The Veterinary Journal 253 (2019) 105377

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The Veterinary Journal

journal homepage: www.elsevier.com/locate/tvjl

Retrospective evaluation of prazosin and diazepam after

thoracolumbar hemilaminectomy in dogs
K.H. Barnes* , K.S. Aulakh, C. Liu
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive, Baton Rouge, LA 70803, USA

A R T I C L E I N F O A B S T R A C T

Article history: Management of urinary retention after spinal cord injury in dogs is often needed and can include use of
Accepted 10 September 2019 medications to relax the urethral sphincter. This was a retrospective study evaluating two such
medications, prazosin and diazepam, and whether dogs treated with these medications had different
Keywords: lengths of hospitalization, urinary continence levels, or development of bacteriuria compared to dogs not
Diazepam receiving these medications after thoracolumbar hemilaminectomy for intervertebral disc herniation
Intervertebral disc disease (IVDH). Electronic medical records were searched for dogs that underwent CT or MRI followed by a
Prazosin
hemilaminectomy between the 3rd thoracic and 3rd lumbar vertebra for treatment of IVDH. Dogs were
Urethral sphincter relaxation
Urinary tract infection
grouped based on whether or not they received a medication to aid in urethral sphincter relaxation
(either prazosin, diazepam, or both medications). The total length of hospitalization, urinary continence
at the time of discharge, and presence of bacteriuria were recorded from the medical file. Medical records
from 71 dogs were included in the analysis.
There were no significant associations between administration of prazosin and/or diazepam and length
of hospitalization or urinary continence scores at the time of discharge from the hospital (P > 0.05).
© 2019 Elsevier Ltd. All rights reserved.

Introduction urinary overflow incontinence may occur. Urinary retention may

Urinary dysfunction in dogs with spinal cord compression due
to thoracolumbar intervertebral disc herniation (IVDH) has been
well investigated (Bubenik and Hosgood, 2008; Bubenik et al.,
2007; Hu et al., 2016; Stiffler et al., 2006). In normal animals,
pressure and volume thresholds within the bladder signal action
potentials which are transmitted to the pontine micturition
center and cerebral cortex. Voluntary urination occurs with
simultaneous contraction of the detrusor muscle and relaxation
of the urethral sphincter. Thoracolumbar spinal cord compression
due to IVDH can cause interruption of this pathway resulting in
increased tone to the urethral musculature and a distended
urinary bladder which is difficult to manually express (Byron,
2015; Carwardine et al., 2017). If left untreated, over-distention of
the urinary bladder due to urinary retention may eventually lead
to irreversible damage to the tight junctions within the detrusor
muscle and subsequent atony (Haagsman et al., 2013). Once
volume within the urinary bladder exceeds urethral pressure,
* Corresponding author. Current address: Department of Small Animal Clinical
Sciences, Texas A&M University, College of Veterinary Medicine, 660 Raymond
Stotzer Parkway, College Station, TX 77843, USA.
E-mail address: kbarnes@cvm.tamu.edu (K.H. Barnes).
also lead to prolonged hospitalization times after surgery to treat
IVDH as many owners may not be comfortable (or capable) of
bladder expression at home. Additionally, prolonged bladder care
may predispose to the development of bacteriuria after spinal
surgery in dogs (Hu et al., 2016).
Pharmacological management of urinary retention in dogs after
thoracolumbar hemilaminectomy is often utilized. Two commonly
used medications, prazosin and diazepam, work by different
mechanisms to relax muscle within the urethral sphincter (Byron,
2015). Prazosin is a sympatholytic drug which blocks the alpha-1
adrenergic receptors of the urethral smooth muscle. It has
previously been shown to decrease urethral pressure in dogs
and has been used to treat several conditions including malignant
urethral obstruction and vesico-urethral reflex dyssynergia
(Haagsman et al., 2013; Noguchi et al., 2008). Diazepam leads to
skeletal muscle relaxation by potentiating the inhibitory amino
acid, gamma-aminobutyric acid (GABA) (Byron, 2015). Previous
reports have documented a decrease in urethral pressure in
animals after treatment with diazepam (Mawby et al., 1991).
