B. Ceclor Product. Monograph. OTITIS 1. Klein JO. ... thrombocytosis, elevated BUN and creatinine, hematuria and pyuria have also been reported. Cases of ...
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Howard N. Fenster, MD, FRCSC Gayle D. Scarrow, RTR
Quadriplegia: Urological Complications SUMMARY
RESUME
Unlike the general public, quadriplegics are prone to various urological complications as a direct/indirect result of spinal cord lesions.
Contrairement a l'ensemble de la population, les quadriplegiques sont enclins aux differentes sont directement/ complications urologiques indirectement dequi lesions a la moelle resultat on retrouve la Parmileces complications,
epiniere. vessie neurogene, les infections des voies urinaires, bladder, urinary tract infections, renal and bladder calculi, obstructive uropathy, renal les calculs renaux et vesicaux, l'uropathie obstructive, l'insuffisance renale et les neoplasies vesicales. Un failure, and bladder neoplasms. A nombre important d'infections urinaires hautes, insignificant portion of upper urinary tract la pye'lone'phrite, I'hypeme6phrose et les calculs signifieantincluding portudion pyelonephritis, pyelonephritiscluant disease, sont habituellement secondaires a une vessie neurogene et attribuables a une dysfonction du sphincter hypernephrosis, and calculi are usually du secondary to neurogenic bladder related to detrusor. Ces complications sont discutees plus en detail dans le rapport qui suit. detrusor sphincter dysfunction. These complications will be discussed in some detail in the following report. (Can Fam Physician 1989; 35:297-299.) Key words: quadriplegia, urological complications, neurogenic bladder, urinary tract infections.
Tlhese complcations include neurogenic
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Dr. Fenster is Head of the Division of Urology, Department of Surgery at University Hospital, Shaughnessy Campus, University of British Columbia. Ms. Scarrow is research assistant in the Department of Surgery at University Hospital, Shaughnessy Campus. Requests for reprints to: Dr. H. Fenster, Department of Surgery, University Hospital, Shaughnessy Campus, 4500 Oak Street, Vancouver, B.C. V6H 3N1
U NLIKE THE GENERAL public, quadriplegics are prone to various urological complications as a direct/indirect result of spinal cord lesions. These complications include neurogenic bladder, urinary tract infections, renal and bladder calculi, obstructive uropathy, renal failure, and bladder neoplasms.
Neurogenic Bladder Neurogenic bladder is the direct result of spinal cord injury with interruption of vesical and sphincteric autonomic and somatic nerve supply. The term 'spinal shock' describes the CAN. FAM. PHYSICIAN Vol. 35: FEBRUARY 1989
period during which there are no neurological functions below the area of injury. The severity of the lesion depends on a variety of factors, including the level of the spinal cord disruption and the completeness of the lesion. The urological result is a loss of detrusor tone without accompanying loss of external sphincter control. ' Unless a catheter is inserted, urine retention eventually increases the intravesical pressure to a point where overflow incontinence results. If the pressure is allowed to continue, overdistention will damage the detrusor. There is also the possibility of uretero-vesical reflux and urinary tract infections (uris). I After the phase of spinal shock is over (24 hours-three months), the bladder's tone returns, and spastic contractions occur.2 In quadriplegia, the nerve supply to bladder and sphincter mechanisms is interrupted with a resultant inco-ordination of these structures, known as detrusor sphincter dyssynergia; this condition inhibits bladder emptying. In a study conducted on 105 patients with spinal cord injuries (scis),
it was found that 86% of those with upper motor neuron lesions who had accompanying involuntary bladder contractions had dyssynergic urethral sphincters.3 The resultant residual urine can become a medium for bacterial growth with resulting uris and functional obstruction with accompanying "dilation of the upper urinary tract (UUT) and impaired renal function". Twenty-eight per cent of patients with non-contractile detrusor muscles were found to have dyssynergic external sphincters. The problem becomes exacerbated by inflammation of the lower urinary tract and decubiti near the urogenital region, both of which can increase the
