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Disordered control of the urinary bladder after human spinal cord injury: what are the problems?
L.C. Weaver and C. Polosa (Eds.) Progress in Brain Research, Vol. 152 ISSN 0079-6123 Copyright r 2006 Published by Elsevier B.V.
CHAPTER 4
Disordered control of the urinary bladder after human spinal cord injury: what are the problems? Patrick J. Potter Regional Spinal Cord Injury Rehabilitation Program, and Physical Medicine and Rehabilitation, St. Joseph’s Health Center, The University of Western Ontario, London, ON, Canada
Abstract: Spinal cord injury has a profound impact on the storage and voiding functions of the urinary bladder. Loss of autonomic and somatic control mechanisms leads to hypo- or hyperactivity of the bladder wall and sphincters causing problems that range from incontinence to complete loss of the capacity to empty the bladder. This chapter outlines the types of bladder dysfunction that occur after spinal cord injury, their relative prevalence and current practices used to manage the problems. With all the interventions that are available, management of bladder function often still remains a compromise, as the medications and physical interventions available may stimulate or block components of the voiding reflex, but are often not fully restorative in this effort. and autonomic functions usually do not recover completely (Menter and Hudson, 1995; Wolfe et al., 2002; Potter et al., 2004). When only partial resolution of the impairment in bladder control occurs, then accommodation to the altered physiological condition requires interventions that range from pharmacological treatments to appliances and mechanical or electrical devices, as presented in the following chapters. For previous reviews of the neurogenic bladder after spinal cord injury see Perkash (2004) and Burns et al. (2001).
Introduction Urinary bladder control is dependent upon coordinated interaction between the somatic and autonomic nervous systems (Burns et al., 2001; de Groat and Yoshimura, 2001). When the supraspinal, coordinated control of these systems is lost, the resulting bladder dysfunction is termed ‘‘neurogenic bladder impairment’’ or a neurogenic bladder. The presence of a neurogenic urinary bladder is extremely common after spinal cord injury (Waites et al., 1993; Cardenas and Hooton, 1995; Vines, 1996; Sapounzi-Krepia et al., 1998; Stover et al., 1989; Chen et al., 1999; Wolfe et al., 2002). In general, this dysfunction is not unique to spinal cord injury as it can arise from disrupted peripheral or central nervous system control. For example, a neurogenic bladder can occur in diseases such as multiple sclerosis (Anderson et al., 1976). Although some neurological recovery may occur following a spinal cord injury, motor, sensory
Brief overview of normal bladder function The urinary bladder is a fluid reservoir that normally empties completely in a well-controlled manner. All of the clinical problems encountered after spinal cord injury are manifestations of impairment in these two basic functions of the bladder: storage and emptying. The lower urinary tract is made up of the bladder, internal sphincter, external sphincter and urethra. The bladder wall is composed of smooth muscle, termed the detrusor muscle, and
Corresponding author. Tel.:+519 685 4080; Fax: +519 685 4081; E-mail: [email protected] DOI: 10.1016/S0079-6123(05)52004-1
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has a base or trigone, a body and a neck. Parasympathetic control of the detrusor muscle originates from preganglionic axons in the pelvic nerve with cell bodies in the 2nd to 4th sacral (S) spinal cord segments. Detrusor contraction is mediated primarily by parasympathetic stimulation. Sympathetic control of this muscle comes from the hypogastric nerve that contains axons of preganglionic neurons that are located in the 10th thoracic (T10) to 2nd lumbar (L2) spinal cord segments. Sensory innervation of the bladder wall travels to the S2–S4 spinal segments via the pelvic nerve. The internal bladder sphincter is made of smooth muscle and is located at the junction of the bladder neck and urethra. This sphincter receives parasympathetic and sympathetic innervation like that of the detrusor. However, in this muscle, sympathetic stimulation causes contraction. The external sphincter is striated muscle that surrounds the urethra and is controlled by somatic innervation from the S2–S4 spinal segments that reach this sphincter via the pudendal nerve. Details of the anatomy and pharmacology of these pathways are presented in later chapters and in reviews by de Groat and Yoshimura (2001) and Burns et al. (2001). To promote the storage function of the urinary bladder, sympathetic innervation plays two key roles. First, through a-adrenergic receptors, the neck and internal sphincter of the bladder are contracted to close the bladder outlet (Ek et al., 1977). Next, via b-adrenergic receptors, the body of the bladder relaxes. Normally, filling of the bladder occurs with minimal increases in pressure. Voiding the bladder is a coordinated process that involves contraction of the detrusor muscle with concomitant relaxation of the striated muscle of the urethra and pelvic floor and relaxation of internal and external sphincters. This requires integrated control from pontine centers in the brain and sacral spinal neurons (see de Groat and Yoshimura, 2001). When the bladder volume increases, sensory input from the bladder wall to the sacral spinal neurons increases until the threshold for the micturition reflex is reached and reflex voiding can be initiated. This process in the able-bodied person is under voluntary control and is accomplished by wellregulated and integrated autonomic and somatic reflexes. After spinal cord injury, changes in the
