1001283 JFM Journal of Feline Medicine and SurgeryHanson et al

Original Article

Journal of Feline Medicine and Surgery

Effect of prazosin on feline 2021, Vol. 23(12) 1176­–1182

© The Author(s) 2021
Article reuse guidelines:
recurrent urethral obstruction sagepub.com/journals-permissions
DOI: 10.1177/1098612X211001283
https://doi.org/10.1177/1098612X211001283
journals.sagepub.com/home/jfm
This paper was handled and processed
by the American Editorial Office (AAFP)
for publication in JFMS
Kayla R Hanson1 , Elke Rudloff1, Lingnan Yuan2,
Jonathan P Mochel2 and Andrew KJ Linklater1

Abstract
Objectives  The aim of this study was to determine if male cats treated with 7 days of prazosin following relief of
urethral obstruction (UO) experienced decreased rates of recurrent urethral obstruction (rUO) within 30 days vs
those treated with 7 days of placebo.
Methods  All castrated male cats presenting for the first time with UO from May 2014 to August 2017 were eligible
for enrollment. Exclusion criteria included the administration of medications or passage of a urinary catheter prior to
referral, the presence of heart disease or hypertension requiring medication, prior treatment with glucocorticoids,
non-steroidal anti-inflammatory medications, prazosin or phenoxybenzamine, or radiographic identification of
cystoliths. Cats were treated with standardized anesthetic and analgesic protocols, standardized indwelling urinary
catheter management, and were hospitalized for care. A random numbers table was generated prior to study
initiation and cats were randomized to receive either prazosin (0.5 mg PO q12h for 7 days) or placebo in a blinded
fashion. A 30-day follow-up with owners via telephone was performed to identify the rate of rUO. Cats that did not
receive the full course of study medication were removed from the analysis. The study was unblinded at the end of
data collection.
Results  Eighty cats were enrolled and 65 cats completed the study; 12 were excluded because they did not
receive the study medication. Sixteen of 65 cats experienced rUO (25%). Of the 16 cats experiencing rUO, five
received placebo (n = 5/28 [18%]) and 11 received prazosin (n = 11/37 [30%]). Ten of the cats that experienced
rUO reblocked while still hospitalized. There was no significant difference in frequency of rUO in cats treated with
prazosin vs placebo (P = 0.27).
Conclusions and relevance Prazosin administered at 0.5 mg PO q12h did not decrease the rate of rUO in this
population of obstructed male cats vs placebo. These results further support evidence suggesting that prazosin
may not be beneficial in prevention of feline rUO.

Keywords: Prazosin; recurrent urethral obstruction; urethral obstruction; urinary obstruction; recurrent urinary
obstruction

