BETHANECHOL CHLORIDE IN NEUROGENIC BLADDER DYSFUNCTION ANANIAS C. DIOKNO, M.D. RON KOPPENHOEFER, M.D. From the Section of Urology, Department of Surgery, and Department of Physical Medicine and Rehabilitation, University of Michigan Medical Center, Ann Arbor, Michigan ABSTRACT - Representative case summaries of patients with different types of neurogenic bladder diagnosed by combined cystometric-perineal electromyography and treated with bethanechol (Ure- choline) are presented. Determination of the activity of the periurethral striated muscle in relation to bladder dysfunction is extremely important in the selection of patients for bethanechol therapy. In the absence of structural obstruction, bethanechol can be used in patients with (1) the early phase of coordinated reflex neurogenic bladder and sphincter when there is incomplete bladder emptying due to feeble or unsustained detrusor contractions, (2) recovery phase of spinal shock when the periure- thral striated muscle has recovered and is under voluntary control, (3) incomplete motor paralytic bladder with coordinated sphincter, and (4) sensory paralytic bladder with decompensaticn. The bethanechol regimen will varu in accordance with the type of bladder being treated. - Bethanechol chloride (Urecholine)* is a parasym- neurogenic bladder dysfunction is now a reality. pathomimetic agent that acts on the post- Therefore, it is possible to screen individuals ganglionic parasympathetic effector cells to en- who will benefit from bethanechol and to avoid hance selectively the contractions of the smooth indiscriminate use of this very potent and ex- muscle of the gastrointestinal tract and the de- pensive drug. trusor muscle of the urinary bladder. Its clinical The purpose of this report is to attempt to use has been described in postoperative urinary clarify the indications for the use of bethanechol retention’,’ and in chronic hypotonic dysfunc- in patients with neurogenic bladder dysfunc- tion of the bladder.3 tions. Representative case summaries will be The use of bethanechol in patients with presented and their significance discussed. neurogenic bladder is well known. It has been used in conjunction with intermittent catheteri- Case Summaries zation in patients with spinal cord injury to Case 1 achieve adequate reflex voiding and a catheter- free state. It has also been used either at the A twenty-year-old white male was involved in onset of an intermittent catheterization program a motorcycle accident and sustained a compres- in all patients if no contraindications exist4,5 or sion fracture of the fourth and fifth dorsal ver- seven to ten days later if no spontaneous voiding tebrae with a resultant complete sensory and has occurred. 6 motor paraplegia of the fourth dorsal vertebra. With the advent of sophisticated instruments, Ten days after the injury a combined cystomet- accurate identification of the nature of the ric and perineal electromyographic study showed a spinal shock bladder and recovery phase of the periurethral striated muscle.7 Dur- *hferck, Sharp and Dohme, West Point, Pennsylvania. ing the combined study, attempted voiding UROLOGY / NOVEMBER 1976 / VOLUME VIII, NUMBER 5 -455 produced no detrusor contractions or relaxation A cystometric-electromyographic study two of the sphincter. weeks later indicated upper and lower motor The patient was placed on an intermittent neuron involvement and a positive bethanechol self-catheterization program.’ One month later a test. Electromyography of the periurethral follow-up cystometric-electromyographic study striated muscle revealed a spastic sphincter with showed a reflex bladder with coordinated de- incomplete relaxation during attempted micturi- trusor and sphincter. ’ During the study, it was tion. She was initially treated by intermittent observed that the detrusor contractions were self-catheterization and an anticholinergic agent. too weak and transient to empty the bladder However, because of her stature catheterization completely in spite of complete relaxation of the was difficult and had to be terminated. periurethral striated muscle. Endoscopy re- Bethanechol, 5 mg. given subcutaneously, was vealed no obstruction. He was then taught vari- associated with severe side effects; the dosage ous methods to trigger reflex voiding. In addi- was then adjusted to 2.5 mg. subcutaneously tion, he was placed on 25 mg. of bethanechol every four hours. She voided small volumes orally every six hours and instructed to ranging from 25 to 30 ml. and had residual catheterize himself mainly for check of residual urines of 250 to 300 ml. Bethanechol therapy urine. He did extremely well on this program; was discontinued, and the patient was placed his urine remained uninfected and residual again on an indwelling