Lidocaine versus Ketamine for Prevention of Postoperative Catheter Related Bladder Discomfort in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomised Controlled Trial

Anuja Pandit. (2025). Lidocaine versus Ketamine for Prevention of Postoperative Catheter Related Bladder Discomfort in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomised Controlled Trial. MAR Oncology and Hematology. (2025) 5:09 Lidocaine versus Ketamine for Prevention of Postoperative Catheter Related Bladder Discomfort in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomised Controlled Trial Rumit Sood1, Anuja Pandit2*, Gitartha Goswami3, Renoxy Bansal4 , Shirali Agarwal5 , Nivisha Sood6 1,2,3,4. All India Institute of Medical Sciences, New Delhi, India. 5. Artemis Hospital , Gurgaon , Haryana 6. Maharaja Agreson sat Narain Gupta hospital, Haryana *Correspondence to: Anuja Pandit, All India Institute of Medical Sciences, New Delhi, India. Copyright. © 2025 Anuja Pandit This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 02 Sep 2025 Published: 16 Sep 2025 MAR Oncology and Hematology (2025) 5:09 Research Article Anuja Pandit, MAR Oncology and Hematology (2025) 5:09. Page 2 of 12 Anuja Pandit. (2025). Lidocaine versus Ketamine for Prevention of Postoperative Catheter Related Bladder Discomfort in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomised Controlled Trial. MAR Oncology and Hematology. (2025) 5:09 Introduction Urinary Bladder catheterisation can result in feeling of discomfort, urgency and frequency. These symptoms have been referred to as catheter related bladder discomfort (CRBD) which can continue in the postoperative period. The incidence of CRBD has been reported to be 40-80% 1-5. CRBD is strongly associated with bladder catheter size more than 18 Fr, male gender and patients undergoing TURBT. 1, 6 Mild CRBD is tolerable in most of the patients but moderate to severe CRBD can be distressing in the postoperative period impacting Abstract Background: Male patients undergoing transurethral resections of bladder tumor (TURBT) commonly suffer from catheter related bladder discomfort (CRBD). Here, the effect of intravenous lidocaine and intravenous ketamine were evaluated and compared in male patients undergoing TURBT. Methods: 130 male patients of age group 18-65 years were randomly allocated to receive intravenous lidocaine (1.5mg/kg bolus followed by 2 mg/kg/hr infusion) and intravenous ketamine (0.5 mg/kg bolus followed by 0.25 mg/kg/hr infusion) during the intraoperative period, which were discontinued once the patient was shifted to recovery room. The primary outcome evaluated was incidence of moderate to severe CRBD at 0 hr post surgery, analysed using the Fischer’s exact test. The secondary outcome was opioid requirement in the 24 hour postoperative period and severity of CRBD at 1, 2, 6 and 24 hrs post surgery, postoperative pain, side effects of lidocaine and ketamine, rescue medications (tramadol and fentanyl) used and any other complications were also assessed. Results: There were no significant differences in incidence and severity of CRBD between the 2 groups. There was a significant reduction in incidence of postoperative pain at 1 hour interval in group B (1.52 ± 1.03 vs 1.17 ± 1.29; p-0.013). Opioid requirement, rescue medication use and drug related side effect did not differ significantly between the 2 groups. Conclusion: Pre emptive administration of lidocaine reduces incidence and severity of CRBD in early postoperative period, similar to ketamine. Keywords: catheter related bladder discomfort, ketamine, lidocaine, bladder catheterization. Anuja Pandit, MAR Oncology and Hematology (2025) 5:09. Page 3 of 12 Anuja Pandit. (2025). Lidocaine versus Ketamine for Prevention of Postoperative Catheter Related Bladder Discomfort in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomised Controlled Trial. MAR Oncology and Hematology. (2025) 5:09 the quality of postoperative care and may require additional analgesic therapy. Therefore appropriate management of CRBD is must to improve patient satisfaction and postoperative outcomes. CRBD is induced by involuntary contractions of the bladder smooth muscle due to activation of the bladder muscarinic receptors or inflammatory stimulation.7 Therefore a range of agents, such as anticholinergics, ketamine, tramadol have been evaluated in various studies for the prevention or treatment of CRBD.2 Despite availability of all these agents, there is a very little evidence of their usage for the treatment without side effects.8,9 Ketamine is known to interact with multiple binding sites, including NMDA and non-NMDA glutamine receptors, mono-aminogenic and opioid receptors, nicotinic and muscarinic cholinergic