Accepted: 11 February 2021

Introduction
Urethral obstruction (UO) is common, accounting for
4.6% of all feline cases and 8.1% of all male cat cases pre-
senting on emergency.1 Causes include urethral plugs,
urolithiasis, crystalluria, urinary tract infection and
idiopathic disease.2–4 Although life-threatening, UO is
treatable, with a 93.6% rate of survival to hospital dis-
charge reported.5 Hospitalization is typically required,
with treatment consisting of analgesia, anesthesia, retro-
grade flushing to relieve the obstruction, placement of an
indwelling catheter connected to a closed urine collection
system for 24–48 h, intravenous (IV) fluid therapy and
correction of electrolyte disturbances.5–7
A high percentage of recurrent UO (rUO) has been
reported. In a study by Gerber et al,8 51% of cats with
UO displayed recurrent lower urinary tract signs, with
36% experiencing rUO within 17 days. Other reports
1Lakeshore Veterinary Specialists, Glendale, WI, USA
2Biomedical Sciences, Iowa State University, Ames, IA, USA
Corresponding author:
Kayla R Hanson DVM, DACVECC, cHPV, cVMA, Animal
Emergency and Referral Center of Minnesota, 1163 Helmo Ave N,
Oakdale, MN 55128, USA
Email: krhanson@aercmn.com
Hanson et al 1177
suggest a rUO rate as low as 15% and as high as 74%
within 7 days.8–10 Euthanasia rates of up to 23% have been
reported in cats after rUO.1,8
Studies have evaluated risks associated with rUO,
including urinary catheter size, duration of catheteriza-
tion and diet.1,6,8,11–14 In addition, urethral spasm has been
hypothesized as a potential contributor to the develop-
ment of rUO.12,15–17 The proximal 28–37% of the feline
urethra is composed primarily of smooth muscle and
contains alpha (α)1-adrenergic receptors that contract
in response to norepinephrine (noradrenaline) release
from the hypogastric nerve.18,19 A number of drugs tar-
geting these receptors have been used to reduce urethral
muscular spasm; however, controlled clinical studies are
lacking and the use of α-adrenergic receptor antagonists
or other urethral relaxants is based largely on clinician
preference. Prazosin, an α1-adrenergic receptor antago-
nist, has been experimentally shown to reduce urethral
pressure.16,18 In the cat, blockade of the α-receptors pre-
vents sympathetically mediated smooth muscle contrac-
tion throughout the preprostatic and prostatic urethral
segments, leading to reduction in urethral wall tension.18
Because of these effects, prazosin may be useful in treat-
ing urethral dyssynergia or trauma associated with ure-
thral catheterization.18
There are few studies evaluating α-adrenergic receptor
antagonists for management of feline UO. A retrospective
study comparing rUO rates in cats treated with prazo-
sin (0.5–1mg PO q8–12h) with those treated with phe-
noxybenzamine, a non-selective α-adrenergic receptor
antagonist, identified a significant decrease in short-term
rUO in those receiving prazosin.1 Although the results of
that study suggest that prazosin may be beneficial in the
management of rUO, it was limited by its retrospective
design, lack of a control group and confounding vari-
ables such as catheter size, duration of catheterization,
and differing anesthetic and analgesic protocols. Another
prospective study evaluating various risk factors for rUO
determined that administration of either prazosin or phe-
noxybenzamine was not associated with a decreased risk
of rUO; however, this study was observational, not ran-
domized and did not include a control group.6 A more
recent double-blinded prospective interventional study
specifically evaluated the effect of prazosin on outcome
in feline UO and failed to find a significant difference in
the incidence of rUO in cats receiving prazosin (0.25 mg/
cat PO q12h) and those receiving placebo for 30 days fol-
lowing relief of obstruction.10 This study was relatively
small, evaluating only 45 cats with several uncontrolled
variables, including the duration of catheterization and
urinary catheter size.10
Our prospective, randomized, placebo-controlled,
blinded study aimed to evaluate statistical differences in
the rate of 30-day rUO in male cats receiving prazosin vs
those receiving placebo.
Materials and methods
Sample size determination
An improvement from an expected frequency of 36% rUO
over 30 days in the control group to 4% in the treated
group using a log rank test with 80% power and 5% con-
fidence assuming a loss to follow-up of 5% or less in each
group was used to determine a necessary sample size of
80 (40 cats per group).
Case selection
Castrated male cats presenting with UO for the first time
to the Emergency Department at a private multispecialty
practice were eligible for inclusion in the study. Written
informed consent was obtained from each owner prior to
enrollment of their cat for treatment and participation in
the study. The study protocol was reviewed and approved
by the hospital Animal Care and Use Committee. A UO
was defined as the presence of a non-expressible blad-
der or non-productive stranguria documented by a vet-
erinarian. All cats were hospitalized for treatment of UO.
Cats were excluded prior to enrollment if they had heart
disease or hypertension requiring medical therapy, and
if they had treatment within the previous 2 weeks with
glucocorticoids, non-steroidal anti-inflammatory medica-
tions, prazosin, phenoxybenzamine or other medications
for UO. Cats were excluded if an indwelling urinary cath-
eter was placed prior to enrollment. Cats whose tempera-
ment prevented administration of oral medications were
excluded, as well as those with radiopaque cystoliths
identified on a lateral abdominal radiograph performed
after relief of the obstruction.
Therapy
Cats had an IV catheter placed and were initially
administered methadone (0.2 mg/kg IV or IM; Mylan
Institutional) and IV crystalloid therapy, and any elec-
trolyte disturbance was corrected. Propofol (Zoetis)
was administered IV to effect for sedation to relieve the
obstruction. Oxygen was provided via a face mask, and
electrocardiogram, blood pressure and pulse oximetry
were monitored throughout sedation. The prepuce and
perineal region were shaved of hair and aseptically pre-
pared. A 3.5 F polypropylene catheter (Covidien) or an
olive-tipped urethral catheter (Jorgensen Laboratories)
was used for relief of the obstruction. An indwelling 3.5 F
