1551Vol. 11 | No. 03 | May - June 2014 |U R O LO G Y J O U R N A L 1 Department of Urology, Endourology Division, Urology Nephrology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 2 Department of Urology, Jahrom University of Medical Sciences, Jahrom, Iran. 3 Department of Anesthesiolo- gy, Jahrom University of Medical Sciences, Jahrom, Iran. 4 Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Mohammad Mehdi Hosseini,1 Abbas Hassanpour,1 Farhad Manaheji,1 Alireza Yousefi,2 Mohammad Hassan Damshenas,3 Sezaneh Haghpanah4 Percutaneous Nephrolithotomy: Is Dis- tilled Water as Safe as Saline for Irrigation? Corresponding Author: Abbas Hassanpour, MD Department of Urology, Urol- ogy and Nephrology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Tel: +98 711 233 1006 Fax: +98 711 233 0724 E-mail: hassanpour74@yahoo. com Received July 2012 Accepted April 2014 Purpose: To compare dilutional effect of distilled water with saline solution as an irrigation fluid in percutaneous nephrolithotomy (PCNL). Materials and Methods: Three hundred twenty eight adult patients (191 men, 137 women) who were candidates for PCNL were randomly assigned into two groups (distilled water, n = 158, group 1; saline solution, n = 162, group 2). Stone size, operation time, irrigation fluid volume, blood hemoglobin level, urea nitrogen, creatinine, sodium and potassium levels were checked before and at 6 and 12 hours after operation. Results: The mean age of the patients was 37.8 years, and the mean stone diameter was 31.5 mm. There was no clinical case of transurethral resection (TUR) syndrome. Serum sodium depletion was significantly more in group 1 than group 2 (P < .0001). Group 1 had significant decreased post-operative serum sodium levels (P < .0003). Similarly in group 2, postoperative serum sodium levels were significantly lower than the preoperative concentration (P < .01), but it was not the same 6 hours after the operation (P = .23). Serum sodium concentrations remained within normal limits in all cases, without causing clinical signs and symptoms of hyponatremia. Conclusion: We found that distilled water is safe irrigation fluid for PCNL in adults. In addi- tion, it is more available and cost effective. Keywords: nephrostomy; percutaneous; postoperative complications; intraoperative care; therapeutic irrigation. ENDOUROLOGY AND STONE DISEASE 1552 | Endourology And Stone Disease INTRODUCTION Nowadays, percutaneous nephrolithotomy (PCNL) is a technique to remove large and complex renal stones which cannot be treated with extracorpor- eal shock wave lithotripsy (SWL). Irrigation fluid is used in endoscopic urological surgeries to dilate the target organ and also for a better vision. Physiologic saline is the most commonly used fluid because it is isotonic and also compatible with interventions, unless electro-cautery is needed. By the use of hypotonic solutions such as distilled water (DW), the visibility would be im- proved; however, it can result in dangerous complications especially in younger age groups.(1) In transurethral resection of the prostate (TURP), this mani- festation is called TUR syndrome which includes cardiovas- cular and neurologic derangements. Absorption of irrigation fluid during PCNL has also been reported, and a variety of significant complications have been reported.(2-5) Some studies have evaluated the absorbed fluid by breath-alcohol test.