JOURNAL OF PALLIATIVE MEDICINE Volume 17, Number 1, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/jpm.2012.0116
Case Discussions in Palliative Medicine Feature Editor: Craig D. Blinderman
Managing Overactive Bladder Symptoms in a Palliative Care Setting Abigail Walton, MBChB, MRCP
Abstract
Background: The combined symptoms of urinary frequency, urgency, nocturia, and incontinence (overactive bladder) are common symptoms within an elderly population but are also seen in palliative care patients and are most often due to detrusor muscle overactivity. These symptoms can lead to a marked reduction in quality of life and pharmacological management is traditionally with anticholinergic drugs. These medications carry a high risk of side effects and are often poorly tolerated by palliative care patients. Other management approaches, however, such as the use of urisheaths may markedly improve quality of life without adding to symptom burden in patients nearing the end of life. Objectives: This article highlights two cases in palliative care where overactive bladder symptoms prove difficult to manage with anticholinergic drugs. Conclusions: The discussion will give an overview of treatment strategies to help aid the clinician in managing these difficult symptoms in patients with a terminal illness.
Introduction
T
he combined symptoms of urinary frequency, urgency, nocturia, and incontinence can be broadly grouped together and defined as symptoms of an ‘overactive bladder.’ In 2008 an estimated 10.7% of the worldwide population (4.3 billion) was affected by overactive bladder symptoms,1 and a European study has suggested the prevalence of these symptoms in individuals over 40 years to be 16.6%.2 Published literature looking at their prevalence in a palliative care setting is sparse. One study however identified that 14% of patients presenting to a palliative care service in the United Kingdom had urinary symptoms of some description.3 In patients with advanced malignancy the symptoms are most commonly due to intrinsic or extrinsic tumor producing irritation of the bladder wall (especially in the region of the trigone of the bladder).4 Previous cancer treatments may also contribute. For example in treatment for prostate cancer, overactive bladder can develop after brachytherapy and radical prostatectomy; but rate, severity, and variability of symptoms is higher with the brachytherapy.5 Symptoms of an overactive bladder can impose a huge burden upon the individual, leading to a marked drop in quality of life. Many palliative patients have reduced mobility and poor skin integrity; and unchecked incontinence can lead to complications including skin breakdown, pressure ulcers,
and urinary infections, while frequency and urgency may lead to falls and even fractures.4 Successful management of an overactive bladder may prove complicated. Pharmacological treatment is traditionally with anticholinergic drugs; however these may be poorly tolerated due to a high side effect profile, impacting further on a patient’s quality of life. They may therefore not be first line in a palliative care setting, and simple alternatives such as the use of a urisheath may dramatically improve the patient’s quality of life with few or no side effects.6 Case Histories First case An 82-year-old gentleman living alone, with an extensive past medical history of ischemic heart disease, was diagnosed a year earlier with a locally advanced high-grade bladder cancer. He underwent a partial resection followed by palliative chemoradiotherapy. He then presented repeatedly to the emergency department with symptoms of urinary frequency and incontinence with occasional bladder spasms and was admitted to hospital. He was given a course of antibiotics despite a negative urine culture and was catheterized. He was started on solifenacin succinate (Vesicare) 10 milligrams daily and given oral buscopan for the spasms without symptomatic improvement;
Palliative Care Department, Hammond Care, Sydney, Australia. Accepted May 21, 2013.
