//Step 2 – Bladder Instillations For IC
Step 2 – Bladder Instillations For IC2018-07-24T16:15:24+00:00

Step 2 – Bladder Instillations

Bladder instillations are a second-line treatment option in the AUA Guidelines for IC/BPS when treatments such as diet modifications, stress management, and over the counter products are not enough. During a bladder instillation (aka intravesical instillation or treatment), the bladder is filled with medication via a catheter. The solution is held for varying periods of time, from a few seconds to 20 minutes (known as “dwell time”), before being drained or voided.  Some treatments are thought to coat and protect the bladder, while others are thought to suppress inflammation. Many physicians instill combinations of ingredients (“bladder cocktails”) that they believe work better than a single agent. The advantage of bladder intravesical therapy is that a high concentration of medication can be delivered to the bladder without increasing systemic concentrations. Thus, there is less risk of systemic side effects. That said,  bladder instillations may cause bladder and/or urethral discomfort of varying degrees.

Heparinoid instillations (Heparin & Hyaluronic Acid)

– Heparin

Heparin is believed to act as a bladder coating. Several concentrations and treatment modalities have been studied. One study used 10,000 IU heparin in 10cm3 sterile water three times a week for three months with a dwell time of one hour. At three months, 56% of patients reported significant improvement.(1) A portion of those patients continued treatment for up to one year with 40% of patients reporting continued relief. Another study used 25,000 IU in 5ml distilled water twice a week. At three months, 72.5% of patients reported significant relief.(2) Heparin is most often used in a cocktail form with other medications.

– Hyaluronic Acid (Cystistat, Hyacyst)

Hyaluronic Acid (HA) is a naturally found in the bladder mucosa where it helps to protect the underlying tissue. It is believed to bind to lymphocytes and endothelial cells where it blocks ICAM-1 receptors and alleviates inflammation.(3)  Clinical trials showed modest success in reducing the symptoms of IC though it failed to meet the standards required for FDA approval in the USA. Cystistat and Hyacyst  are HA bladder instillations approved for use in Canada and Europe. It is believed to provide a bladder coating effect.

  • Hyacyst (40mg and 120mg) is administered weekly for four weeks. For some patients, additional treatments are recommended.
  • Cystistat was discontinued by Mylan Pharmaceuticals in July 2018 with no explanation or notice. Cystistat was given once a week for 4 to 6 weeks and then monthly as needed. Many patients reported improvement after the fifth or sixth instillation.

Alkalinized Lidocaine & Heparin/Elmiron

Heparin is frequently combined lidocaine to create an instillation popularly known as a “rescue instillation.” How does it work? When instilled in the bladder, lidocaine (and/or Marcaine) numbs the nerves that trigger discomfort. Heparin and Elmiron provide a bladder coating effect. Sodium bicrabonate improves the absorption of the medication into the bladder wall and must be used conservatively to avoid systemic effects. A steroid and antibiotic are often included. Several formulas have been used.

– Moldwin Anesthetic Therapy (Robert Moldwin MD – Smith Institute for Urology)

Dr. Robert Moldwin promotes the use of this anesthetic cocktail not only for bladder therapy but as a diagnostic tool.(4)  If it numbs the bladder wall and/or reduces bladder discomfort, it “rules in” the bladder wall as the source of patient symptoms. He feels that this is best suited for patients with clear bladder wall driven pain and encourages patients to learn how to self-catherize so that they can use this instillation during flares and gain empowerment.

  • 1:1 mixture of 0.5% bupivacaine (Marcaine) and 2% lidocaine jelly (about 30 to 40 mL total)
  • 40 mg triamcinolone (usually use 80 mg for Hunner’s ulcer patients)
  • 10-20,000 IU heparin
  • 80 mg gentamicin or a post-procedural prophylactic antibiotic

Administration: Patients are instructed to hold the solution for roughly 30 minutes. It is usually given on a weekly basis for 8 to 12 weeks, with the interval increasing as needed. Some patients may develop urinary retention which can be circumvented by using a lower treatment volume.

