Control Catheter Encrustation with Lemon Juice: A Prospective Randomized Study

Transcription

1 Academia Journal of Biotechnology 4(5): , May 2016 DOI: /ajb ISSN Academia Publishing Research Paper Control Catheter Encrustation with Lemon Juice: A Prospective Randomized Study Accepted 21 st January, 2016 ABSTRACT Chien-Hsing Chang, MD, Chung-Jing Wang*, MD and Po-Chao Tsai, MD Division of Urology, Department of Surgery, Saint Martin De Porres Hospital, Chiayi, Taiwan, R.O.C. *Corresponding author. jing@stm.org.tw.tel: ext: Fax: Lemon juice (LJ) therapy may be a potential treatment for patients on the encrustation of urethral catheters in patients with long-term indwelling urethral catheters. The main objective of this research is to evaluate the effect of long-term LJ therapy on mean change in urinary citrate level. This prospectively randomized controlled trial was conducted from January, 2010 to December, All patients 20 years of age or older, who resided in a long-term care setting or received homecare and who had a long-term indwelling catheter (defined as indwelling catheterization > 30 days) with monthly changing were eligible; of 263 patients, 101 were in the control group, and 103 patients were in the LJ group. Baseline examinations and patient recruitment occurred in LJ therapy consisted of 120 ml concentrated lemon juice (60 meq citric acid) mixed with 2 L water and consumed throughout each day. All patients met with a dietitian and were instructed to maintain a diet restricted to 2 g of sodium and 65 g of protein. The patients were asked to consume sufficient fluid to urinate 2 L daily. The primary outcome was mean change in urinary citrate level. The final analysis included 101 (control) and 103 (LJ) patients. In the LJ group, mean urinary citrate levels increased from ± to ± mg, with a response rate of 61.17% (P<0.001 vs. control). The encrustation index was ± in the control group and ± in the LJ group, differing significantly. (P<0.001) The urinary turbidity ranged from ± to ± in the control group and from ± to ± in the LJ group, respectively, with significant difference. (P<0.001). There was no comparison to a group receiving standard therapy (potassium citrate). LJ therapy delivers increased fluid intake and a high citrate acid load resulting in a lower encrustation index and urinary turbidity. Key words: Encrustation, lemon juice, urethral catheter, hypocitraturic. Abbreviations: LJ: Lemon juice; NTU: National turbidity units; phn: ph nucleation; CCr: Creatinine clearance rate. INTRODUCTION Indications for the use of a long-term (>30 days) indwelling catheter are urinary retention or urinary incontinence in selected patients receiving palliative or end-of-life care as well as, prevention of wound contamination (by urine) in patients with pressure ulcers (Wong, 1983; Clinical Fact Sheet, 2000). Common complications associated with the long-term use of an indwelling catheter include by-passing (leakage around the catheter), irritation of the urethra and bladder neck, urethral erosion or injury, urinary calculi, and a potentially increased risk of bladder cancer (Liedl, 2001). The most prevalent complications are bacteriuria, urinary tract infection (UTI), and blockage by sediment or crystals (Ackerman and Monroe, 1996; Sedor and Mulholland, 1999). Among these, the most troublesome complication in

2 Academia Journal of Biotechnology; Wang et al. 165 the care of patients undergoing long-term indwelling catheterization is catheter encrustation (Stickler and Zimakoff, 1994). This may lead to emergency referrals of patients in discomfort who experience urinary retention or incontinence due to sudden catheter blockage (Kohler- Ockmore and Feneley, 1996). Potassium citrate has been shown to decrease stone formation rates in patients with idiopathic hypocitraturic calcium nephrolithiasis (Barcelo et al., 1993; Pak and Fuller, 1986), hyperuricosuric (Pak and Peterson, 1986), and in thiazide-unresponsive patients (Pak, 1985). Potassium citrate is believed to exert its beneficial effect through its citraturic and urinary alkalinizing actions. An increase in urinary citrate retards spontaneous nucleation and agglomeration of calcium oxalate crystals (Pak, 1991). Moreover, by increasing urinary ph and decreasing the urinary content of undissociated uric acid, this treatment is useful in preventing uric acid stones (Pak and Fuller, 1986). Potassium citrate is widely accepted as a first-line therapy for the treatment of idiopathic hypocitraturic nephrolithiasis (Pak and Fuller, 1986). Despite these effective treatments, however, the disease shows no signs of abating in part due to poor patient compliance with prescribed drug therapies. Citrus fruits and juices are a natural dietary source of citrate and may represent an alternative to pharmacological therapy. Lemon juice (LJ) therapy has been proposed as an alternative to potassium citrate for the treatment of hypocitraturia in recurrent stone formers. Herein, a prospectively randomized trial was undertaken to evaluate the effect of long-term LJ therapy on metabolic parameters in patients with long-term indwelling urethral catheters. For comparison, we concurrently evaluated the turbidity of urine and encrustation of catheters in patients who received either LJ therapy or no medical prophylaxis (control). MATERIALS AND METHODS Study design The study was approved (#99B-018) by the Institutional Review Board of St. Martin De Porres Hospital in