Anesthetic agents affect urodynamic parameters and anesthetic depth at doses necessary to facilitate preclinical testing in felines

Abstract

Urodynamic studies, used to understand bladder function, diagnose bladder disease, and develop treatments for dysfunctions, are ideally performed with awake subjects. However, in small and medium-sized animal models, anesthesia is often required for these procedures and can be a research confounder. This study compared the effects of select survival agents (dexmedetomidine, alfaxalone, and propofol) on urodynamic (Δpressure, bladder capacity, bladder compliance, non-voiding contractions, bladder pressure slopes) and anesthetic (change in heart rate [∆HR], average heart rate [HR], reflexes, induction/recovery times) parameters in repeated cystometrograms across five adult male cats. The urodynamic parameters under isoflurane and α-chloralose were also examined in terminal procedures for four cats. Δpressure was greatest with propofol, bladder capacity was highest with α-chloralose, non-voiding contractions were greatest with α-chloralose. Propofol and dexmedetomidine had the highest bladder pressure slopes during the initial and final portions of the cystometrograms respectively. Cats progressed to a deeper plane of anesthesia (lower HR, smaller ΔHR, decreased reflexes) under dexmedetomidine, compared to propofol and alfaxalone. Time to induction was shortest with propofol, and time to recovery was shortest with dexmedetomidine. These agent-specific differences in urodynamic and anesthetic parameters in cats will facilitate appropriate study-specific anesthetic choices.

Figure 1

Boxplots of (a) bladder capacity, (b) Δpressure, and (c) NVC rate by anesthetic agent. Points represent individual samples. Adjacent triangle icons represent means of individual samples. Boxes represent 1st to 3rd quartile range (interquartile range [IQR]), with the line in the middle of each box representing the median. Tips of whiskers extending below and above box represent 1st quartile – 1.5*IQR and 3rd quartile + 1.5*IQR respectively. Significance: *p < 0.05, **p < 0.01.

Figure 2

(a) Normalized CMG bladder pressure responses averaged by agent. Solid lines represent means, shading around each mean represents standard deviations. (b) Box plots of CMG slopes (slope 1) infusion start to 100 s before void, (slope 2) 100 to 50 s before void, and (slope 3) last 50 s before void. Data represented as in Fig. 1. Significance: *p < 0.05, **p < 0.01.

Figure 3

(a) Averaged continuous HR of last 3 cats during survival CMG trials by agent, normalized by time. Solid lines represent means, shading around each mean represents standard deviations. (b) Box plots of mean HR over all CMG trials by agent. ΔHR is shown for non-terminal agents only. Data represented as in Fig. 1. (c). Box plots for time to induction (approximated by time to lateral recumbency), time to recovery (approximated by time to head up), and time to walking for non-terminal agents. All panels: significance: *p < 0.05, **p < 0.01.

Figure 4

Reflex distribution by survival agents across all trials. Darker colors indicate a lighter plane of anesthesia.

Figure 5

Experimental overview. Cats were implanted with VAPs and anesthetized at the lowest doses necessary to facilitate urodynamic testing. At least 3 sessions of propofol, dexmedetomidine, and alfaxalone each were conducted, in addition to a terminal experiment under isoflurane and α-chloralose in conjunction with another study. During anesthetized sessions at least 2 CMG trials were performed in each session to assess urodynamic parameters. Heart rate and reflexes were used to assess anesthetic depth, and time to induction/recovery was noted.