Reducing urethral tone may help facilitate manual bladder
expression or may aid in faster return of voluntary urination by
decreasing the resistance against which the detrusor muscle must
contract. If voluntary urination can be achieved more rapidly after
surgery, or bladder expression can be facilitated so that owners are

http://dx.doi.org/10.1016/j.tvjl.2019.105377
1090-0233/© 2019 Elsevier Ltd. All rights reserved.
2 K.H. Barnes et al. / The Veterinary Journal 253 (2019) 105377
capable of performing this procedure at home, then total
hospitalization times after thoracolumbar hemilaminectomy
may be reduced. Additionally, it is possible that decreasing
urethral pressure may lead to lower residual bladder volumes
thereby decreasing the risk of bacteriuria in these dogs.
Despite the use of these medications after thoracolumbar
hemilaminectomy in dogs, there is little definitive evidence for
their efficacy in this clinical scenario. The purpose of this study is to
retrospectively investigate the use of prazosin and diazepam after
thoracolumbar hemilaminectomy for IVDH in dogs. Our hypothesis
was that there would be a significant difference in hospitalization
times and urinary continence at the time of discharge in dogs
treated with or without prazosin or diazepam after hemilaminec-
tomy for thoracolumbar IVDH.
Materials and methods
Electronic medical records from 28 July, 2014 to 27 November,
2016 were retrospectively reviewed for dogs that underwent MRI
or CT of the thoracolumbar spine followed by a hemilaminectomy
at the Louisiana State University Veterinary Teaching Hospital.
Cases were included in the analysis if they had a complete medical
record, survived to discharge, had a diagnosis of IVDH between the
3rd thoracic vertebra and the 3rd lumbar vertebra without any
other abnormality of the spinal cord (such as neoplasia or
fibrocartilaginous embolism), and had a modified Frankel score
of 3 or less before surgery. The modified Frankel scoring system
was as follows: (0) absent pain sensation; (1) paraplegic with
intact deep pain perception; (2) paraplegic with intact superficial
pain sensation; (3) non-ambulatory paraparetic; (4) ambulatory
paraparetic; and (5) spinal pain only. A modified Frankel score of 3
or less was chosen for analysis since dogs without motor function
(paraplegia) or with minimal motor function (non-ambulatory
paraparesis) are likely to require assistance with urination. Breed,
age, sex, or bodyweight were not reasons for exclusion from the
study. Dogs that met the inclusion criteria were then divided into
the following groups: dogs that received pharmacological
management of urinary retention (either prazosin [Pfizer],
diazepam [Hospira], or both) after surgery, and dogs that did
not receive pharmacological management of urinary retention.
Dogs that received pharmacological management of urinary
retention were then further subdivided in three groups: prazosin,
diazepam, and both prazosin and diazepam. The decision to
administer medications was at the discretion of the head clinician.
Additional data recorded from the record included breed, age at
presentation, sex, bodyweight, body condition score, nights of
hospitalization after surgery, and the dose and frequency of any
medication used to aid in urine expulsion (if applicable). Additionally,
the duration of clinical signs, bladder management techniques after
surgery, and results of urinalysis and urine culture were recorded.
Each dog’s urinary function at the time of discharge from the
hospital was retrospectively graded according to a scale utilized in
a recently published article (Dixon and Fauber, 2017). Dogs were
assigned a urinary grade of 1 if they had normal urinary function;
grade 2 if they could initiate urination voluntarily but were unable
to completely empty the urinary bladder or were unable to initiate
urination but could maintain a stream of urine after manual
bladder expression was initiated; and a urinary grade 3 if they had
complete urinary incontinence. When noted in the record, the
method for evaluating completion of bladder emptying was
recorded.
Finally, evidence of bacteriuria before discharge from the
hospital was recorded by noting a positive urine culture with
growth of >1000 CFU/mL of any bacteria (Bubenik et al., 2007).
Urinalysis (UA) results and method of urine collection for UA and/
or culture (if available) were also recorded.
Statistical analysis
Data analyses were performed using a commercially available
software package (JMP Pro 13, SAS Institute). A logistic regression and
an ordinal logistic regression were used to evaluate the presence of
bacteriuria (yes and no) and urine grade (1–3) with the effects of
medications to aid in urination/bladder expression, sex, breed, age,
and weight. The number of nights in the hospital was analyzed with
the effect of medications to aid in urination/bladder expression, sex,
and breed. The independence of each effect was accessed with Chi-
square tests, spearmen correlation and one-way ANOVA dependent on
the nature of data. Statistical significance was set at P < 0.05.