red rubber catheter (Covidien) was placed, permitting
collection of a urine sample for urinalysis and culture
if desired, complete drainage of the bladder and flush-
ing with sterile 0.9% saline. The red rubber catheter was
secured in place and connected to a closed urinary col-
lection system. Following catheter placement, a lateral
abdominal radiograph was performed to evaluate for
radiopaque cystoliths. Urinalysis and urine culture and
susceptibility were performed based upon clinician dis-
cretion with antimicrobial therapy initiated if indicated.
1178 Journal of Feline Medicine and Surgery 23(12)
Buprenorphine (0.015–0.02 mg/kg TM or IV q8h; Par
Pharmaceutical) or long-acting buprenorphine (0.24mg/kg
SC q24h [Simbadol; Zoetis]) were administered for
post-procedural pain relief. If cats received alternative
medications that did not lead to study exclusion, these
medications were recorded. An indirect arterial blood
pressure reading was obtained via Doppler within 2 h of
initiating unblocking treatment, and those with a reading
of <80 mmHg were withdrawn from the study. An indi-
rect arterial blood pressure was obtained 1 h after initiat-
ing treatment with the study drug. Cats were randomly
assigned to receive either prazosin (0.5 mg/cat PO q12h
for 7 days; placed in a gel capsule) or a placebo in identi-
cal capsules (1 capsule PO q12h for 7 days) within 8 h of
urinary catheter placement. The prazosin and placebo
were prepared by a licensed pharmacist who identified
the prescriptions by a letter. The study investigators and
cat owners were blinded to the contents of the capsules.
A random number table was created prior to study initia-
tion to randomly distribute patients between groups and
was followed with each enrollment.
The indwelling urinary catheter remained in place for
at least 24 h and no more than 48 h. Each cat received IV
fluids to meet replacement, maintenance and ongoing
fluid losses. Following urinary catheter removal, each cat
was monitored for dysuria.
Each cat was discharged with the study medication
to complete a 7-day course of therapy along with trans-
mucosal buprenorphine for pain control. Standardized
discharge instructions were provided, including rec-
ommendations for litter tray management, strategies
for increasing water consumption, and environmental
modification and enrichment. Transition to a prescription
urinary tract diet was recommended on a case-by-case
basis depending upon the presence of crystalluria in the
initial urine sample.
Data analysis
Patient follow-up was performed via standardized tel-
ephone interview by the primary investigator within 1
week of hospital discharge and again after 30 days. Owner
compliance with administration of the study medication
and occurrence of rUO was recorded. If owners noted
any adverse effects, these were also recorded. If owner
communication was not possible, referring veterinarian
records were evaluated for follow-up information.
Medical records for each cat were reviewed and the
age, weight, presenting vital signs and results of available
laboratory analysis, and duration of catheterization and
hospitalization were recorded. Normality of distribution
was assessed using the Shapiro–Wilk test. The Mann–
Whitney U-test was used for comparison of presenting
variables between cats treated with prazosin and pla-
cebo as well as cats that experienced rUO and those that
did not. Additionally, a two-sample χ2 test for equality of
proportions was used to compare the difference in rUO
between the prazosin and placebo groups. P values <0.05
were considered to be statistically significant. To assess
the impact of study variables on the outcome measure (ie,
odds of developing rUO), a multivariate logistic regres-
sion model was built using a stepwise forward inclusion
(P <0.25) backward elimination approach (P  <0.05).
Multicollinearity was assessed for using variance infla-
tion factor <2.5. Finally, a Cox proportional-hazard
model was used to analyze the risk of rUO development
chronologically between the two study groups. All analy-
ses were performed in R 3.5.1.
Results
From May 2014 to August 2017, 80 cats meeting the cri-
teria were enrolled in the study. Forty cats were rand-
omized into the prazosin group and 40 cats in the placebo
group. Following randomization, one cat from the pla-
cebo group was withdrawn from the study by its owner.
Two cats from the placebo group were lost to follow-up.
Of the 77 cats for which there was follow up information,
65 received the study medication, three received only one
dose and nine cats did not have any of medication admin-
istered following discharge. No specific adverse effects
were reported by owners. The 12 cats that did not receive
the complete course of study medication were excluded
from the data analysis. Sixty-five cats (37 treated with
prazosin and 28 treated with placebo) were therefore
included in the final evaluation.
Of the 65 cats that began the study, there were 47
domestic shorthairs, 11 domestic longhairs, four domes-
tic mediumhairs, two Maine Coons and one Russian
Blue cat. The median weight of the cats was 6 kg (range
3.7–10.8) and median age was 5 years (range 1–19).
Characteristics of cats treated with prazosin and placebo
and those experiencing rUO vs those that did not are dis-
played in Table 1. Based on the results from the Mann–
Whitney U-test, at inclusion, there were no significant
differences between cats treated with prazosin vs placebo
in any of the covariates evaluated except for duration of
catheterization, with prazosin cats having a significantly
shorter duration of urinary catheterization than placebo
cats (Table 1). No significant differences were identified in
any of the covariates evaluated between cats that experi-
enced rUO and those that did not, with the exception of a
significantly lower presenting packed cell volume (PCV)
in cats that experienced rUO (Table 1). No cat experienced
hypotension and there was no significant difference in
post-treatment Doppler blood pressure in cats treated
with prazosin and placebo, and those that experienced
rUO and those that did not.
Sixteen cats experienced recurrent urethral obstruction
(n = 16/65 [25%]). Of the 16 cats experiencing rUO, five
were in the placebo group (n = 5/28 [18%]) and 11 were
in the prazosin group (n = 11/37 [30%]).
Hanson et al 1179

