Abstract
Background and Aims:
Transurethral resection of the prostate (TURP) is the gold standard for benign prostatic hyperplasia. However, the systemic absorption of irrigation fluids, such as glycine or saline, may affect coagulation. Glycine is associated with dilutional coagulopathy and electrolyte imbalance, while saline offers better stability. Conventional coagulation tests may miss early changes; rotational thromboelastometry (ROTEM) offers dynamic assessment. This study compared the coagulation effects of glycine and saline irrigation using ROTEM to inform safer irrigant selection during TURP.
Methods:
In this study, 80 males (50–70 years) undergoing TURP were administered glycine (Group G, n = 40) or saline (Group S, n = 40). Coagulation was evaluated pre- and postoperatively via ROTEM (INTEM, EXTEM, and FIBTEM) and conventional tests (haemoglobin, platelets, prothrombin time, and electrolytes). Statistics included t-tests, Mann-Whitney U, and Chi-square (P < 0.05 significant).
Results:
Glycine significantly prolonged mean INTEM clotting time (CT): 176.05 [standard deviation (SD): 52.97] [95% confidence interval (CI): 160.48, 191.63)] versus 152.58 (SD: 25.23) (95% CI: 144.47, 160.68) (P = 0.013), and reduced mean maximum clot firmness: 55.85 (SD: 15.29) versus 62.73 (SD: 8.60) (P = 0.015). FIBTEM CT and clot formation time were also prolonged in the glycine group (P = 0.013 and P = 0.023, respectively). Postoperative haemoglobin and platelet counts declined in both groups, more so in the glycine group. One patient (2.5%) in Group G developed TUR syndrome.
Conclusion:
Glycine impairs intrinsic coagulation and fibrin polymerisation more than saline. Saline offers better coagulation profiles. ROTEM-guided protocols may optimise perioperative haemostatic management, especially in high-risk patients.
Keywords: Benign prostatic hyperplasia, dilutional coagulopathy, glycine, haemostasis, ROTEM, sodium chloride, thromboelastometry, transurethral resection of prostate, TURP syndrome
INTRODUCTION
Benign prostatic hyperplasia (BPH) is a prevalent condition affecting approximately 50% of males aged 55–60 years.[1] Transurethral resection of the prostate (TURP) remains the gold-standard surgical intervention for BPH,[2] requiring an irrigating fluid to maintain visibility and remove debris. However, systemic absorption of the irrigant[3] can lead to complications such as hyponatremia, electrolyte imbalances, pulmonary oedema, and coagulopathy.
Glycine, a non-electrolytic solution, is widely used due to its optical clarity and compatibility with monopolar diathermy. However, its absorption can cause glycine toxicity,[4] leading to cerebral oedema, visual disturbances, and hyperammonaemia. Normal saline, though safer regarding electrolyte balance, is incompatible with monopolar cautery due to its conductive properties.[5] The bipolar resection technique allows for saline use, reducing the risk of transurethral resection (TUR) syndrome but introducing potential hyperchloremic acidosis.[6]
Coagulopathy during TURP is a critical concern, particularly in elderly patients with comorbidities.[7] Conventional coagulation tests (CCTs) have limitations in real-time assessment, whereas rotational thromboelastometry (ROTEM) provides a comprehensive evaluation of clot formation, strength, and stability.[8] Despite extensive research on electrolyte changes, few studies have compared the effects of glycine and saline on coagulation by using the ROTEM method.
This study aimed to bridge this gap by evaluating ROTEM-based coagulation parameters in patients undergoing TURP with glycine or saline irrigation. The primary objective of this study was to compare the effect of glycine versus saline irrigation fluids on intrinsic coagulation, measured by ROTEM INTEM clotting time (CT), in male patients aged 50–70 years undergoing TURP under spinal anaesthesia. Secondary objectives included comparing other ROTEM parameters [maximum clot firmness (MCF) and clot formation time (CFT)], changes in CCTs [haemoglobin, platelet count, and prothrombin time (PT)], electrolyte levels, and postoperative complications such as TUR syndrome and transfusion requirement. We hypothesised that glycine irrigation would significantly prolong INTEM CT compared to saline, indicating greater impairment of intrinsic coagulation. The findings will guide clinical decisions to optimise patient outcomes and minimise perioperative bleeding risks.