Results
Dogs
A total of 71 records met the inclusion criteria for use in the study.
Breeds included 46 Dachshunds (65%), 10 Mixed breed (14%), two
Bassett Hounds (3%), three French bulldogs (4%), three Chihuahuas
(4%), two Shih Tzus (3%), one German shepherd dog (1%), one
Pekingese (1%), one Brussels Griffon (1%), one Cocker spaniel (1%),
and one Xoloitzcuintli (1%). For the purpose of data analysis, all
breeds besides Dachshund and Mixed breed were grouped together
as “other” breed. The mean age at the time of presentation was 6.5
years (standard deviation [SD], 2.77; range, 2–13 years) and the mean
bodyweight was 8.9 kg (SD, 6.34; range, 2.5–35.1 kg). The mean body
condition score was 6 (range 3–9). Four of 71 dogs were intact
females (6%), 2/71 were intact males (3%), 40/71 were neutered
females (56%), and 25/71 were neutered males (35%).
The duration of clinical signs prior to admission to the hospital
was as follows:  1 day (n = 44/71), 1–2 days (n = 12/71), 2–7 days
(n = 8/71), 8–14 days (n = 3/71), and not noted (n = 4/71). The ability
to urinate at the time of admission into the hospital was only
recorded for three dogs and was not included in analysis.
Modified Frankel scores
Prior to surgery, 6/71 dogs (8%) had a modified Frankel score of
0; 14/71 dogs (20%) had a modified Frankel score of 1; 26/71 dogs
(37%) had a modified Frankel score of 2; and 25/71 dogs (35%) had a
modified Frankel score of 3. A total of 47/71 dogs (66%) received
medication to help with urination after surgery (either prazosin,
diazepam, or the combination of the two medications). Overall, the
total number of dogs that received prazosin alone was 34/71 (48%),
the total number of dogs that received diazepam alone was 5/71
(7%), and the total number of dogs that received both diazepam and
prazosin was 8/71 (11%). Thirty-three of 71 dogs underwent
surgery at the level of the hypogastric nerve roots (L1–L4). Of these
33 dogs, 21/33 (64%) received medication to aid urination. Thirty-
eight of 71 dogs underwent surgery cranial to the hypogastric
nerve roots. Of these 38 dogs, 25/38 (66%) received medication to
aid urination. Each surgery was performed or supervised by one of
14 board certified small animal surgeons. The mean dose of
prazosin was 0.28 mg/kg/day PO (range, 0.1–1.2 mg/kg/day). The
mean dose of diazepam was 0.9 mg/kg/day PO or IV (range, 0.57–
1.8 mg/kg/day). There was no significant association between the
modified Frankel score (0–3) and whether the dog received a
medication to aid urination (P = 0.2630). Bladder care after surgery
was noted in 50 dogs; 30/50 had an indwelling urinary catheter;
20/50 underwent manual bladder expression. Twenty of 30 dogs
that underwent urinary catheterisation also received medication
to relax the urethral sphincter. Fourteen of 20 dogs treated with
manual bladder expression also received medication to relax the
urethral sphincter. Dogs treated that were catheterized after
surgery had bladder care for an average of 4.2 days (SD, 4.3 days;
 K.H. Barnes et al. / The Veterinary Journal 253 (2019) 105377
range 1–17 days). Dogs treated with manual expression after
surgery had bladder care for an average of 4.3 days (SD 2.7; range,
1–11 days).
Duration of hospitalization
The average duration of hospitalization after surgery was 5 days
(SD, 3.44 days; range, 1–17 days). Administration of a medication to
aid in urine expulsion did not affect the duration of hospitalization
after surgery in this group (P = 0.1176).