spinal cord and in the bladder lead to malfunctions in these reflexes and in the storage and voiding functions of the urinary bladder. Clinical presentations of bladder dysfunction after spinal cord injury Neurogenic bladder impairments depend greatly upon the level and extent of central nervous system injury. The lower levels of injury, such as at the level of the conus medullaris, are more likely to result in a flaccid bladder. Thoracic and cervical level injuries commonly generate mixed pictures of detrusor hyperactivity, sphincter spasticity and lack of coordination between the detrusor and sphincters that is termed dyssynergia. Because the urinary bladder is innervated bilaterally, hemi-cord impairments such as the Brown Sequard Syndrome often do not result in significant bladder dysfunction. Furthermore, injuries that spare the central portion of the cord result in relative sparing of bladder function. Issues of bladder dysfunction relate to four major problems: (1) inadequate or excessive detrusor function, (2) inadequate or excessive sphincter function, (3) dyssynergy between detrusor and sphincter actions and (4) impaired ability to sense the bladder (Lisenemayer and Oakley, 2003). Approaches to treatment can therefore be based on manipulation of these functions. Often combinations of approaches are required and the type of bladder management may change through a cord-injured person’s life. For example, during acute care immediately after injury, a Foley catheter is often inserted to drain the flaccid bladder. As some degree of continence develops with time after injury, this approach would likely change to intermittent catheterization during rehabilitation. After discharge from the hospital, some people who are able to regain an active lifestyle, even including participation in sports, rely on condom drainage into a leg bag that obviates the need for strictly timed procedures such as intermittent catheterization. Inadequate detrusor function Inadequate contraction of the detrusor muscle is often associated with spinal cord injuries that
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impair the distal conus medullaris region of the spinal cord. These very low injuries mimic lower motor neuron impairment such as found in peripheral neuropathies, resulting in absent or significantly decreased detrusor contraction. Therefore the approach to remedy this problem is to augment emptying. Such augmentation can be in the form of cholinergic muscarinic receptor stimulation such as the oral administration of bethanecol. Bethanecol must be taken every 4–6 h, and a bladder response occurs 30 min to 1 h after taking the drug. Therefore, drug use has to be timed to coordinate with bladder fullness. Mechanical techniques used by some include increasing intraabdominal pressure with external mechanical pressure such as the Crede´ maneuver that utilizes forward flexion over the subject’s hand as it presses into the abdomen to facilitate voiding. Often emptying with this procedure is incomplete, and to prevent urinary tract infections from occurring as a consequence of the residual urine in the bladder, the Crede´ maneuver may be combined with one catheterization per day to empty the bladder completely. This procedure is not successful in people with detrusor–sphincter dyssynergia as it also can cause contraction of the sphincters, blocking the outflow of urine (Chancellor et al., 1990). The most common approach to the management of an inadequate detrusor response is intermittent catheterization. In some cases of significantly decreased detrusor function, spontaneous detrusor contractions may occur that fail to empty the bladder but are a cause of incontinence. In such cases, an anticholinergic (anti-muscarinic) drug such as oxybutin and intermittent catheterization may be combined.
Excessive detrusor function Increased detrusor tone or spasticity (detrusor hyperreflexia) is part of the upper motor neuron syndrome. In this situation, the detrusor muscle is considered to be ‘‘unstable,’’ contracting at lower bladder volumes and often producing excessive intravesical pressures. Detrusor hyperreflexia often, but not always, occurs with thoracic and cervical cord injuries, and the extent of hyperactivity
of the detrusor muscle is extremely variable between individuals. Clinical approaches to treat this problem include anticholinergic (anti-muscarinic) medication if excessive intravesical pressures prevail. If the detrusor muscle cannot be relaxed adequately with such medication to provide continence between intermittent catherizations, an indwelling catheter or attached device such as a condom catheter is necessary. If, due to lack of sensation, voiding cannot be managed effectively or conveniently, an external appliance (condom drainage) may be used in males. However similar devices are notoriously difficult to maintain in females, resulting, instead, in the use of an indwelling Foley or suprapubic (inserted through the lower abdominal wall) catheter. Decreasing detrusor contractions may also be accomplished by chemically blocking C-fiber bladder afferent neurotransmission with intravesical vanilloids such as capsaicin or resiniferatoxin or by intravesical administration of anticholinergics. Another intravesical approach under investigation is injection of botulinum toxin into the detrusor muscle to cause relaxation (Reitz et al., 2004). Intravesical administration of medication is more invasive than oral medications but does offer options when oral anticholinergic drugs are not effective. When an intravesical route is used for treatment, effects are temporary and repeated treatments are necessary. The ideal time frames for repeated intravesical drug administration are not well established. More invasive approaches for reducing detrusor hyperactivity include denervation procedures such as sacral rhizotomy, a procedure that must be viewed cautiously as it is irreversible. To address reduced bladder capacity due to detrusor hyperreflexia, the bladder size and capacity may be increased by a surgical augmentation cystoplasty using a piece of bowel.
