Assessment of symptomatic response to intravesical alkalinized lidocaine,bupivacaine,heparin and steroids in patients with bladder pain syndrome

Abstract

Bladder Pain Syndrome (BPS) is a puzzling and complicated disorder. 12 such patients, with a mean age 48.3 years, were treated with weekly intravesical instillation of admixture of alkalinized lidocaine, bupivacaine, heparin and steroids for six weeks. Evaluating the benefits of this therapy, patients experienced 82.2% & 90.9% relief at 3_rd & 6_th week of instillation. After completion of six cycles of therapy, patients experienced 68.7% & 65.3% relief at 3_rd & 6_th month follow up, concluding the early and long term relief of BPS.

Keywords

Bladder pain syndrome intravesical alkalinized lidocaine bupivacaine heparin steroids

Background

Bladder pain syndrome (BPS) is commonly treated with a variety of holistic to invasive therapies but none of them provide long-term effective relief. Intravesical instillation of heparin alone or in combination with alkalinized lidocaine has shown promise but the effects were transient. This prompted us to add bupivacaine (a potent and long-acting local anesthetic) and steroids (for their non-specific anti-inflammatory action) to the instillation solution. Evaluating the beneficial effects of 6 weekly intravesical instillation of this admixture we noted early and long-term relief of BPS.

Materials and methods

Ours was a prospective interventional study conducted on patients attending the outpatient department of a tertiary care institute after approval from ethics committee. All adult patients with complaints of chronic pelvic pain, urgency, frequency and nocturia, not responding to oral analgesics were assessed using NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) criteria to identify those with possible bladder pain syndrome (BPS).² Urine culture negative patients with no other obvious pathology on abdominal ultrasound and cystoscopy were included.

After written and informed consent, all patients were given an intravesical instillation of a solution of 25,000 U heparin, 7 ml 2% lidocaine, 7 ml 0.5% bupivacaine, 1 ml 7.5% sodium bicarbonate, 5 ml containing 100 mg hydrocortisone dissolved in 20 ml normal saline. This admixture was given weekly for six consecutive weeks using a Ch10 feeding tube. Patients were instructed to hold their urine for at least 1 h after instillation. The solution was prepared with full aseptic precautions immediately before instillation. Patients were kept under observation for 4 h.

Pelvic Pain Urgency Frequency (PUF) Score³ and Visual Analog Scale (VAS) were used as symptom evaluation tools. We assessed treatment outcomes comparing pre-instillation values with post-instillation at the third and sixth week of therapy (early assessment) and third and sixth month follow-up (late assessment). Outcome was considered successful when baseline PUF and VAS scores were improved by >50%.

Therapeutic outcomes were compared with baseline values. Statistical analysis was done using paired t test, and a P < 0.05 was considered significant.

Results

A total of 15 cases fulfilling the NIDDK criteria were enrolled in the study, of whom 12 (7 females) with a mean age of 48.3 years (SD ± 10.9) completed the treatment and follow-up protocols and were available for analysis. Before intervention 83.3% cases had complaints of daytime frequency, 91.7% cases had urgency and 100% of them had pain and nocturia. Pre-intervention mean PUF score was 23.92 (SD ± 1.51).

The relief of symptoms during intervention phase was better as that of follow up. However, both phases showed statistically significant improvement when compared to baseline (p < 0.0001) (Table 1 and Fig. 1). No serious side effects such as allergic reaction, hematuria, rebound pain and infection were found. Only one patient complained of mild headache during initial instillation. There was an overall average symptomatic improvement of 82.2% after the 3^rd instillation and 90.9% after the 6^th instillation. Long-term response in symptomatic improvement remained as 68.7% at the 3^rd month and 65.3% at 6^th month after treatment completion.

Figure 1.

Showing early and late assessment of symptoms over the course of 6 months.

Table 1.

Early and late assessment of symptoms over the course of 6 months.

Parameters	Relief during early assessment (during intervention)		Relief during late assessment (follow-up)
Parameters	3^rd week	6^th week	3^rd month	6^th month
Frequency	75%	83.3.%	75%	75%
Urgency	66.7%	75%	66.7%	58.3%
Pain	66.7%	66.7%	58.3%	50%
Nocturia	83.3%	91.7%	83.3%	75%
PUF Score	4.25	2.16	5.58	8.42

Discussion

Many drugs and their admixtures have been instilled intravesically for BPS.^4,5 This is a complicated and exasperating disorder and it is a diagnosis of exclusion. Possible aetiology is urothelial inflammation or dysfunction owing to a defect in the impermeable gycosaminoglycan layer over the urothelial surface which exposes the urothelium to urinary irritants, mast cell activation by toxins or stress, inhibition of urothelial proliferation, activation of sensory pain fibres triggering release of substance P, neurokinin A and calcitonin gene-related peptide. Other causative factors such as an auto-immune mechanisms, pelvic organ cross sensitization and nitric oxide metabolism have been also blamed.⁶

Daily intravesical instillation of plain or alkalinized lidocaine for five days gave prompt relief.^4,7 Lidocaine blocks sodium channels in bladder nerves, which stops conductance and relieves pain. Sodium bicarbonate creates an alkaline environment assisting better absorption of lidocaine and reduces bacterial growth.⁸ Heparin was added because of its mucosal integrity restoration property, and results improved.^5,9,10 It mimics the glycosaminoglycan layer of bladder mucosa, thus temporarily repairs it. Weekly instillation of alkalinized lidocaine with heparin showed improved initial results but their efficacy gradually diminished with time.^11,12

The addition of bupivacaine, a long-acting local anesthetic which produces adequate analgesia without significant motor blockade; and steroids for their non-specific properties against all components and stages of inflammation to above combination, was well tolerated. Good short and long term results were obtained (Fig. 1). Indeed, long-term relief is always a primary goal of any treatment; and our admixture is successful in that respect. Weekly intravesical instillation of solution of alkalinized lidocaine, heparin with bupivacaine and steroids for 6 weeks is safe and effective treatment in providing early- and long-term symptomatic relief in patients with BPS.

The limitation of our study is its small sample size and its subjective outcomes. This is a pilot study, and larger patient numbers are obviously required to validate our findings objectively.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Ankush Lokhande

Deepti B Sharma

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