(6) In our center, two cases with hyponatremia were occurred in children using DW as an irrigation fluid for PCNL, which is routine in urology practice; because it is cheaper than sa- line solution and is more available in large amounts at some health centers. In this study, we compared DW and saline so- lution (SS) as irrigation fluid during PCNL in adult patients (≥ 19 years old). MATERIALS AND METHODS In this study, we considered more than 2 meq/L of depletion in serum sodium level as a significant change. Considering α = 0.05 and 90% power, the sample size was calculated as 38. Since we work in a center with a high rate of PCNL opera- tion, 328 patients including 191 men and 137 women were included in this study. Exclusion criteria were patients with solitary kidney and abnormal renal function (serum creati- nine level > 2.3 mg/dL). Thus, 8 patients were excluded from the study and as a results 320 patients were randomly divided into two groups. Group 1 included 158 patients and group 2 consisted of 162 patients. Patients with stone above the ureteropelvic junction level, and more than 2 cm in di- ameter were included. The minimum age for inclusion into this study was 18 years. No upper limit for stone size or age was considered. Informed consent was signed by all patients prior to the operation, and the study was conducted based on the approval of ethical committee of Shiraz University of Medical Sciences. In group 1 DW and in group 2 SS was used as the irriga- tion fluid during the operation. All patients were evaluated by intravenous urography (IVU), and complete blood count (CBC), coagulation profile, blood urea nitrogen (BUN), creatinine (Cr), sodium (Na+) and potassium (K+) levels were determined; urine analysis and urine culture before operation were also performed. The patients were admitted 6 hours before the operation and received intravenous an- tibiotic (cephalotin 1 g) and 125 mL/h of intravenous fluid (33.3% dextrose 5% + 66.6% saline 0.9%) and oral diet was started about 12 hours after the operation. Blood sample was taken just before, at the end, 6 and 12 hours after operation for determining the serum hemoglobin (Hb), BUN, Na+, K+ and Cr levels. PCNL was performed in the prone position, under general anesthesia after insertion of a 6 French (F) ureteral catheter. Fluoroscopy guidance was applied for nephrostomy tract creation, and metal telescopic dilator system was used for tract dilation and pneumatic lithotripsy was used for stone fragmentation. When multiple calyceal stones or a staghorn stone was present, two tracts were created. Since fluid irri- gation was the main variant of the study, operation time was considered from when nephroscopy was started and it lasted until the removal of nephroscope. The patients were visited for clinical signs of hyponatremia such as lethargy, restlessness, headache, nausea, vomiting, confusion and seizure. The diet was started 12 hours after the operation. Stone-free state was defined as no residual stone in postoperative kidney urinary bladder (KUB) X- rays. It is the most common definition for stone-free state in the literature.(7) Urinary tract ultrasonography was requested if the stone was nonopaque in X-ray images. Ureteral stent and urethral catheter were removed 12 to 24 hours after the operation depending on the patients' condi- tion, and the patients were usually discharged from hospital two days post-operatively. No nephrostomy tube was in- serted for patients. The data were analyzed using Chi-square test, student t test or paired t test, and the P value less than .05 was considered as significant. 