Inadequate sphincter function Inadequate sphincter function, whether associated with inadequate or excessive detrusor function, results in incontinence. Sphincter tone can be enhanced by blocking muscarinic cholinergic receptors or by stimulating b-adrenergic receptors. Of
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these two possible approaches, blocking muscarinic cholinergic receptors is usually the superior, although combination therapy may be utilized. In this condition, the goal is to restore the storage function of the bladder. Once this is accomplished, if the person cannot initiate voiding, then emptying is done by intermittent catheterization. If continence cannot be maintained with drugs, then voiding into an appliance such as a condom catheter is possible, and cholinergic muscarinic receptor agonists such as bethanecol can be utilized to facilitate voiding. Operative approaches to enhance the usefulness of the bladder neck in maintaining continence include surgically modifying the bladder neck or implantation of an artificial sphincter. The most common approach for dealing with inadequate sphincter tone is to enhance the contraction pharmacologically and utilize intermittent catheterization for bladder emptying. Excessive sphincter tone a-2 receptor sympathetic adrenergic blockade is the mainstay of pharmacological management of the contracted bladder neck, to allow emptying in the presence of excessive sphincter tone. Originally developed to treat hypertension, this group of medications has evolved, through several generations, to a family of drugs that can be taken once per day and that have infrequent and less severe side effects such as hypotension. Other approaches to the spastic sphincter include sphincterotomy and pudendal nerve section. Detrusor-sphincter dyssynergia After spinal cord injury, the clinical presentation of a person can be an inability to empty the bladder either spontaneously or by self-initiated voiding. With these symptoms, urodynamic studies are required to ascertain whether the impairment stems from inadequate detrusor function, excessive sphincter activity or dyssynergy between the two muscle groups. Approaches to treating dyssynergia usually involve decreasing bladder neck resistance with a drug such as an a-2 receptor
adrenergic antagonist as discussed above, and applying a device for collection of urine such as a condom catheter. Alternatively, detrusor contraction may be blocked pharmacologically and bladder emptying accomplished by intermittent catheterization. Often these approaches are only partially successful and a compromise in bladder management is reached within the tolerance limits for side effects of the medication. Either the person voids more frequently, and experiences urgency, or catheterizes more frequently. The most common approach in males is to reduce sphincter tone and apply an external device. Impaired ability to sense the bladder At this time, 4-aminopyridine is the only pharmacological agent that has been demonstrated to enhance electrical conduction in the spinal cord, enhancing sensation of bladder contraction and fullness in some individuals (Potter et al., 1998). In the absence of such sensation, management must be accomplished by systems that continuously drain the urine such as condom drainage, indwelling catheters (suprapubic or Foley) or diapers or methods that employ timed, regular emptying such as intermittent catheterization. Infection can be a consequence of all management systems Infection is a problem, secondary to almost all methods of managing the neurogenic bladder after spinal cord injury (Bennett et al., 1995; Stover et al., 1989; Esclarin De Ruz et al., 2000). As the prevalence of resistant bacteria increases (Waites et al., 2000; Siroky, 2002) commonly used, inexpensive antibiotics become ineffective. The frequency of urinary tract infections may necessitate antibiotic prophylaxis (Galloway, 1997; Waites et al., 2001; Morton et al., 2002). Alternative preparations such as cranberry juice that contribute to maintenance of the integrity of the bladder urothelium as a barrier to bacteria then become more important considerations for long-term prophylaxis (Reid et al., 2003). For the cord-injured person, often the most sought after management
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strategy is that which, in their mind, most mimics ‘‘normal function’’ (Jamil, 2001).
Incidence and prevalence of urinary bladder dysfunction after cord injury Most people, during the first days after spinal cord injury, have evidence of a neurogenic bladder. In people with incomplete injury, the majority of recovery of bladder function is evident in the first 6–9 months and improvement can continue for 2 years after injury. The negative consequences of the neurogenic bladder to the health and quality of life for cord-injured people are decreasing with current improvements in management and understanding of the causes of the problems. In one of the early papers on urological aspects of rehabilitation, Bors (1951), described up to 80% mortality of spinal cord injured soldiers in World War I, before they were able to return to the United States. By the time of World War II the survival rate had increased to 88%. Bors attributed this improvement to greater understanding of the pathophysiology of the neurogenic bladder and the advent of antibiotics. Mortality due to urological causes is now estimated to be o3% (Jamil, 2001). The current focus of modern rehabilitation medicine and research is directed toward issues of morbidity and not mortality. The prevalence of a neurogenic bladder after spinal cord injury is high (Anson and Shepard, 1996; Noreau et al., 2000). A study by the Model Spinal Cord Injury Systems of Care determined that 81% of persons with spinal cord injury reported some degree of impaired bladder function (McKinley et al., 1999). Even more significant are the secondary sequelae, including frequent urinary tract infections, pain secondary to urinary tract infection and pain secondary to indwelling devices such as Foley catheters. In a survey of Spinal Cord Injured persons (Wolfe et al., 2002; Potter et al., 2004) regarding the long-term sequelae of spinal cord injury, urological problems had a high prevalence. The ‘‘neurological impairment’’ of bladder function does not appear to change with time, but time and aging result in secondary problems such as urethral
strictures, bladder diverticuli, chronic cystitis and increased incidence of bladder cancer. These prevalence studies reveal that, although we are well aware of the high incidence of neurogenic bladder, we are still limited in our ability to manage its consequences. For example, incomplete emptying is associated with high residual urine volume, which is a risk factor for incontinence and infection (Shekelle et al., 1999; Trautner and Darouiche, 2002). Recognizing that continence is the first issue associated with a neurogenic bladder, pain and infection are equally important long-term sequelae (Post et al., 1998). Although continence may be controlled with devices, sepsis, pain and incontinence may result from recurrent urinary tract infections.