Urinary function
At the time of discharge from the hospital, 42/71 dogs (60%) had
a urinary grade of 1; 8/71 (11%) had a urinary grade of 2; and 21/71
(30%) had a urinary grade of 3. Bladder assessment and/or ability to
urinate was assessed every 6–8 h while in hospital. The method for
determining completion of bladder emptying was recorded in 34
dogs. Five dogs had a strong urine stream when taken outside. In 29
dogs, the bladder was measured with ultrasound after urination
and it was determined that they were urinating independently due
to a small residual bladder volume. Of the dogs with a urinary
grade of 1, 17/42 (40%) received prazosin alone; 3/42 (7%) received
diazepam alone; 4/42 (10%) received both prazosin and diazepam;
and 18/42 (43%) did not receive either medication. Of the dogs with
a urinary grade of 2, 7/8 (88%) received prazosin alone and 1/8
(12%) received diazepam alone. Of the dogs with a urinary grade of
3, 10/21 (48%) received prazosin alone; 1/21 (5%) received
diazepam alone; 4/21 (19%) received both medications; and 6/21
(29%) received neither medication. Bodyweight was the only
variable that had a statistically significant effect on urinary grade
(P = 0.0152). There was a 14% increase in likelihood of urinary
continence with every 1 kg increase in bodyweight. There was no
significant difference in urinary grade at the time of discharge
between dogs that received a medication to aid in urine expulsion
and those not pharmacologically managed for urinary retention
(P = 0.1378).
Urinalysis results
Fifteen dogs underwent urinalysis during hospitalization. Urine
was collected by cystocentesis in 11/15 dogs, catheterization in 2/
15 dogs, and via free catch in 2/15 dogs. In dogs that had urine
collected via cystocentesis or catheterization, six dogs had
evidence of bacteriuria on urinalysis, seven dogs had >5 white
blood cells/high power field (WBC/hpf) on urinalysis (5–10 WBC/
hpf, n = 2/7; 10–20 WBC/hpf, n = 1/7; 20–50 WBC/hpf, n = 1/7; 50–
100 WBC/hpf, n = 2/7; >100 WBC/hpf, n = 1/7). Urine culture was
performed in 14 dogs and was positive with >100,000 CFU/mL in 9/
14 dogs. All dogs with bacteriuria noted on UA had positive
bacterial cultures. Bacterial isolates identified included Enterococ-
cus spp. (n = 3/9), Pseudomonas aeruginosa (n = 1/9), Proteus
mirabilis (n = 1/9), Serratia spp. (n = 1/9), Klebsiella spp. (n = 1/9),
Enterobacter spp. (n = 1/9), Corynebacterium urealyticum (n = 1/9),
Staphylococcus pseudointermedius (n = 1/9), and Raoultella spp.
(n = 1/9). All nine dogs that developed bacteriuria after surgery
received medication to aid in urine expulsion (P = 0.0006). Due to
the small number of dogs that received diazepam alone, the effect
of different drug type (prazosin vs. diazepam) on development of
bacteriuria could not be determined. All dogs that developed
bacteriuria were female.
Risk factors
There was no significant difference in total duration of
hospitalization, urinary score, or bacteriuria among different
3
breeds, ages, bodyweights, or body condition scores. Female dogs
were more likely to be diagnosed with bacteriuria compared to
male dogs (P = 0.0189). Intact dogs had significantly shorter
hospitalization lengths compared to neutered dogs (P = 0.0389);
however, care should be taken when interpreting this due to the
small number of intact dogs in this population (n = 6/71).
Follow up
Follow-up was available for 32 dogs (range, 6 days to 2 years).
Owners of dogs that required manual bladder expression at the
time of discharge were instructed to perform this task every 8–12 h
at home. According to dog owners, at the time of follow-up 24/32
dogs were able to urinate on their own without assistance (urine
grade 1); 4/32 had a urine grade of 2; 2/32 were completely
incontinent (urine grade 3); and 2/32 did not report on urination at
the recheck appointment. No dogs that were continent at the time
of discharge became incontinent during the follow-up period.
Twelve of the 32 dogs with follow-up had a urine grade of 3 at the
time of discharge. Of those 12 dogs, 2/12 had no improvement in
urine grade; 3/12 improved 1 grade; and 7/12 improved two
grades. Three of the 32 dogs with follow up had a urine grade of 2 at
the time of discharge. Of these three dogs, one showed no
improvement, and two improved 1 grade. Of the 12 dogs that had
improvement in urine grade after discharge, 6/12 were placed on
prazosin alone after surgery, 1/12 received prazosin and diazepam
after surgery, and 1/12 received diazepam alone after surgery.
