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   Table of Contents      
ORIGINAL ARTICLE
Year : 2020  |  Volume : 6  |  Issue : 2  |  Page : 81-89

Biochemical Changes Using Sterile Water and 1.5% Glycine in TURP: A Randomized Study


Department of Surgery, Maulana Azad Medical College, New Delhi, India

Date of Submission31-May-2020
Date of Decision15-Jun-2020
Date of Acceptance24-Jun-2020
Date of Web Publication29-Aug-2020

Correspondence Address:
Dr. MS, FNB Lovenish Bains
Associate Professor, Department of Surgery, Maulana Azad Medical College, 2-Bahadur Shah Zafar Marg, New Delhi 110002
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mamcjms.mamcjms_50_20

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  Abstract 


Introduction: Endoscopic procedures in urology require irrigating fluid to provide a clear field of vision and to wash away debris. Glycine (1.5%) has been widely used, however sterile water is easily available and inexpensive. Excessive absorption of irrigation fluid can lead to dyselectrolytemia, hemolysis and systemic complications. In this study we compare 1.5% glycine with sterile water as irrigation fluid for Trans Urethral Resection Of Prostate (TURP). Materials and Method: In this prospective randomized study, we analysed 60 patients with symptomatic Benign Prostatic Hyperplasia (BPH) undergoing TURP with either 1.5% glycine or sterile water as irrigation fluid. The duration of surgery, weight of prostate resected, volume of fluid absorbed were compared. Post-operative levels of hemoglobin, hematocrit, electrolytes and renal function tests at 15 mins, 3 hrs and 6 hrs were analysed. Results: The mean decrease in hemoglobin at 6 hrs was more with 1.5% glycine (1.05±0.28 vs 0.89±0.14g/dL) and was statistically significant (P = 0.031). The mean fall in haematocrit at 6 hrs was significantly more with 1.5% glycine (4.87±1.41 vs 3.94±1.32%) (P = 0.046). The post-operative levels of blood urea were significantly less with 1.5% glycine at 15 mins, 3 hrs and 6 hrs (P < 0.05). There was no significant difference in the duration of surgery, weight of prostate resected, volume of irrigant absorbed, serum sodium, potassium and creatinine observed between the two groups (P > 0.05). Nine patients (30%) who received 1.5% glycine and 8 patients (26.6%) receiving sterile water had dilutional hyponatremia at 6 hrs, but there were no significant difference between the two groups (P = 0.38). None of the patients developed TURP syndrome. Conclusion: Biochemical changes with sterile water was significantly less when compared with 1.5% glycine in TURP. Most of the changes observed were at 6 hrs after surgery. Hence sterile water can be considered as a safer and inexpensive alternative to glycine in resource-limited settings of low-income countries.

Keywords: Glycine, hyponatremia, irrigation fluid, sterile water, trans urethral resection of prostate


How to cite this article:
Meena R, Maranna H, Bains L, Lal P, Sawant G. Biochemical Changes Using Sterile Water and 1.5% Glycine in TURP: A Randomized Study. MAMC J Med Sci 2020;6:81-9

How to cite this URL:
Meena R, Maranna H, Bains L, Lal P, Sawant G. Biochemical Changes Using Sterile Water and 1.5% Glycine in TURP: A Randomized Study. MAMC J Med Sci [serial online] 2020 [cited 2020 Nov 23];6:81-9. Available from: https://www.mamcjms.in/text.asp?2020/6/2/81/293889




  Introduction Top


Many endoscopic procedures in urology require irrigating fluid to provide a clear field of vision, to wash debris and blood away from the field.[1] The commonly used solutions in Trans Urethral Resection of Prostate (TURP) include 1.5% glycine, 5% dextrose, sterile water, sorbitol and mannitol solutions. Glycine solution has been used in TURP for more than 50 years and is transparent, yet it is non-physiological as it lacks electrolytes.[2] Five percent dextrose solution is physiological but is not commonly used due to its viscosity. Other irrigants have been used judiciously due to limited efficacies or high costs involved. A dreadful complication is excessive absorption of irrigation fluid leading to systemic manifestations.[3],[4] Sterile water is easily available and can be used for irrigation in resource-limited settings.[5] There is no ideal irrigation fluid and the consensus on the best irrigation fluid for TURP remains controversial and is guided largely by tradition. As there is a paucity of studies in literature in India and rest of the world comparing 1.5% glycine with sterile water, we conducted the present study to compare the biochemical changes with sterile water and 1.5% glycine as the irrigation fluid used in TURP.


