an end point, no significant difference in peritonitis-free "survival" was noted (Figure). However, the four children in whom treatment was switched from CCPD to CAPD incurred less peritonitis with CAPD (six episodes in 39 patient treatment months, or one case per 6.5 patient treatment months) than with CCPD (18 episodes in 67 patient treatment months, or one case per 3.7 patient treatment months). Predisposing factors. Factors that may have contributed to the development of peritonitis were identified in 76% of the cases occurring in our patients receiving CAPD. Accidental contamination was reliably documented in 13 (45%) episodes. We accepted contamination as a possible source of peritonitis if it occurred within 72 hours of the onset, of symptoms. Such events reported included not wearing a mask during a bag exchange, not washing hands prior to a bag exchange, and touching the tubing spike prior to its insertion into a bag of dialysate. An additional six (21%) episodes of peritonitis, all in two children with nephrostomies, occurred within 3 days of a dialysis tubing change performed at home. The above procedure consists of removing the patient's tubing set from its attachment to the peritoneal catheter, which necessitates a break in the dialysis tubing system, and attaching a new patient line. The procedure is performed under sterile conditions at 6-week intervals. A concomitant exit site infection was present in three (10%) episodes of peritonitis, with the identical organism giving rise to both infections in each individual episode. The cause of CAPD-associated peritonitis was unknown in seven episodes (24%). Bacteriology. Among all 58 episodes of peritonitis, 48% were caused by gram-positive bacteria, 41% gram-negative bacteria, and 11% were culture negative. In the CCPD population alone, peritonitis was secondary to gram-

positive bacteria in 66% of cases, gram-negative bacteria in 17%, and was culture negative in the remaining 17%. Staphylococcus epidermidis and Acinetobacter sp. were the predominant gram-positive and gram-negative organisms, respectively. Peritonitis associated with CAPD was secondary to gram-positive bacteria in 31% of cases, gram-negative bacteria in 65%, and 4% were culture negative. Escherichia coli, Klebsiella sp., Pseudomonas aeruginosa, Enterobacter sp. and Acinetobacter sp. were the predominant gram-negative organisms, each being isolated on three occasions; S. epidermidis was the predominant gram-positive organism. Gram-negative organisms accounted for a significantly increased percentage of peritonitis in patients receiving CAPD compared with those receiving CCPD (65% vs 17%, P <0.001) (Table). Two children with nephrostomies had seven of the episodes, or 37% of the gram-negative infections in the CAPD population, with Klebsiella sp. and Enterobacter sp. accounting for three each. Peritonitis treatment. In all of our patients the treatment of peritonitis could be started on an outpatient basis because of early detection and mild symptoms. Outpatient therapy was continued in 83% of cases, and the total days hospitalized for all patients for the treatment of peritonitis was 53 days (0.18 days per patient treatment month). Outcome. Catheter removal was required in three patients in order to successfully treat peritonitis caused by P. aeruginosa (two patients) and Serratia sp. (one). In one of these patients peritoneal dialysis was ultimately resumed. The remaining two patients received hemodialysis because subsequent attempts at peritoneal dialysis provided inadequate clearance. There were no deaths associated with peritonitis. DISCUSSION Our results demonstrate that peritonitis is a significant complication of CAPD and CCPD in the pediatric population. Previous studies of C~APD-assoeiated peritonitis in children have documented rates ranging from one case per 3.3 patient treatment months to one case per 13.1 patient treatment monthsJ '47 Our incidence, one case per 6.1 patient treatment months, falls within this range. As reported by others, the majority of infections arose in a minority of patients within each group? ~ We agree with Baum et al. u that a lack of patient and family motivation may be an important characteristic in patients who do poorly with peritoneal dialysis and~that prospective psychosocial studies may be helpful in this regard. We were able to identify factors that may have predisposed to peritonitis in 76% of the cases seen with CAPD. Accidential contamination is acknowledged as being a common cause of peritonitis in CAPD ~2 and was docu-

Volume 105 Number 5

mented reliably in almost half (45%) of our cases. Contamination was considered a possible source of peritonitis if it occurred within 72 hours of the onset of symptoms, as the presumed incubation period for peritonitis is 1 to 3 days. ~3 The increased risk of peritonitis associated with dialysis tubing changes in children with nephrostomies suggests that the presence of an open urogenital system and the inherent skin contamination may markedly increase the risk of peritonitis after a breakage in the dialysis tubing system. The rate of peritonitis observed with the use of CCPD was higher than that reported in adults. Diaz-Buxo et al. 2 observed rates of one case of peritonitis per 30 patient months in an adult population receiving CCPD. The CCPD peritonitis incidence in our unit's adult population is one case per 5.7 patient treatment months, not significantly different from our pediatric data. Although we did not routinely investigate the potential source of infection in our CCPD-associated peritonitis, as we did with CAPD, the use of air-vented dialysate bottles and the numerous connection sites between dialysis tubing and dialysate bottles were all potential avenues for invading organisms. There does not appear to be any significant difference in the likelihood of developing peritonitis with either CAPD or CCPD. We constructed our life table curve using the first episode of peritonitis as the end point; this assumes that peritonitis occurs in a random distribution.~4 The random distribution of peritonitis is supported by Corey, t5 who has shown that peritonitis follows a Poisson probability distribution suggesting a random occurrence, and by Pierratos et al., TM who demonstrated that the life table curve constructed from the first episode of peritonitis is identical to the curve constructed from all episodes. Although there was no significant difference between the two techniques, four of our patients who had received treatment with both, first CCPD and then CAPD, incurred less peritonitis with CAPD. This may be the result of their accumulated experience with peritoneal dialysis. The bacteriology of our CAPD-associated peritonitis was much different from that normally seen. Whereas the majority of series reveal gram-positive:organisms as the cause of peritonitis in 60% of cases, ~2 65% of ours were gram negative in origin. These discrepant values can, in large part, be accounted for by the episodes of peritonitis noted in our two patients with nephrostomies; seven (37%) of the gram-negative infections in CAPD arose in these two patients. A dialysis tubing change in the presence of nephrostomies may also be an important factor predisposing to gram-negative peritonitis, because six of the seven nephrostomy-associated gram-negative infections occurred soon after a tubing change. The repeated use of antibiotics in these patients and the possible alteration of skin flora