Chia-Yi city, where the work was undertaken. All procedures involving human participants were in accordance with the ethical standards of the institutional and national research committee and in compliance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was designed as a prospectively randomized controlled trial and carried out from January, 2010 to December, Study population We assessed the eligibility of all patients who resided in a long-term care setting or received homecare and who had a long-term indwelling catheter (defined as indwelling catheterization > 30 days) with monthly changing. All the patients were indwelled with 16Fr silicone Cliny Foley catheters. Additional inclusion criteria for participants were 20 years of age or older and a sufficient level of alertness according to the Mini-Mental State Examination (MMSE score> 24) to consent to participate in the study and respond to verbal questions regarding the experiences associated with catheterization. Exclusion criteria included: symptomatic urinary tract infection (UTI), urethral erosion allowing continuous by-passing (leakage) around the urinary catheter; history of bladder cancer, radiation or interstitial cystitis and impaired renal function, as evidenced by a serum creatinine level of 2.0 mg/dl or higher; and gross hematuria. Patients with primary hyperparathyroidism, hyperkalemia and any diseases or medications that could potentially affect acid-base status, gouty diathesis, gastro-intestinal disease, or chronic diarrhea were excluded. Patients with hypercalcemia, calcium phosphate stones, struvite, and uric acid stones were also excluded. All patients were required to sign an informed consent form before participating. Study interventions All patients met with a dietitian and were instructed to maintain a diet restricted to 2 g of sodium and 65 g of protein. The patients were asked to consume enough fluid to urinate at least 2 L daily. This could be any non-caffeinated fluid, with the exception of lemonade or other citrus drinks. All vitamins and dietary supplements were stopped. LJ therapy consisted of 120 ml concentrated lemon juice (60 meq citric acid) (local brand) mixed with 2 L water and was consumed throughout each day. The baseline study included 24-h urine samples for 3 consecutive days, followed by fasting venous blood samples collected on the morning of the following day. Urine was kept refrigerated during collection and analyzed for calcium, sodium, potassium, magnesium, uric acid, citrate, oxalate, and creatinine. Urine volume and urinary ph were measured for all 24-h urine collections. Patients were followed in an outpatient setting monthly, at which time three consecutive 24-h urine samples and venous blood were obtained for the same tests as in the baseline study. To assess the effect of LJ on urinary turbidity and catheter encrustation, pre-therapy and posttherapy data for each patient were reviewed by the same laboratory surveyor. The evaluation of urine turbidity was measured using a spectrophotometer (NTU) (Lenon, Taiwan). A fixed surveyor was used to evaluate the grade of intraluminal encrustation, and the encrustation index could be expressed as a percentage relating to the open lumen of the reference stent. A measurement above 50 % indicates encrustation in more than half a lumen of the catheter. Randomization A total of two hundred and sixty-three (263) patients were

3 Fig.1 Academia Journal of Biotechnology; Wang et al. 166 Assessed for eligibility (n=263) Excluded(n=18) Not meeting inclusion criteria (n=6) Declined to participate (n=12) Randomized (n=245) Allocation Allocated to control (n=120) Received allocated control (n=110) unwilling to be randomized (n=10) Allocated to silodosin (n=125) Received allocated lemon juice (n=114) unwilling to be randomized (n=11) Follow-Up Lost to follow-up (missing primary outcome) (n=6) Discontinued intervention (withdraw the consent) (n=3) Lost to follow-up (missing primary outcome) (n=5) Discontinued intervention (withdraw the consent) (n=2) Analysis Analysed (n=101) Excluded from analysis (n=0) Analysed (n=103) Excluded from analysis (GI distress)(n=4) Figure 1. Summary of study disposition.; Numbers of participants declining further follow-up or not responding are cumulative in direction of participant flow. eligible, and two hundred and forty-five (245) were prospectively randomized (using a random number table) into two groups before they were enrolled in the study. A total of 120 (control) and 125 (LJ) patients were available for consideration for each group. Among them, 10 (control) and 11(LJ) patients who were unwilling to be randomized in each group were not allocated to the trial. The remaining one hundred and ten (110) patients were allocated to the control group and received ordinary hydration. Of these, 6 patients missing the primary outcome and 3 patients withdrawing informed consent were eliminated from the analysis. Another one hundred and twenty-five (125) patients were allocated to the LJ therapy group. Of these, 5 patients missing the primary outcome and 2 patients withdrawing informed consent were eliminated from the analysis. An additional 4 patients in the LJ group could not tolerate lemon juice due to gastro-intestinal distress and were eliminated. Thus, the final analysis was conducted with one hundred and one (101) (control) and one hundred and three (103) (LJ) patients as the denominator in each randomization arm (Figure 1).

