Urethral Obstruction Management Journals August 2022

Aim to report clinical presentation of cats with urethral obstruction (UO) and severe anaemia (UO-A) and to describe the clinical parameters, risk factors and outcome.

Review of medical records of cats with urethral obstruction and anaemia 

Severe anaemia with need for transfusion <20% with Clinical Signs attributed to anaemia (tachycardia, hypotension, tachypnoea, prolonged CRT)

Exclusions included incomplete medical record, mild anaemia (>20) or anaemia attributed to another cause 

Unmatched controls 30 cats with UO and mild to no anaemia was randomly selected 

Treatments administered were at the clinician’s discretion.

Survivors if they were discharged alive from the hospital and non survivors if they died or were euthanized 

During the period of the study, 2132 cats were treated for urethral obstruction at our institution with 17 UO-A cases during this period this equates to an incidence of 0.8%

Signalment of UO-A: Median age - 3.8 years, DSH 16/17, 16/17 MN 

Cases in UO-A group were more likely to have experience a previous obstruction 65% vs 27% in control group

UO-A cases had a significantly longer duration of CSX median 3 days compared to UO controls of 1 day 

UO-A more likely to have gallop or murmur and statistically significant lower MAP  

Median PCV 28% for UO-a compared to 44 UO, with 7 of the UO-A cats having PCV <20 at presentation and all had a PCV <20 at time of transfusion.  3 cats did not receive a transfusion despite PCV <20%.   2 were euthanised prior to transfusion and 1 cats with PCV of 18 survived.  

TP, PCO2, K, lactate was not significantly different 

UO-A cats had a significantly higher BUN and crea conc, lower pH and more negative base excess and lower PCV 

UO-A 24x more likely to have grossly bloody urine 

Length of hospitalisation was not significantly longer with UO-A group but did have a significantly longer duration of U catheter

All UO obstruction cats survived to discharge compared to 76.5% in UO-A cats (all euthanised)

Discussion 

Cats were presumed to have haemorrhage into the urinary bladder as the cause of the severe anaemia.

Cases in this study UO-A group 11/17 (65%) were more likely to have been previously obstructed - contradicts another study by Lee et al J. Vet Emerg. Crit care 2006; 16(2): 104-111

Possible causes for UO-A; significantly longer duration of clinical signs compared to UO controls.  Likely that prolonged bladder wall pressure could cause more significant mucosal injury and haemorrhage.

UO-A cases more metabolically compromised.  In severe uraemia and acid base changes have been reported to contribute to platelet function abnormalities including impairment of platelet-platelet and platelet - vessel wall interactions.  These factors combined with more severe bladder mucosal injury due to previous obstruction and longer duration of clinical signs these may be additive risk factors for haemorrhage.

Length hospitalization was not significantly different between UO-A and UO groups indicating that once hydration and anaemia corrected the cats stabilize quickly.

The findings that urinary catheterization was longer in UO-A cats is not surprising as most clinicians leave U cath in place until urine is grossly clear.  

Mortality greater in UO-A cats 23.5% .  Cases much higher than in previous reports of cats with UO in which mortality ranged from 5.8% to 8.9% 

Limitations 

Retrospective  and Small sample size 

Double blinded placebo-controlled study to determine whether prazosin administration following urethral obstruction (UO) reduces the risk for repeat UO (rUO) and lower urinary tract signs.  An additional aim was to document the adverse effects associated with prazosin administration.

Materials and Methods

Case selection: Male cats hospitalized with UO 

Exclusion criteria: Chronic kidney failure, persistent hypotension (i.e. systolic BP <90mmHg) cardiac disease, or prior to treatment with beta blockers, ACEI, diuretics, prazosin or phenoxybenzamine , owner cannot manage oral medication and an ultrasound with shadowing structures which were presumed to be uroliths >2mm in diameter.

All cats elected had a standard treatment protocol.

Cats randomized into double blinded fashion to receive either prazosin (0.25mg/cat PO q12hr) or placebo (1 capsule PO q12hr) for 30 days.

1 month study of medication period was chosen based on prior studies that reported a median time to rUO of 17 days and a median time to recurrence of lower urinary tract signs within 18 days of hospital discharge.

After hospital discharge, medical records were reviewed for each cat with specific attention paid to the occurrence of previous episodes of UO or lower urinary tract signs ,the type of housing (i.e. indoor, outdoor or indoor and outdoor) , the type of diet (i.e. canned/dry or both) the vaccine status, the number of litter trays in the home and the number of other cats in the household.

Cat’s age, weight , BCS blood gas, size of urinary catheter and duration of hospitalization were recorded.

Standard discharge instructions - litter trays ( = no. of cats in house + 1 ) and litter tray hygiene , strategies for increasing water consumption (Eg circulating water fountains and wet food only diet ) .  Prescription feline urinary tract diet were made on a case-by-case basis depending on the presence or absence of crystalluria in the initial urine sample.

