Document 6517462

Peritoneal Dialysis International, Vol. 26, pp. 336–340
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Copyright © 2006 International Society for Peritoneal Dialysis
WHAT IS THE OPTIMAL DWELL TIME FOR MAXIMIZING ULTRAFILTRATION WITH
ICODEXTRIN EXCHANGE IN AUTOMATED PERITONEAL DIALYSIS PATIENTS?
Tarun K. Jeloka,1 Fevzi F. Ersoy,2 Mahmut Yavuz,3 Krishna M. Sahu,1 Taner Çamsari,4 Cengiz Utas¸,5
Semra Bozfakioglu,6 Çetin Özener,7 Kenan Ates¸,8 Rezzan Ataman,9 Fehmi Akçiçek,10
Tekin Akpolat,11 Ibrahim Karayaylali,12 Turgay Arinsoy,13 Emin Yilmaz Mehmet,14
Gültekin Süleymanlar,2 Dorothy Burdzy,1 and Dimitrios G. Oreopoulos1
♦♦Background: Icodextrin is increasingly being used in automated peritoneal dialysis (APD) for the long dwell exchange to maintain adequate ultrafiltration (UF). However,
the UF reported in the literature varies with different dwell
times: from 200 to 500 mL with 12 – 15 hour dwells. In order
to maximize UF, it is important to know the relationship
between dwell time and UF when using icodextrin in APD
patients. With this knowledge, decisions can be made with
respect to dwell period, and adjustments to the dialysis prescription can be made accordingly.
♦♦Methods: We prospectively studied this relationship in
36 patients from Canada and Turkey. All patients did the
icodextrin day exchange manually after disconnecting
themselves from overnight cycler dialysis. Dwell period was
increased by 1 hour every week, from 10 to 14 hours. Ultrafiltration was noted for each icodextrin exchange. Mean UF
for each week (i.e., dwell period) was compared by repeated
measures ANOVA.
♦♦Results: We found no difference in mean UF with increasing dwell time: 351.73 ± 250.59 mL at 10 hours versus
371.75 ± 258.25 mL at 14 hours (p = 0.83). We also compared mean UF between different subgroups and found that
males (p = 0.02 vs females) and high transporters (p = 0.04
vs low) had higher mean UF. Further analysis of maximal UF
showed no correlation to age, sex, diabetic status, transport category, creatinine clearance, Kt/V, duration on peritoneal dialysis, or duration of icodextrin use.
♦♦Conclusion: Icodextrin-related UF in APD patients is not
related to demographic factors and does not increase significantly beyond 10 hours.
Perit Dial Int 2006; 26:336–340
www.PDIConnect.com
Correspondence to: D.G. Oreopoulos, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8 Canada.
dgo@teleglobal.ca
Received 20 July 2005; accepted 3 October 2005.
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KEY WORDS: Icodextrin; ultrafiltration; automated
peritoneal dialysis.
F
luid removal is an integral part of any dialysis treatment. In peritoneal dialysis (PD), ultrafiltration (UF)
is also correlated with patient survival (1) and technique
survival (2): lower UF is associated with poor patient
survival, and UF failure is the second most common cause
of technique failure. Ultrafiltration failure is commonly
seen in high transporters and in patients with recurrent
peritonitis (membrane failure). Icodextrin, an iso-osmolar (osmolality 285 mOsm/kg) glucose polymer of high
molecular weight (MW 16 800), is beneficial in these situations. It has been shown to produce more UF than standard (1.5%) glucose dialysate (3) and is comparable in
UF to hypertonic (4.25%) glucose dialysate over 8 –
12 hours of dwell (4). It has an added advantage over
hypertonic solutions because hypertonic solutions have
been shown to cause peritoneal membrane damage with
long-term use (5). Icodextrin exchanges have been in
use for more than a decade now, starting with continuous ambulatory peritoneal dialysis (CAPD), where it was
used during the long night dwell (8 – 12 hours); UF was
>500 mL (4,6–8). But, with increasing use in automated
peritoneal dialysis (APD) patients, where the long day
dwell period is prolonged to 14 – 15 hours, reported UF
with icodextrin varies from 200 to 500 mL (Figure 1)
(8–14). On the other hand, using a three-pore computergenerated model, Rippe and Levin showed UF to increase
at least until 17 hours (15). In a retrospective study,
however, we observed that UF in APD patients was lower
than reported in the literature (13) and decided to validate the findings in a prospective trial. We studied the
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University of Toronto,1 Canada; Akdeniz University,2 Antalya; Uludag University,3 Bursa; Dokuz Eylül
University,4 Izmir; Erciyes University,5 Kayseri; Çapa Medical School,6 Istanbul University; Marmara
University,7 Istanbul; Ankara University,8 Ankara; Cerrahpas¸a Medical School,9 Istanbul University,
Istanbul; Ege University,10 Izmir; Ondokuz Mayis University,11 Samsun; Çukurova University,12
Adana; Gazi University,13 Ankara; Dicle University,14 Diyarbakir, Turkey
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MAY 2006 – VOL. 26, NO. 3
Figure 1 — Mean ultrafiltration (in milliliters) with icodextrin
at different dwell times (hours) in different studies. Continuous ambulatory peritoneal dialysis = white bars; automated
PD = shaded bars.