1553Vol. 11 | No. 03 | May - June 2014 |U R O LO G Y J O U R N A L Distilled Water as Safe as Saline for Irrigation | Mehdi Hosseini et al RESULTS No significant preoperative difference was seen between the groups considering the stone size, serum Hb, BUN, K+ and Cr levels, but significant differences in age and serum so- dium level were noted (Table 1). Before the operation, eight patients were excluded from the study because they had one or more exclusion criteria. Fourteen patients were excluded after the operation due to perforation of collecting system, prolonged operation time (> 90 minutes), or high irrigation volume (> 15 liters) used. The stone-free rates were 92.76% and 94.15%; the mean operation times were 57 and 65 min- utes, and the mean irrigation volume were 10.4 and 10.6 lit- ers in groups 1 and 2, respectively. Complications included fever (5 vs. 3), perforation of pelvi- calyceal system (1 vs. 2), bleeding (3 and 5), and transfusion (2 and 2) in groups 1 and 2, respectively (Table 2). Table 1. Demographic and clinical characteristics of study population. Variables Group 1 (n = 158) Group 2 (n = 162) P Gender no. (%) Gender Male 94 (58) 97 (58) NA Women 67 (42) 70 (42) NA Mean age (years) 134 (70-170) 36.8 ± 6.8 .004 Mean stone size (mm) 29 ± 12 30 ± 14 .021 Site of Kidney Right kidney 86 66 NA Left kidney 72 96 .018 Mean serum parameters Hemoglobin (mg/dL) 14.3 ± 2.3 14.6 ± 2.5 .25 BUN (mg/dL) 17.3 ± 3.5 16.9 ± 2.5 .23 Creatinine (mg/dL) 1.2 ± 0.8 1.2 ± 0.9 .75 Sodium (meq/L) 138 ± 75 136 ± 8.3 .02 Potassium (meq/L) 4.4 ± 1.9 4.5 ± 2.1 .65 Key: BUN, blood urea nitrogen. Table 2. Data in study groups. Variables Group 1 (n = 152) Group 2 (n = 154) P Stone-free rate, % 92.76 94.15 .651 Mean operation time (min) 57 ± 34 65 ± 41 .064 Mean irrigant volume (liters) 10.4 ± 5.8 10.6 ± 6.9 .784 Mean hospital stay (days) 2.2 ± 1.1 2.5 ± 1.3 .030 Fever (T ≥ 38◦C), no. (%) 5 (3.28) 3 (1.94) .499 Bleeding, no. (%) 3 (1.97) 5 (3.24) .722 Transfusion, no. (%) 2 (1.3.1) 2 (1.29) 1.0 Pelvicalyceal system perforation, no. (%) 1 (0.65) 2 (1.29) 1.0 Operation time > 90 min, no. (%) 3 (1.97) 4 (2.59) 1.0 Irrigant > 15 liters, no. (%) 2 (1.31) 2 (1.29) 1.0 1554 | The mean serum Na+ level in group 1 significantly de- creased 6 and 12 hours after the operation. Also, it signifi- cantly decreased in group 2 just after the operation, and 12 hours later; however, serum Na+ level in group 2 showed no significant changes 6 hours after the operation. Changes in the serum level of Na+ were significantly greater in group 1 compared to group 2, in all postoperative measurements (Tables 4 and 5). Fortunately, no case of TUR syndrome was seen. The mean blood Hb level decreased at the end of operation in both groups, but it remained in normal range without any significant difference in both groups. The mean serum BUN and Cr levels increased in both groups postoperatively. The mean serum K+ level also showed minimal changes without any statistical significance (Table 3). DISCUSSION PCNL is a commonly used technique for treatment of kid- ney stones, and has significant advantages in comparison to open stone surgery. These advantages include lower morbid- ity rate, decreased amount of postoperative pain, minimal surgical scars, and faster postoperative recovery. Complica- tions include hemorrhage, fever, infection, pneumothorax, colon perforation, extravasation and etc. The absorption of irrigation fluid during this operation causes TUR syndrome in some cases. This dangerous complication occurred when a hypoosmolar fluid is used.(8-14) Most authors have suggested SS as the best fluid for irriga- tion due to its isoosmolar properties. When electro-surgery is used, ion-free fluids such as glycine or DW are preferred. (1,3,15) Hahn found that hyponatremia is depended on both volume of fluid absorption and the time of TURP.(16) Amr Hawary and colleagues reported that the rate of TUR syndrome is related to the type of irrigating fluid, opera- tion time, patient position, prostate size, fluid bag height, surgeon experience, intraprostatic vasopressin injection, Table 3. Perioperative laboratory data in study groups.