Follow up once weekly for 1 month and then at 6 months. 

Standard questionnaire - owner compliance with meds, observation of adverse effects from medication administration evidence of lower urinary tract signs (1-5) frequency and duration of these signs, any diet or environmental modifications or rUO or surgical interventions or death or euthanised as a result of rUO of FLUTD 

Results 

47 cats - 20 placebo and 27 in prazosin groups 

No significant differences between the demographics of cats in the prazosin groups and cats in the placebo group with regard to age, weight, BCS, vaccination, environment, no. of litter trays, number of other cats in household or previous episodes of UO

The prazosin group was more likely to have had a previous episode of FLUTD 44% compared to 10% with placebo group 

The prazosin group had a significantly shorter than the median duration of urinary catheterization and hospitalization for the placebo group 32 hr and 37 hr vs 39 hr and 46 hr respectively.

3 cats developed rUO prior to hospital discharge - 2 cats in the prazosin grp and 1 cat in the placebo group 

4 additional cats 2 in prazosin groups and 2 cats in the placebo group developed rUO in the 1 month study period. 

1 month rUO rate of cats in the prazosin grp was 15% (4/26) while the rUO rate in cats in placebo grp was 17% (3/18)

6 month follow up 25 cats available: 4 rUO (3 prazosin grp and 1 placebo grp) developed rUO at 34, 48, 155 and 180 days following the initial UO 

In cats with complete follow up information at 6 months the total rUO rate was 37% (7/19) in the prazosin grp and 31% (4/13) in the placebo grp 

All owners reported the presence of lower urinary tract signs in cats in both the prazosin and placebo groups at the 1 week follow up, ranging in severity from1 (mild straining) to 5 (continual straining ) but the median score was not significantly different around cats in the prazosin grp (median score 2.25) and placebo (median score 2.0)

There was no difference in severity of these clinical signs between groups as reported by cat owners.

Discussion 

Failed to find a difference in the rate of rUO but the study was underpowered.

Cats receiving prazosin shorter duration of catheter time 

The 7 cats in the prazosin grp that were reported to receive less than 50% of the medication did not experience rUO during the 1 month study medication period 

The most commonly reported adverse effects in the prazosin treated cats included lethargy, diarrhea , malodorous stool, ptyalism and ataxia

Aim of the study

To evaluate the effect of prazosin on the recurrence of urethral obstruction over a 30-day period vs placebo. 

Prospective randomised placebo-controlled blinded trial

Method:

Case selection included MN , 1st UO.

Cats had a standardised treatment protocol

Randomly assigned to 2 groups within 8 hours of unblocking : prazosin group (receiving 0.5 mg/cat prazosin q12h for 7 days) or the placebo group (q12hr for 7 days). Clinicians and owners were blinded to the treatment groups. 

Cats were discharged with 7 days of study medication and TM buprenorphine.   Advice was given on litter tray management, water intake, environmental modification and prescription urinary diets were assigned on a case-by-case basis.

Follow-up involved a standardised telephone interview within 1 week of hospital discharge and after 30 days.  Owner compliance with administration of the study medication and occurrence of rUO was recorded.  

Summary of Results

No statistical difference in rUO between groups

• Incidence of rUO of all cats was 25% which is similar to previous reports 

The only parameters related to ocurrence of rUO were 

• Increase in creatinine increased in probability of rUO

• Increase in total solids decreased in probability of rUO 

• lower packed cell volume (median still within reference interval) increase in probability of rUO

Studies have correlated the degree of azotaemia in cats with UO with the length of hospitalization , the severity of the azotaemia is hypothesized to correlate with a higher level of inflammation and haemorrhage within the bladder and kidneys contributing to more urinary debris , requiring extended hospitalization

The only difference between groups was duration of catheterisation

• shorter in the prazosin group

  • placebo cats 28 hr; prazosin cats 24 hr 

• However; duration of catheterization was not found to be associated with any significant difference in development of rUO

• 10 /16 cats (62%) experienced rUO post u cath removal whilst still in hospital

• median time was 6hr post U cath removal (range 6-16 hr)

• Of the 10 cats 2 were placebo cats and 8 were prazosin cats 

Limitations of Study 

The study was underpowered, needing 199 cats to truly determine statistical significance between groups. 15 cats were lost due to non-compliance and proportionally more from the placebo group, which could have affected results. Variables such as duration of catheterisation and management at discharge were not controlled. 

Relevance to clinical practice

Administration of prazosin does not decrease frequency of recurrent urethral obstruction. 

However, larger studies are needed. 

Appropriate analgesia and environmental modification may be equally or more important than therapy with prazosin. 

Higher doses of  prazosin are commonly used in clinical practice and for a longer duration; further studies are needed 

62% of rUO occurred whilst hospitalized (6-16 hours after u cath removal).  This may influence of the timing of u cath removal

Administration of prazosin at study dose rates does not cause a significant decrease in SBP 

Multicentre observational, retrospective cohort study.  2 Part study.