118
OVERACTIVE BLADDER SYMPTOMS IN PALLIATIVE CARE these were both subsequently stopped and short-acting hydromorphone was initiated instead. The palliative care team was then consulted with regard to his symptoms. They suggested the catheter be removed, which improved his bladder spasms; however he continued to suffer with penile discomfort and was given topical lidocaine gel alongside the hydromorphone. A urisheath (conveen) was fitted which reduced his toileting frequency, and he was commenced on citalopram 20 mg for his mood. The palliative care team suggested a trial of oxybutinin if he had ongoing symptoms postdischarge and this was subsequently started. One week postdischarge he re-presented to the emergency department with dizziness and postural hypotension. His antihypertensives and oxybutinin were ceased and he improved. The urinary frequency and incontinence persisted; however his pain was well controlled. Other anticholinergic drugs were considered, but the patient opted to continue just with the urisheath and his regular pain relief. He was discharged back home with increased social support. Second case An 87-year-old gentleman living alone, with a history of atrial fibrillation (on amiodarone), was diagnosed with a superficial bladder cancer 11 years earlier. This was treated with regular cystoscopies and diathermy and initially remained stable but he re-presented with increasing urinary frequency, urgency, and incontinence. Restaging of his disease confirmed a large bladder tumor with locoregional spread; the patient opted for palliative management. He was visited at home by the palliative care team and a urisheath was fitted in the community, but he found it difficult to use. Subsequent to this he was admitted to hospital with worsening symptoms and was found to have a urinary tract infection which was treated, but his symptoms persisted. Low-dose tolterodine (Detrusitol 1mg bd) was initiated after consultation with the cardiologists, and the patient was transferred to a palliative care unit for ongoing symptom management. The tolterodine appeared to purely reduce his urinary stream rather than frequency and was therefore stopped. Alternative anticholinergics were considered, but due to potential interactions with amiodarone and possible exacerbation of his cardiovascular complaints, the patient opted to pursue nonpharmacological interventions. During his stay in the palliative care unit he was given advice and support on the use of the urisheath, and this improved his compliance and subsequently his symptoms. Discussion These cases highlight the complexities involved in managing overactive bladder symptoms in palliative care patients. The symptoms can be embarrassing and undignified and may quickly lead to a loss of control and independence, resulting in social isolation. Patients are often elderly and frail with multiple comorbidities and treatment options may be limited. Understanding both the pathophysiology and nonpharmacological and pharmacological therapeutic options will aid the clinician in choosing the most appropriate management strategy.
119
Bladder filling and voiding involves a complex pattern of afferent and efferent signaling in parasympathetic (S2–S4), sympathetic (T10–L2), and somatic nerve pathways.7 Parasympathetic nerve stimulation causes contraction of detrusor muscle and relaxation of the bladder neck sphincter (predominantly mediated by acetylcholine), whereas stimulation of the sympathetic system has the opposite effect.4 Neurotransmitters other than acetylcholine have also been implicated in the neuronal control of the lower urinary tract, including norepinephrine, endogenous opioid peptides, 5HT, GABA, and dopamine.8 Calcium and potassium channels are also thought to be involved in the modulation of bladder smooth muscle.7 Before considering the use of an anticholinergic drug, nonpharmacological approaches should be tried first in order to minimize the risk of side effects. Continence care should be focused on maintaining comfort and dignity while relieving symptoms with as few interventions as possible.9 Conventional approaches such as a reduction in caffeine and alcohol intake or reduced fluid intake before bed may have a variable impact on the symptoms. Bladder retraining and pelvic floor exercises are unlikely to be of benefit in patients with advanced malignancy where direct tumor effect is the causative factor. A simple measure such as the use of a urisheath can be very beneficial and has been shown to improve quality of life, self image, odor management, discretion, and skin integrity compared to the use of absorbent pads alone.6 Urisheaths however can be difficult to use6 especially for an elderly frail patient, and therefore appropriately skilled nursing support is essential to the success of their use. An indwelling catheter may be of less overall benefit due to potential for further bladder irritation, infection, and bleeding. Treatment of urinary infections, the