dyssynergia.3 Patients with spinal lesions at T6 or above may also develop autonomic hyperreflexia (or dysreflexia) as the bladder becomes over-distended. This is a condition in which the sympathetic nervous system becomes over-active, resulting in hypertension, bradycardia, and possibly, cerebrovascular hemorrhages. Patients experience sweating, reduced body temperature, headaches, and skin 297
flushing below the injury site. The condition is exacerbated by the fact that the sympathetic nervous system also causes a contraction of the internal sphincter of the bladder, resulting in a further increase in the intravesical pressure. This condition can be caused by renal calculi, a blocked catheter, and uTis that induce visceral stimulation.1 4 Finally, patients with neurogenic bladder may develop reflex spasms, a condition which particularly plagues those patients who use implanted catheter drainage. This group includes the majority of quadriplegic women, as intermittent catheterization is often impossible for them because of the limited use of their hands and the lack of adequate external drainage devices. Reflex spasms can be strong enough to expel the catheter and balloon, which may cause trauma and damage to the bladder neck and urethra. In one study this occurred regularly in one patient and resulted in the formation of a retropubic abscess and osteomyelitis of the pubic bones.5
Urinary Tract Infections Urinary tract infections are the major cause of urological problems for the quadriplegic patient. In the past, uTIs leading to renal failure were the main cause of death for sci patients. Today they rarely result in death but remain the main source of fever and morbidity for the sci. Infections include cystitis, orchitis, urethritis, epididymitis, polynephritis, and periurethral and scrotal abscesses. Renal and/or bladder calculi, which themselves result from repeated infections, may cause additional infections.6 The easiest route of entry for bacteria into the body is through the bladder as a result of frequent catheterizations. Each catheterization carries a one per cent to three per cent chance of a subsequent infection. Of those patients requiring an implanted catheter, virtually 100% will develop an infection. The initial, and perhaps greatest danger of uTI in the sci, relates to the diagnosis of an infection. Such a diagnosis can easily be missed because these patients lack normal sensations that include urgency, dysuria, and back pain. Often the first sign of an infection in the sci is a fever.6 The symptoms of these pa298
tients include malaise, increased skeletal muscle spasticity, elevated white blood cell (wBc) count, incontinence, and a change in the colour and odour of the urine. Generally, bacteria enter the bladder via four routes; first, through the initial catheterization from the periurethral area; secondly via the boundary between the catheter itself and the urethral meatus; thirdly through the retrograde flow of urine from the collecting bag; and fourthly, through the junction of the catheter and the collecting tube.6 The urinary tract itself has been found to be the major source of septicemia in the quadriplegic patient. If the infection is allowed to continue, renal failure may develop.6 Furthermore, repeated infections may result in renal damage, specifically cortical scars in more severe cases, although there is generally no subsequent loss of renal function. Severe pyelonephritis may cause necrosis in the kidneys with resultant anuria, but, again, a chronic loss of renal function would be unusual.6
Renal/Bladder Calculi Calculi form and develop for many causes. Within the sci population, there is an increased incidence of renal and/or bladder calculi formation as compared to that in the general public. This higher incidence is partially related to demineralization of the long bones from lack of use, bed rest, and subsequent excretion of calcium by the kidneys and bladder. In addition, the presence of a Foley catheter, residual urine, and recurrent infections can lead to the development of calculi. Khan found that in patients with implanted catheters, 49.1% had bladder stones while 13% developed renal stones.' The presence of calculi can lead to obstruction, infections and sepsis, reduce renal function, and possibly cause renal failure.1'7'8 The presence of catheters or stones as foreign bodies in the bladder can result in an infection within 48-72 hours.' Gardner and colleagues conducted a study on 819 sci patients over a 37year period.9 They found a six per cent incidence of uur calculi, which is significantly higher than that of the general population. Like uris, calculi are often present asymptomatically,