Table 1  Selected characteristics in 65 cats treated with prazosin and placebo and those that did and did not
experience recurrent urethral obstruction (rUO): results from the Mann–Whitney U test

Variable and Cats treated with Cats treated with P value Cats with rUO Cats without rUO P value
applicable RI prazosin (n = 37) placebo (n = 28)

Age (years) 5 (1–17) 4.5 (1–19) 0.63 5 (2–9) 4 (1–19) 0.94

Weight (kg) 5.8 (3.9–9.9) 6 (3.7–10.8) 0.52 5.6 (3.3–9.0) 6 (4.0–10.8) 0.44
Temperature (°F) 100.9 (97.8–104) 101.7 (99–104.4) 0.07 100.9 (97.8–102.8) 101.3 (98.7–104.4) 0.48
HR (bpm) 210 (160–280) 210 (180–280) 0.78 205 (160–280) 220 (160–280) 0.18
RR (breaths/min) 60 (30–156) 47 (24–124) 0.19 47 (32–120) 60 (24–156) 0.38
SBP post-prazosin/ 123 (92–190) 118 (86–170) 0.75 121 (100–168) 120 (86–190) 0.81
placebo (mmHg)
Creatinine (mg/dl; 1.8 (1.05–12.9) 2.05 (0.91–18.1) 0.21 2.45 (1.35–18.1) 1.86 (0.91–12.3) 0.21
RI 0.7–2.1)
PCV (%; RI 35–55) 44 (31–55) 45 (31–56) 0.42 43 (32–52) 45 (31–56) 0.04
TS (g/dl; RI 5.5–7.5) 8 (6.4–10) 7.6 (6.2–8.6) 0.21 7.8 (6.2–8.6) 8 (6.6–10) 0.33
Potassium (mmol/l; 3.8 (3.2–10) 4 (3–9.3) 0.78 3.8 (3.3–10) 3.9 (3–8.3) 0.74
RI 3.6–5.6)
Duration of 24 (17–44) 28 (22–48) 0.03 29 (24–42) 26 (17–48) 0.16
catheterization (h)
Duration of 40 (24–72) 41 (26–72) 0.81 46 (26–56) 40 (24–72) 0.24
hospitalization (h)

P <0.05 was considered as statistically significant. Data are presented as median (range)
RI = reference interval; HR = heart rate; bpm = beats/min; RR = respiratory rate; SBP = systolic blood pressure; PCV = packed cell volume;
TS = total solids

Table 2  Results of the multivariate logistic regression model with risk factors found to significantly affect the probability
of developing recurrent urethral obstruction