use of absorbent/ continence pads in combination with a urisheath, meticulous skin and pressure area care, the use of barrier creams, and the presence of a commode or urinary bottle by the bedside can all help maintain a patient’s independence and dignity while reducing risk of falls and limiting hospital admissions. There is evidence to show that in the general population the more bothersome the symptoms of an overactive bladder, the more likely the individual is to have low health-related quality of life and high levels of anxiety and depression.10 Relating this to a palliative care setting where many patients face multiple psychosocial issues, this could be assumed to be even more burdensome and should be screened for and treated promptly. As previously mentioned, the pharmacological treatment for overactive bladder symptoms has traditionally been with anticholinergic drugs. These drugs, however, may provide only a modest improvement in quality of life despite a risk of side effects.11 This may be especially relevant in a palliative care population where constipation, dry mouth, and confusion are common preexisting symptoms. A reduced dose of an anticholinergic may be necessary to limit side effects while still achieving some therapeutic benefit. If anticholinergics are deemed a suitable option, then a sound understanding of the drugs available will help guide management. Oxybutynin (2.5 mg–5.0 mg bd-qid) is often first choice, but it can be associated with a high incidence of anticholinergic
120 side effects (in Case 1, oxybutynin was felt to be contributing to the patient’s dizziness and was eventually stopped); the once daily formulation is thought to be better tolerated.4 It has antimuscarinic, direct muscle-relaxant effects and local anaesthetic actions.12 Tolterodine (1 mg–2 mg bd) is thought to have fewer anticholinergic side effects, especially dry mouth (functional selectivity for bladder receptors over salivary receptors13,14); therefore it may be preferable for palliative care patients. It is thought, however, that tolterodine has the potential to prolong the QT interval and this is especially relevant if a patient is on cardiac medications such as amiodarone (Case 2) or drugs used frequently in palliative care, which also carry this potential (methadone and some antipsychotic drugs).15 Solifenacin succinate (evidence of greater bladder selectivity and therefore fewer side effects4) and propantheline (less CNS side effects than peripheral side effects16) are also options. Other anticholinergic drugs may be preferable for palliative care patients if some of the side effects are actually of clinical use, for example in the setting of neuropathic pain or if night sedation is required, e.g., amitriptyline/imipramine. If anticholinergic drugs are contraindicated, then a urinary antispasmodic, flavoxate 200 mg–400 mg tds (not available in Australia), can be used. Side effects such as dry mouth, blurred vision, and tachycardia can occasionally still occur with this drug.17 As discussed previously, there are likely to be multiple mechanisms and receptors involved in the generation of the symptoms of an overactive bladder. With this in mind, alternative pharmacological management strategies have been suggested. Opioid receptors are present in many areas throughout the central nervous system involved in micturition control, and morphine is known to increase bladder capacity and block bladder contractions.7 Serotonergic pathways also play a part in micturition control, with a likely inhibitory effect on bladder contraction.18 As a result of this, there is speculation that tramadol may be more effective than morphine because of its ability to inhibit presynaptic reuptake of serotonin and noradrenaline.7 Selective serotonin reuptake inhibitors (SSRIs) have also been proposed in the management of overactive bladder; however, evidence suggests that when SSRIs (notably sertraline) are given to elderly patients without incontinence they may actually cause urinary incontinence rather than reduce it.19 Gabapentin has been shown to be effective in the treatment of detrusor overactivity in patients who have failed conventional anticholinergic therapy,20 while calcium channel blockers appear to show little clinical benefit in symptoms,21,22 and the therapeutic benefit of dopamine receptor blockers has not been established.22 Intravesical botulinum toxin is thought to be of use in detrusor overactivity by inhibiting the release of acetylcholine and other substances within the bladder.23 To our knowledge there have been no trials looking at alternative treatment strategies in patients with advanced malignancy, and therefore any predicted benefit from the above interventions in this population is purely speculative. Summary Symptoms of urinary frequency, urgency, nocturia, and incontinence (overactive bladder) can occur in patients with