as reported in 78% of the cases in Gardner's study.9 Work done at the National Spinal Cord Injury Data Research Center in Phoenix, Arizona, showed that renal stones were most likely to develop within the first three months post-injury. Such stones generally formed in men with neurologically complete lesions and histories of bladder stones.10 It was noted that neurologically complete quadriplegics are 3.5 times more likely to develop a renal stone before discharge then are neurologically incomplete paraplegics.10 The stones were of the type associated with uri in 98% of the cases recorded in previous studies.10
Obstructive Uropathy Obstruction in the urinary tract can be caused by a variety of factors, including obstruction of a catheter, stones, and detrusor-sphincter dyssynergia resulting in outflow obstruction.1 The mechanism of lower urinary tract obstruction is as follows: the external sphincter becomes spastic and over-active allowing for dyssynergia. This causes various degrees of incomplete urinary retention, with resultant overextension of the bladder. High intravesical pressure leads to increasing ischemia of the detrusor muscle, with breakdown of its various defence mechanisms causing urinary tract infections. As detrusor pressures increase, there can be either increasing obstruction to the vesicle junction or disruption of this junction leading respectively to obstruction or reflux. Increasing obstruction of the bladder can lead to increasing trabeculation and diverticuli. Chronic reflux paves the way for pyelonephephritis, calculi and, finally, renal failure. The persistent infections and residual urine in the bladder can lead to the development and recurrence of bladder calculi. As stated above, over-distention of the bladder resulting in an obstruction caused by sphincter dyssynergia may cause autonomic hyperreflexia. A lower tract obstruction may also result in the development of hydronephrosis, with associated reflux from the bladder.11 Upper-tract dilatation may be caused by an obstruction in the intramural ureter, ureteric orifice or bladder outlet as well as uris and bilateral vesico-ureteric reflux.12 Urinary tract infection caused by a CAN. FAM. PHYSICIAN Vol. 35: FEBRUARY 1989
blocked catheter can lead to further infections of adjacent areas, such as periurethral abscesses or epididymitis.6
Bladder Neoplasms Urinary tract neoplasms are found in a greater percentage of quadriplegic people than in the general public. Trieschmann cited Nyquist and Bors study13 which found that 0.38% of sci patients studied died of some form of urinary cancer whether urethral, bladder, or renal. This percentage is higher than the average (0.008%) found in the non-disabled population13. A more recent study was conducted by the National Spinal Injuries Centre in England.13 They found that 0.37% of the cases studied had bladder cancer. This worked out to a risk factor in sci patients of 20 times the norm found in non-disabled men in England and Wales. Since many of those studied were injured before 1950, when bladder care was vastly different from today, it has been hypothesized that this difference may have something to do with the increase in the presence of bladder cancer in these patients. 13 Incidences of carcinoma in the lower urinary tract after urinary diversion are low, but occurrences have been reported.14 Among those reported, there was found to be a "high incidence of squamous cell carcinoma ... suggesting that chronic irritation may have been an important factor."'14 In a study by Polsky and colleagues,15 90% of those participants with chronic infective bladders showed an incidence of squamous metaplasia. In patients with a post-diversion bladder the incidence was 64%. The relationship between bladder epithelium undergoing precancerous polypoid and metaplastic changes, and columnar and squamous metaplasia as a possible point in this advancement to adenocarcinoma and epidermoid carcinoma has been summarized by Mostofi.16
