The Use of Onabotulinumtoxina for Treatment of Detrusor Overactivity in Older Patients

Research Article

Austin J Urol. 2015; 2(4): 1032.

The Use of Onabotulinumtoxina for Treatment of Detrusor Overactivity in Older Patients

Sammarco AG¹*, Ferry E², Patel D², Benchek P³, Kikano E³, Hijaz A² and Mahajan S¹

¹Department of Obstetrics and Gynecology, University of Hospitals Case Medical Center, USA

²Department of Urology, University of Hospitals Case Medical Center, USA

³Department of Epidemiology and Biostatistics, University of Case Western Reserve, USA

*Corresponding author: Sammarco AG, Department of Obstetrics and Gynecology, University of Hospitals Care Medical Center, 644 N 4th Ave, USA

Received: July 01, 2015; Accepted: November 17, 2015; Published: November 26, 2015


Objective: To evaluate the outcomes of intra-detrusor OnabotulinumtoxinA for the treatment of Detrusor Overactivity (DO) in patients both over and under the age of 70. Our primary end points were subjective improvement, UTI and urinary retention after treatment.

Materials and Methods: A retrospective chart review of 85 male and female patients who received intra detrusor onabotulinumtoxinA for the treatment of DO was conducted. The data was analyzed by fitting generalized linear mixed models using the package ‘lme4’ in R. We examined the association between age over 70 years, Pelvic Organ Prolapse (POP), Neurogenic Detrusor Overactivity (NDO), catheter use, and type II diabetes (DM), with post-injection subjective improvement, Urinary Tract Infection (UTI), and retention.

Results: Subjective Improvement: Odds of reporting improvement are 83% lower in people over the age of 70 (95% CI [22%, 96%]). Odds of reporting improvement are 3.8 times higher in those with DM compared to those without DM (95% CI [0.73, 46]). Post Injection UTI: Odds of UTI are 7.6 times higher in those with NDO than in those without NGB (95% CI [1.2, 47.0]). Odds of UTI are 5.9 times greater in patient’s = 70 than in those under 70 years old (95% CI [0.99, 35]). Urinary retention: No significant associations were found.

Conclusion: Intra-detrusor onabotulinumtoxinA is safe and effective for patient’s = 70 however they are less likely to report subjective improvement of their urgency incontinence symptoms and are more likely to experience UTI after treatment than patients less than 70 years of age. These findings allow for improved counseling of older patients regarding their associated treatment risks and likelihood of symptom improvement.

Keywords: Botulinum toxin; OnabotulinumtoxinA; Urinary urge incontinence; Overactive bladder, Detrusor overactivity

Brief Summary

OnabotulinumtoxinA is effective for patient’s = 70; however they are less likely to report subjective improvement and are more likely to experience UTI.


Overactive Bladder (OAB) syndrome includes the symptoms of urinary urgency, urgency incontinence, frequency, and nocturia [1]. The clinical symptoms of OAB correspond to unsolicited detrusor contractions on urodynamic testing, termed Detrusor Overactivity (DO). When attributed to a neurologic disorder, the condition is termed Neurogenic Detrusor Overactivity (NDO). However, in most cases no neurological explanation for patient symptoms can be found, resulting in the diagnosis of Idiopathic Detrusor Overactivity (IDO).

First line treatment for DO has traditionally consisted of conservative management with lifestyle and fluid intake modifications. Second line treatment consists primarily of antimuscarinic medications, the use of which is limited by side effects, including dry mouth and constipation, and patient compliance [2]. Recently, intra-detrusor onabotulinumtoxinA injections have increased in popularity as a minimally invasive, highly successful and well-tolerated therapy for all DO patients who have failed less invasive treatments [2-6].

In August of 2011, onabotulinumtoxinA was approved by the FDA for use in the treatment of DO secondary to neurogenic causes and then for idiopathic overactive bladder in 2013 [7]. This novel treatment has provided symptomatic relief for many patients with 42-87% of patients reporting complete continence after treatment, revolutionizing the treatment of DO. Despite the potential success of this therapy, possible side effects complicate it’s use including: prolonged urinary retention, increased post void residual, straining to void, gross hematuria, Urinary Tract Infections (UTI) and rarely, generalized weakness [8]. Risk factors for the development of possible adverse effects remain unclear, although our unit has postulated that advanced age may predict a higher incidence of associated side effects and reduced efficacy of treatment in patients undergoing intradetrusor onabotulinumtoxinA injections. Unfortunately, most of the published studies on onabotulinumtoxinA injection into the detrusor muscle for DO enrolled limited numbers of older patients, limiting the generalizability of these studies to older patients [2,9]. As a result, the impact of age on tolerability and treatment outcomes in geriatric patients remains unknown.