WALTON advanced malignancy and can impact significantly on their quality of life. Traditional treatment with anticholinergic drugs should be considered, however can produce significant side effects and may only be of modest therapeutic benefit. A reduction in dose may help minimize some of the side effects while still achieving some clinical improvement in symptoms. Simple measures such as the use of a urisheath, adaptation of the home environment, effective nursing support, and screening for and treating depression and anxiety are all good management strategies in a palliative care setting. If drug treatment is deemed appropriate, the clinician needs to have an understanding of the pathophysiology behind the symptoms and of standard treatments and novel therapeutic approaches available in order to choose the most effective management strategy for a patient nearing the end of life. Although there have been a number of published articles looking at some aspects of overactive bladder management within a palliative setting,24–27 there is an ongoing need for research into and development of management strategies for this patient population. Author Disclosure Statement No competing financial interests exist. References 1. Irwin DE, et al.: Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction. BJU Int 2011;108(7): 1132–1138. 2. Milsom I, et al.: How widespread are the symptoms of an overactive bladder and how are they managed? A populationbased prevalence study. BJU Int 2001;87(9):760–766. 3. Potter J, et al.: Symptoms in 400 patients referred to palliative care services: Prevalence and patterns. Pall Med 2003; 17(4):310–314. 4. Norman RW, Bailly GG: Genitourinary problems in palliative medicine. In: Hanks G, Cherny N, Christakis N, Fallon M, Kaasa S, Portenoy R (eds). Oxford Textbook of Palliative Medicine, 4th ed. Oxford: Oxford University Press, 2010, pp. 983–994. 5. Boettcher M, et al.: Overactive bladder syndrome: An underestimated long term problem after treatment of patients with localised prostate cancer? BJU Int 2012;109(12):1824– 1830. 6. Chartier-Kastler E, et al.: Randomised, crossover study evaluating patient preference and the impact on quality of life of urisheaths vs absorbent products in incontinent men. BJU Int 2011;108(2):241–247. 7. Andersson KE: Neurophysiology and pharmacology of the lower urinary tract. In: Tanagho EA, McAninch JW (eds): Smith’s General Urology, 17th ed. New York: McGraw-Hill, 2008. 8. de Groat WC, Yoshimura N: Pharmacology of the lower urinary tract. Annu Rev Pharmacol Toxicol 2001;41:69–72. 9. Harris A: Providing urinary incontinence care to adults at the end of life. Nursing Times 2009;5(29). 10. Coyne K: The impact of overactive bladder on mental health, work productivity and health-related quality of life in the UK and Sweden: Results from EpiLUTS. BJU Int 2011;108(9): 1459–1471. 11. Nabi G, Cody JD, Ellis G, Herbison P, Hay-Smith J: Cochrane Database Syst Rev 2006:CD003781.
OVERACTIVE BLADDER SYMPTOMS IN PALLIATIVE CARE 12. Andersson KE, et al.: Oxybuynin and the overactive bladder: World J Urol 2001;19:319–323. 13. Hills CJ, et al.: Tolterodine. Drugs 1998;55:813–820. 14. Chapple CR: Muscarinic receptor antagonists in the treatment of overactive bladder. Urology 2000;55(5A suppl):33–46. 15. Monthly Index of Medical Specialities (MIMS) online proxy60 .use.hcn.com.au/publicsite/abbreviated?productId = 72790001 16. Andersson KE, et al.: Pharmacological treatment of urinary incontinence. BJU Int 1999;84(9):923–947. 17. Drug information online: www.drugs.com/pro/flavoxate .html 18. de Groat WC: Influence of central serotonergic mechanisms on lower urinary tract function. Urology 2002;59(5 Suppl 1): 30–36. 19. Movig KL, et al.: Selective serotonin reuptake inhibitorinduced urinary incontinence. Pharmacoepidemiol Drug Saf 2002;11(4):271–279. 20. Kim YT, et al.: Gabapentin for overactive bladder and nocturia after anticholinergic failure. Int Braz J Urol 2004;30(4): 275–278. 21. Naglie, et al.: A randomized, double blind, placebo controlled crossover trial of nimodipine in older persons with detrusor instability and urge incontinence. J Urol 2002;167 (2 Pt 1):586–590.
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22. Andersson KE, Wein AJ: Pharmacology of the lower urinary tract: Basis for current and future treatments. Pharmacol Rev 2004;56(4):581–631. 23. Apostolidis P, et al.: Proposed mechanism for the efficacy of injected botulinum toxin in the treatment of human detrusor overactivity. Europ Urology 2006;49(4):644–650. 24. Degarat F, Lesage C. Measures or palliative treatments for urinary incontinence. Soins 2005;699:19–20. 25. Sabatier MC, et al.: Palliative care of urinary incontinence. Rev Infirm 1997;29:53–60. 26. Gomez Lanza E, et al.: Physiotherapy and palliative management of urinary incontinence in prostate cancer: Start point and end of the road. Arch Esp Urol 2009;62(10);889–895. 27. Hamid R, et al.: Management of oncological and iatrogenic urinary incontinence in malignant disease. Clin Oncol (R Coll Radiol) 2010;22(9);719–726.
