Intravesical Diamorphine for Bladder Spasm

Case Report 

A 57-year-old man with a complex medical history was admitted for control of bladder spasms. He initially presented with episodes of recurrent hypercalcemia and recurrent renal calculi requiring surgery. He was incidentally found to have a medullary thymoma that was surgically removed and treated with postoperative radiotherapy. He was then diagnosed with primary hyperparathyroidism and found to have a multinodular goiter and parathyroid adenoma, both of which were excised. Investigation of increasing breathlessness led to the diagnosis of multiple pulmonary emboli and heart failure secondary to dilated cardiomyopathy.

He was admitted for a bladder neck incision after problems with urinary retention, and while under the care of the urologists, he was found to have a well-differentiated transitional cell carcinoma of the bladder and a high-grade adenocarcinoma of the prostate. This was treated with transurethral resection of the prostate, bicalutamide (Casodex), mitomycin C bladder instillation, and pelvic radiotherapy.

When he was referred to the Palliative Care team, he had been suffering for a couple of months with excruciating bladder spasms radiating from his suprapubic area into both groins and penis. Simple measures, such as bladder washouts, change of catheter, and exclusion of infection, proved ineffective. He was taking morphine sulfate extended-release tablets 120 mg twice daily with oral morphine solution for breakthrough pain, oxybutinin 5 mg three times daily, diazepam 5 mg three times daily and gabapentin 600 mg three times daily. He had unsuccessfully tried other drugs for the spasms, including amitriptyline, flavoxate hydrochloride, and hyoscine butylbromide (both orally and in a syringe driver). His other noteworthy ongoing medications included lofepramine for depression, warfarin, and large doses of diuretics—furosemide 160 mg, metolozone 5 mg, and spironolactone 100 mg.

As he was at increased risk of both gastrointestinal toxicity (long-term warfarin) and nephrotoxicity, nonsteroidal anti-inflammatory drugs (NSAIDs) were avoided (although rectal diclofenac was tried once, without success). We recommended bupivacaine bladder washouts via his catheter, to be clamped for 20 minutes before release. These conferred no benefit and we advised oral clonazepam 2 mg nightly, with limited success. Dexamethasone 6 mg daily was then prescribed in the hope of achieving some anti-inflammatory effect.

We then suggested a trial of diamorphine 10 mg in 20 ml of saline instilled intravesically every 4 hours. None of the team had used this route of administration before, but the resulting pain relief was remarkable. The patient's pain completely resolved within hours and he remained pain-free. He went on to learn to perform intermittent self-catheterization and instill the diamorphine himself. His suprapubic catheter was then removed and he was discharged home on reduced doses of analgesics. Three weeks later, his pain remained controlled using the intravesical diamorphine three times a day. He continued the oral morphine 90 mg twice daily and clonazepam. All other antispasmodic, anticonvulsant, steroid and analgesic medication had been discontinued.

Comment 

Patients with carcinoma of the bladder or other pelvic tumors can experience agonizing spasms of the bladder or urethra. These may be caused by irritation from indwelling catheter, infection, hemorrhage, blood clots, stones, urinary retention, radiation fibrosis, or may be due to increasing tumor bulk within the bladder or pelvis. The pain can be both nociceptive and neuropathic.1, 2

Reversible causes should be identified and managed appropriately along with simple measures such as encouraging oral fluids, bladder washouts, and changing the catheter. Radiotherapy and chemotherapeutic options should be discussed with the patient's oncologist. Conventional analgesics should be prescribed according to the World Health Organization's analgesic ladder. The severity of the pain will often warrant opioid analgesia.1, 2

Prostaglandins E2 and F2-alpha stimulate strips of human bladder muscle in vitro.3 As NSAIDS inhibit prostaglandin synthetase, they should theoretically inhibit this smooth muscle contraction. They have been used for detrusor instability caused by increased bladder activity4 and are themselves analgesics.1, 2

Smooth muscle relaxant drugs, including oxybutinin,5 flavoxate,6 hyoscine butylbromide, dicyclomine, and propantheline, have been used with varying success. It is thought that these work through their anticholinergic effect, blocking the parasympathetic control of the bladder, which results in reduced frequency of bladder contraction.1, 2 Instillation of oxybutinin into the bladder has been attempted.7

Theoretically, if the pain has neuropathic elements, drugs such as tricyclic antidepressants and anticonvulsants should be of some benefit, though no evidence for this was found in the literature. Corticosteroids may be of use when the spasm is due to inflammation or compression from tumor bulk.1 Calcium channel blocking agents have been shown to reduce ureteral activity in vitro, but their use in vivo has not been established.8

Ten milliliters of bupivacaine 0.5% made up to 20 ml with 0.9% saline instilled via an indwelling catheter for 30 minutes has been recommended for bladder spasm.2 This should theoretically work through local anaesthetic action, but no evidence was apparent in the literature.

Instillation of morphine 10–20 mg is cited without reference in one textbook.2 A literature search revealed only one article referring to the intravesical use of opioids. This demonstrated that bladder morphine infusion was effective for postoperative pain in the first 48 hours after bladder surgery in pediatric cases.9 No documentation of use in cancer patients was found.

Epidural opioids have successfully been administered for the treatment of bladder spasm.10 Celiac axis plexus block or lumbar sympathetic block2 may be of use in difficult cases.

In this case, intravesical diamorphine was found to have dramatic and persistent analgesic effect against bladder spasm in a patient with carcinoma of the bladder. Many standard analgesics, including oral opioids, had failed. This suggests that the opioids had a local analgesic effect that was more effective than their central effect. This is an area lacking substantive evidence for many of the drugs we use, and is a potential area for further research.