  Materials and Method Top


The study was a prospective randomised non inferiority single centre blinded study conducted at Maulana Azad Medical College, New Delhi. The study population comprised of all patients with history of Lower Urinary Tract Symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH). A sample size of 60 was calculated having a confidence interval of 95% and α of 5%. The study was approved by the Institutional Ethics Committee (IEC number: IEC/MAMC/2015/317) and written informed consent was taken from all participants involved in the study. Patients included in the study were those with symptomatic BPH with a prostate volume of up to 60 cc. The patients excluded were those with diabetic nephropathy, deranged liver function, deranged kidney function, congestive cardiac failure, associated bladder tumor, stricture urethra, associated bleeding disorders and patients on anticoagulant therapy. Randomization was performed by computer-generated random numbers on the day of surgery. The operating surgeon, anesthetist involved and the patient were blinded to the study. Patients were randomised into two groups with Group A receiving 1.5% glycine and group B receiving sterile water as irrigation fluid. All patients undergoing monopolar TURP were given a preoperative dose of Inj. Amikacin 750 mg and Inj. Ciprofloxacin 200 mg intravenously, one hour before the surgery as per institutional protocol. Spinal anesthesia was administrated to in all the patients. The irrigation fluid was kept at a height of 60 cms from the symphysis pubis. A 26 Fr Karl Storz (Tuttlingen, Germany) resectoscope was used for monopolar TURP. A Valleylab (Medtronic, Minneapolis, USA) electrocautery generator was used with the power setting set to 120W cutting and 80W coagulation. All surgeries were performed by the same surgeon.

The parameters assessed were resection time, duration of surgery, weight of prostate resected, amount of irrigation fluid absorbed, the values of pre-operative and post-operative (at 15 mins, 3 hrs and 6 hrs) levels of haemoglobin, haematocrit, blood urea, serum creatinine, serum sodium and potassium. The resection time was calculated as the duration between the first cut on the prostate till the time of insertion of the three-way Foley’s catheter. At the end of the procedure the amount of irrigating fluid absorbed was calculated as the difference between the amount of irrigating fluid used in the resection and the amount of fluid collected in the suction and evacuation apparatus. Patients were allowed orally 6 hrs after surgery. All patients were monitored and observed for the vital parameters, general condition, input and output monitoring and for any change in haemoglobin, haematocrit, blood urea, serum creatinine, serum sodium and potassium. Foley’s catheter was removed on the next day and observed for satisfactory voiding of urine. Patients were discharged on day 3, unless any complications requiring prolonged hospital stay were noted. A uroflowmetry was performed at 7 days after discharge on out-patient basis.

Statistical Analysis

Statistical analysis was performed by using descriptive and inferential statistics. Student Paired t-test was used to see the change with time within case group and control group. Student unpaired t-test was used to compare mean values between the two groups. P-value less than 0.05 was considered as significant at 95% confidence level. The statistical software statistical package for social sciences (SPSS) version 24.0 was used for the analysis. The power of our study was 80%.