Address correspondence to: Abigail Walton, MBChB, MRCP Cornhill Macmillan Centre Perth Royal Infirmary NHS Tayside Perth, Scotland E-mail: [email protected]
Case Discussions in Palliative Medicine Feature Editor: Craig D. Blinderman
Managing Overactive Bladder Symptoms in a Palliative Care Setting Abigail Walton, MBChB, MRCP
Abstract
Background: The combined symptoms of urinary frequency, urgency, nocturia, and incontinence (overactive bladder) are common symptoms within an elderly population but are also seen in palliative care patients and are most often due to detrusor muscle overactivity. These symptoms can lead to a marked reduction in quality of life and pharmacological management is traditionally with anticholinergic drugs. These medications carry a high risk of side effects and are often poorly tolerated by palliative care patients. Other management approaches, however, such as the use of urisheaths may markedly improve quality of life without adding to symptom burden in patients nearing the end of life. Objectives: This article highlights two cases in palliative care where overactive bladder symptoms prove difficult to manage with anticholinergic drugs. Conclusions: The discussion will give an overview of treatment strategies to help aid the clinician in managing these difficult symptoms in patients with a terminal illness.
Introduction
T
he combined symptoms of urinary frequency, urgency, nocturia, and incontinence can be broadly grouped together and defined as symptoms of an ‘overactive bladder.’ In 2008 an estimated 10.7% of the worldwide population (4.3 billion) was affected by overactive bladder symptoms,1 and a European study has suggested the prevalence of these symptoms in individuals over 40 years to be 16.6%.2 Published literature looking at their prevalence in a palliative care setting is sparse. One study however identified that 14% of patients presenting to a palliative care service in the United Kingdom had urinary symptoms of some description.3 In patients with advanced malignancy the symptoms are most commonly due to intrinsic or extrinsic tumor producing irritation of the bladder wall (especially in the region of the trigone of the bladder).4 Previous cancer treatments may also contribute. For example in treatment for prostate cancer, overactive bladder can develop after brachytherapy and radical prostatectomy; but rate, severity, and variability of symptoms is higher with the brachytherapy.5 Symptoms of an overactive bladder can impose a huge burden upon the individual, leading to a marked drop in quality of life. Many palliative patients have reduced mobility and poor skin integrity; and unchecked incontinence can lead to complications including skin breakdown, pressure ulcers,
and urinary infections, while frequency and urgency may lead to falls and even fractures.4 Successful management of an overactive bladder may prove complicated. Pharmacological treatment is traditionally with anticholinergic drugs; however these may be poorly tolerated due to a high side effect profile, impacting further on a patient’s quality of life. They may therefore not be first line in a palliative care setting, and simple alternatives such as the use of a urisheath may dramatically improve the patient’s quality of life with few or no side effects.6 Case Histories First case An 82-year-old gentleman living alone, with an extensive past medical history of ischemic heart disease, was diagnosed a year earlier with a locally advanced high-grade bladder cancer. He underwent a partial resection followed by palliative chemoradiotherapy. He then presented repeatedly to the emergency department with symptoms of urinary frequency and incontinence with occasional bladder spasms and was admitted to hospital. He was given a course of antibiotics despite a negative urine culture and was catheterized. He was started on solifenacin succinate (Vesicare) 10 milligrams daily and given oral buscopan for the spasms without symptomatic improvement;
Palliative Care Department, Hammond Care, Sydney, Australia. Accepted May 21, 2013.