Conclusions Patients with quadriplegia are prone to a variety of urological complications. It is only by their recognition that they can be adequately treated with the object of decreasing the morbidity and mortality of quad-
riplegics.U CAN. FAM. PHYSICIAN Vol. 35: FEBRUARY 1989
References
Prescribe Ceclore (cefaclor) BRONCHITIS 1. Brown R et al. Am Fam Phy 1987; 36(5):133-139. 2. Toews GB. Seminars In Respiratory Medicine 1986; 8(2):165-170. 4. Grossman 3. PenningtonJE.AmFamPhy 1986;
1. Khan Z. Neurogenic bladder and void- RF (In) Bacterial Bronchitis Emerging31(2):153-160. Concepts of Diagnosis and Treatment. Eli Lilly Canada Inc., Toronto, Ontario 1988. 5. Tremblay ing dysfunction. In: Berczeller PH, Bez- LD, L'Ecuyer J, Provencher P, Bergeron MG. Resistance of Haemokor MF, eds. Medical complications of philus Influenzae in Canada, Universite Laval and Le Centre Hospitalier de l'Universite Laval (C.H.U.L.), Service d'infectilogie, quadriplegia. Chicago & London: Year Quebec, Canada. (Unpublished), 1986. 6. Gleckman RA. Comp Book Medical Publishers, Inc. 1986: 62, Therap 1987; 13(2):44-48. 7. Goodman and Gilman's The Pharma66,69,64,71. cological Basis of Therapeutics. 7th Ed., 1985. B. Ceclor Product Monograph. 2. Hughes S, ed. Short textbook of ortho- OTITIS 1. Klein JO. Reviews of Inf Dis 1986; 8(4):521-562. 2. Henderson FW, Giebink GS. Reviews of Infect Dis 1986; pedics and traumatology. 3rd ed. New 8(4):533-538. 3. Tremblay LD. L'EcuyerJ. Provencher P. Bergeron York, N.Y.: Arco Publishing Inc., 1983. MG. Resistance of Haemophilus Influenzae In Canada, Universite Laval and Le Centre Hospitalier de l'Universite Laval (C.H.U.L.), d'infectiologie, Quebec, Canada. (Unpublished). 4. Mandel 3. Wyndaele JJ. Urethral sphincter dys- Service EM, Bluestone CD et al. PedlnfecDis 1982; 1(5):310-316. 5. Weiss synergia in spinal cord injury patients. JC, Melman ST. Ped Infect Dis J 1988; 7:23-26. 6.Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th Ed., 1985. Paraplegia 1987; 25(1):10, 13. 7. Ceclor Product Monograph. 4. Grundy D, Russell J, Swain A. ABC CECLOR: PRESCRIBING SUMMARY of spinal cord injury Urological manage- INDICATIONS: The treatment of the following infections caused by Strept. pyogenes, Strept. pneumoniae. Staphylococci (including ment. Br Med J 1986; 292(6515):249-53. coagulase-positive, coagulase-negative, and penicillinase-producing strains), E Coli, Proteus mirabilis, Klebsiella pneumoniae, H. 5. Lindan R, Leffler EJ, Bodner D. Uro- influenzae (including ampicillin-resistant strains): media, logical problems in the management of 2.1. Otitis Infections, including pneumonia, bronchitis, Respiratory Lower quadriplegic women. Paraplegia 1987; and pulmonary complications resulting from cystic fibrosis 3. Upper Respiratory Infections, including pharyngitis and tonsillitis, 25(5):382. 4. Skin and Soft-Tissue Infections, 6. Press RA. Urinary tract infections. In: 5. Urinary Tract Infections. Persons who have shown hypersensitivity Berczeller PH, Bezkor MF, eds. Medical CONTRAINDICATIONS: to the cephalosporin antibiotics. complications of quadriplegia. Chicago & WARNINGS: Cephalosporins should be given only with caution to London: Year Book Medical Publishers, penicillin-sensitive patients. There is some evidence of crossallergenicity between penicillins and cephalosporins. Patients have Inc., 1986; 73, 74, 83, 84, 74. been reported to have had severe reactions (including anaphylaxis) 7. Kuhlemeier KV, Lloyd LK, Stover SL. to both. Administer with caution to any patient who has demonstrated form of allergy, particularly to drugs. If an allergic reaction to Long-term follow-up of renal function some the drug should be discontinued and the patient Ceclor after spinal cord injury. J Urol 1985; treated occurs, with the usual agents. Pseudomembranous colitis has been reported with virtually all broad-spectrum antibiotics; therefore, it 134(3):513. is important to consider its diagnosis in patients who develop the use of antibiotics. 