  Results Top


A total of 60 patients were analysed. The patients’ characteristics of both groups and observed results are listed in [Table 1],[Table 2],[Table 3]. The mean age of patients in Group A was 64.15±6.59 years and in Group B was 64.6±7.84 years, which was statistically insignificant (P = 0.946). The volume of irrigation fluid absorbed was 630±94 ml in group A and 684±79 ml in group B, which was statistically insignificant (P = 0.074). The duration of surgery in group A was 38.75±7.31 mins and in group B was 38.00±5.77 mins and was statistically insignificant (P = 0.806). The decrease in haemoglobin at 6 hrs was 1.05±0.28 g/dL in group A and 0.89±0.14 g/dL in group B and was statistically significant (P = 0.031) [Figure 1] and [Figure 2]. There was a significant difference in the mean decrease in haematocrit at 6 hrs (4.87±1.41% vs 3.94±1.32%) between the two groups (P = 0.046) [Figure 3]. There was no significant difference between the two groups with respect to serum creatinine, sodium and potassium in both preoperative and postoperative values (measured at 15 mins, 3 hrs and 6 hrs) (P > 0.05) [Figure 4],[Figure 5],[Figure 6]. The post-operative levels of blood urea were significantly less with 1.5% glycine at 15 mins (23.85±4.46 vs 26.75±4.10 mg/dl, P = 0.039), 3 hrs (22.85±4.42 vs 25.85±4.11 mg/dl, P = 0.032) and 6 hrs (22.00±4.24 vs 24.15±3.75 mg/dl, P = 0.027). There were 17 (28.3%) patients who had dilutional hyponatremia (Serum sodium <135 mEq/L) and were detected at samples taken 6 hours after surgery. In group A, 9 patients (30%) had hyponatremia and 8 patients (26.6%) in group B had hyponatremia and there was no significant difference between the two groups (P = 0.38). The decrease in serum sodium levels at 6 hrs was 5.05±1.50 mEq/L in group A and 5.55±1.10 mEq/L in group B and was statistically insignificant (P = 0.237). Hence, there was no significant difference in the frequency of dilutional hyponatremia and the decrease in serum sodium levels between the two groups. All patients were clinically asymptomatic and had only biochemical hyponatremia. None of the patients showed any signs and symptoms of the TURP syndrome post operatively. No adverse effects or allergic reactions were noted and no patient needed blood transfusion post operatively.
Table 1 Comparison of various parameters in the two groups

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Table 2 Mean decrease in various parameters at 6 hr in both groups

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Table 3 Comparison of mean decrease in various parameters at 6 hrs between the two groups

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Figure 1 Consort diagram of our study

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Figure 2 Graph showing the mean hemoglobin(g/dL) at various time intervals in both groups.

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Figure 3 Graph showing the mean hematocrit (%) at various time intervals in both the groups.

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Figure 4 Graph showing the mean blood urea levels(mg/dL) at various time intervals in both groups.

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Figure 5 Graph showing the mean serum sodium levels(mEq/L) at various time intervals in both groups.

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Figure 6 Graph showing the mean serum potassium levels(mEq/L) at various time intervals in both groups.

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  Discussion Top


TURP is one of the most common urological procedures performed having superceded open prostatectomy procedure for symptomatic BPH. Although several other techniques are performed such as Transurethral Incision of Prostate (TUIP), Holmium Laser assisted Enucleation of Prostate (HOLEP), use of prostatic stents, prostatic artery embolization and microwave therapy, TURP is still the gold standard for the treatment of BPH because of its decreased morbidity and mortality and excellent results.[6],[7],[8]

The ideal irrigation fluid for endoscopic resection would be a fluid that is easily available, a non-conductor medium, which does not interfere with diathermy, has a high degree of translucency, is isotonic and causes only minimal side effects when absorbed.[9] Several irrigation fluids have been used for endoscopic procedures. They include glycine (2.2%, 1.5%, 1.1% solutions), sterile water, 5% dextrose, mannitol (3%, 5%), sorbitol, cytal (sorbitol 2.7% with mannitol 0.54%) and urea 1%.[10],[11] Glycine has an osmolality of 230 mosm/L and is primarily eliminated by hepatic metabolism by formation of ammonia. It is reasonably inexpensive, transparent, does not cause allergy and is an endogenous amino acid.[2],[12] Nausea, vomiting and confusion occur six to nine times more often when 1–2 L of glycine solution is absorbed and even further absorption may lead to hyperammonemic encephalopathy, metabolic acidosis and dreadful TURP syndrome.[13],[14] Sterile water is used due to its easy availability and offers a very clear view of the operating field. However the disadvantages include its extreme hypotonicity (0 mosm) that can lead to intravascular hemolysis, dilutional hyponatremia and renal failure.[15] Cytal is a mixture of sorbitol 2.7% and mannitol 0.54% and with an osmolality of 178 mosm/L is widely used in the US with good results, but is not used in India due to its high cost and limited availability.[16] Five percent dextrose is isotonic (258 mosm/L) and physiological, but problems with stickiness of the instruments or caramelization of the cutting loop diathermy during surgery, transient hyperglycemia and its high viscosity have reduced its usage.[11] sodium chloride (0.9%) solution is isotonic (308mEq/L) and has been used for TURP, however requires the use of a bipolar resectoscope.[17],[18]