Discussion
Based on these results, and contrary to our hypothesis, we
found that administration of prazosin and/or diazepam was not
associated with a different length of hospitalization or urinary
continence score after hemilaminectomy for thoracolumbar IVDH
compared to dogs not receiving these medications. We did find,
however, that development of bacteriuria after surgery was more
likely to occur in dogs being prescribed a medication to aid in
urethral muscle relaxation.
Management of urinary dysfunction after hemilaminectomy for
thoracolumbar IVDH in dogs is often needed due to loss of
inhibitory signals to the hypogastric and pudendal nerves,
vesicosphincter dyssynergia, and urinary overflow incontinence
(Bubenik and Hosgood, 2008; Byron, 2015; Olby et al., 2010).
Management methods include manual bladder expression, inter-
mittent cystocentesis, intermittent urinary catheterization, in-
dwelling urinary catheter placement, monitoring for and
treatment of urinary tract infections, and administration of
medications to relax the urethral sphincter (such as prazosin
and diazepam) (Bubenik et al., 2007; Hu et al., 2016).
Prazosin is an α adrenoceptor antagonist which aids in urination
by inhibiting contraction of the urethral smooth muscle (Erve et al.,
2007; Lopez et al., 2003). It has a high affinity for α-1 receptors (α-1
to α-2 receptor ratio of 500–1000:1) thereby limiting the potential
side effects of dizziness and hypotension that occur with
antagonism of α-2 receptors (Fischer et al., 2003). It has been
previously shown to inhibit contraction of muscle in both the
urethra and the vas deferens in dogs (Noguchi et al., 2008). Several
alternative α-1 antagonists have also been investigated and include
doxazosin, terazocin, alfuzosin, silodosin, and tamsulosin (Lopez
et al., 2003; Noguchi et al., 2008). Unlike some other α-1
antagonists, prazosin is a non-selective agonist of three subtypes
of α-1 adrenergic receptors (α-1A, α-1B, and α-1D) (Noguchi et al.,
2008; Ohtake et al., 2006). It is possible that another more selective
α-1 antagonist may be more effective in aiding urination after back
surgery in dogs. Phenoxybenzamine is also an α-1 antagonist
which has been used previously to decrease urethral muscle
4 K.H. Barnes et al. / The Veterinary Journal 253 (2019) 105377
contraction (Fischer et al., 2003). Use of this medication may have
fallen out of favor, however, due to its higher cost and carcinogenic
potential (Lane et al., 2000). Administration of phenoxybenzamine
has been associated with peritoneal sarcomas, intestinal
malignancies, and lung tumors in lab animals (Lane et al., 2000).
Diazepam is a centrally acting skeletal muscle relaxant which
decreases the tone within the external urethral sphincter through
potentiation of the inhibitory amino acid gamma-aminobutyric
acid (Byron, 2015; Haagsman et al., 2013). Urethral profile pressure
has been shown to decrease after administration of diazepam
experimentally (Mawby et al., 1991). Other medications which
have been used to relax striated muscle within the urethra include
dantrolene, baclofen, methocarbamol, and botulinum toxin (Diaz
Espineira et al., 1998; Haagsman et al., 2013; Mawby et al., 1991).
Infusion of the neuromuscular blocking agent, atracurium
besylate, into the bladder of dogs with spinal cord injury has also
been performed (Galluzzi et al., 2015).
We originally theorized that use of prazosin and/or diazepam
would either enable dogs to regain urinary continence more
rapidly, or would make bladder expression easier, enabling more
rapid discharge from the hospital after surgery. In contrast, we
found that there was no association between length of hospitali-
zation after surgery and administration of a medication to aid in
urine expulsion. As this was a retrospective study, other factors
which could influence the length of hospitalization, such as
concurrent disease (renal insufficiency or endocrine disease),
behavioral issues, or factors unrelated to the animal (such as an
owner who is unable to travel and pick up an animal from the
hospital), could not be controlled for in this study. Information
regarding animal temperament and owner availability for travel
was unfortunately not available for analysis.
