The basic aim of urodynamics is to reproduce the patient's symptomatic complaints or usual voiding pattern during urodynamics, and to provide a pathophysiological explanation by correlating the patient's symptoms with the urodynamic measurements and observations. In principle, urodynamic study should be performed when the patient is awake and not sedated (1). However, it is difficult to perform urodynamic study in uncooperative patients such as all infants and young children in the awake state, even though the specific adaptations is provided, staff training, environment, parental support, etc. In addition, the examination may induce systemic stress, and therefore can either negatively affect urodynamic results or cause difficulties to correctly analyze the data. Therefore, it is necessary to explore more suitable methodology for performing urodynamic study in uncooperative patients.

Urodynamic study is feasible in animal under awake condition (2). However, numerous studies have shown that urodynamic study, especially the cystometry, were often performed under anesthesia or sedation in various experimental animal models by using different anesthetic agents, because it is difficult to perform urodynamic study in conscious animals (3-6). These studies have demonstrated that if suitable doses and/or classes of anesthetic agents were used, the anesthesia-induced adverse effects on urodynamic results can be minimized, thereby more closely simulate normal physiological responses. In addition, such invasive and uncomfortable procedures, including voiding cystourethrography, oral and maxillofacial surgery and gastrointestinal endoscopy were successfully performed under conscious sedation (7-9). Therefore, the aims of this study were to evaluate the effects of level of consciousness on urodynamic procedure, and the feasibility of performing urodynamic study under conscious sedation by comparison of urodynamic results and the extent of examination-induced systemic stress under conscious, conscious sedation and general anesthesia using an animal model.

Urodynamic study is an invasive and uncomfortable procedure that can initiate physical distress due to discomfort, patient embarrassment, and/or pain induced by genital examination and urethral catheterization (10, 11). The novel finding of the present study is that implementation of urodynamic study on reluctant, conscious subjects or performing the examination on uncooperative patients under DA is inappropriate because these conditions can induce significant systemic stress or detrusorsphincter dyssynergia (DSD). In addition, performing urodynamic evaluation on subjects under CS can minimize examination-induced stress while closely simulating normal physiological responses. The present study demonstrated that performing urodynamic studies on reluctant, conscious subjects induces significant increases in systemic stress as shown by increased serum cortisol levels. Cortisol is an important hormone in the body that is secreted by adrenal glands. It is frequently used in various experimental settings as an objective marker when evaluating psychological and laboratory stress (12, 13). Although it remains unclear whether systemic stress induced by urodynamic evaluation adversely influences the examination results, it is necessary to reduce examination-induced systemic stress from an ethical point of view. In the present study, the serum cortisol levels were unchanged under the CS and DA conditions. These results suggest that CS and DA are useful approaches for reducing stress induced by urodynamic evaluation.

Physiologically, the micturition reflex is coordinated by the central, autonomic, and somatic nervous systems. The muscles involved in micturition are controlled by the autonomic and somatic nervous systems. During the storage phase, the urethral sphincter contracts and the detrusor muscle is relaxed by sympathetic stimulation. During micturition, the detrusor muscle contracts and the urethral sphincter is relaxed by parasympathetic stimulation. The micturition reflex is altered by anesthetics, which could cause inhibition of micturition, direct loss of coordination between the detrusor muscle and urethral sphincter, and an imbalance of sympathetic and parasympathetic control of micturition (6). However, several studies have demonstrated that the influence of anesthesia on urodynamic evaluation is dependent on the class of anesthetic agents and degree of anesthesia (3-5). The present study supported these findings and provided new data on the feasibility of performing urodynamic studies of CS subjects. In the present study, the urodynamic evaluation showed that there were no statistical differences in the maximum detrusor pressure and bladder capacity among animals under the three conditions. In addition, bladder contraction accompanied by un-relaxed sphincter activity occurred under the DA condition, whereas the CS condition did not affect the coordination between bladder contraction and external anal sphincter activation. As a result, the residual urine volume was significantly increased under the DA condition. In contrast, the residual urine volume was similar under the CON and CS conditions. These results suggest that CS has no significant adverse effect on urodynamic variables. We also believe that the large residual urine volume observed under CON condition was due to the obstructive effect of the catheter even though a smaller-sized catheter was used.

The American Society of Anesthesiologists has defined four levels of sedation: minimal, moderate, deep, and general anesthesia (14). In the first two categories, cardiorespiratory function is maintained, the cognitive function and coordination are somewhat impaired, and patients can cooperate with the examiner and respond normally to verbal stimulation. The selection of a suitable anesthetic agent is important for the induction and maintenance of sedation. Zoletil, a combination of tiletamine and zolazepam, produces dose-dependent sedation up to general anesthesia (15). It is used for anesthesia in various species of animals such as dogs, cats, and wild and captive animals, and provides rapid induction, excellent muscle relaxation with a wide safety margin, and a smooth recovery. In the present study, subcutaneous injection of 3 mg/kg zoletil provided a sufficient period to perform the urodynamic study. This dose of zoletil produced hypnosis within 3 min of injection, and the cats recovered approximately 30 min after the injection. In addition, 10 mg/kg zoletil induced DA during which continuous regular breathing pattern was maintained without intubation within 5 min of injection and lasted for approximately 2 hr. These findings along with the results of the urodynamic study suggest that zoletil is an appropriate anesthetic agent for urodynamic studies conducted in female cats.

There are limitations associated with the present study. First, a complete urodynamic evaluation was not performed in this study. Therefore, whether other factors of a complete urodynamic study such as pressure flow and a urethral pressure profile could be evaluated in subjects under the CS condition remains to be elucidated. Another limitation of this study is that a single anesthetic agent was used. The suitability of other anesthetic agents, especially the most commonly administered sedatives such as propofol and midazolam, remain unclear. Further studies are required to address these issues.

In conclusion, the results of this study provide evidence that CS has no adverse effects on urodynamic variables, and that it significantly reduces distress in cats undergoing examination. These results may provide novel insights for performing urodynamic studies in uncooperative patients.