receptors. Theoretically, ketamine can reduce the contractile response of the smooth muscles by an effect on the central nervous system, the preganglionic fibres, the nicotinic receptors in the postsynaptic membrane of the intramural ganglion, the postsynaptic fibres, the muscarinic receptors, the chemical signal transmission between the receptors and the contractile elements, the contractile element or any combination above. Durieux demonstrated that clinically relevant concentration of ketamine profoundly inhibit muscarinic receptor signalling.10 Whereas intravenous lidocaine has got multifactorial pharmacological effects including analgesic, anticholinergic, anti-inflammatory and antihyperalgesic properties. Based on these considerations we hypothesized that intravenous lidocaine can reduce the incidence of moderate to severe CRBD. So, in this study we compared the role of intravenous ketamine and intravenous lidocaine for prevention of CRBD in patients undergoing TURBT. The study also notes the postoperative pain, rescue medications used, side effects of both the drugs and any complications during the surgery. Methods This was a prospective randomised trial registered prior to patients enrolment with Clinical trial registry India ICMR-NIMS (CTRI/2022/09/045172, date of registration – 2/09/2022) and was approved by All India Institute of Medical Sciences New Delhi institutional ethical committee. 130 consenting male patients of age group 18-65 yrs, ASA grade I & II undergoing TURBT were assessed for eligibility and included in the study after taking written informed consents. Patients were excluded from the study if there was delayed extubation, admission to intensive care unit, history of opium abuse or chronic pain, patient already catheterized, history of urinary tract obstruction requiring surgical intervention, history of neurological disorder, liver, heart disease, overactive bladder, and morbid obesity. The consort’s flow chart is depicted in the study (fig 1). Anuja Pandit, MAR Oncology and Hematology (2025) 5:09. Page 4 of 12 Anuja Pandit. (2025). Lidocaine versus Ketamine for Prevention of Postoperative Catheter Related Bladder Discomfort in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomised Controlled Trial. MAR Oncology and Hematology. (2025) 5:09 Fig 1 . CONSORT flow diagram of patients included in the study. Group A comprised patients who received intravenous ketamine. Group B comprised patients who received intravenous lidocaine. CONSORT indicates Consolidated standards of reporting trials. All the patients were educated about symptoms of CRBD a day prior to surgery. After shifting patient for surgery, NIBP, pulse oximetry, ECG, capnography, skin temperature probe, and BIS were applied to all patients. General anesthesia induction was performed with an injection of fentanyl 2mcg/kg, propofol 1.5 mg/kg, atracurium 0.5mg/kg. Once the patient was unconscious, laryngeal mask airway (LMA) was inserted and anesthesia was maintained using sevoflurane in an air/oxygen mixture and end tidal concentration of sevoflurane was adjusted to maintain a target BIS value of 40-60 and appropriate vital signs. The lidocaine and ketamine dose regime was determined based on the previous study with some modifications. In group A intravenous bolus of ketamine 0.5mg/kg just prior to induction followed by infusion of ketamine at 0.25 mg/kg/h. In group B intravenous bolus of 2% lidocaine 1.5 mg/kg just prior to induction followed by 2mg/kg/hr infusion was used. To reverse neuromuscular blockade, neostigmine 0.04 mg/kg and glycopyrrolate Anuja Pandit, MAR Oncology and Hematology (2025) 5:09. Page 5 of 12 Anuja Pandit. (2025). Lidocaine versus Ketamine for Prevention of Postoperative Catheter Related Bladder Discomfort in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomised Controlled Trial. MAR Oncology and Hematology. (2025) 5:09 8mcg/kg were administered. At the end of surgery Urinary catheter more than 20 Fr was inserted and balloon was inflated with 10 ml distilled water. A 2% lidocaine gel was used to lubricate the catheter. Normal saline was infused continuously through the urinary catheter to irrigate the bladder. After confirming that the patient is fully conscious and recovered from neuromuscular blockade, Laryngeal mask airway was removed and patient was shifted to Postoperative care unit. In Postoperative care unit, Inj. paracetamol 1 gm was administered as rescue analgesic and inj. fentanyl was given to patients complaining of pain NRS>4 and inj. tramadol 50 mg was given to the patient complaining of moderate to severe CRBD at any point of time .If patient complained of both postoperative pain with NRS >4 and moderate-severe CRBD simultaneously then