Foley catheter. urines were low. Bethanechol was discontinued without difficulty eight months after injury. Case 4 A twenty-six-year-old black male was shot in Case 2 the back. Physical examination showed anes- Complete paraplegia of the fourth dorsal ver- thesia and analgesia on the right from the fourth tebra and acute urinary retention suddenly de- lumbar to first sacral vertebra and anesthesia of veloped in a thirty-year-old male. He was trans- the first sacral vertebra on the left. Motor ferred to the University of Michigan Medical examination revealed paralysis of the right lower Center and a laminectomy (third to fourth dor- extremity from the fourth lumbar vertebra. sal vertebra) was performed; the pathology re- Combined cystometry and electromyography port was consistent with multiple myeloma. He showed an incomplete motor paralytic bladder received postoperative radiation and chemo- with partial denervation of the periurethral therapy but his paraplegia remained unchanged. striated muscle. During this combined study, it A cystometric-electromyographic study one was demonstrated that attempted voiding pro- month after the laminectomy showed a reflex duced no voiding contractions but resulted in neurogenic bladder with an uncoordinated relaxation of the periurethral striated muscle. sphincter. Initial therapy consisted of intermit- Bethanechol (7.5 mg. subcutaneously every six tent self-catheterization and an anticholinergic hours) was given, and the patient voided spon- agent. After more than two years of self- taneously with residual urines in the 30- to catheterization without any problem, urinary lOO-ml. range. Bethanechol was reduced to 5 incontinence developed between catheteriza- mg. subcutaneously every six hours three days tions. A repeat combined study showed a reflex later. The residual urine remained low on this neurogenic bladder with coordinated sphincter dosage, and after two days bethanechol was activity. Reflex voiding was augmented with changed to 50 mg. orally every six hours. The bethanechol 25 mg. orally four times daily. Re- patient continued to void adequately with low sidual urines were approximately 50 to 75 ml. residuals of 35 to 40 ml., and the bethanechol after the sixth day of this regimen. Bethanechol was discontinued after several more days. was discontinued a month later when follow-up visits showed low residual urines. Case 5 A nineteen-year-old white male suffered a Case 3 flexion injury to his cervical spine with a result- A thirty-year-old female achondroplastic ant dislocation at the fourth to fifth cervical ver- dwarf was admitted with spastic paraparesis of tebra. He underwent a laminectomy on May 6, the eighth dorsal vertebra secondary to dor- 1975. On June 3, 1975, the patient was trans- solumbar stenosis. A decompressive laminec- ferred to the University of Michigan Medical tomy from eighth dorsal to third lumbar vertebra Center, and physical examination at that time was performed but paraparesis remained. showed fair to good muscle strength in all 456 UROLOGY / NOVEMBER 1976 / VOLUME VIII, NUMBER 5 extremities, clonus in lower extremities, and During this acute phase, bethanechol is ineffec- bilateral Hoffmann and Babinski signs. Cys- tive. In the recovery phase of spinal shock, the tometrograms and electromyograms showed a bladder is still inactive, but now the periure- spinal shock bladder with recovery phase of the thral striated muscle will reveal varying degrees striated musculature. The periurethral striated of electrical activity. muscle showed increasing electrical activity In incomplete lesions of the spinal cord above with bladder distention. Attempts at voiding the sacral reflex arc, voluntary relaxation of the produced voluntary relaxation of the striated periurethral striated muscle can occur without muscle without any noticeable change in the in- detrusor contraction and may be elicited by ask- travesical pressure. He was treated with ing the patient to attempt voiding. This indi- bethanechol 2.5 mg. subcutaneously every four cates that voluntary somatic control to the hours. With this dosage abdominal cramps de- sphincter has recovere’d or is in the recovery veloped, and the dose was then reduced to 25 phase. We have found bethanechol extremely mg. orally every six hours. He urinated with helpful in rehabilitating this type of bladder high residual urines, and after a week the (Case 5). The dose starts with 2.5 to 5 mg. of bethanechol dosage was increased to 50 mg. or- bethanechol subcutaneously every four to six ally every six hours. He responded well to this hours with catheterization for residuals once or dose and voided with volumes of 300 ml. and twice a day. When residual urine is less than 50 residual urines of 40 to 50 ml. Bethanechol was