Continuous variables were compared using a series
of independent sample t-tests; categorical variables
were compared using a series of chi-square tests. Differences in mean UF for the total group were analyzed
by repeated measures ANOVA. Differences between the
subgroups were analyzed by Friedman test. Differences
in maximal UF (maximum UF for that individual, irrespective of dwell time) between the subgroups were compared by Mann–Whitney U test. A series of tests were
performed to determine whether any of the demographic factors were significantly associated with maximal UF. Linear regression was used to examine the
relationship between continuous demographic factors
and maximal UF; independent sample t-tests were used
to look at the effects of categorical demographic factors on maximal UF. Correlation between variables was
studied by Spearman’s rho. All statistical analyses were
done using SPSS 13 software (SPSS Inc., Chicago, Illinois, USA).
PATIENTS AND METHODS
RESULTS
This was a prospective, multicenter, interventional
study from six different centers in Canada and Turkey.
Inclusion criteria were all APD patients who were on icodextrin day exchange for more than a month and willing
to participate in the study following written informed
consent. Exclusion criteria were history of peritonitis in
the previous 3 months and known chronic liver disease
or congestive heart failure. Research ethics board approval was granted for the study.
Each patient started the study with icodextrin day
exchange with a dwell time of 10 hours and continued
the same, daily, for the first week. Their nocturnal cycler PD prescription was continued as before. Due to concerns with flushing and wasting of some icodextrin by
the machine for the last fill, all patients did the exchange
manually after disconnecting themselves from the overnight cycler. Dwell time was increased for the second and
subsequent weeks by 1 hour so that the dwell period for
the fifth week was 14 hours. The patients were dry for a
short period of the day, depending upon the change in
icodextrin dwell time. Daily UF with the icodextrin exchange was measured for each patient and recorded for
analysis. For Canadian patients, UF was measured by
weighing the drain fluid bag and subtracting the dwell
fluid bag, and for Turks, UF was recorded using a 5-L volume container.
STATISTICAL ANALYSIS
Descriptive statistics are expressed as mean, median,
standard deviation, and standard error of the mean.
Baseline characteristics of the patients, in separate
groups and combined, are shown in Table 1. Mean age of
patients was 47.5 ± 13.4 years; 83% were males, 14%
were diabetics, and 50% were high and high-average
peritoneal transporters. Mean duration of icodextrin use
in these patients was 18.1 ± 12.4 months. Two of 36 patients (1 Canadian and 1 Turk) had 1.5-L icodextrin fill
volume and the rest had 2-L fill volume. There was no
difference in baseline characteristics between Canadians and Turks, except for Canadians having higher Kt/V
compared to Turks (p = 0.001).
TABLE 1
Baseline Characteristics of Patients
Total
Canadians
Turks p Value
N
36
7
29
Age (years)
47.5±13.4 56±16.9 45.4±11.9 0.06
Male gender (%)
83.3
85.7
82.7
1.0a
Diabetes mellitus (%) 13.8
28.5
10.3
0.24a
TS (H+HA) (%)
50
57.1
48.2
1.0a
PD age (months)
51.6±26.1 39.7±15.5 54.5±27.5 0.18
ICO age (months)
18.1±12.4 20±12
17.6±12.7 0.66
Kt/V
2.2±0.53 2.7±0.45 2.0±0.45 0.001
ClCr (L/wk/1.73 m2) 74.8±29.5 93.7±40.9 69.1±23.3 0.16
TS = transport status; H = high transporters; HA = high-average transporters; PD/ICO age = duration on PD/icodextrin
exchange; ClCr = creatinine clearance.
a Due to small number of patients, Fischer’s exact test was used
instead of chi-square test.
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relationship between UF and dwell time with icodextrin
in APD patients.
OPTIMAL DWELL TIME FOR MAXIMIZING UF
JELOKA et al.
MAY 2006 – VOL. 26, NO. 3
and transport characteristics (p = 0.38) were also found
not significantly associated with maximum UF.
DISCUSSION
In high peritoneal transporters and patients with
membrane failure, and because of concerns with damage induced by hypertonic glucose dialysate (5), the icodextrin exchange is increasingly being used to maintain
significant UF. In our clinical practice, we have often
noted that net UF in some patients, despite being on icodextrin exchange, is not significant, requiring an additional midday PD exchange (enhanced continuous
cycling PD). There is a belief (based on simulation studies) that icodextrin UF keeps increasing with increasing
dwell time, but it is better to know the expected UF with
an icodextrin exchange and if a longer dwell will result
in higher UF.
Net icodextrin UF reported in the literature is approximately 500 mL with an overnight dwell of 8 – 12 hours’
exchange on CAPD (4,7,8). In fact, in a computer-generated three-pore model simulating CAPD, Rippe and Levin
showed that icodextrin UF keeps increasing, even after
a 15-hour dwell (15). In APD patients, most studies have
shown that icodextrin UF is around 168 – 270 mL (8–13).