Variable Regression coefficient Odds ratio 95% confidence interval P value

Creatinine 0.195 1.215 1.018–1.475 0.03

Total solids –1.134 0.322 0.093–0.936 0.05

Table 3  Results from the Cox-proportional hazard model showing no significant difference in time to recurrent urethral
obstruction between cats treated with placebo and cats treated with prazosin

Variable Coefficient Hazard ratio 95% confidence interval P value

Treatment group (prazosin vs placebo) 0.626 1.870 0.650–5.385 0.246

Importantly, results from the χ 2 proportional test
showed no significant difference in the incidence of
rUO in cats treated with prazosin vs placebo (P = 0.27).
Of the 16 cats with rUO, 10 (62%: two placebo cats and
eight prazosin cats) experienced rUO after urinary cath-
eter removal while still in hospital (median 6 h; range
6–16) and six (38%; three placebo cats and three prazo-
sin cats) experienced rUO within the 30-day follow-up
period (median 4.5 days; range 1–26). When looking
at the results from the multivariate logistic regression
analysis, only creatinine levels (P = 0.03) and total solids
(TS; P = 0.05) were found to significantly affect the odds
of developing rUO (Table 2). Multicollinearity of these
variables was assessed using the variance inflation fac-
tor (VIF; creatinine VIF 1.201, TS VIF 1.201). Consistent
with the results from the χ2 proportional test, the variable
‘treatment’ was not found to be statistically significant
(P = 0.27). Finally, results from the Cox-proportional haz-
ard model showed no significant difference in time to
rUO between cats treated with placebo and cats treated
with prazosin (P = 0.24) (Table 3 and Figure 1).
After study completion, a posterior sample size com-
putation using the study’s incidence rate of 25% (α: 0.05;
1-beta [β]: 0.8) found that 199 cats would be required
to truly determine statistically significant differences
between study groups.
1180 Journal of Feline Medicine and Surgery 23(12)
Figure 1  Cumulative survival distribution function for time to recurrent urethral obstruction (days) in 65 cats with lower urinary
tract obstruction treated with prazosin (n = 37) or placebo (n = 28), including the number of cats at risk in each treatment group
Discussion
In the current study, the rUO rate of all cats (25%) was
similar to rates previously reported.8–10 Between treat-
ment groups, the rUO rate was not significantly higher
in cats that received placebo (18%) compared with those
that received prazosin (30%). These results compare to
the results of a recently published prospective study10
evaluating the effect of prazosin on outcome in feline UO.
In that study there was no significant difference in rUO
rates in cats treated with 0.25 mg q12h prazosin vs pla-
cebo. The higher prazosin dose used in this study was the
same as the dose used in a retrospective study1 wherein
cats receiving prazosin at 0.5 mg/cat PO q12h had a lower
rate of rUO than cats treated with phenoxybenzamine.
Both the current study and the prior recent prospective
study10 actually identified a higher rate of rUO in cats
treated with prazosin (30% in the current study, 37% at 6
months in Reineke et al10) vs placebo (18% in the current
study, 31% at 6 months in Reineke et al10). Neither study
found this to be statistically significant and both stud-
ies were underpowered, and therefore this finding must
be interpreted with caution, but it is interesting to note.
Future higher-powered studies are necessary to deter-
mine if there is a statistically significant trend towards
higher rUO in cats treated with prazosin and examine
possible causes if this is the case.
The only presenting variable found to be significantly
different between cats treated with prazosin vs placebo
was the duration of catheterization, with placebo cats
having an indwelling urinary catheter in place signifi-
cantly longer than those treated with prazosin (28 h
vs 24 h; P = 0.03). There were a few cats in each group
whose urinary catheter was self-removed by the patient
slightly early (17–22 h). This was a study limitation in
that removal of the urinary catheter occurred during a
time range based upon clinical evaluation of the patient
rather than at a uniform specific time. However, duration
of catheterization was not found to be associated with
any significant difference in development of rUO vs not
(P = 0.24). A previous study found that a shorter duration
of urinary catheterization was significantly associated
with a higher probability of rUO, although this study had
multiple uncontrolled variables.6 Future studies more
specifically evaluating the role of duration of catheteri-
zation on development of rUO are warranted.
Prior studies have suggested that cats with UO may
develop anemia secondary to bladder hemorrhage
related to inflammation and high intraluminal bladder
pressure.13,20 In the present study, cats experiencing rUO
had a significantly lower PCV than those that did not.