either tramadol or fentanyl was administered according to the more significant complaint. The patient was reassessed after 15 minutes. The same analgesic protocol was maintained in ward. The severity of CRBD was recorded at 0, 1, 2, 6 and 24 hrs with none as no complaint, mild as reported by patient only when asked, moderate as reported by patients independently and severe as reported by patients with behavioral response such as flailing limbs, strong vocal response, and attempts to pull out catheter.2 Postoperative pain was also evaluated at 0, 1, 2, 6 and 24 hr with a Numerical rating scale (NRS) in which 0 is no pain and 10 is worst pain. Additionally Postoperative sedation was evaluated with Ramsay sedation scale11 along with postoperative nausea vomiting, hallucinations, diplopia, respiratory depression, cardiovascular depression and seizures. The duration of surgery and rescue medications (fentanyl or tramadol) used were also recorded. All the evaluations were recorded by blinded anaesthesiologist in post operative care unit. Statistical analysis The study of Reza, et al observed that incidence of CRBD at 0 hour was 38.60% and at 1 hour was 22.81% in Ketamine group. Taking these values as reference and assuming difference of 25% in incidence of CRBD between Ketamine and Lidocaine, the minimum required sample size with 80% power of study and 5% level of significance is 59 patients in each study group. To reduce margin of error, total sample size taken was 130 (65 patients per group). Formula used was:- n>=((pc*(1-pc)+pe*(1-pe))*(Zα + Zβ)2)/(pc-pe)2 with pc= incidence of CRBD in Ketamine group pe= incidence of CRBD in Lidocaine group Anuja Pandit, MAR Oncology and Hematology (2025) 5:09. Page 6 of 12 Anuja Pandit. (2025). Lidocaine versus Ketamine for Prevention of Postoperative Catheter Related Bladder Discomfort in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomised Controlled Trial. MAR Oncology and Hematology. (2025) 5:09 Where Zα is value of Z at two sided alpha error of 5% and Zβ is value of Z at power of 80% .Categorical variables were presented in number and percentage (%) and continuous variables was presented as mean ± SD and median. Normality of data was tested by Kolmogorov-Smirnov test. The data normality was checked by using Kolmogorov-Smirnov test. The cases in which the data was not normal, we used non parametric tests. The comparison of the variables which were quantitative and not normally distributed in nature were analysed using Mann-Whitney Test and variables which were quantitative and normally distributed in nature were analysed using Independent t test. The comparison of the variables which were qualitative in nature were analysed using Chi-Square test. If any cell had an expected value of less than 5 then Fisher’s exact test was used. The data entry was done in the Microsoft EXCEL spreadsheet and the final analysis was done with the use of Statistical Package for Social Sciences (SPSS) software, IBM manufacturer, Chicago, USA, version 25.0.Randomization was done with block randomization with sealed envelope system:- In this, we prepared ten randomly generated treatment allocations within sealed opaque envelopes assigning A and B in 5 envelopes each, where A represents ketamine group and B represents lidocaine group. Once a patient consented to enter a trial an envelope was opened and the patient was then offered the allocated group. Hence, patients were randomized in a series of blocks of ten. Results Initially 65 patients were allocated in each group but in group B there was one drop out as the patient was shifted to Intensive care unit. The 2 groups did not have significant differences in anthropometric baseline characteristics (Table 1). Duration of surgery was similar in both the groups (P>0.05; Table 1) but the groups were not similar on the basis of age (P<0.05). In post operative care unit, incidence and severity of CRBD were similar in both the groups at 0, 1, 2, 6 and 24 hours (P>0.05; Table 2,fig 2) There was significant reduction in incidence of pain at 1 hour interval in group B when compared to group A. (P-0.013, Table 3) Incidence of sedation was 1.56% in group B and 0% in group A (P>0.05). Incidence of PONV was similar in both the groups. 