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Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Correspondence to: Dr. Cheuk-Chun Szeto, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China. Phone: 852-2632-3173; Fax: 852-2637-3852; E-mail: ccszeto{at}cuhk.edu.hk
| Abstract |
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| Introduction |
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In Hong Kong, CAPD is the first-line renal replacement therapy for all end-stage renal disease patients (7). When peritonitis develops, Tenckhoff catheter is removed and the patient is put on temporary hemodialysis only if the episode fails to resolve with antibiotics. Tenckhoff catheter reinsertion is attempted in all cases after a period of stabilization. As described in our previous studies (79), patients are only switched to long-term hemodialysis when Tenckhoff catheter reinsertion attempts fail because of peritoneal adhesion or when there is ultrafiltration failure due to peritoneal sclerosis. This policy provides an excellent opportunity for us to examine the prospect of peritoneal dialysis after severe peritonitis that requires Tenckhoff catheter removal in a large unselected group of CAPD patients. Here we demonstrate that peritoneal dialysis can be resumed successfully only in a small number of patients.
| Materials and Methods |
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Peritonitis episodes were treated with standard antibiotic protocol of our center, which was changed systemically over time (9). Initial antibiotics for peritonitis were generally intraperitoneally administered third or fourth generation cephalosporin plus or minus vancomycin or cefazolin plus netilmicin. Antibiotic regimens for individual patients were modified when culture results of PDE were available. We followed standard guidelines for antibiotic dosages (3,4). In general, patients received antibiotics for at least 14 d (3,4). For peritonitis episodes caused by Staphylococcus aureus or Pseudomonas or Xanthomonas species, antibiotic therapy was continued for at least 21 d (3,4,9,11).
In general, if the PDE did not clear up on day 10 despite in vitro sensitivity of the bacterium, the Tenckhoff catheter would be removed. Nevertheless, the actual timing of Tenckhoff catheter removal varied for individual patient because of operating theater availability. After Tenckhoff catheters were removed, patients were put on temporary hemodialysis. The appropriate antibiotic therapy was continued for another 2 wk. Tenckhoff catheter reinsertion was attempted at least 4 wk after the old Tenckhoff catheter was removed. Tenckhoff catheter reinsertion was performed surgically under local anesthesia by paramedian subumbilical incision (12). As described previously (7,8), patients were only switched to long-term hemodialysis when attempts of Tenckhoff catheter reinsertion failed because of peritoneal adhesion or when there was ultrafiltration failure due to peritoneal sclerosis.
Case Selection
With the above definitions, PDE failed to clear up with antibiotic therapy in 162 episodes (13.8%) of peritonitis. Forty-three episodes were excluded from analysis because the patient died before the Tenckhoff catheter could be removed. Another 11 episodes were excluded because the patient died within 4 wk after Tenckhoff catheter removal and before the attempted Tenckhoff catheter reinsertion. We studied the demographic characteristics and clinical course of the remaining 108 episodes of peritonitis in 100 patients. In eight of the patients, there was more than one episode of peritonitis during the study period that required Tenckhoff catheter removal. For these patients, we only used the latter peritonitis episode for statistical analysis to avoid overlapping of data, because a history of severe peritonitis that required Tenckhoff catheter removal was counted as a risk factor of reinsertion failure during calculation (see below).
In 51 of the 100 patients, the reinsertion of Tenckhoff catheter was successful and peritoneal dialysis was resumed. They were designated as the success group. In the other 49 patients, Tenckhoff catheter reinsertion was attempted but failed, usually because of the intraoperative finding of significant peritoneal sclerosis and bowel adhesion. They were designated as the fail group and were put on long-term hemodialysis. During the review, previous severe peritonitis was defined as a peritonitis episode in the past that required Tenckhoff catheter removal. Relapse was defined as recurrence of peritonitis with the same organism within 28 d after the completion of antibiotic therapy.
Clinical Outcome
Actuarial patient survival and technique survival were studied. As described in our previous studies (8,13), transplantation and loss of follow-up were censored observations for actuarial patient survival. Patient deaths after conversion to hemodialysis were counted as events. Technique survival was defined as the patient remaining alive and on CAPD. All surviving patients were administratively censored on March 31, 2001, for survival analysis.