METHODS
This prospective observational comparative study was conducted between September 2022 and February 2024, following Institutional Ethics Committee approval (vide approval no. ESICMC/SNR/IEC-S0141/07-2022, dated 26-07-2022) and registered with Clinical Trials Registry – India (vide registration number CTRI/2023/11/059996, dated 20-11-2023, accessible at https://ctri.nic.in/). Written informed consent was obtained from all participants for their participation in the study and the use of their data for research and educational purposes. The study was conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines.
The study included male patients aged 50–70 years who were selected to reduce confounding from age-related comorbidities with BPH, classified as American Society of Anesthesiologists (ASA) physical status I-III, with prostate sizes under 80 g, no coagulation or metabolic disorders, and scheduled for surgeries lasting less than 90 min. Patients on anticoagulant therapy, diagnosed with malignancies, or suffering from hepatic, renal, or cardiac conditions, as well as those with contraindications to spinal anaesthesia, were excluded.
A total of 80 eligible patients undergoing TURP were included and observed based on the type of irrigation fluid used during surgery. Group G (n = 40) comprised patients who underwent monopolar TURP with 1.5% glycine irrigation, while Group S (n = 40) included those who underwent bipolar TURP using normal saline. The choice of technique and irrigant was determined by the operating surgeon as per institutional practice. All patients were preoperatively fasted, received midazolam for premedication, and underwent spinal anaesthesia using hyperbaric bupivacaine. Intraoperative monitoring included non-invasive blood pressure, electrocardiogram (ECG), and oxygen saturation, with careful documentation of irrigation fluid absorption.
Venous blood samples were obtained preoperatively and 30 min postoperatively to evaluate coagulation and biochemical parameters. These included ROTEM analyses using INTEM (intrinsic pathway), EXTEM (extrinsic pathway), and FIBTEM (fibrinogen-specific with platelet inhibition), measuring CT, CFT, MCF, and α-angle. Additional tests measured haemoglobin, haematocrit, platelet count, electrolytes (sodium, potassium, and chloride), and PT. The 30-min postoperative time point was chosen to detect early coagulation changes attributable to fluid absorption and surgical stress.
The primary outcome was the difference in ROTEM parameters, specifically INTEM CT, between the two groups before and after surgery. Secondary outcomes included all other ROTEM parameters, such as the difference in CT, CFT, and MCF of EXTEM, INTEM, and FIBTEM pre- and postoperatively between the groups, as well as intragroup changes. Additionally, changes in haemoglobin levels, platelet counts, electrolytes, and the incidence of complications, such as TUR syndrome, were also measured and compared.
The sample size was calculated using G Power (version 3.1.9.7, Heinrich-Heine-Universität Düsseldorf, Germany) based on the primary outcome of postoperative differences in ROTEM parameters, specifically INTEM CT. A pilot study conducted on 10 patients (5 in each group) revealed a mean difference of 20 s in INTEM CT between the glycine and saline groups, with a standard deviation (SD) of 25 s. Using a two-tailed alpha of 0.05 and power of 80%, the minimum required sample size was 34 per group. Allowing for a 15% dropout, the final target enrolment was 40 patients per group (total N = 80).
Data were analysed using Statistical Package for the Social Sciences (SPSS) statistics software version 26.0 (International Business Machines Corporation (IBM Corp), Armonk, NY, USA). Normality of distribution was assessed using the Shapiro-Wilk test. Continuous variables with normal distribution (ROTEM parameters, haemoglobin, and electrolytes) were presented as mean (SD) (95 % confidence interval (CI)) and compared using an independent samples t-test (intergroup) or a paired t-test (intragroup). Non-normally distributed data (CFT) were analysed using the Mann-Whitney U test (intergroup) or the Wilcoxon signed-rank test (intragroup). Categorical variables (complications and ASA class) were presented as frequencies (%) and compared using Chi-square or Fisher’s exact test, as appropriate. Primary outcomes (INTEM CT and FIBTEM parameters) were analysed using t-tests, while secondary outcomes (e.g. platelet count and PT) were analysed using Mann-Whitney U tests as they were non-normal. A two-tailed P value of < 0.05 was considered statistically significant.
