|Year : 2018 | Volume
| Issue : 6 | Page : 461-465
Efficacy and safety of Parecoxib for prevention of catheter-related bladder discomfort in patients undergoing transurethral resection of bladder tumor: Prospective randomised trial
Ali Jendoubi1, Wafa Aissi2, Ahmed Abbes1, Abderrazek Bouzouita3, Sami Fourati1, Hatem Necib1, Salma Ghedira1, Mohamed Houissa1
1 Department of Anaesthesia and Intensive Care, Faculty of Medicine of Tunis, Charles Nicolle Hospital of Tunis, University of Tunis El Manar, Tunis, Tunisia
2 Department of Medical Epidemiology, Pasteur Institute of Tunis, Tunis, Tunisia
3 Department of Urology, Faculty of Medicine of Tunis, Charles Nicolle Hospital of Tunis, University of Tunis El Manar, Tunis, Tunisia
|Date of Web Publication||11-Jun-2018|
Dr. Ali Jendoubi
Department of Anaesthesia and Intensive Care, Faculty of Medicine of Tunis, Charles Nicolle Hospital of Tunis, University of Tunis El Manar, Tunis
Source of Support: None, Conflict of Interest: None
Background and Aims: Catheter-related bladder discomfort (CRBD) is the urge to void or discomfort in the suprapubic region secondary to an indwelling urinary catheter. We aimed to evaluate the safety and efficacy of single-dose of intravenous parecoxib in reducing the incidence and severity of CRBD in patients undergoing transurethral resection of bladder tumor (TURBT). Methods: Sixty-one adult patients, American Society of Anesthesiologists physical status I or II, undergoing elective TURBT under spinal anaesthesia, were randomly allocated to receive 40 mg of IV parecoxib (group P; n = 29) or an equal volume of normal saline (control group C; n = 32). CRBD was graded as none, mild, moderate, and severe. Between-group comparisons were made for the incidence and severity of CRBD, postoperative Visual analog scales (VAS), rescue analgesia equirements, and occurrence of adverse events. Statistical analysis done with the Mann–Whitney U-test and Fisher's Exact Test. A P value of ≤ 0.05 was considered statistically significant. Results: Parecoxib significantly reduced the incidence and severity of CRBD at 2, 4, 6, and 12 hours postoperatively compared to placebo (P < 0.05). Median pain VAS scores were lower in the P group at all times except the first hour. Rescue analgesia was given to more patients in group C (16/32, 50%) than in group P (1/29) (P < 0.001). None of the patients who received parecoxib experienced an adverse event. Conclusion: A single intravenous injection of parecoxib is safe and effective in decreasing the incidence and severity of CRBD in patients undergoing TURBT. Trial Registration Identifier: NCT02729935(www.clinicaltrials.gov).
Keywords: Analgesia, catheter-related bladder discomfort, intravenous parecoxib, transurethral resection of bladder tumor
|How to cite this article:|
Jendoubi A, Aissi W, Abbes A, Bouzouita A, Fourati S, Necib H, Ghedira S, Houissa M. Efficacy and safety of Parecoxib for prevention of catheter-related bladder discomfort in patients undergoing transurethral resection of bladder tumor: Prospective randomised trial. Indian J Anaesth 2018;62:461-5
|How to cite this URL:|
Jendoubi A, Aissi W, Abbes A, Bouzouita A, Fourati S, Necib H, Ghedira S, Houissa M. Efficacy and safety of Parecoxib for prevention of catheter-related bladder discomfort in patients undergoing transurethral resection of bladder tumor: Prospective randomised trial. Indian J Anaesth [serial online] 2018 [cited 2018 Sep 20];62:461-5. Available from: http://www.ijaweb.org/text.asp?2018/62/6/461/234010
| Introduction|| |
Catheter-related bladder discomfort (CRBD) is defined as an urge to void or discomfort in the suprapubic region reported postoperatively in patients who have had urinary catheterization intraoperatively. It is characterized by a sensation of frequent and urgent urination, which is similar to overactive bladder syndrome. In the post-anaesthesia care unit (PACU), CRBD is one of the risk factors for the occurrence of emergence agitation.