* Variables Group 1 Group 2 Hb BUN Cr K Hb BUN Cr K Before operation 14.4 17.1 1.14 4.4 14.8 16.2 1.18 4.3 At the end of operation 13.2 22.4 1.3 4.4 13.3 21.8 1.24 4.3 Six hours after operation 13.5 22.6 1.34 4.3 13.4 22.1 1.28 4.3 Twelve hours after operation 13.6 22.1 1.32 4.5 13.7 22.7 1.28 4.6 Keys: Hb, hemoglobin (g/dL); BUN, blood urea nitrogen (mg/dL); Cr, creatinine (mg/dL); K, potassium (meq/L). * Data are presented as means. Table 4. Comparison of serum sodium levels (meq/l) at different times in study groups.* Study Groups Group 1 P Group 2 P Before Operation 138 ± 7.5 136 ± 8.3 NS At the end of operation 132 ± 6.5 < .0001 132 ± 7.1 < .0001 6-hour Postoperatively 132 ± 7.0 .23 135 ± 6.9 < .0001 12-hour Postoperatively 135 ± 7.3 < .0003 134 ± 6.7 4.5 Key: NS, not significant. * All reported P values are compared to baseline. Endourology And Stone Disease 1555Vol. 11 | No. 03 | May - June 2014 |U R O LO G Y J O U R N A L low pressure irrigation and etc. They have mentioned that “an ideal irrigating fluid should be isotonic, nonhemolytic, electrically inert, nontoxic, transparent, easy to sterilize and inexpensive”. Glycine, crystal and physiological saline have been recommended to be used as irrigation fluid in TURP. (17) In the present study, distilled water has been compared to physiological saline in respect of TUR syndrome clinical signs and subclinical hyponatremia. Aghamir and colleagues compared sterile water and isotonic saline solution as irrigation fluid in PCNL. They looked for blood Hb level drop, haptoglobin level, electrolyte level and any sign of TUR syndrome. They found no significant dif- ference between DW and saline for their safety. They intro- duced DW as a safe and inexpensive irrigation fluid during PCNL operation.(18) Gariou and colleagues investigated the amount of glycine ab- sorption during PCNL. They indicated that glycine can cause a significant hemo-dilution in PCNL compared to TURP. They suggested that SS is a proper irrigation fluid for PCNL. (19) In another study, 1.5% glycine induced post-nephrolithot- omy syndrome in 2% of the patients. This study was con- ducted by Fellahi and his colleagues, and they have reported that physiologic saline is a better choice for PCNL.(20) In contrast, some studies showed no significant derangement with hypotonic solution such as water. They have suggested that these solutions are as safe as physiological saline solu- tion during PCNL.(21-23) In the present study, the effect of physiological saline so- lution and DW was compared on blood Hb, BUN, Cr, and especially Na+ levels. Na+ is the main effective ion in TUR syndrome. As we demonstrated, a significant decrease in serum Na+ level was found in group 1 (distilled water) in comparison to group 2 (saline solution). This difference was in the normal range of serum sodium level. Because no clini- cal case of TUR syndrome was observed, this change was considered clinically insignificant. CONCLUSION Distilled water can be used for PCNL in adult patients, while postoperative serum Na is monitored. Its usage needs some precautions. The authors do not recommend DW as an ir- rigation fluid for pediatric patients. ACKNOWLEDGEMENT The authors would like to thank Mr. Abdolhossein Hanaee for his assistance, and Mrs. Salami for her cooperation and typing the draft. CONFLICT OF INTEREST None declared. Distilled Water as Safe as Saline for Irrigation | Mehdi Hosseini et al Table 5. Comparison of serum sodium (meq/L) changes between the study groups compared to baseline. Study Groups At the end of Operation 6-hour Post-operatively 12-hour Post-operatively* Group A -6 ± 2.3 -6 ± 2.3 -3 ± 2.1 Group B -4 ± 1.4 -1 ± 1.3 -2 ± 1.6 P < .0001 < .0001 < .0001 REFERENCES 1. Zeltser I, Pearle MS, Bagley DH. Saline is our friend. Urology. 