Conclusion The consequences of spinal cord injury to the function of the urinary bladder are severe and play a serious role in the health and well-being of the cord-injured person for life. For the bladder to be an effective reservoir, we fully utilize reflex contraction of the sphincter and reflex detrusor relaxation. For the bladder to empty, these processes must be reversed. After minor impairments voiding may still be possible but with greater effort, incontinence, incomplete emptying, increased frequency, urgency or hesitancy. Given that we often cannot fully reverse the effects of impaired neurological control of bladder function, even with the extensive array of available medication, the most effective approach to the management of neurogenic bladder remains to find the best balance between a person’s need for emptying their bladder, their tolerance for medication, assistive devices and appliances, and the social consequences of maintaining continence (Stover et al., 1989; Cardenas and Hooton, 1995, Liguori et al., 1997; Yavuzer et al., 2000; Boschen et al., 2003). Although restoration of normal function is the ultimate goal of research, development of superior management methods is a high priority as well. Newer generations of pharmacological agents are being developed to provide better therapeutic responses with less side effects. Using strategies such
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as administering medications directly into the bladder can minimize side effects of drugs. Methods for intermittent catheterization have been improved by devices such as hydrophilic catheters that can be inserted with much less friction than conventional catheters (Hedlund et al., 2001; Vapnek et al., 2003). Probiotic treatment, the intravesicular administration of healthy bacteria to prevent infection, may reduce the need for antibiotics. Research must be directed toward finding a cure for the bladder dysfunction after cord injury, but also must address the important objective of providing better management of the neurogenic bladder.
References Anderson, J.T. and Bradley, W.E. (1976) Bladder and urethral innervation in multiple sclerosis. Br. J. Urol., 48: 239–243. Anson, C.A. and Shepherd, C. (1996) Incidence of secondary complications in spinal cord injury. Int. J. Rehab. Res., 19: 55–66. Bennett, C.J., Young, M.N. and Darrington, H. (1995) Differences in urinary tract infections in male and female spinal cord injury patients on intermittent catheterization. Paraplegia, 33: 69–72. Bors, E. (1951) Urologic aspects of rehabilitation in SCI. JAMA, 146: 225–229. Boschen, K.A., Tonack, M. and Gargaro, J. (2003) Long-term adjustment and community reintegration following spinal cord injury. Int. J. Rehab. Res., 6(3): 157–164. Burns, A.S., Rivas, D.A. and Ditunno, J.F. (2001). The management of the neurogenic bladder and sexual dysfunction after spinal cord injury, Spine, 26: S129–S136. Cardenas, D.D. and Hooton, T.M. (1995) Urinary tract infection in persons with spinal cord injury. Arch. Phys. Med. Rehab., 76: 272–280. Chancellor, M.B., Kaplan, S.A. and Blaivas, J.G. (1990) Detrusor-external sphincter dyssynergia. In: Block, G. and Whelan, J. (Eds.), Ciba Foundation Symposium. Vol. 51, Neurobiology of Continence. Wiley, Chichester, West Sussex, pp. 195–213. Chen, D., Apple Jr., D.F., Hudson, L.M. and Bode, R. (1999) Medical complications during acute rehabilitation following spinal cord injury—current experience of the Model Systems. Arch. Phys. Med. Rehab., 80(11): 1397–1401. de Groat, W.C. and Yoshimura, N. (2001) Pharmacology of the lower urinary tract. Annu. Rev. Pharmacol. Toxicol., 41: 691–721. Ek, A., Alm, P., Andersson, K.E. and Persson, C.G. (1977) Adrenergic and cholinergic nerves of the human urethra and urinary bladder: a histochemical study. Acta. Physiol. Scand., 99(3): 345–352.
Esclarin De Ruz, A., Garcia Leoni, E. and Herruzo Cabrera, R. (2000) Epidemiology and risk factors for urinary tract infection in patients with spinal cord injury. J. Urol., 164: 1285–1289. Galloway, A. (1997) Prevention of urinary tract infection in patients with spinal cord injury—a microbiological review. Spinal Cord, 35: 198–204. Hedlund, H., Hjelmais, K., Jonsson, O., Klarslov, P. and Talja, M. (2001) Hydrophilic versus non-coated catheters for intermittent catheterization. Scand. J. Urol. Nephrol., 35: 49–53. Jamil, F. (2001) Towards a catheter free status in neurogenic bladder dysfunction: a review of bladder management options in spinal cord injury. Spinal Cord, 39(7): 355–361. Liguori, P.A., Cardenas, D.D. and Ullrich, P. (1997) Social and functional variables associated with urinary tract infections in persons with spinal cord injury. Arch. Phys. Med. Rehab., 78: 156–160. Lisenemayer, T.A. and Oakley, A. (2003) Accuracy of individuals with spinal cord injury at predicting urinary tract infections based on their symptoms. J. Spinal Cord Med. Winter, 26(4): 352–357. McKinley, W.O., Jackson, A.B., Cardenas, D.D. and De Vivo, M.J. (1999) Long-term medical complications after traumatic spinal cord injury: a regional model systems analysis. Arch. Phys. Med. Rehab., 80(11): 1402–1410. Menter, R.R. and Hudson, L.M. (1995) Effects of age at injury and the aging process. In: Stover S.L., DeLisa J.A. and Whiteneck G.G. (Eds.), Spinal Cord Injury Clinical Outcomes from the Model Systems. Aspen Publishers, Gaithersburg, MD, pp. 272–288. Morton, S.C., Shekelle, P.G., Adams, J.L., Bennett, C., Dobkin, B.H., Montgomerie, J. and Vickrey, B.G. (2002) Antimicrobial prophylaxis for urinary tract infection in persons with spinal cord dysfunction. Arch. Phys. Med. Rehab., 83: 129–138. Noreau, L., Proulx, P., Gagnon, L., Drolet, M. and Laramee, M.T. (2000) Secondary impairments after spinal cord injury: a population-based study. Am. J. Phys. Med. Rehab., 79: 526–535. Perkash, I. (2004) Donald Munro Lecture 2003. Neurogenic bladder: past, present and future. J. Spinal Cord Med., 27: 383–386. Post, M.W., de Witte, L.P., van Asbeck, F.W., van Dijk, A.J. and Schrijvers, A.J. (1998) Predictors of health status and life satisfaction in spinal cord injury. Arch. Phys. Med. Rehab., 79(4): 395–401. Potter, P.J., Hayes, K.C., Segal, J.L., Hsieh, J.T.C., Brunnermann, S.R., Delaney, G.A., Tierny, D.S. and Mason, D. (1998) Randomized double-blind crossover trial of fampridine-SR (sustained release 4-aminopyridine) in patients with incomplete spinal cord injury. J. Neurotrauma, 15(10): 837–849. Potter, P.J., Wolfe, D.L., Burkell, T.A. and Hayes, K.C. (2004) Challenges in educating individuals with spinal cord injury to reduce secondary conditions. Topics in Spinal Cord Injury Rehab., 10: 30–40.
