Are there any alternatives to belladonna and opium suppositories for the treatment of bladder spasms before and after surgery?

What are recommended alternatives for Belladonna and Opium (B and O) suppositories?

Comment by InpharmD Researcher

There do not appear to be alternative suppositories other than belladonna/opium for use of bladder spasms/pain. Literature reports the use of antimuscarinic or antiepileptic agents for bladder spasms or catheter-related bladder discomfort; however, none of these agents are supplied as a suppository. Limited literature demonstrates successful use of IV ketorolac and oral solifenacin for prevention of bladder spasms (Tables 1 and 2, respectively); however, their use in place of belladonna/opium remains uncertain. Oxybutynin, trospium, dicyclomine, hyoscyamine, and tolterodine have been used as rescue medications for treatment of postoperative bladder spasms. Published studies claim that morphine 7.5-10.0 mg is equivalent to opium 60 mg but there was no cited evidence supporting these statements.

Background

A 2020 review discusses various agents for the management of catheter-related bladder discomfort (CRBD). Agents with antimuscarinic properties including solifenacin, darifenacin, oxybutynin, and tolterodine have been shown to improve CRBD in surgical patients. Additionally, antiepileptic agents including gabapentin and pregabalin have been observed to improve CRBD for extended periods of time in the hours following surgery. Available data shows intravesical injection of botulinum toxin (onabotulinumtoxinA) may help improve refractory bladder pain and catheter bypass leakage in patients with indwelling urethral or suprapubic catheters. The use of belladonna/opium is not discussed as a treatment option for CRBD, and the agents discussed may not be effective alternatives to belladonna/opium. Another review suggests oxybutynin, flavoxate, dicyclomine, hyoscyamine, and tolterodine can be used for the management of bladder spasms in patients with urinary catheters. Data for the use of these agents in the management of bladder spasms are not included, nor is there any mention of belladonna/opium. [1], [2]

A retrospective, observational study evaluated the use of medications and incidence of bladder spasms following ambulatory urologic procedures at a single institution in Minnesota. Of 2,671 patients who underwent a urologic intervention, 917 (34.3%) developed postoperative bladder spasm. Rescue medications used included oxybutynin (n= 814), trospium (n= 117), belladonna/opium suppository (n= 17), and diazepam (n= 16); forty-seven patients received more than one rescue antispasmodic. Belladonna/opium suppositories were used intraoperatively in 1,158 (43.4%) patients, but no significant protection against bladder spasms was found with the belladonna/opium use. Successful strategies to treat or prevent bladder spasm pain include neuraxial anesthesia, intravesical local anesthesia administration, transcutaneous electrical stimulation, opioids, ketorolac, and acetaminophen. Another effective treatment of bladder spasms is the early removal of urinary catheters when possible. Oral anticholinergics may also reduce urinary catheter bladder discomfort. [3]

A randomized controlled study for vaginal surgery mentioned that the observed dose strategy of belladonna/opium rectal suppository 16.2-60 mg administered once Q8H for a total of 3 doses over 24 hours (180 mg total dose of opium) is equivalent to 30 mg intravenous (IV) morphine (60 mg opium equivalent to 10 mg IV morphine). Another randomized trial for intravesical onabotulinium toxin A injection masked their belladonna/opium suppository by compounding new batches, claiming that morphine 7.5 mg is equivalent to 60 mg powdered opium in commercial suppository. There is a lack of data for the bioavailability of belladonna/opium suppository. A number of factors can affect the pharmacokinetics of rectally administered medications based on the form, placement, characteristics of suspension, drug, and the environment. Therefore, it is difficult to estimate the absorption of suppositories without conducting pharmacokinetic studies. [4], [5], [6]

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

What are recommended alternatives for Belladonna and Opium (B and O) suppositories?

Please see Tables 1-2 for your response.

Ketorolac or fentanyl continuous infusion for post-operative analgesia in children undergoing ureteroneocystostomy
Design	Prospective, randomized, blinded study N= 52
Objective	To compare the efficacy of a continuous infusion of ketorolac and fentanyl in post-operative analgesia and bladder spasm in children who underwent ureteroneocystostomy
Study Groups	Ketorolac (Group K; n= 26) Fentanyl (Group F; n= 26)
Inclusion Criteria	Children aged 1-5 years, scheduled for intravesical ureteroneocystostomy with primary vesicoureteral reflux
Exclusion Criteria	History of allergy to aspirin or NSAIDs, gastric ulcerative disease, coagulopathies, renal function impairment
Methods	Patients were randomized to receive ketorolac 83.3 mg/kg/h or fentanyl 0.17 mcg/kg/h for 48 h in 100 mL of normal saline (equianalgesic doses). Post-operative pain scores were assessed using the FLACC score (face, legs, activity, cry, consolability, five categories each scored 0–2) and the modified Children’s Hospital Eastern Ontario Pain Scale (mCHEOPS; cry, facial, verbal, torso, legs; with each category scored 0–2). If FLACC scores were > 4, mCHEOPS was > 5, or bladder spasm was suspected, intravenous (IV) tramadol 1 mg/kg was administered as a rescue analgesic. If patient-controlled anesthesia-induced nausea or vomiting was severe (scores > 3), the infusion was halted and rescue drugs were administered.
Duration	Follow-up: 48 hours after operation
Outcome Measures	Pain scores, analgesic requirements, incidence of bladder spasms
Baseline Characteristics		Fentanyl (n= 23)	Ketorolac (n= 24)
	Age, years	25.8	25.0
	Weight, kg	13.4	12.5
	Height, cm	89.1	86.3
	Anesthesia time, min	142.7	131.9
	Operation time, min	112.4	104.1
	Time to removal of urinary catheter, h	68.7	73.6
	Discharge time, days	3.6	3.7
Results	Endpoint	Fentanyl (n= 23)	Ketorolac (n= 24)
	Tramadol rescue < 24 h 24-48 h Total	13 (56.5%) 4 (17.4%) 15 (65.2%)	4 (16.7%)* 2 (8.3%) 5 (20.8%)*
	First rescue analgesic time, h < 24 h 24-48 h Total	- 1.9 ± 10.0 -	- 30.4 ± 17.3* -
	Bladder spasms < 24 h 24-48 h Total	5 (21.7%) 5 (24.7%) 7 (30.4%)	0* 1 (4.2%) 1 (4.2%)*
	Post-operative nausea and vomiting < 24 h 24-48 h Total	8 (34.8%) 1 (4.3%) 8 (34.8%)	5 (20.8%) 3 (12.5%) 5 (20.8%)
	Post-operative nausea and vomiting score > 3 at 24-48 h	5/8 (62.5%)	0/5
	Pain scores up to 48 hours post-operation were similar between groups. Pain score results were presented in graphs, with no further comparative statistics provided. *p< 0.05 vs. fentanyl
Adverse Events	No peripheral oxygen desaturation, somnolence, or pruritis was reported. No significant difference was reported between groups or compared to baseline for BUN and Cr levels one day after operation.
Study Author Conclusions	Ketorolac provided analgesic effects similar to those of fentanyl during post-operative 48 h in children who underwent intravesical ureteroneocystostomy with a caudal block combined with general anesthesia. Ketorolac was more effective in reducing bladder spasms and rescue analgesic requirements than fentanyl.
InpharmD Researcher Critique	Pain score assessment was not thorough and consistent during duration of this study, thus, intensity of pain and the level of mitigation provided by each treatment may not have been accurately represented via pain scores directly. The surrogate outcome of rescue analgesia use was utilized to circumvent this limitation.

