The Ice-Water Test (IWT) is a urodynamic test assessing the bladder’s response to the infusion of ice-cold water. This test evokes a reflex detrusor contraction in patients with upper, but not with lower motor neuron lesions (1)(2). In this prospective exploratory study, we tested the presence of a bladder cooling reflex (BCR) using the IWT, in patients with Neurogenic Detrusor Overactivity (NDO), Stress-Urinary Incontinence (SUI) and patients with idiopathic OverActive Bladder (iOAB). The primary aim of the study was to determine the presence of a positive IWT in patients with iOAB, NDO and SUI. Secondly, we aimed to investigate whether a positive IWT is associated with responsiveness to anticholinergics in iOAB patients.

Patients with NDO, SUI or IOAB planned to undergo a UroDynamic Study (UDS) were prospectively enrolled. After standard UDS, the bladder was emptied by means of spontaneous voiding or catheterization. Subsequently, the bladder was rapidly filled with 60 ml ice-cold saline (0-4°C) for 30 seconds. A positive IWT was defined as the occurrence of a detrusor contraction of 15cm H20 or more (3). The instillation of ice-cold saline was repeated up to 3 times with a break of 30 seconds between each instillation or until the IWT was positive. Furthermore, all patients were asked to fill in the validated Urogenital Distress Inventory (UDI-6) questionnaire to quantify the impact of their urological condition on health-related quality of life.

Sixty-two patients (15 men and 47 women) between 20 and 85 years of age underwent an UDS: Group 1: Patients with NDO: 2 patients with a neural tube defect, 4 paraplegic patients and 1 patient with Parkinson’s disease (N=7). Group 2: Patients with Stress Urinary Incontinence (SUI) (N=21). Group 3: Patients with iOAB (N= 34).

All patients with NDO had a positive IWT (100%), whereas only one out of 21 patients with SUI presented a positive IWT (4,8%). Within our study group with iOAB, the IWT was positive in 13 of the 34 patients (38%).

None of the patients in the NDO and SUI groups were using anticholinergics. In contrast, 14 out of 34 patients with iOAB (41%) used anticholinergics at the moment of the UDS. Ten out of the 14 patients (71%) taking anticholinergics had a negative IWT, whereas half of the patients (11/20) not taking anticholinergics showed a negative IWT
 (p= 0.30). 

The relationship between the result of the IWT and the symptomatic response to anticholinergics could be assessed in 20 out of 34 patients in the iOAB group not taking anticholinergics at the moment of the IWT. Seven out of 8 patients (87.5%) with a positive IWT, showed resistance to anticholinergics, whereas 10 out of 12 patients (83%) with a negative IWT responded well to anticholinergics (p = 0.0045) (Figure I).

The UDI-6 questionnaire was used to divide patients in the iOAB-group in two subgroups, based on severity of urgency and frequency symptoms. 16 out of 34 patients with subjective scores of at least ‘moderate’ (2 or 3 points) on both questions and a minimal score of 4 points were categorized in the group with severe OAB. Out of these 16 patients, 11 had a positive IWT (69%). The other 16 patients were considered to have limited symptoms (1 or 2 points) on both questions with a maximum score of 3. In this subgroup only 2 out of 16 patients had a positive IWT (13%). This difference was statistically significant with Fisher's exact test 
(p = 0.0032).

An important subgroup of iOAB patients (38%) present with a positive IWT. In contrast in patients with SUI, less than 5%, presents with a positive response. Moreover, a higher proportion of patients with a positive IWT presented with a higher symptom severity score using the UDI-6 questionnaire. These data suggest there might be an OAB subgroup with a distinct pathophysiology that needs a different treatment strategy.  Therefore, we correlated the use of and response to anticholinergics with the results of the IWT. In the preliminary study, almost 87% of patients with a positive IWT were resistant to therapy with anticholinergics, in comparison to only 17% in the negative IWT group.

These data suggest that the prescription of multiple anticholinergic agents in iOAB patients with a positive IWT has little chance of succeeding. It seems therefore justified in these patients to consider earlier pharmacotherapeutic alternatives such as mirabegron or more invasive treatment.

Thirty-eight percent of iOAB patients present with a positive IWT. These patients presented with more severe storage symptoms and were more likely to be resistant to anticholinergics than iOAB patients with a negative IWT. As such, anticholinergics may not be the best option for first line treatment in this patients subgroup.

Bors E, Blinn K. Spinal reflex activity from the vesical mucosa in parapl patients. AMA Arch Neurol Psychiatry. 1957.
Geirsson G, Lindström S, Fall M, et al. Positive bladder cooling test in neurologically normal young children. The Journal of urology. 1994;151(2):446-8.
Geirsson G, Lindström S, Fall M, et al. Pressure,volume and infusion speed criteria for the ice-water test. British journal of urology. 1994; 73, 498-503.