However, as there was no significant difference identi-
fied in PCV between the treatment groups in general,
it is difficult to place high value on this finding and it is
unlikely that this contributed in any major way to devel-
opment of rUO. Additionally, the clinical implications of
the decreased PCV in cats experiencing rUO are likely to
have been low, as the median PCV in this group was 43%,
well within the RI (35–55%).
Based on the results of multivariate logistic regres-
sion analysis, creatinine levels (P = 0.03) and TS (P = 0.05)
were found to significantly affect the probability of devel-
oping rUO. Increasing creatinine was associated with an
increasing probability of rUO, and increasing TS was
associated with a decreasing probability of rUO. Prior
Hanson et al 1181
studies have correlated the degree of azotemia in cats
with UO with the length of hospitalization.21 The sever-
ity of azotemia is hypothesized to correlate with a higher
level of inflammation and hemorrhage within the bladder
and kidneys, contributing to more urinary debris, requir-
ing extended hospitalization.21 However, no prior studies
have specifically correlated these variables with the risk
of rUO and, based upon our limited sample size, these
findings should be interpreted with caution.
Sample size was an important limiting factor in this
study. Of the 80 cats initially enrolled, 15 had to be
excluded owing to loss to follow-up and non-compliance
with medication administration. A larger number of these
cats were lost from the placebo group than the prazosin
group, leading to an imbalance in the study population
− 28 cats were in the placebo group and 37 in the prazosin
group, as opposed to the even distribution as originally
intended. During the study design, 80 cats were initially
calculated to be necessary; however, based on a posterior
sample size computation using the current study’s inci-
dence rate of 25% (α: 0.05; 1- β: 0.8), 199 cats would need to
be evaluated to truly determine statistically significant dif-
ferences between study groups. This is a smaller popula-
tion than suggested by previous studies and may therefore
be more attainable for future evaluation.10 Administration
of prazosin does not decrease the frequency of rUO based
upon our results, lending support to prior similar conclu-
sions;10 however, owing to the underpowered nature of
our study, this finding must be interpreted cautiously.
Additional limiting factors included the inability to
strictly control for all variables that could contribute to
rUO. A standardized analgesic and anesthetic protocol
was used for this study, as was standardized placement
of a 3.5 F indwelling urinary catheter; however, duration
of catheterization – as discussed above – was not strictly
controlled. Environmental and dietary factors were also
not controlled following discharge. More strict control of
variables between groups should be considered in future
studies.
Larger, more strongly powered prospective studies are
necessary and will help provide further definitive infor-
mation about the potential benefit of prazosin in manage-
ment of feline urethral obstruction.
Conclusions
Administration of prazosin 0.5 mg/cat PO q12h for 7 days
did not reduce the frequency of rUO within 30 days of
treatment for UO in this small population of cats present-
ing with UO for the first time.
Acknowledgements  The authors would like to thank the
pharmacists and staff at The Pet Apothecary compounding
pharmacy in for their assistance with this project. Dr Cheryl
Waldner was very helpful with the statistical design and evalu-
ation. In addition, without the support of the nursing and
­customer care team at Lakeshore Veterinary Specialists, this
study would not have been possible.
Conflict of interest The authors declared no potential
conflicts of interest with respect to the research, authorship,
and/or publication of this article.
Funding  This study was funded by a grant from the Every-
Cat Heath Foundation (formerly the Winn Feline Foundation;
W15-042) and, in part, by Lakeshore Veterinary Specialists.
Ethical approval This work involved the use of non-­
experimental animals only (including owned or unowned
animals and data from prospective or retrospective studies).
Established internationally recognized high standards (‘best
practice’) of individual veterinary clinical patient care were
followed. Ethical approval from a committee was therefore not
necessarily required.
Informed consent  Informed consent (either verbal or writ-
ten) was obtained from the owner or legal custodian of all
animal(s) described in this work (either experimental or non-
experimental animals) for the procedure(s) undertaken (either
prospective or retrospective studies). No animals or humans
are identifiable within this publication, and therefore addi-
tional informed consent for publication was not required.
ORCID iD  Kayla R Hanson https://orcid.org/0000-0001-
7232-5734
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