RESULTS
Eighty male patients (ASA I-III) undergoing TURP were enroled in this study and evenly assigned to two groups based on irrigation fluid: Group G (glycine) and Group S (saline). The demographic characteristics, including age and ASA status, were comparable between the groups, with no statistically significant differences observed [Table 1]. In Group G, 67.5% of patients were over 60 years old, compared to 55% in Group S. All patients belonged to ASA classes I-III, ensuring baseline homogeneity.
Table 1.
Demographic and baseline characteristics
| Parameter | Group G (n=40) | Group S (n=40) | P |
|---|---|---|---|
| Age (years), mean (SD) (95% CI) | 61.2 (8.5) (58.4, 64.0) | 59.8 (7.3) (57.5, 62.1) | 0.072 |
| ASA class I–III, n (%) | 40 (100%) | 40 (100%) | |
| Prostate size (g), mean (SD) (95% CI) | 32.25 (11.16) (28.6, 35.9) | 42.38 (6.09) (40.4, 44.4) | <0.001 |
Data are presented as mean (standard deviation) (95% confidence interval) or number (percentage) as appropriate. ASA=American Society of Anesthesiologists; SD=standard deviation; CI=confidence interval
Intraoperatively, the mean volume of irrigation fluid used was slightly higher in Group G compared to Group S, though this difference was not statistically significant (P = 0.566) [Table 2]. However, the resected prostate weight was significantly greater in the Group S compared to the Group G (P < 0.001). The duration of surgery was similar in both groups, averaging approximately 1.55 h (P = 0.889).
Table 2.
Intraoperative and postoperative outcomes, haematological indices, and ROTEM parameters
| Category | Parameter | Group G (n=40) | Group S (n=40) | P | Risk difference (%) | 95% CI for risk difference |
|---|---|---|---|---|---|---|
| Intraoperative outcomes | Irrigation fluid used (L) | 5.83 (1.99) (5.19, 6.47) | 5.58 (1.88) (4.98, 6.18) | 0.566 | — | — |
| Resection time (h) | 1.55 (0.41) (1.42, 1.68) | 1.54 (0.38) (1.42, 1.66) | 0.889 | — | — | |
| Resected prostate weight (g) | 32.25 (11.16) (28.60, 35.90) | 42.38 (SD: 6.09) (95% CI: 40.40, 44.40) | <0.001 | — | — | |
| Haematological parameters | Haemoglobin (g/dL) (Pre/Post) | 13.59/13.15 (0.80) (12.89, 13.41) | 13.37/13.71 (SD: 0.75) (95% CI: 13.47, 13.95) | 0.064 | — | — |
| Platelet count (×105/μL) (Pre/Post) | 2.85/2.68 (0.60) (2.49, 2.87) | 3.16/3.03 (SD: 0.58) (95% CI: 2.84, 3.22) | 0.044 | — | — | |
| Prothrombin time (s) (Pre/Post) | 11.60/11.82 (0.45) (CI: 11.68, 11.96) | 11.63/11.54 (SD: 0.50) (95% CI: 11.38, 11.70) | 0.166 | — | — | |
| Sodium (mEq/L) (Pre/Post) | 140.33/139.90 (1.20) (139.52, 140.28) | 140.40/140.10 (SD: 1.10) (95% CI: 139.75, 140.45) | 0.848 | — | — | |
| ROTEM – INTEM | Clotting time (CT, s) | 176.05 (52.97) | 152.58 (SD: 25.23) | 0.013 | — | — |
| Maximum clot firmness (MCF, mm) | 55.85 (15.29) | 62.73 (8.60) | 0.015 | — | — | |
| ROTEM – FIBTEM | Clotting time (CT, s) | 73.00 (23.31) | 62.43 (2.41) | 0.013 | — | — |
| Clot formation time (CFT, s) | 66.70 (11.33) | 95.20 (77.15) | 0.023 | — | — | |
| ROTEM – EXTEM | Clotting time (CT, s) | 106.05 (77.37) | 83.78 (44.87) | 0.119 | — | — |
| Postoperative complications | TUR syndrome, n (%) | 1 (2.5%) | 0 (0%) | >0.05 | 2.5 | –2.4, 7.4 |
| Blood transfusion, n (%) | 0 (0%) | 0 (0%) | — | 0.0 | — |
Data are presented as mean (standard deviation) (95% confidence interval) unless stated otherwise. Risk difference is expressed in percentage points. ROTEM=rotational thromboelastometry; TUR=transurethral resection; CI=confidence interval; SD=standard deviation; INTEM=intrinsic pathway); EXTEM=extrinsic pathway; FIBTEM=fibrinogen-specific with platelet inhibition
Haematological analysis revealed a statistically significant postoperative reduction in haemoglobin levels within both groups [Table 2]. Group G demonstrated a preoperative haemoglobin with a significant decline postoperatively (P = 0.03). In Group S, haemoglobin slightly increased from pre- to postoperative (P = 0.007). Although the intergroup difference in postoperative values was not statistically significant (P = 0.064), Group G exhibited a more notable reduction.