118
OVERACTIVE BLADDER SYMPTOMS IN PALLIATIVE CARE these were both subsequently stopped and short-acting hydromorphone was initiated instead. The palliative care team was then consulted with regard to his symptoms. They suggested the catheter be removed, which improved his bladder spasms; however he continued to suffer with penile discomfort and was given topical lidocaine gel alongside the hydromorphone. A urisheath (conveen) was fitted which reduced his toileting frequency, and he was commenced on citalopram 20 mg for his mood. The palliative care team suggested a trial of oxybutinin if he had ongoing symptoms postdischarge and this was subsequently started. One week postdischarge he re-presented to the emergency department with dizziness and postural hypotension. His antihypertensives and oxybutinin were ceased and he improved. The urinary frequency and incontinence persisted; however his pain was well controlled. Other anticholinergic drugs were considered, but the patient opted to continue just with the urisheath and his regular pain relief. He was discharged back home with increased social support. Second case An 87-year-old gentleman living alone, with a history of atrial fibrillation (on amiodarone), was diagnosed with a superficial bladder cancer 11 years earlier. This was treated with regular cystoscopies and diathermy and initially remained stable but he re-presented with increasing urinary frequency, urgency, and incontinence. Restaging of his disease confirmed a large bladder tumor with locoregional spread; the patient opted for palliative management. He was visited at home by the palliative care team and a urisheath was fitted in the community, but he found it difficult to use. Subsequent to this he was admitted to hospital with worsening symptoms and was found to have a urinary tract infection which was treated, but his symptoms persisted. Low-dose tolterodine (Detrusitol 1mg bd) was initiated after consultation with the cardiologists, and the patient was transferred to a palliative care unit for ongoing symptom management. The tolterodine appeared to purely reduce his urinary stream rather than frequency and was therefore stopped. Alternative anticholinergics were considered, but due to potential interactions with amiodarone and possible exacerbation of his cardiovascular complaints, the patient opted to pursue nonpharmacological interventions. During his stay in the palliative care unit he was given advice and support on the use of the urisheath, and this improved his compliance and subsequently his symptoms. Discussion These cases highlight the complexities involved in managing overactive bladder symptoms in palliative care patients. The symptoms can be embarrassing and undignified and may quickly lead to a loss of control and independence, resulting in social isolation. Patients are often elderly and frail with multiple comorbidities and treatment options may be limited. Understanding both the pathophysiology and nonpharmacological and pharmacological therapeutic options will aid the clinician in choosing the most appropriate management strategy.
119
Bladder filling and voiding involves a complex pattern of afferent and efferent signaling in parasympathetic (S2–S4), sympathetic (T10–L2), and somatic nerve pathways.7 Parasympathetic nerve stimulation causes contraction of detrusor muscle and relaxation of the bladder neck sphincter (predominantly mediated by acetylcholine), whereas stimulation of the sympathetic system has the opposite effect.4 Neurotransmitters other than acetylcholine have also been implicated in the neuronal control of the lower urinary tract, including norepinephrine, endogenous opioid peptides, 5HT, GABA, and dopamine.8 Calcium and potassium channels are also thought to be involved in the modulation of bladder smooth muscle.7 Before considering the use of an anticholinergic drug, nonpharmacological approaches should be tried first in order to minimize the risk of side effects. Continence care should be focused on maintaining comfort and dignity while relieving symptoms with as few interventions as possible.9 Conventional approaches such as a reduction in caffeine and alcohol intake or reduced fluid intake before bed may have a variable impact on the symptoms. Bladder retraining and pelvic floor exercises are unlikely to be of benefit in patients with advanced malignancy where direct tumor effect is the causative factor. A simple measure such as the use of a urisheath can be very beneficial and has been shown to improve quality of life, self image, odor management, discretion, and skin integrity compared to the use of absorbent pads alone.6 Urisheaths however can be difficult to use6 especially for an elderly frail patient, and therefore appropriately