57 Reid, G., Potter, P.J., Lam, D., Warren, D., Borrie, M. and Hayes, K.C. (2003) Cranberry juice to reduce Biofilms and infection in geriatric and spinal cord injured patients with dysfunctional bladders. Natraceuticals & Food, 8: 23–28. Reitz, A., Stohrer, M., Kramer, G., Delpopo, G., ChartierKastler, E., Panneck, J., Burgdofer, H., Gocking, K., Madersbacher, H., Scchumacker, S., Richter, R., von Tobel, J. and Schurch, B. (2004) European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity. Eur. Urol., 4: 510–515. Sapounzi-Krepia, D., Soumilas, A., Papadakis, N., Sapkas, G., Nomicos, J., Theodossopoulou, E. and Dimitriadou, A. (1998) Post traumatic paraplegics living in Athens: the impact of pressure sores and UTIs on everyday life activities. Spinal Cord, 36: 432–437. Shekelle, P.G., Morton, S.C., Adams, J.L., Clark, K.A., Pathak, M. and Vickrey, B.G. (1999) Systematic review of risk factors for urinary tract infection in adults with spinal cord dysfunction. J. Spinal Cord Med., 22: 258–272. Siroky, M.B. (2002) Pathogenesis of bacteriuria and infection in the spinal cord injured patient. Am. J. Med., 113(1A): 67S–79S. Stover, S.L., Lloyd, L.K., Waites, K.B. and Jackson, A.B. (1989) Urinary tract infection in spinal cord injury. Arch. Phys. Med. Rehab., 70: 47–54. Trautner, B.W. and Darouiche, R.O. (2002) Prevention of urinary tract infection in patients with spinal cord injury. J. Spinal Cord Med., 25: 277–283.
Vapnek, J.M., Maynard, F.M. and Kim, J. (2003) A prospective randomized trial of the LoFric hydrophilic coated catheter versus conventional plastic catheter for clean intermittent catheterization. J. Urol., 169(3): 994–998. Vines, C.L. (1996) Identifying Secondary Conditions in Arkansas with Spinal Cord Injuries. Arkansas Spinal Cord Commission, Little Rock, AR. Waites, K., Chen, Y., De Vivo, M.J., Canupp, K.C. and Moser, S.A. (2000) Antimicrobial resistance in gram negative bacteria isolated from the urinary tract in community-residing persons with spinal cord injury. Arch. Phys. Med. Rehab., 81: 764–769. Waites, K.B., Canupp, K.C., Chen, Y., De Vivo, M.J. and Moser, S.A. (2001) Bacteremia after spinal cord injury in initial versus subsequent hospitalizations. J. Spinal Cord Med., 24(2): 96–100. Waites, K.B., Canupp, K.C. and De Vivo, M.J. (1993) Epidemiology and risk factors for urinary tract infection following spinal cord injury. Arch. Phys. Med. Rehab., 74(7): 691–695. Wolfe, D.L., Potter, P.J., Jutai, J.W., Beggs, C., Colwell, S., Orenczuk, S., Regan, M.A., Tonack, M., Trujillo, S. and Zarnowiecki, E. (2002) Long-term physical impact of spinal cord injury: the role of rehabilitation in educating consumers to reduce complications over the long-term. J. Spinal Cord Med., 22(Suppl. 1): S50. Yavuzer, G., Gok, H., Tuncer, S., Soygur, T., Arikan, N. and Arasil, T. (2000) Compliance with bladder management in spinal cord injury patients. Spinal Cord, 38(12): 762–765.
CHAPTER 4
Disordered control of the urinary bladder after human spinal cord injury: what are the problems? Patrick J. Potter Regional Spinal Cord Injury Rehabilitation Program, and Physical Medicine and Rehabilitation, St. Joseph’s Health Center, The University of Western Ontario, London, ON, Canada
Abstract: Spinal cord injury has a profound impact on the storage and voiding functions of the urinary bladder. Loss of autonomic and somatic control mechanisms leads to hypo- or hyperactivity of the bladder wall and sphincters causing problems that range from incontinence to complete loss of the capacity to empty the bladder. This chapter outlines the types of bladder dysfunction that occur after spinal cord injury, their relative prevalence and current practices used to manage the problems. With all the interventions that are available, management of bladder function often still remains a compromise, as the medications and physical interventions available may stimulate or block components of the voiding reflex, but are often not fully restorative in this effort. and autonomic functions usually do not recover completely (Menter and Hudson, 1995; Wolfe et al., 2002; Potter et al., 2004). When only partial resolution of the impairment in bladder control occurs, then accommodation to the altered physiological condition requires interventions that range from pharmacological treatments to appliances and mechanical or electrical devices, as presented in the following chapters. For previous reviews of the neurogenic bladder after spinal cord injury see Perkash (2004) and Burns et al. (2001).