Platelet counts decreased significantly postoperatively in both groups. The intergroup difference was also significant, suggesting greater platelet depletion in Group G. The P values for each comparison were 0.024, 0.04, and 0.044, respectively.
PT increased significantly in Group G postoperatively (P = 0.036), while no significant change was observed in Group S, indicating dilutional coagulopathy. Serum sodium levels remained stable in both groups pre- and postoperatively, with no statistically significant intergroup differences.
ROTEM [Figure 1] analysis further substantiated the impact of irrigation fluid on coagulation profiles [Table 2]. EXTEM parameters (CT, CFT, and MCF) did not differ significantly between the groups, indicating similar extrinsic pathway activity.
Figure 1.
Graphical representation of ROTEM assay (EXTEM, INTEM, FIBTEM). ROTEM = Rotational thromboelastometry
However, INTEM analysis revealed a statistically significant prolongation of CT in Group G compared to Group S (P = 0.013) [Table 2], alongside a significant reduction in MCF (P = 0.015), indicating impaired intrinsic coagulation with glycine.
FIBTEM parameters also indicated significant coagulation abnormalities in the glycine group, with CT and CFT values being markedly prolonged (P = 0.013). FIBTEM CFT was also extended with P = 0.023, reflecting delayed fibrin polymerisation. MCF values in FIBTEM were similar between groups; the prolongation of CT and CFT in the glycine group suggested dilutional or functional fibrinogen deficiencies.
The mean intraoperative blood loss was comparable between groups (Group G: 145 (SD: 42) mL; Group S: 138 (38) mL; P = 0.412). No patient in either group required a blood transfusion intraoperatively or within the first 48 h postoperatively.
Postoperative complications were minimal in both groups [Table 2]. One patient (2.5%) in the glycine group developed symptoms consistent with TUR syndrome (hyponatremia and nausea), while no such events occurred in the saline group. However, this difference was not statistically significant (P > 0.05). Postoperative haematuria (assessed via gross inspection and catheter output) was graded as mild (grade I-II) and occurred in 12.5% (5/40) of Group G patients and 10% (4/40) of Group S patients (P = 0.715). None of these cases necessitated transfusion or additional interventions, and no major complications such as arrhythmias or neurological events were reported in either group.
DISCUSSION
This prospective observational study demonstrated that glycine irrigation during TURP significantly impairs coagulation compared to saline, as assessed by ROTEM. The primary finding was a significant prolongation in INTEM CT (P = 0.013) and a reduction in MCF (P = 0.015) in the glycine group, indicating delayed clot initiation and weakened clot strength.
These results are consistent with previous findings on the usage of irrigation fluid-induced coagulation changes.[4,9] Similarly, other studies have shown that hypoosmolar irrigants such as glycine interfere with fibrin polymerisation.[10,11] This aligns with our observation of significantly prolonged FIBTEM CT and CFT in the glycine group. However, unlike some earlier studies, we did not observe a significant reduction in FIBTEM MCF. This suggests that although fibrin polymerisation was delayed, fibrinogen levels remained relatively stable, or platelet-fibrin interactions were at least partially preserved.
