Mixed Incontinence in an Elderly Lady

The Case

A 70-year-old woman from South India presents with the complaint of needing to pass urine throughout the day and night. She says that she gets the urge suddenly and has to rush to the bathroom almost every hour during the day and two to three times at night. Sometimes the urge is so strong that she has to void as often as every 30 minutes during the day.

She also passes small amounts of urine in her clothes every time she coughs or sneezes. Although there is no burning, she complains of pain while passing urine. Another thing that she has noticed is that the problem is more acute after drinking tea or coffee. She avoids long journeys or going to places where there may not be a rest room nearby and also makes sure to find out where the rest room is when in unfamiliar places.

These symptoms started about 2 years earlier, and have gradually progressed to start bothering her and hinder her daily activities and sleep. There is no history of hematuria, pyuria or any other urological problem.

The patient has also been suffering from hypertension for the past 15 years, which is well under control with regular treatment.

On Examination

The patient is an elderly lady, overweight, fully alert and well oriented. Even while waiting to see the clinician, she has been to the rest room twice.

• Pulse: 84/min
• Blood pressure: 140/88 mmHg
• BMI: 30.2 kg/m²
• CVS, CNS, Respiratory system: Normal
• Abdomen: Moderately obese, soft, nontender, no organomegaly or masses, normal bowel sounds
• Rectal examination: Normal sphincter tone, but unable to voluntarily contract pelvic floor muscles around gloved finger on demand, rectal vault normal without masses or tenderness; no occult blood
• Pelvic examination: Atrophic vaginal mucosa, no uterine prolapse; no masses on bimanual examination

Investigations

• Hemoglobin: 11.8 gm/dl
• Hematocrit: 42%
• Random blood glucose: 98 mg/dl
• Urinalysis: Specific gravity 1.015; pH 7.0; WBC 0-2/HPF; RBC 0-2/HPF; no pus cells or casts
• Urine culture and sensitivity: Sterile after 48 hours of incubation

Diagnosis

Symptoms of urgency, frequency and nocturia point towards a diagnosis of urge incontinence. In addition, complaints of loss of urine with sneezing and coughing are consistent with stress incontinence. Thus, the final diagnosis is mixed incontinence.

Management

The patient has predominantly OAB symptoms. Her liquid intake is moderate, but consumption of caffeine is considerable – upto 5-6 cups of coffee in a day. Hence, she is counselled to reduce her caffeine intake in order to improve her OAB symptoms. Due to her high BMI, weight management is advised. For vaginal atrophy, a local estrogen preparation is prescribed. She is also given instructions on how to do pelvic floor exercises and is started on pharmacological therapy in the form of flavoxate hydrochloride orally.

Follow-up

On follow-up examination one month later, the patient is found to have significant improvement in her symptoms. She now urinates 4 to 6 times per day and wakes up only once or twice during the night. There is no pain while urinating. She also feels more comfortable in public places. She has reduced her caffeine intake to one cup in the morning and one in the evening, and limits all fluid intake after 5 PM.

Discussion

Urinary incontinence is a common problem in the elderly, with significant medical, social, and economic implications. Incontinence may be transient or longstanding; reversible causes must be ruled out. Thorough history taking, a targeted physical examination, and simple investigations usually lead to a diagnosis.¹Rosenthal AJ, McMurtry CT. Urinary incontinence in the elderly. Often simple to treat when properly evaluated. Postgrad Med. 1995;97(5):109-16: 121.  

Achieving control of urinary continence is the key to achieving an independent lifestyle. A wide range of interventions and resources exist to assist in the successful management of urinary incontinence.²Controlling urinary incontinence. Aust Fam Physician. 2002;31(1):88-93.   When the type of incontinence is known, appropriate treatment may bring improvement in symptoms or a return to continence.¹Rosenthal AJ, McMurtry CT. Urinary incontinence in the elderly. Often simple to treat when properly evaluated. Postgrad Med. 1995;97(5):109-16: 121.  