However, Finkelstein et al. recently showed mean UF with
icodextrin in APD patients to be >500 mL with a dwell
TABLE 2
Mean Ultrafiltration (in milliliters) with Icodextrin for Each Week of Increasing Dwell Time
Dwell
N
Meana
SD
SE
Minimum
Median
Maximum
Week 1: 10 hours
Week 2: 11 hours
Week 3: 12 hours
Week 4: 13 hours
Week 5: 14 hours
31
35
36
35
35
351.73
348.71
386.63
390.34
371.75
250.59
234.72
240.86
257.68
258.25
45.00
39.67
40.14
43.55
43.65
–330.86
–302.29
–338.00
–388.00
–309.43
312
362
390
376.28
387.42
1126.29
1183.43
1233.43
1240.57
1012.00
a
p = NS, between any of the weeks.
TABLE 3
Differences in Mean Ultrafiltration (in milliliters) with Icodextrin in Different Subgroups with
Increasing Dwell Time (For simplicity, SD has deliberately not been included)
Week
Week 1
Week 2
Week 3
Week 4
Week 5
Canadians
Turks
Males
Females
High transporters
Low transporters
343.78
263.11
304.48
302.47
343.13
352.59
370.11
406.45
408.52
378.90
380.38
376.48
418.42
415.99
392.68
232.38
214.46
227.67
266.39
270.58
402.35
390.73
438.40
444.35
421.54
302.65
295.92
286.19
331.38
357.12
Diabetics Nondiabetics
575.51
562.13
530.04
581.66
575.13
p Values between countries (0.162), gender (0.02), transport categories (0.04), and diabetic status (0.07).
338
298.03
304.55
357.94
350.76
329.67
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Mean UF for the whole group did not show an increase
with increasing dwell time, as shown in Table 2. Mean UF
did not show a change with increasing dwell time even
when patients were divided into subgroups (Table 3).
Median intraindividual standard deviation of UF over the
5-week period was 104.3 (39.3 – 356.9), reflecting the
day-to-day variation of UF, which was also shown to lack
concordance as per Kendall’s test (Kendall’s coefficient
of concordance W = 0.044). When weekly UF was analyzed instead of daily UF to control for daily variation,
again there was no concordance among weekly average
UF during 5 weeks (W = 0.11; Kendall’s W < 0.3 denotes
weak or no concordance). On the other hand, the median interindividual SD of UF was 266.9 (224.7 – 333.9),
reflecting an even higher variation between individuals.
Mean UF was higher in males compared to females and
in high transporters (high + high average) compared to
low transporters (low + low average), as shown in Table 3.
Since mean UF did not differ with increasing dwell time,
we tried to compare maximum UF (maximum UF for all
individuals irrespective of dwell time) between subgroups and determine its association, if at all, with any
of the demographic factors. Maximum UF also did not
differ between the subgroups. There was no correlation
between maximum UF and age, creatinine clearance,
Kt/V, duration on PD, or duration on icodextrin exchange
(data not shown). Gender (p = 0.39), diabetes (p = 0.54),
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MAY 2006 – VOL. 26, NO. 3
teristic, creatinine clearance, Kt/V, duration on PD, or
duration of use of icodextrin beyond 1 month.
ACKNOWLEDGMENTS
We thank Eczacibasi-Baxter Company of Turkey for their
support.
We also thank Sharron Izatt, Nurse Manager of the University Health Network PD program in Toronto, and all PD nurses
in Canada and Turkey for patient care and their support in this
study.
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period of 14 – 16 hours (8). In contrast, our study showed
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Finkelstein’s study does not mention if their patients
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because of increased lymphatic absorption due to increased intra-abdominal pressure from being in an upright posture (16).
In our prospective analysis, mean UF did not differ
with various dwell times of 10 – 14 hours. Mean UF also
remained similar, with no effect of dwell time, in the various subgroups (country of origin, gender, transport
characteristics, and diabetic status). This means that, if
the nocturnal cycler UF is not adequate, then compensating UF can only be achieved by adding an extra midday exchange, rather than attempting to increase the
icodextrin dwell time.
Mean UF was higher in males compared to females,
and higher in high transporters compared to low transporters. The gender difference needs further study as
our study had only 6 females versus 30 males; therefore,
the difference could be falsely positive due to the small
sample size. The difference between transport characteristics (18 high vs 16 low patients), however, has been
substantiated in previous studies (17,18), and our study
confirms the observation.
We also observed significant daily and weekly intraand interindividual differences in icodextrin UF in our
study patients. Since mean UF was similar in all groups,
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any association with demographic factors. This analysis
also showed similar maximal UF between the countries,
sex, diabetic status, and transport characteristics. Maximal UF had no correlation to age of the patient, creatinine clearance, Kt/V, PD age, or icodextrin age.
To conclude, maximum UF with icodextrin dialysis solution in APD patients can be achieved at 10 hours, beyond which, increasing the dwell time will not lead to
any significant increase in UF. Maximum UF did not correlate to age, gender, diabetic status, transport charac-
OPTIMAL DWELL TIME FOR MAXIMIZING UF
JELOKA et al.
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