Objective
We sought to determine if phenazopyridine improves pain in catheterized patients recovering from gynecologic surgery.
Study Design
This trial randomized 240 adult women, who were undergoing gynecologic surgery and requiring an indwelling Foley catheter, to placebo or phenazopyridine hydrocholoride. Group assignment was masked by instillation of orange dye in the Foley bag of both groups. The primary outcome was the mean postoperative visual analog score (VAS). Secondary outcomes were pain medicine utilization and blinding efficacy.
Results
In all, 219 patients received study medications (112 phenazopyridine and 107 placebo). There was no significant difference in demographics, procedure type, bladder VAS, overall VAS, and pain medication use. Only 25 of the 45 participants who responded guessed their group assignment correctly, suggesting adequate blinding.
Conclusion
Postoperative VAS scores and pain medicine usage did not change with using routine phenazopyridine following gynecology surgery. Colored dye adequately masks visual side effects of phenazopyridine.
Indwelling bladder catheters are commonly used after pelvic surgery to avoid bladder distension and bladder-related pain, and to allow urine output assessment. Catheterization produces bladder irritation whose symptoms are similar to the symptoms of an overactive bladder caused by involuntary contractions of the bladder mediated by muscarinic receptors. This catheter-related bladder discomfort may exacerbate postoperative pain because of the presence of adjacent surgical wound.
Techniques to relieve catheter-related discomfort have not received much study. Tauzin-Fin et al demonstrated the use of muscarinic receptor antagonists in patients who had undergone a radical prostatectomy and reported a reduction in postoperative bladder discomfort along with overall visual analog score (VAS), and produced lower pain medicine requirements. In contrast, Frishman et al conducted a prospective randomized double-blinded clinical trial comparing a single dose of phenazopyridine to placebo prior to embryo transfer in vitro fertilization in which the embryo transfer procedure requires a full bladder. The mean VAS scores were not significantly different between the 2 groups.
As a commonly used clinical urinary analgesic, phenazopyridine hydrochloride is an azo dye that exerts local anesthetic or analgesic action on urinary tract mucosa through an unknown mechanism and causes a visible orange color to the urine. Given the commonality of catheter usage associated with subjective bladder discomfort in our patient population, we proposed a randomized clinical trial to determine whether routine phenazopyridine reduces catheter-related bladder discomfort as well as pain medicine usage in women undergoing gynecologic surgery requiring an indwelling Foley catheter. We also sought to prove that a novel blinding technique, colored dye, could be implemented to enhance masking of group assignment.
Materials and Methods
This institutional review board–approved, randomized trial was registered at clinicaltrials.gov ( NCT00771173 ) prior to the date enrollment commenced. Participants were enrolled from September 2008 through December 2009 at the 2 Loyola system hospitals: Loyola University Medical Center and Loyola at Gottlieb Hospital. Eligible candidates were adult women undergoing gynecologic surgery who were expected to require an indwelling catheter for a minimum of 12 postoperative hours and who were expected to tolerate oral medication within 12 postoperative hours. Exclusion criteria included hypersensitivity to phenazopyridine products, known contraindications to phenazopyridine such as renal or hepatic failure, simultaneous suprapubic catheterization, anticipated inability to take oral medication within 12 hours after surgery, and known pregnancy. Surgical procedure type was also recorded. To convey the mix of cases, we categorized the procedures broadly as laparoscopic, abdominal, and vaginal and these were expected to be equally distributed after randomization. Final eligibility of enrollees was assessed prior to randomization to exclude patients with intraoperative urologic injury.
Enrolled participants who remained eligible following surgery were randomized (1:1) to receive either phenazopyridine 200 mg every 8 hours by mouth or placebo while the Foley catheter was in place or for 24 hours postoperatively, whichever came first. Group assignments were known to only the research pharmacist who randomized subjects once an order for the study drug had been placed by the investigator. Randomization was done using sequentially numbered opaque envelopes generated by a randomized block permutation. Orange dye was instilled in the Foley bag of both groups in the operating suite prior to patient’s extubation to mask group assignment, as phenazopyridine is known to color the urine dark orange. Surgical pain was clinically treated by the patient’s attending physician and residents without standardization.
The primary outcome was the mean VAS measurements during the postoperative period. The scores were collected by nurses, residents, and members of the anesthesia team and were extracted from the electronic medical record. The sample size was determined a priori to ensure 80% power to detect a clinically relevant difference of 19% using the Pearson χ 2 test using a .05 alpha level. The reason we used 19% as a clinically relevant difference was based on the results of the prior series by Tauzin-Fin et al and Frishman et al. This was calculated to give us adequate power for our anticipated withdraw of approximately 50 patients and yielded us an even study number of 240 patients. Randomized participants who did not have at least 1 postoperative VAS score were not included in the analysis.
Secondary outcomes were pain medicine utilization, both narcotic and nonnarcotic, as well as assessments of blinding efficacy. Pain medicine use was also quantified by the electronic medical record. Blinding efficacy was assessed by asking participants a series of standardized questions at the postoperative check. In addition to the primary VAS scores that were recorded by nursing staff per Joint Commission on Accreditation of Healthcare Organizations protocol, we also collected bladder-specific VAS scores that were collected by the house staff at the postoperative check. At this time we also asked if they knew whether they were in the medication or placebo arm.
Results
In all, 258 women were enrolled, 240 were randomized, and 219 received study medications (112 phenazopyridine and 107 placebo). The Figure represents the flow of subjects through this study. Demographic data and surgery type are presented in Table 1 . The groups were similar in age and race; most participants (80%) were Caucasian, with a mean age of 55 years. The groups were also similar with respect to surgical type: abdominal procedures (83%), laparoscopic procedures (35%), and vaginal surgery (20%). For analytical purposes, patients who underwent a laparoscopic procedure were categorized to both a laparoscopic group as well as the abdominal group. Our heterogeneous study population consisted of general gynecologic, urologic, and oncologic patients.