Nonpharmacologic (behavioral) management options involve strengthening the muscles that support the bladder, reducing intake of physical irritants such as caffeine and alcohol, and scheduling voiding in an attempt to circumvent episodes of urgency that prompt incontinence. Evidence shows that a combination of both pharmacologic and behavioral treatment strategies maximizes the management of overactive bladder syndrome. One of the important pharmacological agents for treating this condition is flavoxate.

Role of flavoxate in urge incontinence

Flavoxate hydrochloride is a flavone derivative, which relaxes the smooth muscle of the bladder wall by acting specifically on the smooth muscle cells of the urogenital system. It has good therapeutic efficacy and excellent tolerability, and is used in a broad range of disorders, including urge incontinence.³Ruffmann R, Sartani A. Flavoxate, a drug with smooth muscle relaxing activity. Drugs Exp Clin Res. 1987;13(1):57-62.   In fact, flavoxate was the first antispasmodic agent approved by the Food and Drug Administration (FDA) to treat symptoms of OAB.⁴Hesch K. Agents for treatment of overactive bladder: a therapeutic class review. Proc (Bayl Univ Med Cent). 2007;20(3):307-14.  

By relaxing the muscles in the bladder, flavoxate helps to reduce leakage of urine, urgency, frequency and bladder pain. The relaxation of smooth muscle is caused by directly inhibiting phosphodiesterase and blocking the effects of calcium. There is also some degree of local anesthesia,⁵Graziani G, Cazzulani P, Panzarasa R (eds.) In: Flavoxate. Geneva:Bioscience Ediprint, 1983:7-19.  ^,6Graziani G, Cazzulani P, Panzarasa R (eds.) In: Flavoxate. Geneva:Bioscience Ediprint, 1983:20-23.   which helps in relieving bladder pain. Research has shown that flavoxate normalizes a pathologically increased smooth muscle tone while simultaneously regulating it. However, smooth muscle cells with normal tone are not affected.⁷Kaseda M et al. Effects of flavoxate hydrochloride on bladder function in the rat. Clin Physiol 1975;5:11.  

Flavoxate is used mainly in urogenital disorders caused by spasms and increased tonicity of smooth muscle, leading to frequent micturition or severe urge symptomatology. Flavoxate has been shown to improve intravesical pressure and increase bladder capacity by up to 19%.⁸Stanton SLA. A comparison of emepronium bromide and flavoxate hydrochloride in the treatment of urinary incontinence. J Urol 1973;110:529.  ^,9Jonas U, Petri E, Kissel J. Effect of flavoxate on hyperactive detrusor muscle. Eur Urol 1979;5:106-109.   At the same time, bothersome symptoms, such as increased daytime and night time frequency, as well as urgency, have been found to decrease.¹⁰Milani R, Scalambrino S, Milia R et al. Double-blind crossover comparison of flavoxate and oxybutynin in women affected by urinary urge syndrome. Int Urogynecol J 1993;4:3-8.  ^,11Wehnert J, Sage S. Vergleichende Untersuchungen zur Wirkung von Mictonorm (Propiverin hydrochlorid) und Spasuret1 200 (Flavoxat hydrochlorid) auf den Detrusor vesicae. Zeitschr Urol Nephrol 1989;82:259-263.  

In a drug utilization observation study,¹²Fehrmann-Zumpe P, Karbe K, Blessman G. Using flavoxate as primary medication for patients suffering from urge symptomatology. Int Urogynecol J Pelvic Floor Dysfunct. 1999;10(2):91-5.   data on 1800 patients given flavoxate over 2 weeks for urge incontinence were collected to evaluate its efficacy and tolerability. A subgroup of 618 patients without urinary tract infections or benign prostatic hyperplasia was treated with flavoxate only. The subgroup (n = 618) showed a reduction of dysuria (37%), nocturia (53%), and both daytime urge (61%) and night time urge (69%) (Fig. 1). Bladder volume at first urge sensation increased by 36%. In 89.2% of all patients the residual urine volume was stable or decreased. Undesirable side effects occurred

in just 1.8% of cases. These results show that flavoxate is effective and well tolerated, and causes no additional problems due to residual urine or side effects.