References:

Jo YY, Hong JY, Choi EK, Kil HK. Ketorolac or fentanyl continuous infusion for post-operative analgesia in children undergoing ureteroneocystostomy. Acta Anaesthesiol Scand. 2011;55(1):54-59. doi:10.1111/j.1399-6576.2010.02354.x

Effectiveness of Solifenacin for Managing of Bladder Spasms in Patients With Urethroplasty
Design	Randomized controlled trial N= 315
Objective	To evaluate the efficacy and safety of solifenacin in the treatment of bladder spasms after urethroplasty
Study Groups	Solifenacin (n= 165) Control (n= 150)
Inclusion Criteria	Aged 5 to 85 years, underwent urethroplasty surgeries
Exclusion Criteria	Not specified
Methods	After urethroplasty, patients were randomly assigned to receive either solifenacin (5 mg once daily) for 7 days beginning the first day after the operation or vitamin C (10 mg once daily) as a placebo. Patients were uncategorized based on the use of a urethral indwelling catheter or intraoperative cystostomy. All patients received a urethral indwelling catheter or cystostomy catheter after the operation for 3 weeks. The size of all catheters was F18r. The type of catheter used was at the surgeon’s discretion.
Duration	July 2011 to October 2015 Follow-up: postoperative 7 days
Outcome Measures	Postoperative severity (assessed by visual analog scale [VAS]) and duration of bladder spasms, safety profile
Baseline Characteristics		Solifenacin (n= 165)	Control (n= 150)
	Paracentetic suprapubic cystostomy subgroup Age, years Male Average surgery time, minutes Location of the stricture Bulbar Membranous	44 35 81.82% 78 - 28 16	41 38 82.93% 76 - 28 13
	Traditional suprapubic cystostomy subgroup Age, years Male Average surgery time, minutes Location of the stricture Bulbar Membranous	40 31 100% 86 - 24 16	36 34 100% 89 - 23 13
	Former suprapubic cystostomy subgroup Age, years Male Average surgery time, minutes Location of the stricture Bulbar Membranous	58 38 100% 60 - 35 23	48 29 100% 62 - 33 15
	Urethral catheter subgroup Age, years Male Average surgery time, minutes Location of the stricture Bulbar Membranous	23 38 100% 62 - 17 6	25 39 100% 66 - 16 9
Results	All results were presented in figures, and the authors did not provide specific numbers. There were no significant differences in VAS scores (p= 0.78) or mean duration of bladder spasms (n= 0.43) between the study group and control group. Solifenacin recipients in the paracentetic suprapubic cystostomy subgroup experienced a significantly lower VAS score (p= 0.032) and mean duration of bladder spasm (p= 0.043). In a comparison of the daily and nightly frequencies of spasms within the four subgroups, a statistically significant difference was noticed in the control group within 5 days (p= 0.042). However, the difference was not significant within 6 days in the study group (p= 0.13).
Adverse Events	Common Adverse Events: dry mouth (solifenacin vs control 3.64% vs 0), constipation (6.06% vs 4%)
	Serious Adverse Events: not observed
	Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions	In summary, the findings of this study demonstrated that short-term therapy with solifenacin is an effective and safe method for decreasing the frequency of bladder spasms after urethroplasty. Patients should start solifenacin immediately within 6 days after surgery. Patients undergoing paracentetic suprapubic cystostomy might be the only subset benefit from this treatment.
InpharmD Researcher Critique	As the study did not directly compare use of solifenacin to belladonna/opium suppositories, it remained uncertain if solifenacin would provide similar effects as belladonna/opium in the management of postoperative bladder spasms. Without numeric numbers of VAS scores and duration of bladder spasm, extent of clinical benefits from solifenacin could not be further assessed.

References:

Peng XF, Lv XG, Xie H, et al. Effectiveness of Solifenacin for Managing of Bladder Spasms in Patients With Urethroplasty. Am J Mens Health. 2017;11(5):1580-1587. doi:10.1177/1557988317713634