Introduction Urinary bladder control is dependent upon coordinated interaction between the somatic and autonomic nervous systems (Burns et al., 2001; de Groat and Yoshimura, 2001). When the supraspinal, coordinated control of these systems is lost, the resulting bladder dysfunction is termed ‘‘neurogenic bladder impairment’’ or a neurogenic bladder. The presence of a neurogenic urinary bladder is extremely common after spinal cord injury (Waites et al., 1993; Cardenas and Hooton, 1995; Vines, 1996; Sapounzi-Krepia et al., 1998; Stover et al., 1989; Chen et al., 1999; Wolfe et al., 2002). In general, this dysfunction is not unique to spinal cord injury as it can arise from disrupted peripheral or central nervous system control. For example, a neurogenic bladder can occur in diseases such as multiple sclerosis (Anderson et al., 1976). Although some neurological recovery may occur following a spinal cord injury, motor, sensory
Brief overview of normal bladder function The urinary bladder is a fluid reservoir that normally empties completely in a well-controlled manner. All of the clinical problems encountered after spinal cord injury are manifestations of impairment in these two basic functions of the bladder: storage and emptying. The lower urinary tract is made up of the bladder, internal sphincter, external sphincter and urethra. The bladder wall is composed of smooth muscle, termed the detrusor muscle, and
Corresponding author. Tel.:+519 685 4080; Fax: +519 685 4081; E-mail: [email protected] DOI: 10.1016/S0079-6123(05)52004-1
51
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has a base or trigone, a body and a neck. Parasympathetic control of the detrusor muscle originates from preganglionic axons in the pelvic nerve with cell bodies in the 2nd to 4th sacral (S) spinal cord segments. Detrusor contraction is mediated primarily by parasympathetic stimulation. Sympathetic control of this muscle comes from the hypogastric nerve that contains axons of preganglionic neurons that are located in the 10th thoracic (T10) to 2nd lumbar (L2) spinal cord segments. Sensory innervation of the bladder wall travels to the S2–S4 spinal segments via the pelvic nerve. The internal bladder sphincter is made of smooth muscle and is located at the junction of the bladder neck and urethra. This sphincter receives parasympathetic and sympathetic innervation like that of the detrusor. However, in this muscle, sympathetic stimulation causes contraction. The external sphincter is striated muscle that surrounds the urethra and is controlled by somatic innervation from the S2–S4 spinal segments that reach this sphincter via the pudendal nerve. Details of the anatomy and pharmacology of these pathways are presented in later chapters and in reviews by de Groat and Yoshimura (2001) and Burns et al. (2001). To promote the storage function of the urinary bladder, sympathetic innervation plays two key roles. First, through a-adrenergic receptors, the neck and internal sphincter of the bladder are contracted to close the bladder outlet (Ek et al., 1977). Next, via b-adrenergic receptors, the body of the bladder relaxes. Normally, filling of the bladder occurs with minimal increases in pressure. Voiding the bladder is a coordinated process that involves contraction of the detrusor muscle with concomitant relaxation of the striated muscle of the urethra and pelvic floor and relaxation of internal and external sphincters. This requires integrated control from pontine centers in the brain and sacral spinal neurons (see de Groat and Yoshimura, 2001). When the bladder volume increases, sensory input from the bladder wall to the sacral spinal neurons increases until the threshold for the micturition reflex is reached and reflex voiding can be initiated. This process in the able-bodied person is under voluntary control and is accomplished by wellregulated and integrated autonomic and somatic reflexes. After spinal cord injury, changes in the
spinal cord and in the bladder lead to malfunctions in these reflexes and in the storage and voiding functions of the urinary bladder. Clinical presentations of bladder dysfunction after spinal cord injury Neurogenic bladder impairments depend greatly upon the level and extent of central nervous system injury. The lower levels of injury, such as at the level of the conus medullaris, are more likely to result in a flaccid bladder. Thoracic and cervical level injuries commonly generate mixed pictures of detrusor hyperactivity, sphincter spasticity and lack of coordination between the detrusor and sphincters that is termed dyssynergia. Because the urinary bladder is innervated bilaterally, hemi-cord impairments such as the Brown Sequard Syndrome often do not result in significant bladder dysfunction. Furthermore, injuries that spare the central portion of the cord result in relative sparing of bladder function. Issues of bladder dysfunction relate to four major problems: (1) inadequate or excessive detrusor function, (2) inadequate or excessive sphincter function, (3) dyssynergy between detrusor and sphincter actions and (4) impaired ability to sense the bladder (Lisenemayer and Oakley, 2003). Approaches to treatment can therefore be based on manipulation of these functions. Often combinations of approaches are required and the type of bladder management may change through a cord-injured person’s life. For example, during acute care immediately after injury, a Foley catheter is often inserted to drain the flaccid bladder. As some degree of continence develops with time after injury, this approach would likely change to intermittent catheterization during rehabilitation. After discharge from the hospital, some people who are able to regain an active lifestyle, even including participation in sports, rely on condom drainage into a leg bag that obviates the need for strictly timed procedures such as intermittent catheterization. Inadequate detrusor function Inadequate contraction of the detrusor muscle is often associated with spinal cord injuries that
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impair the distal conus medullaris region of the spinal cord. These very low injuries mimic lower motor neuron impairment such as found in peripheral neuropathies, resulting in absent or significantly decreased detrusor contraction. Therefore the approach to remedy this problem is to augment emptying. Such augmentation can be in the form of cholinergic muscarinic receptor stimulation such as the oral administration of bethanecol. Bethanecol must be taken every 4–6 h, and a bladder response occurs 30 min to 1 h after taking the drug. Therefore, drug use has to be timed to coordinate with bladder fullness. Mechanical techniques used by some include increasing intraabdominal pressure with external mechanical pressure such as the Crede´ maneuver that utilizes forward flexion over the subject’s hand as it presses into the abdomen to facilitate voiding. Often emptying with this procedure is incomplete, and to prevent urinary tract infections from occurring as a consequence of the residual urine in the bladder, the Crede´ maneuver may be combined with one catheterization per day to empty the bladder completely. This procedure is not successful in people with detrusor–sphincter dyssynergia as it also can cause contraction of the sphincters, blocking the outflow of urine (Chancellor et al., 1990). The most common approach to the management of an inadequate detrusor response is intermittent catheterization. In some cases of significantly decreased detrusor function, spontaneous detrusor contractions may occur that fail to empty the bladder but are a cause of incontinence. In such cases, an anticholinergic (anti-muscarinic) drug such as oxybutin and intermittent catheterization may be combined.