Significant uptake of irrigation fluid leads to rapid expansion of the intravascular volume and dilutional hyponatraemia. Severe hyponatraemia causes significant osmotic shift leading to cerebral oedema and raised intracranial pressure.[19] There are several factors governing the occurrence of such complications such as open prostatic sinuses, breech of capsule during resection, lengthy duration of surgery and thereby exposing the prostatic sinuses for a longer time, high irrigation pressure due to increased height of the irrigation column or due to small capacity of the bladder and the use of a hypotonic irrigation fluid.[20] The strategies to minimise fluid absorption include performing alternative procedures such as open prostatectomy or HOLEP for large (>80g) prostate, avoiding deep resection, minimising resection time to 60 mins, keeping height of irrigation column at 60 cms, use of a continuous flow resectoscope, and using an isotonic solution.[20] Resection time is of particular importance as the rate of absorption of fluid is 20 ml/min. The physiological changes due to excess fluid absorption most commonly manifest within 30–60 mins after the completion of surgery.[10],[11],[20] Measurement of electrolytes, renal function tests are not necessary after 24 hours provided immediate post-operative values were normal and in the absence of any symptoms.

The decrease in blood urea levels was more in patients who received 1.5% glycine in our study at 6 hrs (P = 0.027). Yari et al. observed no significant reduction in blood urea levels with both sterile water and 1.5% glycine, however the duration of surgery was not analysed in their study.[21]. In our study the mean decrease in hemoglobin was more with 1.5% glycine (P = 0.031) and there was a significant difference in the mean fall in haematocrit between the two groups (P = 0.046). The study conducted by Dissayabutra compared sterile water with 5% dextrose and observed significant intravascular hemolysis after using sterile water (P < 0.001).[22] The volume of irrigation fluid used was more (15.66±8.72 L) and the longer duration of surgery (57.14±26.81 mins) in their study could explain the complications. Another randomized study conducted in 80 patients showed significant decrease in haemoglobin (−1.47±1.96 mg/dl vs −0.46±1.6 mg/dl) and hematocrit (−4.22±4.24% vs −1.3±4.25%) with 1.5% glycine when compared with sterile water (P < 0.05).[21] In our study only the total haemoglobin levels were measured. The measurement of free plasma haemoglobin, haptoglobin and lactate dehydrogenase is a better indicator of hemolysis as free plasma levels can rise with little change in the total hemoglobin.[22],[23] The mean decrease in hematocrit between both groups was compared irrespective of the post-operative levels in our study. However other studies have considered arbitrary cut off levels of hematocrit less than 30% as hematocrit fall, which could be misleading.[24] Hence further detailed studies are required with regards to hematocrit changes after TURP.

There was no significant difference in the frequency of dilutional hyponatremia between the two groups in our study and the same was observed by Pasha et al in which 15.3% of patients receiving 1.5% glycine and in 11.8% of patients receiving sterile water had dilutional hyponatremia (P = 0.501).[25] Overall 26.6% of patients receiving sterile water had asymptomatic dilutional hyponatremia in our study. However in a review of 1600 patients who underwent TURP, the frequency of hyponatremia observed was 2.5%.[24] The mean irrigation fluid absorbed was less (293±25 ml) in their study and could possibly explain the lesser frequency of hyponatremia.

Post-operative hypokalemia and hyperkalemia have been reported in literature with the use of 1.5% glycine and sterile water. In our study there were no significant changes in serum potassium levels.[20],[26] The changes in serum potassium levels rely on both dilutional hypokalemia due to fluid absorption and hyperkalemia due to intravascular hemolysis. Although most often the changes in serum electrolytes and the manifestations of TURP syndrome occur within the first 60 mins after the completion of surgery, we observed that 28.3% patients had asymptomatic biochemical hyponatremia when measured at 6 hrs post-operatively.[10],[11],[20] Hence we suggest that vigilant monitoring of patients up to 24 hrs should be practiced regularly.