Part 1 

• Veterinarians who self reported that they either never or always prescribed prazosin to cats with UO were recruited 

• Exclusions vets who prescribed prazosin intermittently or on the basis of variable individual patient criteria to avoid bias 

• Cat enrolment and data collection were performed via an electronic survey which included patient data BCS (1-9), treatment data , difficulty unblocking , colour and bloodiness of the urine , and whether the cat developed rUO prior to being discharged from the hospital or within 14 days after discharge

• Exclusion of cats is they had developed UO secondary to urolithiasis or lower urinary tract neoplasia, if they developed a urethral tear or if the medical record contained insufficient patent data or treatment data for analysis 

Part 2

• To further evaluate prazosin’s impact on the rate of rUO aggregated the data of this study and 3 most recent published studies while excluding the data from the previous retrospective study 

Results

• 388 Male cats, all but 11 were MN

• 354 (91%) were mixed breed cats, 

• Cats generally received 0.5-1mg of prazosin PO once daily for 14 days 

• Compared with cats that did not receive prazosin, a greater proportion of cats that received the drug were <2 years of age.

• No other diff between the 2 groups were identified 

• Of the 388 cats, 302 (78%) received prazosin while 86 (22%) did not receive prazosin 

• 302 cats receive prazosin - 34 (11%) developed rUO before discharge and cumulatively by 14 days 72 cats (24%) developed rUO 

• Of the 86 cats not receiving prazosin 5 (6%) reobstructed before discharge and 11 (13%) reobstructed within 14 days 

• There was no significant association between prazosin administration and risk of rUO prior to discharge 

• However the cumulative rate of reobstuction was significantly higher in cats that were prescribed prazosin by 14 days following discharge 

• Other associations evaluated for increased risk of rUO included:

• the presence of crystalluria 

• the subjectively reported difficulty or urethral catheterization

• a subjectively gritty feel during catheterization and 

• clarity of the urine at time of u cath removal 

• The only significantly increased risk identified were a gritty feeling and subjectively diff u cath placement 

• 126 cats (32%) had gritty feel on urinary catheterization 

• Of these 8 (6%) experience rUO prior to discharge 

• 20 (16%) experience rUO within 14 days of discharge

• resulting in a cumulative rUO rate of 15%

• There was no significant association between grittiness and rUO prior to discharge 

• There was no significant difference in rates of rUO between cats that did not and did receive prazosin in the groups of cats with a gritty feel 

• There was no statistically significant difference between rates of rUO prior to discharge in cats that were subjectively easy or difficult to unblock , but there was a significant difference between rates of rUO for these groups within 14 days of discharge 

• There was no significant difference in rates of rUO between cats that did not receive prazosin in the groups of cats that were difficult to unblock 

Part 2 

• 700 cats with UO, 128 (18.3) of which experienced rUO at some time point during their retrospective study with 505 receiving prazosin and 195 not receiving prazosin 

• The rates of rUO in these populations were 19.4% and 15.4% respectively and there was no statistically significant difference in the rate of rUO between cats that did and did not receive prazosin 

• However removing the retrospective study by Hetrick and Davidlow and using only the data presented here combined with the prospective data from Hanson et al and Reineke et al revealed that 87 of 365 cats (24%) treated with prazosin developed rUO , while only 17 of the 133 (13%) of cats not prescribed prazosin developed rUO 

Discussion 

• No reduction in risk of rUO in cats treated with prazosin 

• Prazosin cats were more likely to reobstuct within 14 days of hospital discharge 

• Prazosin did not result in reduced risk for rUO 

• Feline urethra is only composed of smooth muscle along the proximal 28-37% of its length with the remainder of the urethral musculature being striated muscle which not is not relaxed by alpha 1 adrenoceptor blockade 

• Most of the urethral obstructions are thought to occur in the distal urethra well out of reach of the pharmacological activity and potential smooth muscle relaxant effect of the prazosin in the pre-prostatic and prostatic urethra 

• Limited evidence that spontaneous urethral spasm occurs in cats 

• Prazosin increases risk rUO within 14 days of discharge from hospital 

• Added stress of giving oral meds to cats 

• Potential hypotension or GIT upset 

• Owners not administering medication as prescribed 

• Grittiness at time of U catheterization results in an  increased risk of rUO in 14 days 

• Increased physical obstruction 

• Management - flush urethra both during cath  and when the urethral cath is removed but study by Dorsey et al failed to show a decreased rate of rUO associated with flushing 

• Increased difficultly of urethral cath was associated with increased risk of rUO within 14 days of discharge 

• Might include increased urethral inflammation and increased urethral trauma to unblock 

• Seitz et al identified that cats with discoloured urine at the time of catheter removal were more likely to reobstruct - this study did not report a difference in rate of rUO 

• Limitations to the study 

• Disparity of cohort size 3.5 x more prazosin cats 

• Observation study and lack of standardization of treatment 

• Lack of follow up