Various muscarinic receptor antagonists including ketamine, tolterodine, tramadol, and butylscopolamine have been evaluated for their ability to prevent the CRBD. However, they induce side effects such as dry mouth, sedation, nausea, and vomiting.,,
Parecoxib sodium is an injectable cyclooxygenase-2 (COX-2) selective inhibitor often administered for the management of postoperative pain in adults and is generally well tolerated.,
Clinically, the effects of parecoxib on CRBD prevention have not been studied. We hypothesised that parecoxib could reduce the incidence of postoperative CRBD.
In the present study, we evaluated parecoxib for preventing CRBD in patients undergoing catheterization after transurethral resection of bladder tumor (TURBT).
| Methods|| |
After approval of the Institutional Ethics Committee and written informed consent, 61 patients undergoing elective TURBT were included in this prospective, randomised, double-blind study. The trial was registered at ClinicalTrials.gov (NCT 02729935).
Inclusion criteria were age ≥18 years and the American Society of Anesthesiologists (ASA) physical status I or II. Patients with cardiac, pulmonary, hepatic, or renal disease and those with a history of alcohol or other substance abuse were excluded.
The day before the surgery patients were instructed to the use of the visual analog scale (VAS; ranging from 0 cm = no pain to 10 cm = worst possible pain). We also educated patients concerning the symptoms of CRBD. No patient received premedication.
On arrival to the operating room, monitoring was performed using 5-lead electrocardiography, noninvasive blood pressure measurement, and pulse oximetry. Intravenous access was secured on the dorsum of the hand with an18-gauge cannula and patients were preloaded with 500 ml of 0.9% normal saline.
Patients were randomised using the sealed envelope method in a rater-blind manner to receive either parecoxib or placebo. For randomization, we referred to a random number table, with sequentially numbered, opaque, sealed envelopes used to conceal the allocation sequence. On the morning of surgery and before induction of anaesthesia, a “blinded” nurse prepared the study solutions. None of the other investigators involved in patient management or data collection were aware of the group assignment. Patients in group P were administered parecoxib sodium (Dynastat®, Pfizer Pharmaceutical) 40 mg (2 ml) intravenously (IV) 30min before spinal anaesthesia. Patients in group C were considered as placebo group and received an equal volume (2 ml) of normal saline 0.9%.
Lumbar subarachnoid block was administered with 2 ml 0.5% hyperbaric bupivacaine and 2.5 μg sufentanil. The need of additional intraoperative sedation (an IV bolus of Midazolam 1 mg) was recorded. At the end of the surgery, urinary catheterization was performed with a 16-Fr Foley's catheter, and the balloon was inflated with 10 ml of 0.9% NaCl. The catheter was fixed with an adhesive tape without any traction on the urethra. The bladder was continuously irrigated through the urinary catheter with normal saline. The Foley catheter was removed 24 h postoperatively.
The primary endpoint was the incidence of postoperative CRBD. Predefined secondary end points included the severity of CRBD, postoperative VAS pain scores, rescue analgesia requirements, and occurrence of adverse events.
CRBD was evaluated with a 4-point scale (1: no discomfort, 2: mild, revealed on questioning only, 3: moderate, stated by the patient without questioning, 4: severe, urinary urgency executed by behavioral responses, such as attempts to remove urinary catheter, restless extremity movements, verbal responses) 30 minutes and 1, 2, 4, 6, and 12 hours postoperatively.
In the PACU, additional postoperative analgesia was provided in the two groups by the combination of 1 g paracetamol IV (Perfalgan®, Bristol-Myers Squibb, Rueil-Malmaison, France) and 20 mg nefopam IV (Acupan®, Biocodex, Gentilly, France) in cases of severe and intolerant CRBD or VAS pain score >3. Good pain relief was defined as VAS score ≤3. Both rescue analgesics were administered on demand and recorded.