5 patients in group A and 6 patients in group B received fentanyl for relief of pain; this difference was not statistically significant. None of the patient in either group had respiratory depression, seizures, delayed extubation and local anesthetic systemic toxicity. Hallucinations were seen in one of the patient in group A, but it resolved without any need for intervention at the 1-hour visit. (Table 4) Anuja Pandit, MAR Oncology and Hematology (2025) 5:09. Page 7 of 12 Anuja Pandit. (2025). Lidocaine versus Ketamine for Prevention of Postoperative Catheter Related Bladder Discomfort in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomised Controlled Trial. MAR Oncology and Hematology. (2025) 5:09 Table 1. Age, Anthropometric characteristics of the patients, and surgery duration between group A and B Group A Group B P value Age (yr) (mean±SD) 52.15 ± 9.82 56.03 ± 8.94 0.021 Weight (kg) (mean±SD) 62.8 ± 11.04 62.62 ± 8.51 0.92 BMI (kg/m2) (mean±SD) 23.01 ± 3.15 23.19 ± 2.52 0.73 Height (m) (mean±SD) 1.65 ± 0.07 1.64 ± 0.05 0.52 Surgery duration (min) (mean±SD) 57.25 ± 42.17 56.97 ± 36.28 0.81 Table 2. Comparison of CRBD between group A and B. CRBD Group A(n=65) Group B(n=64) Total P value At 0 hour None 46 (70.77%) 43 (67.19%) 89 (68.99%) 0.927 Mild 11 (16.92%) 11 (17.19%) 22 (17.05%) Moderate 7 (10.77%) 9 (14.06%) 16 (12.40%) Severe 1 (1.54%) 1 (1.56%) 2 (1.55%) At 1 hour None 41 (63.08%) 45 (70.31%) 86 (66.67%) 0.337 Mild 16 (24.62%) 15 (23.44%) 31 (24.03%) Moderate 8 (12.31%) 3 (4.69%) 11 (8.53%) Severe 0 (0%) 1 (1.56%) 1 (0.78%) At 2 hours None 49 (75.38%) 51 (79.69%) 100 (77.52%) 0.869 Mild 14 (21.54%) 11 (17.19%) 25 (19.38%) Moderate 2 (3.08%) 2 (3.13%) 4 (3.10%) At 6 hours None 62 (95.38%) 63 (98.44%) 125 (96.90%) 0.619 Mild 3 (4.62%) 1 (1.56%) 4 (3.10%) At 24 hours None 65 (100%) 64 (100%) 129 (100%) NA Table 3. Comparison of pain between group A and B. Pain Group A(n=65) Group B(n=64) Total P value At 0 hour Mean ± SD 1.77 ± 1.13 2.05 ± 1.1 1.91 ± 1.12 0.193 Median(25th75th percentile) 2(1-2) 2(1-2) 2(1-2) Range 0-6 1-7 0-7 At 1 hour Mean ± SD 1.52 ± 1.03 1.17 ± 1.29 1.35 ± 1.18 0.013 Anuja Pandit, MAR Oncology and Hematology (2025) 5:09. Page 8 of 12 Anuja Pandit. (2025). Lidocaine versus Ketamine for Prevention of Postoperative Catheter Related Bladder Discomfort in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomised Controlled Trial. MAR Oncology and Hematology. (2025) 5:09 Median(25th75th percentile) 2(1-2) 1(0-2) 1(0-2) Range 0-5 0-5 0-5 At 2 hours Mean ± SD 1.06 ± 1.04 0.83 ± 1.05 0.95 ± 1.05 0.064 Median(25th75th percentile) 1(0-1) 1(0-1) 1(0-1) Range 0-5 0-5 0-5 At 6 hours Mean ± SD 0.34 ± 0.57 0.3 ± 0.46 0.32 ± 0.52 0.91 Median(25th75th percentile) 0(0-1) 0(0-1) 0(0-1) Range 0-2 0-1 0-2 At 24 hours Mean ± SD 0.06 ± 0.24 0.12 ± 0.33 0.09 ± 0.29 0.217 Median(25th75th percentile) 0(0-0) 0(0-0) 0(0-0) Range 0-1 0-1 0-1 Table 4. Comparison of adverse effects between group A and B. Adverse effects Group A(n=65) Group B(n=64) Total P value Post-operative nausea and vomiting 1 (1.54%) 0 (0%) 1 (0.78%) 1 Agitation 1 (1.54%) 2 (3.13%) 3 (2.33%) 0.619 Hallucination 1 (1.54%) 0 (0%) 1 (0.78%) 1 Respiratory depression 0 (0%) 0 (0%) 0 (0%) NA Delayed extubation 0 (0%) 0 (0%) 0 (0%) NA Hypotension/CVS depression 0 (0%) 2 (3.13%) 2 (1.55%) 0.244 Seizures 0 (0%) 0 (0%) 0 (0%) NA LAST 0 (0%) 0 (0%) 0 (0%) NA Anuja Pandit, MAR Oncology and Hematology (2025) 5:09. Page 9 of 12 Anuja Pandit. (2025). Lidocaine versus Ketamine for Prevention of Postoperative Catheter Related Bladder Discomfort in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomised Controlled Trial. MAR Oncology and Hematology. (2025) 5:09 Fig 2. Comparison of catheter related bladder discomfort at 0, 1, 2, 6 and 24 hours between group A and B Discussion Patients undergoing intra operative urinary catheterisation often complains of CRBD. These symptoms are very similar to symptoms of overactive bladder which might be due to involuntary contractions of bladder wall smooth muscles mediated by muscarinic receptors.9 Durieux and Rainer suggested that clinically relevant concentrations of ketamine profoundly inhibit muscarinic receptor signaling.10, 11 They also showed ketamine’s effect as evidenced by reduced incidence and severity of CRBD. Several studies support the preemptive analgesic effects of ketamine while some show no benefit.12-16 Another mechanism underlying the development of CRBD is local inflammation with release of prostaglandins due to mucosal damage during urinary catheterisation.17 Lidocaine due to its action on sodium channel, muscarinic and NMDA receptors and nociceptive transmission pathways has significant antimuscarinic and antiinflammatory properties. 18 As evidenced by the results of our study lidocaine reduced the incidence of moderate to severe CRBD to the similar extent as ketamine. Also, there was no evidence of lidocaine related side effects. Previous studies have shown that lidocaine has a significant inhibitory effect on muscarinic receptors, along with suppression of immune cell–mediated inflammatory reactions.19, 20 In addition, lidocaine has shown antihyperalgesic effects in patiens undergoing laparoscopic nephrectomy.21, 22