From July 1999, we performed standard peritoneal equilibration test (PET) (14) in 10 consecutive patients 4 wk after they returned to CAPD. The results were compared with that before the episode of peritonitis (usually 4 wk after the initiation of dialysis). The standard PET as described by Twardowski et al. (14) was used. Net ultrafiltration volume and dialysate-to-plasma ratios of creatinine (D/P) of creatinine at 4 h were taken as peritoneal transport parameters.
Statistical Analyses
Statistical analyses were performed by SYSTAT 7.0 for Windows software (SPSS Inc., Chicago, IL). All data are expressed as mean ± SD unless otherwise specified. Data were compared by
2 test, Fishers exact test, t test, or Mann-Whitney U test as appropriate. Multivariate analysis by logistic regression with the nested model hypothesis and forward stepwise analysis was used to test for independent factors that predicted successful Tenckhoff catheter reinsertion. All baseline demographic and clinical variables were included in the model construction. The Kaplan-Meier analysis was used to express survival data. Actuarial patient survival was compared by the log rank test. Dialysis adequacy, nutritional indices, and peritoneal transport characteristics before and after peritonitis were compared by paired t test. P < 0.05 was considered significant. All probabilities were two-tailed.
| Results |
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This study focus on the remaining 100 patients, with 108 episodes of peritonitis, who survived 4 wk after Tenckhoff catheter removal. They were followed for 18.5 ± 16.8 mo. The baseline demography and clinical characteristics of the peritonitis episodes are summarized and compared in Tables 1 and 2, respectively. Attempt of Tenckhoff catheter reinsertion was generally a safe procedure. Nevertheless, one patient of the fail group was complicated by accidental small bowel perforation that required laparotomy repair.
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The microbiologic causes of the peritonitis episodes are summarized in Table 3. Although Tenckhoff reinsertion failed in eight of the ten episodes of fungal peritonitis, the result was not statistically significant. Initial choice of antibiotic regimen did not predict failure of Tenckhoff reinsertion (details not shown). With multivariate analysis by logistic regression and forward stepwise analysis, only history of severe peritonitis was an independent predictor of Tenckhoff catheter reinsertion failure.
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On the other hand, 20 patients of the fail group died during the follow-up period. The causes of death were cardiovascular disease (11 patients), intestinal obstruction secondary to peritoneal sclerosis (3 patients), non-peritonitis infections (3 patients), malignancy (2 patients), and unknown (1 patient). Eighteen of the 20 deaths occurred within 12 mo (12 within 6 mo) after conversion to long-term hemodialysis. Six patients received transplants, and three patients were transferred to other dialysis centers. The actuarial patient survival is summarized in Figure 1. The success group had a significantly better actuarial patient survival than the fail group did (survival at 24 mo was 80.3% and 56.2%, respectively; log rank test P = 0.01).
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Peritoneal Permeability and Dialysis Adequacy
In the success group, the standard PET was performed in ten consecutive patients 1 mo after CAPD was resumed. The results were compared with the PET result of the same patient before the development of peritonitis. After resuming CAPD, there was a significant decline in the net ultrafiltration volume at 4 h (0.38 ± 0.16 to 0.21 ± 0.19 L; P = 0.03) (Figure 2) and a trend of rise in D/P creatinine at 4 h (0.664 ± 0.095 to 0.725 ± 0.095; P = 0.15), although the latter was not statistically significant. There was no significant change in peritoneal Kt/V or nutritional indices after resuming CAPD (details not shown). However, 14 patients required additional dialysis exchange (for example, from 4 to 5 exchanges/d) to maintain adequate clearance, and another 31 patients required hypertonic exchanges to maintain adequate ultrafiltration. Only six patients could continue with their original CAPD regimen (i.e., the regimen before the onset of peritonitis).
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| Discussion |
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We found that the success group had a significantly better actuarial patient survival than the fail group. Our observation did not prove that peritoneal dialysis is a better option for long-term renal replacement therapy in this group of patients. It was most likely that the fail group had more severe peritonitis episodes, which would have contributed to peritoneal adhesion as well as high mortality. Nevertheless, our findings highlighted the fact that failure of Tenckhoff catheter reinsertion per se is a predictor of poor survival.