4 Academia Journal of Biotechnology; Wang et al. 167 Table 1. Patients demographics. Characteristic Control group Lemonade group N=101 N=103 P value Age(yr) a Mean ± ± 4.31 Range Gender b * Male 69 (68.32) 75 (72.82) Female 32 (31.68) 28 (27.18) Body mass index a ± ± Male a ± ± Female a ± ± Co-mobilities b CVA 31 (30.69) 29 (28.16) SI 21 (20.79) 24 (23.30) DM 17 (16.83) 19 (18.45) COPD 9 (8.91) 8 (7.77) BPH 5 (4.95) 6 (5.83) CC 2 (1.98) 2 (1.94) HI 16 (15.84) 15 (14.56) Values are presented as mean ± standard deviation or number (%); a Mann-Whitney U test; b Chi-square test. Study outcomes The primary outcome measure was the mean change in urinary citrate level. The secondary outcome measures were the encrustation index, urinary turbidity and citrate response rate. Sample size and statistical analysis Detection of a 40% difference in the mean urinary citrate level in the treatment groups at a significance level of 0.05 and a power of 80% required a sample size of 90 patients per group. All analyses were conducted using SPSS version The differences in mean urinary citrate increase between the LJ and control groups were determined using the Mann-Whitney U test. The demographics were assessed with the Mann-Whitney U test and chi-square test. Mean changes in urinary parameters and the encrustation index were examined and compared with the Mann Whitney U test. Changes in metabolic parameters within both groups were analyzed using the Wilcoxon signed-rank test. RESULTS A total of two hundred and four (204) patients completed the study protocol, one hundred and one (101) in the control group and a hundred and three (103) in the LJ group. No significant statistical differences were observed in patient age, gender distribution, body mass index, and comorbidities (Table 1). The encrustation index was ± in the control group and ± in the LJ group, with significant difference (P<0.001). The urinary turbidity ranged from ± to ± in the control group and from ± to ± in the LJ group, respectively, with significant difference (P<0.001). Mean urinary citrate level elevation from ± to ± mg and mean response rate (61.17%) were observed in the LJ groups after therapy, with significant difference (P<0.001) (Table 2). The baseline urinary citrate did not differ between the two groups. The mean ion activity ratio for calcium/citrate ranged from 0.57 ± 0.08 to 0.60 ± 0.08 in the control group and from 0.57 ± 0.07 to ± 0.16 in the LJ group, respectively, with significant difference(p<0.001). Urinary potassium and magnesium varied from ± 4.62 to ± 7.41 in the control group and from ± 9.00 to ± in the LJ group, respectively, with significant difference (P<0.001). The ph values and total urine volume increased statistically significantly in both groups. No statistically significant changes in CCr (ml/min), calcium, sodium, and uric acid were observed between the two

5 Academia Journal of Biotechnology; Wang et al. 168 Table h urine biochemistry. Variable Control group Lemonade group P value a ph value Baseline 7.36 ± ± weeks 7.46 ± ± 0.25 < *** P value b < 0.01 * < *** Uric acid(mg/day) Baseline ± ± weeks ± ± P value b Oxalate (mg/day) Baseline ± ± weeks ± ± P value b ** ** Total urine volume (ml/day) Baseline ± ± weeks ± ± < 0.05 * P value b ** < *** CCr(ml/min) Baseline ± ± weeks ± ± P value b Sodium (meq/day) Baseline ± ± weeks ± ± P value b Potassium(mEq/day) Baseline ± ± weeks ± ± P value b < *** Citrate (mg/day) Baseline ± ± weeks ± ± ** P value b < *** Calcium(mg/day) Baseline ± ± weeks ± ± 5.44 < *** P value b Magnesium (mg/day) Baseline ± ±

6 Academia Journal of Biotechnology; Wang et al. 169 Table 2 Condt. 