8. Loening S, Kramolowsky E, Weahle diarrhea in association with PRECAUTIONS: Safety during pregnancy has not been established. S. Extracorporeal shock wave lithotripsy Small amounts of Ceclor have been detected in mother's milk in para- and quadriplegic patients. In: following administration of single 500 mg doses. The effect on infants is not known. Caution should be exercised when ASIA-American Spinal Injury Associa- nursing Ceclor is administered to a nursing woman. Prolonged use may tion, Proceedings, 13th Annual Scientific result in the over-growth of non-susceptible organisms. If superinfection occurs, administration of Ceclor should cease and Meeting, Boston, MA., 1987; 185. appropriate measures taken. Positive direct Coombs' tests have been reported during treatment with cephalosporins and may be 9. Gardner BP, Parsons KF, Soni BM, due to the drug. Administer with caution in the presence of markedly Krishnan MS, Krishnan KR. Manage- impaired renal function. The safe dosage is likely to be lower than recommended. A false-positive reaction for glucose that ment of upper urinary tract calculi in spi- in theusually urine may occur with Benedict's or Fehling's solution or nal cord damaged patients. Paraplegia with Clinitest tablets but not with Tes-Tape® (Glucose Enzymatic Test Strip, USP). 1985; 23(6):371, 375. ADVERSE REACTIONS: Of 1,493 patients treated with cefaclor, 87 (5.8%) had adverse reactions or abnormal laboratory values 10. DeVivo MJ, Fine PR, Cutter GR, judged to be drug-related. These included: nausea and vomiting, Maetz HM. Risk of renal calculi in spinal dyspepsia, diarrhea, rash (including urticaria & morbilliform erupCoombs', eosinophilia, genital moniliasis, vaginitis, tions), positive cord injury patients. J Urol 1984; and elevated SGPT. Other adverse reactions experielevated SGOT, 131(5):857, 858, 857. enced less frequently include: pruritus, dizziness, headache, somnolence, abdominal pain, leg cramps, abnormal taste, and fever. 11. Hanak M, Scott A. Spinal cord inju- Leukopenia, decreased hemoglobin and hematocrit, neutrophilia, alkaline phosphatase, lymphocytosis, lymphocytopenia, ry: an illustrated guide for health-care elevated elevated BUN and creatinine, hematuria and pyuria professionals. New York, N.Y.: Springer thrombocytosis, have also been reported. Cases of serum-sickness-like reactions (including skin manifestations, fever and arthralgia/arthritis), Publishing Co., 1983. anaphylaxis, and pseudomembranous colitis have been reported. AND TREATMENT OF OVERDOSAGE: There has 12. Gardner BP, Parsons KF, Machin SYMPTOMS no experience of overdosage with Ceclor. If a large overdose been DG, Galloway A, Krishnan SK. Urologi- has been recently consumed, the patient should be kept under cal management of spinal cord damaged observation and appropriate treatment undertaken as considered patients: a clinical algorithm. Paraplegia necessary. DOSAGE AND ADMINISTRATION: Ceclor is administered orally. 1986; 24(3):141. Adults - The usual adult dosage is 250 mg every 8 to 12 hours. The maximum recommended dosage is 2 g per day, although doses 13. Trieschmann RB. Aging with a of 4 g per day have been administered safely for 28 days. Children - The usual dosage for children is 20 mg/kg/day in disability. New York: Demos Publica- divided doses every 8 to 12 hours. In more serious infections, tions, 1987: 76, 82, 84. otitis media, and those infections caused by less susceptible organisms, 40 mg/kg/day is recommended, up to 1 g per day. For lower respiratory tract infections, the total daily dosage 14. Moloney PJ, Fenster HN, McLoughshould be divided and administered 3 times daily. For B-hemolytic lin MC. Carcinoma in the defunctional- streptococcal infections administer for at least ten days. ized urinary tract. J Urol 1981; DOSAGE FORMS:
126(2):260-1.
15. Polsky MS, Webber Jr. CH, Williams III JE, Nikolewski RF, Barr MT, Ball TP. postand infected Chronically diversionary bladders. Systologic and histopathologic studies. J Urol 1976; 7:531. 16. Mostofi FK. Potentialities of bladder epithelium. J Urol 1954; 71:705.
Ceclor 250 mg Pulvules 3061. Each opaque purple and white capsule contains 250 mg cefaclor. Bottles of 100 capsules. Ceclor 500 mg Pulvules 3062. Each opaque purple and grey capsule contains 500 mg cefaclor. Bottles of 30 and 100 capsules. Ceclor 125 mg for Oral Suspension (M-5057).'Strawberry flavored, 125 mg/S mL. Coclor 250 mg for Oral Suspension (M-5058). Grape flavored, 250 mg/S mL.
Reconstitute suspensions by adding 60 mL of water to each 100 mL bottle or 90 mL for each 150 mL bottle in two portions. Shake well after each addition. After mixing, store in a refrigerator. The mixture may be kept for 14 days without significant loss of potency. Shake well before using. Keep tightly closed. Product Monograph available on request. ~~ Eli Lilly Canada Inc., Toronto, Ontario Licensed user of trademarks owned by t I7.gI 5 _ Eli Lilly and Company