Excessive detrusor function Increased detrusor tone or spasticity (detrusor hyperreflexia) is part of the upper motor neuron syndrome. In this situation, the detrusor muscle is considered to be ‘‘unstable,’’ contracting at lower bladder volumes and often producing excessive intravesical pressures. Detrusor hyperreflexia often, but not always, occurs with thoracic and cervical cord injuries, and the extent of hyperactivity
of the detrusor muscle is extremely variable between individuals. Clinical approaches to treat this problem include anticholinergic (anti-muscarinic) medication if excessive intravesical pressures prevail. If the detrusor muscle cannot be relaxed adequately with such medication to provide continence between intermittent catherizations, an indwelling catheter or attached device such as a condom catheter is necessary. If, due to lack of sensation, voiding cannot be managed effectively or conveniently, an external appliance (condom drainage) may be used in males. However similar devices are notoriously difficult to maintain in females, resulting, instead, in the use of an indwelling Foley or suprapubic (inserted through the lower abdominal wall) catheter. Decreasing detrusor contractions may also be accomplished by chemically blocking C-fiber bladder afferent neurotransmission with intravesical vanilloids such as capsaicin or resiniferatoxin or by intravesical administration of anticholinergics. Another intravesical approach under investigation is injection of botulinum toxin into the detrusor muscle to cause relaxation (Reitz et al., 2004). Intravesical administration of medication is more invasive than oral medications but does offer options when oral anticholinergic drugs are not effective. When an intravesical route is used for treatment, effects are temporary and repeated treatments are necessary. The ideal time frames for repeated intravesical drug administration are not well established. More invasive approaches for reducing detrusor hyperactivity include denervation procedures such as sacral rhizotomy, a procedure that must be viewed cautiously as it is irreversible. To address reduced bladder capacity due to detrusor hyperreflexia, the bladder size and capacity may be increased by a surgical augmentation cystoplasty using a piece of bowel.
Inadequate sphincter function Inadequate sphincter function, whether associated with inadequate or excessive detrusor function, results in incontinence. Sphincter tone can be enhanced by blocking muscarinic cholinergic receptors or by stimulating b-adrenergic receptors. Of
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these two possible approaches, blocking muscarinic cholinergic receptors is usually the superior, although combination therapy may be utilized. In this condition, the goal is to restore the storage function of the bladder. Once this is accomplished, if the person cannot initiate voiding, then emptying is done by intermittent catheterization. If continence cannot be maintained with drugs, then voiding into an appliance such as a condom catheter is possible, and cholinergic muscarinic receptor agonists such as bethanecol can be utilized to facilitate voiding. Operative approaches to enhance the usefulness of the bladder neck in maintaining continence include surgically modifying the bladder neck or implantation of an artificial sphincter. The most common approach for dealing with inadequate sphincter tone is to enhance the contraction pharmacologically and utilize intermittent catheterization for bladder emptying. Excessive sphincter tone a-2 receptor sympathetic adrenergic blockade is the mainstay of pharmacological management of the contracted bladder neck, to allow emptying in the presence of excessive sphincter tone. Originally developed to treat hypertension, this group of medications has evolved, through several generations, to a family of drugs that can be taken once per day and that have infrequent and less severe side effects such as hypotension. Other approaches to the spastic sphincter include sphincterotomy and pudendal nerve section. Detrusor-sphincter dyssynergia After spinal cord injury, the clinical presentation of a person can be an inability to empty the bladder either spontaneously or by self-initiated voiding. With these symptoms, urodynamic studies are required to ascertain whether the impairment stems from inadequate detrusor function, excessive sphincter activity or dyssynergy between the two muscle groups. Approaches to treating dyssynergia usually involve decreasing bladder neck resistance with a drug such as an a-2 receptor
adrenergic antagonist as discussed above, and applying a device for collection of urine such as a condom catheter. Alternatively, detrusor contraction may be blocked pharmacologically and bladder emptying accomplished by intermittent catheterization. Often these approaches are only partially successful and a compromise in bladder management is reached within the tolerance limits for side effects of the medication. Either the person voids more frequently, and experiences urgency, or catheterizes more frequently. The most common approach in males is to reduce sphincter tone and apply an external device. Impaired ability to sense the bladder At this time, 4-aminopyridine is the only pharmacological agent that has been demonstrated to enhance electrical conduction in the spinal cord, enhancing sensation of bladder contraction and fullness in some individuals (Potter et al., 1998). In the absence of such sensation, management must be accomplished by systems that continuously drain the urine such as condom drainage, indwelling catheters (suprapubic or Foley) or diapers or methods that employ timed, regular emptying such as intermittent catheterization. Infection can be a consequence of all management systems Infection is a problem, secondary to almost all methods of managing the neurogenic bladder after spinal cord injury (Bennett et al., 1995; Stover et al., 1989; Esclarin De Ruz et al., 2000). As the prevalence of resistant bacteria increases (Waites et al., 2000; Siroky, 2002) commonly used, inexpensive antibiotics become ineffective. The frequency of urinary tract infections may necessitate antibiotic prophylaxis (Galloway, 1997; Waites et al., 2001; Morton et al., 2002). Alternative preparations such as cranberry juice that contribute to maintenance of the integrity of the bladder urothelium as a barrier to bacteria then become more important considerations for long-term prophylaxis (Reid et al., 2003). For the cord-injured person, often the most sought after management