24-h urine biochemistry. Variable Control group Lemonade group P value a 4 weeks ± ± P value b < 0.05 ** Calcium/ citrate Baseline 0.57 ± ± weeks 0.60 ± ± 0.16 < *** P value b < 0.05 ** < 0.05 * Turbidity(NTU) Baseline ± ± weeks ± ± < *** P value b p < *** p < *** Encrustation index Baseline weeks ± ± < *** Values are presented as mean ± standard deviation. * p < 0.05, ** p < 0.01, *** p < a Mann-Whitney U test and b Wilcoxon signed-rank test. groups. Significant differences within each group were observed in ph value, total urine volume, citrate level, and urinary turbidity. DISCUSSION The primary goal of management for long-term indwelling urethral catheters is the prevention of infection and blockage. A study of the problem of catheter encrustation in spinal cord injury patients by Burr and Nuseibeh. (1997) concluded that a high, uniform rate of fluid intake should be mandatory for patients with a tendency toward recurrent catheter blockage (Suller et al., 2005). This conclusion has a sound basis in physiology and physical chemistry. Experimental evidence also shows that diluting urine increases its ph n and slows the rate of catheter encrustation (Suller, 2005; Stickler and Morgan, 2006). Citrate is a natural chelating agent for divalent metal ions such as Ca 2+ and Mg 2+. In vitro studies confirmed that increased urine citrate content inhibits the crystallization of Ca and Mg phosphates (Wang et al, 1994), increases urinary phn, and inhibits catheter encrustation (Stickler and Morgan, 2006). Thus, the evidence indicates that increasing patient fluid intake with citrate-containing drinks should be an effective strategy to control catheter encrustation. Our results revealed that LJ therapy can lead to elevation of urine ph, urinary citrate, and potassium. The most important finding was that the encrustation index decreased significantly in the LJ group. These results were similar to those reported by Khan et al. (2010). This randomized study also allowed us to examine the effect on ph of increased fluid intake with water and the combined effect of increased fluid and LJ intake. Both groups showed significant elevation of ph values and tidal volume. However, the design is especially useful in this patient group since most were elderly or severely disabled due to neurological conditions, such as stroke or spinal injury. The only adverse effect was that some patients suffered from gastrointestinal distress in the LJ group. Table 2 shows that the LJ therapy produced highly significant increases in urine citrate versus the baseline. Urinary calcium did not change appreciably during the treatment, but urinary magnesium, potassium, and oxalate significantly increased from a mean baseline of ± 9.00 (mg/day), ± 4.62 (meq/day), and ± 1.50 (mg/day), respectively, to ± (mg/day), ± 7.41 (meq/day), and ± 2.23 (mg/day), respectively, while patients were on LJ therapy. The increased fluid intake with an alkali load of urinary citrate may have a deleterious effect on urinary turbidity and catheter encrustation. There was less urinary turbidity and a lower catheter encrustation index in the LJ group. No catheter blockage was noted in our study. Potassium citrate has been used clinically as a therapy in patients with hypocitraturic calcium nephrolithiasis and renal tubular acidosis (Barcelo et al., 1993; Pak et al., 1985; Preminger et al., 1985; Preminger et al., 1985). Due to poor patient compliance with these potassium citrate regimens, Seltzer et al. (1996) suggested a daily intake of 2 L of a

7 Academia Journal of Biotechnology; Wang et al. 170 lemon-based drink as an alternative. They reported that the lemon-based drink was well tolerated by patients and effective for increasing urinary citrate. In our study, LJ therapy is a well tolerated, accepted, and inexpensive approach to retarding catheter encrustation. To the best of our knowledge, our study is the first to evaluate the effect of LJ therapy on long-term indwelling catheters. We demonstrate encouraging results of LJ therapy on catheter encrustation and exhibit clinically and statistically significant increases in citrate levels over a sustained period of time. The LJ therapy led to a clinically significant decrease in urinary turbidity and the encrustation index. Clinicians may consider LJ therapy as a potential long-term alternative to potassium citrate in patients with long-term indwelling catheters. However, there is an important limitation in our study due to the absence of a potassium citrate group as a standard group for comparison. A well-designed study should include three groups namely; lemonade, potassium citrate, and placebo on a metabolic diet to control for any cofounder and to evaluate the effect of each medication. Moreover, a cross-over study would have more power, and the design may be