An unblinded, uncontrolled clinical trial conducted in China¹³Gu FL, Reng ZY, Shang GZ, Shao HX, Wang B, Cheng ZD, Jiang Y, Zhao WP, Zheng JF, Qu CT, et al. Treatment of urgency and urge incontinence with flavoxate in the People’s Republic of China. J Int Med Res. 1987;15(5):312-8.   studied the effects of flavoxate in 336 patients with urgency/urge incontinence. Patients were given flavoxate orally for 2 weeks in doses ranging from 200 mg three times daily to 1200 mg daily. Frequency, urgency, dysuria, nocturia and incontinence were assessed and scored clinically before and after treatment.

The results were as follows:

• Complete cure of urgency/incontinence symptoms in 67% patients
• Improvement in 20% patients
• No change in 13% patients
• Response to flavoxate seen in 77.4% of patients refractory to previous anticholinergic treatment

Response to 1200-mg dose:

• Complete cure in 82% patients
• Improvement in 18% patients
• No side-effects.

The study authors concluded that flavoxate is an effective and well tolerated treatment for urgency/urge incontinence.

Emepronium bromide is another drug used in the treatment of detrusor instability. A study by Melchior¹⁴Melchior H. Drug therapy of detrusor dysfunction. Urologe A. 1983;22(3):167-75.   demonstrated that administration of emepronium bromide and flavoxate for idiopathic unstable bladder and neuropathic detrusor hyperreflexia resulted in improvement of subjective symptoms.

In a similar study,¹⁵Aagaard J, et al. A comparison between the combination emepronium bromide/flavoxate and emepronium bromide in the treatment of detrusor instability. Urol Int. 1983;38(3):191-2.   20 consecutive patients with an uninhibited bladder were randomly allocated to treatment with either emepronium bromide/flavoxate combination or emepronium bromide alone. It was found that adding flavoxate to emepronium bromide resulted in significantly better results than monotherapy with emepronium bromide.

A study by Zeegers et al¹⁶Zeegers AGM., Kiesswetter H, et al. Conservative therapy of frequency, urgency and urge incontinence: A double-blind clinical trial of flavoxate hydrochloride, oxybutinin chloride, emepronium bromide and placebo. World J Urol. 1987;5(1):57-61.   enrolled 60 patients with detrusor overactivity or hypersensitivity, who were randomized to either emepronium bromide, flavoxate hydrochloride, oxybutynin chloride or placebo. Serious side-effects were noted during the administration of emepronium bromide, while flavoxate hydrochloride had even fewer and milder side effects than placebo.

In a study by Bradley and colleagues,¹⁷Bradley DV, Cazort RJ. Relief of bladder spasm by flavoxate. A comparative study. J Clin Pharm J New Drug. 1970;10(1):65-68.   flavoxate hydrochloride produced symptomatic relief comparable to propantheline bromide for the treatment of frequency, urgency, suprapubic pain, dysuria and nocturia in 46 patients. The investigators found flavoxate to be a useful bladder sedative at dose levels relatively free of side effects.

In another comparative study¹⁸Roxburgh C, Cook J, Dublin N. Anticholinergic drugs versus other medications for overactive bladder syndrome in adults. Cochrane Database Syst Rev. 2007;(4):CD003190.   conducted on OAB patients, adverse effects were more frequent with anticholinergic drugs than with flavoxate.

A double-blind multiclinic crossover study¹⁹Milani R, Scalambrino S, Milia R, et al. Double-blind crossover comparison of flavoxate and oxybutynin in women affected by urinary urge syndrome. Int Urogynecol J. 1993;4(1):3-8.   compared the efficacy and tolerability of a 4-week treatment course with flavoxate, given orally at 1200 mg/day, with that of oxybutynin, 15 mg/day orally, in women with idiopathic motor or sensory urgency. The following results were obtained:

• Flavoxate cured or greatly improved the syndrome in 81.6% of cases, while oxybutynin produced the same effects in 78.9% (Table 1).
• Flavoxate led to adverse reactions in 26.8% patients, as against 90.2% with oxybutynin (Table 1).
• Five patients interrupted the treatment because of side effects while taking oxybutynin, whereas no patient stopped the treatment while taking flavoxate (Table 1).
• The severity of the side-effects recorded during flavoxate treatment was significantly less than with oxybutynin.