– Parsons Heparin Cocktail with Alkalinized Lidocaine (C. Lowell Parsons MD – UCSD)

Dr. C. Lowell Parsons developed this formula and created a prepackaged formula known as Hep-Lido-A available at selected pharmacies throughout the USA. (5)

  • Heparin sulfate 40,000iu
  • Lidocaine 2% 8 ml
  • Sodium bicarbonate 8.4% 3ml
  • To reach a total fluid volume of 15ml

Administration: May be given up to twice daily and patients can be taught home instillations. Should be held for 15 to 30 minutes.

– Payne Heparin Cocktail (Christopher Payne MD – Vista Urology)

  • 10,000 IU of heparin
  • 10 mL of bupivacaine (Marcaine)

Administration: Suggested for self-instillation daily or three times a week.(6)

– Whitmore Heparin Cocktail – Kristene Whitmore MD

  • Heparin 10,ooo units
  • Hydrocortisone 100mg
  • Sodium Bicarbonate 8.4% – 40ml
  • Marcaine .5% – 20ml
  • Gentamicin 80mg (optional)

Administration: 1x per week, held for roughly 30 minutes.(6)

– Pentosan Polysulfate Cocktail – Jurjen J. Bade MD

  • Pentosan Polysulfate 300mg (3 pills, 100mg each)
  • Lidocaine 2% 10cc
  • Sodium Bicarbonate 4.2% – 10cc
  • Add, as needed, .9% NACL to reach a total volume of 60cc

Administration: 1x per week for 6 to 8 weeks, then can be gradually tapered to every 2 weeks, 3 weeks, etc.(7)

Ask Questions in Our Rescue Instillation Message Board

DMSO (aka RIMSO-50)

Approved in the early 1970’s by the US Food and Drug Administration, the use of dimethyl sulfoxide (RIMSO-50) has gradually diminished due to the growing popularity of heparin and/or elmiron instillations. DMSO is a dilute, sterile, and purified version of an industrial solvent that was found to have anti-inflammatory, analgesic, muscle relaxant, mast cell stimulation and collagen dissolution properties. Patients may receive six to 8 weekly instillations, holding it for roughly 15 to 20 minutes. If improvement is found, a second course of treatment may be suggested. DMSO is rarely used as a long term therapy, nor should it be used if patients show no response to treatment. Many research studies have been conducted which have shown anywhere from 25 to 90% success rates. Mild adverse events (i.e. discomfort) are common

There has been considerable debate over the years about the proper dosage to use in a DMSO treatment. Research presented at the 2002 and 2003 AUA Annual Meeting by D. Melchior and C. Subah Packer found that DMSO at the FDA approved 50% dosage may cause damage to the muscle of the bladder when used at the 50% dosage. Their research demonstrated that DMSO triggered intense muscle spasms at 30%  which became long lasting and could be irreversible. Clinicians and researchers at the meeting agreed that DMSO should be only administered in a cocktail form to maintain a concentration below 30%.(5) Ray Rackley MD (Cleveland Clinic, OH) stated that the Cleveland Clinic no longer uses DMSO and that he believed that DMSO caused much of the damage in bladders that he later had to remove.