skilled nursing support is essential to the success of their use. An indwelling catheter may be of less overall benefit due to potential for further bladder irritation, infection, and bleeding. Treatment of urinary infections, the use of absorbent/ continence pads in combination with a urisheath, meticulous skin and pressure area care, the use of barrier creams, and the presence of a commode or urinary bottle by the bedside can all help maintain a patient’s independence and dignity while reducing risk of falls and limiting hospital admissions. There is evidence to show that in the general population the more bothersome the symptoms of an overactive bladder, the more likely the individual is to have low health-related quality of life and high levels of anxiety and depression.10 Relating this to a palliative care setting where many patients face multiple psychosocial issues, this could be assumed to be even more burdensome and should be screened for and treated promptly. As previously mentioned, the pharmacological treatment for overactive bladder symptoms has traditionally been with anticholinergic drugs. These drugs, however, may provide only a modest improvement in quality of life despite a risk of side effects.11 This may be especially relevant in a palliative care population where constipation, dry mouth, and confusion are common preexisting symptoms. A reduced dose of an anticholinergic may be necessary to limit side effects while still achieving some therapeutic benefit. If anticholinergics are deemed a suitable option, then a sound understanding of the drugs available will help guide management. Oxybutynin (2.5 mg–5.0 mg bd-qid) is often first choice, but it can be associated with a high incidence of anticholinergic
120 side effects (in Case 1, oxybutynin was felt to be contributing to the patient’s dizziness and was eventually stopped); the once daily formulation is thought to be better tolerated.4 It has antimuscarinic, direct muscle-relaxant effects and local anaesthetic actions.12 Tolterodine (1 mg–2 mg bd) is thought to have fewer anticholinergic side effects, especially dry mouth (functional selectivity for bladder receptors over salivary receptors13,14); therefore it may be preferable for palliative care patients. It is thought, however, that tolterodine has the potential to prolong the QT interval and this is especially relevant if a patient is on cardiac medications such as amiodarone (Case 2) or drugs used frequently in palliative care, which also carry this potential (methadone and some antipsychotic drugs).15 Solifenacin succinate (evidence of greater bladder selectivity and therefore fewer side effects4) and propantheline (less CNS side effects than peripheral side effects16) are also options. Other anticholinergic drugs may be preferable for palliative care patients if some of the side effects are actually of clinical use, for example in the setting of neuropathic pain or if night sedation is required, e.g., amitriptyline/imipramine. If anticholinergic drugs are contraindicated, then a urinary antispasmodic, flavoxate 200 mg–400 mg tds (not available in Australia), can be used. Side effects such as dry mouth, blurred vision, and tachycardia can occasionally still occur with this drug.17 As discussed previously, there are likely to be multiple mechanisms and receptors involved in the generation of the symptoms of an overactive bladder. With this in mind, alternative pharmacological management strategies have been suggested. Opioid receptors are present in many areas throughout the central nervous system involved in micturition control, and morphine is known to increase bladder capacity and block bladder contractions.7 Serotonergic pathways also play a part in micturition control, with a likely inhibitory effect on bladder contraction.18 As a result of this, there is speculation that tramadol may be more effective than morphine because of its ability to inhibit presynaptic reuptake of serotonin and noradrenaline.7 Selective serotonin reuptake inhibitors (SSRIs) have also been proposed in the management of overactive bladder; however, evidence suggests that when SSRIs (notably sertraline) are given to elderly patients without incontinence they may actually cause urinary incontinence rather than reduce it.19 Gabapentin has been shown to be effective in the treatment of detrusor overactivity in patients who have failed conventional anticholinergic therapy,20 while calcium channel blockers appear to show little clinical benefit in symptoms,21,22 and the therapeutic benefit of dopamine receptor blockers has not been established.22 Intravesical botulinum toxin is thought to be of use in detrusor overactivity by inhibiting the release of acetylcholine and other substances within the bladder.23 To our knowledge there have been no trials looking at alternative treatment strategies in patients with advanced malignancy, and therefore any predicted benefit from the above interventions in this population is purely speculative. Summary Symptoms of urinary frequency, urgency, nocturia, and incontinence (overactive bladder) can occur in patients with