After extensive search of literature in Pubmed, Scopus and Google Scholar we have found a total of 3 randomized studies comparing 1.5% glycine and sterile water as irrigation fluid in urological procedures.[5],[21],[25] Kulshreshtha et al.[5] analysed the biochemical changes, hemoglobin, blood urea, creatinine and electrolytes in 60 patients and observed no significant difference between 1.5% glycine group and sterile water group (P > 0.05). A similar study conducted in 80 patients showed significant decrease in haemoglobin and hematocrit with 1.5% glycine when compared with sterile water (P < 0.05).[21] However the duration of surgery was not analysed in this study.[21] Pasha et al. analysed the frequency of post-operative hyponatremia at 6 hrs and frequency of urinary tract infections on the 15th post-operative day and observed no significant difference between glycine and distilled water. In our study several parameters such as hemoglobin, hematocrit changes, electrolytes and renal function tests were analysed over a period of time up to 6 hrs postoperatively. We observed that the mean decrease in hemoglobin and hematocrit at 6 hrs in the 1.5% glycine group was significantly more than with sterile water. The post-operative levels of blood urea were significantly reduced with 1.5% glycine in our study. None of the patients developed TURP syndrome and the frequency of complications were much less in our study due to shorter duration of surgery and less volume of irrigation fluid absorbed. The frequency of post-operative complications can be significantly reduced by limiting the duration of surgery to less than 60 mins.[11],[27].Our study is not without limitations. The small sample size is a limitation in our study. The measurement of the volume of irrigation fluid absorbed by volumetric fluid balance method may not be precise, as there may be surrounding spill of the fluid during surgery and residual fluid in the bladder which could overestimate the volume by about 10%. The measurement of ethanol in the breath by using 1% ethanol mixed with irrigation solution is a more accurate method.[28],[29] Hence a large scale multicentric study with larger sample size is required to substantiate our observations.


  Conclusion Top


We observed that sterile water can be used instead of glycine as an irrigant fluid without significant complications when the duration of surgery was kept less than 45 mins and when the volume of irrigation fluid absorbed was restricted to less than 750 ml. Most of the biochemical changes were observed post-operatively at 6 hrs in our study. Hence we suggest careful and serial monitoring of patients up to 24 hrs. 1.5% glycine has been commonly used worldwide, however there is still no consensus on the choice of ideal irrigation fluid for endoscopic procedures. Although the cost analysis was not performed in our study, the cost of using sterile water would be substantially less and can be considered as a cheaper alternative in resource limited settings and in the low- and middle-income countries.

Acknowledgements

The authors would like to express their gratitude to all the patients who participated in this study.


  Declarations Top


Ethics Approval and Consent to Participate

The study was approved by the Institutional Ethics Committee (IEC number: IEC/MAMC/2015/317) and written informed consent was taken from all the participants in this study. A copy of ethical committee certificate is available.

Consent For Publication

The consent for publication was taken from all participants in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Kulshreshtha K, Tambey R, G Tirpude N. A comparative study of ‘sterile water’ versus ‘glycine (1.5%)’ as irrigation fluid in transurethral resection of prostate. JMSCR 2017;05:21454-62.  Back to cited text no. 5
    
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Gielchinsky I, Pode D, Duvdevani M, Yutkin V, Landau EH, Hidas G et al. The transparency of irrigation fluids used in endoscopic surgery. J Endourol 2017;31:701-4. doi:10.1089/end.2016.0894  Back to cited text no. 12
    
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Collins JW, Macdermott S, Bradbrook RA, Keeley FX Jr, Timoney AG. A comparison of the effect of 1.5% glycine and 5% glucose irrigants on plasma serum physiology and the incidence of transurethral resection syndrome during prostate resection. BJU Int 2005;96:368-72. doi:10.1111/j.1464-410X.2005.05633.x  Back to cited text no. 13
    
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Dissayabutra T, Ungjaroenwathana W, Bunyaratavej C, Prasopsanti K, Tosukhowong P. Irrigation with water during transurethral resection of the prostate (TURP) induces intravascular hemolysis. Asian Biomed (Res Rev News) 2013;7;795-802. doi: https://doi.org/10.5372/ 1905-7415. 0706.242  Back to cited text no. 22
    
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  [Full text]  
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Panovska Petrusheva A, Kuzmanovska B, Mojsova M, Kartalov A, Spirovska T, Shosholcheva M et al. Evaluation of changes in serum concentration of sodium in a transurethral resection of the prostate. Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2015;36:117-27.  Back to cited text no. 27
    
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Gehring H, Hornberger C, Dibbelt L, Dörges V, Eichenauer R, Schmucker P. Detecting and quantifying absorbed irrigation fluid by measuring mannitol and sorbitol concentrations in serum samples, and by ethanol monitoring. BJU Int 2002;89:202-7. doi:10.1046/j. 1464-4096. 2001.01198.x  Back to cited text no. 29
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

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