2009;1:28-9. 2. Mohta M, Bhagchandani T, Tyagi A, Pendse M, Sethi AK. Hemody- namic, electrolyte, and metabolic change during percutaneous nephrolitotomy. Int Urol Nephrol. 2008;40:477-82. 3. Schultz RE, Hanno PM, Wein AJ, Levin RM, Pollack HM, Van Arsdalen KN. Percutaneous ultrasonic lithotripsy: Choice of irrigant. J Urol. 1983;130:858-60. 4. Köroğlu A, Toğal T, Ciçek M, Kiliç S, Ayas A, Ersoy MO. The effect of irrigation time on fluid volume and irrigation time on electrolyte balance and hemodynamics in percutaneous nephrolithotripsy. Int Urol Nephrol. 2003;35:1-6. 5. Chou CH, Chau T, Yang SS, Lin SH. Acute hyponatremia and renal failure following percutaneous nephrolithotomy. Clin Nephrol. 2003;59:237-8. 6. Stalberg HP, Hahn RG, Wayne Jones A. Ethanol monitoring of tran- surethral prostatic resection during inhaled anesthesia. Anesth An- alg. 1992;75:983-8. 7. Deters LA, Jumper CM, Steinberg PL, Paris Jr VM. Evaluating the definition of "stone free status" in contemporary urologic literature. Clin Nephrol. 2011;76:354-7. 8. Alken P, Hutschenreiter G, Gunther R, Marberger M. Percutaneous stone manipulation. J Urol. 1981;125:463-6. 1556 | 9. Grammo E, Balianger P, Dore B, Aubert J. Hemorrhagic complica- tions during percutaneous nephrolithotomy. Retrospective study of 772 cases. Prog urol. 1999;9:460-5. 10. Kukreja RA, Desai MR, Sabins RB, Patel SH. Fluid absorption dur- ing percutaneous nehprolithotomy: Does it matter? J Endourol. 2002;16:221-5. 11. Cadeddu JA, Chen R, Bishoff J, Micali S, Kumar A, Moore RG, Ka- voussi LR. Clinical significance of fever after percutaneous nephroli- thotomy. Urology. 1998;52:48-50. 12. Goswami AK, Shrivastava P, Mukherjee A, Sharma SK. Management of colonic perforation during percutaneous nephrolithotomy in horse-shoe kidney. J Endourol. 2001;15:989-91. 13. Stables DP, Ginsberg NS, Johnson ML. Percutaneous nephros- tomy: A series and review of the literature. AJR Am J Roentgenol. 1978;130:75-82. 14. Rao PN. Fluid absorption during urological endoscopy. Br J Urol. 1987;60:93-9. 15. Hahn RU. Early detection of the TUR syndrome by marking the irriga- tion fluid with 1% ethanol. Acta Anaesthesiol Scand. 1989;33:146-51. 16. Hahn RU. Relations between irrigant absorption rate and hypona- tremia during transurethral resection of the prostate. Acta Anaes- thesia Scand. 1988;32:53-60. 17. Harway A, Mukhtar K, Sinclair A, Pearce I. Transurethral resection of prostate syndrome: Almost gone but not forgotten. J Endourol. 2009;23:2013-20. 18. Aghamir SMK, Alizadeh F, Meysamie A, Assefi Rad S, Edrisi L. Sterile Water Versus Isotonic Saline Solution as Irrigation Fluid in Percuta- neous Nephrolithotomy. Urol J. 2009;6:249-53. 19. Cariou G, Le Duc A, Serrie A, Cortesse A, Teillac P, Ziegler F. Reab- sorption of the irrigation solute during percutaneous nephrolithot- omy. Ann Urol. 1985;19:83-6. 20. Fellahi JL, Richard JP, Bellezza M, Autonini A, Thouvenot JP, Cathala B. The intravascular transfer of glycine during percutaneous kidney surgery. Cah Anesthesiol. 1992;40:343-7. 21. Feizzadeh B, Doosti H, Movrrekh M. Distilled water as an irrigation fluid in percutaneous nephrolithotomy. Urol J. 2006;3:208-11. 22. Falahatkar S, Khosropanah I, Atrkar Roshan Z, Golshan M, Emadi SA. Decreasing the complications of PCNL with alternative technique including complete supine PCNL and subcostal approach. Pak J med Sci. 2009;25:353-8. 23. Grundy PL, Budd DWG, England R. A randomized controlled trial evaluating the use of sterile water as an irrigation fluid during tran- surethral electro vaporization of the prostate. Br J Urol. 1997;80:894-7. Endourology And Stone Disease