Side effects can include intense burning and discomfort, a garlic-like taste and an odor, bladder spasms and irritability. DMSO causes fetal abnormalities in animals and should not be used during pregnancy, within four weeks of a bladder biopsy or if infection is present. Studies showed various levels of success ranging from 25% to 90%. The AUA panel states “If DMSO is used, then the panel suggests limiting instillation dwell time to 15-20 minutes” because longer dwell times are associated with more significant pain. Grade C. Ask Questions in our DMSO Message Board

– DMSO Cocktail – Robert Moldwin MD

  • Rimso-50 – 50cc
  • Heparin Sulfate 10,000-20,000iu
  • Triamcinolone 40mg
  • Sodium bicarbonate 4meq (one ampule)
  • Gentamicin Optional

Administration: The cocktail should be held in the bladder for 20 minutes. It can be administrated once per week for six to eight weeks, followed by monthly maintenance if necessary.(4)

Consumer Alert – Dr. Robert Moldwin warned clinicians at the AUA 2013 Annual Meeting reporting that atleast one compounding pharmacy in the USA had been shipping industrial grade DMSO to urology clinics. An industrial solvent, this form of DMSO causes immediate destruction of the bladder. (Editor’s Note: We are aware of one case where a young patient lost her bladder due to this error). Before treatment, please verify that your physician is using RIMSO-50, the only form of DMSO approved for human use.-

GAG Layer Replacement Therapies

– Chondroitin Sulfate (Uracyst)

Chrondroitin sulfate has also been instilled directly into the bladder for a bladder coating effect. Approved for use in Canada (Uracyst) and Europe (Gepan), it has had a modest effect at reducing urinary symptoms.  Like Hyaluronic Acid above, research studies have shown modest affect but it failed to meet the standards for FDA approval in the USA. In a six-week Canadian trial in 53 patients with moderately severe IC received weekly instillations for six weeks, then monthly over 16 weeks for a total of 10 treatments. At 10 and 24 weeks, symptom scores were significantly reduced.(3)

– Hyaluronic Acid & Chondroitin Sulfate In Combination

When used in combination as a bladder instillation, hyaluronic acid and chondroitin sulfate have been found useful not only in the reduction of bladder pain and discomfort, but also in the prevention of urinary tract infection.(3)

New Treatments In Development

  • Urigen101 (Urigen) – An alkalinized lidocaine bladder instillation
  • LP-08 (Lipella Pharmaceuticals)  – Liposome Therapy
  • Urobex – Pentosan Polysulfate in Liposomes
  • GABA IC – A compounded bladder instillation. The pharmacy, Clinical Apothecaries, had their license suspended in January 2018. They are no longer in business.

Instillations No Longer Recommended

The following treatments are no longer recommended as treatments for IC/BPS.(9)

  • Silver Nitrate – Has an antiseptic and astringent effect believed to strip the bladder wall
  • Chlorpactin / Clorpactin – Used originally to treat TB because of antimicrobial properties
  • Resiniferatoxin (RTX) – Acts to desensitize afferent bladder innervation
  • Bacillus Calmette Guerin (BCG) – Believed to work immunologically and as a treatment for bladder cancer

Updated: July 19, 2019 – Jill H. Osborne

References

  1. Parsons CL, Housley T, Schmidt JD et al: Treatment of interstitial cystitis with intravesical heparin. Br J Urol 1994; 73: 504.
  2. Kuo HC: Urodynamic results of intravesical heparin therapy for women with frequency urgency syndrome and interstitial cystitis. J Formos Med Assoc 2001; 100: 309.
  3. Cervigni M, et al. “Intravesical Therapy” In Bladder Pain Syndrome. Springer 2013. p. 307 to 315
  4. Evans R, Moldwin R, Fariello J. AUA 2018 Course on Chronic Urologic Pelvic Pain. San Francisco CA. 2018
  5. Parsons CL. Successful down regulation of bladder sensory nerves with combination of heparin and lidocaine in patients with IC. Urology 2005. Jan;54(1):45-8
  6. Bladder Cocktails. Interstitial Cystitis Association. July 6, 2015.
  7. Intravesical Instillations. International Painful Bladder Association.
  8. Melchior D, et al. DMSO – Does it change the functional properties in the bladder wall.” AUA 2002 Annual Meeting Poster
  9. Hanno PM, et al. AUA Guidelines for the diagnosis and treatment of IC/BPS J Urol. 2011;185(6):2162-2170