Besides a history of severe peritonitis that required temporary hemodialysis, we could not identify any other clinical factor that could predict failure of Tenckhoff catheter reinsertion. There are two implications. First, our finding provides clinical evidence to support the International Society of Peritoneal Dialysis recommendation (3,4): Tenckhoff catheter reinsertion could be attempted after a period of peritoneal rest (for 4 wk in our present series). Second, there exist important factors that govern the development of peritoneal adhesion in response to peritonitis not yet unidentified. Previous work from our group (15,16) and others (1719) suggest that the individual variation of inflammatory cytokine responses might be important. The role of inflammatory cytokines and fibrosing factors in peritoneal adhesion requires further studies.
We found that most of the deaths in the fail group occurred within 6 to 12 mo after conversion to hemodialysis (Figure 1). Similar observations had been noted by Woodrow et al. (20). Our findings suggest that the excess death early after conversion to hemodialysis, although apparently unrelated, might be an indirect consequence of peritoneal dialysis (for example, inadequate dialysis or poor BP control). As Woodrow et al. (20) pointed out, during the statistical analyses of actuarial patient survival of peritoneal dialysis patients, deaths within 6 to 12 mo after conversion to long-term hemodialysis should be attributed to peritoneal dialysis and counted as events. This definition is different from that applied in most of the published studies on peritoneal dialysis survival (8,21,22). It remains unclear, however, whether a change in the definition of event would have an important effect on the survival analysis and interpretation of published literature.
The 2-yr actuarial patient survival rate of the success group was 80.3% in the present study. The result is similar to the overall peritoneal dialysis population of our center, which had a 2-yr survival rate of 83.0% (8). The 2-yr technique survival rate was 56.3% in the success group of the present series, compared with 72.8% of the overall dialysis population (8). However, direct comparison of technique survival to the general CAPD population may not be appropriate because of the difference in duration of dialysis.
We found that most of the technique failures occur within 6 to 8 mo after resumption of peritoneal dialysis, indicating the presence of severe residual damage after peritonitis. An early assessment of peritoneal function after Tenckhoff catheter reinsertion, for example, either by the standard PET (14) or by the modified PET with 4.25% dextrose solution recently proposed for investigation of ultrafiltration failure (23), may be a logical method to prevent the patient from having inefficient peritoneal dialysis as a result of peritoneal sclerosis.
The optimal timing of assessing peritoneal function in this situation remains undefined. We performed the standard PET 4 wk after the resumption of peritoneal dialysis in 10 consecutive patients since mid-1999. We found that peritoneal transport characteristics were substantially affected by peritonitis. Net ultrafiltration declined, and D/P of creatinine at 4 h possibly increased after an episode of peritonitis that required Tenckhoff catheter removal. It is important to note that the number of cases in this study was small, and we did not have sufficient statistical power to detect a small, though clinically important, change in D/P of creatinine at 4 h. The change of peritoneal transport characteristics in the present series was consistent with our previous study in which serial PET was performed (16).
Despite a change in peritoneal transport, dialysis adequacy and nutritional status could be maintained in most patients, and the change in peritoneal transport characteristics could be compensated by increasing dialysis exchange volume or using hypertonic dialysis solution. In addition, it could be argued that at least part of the reason for increasing dialysis exchange volume was attributed to the concomitant loss of residual renal function. However, it is important to appreciate that both the present study and our previous one (16) inevitably underestimated the impact of peritonitis on peritoneal transport because only those patients who could return to peritoneal dialysis and achieve an edema-free state could have PET performed. In fact, PET was not possible in seven patients of the success group after they returned to CAPD because of persistent fluid overload. They were diagnosed as peritoneal failure by clinical judgment.
In general, Asian dialysis patients enjoyed a better clinical outcome when compared with white patients (7,24). It could be argued on the basis of our findings that all CAPD patients (probably even more important for non-Asian patients) who have severe peritonitis and Tenckhoff catheter removal should be put on long-term hemodialysis without further attempt of Tenckhoff catheter reinsertion. However, the clinical benefit and cost effectiveness of this policy could only be proved by a randomized study.
| Acknowledgments |
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| References |
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