Thus, flavoxate, while possessing efficacy comparable to that of oxybutynin, was found to be associated with fewer and milder side effects.

References

1. Rosenthal AJ, McMurtry CT. Urinary incontinence in the elderly. Often simple to treat when properly evaluated. Postgrad Med. 1995;97(5):109-16: 121.
2. Controlling urinary incontinence. Aust Fam Physician. 2002;31(1):88-93.
3. Ruffmann R, Sartani A. Flavoxate, a drug with smooth muscle relaxing activity. Drugs Exp Clin Res. 1987;13(1):57-62.
4. Hesch K. Agents for treatment of overactive bladder: a therapeutic class review. Proc (Bayl Univ Med Cent). 2007;20(3):307-14.
5. Graziani G, Cazzulani P, Panzarasa R (eds.) In: Flavoxate. Geneva:Bioscience Ediprint, 1983:7-19.
6. Graziani G, Cazzulani P, Panzarasa R (eds.) In: Flavoxate. Geneva:Bioscience Ediprint, 1983:20-23.
7. Kaseda M et al. Effects of flavoxate hydrochloride on bladder function in the rat. Clin Physiol 1975;5:11.
8. Stanton SLA. A comparison of emepronium bromide and flavoxate hydrochloride in the treatment of urinary incontinence. J Urol 1973;110:529.
9. Jonas U, Petri E, Kissel J. Effect of flavoxate on hyperactive detrusor muscle. Eur Urol 1979;5:106-109.
10. Milani R, Scalambrino S, Milia R et al. Double-blind crossover comparison of flavoxate and oxybutynin in women affected by urinary urge syndrome. Int Urogynecol J 1993;4:3-8.
11. Wehnert J, Sage S. Vergleichende Untersuchungen zur Wirkung von Mictonorm (Propiverin hydrochlorid) und Spasuret1 200 (Flavoxat hydrochlorid) auf den Detrusor vesicae. Zeitschr Urol Nephrol 1989;82:259-263.
12. Fehrmann-Zumpe P, Karbe K, Blessman G. Using flavoxate as primary medication for patients suffering from urge symptomatology. Int Urogynecol J Pelvic Floor Dysfunct. 1999;10(2):91-5.
13. Gu FL, Reng ZY, Shang GZ, Shao HX, Wang B, Cheng ZD, Jiang Y, Zhao WP, Zheng JF, Qu CT, et al. Treatment of urgency and urge incontinence with flavoxate in the People’s Republic of China. J Int Med Res. 1987;15(5):312-8.
14. Melchior H. Drug therapy of detrusor dysfunction. Urologe A. 1983;22(3):167-75.
15. Aagaard J, et al. A comparison between the combination emepronium bromide/flavoxate and emepronium bromide in the treatment of detrusor instability. Urol Int. 1983;38(3):191-2.
16. Zeegers AGM., Kiesswetter H, et al. Conservative therapy of frequency, urgency and urge incontinence: A double-blind clinical trial of flavoxate hydrochloride, oxybutinin chloride, emepronium bromide and placebo. World J Urol. 1987;5(1):57-61.
17. Bradley DV, Cazort RJ. Relief of bladder spasm by flavoxate. A comparative study. J Clin Pharm J New Drug. 1970;10(1):65-68.
18. Roxburgh C, Cook J, Dublin N. Anticholinergic drugs versus other medications for overactive bladder syndrome in adults. Cochrane Database Syst Rev. 2007;(4):CD003190.
19. Milani R, Scalambrino S, Milia R, et al. Double-blind crossover comparison of flavoxate and oxybutynin in women affected by urinary urge syndrome. Int Urogynecol J. 1993;4(1):3-8.