Importantly, EXTEM parameters reflecting extrinsic coagulation remained comparable between the two groups. This supports previous research indicating that glycine’s dilutional effects primarily affect the intrinsic and fibrinogen pathways rather than tissue factor-initiated coagulation.[12] Furthermore, the observed decline in platelet counts and PT in the glycine group reinforces the hypothesis of dilutional coagulopathy, consistent with Hahn’s theory on the pathophysiology of TUR syndrome.[13] The occurrence of TUR syndrome in one patient (2.5%) in the glycine group and none in the saline group underscores the continued clinical relevance of these complications.[14,15]
Interestingly, despite higher resected prostate volumes in the saline group (P < 0.001), these patients maintained better coagulative stability. This finding supports the previous studies[16] wherein they used isotonic saline, (bipolar TURP), which maintains osmotic and electrolyte balance, thereby reducing haemodilution and coagulation disturbances. The preserved ROTEM profiles in the saline group, even under increased surgical load, further reinforce the safety and effectiveness of bipolar saline irrigation.
Several mechanisms may underlie these differences. Glycine’s hypoosmolarity (200 mOsm/L) leads to cellular water influx, further diluting coagulation proteins and impairing clot formation. Metabolic byproducts of glycine, such as ammonia, have also been implicated in platelet inhibition and neurological symptoms, compounding its risks. In contrast, saline (308 mOsm/L) offers osmotic stability and is compatible with bipolar electrocautery, resulting in deeper coagulation zones and reduced bleeding.[17,18]
Despite larger resected prostate volumes in the saline group, coagulation stability was preserved, suggesting that saline’s protective effect may offset the expected coagulopathy from increased surgical stress. This contrasts with glycine, where even smaller resections impaired clotting.
In this study, we employed ROTEM to compare glycine and saline irrigation during TURP, providing real-time, dynamic insight into coagulation changes beyond conventional tests. Its prospective design with strict inclusion criteria enhances internal validity and minimises confounding. Standardised anaesthesia and surgical protocols further strengthen intergroup comparability. The findings have strong clinical relevance in the early detection of dilutional coagulopathy, which could guide perioperative haemostatic management, especially in high-risk cases, demonstrating impaired coagulation with glycine irrigation and reinforcing the safety profile of saline in bipolar TURP.
However, limitations include the single-centre design and modest sample size (n = 80), which may limit the generalisability of the findings. ROTEM cannot detect subtle platelet dysfunction or von Willebrand factor deficiency, and postoperative testing at a single time point may miss delayed abnormalities. The lack of long-term follow-up and the low incidence of TUR syndrome also limit the evaluation of outcomes. Future studies should include larger, multicentre cohorts, broader patient populations, complementary platelet function tests, and extended follow-up. Future research should include larger, multicentre trials, evaluation in high-risk cohorts, and investigation of ROTEM-guided transfusion and fluid strategies during TURP procedures.
CONCLUSION
This prospective observational comparative study demonstrated that glycine irrigation during TURP significantly prolongs CT and impairs clot firmness, as assessed by ROTEM, particularly affecting the intrinsic coagulation pathway and resulting in greater impairment of coagulation. These findings support the use of normal saline as a safer irrigant in bipolar TURP, offering better coagulation profiles and haemostatic stability. ROTEM provides valuable real-time insights into perioperative coagulation changes and may guide tailored haemostatic management, particularly in elderly or high-risk patients undergoing TURP.
Conflicts of interest
Prof. Gopinath R, who is one of the co-authors of this manuscript, is an Editor of this journal. He was not involved in any decision-making process, and an independent editor handled this manuscript. Other authors declare no conflicts of interest.
Study data availability
De-identified data may be requested with reasonable justification from the authors (email to the corresponding author) and shall be shared after approval as per the authors’ institution’s policy.
Authors contributions
RKP and AN: Concept and design of the study, manuscript writing. SL: Data collection and statistical analysis. GNR, VP and NT: Literature review and manuscript editing.
Presentation at conferences/CMEs and abstract publication
None.
Disclosure of use of artificial intelligence (AI)-assistive or generative tools
The AI tools or language models (LLM) have not been utilised in the manuscript, except that software has been used for grammar corrections.
Declaration of Use of Permitted Tools
The scales, scores, figures, and tables are freely available and not copyrighted.
Supplementary material
None.
Acknowledgements
None.
Funding Statement
This study was not supported by or received any grant and did not receive funding from any sponsor.
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