Adverse events were assessed using yes/no questions (Postoperative nausea and vomiting PONV, constipation, dizziness), vital signs (blood pressure, heart rate, oxygen saturation) were measured, and blood samples (haemoglobin, platelet count, and serum creatinine measured at baseline and 24 h postoperatively) were collected. Blood loss was evaluated in terms of reduction in the serum haemoglobin level: delta haemoglobin defined as the difference between the preoperative haemoglobin level (Hb H0) and the haemoglobin level on first postoperative day 1 (Hb H24).
A previous study reported that approximately 60% of patients complained of CRBD due to an indwelling urinary catheter. Assuming that this incidence would decrease to 20% after treatment, we calculated that a sample size of 50 patients (25 per group) would be needed to achieve 80% power with a two-sided type 1 error rate of 5%. We added 10 patients because we expected that 20% of all participants will be lost to follow-up or will drop out of the study.
Continuous variables were compared between the two groups using Mann–Whitney test. Incidence and severity of CRBD were compared by Fisher's exact test. P< 0.05 was considered statistically significant. Statistical analyses were performed using STATA version 11.0 software (Stata Corp., College Station, TX, USA).
| Results|| |
Sixty-one patients were selected and all patients completed the present study for the final analysis. Therefore, a total of 61 patients (control group = 32, parecoxib group = 29) were assessed in this study [Figure 1]. The two groups were comparable with respect to demographic data, ASA physical status, duration of surgery, and the duration of motor block [Table 1]. No additional intraoperative sedation and no systemic anaesthetic agents were required.
The incidence of CRBD was significantly lower in the parecoxib group than in the control group at 2, 4, 6, and 12 hours postoperatively [Table 2]. The number of patients who experienced moderate discomfort was significantly lower in group P compared with group C at 2, 4, 6, and 12 hours (P< 0.05). None of the patients in parecoxib group had severe discomfort [Table 2].
|Table 2: Bladder discomfort, severity of pain and rescue analgesia requirements|
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Median pain VAS scores were lower in the parecoxib group than in the control group at all times except the first hour [Table 2].
In group P, only one patient required rescue analgesia, whereas in group C, 16 patients needed additional doses of paracetamol and nefopam [Table 2].
None of the patients who received parecoxib experienced an adverse event. The heart rate and blood pressure were comparable among groups during the postoperative period. There were no significant differences between the two groups in terms of serum creatinine levels and perioperative blood loss estimated by the delta haemoglobin (preoperative haemoglobin H0 –haemoglobin on postoperative day 1)[Table 3].
| Discussion|| |
We observed a significant reduction in the incidence and severity of CRBD in patients treated with parecoxib (P< 0.05). Our study also indicated that 50% of patients who were given saline required rescue analgesia after TURBT in the PACU.
TURBT is associated with a higher risk of CRBD compared with percutaneous nephrolithotomy and non-urologic surgery. In our study, the incidence of CRBD was 60% in the control group. Several factors could explain this high incidence in our series –the predominance of male patients who have a longer urethra than female patients, the cumulative effects of large-sized Foley catheter, resection of the bladder wall, and postoperative continuous bladder irrigation.
CRBD is an extremely distressing condition and interferes with the quality of recovery. Muscarinic receptor activation is the major mechanism in CRBD development. As it has already been reported, most anti-muscarinic agents have significant side-effects, especially in the elderly.,,, Other molecules, including analgesics (Paracetamol), antiepileptic agents (Gabapentin), and recently anaesthetics (Sevoflurane) were found to be effective in reducing the incidence and the severity of CRBD compared with placebo.