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strategy is that which, in their mind, most mimics ‘‘normal function’’ (Jamil, 2001).
Incidence and prevalence of urinary bladder dysfunction after cord injury Most people, during the first days after spinal cord injury, have evidence of a neurogenic bladder. In people with incomplete injury, the majority of recovery of bladder function is evident in the first 6–9 months and improvement can continue for 2 years after injury. The negative consequences of the neurogenic bladder to the health and quality of life for cord-injured people are decreasing with current improvements in management and understanding of the causes of the problems. In one of the early papers on urological aspects of rehabilitation, Bors (1951), described up to 80% mortality of spinal cord injured soldiers in World War I, before they were able to return to the United States. By the time of World War II the survival rate had increased to 88%. Bors attributed this improvement to greater understanding of the pathophysiology of the neurogenic bladder and the advent of antibiotics. Mortality due to urological causes is now estimated to be o3% (Jamil, 2001). The current focus of modern rehabilitation medicine and research is directed toward issues of morbidity and not mortality. The prevalence of a neurogenic bladder after spinal cord injury is high (Anson and Shepard, 1996; Noreau et al., 2000). A study by the Model Spinal Cord Injury Systems of Care determined that 81% of persons with spinal cord injury reported some degree of impaired bladder function (McKinley et al., 1999). Even more significant are the secondary sequelae, including frequent urinary tract infections, pain secondary to urinary tract infection and pain secondary to indwelling devices such as Foley catheters. In a survey of Spinal Cord Injured persons (Wolfe et al., 2002; Potter et al., 2004) regarding the long-term sequelae of spinal cord injury, urological problems had a high prevalence. The ‘‘neurological impairment’’ of bladder function does not appear to change with time, but time and aging result in secondary problems such as urethral
strictures, bladder diverticuli, chronic cystitis and increased incidence of bladder cancer. These prevalence studies reveal that, although we are well aware of the high incidence of neurogenic bladder, we are still limited in our ability to manage its consequences. For example, incomplete emptying is associated with high residual urine volume, which is a risk factor for incontinence and infection (Shekelle et al., 1999; Trautner and Darouiche, 2002). Recognizing that continence is the first issue associated with a neurogenic bladder, pain and infection are equally important long-term sequelae (Post et al., 1998). Although continence may be controlled with devices, sepsis, pain and incontinence may result from recurrent urinary tract infections.
Conclusion The consequences of spinal cord injury to the function of the urinary bladder are severe and play a serious role in the health and well-being of the cord-injured person for life. For the bladder to be an effective reservoir, we fully utilize reflex contraction of the sphincter and reflex detrusor relaxation. For the bladder to empty, these processes must be reversed. After minor impairments voiding may still be possible but with greater effort, incontinence, incomplete emptying, increased frequency, urgency or hesitancy. Given that we often cannot fully reverse the effects of impaired neurological control of bladder function, even with the extensive array of available medication, the most effective approach to the management of neurogenic bladder remains to find the best balance between a person’s need for emptying their bladder, their tolerance for medication, assistive devices and appliances, and the social consequences of maintaining continence (Stover et al., 1989; Cardenas and Hooton, 1995, Liguori et al., 1997; Yavuzer et al., 2000; Boschen et al., 2003). Although restoration of normal function is the ultimate goal of research, development of superior management methods is a high priority as well. Newer generations of pharmacological agents are being developed to provide better therapeutic responses with less side effects. Using strategies such
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as administering medications directly into the bladder can minimize side effects of drugs. Methods for intermittent catheterization have been improved by devices such as hydrophilic catheters that can be inserted with much less friction than conventional catheters (Hedlund et al., 2001; Vapnek et al., 2003). Probiotic treatment, the intravesicular administration of healthy bacteria to prevent infection, may reduce the need for antibiotics. Research must be directed toward finding a cure for the bladder dysfunction after cord injury, but also must address the important objective of providing better management of the neurogenic bladder.
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