We also did not find an association between administration of
prazosin and/or diazepam and urinary continence in this group of
dogs. In order to assess urinary continence, we used a previously
described urinary grading system (Dixon and Fauber, 2017). An
alternative method for evaluating urination, such as ultrasono-
graphic measurement of residual urine volume, may help to fully
investigate the effect of these medications on urinary continence in
the future (Atalan et al., 1999). As this was a retrospective study, we
were also unable to assess whether these medications minimized
the force and time required for manual bladder expression.
Subjective assessment of the ease of bladder expression, or
urethral profile pressures, could also be performed in the future.
Bacteriuria was noted in 13% of dogs in this study which is
similar to the previously reported rates after back surgery in dogs
(Bubenik and Hosgood, 2008; Stiffler et al., 2006). Urinary stasis
and larger than normal residual bladder volumes can occur after
back surgery and may predispose to infection. A recent study
illustrating the importance of residual volumes showed that only
about 50% of the bladder volume could be emptied during manual
expression (Carwardine et al., 2017). Additionally, as animals
regain the ability to urinate after back surgery, residual urine
volumes are initially higher before gradually decreasing during the
recovery process (Atalan et al., 1999; Smarick et al., 2004).
Development of bacteriuria after hemilaminectomy in dogs is
likely multifactorial and other factors previously associated with
this diagnosis include body temperature under anesthesia,
gender, and absence of perioperative antibiotics (Stiffler et al.,
2006). In the current study, all dogs that were diagnosed with
bacteriuria received medication to decrease urethral tone.
Although the reason behind this association is not clear, one
possible explanation is that administration of medications to
decrease urethral sphincter tone may have allowed an easier
passageway for bacteria to ascend into the urinary tract.
Additionally, all the dogs diagnosed with a urinary tract infection
in this study were female. This may be due to the shorter urethral
length in female dogs allowing for an easier passageway for
bacteria to gain access to the bladder.
One limitation regarding the diagnosis of bacteriuria in this
study was that a urinalysis and urine culture were not performed
for every dog. Although our methods for the diagnosis of
bacteriuria are similar to those used previously, (Bubenik and
Hosgood, 2008; Carter et al., 1978; Olby et al., 2010) it is possible
that some dogs with occult disease may have gone undiagnosed. A
previous study documented that up to 60% of urinary tract
infections diagnosed after back surgery in dogs were occult so
performing a urinalysis and urine culture for every dog would
provide the most complete picture of the development of
bacteriuria after surgery (Olby et al., 2010). Differentiating
between urinary tract infection and asymptomatic bacteriuria
may be challenging in dogs with thoracolumbar IVDD as
neurologic deficits may make evaluation of clinical urinary tract
signs challenging.
Serial urine cultures may provide more post-surgical
information, as dogs can develop bacteriuria in the following
months after surgery (Olby et al., 2010). We limited data collection
in this study to the immediate post-operative period as this is a
tertiary referral hospital and many animals were not available for
collection of follow-up information.
Other limitations of this study were related to the retrospective
nature of data collection.
Randomized allocation to treatment group was not possible and
information regarding the decision to start medications, along
with the elected dose, was not readily available from the medical
record. Information required to assess for urinary continence prior
to surgery was also not available for this group of dogs and dogs
were not assessed for the ability to urinate prior to the
administration of medication. Dogs were prescribed prazosin or
diazepam at the discretion of the primary clinician and it is
possible that dogs received medications to aid in urination if they
were already difficult to express, had more severe neurologic signs
and were perceived to be at a greater risk of not being able to
urinate on their own after surgery, or were perceived to be at
greater risk for being difficult to express (aggressive or large dogs).
These limitations should be taken into account when interpreting
the conclusions of this study.
Conclusions
In conclusion, administration of prazosin and/or diazepam were not
associated with a change in hospitalization time or urinary continence
score at the time of discharge from the hospital after hemilaminectomy
for IVDH. We did find that development of bacteriuria was significantly
associated with administration of a medication to aid in urine expulsion.
A randomized prospective clinical trial could help further investigate the
effects of these medications on clinical outcome andguide theiruse after
surgery in dogs.
Conflict of interest
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors. None
of the authors of this paper have a financial or personal
relationship with other people or organizations that could
inappropriately influence or bias the content of the paper.
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