Peritonitis with peritoneal dialysis

729

also may have contributed to the development of peritonitis. Our home-based treatment of peritonitis with CAPD and CCPD resulted in a combined hospitalization rate of only 0.18 days per patient treatment month, These results were thought to be quite acceptable and were better than previous results in children.6 The success of our approach was further emphasized by the fact that only three catheters required removal for the treatment of peritonitis, and no deaths could be attributed directly to peritonitis or peritoneal dialysis. The need to identify the high-risk adult patient receiving peritoneal dialysis (e.g., the noncompliant patient and the individual with diverticulitis) has been suggested by several authorsJ 6,'7 Our work suggests that such high-risk patients can also be identified in the pediatric population. The presence of an open urogenital system can be considered a high-risk factor in the pediatric patient, Once such a risk factor is identified, appropriate intervention or modification of the dialysis approach should be instituted to ensure the best possible results. Attention to these highrisk populations, aggressive patient and parent education centered around several well-recognized predisposing factors, and the institution of new devices designed to prevent bacterial contamination of dialysis fluid may yield improved results, '8 We thank Dr. Dennis Lezotte for statistical assistance; Pat Hoerner for secretarial assistance; and the dialysis nursing staff for their major contribution toward the care of our patients.

REFERENCES 1. Balfe JW, Vigneux A, Willumsen J, et al: The use of CAPD in the treatment of children with end-stage renal disease. Peritoneal Dial Bull 1:35, 1981. 2. Diaz-Buxo JA, Walker PJ, Chandler JT, et ah Advances in peritoneal dialysis: Continuous cyclic peritoneal dialysis. ' Contemp Dial 1:23, 1981. 3. Rubin J, Rogers WA, Taylor HM, et ah Peritonitis during continuous ambulatory peritoneal dialysis. Ann Intern Med 92:7, 1980. 4, Potter DE, McDaid TK, Ramirez JA: Peritoneal dialysis in children. In Atkin RC, Thompson NM, Farrel PE, editors: Peritoneal dialysis. Edinburgh, 1981, Churchill Livingstone, pp 356-367. 5. Alexander S: CAPD in children. Presented at the Second National Conference on Continuous Ambulatory Peritoneal Dialysis, Kansas City, Mo., February 15 to 17, 1982. 6. Fine RN, Salusky IB, Hall T, et al: Peritonitis in children undergoing continuous ambulatory peritoneal dialysis. Pediatrics 71:806, 1983. 7. Fennell RS, Orak JK, Garin EH., et ah Continuous ambulatory peritoneal dialysis in a pediatric population. Am J Dis Child 137:388, 1983. 8. Lure GM, for Southwest Pediatric Nephrology Study Group: Peritoneal dialysis in children: A 6-year comparative analysis [abstract]. Eur J Pediatr 140:150, 1983.

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9. Oreopoulos DG, Vas S, Khanna R: Treatment of peritonitis in patients on CAPD. In Moncrief JW, Popovich RD, editors: CAPD update. New York, 1980, Mason Publishing USA, pp 265-272. 10. Muleyalonso R, Opas LM, Lieberman E: Peritonitis during pediatric continuous ambulatory peritoneal dialysis. Eur J Pediatr 140:149, 1983. 11. Baum M, Powell D, Calvin S, et al: Continuous ambulatory peritoneal dialysis in children: Comparison with hemodialysis. N Engl J Med 307:1537, 1982. 12. Vas SI: Microbiologic aspects of chronic ambulatory peritoneal dialysis. Kidney Int 23:83, 1983. 13. Vas S: Microbiological aspects of peritonitis. In Peritonitis in patients on CAPD [supplement]. Peritoneal Dial Bull 1:11, 1981.

14. Pierratos A, Amair P, Corey P, et ah Statistical analysis of the incidence of peritonitis on continuous ambulatory peritoneal dialysis. Peritoneal Dial Bull 2:32, 1982. 15. Corey P: An approach to the statistical analysis of peritonitis data from patients on CAPD. Peritoneal Dial Bull l(suppl):529, 1981. 16. Fenton SSA: Selection criteria for continuous ambulatory peritoneal dialysis (CAPD). Peritoneal Dial Bull 2:3, 1982. 17. Wu G: A review of peritonitis episodes that caused interruption of CAPD. In CAPD failures [supplement]. Peritoneal Dial Bull 3:11, 1983. 18. Oreopoulos DG, Vas SI, Khanna R: Prevention of peritonitis during continuous ambulatory peritoneal dialysis. In CAPD failures [supplement]. Peritoneal Dial Bull 3:18, 1983.

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