Recently, another mechanism of CRBD was found to be mediated by increased urinary levels of PGE2. The presence of urinary catheter and the mucosal layer damage could trigger local inflammation with increased activation of cyclooxygenase-2 (COX-2) enzyme and release of prostaglandin E2.,,,
Considering this possible mechanism of CRBD, we hypothesised that the use of parecoxib, a highly selective COX-2 inhibitor, would improve the symptoms of CRBD. Parecoxib is a selective COX-2 NSAID, which is widely used for postoperative analgesia. It acts by reducing the surrounding inflammatory response, regulating nociceptors, and attenuating central sensitization. It is an injectable inactive prodrug of valdecoxib. Regarding the pharmacokinetic properties, parecoxib had a rapid onset of action within 10–15 min and reached its maximum concentration around 30 min after administration. Pain is usually well controlled within 2 h after injection and the analgesic effect persisted for about 6–12 hours., Parecoxib is recommended for controlling postoperative pain in a variety of surgery types, including gynecologic and orthopedic procedures.,, However, there is a gap in the literature regarding the use of parecoxib sodium in bladder discomfort.
In our study, parecoxib sodium was administered before the resection because it has been shown that NSAIDS can inhibit the activation of nociceptors due to tissue damage.
Regarding adverse events, parecoxib appears to be safe with some minor adverse effects such as haemodynamic changes associated with its administration. However, these adverse effects were not observed in our study. No other serious adverse events, such as renal dysfunction or increased perioperative bleeding, were observed during the trial period.
Parecoxib tolerability can be explained by the fact the parecoxib sodium does not interfere with platelet aggregation compared to other non-selective NSAIDS. Patients at risk of worsening of renal function and with severe renal impairment (creatinine clearance <30 ml/min) were not included in our study. Adverse renal effects increased with greater dose and duration of parecoxib administration, which is not the case with our study protocol.
The limitations of this study include its single center design and the possibility of misperception between CRBD and suprapubic pain despite preoperative education. A standard dose (40 mg) was given to all patients, and we did not evaluate the effects of parecoxib with different doses.
| Conclusion|| |
In conclusion, we suggest that a single intravenous injection of parecoxib sodium 40 mg is safe and effective in decreasing the incidence and severity of CRBD in patients undergoing TURBT.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Binhas M, Motamed C, Hawajri N, Yiou R, Marty J. Predictors of catheter-related bladder discomfort in the postanaesthesia care unit. Ann Fr Anesth Reanim 2011;30:122-5.
Kim HC, Kim E, Jeon YT, Hwang JW, Lim YJ, Seo JH. Postanaesthetic emergence agitation in adult patients after general anaesthesia for urological surgery. J Int Med Res 2015;43:226-35.
Agarwal A, Raza M, Singhal V, Dhiraaj S, Kapoor R, Srivastava A,et al
. The efficacy of tolterodine for prevention of catheter-related bladder discomfort: A prospective, randomized, placebo-controlled, double-blind study. Anesth Analg 2005;101:1065-7.
Agarwal A, Gupta D, Kumar M, Dhiraaj S, Tandon M, Singh PK. Ketamine for treatment of catheter related bladder discomfort: A prospective, randomized, placebo controlled and double blind study. Br J Anaesth 2006;96:587-9.
Hu B, Li C, Pan M, Zhong M, Cao Y, Zhang N,et al
. Strategies for the prevention of catheter-related bladder discomfort: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 2016;95:e4859.
Papadima A, Lagoudianakis EE, Antonakis PT, Pattas M, Kremastinou F, Katergiannakis V,et al
. Parecoxib vs. lornoxicam in the treatment of postoperative pain after laparoscopic cholecystectomy: A prospective randomized placebo-controlled trial. Eur J Anaesthesiol 2007;24:154-8.
Wei W, Zhao T, Li Y. Efficacy and safety of parecoxib sodium for acute postoperative pain: A meta-analysis. Exp Ther Med 2013;6:525-31.
Agarwal A, Dhiraaj S, Singhal V, Kapoor R, Tandon M. Comparison of efficacy of oxybutynin and tolterodine for prevention of catheter-related bladder discomfort: A prospective, randomized, placebo-controlled, double-blind study. Br J Anaesth 2006;96:377-80.
Bai Y, Wang X, Li X, Pu C, Yuan H, Tang Y,et al
. Management of catheter-related bladder discomfort in patients who underwent elective surgery. J Endourol 2015;29:640-9.