WALTON advanced malignancy and can impact significantly on their quality of life. Traditional treatment with anticholinergic drugs should be considered, however can produce significant side effects and may only be of modest therapeutic benefit. A reduction in dose may help minimize some of the side effects while still achieving some clinical improvement in symptoms. Simple measures such as the use of a urisheath, adaptation of the home environment, effective nursing support, and screening for and treating depression and anxiety are all good management strategies in a palliative care setting. If drug treatment is deemed appropriate, the clinician needs to have an understanding of the pathophysiology behind the symptoms and of standard treatments and novel therapeutic approaches available in order to choose the most effective management strategy for a patient nearing the end of life. Although there have been a number of published articles looking at some aspects of overactive bladder management within a palliative setting,24–27 there is an ongoing need for research into and development of management strategies for this patient population. Author Disclosure Statement No competing financial interests exist. References 1. Irwin DE, et al.: Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction. BJU Int 2011;108(7): 1132–1138. 2. Milsom I, et al.: How widespread are the symptoms of an overactive bladder and how are they managed? A populationbased prevalence study. BJU Int 2001;87(9):760–766. 3. Potter J, et al.: Symptoms in 400 patients referred to palliative care services: Prevalence and patterns. Pall Med 2003; 17(4):310–314. 4. Norman RW, Bailly GG: Genitourinary problems in palliative medicine. In: Hanks G, Cherny N, Christakis N, Fallon M, Kaasa S, Portenoy R (eds). Oxford Textbook of Palliative Medicine, 4th ed. Oxford: Oxford University Press, 2010, pp. 983–994. 5. Boettcher M, et al.: Overactive bladder syndrome: An underestimated long term problem after treatment of patients with localised prostate cancer? BJU Int 2012;109(12):1824– 1830. 6. Chartier-Kastler E, et al.: Randomised, crossover study evaluating patient preference and the impact on quality of life of urisheaths vs absorbent products in incontinent men. BJU Int 2011;108(2):241–247. 7. Andersson KE: Neurophysiology and pharmacology of the lower urinary tract. In: Tanagho EA, McAninch JW (eds): Smith’s General Urology, 17th ed. New York: McGraw-Hill, 2008. 8. de Groat WC, Yoshimura N: Pharmacology of the lower urinary tract. Annu Rev Pharmacol Toxicol 2001;41:69–72. 9. Harris A: Providing urinary incontinence care to adults at the end of life. Nursing Times 2009;5(29). 10. Coyne K: The impact of overactive bladder on mental health, work productivity and health-related quality of life in the UK and Sweden: Results from EpiLUTS. BJU Int 2011;108(9): 1459–1471. 11. Nabi G, Cody JD, Ellis G, Herbison P, Hay-Smith J: Cochrane Database Syst Rev 2006:CD003781.
OVERACTIVE BLADDER SYMPTOMS IN PALLIATIVE CARE 12. Andersson KE, et al.: Oxybuynin and the overactive bladder: World J Urol 2001;19:319–323. 13. Hills CJ, et al.: Tolterodine. Drugs 1998;55:813–820. 14. Chapple CR: Muscarinic receptor antagonists in the treatment of overactive bladder. Urology 2000;55(5A suppl):33–46. 15. Monthly Index of Medical Specialities (MIMS) online proxy60 .use.hcn.com.au/publicsite/abbreviated?productId = 72790001 16. Andersson KE, et al.: Pharmacological treatment of urinary incontinence. BJU Int 1999;84(9):923–947. 17. Drug information online: www.drugs.com/pro/flavoxate .html 18. de Groat WC: Influence of central serotonergic mechanisms on lower urinary tract function. Urology 2002;59(5 Suppl 1): 30–36. 19. Movig KL, et al.: Selective serotonin reuptake inhibitorinduced urinary incontinence. Pharmacoepidemiol Drug Saf 2002;11(4):271–279. 20. Kim YT, et al.: Gabapentin for overactive bladder and nocturia after anticholinergic failure. Int Braz J Urol 2004;30(4): 275–278. 21. Naglie, et al.: A randomized, double blind, placebo controlled crossover trial of nimodipine in older persons with detrusor instability and urge incontinence. J Urol 2002;167 (2 Pt 1):586–590.
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Address correspondence to: Abigail Walton, MBChB, MRCP Cornhill Macmillan Centre Perth Royal Infirmary NHS Tayside Perth, Scotland E-mail: [email protected]