an important limitation of our study. Also, patients with symptomatic UTIs were not included in the trial, so we cannot elucidate the role of UTIs in catheter encrustation and interactions of variable urinary parameters. LJ therapy delivers increased fluid intake and a high citric acid load, resulting in a lower encrustation index and urinary turbidity. It is well tolerated, well accepted, and inexpensive as a form of treatment for selected patients with long-term indwelling catheters. Conclusions LJ therapy may be a supplement or an alternative to conventional pharmacological therapy, especially in patients who are poorly compliant with or unable to tolerate pharmacological potassium citrate. ACKNOWLEDGEMENTS The authors would like to thank Jui-Fang Huang, from the Department of Research and Education, St. Martin De Porres Hospital, Chia-Yi, Taiwan for their assistance with the statistical methods of this research. REFERENCES Ackerman RJ, Monroe PW (1996). Bacteremic UTI in older people. J. Am. Geriatr. Soc. 44(8): Barcelo P, Wuhl O, Servitge E, Rousaud A, Pak CYC (1993). Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis. J. Urol. 150(6): Burr RG, Nuseibeh IM (1997). Urinary catheter blockage depends on urine ph, calcium and rate of flow. Spinal Cord. 35(8): Clinical Fact Sheet (2000). Indwelling Catheter. Mount Laurel, NJ: Wound, Ostomy and Continence Nurses Society. Khan A, Housami F, Melotti R, Timoney A, Stickler D (2010). Strategy to control catheter encrustation with citrated drinks: A randomized crossover study. J. Urol. 183(4): Kohler-Ockmore J, Feneley RCL (1996). Long-term catheterization of the bladder: prevalence and morbidity. Br. J. Urol. Int. 77(3): Liedl B (2001). Catheter-associated urinary tract infections. Curr. Opin. Urol. 11: Pak CY, Fuller C, Sakhaee K, Preminger GM, Britton F (1985). Long-term treatment of calcium nephrolithiasis with potassium citrate. J. Urol. 134(1): Pak CY, Fuller C (1986). Idiopathic hypocitraturic calcium oxalate nephrolithiasis successfully treated with potassium citrate. Ann. Intern. Med. 104(1): Pak CY, Peterson R, Sakhaee K, Fuller C, Preminger G, Reisch J (1985). Correction of hypocitraturia and prevention of stone formation by combined thiazide and potassium citrate therapy in thiazideunresponsive hypercalciuric nephrolithiasis. Am. J. Med. 79(3): Pak CY, Peterson R (1986). Successful treatment of hyperuricosuric calcium oxalate nephrolithiasis with potassium citrate. Arch. Intern. Med. 146(5): Pak CY (1991). Citrate and renal calculi. New sights and future directions. Am. J. Kidney Dis. 17(4): Preminger GM, Harvey JA, Pak CY (1985). Comparative efficacy of specific potassium citrate therapy versus conservative management in nephrolithiasis of mild to moderate severity. J. Urol. 134(4): Preminger GM, Sakhaee K, Pak CY (1985). Prevention of recurrent calcium stone formation with potassium citrate therapy in patients with distal renal tubular acidosis. J. Urol.134(1): Sedor J, Mulholland SG (1996). Hospital-acquired urinary tract infections associated with the indwelling catheter. Urol. Clin. North Am. 26(4): Seltzer MA, Low RK, McDonald M, Shami GS, Stoller ML (1996). Dietary manipulation with lemonade to treat hypocitraturic calcium nephrolithiasis. J. Urol. 156(3): Stickler DJ, Morgan SD (2006). Modulation of crystalline Proteus mirabilis biofilm development on urinary catheters. J. Med. Microbiol. 55(Pt5): Stickler DJ, Zimakoff J (1994). Complications of urinary tract infections associated with devices for long-term bladder management. J. Hosp. Infect. 28(3): Suller MT, Anthony VJ, Mathur S, Feneley RC, Greenman J, Stickler DJ (2005). Factors modulating the ph at which calcium and magnesium phosphates precipitate from human urine. Urol. Res. 33(4): Wang YH, Grenabo L, Hedelin H, Pettersson S (1994). The effects of sodium citrate and oral potassium citrate on urease- induced crystallization. Br. J. Urol. 74(4): Wong ES (1983). Guideline for prevention of catheter-associated urinary tract infections. Am. J. Infect. Control 11(1): Cite this article as: Chang C, Wang C, Tsai P (2016). Control Catheter Encrustation with Lemon Juice: A Prospective Randomized Study. Acad. J. Biotechnol. 4(5): Submit your manuscript at