Agarwal A, Yadav G, Gupta D, Singh PK, Singh U. Evaluation of intra-operative tramadol for prevention of catheter-related bladder discomfort: A prospective, randomized, double-blind study. Br J Anaesth 2008;101:506-10.
Ryu JH, Hwang JW, Lee JW, Seo JH, Park HP, Oh AY,et al
. Efficacy of butylscopolamine for the treatment of catheter-related bladder discomfort: A prospective, randomized, placebo-controlled, double-blind study. Br J Anaesth 2013;111:932-7.
Ergenoglu P, Akin S, Yalcin Cok O, Eker E, Kuzgunbay B, Turunc T,et al
. Effect of intraoperative paracetamol on catheter-related bladder discomfort: A prospective, randomized, double-blind study. Curr Ther Res Clin Exp 2012;73:186-94.
Bala I, Bharti N, Chaubey VK, Mandal AK. Bala I, Efficacy of gabapentin for prevention of postoperative catheter related bladder discomfort in patients undergoing transurethral resection of bladder tumor. Urology 2012;79:853-7.
Kim HC, Park HP, Lee J, Jeong MH, Lee KH. Sevoflurane vs. propofol in post-operative catheter-related bladder discomfort: A prospective randomized study. Acta Anaesthesiol Scand 2017;61:773-80.
Kim JC, Park EY, Seo SI, Park YH, Hwang TK. Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder. J Urol 2006;175:1773-6.
Kim JC, Park EY, Hong SH, Seo SI, Park YH, Hwang TK. Changes of urinary nerve growth factor and prostaglandins in male patients with overactive bladder symptom. Int J Urol 2005;12:875-80.
Aoki K, Hirayama A, Tanaka N. A higher level of prostaglandin E2 in the urinary bladder in young boys and boys with lower urinary tract obstruction. Biomed Res 2009;30:343-7.
Andersson KE. Detrusor myocyte activity and afferent signaling. Neurourol Urodyn 2010;29:97-106.
Reuben SS. Update on the role of nonsteroidal anti-inflammatory drugs and coxibs in the management of acute pain. Curr Opin Anaesthesiol 2007;20:440-50.
Cheer SM, Goa KL. Parecoxib (Parecoxib sodium). Drugs 2001;61:1133-41.
Simon LS. Are the biologic and clinical effects of the COX-2-specific inhibitors an advance compared with the effects of traditional NSAIDs? Curr Opin Rheumatol 2000;12:163-70.
Snabes MC, Jakimiuk AJ, Kotarski J, Katz TK, Brown MT, Verburg KM. Parecoxib sodium administered over several days reduces pain after gynecologic surgery via laparotomy. J Clin Anesth 2007;19:448-55.
Hubbard RC, Naumann TM, Traylor L, Dhadda S. Parecoxib sodium has opioid-sparing effects in patients undergoing total knee arthroplasty under spinal anaesthesia. Br J Anaesth 2003;90:166-72.
Malan TP, Jr, Marsh G, Hakki SI, Grossman E, Traylor L, Hubbard RC. Parecoxib sodium, a parenteral cyclooxygenase 2 selective inhibitor, improves morphine analgesia and is opioid-sparing following total hip arthroplasty. Anesthesiology 2003;98:950-6.
Campbell WI, Kendrick R, Patterson C. Intravenous diclofenac sodium. Does its administration before operation suppress postoperative pain? Anaesthesia 1990;45:763-6.
Zhan J, Ding EL, Song Y. Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: Meta-analysis of randomized trials. JAMA 2006;296:1619.
Graff J, Arabmotlagh M, Cheung R, Geisslinger G, Harder S. Effects of parecoxib and dipyrone on platelet aggregation in patients undergoing meniscectomy: A double-blind, randomized, parallel-group study. Clin Ther 2007;29:438-47.
Zhang J, Ding EL, Song Y. Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: Meta-analysis of randomized trials. JAMA 2006;296:1619-32.
[Table 1], [Table 2], [Table 3]