The objective of our study was to evaluate the efficacy and side effects of intra-detrusor onabotulinumtoxinA injection for DO in patients aged = 70 years old as compared with patients < 70 years of age.

Materials and Methods

This is a retrospective case study of all patients 18 years of age or older who received onabotulinumtoxinA intra-detrusor injections over a 5 year period between January 1, 2008 and October 31, 2013, at University Hospitals Case Medical Center in Cleveland, Ohio, for the treatment of symptoms of DO. Approval for this study was obtained from the University Hospitals Case Medical Center Institutional Review Board. Patients were identified using CPT code 53899U01 and 52000. Data was extracted from the medical charts manually and compiled into a database. Inclusion criteria included male and female patients who received intra-detrusor onabotulinumtoxinA injection for treatment of DO documented on pre-treatment urodynamics, and followed up in clinic within three months of injection. Posttreatment assessment included: post void residual measurement, and assessment of symptoms at a follow up visit.

Patients were excluded if they did not follow up within three months of injection. Those patients with indwelling catheters were not included in evaluation of post procedure urinary retention. Urinary tract infection was defined as an office urine dip or urine culture which was treated with antibiotics within 30 days of onabotulinumtoxinA injection. Urinary retention was defined as a post void residual >150 ml at the post injection visit or the need for de novo catheterization within 30 days of treatment. Data on subjective improvement was gathered from the provider’s notes of the post-operative visit. During this visit, their symptoms were assessed by the provider. Patients must have reported subjective improvement and/or overall satisfaction with the treatment during their post operative visit that was then recorded in the chart to qualify as having experienced subjective improvement of their symptoms. Patients were seen and treated by four different providers in our practice. The decision for dosage of onabotulinumtoxinA was made on an individual basis by each provider regarding each patient. Each dose of onabotulinumtoxinA, ranging from 100-300 units, was reconstituted in 20 cc of sterile normal saline and was followed with a 2cc flush of sterile normal saline. All patients in clinic are routinely checked for infection by urine dip prior to treatment and prescribed 3 days of twice daily oral nitrofurantoin 100mg post intra-detrusor onabotulinumtoxinA injection or a comparable antibiotic for 3 days if allergic.

To analyze the association between age = 70 years and postinjection UTI, retention and subjective improvement we fit generalized linear mixed models using the package ‘lme4’in R. Mixed models were used because some patients had multiple onabotulinumtoxinA injections resulting in multiple outcome measures10. The focal predictor in our statistical models was age = 70 years. In addition to age, we examined the association between Pelvic Organ Prolapse (POP), NDO, pre-injection catheter use (except when the outcome was retention), Type II diabetes (DM) and injection number, with post-injection UTI, retention and subjective improvement.

In the analysis, two statistical models were utilized. The first addressed age > 70 as the focal predictor and all predictor variables that could affect our outcomes including NDO, POP, pre-injection catheter use, DM and injection number. A second model was then used which removed variables that showed no association with the outcome in question. In this model we included variables from our initial model, which were statistically significant or were approaching statistical significance. Here we defined ‘approaching statistical significance’ to be having a p-value < 0.20. This allowed us to control for predictor variables as well as document their association on the outcomes. Statistical significance was set to 0.05.


A total of 88 charts were reviewed. One patient was excluded from the analysis due to having an outlying number of injections over the study period. Two patients were excluded for failure to follow up after treatment. Eighty-five patients were included in our analysis and could have undergone multiple injections during the study period. The majority of the injections were performed in the operating room, and those which were not performed in the operating room were performed in the office setting. When performed in the operating room, general anesthesia was used. Local anesthesia with lidocaine gel was used for office procedures. For analysis, patients were categorized into 2 groups: those = 70 years old and those < 70 years old. (Table 1) shows baseline characteristics of the study population. Fifty patients were < 70 years old and 35 patients > 70 years old. Mean ± SD age of the < 70 was 53.8 ± 11.9 years, and of the > 70 group was 76.8 ± 6.1 years. Both groups had more female than male patients; however the gender distribution across age groups was not significantly different (Table 1). Patients < 70 years old were significantly more likely to have a neurologic diagnosis.